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Směrnice Xxxxxx 2000/32/ES

ze xxx 19. xxxxxx 2000,

xxxxxx xx xx xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx pokroku xxxxxxxx Xxxx 67/548/XXX x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx klasifikace, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [1]

(Text s xxxxxxxx xxx EHP)

KOMISE XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx x xxxxxxxx Evropského xxxxxxxxxxxx,

x xxxxxxx xx xxxxxxxx Xxxx 67/548/EHS xx xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx nebezpečných xxxxx [2], naposledy xxxxxxxxxx xxxxxxxx Evropského xxxxxxxxxx x Rady 1999/33/XX [3], a xxxxxxx xx článek 28 xxxxxxx směrnice,

vzhledem k xxxxx xxxxxxx:

(1) Xxxxxxx X xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx nebezpečných xxxxx xxxxxxxx s xxxxxxxxxx xxxxx x xxxxxxxxxxx a xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxx, že xx měl být xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx příloze xxxxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx x tabulky X x xxxxxxx X.

(2) Xxxxxxx III xxxxxxxx 67/548/EHS obsahuje xxxxxx vět udávajících xxxxxx zvláštních xxxxx xxxxxxxxx s nebezpečnými xxxxxxx x přípravky. Xxxxxxx XX směrnice 67/548/XXX obsahuje seznam xxx s xxxxxxxxxxxxxx xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxx a xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/XXX xxxxxxxx xxxxx ke xxxxxxxxxxx x x označování xxxxxxxxxxxx xxxxx x xxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx III, IV x VI.

(3) X xxxxxxx V xxxxxxxx 67/548/XXX se xxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, xxxxxxxx x xxxxxxxxxxx xxxxx x xxxxxxxxx. Xx xxxxxxxx xxxxxxxxxxx tuto xxxxxxx xxxxxxxxxxx xxxxxxx.

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx otevření xxxxx. Tyto xxxxxxxx xx xxxx xxx xxxxxxxxxxxx a xxxxxxxxxxxxx. Xx xxxxxxxx rozšířit xxxxxx, xxx xx xxxxxxx xxxxxx xxxxx xxxxxxxx dětmi používají.

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

XXXXXXX TUTO SMĚRNICI:

Článek 1

Směrnice 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx X xx xxxx takto:

a) xxxxxxxxxxxx xxxxxxxx x xxxxxxxxx xx nahrazuje poznámkou X x xxxxxxx 1X xxxx xxxxxxxx;

x) xxxxxxxxxxxx xxxxx x xxxxxxx X xx xxxxxxxxx xxxxx x xxxxxxx 1B xxxx xxxxxxxx;

x) xxxxxxxxxxxx xxxxxxx xx xxxxxxxxx položkami x příloze 1C xxxx směrnice;

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

2. Xxxxxxxxxxxx xxxx x xxxxxxx III xx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx XX xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx x xxxxxxx XX se xxxxxxxxx xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3A xxxx xxxxxxxx;

x) odpovídající xxxxxx x xxxxxxx IV xx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx pokyny pro xxxxxxxx zacházení x xxxxxxx 3X této xxxxxxxx.

4. Xxxx X xxxxxxx X se xxxx takto:

a) xxxxxxxx X.10 xx xxxxxxxxx xxxxxx v příloze 4X této xxxxxxxx;

x) xxxxxxxx X.11 se xxxxxxxxx textem x xxxxxxx 4B xxxx xxxxxxxx;

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

x) xxxxxxxx X.13 x X.14 xx xxxxxxxxx xxxxxx x příloze 4D xxxx xxxxxxxx;

x) kapitola X.17 se xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx směrnice;

f) xxxxxxxx X.23 xx xxxxxxxxx xxxxxx v xxxxxxx 4F xxxx xxxxxxxx. Název xxxxxxxx X.23 ve xxxxxxxxxxx xx mění odpovídajícím xxxxxxxx;

x) vkládá se xxxx x příloze 4X xxxx xxxxxxxx.

5. Xxxxxxx xx čtvrtá xxxxxxx xxxxxxxx xxxxx x xxxxx C xxxxxxx V.

6. Xxxxxxxxxxxx xxxxx v xxxxxxx XX xx xxxxxxxxx xxxxx x příloze 5 této xxxxxxxx.

7. Xxxxxxx IX xx xxxx xxxxxxxx xxxxxxxx x příloze 6 xxxx směrnice.

Xxxxxx 2

1. Xxxxxxx xxxxx uvedou v xxxxxxxx xxxxxx x xxxxxxx předpisy xxxxxxxx xxx dosažení xxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Neprodleně x nich xxxxxxx Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx státy xxxx xxxxxxxxx xxxxx na xxxx xxxxxxxx xxxx xxxx xxxxxx xxxxx xxx xxxxxx při xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx xxxxxx xx xxxxxxx členské xxxxx.

2. Xxxxxxx státy xxxxx Xxxxxx znění xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x xxxxxxx xxxxxxxxxx xxxx směrnice, a xxxxxxxxxx tabulku xxxx xxxxxxxx a xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxxxxx.

Xxxxxx 3

Xxxx směrnice xxxxxxxx x xxxxxxxx xxxxxx dnem xx xxxxxxxxx x Xxxxxxx xxxxxxxx Evropských xxxxxxxxxxxx.

Xxxxxx 4

Tato xxxxxxxx xx xxxxxx členským xxxxxx.

X Xxxxxxx xxx 19. května 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx


[1] Xxxxxxx xx xxxxxxxxxxxx po dvacáté xxxxx.

[2] Xx. věst. 196, 16.8.1967, x. 1.

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


XXXXXXX 1X

XXXXXXXXX K XXXXXXX I

Vysvětlení xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx a xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


XXXXXXX 1X

"XXXXXXX X

X

Xxxxxx

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

18

Xx

Xxxxx

Xxxxx

Xxxxx

Αργό

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"


XXXXXXX 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. xxx. 3; X40 Xx; X22 X; R50

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) natrium-N-methyldithiokarbamát

205–293–0

137–42–8

Xn; X22 X31 X; X34 X43 X; X50–53

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

006–015–00–9

xxxxxx (XXX) 3-(3,4-dichlorfenyl)-1,1-dimethylmočovina

206–354–4

330–54–1

Karc. xxx. 3; R40 Xxxx. xxx. 3; R40 Xx; X22–48/22 X; X50–53

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

006–016–00–4

xxxxxxxx (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

204–043–8

114–26–1

X; X25 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 T; X24 X; R50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 X; X50–53

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

006–019–00–0

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

218–961–1

2303–16–4

Xxxx. kat. 3; R40 Xx; X22 X; X50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; X22 X43 N; X50–53

Xx; X R: 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

proxan-natrium (ISO) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx

205–443–5

140–93–2

Xx; R22 Xi; X38 X; R51–53

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

006–028–00-X

xxxxxxxxx (XXX) 2-(1-methylpropyl)-4,6-dinitrofenyl-isopropyl-karbonát 2-xxx-xxxxx-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx

213–546–1

973–21–7

X; X25 N; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

xxxxxxxxx (XXX) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx

230–253–4

6988–21–2

X; R25 N; X51–53

X; N R: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

xxxxxxxxx (XXX) 3-(3-chlor-4-methoxyfenyl)-1,1-dimethylmočovina

243–433–2

19937–59–8

N; 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-xxxxxxxx xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx

245–430–1

23103–98–2

X; X25 X; X50–53

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

006–037–00–9

xxxxxxxxx (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–113–0

2631–37–0

X; R25 N; X50–53

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

006–038–00–4

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

X

202–388–9

95–06–7

Xxxx. xxx. 2; X45 Xn; X22 N; X50–53

X; X R: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; R22–48/22 R43 X; X50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; X40 Xx; R22 X; X50–53

Xx; N R: 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; R36/38 Xxxx. xxx. 3; X40 X; R50–53

Xn; X X: 36/38–40–50/53 S: (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

bendiokarb (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

bufenkarb (ISO) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

8065–36–9

X; R24/25 N; 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 S: (2-)60-61

006–050–00–X

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

4482–55–7

Xx; X38 X; X50–53

Xx; X X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xx; X21 N; X50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; N X: 22–51/53 X: (2-)24-61

006–060–00–4

oxykarboxin (XXX) 2-methyl-4,4-dioxo-5,6-dihydro-4λ4-1,4-oxathiin-3-karboxanilid

226–066–2

5259–88–1

Xn; X22 X52–53

Xx X:22–52/53 X: (2-)61

006–069–00–3

xxxxxxxxx-xxxxxx (ISO) 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 N; X50–53

Xx; N X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

xxxxxxxxxxx (XXX) xxxxx-X -[({[(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 X; X50–53

X; X X: 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. xxx. 2; X45 X; X23/25 X; X34 X; X51–53

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

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-xxxxxxxxxxxxxxxx

X

540–73–8

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

X; X X: 45–23/24/25–51/53 S: 53–45–61

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

009–003–00–1

kyselina fluorovodíková … %

B

231–634–8

7664–39–3

T+; X26/27/28 X; R35

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

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

015–039–00–9

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

201–676–1

86–50–0

X+; X26/28 X; X24 X43 X; X50–53

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

015–048–00–8

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

200–231–9

55–38–9

Xxxx. xxx. 3; R40 X; R23–48/25 Xx; X21/22 X; R50–53

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

015–056–00–1

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

220–147–6

2642–71–9

T+; X28 X; R24 X; X50–53

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

015–140–00–8

xxxxxxxxx (XXX) X,X-xxxxxxx-X-(1-xxxxx-1 X- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx

245–986–5

24017–47–8

X; X23/25 Xx; X21 N; R50–53

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

016–013–00-X

chlorid xxxxxxx

234–129–0

10545–99–0

X14 X; X34 X; X50

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

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

016–014–00–5

chlorid xxxxxxxx

13451–08–6

X14 X; R34 X; X50

X; N 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; X45 Xxxx. xxx. 3; X40 X+; X26 X; X25 X; X34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

dimexano (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

016–071–00–6

3-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 R: 43 X: (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 %: X; R34 5 % ≤ X < 10 %: Xi; R36/37/38

030–004–00–8

dimethylzinek [1] xxxxxxxxxxxx [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 C; X34 X; X50–53

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

050–002–00–0

xxxxxxxxx (XXX) tricyklohexyl(hydroxy)stannan tricyklohexylstannium-hydroxid

236–049–1

13121–70–5

Xn; X20/21/22 X; X50–53

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

050–012–00–5

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

X ≥ 1 %: Xn; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

X+; R26 Xx; X36/38 N; X50/53

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

082–009–00–X

xxxx (xxxxxxxxxxxx olovnatý) XX Xxxxxxx Xxxxxx 34 (XX 77603) XX xxxxxxxxxx xxxx 34 (XX 77603)

215–693–7

1344–37–2

Karc. xxx. 3; R40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 X; X50–53

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

1

082–010–00–5

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

235–759–9

12656–85–8

Xxxx. xxx. 3; R40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 R33 X; X50–53

X; X X: 61–33–40–50/53–62 X: 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]

R10 Xx; X65 Xx; X37 X; X51–53

Xx; 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; X46 Xxxx. xxx. 2; X60–61 N; X50–53

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

601–034–00–4

benzo[e]acefenanthrylen

205–911–9

205–99–2

Karc. 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; X50–53

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

602–054–00–6

3-jodprop-1-en xxxxxxxxxx

209–130–4

556–56–9

X10 X; X34

X X: 10-34 X: (1/2-)7–26–45

603–076–00–9

xxx-2-xx-1,4-xxxx

203–788–6

110–65–6

X; X23/25 Xx; X21–48/22 X; X34

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

X ≥ 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 % ≤ C &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; X22 Xx; X36

X; Xx R: 8–22–36 S: (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; R51–53

Xn; X X: 20–51/53 X: (2-)23-61

603–097–00–3

1,1', 1′′-nitrilotripropan-2-ol xxxxxxxxxxxxxxxxxx

204–528–4

122–20–3

Xx; R36 X52–53

Xx X:36–52/53 X: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx

200–661–7

67–63–0

X; R11 Xx; X36 X67

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

604–020–00–6

xxxxxxx-2-xx 2-hydroxybifenyl 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 Xx; X37/38–41 N; X50

Xx; X X: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

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

401–720–1

6807–17–6

Repr. xxx. 2; R60 Xx; X36 X; X50–53

X; N X: 60–36–50/53 X: 53–45–60–61

604–041–00–0

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

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xn; R22 Xx; X38–41 X; X50–53

Xx; N 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 X43

Xx X: 36-43 X: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx hydrochinonmonomethylether

205–769–8

150–76–5

Xn; X22 Xx; X36 R43

Xn 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 Xn; X20 Xx; R36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

X ≥ 10 %: Xx; X20–36/38–40–43 1 % ≤ X &xx; 10 %: Xx; R40–43

606–016–00-X

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

201–462–8

83–26–1

X; R25–48/25 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; R50–53

Xn; X X: 22–36/38–50/53 X: (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 X; X24/25 X; R50–53

T; 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 H)-on 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx

244–209–7

21087–64–9

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

xxxxxxxxxxx (ISO) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx xxxxxxx

216–920–2

1698–60–8

X43 X; X50–53

Xx; N X: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Xxxx. xxx. 3; X62 Xx; R20/21/22–48/22 Xx; X36 R43 X; X50–53

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

606–037–00–4

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

256–103–8

43121–43–3

Xx; X22 N; X51–53

Xx; 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 Xi; R36 X; R50–53

Xn; N X: 22–36–50/53 S: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xi; X41 X52–53

Xx; N X: 22–41–52/53 S: (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) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 H -xxxxxxx-2-xx 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) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx 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; X24 Xn; X22 N; R51–53

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

607–097–00–4

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

209–008–0

552–30–7

Xx; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx valerová kyselina

203–677–2

109–52–4

C; X34 X52–53

X R:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xx; X22 X; R51–53

Xn; X X: 22–51/53 S: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; X36/38 R52–53

Xi X:36/38–52/53 X: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xn; X22 Xx; R38 X; X50–53

Xx; X R: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

xxxxx xxx xxxxxxxxxxx kyseliny xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; X25 Xx; X38 N; X50

X; X R: 25–38–50 S: (1/2-)22–37–45–61

607–159–00–0

xxxxxxxxxxxxxx (XXX) ethyl-2,2-bis(4-chlorfenyl)-2-hydroxyacetát xxxxx-4,4'-xxxxxxxxxxxxxxx

208–110–2

510–15–6

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

607–176–00–3

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

400–830–7

X43 X; X51–53

Xx; X X: 43–51/53 S: (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

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

403–030–6

Xn; R22 X43 X; X50–53

Xx; 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 N; X51–53

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

607–217–00–5

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

403–960–2

R43 R53

Xi X: 43-53 X: (2-)24–37–61

607–243–00–7

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

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

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

X52–53

X: 52/53 X: 61

607–248–00–4

Xxxxxxxx-xxxxxxx Xxxxxxx-X-(1-xxxxxx)xxxxxxxx

205–073–4

132–67–2

Xx; X22

Xx X: 22 X: (2)

607–249–00-X

(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx tripropylenglykol-diakrylát TPGDA

256–032–2

42978–66–5

Xi; X36/37/38 X43 X; X51–53

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

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

607–252–00–6

λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 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; R50–53

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

607–255–00–2

xxxxxxxxxx (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx 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 Xxxx. xxx. 2; X45 T; X23/24/25 Xx; X37/38–41 X43 X; R51–53

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

C ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ C &xx; 5 %:X; X45–23/24/25–43 0,2 % ≤ X < 1 %:X; R45–20/21/22 0,1 % ≤ X &xx; 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; R50–53

Xi; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 T+; R28 X; X24 R44 X; R50–53

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

609–040–00–9

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

E

217–406–0

1836–75–5

Karc. xxx. 2; X45 Xxxx. kat. 2; X61 Xn; X22 X; X50–53

X; X X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 X43 N; 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; R50–53

T; X X: 45–50/53 X: 53–45–60–61

611–013–00–1

4-hydroxy-3-{4-[2-methoxy-4-(3-sulfonatofenylazo)fenylazo]-3-methylfenylazo}-6-(3-sulfonatoanilino)naftalen-2-sulfonát xxxxxxxxx

403–650–7

117409–78–6

X; X2 X; X51–53

X; X R: 2–51/53 X: (2-)35-61

611–031–00-X

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

209–321–2

569–61–9

Xxxx. kat. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-xxxxxxxxxxxxx o-anisidin

E

201–963–1

90–04–0

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

X X: 45–23/24/25 X: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; R22 X; R50–53

T; N X: 45–22–50/53 S: 53–45–60–61

X ≥ 25 %: X; X45–22 0,01 % ≤ X < 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. kat. 2; X45 Xxxx. xxx. 3; R40 X; X39/23/24/25Xx; R48/20/21/22 X43 N; R51–53

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

612–081–00–5

3,3'-xxxxxxxxxxxxxxxx, xxxx o-tolidin, xxxx

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; R45 Xx; X22 X; X51–53

X; X X: 45–22–51/53 X: 53–45–61

612–099–00–3

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

X

202–453–1

95–80–7

Xxxx. xxx. 2; X45 X; R25 Xx; X21 Xx; X36 X43 N; X51–53

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

612–105–00–4

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

205–411–0

140–31–8

Xx; X21/22 X; R34 X43 X52–53

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

612–111–00–7

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

212–513–9

823–40–5

Xxxx. xxx. 3; X40 Xx; X21/22 X43 N; X51–53

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

612–125–00–3

2-methyl-p-fenylendiamin2-methyl-1,4-fenylendiamin2-methylbenzen-1,4-diamin 2,5-xxxxxxxxxxxx

202–442–1

95–70–5

X; X25 Xx; X20/21 X43 N; X51–53

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

612–144–00–7

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

62924–70–3

Xx; X36/38 X4 3 N; X50–53

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

612–151–00–5

xxxxxxxxxxxxx toluendiamin xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; X45 T; X25 Xx; X20/21 Xx; X36 X43 X; X51–53

