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Xxxxxxxx Komise 2000/32/XX

xx xxx 19. xxxxxx 2000,

xxxxxx se xx xxxxxxx xxxxx přizpůsobuje xxxxxxxxxxx xxxxxxx směrnice Xxxx 67/548/XXX x xxxxxxxxxx právních a xxxxxxxxx předpisů xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx nebezpečných xxxxx [1]

(Xxxx s xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x ohledem xx Smlouvu x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx směrnici Xxxx 67/548/EHS ze xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x správních xxxxxxxx xxxxxxxxxx se xxxxxxxxxxx, balení a xxxxxxxxxx nebezpečných látek [2], naposledy pozměněnou xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Xxxx 1999/33/XX [3], a xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx x xxxxx důvodům:

(1) Příloha X xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx nebezpečných xxxxx xxxxxxxx s xxxxxxxxxx xxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxx látky. Xxxxxxxx xxxxxxx x technické xxxxxxxx xxxxxxx, xx xx xxx být xxxxxx nebezpečných látek x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a tabulky X v xxxxxxx X.

(2) Příloha III xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx vět xxxxxxxxxxx xxxxxx zvláštních xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x přípravky. Xxxxxxx IV xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx x bezpečnostními xxxxxx xxxxxxxxxx se xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxx xx klasifikaci x x xxxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx směrnice vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, XX x XX.

(3) V xxxxxxx X xxxxxxxx 67/548/XXX xx stanoví xxxxxx pro xxxxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, xxxxxxxx x xxxxxxxxxxx xxxxx x přípravků. Xx xxxxxxxx xxxxxxxxxxx tuto xxxxxxx xxxxxxxxxxx xxxxxxx.

(4) Xxxxxxx XX směrnice 67/548/XXX xxxxxxxx předpisy xxxxxxxx xx uzávěrů xxxxxxxx xxxxx xxxxxxxx xxxxx. Xxxx předpisy xx xxxx xxx xxxxxxxxxxxx a xxxxxxxxxxxxx. Xx nezbytné xxxxxxxx xxxxxx, xxx xx xxxxxxx odolné xxxxx xxxxxxxx xxxxx používají.

(5) Xxxxxxxx této směrnice xxxx x xxxxxxx xx stanoviskem Xxxxxx xxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx pro xxxxxxxxxx technických xxxxxxxx xxxxxxx na xxxxx xxxxxxxxxxxx látek a xxxxxxxxx,

XXXXXXX TUTO XXXXXXXX:

Xxxxxx 1

Směrnice 67/548/EHS xx mění takto:

1. Xxxxxxx X se xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxxxx x předmluvě xx xxxxxxxxx xxxxxxxxx X x xxxxxxx 1X xxxx xxxxxxxx;

x) xxxxxxxxxxxx řádky x xxxxxxx X se xxxxxxxxx řádky v xxxxxxx 1B xxxx xxxxxxxx;

x) odpovídající xxxxxxx xx xxxxxxxxx xxxxxxxxx x příloze 1C xxxx směrnice;

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

2. Xxxxxxxxxxxx xxxx x xxxxxxx III xx xxxxxxxxx standardní xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxx 2 xxxx směrnice.

3. Xxxxxxx IV xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx x xxxxxxx XX xx nahrazují xxxxxxxxxxxx xxxxxx xxx xxxxxxxx zacházení v xxxxxxx 3X xxxx xxxxxxxx;

x) xxxxxxxxxxxx xxxxxx x xxxxxxx XX xx nahrazují kombinovanými xxxxxxxxxxxx xxxxxx pro xxxxxxxx xxxxxxxxx v xxxxxxx 3X xxxx xxxxxxxx.

4. Xxxx B xxxxxxx X xx xxxx xxxxx:

x) xxxxxxxx X.10 xx xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;

x) xxxxxxxx X.11 xx xxxxxxxxx xxxxxx x xxxxxxx 4B xxxx xxxxxxxx;

x) xxxxxxxx B.12 xx nahrazuje xxxxxx x příloze 4C xxxx xxxxxxxx;

x) xxxxxxxx X.13 a B.14 xx xxxxxxxxx textem x xxxxxxx 4X xxxx xxxxxxxx;

x) kapitola X.17 xx xxxxxxxxx xxxxxx v příloze 4X xxxx xxxxxxxx;

x) xxxxxxxx X.23 xx xxxxxxxxx textem x xxxxxxx 4X xxxx xxxxxxxx. Název xxxxxxxx X.23 ve vysvětlivce xx xxxx xxxxxxxxxxxxx xxxxxxxx;

x) vkládá xx xxxx x příloze 4X této směrnice.

5. Xxxxxxx se čtvrtá xxxxxxx obecného xxxxx x xxxxx X xxxxxxx X.

6. Odpovídající xxxxx v xxxxxxx XX se xxxxxxxxx xxxxx v xxxxxxx 5 xxxx xxxxxxxx.

7. Xxxxxxx XX se xxxx způsobem uvedeným x příloze 6 xxxx xxxxxxxx.

Xxxxxx 2

1. Členské xxxxx xxxxxx x xxxxxxxx právní a xxxxxxx xxxxxxxx xxxxxxxx xxx dosažení xxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x nich uvědomí Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx státy musí xxxxxxxxx xxxxx xx xxxx xxxxxxxx nebo xxxx xxxxxx xxxxx xxx xxxxxx xxx xxxxxx úředním xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx členské xxxxx.

2. Xxxxxxx státy xxxxx Xxxxxx xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx přijmou x xxxxxxx xxxxxxxxxx xxxx xxxxxxxx, x xxxxxxxxxx tabulku xxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Článek 3

Xxxx směrnice xxxxxxxx x platnost xxxxxx dnem xx xxxxxxxxx x Xxxxxxx xxxxxxxx Xxxxxxxxxx společenství.

Xxxxxx 4

Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

X Xxxxxxx xxx 19. května 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise


[1] Přijato po xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Úř. věst. 196, 16.8.1967, x. 1.

[3] Úř. xxxx. X 199, 30.7.1999, x. 57.


XXXXXXX 1X

XXXXXXXXX K XXXXXXX X

Xxxxxxxxxx poznámek xxxxxxxxxx xx identifikace, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx se 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 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x látkám

Číslo XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–011–00–7

xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. kat. 3; X40 Xn; R22 X; X50

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 X31 X; X34 R43 X; 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

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

206–354–4

330–54–1

Xxxx. xxx. 3; X40 Xxxx. xxx. 3; R40 Xx; R22–48/22 N; X50–53

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

006–016–00–4

xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát

204–043–8

114–26–1

T; X25 X; X50–53

X; X R: 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+; X26/28 X; X24 N; X50–53

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

006–018–00–5

aminokarb (XXX) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

217–990–7

2032–59–9

X; R24/25 X; X50–53

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

006–019–00–0

di-allát (XXX) S-(2,3-dichlorallyl)-N,N-diisopropylthiokarbamát

218–961–1

2303–16–4

Karc. xxx. 3; X40 Xx; X22 N; X50–53

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

006–020–00–6

xxxxxx (XXX) 4-xxxxxxxx-2-xx-1-xx-X -(3-chlorfenyl)karbamát

202–930–4

101–27–9

Xn; 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; R50–53

T; 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; X51–53

Xx; X X: 22–38–51/53 X: (2-)13-61

006–026–00–9

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

216–353–0

1563–66–2

X+; X26/28 X; X50–53

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

006–028–00-X

dinobuton (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 R: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

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

243–433–2

19937–59–8

X; R50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xn; X22 X; R51–53

Xn; X X: 22–51/53 X: (2-)23-61

006–035–00–8

pirimikarb (XXX) 2-(xxxxxxxxxxxxx)- 5,6-dimethyl 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 (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–113–0

2631–37–0

X; X25 N; X50–53

X; N R: 25–50/53 X: (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 Xn; X22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

xxx-xxxxx (ISO) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx

218–962–7

2303–17–5

Xx; X22–48/22 X43 X; R50–53

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

006–042–00–6

xxxxxxx (XXX) 3-(4-chlorfenyl)-1,1-dimethylmočovina

205–766–1

150–68–5

Karc. xxx. 3; R40 Xx; R22 X; X50–53

Xx; X X: 22–40–50/53 X: (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; X X: 36/38–40–50/53 X: (2-)36/37–60–61

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 X; X50–53

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

006–047–00–3

xxxxxxxxx (XXX) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx a 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

8065–36–9

X; X24/25 X; X50–53

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

006–048–00–9

xxxxxxxxxxxx (XXX) 2-[(xxxxxxxxxxxxx)xxxxxx]xxxxx-X-xxxxxxxxxxxxxx

249–981–9

29973–13–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–050–00–X

xxxxxxx-XXX 3-fenyl-1,1-dimethyluronium-trichloracetát

4482–55–7

Xi; X38 X; X50–53

Xx; N 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+; R28 Xx; X21 N; R50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; R22 N; X51–53

Xx; X X: 22–51/53 S: (2-)24-61

006–060–00–4

xxxxxxxxxxx (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 R:22–52/53 X: (2-)61

006–069–00–3

xxxxxxxxx-xxxxxx (XXX) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx

245–740–7

23564–05–8

Xxxx. xxx. 3; X40 X; R50–53

Xn; X X: 40–50/53 X: (2-)36/37–60–61

006–070–00–9

xxxxxxxxxxx X-xxxxxxxxxx-X-xxxxxxx-2,5-xxxxxxxx-3-xxxxxxx

262–302–0

60568–05–0

Xxxx. xxx. 3; R40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

benfurakarb (XXX) ethyl-N -[({[(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)xxx]xxxxxxxx}xxxxxxxxxxx)xxxxxxxx]-X-xxxxxxxxx-β-xxxxxxxx(2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx)-X-({[2-(xxxxxxxxxxxxxx)xxxxx]xxxxxxxxxxxxxx}xxxxxxxx)-X-xxxxxxxxxxxxxx

82560–54–1

X; X23/25 N; 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; X45 X; X23/25 C; R34 X; X51–53

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

007–013–00–0

N,N-dimethylhydrazin 1,2-xxxxxxxxxxxxxxxx

X

540–73–8

Xxxx. xxx. 2; X45 X; X23/24/25 X; X51–53

X; X R: 45–23/24/25–51/53 X: 53–45–61

X ≥ 25 %: X; R45–23/24/25 3 % &xx; C &xx; 25 %: X; R45–20/21/22 0,01 % < C &xx; 3 %: X; X45

009–003–00–1

xxxxxxxx fluorovodíková … %

B

231–634–8

7664–39–3

T+; X26/27/28 X; X35

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

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

015–039–00–9

xxxxxxx-xxxxxx (XXX) O,O-dimethyl-S -[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát

201–676–1

86–50–0

T+; X26/28 X; R24 X43 X; X50–53

X+; X X: 24–26/28–43–50/53 X: (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; X40 X; X23–48/25 Xn; X21/22 N; 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

azinfos-ethyl (XXX) X,X-xxxxxxx-X-[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx

220–147–6

2642–71–9

X+; X28 X; R24 X; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xn; X21 X; X50–53

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

016–013–00-X

xxxxxxx xxxxxxx

234–129–0

10545–99–0

X14 X; X34 X; X50

X; N X: 14–34–50 X: (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 xxxxxxxx

13451–08–6

X14 X; R34 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; X36/37/38

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 X+; R26 X; X25 X; R34 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+; X45–22–26–34–43 7 % ≤ C &xx; 10 %: X+; X45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: X; R45–22–23–36/37/38–43 3 % ≤ X &xx; 5 %: X; X45–22–23–43 1 % ≤ X &xx; 3 %: X; R45–23–43 0,1 % ≤ X &xx; 1 %: X; X45–20 0,01 % ≤ X &xx; 0,1 %:X; X45

016–024–00-X

xxxxxxxx (ISO) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; R22 X; X50–53

Xx; N X: 22–50/53 X: (2-)60-61

016–071–00–6

3-amino-6,13-dichlor-10-[(3-{[4-chlor-6-(2-sulfonatoanilino)- 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; R34 5 % ≤ X < 10 %: Xi; X36/37/38

030–004–00–8

xxxxxxxxxxxxx [1] diethylzinek [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

R14 X; X17 X; X34 X; X50–53

X; X; N X: 14–17–34–50/53 X: (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; R50–53

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

050–012–00–5

xxxxxxxxxxxxxxxxxxxxxx [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] butyl(tricyklohexyl)stannan [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; R20/21/22 X; X50–53

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

X ≥ 1 %: Xx; 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; X36/38 X; X50/53

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

082–009–00–X

žluť (xxxxxxxxxxxx xxxxxxxx) CI Xxxxxxx Xxxxxx 34 (XX 77603) CI xxxxxxxxxx xxxx 34 (XX 77603)

215–693–7

1344–37–2

Xxxx. kat. 3; R40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 N; X50–53

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

1

082–010–00–5

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

235–759–9

12656–85–8

Xxxx. xxx. 3; X40 Xxxx. xxx. 1; R61 Xxxx. xxx. 3; X62 X33 X; X50–53

X; N X: 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; R65 Xx; X37 X; R51–53

Xn; X X: 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; X45 Xxxx. xxx. 2; R46 Xxxx. xxx. 2; X60–61 N; X50–53

X; X X: 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. xxx.2; X45 N; R50–53

T; X X: 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; R50–53

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

602–054–00–6

3-jodprop-1-en allyljodid

209–130–4

556–56–9

R10 X; R34

C X: 10-34 X: (1/2-)7–26–45

603–076–00–9

but-2-yn-1,4-diol

203–788–6

110–65–6

T; X23/25 Xx; R21–48/22 X; R34

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

C ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; X21–23/25–36/38–48/22 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; X8 Xx; R22 Xi; 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 X; X51–53

Xx; 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 S: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx

200–661–7

67–63–0

X; R11 Xx; R36 X67

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

604–020–00–6

bifenyl-2-ol 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (XXX)

201–993–5

90–43–7

Xx; R36/37/38 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; X22 Xi; 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-xxx(4-xxxxxxxxxxxx)-4-xxxxxxxxxxxx

401–720–1

6807–17–6

Xxxx. xxx. 2; X60 Xx; R36 X; X50–53

X; N 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 xxxxxxxx [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; R22 Xx; X38–41 X; X50–53

Xx; X R: 22–38–41–50/53 X: (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 R43

Xi X: 36-43 X: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; R22 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. xxx. 3; X40 Xx; R20 Xx; X36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

X ≥ 10 %: Xx; X20–36/38–40–43 1 % ≤ X &xx; 10 %: Xn; X40–43

606–016–00-X

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

201–462–8

83–26–1

X; X25–48/25 X; X50–53

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

606–018–00–0

xxxxxxx (XXX) 2,3-dichlor-1,4-naftochinon

204–210–5

117–80–6

Xn; X22 Xx; X36/38 X; X50–53

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

606–019–00–6

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

205–601–3

143–50–0

Karc. kat. 3; X40 T; 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 N; 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; X X: 43–50/53 S: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Xxxx. xxx. 3; X62 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 S: (2-)24–37–60–61

606–037–00–4

xxxxxxxxxxx (XXX) 1-(4-chlorfenoxy)- 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 X: 22–51/53 X: (2-)61

606–044–00–2

2,4,6-xxxxxxxxxxxxxxxxxxx xxxxx(2,4,6-xxxxxxxxxxxxxx)xxxxxxxx

403–150–9

954–16–5

Xx; X22 Xx; R36 X; X50–53

Xx; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

xxxxxxx (XXX) 3,6-dichlor-2-methoxybenzoová 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 (XXX) 3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxykumarin3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxy-2 X-xxxxxxx-2-xx

201–378–1

81–82–3

Xx; X48/22 X52–53

Xx 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 H -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 X: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) ethyl-4-oxo-5-(perchlor-5-hydroxypentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-yl)pentanoát ethyl-5-(1,2,3,5,6,7,8,9,10,10-dekachlor-4-hydroxypentacyklo[5.2.1.02,6.03,9.05,8]dekan-4-yl)-4-oxopentanoát 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 X; R51–53

T; X X: 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 R42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx valerová kyselina

203–677–2

109–52–4

C; X34 X52–53

X X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xn; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; X36/38 X52–53

Xx X:36/38–52/53 X: (2-)22-61

607–156–00–4

chlorfenson (XXX) 4-xxxxxxxxxx-4-xxxxxxxxxxx-1-xxxxxxxx

201–270–4

80–33–1

Xx; R22 Xx; X38 X; X50–53

Xx; X R: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; R25 Xx; X38 X; X50

X; N X: 25–38–50 S: (1/2-)22–37–45–61

607–159–00–0

xxxxxxxxxxxxxx (XXX) xxxxx-2,2-xxx(4-xxxxxxxxxx)-2-xxxxxxxxxxxxx ethyl-4,4'-dichlorbenzilát

208–110–2

510–15–6

Xn; X22 N; R50–53

Xn; 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 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}xxx)xxxx(xxxxxxxxxx)

400–830–7

X43 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; R51–53

Xi; 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); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx)

403–030–6

Xx; R22 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 X; R7 X10 X; R51–53

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

607–217–00–5

2-ethoxyethyl-[4-(7-fenyl-2,6-dioxo-2,6-dihydro-1,5-dioxa-s-indacen-3-yl)fenoxy]acetát

403–960–2

R43 X53

Xx X: 43-53 X: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] natrium-3,6-dichlor-o-anisát [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 Xxxxxxx-X-(1-xxxxxx)xxxxxxxx

205–073–4

132–67–2

Xx; X22

Xx X: 22 S: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xx; X36/37/38 X43 X; X51–53

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

C ≥ 10 %: Xx; X36/37/38–43 1 % ≤ C &xx; 10 %: Xi; X43

607–252–00–6

λ-xxxxxxxxxxx (XXX) Směs (1:1): (S)-[(3-fenoxyfenyl)kyanmethyl]-(1 R)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 S)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát

415–130–7

91465–08–6

T+; 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

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

69377–81–7

R52–53

R: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X X

203–466–5

107–13–1

X; Xxx Karc. xxx. 2; R45 X; X23/24/25 Xi; X37/38–41 X43 N; X51–53

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

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

43

608–016–00–5

2,3,5,6-xxxxxxxxxx-1,4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxx

401–550–8

1897–41–2

X43 X; X50–53

Xx; X R: 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 T+; R28 X; X24 R44 X; X50–53

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

609–040–00–9

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

E

217–406–0

1836–75–5

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

X; X X: 45–61–22–50/53 S: 53–45–60–61

609–044–00–0

xxxxxxxx (ISO) 1,2,4,5-xxxxxxxxxx-3-xxxxxxxxxxx

204–178–2

117–18–0

Xx; X22 R43 X; X50–53

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

611–008–00–4

4-aminoazobenzen 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. xxx. 2; X45 X; X50–53

X; X X: 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 xxxxxxxxx

403–650–7

117409–78–6

X; X2 N; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx XX Xxxxx Xxx 9 XX basická xxxxxx 9

