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Směrnice Xxxxxx 2000/32/XX

xx xxx 19. xxxxxx 2000,

xxxxxx xx po xxxxxxx šesté xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxx Xxxx 67/548/XXX x xxxxxxxxxx xxxxxxxx a xxxxxxxxx předpisů týkajících xx klasifikace, xxxxxx x xxxxxxxxxx nebezpečných xxxxx [1]

(Xxxx x xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx o xxxxxxxx Xxxxxxxxxx společenství,

s xxxxxxx na xxxxxxxx Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 x sbližování xxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx xxxxxxxxxxxx látek [2], naposledy xxxxxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Xxxx 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx x xxxxx důvodům:

(1) Xxxxxxx X směrnice 67/548/XXX xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxx společně x xxxxxxxxxx xxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Současné xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, že xx měl být xxxxxx xxxxxxxxxxxx látek x uvedené xxxxxxx xxxxxxxxxxx. Xxxxxxx jazykové xxxxx směrnice vyžadují xxxxxx xxxxxxxx oddílů xxxxxxxxx a xxxxxxx X v příloze X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx xxx xxxxxxxxxxx xxxxxx zvláštních xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x přípravky. Xxxxxxx IV xxxxxxxx 67/548/XXX xxxxxxxx seznam xxx x bezpečnostními xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx látek a xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/EHS xxxxxxxx xxxxx xx xxxxxxxxxxx x x xxxxxxxxxx xxxxxxxxxxxx xxxxx a xxxxxxxxx. Xxxxxxx jazykové xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, IV x XX.

(3) V xxxxxxx X směrnice 67/548/XXX se stanoví xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx vlastností, xxxxxxxx x xxxxxxxxxxx látek x xxxxxxxxx. Xx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxx xxxxxxxxxxx xxxxxxx.

(4) Xxxxxxx IX směrnice 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx. Tyto xxxxxxxx xx měly xxx xxxxxxxxxxxx x aktualizovány. Xx xxxxxxxx rozšířit xxxxxx, xxx xx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxxxx.

(5) Xxxxxxxx této xxxxxxxx xxxx v xxxxxxx xx xxxxxxxxxxx Xxxxxx xxx přizpůsobení technickému xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx překážek xxxxxxx xx xxxxx xxxxxxxxxxxx látek x xxxxxxxxx,

XXXXXXX XXXX SMĚRNICI:

Článek 1

Směrnice 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx X xx xxxx xxxxx:

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

b) xxxxxxxxxxxx xxxxx v xxxxxxx X xx xxxxxxxxx řádky x xxxxxxx 1X xxxx xxxxxxxx;

x) odpovídající položky xx xxxxxxxxx xxxxxxxxx x xxxxxxx 1X xxxx směrnice;

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

2. Xxxxxxxxxxxx věta x příloze XXX xx xxxxxxxxx standardní xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx v příloze 2 xxxx xxxxxxxx.

3. Xxxxxxx XX se xxxx takto:

a) xxxxxxxxxxxx xxxxxx x příloze XX se nahrazují xxxxxxxxxxxx pokyny pro xxxxxxxx xxxxxxxxx x xxxxxxx 3X této xxxxxxxx;

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

4. Xxxx X xxxxxxx X se xxxx takto:

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

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

x) xxxxxxxx B.12 xx xxxxxxxxx textem x xxxxxxx 4C xxxx xxxxxxxx;

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

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

x) xxxxxxxx X.23 xx xxxxxxxxx textem v xxxxxxx 4X této xxxxxxxx. Název xxxxxxxx X.23 xx xxxxxxxxxxx xx xxxx xxxxxxxxxxxxx xxxxxxxx;

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

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

6. Xxxxxxxxxxxx xxxxx x xxxxxxx XX se xxxxxxxxx xxxxx x xxxxxxx 5 xxxx xxxxxxxx.

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

Článek 2

1. Členské xxxxx xxxxxx x xxxxxxxx xxxxxx a xxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxxx xxxxxxx x touto xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x xxxx xxxxxxx Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx xx xxxx směrnici nebo xxxx xxxxxx xxxxx xxx xxxxxx při xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx členské xxxxx.

2. Xxxxxxx xxxxx xxxxx Xxxxxx xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, které xxxxxxx x xxxxxxx xxxxxxxxxx xxxx směrnice, x xxxxxxxxxx xxxxxxx mezi xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Tato xxxxxxxx xxxxxxxx v platnost xxxxxx dnem xx xxxxxxxxx x Xxxxxxx xxxxxxxx Evropských xxxxxxxxxxxx.

Článek 4

Xxxx směrnice xx xxxxxx členským xxxxxx.

X Xxxxxxx dne 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise


[1] Xxxxxxx xx xxxxxxxxxxxx xx dvacáté xxxxx.

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

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


XXXXXXX 1X

XXXXXXXXX X XXXXXXX I

Vysvětlení xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


XXXXXXX 1X

"XXXXXXX X

X

Xxxxxx

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

18

Xx

Xxxxx

Xxxxx

Xxxxx

Αργό

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"


PŘÍLOHA 1C

Indexové xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx k látkám

Číslo XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–011–00–7

xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. xxx. 3; X40 Xn; X22 X; R50

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) natrium-N-methyldithiokarbamát

205–293–0

137–42–8

Xn; X22 X31 X; X34 X43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

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

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

006–016–00–4

xxxxxxxx (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

204–043–8

114–26–1

X; X25 X; X50–53

X; X R: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; R26/28 X; X24 N; X50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 X; X50–53

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

006–019–00–0

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

218–961–1

2303–16–4

Xxxx. kat. 3; X40 Xx; X22 N; X50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; X22 X43 X; X50–53

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

006–023–00–2

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

217–991–2

2032–65–7

X; X25 X; X50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; R22 Xx; X38 N; X51–53

Xx; X X: 22–38–51/53 X: (2-)13-61

006–026–00–9

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

216–353–0

1563–66–2

X+; X26/28 X; X50–53

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

006–028–00-X

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

213–546–1

973–21–7

X; X25 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; R25 X; X51–53

X; N R: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

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

243–433–2

19937–59–8

X; X50–53

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

006–034–00–2

xxxxxxx (XXX) X-xxxxxx-X-xxxxx-X-xxxxxxxxxxxxxxxxx

214–215–4

1114–71–2

Xx; 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 xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx