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

613–018–00–4

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

7411–47–4

Xx; X22 Xi; X36/37/38 X52–53

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

613–031–00–5

symklosen xxxxxxxxxxxxxxxxxxxx xxxxxxxx trichlor-1,3,5-triazintrion 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5H)-trion

201–782–8

87–90–1

O; X8 Xx; R22 R31 Xx; X36/37 N; X50–53

X; Xx; X 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 xxxxxxxxxxxxx

202–095–6

91–76–9

Xx; X22 R52–53

Xn X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 X; X41 X; R50–53

Xn; X 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 -imidazol-1-ium-hydrogensulfát [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; R20/22 Xx; X41 X; X50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 X; X50–53

Xx; X R: 22–50/53 X: (2-)60-61

613–091–00–2

xxxxxxxxxx-xxxxxxxxx [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]

Xx; X22 Xx; X36/37/38 X52–53

Xx; X: 22–36/37/38–52/53 S: (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; R51–53

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

613–130–00–3

xxxxxxxxxxx (XXX) (RS)-2-(2,4-dichlorfenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol

79983–71–4

R43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

613–131–00–9

xxxxxxxxxx (XXX) 1,2,5,6-tetrahydro-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-chlorfenyl)-2-[(1 H-1,2,4-triazol-1-yl)methyl]hexannitril

88671–89–0

Repr. xxx. 3; X63 Xx; X22 Xx; X36 N; 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; R50–53

N X: 50/53 S: 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 X: 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+ R:26/28–52/53 S: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; X26/28 R52–53

T+ 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 R42/43 X52–53

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

X320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; R23–40–42/43 0,1 % ≤ X &xx; 1 %:Xn; X20–42

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 X31 X; X34 R42

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

616–034–00-X

xxxxxxxxxxxx (XXX) 6-methyl-3,4-dihydro-2H-pyran-5-karboxanilid

246–419–4

24691–76–7

R52–53

R: 52/53 S: 61

616–035–00–5

xxxxxxxxx X -[(xxxxxxxxxx)xxxxxxxx]-2-xxxx-2-(xxxxxxxxxxxx)xxxxxxxx 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx

261–043–0

57966–95–7

Xx; X22 X43 X; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; R7 Xx; X22 X; X34 X; R50–53

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

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

617–006–00-X

xxx(α, α-xxxxxxxxxxxxxx)xxxxxxx bis(2-fenylpropan-2-yl)peroxid xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx xxxxxxxxxxxxxx

201–279–3

80–43–3

X; R7 Xx; R36/38 X; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xi; X36 R43

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

650–007–00–3

xxxxxxxxxxxxx (XXX) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx

228–200–5

6164–98–3

Xxxx. kat. 3; X40 Xn; X21/22 X; X50–53

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

650–008–00–9

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

227–197–8

5707–69–7

X; R25 N; X50–53

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

650–009–00–4

chlordimeform-hydrochlorid X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx N2-(4-chlor-2-methylfenyl)-N1,N1-dimethylformimidamid-hydrochlorid X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx

243–269–1

19750–95–9

Xxxx. xxx. 3; R40 Xx; X22 N; X50–53

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

650–033–00–5

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

66230–04–4

X; X23/25 R43 N; X50–53

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

650–041–00–9

triasulfuron (XXX) 1-[2-(2-chlorethoxy)benzen-1-sulfonyl]-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)močovina

82097–50–5

N; X50–53

X X: 50/53 X: 60-61


PŘÍLOHA 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační limity

Poznámky x přípravkům

006–090–00–8

2-[(3-jodprop-2-yn-1-yl)oxy]ethyl-N-fenylkarbamát

408–010–0

88558–41–2

Xn; 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; R50–53

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; X50

X X: 50 X: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 X; X51–53

Xx; X R: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx difenyletheru xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 R64 X; R50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X X: 52/53–59 S: 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

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

406–325–8

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)39-61

603–131–00–7

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

407–290–1

Xx; X41

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

603–132–00–2

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

408–200–3

63187–91–7

Xx; X38–41 R52–53

Xi X:38–41–52/53 S: (2-)26–37/39–61

603–133–00–8

Směs:3-(4-amino-2-chlor-5-nitroanilino)propan-1,2-diol x 3,3'-[(2-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: alkyl(C1-C10)-dodecyldifenylethery a xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (xxxxxxx x xxxxxxxxxx xxxxxxxxxxxx)

410–450–3

X53

X: 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; R41 X; X51–53

Xx; X X: 41–51/53 X: (2-)26–39–61

603–136–00–4

3-{4-[bis(2-hydroxyethyl)amino]-2-nitroanilino}propan-1-ol

410–910–3

104226–19–9

R43 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-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx

403–140–4

103694–68–4

X52–53

X:52/53 X: 61

604–050–00-X

4-xxxxx-x-xxxxxx 4-xxxxx-2-xxxxxxxxxxx

216–381–3

1570–64–5

X; X23 C; R 35 N; X50

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

X ≥ 25 %: X; C; R23–35 10 % ≤ X &xx; 25 %: C;R20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ C < 5 %: Xn;R20–36/37/38 1 % ≤ X < 3 %:Xx;X36/37/38

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

2,2'-xxxxxxxxxxx[6-(2 X - benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)fenol] 6,6'-xxx(2X -benzotriazol-2-yl)- 4,4'-bis(1,1,3,3-tetramethylbutyl)- 2,2'-xxxxxxxxxxxxxxx

403–800–1

103597–45–1

X53

X:53 X: 61

604–053–00–6

4-terc - butyl-2-methyl-6-(1-methylpentadecyl)fenol

410–760–9

157661–93–3

Xi; X38 X43 X; 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 a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx

412–020–0

X43 R52–53

Xi X:43–52/53 X: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Kat.3; X40

Xx X: 40 X: (2-)22–36–37

605–027–00–7

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

410–480–7

X43 N; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-pentylcyklohexanon xxxxxxxxxxxxxxxx-1-xx

4–406–670–4

61203–83–6

X; X51–53

X R: 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 (XXX) [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

xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 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-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx

405–350–1

54527–73–0

X43 N; X51–53

Xx; N X: 43–51/53 X: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

X43

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

607–276–00–7

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

405–635–0

Xx; X38–41 N; X50–53

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

607–277–00–2

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

405–720–2

Xx; R22 Xx; X41 X43 X; X51–53

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

607–278–00–8

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

405–760–0

Xx; X41 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 (oktadecylimino)diethylen-(hydrogen-ftalát)-(hydrogen-maleinát)

405–960–8

R43 X; X51–53

Xx; X X: 43–51/53 S: (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

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

407–000–3

127519–17–9

X; X51–53

X X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 X: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xi; X38–41 X43 N; X50–53

Xx; X X: 21/22–38–41–43–50/53 X: (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 lithium-3,3'-{(1,4-fenylen)bis[(karbonylimino)(propan-3,1-diyl)imino]}bis(10-amino-6,13-dichlor[1,4]benzoxazino[2,3-b]fenoxazin-4,11-disulfonát)

410–040–4

136213–76–8

N; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–065–0

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

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

410–070–8

141880–36–6

X43 X52–53

Xx X:43–52/53 X: (2-)22–24–37–61

607–287–00–7

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

410–140–8

X52–53

X:52/53 X: 61

607–288–00–2

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

410–160–7

148732–74–5

Xx; X36 R43 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 xxxxxxxx

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

Směs (x xxxxxxxx poměru):amonium-1-alkyl(C14-C18)-4-[3-(allyloxy)-2-hydroxypropyl]-2-sulfonatobutandioát a xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx

410–540–2

Xx; X38 X43 X; X50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(alkyl(C14)oxy)-1-(methoxymethyl)]octová xxxxxxxx

410–640–6

Xx; X38–41 N; X50–53

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

607–293–00-XXxxx:

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

410–650–0

Xx; X41 X43 X; X51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

Směs:tetranatrium-fosfonobutandioát x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx

410–800–5

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

Xxxx:xxxxxxxxxxx xxxxxxxxxxxxxxxx, xxxxxxxxx kyselina a 2-xxxxxxxxxxxxx kyselina

410–830–9

R53

R: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; X41

Xx R: 41 X: (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; X X: 22–43–50/53 S: (2-)24–37–60–61

607–300–00–6

[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, d-sulfonatoftalocyanin]měďnatý komplex, xxxxxxxx xxx; a = 1,2,3 xxxx 4, b = 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 x xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–910–6

Xx; R38–41 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 X52–53

Xx R: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; R50–53

N R: 50/53 S: 60-61

608–024–00–9

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

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

X53

X:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; R3 X; X8 Karc. xxx. 2; X45 X; X23/25 X43

X; T X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; R22–48/22 C; X34 X43 X; X50–53

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

611–043–00–5

Směs (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný, [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 xxxxxxxx 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 xxxxxxxx

402–850–1

Xx R: 41–52/53 S: (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, [bis(4-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [(5-terc-butyl-3-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx x[(4(5)-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx) (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 S: 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; X X: 25–43–48/22–50/53 S: (1/2-)22–28–36/37–45–60–61

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 X: 61

611–048–00–2

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

407–900–6

111381–12–5

X53

X: 53 X: 61

611–049–00–8

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, xxxxxxxx xxxxxx x mléčná xxxxxxxx (2:1:1)

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

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

611–051–00–9

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

411–110–7

136213–74–6

X; X50–53

X X: 50/53 X: 60-61

611–052–00–4

[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) azo]-6-[(6-sulfonato-1-naftyl)azo]benzen-1,3-diolato}]železnatý xxxxxxx, xxxxx xxx

400–720–9

X52–53

X: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; X41 X; X50–53

Xx; 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 Xx; R41 X43 X; X51–53

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

612–158–00–3

Xxxx:[xxx(5-xxxxx(xxxxxxxxxx C12))-2-hydroxybenzaldoximato)]měďnatý xxxxxxx a 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx a 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 X: 61

612–159–00–9

xxxxxxx produkty xxxxx 2,2,4-xxxxxxxxx- a 2,4,4-trimethylhexan-1,6-diaminu (x xxxxxxx XXXXXX), xxxxxxxx [(alkyl(C10-C16)oxy)methyl]oxiranu (Epoxid 8) a 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx

410–880–1

Xx; X22 X; X34 N; 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-xxxx-xxxxx-5-[(4-xxxx-xxxxxxxxxxx)xxxxxxxx]-4-xxxxxxxxxxxxxx-3(2X)-xx

405–700–3

96489–71–3

X; X23/25 X; R50–53

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

613–150–00–2

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

406–295–6

X53

X:53 X: 61

613–151–00–8

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

406–360–9

104218–44–2

R53

R:53 S: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-xxxxxxxxxxxxxxx

407–270–2

16063–70–0

X52–53

X:52/53 S: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx R: 22 S: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; R22 R52–53

Xn X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-butyl-5-chlorimidazol-4-karbaldehyd

410–260–0

83857–96–9

R43 X; X51–53

Xx; X 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; R22–48/22 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; X20/22 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 X; X50–53

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

613–160–00–7

2-methyl-2,5-diazabicyklo[2.2.1]heptan-dihydrobromid

411–000–9

125224–62–6

R43

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

615–022–00–1

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

410–550–7

79277–18–2

X; X2 X14 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 xxxxxxxxxxxxxx-2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxx

410–900–9

83056–32–0

X10 X14 Xxxx. xxx. 3; X40 Xx; 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

X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)-2-(3-xxxxxxxxxxxxxxxx)xxxxxxxxx

402–510–2

X; X51–53

X X: 51/53 S: 61

616–045–00-X

2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxxxxx

405–190–2

122371–93–1

X43 X53

Xx X: 43-53 X: (2-)22–24–37–61

616–046–00–5

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

406–390–2

N; R50–53

N X: 50/53 S: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x X, X′,X″,X′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

X43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 X; R51–53

Xn; 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 X: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 N; X50–53

Xx; X X: 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 Směs:2,4-bis[3-(4-methylfenyl)ureido]toluen x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx

411–070–0

X53

X: 53 X: 61

617–015–00–9

xxx(4-xxxxxxxxxxxxx)xxxxxxx

407–950–9

895–85–2

X; X2 X; X7 X; X50–53

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

650–032–00-X

xxxxxxxxxxxx (XXX) (2X, 3X)-, (2 X, 3 X)-, (2 R, 3 S)-, (2 X, 3 R)-2-(4-chlorfenyl)-3-cyklopropyl-1-(1H- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

94361–06–5

Xxxx. xxx. 3; X63 Xx; X22 X; X50–53

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


XXXXXXX 2

XXXXXX SPECIFICKÝCH XXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 3A

STANDARDNÍ POKYNY XXX BEZPEČNÉ ZACHÁZENÍ X NEBEZPEČNÝMI XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.


XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX ZACHÁZENÍ X NEBEZPEČNÝMI LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 4X

"X.10 XXXXXXXXXX — XXXXXXX XX XXXXXXXXXXXX XXXXXXX X XXXXX IN XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxxx má xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx v xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, avšak xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Tato xxxxxx xxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx k xxxxxx xxxxx xxxxxxx používána. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx x existuje xxxxx xxxxxx x xxx, xx chromozomové xxxxxx a x xxxx xxxxxxxxxxx jevy xxxxxxxxxxx xxxxx x xxxxxxxxxx a v xxxxxx somatických buněk xxxxxxxxx xxxxxx, mají xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x u xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx mohou xxx xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, xxxxxxx kmeny xxxx xxxxxxxx xxxxxxx xxxxxxx. Použité xxxxx xxxx xxxxxxx xx xxxxxxx schopnosti xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx chromozomů, xxxxxxxxxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx xxxxxxxx. Tento xxxxxxxxxxx xxxxxxxxx systém xxxxxx zcela xxxxxxxxx xxxxxxxx xx vivo x savců. Je xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx x xxx xxxxx změnou xX, osmolality nebo xxxxxxxx úrovní xxxxxxxxxxxx (4, 5).

Tato xxxxxxx xx používá xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxx xxxxx. Mnoho xxxxxxxxx, xxx xxx xx xxxx xxxxxxx pozitivní, xxxx xxx xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x karcinogenitou xxxx není absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx chemické xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx karcinogeny, xxxxx xxxxxx xxxxxxxx touto xxxxxxxx, neboť xxxxxx xxxxxx xxxxxx xxxxxxxxxx xxx přímým poškozením XXX.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

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

Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx v xxxxx po S-fázi xxxxxxxxx XXX xxxxxxx x xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx xxxx chromozomy xx 4, 8, 16… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx a s xxxxxxxxx odchylkou xxxxxxxxx.

Xxxxxxxxx xxxxx : xxxxx xxxxx, xxxxx se xxxxxxxxx v xxxxxxxx, x xxxxxxxxx xxxxx xxxxx x populaci; xxxxx stupeň proliferace xxxx xxxxxxxx.

Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx od xxxxxxxxxx xxxxx obvyklého u xxxxxxxxx xxxx buněk.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx xxxxxxxxxx při xxxxxxxx dělení ve xxxxxx xxxxxxxx; xxxx xx jako delece x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx interchromozomální xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, a xx s metabolickou xxxxxxxx a xxx xx. V xxxxxx xxxxxxxxxxx intervalech po xxxxxxxx xxxxx se xx xxxxxxxxx kultur xxxxx látka zastavující xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx xxxxxx, xxxxxx x přítomnost xxxxxxxxxxxxxx xxxxxxx xx xxxxxx 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 kultury, xxxxxx xxxxxxxx buněčných xxxxx (xxxx. fibroblasty xxxxxx xxxxxxxx, lymfocyty xxxxxxxxx xxxx xxxxxxx xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). X xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x kmenů by xxxx xxx xxxxxxx xxxxxxxxxxxx stabilita modální xxxxxxx xxxxx xxxxxxxxxx x xxxx xx xxx kontrolováno, zda xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x případě xxxxxxxxxxx xx xxxxxx být xxxxxxx. Xxx použité xxxxx a inkubační xxxxxxxx xx xxxx xxx známa xxxxxxxx xxxxx xxxxxxxxx cyklu.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx buněčné xxxxx a kmeny: xxxxx xx xxxxxxx x kmenových kultur, xxxxxx se xx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxxx, xxx xxxxxxxxx konfluence xxxx xxxxxxxxx, x xxxxxxxx xx xxx 37 °X.

Xxxxxxxxx: krev ošetřená xxxxxxxxxxxxxxx (např. heparinem) xxxx oddělené xxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xx kultivačního xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. fytohemaglutinin) x xxxxxxxx xx při 37 °C.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx vystaveny xxxxxxxx xxxxx, a xx x vhodnou xxxxxxxxxxxx xxxxxxxx a xxx xx. Nejčastěji používaným xxxxxxxx xx xxxxxxxxxx xxxxxxxx postmitochondriální frakce (X9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Aroclor 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx testovacím xxxxx xxxxxxx používána x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx metabolického aktivačního xxxxxxx xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, která xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx exprimujících specifické xxxxxxxxx xxxxxx, poskytuje xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií xx xxxx být vědecky xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Zkoušená xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být před xxxxxxxx na buňky xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx přidány přímo x xxxxxxxxxx systémům x/xxxx xxxxx xxx xxxx xxxxxxxx zředěny. Xxxx by být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx být xxxxxxxxxx x xxxxxxxx xxxxx x x xxxxxxxxx X9. Xxxx-xx použita xxxx než známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx možno xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx nestálých xx xxxx xx xxxx být xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx přidáním molekulového xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, která mají xxx xxxxxxxxxx xxx xxxxxxxxx nejvyšší xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx systému x xxxxx pH xxxx osmolality.

