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Směrnice Xxxxxx 2000/32/XX

xx xxx 19. xxxxxx 2000,

xxxxxx xx po xxxxxxx šesté přizpůsobuje xxxxxxxxxxx pokroku směrnice Xxxx 67/548/XXX x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx týkajících xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx nebezpečných xxxxx [1]

(Text x xxxxxxxx xxx EHP)

KOMISE XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx o xxxxxxxx Evropského společenství,

s xxxxxxx xx xxxxxxxx Xxxx 67/548/XXX ze xxx 27. xxxxxx 1967 o xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx týkajících xx xxxxxxxxxxx, balení x xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], xxxxxxxxx xxxxxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Xxxx 1999/33/ES [3], x xxxxxxx xx xxxxxx 28 xxxxxxx směrnice,

vzhledem k xxxxx důvodům:

(1) Příloha X xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxx společně x xxxxxxxxxx xxxxx o xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx x technické xxxxxxxx ukazují, že xx měl xxx xxxxxx nebezpečných xxxxx x xxxxxxx příloze xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a xxxxxxx X v xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx xxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje seznam xxx x xxxxxxxxxxxxxx xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxx a xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje xxxxx xx xxxxxxxxxxx x x označování xxxxxxxxxxxx látek x xxxxxxxxx. Některé xxxxxxxx xxxxx směrnice xxxxxxxx xxxxxx xxxxxxxx oddílů xxxxxx XXX, XX x XX.

(3) X xxxxxxx X xxxxxxxx 67/548/XXX xx xxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx vlastností, toxicity x xxxxxxxxxxx xxxxx x xxxxxxxxx. Xx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxx xxxxxxxxxxx xxxxxxx.

(4) Xxxxxxx XX směrnice 67/548/XXX obsahuje xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx. Xxxx xxxxxxxx xx měly xxx xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx nezbytné xxxxxxxx xxxxxx, xxx se xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx používají.

(5) Xxxxxxxx xxxx xxxxxxxx xxxx x xxxxxxx xx xxxxxxxxxxx Xxxxxx xxx xxxxxxxxxxxx technickému xxxxxxx xxxxxxx pro xxxxxxxxxx technických xxxxxxxx xxxxxxx na úseku xxxxxxxxxxxx xxxxx x xxxxxxxxx,

XXXXXXX TUTO SMĚRNICI:

Článek 1

Xxxxxxxx 67/548/XXX xx mění takto:

1. Xxxxxxx X xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxxxx x xxxxxxxxx xx nahrazuje poznámkou X v příloze 1X této směrnice;

b) xxxxxxxxxxxx řádky x xxxxxxx X se xxxxxxxxx xxxxx v xxxxxxx 1X této xxxxxxxx;

x) xxxxxxxxxxxx xxxxxxx xx nahrazují xxxxxxxxx x příloze 1X xxxx xxxxxxxx;

x) vkládají xx položky x xxxxxxx 1X xxxx xxxxxxxx.

2. Xxxxxxxxxxxx xxxx x xxxxxxx XXX xx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxx specifickou xxxxxxxxxx v xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx XX se xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx x xxxxxxx XX se xxxxxxxxx xxxxxxxxxxxx xxxxxx pro xxxxxxxx xxxxxxxxx x xxxxxxx 3A této xxxxxxxx;

x) odpovídající xxxxxx x xxxxxxx XX xx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3B xxxx xxxxxxxx.

4. Xxxx B xxxxxxx V se xxxx xxxxx:

x) xxxxxxxx X.10 se xxxxxxxxx xxxxxx v příloze 4X této směrnice;

b) xxxxxxxx X.11 xx xxxxxxxxx xxxxxx v xxxxxxx 4X xxxx xxxxxxxx;

x) xxxxxxxx B.12 xx xxxxxxxxx xxxxxx x příloze 4X xxxx xxxxxxxx;

x) xxxxxxxx X.13 x X.14 xx nahrazují xxxxxx x xxxxxxx 4X xxxx směrnice;

e) xxxxxxxx X.17 se xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;

x) xxxxxxxx X.23 se xxxxxxxxx xxxxxx v xxxxxxx 4X této xxxxxxxx. Xxxxx xxxxxxxx X.23 ve vysvětlivce xx xxxx xxxxxxxxxxxxx xxxxxxxx;

x) xxxxxx xx xxxx v xxxxxxx 4X xxxx xxxxxxxx.

5. Xxxxxxx se xxxxxx xxxxxxx xxxxxxxx xxxxx x části C xxxxxxx X.

6. Odpovídající xxxxx v xxxxxxx XX xx xxxxxxxxx xxxxx x xxxxxxx 5 xxxx směrnice.

7. Xxxxxxx IX se xxxx xxxxxxxx xxxxxxxx x xxxxxxx 6 xxxx směrnice.

Xxxxxx 2

1. Xxxxxxx xxxxx xxxxxx x xxxxxxxx xxxxxx x xxxxxxx předpisy nezbytné xxx xxxxxxxx souladu x xxxxx směrnicí xxxxxxxxxx xx 1. xxxxxx 2001. Neprodleně x xxxx xxxxxxx Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx xx xxxx xxxxxxxx nebo xxxx xxxxxx odkaz xxx xxxxxx při xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx odkazu si xxxxxxx členské státy.

2. Xxxxxxx xxxxx xxxxx Xxxxxx znění hlavních xxxxxxxxxx xxxxxxxxxxxxxx právních xxxxxxxx, xxxxx xxxxxxx x xxxxxxx působnosti xxxx směrnice, x xxxxxxxxxx tabulku mezi xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Xxxx xxxxxxxx xxxxxxxx x xxxxxxxx xxxxxx xxxx xx xxxxxxxxx x Xxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.

Xxxxxx 4

Xxxx xxxxxxxx xx xxxxxx členským xxxxxx.

V Xxxxxxx dne 19. května 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise


[1] Přijato xx xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Xx. xxxx. 196, 16.8.1967, x. 1.

[3] Xx. věst. X 199, 30.7.1999, x. 57.


XXXXXXX 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx poznámek xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x označování xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


XXXXXXX 1X

"XXXXXXX X

X

Xxxxxx

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

18

Xx

Xxxxx

Xxxxx

Xxxxx

Αργό

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"


XXXXXXX 1C

Indexové číslo

Chemický xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační limity

Poznámky x přípravkům

006–011–00–7

karbaryl (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. xxx. 3; X40 Xx; R22 X; X50

Xx; X X: 22–40–50 X: (2-)22–24–36/37–46–61

006–013–00–8

xxxxxx-xxxxxxx (ISO) natrium-N-methyldithiokarbamát

205–293–0

137–42–8

Xn; X22 R31 X; X34 R43 N; X50–53

X; X X: 22–31–34–43–50/53 X: (1/2-)26–36/37/39–45–60–61

006–015–00–9

xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx

206–354–4

330–54–1

Xxxx. kat. 3; X40 Xxxx. xxx. 3; X40 Xx; X22–48/22 X; X50–53

Xx; X R: 22–40–48/22–50/53 X: (2-)13–22–23–37–46–60–61

006–016–00–4

xxxxxxxx (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

204–043–8

114–26–1

X; X25 N; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

xxxxxxxx (XXX) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx

204–123–2

116–06–3

X+; R26/28 T; X24 N; X50–53

X+; X R: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61

006–018–00–5

xxxxxxxxx (ISO) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

217–990–7

2032–59–9

X; X24/25 N; X50–53

X; X X: 24/25–50/53 X: (1/2-)28–36/37–45–60–61

006–019–00–0

xx-xxxxx (XXX) X-(2,3-xxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx

218–961–1

2303–16–4

Xxxx. xxx. 3; R40 Xx; X22 X; X50–53

Xx; X X: 22–40–50/53 X: (2-)25–36/37–60–61

006–020–00–6

xxxxxx (ISO) 4-xxxxxxxx-2-xx-1-xx-X -(3-xxxxxxxxxx)xxxxxxxx

202–930–4

101–27–9

Xx; R22 X43 X; R50–53

Xn; X X: 22–43–50/53 X: (2-)24–36/37–60–61

006–023–00–2

xxxxxxxxxxxxxxxx (XXX) xxxxxxxxxx 3,5-xxxxxxxx-4-(xxxxxxxxxxxxxx)xxxxx-X -xxxxxxxxxxxxxx

217–991–2

2032–65–7

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)22–37–45–60–61

006–024–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx

205–443–5

140–93–2

Xx; X22 Xx; X38 X; R51–53

Xn; X X: 22–38–51/53 X: (2-)13-61

006–026–00–9

xxxxxxxxxx (ISO) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx

216–353–0

1563–66–2

X+; R26/28 X; X50–53

X+; X X: 26/28–50/53 S: (1/2-)36/37–45–60–61

006–028–00-X

xxxxxxxxx (XXX) 2-(1-xxxxxxxxxxxx)-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx 2-xxx-xxxxx-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx

213–546–1

973–21–7

X; X25 X; R50–53

T; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

dioxakarb (ISO) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx

230–253–4

6988–21–2

X; X25 X; X51–53

X; X X: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

metoxuron (XXX) 3-(3-xxxxx-4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx

243–433–2

19937–59–8

X; R50–53

N X: 5 0/ 5 3 X: 60-61

006–034–00–2

xxxxxxx (XXX) S-propyl-N-butyl-N-ethylthiokarbamát

214–215–4

1114–71–2

Xn; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)23-61

006–035–00–8

pirimikarb (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx

245–430–1

23103–98–2

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2)22–37–45–60–61

006–037–00–9

promekarb (ISO) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–113–0

2631–37–0

X; X25 X; X50–53

X; N R: 25–50/53 S: (1/2-)24–37–45–60–61

006–038–00–4

xxxxxxxxx (XXX) 2-xxxxxxxxxx-X,X-xxxxxxxxxxxxxxxxxxxxxx

X

202–388–9

95–06–7

Xxxx. xxx. 2; R45 Xx; X22 N; X50–53

X; X R: 45–22–50/53 X: 53–45–60–61

006–039–00-X

tri-allát (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx

218–962–7

2303–17–5

Xx; X22–48/22 X43 X; X50–53

Xx; X X: 22–43–48/22–50/53 X: (2-)24–37–60–61

006–042–00–6

xxxxxxx (XXX) 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx

205–766–1

150–68–5

Xxxx. xxx. 3; R40 Xx; R22 X; X50–53

Xx; X X: 22–40–50/53 S: (2-)36/37–60–61

006–043–00–1

xxxxxxx-XXX 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx

—

140–41–0

Xx; X36/38 Xxxx. xxx. 3; R40 X; X50–53

Xx; N X: 36/38–40–50/53 S: (2-)36/37–60–61

006–045–00–2

xxxxxxxx (XXX) xxxxxx-X-[(X-xxxxxxxxxxxxxxx)xxx]xxxxxxxxxxxxxx

240–815–0

16752–77–5

X+; X28 N; R50–53

T+; X X: 28–50/53 X: (1/2-)22–36/37–45–60–61

006–046–00–8

xxxxxxxxxx (XXX) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx

245–216–8

22781–23–3

X; X23/25 Xx; X21 X; R50–53

T; X R: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61

006–047–00–3

bufenkarb (ISO) xxxx: 3-(1-methylbutyl)fenyl-N-methylkarbamátu x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

—

8065–36–9

X; R24/25 X; X50–53

X; N R: 24/25–50/53 X: (1/2-)28–36/37–45–60–61

006–048–00–9

xxxxxxxxxxxx (XXX) 2-[(ethylsulfanyl)methyl]fenyl-N-methylkarbamát

249–981–9

29973–13–5

Xn; R22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–050–00–X

xxxxxxx-XXX 3-xxxxx-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx

—

4482–55–7

Xx; X38 X; R50–53

Xi; X X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; R50–53

Xn; X X: 22–50/53 X: (2-)60-61

006–054–00–1

mexakarbát (ISO) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

206–249–3

315–18–4

X+; X28 Xn; X21 X; X50–53

X+; X R: 21–28–50/53 X: (1/2-)36/37–45–60–61

006–057–00–8

nitrapyrin (ISO) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)24-61

006–060–00–4

oxykarboxin (XXX) 2-xxxxxx-4,4-xxxxx-5,6-xxxxxxx-4λ4-1,4-xxxxxxxx-3-xxxxxxxxxxxx

226–066–2

5259–88–1

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

006–069–00–3

xxxxxxxxx-xxxxxx (XXX) 1,2-di[3-(methoxykarbonyl)thioureido]benzen

245–740–7

23564–05–8

Muta. xxx. 3; R40 X; R50–53

Xn; X X: 40–50/53 X: (2-)36/37–60–61

006–070–00–9

xxxxxxxxxxx N-cyklohexyl-N-methoxy-2,5-dimethyl-3-furamid

262–302–0

60568–05–0

Karc. kat. 3; R40 X; X50–53

Xx; N X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

benfurakarb (XXX) ethyl-N -[({[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]karbonyl}methylamino)sulfanyl]-N-isopropyl-β-alaninát(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)-N-({[2-(ethoxykarbonyl)ethyl]isopropylamino}sulfanyl)-N-methylkarbamát

—

82560–54–1

T; X23/25 X; X50–53

X; X R: 23/25–50/53 X: (1/2-)36/37–45–60–61

007–012–00–5

X,X-xxxxxxxxxxxxxxxx 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

X; X11 Xxxx. kat. 2; R45 X; X23/25 C; X34 X; R51–53

F; T; X X: 45–11–23/25–34–51/53 X: 53–45–61

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-xxxxxxxxxxxxxxxx

X

—

540–73–8

Xxxx. xxx. 2; X45 X; R23/24/25 X; X51–53

X; N R: 45–23/24/25–51/53 S: 53–45–61

X ≥ 25 %: X; X45–23/24/25 3 % < X &xx; 25 %: X; X45–20/21/22 0,01 % &xx; X &xx; 3 %: X; X45

009–003–00–1

xxxxxxxx xxxxxxxxxxxxxx … %

X

231–634–8

7664–39–3

X+; X26/27/28 X; R35

T+; X X: 26/27/28–35 S: (1/2-)7/9–26–36/37–45

X ≥ 7 %: X+; C; X26/27/28–35 1 % ≤ C &xx; 7 %: X; X23/24/25–34 0,1 % ≤ X &xx; 1 %: Xx; X20/21/22–36/37/38

015–039–00–9

xxxxxxx-xxxxxx (XXX) O,O-dimethyl-S -[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx

201–676–1

86–50–0

X+; X26/28 X; R24 X43 X; X50–53

X+; N X: 24–26/28–43–50/53 S: (1/2-)28–36/37–45–60–61

015–048–00–8

xxxxxxxx (ISO) X,X-xxxxxxxx-X-[3-xxxxxx-4-(xxxxxxxxxxxxxx)xxxxx]-xxxxxxxxxxxxx

200–231–9

55–38–9

Xxxx. xxx. 3; R40 X; X23–48/25 Xn; X21/22 X; R50–53

T; X X: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61

015–056–00–1

xxxxxxx-xxxxx (XXX) X,X-xxxxxxx-X-[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát

220–147–6

2642–71–9

T+; X28 X; X24 X; X50–53

X+; X X: 24–28–50/53 S: (1/2-)28–36/37–45–60–61

015–140–00–8

xxxxxxxxx (XXX) O,O-diethyl-O-(1-fenyl-1 H- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx

245–986–5

24017–47–8

X; R23/25 Xx; X21 N; R50–53

T; X X: 21–23/25–50/53 X: (1/2-)36/37–45–60–61

016–013–00-X

xxxxxxx sirnatý

234–129–0

10545–99–0

R14 X; R34 X; X50

X; X X: 14–34–50 S: (1/2-)26–36/37/39–45–61

X ≥ 10 %: X; R34 5 % ≤ X &xx; 10 %: Xx; X36/37/38

016–014–00–5

xxxxxxx siřičitý

—

13451–08–6

R14 X; X34 X; X50

X; X X: 14–34–50 X: (1/2-)26–36/37/39–45–61

C ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; R36/37/38

016–023–00–4

dimethyl-sulfát

E

201–058–1

77–78–1

Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; X26 T; X25 X; X34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

X ≥ 25 %: X+; X45–25–26–34–43 10 % ≤ X &xx; 25 %: X+; R45–22–26–34–43 7 % ≤ C &xx; 10 %: X+; R45–22–26–36/ 37/38–43 5 % ≤ X < 7 %: X; R45–22–23–36/37/38–43 3 % ≤ X &xx; 5 %: T; R45–22–23–43 1 % ≤ X &xx; 3 %: X; X45–23–43 0,1 % ≤ X &xx; 1 %: X; X45–20 0,01 % ≤ X &xx; 0,1 %:X; X45

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8

1468–37–7

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

016–071–00–6

3-xxxxx-6,13-xxxxxxx-10-[(3-{[4-xxxxx-6-(2-xxxxxxxxxxxxxxxx)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx xxxxxxxx

410–130–3

136248–03–8

X43

Xx X: 43 S: (2-)22–24–37

022–001–00–5

chlorid xxxxxxxxxx

231–441–9

7550–45–0

X14 X; X34

X X: 14-34 X: (1/2-)7/8–26–36/37/39–45

X ≥ 10 %: C; X34 5 % ≤ X &xx; 10 %: Xi; X36/37/38

030–004–00–8

xxxxxxxxxxxxx [1] xxxxxxxxxxxx [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; R17 C; X34 N; R50–53

F; X; X R: 14–17–34–50/53 S: (1/2-)16–43–45–60–61

050–002–00–0

xxxxxxxxx (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx tricyklohexylstannium-hydroxid

236–049–1

13121–70–5

Xn; X20/21/22 X; X50–53

Xx; X R: 20/21/22–50/53 X: (2-)13–60–61

050–012–00–5

tetracyklohexylstannan [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] xxxxx(xxxxxxxxxxxxx)xxxxxxx [3]

215–910–5 [1] 221–437–5 [2] 230–358–5 [3]

1449–55–4 [1] 3091–32–5 [2] 7067–44–9 [3]

Xx; X20/21/22 X; R50–53

Xn; X X: 20/21/22–50/53 X: (2-)26–28–60–61

X ≥ 1 %: Xn; R20/21/22

1

050–017–00–2

fenbutatinoxid (XXX) 1,1,1,3,3,3-xxxxxxx(2-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxxxx

236–407–7

13356–08–6

X+; X26 Xx; R36/38 X; X50/53

X+; X X: 26–36/38–50/53 X: (1/2-)28–36/37–45–60–61

082–009–00–X

xxxx (xxxxxxxxxxxx xxxxxxxx) XX Xxxxxxx Yellow 34 (XX 77603) XX xxxxxxxxxx xxxx 34 (XX 77603)

215–693–7

1344–37–2

Xxxx. xxx. 3; X40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 N; X50–53

X; X X: 61–33–40–50/53–62 X: 53–45–60–61

1

082–010–00–5

červeň (xxxxxxx-xxxxxxxxxx-xxxxx xxxxxxxx) CI Xxxxxxx Red 104 (XX 77605) XX xxxxxxxxxx xxxxxx 104 (XX 77605)

235–759–9

12656–85–8

Karc. xxx. 3; X40 Repr. xxx. 1; R61 Xxxx. xxx. 3; X62 R33 N; X50–53

X; N R: 61–33–40–50/53–62 S: 53–45–60–61

1

601–024–00-X

xxxxx [1] xxxxxxxxxxxx [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

X10 Xx; X65 Xi; X37 X; X51–53

Xx; X R: 10–37–51/53–65 X: (2-)24–37–61–62

4

601–032–00–3

xxxxx[x]xxxxx xxxxx[xxx]xxxxxxx

200–028–5

50–32–8

Xxxx. xxx.2; R45 Xxxx. xxx. 2; X46 Xxxx. xxx. 2; X60–61 X; X50–53

X; X R: 45–46–60–61–50/53 X: 53–45–60–61

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. kat.2; X45 X; R50–53

T; X R: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 X; X50–53

Xx; X X: 36–50/53 X: (2-)24/25–46–60–61

602–054–00–6

3-xxxxxxx-1-xx allyljodid

209–130–4

556–56–9

R10 X; X34

X X: 10-34 X: (1/2-)7–26–45

603–076–00–9

xxx-2-xx-1,4-xxxx

203–788–6

110–65–6

X; X23/25 Xn; X21–48/22 X; X34

X R: 21–23/25–34–48/22 X: (1/2-)26–36/37/39–45

X ≥ 50 %: X; R21–23/25–34–48/22 25 % ≤ C &xx; 50 %: X; R21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; X20/22–48/22 3 % ≤ X &xx; 10 %: Xx; X20/22

603–091–00–0

xxx-4-xxxxxxxxx-1-xxxxxx-7-xxxxxxxxxx[2.2.1]xxxxxx-2-xx

402–470–6

87172–89–2

X; R8 Xx; X22 Xx; X36

X; Xx R: 8–22–36 X: (2-)26

603–093–00–1

xxx-(±)-4-xxxxxxxxx-1-xxxxxx-2-[(2-xxxxxxxxxxxx)xxx]-7-xxxxxxxxxx[2.2.1]xxxxxx

402–410–9

87818–31–3

Xx; X20 N; R51–53

Xn; X X: 20–51/53 X: (2-)23-61

603–097–00–3

1,1', 1′′-xxxxxxxxxxxxxxxx-2-xx xxxxxxxxxxxxxxxxxx

204–528–4

122–20–3

Xx; X36 R52–53

Xi X:36–52/53 X: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx

200–661–7

67–63–0

X; R11 Xx; X36 R67

F; Xx X: 11–36–67 X: (2-)7–16–24/25–26

604–020–00–6

xxxxxxx-2-xx 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (ISO)

201–993–5

90–43–7

Xi; X36/37/38 X; X50

Xx; X X: 36/37/38–50 X: (2-)22-61

604–021–00–1

2-xxxxxxxxxx, xxxxx sůl xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx xxxxx xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; R22 Xx; X37/38–41 X; X50

Xx; X X: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

4,4'-(4-xxxxxxxxxxxx-2,2-xxxx)xxxxxxx 2,2-bis(4-hydroxyfenyl)-4-methylpentan

401–720–1

6807–17–6

Repr. xxx. 2; X60 Xx; R36 X; X50–53

X; X R: 60–36–50/53 X: 53–45–60–61

604–041–00–0

acifluorfen [1] xxxxxxxxxxx-xxxxxxx [2] 5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxxx kyselina [1] xxxxxxx-5-[2-xxxxx-4-(xxxxxxxxxxxxxx)xxxxxx]-2-xxxxxxxxxxxx [2]

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xx; X22 Xx; X38–41 N; X50–53

Xx; N R: 22–38–41–50/53 S: (2-)24–39–60–61

604–043–00–1

xxxxxxxxxxxxxxxx (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(xxxxxxxxx)xxxxx

203–083–3

103–16–2

Xx; X36 X43

Xx X: 36-43 X: (2-)24/25–26–37

604–044–00–7

mechinol 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; X22 Xx; X36 X43

Xx X: 22–36–43 X: (2-)24/25–26–37/39–46

605–016–00–7

xxxxxxx… % ethandial… %

X

203–474–9

107–22–2

Xxxx. kat. 3; X40 Xx; X20 Xx; R36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

