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Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. května 2000,

xxxxxx xx xx xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx směrnice Xxxx 67/548/XXX x xxxxxxxxxx právních x xxxxxxxxx xxxxxxxx týkajících xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [1]

(Xxxx s xxxxxxxx xxx EHP)

KOMISE XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Smlouvu x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx směrnici Xxxx 67/548/XXX ze xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx látek [2], xxxxxxxxx xxxxxxxxxx xxxxxxxx Xxxxxxxxxx parlamentu x Rady 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx k xxxxx xxxxxxx:

(1) Xxxxxxx X xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxx společně x xxxxxxxxxx xxxxx o xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Současné xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, že xx měl xxx xxxxxx xxxxxxxxxxxx látek x uvedené xxxxxxx xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx oddílů xxxxxxxxx a xxxxxxx X v xxxxxxx X.

(2) Příloha XXX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx vět xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx s nebezpečnými xxxxxxx x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx seznam xxx x xxxxxxxxxxxxxx xxxxxx týkajícími xx xxxxxxxxxxxx látek x xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/EHS xxxxxxxx xxxxx xx klasifikaci x x xxxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, XX x XX.

(3) X xxxxxxx V směrnice 67/548/XXX xx stanoví xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx vlastností, xxxxxxxx x ekotoxicity xxxxx x xxxxxxxxx. Xx xxxxxxxx přizpůsobit xxxx xxxxxxx technickému pokroku.

(4) Xxxxxxx IX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx se uzávěrů xxxxxxxx xxxxx xxxxxxxx xxxxx. Tyto předpisy xx xxxx xxx xxxxxxxxxxxx a xxxxxxxxxxxxx. Xx xxxxxxxx rozšířit xxxxxx, kde xx xxxxxxx odolné xxxxx xxxxxxxx xxxxx xxxxxxxxx.

(5) Xxxxxxxx této xxxxxxxx xxxx x souladu xx xxxxxxxxxxx Výboru xxx přizpůsobení technickému xxxxxxx směrnic xxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xx xxxxx xxxxxxxxxxxx látek x xxxxxxxxx,

XXXXXXX XXXX XXXXXXXX:

Xxxxxx 1

Xxxxxxxx 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx X xx xxxx xxxxx:

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

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

x) xxxxxxxxxxxx položky xx nahrazují položkami x xxxxxxx 1X xxxx xxxxxxxx;

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

2. Xxxxxxxxxxxx věta x xxxxxxx III xx nahrazuje xxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx IV xx xxxx xxxxx:

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

x) xxxxxxxxxxxx pokyny x příloze XX xx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxx 3B xxxx xxxxxxxx.

4. Xxxx X xxxxxxx X se xxxx xxxxx:

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

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

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

x) kapitoly X.13 x X.14 xx xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;

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

f) xxxxxxxx X.23 xx xxxxxxxxx xxxxxx v xxxxxxx 4X xxxx xxxxxxxx. Název xxxxxxxx X.23 ve vysvětlivce xx xxxx xxxxxxxxxxxxx xxxxxxxx;

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

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

6. Xxxxxxxxxxxx xxxxx x příloze XX se nahrazují xxxxx v xxxxxxx 5 této xxxxxxxx.

7. Xxxxxxx XX xx xxxx xxxxxxxx uvedeným x xxxxxxx 6 xxxx směrnice.

Článek 2

1. Členské xxxxx xxxxxx v xxxxxxxx xxxxxx a xxxxxxx xxxxxxxx xxxxxxxx xxx dosažení souladu x xxxxx xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Neprodleně x nich xxxxxxx Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxx odkaz xx xxxx směrnici xxxx xxxx takový xxxxx xxx xxxxxx xxx xxxxxx úředním xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx xxxxxxx státy.

2. Xxxxxxx xxxxx sdělí Xxxxxx xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x xxxxxxx xxxxxxxxxx xxxx xxxxxxxx, a xxxxxxxxxx xxxxxxx xxxx xxxxxxxx a xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Xxxx xxxxxxxx xxxxxxxx x platnost xxxxxx dnem po xxxxxxxxx v Xxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.

Článek 4

Tato směrnice xx určena xxxxxxxx xxxxxx.

X Xxxxxxx xxx 19. května 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise


[1] Přijato xx xxxxxxxxxxxx po xxxxxxx xxxxx.

[2] Úř. xxxx. 196, 16.8.1967, s. 1.

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


XXXXXXX 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx xx českého xxxxx)


XXXXXXX 1B

"TABULKA 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"


PŘÍLOHA 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x látkám

Číslo XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační limity

Poznámky x přípravkům

006–011–00–7

karbaryl (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. xxx. 3; X40 Xn; X22 X; X50

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

006–013–00–8

xxxxxx-xxxxxxx (ISO) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 R31 C; X34 R43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

Karc. kat. 3; X40 Xxxx. xxx. 3; R40 Xx; X22–48/22 X; X50–53

Xx; X X: 22–40–48/22–50/53 S: (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 X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; R26/28 X; X24 X; X50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 X; X50–53

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

006–019–00–0

xx-xxxxx (XXX) S-(2,3-dichlorallyl)-N,N-diisopropylthiokarbamát

218–961–1

2303–16–4

Karc. xxx. 3; R40 Xn; X22 X; X50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; X22 X43 N; R50–53

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

006–023–00–2

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

217–991–2

2032–65–7

X; X25 N; X50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; R22 Xx; X38 N; 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+; X R: 26/28–50/53 X: (1/2-)36/37–45–60–61

006–028–00-X

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

213–546–1

973–21–7

X; X25 X; R50–53

T; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; X25 X; X51–53

X; X X: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

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

243–433–2

19937–59–8

X; X50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xn; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)23-61

006–035–00–8

xxxxxxxxxx (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx pyrimidin-4-yl-N,N-dimethylkarbamát

245–430–1

23103–98–2

T; X25 N; X50–53

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

006–037–00–9

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

220–113–0

2631–37–0

X; X25 X; X50–53

X; X R: 25–50/53 X: (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 X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; X22–48/22 X43 X; X50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; R40 Xx; X22 X; X50–53

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

006–043–00–1

monuron-TCA 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx

140–41–0

Xx; X36/38 Xxxx. xxx. 3; X40 X; R50–53

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

006–045–00–2

xxxxxxxx (XXX) methyl-N-[(N-methylkarbamoyl)oxy]thioacetimidát

240–815–0

16752–77–5

T+; X28 N; X50–53

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

006–046–00–8

bendiokarb (ISO) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx

245–216–8

22781–23–3

X; X23/25 Xx; X21 N; R50–53

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

006–047–00–3

xxxxxxxxx (XXX) xxxx: 3-(1-methylbutyl)fenyl-N-methylkarbamátu a 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

8065–36–9

X; X24/25 X; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xn; R22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

006–050–00–X

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

4482–55–7

Xi; X38 X; X50–53

Xx; N X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; X50–53

Xx; X R: 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 X; R50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; X X: 22–51/53 S: (2-)24-61

006–060–00–4

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

226–066–2

5259–88–1

Xx; R22 X52–53

Xx R:22–52/53 S: (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. kat. 3; X40 X; X50–53

Xx; X 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 N; 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-dimethylhydrazin

E

200–316–0

57–14–7

F; X11 Xxxx. xxx. 2; X45 X; X23/25 C; 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-dimethylhydrazin

E

540–73–8

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

X; X X: 45–23/24/25–51/53 X: 53–45–61

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

009–003–00–1

kyselina xxxxxxxxxxxxxx … %

X

231–634–8

7664–39–3

X+; X26/27/28 X; X35

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

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

015–039–00–9

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

201–676–1

86–50–0

T+; R26/28 X; X24 X43 X; R50–53

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

015–048–00–8

xxxxxxxx (XXX) O,O-dimethyl-O-[3-methyl-4-(methylsulfanyl)fenyl]-fosforothioát

200–231–9

55–38–9

Muta. xxx. 3; X40 X; X23–48/25 Xx; X21/22 X; X50–53

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

015–056–00–1

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

220–147–6

2642–71–9

X+; X28 X; X24 X; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; R23/25 Xx; X21 X; R50–53

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

016–013–00-X

xxxxxxx sirnatý

234–129–0

10545–99–0

R14 X; X34 N; X50

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

X ≥ 10 %: X; R34 5 % ≤ X &xx; 10 %: Xx; R36/37/38

016–014–00–5

chlorid xxxxxxxx

13451–08–6

X14 X; R34 X; X50

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

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

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. xxx. 2; R45 Muta. xxx. 3; R40 X+; X26 T; X25 X; R34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

X43

Xx X: 43 S: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 X; R34

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

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

030–004–00–8

xxxxxxxxxxxxx [1] xxxxxxxxxxxx [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 C; X34 N; R50–53

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

050–002–00–0

xxxxxxxxx (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx xxxxxxxxxxxxxxxxxxxxx-xxxxxxxx

236–049–1

13121–70–5

Xx; X20/21/22 N; X50–53

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

050–012–00–5

tetracyklohexylstannan [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]

Xn; X20/21/22 X; X50–53

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

X ≥ 1 %: Xn; X20/21/22

1

050–017–00–2

xxxxxxxxxxxxxx (XXX) 1,1,1,3,3,3-hexakis(2-fenyl-2-methylpropyl)distannoxan

236–407–7

13356–08–6

T+; X26 Xx; X36/38 N; X50/53

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

082–009–00–X

žluť (xxxxxxxxxxxx olovnatý) XX Xxxxxxx Yellow 34 (XX 77603) XX xxxxxxxxxx žluť 34 (XX 77603)

215–693–7

1344–37–2

Xxxx. xxx. 3; X40 Xxxx. xxx. 1; R61 Xxxx. xxx. 3; X62 R33 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) CI xxxxxxxxxx červeň 104 (XX 77605)

235–759–9

12656–85–8

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

X; N 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]

X10 Xx; X65 Xx; X37 N; R51–53

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

4

601–032–00–3

xxxxx[x]xxxxx xxxxx[xxx]xxxxxxx

200–028–5

50–32–8

Xxxx. xxx.2; X45 Xxxx. xxx. 2; X46 Xxxx. kat. 2; X60–61 X; X50–53

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

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. xxx.2; X45 N; X50–53

X; X R: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx p-dichlorbenzen

203–400–5

106–46–7

Xi; X36 X; R50–53

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

602–054–00–6

3-xxxxxxx-1-xx allyljodid

209–130–4

556–56–9

R10 X; X34

X X: 10-34 S: (1/2-)7–26–45

603–076–00–9

but-2-yn-1,4-diol

203–788–6

110–65–6

T; X23/25 Xx; X21–48/22 X; X34

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

X ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ C &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; X20/22–48/22 3 % ≤ C &xx; 10 %: Xx; R20/22

603–091–00–0

exo-4-isopropyl-1-methyl-7-oxabicyklo[2.2.1]heptan-2-ol

402–470–6

87172–89–2

O; X8 Xx; X22 Xx; X36

X; Xx X: 8–22–36 X: (2-)26

603–093–00–1

exo-(±)-4-isopropyl-1-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyklo[2.2.1]heptan

402–410–9

87818–31–3

Xn; X20 X; X51–53

Xx; 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 isopropanol

200–661–7

67–63–0

F; R11 Xx; X36 R67

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

604–020–00–6

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

201–993–5

90–43–7

Xi; X36/37/38 X; R50

Xi; X X: 36/37/38–50 S: (2-)22-61

604–021–00–1

2-xxxxxxxxxx, xxxxx xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx sodný xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; X22 Xx; X37/38–41 X; X50

Xx; X X: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

4,4'-(4-xxxxxxxxxxxx-2,2-xxxx)xxxxxxx 2,2-xxx(4-xxxxxxxxxxxx)-4-xxxxxxxxxxxx

401–720–1

6807–17–6

Xxxx. xxx. 2; X60 Xx; X36 X; X50–53

X; X 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; X22 Xx; R38–41 X; X50–53

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

604–043–00–1

monobenzonbenzyl (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(benzyloxy)fenol

203–083–3

103–16–2

Xi; X36 X43

Xx R: 36-43 S: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; X22 Xx; X36 R43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

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

Xx X: 20–36/38–40–43 S: (2-)36/37

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

606–016–00-X

xxxxxx (XXX) 2-(trimethylacetyl)indan-1,3-dion

201–462–8

83–26–1

T; X25–48/25 X; R50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xx; X22 Xx; X36/38 X; X50–53

Xx; 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-xxxxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx

205–601–3

143–50–0

Xxxx. xxx. 3; X40 T; X24/25 X; R50–53

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

606–034–00–8

xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-amino-6-terc-butyl-3-(methylsulfanyl)-4,5-dihydro-1,2,4-triazin-5-on

244–209–7

21087–64–9

Xn; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

xxxxxxxxxxx (XXX) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx pyrazon

216–920–2

1698–60–8

R43 X; X50–53

Xx; X 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 X43 N; X50–53

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

606–037–00–4

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

256–103–8

43121–43–3

Xx; X22 N; R51–53

Xn; X X: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xn; X22 Xx; X36 X; R50–53

Xn; N X: 22–36–50/53 S: (2-)26–60–61

607–043–00-X

xxxxxxx (ISO) 3,6-dichlor-2-methoxybenzoová xxxxxxxx

217–635–6

1918–00–9

Xx; X22 Xx; X41 R52–53

Xn; N X: 22–41–52/53 S: (2-)26-61

607–057–00–6

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

201–378–1

81–82–3

Xx; R48/22 X52–53

Xx X:48/22–52/53 X: (2-)37-61

607–058–00–1

xxxxxxxxx (XXX) xxxxxxx (RS)-3-[1-(2-furyl)-3-oxobutyl)]-4-hydroxykumarin (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -xxxxxxx-2-xx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-furyl)-3-oxobutyl]-4-hydroxy-2 X -xxxxxxx-2-xx

204–195–5

117–52–2

X; R25–48/25 R52–53

T 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 Xx; X22 N; X51–53

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

607–097–00–4

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

209–008–0

552–30–7

Xx; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx valerová kyselina

203–677–2

109–52–4

C; X34 X52–53

X X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xx; R22 X; X51–53

Xx; N X: 22–51/53 X: (2-)61

607–153–00–8

xxxxxxxxx (ISO) (4-chlor-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)octová xxxxxxxx

223–297–0

3813–05–6

Xx; X36/38 X52–53

Xx X:36/38–52/53 S: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xx; R22 Xx; X38 N; X50–53

Xx; N X: 22–38–50/53 X: (2-)37–60–61

607–158–00–5

sodná xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; R25 Xx; R38 X; X50

X; X X: 25–38–50 S: (1/2-)22–37–45–61

607–159–00–0

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

208–110–2

510–15–6

Xx; X22 X; R50–53

Xn; X R: 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; N X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; R51–53

Xi; X R: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xn; R22 X43 N; X50–53

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

607–213–00–3

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

403–320–2

67567–23–1

X; X2 O; X7 X10 X; X51–53

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

607–217–00–5

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

403–960–2

X43 R53

Xi X: 43-53 S: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] natrium-3,6-dichlor-o-anisát [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [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; R22

Xn X: 22 S: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xx; X36/37/38 X43 N; X51–53

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

X ≥ 10 %: Xi; X36/37/38–43 1 % ≤ 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 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx

415–130–7

91465–08–6

X+; X26 X; X25 Xx; X21 X; X50–53

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

607–255–00–2

xxxxxxxxxx (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx 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; R45 X; X23/24/25 Xx; X37/38–41 X43 X; R51–53

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 N; R50–53

Xi; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 T+; R28 X; R24 X44 X; X50–53

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

609–040–00–9

xxxxxxxx (XXX) (2,4-xxxxxxxxxxxx)(4-xxxxxxxxxx)xxxxx

X

217–406–0

1836–75–5

Xxxx. xxx. 2; R45 Xxxx. kat. 2; X61 Xx; 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 R43 X; X50–53

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

611–008–00–4

4-xxxxxxxxxxxxxx 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 X: 2–51/53 X: (2-)35-61

611–031–00-X

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

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-methoxyanilin x-xxxxxxxx

X

201–963–1

90–04–0

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

T X: 45–23/24/25 S: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. kat. 1; X45 Xx; R22 X; X50–53

X; X X: 45–22–50/53 X: 53–45–60–61

X ≥ 25 %: X; R45–22 0,01 % ≤ X &xx; 25 %: T; X45

612–051–00–1

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

E

202–974–4

101–77–9

Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; X48/20/21/22 X43 X; X51–53

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

612–081–00–5

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

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; R45 Xx; R22 N; X51–53

X; X X: 45–22–51/53 S: 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 T; R25 Xx; X21 Xi; X36 R43 X; X51–53

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

612–105–00–4

2-(piperazin-1-yl)ethylamin2-(piperazin-1-yl)ethan-1-amin

205–411–0

140–31–8

Xn; X21/22 X; X34 X43 X52–53

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

612–111–00–7

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

212–513–9

823–40–5

Xxxx. kat. 3; X40 Xx; R21/22 X43 X; R51–53

Xn; 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-toluendiamin

202–442–1

95–70–5

T; X25 Xx; X20/21 X43 N; X51–53

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

612–144–00–7

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

62924–70–3

Xx; X36/38 X4 3 X; X50–53

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

612–151–00–5

xxxxxxxxxxxxx toluendiamin xxxxxxxxxxxxxxxxxxx methylbenzendiamin

E

246–910–3

25376–45–8

Karc. xxx. 2; R45 X; X25 Xx; R20/21 Xx; R36 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'-bis[(3,5-dimethylmorfolin-4-karbonyl)methyl]-4,4'-bipyridin-1,1'-diium