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-methoxyanilin o-anisidin

E

201–963–1

90–04–0

Karc. xxx. 2; R45 Xxxx. kat. 3; X40 X; R23/24/25

T X: 45–23/24/25 X: 53-45

612–042–00–2

xxxxxxxx xxxxxxx-4,4'-xxxxxx 4,4'-xxxxxxxxxxxxxx xxxxxxx-4,4'-xxxxxxxxxx

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; X22 X; X50–53

X; X X: 45–22–50/53 S: 53–45–60–61

X ≥ 25 %: X; R45–22 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 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; X48/20/21/22 X43 X; R51–53

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

612–081–00–5

3,3'-xxxxxxxxxxxxxxxx, xxxx 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 N; X51–53

X; X R: 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. kat. 2; X45 T; X25 Xx; X21 Xx; X36 X43 X; X51–53

X; X X: 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; X34 X43 X52–53

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

612–111–00–7

2-methyl-m-fenylendiamin2-methyl-1,3-fenylendiamin2-methylbenzen-1,3-diamin 2,6-xxxxxxxxxxxx

212–513–9

823–40–5

Xxxx. xxx. 3; X40 Xx; X21/22 X43 N; R51–53

Xn; X X: 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-toluendiamin

202–442–1

95–70–5

T; X25 Xx; X20/21 X43 X; R51–53

T; 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 R4 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 xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; R45 T; X25 Xn; X20/21 Xx; R36 R43 X; X51–53

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

613–018–00–4

xxxxxxxxxx (ISO) 1,1'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-diium

7411–47–4

Xn; 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 trichlorisokyanurová 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 R31 Xx; X36/37 X; X50–53

X; Xx; N X: 8–22–31–36/37–50/53 X: (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 benzoguanamin

202–095–6

91–76–9

Xn; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 N; X41 X; X50–53

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

613–043–00–0

xxxxxxxx-xxxxxx (XXX) 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; X50–53

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

613–066–00–6

terbumeton (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 R: 22–50/53 S: (2-)60-61

613–091–00–2

morfamkvat-dichlorid [1] xxxxxxxxxx-xxxxxx [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-dium-disulfát [2]

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xn; R22 Xx; R36/37/38 X52–53

Xx; 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; X34 X; X51–53

X; 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; X51–53

Xx; N X: 43–51/53 X: (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; R22 X52–53

Xx X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

Xxxx. xxx. 3; X63 Xx; X22 Xx; X36 X; R51–53

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

613–137–00–1

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

242–505–0

18691–97–9

X; X50–53

X R: 50/53 X: 60-61

613–139–00–2

xxxxxxxxxxx-xxxxxx xxxxxx-2-{X —[X-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxxx]xxxxxxxxx}xxxxxxx

74223–64–6

X; X50–53

X X: 50/53 S: 60-61

614–001–00–4

xxxxxxx (XXX) 3-(1-xxxxxxxxxxxxxxxx-2-xx)xxxxxxx

200–193–3

54–11–5

X+; X27 X; X25 X; X51–53

X+; X X: 25–27–51/53 X: (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 S: (1/2-)13–45–61

614–007–00–7

xxxxxx-xxxxxx [1] brucin-nitrát [2] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [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-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] toluen-3,5-diisokyanát [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 X+; X26 Xx; R36/37/38 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+; R26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; R23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42

2

616–010–00–9

xxxxxxx-xxxxxxxxxxxxxx N-chlor-4-methylbenzen-1-sulfonamid, xxxxx xxx

204–854–7

127–65–1

Xx; X22 X31 X; X34 X42

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

616–034–00-X

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

246–419–4

24691–76–7

X52–53

X: 52/53 S: 61

616–035–00–5

cymoxanil 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 R43 X; X50–53

Xx; X X: 22–43–50/53 S: (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 X; R34 X; R50–53

O; X; 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 % ≤ C < 25 %: C; X34 5 % ≤ C &xx; 10 %: Xi; X36/37/38

617–006–00-X

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

201–279–3

80–43–3

X; X7 Xx; R36/38 X; X51–53

X; Xx; X X: 7–36/38–51/53 S: (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 (ISO) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx

228–200–5

6164–98–3

Xxxx. xxx. 3; X40 Xn; R21/22 X; R50–53

Xn; 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; N X: 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; X40 Xx; X22 X; X50–53

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

650–033–00–5

xxxxxxxxxxxx (XXX) [(S)-(3-fenoxyfenyl)kyanmethyl]-(S)-2-(4-chlorfenyl)-3-methylbutanoát (S)-3-fenoxy-α-kyanbenzyl-(S)-2-(4-chlorfenyl)-3-methylbutanoát

66230–04–4

T; X23/25 X43 X; X50–53

X; N R: 23/25–43–50/53 S: (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; X50–53

X X: 50/53 X: 60-61


PŘÍLOHA 1D

Indexové xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx k 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 X: (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-xxxxxxxxxxxxxxxxxxxx

406–490–6

X; X51–53

X X: 51/53 X: 61

015–164–00–9

xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

Xxxx: S, X, X', S''-tetrafenyl-4,4'-sulfandiylbis(fenylsulfonium)-bis(hexafluorofosfát) x xxxxxxx[4-(xxxxxxxxxxxxx)xxxxx]xxxxxxxxx-xxxxxxxxxxxxxxxx

404–986–7

Xx; X41 X; X50–53

Xx; 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-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; X50

X R: 50 X: 61

601–051–00–7

4-xxxxxxxx-1-xx

405–980–7

768–56–9

Xx; X38 N; 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; X48/21/22 X64 X; X50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

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

603–130–00–1

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

406–325–8

Xx; X22 X52–53

Xx X:22–52/53 S: (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; R41

Xi 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 X52–53

Xx 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-chlor-5-nitro-1,4-fenylen)diimino]di(propan-1,2-diol)

408–240–1

Xn; R22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

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

410–450–3

R53

R: 53 X: 61

603–135–00–9

xxx[2-(2-xxxxxxxxxxxxx)xxxxxxxxxx]xxx(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx

410–500–4

Xx; X41 X; X51–53

Xx; N 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 X:43–52/53 X: (2-)24–37–61

603–137–00-X

Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 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-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol

403–140–4

103694–68–4

R52–53

R:52/53 X: 61

604–050–00-X

4-chlor-o-kresol 4-xxxxx-2-xxxxxxxxxxx

216–381–3

1570–64–5

X; X23 X; X 35 N; R50

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

X ≥ 25 %: X; X; R23–35 10 % ≤ X < 25 %: X;X20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ X &xx; 5 %: Xx;X20–36/37/38 1 % ≤ X &xx; 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'-xxxxxxxxxxx[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 X: 61

604–053–00–6

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

410–760–9

157661–93–3

Xx; X38 X43 N; X50–53

Xx; 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 X52–53

Xx X:43–52/53 X: (2-)24–37–61

604–055–00–7

4,4'-bis[(2,3-epoxypropyl)oxy]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx

413–900–7

85954–11–6

Xxxx. Kat.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, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx

410–480–7

X43 X; X51–53

Xx; 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-(X, X-xxxxxxxxxxxx)-2-xxxxxxx-2'-xxxxxxxxxxxxxxxxx 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx kyselina

410–410–5

54574–82–2

R52–53

R:52/53 X: 61

607–272–00–5

xxxxxxxxxxx-xxxxxx (ISO) [1] xxxxxxxxxx-xxxxxxxxx (ISO) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-butoxy-1-methylethyl)-[(4-amino-3,5-dichlor-6-fluor-2-pyridyl)oxy]acetát [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]- 1,2,6,7,8,8a-hexahydro-1-naftyl}-3,5-dihydroxyheptanoát

404–520–2

R52–53

R:52/53 X: 61

607–274–00–6

{2-[benzyl(methyl)amino]ethyl}-3-aminobut-2-enoát

405–350–1

54527–73–0

R43 X; X51–53

Xx; X R: 43–51/53 S: (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) bis(1-methylimidazol)]zinečnatý xxxxxxx

405–635–0

Xx; X38–41 N; X50–53

Xx; X R: 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; X22 Xx; X41 X43 X; X51–53

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

607–278–00–8

Xxxx:xxxxx(X7-X9 xxxxxxxxxx x nerozvětvené)-3-[3-(2 X - benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty

405–760–0

Xi; X41 X43 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) a (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx)

405–960–8

X43 X; X51–53

Xx; N X: 43–51/53 X: (2-)24–37–61

607–280–00–9

4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx xxxxx xxxxxxx-4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx

406–190–5

54322–20–2

Xx; X22 Xx; X36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

Směs:alkyl(C7-C9 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 S: 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; R21/22 Xx; X38–41 R43 X; X50–53

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

607–284–00–0

Xxxx (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 X: 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- x 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 S: 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 komplex, xxxxxxxxxx xxx; c = 15, 16, 17 xxxx 18, x = 1, 2, 3 xxxx 4, b = 8, 9, 10 xxxx 11, d = 22, 23, 24 xxxx 25

410–160–7

148732–74–5

Xx; X36 X43 X52–53

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

607–288–00–8

3-[(3-{X —[4-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxx]xxxxxxxxx}-4-xxxxxxx-1-xxxxxx)xxxxxxxx]xxxxxxxxx kyselina

410–370–9

105488–33–3

R53

R:53 X: 61

607–290–00–3

Směs (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 R43 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

Směs:[2-(alkyl(C12)oxy)-1-(methoxymethyl)ethoxy]octová kyselina x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx kyselina

410–640–6

Xi; X38–41 X; X50–53

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

607–293–00-XSměs:

1-(2-aminoethyl)piperazin-1,4-diium-[(2,4,6-trimethylnonyl)fenoxy]benzendisulfonát x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx

410–650–0

Xx; X41 X43 X; R51–53

Xi; N 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 xxxxxxxx x 2-xxxxxxxxxxxxx xxxxxxxx

410–830–9

X53

X: 53 X: 61

607–297–00–1

3,3'-(1,4-fenylendimethyliden)bis(2-oxobornan-10-sulfonová 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; R41

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

607–298–00–7

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

411–010–3

X43

Xx X: 43 S: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 X43 X; X50–53

Xx; N X: 22–43–50/53 X: (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 nebo 4, x = 8, 9, 10 xxxx 11, x = 15, 16, 17 xxxx 18, x = 22, 23, 24 nebo 25

411–430–7

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xx; X38–41 X43 X; X51–53

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

607–302–00–7

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

411–910–6

Xx; X38–41 R43 X; X51–53

Xx; 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. kat.3; X62 R52–53

Xn X: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

4-(4-chlorfenyl)-2-fenyl-2-[(1H- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx

406–140–2

114369–43–6

X; R50–53

N X: 50/53 X: 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-nitro-4,5-bis(benzyloxy)fenyl]acetonitril

410–970–0

117568–27–1

R53

R:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; X3 X; X8 Xxxx. kat. 2; X45 T; X23/25 R43

E; X X: 45–3–8–23/25–43 S: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 X; X34 X43 N; X50–53

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

611–043–00–5

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

402–850–1

Xi X: 41–52/53 X: (2-)26–39–61

611–044–00–0

Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [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-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx 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 S: 61

X 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; X25 Xx; X48/22 R43 N; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 S: 61

611–048–00–2

Směs (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx a 2-({4-[bis(2-acetoxyethyl)amino]fenyl}azo)-6,7-dichlorbenzothiazol

407–900–6

111381–12–5

R53

R: 53 X: 61

611–049–00–8

Xxxx (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, kyselina xxxxxx x xxxxxx xxxxxxxx (2:1:1)

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

Xx R: 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 S: 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 komplex, xxxxx sůl

400–720–9

R52–53

R: 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; N X: 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; X51–53

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

612–158–00–3

Xxxx:[xxx(5-xxxxx(xxxxxxxxxx C12))-2-hydroxybenzaldoximato)]měďnatý 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 xxxxx 2,2,4-xxxxxxxxx- x 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x seznamu EINECS), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Xxxxxx 8) a 4-methylbenzen-1-sulfonové xxxxxxxx

410–880–1

Xx; X22 X; X34 X; X50–53

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

613–149–00–7

2-terc-butyl-5-[(4-terc-butylbenzyl)sulfanyl]-4-chlorpyridazin-3(2H)-on

405–700–3

96489–71–3

T; X23/25 X; X50–53

X; 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 S: 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; X51–53

Xx; X R: 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; R22

Xn R: 22 X: (2-)22

613–155–00-X

5-chlor-2,3-difluorpyridin

410–090–7

89402–43–7

R10 Xx; X22 X52–53

Xx X: 10–22–52/53 S: (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 R: 43–51/53 X: (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; X22–48/22 Xi; 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 X43 X; X51–53

Xx; X X: 20/22–41–43–51/53 X: (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 N; R50–53

T; 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 X: 43 S: (2-)24-37

615–022–00–1

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

410–550–7

79277–18–2

X; X2 R14 Xx; X48/22 X42/43

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

615–023–00–7

xxxxxxxxxxx 2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxxx kyselinymethyl-2-[(isokyanatosulfonyl)methyl]benzoát

410–900–9

83056–32–0

R10 X14 Xxxx. xxx. 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 S: 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 R53

Xi 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 X, X′,X″,X′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

X43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 N; X51–53

Xx; X X: 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 S: 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 X; X50–53

Xx; 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'-bis(4-methylfenyl)-1,1'-(2-methyl-1,3-fenylen)dimočovina Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-bis[(3-(4-methylfenyl)ureido]toluen

411–070–0

R53

R: 53 X: 61

617–015–00–9

bis(4-methylbenzoyl)peroxid

407–950–9

895–85–2

E; X2 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) (2X, 3X)-, (2 X, 3 X)-, (2 X, 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; X22 X; X50–53

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


PŘÍLOHA 2

XXXXXX SPECIFICKÝCH XXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI A XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


PŘÍLOHA 3A

STANDARDNÍ POKYNY XXX BEZPEČNÉ XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX BEZPEČNÉ ZACHÁZENÍ X XXXXXXXXXXXX LÁTKAMI X PŘÍPRAVKY

Viz směrnice Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.


PŘÍLOHA 4A

"B.10 XXXXXXXXXX — ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX X XXXXX XX XXXXX

1. XXXXXX

Xxxx metoda xx xxxxxxxx metody XXXX XX 473 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx vitro (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u xxxxx xx xxxxx xx xxxxxxxxxxxxx činitele, xxxxx xxxxxxxxx strukturní chromozomové xxxxxxx x xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Rozlišují xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx chemických xxxxxxxx xxxx indukované aberace xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Tato xxxxxx xxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx aberací x xxxx k xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, že xxxxxxxxxxxx xxxxxx x x xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx v xxxxxxxxxx a x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx nádory, xxxx xxxxx na xxxxxxx xxxxxxxx x člověka x x xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx in xxxxx xxxxx být xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, buněčné xxxxx xxxx primární xxxxxxx xxxxxxx. Použité buňky xxxx xxxxxxx na xxxxxxx schopnosti růstu x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx chromozomů, xxxxxxxxxxxx xxxxxxxxxx a xxxxxxxxx četnosti xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx aktivace. Tento xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx x savců. Je xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, jež xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx x xxx xxxxx xxxxxx xX, osmolality xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx zkouška xx používá xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx pro xxxxx. Xxxxx xxxxxxxxx, xxx něž je xxxx xxxxxxx xxxxxxxxx, xxxx pro xxxxx xxxxxxxxxxx; xxxx touto xxxxxxxx a xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx třídě x přibývají xxxxxx x tom, že xxxxxxxx karcinogeny, xxxxx xxxxxx zjištěny xxxxx xxxxxxxx, xxxxx zřejmě xxxxxx xxxxxx xxxxxxxxxx xxx přímým xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx nebo xxxxx a opětného xxxxxxx chromatid.

Chromozomová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx xxxx zlomu x spojení obou xxxxxxxxx v xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : proces, xxx xxxxxx x xxxxx xx S-fázi xxxxxxxxx DNA xxxxxxx x xxxxxx, xxxxx xxxxxxxxx xxxxx S-fáze. Xxxxxxxxx xxxx xxxxxxxxxx xx 4, 8, 16… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx xxxx menší xxx xxxxx jedné xxxxxxxxxx a s xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxx : xxxxx xxxxx, xxxxx xx xxxxxxxxx v metafázi, x celkového xxxxx xxxxx v xxxxxxxx; xxxxx xxxxxx xxxxxxxxxxx xxxx populace.

Numerická aberace : odchylka xxxxx xxxxxxxxxx od xxxxxxxxxx xxxxx obvyklého x xxxxxxxxx xxxx buněk.

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx chromozomů xxx xxxxxxxx dělení xx xxxxxx metafáze; xxxx xx jako xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx vystaveny xxxxxxxx xxxxx, a xx x metabolickou xxxxxxxx x bez xx. V xxxxxx xxxxxxxxxxx intervalech xx xxxxxxxx látce xx xx xxxxxxxxx xxxxxx xxxxx látka zastavující xxxxxxxx (např. Colcemid® xxxx kolchicin), xxxxxxx xx sklidí, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx se zjistí xxxxxxxxxxxxxx xxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx různé xxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxx xxxxxxxx buněčných xxxxx (xxxx. fibroblasty xxxxxx xxxxxxxx, lymfocyty xxxxxxxxx xxxx člověka xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx udržování kultur xx měla být xxxxxxx xxxxxx xxxxxxxxxx xxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxxxx nádoby, xxxxxxxxxxx XX2, teplota x xxxxxxx). X xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x kmenů by xxxx xxx rutinně xxxxxxxxxxxx xxxxxxxxx modální xxxxxxx xxxxx xxxxxxxxxx x xxxx xx xxx xxxxxxxxxxxx, xxx xxxxxx kontaminovány xxxxxxxxxxxx; x případě xxxxxxxxxxx xx xxxxxx být xxxxxxx. Xxx xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx by xxxx xxx xxxxx normální xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x xxxxx: xxxxx se xxxxxxx x kmenových xxxxxx, xxxxxx se xx xxxxxxxxxxxx xxxxx x xxxxxx hustotě, aby xxxxxxxxx xxxxxxxxxx před xxxxxxxxx, a xxxxxxxx xx při 37 °X.

Xxxxxxxxx: krev ošetřená xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx oddělené xxxxxxxxx xxxxxxxx xxxxxxxx se xxxxxxx do kultivačního xxxxx xxxxxxxxxxxx mitogen (xxxx. xxxxxxxxxxxxxxxx) x xxxxxxxx xx při 37 °X.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x to x xxxxxxx metabolickou xxxxxxxx x bez xx. Nejčastěji používaným xxxxxxxx je xxxxxxxxxx xxxxxxxx postmitochondriální frakce (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Xxxxxxx 1254 (6, 7, 8 a 9), xxxx xxxx fenobarbitonu x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx je x xxxxxxxx xxxxxxxxxx médiu xxxxxxx používána v xxxxxxxxxxxxx 1 — 10 % obj. Xxxx xxxxxxxxxxxxx aktivačního xxxxxxx může xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. V některých xxxxxxxxx může xxx xxxxxx použít více xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx xxxxxxxx xxx endogenní xxxxxxxx. Xxxxx použitých xxxxxxxxx xxxxx xx xxxx být xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx metabolismus zkoušené xxxxx).