X ≥ 10 %: Xx; R20–36/38–40–43 1 % ≤ X &xx; 10 %: Xx; X40–43

606–016–00-X

xxxxxx (XXX) 2-(xxxxxxxxxxxxxxx)xxxxx-1,3-xxxx

201–462–8

83–26–1

X; R25–48/25 X; R50–53

T; X X: 25–48/25–50/53 X: (1/2-)37–45–60–61

606–018–00–0

xxxxxxx (ISO) 2,3-xxxxxxx-1,4-xxxxxxxxxxx

204–210–5

117–80–6

Xx; X22 Xx; X36/38 X; X50–53

Xx; N X: 22–36/38–50/53 X: (2-)26–60–61

606–019–00–6

xxxxxxxxxx (XXX) perchlorpentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-on xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-xxxxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx

205–601–3

143–50–0

Xxxx. xxx. 3; R40 X; X24/25 X; X50–53

X; X X: 24/25–40–50/53 X: (1/2-)22–36/37–45–60–61

606–034–00–8

xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx

244–209–7

21087–64–9

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

chloridazon (XXX) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx xxxxxxx

216–920–2

1698–60–8

X43 X; X50–53

Xx; N X: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

chinomethionát (XXX) 6-xxxxxx-2 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx

219–455–3

2439–01–2

Xxxx. xxx. 3; R62 Xx; X20/21/22–48/22 Xx; X36 X43 X; X50–53

Xx; X X: 20/21/22–36–43–48/22–50/53–62 X: (2-)24–37–60–61

606–037–00–4

triadimefon (XXX) 1-(4-xxxxxxxxxxx)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

256–103–8

43121–43–3

Xx; X22 X; R51–53

Xn; X R: 22–51/53 X: (2-)61

606–044–00–2

2,4,6-xxxxxxxxxxxxxxxxxxx fenyl(2,4,6-trimethylfenyl)methanon

403–150–9

954–16–5

Xn; X22 Xx; X36 X; X50–53

Xx; X X: 22–36–50/53 S: (2-)26–60–61

607–043–00-X

xxxxxxx (XXX) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx

217–635–6

1918–00–9

Xx; X22 Xx; X41 X52–53

Xx; X X: 22–41–52/53 X: (2-)26-61

607–057–00–6

xxxxxxxxx (ISO) 3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X-xxxxxxx-2-xx

201–378–1

81–82–3

Xx; X48/22 R52–53

Xn X:48/22–52/53 X: (2-)37-61

607–058–00–1

xxxxxxxxx (XXX) fumarin (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -chromen-2-on 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X -xxxxxxx-2-xx

204–195–5

117–52–2

X; X25–48/25 X52–53

X X:25–48/25–52/53 S: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx

—

4234–79–1

X; R24 Xx; X22 N; R51–53

T; X R: 22–24–51/53 X: (1/2-)36/37–45–61

607–097–00–4

xxxxxx-1,2,4-xxxxxxxxx-1,2-xxxxxxxx 1,2-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxx

209–008–0

552–30–7

Xx; X37–41 X42/43

Xx R: 37–41–42/43 X: (2-)22–26–36/37/39

607–143–00–3

xxxxxxxxx xxxxxxxx valerová xxxxxxxx

203–677–2

109–52–4

X; X34 R52–53

C X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

2,3,6-XXX (XXX) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx

200–026–4

50–31–7

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

607–153–00–8

xxxxxxxxx (ISO) (4-xxxxx-2-xxx-2,3-xxxxxxx-1,3-xxxxxxxxxxxx-3-xx)xxxxxx xxxxxxxx

223–297–0

3813–05–6

Xx; X36/38 R52–53

Xi X:36/38–52/53 S: (2-)22-61

607–156–00–4

xxxxxxxxxxx (XXX) 4-chlorfenyl-4-chlorbenzen-1-sulfonát

201–270–4

80–33–1

Xn; X22 Xx; R38 X; X50–53

Xx; N X: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

xxxxx xxx xxxxxxxxxxx kyseliny xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; X25 Xx; X38 X; X50

X; X X: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

chlorobenzilát (XXX) xxxxx-2,2-xxx(4-xxxxxxxxxx)-2-xxxxxxxxxxxxx xxxxx-4,4'-xxxxxxxxxxxxxxx

208–110–2

510–15–6

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

607–176–00–3

Xxxx: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}-ω-({3-[3-(2 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}oxy)poly(oxyethylen)

400–830–7

—

R43 X; R51–53

Xi; X X: 43–51/53 X: (2-)36/37–61

607–188–00–9

xxxxxxx-xxxxxxxx-X-(2-xxxxxxxxxxxx)-X-(xxxxxxx-9-xx-1-xx)xxxxxxxxxx

402–970–4

—

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

Xxxx: X,X′-xxxxxxxxxxx-xxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); O,O′-diisopropyl-pentasulfanbis(karbothioát)

403–030–6

—

Xn; X22 X43 N; R50–53

Xn; X X: 22–43–50/ 53 X: (2-)36/37–60–61

607–213–00–3

xxxxx-3,3-xxx(xxxx-xxxxxxxxxxxx)xxxxxxxx

403–320–2

67567–23–1

X; X2 O; X7 X10 N; X51–53

X; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61

607–217–00–5

2-xxxxxxxxxxx-[4-(7-xxxxx-2,6-xxxxx-2,6-xxxxxxx-1,5-xxxxx-x-xxxxxxx-3-xx)xxxxxx]xxxxxx

403–960–2

—

X43 X53

Xx X: 43-53 S: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]

217–846–3 [1] 246–590–5 [2] 258–527–9 [3]

1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3]

X52–53

X: 52/53 X: 61

607–248–00–4

Xxxxxxxx-xxxxxxx Natrium-N-(1-naftyl)ftalamát

205–073–4

132–67–2

Xn; X22

Xx X: 22 X: (2)

607–249–00-X

(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx xxxxxxxxxxxxxxxxx-xxxxxxxxx TPGDA

256–032–2

42978–66–5

Xi; X36/37/38 X43 N; X51–53

Xx; X X:36/37/38–43–51/53 X: (2-)24–37–61

X ≥ 10 %: Xi; X36/37/38–43 1 % ≤ X < 10 %: Xx; X43

607–252–00–6

λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (S)-[(3-fenoxyfenyl)kyanmethyl]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx

415–130–7

91465–08–6

X+; R26 X; R25 Xx; X21 X; X50–53

X+; X X: 21–25–26–50/53 X: (1/2-)28–36/37/39–38–45–60–61

607–255–00–2

xxxxxxxxxx (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx xxxxxxxx

—

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X E

203–466–5

107–13–1

F; Xxx Karc. kat. 2; X45 T; X23/24/25 Xi; X37/38–41 X43 N; X51–53

X; X; X R: 45–11–23-/24/25–37/38–41–43–51/53 X: 9–16–53–45–61

X ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; R45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ X &xx; 5 %:X; X45–23/24/25–43 0,2 % ≤ X &xx; 1 %:T; X45–20/21/22 0,1 % ≤ X < 0,2 %: X; R45

43

608–016–00–5

2,3,5,6-tetrachlor-1,4-dikyanbenzen xxxxxxxxxxxxxxxxxxxxxxxxx

401–550–8

1897–41–2

X43 N; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

xxxxxxxx (XXX) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; X28 X; X24 X44 X; R50–53

T+; X X: 61–24–28–44–50/53 S: 53–45–60–61

609–040–00–9

xxxxxxxx (XXX) (2,4-dichlorfenyl)(4-nitrofenyl)ether

E

217–406–0

1836–75–5

Karc. xxx. 2; X45 Xxxx. xxx. 2; X61 Xn; R22 X; X50–53

X; X X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

xxxxxxxx (ISO) 1,2,4,5-tetrachlor-3-nitrobenzen

204–178–2

117–18–0

Xn; X22 R43 X; X50–53

Xx; X R: 22–43–50/53 S: (2-)24–37–60–61

611–008–00–4

4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. kat. 2; X45 X; X50–53

X; X R: 45–50/53 X: 53–45–60–61

611–013–00–1

4-xxxxxxx-3-{4-[2-xxxxxxx-4-(3-xxxxxxxxxxxxxxxxx)xxxxxxxx]-3-xxxxxxxxxxxxxx}-6-(3-xxxxxxxxxxxxxxxx)xxxxxxxx-2-xxxxxxxx trilithný

403–650–7

117409–78–6

E; X2 N; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-iminocyklohexa-2,5-dien-1-yliden)methylen]dianilin-hydrochlorid XX Xxxxx Red 9 XX xxxxxxx xxxxxx 9

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-xxxxxxxxxxxxx x-xxxxxxxx

X

201–963–1

90–04–0

Xxxx. xxx. 2; X45 Xxxx. kat. 3; X40 X; X23/24/25

X X: 45–23/24/25 X: 53-45

612–042–00–2

xxxxxxxx bifenyl-4,4'-diamin 4,4'-diaminobifenyl xxxxxxx-4,4'-xxxxxxxxxx

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; X22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

X ≥ 25 %: T; X45–22 0,01 % ≤ X &xx; 25 %: X; X45

612–051–00–1

4,4'-xxxxxxxxxxxxxxxxxxxx xxx(4-xxxxxxxxxx)xxxxxx 4,4'-xxxxxxxxxxxxxxxx

X

202–974–4

101–77–9

Xxxx. xxx. 2; X45 Muta. xxx. 3; X40 X; R39/23/24/25Xn; R48/20/21/22 X43 X; X51–53

X; X X: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61

612–081–00–5

3,3'-xxxxxxxxxxxxxxxx, soli x-xxxxxxx, xxxx

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; X45 Xx; X22 X; X51–53

X; X X: 45–22–51/53 X: 53–45–61

612–099–00–3

4-xxxxxx-x-xxxxxxxxxxxxx4-xxxxxx-1,3-xxxxxxxxxxxxx4-xxxxxxxxxxxx-1,3-xxxxxx 2,4-xxxxxxxxxxxx

X

202–453–1

95–80–7

Xxxx. xxx. 2; X45 X; X25 Xx; R21 Xx; X36 R43 X; X51–53

X; X R: 45–21–25–36–43–51/53 X: 53–45–61

612–105–00–4

2-(xxxxxxxxx-1-xx)xxxxxxxxx2-(xxxxxxxxx-1-xx)xxxxx-1-xxxx

205–411–0

140–31–8

Xx; X21/22 X; R34 X43 R52–53

C X: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61

612–111–00–7

2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,3-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,3-xxxxxx 2,6-xxxxxxxxxxxx

212–513–9

823–40–5

Xxxx. kat. 3; X40 Xx; R21/22 X43 N; X51–53

Xx; X R: 21/22–40–43–51/53 X: (2-)24–36/37–61

612–125–00–3

2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,4-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,4-xxxxxx 2,5-xxxxxxxxxxxx

202–442–1

95–70–5

X; X25 Xx; R20/21 X43 X; X51–53

X; X R: 20/21–25–43–51/53 X: (1/2-)24–37–45–61

612–144–00–7

flumetralin (XXX) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx

—

62924–70–3

Xx; X36/38 X4 3 N; X50–53

Xx; X R: 36/38–43–50/53 X: (2-)36/37–60–61

612–151–00–5

xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx methylbenzendiamin

E

246–910–3

25376–45–8

Karc. kat. 2; R45 X; X25 Xx; X20/21 Xx; X36 R43 X; X51–53

X; X X: 45–20/21–25–36–43–51/53 X: 53–45–61

613–018–00–4

xxxxxxxxxx (XXX) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx

—

7411–47–4

Xx; X22 Xx; R36/37/38 X52–53

Xx R: 22–36/37/38–52/53 X: (2-)22–36–61

613–031–00–5

xxxxxxxxx xxxxxxxxxxxxxxxxxxxx xxxxxxxx trichlor-1,3,5-triazintrion 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5X)-xxxxx

201–782–8

87–90–1

X; R8 Xx; X22 X31 Xx; X36/37 X; X50–53

X; Xn; X X: 8–22–31–36/37–50/53 S: (2-)8–26–41–60–61

613–038–00–3

6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-fenyl-1,3,5-triazin-2,4-diamin xxxxxxxxxxxxx

202–095–6

91–76–9

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–042–00–5

xxxxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 X-xxxxxxxx

252–615–0

35554–44–0

Xx; X20/22 X; R41 X; X50–53

Xx; X X: 20/22–41–50/53 X: (2-)26–39–60–61

613–043–00–0

xxxxxxxx-xxxxxx (ISO) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xx; X41 X; R50–53

Xn; X R: 20/22–41–50/53 X: (2-)26–39–60–61

613–066–00–6

xxxxxxxxxx (XXX) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx

251–637–8

33693–04–8

Xx; R22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

613–091–00–2

xxxxxxxxxx-xxxxxxxxx [1] morfamkvat-sulfát [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxx-xxxxxxxx [2]

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; X22 Xx; X36/37/38 R52–53

Xn; X: 22–36/37/38–52/53 X: (2-)22–36–61

613–098–00–0

1-xxxxxxxxxxxxxxx-2-xx 1-xxxxx-2-xxxxxxxxxx

403–700–8

2687–94–7

X; R34 X; R51–53

C; N X: 34–51/53 X: (1/2-)23–26–36/37/39–45–61

613–130–00–3

xxxxxxxxxxx (XXX) (XX)-2-(2,4-xxxxxxxxxxxx)-1-(1X-1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

—

79983–71–4

X43 X; R51–53

Xi; N X: 43–51/53 S: (2-)24–37–61

613–131–00–9

xxxxxxxxxx (XXX) 1,2,5,6-xxxxxxxxxx-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx

—

57369–32–1

Xx; X22 R52–53

Xn X:22–52/53 S: (2-)61

613–134–00–5

xxxxxxxxxxxx (XXX) 2-(4-xxxxxxxxxx)-2-[(1 H-1,2,4-triazol-1-yl)methyl]hexannitril

—

88671–89–0

Repr. xxx. 3; X63 Xx; R22 Xx; X36 X; X51–53

Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61

613–137–00–1

methabenzthiazuron (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx

242–505–0

18691–97–9

X; R50–53

N X: 50/53 X: 60-61

613–139–00–2

xxxxxxxxxxx-xxxxxx xxxxxx-2-{X —[N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)karbamoyl]sulfamoyl}benzoát

—

74223–64–6

N; X50–53

X X: 50/53 X: 60-61

614–001–00–4

xxxxxxx (XXX) 3-(1-methylpyrrolidin-2-yl)pyridin

200–193–3

54–11–5

T+; X27 X; R25 X; X51–53

X+; X X: 25–27–51/53 S: (1/2-)36/37–45–61

614–006–00–1

xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx

206–614–7

357–57–3

X+; X26/28 X52–53

X+ X:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

xxxxxx-xxxxxx [1] brucin-nitrát [2] brucin-(R)-(1-methylheptyl)-hydrogen-ftalát [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]

225–432–9 [1] 227–317–9 [2] 269–439–5 [3] 269–710–8 [4]

4845–99–2 [1] 5786–97–0 [2] 68239–26–9 [3] 68310–42–9 [4]

X+; X26/28 X52–53

X+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-methyl-1,3-fenylendiisokyanát [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] m-tolylidendiisokyanát [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] xxxxxx-3,5-xxxxxxxxxxx [3]

X

202–039–0 [1] 209–544–5 [2] 247–722–4 [3]

91–08–7 [1] 584–84–9 [2] 26471–62–5 [3]

Xxxx. xxx. 3; X40 T+; X26 Xx; X36/37/38 X42/43 X52–53

X+ X: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61

C320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42

2

616–010–00–9

xxxxxxx-xxxxxxxxxxxxxx X-xxxxx-4-xxxxxxxxxxxx-1-xxxxxxxxxx, xxxxx xxx

204–854–7

127–65–1

Xx; X22 R31 X; R34 R42

C X: 22–31–34–42 X: (1/2-)7–22–26–36/37/39–45

616–034–00-X

xxxxxxxxxxxx (ISO) 6-xxxxxx-3,4-xxxxxxx-2X-xxxxx-5-xxxxxxxxxxxx

246–419–4

24691–76–7

X52–53

X: 52/53 X: 61

616–035–00–5

xxxxxxxxx X -[(xxxxxxxxxx)xxxxxxxx]-2-xxxx-2-(xxxxxxxxxxxx)xxxxxxxx 1-ethyl-3-[2-kyan-2-(methoxyimino)acetyl]močovina

261–043–0

57966–95–7

Xn; X22 X43 X; X50–53

Xx; X R: 22–43–50/53 X: (2-)36/37–60–61

617–004–00–9

(1,2,3,4-tetrahydro-1-naftyl)hydroperoxid xxxxxxxxxxxxxxxxxxxx

212–230–0

771–29–9

X; R7 Xn; X22 C; X34 X; X50–53

X; C; X X: 7–22–34–50/53 X:(1/2-)3/7–14–26–36/37/39–45–60–61

X325 %: X; X22–34 10 % ≤ X &xx; 25 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38

617–006–00-X

xxx(α, α-dimethylbenzyl)peroxid xxx(2-xxxxxxxxxxx-2-xx)xxxxxxx xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx xxxxxxxxxxxxxx

201–279–3

80–43–3

X; X7 Xx; X36/38 X; X51–53

X; Xi; N X: 7–36/38–51/53 X: (2-)3/7–14–36/37/39–61

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xx; X36 X43

X; Xx; X: 2–36–43 X: (2-)3/7–14–36/37/39

650–007–00–3

xxxxxxxxxxxxx (XXX) N2-(4-chlor-2-methylfenyl)-N1,N1-dimethylformimidamid X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx

228–200–5

6164–98–3

Xxxx. kat. 3; X40 Xx; R21/22 X; X50–53

Xx; X X: 21/22–40–50/53 X: (2-)22–36/37–60–61

650–008–00–9

xxxxxxxxxx (XXX) 4-[(2-xxxxxxxxxx)xxxxxxxxx]-3-xxxxxxxxxxxxxx-5(4 X)-xx

227–197–8

5707–69–7

X; X25 N; X50–53

X; X R: 25–50/53 S: (1/2-)22–24–36/37–45–60–61

650–009–00–4

xxxxxxxxxxxxx-xxxxxxxxxxxx X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx

243–269–1

19750–95–9

Xxxx. xxx. 3; R40 Xx; X22 N; X50–53

Xx; X R: 22–40–50/53 X: (2-)22–36/37–60–61

650–033–00–5

xxxxxxxxxxxx (XXX) [(X)-(3-xxxxxxxxxxx)xxxxxxxxxx]-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx

—

66230–04–4

X; X23/25 X43 N; X50–53

X; X X: 23/25–43–50/53 X: (1/2-)24–36/37/39–45–60–61

650–041–00–9

triasulfuron (XXX) 1-[2-(2-xxxxxxxxxxx)xxxxxx-1-xxxxxxxx]-3-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxx

—

82097–50–5

X; R50–53

N X: 50/53 X: 60-61


PŘÍLOHA 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x látkám

Číslo XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–090–00–8

2-[(3-xxxxxxx-2-xx-1-xx)xxx]xxxxx-X-xxxxxxxxxxxxx

408–010–0

88558–41–2

Xx; X20 Xx; X41 X52–53

Xx X: 20–41–52/53 S: (2-)22–26–39–61

014–016–00–0

Xxxx: 1,3-xx(xxx-5-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-tetramethyldisiloxan

406–490–6

—

N; X51–53

X X: 51/53 X: 61

015–164–00–9

xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx dihydrát

400–480–5

36669–85–9

R52–53

R:52/53 X: 61

015–165–00–4

Xxxx: X, X, S', X''-xxxxxxxxxx-4,4'-xxxxxxxxxxxxx(xxxxxxxxxxxxxx)-xxx(xxxxxxxxxxxxxxxx) x xxxxxxx[4-(xxxxxxxxxxxxx)xxxxx]xxxxxxxxx-xxxxxxxxxxxxxxxx

404–986–7

—

Xx; R41 X; R50–53

Xi; X X: 41–50/53 S: (2-)15–26–39–60–61

015–166–00-X

3,9-xxx(2,6-xx-xxxx-xxxxx-4-xxxxxxxxxxxx)-2,4,8,10-xxxxxxxx-3,9-xxxxxxxxxxxx[5.5]xxxxxxx

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[hydroxy(fenyl)fosfinoyl]propanová xxxxxxxx

411–200–6

14657–64–8

Xx; X41

Xx X: 41 S: (2-)26-39

601–050–00–1

C10-C13-alkylderiváty xxxxxxx

267–051–0

67774–74–7

X; X50

X X: 50 X: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 X; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; R48/21/22 X64 X; X50–53

Xx; X X: 48/21/22–50/53–64 X: (1/2-)36/37–45–60–61

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; R52–53–59

N R: 52/53–59 X: 59-61

603–128–00–0

2-(xxxxxxxxxxxx)xxxxxxxx

405–490–3

613–62–7

X53

X:53 X: 61

603–129–00–6

1-terc-butoxypropan-2-ol

406–180–0

57018–52–7

R10 Xx; X41

Xx R: 10-41 X: (2-)26-39

603–130–00–1

Xxxx xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx)

406–325–8

—

Xx; X22 R52–53

Xn X:22–52/53 X: (2-)39-61

603–131–00–7

Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxxx)xxxxx]-X-xxxxxxxx

407–290–1

—

Xx; X41

Xx X: 41 X: (2-)26-39

603–132–00–2

2-(xxxxxxxxxxxxx)-6-xxxxxxxxx-9-xxxxxx-1,4-xxxxxxxxxx[4.5]xxxxx

408–200–3

63187–91–7

Xx; R38–41 R52–53

Xi X:38–41–52/53 S: (2-)26–37/39–61

603–133–00–8

Směs:3-(4-amino-2-chlor-5-nitroanilino)propan-1,2-diol x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)

408–240–1

—

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx a xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (dodecyl x xxxxxxxxxx nerozvětvené)

410–450–3

—

R53

R: 53 X: 61

603–135–00–9

bis[2-(2-methoxyethoxy)ethanolato]bis(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx

410–500–4

—

Xx; R41 N; X51–53

Xx; X X: 41–51/53 S: (2-)26–39–61

603–136–00–4

3-{4-[xxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxxx}xxxxxx-1-xx

410–910–3

104226–19–9

X43 X52–53

Xx R:43–52/53 X: (2-)24–37–61

603–137–00-X

Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx a 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx

411–130–6

—

Xx; X41

Xx X: 41 X: (2-)26-39

603–138–00–5

3-(2,2-dimethyl-3-hydroxypropyl)toluen 2,2-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx

403–140–4

103694–68–4

X52–53

X:52/53 X: 61

604–050–00-X

4-chlor-o-kresol 4-chlor-2-methylfenol

216–381–3

1570–64–5

T; X23 X; R 35 N; X50

X; X; X X: 23–35–50 X: (1/2-)26–36/37/39–45–61

C ≥ 25 %: X; X; X23–35 10 % ≤ X &xx; 25 %: C;R20–35 5 % ≤ C &xx; 10 %: X;X20–34 3 % ≤ X &xx; 5 %: Xx;X20–36/37/38 1 % ≤ X < 3 %:Xx;X36/37/38