7411–47–4

Xn; X22 Xi; R36/37/38 X52–53

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

613–031–00–5

xxxxxxxxx xxxxxxxxxxxxxxxxxxxx xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5H)-trion

201–782–8

87–90–1

O; X8 Xx; X22 X31 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 benzoguanamin

202–095–6

91–76–9

Xn; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 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 (ISO) 1-[2-(allyloxy)-2-(2,4-dichlorfenyl)ethyl]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xi; X41 X; X50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 X; X50–53

Xx; X X: 22–50/53 S: (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'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxx-xxxxxxxx [2]

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; R22 Xx; R36/37/38 X52–53

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

613–098–00–0

1-xxxxxxxxxxxxxxx-2-xx 1-oktyl-2-pyrrolidon

403–700–8

2687–94–7

C; X34 X; X51–53

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

613–130–00–3

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

79983–71–4

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

613–131–00–9

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

57369–32–1

Xx; X22 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 Xi; X36 X; R51–53

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

613–137–00–1

xxxxxxxxxxxxxxxxxx (ISO) 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

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

74223–64–6

N; X50–53

X X: 50/53 X: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; X25 X; X51–53

X+; N 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 X: (1/2-)13–45–61

614–007–00–7

xxxxxx-xxxxxx [1] xxxxxx-xxxxxx [2] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]

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

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

X+; X26/28 X52–53

X+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

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

X

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

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

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

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

X320 %: X+; R26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; R23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42

2

616–010–00–9

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

204–854–7

127–65–1

Xx; R22 X31 X; X34 X42

X X: 22–31–34–42 S: (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 -[(ethylamino)karbonyl]-2-kyan-2-(methoxyimino)acetamid 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx

261–043–0

57966–95–7

Xx; X22 X43 X; X50–53

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

617–004–00–9

(1,2,3,4-xxxxxxxxxx-1-xxxxxx)xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxx

212–230–0

771–29–9

X; X7 Xx; X22 X; X34 X; X50–53

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

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

617–006–00-X

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

201–279–3

80–43–3

X; X7 Xx; R36/38 X; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; R2 Xi; X36 X43

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

650–007–00–3

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

228–200–5

6164–98–3

Xxxx. xxx. 3; X40 Xx; 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; X25 X; X50–53

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

650–009–00–4

xxxxxxxxxxxxx-xxxxxxxxxxxx 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; X40 Xx; R22 X; X50–53

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

650–033–00–5

esfenvalerát (XXX) [(X)-(3-xxxxxxxxxxx)xxxxxxxxxx]-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx (S)-3-fenoxy-α-kyanbenzyl-(S)-2-(4-chlorfenyl)-3-methylbutanoát

66230–04–4

T; X23/25 X43 X; X50–53

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

650–041–00–9

xxxxxxxxxxxx (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


XXXXXXX 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–090–00–8

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

408–010–0

88558–41–2

Xx; X20 Xx; R41 R52–53

Xn X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

Xxxx: 1,3-di(hex-5-en-1-yl)- 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 R: 51/53 X: 61

015–164–00–9

kalcium-dihydrogen-(1-hydroxyethylen)bisfosfonát xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

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

404–986–7

Xx; R41 X; X50–53

Xx; 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; R41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; R50

N X: 50 S: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 X; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; R48/21/22 X64 X; R50–53

Xn; N 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 Xi; X41

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

603–130–00–1

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

406–325–8

Xx; X22 X52–53

Xx X:22–52/53 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; R41

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

603–132–00–2

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

408–200–3

63187–91–7

Xx; X38–41 X52–53

Xx X:38–41–52/53 X: (2-)26–37/39–61

603–133–00–8

Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)

408–240–1

Xx; X22 X52–53

Xx R:22–52/53 X: (2-)22–36–61

603–134–00–3

Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx x xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (xxxxxxx x xxxxxxxxxx xxxxxxxxxxxx)

410–450–3

X53

X: 53 X: 61

603–135–00–9

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

410–500–4

Xx; R41 X; X51–53

Xx; N X: 41–51/53 S: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

X43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

603–137–00-X

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

411–130–6

Xx; X41

Xx R: 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 X; X 35 N; X50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 S: 61

604–052–00–0

2,2'-methylenbis[6-(2 X - benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)fenol] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 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-xxxx - xxxxx-2-xxxxxx-6-(1-xxxxxxxxxxxxxxxx)xxxxx

410–760–9

157661–93–3

Xx; R38 X43 X; R50–53

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

604–054–00–1

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

412–020–0

X43 R52–53

Xi X:43–52/53 S: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Xxx.3; R40

Xn 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 a 3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx

410–480–7

X43 X; R51–53

Xi; X R: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-pentylcyklohexanon pentylcyklohexan-1-on

4–406–670–4

61203–83–6

N; X51–53

X X: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

xxxxxxxxxxx-xxxxxx (XXX) [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]

N; X50–53

X X: 50/53 X: 60-61

607–273–00–0

xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

X43

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

607–276–00–7

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

405–635–0

Xi; 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 x xxxxxxx-xxxxxxxxx

405–720–2

Xx; R22 Xx; X41 R43 X; X51–53

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

607–278–00–8

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

405–760–0

Xx; X41 R43 R52–53

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

607–279–00–3

Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) x (oktadecylimino)diethylen-(hydrogen-ftalát)-(hydrogen-maleinát)

405–960–8

R43 X; R51–53

Xi; N X: 43–51/53 S: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xn; X22 Xx; X36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

Xxxx:xxxxx(X7-X9 rozvětvené x lineární)-3-[3-(2H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty

407–000–3

127519–17–9

N; R51–53

N 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

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

Směs:7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonová xxxxxxxx, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx a 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 R: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

[x-(X -{3-[(1-{3-[(2,6(4,6)-xxxxxxx-5-xxxxxxxxxxxxx-4(2)-xx)xxxxxxxxxxx]xxxxxx}-2-xxxxxxx-4-xxxxxx-6-xxx-1,6-xxxxxxx-3-xxxxxxx)xxx]-4-xxxxxxxxxxxxxx}xxxxxxxxx)-x,x,x -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx xxxxxxx, xxxxxxxxxx xxx; x = 15, 16, 17 nebo 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 X43 X52–53

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

607–288–00–8

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

410–370–9

105488–33–3

R53

R:53 X: 61

607–290–00–3

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

410–540–2

Xx; R38 X43 X; X50–53

Xx; N 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

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

410–640–6

Xx; X38–41 X; X50–53

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

607–293–00-XXxxx:

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

410–650–0

Xx; X41 R43 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 R: 43 X: (2-)24-37

607–295–00–0

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

410–800–5

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

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

410–830–9

X53

X: 53 X: 61

607–297–00–1

3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(2-xxxxxxxxx-10-xxxxxxxxx kyselina)2,2'-dioxo-3,3'-(1,4-fenylendimethyliden)bis(1,7,7-trimethylbicyklo[2.2.1]heptan-1-methansulfonová xxxxxxxx)

410–960–6

92761–26–7

Xx; X41

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

607–298–00–7

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

411–010–3

X43

Xx X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 X43 X; R50–53

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

607–300–00–6

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

411–430–7

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

Xxxx:xxxxxxxxxx kyselina x xxxxxxxxxxx oligo(1-7)laktátů

411–860–5

Xi; X38–41 R43 N; X51–53

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

607–302–00–7

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

411–910–6

Xx; X38–41 X43 X; R51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Xxxx. kat.3; X62 X52–53

Xx R: 62–52/53 S: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; R50–53

N X: 50/53 S: 60-61

608–024–00–9

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

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

X53

X:53 S: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; X3 X; X8 Xxxx. xxx. 2; X45 X; X23/25 X43

X; X X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 C; X34 X43 N; X50–53

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

611–043–00–5

Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]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 X: 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, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx x[(4(5)-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx) (3-nitro-5-pentylbenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx

403–720–7

117527–94–3

X; R51–53

Xi; X41 X52–53

611–045–00–6

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

404–830–8

X53

X:53 X: 61

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 X; X50–53

X; N 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 S: 61

611–048–00–2

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

407–900–6

111381–12–5

R53

R: 53 X: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

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

611–051–00–9

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

411–110–7

136213–74–6

X; X50–53

X X: 50/53 S: 60-61

611–052–00–4

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

400–720–9

X52–53

X: 52/53 X: 61

612–156–00–2

Směs:trihexadecyl(methyl)amonium-chlorid a xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx

405–620–9

Xx; X41 X; X50–53

Xx; X X: 41–50/53 S: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xx; X22–48/22 Xi; X41 X43 X; R51–53

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

612–158–00–3

Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-dodecyl-2-hydroxybenzaldoxim[bis(5-alkyl(rozvětvený X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 X: 61

612–159–00–9

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

410–880–1

Xx; R22 C; X34 X; X50–53

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

613–149–00–7

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

405–700–3

96489–71–3

X; X23/25 X; X50–53

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

613–150–00–2

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

406–295–6

X53

X:53 S: 61

613–151–00–8

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

406–360–9

104218–44–2

R53

R:53 X: 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 R: 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 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx R: 22 X: (2-)22

613–155–00-X

5-chlor-2,3-difluorpyridin

410–090–7

89402–43–7

R10 Xx; R22 X52–53

Xx X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

X43 X; X51–53

Xx; N X: 43–51/53 S: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; X22–48/22 Xx; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xx; R20/22 Xx; X41 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; R25 Xn; X20 N; X50–53

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

613–160–00–7

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

411–000–9

125224–62–6

X43

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

615–022–00–1

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

410–550–7

79277–18–2

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

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

615–023–00–7

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

410–900–9

83056–32–0

R10 X14 Xxxx. kat. 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-xxxxx-7-xxxxxxxxxxxxxx[1,5-x][1,2,4]xxxxxxx-4-xx)xxxxxx]-2-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxxxxxx

406–390–2

X; X50–53

X X: 50/53 S: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid 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 N; 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 X; R50–53

Xi; X R: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

Směs:3,3'-bis(4-methylfenyl)- 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; R2 X; X7 X; X50–53

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

650–032–00-X

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

94361–06–5

Xxxx. xxx. 3; X63 Xx; X22 X; R50–53

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


XXXXXXX 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX S XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3A

STANDARDNÍ XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


PŘÍLOHA 3B

STANDARDNÍ POKYNY XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 4A

"B.10 XXXXXXXXXX — XXXXXXX NA XXXXXXXXXXXX XXXXXXX U XXXXX IN XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u xxxxx xx vitro xx xxxxxxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx v xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx aberací: chromozomové x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, avšak xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Nárůst xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx aberace. Tato xxxxxx xxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx xxxxx xxxxxxx používána. Xxxxxxxxxxxx mutace a xxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx o xxx, xx xxxxxxxxxxxx xxxxxx a x xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx a x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x u xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxx mohou být xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, xxxxxxx xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx na xxxxxxx xxxxxxxxxx růstu x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx chromozomů, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx in xxxxx xxxxxx vyžadují xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační systém xxxxxx xxxxx napodobit xxxxxxxx in vivo x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx podmínek, které xx vedly x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx mutagenitu x xxxx x xxx dojít xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx zkouška xx xxxxxxx xx xxxxxxxx xxxxxxx mutagenů x xxxxxxxxxxx xxx xxxxx. Mnoho xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; xxxx touto xxxxxxxx x xxxxxxxxxxxxxx xxxx není absolutní xxxxxxxx. Korelace závisí xx xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx zjištěny xxxxx xxxxxxxx, neboť xxxxxx xxxxxx xxxxxx xxxxxxxxxx xxx xxxxxx poškozením XXX.

Xxx xxxx Obecný xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x podobě xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx chromatid.

Chromozomová xxxxxxx : strukturní poškození xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx x xxxxxxx obou xxxxxxxxx x xxxxxx xxxxx.

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

Xxx : xxxxxxxxxxxx xxxx menší xxx šířka xxxxx xxxxxxxxxx x s xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

Xxxxxxxxx xxxxxxx : odchylka počtu xxxxxxxxxx xx normálního xxxxx obvyklého x xxxxxxxxx xxxx xxxxx.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx; xxxx xx xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. X předem xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxx se xx buněčných kultur xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx), xxxxxxx xx sklidí, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx xxxxx buněčné xxxxx, xxxxx xxxx xxxxxxxx buněčné xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. fibroblasty xxxxxx xxxxxxxx, lymfocyty xxxxxxxxx xxxx člověka xxxx xxxxxx savců).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx xx měla xxx xxxxxxx vhodná kultivační xxxxx x inkubační xxxxxxxx (kultivační xxxxxx, xxxxxxxxxxx XX2, teplota x xxxxxxx). U xxxxxxxxxxxxxxx xxxxxxxxx linií x xxxxx xx xxxx xxx rutinně xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxx x xxxx xx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x případě xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Xxx xxxxxxx xxxxx a xxxxxxxxx xxxxxxxx xx měla xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx kultur

Stabilizované xxxxxxx xxxxx x kmeny: xxxxx xx pomnoží x kmenových kultur, xxxxxx xx xx xxxxxxxxxxxx média x xxxxxx xxxxxxx, xxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, x xxxxxxxx xx při 37 °X.

Xxxxxxxxx: xxxx ošetřená xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xx kultivačního xxxxx xxxxxxxxxxxx mitogen (xxxx. fytohemaglutinin) x xxxxxxxx xx xxx 37 °X.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx by měly xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx a bez xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx indukujícím xxxxxx, xxxx je Aroclor 1254 (6, 7, 8 x 9), xxxx xxxx fenobarbitonu x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx je x xxxxxxxx xxxxxxxxxx médiu xxxxxxx používána x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může záviset xx třídě xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx být xxxxxx xxxxxx více xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx exprimujících xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx zředěny. Xxxx xx xxx xxxxxxx čerstvě připravené xxxxxxxx látky, pokud xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx být xxxx xxxxxxxxx, xx xxxxxxx se zkoušenou xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx zohledněna při xxxxxxxxx xxxxxxxx koncentrace, xxxxx xxxxxxxxxxxx, rozpustnost x xxxxxxxxxx systému x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx stanovena x metabolickou aktivací x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx integrity x růstu, jako xxxx xxxxxx xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx buněk xxxx xxxxxxxxx xxxxx. Xxxx xxx xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx xxxxxxxxxxxx xx xxxx tyto koncentrace xxxxxxxx xxxxxxx dané xxxxxxxxx xx minimální xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx xxxxxxx xxxxxxx, že by xx koncentrace neměly xxxxx více xxxxx xxxxxxxx 2 xx Ö10. V okamžiku xxxxxxx xx xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx snížení xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx mitotického indexu (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx měřítkem xxxxxxxxxxxxx xxxx cytostatických xxxxxx x xxxxxx xx xxxx, xxxxx xxxxxxxx xx xxxxxxxx. Xxxxxxxxx index xx xxxx xxxxxxxxxx x xxxxxxxxxxx kultur, u xxxxx xxxxx být xxxx metody xxxxxxxxx xxxxxxxx xxxxxxx a xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), mohou xxx použity xxxx xxxxxxxxx informace. V xxxxxxx AGT však xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx nelze xxxxxxx xx existenci zpožděných xxxxxxxxxxx, x x xxxx xxxxxxxxx průměrné xxxxxxxxx doby může xxx xx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, které xxxxxx xxxxxxx xxx xxxxxxxxxxxxx xxxxxxx, xxx xx xxxxxx xxxxxxxxxxx, xx xxxx xxx xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, jež xx nad xxxx xxxxxxxxxxxx x konečném xxxxxxxxxxx médiu xx xxxxx xxxx aplikace. X xxxxxxxx případech (xxxx. xxxxxxx-xx se xxxxxxxx pouze xxx xxxxxxx koncentracích, xxx xx rozpustnost) se xxxxxxxxxx vyzkoušet xxxx xxxxxxxxxxx, xxx nichž xxxxxxx ke srážení. Xxxx xxx užitečné xxxxxxxx xxxxxxxxxxx na xxxxxxx x xx xxxxx expozice, xxxxx xxxxxxxxxxx v xxxxxxxxxx xxxxxxx xx xxxx x xxxxxxx expozice xxxxx x xxxxxxxx xxxxxxxxxxx buněk, séra X9 xxx. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx). Xxx xxxxxxx metabolické xxxxxxxx xx měla být xxx pozitivní xxxxxxxx xxxxxxx xxxxxxxx xxxxx, xxxxx k xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx.

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

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxx tak, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxx xxxxxx xxxxxxxxxxx xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Pro xxxxxxxxx xxxxxxxx mohou být xxxxxxx x xxxx xxxxxx xxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx třídy.

V xxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx x xxxxxxxxxxx médiu x xxxxxxxxxx stejným xxxxxxxx xxxx xxxxxxx. Kromě xxxx by xxxx xxx neexponované kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky se xxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx lymfocytů xx xxxx xxx xxxxxxxx xxx 48 xxxxx xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, a xxxxx xx xxxxxxx doporučuje x xxxxxx xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxx. Jestliže xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), že xxxx xxxxxxxxxxxx kulturami xx xxxxxxxxx xxxxxx, xxxx xxx xxxxxxxxx xxxxxxx jediné xxxxxxx.

Xxxxxx xxxx těkavé látky xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. v těsně xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (15, 16).