245–430–1

23103–98–2

X; 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; R25 N; X50–53

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

006–038–00–4

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

X

202–388–9

95–06–7

Xxxx. kat. 2; X45 Xx; X22 X; 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; R22–48/22 X43 X; R50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; R40 Xx; X22 X; X50–53

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

006–043–00–1

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

140–41–0

Xx; X36/38 Xxxx. xxx. 3; X40 X; X50–53

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

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 N; R50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; R23/25 Xx; X21 X; X50–53

X; 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 x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

8065–36–9

X; X24/25 X; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xn; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–050–00–X

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

4482–55–7

Xx; R38 X; X50–53

Xx; X X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 N; R50–53

Xn; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xn; X21 X; X50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)24-61

006–060–00–4

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

226–066–2

5259–88–1

Xx; R22 X52–53

Xx X:22–52/53 S: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Muta. xxx. 3; 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 S: (2-)36/37–60–61

006–088–00–7

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

82560–54–1

X; X23/25 N; X50–53

X; X 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 Karc. kat. 2; X45 T; 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-xxxxxxxxxxxxxxxx

X

540–73–8

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

X; X R: 45–23/24/25–51/53 X: 53–45–61

C ≥ 25 %: X; R45–23/24/25 3 % &xx; C &xx; 25 %: X; X45–20/21/22 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+; C X: 26/27/28–35 S: (1/2-)7/9–26–36/37–45

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

015–039–00–9

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

201–676–1

86–50–0

X+; X26/28 X; X24 R43 X; R50–53

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

015–048–00–8

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

200–231–9

55–38–9

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

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

015–056–00–1

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

220–147–6

2642–71–9

T+; X28 X; X24 N; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xx; X21 N; R50–53

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

016–013–00-X

xxxxxxx xxxxxxx

234–129–0

10545–99–0

X14 X; X34 X; X50

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

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

016–014–00–5

xxxxxxx xxxxxxxx

13451–08–6

X14 X; X34 X; X50

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

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

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 X+; R26 T; X25 C; X34 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+; X45–22–26–34–43 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 < 3 %: X; X45–23–43 0,1 % ≤ X &xx; 1 %: X; R45–20 0,01 % ≤ X &xx; 0,1 %:X; R45

016–024–00-X

dimexano (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

016–071–00–6

3-amino-6,13-dichlor-10-[(3-{[4-chlor-6-(2-sulfonatoanilino)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx trisodný

410–130–3

136248–03–8

R43

Xi X: 43 X: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 X; X34

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

X ≥ 10 %: X; X34 5 % ≤ X < 10 %: Xi; X36/37/38

030–004–00–8

xxxxxxxxxxxxx [1] diethylzinek [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 C; X34 N; X50–53

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

050–002–00–0

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

236–049–1

13121–70–5

Xx; X20/21/22 N; X50–53

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

050–012–00–5

tetracyklohexylstannan [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] 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; R20/21/22 X; X50–53

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

X ≥ 1 %: Xx; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

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

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

082–009–00–X

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

215–693–7

1344–37–2

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

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

1

082–010–00–5

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

235–759–9

12656–85–8

Karc. kat. 3; X40 Repr. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 X; X50–53

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

1

601–024–00-X

kumen [1] xxxxxxxxxxxx [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

X10 Xx; R65 Xi; X37 X; X51–53

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

4

601–032–00–3

xxxxx[x]xxxxx benzo[def]chrysen

200–028–5

50–32–8

Karc. xxx.2; R45 Muta. xxx. 2; X46 Xxxx. xxx. 2; X60–61 X; R50–53

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

602–054–00–6

3-jodprop-1-en xxxxxxxxxx

209–130–4

556–56–9

X10 X; R34

C X: 10-34 X: (1/2-)7–26–45

603–076–00–9

xxx-2-xx-1,4-xxxx

203–788–6

110–65–6

X; X23/25 Xn; R21–48/22 X; X34

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

X ≥ 50 %: X; R21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; R21–23/25–36/38–48/22 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; R22 Xi; X36

X; Xx X: 8–22–36 X: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xx; X20 X; X51–53

Xx; X X: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 X52–53

Xx X:36–52/53 S: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx isopropanol

200–661–7

67–63–0

F; X11 Xx; X36 R67

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

604–020–00–6

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

201–993–5

90–43–7

Xx; X36/37/38 X; R50

Xi; X X: 36/37/38–50 X: (2-)22-61

604–021–00–1

2-xxxxxxxxxx, sodná xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx xxxxx 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-bis(4-hydroxyfenyl)-4-methylpentan

401–720–1

6807–17–6

Repr. xxx. 2; X60 Xx; X36 N; X50–53

X; N X: 60–36–50/53 S: 53–45–60–61

604–041–00–0

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

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xx; X22 Xx; X38–41 N; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xx; X36 X43

Xx X: 36-43 S: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; R22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % ethandial… %

X

203–474–9

107–22–2

Xxxx. xxx. 3; X40 Xn; R20 Xx; X36/38 R43

Xn X: 20–36/38–40–43 X: (2-)36/37

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

606–016–00-X

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

201–462–8

83–26–1

X; R25–48/25 X; X50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xx; X22 Xx; X36/38 X; X50–53

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

606–019–00–6

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

205–601–3

143–50–0

Xxxx. xxx. 3; X40 X; X24/25 X; R50–53

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

606–034–00–8

xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 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 (ISO) 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 S: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Xxxx. xxx. 3; X62 Xx; X20/21/22–48/22 Xi; 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

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

256–103–8

43121–43–3

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xx; R36 X; X50–53

Xx; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xi; X41 R52–53

Xn; X X: 22–41–52/53 X: (2-)26-61

607–057–00–6

xxxxxxxxx (ISO) 3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxykumarin3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxy-2 X-xxxxxxx-2-xx

201–378–1

81–82–3

Xx; R48/22 X52–53

Xx X:48/22–52/53 X: (2-)37-61

607–058–00–1

kumafuryl (XXX) fumarin (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (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; X25–48/25 X52–53

X X:25–48/25–52/53 S: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) ethyl-4-oxo-5-(perchlor-5-hydroxypentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-yl)pentanoát xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx

4234–79–1

X; X24 Xn; X22 X; 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 trimellitanhydrid

209–008–0

552–30–7

Xi; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx xxxxxxxx kyselina

203–677–2

109–52–4

C; X34 X52–53

X R:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xx; R22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; X36/38 R52–53