604–051–00–5

3,5-xxx(3,5-xx-xxxx-xxxxx-4-xxxxxxxxxxxxx)-2,4,6-xxxxxxxxxxxxxx

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

2,2'-methylenbis[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx

403–800–1

103597–45–1

X53

X:53 S: 61

604–053–00–6

4-xxxx - xxxxx-2-xxxxxx-6-(1-xxxxxxxxxxxxxxxx)xxxxx

410–760–9

157661–93–3

Xx; X38 X43 N; R50–53

Xi; X X: 38–43–50/53 X: (2-)24–37–60–61

604–054–00–1

Xxxx:2-xxxxxxx-4-(4-xxxxxxxxxxxxxxxxxxxxxxxxx-2-xx)xxxxx x 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx

412–020–0

—

X43 R52–53

Xi X:43–52/53 S: (2-)24–37–61

604–055–00–7

4,4'-xxx[(2,3-xxxxxxxxxxx)xxx]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx

413–900–7

85954–11–6

Xxxx. Xxx.3; X40

Xx X: 40 S: (2-)22–36–37

605–027–00–7

Xxxx:3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X-xxxxx-6-xxxxxxxxxxx a 3x, 4,5,6,7,7a-hexahydro-4,7-methano-1H - xxxxx-5-xxxxxxxxxxx

410–480–7

—

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxx-1-xx

4–406–670–4

61203–83–6

X; X51–53

X X: 51/53 X: 61

606–052–00–6

4-(N, X-xxxxxxxxxxxx)-2-xxxxxxx-2'-xxxxxxxxxxxxxxxxx 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx xxxxxxxx

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

xxxxxxxxxxx-xxxxxx (ISO) [1] xxxxxxxxxx-xxxxxxxxx (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-xxxxxx-1-xxxxxxxxxxx)-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [2]

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

X; X50–53

X X: 50/53 X: 60-61

607–273–00–0

amonium-7-{2,6-dimethyl-8-[(2,2-dimethylbutanoyl)oxy]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx

404–520–2

—

X52–53

X:52/53 X: 61

607–274–00–6

{2-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx

405–350–1

54527–73–0

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–275–00–1

xxxxxxx-4-(xxxxxxxxxx)xxxxxx-1-xxxxxxxx

405–450–5

66531–87–1

X43

Xx X: 43 X: (2-)24-37

607–276–00–7

[xxx(2-xxxxxxxxxxxxxx) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx xxxxxxx

405–635–0

—

Xx; X38–41 X; X50–53

Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61

607–277–00–2

Xxxx:2-(xxxxxxxxxxxxx)xxxxxxxxx-xxxxxxxxxxxx x xxxxxxx-xxxxxxxxx

405–720–2

—

Xx; R22 Xx; X41 X43 X; X51–53

Xx; X X: 22–41–43–51/53 S: (2-)24–26–37/39–61

607–278–00–8

Směs:alkyl(C7-C9 xxxxxxxxxx x xxxxxxxxxxxx)-3-[3-(2 X - xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx

405–760–0

—

Xx; X41 R43 R52–53

Xi X: 41–43–52/53 X: (2-)24–26–37/39–61

607–279–00–3

Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx)

405–960–8

—

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–280–00–9

4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx xxxxx natrium-4-chlor-1-hydroxybutan-1-sulfonát

406–190–5

54322–20–2

Xn; X22 Xx; R36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

Xxxx:xxxxx(X7-X9 xxxxxxxxxx x xxxxxxxx)-3-[3-(2X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx

407–000–3

127519–17–9

X; X51–53

X X: 51/53 X: 61

607–282–00-X

2-(xxxxxxxxxxxxx)-4-(xxxxxxxxx)xxxxx-xxxxxx

407–140–5

131266–10–9

X52–53

X: 52/53 X: 61

607–283–00–5

xxxxx-(X)-4-xxxxx-4-xxxxxx-2-xxxxxxxxxx-(X)-4-xxxxx-4-xxxxxxxxxxx

408–040–4

15121–89–8

Xx; X21/22 Xi; X38–41 X43 X; X50–53

Xx; X X: 21/22–38–41–43–50/53 X: (2-)26–36/37/39–60–61

607–284–00–0

Směs (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) x xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx)

410–040–4

136213–76–8

X; X51–53

X R: 51/53 X: 61

607–285–00–6

Xxxx:7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxxx xxxxxxxx, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x xxxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx

410–065–0

—

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

Xxxx:xxxxxx- a xxxxxxx-7-[4-({4-[(2-xxxxxxx-1-xxxxxx)xxx]xxxxx}xxx)xxxxxxxxxxxxxxxxx]xxxxxxxx-1,3-xxxxxxxxxx

410–070–8

141880–36–6

X43 X52–53

Xx X:43–52/53 X: (2-)22–24–37–61

607–287–00–7

xxxxxx-[1-xxxxxx-2-(xxxxxxxxxxxxxxx)xxxxx]-1,2,3,6-xxxxxxxxxxxxxxxx

410–140–8

—

X52–53

X:52/53 X: 61

607–288–00–2

[c-(N -{3-[(1-{3-[(2,6(4,6)-xxxxxxx-5-xxxxxxxxxxxxx-4(2)-xx)xxxxxxxxxxx]xxxxxx}-2-xxxxxxx-4-xxxxxx-6-xxx-1,6-xxxxxxx-3-xxxxxxx)xxx]-4-xxxxxxxxxxxxxx}xxxxxxxxx)-x,x,x -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx xxxxxxx, xxxxxxxxxx sůl; x = 15, 16, 17 xxxx 18, x = 1, 2, 3 xxxx 4, x = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25

410–160–7

148732–74–5

Xi; X36 X43 R52–53

Xi X: 36–43–52/53 X: (2-)22–26–36/37–61

607–288–00–8

3-[(3-{X —[4-(2,4-di-terc-pentylfenoxy)butyl]karbamoyl}-4-hydroxy-1-naftyl)sulfanyl]propanová kyselina

410–370–9

105488–33–3

R53

R:53 X: 61

607–290–00–3

Xxxx (x xxxxxxxx xxxxxx):xxxxxxx-1-xxxxx(X14-X18)-4-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx x xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx

410–540–2

—

Xx; X38 X43 X; X50–53

Xx; N X: 38–43–50/53 S: (2-)24–37–60–61

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx xxxxxxxx

410–640–6

—

Xx; X38–41 X; R50–53

Xi; X R: 38–41–50/53 X: (2-)26–37/39–60–61

607–293–00-XXxxx:

1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx

410–650–0

—

Xx; R41 R43 X; R51–53

Xi; X X: 41–43–51/53 X: (2-)26–36/37/39–61

607–294–00–5

xxxxxxx-2-(xxxxxxxxxx)-1-xxxxxxxxxxxx-1-xxxxxxxx

410–680–4

—

X43

Xx X: 43 X: (2-)24-37

607–295–00–0

Xxxx:xxxxxxxxxxxx-xxxxxxxxxxxxxxxxx x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx

410–800–5

—

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

Xxxx:xxxxxxxxxxx xxxxxxxxxxxxxxxx, xxxxxxxxx kyselina x 2-xxxxxxxxxxxxx xxxxxxxx

410–830–9

—

X53

X: 53 X: 61

607–297–00–1

3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(2-xxxxxxxxx-10-xxxxxxxxx xxxxxxxx)2,2'-xxxxx-3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(1,7,7-xxxxxxxxxxxxxxxx[2.2.1]xxxxxx-1-xxxxxxxxxxxxxxx xxxxxxxx)

410–960–6

92761–26–7

Xx; X41

Xx X: 41 X: (2-)26-39

607–298–00–7

[2-(xxxxxxxxxxxxxxx)xxxxx]-4-xxxxxxxxxxxxxxxx

411–010–3

—

X43

Xx X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 R43 X; X50–53

Xx; N X: 22–43–50/53 S: (2-)24–37–60–61

607–300–00–6

[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx xxxxxxx, xxxxxxxx xxx; x = 1,2,3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 15, 16, 17 xxxx 18, x = 22, 23, 24 xxxx 25

411–430–7

—

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

Xxxx:xxxxxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–860–5

—

Xx; X38–41 X43 N; X51–53

Xx; X X: 38–41–43–51/53 X: (2-)24–26–37/39–61

607–302–00–7

Xxxx:xxxxxxxxxxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–910–6

—

Xx; X38–41 X43 X; R51–53

Xi; X X: 38–41–43–51/53 X: (2-)24–26–37/39–61

607–303–00–2

1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx xxxxxxxx

413–760–7

93107–30–3

Xxxx. xxx.3; X62 X52–53

Xx R: 62–52/53 S: (2-)22–36/37–61

608–023–00–3

4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx

406–140–2

114369–43–6

X; X50–53

X X: 50/53 S: 60-61

608–024–00–9

2-{4-[xxxxx(xxxxxxxx)xxxxx]xxxxx}xxxxx-1,1,2-xxxxxxxxxxxxxx

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

[2-xxxxx-4,5-xxx(xxxxxxxxx)xxxxx]xxxxxxxxxxx

410–970–0

117568–27–1

X53

X:53 S: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

—

X; R3 X; X8 Xxxx. xxx. 2; R45 X; X23/25 X43

X; X X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

1-xxxx-2-(2-xxxxx)-1-xxxxxxxxxx

406–110–9

35950–52–8

Xx; R22–48/22 C; X34 X43 X; X50–53

X; X X: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61

611–043–00–5

Směs (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx x[{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx

402–850–1

Xx X: 41–52/53 X: (2-)26–39–61

611–044–00–0

Směs:[bis(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [bis(4-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx a[(4(5)-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato) (3-nitro-5-pentylbenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx

403–720–7

117527–94–3

X; X51–53

Xx; X41 X52–53

611–045–00–6

2-({4-[(4-xxxxxxxxxxxx)xxxxxxxxxx]-2-xxxxxxxxxxx}xxx)-3-xxxxxx-5-xxxxxxxxxxxx

404–830–8

—

X53

X:53 X: 61

N X: 51/53 X: 61

611–046–00–1

4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx

407–590–2

43151–99–1

X; R25 Xx; X48/22 R43 N; X50–53

X; X X: 25–43–48/22–50/53 X: (1/2-)22–28–36/37–45–60–61

611–047–00–7

Xxxx (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx

407–890–3

111381–11–4

X53

X: 53 X: 61

611–048–00–2

Směs (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx

407–900–6

111381–12–5

X53

X: 53 X: 61

611–049–00–8

Směs (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, xxxxxxxx xxxxxx x xxxxxx kyselina (2:1:1)

408–000–6

118658–98–3

Xx; X48/22 R43 X52–53

Xx X: 43–48/22–52/53 X: (2-(22–36/37–61

611–051–00–9

2-({4-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx

411–110–7

136213–74–6

X; X50–53

X X: 50/53 X: 60-61

611–052–00–4

[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx xxxxxxx, xxxxx xxx

400–720–9

—

X52–53

X: 52/53 X: 61

612–156–00–2

Xxxx:xxxxxxxxxxxx(xxxxxx)xxxxxxx-xxxxxxx x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx

405–620–9

—

Xx; X41 X; X50–53

Xx; X R: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

(X)-1-(1-xxxxxxxxxxxx-2-xx)xxxxx-1-xx-xxxx-xxxxxxxxxxxx

410–780–8

—

Xx; X22–48/22 Xi; X41 X43 X; R51–53

Xn; X X: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61

612–158–00–3

Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

—

X53

X: 53 S: 61

612–159–00–9

xxxxxxx xxxxxxxx směsi 2,2,4-xxxxxxxxx- x 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Xxxxxx 8) a 4-methylbenzen-1-sulfonové xxxxxxxx

410–880–1

—

Xx; X22 X; X34 N; X50–53

X; X X: 22–34–50/53 X: (1/2-)23–26–36/37/39–45–60–61

613–149–00–7

2-xxxx-xxxxx-5-[(4-xxxx-xxxxxxxxxxx)xxxxxxxx]-4-xxxxxxxxxxxxxx-3(2X)-xx

405–700–3

96489–71–3

X; X23/25 X; R50–53

T; X X: 23/25–50/53 X: (1/2-)36/37–45–60–61

613–150–00–2

2,2'-[xxxxxxxxx-1,4-xxxxxx(xxxxxx-1,3-xxxx)]xxx(xxxxxxxxxxx[2,1-x]xxxxx[xxx][3,8]xxxxxxxxxxxx-1,3,6-xxxxx)

406–295–6

—

X53

X:53 X: 61

613–151–00–8

1-(2-xxxxx-3-X-xxxxx-5-X-xxxxxx-β-X-xxxxx-xxxxxxxxxxxxxx)-5-xxxxxxxxxxxxxxx-2(1X), 4(3 X)-xxxx

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

xxxxx-X-(4,6-xxxxxxxxxxxxxxxxxx-2-xx)xxxxxxxx

406–600–2

89392–03–0

X43 N; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-trichlorpyridin

407–270–2

16063–70–0

R52–53

R:52/53 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx X: 22 S: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 X52–53

Xx X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-xxxxx-5-xxxxxxxxxxxxx-4-xxxxxxxxxxx

410–260–0

83857–96–9

X43 N; X51–53

Xx; N X: 43–51/53 S: (2-)24–37–61

613–157–00–0

2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx

410–330–0

54236–98–5

Xx; R22–48/22 Xx; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

2,3-xxxxxxx-5-(xxxxxxxxxxxxxx)xxxxxxx

410–340–5

69045–84–7

Xx; R20/22 Xx; X41 R43 X; R51–53

Xn; N X: 20/22–41–43–51/53 S: (2-)24–26–37/39–61

613–159–00–1

4-[2-(4-xxxx-xxxxxxxxxx)xxxxxx]xxxxxxxxxx

410–580–0

120928–09–8

X; X25 Xx; X20 X; X50–53

X; X X: 20–25–50/53 X: (1/2-)37–45–60–61

613–160–00–7

2-xxxxxx-2,5-xxxxxxxxxxxx[2.2.1]xxxxxx-xxxxxxxxxxxxx

411–000–9

125224–62–6

X43

Xx R: 43 X: (2-)24-37

615–022–00–1

xxxxxx-3-(xxxxxxxxxxxxxxxxxx)xxxxxxx-2-xxxxxxxxxx

410–550–7

79277–18–2

X; X2 X14 Xn; X48/22 R42/43

E; Xx X: 2–14–42/43–48/22 X: (2-)22–30–35–36/37

615–023–00–7

xxxxxxxxxxx 2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxxx xxxxxxxxxxxxxx-2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxx

410–900–9

83056–32–0

X10 X14 Muta. kat. 3; X40 Xn; X20–48/22 Xx; X41 X42

Xx X: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39

616–044–00–4

N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)-2-(3-pentadecylfenoxy)butanamid

402–510–2

—

N; X51–53

X X: 51/53 X: 61

616–045–00-X

2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(diethylamino)-2-methoxyacetanilid

405–190–2

122371–93–1

R43 X53

Xx X: 43-53 X: (2-)22–24–37–61

616–046–00–5

X -[2-(6-chlor-7-methylpyrazolo[1,5-b][1,2,4]triazol-4-yl)propyl]-2-(2,4-di-terc-pentylfenoxy)oktanamid

406–390–2

—

N; R50–53

N X: 50/53 X: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - tetraalkyl(C16)-2,2′, 2″, 2′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x N, N′,N″,N′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

—

X43

Xx R: 43 X: (2-)24-37

616–048–00–6

3'-(trifluormethyl)isobutyranilid

406–740–4

1939–27–1

Xn; X48/22 X; R51–53

Xn; X R: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

2-(2,4-di-terc-butylfenoxy)-N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)hexanamid

408–150–2

99141–89–6

R53

R:53 X: 61

616–050–00–7

1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx

410–690–9

103055–07–8

X43 N; R50–53

Xi; X R: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

Xxxx:3,3'-xxx(4-xxxxxxxxxxx)- 1,1'-(4-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx x 3,3'-xxx(4-xxxxxxxxxxx)-1,1'-(2-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx

411–070–0

—

X53

X: 53 X: 61

617–015–00–9

xxx(4-xxxxxxxxxxxxx)xxxxxxx

407–950–9

895–85–2

X; R2 X; X7 X; X50–53

X; X X: 2–7–50/53 X: (2-)7–14–36/37/39–47–60–61

650–032–00-X

xxxxxxxxxxxx (XXX) (2R, 3X)-, (2 X, 3 X)-, (2 R, 3 X)-, (2 X, 3 X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxx-1-(1X- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

—

94361–06–5

Xxxx. kat. 3; X63 Xx; R22 X; X50–53

Xx; N X: 22–50/53–63 X: (2-)36/37–60–61


XXXXXXX 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX S XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX,

Xx. xxxx. X 332, 28.12.2000, x. 81.


XXXXXXX 3X

XXXXXXXXXX POKYNY XXX BEZPEČNÉ ZACHÁZENÍ X NEBEZPEČNÝMI LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3B

STANDARDNÍ XXXXXX XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. xxxx. X 332, 28.12.2000, x. 81.


PŘÍLOHA 4X

"X.10 XXXXXXXXXX — ZKOUŠKA XX XXXXXXXXXXXX ABERACE X XXXXX XX XXXXX

1. XXXXXX

Xxxx xxxxxx je xxxxxxxx xxxxxx XXXX XX 473 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u xxxxx xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx vitro xx xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Rozlišují xx xxx xxxx xxxxxxxxxxxx aberací: chromozomové x xxxxxxxxxxxx. U xxxxxxx chemických mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxx. Tato xxxxxx však xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx aberací x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxx jevy jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x existuje xxxxx důkazů x xxx, xx chromozomové xxxxxx a x xxxx související xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx x x xxxxxx somatických buněk xxxxxxxxx xxxxxx, mají xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x u xxxxxxxxx xxxxxx.

Xx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxx mohou xxx xxxxxxx stabilizované buněčné xxxxx, xxxxxxx xxxxx xxxx primární xxxxxxx xxxxxxx. Xxxxxxx buňky xxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxx x kultuře, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx chromozomů x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx zcela xxxxxxxxx xxxxxxxx in xxxx x xxxxx. Je xxxxx se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx vlastní mutagenitu x může x xxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx úrovní xxxxxxxxxxxx (4, 5).

Tato zkouška xx xxxxxxx xx xxxxxxxx možných xxxxxxxx x karcinogenů xxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx savce xxxxxxxxxxx; xxxx touto xxxxxxxx x xxxxxxxxxxxxxx xxxx není xxxxxxxxx xxxxxxxx. Xxxxxxxx závisí xx chemické xxxxx x xxxxxxxxx xxxxxx x tom, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, neboť xxxxxx xxxxxx jinými xxxxxxxxxx xxx xxxxxx poškozením XXX.

Xxx xxxx Xxxxxx xxxx, část B.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx nebo xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : proces, xxx kterém v xxxxx xx X-xxxx xxxxxxxxx XXX nedojde x xxxxxx, xxxxx xxxxxxxxx další X-xxxx. Xxxxxxxxx xxxx xxxxxxxxxx xx 4, 8, 16… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx xxxx menší xxx xxxxx jedné xxxxxxxxxx x s xxxxxxxxx odchylkou chromatid.

Mitotický xxxxx : xxxxx xxxxx, xxxxx xx xxxxxxxxx x xxxxxxxx, x xxxxxxxxx xxxxx xxxxx x xxxxxxxx; xxxxx stupeň proliferace xxxx populace.

Numerická xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx typu buněk.

Polyploidie : xxxxxxx haploidního xxxxx xxxxxxxxxxxxxx xxx (x), xxxx xxx xxxxxxxxx (tj. 3 x, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx dělení ve xxxxxx xxxxxxxx; xxxx xx xxxx delece x fragmenty, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxxxxx xxxx vystaveny xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. X xxxxxx xxxxxxxxxxx intervalech xx xxxxxxxx xxxxx se xx xxxxxxxxx kultur xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx xxxxxx, xxxxxx x přítomnost xxxxxxxxxxxxxx xxxxxxx xx zjistí xxxxxxxxxxxxxx pozorováním buněk.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx xxxxx xxxxxxx xxxxx, kmeny xxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxx lidských buněčných xxxxx (např. xxxxxxxxxxx xxxxxx čínského, xxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx a xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx kultur xx xxxx xxx xxxxxxx xxxxxx kultivační xxxxx a inkubační xxxxxxxx (xxxxxxxxxx nádoby, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). X xxxxxxxxxxxxxxx buněčných xxxxx x kmenů xx xxxx být xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxx x xxxx xx xxx kontrolováno, xxx xxxxxx kontaminovány xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx neměly xxx xxxxxxx. Xxx použité xxxxx x inkubační xxxxxxxx by xxxx xxx xxxxx xxxxxxxx xxxxx buněčného cyklu.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x kmeny: xxxxx xx xxxxxxx x xxxxxxxxx xxxxxx, xxxxxx se xx xxxxxxxxxxxx média v xxxxxx hustotě, aby xxxxxxxxx xxxxxxxxxx před xxxxxxxxx, x inkubují xx xxx 37 °X.

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxx se xxxxxxx do xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. fytohemaglutinin) x xxxxxxxx se xxx 37 °X.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx xxxx xxx vystaveny xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx x xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (6, 7, 8 x 9), xxxx xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Xxxx metabolického aktivačního xxxxxxx může xxxxxxx xx xxxxx xxxxxxxx xxxxx, která xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx může xxx xxxxxx použít více xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx specifické xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx by xxxx xxx xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx vhodných rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx systémům x/xxxx xxxxx xxx xxxx xxxxxxxx zředěny. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x stálosti xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx podezření, xx xxxxxxx xx zkoušenou xxxxxx, a xxxx xx být xxxxxxxxxx x přežitím buněk x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx látek xxxxxxxxx xx xxxx xx xxxx xxx použita xxxxxxxxx rozpouštědla neobsahující xxxx. Vodu xxx xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx mají xxx xxxxxxxxxx xxx xxxxxxxxx nejvyšší koncentrace, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx osmolality.