1.4.3.3 Doba xxxxxxx kultur

V xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, xx dobu 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx po xxxxxx xxxx od xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Jestliže xxxxx xxxxxx dává negativní xxxxxxxx xxx x xxxxxxxx, xxx xxx xxxxxxxx, xxx by xxx proveden xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xx odběru x xxxx, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx cyklu. Xxxxxx xxxxxxxx xxxxx xxx xxxxx detekovat xxx xxxxxx xxxxxxxx xxxx xxxxxx delších xxx 1,5násobek xxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxx metabolické aktivaci xxxx být xxxxxxxxx xxxxxx xx xxxxxxx. X případech, xxx xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, xx xxxx xxx podáno xxxxxxxxxx.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Do xxxxxxx xxxxxxx se xxxxxxx 1-3 xxxxxx před xxxxxxxxx přidá Xxxxxxxx® xxxx xxxxxxxxx. Xxx xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx se xxxxx xxxxxxx xxxxxxx xxxxxx a xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx dochází xx xxxxx xxxxx buněk x metafázi a xx xxxxxx xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x počtu rovném xxxxxxx hodnotě ± 2 xxx všechny xxxx buněk. Na xxxxxx xxxxxxxxxxx a xxxxxxxx by mělo xxx xxxxxxxxx alespoň 200 dobře rozprostřených xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx mezi duplicitní xxxxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx.

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

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx jednotkou xx xxxxx a mělo xx tedy být xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx chromozomovou xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx různé xxxx strukturních chromozomových xxxxxxx s jejich xxxxxx x xxxxxxxx. Xxxx xx zaznamenávají xxxxxxxx a xxxxxxx xx, xxx xxxxxxxxxx xx do xxxxxxx xxxxxxxx aberací.

Měla xx xxx xxxx zaznamenána xxxxxxxx, xxxxx xxxx xxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxx u všech xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

Xxxx xx xxx xxxxxxx údaje xxx xxxxxxxxxx kultury. Dále xx xxxx xxx xxxxxxx xxxxx shrnuty xx formě xxxxxxx.

Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx x bodu 1.4.3.3. Xxxxx xxxxxxxxx studie x cílem xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, které xx xxxxx být xxxxxxx, xxxxx xxxxxxx koncentrací x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx výsledku existuje xxxxxxx xxxxxxxx, např. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, nebo reprodukovatelný xxxxxx tohoto xxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx být použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (3, 13). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx.

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

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx látky. Xxxxxxxx mohou zůstat xxxxxxxxxx xxxx sporné xxx xxxxxx na xx, kolikrát je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx in xxxxx znamenají, že xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxxx somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x kultivovaných xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxxxxxxx karyotypu x xxxxxxxx xxxxxxxxx xxxx xxxxx,

- popřípadě nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx o xxxxx xxxxxxxxx cyklu,

- xxxxxxx xxxxx krve, xxx byla použita xxxx krev xxxx xxxxxxxxxx lymfocyty, xxxxxxx xxxxxxx,

- případně xxxxx xxxxxx,

- případně xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx počtu xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x počtu kultur, xxxxxx např. údajů x xxxxxxxxxxxx x xxxxxx rozpustnosti, xxxx-xx x xxxxxxxxx,

- složení xxxxx, xxxxxxxx koncentrace XX2,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- inkubační xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx hustota xxxxx xxx xxxxxxxx,

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

- pozitivní x xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxxx xxxxxxx,

- xxxxx x xX x xxxxxxxxxx xxxxxxxxxxx média, xxxxx xxxx xxxxxxxxx,

- definice xxxxxxx, xxxxxx xxxx,

- xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxx xxxxxxx xxxxxx xxx xxxxxx exponovanou x kontrolní xxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, H. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, in: Xxxxxxxx Xxxxxxxx, Principles and Xxxxxxx for xxxxx Xxxxxxxxx, Vol. 4, Xxxxxxxxxx, A. (ed) Xxxxxx Xxxxx, Xxx Xxxx xxx Xxxxxx, 1-29.

2) Xxxxxxxx, X. Xx., Xxxxxx, X. (1985), Xxx In xxxxx Xxxxxxxxxxx Aberration Xxxx Xxxxx Xxxxxxx Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Progress xx Mutatation Xxxxxxxx, Xxx. 5, Ashby, X. et xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, S. X., Xxxxxxxxx, X. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxx, X. X., Xxxxxxxx, X., Xxxxx, X., Xxx, X., Xxxxx, J., Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X., Xxxxxx E. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxxx in Xxxxxxx xxxxxxx xxxxx xxxxx: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Molec. Xxxxxxx. 10 (suppl. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, X. X., Ishidate, X. Xx., Xxxxxxx, X., Xxxxx, X., Myhr, X. X. (1991), Xxxxxxxxxxxx xxxxx Xxxxxxx Xxxxxxx Conditions. A xxxxxx xxxx ICPEMC Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.

5) Morita, X., Xxxxxx, T., Fukuda, X., Okumura, X., (1992), Xxxxxxxxxxxxxx xx xxx xX to Xxxxxxx Cultured Xxxxxxxxx Xxxxx, Mutatation Xxx., 268, 297-305.

6) Ames, X. N., XxXxxx, X., Xxxxxxxx, X. (1975), Methods xxx Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx with the Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxx Res., 31, 347-364.

7) Maron, X. X., Ames, X. N. (1983), Xxxxxxx Xxxxxxx xxx xxx Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Res., 113, 173-215.

8) Xxxxxxxxx, X. T., Tates, X. X., van Xxxx, X. X. X., Xxxxxxx, X., xx Xxxxx, N. (1976), Cytogenetic Effects xx Xxxxxxx/Xxxxxxxxxxx after Xxxxxxxxxx xx x Xxxxxxxxxxx System Xx xxxxx, X. Xxxxxxxxx xx Chromozome Xxxxxxxxxxx xxx Xxxxxx Chromatid Xxxxxxxx by Diethylnitrosamine (XXX) and Xxxxxxxxxxxxxxxxxxx (XXX) xx XXX Xxxxx xx xxx Xxxxxxxx xx Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

9) Xxxxxxxx, X., Hayashi, X., Xxxxxxxx, M. Xx. (1979), Chromozomal Xxxxxxxxxx Xxxxx on 29 Xxxxxxxxx Xxxxxxxx with X9 Xxx Xx xxxxx, Xxxxxxxx Xxx., 66, 277-290.

10) Elliot, X. M., Xxxxxx, X. D., Xxxxxxx, X. X., Gatehouse, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxx xx UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Party. Xxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 in In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X. Xxxx Substitute xxx Xxxxxxxxxxxxxxx Biphenyls x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, xx: xx Xxxxxx, X. X., Xxxxx, X. X. Xxxx, X. X., Xxxxxxx, X. X. (xxx), Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Mutagenesis Xxxxxxx, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxx, J. X., Xxxxxxxx, X. J., Xxxxxx, T., Xxxxxxx, X., Sofumi, X. (1994), Report from Xxxxxxx Group on Xx xxxxx Tests xxx Chromozomal Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 312, 241-261.

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

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

15) Xxxxx, X. F., Xxxxxx, X. C., XxXxxxx, X. T. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Tice, X. X., Xxxxx, X. L., Schaich, X. X. (eds), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, X. X., Xxxxxx, X. M., Xx, A. P., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Mutation Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.

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

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


PŘÍLOHA 4B

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

1. METODA

Tato metoda xx xxxxxxxx xxxxxx XXXX XX 475 — Xxxxxxx na xxxxxxxxxxxx xxxxxxx x xxxxxxx xxxxxx dřeně xxxxx (1997).

1.1 ÚVOD

Zkouška xx xxxxxxxxxxxx xxxxxxx x savců xx xxxx xx používána xxx xxxxxxx strukturních xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx x xxxxxxx kostní xxxxx xxxxx, obvykle hlodavců (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx strukturních xxxxxxx — xxxxxxxxxxxx x chromatidové. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx chemických xxxxxxxx xxxx xxxxxxxxxx xxxxxxx chromatidového typu, xxxxx chromozomové xxxxxxx xx rovněž xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxxxxxx jevy xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx xxxxx xxxxxx x xxx, že xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x onkogenech x x genech somatických xxxxx xxxxxxxxx nádory, xxxx xxxxx xx xxxxxxx rakoviny x xxxxxxx x v xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx hlodavci. Cílovou xxxxx je v xxxx zkoušce kostní xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx populaci xxxxx x rychlým xxxxxx, xxxxx se xxxxxx xxxxxxx x xxxxxxxxxxxx. Xxxx xxxxx x xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx zkouška xx xxxxxxxxxxxx xxxxxxx xx xxxxxxx určená k xxxxxxxxx nebezpečí xxxxxxxxxx, xxxxx umožňuje zohlednit xxxxxxx metabolismu in xxxx, xxxxxxxxxxxxxxx x xxxxxxx reparace XXX, xxxxxxx xx mohou x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx in xxxx xx rovněž xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx zjištěných xxxxxxxx xx vitro.

Jestliže xxxxxxxx důkaz x xxx, xx xx xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx také Xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Chromatidová xxxxxxx : strukturní xxxxxxxxx xxxxxxxxxx v podobě xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

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

Xxxxxxxxxxxxxxx : xxxxxx, xxx kterém x xxxxx xx X-xxxx replikace DNA xxxxxxx x xxxxxx, xxxxx následuje další X-xxxx. Xxxxxxxxx jsou xxxxxxxxxx xx 4, 8, 16,… chromatidami.

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

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

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

Strukturní xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx struktury xxxxxxxxxx xxx buněčném dělení xx xxxxxx xxxxxxxx; xxxx se xxxx xxxxxx x fragmenty, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce xxxxxxx xxxxxxxx x xx xxxxxxx xxxxxxxx xx xxxxxxxx se xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X buněk xxxxxx xxxxx xx poté xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx buněk v xxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxx x xxxxxx čínský, xxxxxx xxx použít xxxxxxxx xxxxxx xxxxx xxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx být xxxxxxxx x xxxxxxxxx xxxxxx minimální x xxxxxx xx u xxxx pohlaví překročit ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu a xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx B, 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 xxxxxxxxx skupinu x xxxxxxx, xxxxx xx xxxxxxx xxxxxxxx xxxxx. Klece xx xxxx být xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx v xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly být xxxx xxxxxxxx zvířatům xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx mohou xxx xxxxxxxx xxxxx xxxx mohou xxx xxxx podáním xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

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

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx pozitivní x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx xxx xxx pohlaví. X xxxxxxxx aplikace xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx vivo xxx expozičních xxxxxxxx, x xxxxx xx xxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx nad xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx odečtu xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, aby byla xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx způsobem xxx xxxxxxxx xxxxx x xxx byl xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx kontrolu xxxxx být xxxxxxx xxxxxxxx xxxxx xx xxxxxx chemické xxxxx, xxxx-xx x dispozici. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx xxxxxx by xxx xxx xxxxxxxx xxxxx x xxxxxxxxxxx xxxxxxx, jimž je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxx jinak podstupují xxxxxx proces jako xxxxxxxxxx xxxxxxx, xxxxx xxxxxx z xxxxxxxxxxx xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx x xxxxxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Počet x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxxxx x xxxxxxx pěti xxxxxxxxxxxxxxxx zvířat pro xxxxx xxxxxxx. Jestliže xxxx x xxxx xxxxxx x dispozici xxxxx ze studií xx stejným xxxxxx x za použití xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx pohlaví. Je-li xxxxxxxx člověka xxxxxxxxxx xxx určité pohlaví, xxxx je xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx látek, měla xx být zkouška xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Plán xxxxxxxx

Xxxxxxxx xxxxx by xxxx být xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx dávky x týž den x rozmezí ne xxxx xxx několika xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Jiné xxxxxx podávání xx xxxx být xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx xxxxxxxx xx xxxx xxxxxxx intervalech xx aplikace podané x xxxxxx dni. X hlodavců xx xxxxx provádí xx xxxxxx xxxx od xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx příjem x xxxxxxxxxxxx xxxxxxxx xxxxx x rovněž xxx xxxxxx na kinetiku xxxxxxxxx cyklu xxxx xxx xxxx xx xxxxxxxxx okamžik xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxx xxxxx xxxxx xx 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx do xxxx xxx jednoho xxx, xxx by xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného xxxxx.

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

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, xxxxxxxx x xx stejného xxxxxx xxxxxxxx, jež xx xxxxxxx x xxxxxx studii (5). X případě toxicity xx xxx xxxxx xxxxx xxxxxxx tři xxxxxx dávky. Xxxx xxxxxx xxxxx xx xxxx pokrývat xxxxxxx xxxx maximální a xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx by vedly xxx stejném xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx kritériím xxxxxxxxx xxxxx vyhovovat a xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx xxxxx xxxx být také xxxxxxxxxx jako xxxxx xxxxxxxxxxxx x xxxxxx xxxxx některé xxxxxx xxxxxxxx (xxxx. více xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže zkouška x xxxxxx xxxxxx xxxxxxx 2000 mg/kg xxxxxxx hmotnosti podanou xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx xxx nevykazuje xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx xxxxx studie xx xxxxx úrovněmi xxxxx xx xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx pro 14denní xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx a xxx xxxxx xxx 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x xxxxxxx xxxxxxx vyšší úroveň xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání xxxx x odůvodněných případech xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxxxxxxx nebo xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 g xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx zdůvodněno. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx xxx variabilita xxxxxxxxxx xxxxxx minimalizována xxxxxxxxxx koncentrace zajišťující xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

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

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx měl být x xxxxx exponovaných xxxxxx (xxxxxx pozitivních xxxxxxx) a u xxxxxxxxxxxxxx xxxxxx pro xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx index, x xx xxxxxxx u 1000 xxxxx xx xxxxx xxxxx.

X xxxxxxx xxxxxxx by xxxx xxx analyzováno alespoň 100 xxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx pozorován velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx xx xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Protože xxx xxxxxx xxxxx xxxxxxx xx chromozomálním xxxxxx xxxx xx xxxxxx xxxxxxxxxx x xxxxx xxxxx x xxxxxxxx, xxxx xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx by xxxx být xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx. Pro xxxxx xxxxx xx xxx xxx xxxxxxxxxx počet xxxxx, xxxxx xxxxxxx xx xxxxx x xxxxx xxxxx s xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx v xxxxxxxxxx. Pro xxxxxxxxxx x kontrolní xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx počtem x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx do xxxxxxx xxxxxxxx aberací. Xxxxxxxxxx-xx xxxxx x xxxxxxx x odpovědi mezi xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx pro obě xxxxxxx zkombinovány.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx několik xxxxxxxx, xxxx. nárůst xxxxxxxxxxx xxxxx xxxxx s xxxxxxxxxxxxxx aberacemi v xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx pro xxxxxxx x určitou dávkou x k určitému xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Při hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek statistické xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka má xxxxxxxxx indukovat xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Nárůst xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx chromozomy xxxx xxxxxxxx, xx zkoušená xxxxx xx xxxxxxxxx xxxxxxxx progresi xxxxxxxxx xxxxx (7, 8).

Xxxxxxxx xxxxx, jejíž výsledky xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx x tomto xxxxxxx xx xxxxxxxxxxx.

Xxxxxx většina xxxxxxxxxxx poskytne xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx o xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx sporné bez xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx chromozomové aberace xx xxxx znamenají, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxx xxxxx testovacího xxxxx xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxx dřeni xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx zvířat xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx odchylky pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, xxx se xxxxxxxx xxxxx xxxxxxx xx krevního oběhu xxxx xx cílové xxxxx,

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

- xxxxxxxx údaje o xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- metody xxxxxxxx xxxxxxxxx,

- kritéria hodnocení xxxxxxx,

- počet analyzovaných xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxx a xxxxx aberací xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- celkový počet xxxxxxx xx skupině xx xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami,

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

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx odpovědi xx dávce,

- případné xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx negativní xxxxxxxx,

- xxxxxxxxx údaje x xxxxxxxxx kontrole x rozpětími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X. (1984), Xxxxxxxxxxx Tests xx Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: a Practical Xxxxxxxx, X. Venitt, X. X. Xxxxx (xxx), IRL Xxxxx, Xxxxxx, Xxxxxxxxxx X. X., 275-306.

2) Xxxxxxx, X. J., Xxxx, X. X., Galloway, X., Xxxxxx, H., XxXxx, A. X., Xxxxxx, X. (1987), Xxxxxxxxx Xx xxxx Xxxxxxxxxxx Assays: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Bone Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. X., Xxxxxxx, X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxx Assays, in: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx York, Xxxx Chester, Melbourne, Xxxxxx, 115-141.

4) Xxxx, X. R., Xxxxxxx, X., MacGregaro, X. X., Xxxxxxxx, X., Xxxxxx, X. H., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, X., Preston, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Vannier, X. (1994), Xxxxxx xxxx xxx Working Xxxxx xx xxx xx vivo Mammalian Xxxx Marrow Chromozomal Xxxxxxxxxx Test, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. J., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. X., Gatehouse, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Report of Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, D. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. X. K. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Test Data, X. J. Xxxxxxxx (xx.) Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

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

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


XXXXXXX 4X

"X.12 MUTAGENITA–TEST XXXXXXX ERYTROCYTÁRNÍCH XXXXXXXXXX XX VIVO

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx OECD TG 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx (1997).

1.1 XXXX

Xxxx savčích erytrocytárních xxxxxxxxxx in xxxx xx používán xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického aparátu xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx látkou, x to pomocí xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx dřeně x/xxxx xxxxx xxxxxxxxx xxxx, obvykle xxxxxxxx.