Xi X:36/38–52/53 S: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xn; R22 Xx; R38 X; X50–53

Xx; X X: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

xxxxx xxx chloroctové xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; R25 Xx; X38 X; X50

X; N X: 25–38–50 X: (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; X50–53

Xx; 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 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-({3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}xxx)xxxx(xxxxxxxxxx)

400–830–7

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xn; X22 X43 X; R50–53

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

607–213–00–3

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

403–320–2

67567–23–1

X; X2 O; X7 X10 X; X51–53

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

607–217–00–5

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

403–960–2

X43 X53

Xx X: 43-53 X: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] natrium-3,6-dichlor-o-anisát [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-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 X: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xi; X36/37/38 X43 X; X51–53

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

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

607–252–00–6

λ-xxxxxxxxxxx (ISO) Směs (1:1): (X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 R)-cis-3-((Z)-2-chlor-3,3,3-trifluorprop-1-en-1-yl)-2,2-dimethylcyklopropan-1-karboxylát x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx

415–130–7

91465–08–6

X+; R26 X; 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

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

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X X

203–466–5

107–13–1

X; Xxx Xxxx. xxx. 2; R45 X; X23/24/25 Xx; X37/38–41 X43 X; X51–53

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

C ≥ 20 %: X; R45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ X &xx; 5 %:X; X45–23/24/25–43 0,2 % ≤ X &xx; 1 %:T; R45–20/21/22 0,1 % ≤ X &xx; 0,2 %: T; 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 (ISO) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; X28 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 (ISO) (2,4-xxxxxxxxxxxx)(4-xxxxxxxxxx)xxxxx

X

217–406–0

1836–75–5

Xxxx. xxx. 2; X45 Xxxx. xxx. 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 N; X50–53

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

611–008–00–4

4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. xxx. 2; X45 N; R50–53

T; X R: 45–50/53 X: 53–45–60–61

611–013–00–1

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

403–650–7

117409–78–6

X; X2 N; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

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

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-xxxxxxxxxxxxx x-xxxxxxxx

X

201–963–1

90–04–0

Xxxx. xxx. 2; R45 Xxxx. kat. 3; X40 X; X23/24/25

X X: 45–23/24/25 X: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; R22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

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

612–051–00–1

4,4'-xxxxxxxxxxxxxxxxxxxx xxx(4-xxxxxxxxxx)xxxxxx 4,4'-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 X: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61

612–081–00–5

3,3'-xxxxxxxxxxxxxxxx, xxxx 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; X22 N; X51–53

X; X R: 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. kat. 2; X45 T; R25 Xx; X21 Xx; X36 R43 N; X51–53

X; N X: 45–21–25–36–43–51/53 S: 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 X: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61

612–111–00–7

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

212–513–9

823–40–5

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

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

612–125–00–3

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

202–442–1

95–70–5

T; X25 Xx; R20/21 X43 X; X51–53

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

612–144–00–7

flumetralin (ISO) 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 xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; R45 T; X25 Xx; X20/21 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'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx

7411–47–4

Xx; X22 Xx; R36/37/38 X52–53

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

613–031–00–5

xxxxxxxxx trichlorisokyanurová xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5X)-xxxxx

201–782–8

87–90–1

X; R8 Xx; X22 R31 Xx; X36/37 N; X50–53

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

613–038–00–3

6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-fenyl-1,3,5-triazin-2,4-diamin 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; N X: 20/22–41–50/53 X: (2-)26–39–60–61

613–043–00–0

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

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xx; X41 N; R50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

613–091–00–2

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

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; X22 Xx; R36/37/38 X52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; R34 X; X51–53

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

613–130–00–3

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

79983–71–4

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–131–00–9

xxxxxxxxxx (ISO) 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 S: (2-)61

613–134–00–5

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

88671–89–0

Repr. xxx. 3; X63 Xx; X22 Xx; X36 N; X51–53

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

613–137–00–1

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

242–505–0

18691–97–9

X; R50–53

N X: 50/53 X: 60-61

613–139–00–2

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

74223–64–6

X; R50–53

N X: 50/53 S: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; R25 X; R51–53

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

614–006–00–1

xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx

206–614–7

357–57–3

X+; X26/28 X52–53

X+ X:26/28–52/53 S: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; X26/28 R52–53

T+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] m-tolylidendiisokyanát [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. kat. 3; X40 T+; X26 Xx; R36/37/38 R42/43 X52–53

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

X320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ C &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42

2

616–010–00–9

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

204–854–7

127–65–1

Xx; R22 X31 X; X34 X42

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

616–034–00-X

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

246–419–4

24691–76–7

X52–53

X: 52/53 X: 61

616–035–00–5

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

261–043–0

57966–95–7

Xx; X22 X43 X; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; X7 Xn; X22 X; R34 X; R50–53

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

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

617–006–00-X

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

201–279–3

80–43–3

X; X7 Xx; R36/38 N; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xi; X36 X43

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

650–007–00–3

xxxxxxxxxxxxx (ISO) 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 Xn; X21/22 X; R50–53

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

650–008–00–9

xxxxxxxxxx (XXX) 4-[(2-chlorfenyl)hydrazono]-3-methylisoxazol-5(4 X)-xx

227–197–8

5707–69–7

X; X25 N; X50–53

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

650–009–00–4

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

243–269–1

19750–95–9

Xxxx. xxx. 3; R40 Xx; X22 X; X50–53

Xx; X R: 22–40–50/53 X: (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 N; X50–53

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

650–041–00–9

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

82097–50–5

X; X50–53

X X: 50/53 X: 60-61


XXXXXXX 1D

Indexové xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x přípravkům

006–090–00–8

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

408–010–0

88558–41–2

Xn; X20 Xx; X41 R52–53

Xn X: 20–41–52/53 S: (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; X41 X; R50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 S: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; X50

X X: 50 X: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 N; X51–53

Xx; X R: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 X64 X; X50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X X: 52/53–59 X: 59-61

603–128–00–0

2-(fenylmethoxy)naftalen

405–490–3

613–62–7

R53

R:53 X: 61

603–129–00–6

1-xxxx-xxxxxxxxxxxx-2-xx

406–180–0

57018–52–7

X10 Xi; X41

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

603–130–00–1

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

406–325–8

Xx; R22 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-deoxy-1-[methyl(1-oxotetradecyl)amino]-D-glucitol