Cytotoxicita by xxxx být stanovena x xxxxxxxxxxxx aktivací x xxx ní x hlavním xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx integrity x růstu, xxxx xxxx stupeň xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx buněk xxxx xxxxxxxxx xxxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx alespoň tři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx by xxxx xxxx koncentrace xxxxxxxx rozmezí dané xxxxxxxxx xx minimální xxxxxxxxx, případně žádnou xxxxxxxxx, což xxxxxxx xxxxxxx, že xx xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. X xxxxxxxx xxxxxxx by měla xxxxxxxx xxxxxxxxxxx vykazovat xxxxxxxx snížení xxxxxx xxxxxxxxxx, xxxxx buněk xxxx xxxxxxxxxxx indexu (xxx x xxxx xxx 50 %). Xxxxxxxxx index xx xxxxx nepřímým xxxxxxxx xxxxxxxxxxxxx xxxx cytostatických xxxxxx x xxxxxx xx xxxx, která xxxxxxxx xx xxxxxxxx. Xxxxxxxxx index xx xxxx xxxxxxxxxx u xxxxxxxxxxx xxxxxx, x xxxxx mohou xxx xxxx metody xxxxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxxx. Informace o xxxxxxxx buněčného xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), mohou xxx xxxxxxx jako xxxxxxxxx informace. X xxxxxxx XXX xxxx xxx x celkovou xxxxxxxxx xxxxxxx, z xxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, x i xxxx přírůstek xxxxxxxx xxxxxxxxx xxxx xxxx xxx xx následek xxxxx podstatné xxxxxxxx xxxxxxxx optimálního výtěžku xxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 M, xxxxx toho, xxxxx x nich je xxxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx při xxxxxxxxxxxxx xxxxxxx, než xx jejich xxxxxxxxxxx, xx měla xxx xxxxxxx xxxxxxxx dávka x xxxxxxxxxxx, xxx xx xxx xxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx médiu xx xxxxx xxxx aplikace. X určitých xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx xxx xxxxxxx koncentracích, xxx xx xxxxxxxxxxx) se xxxxxxxxxx xxxxxxxxx více xxxxxxxxxxx, xxx xxxxx xxxxxxx xx srážení. Xxxx xxx užitečné xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxxx xx xxxx x průběhu xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, séra X9 xxx. Xxxxxxxxxxxxx xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx a negativní xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx vehikula). Xxx xxxxxxx metabolické xxxxxxxx xx xxxx být xxx pozitivní xxxxxxxx xxxxxxx xxxxxxxx látka, xxxxx x mutagenní xxxxxx xxxxxxxx aktivaci.

K xxxxxxxxx xxxxxxxx by xxx být použit xxxxx elastogen x xxxxxxxxxxx xxxxxxxxxxxxx, které xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x detekovatelný xxxxxx xxx xxxxxx, čímž xx xxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx pozitivních xxxxxxx xx xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxxxxxxxx a negativních xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxx xxxxxx xxxxxxxxxxx xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx metabolickou xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Pro pozitivní xxxxxxxx xxxxx xxx xxxxxxx x xxxx xxxxxx xxxxx. Pro xxxxxxxxx xxxxxxxx by xxxx být xxxxx xxxxx vzato v xxxxx použití chemických xxxxx xx xxxxxx xxxxxxxx třídy.

V okamžiku xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající se xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula x xxxxxxxxxxx xxxxx x xxxxxxxxxx xxxxxxx xxxxxxxx xxxx kultury. Kromě xxxx by xxxx xxx neexponované xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx xxxxxxx xxxxxxxx xxxxx xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx xxx xxxx. Xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxxx xxx 48 xxxxx xx xxxxxxxxx stimulaci.

1.4.3.2 Xxx každou xxxxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx xxxxxxxx xxxx xxxxxxxx rozpouštědla. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxx prokázat (13, 14), xx xxxx duplicitními kulturami xx xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxx xxxxxx kultury.

Plynné xxxx xxxxxx xxxxx xx xxxx xxx xxxxxxxx vhodnými xxxxxxxx, xxxx. x těsně xxxxxxxxxx kultivačních nádobách (15, 16).

1.4.3.3 Doba xxxxxxx xxxxxx

X prvním xxxxxxxxxxx by xxxx xxx xxxxx vystaveny xxxxxxxx látce, xxx x metabolickou xxxxxxxx, xxx xxx xx, xx dobu 3 — 6 xxxxx, x měly by xxx xxxxxxxx xx xxxxxx době xx xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx buněčného xxxxx (12). Jestliže xxxxx xxxxxx dává xxxxxxxxx xxxxxxxx jak x xxxxxxxx, xxx bez xxxxxxxx, měl xx xxx proveden xxxxxxxxx xxxxxxxxxx xxx aktivace x nepřetržitou xxxxxxxx xx xx xxxxxx x xxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx xxxxx xxx xxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx xxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. X xxxxxxxxx, kdy xx xxxxxxxxxx potvrzení xxxxxxxxxxx výsledků xx xxxxxxxx, by mělo xxx xxxxxx zdůvodnění.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xx xxxxxxx xxxxxxx xx obvykle 1-3 xxxxxx před xxxxxxxxx xxxxx Xxxxxxxx® xxxx kolchicin. Xxx xxxxxxxx preparátů xxx xxxxxxx chromozomů se xxxxx xxxxxxx kultura xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx buněk, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx preparátů xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx měly xxx xxxx analýzou xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx fixaci xxxxx dochází xx xxxxx části xxxxx x xxxxxxxx a xx xxxxxx xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x počtu xxxxxx xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx xxxxx. Xx xxxxxx xxxxxxxxxxx a xxxxxxxx xx mělo xxx hodnoceno alespoň 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, případně xxxxxxxxxx xxxxxxxxxxx mezi xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx xxxxxx, je-li xxxxxxxxx xxxxx xxxxx xxxxxxx.

Xxxxxx xx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx, xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxxxxxx, xxxx-xx xxxxxxxxxx.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx jednotkou xx xxxxx a xxxx xx xxxx xxx xxxxxxxxxxx množství xxxxx xx strukturní chromozomovou xxxxxxx (xxxxxxxxx) vyjádřené x xxxxxxxxxx. Xxx xxxxxxxxx a xxxxxxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxx xxxxx xxxx strukturních xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx a xxxxxxxx. Xxxx xx zaznamenávají xxxxxxxx x uvádějí xx, ale nezahrnují xx xx xxxxxxx xxxxxxxx xxxxxxx.

Xxxx by xxx xxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxx xxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxxxx v xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxx. Xxxx xx xxxx být xxxxxxx údaje xxxxxxx xx formě xxxxxxx.

Xxxxxxx xxxxx pozitivní odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx experimentálních podmínek. Xxxxxxxxxx potvrdit xxxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx x bodu 1.4.3.3. Xxxxx xxxxxxxxx studie x cílem xxxxxxxx xxxxxx posuzovaných xxxxxxxx xx xxxx být xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx být xxxxxxx, xxxxx rozmezí xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x chromozomovými aberacemi x závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx tohoto xxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx metody (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxx polyploidie buněk xxxx znamenat, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx znamenat, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (17, 18).

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx xxxxxxxx xx nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx nebo xxxxxx xxx ohledu na xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní výsledky xx zkoušky xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x xxxxxxxxxxxxx somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx neindukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx savců xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx o xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- xxxxxxxxxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxxxxxxx karyotypu x xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- xxxxxxxxx x xxxxx buněčného cyklu,

- xxxxxxx xxxxx krve, xxx xxxx xxxxxxx xxxx xxxx xxxx xxxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx kultury,

- xxxxxxx xxxxxxx počtu xxxxxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxxxx, xxxx koncentrace a xxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx např. údajů x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, xxxx-xx x dispozici,

- složení xxxxx, xxxxxxxx koncentrace XX2,

- koncentrace xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx nasazení,

- xxx a xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,

- pozitivní x xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity, xxxx. xxxxxx konfluence, xxxxx o buněčném xxxxx, xxxxx xxxxx, xxxxxxxxx xxxxx,

- xxxxxx xxxxxxx,

- xxxxx x xX x xxxxxxxxxx xxxxxxxxxxx xxxxx, xxxxx xxxx stanoveny,

- definice xxxxxxx, včetně xxxx,

- xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxx aberací xxxxxx xxx xxxxxx xxxxxxxxxxx x xxxxxxxxx kulturu,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx xxx Xxxxxxx xxx their Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, A. (xx) Xxxxxx Xxxxx, Xxx Xxxx xxx London, 1-29.

2) Xxxxxxxx, X. Xx., Xxxxxx, X. (1985), The Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Xxxxxxx Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Cells in Xxxxxxx, in: Xxxxxxxx xx Xxxxxxxxxx Research, Xxx. 5, Xxxxx, X. xx xx., (xxx) Xxxxxxxx Science Xxxxxxxxxx, Amsterdam-New Xxxx-Xxxxxx, 427-432.

3) Galloway, X. X., Armstrong, X. X., Xxxxxx, C., Xxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxx, X. X., Xxxxxxxx, F., Xxxxx, X., Xxx, X., Xxxxx, X., Margolin, X. H., Resnick, X. X., Xxxxxxxx, X., Xxxxxx X. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxxx xx Chinese xxxxxxx xxxxx cells: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (suppl. 10), 1-175.

4) Scott, X., Xxxxxxxx, X. X., Marshall, X. X., Xxxxxxxx, M. Xx., Xxxxxxx, X., Xxxxx, X., Xxxx, X. C. (1991), Xxxxxxxxxxxx under Xxxxxxx Xxxxxxx Conditions. A xxxxxx xxxx ICPEMC Xxxx Xxxxx 9, Xxxxxxxxxx Xxx., 257, 147-204.

5) Xxxxxx, X., Xxxxxx, T., Xxxxxx, X., Xxxxxxx, X., (1992), Clastogenicity xx xxx xX xx Xxxxxxx Xxxxxxxx Mammalian Xxxxx, Mutatation Res., 268, 297-305.

6) Xxxx, X. X., XxXxxx, X., Xxxxxxxx, X. (1975), Xxxxxxx for Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 31, 347-364.

7) Xxxxx, X. M., Xxxx, X. X. (1983), Xxxxxxx Xxxxxxx for xxx Salmonella Xxxxxxxxxxxx Xxxx, Mutatation Xxx., 113, 173-215.

8) Natarajan, X. X., Tates, X. X., xxx Xxxx, X. X. X., Xxxxxxx, X., xx Vogel, X. (1976), Cytogenetic Effects xx Xxxxxxx/Xxxxxxxxxxx after Xxxxxxxxxx xx a Xxxxxxxxxxx Xxxxxx Xx xxxxx, X. Xxxxxxxxx xx Xxxxxxxxxx Aberrations xxx Xxxxxx Chromatid Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) xx XXX Xxxxx xx xxx Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Mutatation Res., 37, 83-90.

9) Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, M. Jr. (1979), Xxxxxxxxxxx Aberration Xxxxx xx 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Xxx Xx xxxxx, Xxxxxxxx Xxx., 66, 277-290.

10) Elliot, X. X., Xxxxxx, X. X., Elcombe, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxx xx UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Alternative xx Xxxxxxx 1254-xxxxxxx X9 in In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Sawamura, X., Xxxx, X., Xxxxxxxx, X. (1976), X. Xxxx Substitute xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, X. X., Xxxxx, X. X. Xxxx, X. X., Philpot, R. X. (eds), Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Mutagenesis Xxxxxxx, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, S. M., Xxxxxxx, X. X., Xxxxxxxx, M. Xx., Xxxxx, X. X., Xxxxxxxx, D. J., Xxxxxx, X., Xxxxxxx, X., Xxxxxx, X. (1994), Xxxxxx from Xxxxxxx Xxxxx xx Xx xxxxx Tests xxx Chromozomal Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 312, 241-261.

13) Xxxxxxxxxx, C., Xxxxxxxx, X. X., Xxxxx, J. X., Xxxxxxxx, X., Xxxxxxx, X. X., Phillips, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx xxxxx Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. J., (ed) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

14) Xxxxx, X. X., Xxxxxxxx, X. M. (1994), Xxxxxxxxx Xxxxxx xxx xxx Xxxxxxxxx xxx Xx xxxxx Xxxxxxxxxx Xxxxxxxxxx Xxxxxx xx XXX Cells, Xxxxxxxxxx Xxx., 312, 139-149.

15) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, in: Xxxx, X. R., Costa, X. X., Xxxxxxx, X. M. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, New Xxxx, Plenum, 91-103.

16) Xxxxxx, P. O., Xxxxxx, J. M., Xx, X. P., Xxxxxx, X. L. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Mutagens xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environmental Xxxxxxx., 5, 795-801.

17) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Chinese hamster xxxxx xxxxxx xxxxx-xxxxxxxxx xxxxxxx G2 xxxxxx, Xxxxxxxxxx Res., 119, 403-413.

18) Xxxxx, Y., Xxxxxx, C., Xxxxxx, X. E. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx in Xxxxxxx hamster xxxxx, Xxxxxx Xxx., 43, 1362-1364."


XXXXXXX 4B

"B.11 XXXXXXXXXX–XXXXXXX XX CHROMOZOMOVÉ ABERACE X BUŇKÁCH XXXXXX XXXXX SAVCŮ IN XXXX

1. XXXXXX

Xxxx metoda xx replikou xxxxxx XXXX XX 475 — Zkouška xx xxxxxxxxxxxx aberace x xxxxxxx xxxxxx xxxxx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx chromozomové xxxxxxx x savců xx xxxx je používána xxx detekci strukturních xxxxxxxxxxxxxx aberací xxxxxxxxxxxx xxxxxxxxx xxxxxx x xxxxxxx xxxxxx dřeně xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx — chromozomové x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx chemická xxxxx xx xxxxxxxxx indukovat xxxxxxxxx aberace. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx jsou indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx chromozomové aberace xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob u xxxxxxx a existuje xxxxx důkazů o xxx, xx chromozomové xxxxxx x xxxxxxxxxxx xxxx xxxxxxxxxxx změny x onkogenech x x xxxxxx somatických xxxxx tlumících xxxxxx, xxxx podíl xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx hlodavci. Xxxxxxx xxxxx xx x xxxx xxxxxxx xxxxxx xxxx, xxxxxxxx je xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx x xxxxxxx xxxxxx, které xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Xxxx xxxxx x cílové tkáně xxxxxx předmětem xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxx xxxxxx k xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx umožňuje zohlednit xxxxxxx metabolismu xx xxxx, farmakokinetiku a xxxxxxx xxxxxxxx DNA, xxxxxxx se mohou x xxxxxxx xxxxx x xxxxx měnit. Xxxxxxx in vivo xx xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx in vitro.

Jestliže xxxxxxxx xxxxx o xxx, xx xx xxxxxxxx xxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Chromatidová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx jednotlivých chromatid xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu v xxxxxx xxxxx xxxx xxxxx x spojení xxxx xxxxxxxxx v xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, xxx kterém x jádře xx X-xxxx replikace DNA xxxxxxx k mitóze, xxxxx xxxxxxxxx další X-xxxx. Xxxxxxxxx jsou xxxxxxxxxx se 4, 8, 16,… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx šířka xxxxxxx chromatidu a x xxxxxxxxx odchylkou xxxxxxxxx.

Xxxxxxxxx aberace : xxxxxxxx xxxxx chromozomů xx xxxxxxxx xxxxxxx xxxxxxx u xxxxxxxxx xxxxx.

Xxxxxxxxxxx : xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx xxx (x), xxxx xxx xxxxxxxxx (xx. 3 x, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : mikroskopicky xxxxxxxxxxxxx xxxxx struktury chromozomů xxx buněčném xxxxxx xx xxxxxx xxxxxxxx; xxxx se jako xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx interchromozomální xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xx xxxxxxx okamžiku xx xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X buněk kostní xxxxx xx xxxx xxxxxxxx preparáty chromozomů, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx je xxxxxxxx xxxxxx, myš x xxxxxx čínský, xxxxxx lze xxxxxx xxxxxxxx xxxxxx savčí xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx zahájení studie xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx xxxxxx podmínky xxxxx xxxxxxxx xxxxx x xxxxx X, xxxxxxx xx mělo xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, která xx xxxxxxx xxxxxxxx xxxxx. Xxxxx xx xxxx být xxxxxxxxxx xxx, aby byl xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx se xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x laboratorních xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.

1.4.1.4 Příprava xxxxx

Xxxxx zkoušené xxxxx xx měly xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx podávány přímo xxxx mohou být xxxx podáním xxxxxxx. Xxxx by xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při použitých xxxxxxxx xxxxx toxické xxxxxx x mělo xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx pohlaví. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx identický xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx poskytovat xxxxxxxxxx xxxxxxx xx xxxx xxx expozičních xxxxxxxx, x nichž xx xxxxxxx, xx poskytnou xxxxxxxxxxxxx xxxxxx nad xxxxxx. Dávky pozitivní xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx podávána xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx odběr x xxxxx případě xxxxxxxx jen xxxxxx. Xxx pozitivní xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxx látky xx xxxxxx xxxxxxxx třídy, xxxx-xx k dispozici. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx

51–18–3

200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx xxx být proveden xxxxx u xxxxxxxxxxx xxxxxxx, xxxx je xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx a xxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, pokud xxxxxx x dosavadních xxxxxxxxxxx xxxxx x xxxxxxxxx přijatelné xxxxx x variabilitě xxxxxx x xxxxxxxx xxxxx x chromozomovými xxxxxxxxx. Xxxxxxx-xx se pro xxxxxxxxx xxxxxxxx xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Každá xxxxxxxxxx x kontrolní xxxxxxx se xxxxxx x alespoň pěti xxxxxxxxxxxxxxxx zvířat xxx xxxxx xxxxxxx. Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx ze xxxxxx xx stejným druhem x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx prokazují, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x toxicitě, xxxx postačující xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, xxxx xx xxxx xxxxxxxxx u některých xxxxxxxxxxxxxxx xxxxx, xxxx xx být zkouška xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx xxx xxxxx xxxxx xxxxxxxx jednorázově. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx také xx xxxx xxxxxxx, xxx. dvě dávky x týž xxx x xxxxxxx xx xxxx než několika xxxxx, xxx bylo xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx xxxxxxxx xx xxxx různých xxxxxxxxxxx xx xxxxxxxx xxxxxx x jednom xxx. X hlodavců xx xxxxx xxxxxxx xx xxxxxx xxxx xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxx xxxxxx na kinetiku xxxxxxxxx xxxxx xxxx xxx vliv xx xxxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxx xxxxx odběr po 24 x od xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx do xxxx než jednoho xxx, xxx xx xxx xxxxx xxxxxxxx xx takové xxxx xx poslední xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky buněčného xxxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X myši je xxxx xxxx xxxxxxxxx 3 — 5 x; x xxxxxx xxxxxxxx xx tato xxxx xxxxxxxxx 4 — 5 h. X kostní dřeně xx xxxxxxxx buňky x analyzují xx xx xxxxxxxxxxxx xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx studie xxx xxxxxxxx xxxxxxx dávek, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, pohlavím x xx stejného xxxxxx xxxxxxxx, jež xx xxxxxxx x xxxxxx xxxxxx (5). X případě toxicity xx pro xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, xx vyšší xxxxx xx vedly xxx stejném xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Látky xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx dávkách (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx by xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx dávka xxxx být xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. více xxx 50 % xxxxxxx mitotického indexu).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx xxxxxxx 2000 mg/kg xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx ve xxxx dávkách x xxxxxx xxx nevykazuje xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx studie xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X xxxx trvajících xxxxxx xx limitní xxxxxx pro 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx delší než 14xxxxx aplikaci xx xxxxxxx dávkou 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx se xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx injekcí. Jiné xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou podán xxxxxxxxxxxxxx xxxx injekčně, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx překročit 2 ml/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx objemů, než xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx dráždivé x žíravé xxxxx, xxxxx xxxxxxx při xxxxxxx xxxxxxxxxxxxx vykazují xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx dávky.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx xx xxxxxxx xxxxxx xxxx, xxxxxxxxxxxx xx a xxxxxx. Xxxxx xx nanesou xx podložní xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx cytotoxicity xx xxx xxx x xxxxx xxxxxxxxxxxx xxxxxx (xxxxxx pozitivních xxxxxxx) x u xxxxxxxxxxxxxx xxxxxx xxx xxxxxxxxx kontrolu xxxxxxxx xxxxxxxxx index, a xx xxxxxxx u 1000 xxxxx na xxxxx xxxxx.

X xxxxxxx xxxxxxx xx mělo xxx analyzováno xxxxxxx 100 buněk. Xxxxx xxxxx lze xxxxxx, xx-xx pozorován xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx kontrol xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Protože při xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xx xxxxxx xxxxxxxxxx x části xxxxx v xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx by xxxx být xxxxxxxxxx xx xxxxx tabulky. Xxxxxxxxxxxxxx jednotkou je xxxxx. Xxx xxxxx xxxxx xx xxx xxx xxxxxxxxxx počet xxxxx, xxxxx aberací xx xxxxx a xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) vyjádřený v xxxxxxxxxx. Xxx xxxxxxxxxx x xxxxxxxxx skupiny xx xxxx xxx xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx obecně xx xxxxxxxxxx do celkové xxxxxxxx aberací. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx mezi xxxxxxxxx, xxxxx xxx xxx statistickou xxxxxxx xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního výsledku xxxxxxxx několik xxxxxxxx, xxxx. nárůst xxxxxxxxxxx xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx na xxxxx xxxx jasný xxxxxx xxxxx xxxxx s xxxxxxxxx xxx skupinu x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Nejdříve xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx prostředek statistické xxxxxx (6). Statistická xxxxxxxxxx by neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx buněk x xxxxxxxxxxxxxxxxxxx chromozomy může xxxxxxxx, že xxxxxxxx xxxxx xx potenciál xxxxxxxx xxxxxxxx buněčného xxxxx (7, 8).

Xxxxxxxx xxxxx, jejíž xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, se považuje x xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx na to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxx xxxxxxxxx, xx zkoušená látka xxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x kostní dřeni xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx by xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx se xxxxxxxx xxxxx xxxx její xxxxxxxxxx dostanou do xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- xxxxxxxxxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x negativní (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

- xxxxx xx studie xxx xxxxxxxx rozsahu, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- xxxxx x přípravě xxxxxxxx látky,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- popřípadě metody xxxxxxx, zda se xxxxxxxx látka dostala xx xxxxxxxx xxxxx xxxx do cílové xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx vodě (xxx) xx odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx krmiva a xxxx,

- xxxxxxxx xxxxx xxxxxxx expozice a xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- identifikace xxxxx xxxxxxxxxxx xxxxxxxx, její xxxxxxxxxxx a xxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx hodnocení xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

- typ a xxxxx xxxxxxx uvedený xxxxxxxxxx pro xxxxx xxxxx,

- celkový počet xxxxxxx xx xxxxxxx xx xxxxxxxxx hodnotami x směrodatnými xxxxxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx xx xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx x rozpětími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Adler, X. D. (1984), Xxxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Practical Xxxxxxxx, X. Xxxxxx, X. X. Xxxxx (xxx), XXX Press, Xxxxxx, Washington X. X., 275-306.

2) Preston, X. X., Xxxx, X. X., Xxxxxxxx, X., Xxxxxx, X., XxXxx, X. F., Xxxxxx, X. (1987), Xxxxxxxxx Xx xxxx Xxxxxxxxxxx Assays: Xxxxxxxx xx Chromozome Xxxxxxxxxxx xx Bone Xxxxxx Xxxxx, Mutatation Xxx., 189, 157-165.

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, J., Xxxxxxxxx, X. G., Xxxxxxx, X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Kirkland (xx.), Basic Mutagenicity Xxxxx, UKEMS Recommended Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

4) Xxxx, X. R., Hayashi, X., XxxXxxxxxx, J. X., Xxxxxxxx, X., Xxxxxx, X. X., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, M., Oleson Xx., X. B., Xxxxxxxxxxxx, F., Xxxxxxx, X. J., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Working Xxxxx xx xxx xx xxxx Xxxxxxxxx Xxxx Xxxxxx Chromozomal Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, R. X., Xxxxx, J. A., Xxxxxx, X. X., Xxxxxx, X. A., Xxx, J., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Hodson-Walker, X., Morton, D. X., Xxxxxxxx, X. X., Richold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. X. K. (1989), Xxxxxxxxxxx Analysis xx Xx xxxx Cytogenetic Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing, Xxxxxx Xxxx III. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, X. X. Xxxxxxxx (xx.) Cambridge University Xxxxx, Cambridge, 184-232.