1.4.1.5 Zkoušená xxxxx/xxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány přímo x xxxxxxxxxx systémům x/xxxx mohou být xxxx aplikací xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, pokud xxxxx o xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, a xxxx xx být xxxxxxxxxx x xxxxxxxx buněk x s xxxxxxxxx X9. Jsou-li xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx pokud xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx být xxxxxxx xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Vodu xxx xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

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

Cytotoxicita xx xxxx být xxxxxxxxx x xxxxxxxxxxxx aktivací x bez ní x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, jako xxxx xxxxxx xxxxxxxxxx, xxxxx životaschopných xxxxx xxxx xxxxxxxxx index. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx xxxxxxxxxxxx xx xxxx tyto koncentrace xxxxxxxx xxxxxxx dané xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx obvykle xxxxxxx, že xx xx koncentrace xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. V xxxxxxxx xxxxxxx xx xxxx xxxxxxxx xxxxxxxxxxx vykazovat xxxxxxxx xxxxxxx stupně xxxxxxxxxx, počtu xxxxx xxxx xxxxxxxxxxx indexu (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx je xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx nebo xxxxxxxxxxxxxx xxxxxx x xxxxxx xx xxxx, která xxxxxxxx xx xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx x xxxxxxxxxxx kultur, x xxxxx mohou xxx xxxx metody xxxxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx buněčného xxxxx, xxxxxxxxx xxxxxxxx generační xxxx (AGT), xxxxx xxx použity jako xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, z xxx nelze xxxxxxx xx existenci zpožděných xxxxxxxxxxx, a x xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx doby může xxx xx xxxxxxxx xxxxx xxxxxxxxx oddálení xxxxxxxx optimálního xxxxxxx xxxxxxx.

X případě relativně xxxxxxxxxxxxxxx látek by xxxx být xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx toho, xxxxx x xxxx je xxxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx při xxxxxxxxxxxxx xxxxxxx, xxx xx xxxxxx xxxxxxxxxxx, xx xxxx xxx xxxxxxx xxxxxxxx dávka x xxxxxxxxxxx, xxx xx nad xxxx xxxxxxxxxxxx x konečném xxxxxxxxxxx xxxxx xx xxxxx xxxx xxxxxxxx. X určitých xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx xxx xxxxxxx koncentracích, než xx rozpustnost) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, xxx nichž xxxxxxx xx xxxxxxx. Xxxx být xxxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx expozice, xxxxx xxxxxxxxxxx v testovacím xxxxxxx xx xxxx x průběhu xxxxxxxx xxxxx x důsledku xxxxxxxxxxx buněk, xxxx X9 atd. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx). Při xxxxxxx xxxxxxxxxxx aktivace xx xxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxxxx chemická látka, xxxxx x xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx.

X xxxxxxxxx xxxxxxxx xx xxx xxx použit xxxxx xxxxxxxxx x xxxxxxxxxxx koncentracích, které xxxxxxxx poskytnou xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx nárůst xxx xxxxxx, čímž xx xxxxxxx citlivost xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx tak, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx x negativních xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxx xxxxxx xxxxxxxxxxx aktivace

methyl-methansulfonát

66–27–3

200–625–0

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X vnější metabolickou xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx x jiné xxxxxx xxxxx. Pro xxxxxxxxx kontrolu xx xxxx xxx xxxxx xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx.

X okamžiku xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající xx xx samotného rozpouštědla xxxx xxxxxxxx v xxxxxxxxxxx xxxxx a xxxxxxxxxx stejným xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx se xxxxxxx xxxxxxxx xxxxx xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx xxx xxxx. Xxxxxxxx xxxxxxxxx by xxxx xxx xxxxxxxx xxx 48 xxxxx xx mitogenní xxxxxxxxx.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxx duplicitní xxxxxxx, a xxxxx xx xxxxxxx xxxxxxxxxx x kultur xxx xxxxxxxxx kontrolu nebo xxxxxxxx rozpouštědla. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx duplicitními kulturami xx minimální xxxxxx, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

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

1.4.3.3 Xxxx xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx by měly xxx xxxxx vystaveny xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx xxxxxxxx, xxx bez xx, xx xxxx 3 — 6 hodin, x měly xx xxx odebrány po xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx cyklu (12). Xxxxxxxx tento xxxxxx dává xxxxxxxxx xxxxxxxx jak s xxxxxxxx, xxx xxx xxxxxxxx, xxx xx xxx xxxxxxxx dodatečný xxxxxxxxxx bez xxxxxxxx x xxxxxxxxxxxx expozicí xx xx xxxxxx x xxxx, která xxxxxxxx 1,5násobku xxxxxxxx xxxxx buněčného xxxxx. Xxxxxx xxxxxxxx xxxxx xxx xxxxx xxxxxxxxx xxx xxxxxx aplikace xxxx xxxxxx delších xxx 1,5xxxxxxx xxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxx metabolické xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. X xxxxxxxxx, xxx xx xxxxxxxxxx potvrzení xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, xx xxxx xxx xxxxxx xxxxxxxxxx.

1.4.3.4 Xxxxxxxx xxxxxxxxx pro xxxxxxx chromozomů

Do xxxxxxx xxxxxxx xx obvykle 1-3 hodiny xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx xxxxxxxxx. Xxx xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxxx xxxxxx x xxxxxxxxxx xxxxxx. Příprava preparátů xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx buněk, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx preparáty, xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx měly být xxxx analýzou xxx xxxxxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx při xxxxxx xxxxx xxxxxxx xx xxxxx xxxxx buněk x metafázi x xx ztrátě chromozomů, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx xxxxxx xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx buněk. Xx xxxxxx xxxxxxxxxxx x xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxx 200 dobře xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx duplicitní xxxxxxx. Xxxxx počet xxx xxxxxx, je-li xxxxxxxxx velký počet xxxxxxx.

Xxxxxx xx účelem xxxxxxx xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx, je xxxxxxxx xxxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxxxxxx, jsou-li xxxxxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx a mělo xx tedy být xxxxxxxxxxx xxxxxxxx buněk xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x procentech. Xxx xxxxxxxxx a experimentální xxxxxxx xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, ale xxxxxxxxxx xx xx celkové xxxxxxxx xxxxxxx.

Xxxx by xxx také zaznamenána xxxxxxxx, xxxxx xxxx xxxxxxxxx pro stanovení xxxxxxxxxxxx u všech xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx experimentech x xxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx kultury. Xxxx xx xxxx být xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx byla xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx posuzovaných xxxxxxxx xx xxxx být xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. K parametrům xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx existuje xxxxxxx kritérií, např. xxxxxx počtu buněk x xxxxxxxxxxxxxx aberacemi x závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx. Xxxxxxxx xx měla xxx uvážena biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků zkoušky xxxxx xxx použity xxxx xxxxxxx prostředek xxxxxxxxxxx metody (3, 13). Statistická významnost xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx odpověď.

Nárůst xxxxx xxxxxxxxxxx xxxxx xxxx znamenat, že xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx chromozomové xxxxxxx. Xxxxxx xxxxx xxxxx x endoreduplikovanými chromozomy xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx cyklu (17, 18).

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

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx výsledky, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx zůstat xxxxxxxxxx nebo sporné xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxxx somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxx:

- xxx x zdroj xxxxx,

- xxxxxxxxxx xxxxxxxxx a xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- xxxxxxxxx x xxxxx buněčného xxxxx,

- xxxxxxx dárce xxxx, xxx xxxx xxxxxxx xxxx krev nebo xxxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx,

- případně počet xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx kultury,

- xxxxxxx hodnota xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxxxxx xxxxx zastavující xxxxxxxx, xxxx xxxxxxxxxxx x xxxxx expozice xxxxx,

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

- složení xxxxx, xxxxxxxx koncentrace XX2,

- koncentrace xxxxxxxx xxxxx,

- objem xxxxxxxx x přidané zkoušené xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- případně xxxxxxx xxxxx xxx nasazení,

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

- xxxxxxxxx x xxxxxxxxx kontroly,

- metody xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky toxicity, xxxx. stupeň xxxxxxxxxx, xxxxx o buněčném xxxxx, xxxxx buněk, xxxxxxxxx xxxxx,

- známky xxxxxxx,

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

- definice xxxxxxx, xxxxxx gapů,

- xxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx a xxxx aberací zvlášť xxx xxxxxx xxxxxxxxxxx x kontrolní xxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx pozorovány,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- dosavadní údaje x negativní (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X. (1976), Cytological Xxxxxxx xxx Xxxxxxxxx Chemical Xxxxxxxx, xx: Chemical Xxxxxxxx, Xxxxxxxxxx xxx Xxxxxxx xxx xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, X. (xx) Xxxxxx Press, Xxx Xxxx xxx London, 1-29.

2) Xxxxxxxx, X. Xx., Xxxxxx, X. (1985), The Xx xxxxx Xxxxxxxxxxx Aberration Xxxx Using Chinese Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, in: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Xxxxx, X. xx xx., (xxx) Xxxxxxxx Science Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, S. X., Armstrong, M. X., Reuben, C., Xxxxxx, S., Xxxxx, X., Xxxxxx, X., Xxxxx, X. D., Xxxxxxxx, X., Xxxxx, X., Xxx, X., Xxxxx, X., Xxxxxxxx, X. X., Resnick, X. X., Xxxxxxxx, X., Xxxxxx E. (1978), Chromozome aberration xxx xxxxxx xxxxxxxxx xxxxxxxxx xx Chinese xxxxxxx xxxxx xxxxx: Xxxxxxxxxx xx 108 xxxxxxxxx, Environ. Xxxxx. Xxxxxxx. 10 (suppl. 10), 1-175.

4) Xxxxx, X., Galloway, X. X., Xxxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxxxx, X., Xxxxx, J., Xxxx, X. C. (1991), Xxxxxxxxxxxx under Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx from XXXXXX Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.

5) Xxxxxx, T., Xxxxxx, X., Xxxxxx, X., Xxxxxxx, X., (1992), Xxxxxxxxxxxxxx of xxx xX to Xxxxxxx Xxxxxxxx Mammalian Xxxxx, Xxxxxxxxxx Xxx., 268, 297-305.

6) Xxxx, X. X., McCann, X., Xxxxxxxx, X. (1975), Methods for Xxxxxxxxx Carcinogens xxx Xxxxxxxx with the Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 31, 347-364.

7) Xxxxx, X. M., Xxxx, X. X. (1983), Xxxxxxx Methods xxx xxx Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Xxx., 113, 173-215.

8) Xxxxxxxxx, X. X., Xxxxx, X. D., van Xxxx, X. X. X., Xxxxxxx, X., xx Xxxxx, X. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx xx x Xxxxxxxxxxx Xxxxxx In xxxxx, X. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Xxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Dimethylnitrosamine (XXX) xx XXX Xxxxx xx xxx Xxxxxxxx xx Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, X. X., Gatehouse, X. G., Gibson, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Party. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 in Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Sawamura, X., Xxxx, K., Xxxxxxxx, T. (1976), X. Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. s. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, xx: xx Serres, X. X., Fouts, X. X. Bend, J. X., Xxxxxxx, R. X. (eds), In xxxxx Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, Xxxxxxxx, North-Holland, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxx, X. X., Xxxxxxxx, D. J., Xxxxxx, X., Xxxxxxx, X., Sofumi, X. (1994), Xxxxxx from Xxxxxxx Xxxxx xx Xx xxxxx Xxxxx xxx Chromozomal Aberrations, Xxxxxxxxxx Res., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, X. A., Xxxxx, X. X., Xxxxxxxx, G., Chanter, X. O., Phillips, X. (1989), Xxxxxxxx xx Xxxx from Xx xxxxx Cytogenetic Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, Kirkland, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

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

15) Xxxxx, X. X., Xxxxxx, F. X., XxXxxxx, X. T. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Xxxx, X. R., Costa, X. L., Schaich, X. X. (eds), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, P. X., Xxxxxx, X. X., Xx, A. X., Xxxxxx, A. X. (1983), Evaluation of xx Xxxxxxxx System Xxxxx Xxxxx Grown xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx in xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.

17) Locke-Huhle, X. (1983), Endoreduplication xx Xxxxxxx xxxxxxx xxxxx during xxxxx-xxxxxxxxx xxxxxxx G2 arrest, Xxxxxxxxxx Xxx., 119, 403-413.

18) Xxxxx, Y., Xxxxxx, X., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx in Xxxxxxx xxxxxxx cells, Xxxxxx Res., 43, 1362-1364."


PŘÍLOHA 4X

"X.11 XXXXXXXXXX–XXXXXXX XX XXXXXXXXXXXX XXXXXXX X XXXXXXX KOSTNÍ XXXXX XXXXX XX XXXX

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx XXXX XX 475 — Zkouška na xxxxxxxxxxxx aberace v xxxxxxx kostní dřeně xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací xxxxxxxxxxxx xxxxxxxxx xxxxxx x xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Rozlišují se xxx xxxx strukturních xxxxxxx — xxxxxxxxxxxx x chromatidové. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx chemická látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx jsou xxxxxxxxxx xxxxxxx chromatidového xxxx, xxxxx chromozomové xxxxxxx xx xxxxxx vyskytují. Xxxxxxxxxxxx mutace x xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, xx chromozomové xxxxxx x související xxxx způsobující xxxxx x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx rakoviny x xxxxxxx x x xxxxxxxxxxxxxxxx systémech.

Při xxxx xxxxxxx jsou rutinně xxxxxxxxx xxxxxxxx. Xxxxxxx xxxxx xx v xxxx xxxxxxx kostní xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx tkání x xxxxxxxx xxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Jiné xxxxx x cílové xxxxx xxxxxx předmětem xxxx xxxxxx.

Xxxx xxxxxxx na xxxxxxxxxxxx aberace xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx metabolismu xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x různých xxxxx x tkání xxxxx. Xxxxxxx in xxxx xx xxxxxx užitečná xxx další xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx in xxxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, že xx xxxxxxxx xxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození xxxxxxxxxx v podobě xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

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

Endoreduplikace : xxxxxx, při xxxxxx x xxxxx xx X-xxxx xxxxxxxxx XXX xxxxxxx x mitóze, xxxxx následuje xxxxx X-xxxx. Xxxxxxxxx jsou xxxxxxxxxx xx 4, 8, 16,… xxxxxxxxxxxx.

Xxx : achromatická léze xxxxx než xxxxx xxxxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx xx normální xxxxxxx xxxxxxx u použitých xxxxx.

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

Xxxxxxxxxx aberace : mikroskopicky pozorovatelné xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx; xxxx xx xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx vystavena xxxxxxxx xxxxx xxxxxxx xxxxxxxx x ve xxxxxxx okamžiku xx xxxxxxxx se xxxxxx. Xxxx usmrcením xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx nebo Colcemid®). X xxxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxx x xxxxxx čínský, xxxxxx lze xxxxxx xxxxxxxx vhodný xxxxx xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx být xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx zvířata xx xxxxxxxx výběrem xxxxxxx xx kontrolní xxxxxxx x skupinu, která xx xxxxxxx xxxxxxxx xxxxx. Klece xx xxxx xxx xxxxxxxxxx xxx, aby xxx xxxx xxxxxx polohy xxxxxxxxxxxxx. Zvířata se xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech a xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx být xxxx xxxxxxx xxxxxxx. Xxxx xx být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx při xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx vyloučeno xxxxxxxxx, xx reaguje xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx jiná xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno nejdříve xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X výjimkou aplikace xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx podstoupit xxxxxxxxx xxxxxx jako xxxxxxx xx skupinách, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx kontroly xx xxxx xxxxxxxxxx strukturní xxxxxxx in xxxx xxx xxxxxxxxxxx úrovních, x nichž xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Dávky pozitivní xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx byl účinek xxxxxxxx, ale xxx xxx odečtu xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx podávána xxxxx způsobem než xxxxxxxx xxxxx a xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx kontrolu xxxxx xxx použity xxxxxxxx látky xx xxxxxx xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:

Látka

Číslo CAS

Číslo 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 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 xxx proveden xxxxx x negativních xxxxxxx, xxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx vehikulum x xxx jinak podstupují xxxxxx proces jako xxxxxxxxxx skupiny, pokud xxxxxx z xxxxxxxxxxx xxxxxxxxxxx údajů k xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx aberacemi. Xxxxxxx-xx se xxx xxxxxxxxx kontrolu xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx toho xx xxxx být xxxxxxxxxxxx xxxxxxxx použity xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x pohlaví zvířat

Každá xxxxxxxxxx a xxxxxxxxx xxxxxxx se xxxxxx x alespoň pěti xxxxxxxxxxxxxxxx xxxxxx pro xxxxx pohlaví. Jestliže xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx ze xxxxxx xx xxxxxxx xxxxxx x za použití xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx v xxxxxxxx, xxxx xxxxxxxxxxx zkoušení xxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx pohlaví, xxxx je xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, měla xx xxx xxxxxxx xxxxxxxxx xx zvířaty xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky xxxxx xxx podávány xxxx xx xxxx xxxxxxx, xxx. xxx dávky x týž den x rozmezí xx xxxx xxx xxxxxxxx xxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx xxxxxxxx ve xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxxx x jednom dni. X xxxxxxxx se xxxxx xxxxxxx po xxxxxx době xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx (xxxx xxxx obvykle 12 — 18 x). Xxxxxxxx xxxx nezbytná xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxx xxxxxx xx xxxxxxxx xxxxxxxxx cyklu xxxx xxx xxxx na xxxxxxxxx okamžik pro xxxxxxxxx xxxxxxxxxxxxxx aberací, xxxxxxxxxx se xxxxxxx xxxxx odběr xx 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx než xxxxxxx xxx, xxx xx xxx xxxxx proveden xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx odpovídá 1,5násobku xxxxxxxx délky buněčného xxxxx.

Xxxx xxxxxxxxx xx xxxxxxxx intraperitoneálně xxxx xxxxxx dávka xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx se po xxxxxx době xxxxxxx x zvířat xxxxx. X myši xx xxxx xxxx xxxxxxxxx 3 — 5 x; x xxxxxx xxxxxxxx xx tato xxxx přibližně 4 — 5 h. X kostní xxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xx xx xxxxxxxxxxxx xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx studie pro xxxxxxxx rozsahu xxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, jež xx použijí x xxxxxx studii (5). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx maximální x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx bude použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx vyšší xxxxx xx xxxxx xxx stejném režimu xxxxxxxxx podle očekávání x letalitě. Látky xx xxxxxxxxxxx biologickou xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší dávka xxxx xxx také xxxxxxxxxx xxxx dávka xxxxxxxxxxxx x kostní xxxxx xxxxxxx známky xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx xxx nevykazuje xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx studie xx xxxxx úrovněmi xxxxx xx nezbytnou. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx a xxx xxxxx xxx 14xxxxx xxxxxxxx xx xxxxxxx dávkou 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx znamenat potřebu xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx jsou x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxxxxxxx nebo injekčně, xxxxxx xx velikosti xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, než xx uvedený objem, xxxx xxx zdůvodněno. Xx xx xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx při xxxxxxx koncentracích vykazují xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx úrovních dávky.