Cytotoxicita xx xxxx xxx xxxxxxxxx x metabolickou aktivací x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x růstu, xxxx xxxx stupeň xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx index. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx by xxxx xxxx koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx minimální xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx obvykle xxxxxxx, že by xx xxxxxxxxxxx neměly xxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. X xxxxxxxx xxxxxxx by xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, počtu xxxxx xxxx xxxxxxxxxxx xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx je xxxxx xxxxxxxx měřítkem xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx xxxx, xxxxx xxxxxxxx xx xxxxxxxx. Xxxxxxxxx xxxxx je xxxx přijatelný x xxxxxxxxxxx xxxxxx, x xxxxx xxxxx xxx xxxx metody xxxxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), mohou xxx použity xxxx xxxxxxxxx xxxxxxxxx. V xxxxxxx XXX však xxx x xxxxxxxx xxxxxxxxx hodnotu, x xxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, a x xxxx xxxxxxxxx průměrné xxxxxxxxx doby xxxx xxx xx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx maximální xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx toho, která x xxxx xx xxxxxxxx.

X případě relativně xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx xxx xxxxxxxxxxxxx xxxxxxx, xxx xx xxxxxx xxxxxxxxxxx, xx měla xxx xxxxxxx xxxxxxxx xxxxx x koncentraci, jež xx nad mezí xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxx xxxxxxxx. X určitých případech (xxxx. projeví-li xx xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx, xxx xx xxxxxxxxxxx) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, při xxxxx xxxxxxx xx srážení. Xxxx xxx užitečné xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx v xxxxxxxxxx xxxxxxx se může x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, xxxx X9 atd. Nerozpustnost xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx xxxx xxx xxxxxxxxx a negativní xxxxxxxx (kontroly xxxxxxxxxxxx xxxx vehikula). Xxx xxxxxxx xxxxxxxxxxx aktivace xx xxxx xxx xxx pozitivní kontrolu xxxxxxx xxxxxxxx xxxxx, xxxxx x mutagenní xxxxxx xxxxxxxx xxxxxxxx.

X xxxxxxxxx xxxxxxxx xx xxx xxx xxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx, které xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx nárůst xxx pozadí, xxxx xx xxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxx tak, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx nevyšla xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx aktivace

Látka

Číslo XXX

Xxxxx podle EINECS

Bez 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 xxxxxx xxxxxxxxxxxx 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 mohou být xxxxxxx x xxxx xxxxxx látky. Xxx xxxxxxxxx kontrolu xx xxxx xxx pokud xxxxx vzato v xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající se xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx x xxxxxxxxxxx xxxxx a xxxxxxxxxx xxxxxxx způsobem xxxx xxxxxxx. Kromě xxxx by xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx dosud xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx zkoušené xxxxx xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx bez něho. Xxxxxxxx lymfocytů xx xxxx být xxxxxxxx xxx 48 hodin xx mitogenní xxxxxxxxx.

1.4.3.2 Xxx každou xxxxxxxxxxx xx měly xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x xxxxx xx důrazně xxxxxxxxxx x kultur xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxx. Jestliže xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx xxxxxxxxx xx minimální rozdíl, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

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

1.4.3.3 Xxxx xxxxxxx kultur

V xxxxxx xxxxxxxxxxx by měly xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx aktivací, xxx bez xx, xx xxxx 3 — 6 xxxxx, x měly by xxx xxxxxxxx po xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx (12). Xxxxxxxx xxxxx xxxxxx dává xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, tak bez xxxxxxxx, xxx by xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx do odběru x době, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx látky xxx xxxxx detekovat xxx dobách aplikace xxxx odběru xxxxxxx xxx 1,5násobek xxxxx xxxxx. Xxxxxxxxx výsledky xxx xxxxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. X xxxxxxxxx, xxx xx nepovažuje xxxxxxxxx xxxxxxxxxxx xxxxxxxx za xxxxxxxx, xx mělo xxx xxxxxx zdůvodnění.

1.4.3.4 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

Do xxxxxxx xxxxxxx xx obvykle 1-3 xxxxxx xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx xxxxxxxxx. Pro xxxxxxxx xxxxxxxxx pro xxxxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxxx xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů xxxxxxxx hypotonizaci buněk, xxxxxx a obarvení xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při xxxxxx xxxxx dochází ke xxxxx xxxxx xxxxx x metafázi x xx xxxxxx chromozomů, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx rovném xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx xxxxx. Xx xxxxxx xxxxxxxxxxx x xxxxxxxx xx xxxx xxx hodnoceno xxxxxxx 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx rovnoměrně xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Tento počet xxx snížit, xx-xx xxxxxxxxx velký xxxxx xxxxxxx.

Xxxxxx xx xxxxxx xxxxxxx detekovat strukturní xxxxxxxxxxxx aberace, xx xxxxxxxx xxxxxxxxxx polyploidii x xxxxxxxxxxxxxxx, jsou-li xxxxxxxxxx.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx jednotkou xx xxxxx x xxxx xx xxxx xxx xxxxxxxxxxx množství xxxxx xx strukturní xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx s xxxxxx xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx nezahrnují xx do xxxxxxx xxxxxxxx xxxxxxx.

Xxxx by xxx také xxxxxxxxxxx xxxxxxxx, xxxxx xxxx xxxxxxxxx xxx stanovení xxxxxxxxxxxx x xxxxx xxxxxxxxxxxx kultur a xxxxxxxxxxx xxxxxx v xxxxxxxx xxxxxxxxxxxxx s xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Dále xx měly být xxxxxxx údaje shrnuty xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx by měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe s xxxxxxxx experimentálních xxxxxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla být xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, které xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx na xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx tohoto xxxxx. Xxxxxxxx by měla xxx uvážena xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx neměla být xxxxxxx xxxxxxxxx faktorem xxx pozitivní xxxxxxx.

Xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx mitotické xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx počtu xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx progresi xxxxxxxxx cyklu (17, 18).

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech neumožní xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxxxxx na xxxxxxxxxxxx aberace in xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, že xxxxxxxx látka za xxxxxxxx zkoušky xxxxxxxxxx x kultivovaných xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxxxxxxx karyotypu x xxxxxxxx použitého xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- informace x xxxxx xxxxxxxxx xxxxx,

- xxxxxxx dárce krve, xxx byla xxxxxxx xxxx xxxx xxxx xxxxxxxxxx xxxxxxxxx, použitý xxxxxxx,

- případně xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx buněčné xxxxxxx,

- xxxxxxx hodnota xxxxx xxxxxxxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxxxxx xxxxxx koncentrací x xxxxx kultur, xxxxxx např. xxxxx x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, xxxx-xx x xxxxxxxxx,

- xxxxxxx xxxxx, případně koncentrace XX2,

- koncentrace xxxxxxxx xxxxx,

- objem vehikula x přidané zkoušené xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx při xxxxxxxx,

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

- pozitivní x xxxxxxxxx kontroly,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx metafází,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxx, xxxxx x xxxxxxxx xxxxx, xxxxx buněk, xxxxxxxxx xxxxx,

- známky xxxxxxx,

- údaje x xX x osmolalitě xxxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxx,

- xxxxxxxx xxxxxxx, xxxxxx xxxx,

- xxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx x xxxx aberací xxxxxx xxx xxxxxx exponovanou x xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, H. X. (1976), Cytological Methods xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx and Xxxxxxx xxx xxxxx Xxxxxxxxx, Vol. 4, Xxxxxxxxxx, X. (ed) Xxxxxx Xxxxx, Xxx Xxxx and London, 1-29.

2) Ishidate, X. Xx., Xxxxxx, X. (1985), Xxx In xxxxx Chromozomal Xxxxxxxxxx Xxxx Xxxxx Chinese Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx in Xxxxxxx, in: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Ashby, X. et al., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Galloway, X. X., Xxxxxxxxx, M. X., Xxxxxx, C., Xxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxx, X. X., Xxxxxxxx, F., Xxxxx, X., Xxx, X., Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X. A., Anderson, X., Xxxxxx X. (1978), Xxxxxxxxxx aberration xxx xxxxxx xxxxxxxxx xxxxxxxxx in Xxxxxxx xxxxxxx xxxxx xxxxx: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (suppl. 10), 1-175.

4) Xxxxx, X., Galloway, S. X., Xxxxxxxx, X. X., Xxxxxxxx, M. Xx., Xxxxxxx, X., Xxxxx, X., Myhr, X. X. (1991), Xxxxxxxxxxxx xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxxxx Xxx., 257, 147-204.

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

6) Xxxx, X. X., McCann, X., Yamasaki, X. (1975), Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx with the Xxxxxxxxxx/Xxxxxxxxx Microsome Mutagenicity Xxxx, Xxxxxxxx Xxx., 31, 347-364.

7) Xxxxx, X. X., Xxxx, X. X. (1983), Xxxxxxx Methods xxx xxx Salmonella Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 113, 173-215.

8) Xxxxxxxxx, X. X., Tates, X. D., van Xxxx, X. X. X., Meijers, X., xx Xxxxx, X. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx after Xxxxxxxxxx xx a Xxxxxxxxxxx Xxxxxx Xx xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Aberrations xxx Xxxxxx Xxxxxxxxx Xxxxxxxx by Xxxxxxxxxxxxxxxxxx (XXX) xxx Dimethylnitrosamine (XXX) in CHO Xxxxx xx xxx Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Xxxxxx, X. M., Combes, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Wolf, X. X. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, K., Xxxxxxxx, X. (1976), X. Xxxx Substitute xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. s. an Xxxxxxx xx Metabolic Xxxxxxxxxx Systems, xx: xx Xxxxxx, X. X., Fouts, J. X. Xxxx, X. X., Philpot, R. X. (xxx), In xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, S. X., Xxxxxxx, M. X., Xxxxxxxx, X. Xx., Xxxxx, X. L., Xxxxxxxx, D. X., Xxxxxx, X., Xxxxxxx, X., Xxxxxx, T. (1994), Xxxxxx from Xxxxxxx Group xx Xx vitro Xxxxx xxx Xxxxxxxxxxx Aberrations, Xxxxxxxxxx Res., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, D. X., Xxxxx, J. X., Xxxxxxxx, X., Chanter, X. O., Phillips, X. (1989), Xxxxxxxx xx Data xxxx Xx xxxxx Xxxxxxxxxxx Xxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. X., (ed) Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, 141-154.

14) Xxxxx, X. X., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Xxxxxx xxx xxx Necessary 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), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, in: Tice, X. X., Xxxxx, X. L., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Effects of Xxxxxxxx Agents, New Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, X. O., Xxxxxx, X. X., Xx, X. P., Xxxxxx, X. X. (1983), Evaluation xx xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Detecting Xxxxxx Xxxxxxxx Mutagens xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Mutagen., 5, 795-801.

17) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx xxxxxxx X2 arrest, Xxxxxxxxxx Xxx., 119, 403-413.

18) Huang, X., Xxxxxx, X., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx xx Xxxxxxx hamster cells, Xxxxxx Res., 43, 1362-1364."


PŘÍLOHA 4X

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

1. XXXXXX

Xxxx metoda xx xxxxxxxx metody XXXX XX 475 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxxxx xxxxxx xxxxx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx xx xxxxxxxxx xxx detekci xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx indukovaných xxxxxxxxx xxxxxx v xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx se xxx xxxx xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx chemická látka xx xxxxxxxxx indukovat xxxxxxxxx aberace. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, že xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx způsobující změny x xxxxxxxxxx a x xxxxxx xxxxxxxxxxx xxxxx tlumících nádory, xxxx podíl xx xxxxxxx rakoviny u xxxxxxx x v xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx této xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Cílovou xxxxx je x xxxx zkoušce kostní xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx s xxxxxxx xxxxxx, xxxxx xx xxxxxx izolují x xxxxxxxxxxxx. Jiné xxxxx x xxxxxx tkáně xxxxxx předmětem xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx aberace je xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx metabolismu xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx in xxxx xx xxxxxx užitečná xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx vitro.

Jestliže xxxxxxxx xxxxx x xxx, že se xxxxxxxx látka xxxx xxxxxxxxx metabolity xxxxxxxxxx xx xxxxxx tkáně, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx také Xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

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

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

Endoreduplikace : xxxxxx, xxx xxxxxx x jádře xx X-xxxx xxxxxxxxx XXX xxxxxxx k mitóze, xxxxx xxxxxxxxx xxxxx X-xxxx. Výsledkem jsou xxxxxxxxxx xx 4, 8, 16,… xxxxxxxxxxxx.

Xxx : xxxxxxxxxxxx léze xxxxx než xxxxx xxxxxxx xxxxxxxxxx a x xxxxxxxxx odchylkou xxxxxxxxx.

Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx x použitých xxxxx.

Xxxxxxxxxxx : xxxxxxx xxxxxxxxxxx xxxxx chromozomových xxx (x), jiný xxx diploidní (tj. 3 n, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : mikroskopicky pozorovatelné xxxxx struktury xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx; xxxx se xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx interchromozomální xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxx vystavena xxxxxxxx látce xxxxxxx xxxxxxxx x xx xxxxxxx xxxxxxxx po xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx se poté xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx x xxxxxxxxx xx chromozomové xxxxxxx xxxxx x xxxxxxxx.

1.4 POPIS ZKUŠEBNÍ XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx zvířete

Běžně je xxxxxxxx xxxxxx, xxx x xxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx vhodný xxxxx xxxx. Xxxx by xxx použity xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx zdravých xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx zahájení studie xx xxxx být xxxxxxxx v xxxxxxxxx xxxxxx minimální a xxxxxx by u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx rozdělí xx kontrolní xxxxxxx x skupinu, která xx xxxxxxx xxxxxxxx xxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx jejich xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x laboratorních xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx látky xx měly xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx mohou xxx xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při použitých xxxxxxxx dávek toxické xxxxxx x mělo xx být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx podloženo xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx možno xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx by xxxx xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X výjimkou xxxxxxxx xxxxxxxx látky by xxxx zvířata kontrolní xxxxxxx podstoupit identický xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx kontroly xx xxxx xxxxxxxxxx strukturní xxxxxxx in vivo xxx expozičních úrovních, x nichž se xxxxxxx, xx poskytnou xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky pozitivní xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx byla xxxxxxxxx xxxxxxxx podávána xxxxx způsobem než xxxxxxxx látka x xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx pozitivní xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxx látky xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx látek pro xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

V xxxxxxxx xxxxxxx odběru xx xxx xxx proveden xxxxx u xxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxx xxxxx xxxxxxxxxx xxxxxx proces xxxx xxxxxxxxxx skupiny, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat x četnosti xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx jeden xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, neexistují-li xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx se xxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx zvířat xxx xxxxx pohlaví. Xxxxxxxx xxxx x době xxxxxx x dispozici xxxxx xx xxxxxx xx xxxxxxx xxxxxx x za xxxxxxx xxxxxxxx způsobu expozice, xxx xxxxxxxxx, xx xxxxxxxxxx mezi pohlavími xxxxxx v xxxxxxxx, xxxx postačující xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je tomu xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx být xxxxxxx xxxxxxxxx se xxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky xxxxx xxx podávány xxxx xx dvou xxxxxxx, xxx. xxx xxxxx x xxx den x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Jiné xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx odebrány xx xxxx různých intervalech xx xxxxxxxx podané x xxxxxx xxx. X hlodavců xx xxxxx xxxxxxx po xxxxxx době xx xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx a xxxxxxxxxxxx xxxxxxxx látky x xxxxxx xxx xxxxxx xx xxxxxxxx xxxxxxxxx xxxxx xxxx xxx vliv xx xxxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx se provést xxxxx odběr xx 24 x xx xxxxxxx odběru. Je-li xxxxxxxx xxxxxxxxx do xxxx než xxxxxxx xxx, xxx xx xxx odběr xxxxxxxx xx takové xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky buněčného xxxxx.

Xxxx usmrcením xx xxxxxxxx intraperitoneálně xxxx xxxxxx dávka xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X xxxx je xxxx xxxx přibližně 3 — 5 x; x křečka xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx odeberou buňky x analyzují xx xx chromozomové aberace.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx xxxxxxxx dostupných xxxxx studie xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx stejným xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx xx xxxxxxx v xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx rozpětí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx xx vedly xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Látky xx specifickou biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx případ od xxxxxxx. Nejvyšší dávka xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. více xxx 50 % xxxxxxx xxxxxxxxxxx indexu).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx ve xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné toxické xxxxxx a xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx studie xx xxxxx xxxxxxxx xxxxx xx nezbytnou. X xxxx trvajících xxxxxx xx limitní xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx aplikaci je xxxxxxx dávkou 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx expozice člověka xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx nebo vhodnou xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, který může xxx najednou xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený objem, xxxx být xxxxxxxxxx. Xx na xxxxxxxx x žíravé látky, xxxxx obvykle xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx minimalizována xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Ihned po xxxxxxxx se odebere xxxxxx dřeň, hypotonizuje xx x xxxxxx. Xxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx cytotoxicity xx měl xxx x xxxxx xxxxxxxxxxxx xxxxxx (xxxxxx xxxxxxxxxxx xxxxxxx) x x xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx index, x xx xxxxxxx u 1000 xxxxx na xxxxx xxxxx.

X každého xxxxxxx xx mělo xxx xxxxxxxxxxx alespoň 100 buněk. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx aberací. Všechny xxxxxxxxx pozitivních a xxxxxxxxxxx xxxxxxx by xxxx být xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xx xxxxxx xxxxxxxxxx x xxxxx xxxxx v xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx xxxxx xxxxx xx měl xxx vyhodnocen xxxxx xxxxx, xxxxx xxxxxxx xx buňku x xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) vyjádřený v xxxxxxxxxx. Pro exponované x xxxxxxxxx skupiny xx měly být xxxxxxx různé typy xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x jejich xxxxxx x četností. Xxxx xx zaznamenávají xxxxxxxx x uvádějí se, xxx xxxxxx se xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx. Neexistuje-li xxxxx x rozdílu x odpovědi xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx xxx xxxxxxx x xxxxxxx dávkou x x určitému xxxxxxxx odběru. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx považuje x tomto xxxxxxx xx nemutagenní.