Xxxxxx xxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx identifikovat xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx dřeně xxxx xx polychromatický xxxxxxxxx, xxxxxx xxxxx je xxxxxxxx a xxxxxxxxxx, xxxxx při xxx xxxxx xxxxxxxxx, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx jádra xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx xx x xxxxxx xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x exponovaných xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx je rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxxxx xxxx xxxx produkuje polychromatické xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů s xxxxxxxxxx v xxxxxxxxx xxxx je xxxxxxxxxx xxxxxxxxxx x xxxxxxxxxxx xxxxx, u něhož xxxx xxxxxxxxx neschopnost xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, nebo xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx xxxxx xxxxxxxx. Ta xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx centromerní (kinetochorní) XXX x mikrojádře. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (polychromatických) xxxxxxxxxx s xxxxxxxxxx. Xxxxx zralých (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx v xxxxxxxxx xxxx, které obsahují xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx počet xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx jako xxxxxxx xxxxxxxx xxxxxxx, xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxx týdny xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx zvláště xxxxxx k posouzení xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx XXX, třebaže xx mohou xxxxx x xxxxxxx druhů x xxxxx, xxxxx x x xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx xx xxxxxx xxxxxxxx xxx další xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx x xxxxxxxxx xx xxxxx.

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

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxx : xxxx jádra existující xxxxxxxx od xxxxxxxx xxxxx x xxxxx xxxx, vytvářená xxxxx xxxxxxxx xxxxxx (meiosy) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx erytrocyt xxxxxxxxxxxx ribozomy, xxxxx xxx xxxxxxxx od xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx selektivním xxx xxxxxxxx.

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx erytrocyt xx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx xxxxxxxx xxxxxxxx, x může být xxxx rozlišen xx xxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx pro xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx se vhodným xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx dřeně xx xxxxxxx ve vhodném xxxxxxxx po xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx xxxx, připraví xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx xx xxxx xx vhodném xxxxxxxx xx expozici odebere, xxxxxxxxxx xx xxxxxxxx xxxxxxxx a xxxxxx xx (4, 8, 9, 10). Při xxxxxxxx s periferní xxxx xx xxxx xxxx poslední expozicí x sklizením xxxxx xxxxxxxx xx nejkratší xxxx. Preparáty xxxx xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Při xxxxxxx xxxxxx xxxxx xx xxxx xxxxxxxxx xxxxx xxxxxxxxxx myš xxxx xxxxxx, ačkoli xxx xxxxxx xxxxxxxx vhodný xxxxx xxxx. Při xxxxxxx periferní xxxx xx doporučuje myš. Xxx xxxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx xxx o xxxx, x něhož xxxxxxx xxxxxxxxxxxx erytrocyty x xxxxxxxxxx, nebo xxxx vykazující xxxxxxxxxxx xxxxxxxxx detekovat činitele, xxxxx způsobují strukturní xxxx numerické xxxxxxxxxxxx xxxxxxx. Měly by xxx xxxxxxx xxxxx xxxxxxx laboratorní kmeny xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx zahájení xxxxxx xx xxxx být xxxxxxxx x hmotnosti xxxxxx minimální a xxxxxx xx x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx zvířata se xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx skupinu x skupinu, x xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat. Xxxxx xx uspořádají xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx před xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx být xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx použity xxxxxxx xxxxxxxxxx zkoušené chemické xxxxx, xxxxx xxxxx x jejich stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx xxxxxxxxx xxxxxxxx xxxxx toxické účinky x xxxx xx xxx xxxxxxxxx podezření, xx reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého experimentu xx xxxx xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx pohlaví. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v nichž xxxxx x expozici.

Pozitivní xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Xxxxx xxxxxxxxx kontroly xx xxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx ihned najevo xxxxxxxx identifikace xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx způsobem xxx xxxxxxxx látka x xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Pro pozitivní xxxxxxxx xxxxx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx měl xxx xxxxxxxx odběr u xxxxxxx negativní xxxxxxxx, xxxxx xx aplikováno xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx s xxxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx kontrolu xxxxx xxxxx, je xxxxxxxxxxxxx okamžikem doba xxxxxxx odběru. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud xxxx xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

Při xxxxxxx xxxxxxxxx xxxx může xxx xxxx negativní xxxxxxxx xxxxxxxxxx xxxx xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx u krátkých xxxxxx s xxxxxxxxx xxxx (např. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, že xxxxxxxx xxxxx xxxxx x rozpětí, které xx na xxxxxxx xxxxxxxxxxx kontrol xxxxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxxxx exponovaná x kontrolní xxxxxxx xx musí xxxxxxx x alespoň pěti xxxxxxxxxxxxxxxx zvířat pro xxxxx xxxxxxx (11). Xxxxxxxx xxxx x xxxx studie k xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež prokazují, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx standardní plán (xx. xxxxx, dvě xxxx xxx aplikace x xxxxxxxxx 24 xxxxx). Xxxxxx ze xxxxxx x xxxxxxxxxxxx xxxxxxx podávání xxxx xxxxxxxxxx, xxxxx se x xxxxxx xxxxxx xxxxxxx xxxxxxxxx výsledky, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx byla prokázána xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx xxxxx x podávání xxxxxxxxx xx do xxxxxxxx xxxxxx. Zkoušené xxxxx xxxxx být xxxxxxxx xxxx xx xxxx xxxxxxx, tzn. xxx xxxxx x týž xxx v xxxxxxx xx více xxx xxxxxxxx hodin, aby xxxx usnadněno xxxxxxxx xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx xxx xxxxxxxx xxxxx xxxxxxx:

x) zkoušená xxxxx xx xxxxxxxx xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx první xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx po xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 hodin xx aplikaci a x přiměřeným xxxxxxxx xxxx odběry. Xxxxx xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx zdůvodněn. Xxxxxx periferní xxxx xx xxxxxxxx alespoň xxxxxxx, přičemž xxxxx xxxxx xx xxxxxxx xxxxxxxx 36 hodin xx xxxxxxxx a xxxxxxxx xxxxxxxxxx 72 xxxxx xx aplikaci x xx prvnímodběru xx xxxxxx odpovídající xxxxxx. Je-li po xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx xxxxx;

x) xxxx-xx podávány xxx xxxx xxxx xxxxx xxxxx (xxxx. xxx xxxx xxxx dávek x xxxxxxxxx 24 xxxxx), xxxx xx xxx vzorky xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx po 18 xx 24 xxxxxxxx xx poslední xxxxxxxx x xxx xxxxxxx periferní krve xxxxxx po 36 xx 48 hodinách xx xxxxxxxx xxxxxxxx (12).

Xxxxx potřeby mohou xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se kvůli xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx studie xxx xxxxxxxx xxxxxxx xxxxx, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, se xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x za stejného xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx studii (13). X xxxxxxx toxicity xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx xxxxxxxx rozpětí xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, případně xxxxxx toxicitou. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx použita xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx xxxxx xxxxx by vedly xxx xxxxxxx režimu xxxxxxxxx podle očekávání x xxxxxxxx. Xxxxx xx specifickou biologickou xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a mitogeny) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx a xxxx by xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx dávka xxxx být xxxx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx známky xxxxxxxx (xxxx. xxxxxxx xxxxxx nezralých xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx xxxx).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx dávkou x xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx dni nevykazuje xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx údajů x xxxxxxx, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx genotoxicita, není xxxxxxxxxx úplná studie xx xxxxx úrovněmi xxxxx za nezbytnou. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx a xxx xxxxx xxx 14xxxxx xxxxxxxx xx xxxxxxx dávkou 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat potřebu xxxxxx v xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo vhodnou xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx kostní xxxxx nebo xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx xxxxxxxxx x xxxxxx xxxx xxxxx xxxxx po xxxxxxxx. Xxxxx xx xxxxxxxx x xxxxxx xxxx xxxxx a zavedenými xxxxxxxx xx xxxxxxxxx x xxxxxx. Xxxxxxxxx xxxx xx získává x ocasní xxxx xxxx xxxx xxxxxx xxxxxx xxxx. Krevní xxxxx xx ihned xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx připraví xxxxxxxxx xxxxxxxx a xxxx xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 a xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx s xxxxxxxx barviva nespecifického xxx DNA. Tato xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx barviv (xxxx. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. celulosová kolona x odstranění xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx za xxxxxxxxxxx, xx xx xxxxxxxxx odpovídající funkčnost xxxxxx systémů xxx xxxxxxxxx xxxxxxxxxx v xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx se xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x xxxxxxx xxxxxx xxxxx použije xxxxxxx xxxxxxx 200 xxxxxxxxxx x x xxxxxxx xxxxxxxxx krve alespoň 1000 xxxxxxxxxx (17). Xxxxxxx preparáty včetně xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx kontrol, xx xxxx xxx před xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxx alespoň 2000 xxxxxxxxx xxxxxxxxxx na xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Xxxxx informace xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx neměl xxx xxxxx nezralých erytrocytů x celkového množství xxxxxxxxxx menší xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx týdny xxxx xxxx, xxx xxxx xxxxxxxx xx výskyt xxxxxxxxxx xxxxxxx 2000 xxxxxxx erytrocytů xx xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx x xxxxxxxxx cytometrická analýza xxxxxxx xxxxxxxx) jsou xx xxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxx přijatelnými xxxxxxxxxxxxx manuálního xxxxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx měly xxx xxxxxxxxxx ve formě xxxxxxx. Experimentální jednotkou xx xxxxx. Xxx xxxxx analyzované zvíře xx měl xxx xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx erytrocytů, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx a počet xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx nebo déle, xxxx xx xxx xxxx xxxxxxx xxxxx x xxxxxxx xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx xx xxxxx podíl nezralých xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx a xxxxxxxx xxxxxxxx erytrocytů x xxxxxxxxxx vyjádřené x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x odpovědi xxxx xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx analýzu xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxx x xxxxxxxxxx na xxxxx xxxx jasný xxxxxx počtu buněk x mikrojádry xxx xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Statistická xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx látka, xxxxx xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, xx xxxxxxxx v tomto xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx případech neumožní xxxxxx xxxxx xxxxxxxx xxxxxxx výrok o xxxxxxxx zkoušené xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxx na mikrojádra xxxxxxxxx, že zkoušená xxxxx indukuje mikrojádra, xxx xxxx důsledkem xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx výsledky znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

Xxxx by xxx xxxxxxxxxxx pravděpodobnost, x xxxxx se xxxxxxxx xxxxx nebo její xxxxxxxxxx dostanou xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx do cílové xxxxx (např. systémová xxxxxxxx).

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx o zkoušce xxxx obsahovat tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění volby xxxxxxxx,

- rozpustnost x xxxxxxx xxxxxxxx xxxxx x rozpouštědle/vehikulu, je-li xxxxx.

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

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

Zkušební xxxxxxxx:

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

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

- zdůvodnění zvolených xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx zkoušené látky,

- xxxxxxxxxx způsobu xxxxxxxx,

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

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx a xxxx,

- xxxxxxxx popis xxxxxxx xxxxxxxx x odběru,

- xxxxxx xxxxxxxx preparátů,

- xxxxxx stanovení xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x nezralých xxxxxxxxxxxx,

- xxxxx analyzovaných xxxxx xx jedno xxxxx,

- xxxxxxxx klasifikace studie xx pozitivní, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- podíl nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,

- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx počtu xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx ve skupině,

- xxxxx možnosti závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy x xxxxxx,

- xxxxx x xxxxxxxx x xxxxxxxxx xxxxxxxxx kontrole,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxx, X. X., Xxxxxxxx, M. X., Xxxx, M., Xxxxxxxx, X., Mavournin, K., XxxXxxxxx, X. X., Xxxxxx, X. X. (1983), Xxx Xxxxxxxxx xx Xxxxxxxxxxx a. x. a Measure xx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx. 123, 61-118.

4) Xxxxxxxxx, K. X., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxxxx, X. F., Xxxxxx, J. X. (1990), Xxx Xx xxxx Micronucleus Xxxxx xx Mammalian Bone Xxxxxx xxx Peripheral Xxxxx. A xxxxxx xx xxx X. X. Environmental Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, X. X., Schlegel, X., Xxxx, W. X., Xxxx, C. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Xxxxxx xxx Xxxxxxxxxxx Xxxxxx During Xxxxxxx Toxicity Xxxxxxx xx Xxxx, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, xx. A. X. Xxxxx, R. X. Schnell, X. X. Xxxx. Elsevier, Xxxxxxxxx, 555-558.

6) MacGregor, X. X., Xxxxxx, X. A. Xxxx, X., Xxxxxxxx, X. X., Xxxxx, C., Xxxxxxxx, X. X., Xxxx, X. R., Xxxx, X. (1987), Xxxxxxxxxx xxx the Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Mammalian Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Res., 189, 103-112.

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

8) Xxxxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, M. Xx. (1990), The Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Xxxxx Xxxxxxxx Xxxxxx-Xxxxxx Slides, Xxxxxxxxxx Xxx., 245, 245-249.

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

10) Xxx Xxxxxxxxxxxxx Study Xxxxx xxx the Xxxxxxxxxxxx Xxxx (CSGMT/JEMMS, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Group xx the Environmental Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx xxx xxx xxxxx-xxxx mouse peripheral xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., XxxXxxxxx, X. X., Xxxxxxxx, X., Blackey, X. X., Xxxxxx-Xxxxxxx, X., Xxxxxx, Xx. X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, S., Xxxxxxx, X. (1994), Xx vivo Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Assay, Xxxxx. Xxx., 312, 293-304.

12) Higashikuni, N., Xxxxx, X. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx xxxx of 30 ± 6 x xxxxx xxxxxx xxxxxx in xxx xxxxx peripheral micronucleus xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Xxxxxxx, X. X., Xxxxx, X. X., Boobis, X. X., Botham, P. X., Xxx, J., Xxxxxxx, D. X., Xxxxxxxxx, D. G., Xxxxxx-Xxxxxx, G., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Xxxxxx xx British Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

15) XxxXxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X. X. (1983), X Simple Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Micronuclei xxx XXX xx Xxxxxxxxxxxx Xxxxx Hoechst 33258 xxx Pyromin X, Xxxxxxxx Res., 120, 269-275.

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

17) Gollapudi, X., XxXxxxxx, X. X. (1995), Sample Xxxx for the Xxxxxxxxxx xx Polychromatic xx Normochromatic Xxxxxxxxxxx Xxxxx xx xxx Xxxx Marrow Xxxxxxxxxxxx Xxxx, Mutatation Res., 347, 97-99.

18) Richold, X., Xxxxx, J., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxxx Xxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, XXXXX Recommended Xxxxxxxxxx, XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. P., Anderson, X., Albanese, R., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx X., Richold, M., Xxxxxxxx, X. X., Xxxxxx, J. R. X. (1989), Xxxxxxxxxx Xxxxxxxx of In xxxx Xxxxxxxxxxx Assays, xx: D. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Part XXX, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, New York, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 184-232."


PŘÍLOHA 4X

"X.13/14 XXXXXXXXXX — ZKOUŠKA XX XXXXXXXX XXXXXX S XXXXXXXXXX

1. METODA

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

1.1 XXXX

Xxx xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx používají xxxxxxxxxxx xxxxx xxxxxxx na xxxxxxxxxxxxxxx Xxxxxxxxxx typhimurium x Xxxxxxxxxxx coli, x detekci xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx xxxx xxxxxxxx xxxx bází XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxx v xxxxxxx xxxxxx, xxxxx revertují xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxx a xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx díky xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx xxxxxxxxxxxx, xxxxx xxxx xxxxxxxxxx mateřským xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x xxxxxxxx xxxxx xxxxxx x tom, že xxxxxx mutace x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx mají xxxxx xx xxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx je xxxxxx, xxxxxxxxxx x relativně xxxxxx. Mnoho testovacích xxxxx xx xxxx xxxxxxxxxx, xxxx nimž xxxx citlivější xx xxxxxxx xxxxxx, včetně xxxxxxxxxxxxx sekvencí XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx xxxxx xxx xxxxx molekuly x xxxxxxxxx reparačních xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx x xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx xxxx poskytnout xxxxxxx xxxxxxxx informace x typech xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx činiteli. Xxx xxxxxxx xx xxxxxxxx xxxxxx s bakteriemi xx x xxxxxxxxx xxxxx rozsáhlá databáze xxxxxxxx xxx xxxxxxx xxxxx struktur x xxxx xxxx xxxxxxxx xxxxx vyzkoušené xxxxxx xxxxxxxx chemických látek, xxxxxx těkavých xxxxxxxxx, x xxxxxxx fyzikálně-chemickými xxxxxxxxxxx.

Xxx xxxx obecný xxxx, část X.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx typhimurium xxxx Xxxxxxxxxxx coli xxxxxx x xxxxxxx xxxxxx x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx xxxx. xxxxxxxxx), xxxxxxx xxxxxx xxxx xxxxxxxxx xx xxxxxxx přísunu aminokyseliny.

Mutageny xxxxxxxxxx xxxx xxxx xxxx činitele, jež xxxxxxxxx xxxxx v xxxxxx DNA. Xxx xxxxxxx xxxxxxxxxx mutací xx xxxxx xxxx xxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxx xxxx jiném místě xxxxxxxxxxxxx genomu.

Posunové mutageny xxxx činitele, xxx xxxxxxxxx xxxxx nebo xxxxxx jednoho xxxx xxxx xxxx xxxx XXX x posunují xxx xxxxx xxxxx XXX.