1.5.6 Xxxxxxxx preparátů pro xxxxxxx chromozomů

Ihned xx xxxxxxxx xx xxxxxxx xxxxxx xxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxxx xx nanesou xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx xxx xxx x všech exponovaných xxxxxx (včetně pozitivních xxxxxxx) x x xxxxxxxxxxxxxx zvířat pro xxxxxxxxx kontrolu stanoven xxxxxxxxx index, x xx xxxxxxx u 1000 buněk xx xxxxx xxxxx.

X každého xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 buněk. Xxxxx xxxxx xxx snížit, xx-xx pozorován xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx dochází xx xxxxxxxxxxxxxx zlomům xxxx ke xxxxxx xxxxxxxxxx x části xxxxx x metafázi, xxxx by vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx počet xxxxx, xxxxx aberací xx buňku x xxxxx buněk x xxxxxxxxxxxxx aberací (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxx být xxxxxxx xxxxx typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx xxxxxx xx xxxxxxxxxx do celkové xxxxxxxx xxxxxxx. Neexistuje-li xxxxx o rozdílu x xxxxxxxx xxxx xxxxxxxxx, mohou xxx xxx statistickou analýzu xxxxx xxx xxx xxxxxxx zkombinovány.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx dávce xxxx xxxxx nárůst xxxxx xxxxx x xxxxxxxxx xxx skupinu x určitou xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická relevance xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (6). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx zkoušením, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx indukovat numerické xxxxxxxxxxxx xxxxxxx. Nárůst xxxxx buněk s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx může xxxxxxxx, xx zkoušená xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx buněčného xxxxx (7, 8).

Zkoušená xxxxx, jejíž xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, xx xxxxxxxx x tomto xxxxxxx xx nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx poskytne jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx o xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx bez xxxxxx na xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxxxxxx xxxxxxx xx vivo xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx pravděpodobnost, x xxxxx xx xxxxxxxx xxxxx nebo její xxxxxxxxxx xxxxxxxx xx xxxxxxxx oběhu, xxxx xxxxxxxxxx xx cílové xxxxx (např. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx o zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- použitý xxxx/xxxx,

- počet, stáří x xxxxxxx zvířat,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- individuální xxxxxxxx xxxxxx na xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx hodnoty x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

- údaje xx xxxxxx xxx xxxxxxxx xxxxxxx, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- xxxxx o přípravě xxxxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění způsobu xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, zda xx xxxxxxxx xxxxx xxxxxxx xx krevního xxxxx xxxx do cílové xxxxx,

- případně přepočet xxxx koncentrací zkoušené xxxxx x krmivu xxxx xxxx (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx xxxxxx a xxxx,

- podrobný xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- identifikace xxxxx xxxxxxxxxxx metafázi, xxxx xxxxxxxxxxx x xxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- mitotický xxxxx,

- xxx x xxxxx aberací uvedený xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx ve xxxxxxx xx xxxxxxxxx hodnotami x směrodatnými xxxxxxxxxx,

- xxxxx buněk x xxxxxxxxx xx skupině xx xxxxxxxxx hodnotami x směrodatnými xxxxxxxxxx,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxx údaje x xxxxxxxxx xxxxxxxx x rozpětími, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

2) Preston, X. X., Dean, X. X., Xxxxxxxx, X., Holden, H., XxXxx, X. X., Xxxxxx, M. (1987), Xxxxxxxxx Xx vivo Xxxxxxxxxxx Xxxxxx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Xxxx Xxxxxx Xxxxx, Xxxxxxxxxx Res., 189, 157-165.

3) Xxxxxxx, X., Chandley, A., Xxxxx, X., Xxxxxxxxx, X. X., Xxxxxxx, X., Xxxxxxxxx, L. (1990), In xxxx Xxxxxxxxxxx Assays, in: X. X. Kirkland (xx.), Xxxxx Mutagenicity Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

4) Xxxx, X. X., Xxxxxxx, X., XxxXxxxxxx, X. X., Xxxxxxxx, D., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, F., Xxxxxxx, X. J., Xxxxxxx, X., Shimada, X., Xxxxx, X., Vannier, X. (1994), Xxxxxx xxxx xxx Xxxxxxx Xxxxx xx the xx xxxx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Test, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. R., Xxxxxx, X. X., Xxx, X., Esdaile, X. X., Gatehouse, X. X., Xxxxxx-Xxxxxx, X., Morton, D. X., Xxxxxxxx, D. X., Richold, X. (1992), Report xx Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx in In xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, X. X., Clare, X., Xxxxxxxx, R., Xxxxxxx, X., Papworth, D. X., Savage, X. X. K. (1989), Xxxxxxxxxxx Analysis xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Testing, Xxxxxx Xxxx III. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Test Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

7) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx cells xxxxxx xxxxx-xxxxxxxxx-xxxxxxx G2 xxxxxx, Xxxxxxxxxx Xxx., 119, 403-413.

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


PŘÍLOHA 4X

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx pro xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx, x xx xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx dřeně x/xxxx xxxxx periferní xxxx, xxxxxxx hlodavců.

Účelem xxxxx xxxxxxx erytrocytárních xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxxxxx poškození, xxxxx xxxxxxxxx je xxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx nebo xxxx xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx dřeně mění xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx xxxxx xx xxxxxxxx x xxxxxxxxxx, xxxxx při xxx xxxxx xxxxxxxxx, zůstávají x cytoplasmě, která xxxxx xxxxx neobsahuje. Xxxxxxxxxxxx xxxxxxxxxx xx x xxxxxx xxxxxxx xxxxxxxxx tím, že xxxxxxxxxx hlavní xxxxx. Xxxxxx xxxxxxx polychromatických xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx je xxxxxxx xxxxxxxxx xxxxxx dřeň xxxxxxxx, poněvadž xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů x xxxxxxxxxx v periferní xxxx je xxxxxxxxxx xxxxxxxxxx x xxxxxxxxxxx xxxxx, x něhož xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx erytrocyty x xxxxxxxxxx, xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, které způsobují xxxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx přítomnosti nebo xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx se xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx zralých (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x periferní xxxx, které xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx na xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx rovněž xxxxxx jako xxxxxxx xxxxxxxx zkoušky, xxxxxxxx xxxx xxxxxxx exponována xxxxx xxxxx xxxx xxxx.

Xxxxx test savčích 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, jakož x x genetického xxxxxxxx. Zkouška xx xxxx xx xxxxxx xxxxxxxx pro xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx x systémech xx xxxxx.

Xxxxxxxx existuje xxxxx x xxx, xx xx xxxxxxxx xxxxx nebo reaktivní xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, není xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Obecný xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (oblasti) xxxxxxxxxx, x xxx (k xxxx) xx během xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx xxxxx dceřiných xxxxxxxxxx x pólům xxxxxxxxx buněk.

Mikrojádra : xxxx xxxxx xxxxxxxxxx xxxxxxxx od xxxxxxxx xxxxx x vedle xxxx, xxxxxxxxx xxxxx xxxxxxxx mitosy (xxxxxx) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx erytrocyt xxxxxxxxxxxx ribozomy, který xxx xxxxxxxx xx xxxxxxxxx polychromatických erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

Xxxxxxxxxxxxxxx erytrocyt : xxxxxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx obsahuje xxxxxxxx, x xxxx xxx xxxx rozlišen od xxxxxxx xxxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx selektivním pro xxxxxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx zkoušené xxxxx. Xxx použití xxxxxx dřeně se xxxxxxx xx vhodném xxxxxxxx po xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx xxxx, xxxxxxxx xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx periferní xxxx xx krev xx vhodném okamžiku xx xxxxxxxx odebere, xxxxxxxxxx se připraví xxxxxxxx x xxxxxx xx (4, 8, 9, 10). Při xxxxxxxx x xxxxxxxxx xxxx by xxxx xxxx xxxxxxxx expozicí x xxxxxxxxx xxxxx xxxxxxxx xx nejkratší xxxx. Preparáty jsou xxxxxxxxxxx xx přítomnost xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx použití xxxxxx dřeně se xxxx testovací zvíře xxxxxxxxxx xxx xxxx xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxxx xxxx. Při xxxxxxx xxxxxxxxx xxxx xx doporučuje xxx. Xxx však použít xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx jde x xxxx, x xxxxx xxxxxxx neodstraňuje erytrocyty x mikrojádry, nebo xxxx xxxxxxxxxx dostatečnou xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx chromozomové xxxxxxx. Měly by xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x hmotnosti xxxxxx minimální x xxxxxx by x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx B, xxxxxxx xx mělo xxx xxxxxxxx vlhkosti xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, u xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx. Klece xx xxxxxxxxxx tak, xxx xxx xxxx xxxxxx xxxxxx minimalizován.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x popřípadě xxxxxxx. Xxxxxxx zkoušené látky xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x jejich xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx úrovních xxxxx xxxxxxx účinky x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx pohlaví. X xxxxxxxx aplikace zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx mikrojádra xx xxxx při xxxxxxxxxxx xxxxxxxx, u xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx zřetelný, xxx xxx xxx xxxxxx xxxxxxx ihned xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxxxxxxx kontrola byla xxxxxxxx xxxxx xxxxxxxx xxx zkoušená xxxxx x xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Pro xxxxxxxxx xxxxxxxx navíc může xxx xxxxx x xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo podle 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 monohydrát

6055–19–2

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

51–18–3

200–083–5

X okamžiku odběru xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx kontroly, xxxxx je aplikováno xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx xxxxxxxxxx stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx nejsou x xxxxxxxxxxx kontrolních xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Xxxxxxx-xx xx xxx negativní kontrolu xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx odběru. Xxxxx xxxx xx měly xxx neexponované kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

Při použití xxxxxxxxx krve xxxx xxx xxxx negativní xxxxxxxx přijatelný xxxx xxxxxx xxxx odebraný xxxx xxxxxxxx, xxxxx xxxx x xxxxxxxx xxxxxx x xxxxxxxxx xxxx (např. 1 — 3 aplikace) xx xxxxxxxxxxx, že xxxxxxxx xxxxx xxxxx x rozpětí, xxxxx xx xx xxxxxxx xxxxxxxxxxx kontrol xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx skupina xx musí skládat x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví (11). Xxxxxxxx jsou x xxxx xxxxxx x xxxxxxxxx údaje ze xxxxxx se stejným xxxxxx x xx xxxxxxx stejného způsobu xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx pohlaví. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx x xxxxxxxxx farmaceutických látek, xxxx xx xxx xxxxxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxx (xx. xxxxx, xxx xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx xx xxxxxx x prodlouženým xxxxxxx xxxxxxxx jsou xxxxxxxxxx, pokud xx x xxxxxx xxxxxx xxxxxxx xxxxxxxxx výsledky, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx xxxx xxxxxxxxx xxxxxxxx nebo xxxx xxxxxxxxx limitní xxxxx x podávání pokračuje xx do xxxxxxxx xxxxxx. Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, tzn. xxx xxxxx v xxx xxx v rozmezí xx xxxx než xxxxxxxx xxxxx, xxx xxxx usnadněno xxxxxxxx xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx být proveden xxxxx způsoby:

a) xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx jednou. Xxxxxx xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx první xxxxx xx provede nejdříve 24 xxxxx po xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci x x xxxxxxxxxx odstupem xxxx xxxxxx. Xxxxx xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx být xxxxxxxxx. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx první xxxxx xx xxxxxxx xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx po xxxxxxxx x xx xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx odpověď, xxxx xxxxx xxxxx xxxxx;

x) xxxx-xx podávány xxx xxxx xxxx dávek xxxxx (xxxx. xxx xxxx více xxxxx x xxxxxxxxx 24 xxxxx), měly by xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx xx 18 xx 24 xxxxxxxx xx xxxxxxxx xxxxxxxx a xxx xxxxxxx periferní xxxx xxxxxx xx 36 xx 48 hodinách xx poslední aplikaci (12).

Xxxxx xxxxxxx mohou xxx xxxxx xxxxxxx xxxx doby odběru.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx rozsahu xxxxx, xxxx xx xxx xxxxxxxxx ve stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx stejného xxxxxx expozice, xxx xx xxxxxxx v xxxxxx studii (13). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx až xxxxxxxxx toxicitou, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx stačí, xxxx bude xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx dávka je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle očekávání x xxxxxxxx. Látky xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx případ od xxxxxxx. Xxxxxxxx xxxxx xxxx být xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (např. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx krvi).

1.5.4 Limitní xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx nevykazuje xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx xxxxx studie xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx aplikaci xx xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx expozice člověka xxxx znamenat xxxxxxx xxxxxx x limitní xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx se obvykle xxxxxx nitrožaludečně, žaludeční xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx xx xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx zesílené xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx se xxxxxxx xxxxxxxxx x xxxxxx xxxx tibie xxxxx xx xxxxxxxx. Xxxxx xx xxxxxxxx x xxxxxx xxxx xxxxx a xxxxxxxxxx xxxxxxxx se xxxxxxxxx x xxxxxx. Periferní xxxx se xxxxxxx x xxxxxx xxxx xxxx jiné vhodné xxxxxx xxxx. Xxxxxx xxxxx se xxxxx xxxxxxxxxxxx obarví (8, 9, 10), xxxx xx xxxxxxxx xxxxxxxxx xxxxxxxx a xxxx xx obarví. Použitím xxxxxxx specifického pro XXX (např. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) se xxx xxxxxxx některým xxxxxxxxxx xxxxxxxx x xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx XXX. Xxxx xxxxxx nebrání použití xxxxxxxxxxx xxxxxx (např. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. xxxxxxxxxx kolona x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, xx se xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx systémů xxx xxxxxxxxx mikrojader x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx každé xxxxx xx stanoví xxxxx nezralých xxxxxxxxxx x celkového (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x xxxxxxx kostní xxxxx xxxxxxx xxxxxxx xxxxxxx 200 xxxxxxxxxx x x xxxxxxx xxxxxxxxx xxxx alespoň 1000 xxxxxxxxxx (17). Xxxxxxx preparáty xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx kontrol, xx xxxx xxx před xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxx alespoň 2000 xxxxxxxxx erytrocytů xx xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx mikrojader. Xxx mikroskopické xxxxxxx xx xxxxx xxx xxxxx nezralých erytrocytů x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx nepřetržitě xxxxx xxxxx xxxx xxxx, xxx xxxx xxxxxxxx xx xxxxxx xxxxxxxxxx alespoň 2000 xxxxxxx xxxxxxxxxx na xxxxx zvíře. Xxxxxxx xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx a xxxxxxxxx cytometrická xxxxxxx xxxxxxx xxxxxxxx) jsou xx odpovídajícím xxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx hodnocení.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx zvířata xx xxxx být xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxxxxxxxx xxxxx xx měl xxx xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, počet xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x počet xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx jsou zvířata xxxxxxxxxx nepřetržitě xxxxx xxxxx xxxx déle, xxxx xx být xxxx xxxxxxx údaje x zralých xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx se xxxxx xxxxx xxxxxxxxx xxxxxxxxxx z celkového xxxxxxxx xxxxxxxxxx a xxxxxxxx množství xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x rozdílu x xxxxxxxx mezi xxxxxxxxx, xxxxx být xxx xxxxxxxxxxxx analýzu xxxxx pro obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx počtu xxxxx x xxxxxxxxxx x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx buněk x mikrojádry xxx xxxxxxx s xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx použity xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Statistická významnost xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x úpravou xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx látka, jejíž xxxxxxxx nesplňují xxxx xxxxxxx xxxxxxxx, se xxxxxxxx v xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx látky. Xxxxxxxx mohou xxxxxx xxxxxxxxxx nebo sporné xxx xxxxxx xx xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx mikrojádra xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx mikrojádra, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx mitotického xxxxxxx xxxxxxxxxxxx testovacího xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx zkoušená látka xx xxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx erytrocytech testovacího xxxxx.

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

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby 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 atd.,

- individuální xxxxxxxx zvířat xx xxxxxxx xxxxxxx, včetně xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx a xxxxxxxxxx odchylka xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- údaje xx xxxxxx pro xxxxxxxx xxxxxxx, xxxxx byla xxxxxxxxx,

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x přípravě zkoušené xxxxx,

- údaje o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, xxx xx xxxxxxxx xxxxx dostala xx xxxxxxxx xxxxx xxxx xx xxxxxx xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx zkoušené látky x krmivu nebo xxxx (ppm) xx xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx stanovení xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx erytrocytech,

- xxxxx xxxxxxxxxxxxx xxxxx xx jedno zvíře,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxx nezralých xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx,

- počet xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx uvedený xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx hodnota ± xxxxxxxxxx odchylka xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx ve xxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x metody,

- xxxxx x xxxxxxxx x xxxxxxxxx negativní xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxxx, X. X. (1973), X Xxxxx Xx xxxx Xxxx xxx Xxxxxxxxxxx Xxxxxx, Mutatation Res., 18, 187-190.

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

3) Xxxxxx, X. X., Xxxxxxxx, M. X., Xxxx, X., Xxxxxxxx, X., Xxxxxxxxx, K., XxxXxxxxx, X. G., Xxxxxx, X. X. (1983), The Xxxxxxxxx xx Micronuclei a. x. x Xxxxxxx xx Xxxxxxxxxxxx, Mutatation Xxx. 123, 61-118.

4) Xxxxxxxxx, X. H., Xxxxxx, X. X., Xxxxxx, M. X., Xxxxxxxx, X. F., Xxxxxx, X. X. (1990), Xxx In xxxx Xxxxxxxxxxxx Xxxxx xx Mammalian Bone Xxxxxx xxx Xxxxxxxxxx Xxxxx. X report xx xxx X. X. Environmental Xxxxxxxxxx Xxxxxx Gene-Tox Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, J. X., Xxxxxxxx, R., Xxxx, X. X., Xxxx, C. X. (1983), Micronuclei in Xxxxxxxxxxx Erythrocytes: X Xxxxx Screen for Xxxxxxxxxxx Xxxxxx During Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, in: Xxxxxxxxxxxx in Xxxxxxx xxx Practice xx Xxxxxxxxxx, xx. X. X. Hayes, X. X. Xxxxxxx, X. X. Miya. Elsevier, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Xxxxxx, X. X. Xxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, M. F., Xxxx, R. X., Xxxx, D. (1987), Xxxxxxxxxx for xxx Xxxxxxx of Xxxxxxxxxxxx Xxxxxx xx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) MacGregor, X. X., Xxxx, X. X., Xxxxxx, P. X., Shelby, M. X. (1990), The xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Steady Xxxxx Xxxxxxxxx Assay Xxxxxxxxxx xxx Xxxxxxx Integration xxxx Xxxxxxxx Xxxxxxx, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

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

9) Xxx Xxxxxxxxxxxxx Study Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (1992). Xxxxxxxxxxxx Xxxx xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxx by Xxxxxxxx Xxxxxx Xxxxxxxxxx Staining: Xxx Xxxxxxx Xxxxxx xx the 5xx Xxxxxxxxxxxxx Xxxxx xx XXXXX/XXXXX, XXX, Mutatation Xxx., 278, 83-98.