Ačkoli většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx na xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx aberace. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx xxxxxxxx xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, nebo xxxxxxxxxx xx xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky chovu, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxx x podávání zkoušené xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, zda se xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx xx xxxxxx xxxxx,

- případně xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx vodě (xxx) xx xxxxxxxxxxxx dávku (xx/xx tělesné xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx látky xxxxxxxxxxx xxxxxxxx, xxxx xxxxxxxxxxx x xxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx analyzovaných xxxxx na xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- mitotický xxxxx,

- xxx x xxxxx aberací xxxxxxx xxxxxxxxxx xxx každé xxxxx,

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

- xxxxx xxxxx x xxxxxxxxx ve xxxxxxx xx středními xxxxxxxxx x směrodatnými odchylkami,

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx analýzy,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Adler, X. X. (1984), Xxxxxxxxxxx Tests xx Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, S. Xxxxxx, X. M. Parry (xxx), IRL Press, Xxxxxx, Washington D. X., 275-306.

2) Xxxxxxx, X. X., Dean, X. J., Xxxxxxxx, X., Xxxxxx, X., XxXxx, X. X., Xxxxxx, M. (1987), Xxxxxxxxx In xxxx Xxxxxxxxxxx Assays: Xxxxxxxx xx Chromozome Aberrations xx Bone Marrow Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. X., Bootman, X., Xxxxxxxxx, L. (1990), Xx vivo Xxxxxxxxxxx Assays, xx: X. J. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, New York, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

4) Xxxx, X. R., Xxxxxxx, X., MacGregaro, X. X., Anderson, X., Xxxxxx, X. X., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., X. B., Xxxxxxxxxxxx, F., Preston, X. J., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, S., Xxxxxxx, X. (1994), Report xxxx xxx Working Xxxxx xx xxx xx xxxx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. A., Xxx, J., Xxxxxxx, X. X., Gatehouse, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Richold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, D. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Richold, X., Xxxxxxxx, X. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxxx Analysis xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Part XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, X. J. Xxxxxxxx (xx.) Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

7) Xxxxx-Xxxxx, C. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx cells xxxxxx xxxxx-xxxxxxxxx-xxxxxxx X2 xxxxxx, Xxxxxxxxxx Xxx., 119, 403-413.

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


XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx replikou xxxxxx XXXX XX 474 — Test xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxx poškození chromozomů xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, které je xxxxxxxxxx xxxxxxxxx xxxxxx, x xx xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x kostní dřeně x/xxxx xxxxx xxxxxxxxx xxxx, xxxxxxx xxxxxxxx.

Xxxxxx xxxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx identifikovat xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx poškození, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx nereplikující xx (xxxxxxx) chromozomové xxxxxxxxx nebo celé xxxxxxxxxx.

Xxxx se xxxxxxxxxxx xxxxxx dřeně xxxx xx polychromatický erytrocyt, xxxxxx xxxxx xx xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx xxxxxxxxx, xxxxxxxxx x cytoplasmě, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader xx x xxxxxx xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx xx rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxxxx tato xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů x xxxxxxxxxx x periferní xxxx xx xxxxxxxxxx xxxxxxxxxx u kteréhokoli xxxxx, x xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx erytrocyty x xxxxxxxxxx, xxxx xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx aberace. Mikrojádra xxx xxxxxxxx xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX v xxxxxxxxxx. Xxxxxxxxx xx zejména xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx v xxxxxxxxx xxxx, které obsahují xxxxxxxxxx, připadající xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx jako xxxxxxx xxxxxxxx xxxxxxx, jestliže xxxx zvířata xxxxxxxxxx xxxxx týdny nebo xxxx.

Xxxxx test xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx zvláště xxxxxx x xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a procesy xxxxxxxx XXX, třebaže xx xxxxx xxxxx x různých xxxxx x xxxxx, xxxxx x z xxxxxxxxxxx xxxxxxxx. Xxxxxxx in xxxx je xxxxxx xxxxxxxx xxx xxxxx xxxxxx mutagenních xxxxxx xxxxxxxxxx x xxxxxxxxx xx xxxxx.

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

Xxx xxxx Obecný xxxx, část X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) xxxxxxxxxx, x xxx (x xxxx) xx xxxxx xxxxxx buněk xxxxxxx xxxxxx vřeténko xxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx k xxxxx xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx xxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx x xxxxx xxxx, xxxxxxxxx xxxxx xxxxxxxx mitosy (meiosy) xxxxxxxxxxxxxxx se (lagging) xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxx chromozomy.

Normochromatický xxxxxxxxx : xxxxx erytrocyt xxxxxxxxxxxx xxxxxxxx, xxxxx xxx rozlišit xx xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx erytrocyt xx xxxxxxxxx mezistadiu, xxxxx xxxxx obsahuje xxxxxxxx, x může xxx xxxx xxxxxxxx xx xxxxxxx normochromatických xxxxxxxxxx xxxxxxxx selektivním xxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Při xxxxxxx xxxxxx xxxxx se xxxxxxx ve xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxx, odebere se xxxxxx xxxx, xxxxxxxx xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx periferní xxxx se xxxx xx xxxxxxx okamžiku xx xxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Při xxxxxxxx x xxxxxxxxx xxxx xx měla xxxx xxxxxxxx expozicí x sklizením xxxxx xxxxxxxx co xxxxxxxxx xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx na přítomnost xxxxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx použití xxxxxx dřeně xx xxxx xxxxxxxxx zvíře xxxxxxxxxx myš xxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx vhodný xxxxx druh. Xxx xxxxxxx xxxxxxxxx xxxx xx xxxxxxxxxx xxx. Xxx však použít xxxxxxxx xxxxxx druh xxxxx za předpokladu, xx xxx x xxxx, x něhož xxxxxxx neodstraňuje xxxxxxxxxx x xxxxxxxxxx, xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx použity běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx x xxxx xxxxxxx překročit ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, u xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx v xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat. Xxxxx xx xxxxxxxxxx tak, xxx byl xxxx xxxxxx xxxxxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx by xxxx xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx podávány xxxxx nebo xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx údaje x jejich stálosti xxxxxxxxxxx možnost skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx nemělo xxx xxx xxxxxxxxx úrovních xxxxx xxxxxxx účinky x xxxx xx xxx vyloučeno podezření, xx reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx rozpouštědla/vehikula, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx měly být xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx identický xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx očekává, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx zřetelný, xxx xxx při odečtu xxxxxxx ihned najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx xxxxx x xxxxx xxxxxxx prováděn xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxxx xxx vzato x xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx třídy, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx pro pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx měl xxx xxxxxxxx xxxxx u xxxxxxx negativní xxxxxxxx, xxxxx je aplikováno xxxxx rozpouštědlo nebo xxxxxxxxx x která xxxxx podstupuje stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx zhoubné nebo xxxxxxxxx účinky.

Při xxxxxxx xxxxxxxxx krve xxxx xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx x xxxxxxxx xxxxxx x xxxxxxxxx xxxx (např. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, xx xxxxxxxx údaje xxxxx x rozpětí, xxxxx xx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Počet a xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní skupina xx xxxx xxxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx zvířat xxx xxxxx xxxxxxx (11). Xxxxxxxx xxxx x xxxx studie x xxxxxxxxx údaje xx xxxxxx xx stejným xxxxxx x xx xxxxxxx stejného xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx neexistuje mezi xxxxxxxxx xxxxxx x xxxxxxxx, xxxx postačující xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx doporučit xxxxx xxxxxxxxxx xxxx (xx. xxxxx, dvě xxxx tři xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx ze xxxxxx s xxxxxxxxxxxx xxxxxxx podávání jsou xxxxxxxxxx, xxxxx xx x xxxxxx studií xxxxxxx pozitivní xxxxxxxx, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx byla prokázána xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxx xx xx xxxxxxxx xxxxxx. Zkoušené xxxxx xxxxx být xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx xxxxx x xxx xxx x xxxxxxx xx více než xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx xxx proveden xxxxx xxxxxxx:

x) zkoušená xxxxx xx aplikuje xxxxxxxx jednou. Xxxxxx xxxxxx xxxxx xx xxxxxxxx xxxxxxx dvakrát, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx xx xxxxxxxx x poslední xxxxxxxxxx 48 xxxxx xx xxxxxxxx a x xxxxxxxxxx xxxxxxxx xxxx odběry. Odběr xxxxx xxx 24 xxxxx po xxxxxxxx xxxx být zdůvodněn. Xxxxxx xxxxxxxxx xxxx xx odeberou alespoň xxxxxxx, xxxxxxx první xxxxx xx xxxxxxx xxxxxxxx 36 hodin xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx po xxxxxxxx x po prvnímodběru xx xxxxxx xxxxxxxxxxxx xxxxxx. Je-li xx xxxxxx xxxxxx pozorována xxxxxxxxx odpověď, xxxx xxxxx odběr xxxxx;

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

Xxxxx potřeby xxxxx xxx navíc použity xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx xxxxx, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, pohlavím x xx xxxxxxxx xxxxxx expozice, jež xx použijí v xxxxxx xxxxxx (13). X xxxxxxx toxicity xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx xxxxxxxx rozpětí xxxx xxxxxxxxx xx xxxxxxxxx toxicitou, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx odběru xxxxx, xxxx xxxx použita xxxxx xxxxxxxx dávka. Xxxxxxxx dávka je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x letalitě. Látky xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx být xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší dávka xxxx xxx také xxxxxxxxxx jako xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx erytrocytů x xxxxxxxxx množství xxxxxxxxxx x xxxxxx xxxxx nebo v xxxxxxxxx krvi).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška s xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, není xxxxxxxxxx xxxxx studie xx třemi xxxxxxxx xxxxx xx xxxxxxxxx. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx delší xxx 14xxxxx aplikaci xx xxxxxxx xxxxxx 1000 xx/xx tělesné hmotnosti/den. Xxxxxxxxx xxxxxxxx člověka xxxx znamenat xxxxxxx xxxxxx x limitní xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Podávání dávek

Zkoušená xxxxx se xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx v xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx uvedený xxxxx, musí xxx xxxxxxxxxx. Až xx xxxxxxxx a xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx xxxxxxxxx x xxxxxx xxxx xxxxx xxxxx xx usmrcení. Xxxxx xx xxxxxxxx x xxxxxx xxxx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x obarví. Xxxxxxxxx xxxx xx xxxxxxx x ocasní xxxx xxxx jiné xxxxxx xxxxxx xxxx. Krevní xxxxx xx xxxxx xxxxxxxxxxxx obarví (8, 9, 10), xxxx xx xxxxxxxx xxxxxxxxx xxxxxxxx x xxxx xx obarví. Xxxxxxxx xxxxxxx xxxxxxxxxxxx pro XXX (xxxx. akridinová xxxxx (14) nebo Xxxxxxx 33258 a xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx spojeným x xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx XXX. Xxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. celulosová kolona x xxxxxxxxxx buněk xxxxxxxxxxxx jádra (16)) xxx xxxxxx xx xxxxxxxxxxx, xx se xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxx v xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx xx xxxxxxx xxxxx nezralých erytrocytů x celkového (nezralé + zralé) množství xxxxxxxxxx, xxxxxxx se x případě xxxxxx xxxxx použije xxxxxxx xxxxxxx 200 xxxxxxxxxx x x případě xxxxxxxxx xxxx alespoň 1000 erytrocytů (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx být xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx kódovány. X xxxxxxx xxxxxxx xx xxxxxxx alespoň 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx xxx získány xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx mikroskopické analýze xx xxxxx xxx xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx množství xxxxxxxxxx menší xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx exponována xxxxxxxxxxx xxxxx xxxxx nebo xxxx, lze také xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx zvíře. Systémy xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx x xxxxxxxxx cytometrická xxxxxxx xxxxxxx suspenze) xxxx xx xxxxxxxxxxxxx xxxxxxxxxx x validaci xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx xxxxx analyzované xxxxx xx xxx být xxxxxx xxxxx vyšetřených xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů. Xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx nebo déle, xxxx xx xxx xxxx xxxxxxx xxxxx x zralých xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx zvíře xx xxxxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx erytrocytů x xxxxxxxx xxxxxxxx xxxxxxxxxx x mikrojádry xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx několik kritérií, xxxx. xxxxxx počtu xxxxx s mikrojádry x xxxxxxxxxx xx xxxxx xxxx jasný xxxxxx počtu xxxxx x xxxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx a x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx výsledků zkoušky xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Statistická významnost xx neměla být xxxxxxx xxxxxxxxx faktorem xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx xxxxxxxx, se xxxxxxxx x xxxxx xxxxxxx xx nemutagenní.

Ačkoli xxxxxxx experimentů poskytne xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní výsledky xxxxx na xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxx, xxx jsou xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxx aparátu xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx zkoušená xxxxx xx podmínek xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx testovacího xxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx se xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx do cílové xxxxx (xxxx. systémová xxxxxxxx).

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, stáří x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx zkoušky, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxx k xxxxxxxxx x negativní (vehikulum/rozpouštědlo) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

- xxxxxxxx přepočet xxxx xxxxxxxxxxx xxxxxxxx xxxxx x krmivu xxxx xxxx (xxx) na xxxxxxxxxxxx dávku (xx/xx xxxxxxx hmotnosti/den),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x vody,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx a odběru,

- xxxxxx xxxxxxxx preparátů,

- xxxxxx stanovení xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx analyzovaných xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky xxxxxxxx,

- podíl xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx,

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

- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx ve skupině,

- xxxxx možnosti závislost xxxxxxxx na dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxx,

- údaje x xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxxx, J. X. (1973), A Xxxxx Xx vivo Xxxx for Chromozomal Xxxxxx, Xxxxxxxxxx Xxx., 18, 187-190.

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

3) Xxxxxx, J. X., Xxxxxxxx, X. F., Xxxx, X., Kirkhart, X., Xxxxxxxxx, K., XxxXxxxxx, X. G., Xxxxxx, X. X. (1983), Xxx Xxxxxxxxx xx Micronuclei a. x. a Xxxxxxx xx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx. 123, 61-118.

4) Xxxxxxxxx, X. H., Xxxxxx, D. X., Xxxxxx, X. C., Xxxxxxxx, M. X., Xxxxxx, X. X. (1990), Xxx Xx xxxx Xxxxxxxxxxxx Assay xx Mammalian Bone Xxxxxx xxx Peripheral Xxxxx. X xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, X. X., Xxxxxxxx, X., Xxxx, X. X., Xxxx, C. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Screen xxx Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Xxxxxxxx Testing xx Mice, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Practice xx Xxxxxxxxxx, ed. X. X. Hayes, R. X. Schnell, X. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Xxxxxx, X. X. Xxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X. X., Xxxx, X. X., Xxxx, D. (1987), Xxxxxxxxxx for the Xxxxxxx of Xxxxxxxxxxxx Xxxxxx xx Mammalian Xxxx Xxxxxx Erythrocytes, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, X. X., Wehr, C. X., Xxxxxx, P. X., Xxxxxx, X. X. (1990), Xxx xx xxxx Erythrocyte Xxxxxxxxxxxx Test: Measurement xx Xxxxxx Xxxxx Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Xxxxxxx Xxxxxxxxxxx xxxx Toxicity Xxxxxxx, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, T., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, M. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx with Xxxxx Peripheral Xxxxx Xxxxxxxxxxxxx Xxxxx Xxxxxxxx Xxxxxx-Xxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 245, 245-249.

9) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx the Xxxxxxxxxxxx Test (1992). Xxxxxxxxxxxx Xxxx with Xxxxx Peripheral Xxxxx Xxxxxxxxxxxx xx Acridine Xxxxxx Xxxxxxxxxx Staining: Xxx Xxxxxxx Report xx xxx 5th Xxxxxxxxxxxxx Xxxxx xx XXXXX/XXXXX, XXX, Xxxxxxxxxx Xxx., 278, 83-98.

10) Xxx Collaborative Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Xxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxx Society xx Xxxxx) (1995), Protocol xxxxxxxxxxx for the xxxxx-xxxx mouse peripheral xxxxx xxxxxxxxxxxx test, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. R., MacGregor, X. X., Anderson, X., Xxxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Xx. X. X., Pacchicrotti, X., Xxxxxxx, F., Xxxxxxx, X., Xxxxx, S., Xxxxxxx, X. (1994), Xx vivo Xxxxxx Xxxxxxxxxxx Micronucleus Xxxxx, Xxxxx. Xxx., 312, 293-304.

12) Higashikuni, N., Xxxxx, X. (1995), Xx optimal, generalised xxxxxxxx xxxx of 30 ± 6 x after xxxxxx xxxxxx in the xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxx, Mutagenesis, 10, 313-319.

13) Fielder, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, X. X., Doe, J., Xxxxxxx, D. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Rochold, X. (1992), Report xx Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Mutagenesis, 7, 313-319.

14) Xxxxxxx, M., Xxxxxx, X., Ishidate, X. Jr. (1983), Xx Xxxxxxxxxxx xx Xxxxxxxx Orange Xxxxxxxxxxx Xxxxxxxx xx xxx Xxxxxxxxxxxx Xxxx, Mutation Xxx., 120, 241-247.

15) XxxXxxxxx, J. X., Xxxx, C. M., Xxxxxxxx, R. X. (1983), X Xxxxxx Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Micronuclei xxx XXX in Xxxxxxxxxxxx Xxxxx Xxxxxxx 33258 xxx Xxxxxxx Y, Xxxxxxxx Res., 120, 269-275.

16) Xxxxxxx, X., Xxxxxxxxxx, X. D. (1989), The automated xxxx xxxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxx Xxx., 213, 91-104.

17) Xxxxxxxxx, X., XxXxxxxx, X. X. (1995), Xxxxxx Xxxx for the Xxxxxxxxxx xx Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx xx the Xxxx Marrow Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 347, 97-99.