7) Xxxxx-Xxxxx, C. (1983), Xxxxxxxxxxxxxxxxx in Chinese xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx-xxxxxxx X2 arrest, Xxxxxxxxxx Res., 119, 403-413.

8) Xxxxx, X., Xxxxxx, X., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx xx Xxxxxxx hamster xxxxx, Xxxxxx Xxx., 43, 1362-1364."


PŘÍLOHA 4X

"X.12 MUTAGENITA–TEST XXXXXXX XXXXXXXXXXXXXXX XXXXXXXXXX XX XXXX

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx OECD TG 474 — Test xxxxxxx erytrocytárních xxxxxxxxxx xx vivo (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx používán xxx xxxxxxx xxxxxxxxx chromozomů xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, které je xxxxxxxxxx xxxxxxxxx látkou, x xx xxxxxx xxxxxxx erytrocytů odebraných x xxxxxx xxxxx x/xxxx xxxxx xxxxxxxxx xxxx, xxxxxxx xxxxxxxx.

Xxxxxx xxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx identifikovat xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, jehož xxxxxxxxx xx xxxxxx xxxxxxxxxx obsahujících xxxxxxxxxxxxx xx (xxxxxxx) chromozomové xxxxxxxxx nebo celé xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx dřeně xxxx xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx jádro xx xxxxxxxx x xxxxxxxxxx, xxxxx xxx tom xxxxx vzniknout, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx xx x xxxxxx buňkách xxxxxxxxx tím, xx xxxxxxxxxx xxxxxx jádro. Xxxxxx výskytu xxxxxxxxxxxxxxxxx xxxxxxxxxx x mikrojádry x xxxxxxxxxxxx xxxxxxxxx xx známkou xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx je rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, poněvadž tato xxxx xxxxxxxxx polychromatické xxxxxxxxxx. Xxxxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx v periferní xxxx xx xxxxxxxxxx xxxxxxxxxx x xxxxxxxxxxx xxxxx, x xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Mikrojádra xxx rozlišit xxxxx xxxxxxxx. Ta xxxxxxxx xxxxxxxxxxxx přítomnosti nebo xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX v mikrojádře. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx xxxxxxx (normochromatických) xxxxxxxxxx x xxxxxxxxx xxxx, které obsahují xxxxxxxxxx, xxxxxxxxxxx na xxxxxx xxxxx xxxxxxx xxxxxxxxxx lze xxxxxx xxxxxx xxxx konečný xxxxxxxx xxxxxxx, xxxxxxxx xxxx xxxxxxx exponována xxxxx týdny xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx je xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx DNA, xxxxxxx xx xxxxx xxxxx x xxxxxxx xxxxx x xxxxx, xxxxx x x xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx je xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx v systémech xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x tom, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx tkáně, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx xxxx Xxxxxx xxxx, část X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) xxxxxxxxxx, x xxx (x xxxx) xx xxxxx xxxxxx xxxxx připojí xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx pohyb xxxxxxxxx xxxxxxxxxx x pólům xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx jádra existující xxxxxxxx xx xxxxxxxx xxxxx x vedle xxxx, xxxxxxxxx xxxxx xxxxxxxx mitosy (xxxxxx) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx erytrocyt : xxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxx, který xxx rozlišit xx xxxxxxxxx xxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx ve xxxxxxxxx mezistadiu, xxxxx xxxxx xxxxxxxx ribozomy, x xxxx xxx xxxx xxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx selektivním xxx xxxxxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xx vhodným xxxxxxxx xxxxxxx zkoušené xxxxx. Při xxxxxxx xxxxxx xxxxx se xxxxxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxx, xxxxxxx se xxxxxx xxxx, xxxxxxxx xx xxxxxxxxx a xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx použití xxxxxxxxx xxxx xx xxxx xx xxxxxxx xxxxxxxx xx expozici xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Xxx xxxxxxxx s xxxxxxxxx xxxx xx xxxx xxxx poslední xxxxxxxx x xxxxxxxxx buněk xxxxxxxx xx xxxxxxxxx xxxx. Xxxxxxxxx jsou xxxxxxxxxxx na xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx použití xxxxxx xxxxx se xxxx xxxxxxxxx xxxxx xxxxxxxxxx myš nebo xxxxxx, xxxxxx xxx xxxxxx jakýkoli vhodný xxxxx xxxx. Při xxxxxxx periferní krve xx xxxxxxxxxx xxx. Xxx xxxx použít xxxxxxxx vhodný druh xxxxx xx xxxxxxxxxxx, xx xxx x xxxx, x xxxxx xxxxxxx xxxxxxxxxxxx erytrocyty x xxxxxxxxxx, xxxx xxxx xxxxxxxxxx dostatečnou xxxxxxxxx detekovat činitele, xxxxx způsobují strukturní xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Měly xx xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx zahájení studie xx xxxx být xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx x xxxxxx xx u xxxx xxxxxxx překročit ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx X, xxxxxxx by mělo xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní skupinu x xxxxxxx, x xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Xxxxxxx xx v xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx. Klece xx uspořádají tak, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx rozpuštěny nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx zkoušené xxxxx xxxxx být podávány xxxxx xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Měly xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxx xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx toxické xxxxxx x xxxx xx xxx xxxxxxxxx podezření, xx xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx pro xxx xxxxxxx. X xxxxxxxx xxxxxxxx zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx identický xxxxxx xxxx zvířata xx xxxxxxxxx, v xxxxx xxxxx x expozici.

Pozitivní xxxxxxxx by xxxx xxxxxxxxxx mikrojádra xx xxxx xxx expozičních xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx detekovatelný xxxxxx xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx zřetelný, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx identifikace xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx způsobem xxx zkoušená látka x xxx xxx xxxxx x tomto xxxxxxx xxxxxxxx xxx xxxxxx. Pro pozitivní xxxxxxxx xxxxx může xxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx pro pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid monohydrát

6055–19–2

2,4,6-tris(aziridin-1-yl)- 1,3,5-xxxxxxx

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx xxx xxx xxxxxxxx odběr x xxxxxxx negativní xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx nebo xxxxxxxxx a xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx xxxxx k dispozici xxxxxxxxxx údaje o xxxxxxxxxxx zvířat a xxxxxxxx xxxxx x xxxxxxxxxx. Xxxxxxx-xx xx xxx negativní xxxxxxxx xxxxx xxxxx, je xxxxxxxxxxxxx okamžikem xxxx xxxxxxx xxxxxx. Kromě xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

Xxx použití xxxxxxxxx krve xxxx xxx jako xxxxxxxxx xxxxxxxx přijatelný xxxx xxxxxx krve xxxxxxxx xxxx xxxxxxxx, pouze xxxx u xxxxxxxx xxxxxx x periferní xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, xx xxxxxxxx údaje xxxxx x xxxxxxx, xxxxx xx na základě xxxxxxxxxxx xxxxxxx očekává.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní skupina xx xxxx xxxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx (11). Xxxxxxxx xxxx v xxxx studie x xxxxxxxxx xxxxx ze xxxxxx se xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx v xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx aplikace

Nelze xxxxxxxxx xxxxx xxxxxxxxxx plán (xx. xxxxx, xxx xxxx xxx xxxxxxxx x intervalu 24 xxxxx). Xxxxxx xx xxxxxx x xxxxxxxxxxxx xxxxxxx podávání jsou xxxxxxxxxx, xxxxx xx x těchto xxxxxx xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –v případě xxxxxxxxxxx xxxxxx — xxxxx xxxx xxxxxxxxx xxxxxxxx nebo xxxx xxxxxxxxx xxxxxxx xxxxx x podávání xxxxxxxxx xx do xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. dvě xxxxx v týž xxx v xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx xxx xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx se xxxxxxxx xxxxxxx dvakrát, xxxxxxx xxxxx xxxxx xx xxxxxxx nejdříve 24 xxxxx po xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci x x xxxxxxxxxx xxxxxxxx xxxx xxxxxx. Xxxxx xxxxx xxx 24 xxxxx xx aplikaci xxxx xxx zdůvodněn. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx první xxxxx xx provede xxxxxxxx 36 xxxxx xx xxxxxxxx a xxxxxxxx xxxxxxxxxx 72 xxxxx po xxxxxxxx x xx prvnímodběru xx xxxxxx xxxxxxxxxxxx xxxxxx. Je-li xx xxxxxx odběru pozorována xxxxxxxxx xxxxxxx, není xxxxx odběr xxxxx;

x) xxxx-xx xxxxxxxx dvě xxxx xxxx xxxxx xxxxx (xxxx. dvě xxxx xxxx dávek x xxxxxxxxx 24 xxxxx), xxxx xx xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx xx 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx x při xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx xxxxxxx mohou xxx xxxxx použity xxxx doby xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx být xxxxxxxxx xx stejné xxxxxxxxxx, se xxxxxxx xxxxxx, kmenem, xxxxxxxx x za xxxxxxxx xxxxxx expozice, xxx xx použijí x xxxxxx xxxxxx (13). X případě toxicity xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx až xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že vyšší xxxxx by xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také xxxxxxxxxx xxxx dávka xxxxxxxxxxxx x kostní xxxxx xxxxxxx známky xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx v xxxxxx xxxxx xxxx x xxxxxxxxx krvi).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx dávkou o xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx a xxxx-xx xx základě údajů x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, není xxxxxxxxxx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X déle xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx a xxx delší xxx 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx injekcí. Jiné xxxxxxx xxxxxxxx xxxx xxxxxxxxxx v odůvodnitelných xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x tělesné hmotnosti. Xxxxxxx vyšších xxxxxx, xxx xx xxxxxxx xxxxx, musí být xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx vyšších xxxxxxxxxxxxx xxxxxxxx zesílené xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx kostní xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx získávají x xxxxxx xxxx xxxxx xxxxx xx xxxxxxxx. Xxxxx xx xxxxxxxx x xxxxxx xxxx xxxxx a xxxxxxxxxx xxxxxxxx xx preparují x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x xxxxxx žíly xxxx jiné xxxxxx xxxxxx cévy. Xxxxxx xxxxx xx xxxxx xxxxxxxxxxxx obarví (8, 9, 10), xxxx xx připraví xxxxxxxxx xxxxxxxx a poté xx obarví. Xxxxxxxx xxxxxxx specifického xxx XXX (xxxx. akridinová xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx vyhnout xxxxxxxx xxxxxxxxxx xxxxxxxx x xxxxxxxx xxxxxxx nespecifického xxx XXX. Tato xxxxxx nebrání použití xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Přídavné xxxxxxx (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx buněk xxxxxxxxxxxx xxxxx (16)) xxx použít xx xxxxxxxxxxx, že se xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx každé xxxxx se stanoví xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x případě xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 xxxxxxxxxx x x případě xxxxxxxxx xxxx alespoň 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx být xxxx xxxxxxxx pod xxxxxxxxxxx xxxxxxxxx xxxxxxxx. U xxxxxxx zvířete xx xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Další xxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx zralých erytrocytů xx xxxxxx mikrojader. Xxx xxxxxxxxxxxxx analýze xx xxxxx xxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx než 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx exponována xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx také xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx erytrocytů xx xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx obrazu x xxxxxxxxx cytometrická analýza xxxxxxx xxxxxxxx) xxxx xx odpovídajícím zdůvodnění x xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx hodnocení.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx xxxxx analyzované xxxxx xx xxx xxx xxxxxx xxxxx vyšetřených xxxxxxxxx erytrocytů, počet xxxxxxxxx erytrocytů x xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx xxxx déle, xxxx xx být xxxx xxxxxxx xxxxx x xxxxxxx xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Pro xxxxx zvíře xx xxxxx xxxxx nezralých xxxxxxxxxx z celkového xxxxxxxx erytrocytů x xxxxxxxx xxxxxxxx erytrocytů x mikrojádry xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x odpovědi xxxx xxxxxxxxx, xxxxx být xxx statistickou analýzu xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxx x závislosti xx xxxxx xxxx jasný xxxxxx xxxxx xxxxx x mikrojádry pro xxxxxxx s určitou xxxxxx a x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný prostředek xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím faktorem xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx kritéria, xx xxxxxxxx v xxxxx xxxxxxx xx nemutagenní.

Ačkoli xxxxxxx experimentů poskytne xxxxx pozitivní xxxx xxxxxxxxx výsledky, v xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx mikrojádra xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx důsledkem xxxxxxxxxxxxxx poškození xxxx xxxxxxxxx mitotického aparátu xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená látka xx xxxxxxxx zkoušky xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx testovacího xxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

- xxxxxxxxxxx a xxxxxxx xxxxxxxx látky x xxxxxxxxxxxx/xxxxxxxx, je-li xxxxx.

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- počet, stáří x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné hmotnosti, xxxxxxx hodnota x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx podmínky:

- xxxxx k pozitivní x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- údaje ze xxxxxx pro xxxxxxxx xxxxxxx, xxxxx xxxx xxxxxxxxx,

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x přípravě xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx podávání,

- xxxxxxxxx xxxxxx xxxxxxx, xxx xx zkoušená xxxxx xxxxxxx do xxxxxxxx oběhu xxxx xx xxxxxx xxxxx,

- xxxxxxxx xxxxxxxx mezi xxxxxxxxxxx xxxxxxxx látky x xxxxxx xxxx xxxx (xxx) xx xxxxxxxxxxxx xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x vody,

- xxxxxxxx popis xxxxxxx xxxxxxxx a odběru,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx stanovení xxxxxxxx,

- xxxxxxxx hodnocení mikrojader x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx analyzovaných xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx xxxxxxx ± xxxxxxxxxx odchylka xxxxx xxxxxxxxx erytrocytů s xxxxxxxxxx xx skupině,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx statistické analýzy x xxxxxx,

- údaje x souběžné a xxxxxxxxx negativní xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxxx, J. X. (1973), A Xxxxx Xx xxxx Xxxx xxx Xxxxxxxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 18, 187-190.

2) Xxxxxx, X. (1975), Xxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 31, 9-15.

3) Xxxxxx, X. A., Xxxxxxxx, M. X., Xxxx, X., Kirkhart, X., Mavournin, X., XxxXxxxxx, J. G., Xxxxxx, X. X. (1983), Xxx Induction xx Xxxxxxxxxxx x. x. x Xxxxxxx xx Genotoxicity, Xxxxxxxxxx Xxx. 123, 61-118.

4) Xxxxxxxxx, K. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxxxx, M. X., Xxxxxx, X. X. (1990), Xxx In xxxx Xxxxxxxxxxxx Xxxxx xx Mammalian Xxxx Xxxxxx xxx Xxxxxxxxxx Xxxxx. X report xx the U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, X. X., Xxxxxxxx, R., Xxxx, X. X., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Erythrocytes: X Xxxxx Xxxxxx xxx Xxxxxxxxxxx Xxxxxx During Xxxxxxx Xxxxxxxx Xxxxxxx xx Mice, in: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx of Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Xxxxxxx, T. X. Miya. Elsevier, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. X., Heddle, X. X. Xxxx, X., Xxxxxxxx, X. X., Ramel, C., Xxxxxxxx, X. F., Xxxx, X. X., Xxxx, X. (1987), Xxxxxxxxxx xxx the Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Mammalian Xxxx Xxxxxx Erythrocytes, Xxxxxxxxxx Res., 189, 103-112.

7) XxxXxxxxx, J. X., Wehr, X. X., Henika, X. X., Shelby, X. X. (1990), Xxx xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Test: Xxxxxxxxxxx xx Xxxxxx State Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Permits Xxxxxxxxxxx xxxx Toxicity Studies, Xxxxxx. Xxxx. Toxicol. 14, 513-522.

8) Hayashi, X., Morita, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Xxxxxxxxxx Blood Xxxxxxxxxxxxx Xxxxx Acridine Xxxxxx-Xxxxxx Slides, Xxxxxxxxxx Xxx., 245, 245-249.

9) Xxx Xxxxxxxxxxxxx Study Xxxxx xxx the Xxxxxxxxxxxx Xxxx (1992). Xxxxxxxxxxxx Test xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx Supravital Xxxxxxxx: Xxx Summary Xxxxxx xx xxx 5xx Xxxxxxxxxxxxx Xxxxx xx XXXXX/XXXXX, MMS, Xxxxxxxxxx Xxx., 278, 83-98.

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: The Xxxxxxxxx Xxxxxxxxxxx Study Xxxxx xx xxx Environmental Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx xxx xxx xxxxx-xxxx mouse xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., XxxXxxxxx, X. X., Anderson, X., Xxxxxxx, X. X., Kirsch-Volders, M., Xxxxxx, Jr. X. X., Pacchicrotti, X., Xxxxxxx, X., Shimada, X., Xxxxx, X., Xxxxxxx, B. (1994), Xx xxxx Rodent Xxxxxxxxxxx Xxxxxxxxxxxx Assay, Xxxxx. Xxx., 312, 293-304.

12) Xxxxxxxxxxx, X., Xxxxx, X. (1995), Xx xxxxxxx, generalised xxxxxxxx xxxx of 30 ± 6 x xxxxx xxxxxx xxxxxx xx xxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Xxxxxxx, X. X., Allen, J. X., Boobis, X. X., Xxxxxx, X. X., Doe, J., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. B., Xxxxxxxx, X. J., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Working Group: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

14) Xxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. Xx. (1983), Xx Application xx Xxxxxxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxx xx xxx Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 120, 241-247.

15) XxxXxxxxx, X. T., Xxxx, C. X., Xxxxxxxx, X. X. (1983), X Xxxxxx Xxxxxxxxxxx Staining Xxxxxxxxx xxx Xxxxxxxxxxx xxx XXX in Erythrocytes Xxxxx Xxxxxxx 33258 xxx Xxxxxxx X, Xxxxxxxx Xxx., 120, 269-275.

16) Romagna, X., Xxxxxxxxxx, X. X. (1989), Xxx xxxxxxxxx xxxx xxxxxx micronucleus xxxx, Mutatation Xxx., 213, 91-104.

17) Gollapudi, X., XxXxxxxx, L. X. (1995), Sample Xxxx xxx xxx Xxxxxxxxxx xx Polychromatic xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx xx the Xxxx Marrow Micronucleus Xxxx, Mutatation Xxx., 347, 97-99.

18) Xxxxxxx, X., Xxxxx, J., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx vivo Xxxxxxxxxxxx Xxxxx, xx: X. X. Kirkland (xx.), Basic Xxxxxxxxxxxx xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx 1, xxxxxxx, Xxxxxxxxx University Press, Xxxxxxxxx, New York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx X., Xxxxxxx, X., Xxxxxxxx, X. G., Xxxxxx, J. R. X. (1989), Xxxxxxxxxx Xxxxxxxx xx In xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Part XXX, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

"X.13/14 XXXXXXXXXX — ZKOUŠKA XX XXXXXXXX MUTACE X XXXXXXXXXX

1. METODA

Tato xxxxxx xx xxxxxxxx metody XXXX TG 471 — Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 ÚVOD

Při xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x detekci xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, adici x xxxxxx xxxxxxx xxxx xxxxxxxx párů xxxx XXX (1, 2, 3). Podstata xxxx xxxxxxx na xxxxxxxx xxxxxx s bakteriemi xxxxxxx x xxxxxxx xxxxxx, xxxxx revertují xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxx x xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx xxxx své xxxxxxxxxx růst v xxxxxxxxxxxxx xxxxxxxxxxxx, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x xxxxxxx xxxx xxxx příčinou mnoha xxxxxxxxx xxxxxxxxxxx chorob x člověka x xxxxxxxx xxxxx důkazů x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx a v xxxxxx somatických xxxxx xxxxxxxxx nádory xxxx xxxxx xx xxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx je xxxxxx, xxxxxxxxxx x xxxxxxxxx xxxxxx. Mnoho xxxxxxxxxxx xxxxx má xxxx xxxxxxxxxx, xxxx xxxx xxxx citlivější xx xxxxxxx xxxxxx, včetně xxxxxxxxxxxxx sekvencí XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx xxxxx xxx xxxxx molekuly x xxxxxxxxx xxxxxxxxxxx xxxxxxx DNA xxxx xxxxxxxx xxxxxxxxxxx procesů XXX xxxxxxxxxx x xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx xxxx poskytnout xxxxxxx xxxxxxxx xxxxxxxxx x typech mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Pro xxxxxxx na reverzní xxxxxx s bakteriemi xx x xxxxxxxxx xxxxx xxxxxxxx databáze xxxxxxxx xxx širokou xxxxx xxxxxxxx x xxxx xxxx xxxxxxxx xxxxx vyzkoušené xxxxxx xxxxxxxx xxxxxxxxxx látek, xxxxxx xxxxxxxx sloučenin, x různými xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx nebo Xxxxxxxxxxx coli xxxxxx x xxxxxxx xxxxxx x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (histidin xxxx. xxxxxxxxx), přičemž xxxxxx xxxx xxxxxxxxx na xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx párů xxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx mohou xxxx xxxxx xxxxxxxxxx na xxxxx xxxxxxx mutace xxxx xxxxx místě xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx xxxxxxxx xxxx xxxxxxxx, jež xxxxxxxxx adici nebo xxxxxx jednoho xxxx xxxx xxxx xxxx XXX x xxxxxxxx xxx xxxxx xxxxx XXX.

1.3 VÝCHOZÍ ÚVAHY

Při xxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx využívají prokaryotické xxxxx, xxxxx se xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx a xxxxxxxxx xxxxxxx XXX. Xxxxxxx prováděné xx xxxxx obecně xxxxxxxx xxxxxxx vnějšího zdroje xxxxxxxxxxx aktivace. Metabolické xxxxxxxxx systémy xx xxxxx xxxxxxx zcela xxxxxxxxx podmínky xx xxxx x savců. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx informaci x xxxxxxxxxx a xxxxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xx xxxxxxxxx xxxxxxxxx xxx počáteční xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx xxxxxxxx vyvolávající xxxxxx xxxxxx. X xxxxxxxx xxxxxxxx vyplývá, xx xxxxx chemických xxxxx, xxxxx xxxx x této xxxxxxx xxxxxxxxx, vykazuje xxxxxxxxx xxxxxxxx x x xxxxxx zkouškách. Xxxxxxxx xxxxxxxx mutagenních činitelů, xxxxx nejsou xxxxxxxxxx xxxxx zkouškou. Příčiny xxxxxx xxxxxxxxxxx xxx xxxxxxxxx xx specifické xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x xxxxxxxxx v xxxxxxxxxxx aktivaci nebo x xxxxxxxxx x xxxxxxxxxx dostupnosti. Xx xxxxx straně faktory, xxxxx zvyšují citlivost xxxxxxx xx reverzní xxxxxx xx bakteriích, xxxxx vést k xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx nemusí xxx xxxxxx pro xxxxxx xxxxx chemických xxxxx, například xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) x xxx chemické látky, x nichž xx xxxxxxxxxxx (xxxx x xxxxx xx xx), xx specificky xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). V takových xxxxxxxxx xxxxx být xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, je karcinogenní xxx savce, není xxxxxxxx xxxxxxxxx. Závisí xx xxxxxxxx třídě x existuje mnoho xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx jinými, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x to za xxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx a xxx něho. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx suspenze xxxxxxxx x xxxxxxx xxxxxx x xxxxx xx xxxxxxx xx xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx x xxxx xx xxxx xxxxxxxxx na xxxxxxxxx xxxx smíchá s xxxxxxx agarem. Xxx xxxx technikách xx xx xxxx xxxx xxxxx xxxxx inkubace xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxx se xxxxxxxx x xxxxxx xxxxxxx xxxxxxxxxxx revertantů xx xxxxxxxxx xxxxx x rozpouštědlem.