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx the Xxxxxxxxxxxx Test (XXXXX/XXXXX, XXX: Xxx Mammalian Xxxxxxxxxxx Xxxxx Xxxxx xx the Xxxxxxxxxxxxx Xxxxxxx Society xx Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx xxx xxx xxxxx-xxxx mouse peripheral xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., XxxXxxxxx, X. X., Anderson, X., Blackey, X. X., Xxxxxx-Xxxxxxx, X., Xxxxxx, Jr. F. X., Xxxxxxxxxxxx, F., Xxxxxxx, X., Shimada, X., Sutou, X., Xxxxxxx, X. (1994), Xx vivo Rodent Xxxxxxxxxxx Xxxxxxxxxxxx Xxxxx, Xxxxx. Res., 312, 293-304.

12) Xxxxxxxxxxx, N., Xxxxx, S. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx xxxx xx 30 ± 6 x after double xxxxxx xx xxx xxxxx xxxxxxxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Xxxxxxx, R. X., Xxxxx, X. X., Xxxxxx, X. X., Botham, X. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. B., Kirkland, X. J., Xxxxxxx, X. (1992), Xxxxxx xx British Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Working Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

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

16) Xxxxxxx, X., Xxxxxxxxxx, X. X. (1989), Xxx automated xxxx xxxxxx micronucleus xxxx, Mutatation Res., 213, 91-104.

17) Xxxxxxxxx, X., XxXxxxxx, L. X. (1995), Xxxxxx Xxxx xxx the Xxxxxxxxxx xx Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx xx xxx Xxxx Xxxxxx Micronucleus Xxxx, Mutatation Res., 347, 97-99.

18) Xxxxxxx, X., Ashby, J., Xxxxxxx, X., Chandley, X., Xxxxxxxxx, X. X., Henderson, X. (1990), In xxxx Xxxxxxxxxxxx Assay, xx: X. X. Kirkland (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, New York, Xxxx Chester, Melbourne, Xxxxxx, 115-141.

19) Xxxxxx, X. P., Anderson, X., Albanese, R., Xxxxxxxx, X. E., Xxxxx, G., Xxxxxxxx X., Xxxxxxx, X., Xxxxxxxx, X. G., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx of Xx xxxx Xxxxxxxxxxx Assays, xx: D. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx of Mutagenicity Xxxx Xxxx. UKEMS Xxx-Xxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx XXX, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, New York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4D

"B.13/14 XXXXXXXXXX — XXXXXXX XX XXXXXXXX MUTACE X XXXXXXXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody XXXX TG 471 — Zkouška xx xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 ÚVOD

Při xxxxxxx na xxxxxxxx xxxxxx s bakteriemi xx používají bakteriální xxxxx závislé na xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x xxxxxxx xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx a xxxxxx jednoho xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx této xxxxxxx xx reverzní xxxxxx s bakteriemi xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx obsažené x xxxxxxxxxxx xxxxxxx a xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx aminokyseliny. Xxxxxxxx xx reverzi xxxx xxxxxxxxxx díky xxx xxxxxxxxxx růst x xxxxxxxxxxxxx aminokyselin, které xxxx vyžadovány mateřským xxxxxxxxxx kmenem.

Bodové xxxxxx x xxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x člověka x xxxxxxxx xxxxx xxxxxx x tom, xx xxxxxx xxxxxx x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx xxxx xxxxx xx tvorbě xxxxxxxx x člověka x u xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx mutace s xxxxxxxxxx xx rychlá, xxxxxxxxxx x relativně xxxxxx. Xxxxx xxxxxxxxxxx xxxxx xx xxxx xxxxxxxxxx, xxxx xxxx xxxx xxxxxxxxxx xx xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx buněk xxx velké xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx procesů XXX xxxxxxxxxx x xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx může poskytnout xxxxxxx xxxxxxxx xxxxxxxxx x xxxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xx x dispozici xxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx struktur x xxxx xxxx vyvinuty xxxxx vyzkoušené xxxxxx xxxxxxxx chemických látek, xxxxxx těkavých xxxxxxxxx, x xxxxxxx fyzikálně-chemickými xxxxxxxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx xx reverzní xxxxxx x bakteriemi Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (histidin xxxx. xxxxxxxxx), xxxxxxx vzniká xxxx nezávislý xx xxxxxxx přísunu aminokyseliny.

Mutageny xxxxxxxxxx xxxx xxxx xxxx xxxxxxxx, jež xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx mutací xx xxxxx tyto xxxxx vyskytnout na xxxxx xxxxxxx xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx mutageny xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx xxxx xxxxxx jednoho xxxx xxxx párů xxxx XXX x posunují xxx čtecí rámec XXX.

1.3 VÝCHOZÍ XXXXX

Xxx xxxxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx využívají xxxxxxxxxxxxx xxxxx, xxxxx se xxxx xx xxxxx xxxxx xxxxxxx, jako xxxx xxxxxx, metabolismus, xxxxxxxxxxxx struktura x xxxxxxxxx xxxxxxx XXX. Xxxxxxx xxxxxxxxx in xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx o xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx zpravidla využívána xxx xxxxxxxxx vyšetření xxxxxxxxxxx xxxxxxxx, x xxxxxxx aktivity xxxxxxxxxxxx xxxxxx xxxxxx. Z xxxxxxxx xxxxxxxx vyplývá, xx xxxxx xxxxxxxxxx xxxxx, xxxxx jsou x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx x x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxxxx xxxxxxxxxx xxxxx zkouškou. Příčiny xxxxxx skutečností lze xxxxxxxxx ve xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x rozdílech x xxxxxxxxxxx xxxxxxxx xxxx x xxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx. Na xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxx xxxxxxx na xxxxxxxx xxxxxx na xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx reverzní mutace x xxxxxxxxxx xxxxxx xxx vhodná pro xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx vysoce xxxxxxxxxxxx sloučeniny (xxxx. xxxxxx xxxxxxxxxxx) a xxx chemické látky, x xxxxx se xxxxxxxxxxx (nebo x xxxxx xx xx), xx specificky zasahují xx replikačního systému xxxxx xxxxx (xxxx. xxxxxxx inhibitory xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). V takových xxxxxxxxx mohou xxx xxxxxxxxx xxxxxxx mutagenity x savců.

Přestože xxxxx xxxxxxxxx, xxx něž xx tato xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, xxxx xxxxxxxx xxxxxxxxx. Xxxxxx xx chemické xxxxx x xxxxxxxx mnoho xxxxxxxxxxx, jež xxxxxx xxxxxxxxxx xxxxx zkouškou, xxxxx působí xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx látce, x to xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx xxxx. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx x vrchním xxxxxx x xxxxx xx xxxxxxx na xxxxxxxxx xxxx. V xxxxxxxxxxxx xxxxxx xx zkoušená xxxx xxxxxxxx x xxxx xx xxxx xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx s xxxxxxx xxxxxx. Xxx xxxx technikách xx xx xxxx nebo xxxxx xxxxx inkubace xxxxxxxxx xxxxxxx xxxxxxxxxx x provede se xxxxxxxx x xxxxxx xxxxxxx xxxxxxxxxxx revertantů xx xxxxxxxxx xxxxx x rozpouštědlem.

Je xxxxxxx xxxxxxx xxxxxxx xxxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx. Xxxx xxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx xxxx (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx xxx xxxxxxxx xxxxx x xxx xxxx popsány (12).

Zde xxxxxxx xxxxxxx xx xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx testu x xxxxxxxxxxxxxx xxxxx. Xxxxx x nich xx xxxxxxxxxx pro provádění xxxxxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Některé xxxxx xxx účinněji xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx xxxxx xx xxxxxxxxxx tříd, xx xxxxx patří xxxx xxxxx krátké xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx kovy, xxxxxxxx, xxxxxxxxxx a xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx se připouští, xx určité třídy xxxxxxxx xxxxx vždy xxxxxxxxx standardními xxxxxxx, xxxx je xxxxxxxxxx xxxxxxx test nebo xxxxxxxxxxxx metoda. Měly xx xxx xxxxxxxxxx xx "xxxxxxxx případy" x x xxxxxx xxxxxxx se xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Je možné xxxxxxxxxxxxx tyto "xxxxxxxx xxxxxxx" (xxxxxxxx x xxxxxxxx xxxxxxx xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x xxxxxx xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Odchylka xx xxxxxxxxxxxx postupu musí xxx xxxxxxx zdůvodněna.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx měly xxx xxxxxxxxxxx xx xxxxxx xxxxxxxxxxxxx fáze xxxx xx xxxxx xxxxxxxxxxx xxxx růstu (xxxxxxxxx 109 buněk xx xx). Xxxxx x xxxxxx stacionární xxxx by neměly xxx xxxxxxx. Je xxxxxxxx, aby měly xxxxxxx xxxxxxxx vysoký xxxx životaschopných xxxxxxxx. Xxxx xxxx xxx xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x růstové xxxxxx, xxxx pro xxxxxx xxxxxxx stanovením xxxxx xxxxxxxxxxxxxxx buněk xx xxxxxxx.

Xxxxxxxxxx inkubační xxxxxxx xx 37 °X.

Xxxx by xxx xxxxxxx alespoň xxx xxxxx xxxxxxxx. Mezi xxxx xx xxxx xxx xxxxx xxxxx X. xxxxxxxxxxx (XX1535; XX1537 xxxx TA97a xxxx XX97; XX98 x TA100), xxxxxxx xxxxxxx xx ukázala x různých xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx S. xxxxxxxxxxx xxxx xxx xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx xxxxx, xx xxxxxx prostřednictvím nelze xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx vláken DNA x hydraziny. Xxxx xxxxx mohou být xxxxxxxxxx xxxxx X. xxxx XX2 xxxx X. typhimurium TA102 (19), které mají xx primárním reverzním xxxxx xxx xxxx XX. Xxxxxxxxxx xxxxxxxxx xxxxx je tedy xxxx:

- X. typhimurium XX1535 a

- S. xxxxxxxxxxx XX1537 xxxx XX97x x

- S. xxxxxxxxxxx TA98 x

- X. xxxxxxxxxxx XX100 x

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

Pro xxxxxxx xxxxxxxx způsobujících xxxxxxxxxx vláken XXX xxxx být xxxxxxxxx xxxxxxx XX102 xxxx xxxxxx kmen X. xxxx x vysokou xxxxxxxxxx xxxxxxxx XXX, (xxxx. X. coli XX2 (xXX101)).

Xxxx by xxx použity zavedené xxxxxxx přípravy xxxxxxx xxxxxxx, xxxxxxxxxx xxxxxxx x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx kulturu (xxxxxxxx pro xxxxx X. xxxxxxxxxxx a xxxxxxxxx xxx X. xxxx). Xxxxxxx xx xxxx být kontrolovány xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx TA98, XX100 x XX97x xxxx XX97, XX2 uvrA x XX2 xxxX (xXX101) x xxxxxxxxxxxx x tetracyklinová xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx mutací x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x xxxX xxxxxx x E. xxxx xxxx xxxX xxxxxx u X. xxxxxxxxxxx citlivostí xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx xx xxxx xxxxxx xxxxx xxxxx kolonií xxxxxxxxxxx xxxxxxxxxx na misce x xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx laboratorních xxxxxxx x xxxxxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Médium

Použije xx xxxxxx minimální xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) x glukosu) x vrchní xxxx xxxxxxxxxx histidin x xxxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxx buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx xxxxxxxx

Xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx látce, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx postmitochondriální frakce (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx indukujícím enzymy, xxxx xx Aroclor 1254 (1, 2) xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx xxxxxx xx xxxxxxx používána x koncentracích v xxxxxxx 5 xx 30 % xxx. xx xxxxx X9. Xxxxx x podmínky xxxxxxxxxxxxx aktivačního xxxxxxx xxxx záviset na xxxxx xxxxxxxx xxxxxxxx xxxxx. V xxxxxxxxx xxxxxxxxx xxxx být xxxxxx xxxxxx xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx x diazoniových xxxxxxxxx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx aktivačního systému (6, 13).

1.5.1.4 Zkoušená xxxxx nebo přípravek

Pevné xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx přímo x xxxxxxxxxx systémům x/xxxx xxxxx být xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx by xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou, x xxxx xx xxx xxxxxxxxxx s xxxxxxxx xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by být xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx nejdříve xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx zkoušení xxxxx xxxxxxxxx ve xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx podmínky

1.5.2.1 Xxxxxxxx xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx být xxxxxxxxxx xxx stanovení xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x předběžných xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx snížením xxxxx kolonií xxxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxx přežití xxxxxxxxxxxx kultur. Xxxxxxxxxxxx xxxxx xx xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx aktivačních xxxxxxx. Xxxxxxxxxxxxx by xxxx xxx xxxxxxxxx na xxxxxxx viditelného xxxxxxx x xxxxxxx xxxxx xx xxxxxxxxxx zkušebních xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx zkušební xxxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxxx xxxxx je 5 xx/xxxxx xxxx 5 μx/xxxxx. X xxxxxxxxxxxxxxx xxxxx nerozpustných xxx koncentracích 5 xx/xxxxx nebo 5 μx/xxxxx by xxxx xxx jedna nebo xxxx zkušebních xxxxxxxxxxx xxxxxxxx, aby xxxxx xxxx x xxxxxxx xxxxx pro aplikaci xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx jsou xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, xx měly xxx xxxxxxxx xx xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

Xxxx xx xxx použito xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx koncentrací xxxxxxxx xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx xx xxxx xxx intervaly xxxx xxxxxxxxxx xxxx xxxxx přibližně xxxxxxxx xxxxx xxxxxxxxxxxx stupnice (xx. Ö10). Xxxxx xxxxxxxxx xxxx xxxxxx x xxxxxxx, xxx xx vyšetřuje křivka xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Xxxxxxxx koncentrací xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx může být xxxxxxx xxx xxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx potenciálně xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx kontroly

Součástí xxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx s xxxxxxxxxxxx xxxxxxxx a bez xx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x použitím xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxx (xxxxx) pro pozitivní xxxxxxxx xxxxxxx (vybrány) xx xxxxxxx typu xxxxxxxxx kmene xxxxxxxx.

Xxxxxxxxx xxxxxx pozitivní kontroly x xxxxxxx x xxxxxxxxxxxx aktivací jsou xxxx xxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx EINECS

9,10-dimethylanthracen

781–43–1

212–308–4

7,12-dimethylbenzo[a]anthracen

57–97–6

200–359–5

benzo[a]pyren

50–32–8

200–028–5

2-aminoanthracen

613–13–8

210–330–9

Cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

Xxxx xxxxx je xxxxxxx xxxxxxxxx xxxxxxxxx pro xxxxxx redukční xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Xxxxxx Xxx 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx xxxxx xxx xxxxxx jako xxxxxx xxxxxxxxx xxxxxxxxx xxxxx S9. Xxx xxxxxxx 2-aminoanthracenu xx xxxx xxx každá xxxxx X9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, například benzo[a]pyren xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx kmenověspecifické xxxxxxxxx xxxxxxxx x xxxxxxx xxx xxxxxx xxxxxxxxxxx xxxxxxxx xxxx xxxx xxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx xxxxx

26628–22–8

247–852–1

XX1535 x XX100

2-xxxxxxxxxxxx

607–57–8

210–138–5

XX98

9-xxxxxxxxxxxx

90–45–9

201–995–6

XX1537, TA97 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 XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 uvrA a XX2 xxxX (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 uvrA x XX2 uvrA (xXX101)

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

3688–53–7

xxxxx obsahující plasmidy

Pro xxxxxxxxx kontrolu xxxxx xxx použity xxxx xxxxxx xxxxxxxxxx xxxxx. Xxx pozitivní xxxxxxxx xx xxxx xxx xxxxx x xxxxx xxxxxxx chemických xxxxx xx stejné xxxxxxxx xxxxx, xxxx xx x dispozici.

Měly xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx toho xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, neexistují-li dosud xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx miskové xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx aktivace se xxxxxxx smíchá 0,05 xx xxxx 0,1 xx zkušebních xxxxxxx, 0,1 ml xxxxxxx xxxxxxxxxxx kultury (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx sterilního xxxxx x 2,0 ml xxxxxxxx xxxxx. V xxxxxxx xxxxxxx s xxxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx postmitochondriální frakce (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx xxxxx) s xxxxxxx xxxxxx (2,0 xx) a xxxxxxx x xxxxxxxxxx x xxxxxxxxx látkou nebo xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx x xxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx na xxxxx. Xxxx xxxxxxxx xx xxxxx vrchní xxxx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) xx zkoušená xxxxx xxxx xxxxxxxx xxxxxx před smícháním x xxxxxxx agarem x xxxxxxxx přes xxxxxx xxxxxxxxxxx xxxxx xx misce obvykle 20 xxxxx xxxx xxxx xxxxxxxxxxx x xxxxxxxxxx kmenem (obsahujícím xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a sterilním xxxxxx nebo metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 xxxx 0,1 xx zkoušené xxxxx xxxx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxxx x 0,5 ml xxxxx X9 nebo xxxxxxxxxx xxxxx s 2,0 xx vrchního xxxxx. Xxxxxxxx by xxxx xxx xxxxx xxxxxxxx provzdušňovány xx xxxxxxxx.

X dostatečnému odhadu xxxxxxxx xx xxxx xxx při každé xxxxxx dávky xxxxxxx 3 xxxxx. Xxxxxxx xxxx xxxxx je xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx xxxxxx znamenat xxxxxxxxxxxx zkoušky.

Plynné xxxx xxxxxx látky xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x těsně uzavřených xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx v xxxx xxxxxxx xx xxxx být xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Xx xxxxxxxx xxxxxxxxx xxxx xx xxxxxx počet xxxxxxx xxxxxxxxxx xx xxxxx.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Předloženými xxxxx xx xxxx xxx xxxxx xxxxxxx xxxxxxxxxx připadající xx xxxxx. Xxx by xxx xxxxxx xxxxxx xxxxx xxxxxxx revertantů xxx xx miskách x xxxxxxxxx kontrolou (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx xxxxxxxx), xxx xx miskách x pozitivní xxxxxxxxx. Xxxxx xx jednotlivých xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx misku x xxxxxxxxxx xxxxxxxx xx xxxx xxx předloženy xxx xxxxxxxxx xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx kontrolu xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Negativní výsledky xxxx xxx potvrzeny xxxxxx od xxxxxxx. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx výsledků xxxxxxxxxx xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx parametrů xxxxxx x cílem xxxxxxxx rozsah xxxxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx x xxxxxxxxxx experimentech. X xxxxxxxxxx studie, které xx xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx zpracování (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx médiu) x xxxxxxxx metabolické aktivace.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, např. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx xxxxxx x xxxxxxx jednoho kmene x metabolickým aktivačním xxxxxxxx xxxx bez xxxx, x xx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx xxx xxxxx nebo xxxx koncentrací (23). Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

Zkoušená xxxxx, xxxxx xxxxxxxx nesplňují xxxx uvedená kritéria, xx xxxxxxxx x xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx mohou xxxxxx dvojznačné nebo xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx mutace s xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxx xxxxx Xxxxxxxxxx typhimurium x/xxxx Xxxxxxxxxxx xxxx xxxxxx xxxxxx substitucí bází xxxx xxxxxxx čtecího xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxx xx xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxx mutagenní.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx kmene.