18) Xxxxxxx, X., Ashby, X., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, L. (1990), In xxxx Xxxxxxxxxxxx Assay, xx: X. J. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx xxxxx, XXXXX Recommended Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Anderson, X., Albanese, X., Xxxxxxxx, G. E., Xxxxx, G., Xxxxxxxx X., Xxxxxxx, M., Xxxxxxxx, D. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx XXX, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, New York, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4D

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

1. METODA

Tato xxxxxx xx xxxxxxxx metody XXXX XX 471 — Zkouška xx xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx na xxxxxxxx xxxxxx x bakteriemi xx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx na xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Escherichia xxxx, x xxxxxxx xxxxxxxx xxxxxx, xxxxx zahrnují xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx nebo xxxxxxxx xxxx bází XXX (1, 2, 3). Podstata xxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxx v xxxxxxx xxxxxx, které xxxxxxxxx xxxxxx obsažené v xxxxxxxxxxx xxxxxxx x xxxxxxxx tak xxxxxxx xxxxxxxxx xxxxxxxx syntetizovat xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx xxxx své xxxxxxxxxx xxxx x xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x podobné xxxx xxxx příčinou xxxxx xxxxxxxxx podmíněných chorob x člověka x xxxxxxxx xxxxx xxxxxx x tom, xx xxxxxx xxxxxx x xxxxxxxxxx a v xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxx xx tvorbě xxxxxxxx x člověka x u pokusných xxxxxx. Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx je rychlá, xxxxxxxxxx a xxxxxxxxx xxxxxx. Xxxxx xxxxxxxxxxx xxxxx xx xxxx xxxxxxxxxx, díky nimž xxxx xxxxxxxxxx xx xxxxxxx mutací, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx buněk xxx xxxxx molekuly x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx k xxxxxx. Specifičnost testovacích xxxxx xxxx poskytnout xxxxxxx xxxxxxxx informace x xxxxxx mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx reverzní xxxxxx x bakteriemi xx x xxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx xxxxxxxx a xxxx byly xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx chemických látek, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxx xxxxxxxxxx párů xxxx xxxx xxxxxxxx, jež xxxxxxxxx změny x xxxxxx DNA. Xxx xxxxxxx xxxxxxxxxx mutací xx mohou tyto xxxxx xxxxxxxxxx xx xxxxx původní xxxxxx xxxx xxxxx místě xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx xxxxxxxx xxxx činitele, xxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx xxxx xxxx párů xxxx XXX x xxxxxxxx xxx xxxxx xxxxx XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, které xx xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx a xxxxxxxxx procesy XXX. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx in xxxxx xxxxxxx xxxxx xxxxxxxxx podmínky in xxxx x savců. Xxxxxxx tedy xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx a xxxxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx na reverzní xxxxxx x bakteriemi xx xxxxxxxxx využívána xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx aktivity, x xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx mutace. Z xxxxxxxx xxxxxxxx vyplývá, xx mnoho chemických xxxxx, xxxxx xxxx x této zkoušce xxxxxxxxx, vykazuje xxxxxxxxx xxxxxxxx i x xxxxxx zkouškách. Existují xxxxxxxx xxxxxxxxxxx činitelů, xxxxx nejsou detekovány xxxxx zkouškou. Xxxxxxx xxxxxx skutečností xxx xxxxxxxxx ve xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x xxxxxxxxx v xxxxxxxxxxx aktivaci xxxx x xxxxxxxxx x xxxxxxxxxx dostupnosti. Xx xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxx xxxxxxx na reverzní xxxxxx xx bakteriích, xxxxx xxxx k xxxxxxxxxxxx mutagenní xxxxxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxx xxx vhodná pro xxxxxx třídy xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (např. xxxxxx xxxxxxxxxxx) a xxx xxxxxxxx xxxxx, x xxxxx xx xxxxxxxxxxx (xxxx x xxxxx xx xx), xx specificky zasahují xx replikačního xxxxxxx xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x xxxxxxx xxxxxxx xxxxxxxxxx). V takových xxxxxxxxx xxxxx být xxxxxxxxx zkoušky xxxxxxxxxx x xxxxx.

Xxxxxxxx xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, není xxxxxxxx xxxxxxxxx. Xxxxxx xx xxxxxxxx xxxxx x xxxxxxxx xxxxx xxxxxxxxxxx, xxx nejsou xxxxxxxxxx xxxxx zkouškou, xxxxx xxxxxx jinými, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které v xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxxx xxxxxxxxxxxxx buněk xxxx xxxxxxxxx zkoušené xxxxx, x to xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx něho. Ve xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx x xxxxxxx xxxxxx x xxxxx xx xxxxxxx na xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx se xxxxxxxx xxxx inkubuje a xxxx xx xxxx xxxxxxxxx xx xxxxxxxxx xxxx smíchá x xxxxxxx agarem. Xxx xxxx xxxxxxxxxx xx xx dvou xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx x provede xx xxxxxxxx s počtem xxxxxxx xxxxxxxxxxx revertantů xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

Xx xxxxxxx xxxxxxx xxxxxxx xxxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx. Xxxx běžně xxxxxxxxx xxxxx xxxxxxxxxx miskový xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), fluktuační xxxx (9, 10) x xxxxxxxxx metoda (11). Xxxxxx pro xxxxxxxx xxxxx x xxx xxxx xxxxxxx (12).

Xxx xxxxxxx xxxxxxx se xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx metod. Xxxxx x xxxx xx xxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Některé xxxxx xxx xxxxxxxx xxxxxxxxx za xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx patří do xxxxxxxxxx tříd, do xxxxx patří mezi xxxxx krátké alifatické xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, azobarviva x xxxxxxxxxx sloučeniny, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx sloučeniny x nitrosloučeniny (3). Xxxxxx xx připouští, xx xxxxxx třídy xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx test xxxx xxxxxxxxxxxx metoda. Xxxx xx xxx xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx důrazně xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Je xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (xxxxxxxx s xxxxxxxx postupů jejich xxxxxxx): xxxxxxxxxx a xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx a těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Odchylka od xxxxxxxxxxxx postupu musí xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX ZKUŠEBNÍ XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx by xxxx xxx kultivovány xx xxxxxx xxxxxxxxxxxxx xxxx xxxx xx xxxxx xxxxxxxxxxx xxxx růstu (xxxxxxxxx 109 buněk xx xx). Buňky x xxxxxx stacionární xxxx by neměly xxx použity. Je xxxxxxxx, xxx xxxx xxxxxxx bakterie xxxxxx xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx může xxx xxxxxxxx xxx na xxxxxxx dosavadních xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx xxxxx xx miskách.

Doporučená xxxxxxxxx xxxxxxx je 37 °X.

Xxxx xx xxx xxxxxxx xxxxxxx pět xxxxx xxxxxxxx. Mezi xxxx by měly xxx xxxxx xxxxx X. typhimurium (XX1535; XX1537 nebo TA97a xxxx XX97; XX98 x TA100), xxxxxxx xxxxxxx se xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx čtyři xxxxx S. typhimurium xxxx xxx bází XX na primárním xxxxxxxxx místě x xx známo, že xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Xxxx xxxxx xxxxx xxx xxxxxxxxxx xxxxx E. xxxx WP2 xxxx X. xxxxxxxxxxx XX102 (19), které xxxx xx primárním xxxxxxxxx xxxxx xxx bází XX. Xxxxxxxxxx kombinace xxxxx xx xxxx xxxx:

- X. xxxxxxxxxxx XX1535 a

- S. xxxxxxxxxxx XX1537 xxxx XX97x x

- X. xxxxxxxxxxx TA98 x

- X. xxxxxxxxxxx XX100 x

- E. coli XX2 xxxX, xxxx X. xxxx XX2 xxxX (xXX101), nebo X. xxxxxxxxxxx TA102.

Pro xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx DNA xxxx xxx xxxxxxxxx xxxxxxx TA102 xxxx xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. X. coli XX2 (xXX101)).

Xxxx by xxx xxxxxxx zavedené xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, verifikace xxxxxxx x skladování. Potřeba xxxxxxxxxxxxx pro xxxx xx xxxx být xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx x xxxxxxxxx xxx X. xxxx). Xxxxxxx xx xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx podle potřeby xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx plasmidů (xx. xxxxxxxxxxxx xxxxxxxxxx u xxxxx XX98, XX100 x TA97a xxxx XX97, XX2 xxxX x WP2 xxxX (xXX101) x xxxxxxxxxxxx x tetracyklinová xxxxxxxxxx x xxxxx TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. xxx mutací x X. xxxxxxxxxxx xxxxxxxxxx na xxxxxxxxxxx xxxxxx x xxxX xxxxxx x X. xxxx nebo xxxX xxxxxx u X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx by xxxx xxxxxx dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx misce x xxxxxxx xxxxxxxx xxxxxxxxxxx na základě xxxxxxxxxxx xxxxx laboratorních xxxxxxx x nejlépe x xxxxxxx xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx vhodný xxxxxxxxx xxxx (xxxx. obsahující xxxxxxxxx půdu X (Xxxxx-Xxxxxx) x xxxxxxx) x vrchní xxxx xxxxxxxxxx histidin a xxxxxx xxxx tryptofan xxxxxxxxxx několik buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx xxxx být xxxxxxxxx xxxxxxxx xxxxx, x to s xxxxxxx xxxxxxxx metabolické xxxxxxxx x bez xxxx. Nejčastěji xxxxxxxxxx xxxxxxxx je kofaktorem xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx z xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Xxxxxxx 1254 (1, 2) xxxx fenobarbitonu a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx obvykle xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 až 30 % obj. xx xxxxx S9. Xxxxx a xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx na xxxxx xxxxxxxx xxxxxxxx xxxxx. X některých xxxxxxxxx xxxx být xxxxxx xxxxxx xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx aplikací xxxxxxx. Xxxx by být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou, a xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxxxxx a s xxxxxxxxx X9 (22). Xxxx-xx použita jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx nestálých xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Zkušební xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx koncentrace

Mezi kritéria, xxxxx xxxx být xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx množství zkoušené xxxxx xxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxx xxxxx pro xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx a xxxxxxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx snížením xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx přežití xxxxxxxxxxxx kultur. Cytotoxicita xxxxx se xxxx xxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx by měla xxx posouzena xx xxxxxxx viditelného srážení x xxxxxxx směsi xx xxxxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx pro rozpustné xxxxxxxxxxxxx xxxxx xx 5 mg/misku xxxx 5 μl/misku. U xxxxxxxxxxxxxxx xxxxx nerozpustných xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx xx xxxx xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx xxxxx xxxx x xxxxxxx xxxxx xxx aplikaci xxxxxxxxxxx. Zkoušené xxxxx, xxxxx xxxx cytotoxické xxx xxx xxxxxxxxxxxxx xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx xxxxxxxx xx xx xxxxxxxxxxx koncentrace. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

Mělo xx xxx xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx zkoušené xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx by xxxx xxx xxxxxxxxx xxxx xxxxxxxxxx body xxxxx přibližně polovině xxxxx logaritmické xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx xxxx vhodné x xxxxxxx, xxx xx vyšetřuje xxxxxx xxxxxxxxxx odpovědi na xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx být xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx potenciálně xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx a xxxxxxxxx kontroly

Součástí každého xxxxxxxxx xx xxxx xxx xxxxxxx specifické xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx s xxxxxxxxxxxx xxxxxxxx x bez xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx vybrány xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x použitím metabolického xxxxxxxxxxx xxxxxxx by xxxx xxx látka (xxxxx) pro xxxxxxxxx xxxxxxxx vybrána (xxxxxxx) xx základě xxxx xxxxxxxxx xxxxx bakterií.

Příkladem xxxxxx pozitivní kontroly x xxxxxxx s xxxxxxxxxxxx aktivací xxxx xxxx látky:

Látka

Číslo CAS

Číslo xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Xxxxxx Xxx 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx xxxxx xxx xxxxxx xxxx xxxxxx xxxxxxxxx xxxxxxxxx xxxxx S9. Xxx xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx xxx každá xxxxx S9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx vyžaduje xxxxxxxxxxxx aktivaci mikrosomálními xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-dimethylbenzo[a]anthracen.

Příkladem xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx u 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, XX97 x TA97a

ICR 191

17070–45–0

241–129–4

XX1537, XX97 x XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX a TA102

1-methyl-3-nitro-1-nitrosoguanidin

70–25–7

200–730–1

WP2, XX2 uvrA x XX2 uvrA (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX a XX2 xxxX (pKM101)

α-[(5-nitro-2-furyl)methyliden]furan-2-acetamid (XX2)

3688–53–7

xxxxx xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx kontrolu xxxxx xxx xxxxxxx xxxx xxxxxx referenční látky. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx v úvahu xxxxxxx xxxxxxxxxx látek xx stejné xxxxxxxx xxxxx, xxxx li x xxxxxxxxx.

Xxxx xx xxx použity xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx samotného xxxxxxxxxxxx xxxx vehikula, xxx xxxxxxxx xxxxx, zpracované xxxxx xxxxxxx xxxxxxxx xxxx exponované skupiny. Xxxxx toho by xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud xxxxxxxxx údaje prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx čerstvé xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x 0,5 xx sterilního xxxxx x 2,0 ml xxxxxxxx xxxxx. X xxxxxxx xxxxxxx s xxxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx aktivační xxxxx xxxxxxxxxx přiměřené xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x xxxxxxx 5 xx 30 % xxx. x metabolické xxxxxxxxx směsi) x xxxxxxx agarem (2,0 xx) a zároveň x bakteriemi x xxxxxxxxx xxxxxx xxxx xxxxxxxxx roztokem. Obsah xxxxx zkumavky se xxxxxxxx x xxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx. Xxxx inkubací xx xxxxx vrchní xxxx xxxxxxxx.

X xxxxxxxxxxxx metody (2, 3, 5, 6) se xxxxxxxx xxxxx nebo xxxxxxxx xxxxxx xxxx smícháním x xxxxxxx xxxxxx x přelitím přes xxxxxx xxxxxxxxxxx agaru xx xxxxx obvykle 20 minut xxxx xxxx preinkubuje s xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 životaschopných xxxxx) x xxxxxxxxx xxxxxx xxxx metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 xxxx 0,1 xx xxxxxxxx látky xxxx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxxx x 0,5 xx xxxxx S9 xxxx xxxxxxxxxx pufru x 2,0 xx xxxxxxxx xxxxx. Xxxxxxxx xx xxxx být xxxxx xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.

X dostatečnému odhadu xxxxxxxx by xxxx xxx xxx xxxxx xxxxxx dávky xxxxxxx 3 misky. Použití xxxx misek je xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxx.

Xxxxxx xxxx xxxxxx xxxxx xx xxxx být zkoušeny xxxxxxxx metodami, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx misky x xxxx zkoušce xx xxxx xxx xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Xx uplynutí xxxxxxxxx xxxx se xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx xxxxx kolonií xxxxxxxxxx připadající xx xxxxx. Xxx xx xxx xxxxxx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx na xxxxxxx x xxxxxxxxx xxxxxxxxx (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx neexponovaná kontrola), xxx na xxxxxxx x xxxxxxxxx xxxxxxxxx. Xxxxx xx xxxxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx revertantů xx misku x xxxxxxxxxx odchylka xx xxxx být xxxxxxxxxx xxx xxxxxxxxx látku x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní výsledky xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx xx potvrzení xxxxxxxxxxx výsledků xxxxxxxxxx xx nezbytné, xxxx xx být xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx posuzovaných xxxxxxxx by xxxx xxx zvážena v xxxxxxxxxx experimentech. K xxxxxxxxxx studie, xxxxx xx xxxxx xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx, metoda zpracování (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) a xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx kolonií xxxxxxxxxx xx xxxxx xxx xxxxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx nebo bez xxxx, a xx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx xxx jednu xxxx xxxx koncentrací (23). Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Při xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

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

Xxxxxx xxxxxxx experimentů xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx,

- xxx a xxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, včetně kritérií xxxxxxxxxxxxx,

- postup xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- známky xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx misku x směrodatná xxxxxxxx,

- xxxxx možnosti závislost xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) a xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxx, X. N., XxXxxx, X., Xxxxxxxx X. (1975), Methods xx Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 31, 347-364.

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

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

4) Kier, X. X., Xxxxxxx X. X., Auletta, A. X., Von Halle, X. S., Brown, X. X., Xxxxxx, X. X., Xxxxxx, X., XxXxxx, J., Xxxxxxxxxx, K., Prival, X., Xxx, T. X., Xxx X. (1986), Xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Microsomal Xxxxx: X Report xx xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, X., Xxxxxx, X., Xxxxx, X. X., Matsushima, X., Xxxxx, M., Xxxxxxxx, X., Xxxxxxxxx, X. (1975), Mutagenicity of Xxxxxxxxxx Xxx Xxxx xxx their Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

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

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

8) Aeschacher, X. X., Xxxxxx, U., Xxxxxxx, X. (1987), Xxxxxx Xxxxxxxxxxxxx Mutagenicity Xxxx xxx Xxxxx, X. Xxxx Xxxxxx., 8, 167-177.

9) Xxxxx, X. H. L., Xxxxxx, W. X., Xxxxxxx, X. X. (1976), Xxx xx x xxxxxxxxxx fluctuation xxxx xx xxxxxx xxx xxxxxx of xxxxxxxx, Mutatation Xxx., 38, 33-42.

10) Xxxxxxx, X. X., Xxxxx, X. X. X., Xxxxxxxxx, D., Bridges, X. X. (1984), Xxx Xxxxxxxxxxx Test xx Xxxxxxxx, xx: Xxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, 2. xxx., Kilbey, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (eds.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, E. X., Xxxxxxx, X. J. (1981), An Examination xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Assay for Xxxxxxxxxxx with Xxxxxxx xx Salmonella typhimurium, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Xxxxx, X., Xxxxxxx, X., Kato, X., Matsushima, X. (1994), Improved Xxxxxx xxx Xxxxxxxxxxxx Xxxxxxx xx Xxxxxxx Xxxxxxxxx xx Xxxxx a Xxx Xxxxxxxx Bag, Xxxxxxxxxx Xxx., 307, 335-344.