407–290–1

Xi; X41

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

603–132–00–2

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

408–200–3

63187–91–7

Xx; R38–41 X52–53

Xx X:38–41–52/53 X: (2-)26–37/39–61

603–133–00–8

Směs:3-(4-amino-2-chlor-5-nitroanilino)propan-1,2-diol x 3,3'-[(2-chlor-5-nitro-1,4-fenylen)diimino]di(propan-1,2-diol)

408–240–1

Xn; X22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx x xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (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-nitrilotriethan-1-olato-N,O)titaničitý xxxxxxx

410–500–4

Xx; X41 X; X51–53

Xx; X R: 41–51/53 X: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

R43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

603–137–00-X

Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-deoxy-1-[methyl(1-oxooktadecyl)amino]-D-glucitol

411–130–6

Xi; X41

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

603–138–00–5

3-(2,2-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx

403–140–4

103694–68–4

X52–53

X:52/53 X: 61

604–050–00-X

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

216–381–3

1570–64–5

T; X23 C; R 35 X; R50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 S: 61

604–052–00–0

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

403–800–1

103597–45–1

X53

X:53 S: 61

604–053–00–6

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

410–760–9

157661–93–3

Xx; R38 X43 X; X50–53

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

604–054–00–1

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

412–020–0

X43 R52–53

Xi X:43–52/53 S: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Xxx.3; X40

Xx X: 40 X: (2-)22–36–37

605–027–00–7

Xxxx:3x, 4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-karbaldehyd x 3x, 4,5,6,7,7a-hexahydro-4,7-methano-1H - xxxxx-5-xxxxxxxxxxx

410–480–7

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx 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]

X; X50–53

X X: 50/53 X: 60-61

607–273–00–0

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

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

X43 X; 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; X22 Xi; X41 X43 N; X51–53

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

607–278–00–8

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

405–760–0

Xx; X41 X43 X52–53

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

607–279–00–3

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

405–960–8

X43 X; X51–53

Xx; N X: 43–51/53 X: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xn; X22 Xi; X36 X43

Xx R: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

Směs:alkyl(C7-C9 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 X; X50–53

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

607–284–00–0

Směs (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) x lithium-3,3'-{(1,4-fenylen)bis[(karbonylimino)(propan-3,1-diyl)imino]}bis(10-amino-6,13-dichlor[1,4]benzoxazino[2,3-b]fenoxazin-4,11-disulfonát)

410–040–4

136213–76–8

N; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–065–0

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

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

410–070–8

141880–36–6

X43 X52–53

Xx 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 S: 61

607–288–00–2

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

410–160–7

148732–74–5

Xi; X36 X43 X52–53

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

607–288–00–8

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

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

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

410–540–2

Xx; R38 X43 X; X50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx cyklohexyl)alkanoát

410–630–1

104051–92–5

R53

R: 53 X: 61

607–292–00–4

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

410–640–6

Xi; X38–41 X; X50–53

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

607–293–00-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; N X: 41–43–51/53 X: (2-)26–36/37/39–61

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 X; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

607–296–00–6

Směs:tetraestery pentaerythritolu, xxxxxxxxx xxxxxxxx x 2-xxxxxxxxxxxxx kyselina

410–830–9

R53

R: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; X41

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

607–298–00–7

[2-(trimethylamonio)ethyl]-4-sulfonatobenzoát

411–010–3

R43

Xi X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; R22 X43 X; X50–53

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

607–300–00–6

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

411–430–7

X43

Xx R: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xx; X38–41 X43 N; X51–53

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

607–302–00–7

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

411–910–6

Xx; R38–41 X43 X; X51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Xxxx. xxx.3; X62 X52–53

Xx R: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; X50–53

X X: 50/53 S: 60-61

608–024–00–9

2-{4-[butyl(fenethyl)amino]fenyl}ethen-1,1,2-trikarbonitril

407–650–8

97460–76–9

R53

R:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

X53

X:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

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

X; T X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 C; X34 X43 X; X50–53

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

611–043–00–5

Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx, [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 R: 41–52/53 X: (2-)26–39–61

611–044–00–0

Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [bis(4-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx 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; X51–53

Xx; R41 X52–53

611–045–00–6

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

404–830–8

X53

X:53 S: 61

X X: 51/53 X: 61

611–046–00–1

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

407–590–2

43151–99–1

X; X25 Xx; X48/22 R43 X; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 X: 61

611–048–00–2

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

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

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

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

611–051–00–9

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

411–110–7

136213–74–6

X; R50–53

N X: 50/53 X: 60-61

611–052–00–4

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

400–720–9

X52–53

X: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; R41 N; X50–53

Xx; X X: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xx; X22–48/22 Xx; R41 X43 X; X51–53

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

612–158–00–3

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

410–820–4

X53

X: 53 S: 61

612–159–00–9

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

410–880–1

Xx; R22 X; 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; R23/25 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 X: 61

613–151–00–8

1-(2-deoxy-3-O-mesyl-5-O-trityl-β-D-threo-pentofuranosyl)-5-methylpyrimidin-2(1H), 4(3 X)-xxxx

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-trichlorpyridin

407–270–2

16063–70–0

R52–53

R:52/53 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx R: 22 X: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 X52–53

Xx X: 10–22–52/53 S: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

X43 X; X51–53

Xx; N R: 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 R: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xx; X20/22 Xx; X41 X43 X; X51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; R25 Xx; X20 X; X50–53

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

613–160–00–7

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

411–000–9

125224–62–6

X43

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

615–022–00–1

methyl-3-(isokyanatosulfonyl)thiofen-2-karboxylát

410–550–7

79277–18–2

E; X2 X14 Xx; X48/22 R42/43

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

615–023–00–7

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

410–900–9

83056–32–0

X10 X14 Xxxx. xxx. 3; X40 Xn; X20–48/22 Xx; X41 X42

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

616–044–00–4

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

402–510–2

N; R51–53

N X: 51/53 X: 61

616–045–00-X

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

405–190–2

122371–93–1

R43 R53

Xi X: 43-53 X: (2-)22–24–37–61

616–046–00–5

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

406–390–2

N; X50–53

X X: 50/53 S: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x X, N′,N″,N′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

X43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 N; X51–53

Xx; X R: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

2-(2,4-xx-xxxx-xxxxxxxxxxx)-X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)xxxxxxxxx

408–150–2

99141–89–6

X53

X:53 S: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 X; X50–53

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

411–070–0

X53

X: 53 X: 61

617–015–00–9

bis(4-methylbenzoyl)peroxid

407–950–9

895–85–2

E; X2 X; R7 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 R, 3 X)-, (2 X, 3 R)-2-(4-chlorfenyl)-3-cyklopropyl-1-(1H- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx

94361–06–5

Xxxx. kat. 3; X63 Xx; X22 X; R50–53

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


PŘÍLOHA 2

XXXXXX XXXXXXXXXXXX XXXXX SPOJENÝCH S XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


PŘÍLOHA 3X

XXXXXXXXXX POKYNY XXX BEZPEČNÉ XXXXXXXXX X NEBEZPEČNÝMI LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3B

STANDARDNÍ XXXXXX XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.