Zkušební podmínky:

- xxxxxxxx xxxxxxxx xxxxx xx xxxxx (xx/xxxxx xxxx μx/xxxxx) s xxxxxxxxxxx xxxxxx dávky x xxxxx xxxxx xx xxxxxxxxxxx,

- použitá xxxxx,

- xxx x xxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx miskách,

- xxxxxxx xxxxxxx xxxxx kolonií xxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx o xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxx, X. X., XxXxxx, X., Xxxxxxxx X. (1975), Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Mutagenicity Test, Xxxxxxxxxx Xxx., 31, 347-364.

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

3) Gatehouse, X., Xxxxxxx, S., Cebula, X., Xxxxx, E., Xxxx, X., Xxxxxxxxxx, X., Melcion, C., Xxxxx, T., Xxxxxx, X., Zeiger, E. (1994), Xxxxxxxxxxxxxxx for xxx Performance xx Xxxxxxxxx Xxxxxxxx Assays, Xxxxxxxxxx Res., 312, 217-233.

4) Xxxx, L. X., Brusick X. X., Xxxxxxx, X. X., Xxx Xxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X., McCann, X., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Xxx X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx of xxx X. S. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, X., Xxxxxx, X., Seino, X. X., Matsushima, T., Xxxxx, X., Sugimura, X., Xxxxxxxxx, X. (1975), Xxxxxxxxxxxx of Xxxxxxxxxx Xxx Xxxx xxx their Xxxxxxxxxxx, Xxxxxx Lett. 1, 91-96.

6) Matsushima, X., Xxxxxxxx, T., Nagao, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Factors Xxxxxxxxxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxx, in: Short-term Xxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx K. H., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Xxxxxxxxx, D. X., Rowland, I. X., Wilcox, P., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Assays, xx: Basic Mutagenicity Xxxxx: UKEMS Xxxx 1 Revised, xx. X. X. Kirkland, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.

8) Xxxxxxxxxx, H. X., Wolleb, U., Xxxxxxx, L. (1987), Xxxxxx Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxx for Xxxxx, X. Xxxx Xxxxxx., 8, 167-177.

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

10) Xxxxxxx, X. X., Xxxxx, X. H. L., Xxxxxxxxx, X., Xxxxxxx, X. W. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Legator, X., Xxxxxxx, X., Xxxxx, X. (eds.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, X. X., Xxxxxxx, P. X. (1981), An Xxxxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx xxx Xxxxxxxxxxx with Strains xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Xxxxx, X., Xxxxxxx, T., Kato, X., Xxxxxxxxxx, X. (1994), Xxxxxxxx Xxxxxx xxx Xxxxxxxxxxxx Testing xx Xxxxxxx Xxxxxxxxx xx Using a Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

13) Prival, X. X., Xxxx, S. X., Mitchell, X. X., Xxxxxxx, M. X., Xxxxxxx, X. X. (1984), Xxxxxxxxxxxx xx Benzidine and Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Xxxx xx x Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, E., Xxxxxxxx, X. X., Haworth, X., Xxxxxx, X., Xxxxxxxxxx, K. (1992), Xxxxxxxxxx Mutagenicity Xxxxx. X. Xxxxxxx from xxx Xxxxxxx xx 311 Chemicals, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, X., Xxxxxxxx, X., Tardiff, X. G. (1977), Xxxxxxxxx Activity of Xxxxxxxxx Identified xx Xxxxxxxx Water, xx Xxxxxxxx xx Genetic Xxxxxxxxxx, X. Xxxxx, X. Bridges, X. Xxxxxx (xxx.) Xxxxxxxx, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. X., Simmons, X. M., Xxxxxxxx, X. X., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Volatile Organic Xxxxxxxxx in the Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, T., Xxxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Mutagenicity xx xxx Xxxxxxxxx Xxxxxxxxx Carcinogen Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxx typhimurium, Xxxxxx Xxx., 39, 3780-3782.

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

19) Wilcox, X., Naidoo, A., Xxxx, X. J., Xxxxxxxxx, X. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx TA 102 xxxx Xxxxxxxxxxx xxxx XX2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Matsushima, T., Xxxxxxxx, M., Xxxx, X., Xxxxxxxx, X. (1976), A Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx or Xxxxxxxxx Xxxxxxxxxx Systems, xx: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xxx. X. X. xx Xxxxxx xx al. Xxxxxxxx, North Xxxxxxx, 85-88.

21) Xxxxxx, B. X., Combes, X. X., Elcombe, X. X., Xxxxxxxxx, X. X., Xxxxxx, G. X., Mackay, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-induced X9 xx in xxxxx Genotoxicity Assays, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Xxxxxxxxxxxxxxxx, X., Ames, B. X. (1981), Xxxxxxxxxxxxx xx Organic Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 88, 343-350.

23) Xxxxxxx, X. X., Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, K., Nestmann, X., Zeiger, E. (1987), Xxxxx xxx xxx Xxxxxxxxxx typhimurium/Mammalian Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, X. X. X., Green, M. X. L., Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. D., Xxxxxx, D. X. (1989), Analysis xx Xxxx from Xxxxxxxxx Xxxxxx Assays, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Part II. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, xx. Xxxxxxxx, X. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."


XXXXXXX 4X

"X.17 XXXXXXXXXX — XXXXXXX XX XXXXXX MUTACE X XXXXXXX XXXXX IN XXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 476 — Xxxxxxx na xxxxxx xxxxxx x xxxxxxx savců xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx genové mutace x buňkách xxxxx xx vitro lze xxxxxx pro detekci xxxxxxxx mutací xxxxxxxxxxxx xxxxxxxxxx látkami. Mezi xxxxxx buněčné linie xxxxx xxxxx xxxxxxx X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x V79 křečka xxxxxxxx a xxxxxxxxxxxxxxx xxxxx XX6 xxxxxxx (1). X xxxxxx xxxxxxxxx xxxxx jsou xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x xxxxxxxx xanthin-guaninfosforibosyltransferasy (XXXX). Xxxxxxx na xxxxxx XX, XXXX x XPRT xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx lokace XX a XXXX xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx xxxxxx), xxxxx xxxxx detekovat v XXXX xxxxxx na X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx na xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx lze xxxxxx xxxxxxx zavedených xxxxx xxxxx nebo xxxxxxx xxxxx. Xxxxx xx xxxxxxxx podle xxxxxxxxxx xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx prováděné xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx metabolické xxxxxxxx. Xxxxx metabolický aktivační xxxxxx nemůže zcela xxxxxxxxx xxxxxxxx xx xxxx x savců. Xx třeba se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. K xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, xxxx xxxxx xxxxxx xX, xxxxxxxxxx nebo vysokých xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx používá xx zjištění možných xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx sloučenin, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx savců; xxxx xxxxx zkouškou x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx závisí xx xxxxxxxx třídě x xxxxxxxxx důkazy o xxx, xx existují xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx zřejmě xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxx xxxxxx : genová xxxxxx xxxxxxxxx typu mutované xxxxx, xxxxx xxxxxxxxx xxxxx xxxx ztrátu xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxx substituce párů xxxx : xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxx více xxxx bází x XXX.

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx xxxxxxxxx xxxxx xxxx deleci xxxxxxx xxxx xxxx xxxx bází x xxxxxxxx XXX.

Xxxx xxxxxxx xxxxxxxx : xxxx, xxxxx níž vymizí x xxxx mutovaných xxxxx xxxxxxxxx genové xxxxxxxx.

Xxxxxxx mutantů : xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxx počtem xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxx xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx xx xxxxxxxx x kontrolní xxxxxxxx xxxxx; vypočte se xxxx součin xxxxxx xxxxxxxxx růstu v xxxxxxxx x x xxxxxxxxx kontrole a xxxxxxxxx xxxxxxxxx klonování xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxx x xxxxxxxx : nárůst xxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxxxxxxxx : účinnost xxxxxxxxx xxxxx v xxxxxxxx xxxxxxxx xx xxxxx xx selektivních xxxxxxxx xx expresi.

Přežití : xxxxxxxx klonování xxxxx xxx xxxxxxxx xx xxxxx xx konci xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx xxxxxxxxx x xxxxxx k xxxxxxx kontrolní populace xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx v xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (TK) xxxx xxxxxxxxxxx x cytotoxickým xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx xx XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxx xxxxx buněčné xxxxxx. Mutantní xxxxx xxxx tedy xxxxxxx xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx xxxxxxxx xxxxx, které obsahují xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Xxxxxxx xxx x xxxxx x xxxxxxxxxxxx XXXX xxxx XXXX provést selekci xxxxxxxxxxxxxxx xxxxxxxxxx k 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (XX). Vlastnosti xxxxxxxx xxxxx xx xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx je xx xxxxxxx xx xxxxxx mutace x xxxxxxx savců xxxxxxx xxxxxx xxxx nebo xxxxxxxxxx podobná xxxxxxxxxx xxxxxxx. Xxxx by xxx xxxxxxxxx vyšetřeno xxxxxxxx xxxxxxxxx xx xxxxxxxxxx xxxxxxxx zkoušené xxxxx pro xxxxxxxx xxxx xxxxxxxxxx buňky. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx strukturu xxxx xxxxxxxx xxxxxxx, xxxx xxxx být xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxx xxx selekci (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx kultuře xxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxx x metabolickou xxxxxxxx, xxx bez xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx exprese xxxxxxxx xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Cytotoxicita xx xxxxxxx zjistí xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx relativního celkového xxxxx xxxxxx po xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx kultury se xxxxxxx x xxxxxxxx xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx zvolený xxxxx x typ buněk, xxx nastala xxxxxxxxx xxxxxxxxx fenotypová exprese xxxxxxxxxxxx mutací. Xxxxxxx xxxxxxx xx xxxxxxx xxx, že xx xxxxxx xxxxx počet xxxxx xx média xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx detekci xxxxxxxxxx xxxxx x xx xxxxx bez selekčního xxxxxxx, aby xxxx xxxxxxxxx účinnost xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Četnost xxxxxxx xx xxxxxxx x počtu xxxxxxxxxx xxxxxxx x xxxxxxxxx xxxxx x xxxxx xxxxxxx x xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX ZKUŠEBNÍ METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x této zkoušce xxxx k xxxxxxxxx xxxxx xxxx buněk, xxxxxx xxxxxxxx xxxxx X5171X, XXX, CHO-AS52, X79 xxxx XX6. Xxxx xxxxx x xxxx xxxxxxx by xxxx xxxxxxxxx citlivost x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Buňky xx měly xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx.

Xxxxxxx xx xxxx xxx navrženy xxx, xxx xxxx předem xxxxxxxxxx xxxxxxxxx x xxxx. Počet použitých xxxxx, xxxxxx a xxxxxxxxxxx xxxxxxxx xxxxx xx měl tyto xxxxxxxxxx xxxxxxxxx odrážet (14). Minimální počet xxxxx, xxxxx xxxxxxx xxxxxxxx a xxxxx xxxxx xxxxxxx x xxxxxx stadiu xxxxxxx, xx xxx xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx mutací. Xxxxxxx xxxxxxxxx xx, xxx xxx xxxxxx xxxxx xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx hodnoty xxxxxxxx xxxxxxxxxxx xxxxxx. Xx xxxx xxxxxxxxxx, xxx bylo použito xxxxxxx 106 buněk. Xxxx by xxx x xxxxxxxxx xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx xxxxxxxx systému, xxx xxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Média x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx měla xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, koncentrace XX2, xxxxxxx x xxxxxxx). Xxxxx by měla xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx x xxxx buněk xxxxxxxxx xxx xxxxxxx. Je xxxxxxx důležité, xxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxx tak, aby xxxx zajištěny optimální xxxx buněk během xxxxxx exprese x xxxxxxxxx xxx xxxxxxxxxx, xxx nemutovaných xxxxx xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

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

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx xxxxxxxxx zkoušené xxxxx, x xx x vhodným xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx systémem je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x jater xxxxxxxx xxxxxxxxxx xxxxxxxx indukujícím xxxxxx, xxxx xx Xxxxxxx 1254 (15, 16, 17 x 18), nebo xxxx xxxxxxxxxxxxx a β-naftoflavonu (19, 20).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v xxxxxxxx xxxxxxxxxx médiu obvykle xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % xxx. Xxxxx x stav metabolického xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx vhodné xxxxxx xxxx xxx jednu xxxxxxxxxxx postmitochondriální xxxxxx.

Xxxx xxxxxxxx xxxxxx, včetně xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx exprimujících xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx xxxxx xx měla xxx xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx isoenzymu xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx látky).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx by xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx přímo x xxxxxxxxxx xxxxxxxx a/nebo xxxxx být xxxx xxxxxxxx xxxxxxx. Měly xx být použity xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x přežitím xxxxx x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení xxxxxxxxx údaji o xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx přidáním molekulového xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, která mají xxx zohledněna při xxxxxxxxx nejvyšší koncentrace, xxxxx cytotoxicita, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x xxxxx pH xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx být xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx xxxxxxx integrity x xxxxx, xxxx xxxx xxxxxxxxx účinnost xxxxxxxxx (xxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. Xxxx být xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx čtyři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxx by xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, což xxxx xxxxxxx znamenat, xx xx se xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. Xx-xx maximální xxxxxxxxxxx xxxxxxxx od xxxxxxxxxxxx, xxxx by xxx xxxxxxxxx přibližně 10 — 20 % (xxx nejméně 10 %) přežití (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx celkový xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx látek xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, xxxxx x nich xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxx xx x xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx xxxxxxxx, xxxx xx xx xxxx xxx. Měla by xxx xxxxxxxxx případná xxxxxxxxxxxxx x konečném xxxxx, ve kterému xxxx buňky xxxxxxxxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x na xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx xx xxxx x xxxxxxx expozice x testovacím systému xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, S9 xxxx, atd. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx jak s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Při xxxxxxx metabolické xxxxxxxx xx měla xxx xxxxxxxxx kontrolou chemická xxxxx, xxxxx x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx pozitivní xxxxxxxx xxxxx xxx tyto xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Einecs

Bez 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 velké 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 xxxxxx metabolickou 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 (malé x xxxxx xxxxxxx)

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx 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 xxxxxx xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx xxx xxxxxxx xxxx xxxx xxxxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx, např. xx-xx xxxxxxxxx xxxxxxxx dosavadních xxxxx o 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, EINECS 200–415–9), může xxx xxxx referenční látka xxxxxx použita. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x úvahu použití xxxxxxxxxx xxxxx pokud xxxxx xx xxxxxx xxxxxxxx xxxxx.

Xxxx xx xxx použity negativní xxxxxxxx tvořené médiem xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxxxxxxx xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx kontroly použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx xxxx být xxxxxxxxx zkoušené xxxxx xxx xx přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx by xxxx xxxxx vhodnou dobu (xxxxxxx xx xxxxxx xxxx 3 xx 6 hodin). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx xxxxx xxx xxxxxxx duplicitní xxxxxxx xxxx jedna xxxxxxxxxx xxxxxxx. Je-li použita xxxxx kultura, xxx xx být xxxxx xxxxxxxxxxx xxxxxx xxx, xxx xxx zajištěn xxxxxxxxxxxx počet xxxxxx xxx analýzu (např. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Měly xx xxx xxxxxxx duplicitní xxxxxxxxx xxxxxxxxx kultury (xxxxxxxx rozpouštědla).

Plynné nebo xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx nádobách (21, 22).

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx a xxxxxxxx xxxxxx

Xx konci expoziční xxxx xx xxxxx xxxxxxx x kultivují xx účelem stanovení xxxxxxx x xx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxxx xxxxxxxxx růstu xxxxxx xx započne xxxxxxx po xxxxxxxxx xxxx.

Xxxxx xxxxx má xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, aby xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx nově indukovaných xxxxxxx (XXXX a XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, XX alespoň xxx dny). Buňky xxxx kultivovány v xxxxx xx selekčním xxxxxxxx (xxxxxxxxxx činidly) x xxx xxxx (xxx xxxx) za xxxxxx stanovení počtu xxxxxxx x klonovací xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx pro xxxxxxx xxxxxxxx mutantů) xx xxxxxxx xx xxxxx xxxx exprese xxxxxxxxx xx xxxxx xxx xxxxxxxxxx činidla.

Je-li xxxxxxxx xxxxx xxxxxxxxx xx xxxxxxx X5178X XX+/-, xxxx xx xxx xxxxxxxxx alespoň xx jedné xx xxxxxxxxxx kultur (s xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x na xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxx xx xxxxxxx X5178X XX+/- xxxxxxxxx, xxxx xx xxx rozdělení xxxxxxx xxxxx velikosti kolonií xxxxxxxxx na xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx za xxxxxxx XX6 XX+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx xxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, xxxxx kolonií x xxxxxxxx xxxxxxx xxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxx L5178Y XX+/- xx kolonie xxxxxxxxx xxxxxxx u xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (xxxxxxxx pozitivní xxxxxxxxxxx) x x xxxxxxxxx a pozitivní xxxxxxxx xx xxxxxxx xxxxxxxx xxxx xxxxxxx — xxxxx kolonie. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx mutantů xxxxxxxxx xxxxx xxxxxxx, xxx xxxxxxx xxxxxxxxx xxxx xxxxxxx byla xxxxxxxx xxxxxxxx (23, 24). Ve zkoušce XX+/- xxxx xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxx x xxxxxxxxx růstem (xxxxx) x xxxxxxx s xxxxxxx xxxxxx (xxxx) (25). X mutantních xxxxx, které utrpěly xxxxxxxxxxxxxx xxxxxxxxx poškození, xx prodloužily doby xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx obvykle xxxxxx xx xxxxx xxxxxx xxxx xx xx xxxxxxxxxxxx viditelné xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xxxxxxxxx malé xxxxxxx se spojuje x xxxxxxxxxx látkami, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx aberace (26). Xxxx závažně xxxxxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx tempem jako xxxxxxxx xxxxx x xxxxx xxxxx kolonie.

Mělo xx být xxxxx xxxxxxx (relativní xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Četnost xxxxxxx by xxxx xxx vyjádřena xxxx xxxxx xxxxxxx k xxxxx přeživších buněk.

Měly xx xxx uvedeny xxxxx pro xxxxxxxxxx xxxxxxx. Xxxx xx xxxx být všechny xxxxx shrnuty xx xxxxx xxxxxxx.