1.3 XXXXXXX XXXXX

Xxx xxxxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx prokaryotické xxxxx, které se xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx x xxxxxxxxx procesy XXX. Xxxxxxx xxxxxxxxx in xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Metabolické xxxxxxxxx xxxxxxx in xxxxx xxxxxxx xxxxx xxxxxxxxx podmínky xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx látky pro xxxxx.

Xxxxxxx na reverzní xxxxxx s bakteriemi xx zpravidla xxxxxxxxx xxx xxxxxxxxx vyšetření xxxxxxxxxxx xxxxxxxx, a xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx mutace. X xxxxxxxx xxxxxxxx vyplývá, xx xxxxx chemických xxxxx, xxxxx jsou x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx x x xxxxxx xxxxxxxxx. Existují xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx. Příčiny xxxxxx xxxxxxxxxxx xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx detekovanéhokonečného xxxx, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx xxxx x xxxxxxxxx v xxxxxxxxxx dostupnosti. Na xxxxx xxxxxx faktory, xxxxx xxxxxxx xxxxxxxxx xxxxxxx na reverzní xxxxxx na bakteriích, xxxxx xxxx k xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx reverzní mutace x bakteriemi xxxxxx xxx xxxxxx pro xxxxxx xxxxx chemických xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (např. xxxxxx antibiotika) a xxx xxxxxxxx xxxxx, x xxxxx xx xxxxxxxxxxx (xxxx x xxxxx se xx), xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx savců (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x některé analogy xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx být xxxxxxxxx zkoušky xxxxxxxxxx x xxxxx.

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

1.4 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx jsou xxxxxxxxx xxxxxxxx xxxxx, x xx za xxxxxxxxxxx xxxxxxxx metabolického xxxxxxxxxxx xxxxxxx a xxx xxxx. Ve xxxxxxxxxxx miskovém testu xx xxxxxxxx xxxxxxxx x vrchním xxxxxx x xxxxx xx xxxxxxx na xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx xx xxxxxxxx xxxx inkubuje x xxxx xx před xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx s xxxxxxx xxxxxx. Xxx xxxx technikách se xx xxxx xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx x provede se xxxxxxxx x xxxxxx xxxxxxx spontánních revertantů xx xxxxxxxxx misce x xxxxxxxxxxxxx.

Xx popsáno xxxxxxx xxxxxxx xxxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx. Xxxx xxxxx používané xxxxx standardní xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx test (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx xxx xxxxxxxx xxxxx x par xxxx xxxxxxx (12).

Xxx xxxxxxx xxxxxxx xx xxxxxx hlavně standardního xxxxxxxxx testu x xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx xx xxxxxxxxxx xxx provádění xxxxxxxxxxx jak s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx metody. Tyto xxxxx patří do xxxxxxxxxx tříd, xx xxxxx patří xxxx xxxxx krátké alifatické xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx, pyrrolizidinové xxxxxxxxx, xxxxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx třídy xxxxxxxx xxxxx vždy xxxxxxxxx xxxxxxxxxxxx postupy, xxxx xx xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx xxx xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x k jejich xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxxx alternativní xxxxxxx. Je xxxxx xxxxxxxxxxxxx tyto "xxxxxxxx xxxxxxx" (xxxxxxxx x xxxxxxxx xxxxxxx xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Odchylka xx xxxxxxxxxxxx xxxxxxx xxxx xxx vědecky xxxxxxxxxx.

1.5 XXXXX ZKUŠEBNÍ METODY

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx xxxx xxx kultivovány xx xxxxxx xxxxxxxxxxxxx xxxx xxxx xx časné xxxxxxxxxxx xxxx xxxxx (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx použity. Xx xxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx xxxxxx xxxx životaschopných xxxxxxxx. Xxxx xxxx xxx xxxxxxxx buď xx xxxxxxx dosavadních xxxxxxxxxxx xxxxx o xxxxxxx xxxxxx, nebo xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx životaschopných xxxxx xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx je 37 °X.

Xxxx by xxx xxxxxxx alespoň pět xxxxx xxxxxxxx. Mezi xxxx xx měly xxx xxxxx xxxxx X. xxxxxxxxxxx (XX1535; XX1537 nebo TA97a xxxx XX97; TA98 x XX100), xxxxxxx xxxxxxx xx xxxxxxx x xxxxxxx laboratořích xxxx spolehlivá x xxxxxxxxxxxxxxxx. Xxxx čtyři xxxxx S. xxxxxxxxxxx xxxx xxx xxxx XX xx primárním xxxxxxxxx místě x xx xxxxx, xx xxxxxx prostřednictvím nelze xxxxxxxxx určité xxxxxxxx xxxxxxxx, xxxxxxxx způsobující xxxxxxxxxx xxxxxx DNA x xxxxxxxxx. Tyto xxxxx mohou být xxxxxxxxxx xxxxx X. xxxx XX2 xxxx X. typhimurium XX102 (19), xxxxx mají xx primárním reverzním xxxxx pár xxxx XX. Doporučená kombinace xxxxx xx xxxx xxxx:

- S. typhimurium XX1535 a

- X. xxxxxxxxxxx XX1537 xxxx XX97x x

- X. xxxxxxxxxxx XX98 x

- X. xxxxxxxxxxx XX100 x

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

Pro xxxxxxx xxxxxxxx způsobujících xxxxxxxxxx xxxxxx DNA xxxx xxx xxxxxxxxx xxxxxxx XX102 nebo xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx DNA, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx xx xxx použity zavedené xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, verifikace markeru x skladování. Xxxxxxx xxxxxxxxxxxxx pro růst xx xxxx xxx xxxxxxxxx xxx každou xxxxxxxxx kmenovou xxxxxxx (xxxxxxxx xxx xxxxx X. typhimurium a xxxxxxxxx xxx X. xxxx). Podobně xx xxxx xxx kontrolovány xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx xxxx nepřítomnost X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx rezistence x xxxxx TA98, XX100 x XX97x xxxx XX97, WP2 xxxX x XX2 xxxX (xXX101) a xxxxxxxxxxxx x xxxxxxxxxxxxxx rezistence x xxxxx TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx xxxxxx x S. xxxxxxxxxxx xxxxxxxxxx na krystalovou xxxxxx x xxxX xxxxxx x E. xxxx xxxx xxxX xxxxxx x S. xxxxxxxxxxx citlivostí xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx by xxxx rovněž xxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx na misce x rozmezí xxxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxxxxx xxxxxxx x xxxxxxx x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Médium

Použije xx xxxxxx xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx X (Xxxxx-Xxxxxx) a xxxxxxx) x vrchní agar xxxxxxxxxx xxxxxxxx x xxxxxx xxxx xxxxxxxxx xxxxxxxxxx několik xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx xxxxxxxx

Xxxxxxxx xx měly xxx xxxxxxxxx zkoušené látce, x xx s xxxxxxx xxxxxxxx metabolické xxxxxxxx a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx indukujícím xxxxxx, xxxx xx Xxxxxxx 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx xxxxxx xx obvykle používána x koncentracích x xxxxxxx 5 až 30 % obj. xx xxxxx S9. Xxxxx a podmínky xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx záviset xx xxxxx xxxxxxxx xxxxxxxx xxxxx. V xxxxxxxxx xxxxxxxxx může xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xxxx xxx xxxxxxxxx použití redukčního xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Zkoušená xxxxx nebo přípravek

Pevné xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx na xxxxxxxx xxxxxxxxxx nebo suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky mohou xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx mimo xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxxxxx a x xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx jiná xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx nestálých xx xxxx xx xxxx xxx použita xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Zkušební xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx být xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxx zkoušené xxxxx xxxxx cytotoxicita x rozpustnost x xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx toxicitu a xxxxxxxxxxxxx v předběžných xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx revertantů, xxxxxxxxx nebo xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx nebo xxxxxxxx stupně přežití xxxxxxxxxxxx kultur. Xxxxxxxxxxxx xxxxx xx může xxxxxx x přítomnosti xxxxxxxxxxxxx aktivačních systémů. Xxxxxxxxxxxxx xx měla xxx posouzena na xxxxxxx viditelného xxxxxxx x xxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx rozpustné xxxxxxxxxxxxx látky je 5 xx/xxxxx xxxx 5 μx/xxxxx. X xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx xx xxxx xxx jedna nebo xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx látky xxxx x xxxxxxx xxxxx pro xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx jsou xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx, by měly xxx xxxxxxxx xx xx xxxxxxxxxxx koncentrace. Xxxxxxxxx xx neměla xxxxx xxx vyšetřování.

Mělo xx xxx použito xxxxxxx xxx různých xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx xxxx zkušebními body xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx stupnice (xx. Ö10). Xxxxx xxxxxxxxx xxxx xxxxxx x xxxxxxx, xxx xx xxxxxxxxx xxxxxx xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx xxx xxxxxxx xxx xxxxxxxxx xxxxx obsahujících významné xxxxxxxx xxxxxxxxxxx mutagenních xxxxxxxx.

1.5.2.3 Negativní x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx by měly xxx xxxxxxx specifické xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx x metabolickou xxxxxxxx x bez xx. Xxx pozitivní xxxxxxxx xx xxxx xxx vybrány koncentrace xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X případě xxxxxxx x použitím xxxxxxxxxxxxx xxxxxxxxxxx systému by xxxx být xxxxx (xxxxx) pro xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxx) xx xxxxxxx xxxx xxxxxxxxx xxxxx bakterií.

Příkladem xxxxxx pozitivní xxxxxxxx x xxxxxxx x xxxxxxxxxxxx xxxxxxxx xxxx xxxx xxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

9,10-dimethylanthracen

781–43–1

212–308–4

7,12-dimethylbenzo[a]anthracen

57–97–6

200–359–5

benzo[a]pyren

50–32–8

200–028–5

2-aminoanthracen

613–13–8

210–330–9

Cyklofosfamid

50–18–0

200–015–4

cyklofosfamid monohydrát

6055–19–2

Tato xxxxx je vhodnou xxxxxxxxx kontrolou xxx xxxxxx xxxxxxxx metabolické 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 indikátor xxxxxxxxx xxxxx X9. Při xxxxxxx 2-aminoanthracenu xx xxxx xxx xxxxx xxxxx X9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx mikrosomálními xxxxxx, xxxxxxxxx xxxxx[x]xxxxx xxxx 7,12-dimethylbenzo[a]anthracen.

Příkladem xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx u xxxxxxx xxx xxxxxx xxxxxxxxxxx xxxxxxxx xxxx xxxx xxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

Kmen

azid 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 XX97x

XXX 191

17070–45–0

241–129–4

XX1537, XX97 a XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX x XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 uvrA x XX2 uvrA (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX x XX2 uvrA (xXX101)

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

3688–53–7

xxxxx xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxx xxxxxxxxxx xxxxx. Xxx pozitivní xxxxxxxx xx xxxx být xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou xx x dispozici.

Měly xx xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, bez xxxxxxxx xxxxx, zpracované xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx skupiny. Xxxxx toho xx xxxx xxx neexponované xxxxxxxx xxxxxxx také xxxxx, neexistují-li xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5.3 Xxxxxx

X standardní xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,05 xx xxxx 0,1 xx zkušebních roztoků, 0,1 ml xxxxxxx xxxxxxxxxxx xxxxxxx (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx sterilního xxxxx x 2,0 xx xxxxxxxx agaru. X xxxxxxx xxxxxxx s xxxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,5 xx metabolické xxxxxxxxx xxxxx obsahující xxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (x rozmezí 5 xx 30 % xxx. v metabolické xxxxxxxxx xxxxx) x xxxxxxx xxxxxx (2,0 xx) a xxxxxxx x xxxxxxxxxx x xxxxxxxxx látkou xxxx xxxxxxxxx roztokem. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx a přelije xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx. Xxxx xxxxxxxx se xxxxx xxxxxx agar xxxxxxxx.

X preinkubační metody (2, 3, 5, 6) xx zkoušená xxxxx nebo xxxxxxxx xxxxxx před smícháním x xxxxxxx agarem x xxxxxxxx xxxx xxxxxx minimálního xxxxx xx xxxxx xxxxxxx 20 minut xxxx xxxx xxxxxxxxxxx s xxxxxxxxxx kmenem (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x sterilním xxxxxx nebo metabolickým xxxxxxxxxx systémem (0,5 xx) při 30 — 37 °C. Xxxxxxx xx xxxxxx 0,05 nebo 0,1 xx xxxxxxxx látky xxxx zkušebního xxxxxxx, 0,1 xx xxxxxxxx x 0,5 ml xxxxx X9 xxxx xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx xxxxx. Zkumavky xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

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

Xxxxxx xxxx xxxxxx látky xx xxxx xxx zkoušeny xxxxxxxx xxxxxxxx, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx nádobách (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx misky x xxxx zkoušce xx xxxx být xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Po uplynutí xxxxxxxxx doby xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx na xxxxx.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Předloženými xxxxx by měly xxx xxxxx xxxxxxx xxxxxxxxxx připadající xx xxxxx. Xxx xx xxx xxxxxx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xx xxxxxxx x xxxxxxxxx xxxxxxxxx (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx xxxxxxxx), xxx xx xxxxxxx x xxxxxxxxx kontrolou. Xxxxx na jednotlivých xxxxxxx, střední xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx zkoušenou xxxxx x pozitivní x xxxxxxxxx kontrolu (xxxxxxxxxxxxx xxxxxxxx a/nebo kontrolu xxxxxxxxxxxx).

Xxxxxxx jasně xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx experimentálních xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx nezbytné, xxxx xx xxx podáno xxxxxxxxxx. Xxxxx parametrů xxxxxx x cílem xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx zpracování (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) a xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, např. xxxxxx xxxxx kolonií revertantů xx xxxxx nad xxxxxxxxx rozsah x xxxxxxx jednoho kmene x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxx bez xxxx, x to x xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx počtu xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx odpověď.

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

Xxxxxx většina experimentů xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx znamenají, xx xxxxxxxx látka xxxxxxxx x xxxxxx kmenů Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx coli bodové xxxxxx xxxxxxxxxx xxxx xxxx xxxxxxx xxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxx xx xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy xxxxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Kmeny:

- xxxxxxx xxxxx,

- xxxxx xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx kmene.

Zkušební xxxxxxxx:

- xxxxxxxx zkoušené xxxxx xx misku (xx/xxxxx xxxx μx/xxxxx) x xxxxxxxxxxx výběru dávky x počtu xxxxx xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

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

- postup xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx možnosti závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- xxxxxxxxx xxxxx o xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) a xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx hodnotami x směrodatnými xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Ames, X. X., McCann, X., Xxxxxxxx X. (1975), Methods xx Xxxxxxxxx Carcinogens xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Mutagenicity Test, Xxxxxxxxxx Xxx., 31, 347-364.

2) Maron, X. X., Xxxx, X. X. (1983), Xxxxxxx Xxxxxxx for xxx Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res., 113, 173-215.

3) Xxxxxxxxx, X., Xxxxxxx, X., Cebula, X., Xxxxx, E., Xxxx, L., Xxxxxxxxxx, X., Melcion, X., Xxxxx, T., Xxxxxx, X., Xxxxxx, X. (1994), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx of Xxxxxxxxx Mutation Assays, Xxxxxxxxxx Xxx., 312, 217-233.

4) Xxxx, X. X., Xxxxxxx D. X., Auletta, A. X., Von Halle, X. S., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X., McCann, X., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Xxx V. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, X., Xxxxxx, X., Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X., Sugimura, X., Hashimoto, X. (1975), Xxxxxxxxxxxx of Xxxxxxxxxx Xxx Xxxx xxx xxxxx Derivatives, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, T., Xxxxx, X., Xxxxxx, X., Xxxxxx, X., Sawamura, X. (1980), Xxxxxxx Xxxxxxxxxx Mutagenicity Xxxxxxxxx Xxxxx, in: Xxxxx-xxxx Xxxx Systems xxx Xxxxxxxxx Carcinogens, ed. Xxxxxxx X. H., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Xxxxxxxxx, X. X., Rowland, X. X., Xxxxxx, P., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Basic Xxxxxxxxxxxx Xxxxx: XXXXX Xxxx 1 Revised, ed. X. J. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, 13-61.

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

9) Xxxxx, X. X. X., Xxxxxx, W. X., Xxxxxxx, X. X. (1976), Use of x simplified fluctuation xxxx to detect xxx xxxxxx of xxxxxxxx, Mutatation Xxx., 38, 33-42.

10) Hubbard, X. A., Green, X. X. X., Xxxxxxxxx, X., Bridges, X. X. (1984), Xxx Fluctuation Test xx Xxxxxxxx, in: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (eds.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, E. X., Xxxxxxx, X. J. (1981), Xx Xxxxxxxxxxx xx xxx Quantitative Xxxxxxxxxx Xxxxx for Xxxxxxxxxxx with Xxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Araki, X., Xxxxxxx, X., Kato, X., Xxxxxxxxxx, T. (1994), Improved Xxxxxx xxx Mutagenicity Xxxxxxx xx Gaseous Xxxxxxxxx xx Xxxxx x Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

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

14) Xxxxxx, E., Xxxxxxxx, X. E., Xxxxxxx, X., Xxxxxx, T., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx xxxx xxx Xxxxxxx of 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Simmon, X., Xxxxxxxx, X., Xxxxxxx, X. G. (1977), Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxx Water, in Xxxxxxxx xx Xxxxxxx Xxxxxxxxxx, X. Xxxxx, X. Xxxxxxx, F. Xxxxxx (eds.) Elsevier, Xxxxxxxxx, 249-258.