XXXXXXX 4A

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x savců xx xxxxx xx xxxxxxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x kultivovaných xxxxxxx savců (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx aberací: chromozomové x chromatidové. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx aberace xx xxxxxx vyskytují. Nárůst xxxxxxxxxxx může znamenat, xx chemická xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxx však xxxx xxxxxx xx stanovení xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx xxxxx rutinně xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx jsou xxxxxxxx xxxxx geneticky xxxxxxxxxxx xxxxxx x xxxxxxx a existuje xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx x s xxxx xxxxxxxxxxx jevy xxxxxxxxxxx změny v xxxxxxxxxx x v xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx indukci xxxxxxxx x člověka x x pokusných xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, xxxxxxx xxxxx xxxx primární xxxxxxx xxxxxxx. Xxxxxxx buňky xxxx vybrány na xxxxxxx xxxxxxxxxx xxxxx x xxxxxxx, stálosti xxxxxxxxx, xxxxx chromozomů, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Tento xxxxxxxxxxx xxxxxxxxx systém xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx vivo x savců. Xx xxxxx xx xxxxx xxxxxxxxx podmínek, které xx vedly k xxxxxxxxxx výsledkům, jež xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx x xxx dojít změnou xX, osmolality xxxx xxxxxxxx xxxxxx cytotoxicity (4, 5).

Xxxx zkouška xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxx xxxxx. Xxxxx xxxxxxxxx, xxx něž xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx chemické xxxxx x xxxxxxxxx xxxxxx x xxx, že xxxxxxxx karcinogeny, které xxxxxx xxxxxxxx xxxxx xxxxxxxx, neboť xxxxxx xxxxxx jinými xxxxxxxxxx xxx xxxxxx poškozením XXX.

Xxx xxxx Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

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

Chromozomová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x podobě xxxxx nebo xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

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

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

Mitotický xxxxx : podíl xxxxx, xxxxx xx xxxxxxxxx x metafázi, x xxxxxxxxx xxxxx xxxxx x populaci; xxxxx stupeň xxxxxxxxxxx xxxx xxxxxxxx.

Xxxxxxxxx xxxxxxx : odchylka xxxxx xxxxxxxxxx xx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx xxxx buněk.

Polyploidie : násobek xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx sad (x), jiný xxx xxxxxxxxx (xx. 3 x, 4 n xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx chromozomů xxx xxxxxxxx xxxxxx xx xxxxxx metafáze; xxxx xx xxxx xxxxxx x xxxxxxxxx, intrachromozomální xxxx interchromozomální xxxxx.

1.3 XXXXXXXX XXXXXXXX METODY

Buněčné xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, a xx x metabolickou xxxxxxxx a xxx xx. X xxxxxx xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxx xx xx xxxxxxxxx kultur xxxxx látka xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx), xxxxxxx xx xxxxxx, obarví x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xx zjistí xxxxxxxxxxxxxx pozorováním xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Mohou xxx xxxxxxx xxxxx buněčné xxxxx, xxxxx xxxx xxxxxxxx xxxxxxx kultury, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. xxxxxxxxxxx xxxxxx xxxxxxxx, lymfocyty xxxxxxxxx xxxx člověka xxxx jiných savců).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx kultur xx xxxx xxx xxxxxxx vhodná kultivační xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx CO2, xxxxxxx x xxxxxxx). X xxxxxxxxxxxxxxx xxxxxxxxx linií x kmenů xx xxxx xxx rutinně xxxxxxxxxxxx stabilita xxxxxxx xxxxxxx počtu xxxxxxxxxx x mělo xx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty; x xxxxxxx xxxxxxxxxxx xx xxxxxx být xxxxxxx. Xxx xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx by xxxx xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu.

1.4.1.3 Xxxxxxxx kultur

Stabilizované xxxxxxx xxxxx x kmeny: xxxxx xx xxxxxxx x xxxxxxxxx xxxxxx, xxxxxx se do xxxxxxxxxxxx média v xxxxxx xxxxxxx, xxx xxxxxxxxx xxxxxxxxxx před xxxxxxxxx, x xxxxxxxx xx při 37 °X.

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (xxxx. heparinem) xxxx oddělené xxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx do xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. fytohemaglutinin) a xxxxxxxx xx xxx 37 °X.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx, a xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx x xxx xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je kofaktorem xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx zpracovaná xxxxxxxx indukujícím enzymy, xxxx xx Xxxxxxx 1254 (6, 7, 8 a 9), xxxx směs fenobarbitonu x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx metabolického xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, která je xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx použít xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada výsledků xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx specifické xxxxxxxxx enzymy, poskytuje xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx xxxxx by xxxx být xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx P450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xx xxxxx xxxxxxxxxx nebo suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx mohou xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx aplikací zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, x xxxx xx xxx slučitelné x xxxxxxxx xxxxx x x aktivitou X9. Jsou-li použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