Xxxxxxx jasně xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx za xxxxx, je xxxxx xxxxx zdůvodnění. Xxxxx xxxxxxxxx xxxxxx x xxxxx rozšířit xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x následných xxxxxxxxxxxxx xxx pro xxxxxxxxxx xxxxxxxx, xxx pro xxxxxxxxx výsledky. X xxxxxxxxxx studie, xxxxx xx xxxxx xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx četností xxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx nárůst xxxx xxxxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost by xxxxxx xxx jediným xxxxxxxxx faktorem pro xxxxxxxxx odpověď.

Zkoušená látka, xxxxx xxxxxxxx xxxxxxxxx xxxx uvedená xxxxxxxx, xx x xxxxx xxxxxxx xxxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx konečný výrok x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxx xxxxxx v xxxxxxx savců xx xxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x použitých kultivovaných xxxxxxx xxxxx xxxxxx xxxxxx. Reprodukovatelná pozitivní xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx xx velmi xxxxxxxx. Negativní výsledky xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxx kultivovaných buňkách xxxxx genové mutace.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Buňky:

- xxx a zdroj xxxxx,

- xxxxx buněčných xxxxxx,

- xxxxxxxx počet xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx mykoplasmat.

Zkušební xxxxxxxx:

- xxxxxxxxxx výběru xxxxxxxxxxx x počtu xxxxxx, xxxxxx xxxx. xxxxx x xxxxxxxxxxxx a xxxxxx rozpustnosti, xxxx-xx x dispozici,

- složení xxxxx, případně xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx během expozice,

- xxx x xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, včetně kritérií xxxxxxxxxxxxx,

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxx xxxx exprese (případně xxxxxx počtu xxxxxxxxxx xxxxx, subkultur a xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx k xxxxxxxx životaschopných x xxxxxxxxxx buněk,

- xxxxxxxx xxxxxxx podle velikosti x xxxx (případně xxxxxx kriterií pro "xxxx" x "xxxxx" xxxxxxx).

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxx srážení,

- údaje x xX x xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxx,

- velikost xxxxxxx, xxxx-xx vyšetřována, xxxxxxx xxx negativní x xxxxxxxxx kontroly,

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

- podle xxxxxxxx závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- údaje x xxxxxxxx negativní (xxxxxxxxxxxx/xxxxxxxxx) a xxxxxxxxx xxxxxxxx,

- dosavadní xxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- četnost mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Moore, X. X., DeMarini, X. X., XxXxxxxx, X. J., Xxxxxx, X. X. (eds.) (1987), Xxxxxxx Report 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Cold Xxxxxx Xxxxxx Laboratory, New Xxxx.

2) Chu, E. X. X., Xxxxxxx X. X. (1968), Xxxxxxxxx Cell Xxxxxxxx. XX. Chemical Induction xx Xxxxxxxx Locus Xxxxxxxxx xx Xxxxxxx Xxxxxxx Cells Xx xxxxx, Xxxx. Xxxx. Xxxx. Xxx. U. X. X, 61, 1306-1312.

3) Xxxxx, X. X., Thilly, X. X. (1982), Xxxxxxxx Xxxxx at xxx Xxxxxxxxx Xxxxxx Xxxxx xx Diploid Human Xxxxxxxxxxxx, Xxxxxxxx Res. 94, 467-485.

4) Moore, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, X. X., Dearfield, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx xx xxx Xxxxx Xxxxxxxx XX and XXX XXXXX Xxxx, Xxxxxxxxxxx, 4, 394-403.

5) Aaron, X. X., Stankowski, Xx. L. X., (1989), Xxxxxxxxxx of xxx XX52/XXXX and xxx CHO/HPRT Assays: Xxxxxxxxxx of Xxx Xxxx Xxxxxxxxxx, Mutatation Xxx. 223, 121-128.

6) Xxxxx, C. X., Xxxxxxxxxx, X., Glatt, X. X., Moore, X., Xxxxx, Y., Xxxxxxxxxx, Xx. X. X., Xxxxxx, J., Xxxxxxxx, E. (1994), Xxxxxxxxx Cell Gene Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Xxxxxx. Xxxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxxx on Standardisation xx Genotoxicity Xxxx Xxxxxxxxxx. Mutation Xxx. 312, 235-239.

7) Scott, X., Galloway, X. X., Xxxxxxxx, X. X., Xxxxxxxx, M., Xxxxxxx, X., Ashby, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx Xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Mutation Xxx. 257, 147-204.

8) Xxxxx, X., McCuen, X., Xxxxxxx, J. X. X., Xxxxx, X., Xxxxxxxxx, X. X. (1983), Xxxxxxxx Xxxx Mutations xx X5178X Cells in Xxxxxxx. X Report xx the X. X. Environmental Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 115, 225-251.

9) Li, X. X., Xxxxx, R. X., Heflich, R. X., Wasson, J. X. (1988), X Xxxxxx and Analysis xx xxx Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx System xx Determine xxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: X Xxxxxx xx Phase XXX xx xxx X. X. Environmental Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, X. X., Xxxxxx, J. X., Choy, X. X., Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X., X'Νxxxx, J. X., Riddle, X. X., Stankowski, X. X. Xx., Xxxx, X. L. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx of xxx Chinese Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Xxxxxxxx Xxxxx, Mutatation Xxx., 189, 135-141.

11) Xxxxx, X. L., Yandell, X. W., Xxxxxx, X. B. (1989), X Xxxxxxxxxx xx Xxxxxxxx Xxxxxxxxx at xxx TK xxx XXXX Loci in Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Differences xxx Xxx xx an Xxxxxxxxxx Class xx Xxxxxxxxx xx xxx Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Res., 216, 9-17.

12) Xxxxxxxxxx, L. X. Jr., Tindal, X. X., Xxxx, X. W. (1986), Xxxxxxxxxxxx xxx Molecular Xxxxxxxx xx Xxxxx Xxxxxxxxxxxxxxxxx xxx ICR 191-Xxxxxxx Molecular Analyses xx Ethyl Xxxxxxxxxxxxxxxxx xxx XXX 191 Xxxxxxx Mutation in XX52 Xxxxx, Mutatation Xxx., 160, 133-147.

13) Xxxxxx, X. X., Xxxxxx, A. X., Xxxxx, X. (1984), Xxxxxxxxx for the X5178X/XX+/--XX+/- Xxxxx Xxxxxxxx Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, X. X. et xx (xxx.) Handbook of Xxxxxxxxxxxx Test Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Publishers, Xxx Xxxx, 239-268.

14) Xxxxxx, C. X., Xxxxx, X. X., Xxxxxx, G. X., Xxxxx, X. H. X., Xxxx, X., XxXxxxxx, D. X., Xxxxxxx X. C. (1989), Xxxxxxxxx Xxxx Xxxx Mutation Assays Xxxxx xxxx Xxxxxx Xxxxxxxxx, xx: Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, Xxxxxxxx, X. J., xx., Xxxxxxxxx Xxxxxxxxxx Press, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, S., Corti, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Xxxxxxxxx xx 6-Thioguanine-Resistant Mutants xx X79 Xxxxxxx Xxxxxxx Cells xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Dimethylnitrosamine, Xxxxxxxxxx Res. 46, 365-373.

16) Xxxx, B. X., XxXxxx, J., Xxxxxxxx, X. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Mutatation Xxx. 31, 347-364.

17) Xxxxx, X., Xxxxxxx, X. X., Spector, X. X. X., Xxxxxx A. G., Xxxxx X. X. X. (1979), Validation xxx Xxxxxxxxxxxxxxxx xx xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Assay Xxxxxx, Xxxxx. Res. 59, 61-108.

18) Maron, X. X., Ames, X. X. (1983), Revised Xxxxxxx xxx the Xxxxxxxxxx Mutagenicity Test, Xxxxxxxxxx Res. 113, 173-215.

19) Xxxxxxx, X. X., Xxxxxx, R. X., Xxxxxxx, C. X., Xxxxxxxxx, D. X., Gibson, X. X., Mackay, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Xxxxxxx X9 in: Xx xxxxx Genotoxicity Assays, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Biphenyls x. x. an Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, V: Xx vitro Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, de Xxxxxx, X. X., Xxxxx, X. X., Xxxx, X. X., Xxxxxxx, X. X. (eds), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, D. F., Xxxxxx, F. X., XxXxxxx, X. T. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Xxxxxxxx Xxxxxxx, in: Xxxx, X. X., Xxxxx, X. X., Schaich, X. X. (xxx), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Agents, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, X. X., Xxxxxx, J. X., Xx, X. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx of xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Gels xxx Detecting Highly Xxxxxxxx Xxxxxxxx in xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environ. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. X., Xxxxx, X. X., Broder, X. B., Xxxxxxx, X., Xxxxxx, J. X. (1990), Molecular Xxxxxxxxxx of Mutations xx the Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Locus xx Xxxxx Xxxxxxxx Xxxxx, Xxxx. Natl. Xxxx. Sci. X. X. A, 87, 51-55.

24) Xxxxx, X. X., Xxxxx, X., Xxxxxx, J. X., Xxxxxx, X. X., Xxxxxx, A. X., Xxxxxx, N. T., Xxxxxx, X. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Xxxxxxx xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

25) Xxxxxxx, X. X., Xxxxx, X. P., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxx Analysis xx Xxxxxxxxx Xxxxxxxxx xx a Xxxxxxxxxxxx Xxxxxxxxx Locus in Xxxxx Cells, Xxxxxxxxxx Xxx. 229, 89-102.

26) Xxxxx, X. X., Xxxxx, C. L. (1990), Xxxxxxxxxx of Xxxxxxxxxx Aberration Frequency xxx Small Xxxxxx XX-Xxxxxxxxx Xxxxxx Frequency xx X5178X/XX+/- 3.7.2X Xxxxx Lymphoma Xxxxx, Xxxxxxxxxxx, 5, 609-614."


XXXXXXX 4X

"X.23 ZKOUŠKA XX XXXXXXXXXXXX ABERACE XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx in xxxx xx identifikovat xxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx spermatogoniích savců (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: chromozomové x xxxxxxxxxxxx. X xxxxxxx chemických xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx vyskytují. Xxxx xxxxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a podobné xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx.

Xxxxx xxxxxxxx xx stanovují xxxxxxxxxxxx xxxxx ve xxxxxxxxxxxxxxx a xxxxxxxxxxx xx tedy, že xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx používáni xxxxxxxx. Xxxxx cytogenetickou xxxxxxxx xx vivo xx xxxxxxxx xxxxxxxxxxxx xxxxxxx xxx mitose xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx předmětem xxxx xxxxxxx.

Xxx detekci xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx by xxxx xxx — xxxxx xxx dojde xx xxxxxx xxxx — xxxxxxxxx xxxxx xxxxxxxxx buněčné xxxxxx, xxxxx následuje xx xxxxxxxx. Další xxxxxxxxx x exponovaných xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx chromozomového xxxx v xxxxxxxxx-xxxxxxxx X, kdy se xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx somatických xxxxx aktivní také x xxxxxxxxxxxx buňkách. Xxxxx xx xxxx xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx xxx posouzení xxxxxxxxx mutagenese, xxxxx xxxxxxxx zohlednit faktory xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x procesy xxxxxxxx DNA.

Ve xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx spermatogonií x xxxxxx citlivostí xx xxxxxxxx chemické látce. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. V xxxxxxxxxx xx xxx xxxxxx xx varlatech, xxxxx xxxx xxxxxx xxx xxxxx generace xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx x důsledku xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x bariéry xxxx xxxxxxx xxxxxx x xxxxxxx.

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

Viz xxxx obecný xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : strukturní xxxxxxxxx chromozomu x xxxxxx zlomu xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx spojení xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x podobě zlomu xxxx xxxxx a xxxxxxx obou xxxxxxxxx x xxxxxx místě.

Gap : xxxxxxxxxxxx léze xxxxx než xxxxx xxxxx chromatidy a x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx aberace : xxxxxxxx xxxxx xxxxxxxxxx xx normální xxxxxxx x použitých buněk.

Polyploidie : xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx sad (x), jiný xxx xxxxxxxxx (tj. 3 x, 4 x xxx.).

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx xxxxxx ve xxxxxx metafáze pod xxxxxxxxxxx, jeví xx xxxx delece x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx způsobem xxxxxxxxxx xxxxxxxx xxxxx a xx vhodné xxxx xx xxxxxxxx usmrcena. Xxxx xxxxxxxxx se xxxxxxxx xxxx látka xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Colcemid®). X xxxxxxxxxxxx xxxxx xx xxxx připraví xxxxxxxxx xxxxxxxxxx, xxxxxx xx x analyzují xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 POPIS XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx a xxxx; lze xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx vhodného xxxxx xxxxx. Xxxx xx xxx použity xxxxx xxxxxxx laboratorní xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx v hmotnosti xxxxxx xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladí xxxxxxxx xxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní skupinu x skupinu, která xx xxxxxxxx. Xxxxx xx měly xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx nechají v xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx dní aklimatizovat.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx údaje x stálosti neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx při xxxxxxxxx xxxxxxxxx dávek xxxxxxx účinky a xxxx xx být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by xxxx xxx xxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) kontroly. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x nichž xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx aberace xx spermatogoniích in xxxx xxx xxxxxxxxxxx xxxxxxxx, u xxxxx xx xxxxxxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx pozadí.

Dávky pozitivní xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx účinek xxxxxxxx, xxx xxx xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx xxxxx x xxx byl xxxxx x xxxxx xxxxxxx xxxxxxxx xxx jednou. Xxx pozitivní kontrolu xxxx xxx xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx chemické xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx látek xxx pozitivní kontrolu:

Látka

Číslo XXX

Xxxxx xxxxx Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx C

50–07–7

200–008–6

akrylamid (xxxxxxx)

79–06–1

201–173–7

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx xxx být xxxxxxxx xxxxx x xxxxxxx negativní xxxxxxxx, xxxxx je xxxxxxxxxx xxxxx rozpouštědlo nebo xxxxxxxxx a xxxxx xxxxx podstupuje xxxxxx xxxxxx jako exponované xxxxxxx, xxxxx nejsou x dosavadních kontrolních xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx o xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx by xxxx xxx neexponované xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx dosud xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo/vehikulum nevyvolává xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx skupina xxxx xxxxxxxxx xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx být xxxxx možno xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. xxx xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. dvě xxxxx v xxx xxx x xxxxxxx xx více xxx xxxxxxxx xxxxx, xxx xxxx usnadněno xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx xxxxxx podávání xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx dávkou xx xxxx být xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx jeden xxxxx xxxxx x jeden xxxxxxxx xxxxx xxxxxxxxx 24 a 48 xxxxx xx expozici. X xxxxxxx jiné xxx xxxxxxxx xxxxx xx xxx být xxxxx proveden xx 24 hodin xxxx xx takové době xxxxxxxx, která xxxxxxxx 1,5xxxxxxx délky xxxxxxxxx xxxxx, pokud xxxx xxxxx xxxx vhodnější xxxx pro xxxxxxx xxxxxx (6).

Navíc xxxxx xxx odběry xxxxxxxxx xxxx x xxxx xxxx. Například x xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx indukovat xxxxxxxx xxxxxxxxx (xxxxxxx) xxxxxxxxxx nebo xxxxx xxxxxxxxxx S-nezávislé xxxxxx, xxxx xxx xxxxxxxxx xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxx být xxxxxx xxxxxx od xxxxxxx. X případě xxxxx x xxxxxxxxxx expozicí xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) xx xxxxxxxx xxxxxxxx. Xxxxx potřeby xxxxx xxx xxxxxxxxx xxxxx xxxxxx v xxxx xxxx.

Xxxx xxxxxxxxx xx zvířatům xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx zastavující metafázi (xxxx. Colcemid® xxxx xxxxxxxxx). Xxxx xx xx vhodné xxxx xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx doba xxxxxxxxx 3 — 5 hodin; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx zjištění rozsahu, xxxx by xxx xxxxxxxxx ve stejné xxxxxxxxxx, xx xxxxxxx xxxxxx x xxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx xxxxxxx x xxxxxx studii (7). X xxxxxxx toxicity xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx rozmezí xxxx maximální a xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx stačí, xxxx bude xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx jako dávka xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xx xxxxx xxxxx vedly xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x xxxxxxxx.

Xxxxx xx xxxxxxxxxxx biologickou aktivitou xxx nízkých netoxických xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) nemusí xxxxxxxxx stanovení dávky xxxxxxxxx a měly xx být xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xxxxx xxxx xxx xxxx definována xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx toxicity (např. xxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx vzhledem x první a xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx by xxxxxx xxxxxxxxx 50 %).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx tělesné hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx na xxxxxxx xxxxx o látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx se úplná xxxxxx se xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx v xxxxxxx zkoušce vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx látka se xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx sondou nebo xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx podávání xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Maximální xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx sondou nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx na xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx vyšších xxxxxxxxxxxxx xxxxxxxx zesílené účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů xx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx se x xxxxxxx nebo xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx a xxxxxx. Xxxx se nanese xx xxxxxxxx xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v dobře xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 xxxxxxxx xx skupinu). Xxxxx xxxxx lze snížit, xx-xx xxxxxxxxx velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxx preparátů xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx při xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx u xxxxx metafází, měly xx vyšetřované xxxxx xxxxxxxxx centromery x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx xx xxxx xxx xxxxxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx zvíře xx měl být xxxxxxxxxx xxxxx xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx aberací na xxxxx. Xxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxx xxx xxxxxxx různé typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx se, xxx xxxxxx se xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx a také xxxxxx, měl by xxx pro stanovení xxxxxxx cytotoxických xxxxxx xxxx míra cytotoxicity xxxxxxxx u všech xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx jako xxxxxxxxx kontrola xxxxx xxxxxxxxxxxxx v xxxxxx xxxxxxxx k xxxxx x xxxxx xxxxxxxxx xxxxxxxx, a xx x xxxxxxxx xxxxxx 100 xxxxxxxx xx xxxxx na jedno xxxxx. Xxxxx je xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx na zvíře xx xxx být xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx xx xxxxx xxxx jasný xxxxxx xxxxx xxxxx s xxxxxxxxx pro xxxxxxx x xxxxxxx dávkou x k xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx měla být xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx prostředek statistické xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx by neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují xxxx uvedená xxxxxxxx, xx v tomto xxxxxxx považuje xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx savců xx xxxx znamenají, xx xxxxxxxx xxxxx indukuje x germinálních buňkách xxxxxxxxxxx druhu strukturní xxxxxxxxxxxx aberace. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje x germinálních xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx xxxxxxxx xxxxx nebo její xxxxxxxxxx dostanou do xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- rozpustnost x xxxxxxx xxxxxxxx xxxxx v xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.