13) Prival, X. X., Bell, X. X., Xxxxxxxx, X. X., Reipert, X. X., Xxxxxxx, X. X. (1984), Mutagenicity xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Dyes and Xxxxxxxx Xxxxxxx Dyes xx x Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X., Lawlor, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Mutagenicity Xxxxx. X. Results xxxx xxx Xxxxxxx xx 311 Xxxxxxxxx, Environ. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, X., Xxxxxxxx, X., Tardiff, X. G. (1977), Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxx Identified xx Xxxxxxxx Xxxxx, in Xxxxxxxx in Genetic Xxxxxxxxxx, X. Xxxxx, X. Xxxxxxx, X. Xxxxxx (xxx.) Elsevier, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. J., Xxxxxxx, X. M., Xxxxxxxx, X. G., Claxton, X. X. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Mutagenic Activity xx Xxxxxxxx Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Matsumoto, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Cycasin xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxx typhimurium, Cancer Xxx., 39, 3780-3782.

18) Xxxxxx, X., Xxxx, X., Ferro-Luzzi, X., Xxxx, B. X. (1980), Fecalase: A Xxxxx for Xxxxxxxxxx xx Xxxxxxx Glycosides xx Xxxxxxxx xx Xxxxxxxxxx Flora, Proc. Xxxx. Xxxx. Xxx. X. X. X, 77, 4961-4965.

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

20) Xxxxxxxxxx, T., Xxxxxxxx, M., Hara, X., Sugimura, X. (1976), A Safe Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xxx. X. J. xx Xxxxxx xx al. Xxxxxxxx, Xxxxx Holland, 85-88.

21) Elliot, B. X., Combes, X. X., Xxxxxxx, X. X., Xxxxxxxxx, D. X., Xxxxxx, X. X., Xxxxxx, J. X., Wolf, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, D., Xxxxxxxxxxxxxxxx, X., Xxxx, X. X. (1981), Xxxxxxxxxxxxx xx Xxxxxxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxx, Mutatation Xxx., 88, 343-350.

23) Xxxxxxx, X. X., Allen, X., Xxxxxxx, A., Xxxxxxxxxx, K., Xxxxxxxx, X., Zeiger, X. (1987), Xxxxx for xxx Salmonella typhimurium/Mammalian Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Mutagenicity, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, X. A. X., Xxxxx, X. X. L., Middleton, X., Mitchel, X., Xxxxxxxx, X. X., Xxxxxx, D. J. (1989), Analysis xx Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Part XX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Data, xx. Kirkland, X. X., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 28-65."


PŘÍLOHA 4X

"X.17 MUTAGENITA — XXXXXXX NA XXXXXX XXXXXX X XXXXXXX XXXXX XX XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x buňkách xxxxx xx xxxxx xxx xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxx xxxxxxx X5178X xxxx, buněčné xxxxx XXX, CHO-AS52 x X79 xxxxxx xxxxxxxx x xxxxxxxxxxxxxxx xxxxx XX6 člověka (1). X xxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx genetických xxxxxx xxxxxx xxxx xxx thymidinkinasu (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (HPRT) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx xx xxxxxx TK, XXXX x XPRT xxxxxxxx xxxxx xxxxxxxx genetických xxxxxxxx. Autosomální xxxxxx XX a XXXX xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx xxxxxx), které xxxxx xxxxxxxxx x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx zkoušce xx xxxxxx mutace x xxxxxxx savců in xxxxx lze xxxxxx xxxxxxx xxxxxxxxxx linií xxxxx nebo buněčné xxxxx. Xxxxx xx xxxxxxxx xxxxx xxxxxxxxxx xxxxx x kultuře x xxxxxxxx četnosti xxxxxxxxxxx mutací.

Zkoušky xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx použití xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx metabolický xxxxxxxxx xxxxxx nemůže zcela xxxxxxxxx xxxxxxxx xx xxxx u savců. Xx xxxxx se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X pozitivním xxxxxxxxx, xxx neodrážejí xxxxxxx mutagenitu, xxxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx vysokých xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx se xxxxxxx xx zjištění xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx sloučenin, xxx něž xx xxxx zkouška xxxxxxxxx, xxxx xxxxxxxxxxx xxxxx; xxxx xxxxx zkouškou x karcinogenitou však xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx touto xxxxxxxx, xxxxx xxxxxx působí xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxx xxxxxx : xxxxxx xxxxxx xxxxxxxxx typu xxxxxxxx xxxxx, která způsobuje xxxxx xxxx xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxxxxxxx párů xxxx : látky, xxxxx způsobují xxxxxxxxxx xxxxxxx xxxx xxxx xxxx xxxx x XXX.

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

Xxxx exprese xxxxxxxx : doba, xxxxx xxx vymizí x nově xxxxxxxxxx xxxxx xxxxxxxxx genové xxxxxxxx.

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

Xxxxxxxxx xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx ve xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx se xxxx xxxxxx xxxxxx xxxxxxxxx xxxxx x xxxxxxxx x v xxxxxxxxx xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx růst x xxxxxxxx : xxxxxx xxxxx xxxxx v xxxxxxx exprese vzhledem x negativní xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx v okamžiku xxxxxxxx xx xxxxx xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx xx xxxxx xx xxxxx xxxxxx xxxxxxxx; přežití xx xxxxxxx xxxxxxxxx x poměru x xxxxxxx kontrolní populace xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxx, které v xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) jsou xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx analogu xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Buňky xxxxxxxxxxx xxxxxxxxxxxxxx jsou xxxxxxx xx TFT, xxx způsobuje inhibici xxxxxxxxx metabolismu x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxx xxxx xxxxxxx xxxxxxxxxxx za xxxxxxxxxxx XXX, xxxxxxx xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Xxxxxxx xxx x xxxxx x xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (XX). Vlastnosti xxxxxxxx xxxxx by xxxx xxx xxxxxxx xxxxxxx, jestliže xx xx xxxxxxx na xxxxxx xxxxxx x xxxxxxx savců zkoušen xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx by xxx například xxxxxxxxx xxxxxxxx podezření xx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx pro xxxxxxxx xxxx xxxxxxxxxx buňky. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx činidlo, xxxx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxx pro xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx jednovrstevné xxxxxxx xxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxx x metabolickou xxxxxxxx, xxx xxx xx, a xxxxxxxxxxxxxx xx účelem stanovení xxxxxxxxxxxx x xx xxxxxx exprese fenotypu xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx po xxxxxxxx doby xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx x xxxxxxxx xxxxx po xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx xxxxxxx lokus x xxx xxxxx, xxx nastala xxxxxxxxx xxxxxxxxx xxxxxxxxxx exprese xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se xxxxxxx xxx, xx se xxxxxx známý xxxxx xxxxx xx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxx x do xxxxx xxx xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx účinnost xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx xx xxxxxxxxx kolonie. Xxxxxxx xxxxxxx xx vypočte x xxxxx xxxxxxxxxx xxxxxxx v xxxxxxxxx xxxxx x xxxxx xxxxxxx v xxxxx xxx selekčního činidla.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx použití x této xxxxxxx xxxx x xxxxxxxxx xxxxx xxxx buněk, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 nebo XX6. Xxxx xxxxx x xxxx xxxxxxx by xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx mutagenům, xxxxxxx klonovací schopnost x stabilní xxxxxxxxx xxxxxxxxxxx mutací. Xxxxx xx xxxx xxx xxxxxxxxxxxx, zda nejsou xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx kontaminace xx neměly xxx xxxxxxx.

Xxxxxxx by měly xxx xxxxxxxx xxx, xxx měly předem xxxxxxxxxx xxxxxxxxx x xxxx. Xxxxx xxxxxxxxx xxxxx, kultur x xxxxxxxxxxx xxxxxxxx xxxxx xx xxx tyto xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, které xxxxxxx xxxxxxxx x xxxxx xxxxx použity x xxxxxx xxxxxx zkoušky, xx měl xxx xxxxxxx na četnosti xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, xxx xxx xxxxxx xxxxx xxxxx, xxxxx xx xxxxxxxxxxxxxx převrácené xxxxxxx xxxxxxxx xxxxxxxxxxx mutací. Xx xxxx doporučeno, xxx xxxx použito xxxxxxx 106 xxxxx. Xxxx xx xxx x dispozici dostatečné xxxxxxxxx údaje o xxxxxxxx xxxxxxxx xxxxxxx, xxx byla xxxxxxxx xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx podmínky (kultivační xxxxxx, xxxxxxxxxxx CO2, xxxxxxx x xxxxxxx). Xxxxx xx xxxx xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx a xxxx xxxxx použitých xxx xxxxxxx. Xx xxxxxxx xxxxxxxx, xxx xxxxxxxxxx podmínky xxxx xxxxxxx xxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxx xxxxx během xxxxxx xxxxxxx a xxxxxxxxx xxx mutovaných, xxx nemutovaných xxxxx xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx by měly xxx xxxxxxxxx x xxxxxxxxx kultur, nasazeny xx kultivačního xxxxx x xxxxxxxxxx při 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx xxxx xxx xxxxxxxx odstranit x xxxxxxx již xxxxxxxx xxxxxxxx buňky.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx aktivace x xxx něho. Xxxxxxxxxx xxxxxxxxxx systémem je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx činidlem indukujícím xxxxxx, xxxx je Xxxxxxx 1254 (15, 16, 17 x 18), xxxx xxxx xxxxxxxxxxxxx x β-naftoflavonu (19, 20).

Postmitochondriální xxxxxx xx x konečném xxxxxxxxxx médiu obvykle xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxxx x xxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx vhodné xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx xxxxxx, xxxxxx xxxxxxxx geneticky modifikovaných xxxxxxxxx xxxxx exprimujících xxxxxxxxxx aktivační enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx aktivaci. Xxxxx xxxxxxxxx buněčných xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 pro xxxxxxxxxxxx xxxxxxxx látky).

1.4.1.5 Xxxxxxxx xxxxxxxx látky

Pevné xxxxxxxx xxxxx xx xxxx xxx xxxx aplikací xx buňky xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx a popřípadě xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx a/nebo xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx x stálosti xxxxxxxxxxx možnost skladování.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx xxx slučitelné x xxxxxxxx buněk x s xxxxxxxxx X9. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud možno xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Xxxxxxxxxxxx xx xxxx xxx stanovena x metabolickou xxxxxxxx x bez xx x hlavním xxxxxxxxxxx xx xxxxxxx vhodných xxxxxxxxxx buněčné integrity x růstu, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx být xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx toxicity by xxxx tyto xxxxxxxxxxx xxxxxxxx rozmezí xxxx xxxxxxxxx x minimální xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx, že xx xx koncentrace xxxx xxxxx xxxxxxxx 2 xx Ö10. Xx-xx maximální koncentrace xxxxxxxx xx cytotoxicity, xxxx xx xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx klonování) xxxx xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx xxxx, xxxxx x nich xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx látky xx xxxx xxx xxxxxxxx xx x xxxx rozpustnosti za xxxxxxxxxxxx xxxxxxxx, xxxx xx xx xxxx xxx. Xxxx xx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx, xx xxxxxxx xxxx xxxxx exponovány. Xxxx být xxxxxxx xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx aplikace, xxxxx xxxxxxxxxxx se může x xxxxxxx expozice x xxxxxxxxxx xxxxxxx xxxxx x důsledku xxxxxxxxxxx xxxxx, X9 xxxx, xxx. Nerozpustnost xxx xxxxxxx vizuálně. Xxxxxxxxx xx neměla xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx xxxx být xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx x xxxxxxxxxxxx aktivací, xxx xxx xx. Xxx xxxxxxx xxxxxxxxxxx aktivace xx xxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx k xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx být tyto xxxxx:

Xxxx xxxxxxxxxxx aktivace

Lokus

Látka

Číslo XXX

Xxxxx xxxxx Xxxxxx

Xxx xxxxxx xxxxxxxxxxx xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx a xxxxx xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx xxxxxxxxxxxx xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (malé a xxxxx kolonie)

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid monohydrát

6055–19–2

benzo[a]pyren

50–32–8

200–028–5

3-methylcholanthren

56–49–5

200–276–5

XPRT

N-nitrosodimethylamin (xxx vysoké xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx být xxxxxxx xxxx jiné referenční xxxxx xxx xxxxxxxxx xxxxxxxx, xxxx. xx-xx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx o 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, EINECS 200–415–9), xxxx být xxxx referenční xxxxx xxxxxx xxxxxxx. Xxx xxxxxxxxx kontrolu xx xxxx být xxxxx x úvahu xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx negativní xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx samotné xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx tehdy, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo mutagenní xxxxxx.

1.4.3 Postup

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxx být xxxxxxxxx xxxxxxxx xxxxx xxx xx přítomnosti xxxxxxxxxxxxx aktivačního systému, xxx xxx něho. Xxxxxxxx by měla xxxxx xxxxxxx xxxx (xxxxxxx xx xxxxxx xxxx 3 až 6 xxxxx). Expoziční xxxx xxxx xxx xxxxxxxxxxx xx jeden xxxx více xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxx xxx xxxxxxx duplicitní xxxxxxx xxxx xxxxx xxxxxxxxxx xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, měl xx xxx xxxxx xxxxxxxxxxx xxxxxx tak, xxx xxx xxxxxxxx xxxxxxxxxxxx počet xxxxxx xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Měly xx xxx xxxxxxx duplicitní xxxxxxxxx xxxxxxxxx kultury (xxxxxxxx xxxxxxxxxxxx).

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

1.4.3.2 Stanovení xxxxxxx, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx konci xxxxxxxxx xxxx xx buňky xxxxxxx a xxxxxxxxx xx účelem stanovení xxxxxxx x za xxxxxx xxxxxxxx xxxxxxx xxxxxxxx mutantu. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx započne xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx minimální xxxxxx xxxxxx, xxx umožnil xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (XXXX x XXXX xxxxxxxx alespoň 6 až 8 xxx, TK xxxxxxx xxx dny). Buňky xxxx kultivovány x xxxxx se xxxxxxxxx xxxxxxxx (xxxxxxxxxx činidly) x xxx xxxx (xxx xxxx) za xxxxxx xxxxxxxxx xxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxxxxxx (použité pro xxxxxxx xxxxxxxx xxxxxxx) xx započne xx xxxxx xxxx xxxxxxx xxxxxxxxx na misku xxx selekčního xxxxxxx.

Xx-xx xxxxxxxx látka pozitivní xx zkoušce X5178X XX+/-, xxxx xx xxx provedeno xxxxxxx xx xxxxx ze xxxxxxxxxx xxxxxx (x xxxxxxxx pozitivní koncentrací) x xx xxxxxxxxxxx x pozitivních xxxxxxxxxx xxxxxxxxx kultury podle xxxxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxx xx xxxxxxx X5178X TK+/- xxxxxxxxx, mělo by xxx xxxxxxxxx xxxxxxx xxxxx velikosti xxxxxxx xxxxxxxxx na negativních x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx za xxxxxxx XX6 TK+/- xxxx xxx také xxxxxxxxx xxxxxxxxx kultury xxxxx velikosti kolonií.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xx xxxx zahrnovat xxxxxxxxx cytotoxicity x xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx mutantů xxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. X xxxxxxx pozitivní xxxxxxxx xx xxxxxxx L5178Y XX+/- se kolonie xxxxxxxxx alespoň x xxxxx xxxxxxxxxxx zkoušené xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x u xxxxxxxxx x xxxxxxxxx xxxxxxxx za xxxxxxx xxxxxxxx xxxx kolonie — xxxxx xxxxxxx. Xxxxxxxxxxx x cytogenetická xxxxxx xxx mutantů xxxxxxxxx velké kolonie, xxx xxxxxxx tvořících xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx zkoušce XX+/- xxxx kolonie xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx s xxxxxxxxx růstem (xxxxx) x xxxxxxx x xxxxxxx růstem (xxxx) (25). U xxxxxxxxxx xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx doby xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx má obvykle xxxxxx od xxxxx xxxxxx genu xx xx xxxxxxxxxxxx viditelné xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx tvořících xxxx xxxxxxx xx xxxxxxx x xxxxxxxxxx látkami, xxxxx indukují silné xxxxxxxxxxxx xxxxxxx (26). Xxxx závažně postižené xxxxx mutantů xxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxx xxxxx x xxxxx velké xxxxxxx.

Xxxx xx xxx xxxxx xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx růst. Xxxxxxx xxxxxxx xx měla xxx xxxxxxxxx xxxx xxxxx mutantů x xxxxx xxxxxxxxxx buněk.

Měly xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxx. Dále by xxxx xxx xxxxxxx xxxxx shrnuty xx xxxxx xxxxxxx.

Xxxxxxx jasně xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx musí xxx xxxxxxxxx xxxxxx xx xxxxxxx. Tam, xxx xxxx potvrzení xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxx, je xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx rozšířit xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx pro xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx xxxxxxxx. K xxxxxxxxxx studie, které xx mohly xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx a xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. nárůst xxxxxxxx xxxxxxx x závislosti xx koncentraci, nebo xxxxxxxxxxxxxxxx nárůst xxxx xxxxxxxx. Nejdříve by xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxxxx xxxxx, xxxxx výsledky xxxxxxxxx xxxx xxxxxxx kritéria, xx x xxxxx xxxxxxx považuje xx xxxxxxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x aktivitě zkoušené xxxxx. Výsledky mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx. Reprodukovatelná xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx je xxxxx xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx genové mutace.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx musí xxxxxxxxx tyto informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Buňky:

- xxx x xxxxx xxxxx,

- xxxxx buněčných xxxxxx,

- xxxxxxxx počet xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx mykoplasmat.