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

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx ní x xxxxxxx experimentu xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx integrity x xxxxx, jako xxxx xxxxxx konfluence, xxxxx životaschopných xxxxx xxxx xxxxxxxxx xxxxx. Xxxx xxx výhodné xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx by xxx xxxxxxx alespoň xxx xxxxxxxxxxxxxx koncentrace. V xxxxxxx xxxxxxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx až minimální xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx xxxxxxx xxxxxxx, že xx xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. X okamžiku xxxxxxx xx měla xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, počtu buněk xxxx xxxxxxxxxxx xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx index je xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x závisí xx době, xxxxx xxxxxxxx od xxxxxxxx. Xxxxxxxxx index xx xxxx xxxxxxxxxx x xxxxxxxxxxx kultur, x xxxxx xxxxx xxx xxxx xxxxxx stanovení xxxxxxxx xxxxxxx x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), mohou xxx použity jako xxxxxxxxx informace. V xxxxxxx AGT však xxx o xxxxxxxx xxxxxxxxx xxxxxxx, z xxx nelze xxxxxxx xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, a i xxxx xxxxxxxxx průměrné xxxxxxxxx xxxx může xxx xx následek xxxxx podstatné oddálení xxxxxxxx optimálního xxxxxxx xxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx látek by xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx je xxxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx toxické při xxxxxxxxxxxxx nižších, xxx xx xxxxxx rozpustnost, xx xxxx xxx xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, xxx xx nad mezí xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx médiu na xxxxx xxxx aplikace. X určitých případech (xxxx. xxxxxxx-xx se xxxxxxxx xxxxx při xxxxxxx xxxxxxxxxxxxx, xxx xx rozpustnost) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, xxx xxxxx xxxxxxx xx xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx x testovacím xxxxxxx se xxxx x průběhu xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx buněk, séra X9 xxx. Nerozpustnost xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx měly xxx xxxxxxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx). Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx být xxx xxxxxxxxx xxxxxxxx xxxxxxx chemická xxxxx, xxxxx x xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx.

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

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx účinek xxxxxxxx, ale xxx xxx xxxxxx nevyšla xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx podle EINECS

Bez xxxxxx metabolické aktivace

methyl-methansulfonát

66–27–3

200–625–0

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxx pozitivní xxxxxxxx mohou být xxxxxxx x xxxx xxxxxx látky. Xxx xxxxxxxxx kontrolu xx xxxx xxx xxxxx xxxxx xxxxx x xxxxx použití xxxxxxxxxx xxxxx ze xxxxxx xxxxxxxx třídy.

V okamžiku xxxxxxxx xx xxxx xxx použity xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx samotného xxxxxxxxxxxx xxxx vehikula v xxxxxxxxxxx xxxxx x xxxxxxxxxx stejným xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx xx měly xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx žádné xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx rozpouštědlo xxxxxxxxxx žádné xxxxxxx xxxx xxxxxxxxx účinky.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx zkoušené xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx xxxxxxxx xxxxx xxx za xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx bez xxxx. Xxxxxxxx lymfocytů xx xxxx xxx xxxxxxxx xxx 48 xxxxx xx mitogenní stimulaci.

1.4.3.2 Xxx xxxxxx xxxxxxxxxxx xx xxxx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxx. Jestliže xxx xx xxxxxxx xxxxxxxxxxx xxxxx prokázat (13, 14), že xxxx xxxxxxxxxxxx xxxxxxxxx xx minimální xxxxxx, xxxx být přípustné xxxxxxx jediné xxxxxxx.

Xxxxxx xxxx xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. v xxxxx xxxxxxxxxx kultivačních xxxxxxxx (15, 16).

1.4.3.3 Xxxx xxxxxxx kultur

V xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx látce, xxx x xxxxxxxxxxxx xxxxxxxx, xxx bez xx, xx dobu 3 — 6 xxxxx, x xxxx xx xxx odebrány xx xxxxxx xxxx od xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx (12). Jestliže xxxxx xxxxxx dává xxxxxxxxx xxxxxxxx jak s xxxxxxxx, xxx xxx xxxxxxxx, xxx xx xxx proveden xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xx xxxxxx x xxxx, která xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx xxxxx xxx snáze detekovat xxx dobách xxxxxxxx xxxx xxxxxx delších xxx 1,5xxxxxxx xxxxx xxxxx. Negativní xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx xxxxxx od xxxxxxx. X xxxxxxxxx, xxx xx xxxxxxxxxx potvrzení xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, xx xxxx xxx xxxxxx xxxxxxxxxx.

1.4.3.4 Xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx

Xx xxxxxxx xxxxxxx se xxxxxxx 1-3 hodiny před xxxxxxxxx přidá Xxxxxxxx® xxxx xxxxxxxxx. Pro xxxxxxxx xxxxxxxxx pro xxxxxxx xxxxxxxxxx xx xxxxx xxxxxxx kultura xxxxxx a zpracovává xxxxxx. Příprava preparátů xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx buněk, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx kontrol, xx měly xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx dochází xx xxxxx části xxxxx x metafázi x xx ztrátě chromozomů, xxxx xx xxxxxxxxxxx xxxxx obsahovat centromery x počtu xxxxxx xxxxxxx xxxxxxx ± 2 pro všechny xxxx buněk. Na xxxxxx xxxxxxxxxxx x xxxxxxxx by xxxx xxx xxxxxxxxx xxxxxxx 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx xxxxxx, je-li xxxxxxxxx velký xxxxx xxxxxxx.

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

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx jednotkou je xxxxx a xxxx xx tedy xxx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) vyjádřené x xxxxxxxxxx. Pro xxxxxxxxx x experimentální xxxxxxx by xxxx xxx xxxxxxx xxxxx xxxx strukturních xxxxxxxxxxxxxx xxxxxxx s xxxxxx xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxxxxxx xx xx celkové xxxxxxxx xxxxxxx.

Xxxx by xxx také zaznamenána xxxxxxxx, xxxxx byla xxxxxxxxx pro stanovení xxxxxxxxxxxx x všech xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx kultur v xxxxxxxx xxxxxxxxxxxxx s xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Xxxx xx měly xxx xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx byla xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x cílem rozšířit xxxxxx posuzovaných podmínek xx xxxx být xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, které by xxxxx xxx xxxxxxx, xxxxx xxxxxxx koncentrací x xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, např. xxxxxx počtu xxxxx x chromozomovými aberacemi x závislosti na xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx tohoto xxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx výsledků zkoušky xxxxx být xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx.

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

Xxxxxxxx látka, jejíž xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx x xxxxx xxxxxxx xxxxxxxx za xxxxxxxxxxx.

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

Xxxxxxxxx výsledky xx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx savců xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- zdůvodnění xxxxx vehikula,

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

Xxxxx:

- xxx x zdroj buněk,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx použitého typu xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- informace o xxxxx xxxxxxxxx xxxxx,

- xxxxxxx dárce xxxx, xxx xxxx xxxxxxx xxxx xxxx nebo xxxxxxxxxx lymfocyty, xxxxxxx xxxxxxx,

- xxxxxxxx počet xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx xxxx. údajů x cytotoxicitě x xxxxxx xxxxxxxxxxxx, xxxx-xx x xxxxxxxxx,

- složení xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx xxx xxxxxxxx,

- xxx a xxxxxxx xxxxxxxxx metabolického aktivačního xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- pozitivní x xxxxxxxxx kontroly,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, negativní nebo xxxxxxxxxxx.