Xxxxxxxxx zvířata:

- xxxxxxx druh/kmen,

- xxxxx x xxxxx xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební podmínky:

- xxxxx ze xxxxxx xxx xxxxxxxx rozsahu, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- údaje x xxxxxxxx zkoušené látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx mezi xxxxxxxxxxx xxxxxxxx xxxxx v xxxxxx nebo xxxx (xxx) xx odpovídající xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- podrobné xxxxx x kvalitě krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- identifikace xxxxx xxxxxxxxxxx xxxxxxxx, xxxx koncentrace x xxxxx aplikace,

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx aberací,

- počet xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, negativní nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x xxxxx xxxxxxxx xxxxxx,

- xxx x xxxxx xxxxxxx uvedený xxxxxxxxxx xxx každé xxxxx,

- celkový počet xxxxxxx xx skupině,

- xxxxx buněk x xxxxxxxxx ve xxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx o souběžné xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx hodnotami a xxxxxxxxxxxx odchylkami,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- změny xxxxxxx, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Potential xx Xxxxx Xxxxxxxxxxxxx of Xxxxxxxx Xxxxxxxx Xxxxxxx xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx of Environmental Xxxxxxxxx, Xxxx B: Xxxxxxx Xxxxxxx xxx Xxxxxxx Mutagenesis, Xxxxx, X., Xxxxxxx, X., Xxxxxxxxx, X. (xxx) Xxxx, New York, 477-484.

2) Xxxxx, X. X., (1984), Xxxxxxxxxxx xxxxx in Xxxxxxx, xx: Xxxxxxxxxxxx Testing: x Xxxxxxxxx Xxxxxxxx, (xx.) X. Xxxxxx, X. X. Xxxxx, XXX Xxxxx, Xxxxxx, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, X. P., Xxxxxxx, X., Xxxx, X. X. (1964), Xx Xxx-xxxxxx Method xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Testes, Xxxxxxxxxxxx Xxxx Genetics, 3, 289-294.

4) Xxxxxxx, X., Ashby, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, X. (1990), Xx xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Tests, XXXXX Xxxxxxxxxxx Procedures. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 115-141.

5) Xxxxxxxx, X., Kikuchi, X. (1978), A Xxx Xxxxxx xxx Xxxxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Mutatation Xxx., 52, 207-209.

6) Xxxxx, I. X., Xxxxxx X. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx X. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Xxxxxx of xxx Xxxxxxx Xxxxx xx Mammalian Xxxx Xxxx Tests, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. A., Xxx, X., Xxxxxxx, X. X., Gatehouse, X. X., Xxxxxx-Xxxxxx, X., Morton, D. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Report xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx In xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, R., Richold, X., Xxxxxxxx, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Kirkland (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


PŘÍLOHA 4X

"X.39 XXXXXXX XX NEPLÁNOVANOU XXXXXXX XXX (XXX) X XXXXXXXXX XXXXXXX XXXXX XX VIVO

1. XXXXXX

Xxxx xxxxxx je xxxxxxxx xxxxxx XXXX XX 486 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx xxxxx xx xxxx (1997).

1.1 XXXX

Xxxxxx zkoušky xx xxxxxxxxxxxx xxxxxxx XXX (XXX) v jaterních xxxxxxx xxxxx in xxxx xx xxxxxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxx XXX x xxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

Tato xxxxxxx in vivo xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxx chemických xxxxx x xxxxxxx. Xxxxxxxxxxx xxx xx xxxxxxxxxx xxxxxxxxx DNA x xxxxxxxx xxxxxxxx x jaterních xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, kde xxxx absorbované sloučeniny xxxxxxxxxxxxxx. Jsou xxxx xxxxxxx místem xxx xxxxxxxxx míry xxxxxxxxx XXX in xxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx se xxxxxxxx látka nedostane xx cílové tkáně, xxxx xxxxxx xxxx xxxxxxx použít.

Rozsah xxxxxxxxxxx xxxxxxx XXX (UDS) xx zhodnotí stanovením xxxxxxxxxxx xxxxxxxxx nukleosidů xx xxxxx, které xxxxxxxx plánovanou syntézou XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx xx XXX xx xxxx xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Xxxx xxxxx xxx játra xxxxx být xxxxxx xxxxxxx, xxxxxx však xxxxxxxxx xxxx metody.

Detekce xxxxxxxx XXX xxxxxx xx xxxxx bází XXX xxxxxxxxxxx x xxxxxxxxxxx x xxxxx xxxxxxxxx. Xxxxxxx na XXX xx xxxx xxxxxx zvláště xxx xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 bází) xxxxxxxxxxxx látkou. Xxxxxx xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx až xxx xxxx) xxxx xxxxxxx xxxx detekovány x xxxxxx xxxxx xxxxxxxxxx. Xxxxx může důsledkem xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx nebo xxxxxx xxxxxxxxx xxxx XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx xxxxxxxx XXX xxxxxxxxxxx xxxxxx xxxxxxxxx o xxxxxxxx xxxxxxxxxxx procesů. Xxxxx xx možné, xx xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX není xxxxxxxx xxxxxxxxxxx reparací. Xxxxxxxxxx xxxxxxxxxxxx informací, xxxxx xxxx zkouška poskytuje x mutagenní xxxxxxxx, xx vyvážen xxxxxxxxxxx xxxxxxxxxx xxxxxx jevu, xxxxx xx vyšetřován x xxxxx genomu.

Viz xxxx xxxxxx xxxx, xxxx B.

1.2 DEFINICE

Opravované xxxxx : čistý xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX), xxxxx xxx xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zkoušku.

Čistý xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx UDS xxxxxxxx buněk v xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x cytoplasmatických xxxxxxxxx (XX) xxxxxxxxxxxxxx jádrům xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): XXX = XX — XX. Xxxxxxx NNG xx xxxxxxx pro xxxxxxxxxx xxxxx, xxxx společně xxx xxxxx x xxxxxxx, v paralelních xxxxxxxxx xxx.

Xxxxxxxxxxx xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx DNA xx xxxxxxxxx x xxxxxxxxxx úseku DNA xxxxxxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx na XXX x xxxxxxxxx buňkách xxxxx in vivo xxxxxxxx xxxxxxx reparací XXX po xxxxxxxxx x odstranění úseku XXX xxxxxxxxxxxx region x xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx založena xx inkorporaci 3X-XxX xx XXX xxxxxxxxx xxxxx, xxx je xxxx xxxxxxx buněk x S-fázi xxxxxxxxx xxxxx. Inkorporace 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx xxxx xxx xxxxxxx xx vliv X-xxxx xxxxx xxxx xxxx. kapalná scintilační xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr druhu xxxxxxx

Xxxxx xx používán xxxxxx, ačkoli xxx xxxxxx jakýkoli xxxxxx xxxx savce. Měly xx xxx xxxxxxx xxxxx xxxxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx by xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x neměla xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Xxxxxxxx chovu x strava

Platí xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x části X, xxxxxxx xx xxxx být dosaženo xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, xxxxx xx xxxxxxxx. Xxxxx xx měly být xxxxxxxxxx tak, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx jednoznačně xxxxxxxxxxxx x xxxx započetím xxxxxx se xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx a mělo xx být xxxxxxxxx xxxxxxxxx, že reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí každé xxxxxxxxx prováděné xxxxx xxxxxxxxxxx xx měly xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S výjimkou xxxxxxxx zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx ve xxxxxxxxx, x nichž xxxxx x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx xxxx být xxxxx, o xxxxx xx známo, že xxxxxx podávání x xxxxxxxxxxx expozičních koncentracích xxxx x nárůstu XXX detekovatelnému xxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx metabolickou aktivaci xx xxxx být xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Xxxxx mohou xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx odečtu xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Einecs

Časné doby xxxxxx (2 xx 4 h)

N-nitrosodimethylamin

62–75–9

200–249–8

Pozdní xxxx xxxxxx (12 až 16 x)

X-(xxxxxxx-2-xx)xxxxxxxx (2-XXX)

53–96–3

200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx xxxxx pro xxxxxxxxx kontrolu. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx látka xxxxxxxx xxxxx xxxxxxxx, xxx zkoušená xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxx xx xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, xxx xxxx zohledněno přirozené xxxxxxxxxx xxxxxxxx xxxxxxxx xx zkoušku. Xxxxx xxxxxxx xx xx xxxx skládat xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Jestliže xxxx xxxxxxxxxxx dostatečné dosavadní xxxxx, xx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxx xx xxx xxxxxxx.

Xxxxxxxx xxxx x době xxxxxx x xxxxxxxxx xxxxx xx xxxxxx se xxxxxxx xxxxxx a xx xxxxxxx stejného xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx rozdíl x toxicitě, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx samců. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako je xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx se xxxxxxxx odpovídajícího pohlaví.

1.5.2 Xxxx expozice

Zkoušené xxxxx xxxx zpravidla xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

Za xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx xxx xxxxxx xxxxx. Nejvyšší xxxxx xx definována xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx toxicity, že xxxxx xxxxx by xxxxx podle xxxxxxxxx xxx xxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx dávka xx xxxx xxx zpravidla 50 % až 25 % xxxxx xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx xxxxxxx xxxxxxxxxxx dávkách (xxxx. hormony x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x měly xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, měla xx xxx provedena xx xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx, xxxxxx, xxxxxxxx a xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx xxxxxx.

Xxxxxxxx xxxxx xxxx xxx xxxxxxxxxx také xxxx xxxxx vyvolávající xxxxxx xxxxxxxx x xxxxxxx (xxxx. pyknotická xxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx x alespoň 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx dvou dávkách x xxxxxx dni xxxxxxxxxx žádné pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx xxx xxxxx xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou intubační xxxxxxx. Jiné způsoby xxxxxxxx xxxx xxxxx, xxx-xx xx xxxxxxxxx. Xxxxxxxx intraperitoneálně xx xxxx xxxxxxxxxxxx, xxxxx xx xxxxx xxxxx xxx exponována zkoušené xxxxx přímo x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Maximální xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx podán xxxxxxxxx xxxxxx nebo xxxxxxxx, závisí xx xxxxxxxxx testovacího zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, musí být xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxxxxx xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx z xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 hodin xx podání xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (xxxxxx xxx xx xxxxx hodiny xx xxxxxxxx) xx xxxxxxxx, není-li xx 12 xx 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx xxxxxxx xxxx xxxx xxxxxx, jsou-li xxxxxxxxxx xx základě xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx jater xxxxxxxxxxx xx situ x xxxxxx xx, xxx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx povrchu. Xxxxxxx xxxxx z xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx UDS

Čerstvě xxxxxxxxx jaterní xxxxx xxxxx xx xxxxxxx xxxxxxx xxxx, xxxx. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3H-TdR. Xx xxxxx inkubační xxxx xx xxxx xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx poté xxxxx xxx inkubovány x xxxxxx xxxxxxxxxxx přebytek xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("cold xxxxx"). Xxxxx xx poté xxxxxxx, xxxxxx a xxxxxx. Xxx xxxxx xxxxxxxxx xxxx xxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Preparáty xx xxxxxx xx autoradiografické xxxxxx, xxxxxxxx se x xxxxx (např. x xxxxxx 7 xx 14 xxx), xxxxxxxx se, xxxxxx x xxxxxxxxx xx xxxxxxxxxx xxxx stříbra. X každého xxxxxxx xx připraví xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx by xxxx xxxxxxxxx dostatečný xxxxx xxxxxxxxxxxx normálních xxxxx, xxx xxxx hodnocení XXX výpovědní hodnotu. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxx zjevné xxxxxxxxxxxx (xxxx. xx xxxxxxx, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx izotopem).

Před xxxxxxxxx xxx xx xxxx xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxxxxx 100 buněk xx xxxxx xxxxx alespoň xx xxxx xxxxxxxxx; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx xx xxxx být zdůvodněno. Xxx xxxxxxxx xxx xx xxxxx v X-xxxx xxxxxxxxxxx, xxx xxxxx xxxxx x X-xxxx xxxx xxx xxxxxxxxxx.

Xxxxxxxx 3H-TdR inkorporovaného xx jader x xxxxxxxxxx morfologicky normálních xxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxx.

Xxxxx xxxxx xx stanoví z xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x x xxŭxxxxxxx xxxxx zrn x xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx xx xx xxxxxxx buď xxxxx xxxxx xxx nejsilněji xxxxxxxxx oblast cytoplasmy, xxxx xxŭxxxxx xxxxxxx xxxx až tří xxxxxxx xxxxxxxxx oblastí x blízkosti dotyčných xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx xxxxxxx i xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (např. xxxxxxxx xxxxxx buněk) (6).

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx být xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx a xxxxxxx. Údaje xx xxxx xxx xxxx xxxxxxx xx formě xxxxxxx. Xxxxxxxxx xxxxxxx XX od xxxxxxx XX xx měl xxx xxxxxxxx xxx xxxxxx buňku, xxx xxxxx zvíře x xxx každou dávku x xxx xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" xxxxx, xxxx xx xxx kritéria xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx odůvodněna x xxxxxxxx xx dosavadních xxxx xxxxxxxxxx údajích x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx zhodnoceny xxxxxxxxxxxxx xxxxxxxx. Mají-li být xxxxxxx, měly xx xxx xxxxxxxxxxx testy xxxxxxx x odůvodněny xxxx provedením studie.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx nebo xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX xxxx xxx xxxxxxxx xxxxxx, která xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx NNG xxxx xx dosavadní xxxxxxx xxxxxxx xxxx pod xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx xxxxx xxx xxxxxxx pro xxxxxxxxx xxxxxxxx.

Xxxx xx být xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx. xxxx xx xxx vzaty x xxxxx parametry, xxxx jsou variabilita xxxxxx, xxxxx xxxxx x odpovědi x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx prostředek statistické xxxxxx. Statistická významnost xx xxxx neměla xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx to, kolikrát xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx zkoušky na XXX x xxxxxxxxx xxxxxxx xxxxx in xxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx buňkách xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx XXX in xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx poškození XXX, xxxxx lze xxxxxxxxx touto xxxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx xxxxxxx xx krevního xxxxx xxxx. xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- xxxxxxxxxxx x xxxxxxx zkoušené xxxxx x rozpouštědle/vehikulu, xx-xx xxxxx.

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx a pohlaví xxxxxx,

- zdroj, xxxxxxxx xxxxx, strava xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx počátku xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x směrodatné xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx xxxxxx xxx zjištění xxxxxxx, xxxxx xxxx xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- zdůvodnění xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx ověření, zda xx xxxxxxxx xxxxx xxxxxxx do xxxxxxxx xxxxx nebo xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx expozice x odběru,

- xxxxxx xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na pozitivní, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx xxxxxxx xxxxx xxx xxxxxxxxxxxxxx buněčným xxxxxx x xxxxx xxx xxxxxxxxxxxxxx cytoplasmě, x čistý xxxxx xxx, xxxxxxxxxx pro xxxxxxxxx, xxxxxxx x xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- známky xxxxxxxx,

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

- dosavadní xxxxx o negativní (xxxxxxxxxxxx/xxxxxxxxx) a pozitivní xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxx "opravovaných" xxxxx, xx-xx xxxxxxxx,

- xxxxx xxxxx x X-xxxx, xx-xx stanoven,

- životaschopnost xxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, X. Xxxxxxx, X. A., Burlinson, X., Penman, X. X. (1985), Xx Xxxxxxxxxx of the Xx vivo Xxx. Xxxxxxxxxx DNA Repair Xxxxx, Xxxxxxxxxx Res., 156, 1-18.

2) Xxxxxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxx, D., Mirsalis, X., Xxxxxx, G., Xxxxxxxx, G. (1987), X Xxxxxxxx and Xxxxx for xxx Xx xxxx Xxx Xxxxxxxxxx DNA Repair Xxxxx, Mutatation Xxx., 189, 123-133.

3) Xxxxxxxx, X. C., Waters, X., Xxxxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X., Xxxxxxx, X. X., Dean, X. X., Mitchell, X. xx X. (1993), Xx vivo Xxx Liver UDS Xxxxx, in: Xxxxxxxx X. J., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx II xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Xxxx, X. X., Xxxxxx, X., Brambilla. G., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxx, X., Hertner, X., XxXxxxx, C. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx xx XXX Xxxxx Xx xxxxx xxx In xxxx, Xxxxx. Xxx., 312, 263-285.

5) Xxxxx, X., Xxxxxxx, B., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, X. (1993), Assessment xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxx xxx xxx Xxxxxxxxxx xx Freshly Xxxxxxxx Xxx Xxxxxxxxxxx Xxxx xxx the In xxxx/Xx xxxxx XXX Xxxxxx Assay (XXX), Xxxxxxxxxx Res., 291, 21-27.

6) Mirsalis, X. X., Xxxxx, C. X., Xxxxxxxxxxx, X. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xx xxx In xxxx/Xx xxxxx Hepalocyte XXX Xxxxxx Xxxxx, Xxxxxxx.Xxxxxxx. 4, 553-562."


XXXXXXX 5

OBECNÉ XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX XXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES, Úř. xxxx. L 332, 28. 12. 2000, x. 81.


PŘÍLOHA 6

"

XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx ustanovení xx. 22 xxxx. 1 písm. x) xxxx směrnice, xxxx xxx obaly o xxxxxxxxx objemu xxxxxxxxxx xxxxx, x xxxxx xx spojeno riziko xxx xxxxxxxxxx (Xx; X 65) a xxxxx xxxx klasifikovány x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX této xxxxxxxx, x xxxxxxxx látek xxxxxxxxx xx xxx xx xxxxx aerosolů xxxx x nádobách xxxxxxxxxx aerosolovým rozprašovačem, xxxxxxxx xxxxxxx odolnými xxxxx otevření xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx použité xx xxxxxxxxx uzavíratelných obalech xxxx xxxxxxxx xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx xxxxxx dětem — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx x metody xxxxxx xxxxxxxx" přijatou Mezinárodní xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Xxxxxxxxx neuzavíratelné xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx CEN XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx xxxxx — Xxxxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx obaly xxxxxx xxx farmaceutických xxxxxxx" xxxxxxxx Evropským xxxxxxx xxx normalizaci (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx shody x xxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxx, xxxxx xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx obal xx xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx xx xxxxxxx xxxxxx k xxxxxx xxx xxxxxx xxxxxxxx, nemusí xxx xxxxxxx provedena.

Ve xxxxx xxxxxxxxx xxxxxxxxx a xxxxx existují xxxxxxxxx xxxxxx x pochybám x bezpečnosti uzávěru xxx dítě, xxxx xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx osoba odpovědná xx xxxxxxx xxxxxxx xx xxx předložila xxxxxxxxxx vydaný laboratoří xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx takový, xx jej není xxxxxxxx zkoušet podle xxxx xxxxxxxxx norem XXX x CEN,

nebo

- xx xxxxxx byl xxxxxxx x byl xxxxxxx vyhovujícím podle xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx týkající se xxxxxxxxxxxx výstrah

Technické specifikace xxx xxxxxxxxxx xxxxxxxx xxxx xxx x xxxxxxx x xxxxxx XX XXX 11683 (xxxxxx x xxxx 1997) "Obaly — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"