Zkušební xxxxxxxx:

- xxxxxxxxxx výběru xxxxxxxxxxx x počtu kultur, xxxxxx xxxx. xxxxx x xxxxxxxxxxxx x xxxxxx rozpustnosti, xxxx-xx x xxxxxxxxx,

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- objem xxxxxxxx x přidané xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- případně xxxxxxx xxxxx během xxxxxxxx,

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

- pozitivní x xxxxxxxxx xxxxxxxx,

- délka xxxx xxxxxxx (případně xxxxxx počtu nasazených xxxxx, xxxxxxxxx a xxxxxx xxxxx),

- selekční xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou,

- xxxxxx použité k xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx xxxxx,

- definice xxxxxxx xxxxx xxxxxxxxx x xxxx (xxxxxxxx xxxxxx xxxxxxxx pro "xxxx" a "velké" xxxxxxx).

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx srážení,

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

- velikost xxxxxxx, xxxx-xx xxxxxxxxxxx, xxxxxxx pro xxxxxxxxx x xxxxxxxxx kontroly,

- xxxxxxxxx předpoklady laboratoře xxxxxxxxx xxxxxxx tvořící xxxx xxxxxxx systémem X5178X XX+/-,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., DeMarini, X. X., XxXxxxxx, X. X., Xxxxxx, X. X. (eds.) (1987), Xxxxxxx Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Xxxx Spring Xxxxxx Laboratory, Xxx Xxxx.

2) Xxx, X. X. X., Malling X. V. (1968), Xxxxxxxxx Xxxx Xxxxxxxx. XX. Chemical Xxxxxxxxx xx Xxxxxxxx Xxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxx Xxxxx Xx xxxxx, Proc. Xxxx. Xxxx. Sci. X. X. X, 61, 1306-1312.

3) Xxxxx, X. X., Thilly, W. X. (1982), Xxxxxxxx Xxxxx at xxx Xxxxxxxxx Kinase Xxxxx xx Xxxxxxx Human Xxxxxxxxxxxx, Mutation Xxx. 94, 467-485.

4) Xxxxx, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, X. X., Dearfield, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Quantitation at xxx Xxxxx Lymphoma XX and XXX XXXXX Xxxx, Mutagenesis, 4, 394-403.

5) Xxxxx, X. S., Xxxxxxxxxx, Xx. X. F., (1989), Xxxxxxxxxx xx xxx XX52/XXXX xxx xxx CHO/HPRT Xxxxxx: Xxxxxxxxxx of Xxx Xxxx Xxxxxxxxxx, Mutatation Xxx. 223, 121-128.

6) Xxxxx, C. X., Xxxxxxxxxx, G., Xxxxx, X. X., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Jr. L. X., Theiss, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Xxxx Xxxxxxxx Assays Working Xxxxx Xxxxxx. Xxxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

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

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

9) Xx, X. X., Xxxxx, R. X., Xxxxxxx, X. X., Wasson, X. X. (1988), X Xxxxxx xxx Analysis xx xxx Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Guanine Xxxxxxxxxxxxxx Xxxxxxxxxxx System xx Determine xxx Xxxxxxxxxxxx of Chemical Xxxxxx: X Report xx Xxxxx XXX xx the X. X. Environmental Xxxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Res., 196, 17-36.

10) Li, A. X., Xxxxxx, X. X., Xxxx, X. X., Hsie, X. X., Xxxxx, X. X., Loveday, X. X., X'Νxxxx, J. X., Riddle, J. X., Stankowski, X. X. Xx., Xxxx, X. X. (1987), X Guide xxx xxx Xxxxxxxxxxx xx xxx Chinese Xxxxxxx Xxxxx Cell/Hypoxanthine-Guanine Phosphoribosyl Xxxxxxxxxxx Xxxx Mutation Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Xxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, X. X. (1989), X Comparison xx Xxxxxxxx Xxxxxxxxx at xxx TK and XXXX Loci xx Xxxxx Xxxxxxxxxxxxxx Cells: Xxxxxxxxxxxx Differences xxx Xxx xx xx Xxxxxxxxxx Xxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxx TK Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

12) Xxxxxxxxxx, X. X. Jr., Tindal, X. R., Xxxx, X. W. (1986), Xxxxxxxxxxxx xxx Xxxxxxxxx Xxxxxxxx xx Ethyl Xxxxxxxxxxxxxxxxx xxx XXX 191-Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxx Xxxxxxxxxxxxxxxxx xxx XXX 191 Xxxxxxx Mutation xx XX52 Cells, Xxxxxxxxxx Xxx., 160, 133-147.

13) Xxxxxx, X. X., Xxxxxx, X. X., Xxxxx, D. (1984), Xxxxxxxxx xxx xxx X5178X/XX+/--XX+/- Mouse Lymphoma Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, X. X. xx xx (xxx.) Handbook xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxx York, 239-268.

14) Xxxxxx, X. X., Xxxxx, D. X., Xxxxxx, X. X., Xxxxx, M. H. X., Cole, J., XxXxxxxx, D. X., Xxxxxxx X. X. (1989), Mammalian Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxx upon Xxxxxx Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Data, Xxxxxxxx, X. X., xx., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, S., Corti, X., Xxxxxx, X., Xxxxxxxx, X., Mazzaccoro, X. (1977), Induction xx 6-Xxxxxxxxxxx-Xxxxxxxxx Xxxxxxx xx X79 Xxxxxxx Xxxxxxx Xxxxx by Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Xxx. 46, 365-373.

16) Xxxx, B. X., McCann, X., Xxxxxxxx, X. (1975), Xxxxxxx for Xxxxxxxxx Xxxxxxxxxxx and Mutagens xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx. 31, 347-364.

17) Xxxxx, X., Johnson, X. X., Xxxxxxx, X. X. X., Xxxxxx X. X., Xxxxx X. M. X. (1979), Xxxxxxxxxx xxx Xxxxxxxxxxxxxxxx xx xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Xxxxx Xxxxxx, Xxxxx. Res. 59, 61-108.

18) Xxxxx, X. X., Xxxx, X. X. (1983), Revised Xxxxxxx for xxx Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Res. 113, 173-215.

19) Xxxxxxx, B. X., Xxxxxx, X. X., Elcombe, C. X., Xxxxxxxxx, D. X., Xxxxxx, G. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Xxxxxxx X9 xx: Xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Sawamura, X., Xxxx, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Biphenyls x. x. xx Xxxxxxx of Xxxxxxxxx Xxxxxxxxxx Systems, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxxxxx Xxxxxxx, xx Serres, X. X., Fouts, X. X., Xxxx, X. X., Xxxxxxx, X. M. (eds), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, D. X., Xxxxxx, X. X., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx and Xxxxxxxx Xxxxxxx, in: Xxxx, X. X., Xxxxx, X. L., Xxxxxxx, X. M. (eds), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Agents, Xxx Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, P. X., Xxxxxx, X. X., Xx, X. X., Xxxxxx, A. L. (1983), Evaluation xx xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Mutagens in xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environ. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. X., Moore, X. M., Broder, X. B., Xxxxxxx, X., Xxxxxx, X. X. (1990), Molecular Xxxxxxxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxx Kinase Locus xx Mouse Lymphoma Xxxxx, Xxxx. Natl. Xxxx. Xxx. X. X. A, 87, 51-55.

24) Xxxxx, X. X., Xxxxx, D., Xxxxxx, J. X., Xxxxxx, B. X., Xxxxxx, X. G., Xxxxxx, X. X., Xxxxxx, X. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Xxxxxxx xx X5178X/XX+/--Xxxxx Lymphoma Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

25) Yandell, X. W., Dryja, X. X., Little, X. X. (1990), Xxxxxxxxx Genetic Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxx xx x Heterozygous Xxxxxxxxx Xxxxx xx Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

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


XXXXXXX 4F

"B.23 XXXXXXX XX CHROMOZOMOVÉ XXXXXXX XX XXXXXXXXXXXXXXX SAVCŮ

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx xx xxxx xx xxxxxxxxxxxxx xxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx dva typy xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx chemických mutagenů xxxx indukované aberace xxxxxxxxxxxxxx typu, avšak xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx xxxxx xxxxxxx používána. Chromozomové xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx se xxxxxxxxx xxxxxxxxxxxx xxxxx ve xxxxxxxxxxxxxxx a předpokládá xx xxxx, že xxxx zkouška xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx zkoušce xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx detekují xxxxxxxxxxxx xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Jiné cílové xxxxx xxxxxx předmětem xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx chromatidového xxxx xx spermatogoniích by xxxx xxx — xxxxx xxx xxxxx xx xxxxxx léze — xxxxxxxxx první xxxxxxxxx buněčné dělení, xxxxx následuje po xxxxxxxx. Xxxxx xxxxxxxxx x exponovaných xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx meiotickou xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx v diakinese-metafázi X, xxx xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx je navržena xxx vyšetření, xxx xxxx xxxxxxxx somatických xxxxx aktivní xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx xx tato xxxxxxx xx spermatogoniemi xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.

Xx varlatech xx xxxxxxxx xxxx xxxxxxxx spermatogonií x xxxxxx xxxxxxxxxx na xxxxxxxx chemické xxxxx. Xxxxxxxxxx xxxxxxx tedy xxxxxxxxxxx souhrnnou xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx xxxxxx xx xxxxxxxxx, mohou xxxx xxxxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx krevnímu xxxxx x xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx buněk x bariéry xxxx xxxxxxx oběhem a xxxxxxx.

Xxxxxxxx xxxxxxxx xxxxx x tom, xx xx zkoušená látka xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, není vhodné xxxx xxxxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v xxxxxx zlomu jednotlivých xxxxxxxxx nebo zlomu x opětného xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx zlomu xxxx zlomu x xxxxxxx xxxx xxxxxxxxx x tomtéž xxxxx.

Xxx : xxxxxxxxxxxx léze xxxxx než xxxxx xxxxx chromatidy x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

Xxxxxxxxxxx : násobek xxxxxxxxxxx xxxxx chromozomových xxx (x), jiný xxx xxxxxxxxx (xx. 3 x, 4 n xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx při xxxxxxxx xxxxxx ve xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx se xxxx delece a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx xxxxxxxx exponována xxxxxxxx látce a xx xxxxxx xxxx xx expozici xxxxxxxx. Xxxx xxxxxxxxx se xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx připraví xxxxxxxxx chromozomů, obarví xx a analyzují xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx buněk.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx x xxxx; xxx však xxxxxx samce xxxxxxxxxx xxxxxx xxxxxxxx druhu xxxxx. Měly by xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx být xxxxxxxx v hmotnosti xxxxxx minimální x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx mladí xxxxxxxx xxxxxxx xxxxx se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx xxxxxx minimalizován. Xxxxxxx xx xxxxxxxxxxx identifikují. Xxxx xxxxxxxxx studie xx nechají x xxxxxxxxxxxxx podmínkách alespoň xxx dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné zkoušené xxxxx xx xxxx xxx před aplikací xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Měly xx xxx použity xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, pokud xxxxx x stálosti xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx hladinách xxxxx xxxxxxx xxxxxx a xxxx by xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Jsou-li použita xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx zařazení xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx aplikace xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata xx xxxxxxxxx, v nichž xxxxx x expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xx xxxx xxx expozičních xxxxxxxx, x nichž xx xxxxxxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale xxx xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx byla xxxxxxxxx xxxxxxxx podávána xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx kontrolu xxxx xxx navíc xxxxx x úvahu xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou-li x xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx podle Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxx (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 odběru xx měl být xxxxxxxx xxxxx x xxxxxxx negativní xxxxxxxx, xxxxx xx aplikováno xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxx xxxxx podstupuje xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx x xxxxxxxxxxxxxx aberacemi. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx rozpouštědlo/vehikulum nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní skupina xxxx zahrnovat xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx být xxxxx možno podávány xxxxxxxxxxx xxxx xxxxxxxxx (xx. xxx xxxxx xxxxxxxx nebo dvou xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx xxxxx x týž xxx x rozmezí xx xxxx než xxxxxxxx hodin, xxx xxxx xxxxxxxxx podávání xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x nejvyšší dávkou xx xxxx xxx xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx buněčného cyklu xxxx xxx zkoušenou xxxxxx xxxxxxxxx, xxxxxxx xx xxxxx xxxxx xxxxx a jeden xxxxxxxx xxxxx xxxxxxxxx 24 x 48 xxxxx po xxxxxxxx. X xxxxxxx jiné xxx xxxxxxxx xxxxx xx měl být xxxxx xxxxxxxx po 24 hodin xxxx xx xxxxxx době xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx není xxxxx xxxx xxxxxxxxx xxxx pro xxxxxxx xxxxxx (6).

Navíc xxxxx xxx odběry xxxxxxxxx xxxx x xxxx xxxx. Xxxxxxxxx x xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx replikace (lagging) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx X-xxxxxxxxx účinky, xxxx xxx xxxxxxxxx xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx xxxxxxxxx expozice xxxx xxx xxxxxx xxxxxx xx případu. X xxxxxxx xxxxx x xxxxxxxxxx expozicí xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5násobek xxxxx xxxxx) po xxxxxxxx xxxxxxxx. Xxxxx xxxxxxx xxxxx xxx xxxxxxxxx xxxxx xxxxxx v xxxx xxxx.

Xxxx xxxxxxxxx xx xxxxxxxx intraperitoneálně xxxx vhodná dávka xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. U xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 xxxxx; u xxxxxx xxxxxxxx je xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, se xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx expozice, který xx xxxxxxx x xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx toxicitou, případně xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru stačí, xxxx bude xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že by xxxxx dávky xxxxx xxx xxxxxxx režimu xxxxxxxxx podle xxxxxxxxx x xxxxxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx nízkých netoxických xxxxxxx (např. xxxxxxx x mitogeny) nemusí xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx definována xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx toxicity (např. xxxxxxx počtu xxxxxxxxxxxxx x xxxxxx vzhledem x první a xxxxx xxxxxxxxx xxxxxxxx; xxxx snížení by xxxxxx xxxxxxxxx 50 %).

1.5.4 Limitní zkouška

Jestliže xxxxxxx x jednou xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx dvou dávkách x xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx základě xxxxx o látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx se třemi xxxxxxxx dávky za xxxxxxxxx. Očekávaná expozice xxxxxxx může xxxxxxxx xxxxxxx použít x xxxxxxx xxxxxxx vyšší xxxxxx dávky.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx se xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační xxxxxxx, xxxx intraperitoneální xxxxxxx. Xxxx způsoby xxxxxxxx xxxx přijatelné, jsou-li xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx je xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxxxxx xx analýzu chromozomů

Ihned xx xxxxxxxx xx x xxxxxxx nebo xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, hypotonizuje xx x xxxxxx. Xxxx xx xxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx zvířete xx mělo být xxxxxxxxxxx alespoň 100 xxxxx x dobře xxxxxxxxxxxx metafázi (xx. xxxxxxxxx 500 metafází xx xxxxxxx). Xxxxx xxxxx lze xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx měly xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx ke xxxxxxxxxxxxxx xxxxxx nebo xxxxxx xxxxxxxxxx x xxxxx xxxxxxxx, xxxx xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx každé xxxxx xx xxx být xxxxxxxxxx počet xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxxxx na xxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x xxxxxxxx. Gapy xx xxxxxxxxxxxxx odděleně x uvádějí xx, xxx obecně xx xxxxxxxxxx do xxxxxxx xxxxxxxx aberací.

Je-li pozorována xxxxxx x také xxxxxx, xxx xx xxx pro xxxxxxxxx xxxxxxx xxxxxxxxxxxxx účinků xxxx xxxx xxxxxxxxxxxx xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx jako xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x xxxxx meiotické xxxxxxxx, x to x xxxxxxxx xxxxxx 100 dělících xx xxxxx xx xxxxx xxxxx. Xxxxx je xxxxxxxxx pouze xxxxxx, xxxxxxx x 1000 xxxxxxx xx zvíře xx měl xxx xxxxxxxx mitotický index.

2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx jasný xxxxxx xxxxx xxxxx x xxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Při hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx pro pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky mohou xxxxxx xxxxxxxxxx xxxx xxxxxx bez ohledu xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx xxxxx xx xxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xx xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxx buňkách xxxxxxxxxxx xxxxx chromozomové xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx pravděpodobnost, x xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxx tkáně.

3. ZPRÁVY

PROTOKOL X ZKOUŠCE

Protokol o xxxxxxx xxxx obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx x xxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnoty a xxxxxxxxxx odchylky pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- zdůvodnění způsobu xxxxxxxx,

- údaje o xxxxxxxx zkoušené xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxx xxxxxxxx,

- případně xxxxxxxx xxxx koncentrací xxxxxxxx xxxxx x xxxxxx xxxx vodě (xxx) xx xxxxxxxxxxxx xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x odběru,

- xxxxxx xxxxxxxxx toxicity,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxxxx xxxxxxxxxxxxx v xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxx xxxxxx,

- xxx x xxxxx aberací uvedený xxxxxxxxxx pro xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx xx xxxxxxx,

- xxxxx xxxxx s xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx statistické analýzy,

- xxxxx o xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x negativní xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- údaje x souběžné xxxxxxxxx xxxxxxxx,

- změny xxxxxxx, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Adler, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Xxxxxxxxxxxxx of Xxxxxxxx Xxxxxxxx Related xx their Xxxx-Xxxxx Xxxxxxxxxxxxxx, in: Genetic Xxxxxxxxxx of Environmental Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx and Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, B., Xxxxxxxxx, X. (xxx) Xxxx, Xxx Xxxx, 477-484.

2) Xxxxx, I. X., (1984), Cytogenetic xxxxx xx Mammals, xx: Xxxxxxxxxxxx Xxxxxxx: x Practical Approach, (xx.) X. Xxxxxx, X. X. Parry, XXX Xxxxx, Xxxxxx, Xxxxxxxxxx DC, 275-306.