Xxxxxxxx:

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

- známky xxxxxxx,

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

- definice xxxxxxx, xxxxxx xxxx,

- xxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx x xxxx xxxxxxx xxxxxx xxx xxxxxx xxxxxxxxxxx x kontrolní xxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx závislost odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, H. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Chemical Xxxxxxxx, in: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx xxx Xxxxxxx for xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, X. (xx) Xxxxxx Press, Xxx Xxxx and Xxxxxx, 1-29.

2) Ishidate, X. Xx., Xxxxxx, X. (1985), The In xxxxx Xxxxxxxxxxx Aberration Xxxx Xxxxx Chinese Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Progress xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Xxxxx, X. xx xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Amsterdam-New Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, S. X., Xxxxxxxxx, X. X., Xxxxxx, C., Xxxxxx, S., Brown, X., Xxxxxx, X., Xxxxx, A. X., Xxxxxxxx, X., Xxxxx, X., Duk, S., Xxxxx, X., Xxxxxxxx, X. H., Xxxxxxx, X. A., Xxxxxxxx, X., Zeiger X. (1978), Xxxxxxxxxx xxxxxxxxxx xxx sister xxxxxxxxx xxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx xxxxx: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, X. X., Marshall, R. X., Ishidate, X. Xx., Brusick, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx from ICPEMC Xxxx Xxxxx 9, Xxxxxxxxxx Xxx., 257, 147-204.

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

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

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

8) Natarajan, X. T., Xxxxx, X. D., xxx Xxxx, X. X. X., Meijers, X., xx Xxxxx, X. (1976), Cytogenetic Effects xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx in x Xxxxxxxxxxx System Xx xxxxx, X. Xxxxxxxxx xx Chromozome Xxxxxxxxxxx xxx Xxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) and Xxxxxxxxxxxxxxxxxxx (XXX) xx XXX Xxxxx in the Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

9) Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. Xx. (1979), Chromozomal Xxxxxxxxxx Xxxxx on 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Mix Xx xxxxx, Xxxxxxxx Res., 66, 277-290.

10) Xxxxxx, X. M., Xxxxxx, X. X., Elcombe, X. R., Gatehouse, X. G., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, K., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx of Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, in: xx Serres, X. X., Xxxxx, J. X. Xxxx, X. X., Xxxxxxx, X. X. (xxx), In xxxxx Xxxxxxxxx Xxxxxxxxxx xx Mutagenesis Xxxxxxx, Xxxxxxxx, North-Holland, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxx, X. X., Xxxxxxxx, X. X., Xxxxxx, X., Xxxxxxx, X., Xxxxxx, X. (1994), Report xxxx Xxxxxxx Xxxxx on Xx vitro Tests xxx Xxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, X. A., Xxxxx, X. A., Xxxxxxxx, G., Xxxxxxx, X. O., Phillips, X. (1989), Analysis xx Xxxx xxxx Xx vitro Xxxxxxxxxxx Xxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. J., (ed) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 141-154.

14) Xxxxx, X. X., Galloway, X. X. (1994), Xxxxxxxxx Xxxxxx are xxx Xxxxxxxxx xxx Xx xxxxx Xxxxxxxxxx Xxxxxxxxxx Xxxxxx in XXX Cells, Xxxxxxxxxx Xxx., 312, 139-149.

15) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, X. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx and Volatile Xxxxxxx, xx: Tice, X. R., Xxxxx, X. X., Xxxxxxx, X. X. (eds), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, P. O., Xxxxxx, J. X., Xx, A. P., Xxxxxx, X. L. (1983), Xxxxxxxxxx of xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Grown xx Xxxxxxxx Gels xxx Detecting Highly Xxxxxxxx Xxxxxxxx in xxx XXX/XXXXX Mutation Xxxxx, Environmental Mutagen., 5, 795-801.

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

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


PŘÍLOHA 4X

"X.11 MUTAGENITA–ZKOUŠKA XX CHROMOZOMOVÉ ABERACE X XXXXXXX XXXXXX XXXXX SAVCŮ XX XXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x savců xx xxxx xx xxxxxxxxx xxx xxxxxxx strukturních xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx x xxxxxxx kostní dřeně xxxxx, xxxxxxx hlodavců (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx strukturních xxxxxxx — chromozomové x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx chromozomové xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxxxxxx xxxx jsou xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x existuje xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx způsobující xxxxx x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx nádory, xxxx podíl na xxxxxxx rakoviny x xxxxxxx a v xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx xxxx rutinně xxxxxxxxx xxxxxxxx. Xxxxxxx xxxxx je v xxxx xxxxxxx xxxxxx xxxx, poněvadž xx xxxxxx xxxxxxxxxxxxxxxx tkání x obsahuje populaci xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx izolují x xxxxxxxxxxxx. Xxxx druhy x cílové xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx zkouška xx xxxxxxxxxxxx aberace xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, farmakokinetiku a xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx xx xxxx xx xxxxxx xxxxxxxx xxx další xxxxxx xxxxxxxxxxx účinků zjištěných xxxxxxxx xx vitro.

Jestliže xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx nedostanou xx xxxxxx xxxxx, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxx také Xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Chromatidová xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx xxxxxxxxxxxx chromatid xxxx xxxxx x xxxxxxxx spojení chromatid.

Chromozomová xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx zlomu nebo xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx místě.

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

Xxx : xxxxxxxxxxxx léze xxxxx xxx xxxxx xxxxxxx xxxxxxxxxx x x minimální odchylkou xxxxxxxxx.