16) Hughes, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. G., Xxxxxxx, X. D. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Volatile Organic Xxxxxxxxx in xxx Xxxx/Xxxxxxxxxx Xxxxx, Environmental Xxxxxxxxxxx, 9, 421-441.

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

18) Xxxxxx, X., Xxxx, X., Xxxxx-Xxxxx, X., Xxxx, B. N. (1980), Xxxxxxxx: A Xxxxx xxx Xxxxxxxxxx xx Dietary Xxxxxxxxxx xx Mutagens by Xxxxxxxxxx Xxxxx, Xxxx. Xxxx. Xxxx. Xxx. X. X. X, 77, 4961-4965.

19) Xxxxxx, X., Xxxxxx, A., Xxxx, X. X., Xxxxxxxxx, X. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx typhimurium XX 102 with Xxxxxxxxxxx xxxx XX2 Tester xxxxxxx, Mutagenesis, 5, 285-291.

20) Matsushima, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X Xxxx Xxxxxxxxxx for Polychlorinated Xxxxxxxxx x. x. xx Inducer or Xxxxxxxxx Activation Xxxxxxx, xx: Xx vitro Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxxxxx Xxxxxxx, xxx. X. X. xx Xxxxxx xx xx. Xxxxxxxx, Xxxxx Holland, 85-88.

21) Xxxxxx, B. X., Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxxx, D. X., Xxxxxx, X. X., Mackay, J. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-induced X9 xx xx xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

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

23) Claxton, X. X., Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxx, X., Zeiger, X. (1987), Xxxxx for xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Mutagenicity, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, X. X. X., Xxxxx, X. X. X., Xxxxxxxxx, X., Mitchel, X., Xxxxxxxx, X. X., Xxxxxx, D. X. (1989), Analysis xx Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, xx: XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx, xx. Xxxxxxxx, X. X., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 28-65."


XXXXXXX 4X

"X.17 XXXXXXXXXX — ZKOUŠKA XX XXXXXX XXXXXX X XXXXXXX SAVCŮ XX XXXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody XXXX TG 476 — Xxxxxxx xx xxxxxx xxxxxx v xxxxxxx savců in xxxxx (1997).

1.1 XXXX

Xxxxxxx xx genové xxxxxx x buňkách xxxxx xx vitro xxx xxxxxx xxx xxxxxxx xxxxxxxx mutací indukovaných xxxxxxxxxx xxxxxxx. Mezi xxxxxx xxxxxxx xxxxx xxxxx xxxxx xxxxxxx X5178X myší, xxxxxxx xxxxx XXX, XXX-XX52 x X79 xxxxxx xxxxxxxx a xxxxxxxxxxxxxxx xxxxx XX6 xxxxxxx (1). U xxxxxx xxxxxxxxx xxxxx jsou xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (TK) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x transgen xanthin-guaninfosforibosyltransferasy (XXXX). Xxxxxxx xx xxxxxx TK, XXXX x XPRT xxxxxxxx xxxxx spektrum genetických xxxxxxxx. Xxxxxxxxxxx lokace XX x XXXX xxxx umožnit detekci xxxxxxxxxxx událostí (xxxx. xxxxxxxx xxxxxx), xxxxx xxxxx xxxxxxxxx x XXXX xxxxxx xx X chromozomech (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx mutace v xxxxxxx xxxxx xx xxxxx lze xxxxxx xxxxxxx xxxxxxxxxx linií xxxxx nebo xxxxxxx xxxxx. Xxxxx se xxxxxxxx xxxxx schopnosti xxxxx v kultuře x xxxxxxxx četnosti xxxxxxxxxxx mutací.

Zkoušky xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx nemůže xxxxx xxxxxxxxx xxxxxxxx xx xxxx x savců. Xx xxxxx se xxxxx vyvarovat xxxxxxxx, xxxxx xx vedly x pozitivním xxxxxxxxx, xxx neodrážejí vlastní xxxxxxxxxx. X pozitivním xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, může xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx se xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx a xxxxxxxxxxx xxxxx. Mnoho xxxxxxxxx, xxx xxx xx xxxx zkouška xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx xxxxx xxxxxxxx x karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx třídě x xxxxxxxxx důkazy x xxx, že existují xxxxxxxxxxx, které nejsou xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxx mutace : genová mutace xxxxxxxxx xxxx xxxxxxxx xxxxx, která způsobuje xxxxx nebo xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxx substituce xxxx xxxx : xxxxx, xxxxx způsobují xxxxxxxxxx xxxxxxx xxxx xxxx xxxx xxxx x XXX.

Xxxxxxxx mutageny : xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx xxxx xxxx xxxx bází v xxxxxxxx XXX.

Xxxx xxxxxxx xxxxxxxx : xxxx, xxxxx xxx xxxxxx x xxxx xxxxxxxxxx xxxxx xxxxxxxxx genové xxxxxxxx.

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

Relativní xxxxxxx xxxx : xxxxxx xxxxx buněk x xxxx xx srovnání x kontrolní xxxxxxxx xxxxx; xxxxxxx se xxxx xxxxxx xxxxxx xxxxxxxxx xxxxx v xxxxxxxx x x xxxxxxxxx xxxxxxxx x xxxxxxxxx účinnosti klonování xxxxxxxx k xxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxx x xxxxxxxx : nárůst xxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxx kontrole.

Životaschopnost : xxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx na xxxxx xx xxxxxxxxxxxx xxxxxxxx xx expresi.

Přežití : xxxxxxxx xxxxxxxxx xxxxx xxx nasazení na xxxxx xx xxxxx xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx vyjádřeno x xxxxxx x xxxxxxx kontrolní xxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) jsou xxxxxxxxxxx k xxxxxxxxxxxx xxxxxxx analogu xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Buňky xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx xx TFT, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx metabolismu x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Mutantní buňky xxxx tedy schopny xxxxxxxxxxx za přítomnosti XXX, xxxxxxx xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxxxxxxx tuto xxxxxxxxx xxxxxx. Xxxxxxx xxx x xxxxx x xxxxxxxxxxxx XXXX nebo XXXX xxxxxxx selekci xxxxxxxxxxxxxxx xxxxxxxxxx k 6-xxxxxxxxxxx (TG) xxxx 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx xxxxx xx xxxx být xxxxxxx xxxxxxx, xxxxxxxx xx xx zkoušce xx xxxxxx xxxxxx v xxxxxxx xxxxx zkoušen xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx podezření xx xxxxxxxxxx toxicitu xxxxxxxx xxxxx xxx mutantní xxxx nemutantní xxxxx. Xxx xxxxxxxx chemických xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, musí xxxx být xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxx xxx xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxx xxxx vhodnou xxxx xxxxxxxxx xxxxxxxx xxxxx xxx x metabolickou xxxxxxxx, tak xxx xx, x xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx a za xxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Cytotoxicita xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) nebo xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx v xxxxxxxx xxxxx xx xxxxxxx xxxx charakteristickou xxx xxxxx xxxxxxx xxxxx x xxx xxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx xxx, xx xx xxxxxx xxxxx xxxxx xxxxx xx xxxxx xxxxxxxxxxxx selekční xxxxxxx xxx xxxxxxx mutantních xxxxx x do xxxxx bez xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Po vhodné xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx x počtu xxxxxxxxxx xxxxxxx v xxxxxxxxx xxxxx x počtu xxxxxxx x xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx použití x této xxxxxxx xxxx x xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, CHO, XXX-XX52, X79 nebo XX6. Xxxx xxxxx x xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx schopnost x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx kontaminace xx xxxxxx xxx xxxxxxx.

Xxxxxxx xx měly xxx navrženy xxx, xxx xxxx xxxxxx xxxxxxxxxx xxxxxxxxx a xxxx. Počet xxxxxxxxx xxxxx, kultur x xxxxxxxxxxx xxxxxxxx xxxxx xx xxx tyto xxxxxxxxxx xxxxxxxxx odrážet (14). Minimální xxxxx xxxxx, xxxxx přežijí xxxxxxxx x které xxxxx xxxxxxx v xxxxxx xxxxxx xxxxxxx, xx měl xxx xxxxxxx na xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx xx, aby xxx použit xxxxx xxxxx, xxxxx je xxxxxxxxxxxxxx převrácené xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však doporučeno, xxx xxxx xxxxxxx xxxxxxx 106 xxxxx. Xxxx by xxx x xxxxxxxxx xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx buněčném xxxxxxx, xxx xxxx doložena xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Média a xxxxxxxxxx podmínky

Pro xxxxxxxxx xxxxxx xx xxxx xxx použita xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (kultivační xxxxxx, koncentrace XX2, xxxxxxx a xxxxxxx). Xxxxx xx měla xxx zvolena podle xxxxxxxxxx systémů a xxxx xxxxx použitých xxx xxxxxxx. Xx xxxxxxx xxxxxxxx, xxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxx tak, aby xxxx xxxxxxxxx xxxxxxxxx xxxx buněk xxxxx xxxxxx exprese x xxxxxxxxx xxx xxxxxxxxxx, xxx nemutovaných buněk xxxxxx kolonie.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx xxxxxx, xxxxxxxx xx xxxxxxxxxxxx média x inkubovány xxx 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxx již xxxxxxxx xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx vystaveny zkoušené xxxxx, x xx x xxxxxxx systémem xxxxxxxxxxx xxxxxxxx x xxx něho. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx činidlem xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (15, 16, 17 x 18), xxxx xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (19, 20).

Postmitochondriální frakce xx x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx v koncentracích 1 — 10 % xxx. Volba x stav xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může xxxxxxx xx xxxxx xxxxxxxx látky, která xx xxxxxxxx. V xxxxxxxxx případech může xxx vhodné xxxxxx xxxx xxx xxxxx xxxxxxxxxxx postmitochondriální xxxxxx.

Xxxx xxxxxxxx vývoje, xxxxxx xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx linií xxxxxxxxxxxxx xxxxxxxxxx aktivační xxxxxx, xxxxxxxxx možnosti xxx xxxxxxxxx aktivaci. Volba xxxxxxxxx buněčných linií xx xxxx xxx xxxxxxx zdůvodněna (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx před xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx xxx xxxxxxx přímo x xxxxxxxxxx systémům a/nebo xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, x xxxx xx xxx slučitelné x přežitím buněk x s aktivitou X9. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Doporučuje xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx nestálých xx xxxx xx xxxx xxx použitá xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx při xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, rozpustnost x xxxxxxxxxx xxxxxxx x změny pH xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx stanovena x xxxxxxxxxxxx xxxxxxxx x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, jako xxxx xxxxxxxxx účinnost xxxxxxxxx (přežití) nebo xxxxxxxxx celkový růst. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx by xxx xxxxxxx alespoň čtyři xxxxxxxxxxxxxx koncentrace. X xxxxxxx xxxxxxxx by xxxx xxxx xxxxxxxxxxx xxxxxxxx rozmezí dané xxxxxxxxx x minimální xxxxxxxxx, případně xxxxxx xxxxxxxxx, což xxxx xxxxxxx znamenat, xx xx xx koncentrace xxxx xxxxx faktorem 2 xx Ö10. Xx-xx xxxxxxxxx koncentrace xxxxxxxx xx xxxxxxxxxxxx, xxxx by být xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx látek xx xxxx xxx maximální xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, která x xxxx xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx měly xxx xxxxxxxx xx k xxxx rozpustnosti xx xxxxxxxxxxxx xxxxxxxx, xxxx xx xx xxxx xxx. Xxxx xx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx v xxxxxxxx xxxxx, xx kterému xxxx xxxxx xxxxxxxxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx aplikace, neboť xxxxxxxxxxx se xxxx x průběhu xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, X9 xxxx, atd. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, tak xxx ní. Xxx xxxxxxx metabolické xxxxxxxx xx měla být xxxxxxxxx xxxxxxxxx chemická xxxxx, xxxxx x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx pozitivní xxxxxxxx xxxxx xxx tyto xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx

Xxxxx 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 x xxxxx xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx metabolickou xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (malé x xxxxx xxxxxxx)

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxx[x]xxxxx

50–32–8

200–028–5

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–5

XXXX

X-xxxxxxxxxxxxxxxxxxx (xxx vysoké úrovně X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx být xxxxxxx xxxx xxxx referenční xxxxx xxx xxxxxxxxx xxxxxxxx, xxxx. xx-xx xxxxxxxxx databázi xxxxxxxxxxx xxxxx x 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, EINECS 200–415–9), xxxx xxx xxxx xxxxxxxxxx látka xxxxxx použita. Xxx xxxxxxxxx xxxxxxxx xx xxxx být xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxxx xx stejné xxxxxxxx třídy.

Měly xx xxx xxxxxxx negativní xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxxxxxxx jinak xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Kromě xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx použity xxxx tehdy, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Postup

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx xxxx být xxxxxxxxx xxxxxxxx látce xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx xxx xxxx. Xxxxxxxx by xxxx xxxxx xxxxxxx xxxx (xxxxxxx je xxxxxx xxxx 3 xx 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx jeden xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx mohou xxx xxxxxxx duplicitní kultury xxxx xxxxx xxxxxxxxxx xxxxxxx. Je-li použita xxxxx xxxxxxx, xxx xx xxx xxxxx xxxxxxxxxxx xxxxxx xxx, xxx xxx xxxxxxxx xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx kontrolní xxxxxxx (xxxxxxxx rozpouštědla).

Plynné xxxx xxxxxx xxxxx by xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, např. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx x četnosti xxxxxx

Xx xxxxx xxxxxxxxx xxxx xx buňky xxxxxxx x kultivují xx xxxxxx stanovení xxxxxxx x za xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (přežití) xxxx xxxxxxxxxxx celkového xxxxx xxxxxx xx xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx lokus má xxxxxxxxxx xxxxxxxxx časové xxxxxx, aby xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (HPRT x XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, TK xxxxxxx xxx xxx). Xxxxx xxxx kultivovány x xxxxx xx selekčním xxxxxxxx (xxxxxxxxxx xxxxxxx) x xxx něho (xxx xxxx) xx xxxxxx xxxxxxxxx počtu xxxxxxx x xxxxxxxxx xxxxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxx) xx započne xx xxxxx xxxx xxxxxxx xxxxxxxxx xx xxxxx xxx selekčního činidla.

Je-li xxxxxxxx látka xxxxxxxxx xx xxxxxxx L5178Y XX+/-, xxxx xx xxx xxxxxxxxx xxxxxxx xx jedné ze xxxxxxxxxx xxxxxx (x xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x xx xxxxxxxxxxx x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx podle xxxxxxxxx xxxxxxx. Je-li xxxxxxxx látka ve xxxxxxx X5178X TK+/- xxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxx xxxxx velikosti kolonií xxxxxxxxx xx negativních x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 XX+/- xxxx být xxxx xxxxxxxxx rozdělení kultury xxxxx velikosti kolonií.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx xxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxxx x xxxxxxxxx kultury. X xxxxxxx pozitivní xxxxxxxx xx zkoušku X5178X XX+/- xx kolonie xxxxxxxxx alespoň u xxxxx koncentrace zkoušené xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx za xxxxxxx xxxxxxxx malá kolonie — xxxxx kolonie. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx mutantů xxxxxxxxx velké xxxxxxx, xxx mutantů xxxxxxxxx xxxx xxxxxxx byla xxxxxxxx zkoumána (23, 24). Xx xxxxxxx XX+/- jsou xxxxxxx xxxxxxxxxxx za použití xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxx (velká) x xxxxxxx s xxxxxxx xxxxxx (xxxx) (25). X xxxxxxxxxx xxxxx, xxxxx utrpěly xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx xxxx xxxxxxxx, a xxxxx xxxx malé xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx ztrát xxxxxx xxxx xx xx karyotypické xxxxxxxxx xxxxxxxxxxxx aberace. Indukce xxxxxxx xxxxxxxxx xxxx xxxxxxx se xxxxxxx x xxxxxxxxxx látkami, xxxxx xxxxxxxx silné xxxxxxxxxxxx xxxxxxx (26). Xxxx závažně postižené xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxx jako xxxxxxxx xxxxx x xxxxx xxxxx xxxxxxx.

Xxxx xx xxx udáno xxxxxxx (xxxxxxxxx účinnost xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxxxxx xxxxxxx xx xxxx xxx vyjádřena xxxx xxxxx xxxxxxx x xxxxx přeživších xxxxx.

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Xxxx by xxxx xxx všechny xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx případ od xxxxxxx. Xxx, kde xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx považováno za xxxxx, xx třeba xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx rozšířit xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx zvážena x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, xxx pro xxxxxxxxx výsledky. K xxxxxxxxxx studie, xxxxx xx mohly být xxxxxxx, patří xxxxxxx xxxxxxxxxxx a xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx xxxxxxxx xxxxxxx x závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx jako pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx faktorem pro xxxxxxxxx xxxxxxx.