3) Xxxxx, E. X., Xxxxxxx, G., Xxxx, X. X. (1964), Xx Xxx-xxxxxx Xxxxxx xxx Meiotic Preparations xxxx Xxxxxxxxx Xxxxxx, Xxxxxxxxxxxx Xxxx Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, xx: D. J. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 115-141.

5) Xxxxxxxx, X., Xxxxxxx, X. (1978), A Xxx Xxxxxx for Xxxxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 52, 207-209.

6) Xxxxx, X. X., Xxxxxx X. X., Xxxxxxx, J., Favor, X., Xxxxxxxx, W., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx X. (1994), Xxxxxxxxxxxxx Workshop xx Standardisation xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxx Xxxxxx xx xxx Working Xxxxx xx Xxxxxxxxx Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. J., Gatehouse, X. X., Xxxxxx-Xxxxxx, X., Morton, D. X., Xxxxxxxx, X. X., Richold, X. (1992), Report of Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Group: Xxxx Xxxxxxx in Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Clarc, X., Xxxxxxxx, X., Richold, X., Papworth, D. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx vivo Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Part XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Sydney, 184-232."


XXXXXXX 4X

"X.39 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XXX (XXX) X XXXXXXXXX XXXXXXX XXXXX XX XXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx syntézu DNA (XXX) v xxxxxxxxx xxxxxxx xxxxx xx xxxx je identifikovat xxxxxxxx xxxxx, xxxxx xxxxxxxx reparace XXX x xxxxxxxxx xxxxxxx xxxxxxxxxxxx zvířat (1, 2, 3, 4).

Xxxx xxxxxxx in xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx x játrech. Xxxxxxxxxxx xxx je xxxxxxxxxx xxxxxxxxx XXX x xxxxxxxx xxxxxxxx x xxxxxxxxx buňkách. Xxxxx xxxx obvykle xxxxxxx xxxxxx, xxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx místem xxx xxxxxxxxx xxxx xxxxxxxxx XXX in xxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, že se xxxxxxxx látka xxxxxxxxx xx cílové xxxxx, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (XXX) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx nukleosidů xx buněk, xxxxx xxxxxxxx plánovanou xxxxxxxx XXX (S-fází). Xxxxxxxxxxxxxxx xxxxxxxxx je xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx thymidinu xxxxxxxxx xxxxxxx (3H-TdR). Xxx xxxxxxx xx XXX xx xxxx xx přednostně xxxxxxxxx xxxxx xxxxxxx. Xxxx xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, xxxxxx však xxxxxxxxx xxxx metody.

Detekce xxxxxxxx XXX závisí xx xxxxx bází XXX xxxxxxxxxxx x xxxxxxxxxxx x místě xxxxxxxxx. Xxxxxxx na XXX je xxxx xxxxxx xxxxxxx xxx xxxxxxx dlouhých reparací ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Krátké xxxxxx ("short-patch xxxxxx") (xxxxx až tři xxxx) xxxx xxxxxxx xxxx detekovány x xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, chybné xxxxxxxx xxxx chybné xxxxxxxxx lézí XXX xxxxx x mutagenním xxxxxxxxx. Xxxxxx xxxxxxxx XXX xxxxxxxxxxx xxxxxx xxxxxxxxx o věrnosti xxxxxxxxxxx xxxxxxx. Xxxxx xx možné, že xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX není opraveno xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, které xxxx xxxxxxx xxxxxxxxx x xxxxxxxxx aktivitě, xx vyvážen xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx je xxxxxxxxxx x xxxxx xxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrům (XXX), xxxxx než xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zkoušku.

Čistý xxxxx xxx odpovídajících xxxxxxxx xxxxxx (NNG) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx buněk v xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) odpovídajících jádrům xx xxxxx zrn xxxxxxxxxxxxxx buněčným jádrům (XX): XXX = XX — XX. Xxxxxxx XXX xx xxxxxxx xxx xxxxxxxxxx xxxxx, poté společně xxx buňky x xxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx úseku XXX xxxxxxxxxxxx region s xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx nebo fyzikálními xxxxxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx na XXX x xxxxxxxxx xxxxxxx xxxxx xx vivo xxxxxxxx xxxxxxx xxxxxxxx XXX po xxxxxxxxx x xxxxxxxxxx xxxxx XXX obsahujícího xxxxxx x xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx inkorporaci 3X-XxX xx XXX xxxxxxxxx xxxxx, kde je xxxx xxxxxxx buněk x S-fázi xxxxxxxxx xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, jelikož xxxx xxxxxxxx xxxx tak xxxxxxx xx xxxx X-xxxx xxxxx xxxx xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 POPIS XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Xxxx xx xxx použity xxxxx používané laboratorní xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x neměla xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Podmínky chovu x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx obecného xxxxx x xxxxx X, xxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx zvířat

Zdravá pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx xxxxxxxx. Xxxxx xx měly xxx xxxxxxxxxx tak, aby xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx xx nechají x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx dní xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx měly být xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx chemické xxxxx, xxxxx xxxxx o xxxxxxxx neprokazují možnost xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx xx xxx vyloučeno xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx použita xxxx xxx xxxxx rozpouštědla/vehikula, xxxx by být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx zvážit xxxxxxx xxxxx xxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx pozitivní x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxx xx skupinách, x nichž dojde x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxx, o xxxxx xx známo, že xxxxxx xxxxxxxx v xxxxxxxxxxx expozičních xxxxxxxxxxxxx xxxx k xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx x xxxxxxx xxxxxxxxxxxx mírnou odpověď (4). Xxxxx mohou xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxx xxx pozitivní xxxxxxxx:

Xxxx odběru

Látka

Číslo CAS

Číslo xxxxx Xxxxxx

Xxxxx doby xxxxxx (2 až 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx doby xxxxxx (12 xx 16 x)

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

53–96–3

200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx látky xxx xxxxxxxxx kontrolu. Je xxxxxxxxx, xxx byla xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxx jiným způsobem, xxx zkoušená látka.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxx xx xxx použit xxxxxxxxxx xxxxx zvířat, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx kolísání xxxxxxxx xx xxxxxxx. Každá xxxxxxx xx xx xxxx xxxxxxx alespoň xx xxx analyzovatelných xxxxxx. Jestliže jsou xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx pro xxxxxxxxx a pozitivní xxxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxx až xxx xxxxxxx.

Xxxxxxxx xxxx x době xxxxxx x dispozici xxxxx xx studií xx xxxxxxx xxxxxx x xx xxxxxxx stejného xxxxxxx xxxxxxxx, jež xxxxxxxxx, že neexistuje xxxx xxxxxxxxx xxxxxx x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx pro xxxxxx xxxxxxx, jako xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx xxx xxxxxxx provedena se xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx expozice

Zkoušené xxxxx xxxx zpravidla podávány xxxxxxxxxxx.

1.5.3 Dávkování

Za xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx vyvolávající takové xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxxxx očekávání xxx stejném xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx by xxxx být xxxxxxxxx 50 % až 25 % xxxxx xxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx kritériím xxxxxxxxx dávky vyhovovat x xxxx xx xxx xxxxxxxxx xxxxxx xx případu. Provádí-li xx xxxxx neexistenci xxxxxxxx dostupných údajů xxxxxx xxx xxxxxxxx xxxxxxx, měla xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx xxxxxxx druhem, kmenem, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx studii.

Nejvyšší xxxxx může xxx xxxxxxxxxx xxxx jako xxxxx xxxxxxxxxxxx známky xxxxxxxx x játrech (xxxx. xxxxxxxxxx jádra).

1.5.4 Xxxxxxx zkouška

Jestliže zkouška x xxxxxx dávkou x alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx na xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána xxxxxxxxxxxx, xxxxxx být xxxxx xxxxxx nezbytná. Očekávaná xxxxxxxx člověka může xxxxxxxx potřebu xxxxxx x xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle podává xxxxxxxxxxxxxx, žaludeční sondou xxxx vhodnou xxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx xxxx xxxxx, xxx-xx je zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx se xxxx nedoporučuje, neboť xx xxxxx mohla xxx exponována xxxxxxxx xxxxx přímo x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který může xxx xxxxxxxx podán xxxxxxxxx xxxxxx nebo xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx z exponovaných xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx xxxxxx dávky. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (xxxxxx xxx xx čtyři hodiny xx xxxxxxxx) je xxxxxxxx, xxxx-xx xx 12 až 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Mohou však xxx xxxxxxx xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx základě xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx kultury xxxxxxxxx xxxxx savců xx zpravidla xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxxx xx situ x xxxxxx se, xxx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx vhodném povrchu. Xxxxxxx xxxxx z xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) alespoň 50 %.

1.5.7 Stanovení XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxx xxxx, xxxx. xxx xx osm xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3H-TdR. Xx xxxxx inkubační xxxx xx xxxx xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx xxxx xxxxx xxx xxxxxxxxxx s xxxxxx xxxxxxxxxxx přebytek xxxxxxxxxxx thymidinu, aby xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx delší xxxxxxxxx době xxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xx autoradiografické xxxxxx, xxxxxxxx xx x xxxxx (xxxx. x xxxxxx 7 xx 14 xxx), xxxxxxxx xx, obarví x xxxxxxxxx se xxxxxxxxxx zrna stříbra. X každého xxxxxxx xx xxxxxxxx dva xx xxx preparáty.

1.5.8 Xxxxxxx

Xxxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxx počet xxxxxxxxxxxx xxxxxxxxxx buněk, xxx xxxx xxxxxxxxx XXX xxxxxxxxx hodnotu. Xxxxxxxxx xx xxx xxxxxxxxxxx prohlédnou xx xxxxxx xxxxxx cytotoxicity (xxxx. na xxxxxxx, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx).

Xxxx počítáním xxx xx xxxx xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxxxxx 100 buněk na xxxxx zvíře xxxxxxx xx xxxx xxxxxxxxx; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx by xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx zrn xx jádra x X-xxxx nevyšetřují, xxx xxxxx xxxxx x X-xxxx xxxx být xxxxxxxxxx.

Xxxxxxxx 3H-TdR xxxxxxxxxxxxxxx xx xxxxx x xxxxxxxxxx morfologicky xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxx xx xxxx být xxxxxxxxx xxxxxxx xxxxxxx.

Xxxxx xxxxx xx xxxxxxx z xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x z prŭměrného xxxxx xxx v xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx xx se xxxxxxx xxx xxxxx xxxxx xxx nejsilněji xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx xxŭxxxxx xxxxxxx xxxx až tří xxxxxxx xxxxxxxxx xxxxxxx x blízkosti xxxxxxxxx xxxxxxxxx jader. xx xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx použity i xxxx postupy xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx a xxxxxxx. Údaje by xxxx být dále xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX xx hodnoty XX xx xxx xxx xxxxxxxx xxx xxxxxx xxxxx, pro xxxxx xxxxx a xxx xxxxxx xxxxx x čas xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrům (XXX). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" xxxxx, měla xx xxx kritéria xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx odůvodněna x xxxxxxxx na xxxxxxxxxxx xxxx souběžných xxxxxxx x negativních xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx zhodnoceny xxxxxxxxxxxxx xxxxxxxx. Mají-li xxx xxxxxxx, xxxx xx xxx xxxxxxxxxxx testy xxxxxxx x xxxxxxxxxx xxxx xxxxxxxxxx xxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxxx xxxxxxxx kritérií xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx patří:

pozitivní

i)

hodnota XXX leží xxx xxxxxxxx xxxxxx, xxxxx xx zdůvodněna na xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxx;

xxxx

xx)

xxxxxxx NNG je xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX xxxx xx dosavadní xxxxxxx xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx xxxxx xxx xxxxxxx pro xxxxxxxxx xxxxxxxx.

Xxxx by být xxxxxxxxx biologická relevance xxxxx, tj. měly xx xxx vzaty x xxxxx xxxxxxxxx, xxxx jsou xxxxxxxxxxx xxxxxx, vztah xxxxx x odpovědi x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx použity jako xxxxxxx prostředek statistické xxxxxx. Statistická významnost xx xxxx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx.

Xxxxxx většina experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x aktivitě zkoušené xxxxx. Xxxxxxxx mohou xxxxxx dvojznačné nebo xxxxxx xxx xxxxxx xx xx, kolikrát xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx XXX x jaterních xxxxxxx savců xx xxxx znamenají, xx xxxxxxxx látka xxxxxxxx x jaterních buňkách xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx XXX xx xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx podmínek xxxxxxx neindukuje xxxxxxxxx XXX, které xxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx xxx diskutována xxxxxxxxxxxxxxx, s xxxxx xx zkoušená látka xxxxxxx xx krevního xxxxx popř. do xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx musí obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

- rozpustnost x stálost zkoušené xxxxx v xxxxxxxxxxxx/xxxxxxxx, xx-xx xxxxx.

Xxxxxxxxx zvířata:

- xxxxxxx druh/kmen,

- xxxxx, xxxxx a pohlaví xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx rozpětí tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- popřípadě xxxxxx xxxxxxx, xxx xx xxxxxxxx látka xxxxxxx do xxxxxxxx xxxxx xxxx do xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x odběru,

- xxxxxx xxxxxxxxx toxicity,

- metody xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx technika,

- počet xxxxxxxxx a počet xxxxxxxxxxx buněk,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx xxxxxxx počtu xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx x xxxxx xxx odpovídajících xxxxxxxxxx, x čistý xxxxx xxx, xxxxxxxxxx xxx xxxxxxxxx, xxxxxxx x xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxx,

- xxxxx x souběžné xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole,

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

- xxxxx xxxxx "xxxxxxxxxxxx" xxxxx, xx-xx xxxxxxxx,

- xxxxx xxxxx x S-fázi, xx-xx stanoven,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. Xxxxxxx, X. X., Xxxxxxxxx, X., Penman, X. X. (1985), An Xxxxxxxxxx xx the Xx vivo Xxx. Xxxxxxxxxx XXX Repair Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Xxxxxxxxxxx, X. E., Ashby, X., Xxxxxxxx, X., Xxxxxxxx, D., Xxxxxxxx, X., Probst, G., Xxxxxxxx, X. (1987), X Xxxxxxxx xxx Xxxxx for the Xx vivo Xxx Xxxxxxxxxx DNA Repair Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.

3) Xxxxxxxx, X. X., Waters, X., Xxxxx, J., Xxxxxxx, X. A., Xxxxxxxxx, X., Benford, X. J., Xxxx, X. X., Xxxxxxxx, X. xx X. (1993), Xx xxxx Xxx Liver UDS Xxxxx, in: Xxxxxxxx X. J., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Tests: XXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx II xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Sydney, 52-77.

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

5) Xxxxx, X., Xxxxxxx, X., Efstathiou, X., Hechenberger-Freudl, X. (1993), Xxxxxxxxxx xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxx xxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxx Xxx Xxxxxxxxxxx Xxxx xxx xxx In xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Xxx., 291, 21-27.

6) Xxxxxxxx, X. X., Tyson, X. X., Butterworth, B. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xx xxx Xx xxxx/Xx xxxxx Hepalocyte XXX Repair Assay, Xxxxxxx.Xxxxxxx. 4, 553-562."


PŘÍLOHA 5

XXXXXX XXXXXXXXX XX KLASIFIKACI X XXXXXXXXXX XXXXXXXXXXXX XXXXX X PŘÍPRAVKŮ

Viz xxxxxxxx Xxxxxx 2001/59/XX, Úř. xxxx. X 332, 28. 12. 2000, x. 81.


XXXXXXX 6

"

XXXXXXX XX

XXXX X

xxxxxxxx týkající xx xxxxxxx odolných proti xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. e) xxxx xxxxxxxx, xxxx xxx xxxxx x xxxxxxxxx objemu xxxxxxxxxx xxxxx, x xxxxx xx xxxxxxx xxxxxx xxx xxxxxxxxxx (Xx; X 65) x xxxxx xxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x výjimkou xxxxx xxxxxxxxx xx xxx xx xxxxx aerosolů xxxx x xxxxxxxx xxxxxxxxxx aerosolovým rozprašovačem, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx otevření xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx dne 1. xxxxxxxx 1989) "Xxxxx xxxxxx xxxxx — Xxxxxxxxx na xxxxxxxxx xxxxxxxxxxxx obaly x metody xxxxxx xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Opakovaně neuzavíratelné xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx dětmi xxxxxxx xx opakovaně xxxxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX XX 862 (vydání x března 1997) "Xxxxx — Xxxxx xxxxxx xxxxx — Xxxxxxxxx a zkušební xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx obaly xxxxxx xxx farmaceutických xxxxxxx" xxxxxxxx Evropským xxxxxxx xxx normalizaci (CEN).

3. Xxxxxxxx

1. Xxxxxxxxx shody x výše xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx laboratoře, které xxxxxxx xxxxxxxx normy xxxx XX 45000.

2. Xxxxxxxxxx případy

Je-li xxxxxx, xx xxxx xx xxxxxxxxxx xxxxxxxx xxx xxxx, neboť se xxxxxxx dostat x xxxxxx xxx xxxxxx xxxxxxxx, nemusí xxx xxxxxxx provedena.

Ve všech xxxxxxxxx případech x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x xxxxxxxx x xxxxxxxxxxx uzávěru xxx dítě, xxxx xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx osoba odpovědná xx uvedení xxxxxxx xx trh xxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx buď

- typ xxxxxxx xx xxxxxx, xx xxx xxxx xxxxxxxx xxxxxxx xxxxx xxxx uvedených xxxxx XXX x XXX,

xxxx

- xx uzávěr xxx xxxxxxx x xxx xxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxx norem.

ČÁST X

Xxxxxxxx xxxxxxxx se xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx specifikace xxx hmatatelné xxxxxxxx xxxx být v xxxxxxx x xxxxxx XX XXX 11683 (xxxxxx z xxxx 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"