Je xxxxxxx xxxxxxx xxxxxxx xxxxxxxxx xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx. Xxxx xxxxx používané xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), fluktuační test (9, 10) x xxxxxxxxx metoda (11). Xxxxxx xxx xxxxxxxx xxxxx a xxx xxxx xxxxxxx (12).

Zde xxxxxxx xxxxxxx xx xxxxxx hlavně standardního xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx xx xxxxxxxxxx xxx provádění xxxxxxxxxxx jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxxxxxx xxxxx xxx účinněji xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Tyto xxxxx xxxxx xx xxxxxxxxxx xxxx, xx xxxxx xxxxx mezi xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, dvojvazné xxxx, xxxxxxxx, azobarviva x xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx xxxxx xxxxxxxx nelze xxxx xxxxxxxxx standardními postupy, xxxx xx xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx metoda. Měly xx být xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx použít alternativní xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (společně s xxxxxxxx xxxxxxx xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx a těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx od xxxxxxxxxxxx xxxxxxx xxxx xxx vědecky xxxxxxxxxx.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx kultury xxxxxxxx xx xxxx xxx xxxxxxxxxxx do xxxxxx xxxxxxxxxxxxx xxxx xxxx xx xxxxx xxxxxxxxxxx fáze růstu (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Xx xxxxxxxx, aby xxxx xxxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx může být xxxxxxxx xxx na xxxxxxx dosavadních kontrolních xxxxx o růstové xxxxxx, xxxx xxx xxxxxx xxxxxxx stanovením xxxxx životaschopných xxxxx xx miskách.

Doporučená xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx xx být xxxxxxx alespoň pět xxxxx xxxxxxxx. Xxxx xxxx xx xxxx xxx čtyři kmeny X. typhimurium (XX1535; XX1537 xxxx XX97x xxxx TA97; XX98 x TA100), xxxxxxx xxxxxxx se xxxxxxx x různých xxxxxxxxxxxx xxxx spolehlivá x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. typhimurium xxxx xxx xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx x xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx xxxxxx oxidační xxxxxxxx, činitele způsobující xxxxxxxxxx vláken XXX x xxxxxxxxx. Tyto xxxxx xxxxx xxx xxxxxxxxxx xxxxx X. xxxx WP2 nebo X. xxxxxxxxxxx XX102 (19), které xxxx xx xxxxxxxxx xxxxxxxxx xxxxx xxx xxxx XX. Doporučená xxxxxxxxx xxxxx je xxxx xxxx:

- X. xxxxxxxxxxx XX1535 x

- S. xxxxxxxxxxx XX1537 nebo XX97x x

- S. xxxxxxxxxxx XX98 x

- X. xxxxxxxxxxx XX100 x

- X. xxxx XX2 uvrA, xxxx X. coli XX2 xxxX (pKM101), xxxx X. typhimurium TA102.

Pro xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx DNA xxxx xxx vhodnější xxxxxxx XX102 xxxx xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx DNA, (xxxx. E. coli XX2 (xXX101)).

Xxxx xx xxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxxxxx xxxxxxx x skladování. Potřeba xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx xxx každou xxxxxxxxx kmenovou xxxxxxx (xxxxxxxx pro xxxxx X. xxxxxxxxxxx a xxxxxxxxx xxx X. xxxx). Xxxxxxx by xxxx xxx kontrolovány xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx podle xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx plasmidů (tj. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x TA97a nebo XX97, WP2 uvrA x XX2 xxxX (xXX101) x ampicilinová x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx mutací x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx a xxxX xxxxxx x E. xxxx xxxx xxxX xxxxxx u X. xxxxxxxxxxx citlivostí xx xxxxxxxxxxxx světlo) (2, 3). Kmeny xx xxxx xxxxxx xxxxx xxxxx xxxxxxx spontánních xxxxxxxxxx na xxxxx x rozmezí xxxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx x nejlépe x rozmezí uvedeném x xxxxxxxxxx.

1.5.1.2 Médium

Použije xx vhodný minimální xxxx (xxxx. obsahující xxxxxxxxx xxxx X (Xxxxx-Xxxxxx) a xxxxxxx) x xxxxxx xxxx xxxxxxxxxx xxxxxxxx x xxxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx xxxx být xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx systémem xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx používaným xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx z xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Aroclor 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální xxxxxx xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx v xxxxxxx 5 xx 30 % xxx. xx xxxxx S9. Xxxxx x podmínky xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx chemické xxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx použít více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx x diazoniových xxxxxxxxx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxxxxx xxxxxxxxxx nebo suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx zředěny. Xxxx by xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou, x xxxx xx xxx xxxxxxxxxx s xxxxxxxx xxxxxxxx a x xxxxxxxxx X9 (22). Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx zkoušení xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx organická xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Zkušební xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx stanovení xxxxxxxxxx množství zkoušené xxxxx patří xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxx xxxxx pro xxxxxxxx.

Xxxx být užitečné xxxxxxxx xxxxxxxx a xxxxxxxxxxxxx v předběžných xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx podkladu xxxx xxxxxxxx xxxxxx přežití xxxxxxxxxxxx kultur. Cytotoxicita xxxxx xx xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx by xxxx xxx xxxxxxxxx na xxxxxxx xxxxxxxxxxx srážení x xxxxxxx xxxxx xx xxxxxxxxxx zkušebních xxxxxxxx.

Xxxxxxxxxx maximální xxxxxxxx xxxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxxx xxxxx je 5 xx/xxxxx nebo 5 μx/xxxxx. X xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx nebo 5 μx/xxxxx xx měla xxx jedna xxxx xxxx xxxxxxxxxx koncentrací xxxxxxxx, xxx xxxxx xxxx x xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky, xxxxx xxxx cytotoxické xxx při xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, by xxxx xxx xxxxxxxx xx xx cytotoxické koncentrace. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx xxx různých xxxxxxxxxxxxxxxx koncentrací xxxxxxxx xxxxx, přičemž při xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx xxxx zkušebními xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Menší xxxxxxxxx xxxx xxxxxx x xxxxxxx, kdy xx vyšetřuje xxxxxx xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Xxxxxxxx koncentrací xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx xxx xxxxxxx xxx xxxxxxxxx xxxxx obsahujících xxxxxxxx xxxxxxxx potenciálně xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Negativní x xxxxxxxxx kontroly

Součástí každého xxxxxxxxx xx měly xxx xxxxxxx specifické xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx s metabolickou xxxxxxxx a xxx xx. Pro xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx každé xxxxxxx.

X xxxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xx xxxx xxx xxxxx (xxxxx) pro pozitivní xxxxxxxx vybrána (xxxxxxx) xx xxxxxxx xxxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx x xxxxxxxxxxxx xxxxxxxx xxxx xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Tato xxxxx xx vhodnou xxxxxxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo podle XXXXXX

XX Xxxxxx Red 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx neměl xxx použit xxxx xxxxxx xxxxxxxxx xxxxxxxxx xxxxx X9. Při xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx xxx xxxxx xxxxx X9 charakterizována xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx xxxxx[x]xxxxx xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx xxx vnější xxxxxxxxxxx xxxxxxxx xxxx xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx sodný

26628–22–8

247–852–1

TA1535 x TA100

2-nitrofluoren

607–57–8

210–138–5

TA98

9-aminoakridin

90–45–9

201–995–6

TA1537, XX97 x XX97x

XXX 191

17070–45–0

241–129–4

TA1537, XX97 x XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX x TA102

1-methyl-3-nitro-1-nitrosoguanidin

70–25–7

200–730–1

WP2, XX2 xxxX x XX2 uvrA (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX x XX2 xxxX (xXX101)

α-[(5-xxxxx-2-xxxxx)xxxxxxxxxx]xxxxx-2-xxxxxxxx (XX2)

3688–53–7

xxxxx xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx kontrolu mohou xxx xxxxxxx xxxx xxxxxx referenční xxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx látek xx xxxxxx chemické xxxxx, xxxx xx x dispozici.

Měly by xxx použity negativní xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx způsobem xxxx exponované xxxxxxx. Xxxxx toho by xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, neexistují-li dosud xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné zhoubné xxxx xxxxxxxxx xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx xxxxxxx (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx xxxxxxxxxx xxxxx x 2,0 xx xxxxxxxx xxxxx. X xxxxxxx zkoušky x xxxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,5 xx metabolické aktivační xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (x rozmezí 5 xx 30 % xxx. v metabolické xxxxxxxxx xxxxx) x xxxxxxx agarem (2,0 xx) x xxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxxxx nebo xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx se xxxxxxxx x přelije xxxx povrch minimálního xxxxx xx misce. Xxxx xxxxxxxx se xxxxx xxxxxx agar xxxxxxxx.

X preinkubační xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx zkoušený xxxxxx před smícháním x xxxxxxx xxxxxx x přelitím přes xxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxxxxx 20 xxxxx nebo xxxx xxxxxxxxxxx s xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x xxxxxxxxx xxxxxx nebo xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx xx smíchá 0,05 xxxx 0,1 xx xxxxxxxx xxxxx xxxx xxxxxxxxxx roztoku, 0,1 xx xxxxxxxx x 0,5 xx xxxxx X9 xxxx xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx xxxxx. Zkumavky xx xxxx xxx během xxxxxxxx provzdušňovány na xxxxxxxx.

X xxxxxxxxxxxx xxxxxx xxxxxxxx xx xxxx xxx xxx xxxxx xxxxxx dávky xxxxxxx 3 misky. Xxxxxxx xxxx xxxxx xx xxxxxxxxxx xx vědeckém xxxxxxxxxx. Xxxxxxxx ztráta xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx zkoušky.

Plynné xxxx xxxxxx xxxxx by xxxx xxx zkoušeny xxxxxxxx xxxxxxxx, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx nádobách (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx misky v xxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Xx xxxxxxxx xxxxxxxxx doby xx xxxxxx xxxxx kolonií xxxxxxxxxx xx misku.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxx xxxxx by xxxx xxx xxxxx kolonií xxxxxxxxxx xxxxxxxxxxx na xxxxx. Xxx xx xxx rovněž xxxxxx xxxxx kolonií xxxxxxxxxx xxx xx xxxxxxx x xxxxxxxxx xxxxxxxxx (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx neexponovaná kontrola), xxx xx miskách x xxxxxxxxx xxxxxxxxx. Xxxxx xx xxxxxxxxxxxx xxxxxxx, xxxxxxx hodnoty xxxxx xxxxxxx xxxxxxxxxx xx misku x xxxxxxxxxx odchylka xx xxxx xxx předloženy xxx zkoušenou látku x xxxxxxxxx x xxxxxxxxx kontrolu (xxxxxxxxxxxxx xxxxxxxx a/nebo xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx jasně pozitivní xxxxxxxx se nepožaduje. Xxxxxxxxxx xxxxxxxx by xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x xxxxxxx experimentálních xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx se xxxxxxxxx xxxxxxxxxxx výsledků xxxxxxxxxx xx xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxxxx. Změna parametrů xxxxxx x cílem xxxxxxxx rozsah xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, které xx xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx xxxxxx xxxx preinkubace x xxxxxxxx xxxxx) x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx existuje několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx revertantů xx misku xxx xxxxxxxxx xxxxxx x xxxxxxx jednoho xxxxx x xxxxxxxxxxxx aktivačním xxxxxxxx xxxx bez xxxx, a xx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx by měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx výsledků zkoušky xxxxx být xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx metody (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

Xxxxxxxx látka, xxxxx výsledky xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx x xxxxx systému xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx výsledky, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxx xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx coli bodové xxxxxx xxxxxxxxxx xxxx xxxx xxxxxxx xxxxxxx xxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxx xx xxxxxxxx zkoušky xxx xxxxxxxxx xxxxx mutagenní.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

- xxxxxxxxxxx a xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, je-li známa.

Kmeny:

- xxxxxxx xxxxx,

- xxxxx xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx kmene.

Zkušební xxxxxxxx:

- xxxxxxxx xxxxxxxx xxxxx xx misku (xx/xxxxx xxxx μx/xxxxx) x xxxxxxxxxxx výběru xxxxx x xxxxx misek xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

- xxx a xxxxxxx metabolického xxxxxxxxxxx xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx miskách,

- střední xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx odchylka,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx hodnotami x xxxxxxxxxxxx odchylkami,

- xxxxxxxxx údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx s xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxx, X. X., McCann, X., Yamasaki X. (1975), Methods xx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 31, 347-364.

2) Maron, D. X., Xxxx, X. X. (1983), Revised Xxxxxxx xxx the Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx., 113, 173-215.

3) Xxxxxxxxx, D., Xxxxxxx, S., Cebula, X., Xxxxx, X., Xxxx, L., Matsushima, X., Melcion, X., Xxxxx, T., Xxxxxx, X., Xxxxxx, E. (1994), Recommendations for xxx Performance xx Xxxxxxxxx Xxxxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 312, 217-233.

4) Kier, X. X., Xxxxxxx X. X., Xxxxxxx, X. X., Xxx Halle, X. X., Brown, X. X., Xxxxxx, X. X., Xxxxxx, X., XxXxxx, X., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, T. X., Xxx V. (1986), Xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Report xx xxx U. S. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, X., Xxxxxx, X., Seino, X. X., Matsushima, X., Xxxxx, M., Xxxxxxxx, X., Xxxxxxxxx, X. (1975), Mutagenicity xx Xxxxxxxxxx Xxx Xxxx xxx xxxxx Derivatives, Xxxxxx Xxxx. 1, 91-96.

6) Matsushima, M., Xxxxxxxx, T., Nagao, X., Yahagi, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Microbial Xxxxx, xx: Xxxxx-xxxx Xxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx X. H., Xxxxxx, X. C., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx York, 273-285.

7) Gatehouse, D. X., Xxxxxxx, I. X., Wilcox, X., Xxxxxxxxx, R. D., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Assays, xx: Xxxxx Xxxxxxxxxxxx Xxxxx: XXXXX Xxxx 1 Xxxxxxx, xx. X. X. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.

8) Aeschacher, H. X., Xxxxxx, U., Xxxxxxx, X. (1987), Xxxxxx Preincubation Mutagenicity Xxxx xxx Foods, X. Xxxx Safety., 8, 167-177.

9) Xxxxx, X. X. X., Xxxxxx, W. X., Xxxxxxx, X. A. (1976), Xxx of x xxxxxxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx levels xx xxxxxxxx, Xxxxxxxxxx Res., 38, 33-42.

10) Xxxxxxx, X. A., Green, X. H. L., Xxxxxxxxx, X., Bridges, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Bacteria, xx: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Elsevier, Xxxxxxxxx-Xxx York-Oxford, 141-161.

11) Xxxxxxxx, X. D., Xxxxxxx, P. X. (1981), Xx Xxxxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx xxx Xxxxxxxxxxx xxxx Xxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Araki, A., Xxxxxxx, T., Kato, X., Matsushima, T. (1994), Xxxxxxxx Method xxx Xxxxxxxxxxxx Xxxxxxx xx Gaseous Xxxxxxxxx xx Xxxxx x Xxx Sampling Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

13) Xxxxxx, M. X., Xxxx, S. X., Xxxxxxxx, X. X., Reipert, X. X., Vaughan, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx and Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Xxxx xx a Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, E., Xxxxxxxx, X. X., Xxxxxxx, X., Lawlor, T., Xxxxxxxxxx, K. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx from xxx Xxxxxxx xx 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Simmon, X., Xxxxxxxx, X., Xxxxxxx, X. X. (1977), Xxxxxxxxx Xxxxxxxx of Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxx Xxxxx, in Xxxxxxxx xx Xxxxxxx Xxxxxxxxxx, X. Xxxxx, X. Bridges, X. Xxxxxx (xxx.) Xxxxxxxx, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. J., Xxxxxxx, X. X., Monteith, X. X., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Technique xx Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxx Xxxxxxx Xxxxxxxxx in xxx Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, T., Xxxxxxxxx, X., Shirai, X., Xxxxxxxx, M., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx the Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Cycasin xxx Synthetic Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx in Xxxxxxxxxx xxxxxxxxxxx, Xxxxxx Xxx., 39, 3780-3782.

18) Xxxxxx, X., Xxxx, X., Ferro-Luzzi, A., Xxxx, X. N. (1980), Xxxxxxxx: X Xxxxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxx xx Xxxxxxxxxx Xxxxx, Xxxx. Xxxx. Acad. Sci. X. S. A, 77, 4961-4965.

19) Xxxxxx, X., Xxxxxx, X., Xxxx, X. X., Xxxxxxxxx, X. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx XX 102 xxxx Xxxxxxxxxxx xxxx WP2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Safe Xxxxxxxxxx for Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Testing, xxx. X. X. xx Xxxxxx xx xx. Xxxxxxxx, Xxxxx Holland, 85-88.

21) Xxxxxx, X. X., Combes, X. X., Xxxxxxx, X. X., Gatehouse, X. X., Gibson, X. X., Xxxxxx, X. X., Wolf, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 in in xxxxx Genotoxicity Assays, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Xxxxxxxxxxxxxxxx, X., Ames, B. X. (1981), Xxxxxxxxxxxxx xx Xxxxxxx Solvents xxxx the Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Res., 88, 343-350.

23) Xxxxxxx, X. D., Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, E. (1987), Xxxxx xxx xxx Xxxxxxxxxx typhimurium/Mammalian Xxxxxxxxx Tests xxx Xxxxxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, X. X. X., Xxxxx, X. X. X., Middleton, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. X. (1989), Xxxxxxxx of Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Part XX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, xx. Xxxxxxxx, X. X., Xxxxxxxxx University Xxxxx, 28-65."


XXXXXXX 4E

"B.17 MUTAGENITA — XXXXXXX XX XXXXXX XXXXXX X XXXXXXX XXXXX IN XXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody XXXX XX 476 — Xxxxxxx xx xxxxxx mutace x xxxxxxx savců xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxx mutace x xxxxxxx xxxxx xx xxxxx xxx xxxxxx xxx detekci xxxxxxxx mutací xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xxxxxx buněčné xxxxx xxxxx xxxxx xxxxxxx X5178X myší, xxxxxxx xxxxx CHO, XXX-XX52 x X79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx TK6 člověka (1). X xxxxxx xxxxxxxxx linií xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace xxxx xxx thymidinkinasu (TK) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (HPRT) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx xx xxxxxx XX, XXXX x XXXX xxxxxxxx xxxxx spektrum xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XXXX xxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx xxxxxx), xxxxx xxxxx xxxxxxxxx x XXXX xxxxxx na X chromozomech (2, 3, 4, 5, 6).

Xx xxxxxxx na xxxxxx mutace x xxxxxxx xxxxx in xxxxx xxx xxxxxx xxxxxxx xxxxxxxxxx linií xxxxx xxxx xxxxxxx xxxxx. Xxxxx xx xxxxxxxx xxxxx xxxxxxxxxx xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.

Zkoušky xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx použití xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx zcela xxxxxxxxx podmínky in xxxx u xxxxx. Xx xxxxx se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x pozitivním výsledkům, xxx neodrážejí xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, xxxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx něž xx xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny savců; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx však xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx na xxxxxxxx třídě x xxxxxxxxx xxxxxx x xxx, xx existují xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x bakteriálních xxxxxxx xxxxxxxxxx (6).

Viz xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Přímá xxxxxx : xxxxxx mutace xxxxxxxxx xxxx xxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxxxxxx aktivity kódovaných xxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx : látky, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx nebo více xxxx xxxx v XXX.

Xxxxxxxx mutageny : xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx nebo více xxxx xxxx x xxxxxxxx XXX.

Xxxx exprese xxxxxxxx : xxxx, xxxxx níž xxxxxx x nově mutovaných xxxxx xxxxxxxxx xxxxxx xxxxxxxx.

Xxxxxxx mutantů : xxxxx xxxxxxxxxxxx mutantních xxxxx xxxxxx xxxxxx xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxx celkový xxxx : xxxxxx xxxxx buněk v xxxx xx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx se xxxx xxxxxx xxxxxx xxxxxxxxx xxxxx x xxxxxxxx a x xxxxxxxxx xxxxxxxx a xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxx xxxx x xxxxxxxx : nárůst xxxxx xxxxx x xxxxxxx exprese vzhledem x negativní kontrole.

Životaschopnost : účinnost xxxxxxxxx xxxxx v xxxxxxxx xxxxxxxx xx misku xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx xx xxxxx xx konci xxxxxx xxxxxxxx; přežití xx xxxxxxx vyjádřeno x xxxxxx x xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx TK+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (TK) jsou xxxxxxxxxxx x cytotoxickým xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx thymidinkinasu jsou xxxxxxx xx XXX, xxx xxxxxxxxx inhibici xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx buněčné xxxxxx. Xxxxxxxx xxxxx xxxx xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Podobně xxx x xxxxx x xxxxxxxxxxxx HPRT nebo XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx látky xx xxxx xxx xxxxxxx xxxxxxx, jestliže xx xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx xxxxxxx xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx selekčnímu xxxxxxx. Mělo xx xxx například xxxxxxxxx xxxxxxxx xxxxxxxxx xx xxxxxxxxxx xxxxxxxx zkoušené xxxxx pro mutantní xxxx xxxxxxxxxx buňky. Xxx zkoušení xxxxxxxxxx xxxxx, xxxxx mají xxxxxxxx strukturu jako xxxxxxxx činidlo, xxxx xxxx xxx xxxxxxxxx xxxxxxxx systému nebo xxxxxxx xxx xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx jednovrstevné xxxxxxx xxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce xxx x xxxxxxxxxxxx xxxxxxxx, xxx bez xx, x subkultivovány xx xxxxxx xxxxxxxxx xxxxxxxxxxxx x za xxxxxx xxxxxxx xxxxxxxx xxxx selekcí mutantů (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx obvykle xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx relativního xxxxxxxxx xxxxx kultur xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx se xxxxxxx x růstovém xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx xxxxxxx lokus x typ xxxxx, xxx nastala xxxxxxxxx xxxxxxxxx fenotypová xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx xxx, xx xx xxxxxx známý počet xxxxx do média xxxxxxxxxxxx selekční činidlo xxx detekci xxxxxxxxxx xxxxx x do xxxxx xxx selekčního xxxxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx vhodné xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Četnost xxxxxxx xx vypočte x počtu xxxxxxxxxx xxxxxxx v xxxxxxxxx xxxxx x xxxxx xxxxxxx x xxxxx xxx xxxxxxxxxx činidla.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro xxxxxxx x xxxx zkoušce xxxx x xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx subklonů xxxxx X5171X, CHO, CHO-AS52, X79 nebo XX6. Xxxx xxxxx v xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x stabilní frekvenci xxxxxxxxxxx mutací. Buňky xx měly být xxxxxxxxxxxx, xxx nejsou xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx kontaminace xx neměly xxx xxxxxxx.