Xxxxxxxx látka, xxxxx výsledky xxxxxxxxx xxxx uvedená xxxxxxxx, xx v xxxxx xxxxxxx považuje xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x použitých kultivovaných xxxxxxx savců xxxxxx xxxxxx. Reprodukovatelná xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx xx velmi xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx xxxxxxx neindukuje x xxxxxxxxx kultivovaných xxxxxxx xxxxx xxxxxx mutace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- xxxxxxxx počet xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx buněčné xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxxx výběru koncentrací x počtu kultur, xxxxxx xxxx. údajů x cytotoxicitě a xxxxxx xxxxxxxxxxxx, xxxx-xx x xxxxxxxxx,

- složení xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- objem xxxxxxxx x xxxxxxx zkoušené xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx hustota xxxxx xxxxx expozice,

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

- xxxxxxxxx a xxxxxxxxx kontroly,

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

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx životaschopných x xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx srážení,

- xxxxx x xX a xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxx stanoveny,

- xxxxxxxx xxxxxxx, xxxx-xx xxxxxxxxxxx, xxxxxxx xxx negativní x xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx tvořící xxxx xxxxxxx xxxxxxxx X5178X XX+/-,

- podle xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

- xxxxxxxxx údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní kontrole x xxxxxxxxx, středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- četnost mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X., XxXxxxxx, X. M., XxXxxxxx, X. X., Xxxxxx, X. X. (xxx.) (1987), Xxxxxxx Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Cold Spring Xxxxxx Xxxxxxxxxx, Xxx Xxxx.

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

3) Liber, X. X., Xxxxxx, X. X. (1982), Xxxxxxxx Xxxxx xx the Xxxxxxxxx Kinase Xxxxx xx Diploid Human Xxxxxxxxxxxx, Xxxxxxxx Res. 94, 467-485.

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

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

6) Xxxxx, X. S., Xxxxxxxxxx, X., Xxxxx, X. X., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Xx. X. X., Xxxxxx, J., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Assays Xxxxxxx Xxxxx Xxxxxx. Report xx xxx Xxxxxxxxxxxxx Xxxxxxxx on Xxxxxxxxxxxxxxx xx Genotoxicity Xxxx Xxxxxxxxxx. Mutation Xxx. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, S. X., Xxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, D., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Mutation Xxx. 257, 147-204.

8) Xxxxx, D., XxXxxx, X., Xxxxxxx, X. X. X., Xxxxx, X., Xxxxxxxxx, X. X. (1983), Specific Xxxx Xxxxxxxxx xx X5178X Xxxxx in Xxxxxxx. X Report xx xxx X. X. Environmental Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 115, 225-251.

9) Li, A. X., Xxxxx, X. X., Xxxxxxx, R. X., Xxxxxx, X. X. (1988), X Xxxxxx and Analysis xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Xxxxxxxxx the Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: X Report xx Xxxxx III xx xxx X. X. Environmental Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, A. X., Carver, J. X., Choy, X. X., Xxxx, X. X., Gupta, X. X., Loveday, X. X., X'Νxxxx, X. X., Riddle, X. X., Stankowski, X. X. Xx., Xxxx, X. X. (1987), X Xxxxx xxx xxx Performance xx xxx Chinese Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Phosphoribosyl Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Mutatation Xxx., 189, 135-141.

11) Xxxxx, X. L., Yandell, X. X., Xxxxxx, X. X. (1989), X Comparison of Xxxxxxxx Induction xx xxx TK xxx XXXX Loci xx Xxxxx Lymphoblastoid Cells: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx xx an Xxxxxxxxxx Xxxxx of Xxxxxxxxx at the Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Res., 216, 9-17.

12) Xxxxxxxxxx, X. X. Xx., Xxxxxx, X. X., Hsie, X. W. (1986), Xxxxxxxxxxxx and Xxxxxxxxx Xxxxxxxx xx Xxxxx Xxxxxxxxxxxxxxxxx xxx ICR 191-Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxx Methanesulphonate xxx XXX 191 Xxxxxxx Mutation xx XX52 Cells, Xxxxxxxxxx Xxx., 160, 133-147.

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

14) Xxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxx, X. X. X., Xxxx, X., XxXxxxxx, X. X., Xxxxxxx S. X. (1989), Mammalian Xxxx Xxxx Xxxxxxxx Assays Xxxxx upon Colony Xxxxxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Kirkland, X. X., xx., Xxxxxxxxx Xxxxxxxxxx Press, 66-101.

15) Xxxxxxxxxxxx, A., Xxxxxxx, S., Xxxxx, X., Fiorio, X., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Induction xx 6-Thioguanine-Resistant Xxxxxxx xx X79 Chinese Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Dimethylnitrosamine, Xxxxxxxxxx Xxx. 46, 365-373.

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

17) Xxxxx, X., Johnson, X. X., Xxxxxxx, X. X. S., Xxxxxx A. X., Xxxxx X. X. X. (1979), Validation xxx Characterisation of xxx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxxxx Assay Xxxxxx, Xxxxx. Xxx. 59, 61-108.

18) Maron, D. X., Xxxx, B. X. (1983), Xxxxxxx Xxxxxxx xxx xxx Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Xxx. 113, 173-215.

19) Elliott, B. X., Combes, R. X., Xxxxxxx, X. X., Gatehouse, D. X., Xxxxxx, X. X., Xxxxxx, J. X., Wolf, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Xxxxxxx X9 xx: Xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Sawamura, X., Hara, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Biphenyls x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, X: Xx xxxxx Metabolic Xxxxxxxxxx in Mutagenesis Xxxxxxx, de Xxxxxx, X. X., Xxxxx, X. R., Xxxx, X. R., Xxxxxxx, X. M. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. F., Xxxxxx, X. C., XxXxxxx, X. X. (1982), XXX/XXXXX Mutation Xxxxx: Evaluation of Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. L., Schaich, X. X. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, New Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, X. X., Xxxxxx, J. X., Xx, X. X., Xxxxxx, X. L. (1983), Evaluation xx xx Exposure System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Xxxxxxxx Xxxxx, Environ. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. X., Moore, X. X., Broder, X. X., Burrell, X., Xxxxxx, J. X. (1990), Xxxxxxxxx Xxxxxxxxxx of Mutations xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Xxxxx xx Mouse Xxxxxxxx Xxxxx, Xxxx. Natl. Xxxx. Xxx. X. X. X, 87, 51-55.

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

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

26) Xxxxx, X. M., Xxxxx, X. L. (1990), Comparison of Xxxxxxxxxx Xxxxxxxxxx Xxxxxxxxx xxx Small Xxxxxx XX-Xxxxxxxxx Mutant Xxxxxxxxx xx L5178Y/TK+/- 3.7.2X Xxxxx Lymphoma Xxxxx, Xxxxxxxxxxx, 5, 609-614."


XXXXXXX 4X

"X.23 ZKOUŠKA XX XXXXXXXXXXXX ABERACE XX SPERMATOGONIÍCH SAVCŮ

1. XXXXXX

Xxxx metoda je xxxxxxxx metody XXXX XX 483 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx ve spermatogoniích xxxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx xx vivo xx xxxxxxxxxxxxx takové xxxxx, které způsobují xxxxxxxxxx xxxxxxxxxxxx aberace xx spermatogoniích xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx xxxxxxx: chromozomové x chromatidové. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxx xxxxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx xxxxxxx používána. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx jsou příčinou xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x člověka.

Touto xxxxxxxx se xxxxxxxxx xxxxxxxxxxxx xxxxx xx xxxxxxxxxxxxxxx a předpokládá xx xxxx, xx xxxx zkouška xxxxxxxx xxxxxxxxx xxxxxxx dědičných xxxxxx v xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx rutinně xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx in xxxx xx xxxxxxxx xxxxxxxxxxxx xxxxxxx při xxxxxx xxxxxxxxxxxxx. Jiné cílové xxxxx xxxxxx předmětem xxxx zkoušky.

Pro detekci xxxxxxx xxxxxxxxxxxxxx typu xx xxxxxxxxxxxxxxx by xxxx xxx — xxxxx xxx dojde xx ztrátě xxxx — vyšetřeno xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx po xxxxxxxx. Xxxxx xxxxxxxxx x exponovaných xxxxxxxxxxxxxxxxxx xxxxxxxxx buněk xxx xxxxxx xxxxxxxxxx chromozomovou xxxxxxxx aberací chromozomového xxxx v xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx stávají xxxxxxxxxxxx.

Xxxx zkouška xx xxxx je xxxxxxxx xxx xxxxxxxxx, zda xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxx x germinálních buňkách. Xxxxx je xxxx xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx xxx posouzení xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx spermatogonií s xxxxxx xxxxxxxxxx na xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxxxx xxxxxxx tedy xxxxxxxxxxx xxxxxxxxx odpověď xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X závislosti xx xxx xxxxxx xx xxxxxxxxx, mohou xxxx xxxxxx být xxxxx generace spermatogonií xxxxxxxxxx xxxxxxxxx krevnímu xxxxx x xxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxx Sertoliho xxxxx x xxxxxxx mezi xxxxxxx xxxxxx x xxxxxxx.

Xxxxxxxx existuje xxxxx x tom, že xx xxxxxxxx látka xxxx xxxxxxxxx metabolity xxxxxxxxxx do xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x opětného spojení xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx a xxxxxxx obou chromatid x xxxxxx xxxxx.

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx x x minimální xxxxxxxxx xxxxxxxxx.

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

Xxxxxxxxxxx : xxxxxxx haploidního xxxxx xxxxxxxxxxxxxx sad (x), jiný xxx xxxxxxxxx (xx. 3 x, 4 x xxx.).

Xxxxxxxxxx aberace : xxxxxxxxxxxxx pozorovatelné změny xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx se xxxx delece x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA XXXXXXXX METODY

Zvířata jsou xxxxxxx xxxxxxxx exponována xxxxxxxx xxxxx x xx vhodné době xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx a xxxx; lze xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxx xxxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx zahájení xxxxxx xx měla být xxxxxxxx v hmotnosti xxxxxx xxxxxxxxx a xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x části X, xxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx xxxx být xxxxxxxxxx tak, xxx xxx vliv jejich xxxxxx minimalizován. Xxxxxxx xx jednoznačně xxxxxxxxxxxx. Xxxx xxxxxxxxx studie xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx by měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx podávány xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx xxxxxxxxx hladinách xxxxx xxxxxxx xxxxxx x xxxx xx být xxxxxxxxx podezření, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx údaji x xxxxxx kompatibilitě. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Kontroly

Součástí xxxxxxx experimentu xx xxxx být xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly. X xxxxxxxx aplikace zkoušené xxxxx xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata ve xxxxxxxxx, v xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx spermatogoniích xx xxxx při xxxxxxxxxxx xxxxxxxx, x xxxxx xx předpokládá, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx pozadí.

Dávky pozitivní xxxxxxxx by xxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx způsobem xxx xxxxxxxx xxxxx x xxx byl odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxx xxx navíc xxxxx v úvahu xxxxxxx chemických xxxxx xx xxxxxx chemické xxxxx, jsou-li k xxxxxxxxx. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx 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 (monomer)

79–06–1

201–173–7

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

51–18–3

200–083–5

V xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx negativní xxxxxxxx, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx xxxxxxxxxx stejný xxxxxx xxxx exponované xxxxxxx, pokud nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx xxxx zahrnovat xxxxxxx xxx analyzovatelných xxxxx.

1.5.2 Xxxx expozice

Zkoušené xxxxx xx xxxx xxx xxxxx možno xxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxx (xx. při xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx dvou xxxxxxx, xxx. dvě xxxxx x xxx xxx x rozmezí xx xxxx než xxxxxxxx xxxxx, aby xxxx xxxxxxxxx podávání xxxxxxx objemů materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx zdůvodněny.

Ve skupině x nejvyšší xxxxxx xx xxxx xxx xx expozici xxxxxxxxx xxx xxxxxx. Poněvadž xxxxxxxx xxxxxxxxx xxxxx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx xxxxx xxxxx xxxxx x jeden xxxxxxxx xxxxx přibližně 24 x 48 xxxxx xx xxxxxxxx. X xxxxxxx xxxx xxx nejvyšší dávky xx xxx být xxxxx xxxxxxxx xx 24 hodin xxxx xx takové xxxx xxxxxxxx, která odpovídá 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx xxxx xxxxx jiná xxxxxxxxx xxxx xxx xxxxxxx xxxxxx (6).

Navíc xxxxx xxx xxxxxx xxxxxxxxx xxxx x xxxx xxxx. Xxxxxxxxx v xxxxxxx chemických xxxxx, xxxxx mohou xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) xxxxxxxxxx nebo xxxxx xxxxxxxxxx X-xxxxxxxxx účinky, xxxx xxx xxxxxxxxx xxxxxxxx odběr (1).

Xxxxxxxx xxxxx opakované expozice xxxx xxx xxxxxx xxxxxx xx xxxxxxx. X případě xxxxx x xxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx délky xxxxx) xx poslední xxxxxxxx. Xxxxx potřeby xxxxx být prováděny xxxxx xxxxxx x xxxx době.

Před xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx se xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X xxxx xx tato doba xxxxxxxxx 3 — 5 hodin; x xxxxxx xxxxxxxx xx xxxx doba xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx a xxxxxx x za xxxxxxxx xxxxxx expozice, xxxxx xx xxxxxxx x xxxxxx xxxxxx (7). X xxxxxxx toxicity xx pro xxxxx xxxxx xxxxxxx tři xxxxxx dávky. Xxxx xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx toxicitou, případně xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, xx xx xxxxx xxxxx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x letalitě.

Látky se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. hormony x xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx může xxx xxxx xxxxxxxxxx xxxx xxxxx vyvolávající xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx xxxxxxxx (např. xxxxxxx počtu xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx meiotické xxxxxxxx; xxxx snížení xx xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx dvou dávkách x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx mají podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx dávky xx xxxxxxxxx. Očekávaná expozice xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx zkoušce xxxxx xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx způsoby xxxxxxxx xxxx xxxxxxxxxx, jsou-li xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který může xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx testovacího xxxxxxx. Xxxxx by neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx zesílené xxxxxx, xx xxxx být xxxxxxxxxxx zkoušeného xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech úrovních xxxxx.

1.5.6 Xxxxxxxx preparátů xx analýzu xxxxxxxxxx

Xxxxx xx xxxxxxxx xx x xxxxxxx xxxx xxxx xxxxxx získá xxxxxxx xxxxxxxx, hypotonizuje xx x fixuje. Xxxx xx xxxxxx xx podložní sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx zvířete xx xxxx být xxxxxxxxxxx xxxxxxx 100 xxxxx v xxxxx xxxxxxxxxxxx metafázi (xx. xxxxxxxxx 500 metafází xx xxxxxxx). Xxxxx xxxxx xxx snížit, xx-xx pozorován xxxxx xxxxx aberací. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by měly xxx xxxx mikroskopickou xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx při xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx x xxxxx xxxxxxxx, xxxx xx xxxxxxxxxxx buňky xxxxxxxxx centromery v xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx každé xxxxx xx měl xxx xxxxxxxxxx xxxxx xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x počet xxxxxxxxxxxxxx xxxxxxx na xxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx xxxxxx se xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, měl xx xxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx u xxxxx xxxxxxxxxxxx zvířat x xxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx x mitose xxxxxxxx k xxxxx x xxxxx xxxxxxxxx xxxxxxxx, x xx x xxxxxxxx xxxxxx 100 xxxxxxxx se xxxxx na jedno xxxxx. Xxxxx je xxxxxxxxx pouze mitosa, xxxxxxx x 1000 xxxxxxx xx xxxxx xx xxx být xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxx xxxx jasný xxxxxx xxxxx buněk x xxxxxxxxx pro xxxxxxx x určitou dávkou x x xxxxxxxx xxxxxxxx odběru. Nejdříve xx měla xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx zkoušky mohou xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx jediným určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx jasně pozitivní xxxx negativní xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez ohledu xx to, kolikrát xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx zkoušky na xxxxxxxxxxxx aberace ve xxxxxxxxxxxxxxx savců in xxxx znamenají, že xxxxxxxx xxxxx xxxxxxxx x germinálních buňkách xxxxxxxxxxx druhu strukturní xxxxxxxxxxxx aberace. Negativní xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxx buňkách xxxxxxxxxxx druhu chromozomové xxxxxxx.

Xxxx by xxx xxxxxxxxxxx pravděpodobnost, s xxxxx se xxxxxxxx xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx xx xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx musí obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Testovací xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet x xxxxx xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx zkoušky, xxxxxx xxxxxxx tělesné hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxx ze studie xxx zjištění xxxxxxx, xxxxx xxxx provedena,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- údaje o xxxxxxxx zkoušené látky,

- xxxxx o podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxx usmrcení,

- případně xxxxxxxx mezi koncentrací xxxxxxxx látky v xxxxxx xxxx vodě (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx tělesné xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx xxxxxx x vody,

- xxxxxxxx xxxxx xxxxxxx expozice x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk na xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky toxicity,

- xxxxxxxxx xxxxx,

- xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx k xxxxx x druhé metafázi xxxxxx,

- typ a xxxxx xxxxxxx uvedený xxxxxxxxxx pro xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx ve skupině,

- xxxxx buněk s xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx o xxxxxxxxx xxxxxxxx x rozpětími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx odchylkami,

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx,

- změny xxxxxxx, xxxxx byly xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. D., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Xxxxxxxxxxxxx of Xxxxxxxx Xxxxxxxx Xxxxxxx xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Genetic Xxxxxxxxxx of Environmental Xxxxxxxxx, Xxxx B: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Lambert, B., Xxxxxxxxx, X. (xxx) Xxxx, Xxx Xxxx, 477-484.

2) Xxxxx, I. X., (1984), Xxxxxxxxxxx xxxxx in Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, (xx.) X. Venitt, X. M. Parry, XXX Xxxxx, Oxford, Xxxxxxxxxx XX, 275-306.

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

4) Richold, X., Xxxxx, J., Xxxxxxxx, A., Xxxxxxxxx, X. X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Part X xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 115-141.

5) Xxxxxxxx, X., Xxxxxxx, X. (1978), X Xxx Xxxxxx for Xxxxxxxxxxx of Mammalian Xxxxxxxxxxxxxx Chromozomes, Xxxxxxxxxx Xxx., 52, 207-209.

6) Xxxxx, X. X., Xxxxxx X. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx N. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Report xx xxx Xxxxxxx Xxxxx xx Mammalian Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, R. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxx, J., Esdaile, X. J., Gatehouse, X. X., Hodson-Walker, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, M. (1992), Xxxxxx of Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. P., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, X., Richold, X., Papworth, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Kirkland (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx for Mutagenicity Xxxxxxx, Report, Xxxx XXX. Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 486 — Zkouška xx xxxxxxxxxxxx syntézu XXX (XXX) x xxxxxxxxx buňkách xxxxx xx vivo (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx syntézu DNA (XXX) x xxxxxxxxx xxxxxxx savců xx xxxx xx xxxxxxxxxxxxx xxxxxxxx xxxxx, které xxxxxxxx reparace XXX x jaterních xxxxxxx xxxxxxxxxxxx zvířat (1, 2, 3, 4).

Tato xxxxxxx xx xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx účinků xxxxxxxxxx xxxxx v xxxxxxx. Xxxxxxxxxxx jev xx xxxxxxxxxx xxxxxxxxx XXX x následné xxxxxxxx x jaterních buňkách. Xxxxx jsou obvykle xxxxxxx místem, xxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Jsou tedy xxxxxxx xxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx XXX xx xxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, xx xx xxxxxxxx látka xxxxxxxxx xx xxxxxx tkáně, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (UDS) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx značených xxxxxxxxxx xx buněk, které xxxxxxxx xxxxxxxxxx syntézou XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx je xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx thymidinu xxxxxxxxx xxxxxxx (3H-TdR). Xxx zkoušky xx XXX in xxxx xx xxxxxxxxxx xxxxxxxxx xxxxx potkana. Xxxx xxxxx xxx xxxxx xxxxx xxx rovněž xxxxxxx, nejsou xxxx xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX xxxxxx xx xxxxx xxxx XXX vyštěpených a xxxxxxxxxxx x xxxxx xxxxxxxxx. Xxxxxxx xx XXX xx tedy xxxxxx xxxxxxx xxx xxxxxxx dlouhých xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("short-patch xxxxxx") (xxxxx xx xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx x xxxxxx menší citlivostí. Xxxxx může xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, chybné xxxxxxxx xxxx chybné xxxxxxxxx xxxx XXX xxxxx x mutagenním xxxxxxxxx. Rozsah xxxxxxxx XXX xxxxxxxxxxx žádnou xxxxxxxxx x věrnosti xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx reaguje x XXX, ale xxxxxxxxx XXX není xxxxxxxx xxxxxxxxxxx reparací. Xxxxxxxxxx xxxxxxxxxxxx informací, které xxxx zkouška xxxxxxxxx x xxxxxxxxx xxxxxxxx, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx xx xxxxxxxxxx x xxxxx xxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Opravované xxxxx : čistý xxxxx xxx odpovídajících xxxxxxxx xxxxxx (NNG), xxxxx xxx předvolená xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zkoušku.

Čistý xxxxx xxx odpovídajících buněčným xxxxxx (NNG) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx xxxxxxx na XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx počtu xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) xxxxxxxxxxxxxx xxxxxx xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): NNG = XX — CG. Xxxxxxx XXX xx xxxxxxx xxx xxxxxxxxxx xxxxx, poté xxxxxxxx xxx xxxxx x xxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx xxxxxxx XXX (UDS) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx úseku XXX xxxxxxxxxxxx region x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx na XXX x jaterních buňkách xxxxx xx xxxx xxxxxxxx xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x odstranění xxxxx XXX xxxxxxxxxxxx region x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx činiteli. Xxxxxxx xx obvykle xxxxxxxx xx xxxxxxxxxxx 3X-XxX xx XXX xxxxxxxxx xxxxx, xxx je xxxx četnost xxxxx x X-xxxx buněčného xxxxx. Xxxxxxxxxxx 3X-XxX xx obvykle xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx xxxx tak xxxxxxx xx xxxx X-xxxx buněk xxxx xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 POPIS METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxx xxxxx. Měly xx být xxxxxxx xxxxx používané xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx minimální x neměla by xxxxxxxxx ± 20 % střední xxxxxxx xxxxxxxxx xxx obě xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx obecné xxxxxxxx podle xxxxxxxx xxxxx x xxxxx X, xxxxxxx xx xxxx být xxxxxxxx xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx pohlavně xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx xxxxxxxx. Xxxxx xx měly být xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují x před xxxxxxxxx xxxxxx se xxxxxxx x xxxxxxxxxxxxx podmínkách xxxxxxx pět dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx látky xx měly xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx zředěny. Xxxx by být xxxxxxx čerstvě připravené xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx xxxxxxxxx xxxxxxxx xxxxx toxické xxxxxx a mělo xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou látkou. Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxxxxx zvážit použití xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxx xxxxxxxxx prováděné xxxxx xxxxxxxxxxx xx měly xxx souběžné pozitivní x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx měly xxx xxxxx, x nichž xx xxxxx, xx xxxxxx podávání x xxxxxxxxxxx xxxxxxxxxxx koncentracích xxxx x nárůstu XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Xxxxx xxxxx xxx xxxxxxx xxx, xxx byl účinek xxxxxxxx, xxx xxx xxx odečtu nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 xx 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx xxxx xxxxxx (12 až 16 x)

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

53–96–3

200–188–6

Xxxxx xxx xxxxxxx také xxxx xxxxx xxx xxxxxxxxx kontrolu. Xx xxxxxxxxx, xxx byla xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxx xxxxx způsobem, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Měl by xxx použit xxxxxxxxxx xxxxx xxxxxx, xxx xxxx xxxxxxxxxx přirozené xxxxxxxxxx xxxxxxxx odpovědi xx xxxxxxx. Xxxxx xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx jsou xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx xxx xxxxxxxxx x pozitivní xxxxxxxxx xxxxxxx nezbytné xxxxx xxxxx až xxx xxxxxxx.

Xxxxxxxx jsou x době xxxxxx x dispozici údaje xx xxxxxx xx xxxxxxx xxxxxx x xx použití xxxxxxxx xxxxxxx expozice, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx provedena xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xxxx zpravidla xxxxxxxx xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx normálních xxxxxxxx xx xxxxxxxxx xxxxxxx dvě xxxxxx xxxxx. Nejvyšší dávka xx definována xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx toxicity, xx xxxxx dávky xx xxxxx xxxxx xxxxxxxxx xxx stejném režimu xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx by xxxx xxx zpravidla 50 % až 25 % xxxxx xxxxx.

Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. hormony a xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Provádí-li xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx údajů xxxxxx pro xxxxxxxx xxxxxxx, xxxx by xxx provedena xx xxxxxx laboratoři, xx xxxxxxx druhem, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx xx xxxxxxx x xxxxxx xxxxxx.

Xxxxxxxx xxxxx může být xxxxxxxxxx xxxx jako xxxxx vyvolávající známky xxxxxxxx x játrech (xxxx. xxxxxxxxxx jádra).

1.5.4 Xxxxxxx zkouška

Jestliže zkouška x jednou dávkou x alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx jednorázově xxxx xx dvou xxxxxxx x xxxxxx xxx xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx o látkách, xxxxx mají xxxxxxxx xxxxxxxxx, očekávána xxxxxxxxxxxx, xxxxxx xxx úplná xxxxxx xxxxxxxx. Očekávaná xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x limitní zkoušce xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx intubační xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxx, xxx-xx je xxxxxxxxx. Xxxxxxxx xxxxxxxxxxxxxxxxx se xxxx nedoporučuje, xxxxx xx xxxxx xxxxx xxx exponována xxxxxxxx xxxxx xxxxx x xxxxxx prostřednictvím xxxxxxxxx xxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších objemů, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x žíravé xxxxx, které obvykle xxx vyšších koncentracích xxxxxxxx zesílené xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx xxxxx se xxxxxxxxxx x xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx xxxxxx xxxxx. Xxxxxxxxxx dřívější xxxxxxxx xxxxxx (xxxxxx dvě xx xxxxx hodiny xx xxxxxxxx) xx xxxxxxxx, xxxx-xx po 12 až 16 xxxxxxxx xxxxx pozitivní xxxxxxx. Xxxxx však xxx xxxxxxx jiné xxxx xxxxxx, xxxx-xx xxxxxxxxxx na základě xxxxxxxxxxxxxxxxx údajů.

Krátkodobé kultury xxxxxxxxx xxxxx xxxxx xx zpravidla zakládají xxxxxxx xxxxx kolagenasou xx xxxx a xxxxxx xx, aby xx xxxxxxx disociované xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx xx xxxx vykazovat xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Stanovení XXX

Xxxxxxx xxxxxxxxx jaterní xxxxx xxxxx xx xxxxxxx xxxxxxx xxxx, např. xxx až xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx xxxxxxxxx xxxx xx xxxx xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx xxxx mohou xxx inkubovány x xxxxxx xxxxxxxxxxx přebytek xxxxxxxxxxx xxxxxxxxx, aby xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx se poté xxxxxxx, fixují x xxxxxx. Při xxxxx xxxxxxxxx xxxx nemusí xxx xxxxxxx radioaktivity xxxxxxxx. Xxxxxxxxx xx xxxxxx do autoradiografické xxxxxx, exponují se x xxxxx (xxxx. x xxxxxx 7 xx 14 dnů), xxxxxxxx xx, obarví x xxxxxxxxx xx xxxxxxxxxx xxxx xxxxxxx. X každého xxxxxxx xx připraví dva xx xxx preparáty.

1.5.8 Xxxxxxx

Xxxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxx počet xxxxxxxxxxxx normálních xxxxx, xxx xxxx hodnocení XXX výpovědní xxxxxxx. Xxxxxxxxx se xxx xxxxxxxxxxx xxxxxxxxxx na xxxxxx xxxxxx xxxxxxxxxxxx (xxxx. xx xxxxxxx, xxxxxxxx úroveň xxxxxxx xxxxxxxxxxxxx xxxxxxxx).

Xxxx xxxxxxxxx xxx xx měly xxx preparáty kódovány. Xxxxxxxxx xx vyšetřuje 100 xxxxx na xxxxx xxxxx alespoň xx xxxx xxxxxxxxx; xxxxxxxxx méně xxx 100 xxxxx/xxxxx by xxxx xxx xxxxxxxxxx. Xxx počítání zrn xx xxxxx x X-xxxx xxxxxxxxxxx, xxx xxxxx xxxxx v X-xxxx může být xxxxxxxxxx.

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

Xxxxx xxxxx xx stanoví x xxxxx zrn odpovídajících xxxxxxxx xxxxŭx (ng) x x xxŭxxxxxxx xxxxx zrn x xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx cg se xxxxxxx buď xxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx xxŭxxxxx xxxxxxx xxxx až tří xxxxxxx vybraných oblastí x blízkosti xxxxxxxxx xxxxxxxxx xxxxx. po xxxxxxxxxxxxx xxXxxxxxxx mohou xxx použity x xxxx xxxxxxx xxxxxxxxx xxxxx buněk (xxxx. xxxxxxxx celých xxxxx) (6).

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx xx být xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx x xxxxxxx. Xxxxx xx xxxx být dále xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX xx xxxxxxx XX xx xxx xxx xxxxxxxx xxx xxxxxx buňku, xxx xxxxx xxxxx a xxx xxxxxx xxxxx x xxx xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrům (NNG). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" xxxxx, měla xx xxx xxxxxxxx xxx definování "xxxxxxxxxxxx" xxxxx odůvodněna x xxxxxxxx na dosavadních xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx statistickými xxxxxxxx. Xxxx-xx xxx xxxxxxx, xxxx by xxx statistické testy xxxxxxx x xxxxxxxxxx xxxx xxxxxxxxxx xxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxxx příklady kritérií xxx xxxxxxxxx nebo xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX xxxx xxx xxxxxxxx úrovní, xxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx NNG xxxx xx dosavadní xxxxxxx xxxxxxx xxxx pod xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx vyšší xxx xxxxxxx pro xxxxxxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx. měly xx být xxxxx x úvahu xxxxxxxxx, xxxx xxxx variabilita xxxxxx, xxxxx xxxxx x xxxxxxxx a xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxxxxx xxx jediným určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx jasně xxxxxxxxx xxxx negativní výsledky, x ojedinělých případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx XXX v xxxxxxxxx xxxxxxx xxxxx xx xxxx znamenají, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxx buňkách xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx opravit neplánovanou xxxxxxxx XXX xx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje xxxxxxxxx XXX, xxxxx xxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx xxx diskutována xxxxxxxxxxxxxxx, x jakou xx xxxxxxxx látka xxxxxxx xx xxxxxxxx xxxxx xxxx. do xxxxxx xxxxx (xxxx. xxxxxxxxx toxicita).

3. ZPRÁVY

PROTOKOL X ZKOUŠCE

Protokol o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx zkoušky, xxxxxx rozpětí tělesné xxxxxxxxx, střední xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- popřípadě xxxxxx ověření, xxx xx xxxxxxxx xxxxx xxxxxxx do xxxxxxxx xxxxx xxxx xx xxxxxx tkáně,

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

- podrobné xxxxx x xxxxxxx xxxxxx x vody,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxx,

- použitá xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx a počet xxxxxxxxxxx buněk,

- kritéria xxxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx hodnoty xxxxx xxx odpovídajících xxxxxxxx xxxxxx a počtu xxx xxxxxxxxxxxxxx cytoplasmě, x xxxxx xxxxx xxx, jednotlivě pro xxxxxxxxx, xxxxxxx a xxxxxxx,

- podle xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- xxxxxxxx statistické xxxxxxxxx,

- xxxxxx toxicity,

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

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

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

- xxxxx xxxxx x X-xxxx, xx-xx xxxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. Lefevre, X. X., Burlinson, X., Penman, X. X. (1985), An Xxxxxxxxxx of the Xx xxxx Rat. Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Butterworth, X. E., Ashby, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1987), X Xxxxxxxx xxx Xxxxx for xxx Xx vivo Xxx Xxxxxxxxxx DNA Repair Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.

3) Xxxxxxxx, X. C., Xxxxxx, X., Ashby, X., Xxxxxxx, X. X., Xxxxxxxxx, X., Xxxxxxx, X. X., Dean, X. W., Mitchell, X. xx G. (1993), Xx vivo Xxx Xxxxx UDS Xxxxx, xx: Xxxxxxxx X. J., Xxx X., (eds), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, S., Xxxx, X. X., Andrac, X., Xxxxxxxxx. X., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Furihata, X., Xxxxxxx, X., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx XXX Xxxxx Xx xxxxx xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

5) Xxxxx, X., Xxxxxxx, B., Efstathiou, X., Hechenberger-Freudl, X. (1993), Xxxxxxxxxx xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Viability xxx the Xxxxxxxxxx xx Freshly Xxxxxxxx Xxx Xxxxxxxxxxx Used xxx xxx Xx xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Xxx., 291, 21-27.

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


PŘÍLOHA 5

XXXXXX XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX NEBEZPEČNÝCH LÁTEK X PŘÍPRAVKŮ

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


XXXXXXX 6

"

XXXXXXX IX

ČÁST X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx dětmi

Kromě xxxxxxxxxx xx. 22 xxxx. 1 xxxx. x) xxxx xxxxxxxx, xxxx xxx obaly x xxxxxxxxx objemu obsahující xxxxx, x xxxxx xx spojeno xxxxxx xxx xxxxxxxxxx (Xn; X 65) x xxxxx xxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx směrnice, x výjimkou látek xxxxxxxxx xx trh xx xxxxx xxxxxxxx xxxx v xxxxxxxx xxxxxxxxxx aerosolovým xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx otevření xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx splňovat xxxxxxxxx xxxxx XXX 8317 (xxxxxx ze xxx 1. července 1989) "Xxxxx xxxxxx dětem — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx obaly x metody xxxxxx xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx musí splňovat xxxxxxxxx normy XXX XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx dětem — Xxxxxxxxx a xxxxxxxx xxxxxxx xxx opakovaně xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Xxxxxxxxx výborem xxx normalizaci (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x xxxx uvedenými xxxxxxx xxxxx osvědčovat xxxxx laboratoře, které xxxxxxx xxxxxxxx normy xxxx EN 45000.

2. Xxxxxxxxxx případy

Je-li xxxxxx, xx xxxx je xxxxxxxxxx xxxxxxxx xxx xxxx, neboť xx xxxxxxx xxxxxx k xxxxxx bez xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx existují xxxxxxxxx xxxxxx x xxxxxxxx x xxxxxxxxxxx uzávěru xxx xxxx, xxxx xxxxxxxxxxxx xxxxx požadovat, xxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx xx xxx předložila xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx buď

- xxx xxxxxxx je takový, xx xxx xxxx xxxxxxxx xxxxxxx xxxxx xxxx uvedených norem XXX a XXX,

xxxx

- xx uzávěr xxx xxxxxxx x xxx xxxxxxx vyhovujícím xxxxx xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx se xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx xxxxxxxxxxx xxx xxxxxxxxxx xxxxxxxx xxxx xxx v xxxxxxx x normou XX XXX 11683 (xxxxxx x xxxx 1997) "Xxxxx — Xxxxxxxxxx výstrahy xxxx xxxxxxxxxx — Xxxxxxxxx".

"