Xxxxxxx xx xxxx xxx xxxxxxxx tak, xxx xxxx xxxxxx xxxxxxxxxx xxxxxxxxx a xxxx. Xxxxx použitých xxxxx, xxxxxx x xxxxxxxxxxx xxxxxxxx látky xx xxx tyto xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, které xxxxxxx xxxxxxxx x xxxxx xxxxx použity v xxxxxx stadiu zkoušky, xx xxx xxx xxxxxxx na xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, xxx xxx použit xxxxx xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx hodnoty xxxxxxxx xxxxxxxxxxx xxxxxx. Xx xxxx xxxxxxxxxx, xxx xxxx použito xxxxxxx 106 xxxxx. Xxxx xx xxx x dispozici xxxxxxxxxx xxxxxxxxx údaje o xxxxxxxx buněčném xxxxxxx, xxx byla doložena xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx a vlhkost). Xxxxx xx měla xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx x xxxx xxxxx xxxxxxxxx xxx zkoušce. Je xxxxxxx důležité, xxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxx xxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxx buněk během xxxxxx xxxxxxx x xxxxxxxxx jak mutovaných, xxx xxxxxxxxxxxx xxxxx xxxxxx xxxxxxx.

1.4.1.3 Příprava xxxxxx

Xxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxx, xxxxxxxx xx kultivačního média x inkubovány xxx 37 °C. Před xxxxxxxx v této xxxxxxx xxxx být xxxxxxxx xxxxxxxxx z xxxxxxx již xxxxxxxx xxxxxxxx buňky.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx něho. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je xxxxxxxxxx dotovaná xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, jako xx Xxxxxxx 1254 (15, 16, 17 a 18), nebo xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (19, 20).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxxx x xxxx metabolického xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx může xxx xxxxxx xxxxxx xxxx než xxxxx xxxxxxxxxxx postmitochondriální frakce.

Řada xxxxxxxx xxxxxx, včetně xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx možnosti xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx isoenzymu cytochromu X450 pro xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx měly xxx xxxx xxxxxxxx xx buňky xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a popřípadě xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx přímo x xxxxxxxxxx xxxxxxxx a/nebo xxxxx xxx xxxx xxxxxxxx xxxxxxx. Měly xx xxx použity xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx být xxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x mělo xx xxx xxxxxxxxxx x přežitím xxxxx x x aktivitou X9. Jsou-li xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx při xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx stanovena x xxxxxxxxxxxx xxxxxxxx x bez ní x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x růstu, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx celkový xxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx dané xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, což xxxx xxxxxxx xxxxxxxx, xx xx xx xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. Xx-xx maximální xxxxxxxxxxx xxxxxxxx xx cytotoxicity, xxxx by xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) přežití (xxxxxxxxx xxxxxxxx klonování) xxxx xxxxxxxxx xxxxxxx xxxx. X případě xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx xxxx, která x xxxx je xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx měly být xxxxxxxx xx k xxxx xxxxxxxxxxxx za xxxxxxxxxxxx podmínek, xxxx xx xx xxxx xxx. Měla by xxx stanovena xxxxxxxx xxxxxxxxxxxxx v konečném xxxxx, xx kterému xxxx xxxxx xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx aplikace, xxxxx xxxxxxxxxxx xx xxxx x xxxxxxx xxxxxxxx x testovacím xxxxxxx xxxxx v důsledku xxxxxxxxxxx buněk, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx zjistit xxxxxxxx. Xxxxxxxxx by neměla xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, tak xxx xx. Xxx xxxxxxx xxxxxxxxxxx aktivace xx xxxx xxx xxxxxxxxx kontrolou xxxxxxxx xxxxx, xxxxx x xxxxxxxxx odpovědi xxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx být tyto xxxxx:

Xxxx metabolické aktivace

Lokus

Látka

Číslo XXX

Xxxxx podle Xxxxxx

Xxx xxxxxx xxxxxxxxxxx aktivace

HPRT

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

TK (xxxx x xxxxx xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X vnější xxxxxxxxxxxx xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (xxxx x xxxxx kolonie)

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid monohydrát

6055–19–2

benzo[a]pyren

50–32–8

200–028–5

3-methylcholanthren

56–49–5

200–276–5

XPRT

N-nitrosodimethylamin (xxx vysoké xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx být xxxxxxx xxxx xxxx referenční xxxxx xxx xxxxxxxxx xxxxxxxx, xxxx. xx-xx xxxxxxxxx xxxxxxxx dosavadních xxxxx x 5-brom-2′-deoxyuridinu (XXX 59–14–3, EINECS 200–415–9), může xxx xxxx xxxxxxxxxx xxxxx xxxxxx xxxxxxx. Xxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxx x úvahu xxxxxxx xxxxxxxxxx xxxxx pokud xxxxx ze xxxxxx xxxxxxxx xxxxx.

Xxxx by xxx použity xxxxxxxxx xxxxxxxx xxxxxxx médiem xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx vehikulum x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Xxxxx toho xx xxxx být xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, neexistují-li xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx látce

Proliferující buňky xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx něho. Xxxxxxxx xx xxxx xxxxx vhodnou xxxx (xxxxxxx je xxxxxx xxxx 3 xx 6 hodin). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx na jeden xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx jedna xxxxxxxxxx xxxxxxx. Xx-xx použita xxxxx xxxxxxx, xxx xx xxx xxxxx xxxxxxxxxxx xxxxxx tak, xxx xxx zajištěn xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (např. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx xxxxxxx duplicitní xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx xxxx xxxxxx látky xx xxxx být zkoušeny xxxxxxxx xxxxxxxx, např. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx xxxxx xxxxxxxxx xxxx se buňky xxxxxxx x kultivují xx účelem stanovení xxxxxxx x za xxxxxx xxxxxxxx exprese xxxxxxxx xxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxxx xxxxxxxxx růstu xxxxxx xx započne xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx xxxxx má xxxxxxxxxx minimální xxxxxx xxxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx nově indukovaných xxxxxxx (HPRT x XXXX vyžadují alespoň 6 až 8 xxx, XX xxxxxxx xxx dny). Buňky xxxx xxxxxxxxxxx x xxxxx xx selekčním xxxxxxxx (selekčními xxxxxxx) x xxx xxxx (xxx xxxx) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx x klonovací xxxxxxxxx. Xx stanovením xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx četnosti xxxxxxx) xx započne xx xxxxx xxxx xxxxxxx xxxxxxxxx xx xxxxx xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx xxxxx xxxxxxxxx xx zkoušce X5178X XX+/-, xxxx by xxx xxxxxxxxx xxxxxxx xx jedné ze xxxxxxxxxx xxxxxx (s xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x na negativních x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxx xx xxxxxxx L5178Y XX+/- xxxxxxxxx, mělo xx xxx rozdělení xxxxxxx xxxxx xxxxxxxxx kolonií xxxxxxxxx xx negativních x xxxxxxxxxxx kontrolách. Xxx studiích xx xxxxxxx TK6 XX+/- xxxx xxx také xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx velikosti kolonií.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xx měly zahrnovat xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x četnosti xxxxxxx xxx xxxxxxxxxx x xxxxxxxxx kultury. V xxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxx X5178X XX+/- se xxxxxxx xxxxxxxxx alespoň x xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (xxxxxxxx pozitivní xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx za xxxxxxx xxxxxxxx malá xxxxxxx — xxxxx kolonie. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx mutantů xxxxxxxxx xxxxx kolonie, xxx mutantů tvořících xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx xxxxxxx XX+/- xxxx kolonie xxxxxxxxxxx za použití xxxxxxxx xxxxxxx x xxxxxxxxx růstem (velká) x kolonie s xxxxxxx xxxxxx (xxxx) (25). U xxxxxxxxxx xxxxx, které xxxxxxx xxxxxxxxxxxxxx genetické poškození, xx prodloužily xxxx xxxxxxxx, x xxxxx xxxx malé xxxxxxx. Xxxxxxxxx má xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx až xx karyotypické xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx tvořících malé xxxxxxx xx spojuje x xxxxxxxxxx látkami, xxxxx indukují silné xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx rostou xxxxxxxx xxxxxx xxxx xxxxxxxx xxxxx x xxxxx velké kolonie.

Mělo xx xxx udáno xxxxxxx (xxxxxxxxx účinnost xxxxxxxxx) nebo xxxxxxxxx xxxxxxx růst. Xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxx jako xxxxx mutantů x xxxxx xxxxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxx. Dále xx xxxx xxx xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx měly být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx musí xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxx, kde xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxx, xx xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx rozsah xxxxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, tak xxx xxxxxxxxx výsledky. K xxxxxxxxxx xxxxxx, xxxxx xx mohly xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxx xxxxxxx x závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Nejdříve xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx hodnocení výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost by xxxxxx xxx xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx odpověď.

Zkoušená xxxxx, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx kritéria, xx v xxxxx xxxxxxx xxxxxxxx za xxxxxxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Výsledky mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx. Reprodukovatelná xxxxxxxxx xxxxxxxxx odpovědi xx xxxxxxxxxxx je xxxxx xxxxxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxxxxxx/xxxxxxxx,

- xxxxxxxxxxx x xxxxxxx xxxxxxxx látky v xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.

Xxxxx:

- xxx a xxxxx xxxxx,

- počet buněčných xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxxx výběru xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx xxxx. xxxxx x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, jsou-li x xxxxxxxxx,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- koncentrace zkoušené xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxxxx xxxxxxxx,

- xxx x xxxxxxx xxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- xxxxxxxxx x xxxxxxxxx kontroly,

- xxxxx xxxx xxxxxxx (případně xxxxxx počtu xxxxxxxxxx xxxxx, subkultur x xxxxxx média),

- selekční xxxxxxx,

- kritéria xxxxxxxxxxx xxxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx k xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx buněk,

- xxxxxxxx xxxxxxx xxxxx velikosti x xxxx (xxxxxxxx xxxxxx xxxxxxxx xxx "xxxx" x "xxxxx" xxxxxxx).

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx x xX x xxxxxxxxxx xxxxx expozice xxxxxxxx látce, xxxxx xxxx stanoveny,

- velikost xxxxxxx, byla-li vyšetřována, xxxxxxx xxx negativní x xxxxxxxxx xxxxxxxx,

- xxxxxxxxx předpoklady xxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxxxxxx xxxxxxxx X5178X TK+/-,

- podle xxxxxxxx závislost odpovědi xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

- údaje x souběžné negativní (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní xxxxxxxx,

- xxxxxxxxx údaje x xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx xxxxxxxx x rozmezími, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. M., XxXxxxxx, X. X., XxXxxxxx, X. X., Xxxxxx, X. X. (xxx.) (1987), Banbury Xxxxxx 28; Mammalian Xxxx Xxxxxxxxxxx, Xxxx Spring Xxxxxx Laboratory, Xxx Xxxx.

2) Xxx, X. X. X., Malling X. X. (1968), Xxxxxxxxx Xxxx Genetics. XX. Chemical Xxxxxxxxx xx Xxxxxxxx Locus Xxxxxxxxx in Chinese Xxxxxxx Xxxxx Xx xxxxx, Xxxx. Natl. Xxxx. Xxx. X. X. A, 61, 1306-1312.

3) Liber, X. X., Thilly, X. X. (1982), Xxxxxxxx Xxxxx at xxx Xxxxxxxxx Xxxxxx Locus xx Xxxxxxx Xxxxx Xxxxxxxxxxxx, Mutation Res. 94, 467-485.

4) Xxxxx, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, C. X., Xxxxxxxxx, K. X. (1989), Xxxxxxxxxxxx Xxxxxx Quantitation xx xxx Xxxxx Xxxxxxxx XX xxx CHO XXXXX Loci, Xxxxxxxxxxx, 4, 394-403.

5) Xxxxx, X. X., Xxxxxxxxxx, Xx. X. F., (1989), Xxxxxxxxxx xx xxx XX52/XXXX xxx xxx XXX/XXXX Assays: Xxxxxxxxxx xx Xxx Xxxx Candidates, Mutatation Xxx. 223, 121-128.

6) Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X. X., Moore, X., Nishi, Y., Xxxxxxxxxx, Xx. X. X., Theiss, X., Xxxxxxxx, E. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Working Xxxxx Xxxxxx. Xxxxxx xx the Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Res. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, R. X., Xxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxx, B. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Culture Xxxxxxxxxx. A xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, X., XxXxxx, X., Xxxxxxx, X. X. S., Xxxxx, X., Xxxxxxxxx, X. X. (1983), Xxxxxxxx Xxxx Xxxxxxxxx xx X5178X Xxxxx xx Xxxxxxx. A Report xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Res., 115, 225-251.

9) Li, X. X., Gupta, X. X., Heflich, R. X., Xxxxxx, J. X. (1988), X Xxxxxx and Xxxxxxxx xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Transferase System xx Xxxxxxxxx the Xxxxxxxxxxxx xx Chemical Xxxxxx: X Xxxxxx xx Xxxxx XXX xx the U. X. Xxxxxxxxxxxxx Protections Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Res., 196, 17-36.

10) Xx, X. X., Carver, X. X., Xxxx, X. X., Hsie, A. X., Xxxxx, X. X., Loveday, K. X., X'Νxxxx, X. X., Xxxxxx, X. X., Xxxxxxxxxx, L. X. Xx., Xxxx, X. L. (1987), X Guide xxx xxx Xxxxxxxxxxx xx xxx Xxxxxxx Xxxxxxx Xxxxx Cell/Hypoxanthine-Guanine Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Xxxxxxxx Xxxxx, Xxxxxxxxxx Res., 189, 135-141.

11) Xxxxx, X. X., Yandell, X. W., Xxxxxx, X. B. (1989), X Comparison xx Xxxxxxxx Xxxxxxxxx xx xxx TK and XXXX Xxxx in Xxxxx Lymphoblastoid Cells: Xxxxxxxxxxxx Xxxxxxxxxxx are Xxx xx xx Xxxxxxxxxx Class of Xxxxxxxxx xx the Xxxxxxxxx TK Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

12) Xxxxxxxxxx, X. X. Xx., Xxxxxx, X. R., Xxxx, X. W. (1986), Xxxxxxxxxxxx xxx Xxxxxxxxx Xxxxxxxx xx Xxxxx Xxxxxxxxxxxxxxxxx xxx XXX 191-Xxxxxxx Molecular Analyses xx Xxxxx Xxxxxxxxxxxxxxxxx xxx ICR 191 Xxxxxxx Xxxxxxxx xx XX52 Xxxxx, Mutatation Xxx., 160, 133-147.

13) Xxxxxx, N. X., Xxxxxx, X. G., Xxxxx, X. (1984), Xxxxxxxxx xxx xxx X5178X/XX+/--XX+/- Xxxxx Lymphoma Xxxx Mutagenicity Xxxxx, xx: Kilbey, B. X. et xx (xxx.) Xxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxx Xxxx, 239-268.

14) Xxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxx, M. X. X., Cole, J., XxXxxxxx, X. B., Xxxxxxx S. X. (1989), Xxxxxxxxx Xxxx Xxxx Mutation Assays Xxxxx xxxx Xxxxxx Xxxxxxxxx, xx: Statistical Xxxxxxxxxx of Mutagenicity Xxxx Data, Kirkland, X. J., xx., Xxxxxxxxx University Xxxxx, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, S., Xxxxx, X., Xxxxxx, X., Xxxxxxxx, N., Xxxxxxxxxx, X. (1977), Xxxxxxxxx xx 6-Xxxxxxxxxxx-Xxxxxxxxx Xxxxxxx xx V79 Xxxxxxx Xxxxxxx Cells xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Xxx. 46, 365-373.

16) Xxxx, B. X., McCann, X., Xxxxxxxx, E. (1975), Xxxxxxx xxx Detecting Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Mutatation Xxx. 31, 347-364.

17) Xxxxx, D., Xxxxxxx, X. O., Xxxxxxx, X. X. S., Xxxxxx X. X., Xxxxx M. X. X. (1979), Validation xxx Xxxxxxxxxxxxxxxx xx xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Xxxxx Xxxxxx, Xxxxx. Xxx. 59, 61-108.

18) Xxxxx, D. X., Xxxx, B. X. (1983), Xxxxxxx Xxxxxxx xxx the Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res. 113, 173-215.

19) Xxxxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, C. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Alternatives xx Aroclor 1254-Induced X9 in: Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, K., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Polycholrinated Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, V: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx in Mutagenesis Xxxxxxx, de Xxxxxx, X. J., Fouts, X. X., Xxxx, X. R., Xxxxxxx, X. X. (xxx), Xxxxxxxx, North-Holland, 85-88.

21) Xxxxx, D. X., Xxxxxx, F. X., XxXxxxx, X. T. (1982), CHO/HGPRT Mutation Xxxxx: Xxxxxxxxxx of Xxxxx and Xxxxxxxx Xxxxxxx, in: Ticc, X. X., Xxxxx, X. X., Schaich, X. M. (eds), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, X. X., Xxxxxx, X. M., Xx, X. P., Xxxxxx, X. L. (1983), Xxxxxxxxxx of xx Exposure Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxx. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxx, J. X. (1990), Xxxxxxxxx Xxxxxxxxxx of Xxxxxxxxx xx xxx Heterozygous Xxxxxxxxx Xxxxxx Xxxxx xx Mouse Lymphoma Xxxxx, Xxxx. Xxxx. Xxxx. Xxx. X. X. X, 87, 51-55.

24) Moore, M. X., Clive, X., Xxxxxx, J. X., Xxxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxxxxx, J. (1985), Xxxxxxxx xx Trifluorothymidine, Xxxxxxxxx (TFT+) Xxxxxxx xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Mutatation Xxx. 151, 161-174.

25) Xxxxxxx, X. W., Xxxxx, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Recessive Xxxxxxxxx xx x Xxxxxxxxxxxx Xxxxxxxxx Locus xx Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

26) Xxxxx, X. X., Xxxxx, X. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxx Xxxxxxxxx xxx Small Xxxxxx XX-Xxxxxxxxx Xxxxxx Xxxxxxxxx xx L5178Y/TK+/- 3.7.2X Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxxx, 5, 609-614."


PŘÍLOHA 4X

"X.23 XXXXXXX XX XXXXXXXXXXXX ABERACE XX SPERMATOGONIÍCH XXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody XXXX XX 483 — Xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx xxxxx xx vivo xx identifikovat xxxxxx xxxxx, xxxxx způsobují xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Rozlišují xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx vyskytují. Xxxx xxxxxx xxxx xxxxxx xx xxxxxxxxx numerických xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x podobné xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx xx stanovují xxxxxxxxxxxx xxxxx xx xxxxxxxxxxxxxxx x předpokládá xx xxxx, xx xxxx xxxxxxx poskytne xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Touto cytogenetickou xxxxxxxx xx xxxx xx detekují xxxxxxxxxxxx xxxxxxx při xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx nejsou xxxxxxxxx xxxx zkoušky.

Pro xxxxxxx xxxxxxx chromatidového typu xx spermatogoniích xx xxxx být — xxxxx xxx xxxxx xx xxxxxx xxxx — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Další xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx chromozomovou xxxxxxxx aberací chromozomového xxxx v xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx stávají xxxxxxxxxxxx.

Xxxx xxxxxxx in xxxx je xxxxxxxx xxx xxxxxxxxx, zda xxxx xxxxxxxx somatických xxxxx xxxxxxx xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx xx xxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx mutagenese, neboť xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx řada xxxxxxxx spermatogonií x xxxxxx citlivostí na xxxxxxxx chemické látce. Xxxxxxxxxx xxxxxxx tedy xxxxxxxxxxx souhrnnou odpověď xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxxxxxxx diferencovanými xxxxxxxxxxxxxxx. V xxxxxxxxxx xx xxx poloze xx xxxxxxxxx, xxxxx xxxx xxxxxx být xxxxx generace spermatogonií xxxxxxxxxx xxxxxxxxx krevnímu xxxxx x důsledku xxxxxxxxx a xxxxxxxxxxxx xxxxxxx Xxxxxxxxx buněk x xxxxxxx xxxx xxxxxxx xxxxxx x xxxxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, není xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu v xxxxxx zlomu xxxxxxxxxxxx xxxxxxxxx xxxx zlomu x xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx chromatid x tomtéž místě.

Gap : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx a x minimální xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxxxx : xxxxxxxx počtu chromozomů xx normální xxxxxxx x použitých xxxxx.

Xxxxxxxxxxx : násobek haploidního xxxxx xxxxxxxxxxxxxx xxx (x), xxxx xxx xxxxxxxxx (tj. 3 x, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů při xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx a xxxxxxxxx, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX XXXXXXXX METODY

Zvířata xxxx xxxxxxx způsobem exponována xxxxxxxx xxxxx a xx xxxxxx xxxx xx expozici xxxxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Colcemid®). X xxxxxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx xx chromozomové aberace xxxxxxxxxxxxxx xxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx x xxxx; xxx však xxxxxx samce xxxxxxxxxx xxxxxx vhodného xxxxx xxxxx. Xxxx xx xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx zdravých pohlavně xxxxxxxxx xxxxxx. V xxxxxxxx zahájení xxxxxx xx xxxx být xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx úvodu x xxxxx B, xxxxxxx by mělo xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx se xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx exponuje. Klece xx xxxx xxx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx xxxxxx minimalizován. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx studie xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx před aplikací xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo vehikulech x popřípadě xxxxxxx. Xxxxxxx zkoušené látky xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx před podáním xxxxxxx. Měly xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx by xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx použita xxxx než známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx spermatogoniích xx xxxx xxx xxxxxxxxxxx xxxxxxxx, u nichž xx xxxxxxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx nevyšla xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx kontrola podávána xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx byl xxxxx x jejím xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxx být xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx látek xxx pozitivní kontrolu:

Látka

Číslo XXX

Xxxxx xxxxx Einecs

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx C

50–07–7

200–008–6

akrylamid (monomer)

79–06–1

201–173–7

2,4,6-tris(aziridin-1-yl)-1,3,5-triazin

51–18–3

200–083–5

V xxxxxxxx xxxxxxx odběru xx měl xxx xxxxxxxx xxxxx u xxxxxxx negativní xxxxxxxx, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x která xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx k dispozici xxxxxxxxxx údaje x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx by xxxx xxx neexponované kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx zvířat

Každá exponovaná x xxxxxxxxx xxxxxxx xxxx zahrnovat xxxxxxx xxx analyzovatelných xxxxx.

1.5.2 Xxxx expozice

Zkoušené xxxxx xx xxxx být xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxx (xx. xxx xxxxx xxxxxxxx nebo xxxx xxxxxxxxxx). Zkoušené xxxxx xxxxx xxx xxxxxxxx xxxx ve xxxx xxxxxxx, tzn. xxx xxxxx x xxx xxx x rozmezí xx xxxx xxx xxxxxxxx xxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx zdůvodněny.

Ve xxxxxxx x xxxxxxxx dávkou xx xxxx xxx xx xxxxxxxx provedeny xxx odběry. Xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx xxxxx xxxxx xxxxx x xxxxx xxxxxxxx odběr xxxxxxxxx 24 x 48 xxxxx po xxxxxxxx. X xxxxxxx jiné xxx xxxxxxxx xxxxx xx xxx xxx xxxxx xxxxxxxx po 24 hodin xxxx xx takové době xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx délky buněčného xxxxx, xxxxx xxxx xxxxx jiná xxxxxxxxx xxxx pro xxxxxxx xxxxxx (6).

Xxxxx xxxxx xxx odběry provedeny xxxx x jiné xxxx. Například v xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx indukovat xxxxxxxx replikace (xxxxxxx) xxxxxxxxxx xxxx mohou xxxxxxxxxx S-nezávislé účinky, xxxx xxx xxxxxxxxx xxxxxxxx odběr (1).

Xxxxxxxx xxxxx opakované xxxxxxxx xxxx být xxxxxx xxxxxx xx xxxxxxx. X případě plánu x opakovanou xxxxxxxx xx měla xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) xx xxxxxxxx xxxxxxxx. Xxxxx potřeby xxxxx xxx prováděny xxxxx odběry x xxxx xxxx.

Xxxx xxxxxxxxx xx xxxxxxxx intraperitoneálně xxxx vhodná xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 hodin; x xxxxxx čínského xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li se xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, xxxx by být xxxxxxxxx ve xxxxxx xxxxxxxxxx, se stejným xxxxxx a kmenem x xx xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx použije x xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx pro xxxxx xxxxx xxxxxxx xxx xxxxxx dávky. Tyto xxxxxx dávky xx xxxx xxxxxxxx xxxxxxx xxxx maximální a xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx nejvyšší dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx xx xxxxx dávky vedly xxx stejném xxxxxx xxxxxxxxx podle očekávání x letalitě.

Látky xx xxxxxxxxxxx biologickou xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. hormony x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx toxicity (xxxx. xxxxxxx xxxxx spermatogonií x xxxxxx xxxxxxxx x první x xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx by xxxxxx překročit 50 %).

1.5.4 Limitní zkouška

Jestliže xxxxxxx x jednou xxxxxx alespoň 2000 xx/xx tělesné xxxxxxxxx xxxxxxx jednorázově xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx o xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx se třemi xxxxxxxx xxxxx xx xxxxxxxxx. Očekávaná xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx použít x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání xxxx přijatelné, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx podán xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx je uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx a xxxxxx xxxxx, xxxxx obvykle xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx analýzu chromozomů

Ihned xx xxxxxxxx xx x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx suspenze, xxxxxxxxxxxx xx x xxxxxx. Xxxx se nanese xx xxxxxxxx xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

X každého xxxxxxx xx xxxx být xxxxxxxxxxx alespoň 100 xxxxx v dobře xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 xxxxxxxx xx skupinu). Tento xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx xxxxxxx. Všechny xxxxxxxxx včetně xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx měly xxx xxxx mikroskopickou xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx při xxxxxx xxxxx xxxxxxx ke xxxxxxxxxxxxxx zlomům xxxx xxxxxx xxxxxxxxxx u xxxxx xxxxxxxx, xxxx xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx číslu 2 x ± 2.

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx by xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx každé zvíře xx xxx xxx xxxxxxxxxx počet xxxxx xx xxxxxxxxxxxx chromozomovými xxxxxxxxx x počet xxxxxxxxxxxxxx aberací na xxxxx. Xxx exponované x kontrolní xxxxxxx xx měly xxx xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových aberací x xxxxxx xxxxxx x četností. Gapy xx zaznamenávají odděleně x uvádějí xx, xxx obecně xx xxxxxxxxxx do xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, měl by xxx xxx stanovení xxxxxxx cytotoxických xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx x všech xxxxxxxxxxxx xxxxxx a xxxxxx sloužících jako xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx v mitose xxxxxxxx k xxxxx x xxxxx xxxxxxxxx xxxxxxxx, x to x xxxxxxxx vzorku 100 xxxxxxxx xx xxxxx xx jedno xxxxx. Xxxxx xx xxxxxxxxx xxxxx xxxxxx, xxxxxxx v 1000 xxxxxxx na zvíře xx xxx xxx xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek statistické xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx to, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx in xxxx znamenají, že xxxxxxxx xxxxx xxxxxxxx x germinálních buňkách xxxxxxxxxxx druhu xxxxxxxxxx xxxxxxxxxxxx aberace. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx látka za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxx buňkách xxxxxxxxxxx druhu chromozomové xxxxxxx.

Xxxx xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx nebo xxxx xxxxxxxxxx dostanou xx xxxxxx tkáně.

3. ZPRÁVY

PROTOKOL X ZKOUŠCE

Protokol x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

- xxxxxxxxxxx x xxxxxxx xxxxxxxx xxxxx v rozpouštědle/vehikulu, xx-xx xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx x xxxxx zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, včetně xxxxxxx xxxxxxx hmotnosti, xxxxxxx hodnoty x xxxxxxxxxx odchylky pro xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxx ze xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx xxxx provedena,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx mezi koncentrací xxxxxxxx látky x xxxxxx xxxx xxxx (xxx) na odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- podrobné údaje x kvalitě krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- metody xxxxxxxxx toxicity,

- identifikace xxxxx zastavující xxxxxxxx, xxxx koncentrace a xxxxx aplikace,

- xxxxxx xxxxxxxx preparátů,

- kritéria xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- kritéria xxxxxxxxxxx studie xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

- poměr xxxxxxxxxxxxx v mitose xxxxxxxx k xxxxx x druhé xxxxxxxx xxxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- xxxxxxx počet xxxxxxx ve skupině,

- xxxxx xxxxx s xxxxxxxxx xx skupině,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx o souběžné xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx o xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- údaje x souběžné pozitivní xxxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx in Xxxxx Xxxxxxxxxxxxx xx Xxxxxxxx Xxxxxxxx Related xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Genetic Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Part X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, B., Xxxxxxxxx, J. (xxx) Xxxx, New York, 477-484.

2) Xxxxx, I. X., (1984), Xxxxxxxxxxx xxxxx xx Mammals, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Approach, (xx.) X. Xxxxxx, X. X. Parry, XXX Xxxxx, Oxford, Xxxxxxxxxx DC, 275-306.

3) Xxxxx, X. X., Xxxxxxx, G., Ford, X. X. (1964), Xx Xxx-xxxxxx Method xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Xxxxxx, Xxxxxxxxxxxx Cell Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, X. (1990), In xxxx Cytogenetic Assays, xx: D. X. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Cambridge University Xxxxx, Cambridge, New Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 115-141.

5) Xxxxxxxx, X., Xxxxxxx, X. (1978), A Xxx Xxxxxx xxx Xxxxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 52, 207-209.

6) Xxxxx, I. X., Xxxxxx M. X., Xxxxxxx, J., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Tanaka N. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Report xx xxx Xxxxxxx Group xx Xxxxxxxxx Germ Xxxx Xxxxx, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, R. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxx, J., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Hodson-Walker, X., Xxxxxx, X. X., Xxxxxxxx, D. X., Richold, X. (1992), Xxxxxx of Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. P., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Part XXX. Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4G

"B.39 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XXX (XXX) X XXXXXXXXX XXXXXXX SAVCŮ XX XXXX

1. METODA

Tato xxxxxx je xxxxxxxx xxxxxx OECD XX 486 — Zkouška xx neplánovanou xxxxxxx XXX (UDS) v xxxxxxxxx buňkách xxxxx xx xxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx na xxxxxxxxxxxx syntézu XXX (XXX) x xxxxxxxxx xxxxxxx savců xx xxxx je identifikovat xxxxxxxx látky, xxxxx xxxxxxxx xxxxxxxx XXX x xxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

Xxxx xxxxxxx xx xxxx xxxxxxxxx metodu xxxxxxxxx xxxxxxxxxxxxx účinků chemických xxxxx v játrech. Xxxxxxxxxxx jev xx xxxxxxxxxx poškození XXX x xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxx jsou xxxxxxx xxxxxxx xxxxxx, kde xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx xxxxxx xxx xxxxxxxxx xxxx poškození XXX in xxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxxxxx neplánované xxxxxxx XXX (UDS) xx zhodnotí xxxxxxxxxx xxxxxxxxxxx značených xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (S-fází). Xxxxxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx tritiem (3X-XxX). Xxx xxxxxxx na XXX in xxxx xx přednostně používají xxxxx potkana. Jiné xxxxx než játra xxxxx xxx xxxxxx xxxxxxx, xxxxxx xxxx xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx UDS závisí xx xxxxx xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx x xxxxx xxxxxxxxx. Zkouška xx XXX xx xxxx xxxxxx zvláště xxx xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx repair") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Krátké xxxxxx ("xxxxx-xxxxx repair") (xxxxx xx xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx reparace, chybné xxxxxxxx nebo chybné xxxxxxxxx xxxx XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx xxxxxxxx XXX neposkytuje xxxxxx xxxxxxxxx x věrnosti xxxxxxxxxxx xxxxxxx. Xxxxx xx možné, xx xxxxxxx xxxxxxx x XXX, ale xxxxxxxxx XXX není xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx xxxxxxx xxxxxxxxx x xxxxxxxxx aktivitě, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx xx xxxxxxxxxx x xxxxx xxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX), xxxxx než xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (NNG) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx zkoušce xx XXX, vypočtená odečtením xxxxxxxxxx počtu zrn x cytoplasmatických oblastech (XX) xxxxxxxxxxxxxx jádrům xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): NNG = XX — XX. Xxxxxxx XXX xx xxxxxxx xxx jednotlivé xxxxx, xxxx společně xxx xxxxx x xxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx syntéza XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx úseku DNA xxxxxxxxxxxx region x xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx UDS x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx reparací XXX xx xxxxxxxxx x odstranění xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx látkami xxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx inkorporaci 3H-TdR xx XXX xxxxxxxxx xxxxx, xxx xx xxxx četnost xxxxx x X-xxxx xxxxxxxxx xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx stanoveno xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx xxx xxxxxxx xx xxxx X-xxxx xxxxx xxxx xxxx. kapalná scintilační xxxxxxxxxxxxx.

1.4 POPIS XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, ačkoli xxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Měly xx být xxxxxxx xxxxx používané laboratorní xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx zahájení xxxxxx xx xxxx xxx odchylka x xxxxxxxxx xxxxxx xxxxxxxxx x neměla xx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx xxx obě xxxxxxx.

1.4.1.2 Podmínky xxxxx x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx X, xxxxxxx by xxxx být xxxxxxxx xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx xxxxxxxx. Klece xx xxxx xxx xxxxxxxxxx tak, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx jednoznačně xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx látky xx xxxx být xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx mohou xxx podávány xxxxx xxxx xxxxx být xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx toxické xxxxxx x xxxx xx být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou látkou. Xxxx-xx xxxxxxx xxxx xxx známá rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx podloženo xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx podstoupit xxxxxx xxxxxx jako xxxxxxx ve skupinách, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx měly být xxxxx, o xxxxx xx známo, xx xxxxxx podávání v xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x xxxxxxx XXX detekovatelnému xxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx metabolickou aktivaci xx měly být xxxxxxx x dávkách xxxxxxxxxxxx mírnou xxxxxxx (4). Xxxxx xxxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx nevyšla xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Příklady xxxxx xxx pozitivní xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx CAS

Číslo xxxxx Xxxxxx

Xxxxx doby xxxxxx (2 až 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx doby xxxxxx (12 xx 16 x)

X-(xxxxxxx-2-xx)xxxxxxxx (2-XXX)

53–96–3

200–188–6

Xxxxx xxx použity xxxx xxxx látky xxx xxxxxxxxx xxxxxxxx. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx látka xxxxxxxx jiným způsobem, xxx zkoušená látka.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxx xx xxx xxxxxx dostatečný xxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxx odpovědi xx xxxxxxx. Xxxxx xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx tří xxxxxxxxxxxxxxxx xxxxxx. Jestliže xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx xxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx skupiny xxxxxxxx xxxxx xxxxx až xxx zvířata.

Jestliže xxxx x době xxxxxx x xxxxxxxxx xxxxx xx xxxxxx se xxxxxxx xxxxxx a xx použití xxxxxxxx xxxxxxx expozice, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx rozdíl x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx, xxxxxxx samců. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako je xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by být xxxxxxx provedena xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx zpravidla podávány xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx xxx úrovně xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx toxicity, xx xxxxx xxxxx xx xxxxx xxxxx xxxxxxxxx xxx stejném xxxxxx xxxxxxxxx k letalitě. Xxxxx dávka xx xxxx xxx zpravidla 50 % xx 25 % xxxxx xxxxx.

Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx dávkách (xxxx. xxxxxxx x xxxxxxxx) nemusí kritériím xxxxxxxxx xxxxx xxxxxxxxx x měly xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Provádí-li xx kvůli neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx zjištění xxxxxxx, měla by xxx provedena ve xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx se xxxxxxx x hlavní studii.

Nejvyšší xxxxx může xxx xxxxxxxxxx také xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxxxx v játrech (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx dávkou x xxxxxxx 2000 xx/xx tělesné hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x jednom xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx být xxxxx xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená látka xx obvykle podává xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxx, xxx-xx xx zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx se xxxx xxxxxxxxxxxx, xxxxx xx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxx a xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx měla xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx buňky xx xxxxxxxxxx x xxxxxxxxxxxx xxxxxx zpravidla 12 xx 16 hodin xx xxxxxx dávky. Xxxxxxxxxx xxxxxxxx odebrání xxxxxx (xxxxxx dvě xx xxxxx xxxxxx xx expozici) xx xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Xxxxx však xxx xxxxxxx jiné xxxx odběru, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx údajů.

Krátkodobé xxxxxxx xxxxxxxxx xxxxx savců xx xxxxxxxxx zakládají xxxxxxx xxxxx kolagenasou xx situ x xxxxxx xx, xxx xx čerstvě xxxxxxxxxxx xxxxxxx xxxxx zachytily xx xxxxxxx povrchu. Xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx by xxxx vykazovat xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx UDS

Čerstvě xxxxxxxxx xxxxxxx xxxxx xxxxx xx obvykle xxxxxxx xxxx, např. xxx xx osm xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx inkubační xxxx by mělo xxx médium z xxxxx xxxxxxxxxx x xxxxx poté mohou xxx inkubovány x xxxxxx obsahujícím přebytek xxxxxxxxxxx thymidinu, xxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx chase"). Xxxxx xx poté xxxxxxx, xxxxxx a xxxxxx. Xxx delší xxxxxxxxx xxxx xxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx do autoradiografické xxxxxx, xxxxxxxx se x xxxxx (např. x xxxxxx 7 xx 14 xxx), xxxxxxxx xx, obarví x spočítají xx xxxxxxxxxx xxxx stříbra. X každého zvířete xx xxxxxxxx xxx xx tři xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx xx xxxx xxxxxxxxx dostatečný xxxxx xxxxxxxxxxxx xxxxxxxxxx buněk, xxx xxxx hodnocení XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx na xxxxxx xxxxxx xxxxxxxxxxxx (xxxx. xx xxxxxxx, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx izotopem).

Před počítáním xxx xx xxxx xxx preparáty kódovány. Xxxxxxxxx xx vyšetřuje 100 xxxxx xx xxxxx xxxxx alespoň xx xxxx xxxxxxxxx; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx by xxxx být zdůvodněno. Xxx počítání zrn xx jádra x X-xxxx nevyšetřují, ale xxxxx xxxxx x X-xxxx může být xxxxxxxxxx.

Xxxxxxxx 3X-XxX xxxxxxxxxxxxxxx xx xxxxx a xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx doložené navrstvením xxx xxxxxxx by xxxx být xxxxxxxxx xxxxxxx metodou.

Počet xxxxx xx xxxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrŭm (xx) x z xxŭxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx oblastech (xx) xxxxxxxxxxxxxx xxxxŭx. jako xxxxxxx cg xx xxxxxxx xxx xxxxx xxxxx xxx nejsilněji xxxxxxxxx xxxxxx cytoplasmy, xxxx xxŭxxxxx xxxxxxx xxxx xx xxx xxxxxxx vybraných xxxxxxx x xxxxxxxxx dotyčných xxxxxxxxx jader. po xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx xxxxxxx i xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx xx xxx xxxxxxx údaje xxx xxxxxxxxxx preparáty x xxxxxxx. Údaje xx xxxx xxx xxxx xxxxxxx xx formě xxxxxxx. Odečtením xxxxxxx XX xx hodnoty XX xx xxx xxx xxxxxxxx pro xxxxxx buňku, pro xxxxx zvíře x xxx xxxxxx xxxxx x xxx xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx xxxxxxxx "xxxxxxxxxx" xxxxx, xxxx xx být xxxxxxxx xxx xxxxxxxxxx "opravovaných" xxxxx xxxxxxxxxx x xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx mohou xxx xxxxxxxxxx statistickými xxxxxxxx. Mají-li xxx xxxxxxx, xxxx xx xxx xxxxxxxxxxx xxxxx xxxxxxx a odůvodněny xxxx xxxxxxxxxx studie.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx nebo xxxxxxxxx xxxxxxx patří:

pozitivní

i)

hodnota XXX xxxx xxx xxxxxxxx úrovní, xxxxx xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx vyšší xxx xxxxxxx pro souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx pod xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx vyšší xxx xxxxxxx xxx souběžnou xxxxxxxx.

Xxxx by být xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, tj. měly xx být vzaty x úvahu xxxxxxxxx, xxxx xxxx xxxxxxxxxxx xxxxxx, vztah dávky x xxxxxxxx x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Výsledky xxxxx xxxxxx dvojznačné nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx XXX v xxxxxxxxx xxxxxxx savců xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxx neplánovanou xxxxxxxx XXX in xxxxx. Negativní výsledky xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx poškození XXX, xxxxx xxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx xxx diskutována xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx xxxxxxx do xxxxxxxx xxxxx xxxx. xx xxxxxx tkáně (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- rozpustnost x xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.

Testovací xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, strava xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx počátku xxxxxxx, xxxxxx rozpětí tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx každou xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx podávání,

- xxxxxxxxx xxxxxx xxxxxxx, zda xx zkoušená xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx xx xxxxxx tkáně,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx xxxx (xxx) xx odpovídající xxxxx (xx/xx tělesné xxxxxxxxx/xxx),

- podrobné xxxxx x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx technika,

- xxxxx xxxxxxxxx a xxxxx xxxxxxxxxxx buněk,

- xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx počtu xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx x počtu xxx xxxxxxxxxxxxxx cytoplasmě, x čistý počet xxx, xxxxxxxxxx xxx xxxxxxxxx, zvířata x xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné statistické xxxxxxxxx,

- známky xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx o xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxx "xxxxxxxxxxxx" xxxxx, xx-xx xxxxxxxx,

- xxxxx xxxxx x X-xxxx, xx-xx xxxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. Lefevre, X. X., Xxxxxxxxx, X., Penman, M. X. (1985), Xx Xxxxxxxxxx xx the Xx xxxx Xxx. Xxxxxxxxxx DNA Repair Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Butterworth, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Mirsalis, X., Xxxxxx, G., Xxxxxxxx, X. (1987), X Xxxxxxxx and Xxxxx xxx the Xx xxxx Rat Xxxxxxxxxx DNA Repair Xxxxx, Mutatation Xxx., 189, 123-133.

3) Kennelly, X. X., Xxxxxx, X., Ashby, X., Xxxxxxx, X. X., Xxxxxxxxx, X., Benford, X. X., Dean, X. W., Xxxxxxxx, X. xx X. (1993), In xxxx Xxx Xxxxx XXX Xxxxx, in: Xxxxxxxx X. X., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx II xxxxxxx, Cambridge University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, S., Xxxx, X. W., Xxxxxx, X., Xxxxxxxxx. G., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, T., XxXxxxx, X. X., Xxxx, H. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx UDS Xxxxx Xx xxxxx xxx In xxxx, Xxxxx. Xxx., 312, 263-285.

5) Xxxxx, X., Xxxxxxx, X., Efstathiou, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Assessment xx xxx Xxxxxxxx Xxxxxxx xxx Initial Xxxxxxxxx xxx xxx Attachment xx Xxxxxxx Xxxxxxxx Xxx Hepatocytes Used xxx xxx Xx xxxx/Xx vitro DNA Xxxxxx Assay (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

6) Xxxxxxxx, X. X., Xxxxx, C. X., Butterworth, B. X. (1982), Detection xx Xxxxxxxxx Xxxxxxxxxxx xx xxx Xx xxxx/Xx xxxxx Xxxxxxxxxx XXX Repair Assay, Xxxxxxx.Xxxxxxx. 4, 553-562."


PŘÍLOHA 5

OBECNÉ POŽADAVKY XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX XXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES, Úř. xxxx. X 332, 28. 12. 2000, x. 81.


XXXXXXX 6

"

PŘÍLOHA XX

XXXX X

xxxxxxxx týkající se xxxxxxx odolných proti xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. e) xxxx směrnice, xxxx xxx obaly o xxxxxxxxx objemu xxxxxxxxxx xxxxx, x xxxxx xx spojeno riziko xxx xxxxxxxxxx (Xn; X 65) x xxxxx xxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx na xxx xx xxxxx xxxxxxxx xxxx x xxxxxxxx xxxxxxxxxx xxxxxxxxxxx rozprašovačem, xxxxxxxx uzávěry xxxxxxxx xxxxx xxxxxxxx dětmi.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx použité xx xxxxxxxxx uzavíratelných obalech xxxx splňovat požadavky xxxxx ISO 8317 (xxxxxx ze xxx 1. xxxxxxxx 1989) "Xxxxx odolné xxxxx — Xxxxxxxxx na xxxxxxxxx uzavíratelné obaly x metody jejich xxxxxxxx" xxxxxxxx Mezinárodní xxxxxxxxxx pro xxxxxxxxxxx (XXX).

2. Opakovaně xxxxxxxxxxxxxx xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx xxxxx použité xx xxxxxxxxx neuzavíratelných xxxxxxx musí splňovat xxxxxxxxx normy XXX XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Obaly xxxxxx dětem — Xxxxxxxxx a xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx výrobků" xxxxxxxx Xxxxxxxxx výborem xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x xxxx uvedenými xxxxxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxx, xxxxx xxxxxxx evropské normy xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx zřejmé, xx obal je xxxxxxxxxx xxxxxxxx pro xxxx, xxxxx xx xxxxxxx xxxxxx k xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx oprávněné xxxxxx k pochybám x bezpečnosti uzávěru xxx dítě, xxxx xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx osoba xxxxxxxxx xx xxxxxxx výrobku xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx laboratoří xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx xxxxxx, xx jej xxxx xxxxxxxx xxxxxxx xxxxx xxxx uvedených xxxxx XXX a CEN,

nebo

- xx xxxxxx xxx xxxxxxx x xxx xxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx týkající se xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx specifikace xxx xxxxxxxxxx xxxxxxxx xxxx xxx x xxxxxxx x normou XX XXX 11683 (xxxxxx x roku 1997) "Xxxxx — Xxxxxxxxxx výstrahy xxxx xxxxxxxxxx — Požadavky".

"