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

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

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx vhodným xxxxxxxx x ve xxxxxxx xxxxxxxx xx xxxxxxxx xx usmrtí. Xxxx xxxxxxxxx xx xxxxxxxx xxxx látka xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx nebo Xxxxxxxx®). X xxxxx xxxxxx xxxxx se poté xxxxxxxx xxxxxxxxx chromozomů, xxxxxx se x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx zvířete

Běžně xx xxxxxxxx xxxxxx, xxx x xxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxxx by xxx použity běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx obecné podmínky 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 xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, která xx xxxxxxx xxxxxxxx xxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx byl xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené látky xx xxxx být xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx být xxxx podáním xxxxxxx. Xxxx xx být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické látky, xxxxx údaje o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx toxické xxxxxx a xxxx xx xxx vyloučeno xxxxxxxxx, xx reaguje xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx použití vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

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

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx vivo xxx xxxxxxxxxxx úrovních, x nichž xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx xxxx xxx zvoleny tak, xxx byl xxxxxx xxxxxxxx, xxx aby xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx byl xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx 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 okamžiku xxxxxxx odběru xx xxx xxx xxxxxxxx xxxxx u negativních xxxxxxx, xxxx xx xxxxxxxxxx pouze rozpouštědlo xxxx xxxxxxxxx x xxx xxxxx xxxxxxxxxx xxxxxx proces xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě xxxxxx x četnosti xxxxx x chromozomovými aberacemi. Xxxxxxx-xx xx xxx xxxxxxxxx kontrolu xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx xxxx prvního xxxxxx. Xxxxx toho xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, neexistují-li xxxxx kontrolní údaje xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x pohlaví xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx zvířat xxx xxxxx pohlaví. Xxxxxxxx xxxx v xxxx xxxxxx k xxxxxxxxx xxxxx xx studií xx stejným xxxxxx x za xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx postačující zkoušení xxxxxxx pohlaví. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky by xxxx xxx xxxxx xxxxx xxxxxxxx jednorázově. Xxxxxxxx xxxxx mohou xxx xxxxxxxx xxxx xx xxxx dávkách, xxx. dvě xxxxx x xxx den x rozmezí xx xxxx xxx xxxxxxxx xxxxx, aby bylo xxxxxxxxx xxxxxxxx velkých xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx by měly xxx xxxxxxxx xx xxxx xxxxxxx xxxxxxxxxxx xx aplikace xxxxxx x xxxxxx xxx. X xxxxxxxx xx xxxxx provádí po xxxxxx době od xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 h). Xxxxxxxx xxxx nezbytná xxx xxxxxx x xxxxxxxxxxxx zkoušené látky x rovněž xxx xxxxxx xx xxxxxxxx xxxxxxxxx cyklu xxxx xxx xxxx xx xxxxxxxxx xxxxxxx xxx xxxxxxxxx chromozomových xxxxxxx, xxxxxxxxxx se xxxxxxx xxxxx xxxxx po 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx než xxxxxxx xxx, xxx by xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx aplikace, xxxxx odpovídá 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx.

Xxxx usmrcením xx xxxxxxxx xxxxxxxxxxxxxxxxx podá xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x zvířat odběr. X xxxx je xxxx xxxx xxxxxxxxx 3 — 5 x; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx odeberou buňky x xxxxxxxxx xx xx chromozomové aberace.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx studie pro xxxxxxxx rozsahu xxxxx, xxxx xx být xxxxxxxxx xx stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, pohlavím x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx pro xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Tyto xxxxxx dávky xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx jako dávka xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také xxxxxxxxxx jako xxxxx xxxxxxxxxxxx x xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (např. xxxx xxx 50 % xxxxxxx mitotického indexu).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x jednou xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti podanou xxxxxxxxxxx xxxx xx xxxx xxxxxxx v xxxxxx xxx nevykazuje xxxxx xxxxxxxxxxxxx toxické xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X déle xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx delší xxx 14xxxxx xxxxxxxx je xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx vyšší úroveň xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx podávání xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, který může xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx objem, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx vykazují xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx

Xxxxx po xxxxxxxx xx xxxxxxx xxxxxx xxxx, xxxxxxxxxxxx xx a xxxxxx. Xxxxx se xxxxxxx xx xxxxxxxx xxxxxxx x xxxxxx se.

1.5.7 Xxxxxxx

Xxxx xxxxxxx cytotoxicity xx měl xxx x všech xxxxxxxxxxxx xxxxxx (xxxxxx pozitivních xxxxxxx) x x xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx kontrolu xxxxxxxx xxxxxxxxx index, x xx xxxxxxx u 1000 buněk xx xxxxx xxxxx.

X xxxxxxx xxxxxxx xx mělo xxx analyzováno alespoň 100 xxxxx. Tento xxxxx xxx xxxxxx, xx-xx pozorován xxxxx xxxxx aberací. Xxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Protože xxx xxxxxx často dochází xx chromozomálním xxxxxx xxxx xx ztrátě xxxxxxxxxx x xxxxx xxxxx x xxxxxxxx, xxxx by vyšetřované xxxxx obsahovat centromery x počtu xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx xxxxxxx by xxxx být xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Pro xxxxx xxxxx xx xxx xxx vyhodnocen xxxxx xxxxx, xxxxx aberací xx xxxxx a xxxxx buněk x xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Pro xxxxxxxxxx x xxxxxxxxx skupiny xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx xx zaznamenávají xxxxxxxx x uvádějí xx, xxx obecně se xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx. Neexistuje-li xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, mohou xxx xxx statistickou xxxxxxx xxxxx pro xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx relativního xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx pro skupinu x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Nejdříve xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx (6). Statistická xxxxxxxxxx by xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx s úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxxxx xxxxx, jejíž výsledky xxxxxxxxx výše xxxxxxx xxxxxxxx, xx považuje x xxxxx xxxxxxx xx nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx negativní xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx zůstat xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx chromozomové xxxxxxx xx xxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx v kostní xxxxx testovacího druhu xxxxxxxxxxxx aberace. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx pravděpodobnost, s xxxxx se zkoušená xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, nebo xxxxxxxxxx do xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění volby xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, stáří x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

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

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x negativní (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

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

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx o přípravě xxxxxxxx látky,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- metody xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- mitotický xxxxx,

- typ x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx počet xxxxxxx xx skupině xx xxxxxxxxx xxxxxxxxx x směrodatnými odchylkami,

- xxxxx buněk x xxxxxxxxx xx skupině xx xxxxxxxxx xxxxxxxxx x směrodatnými odchylkami,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- údaje x xxxxxxxx pozitivní xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

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

3) Xxxxxxx, X., Chandley, X., Xxxxx, J., Gatehouse, X. X., Bootman, X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxx Mutagenicity Xxxxx, UKEMS Recommended Xxxxxxxxxx. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Tice, X. X., Xxxxxxx, X., MacGregaro, J. X., Xxxxxxxx, X., Xxxxxx, D. H., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. B., Xxxxxxxxxxxx, F., Xxxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Xxxxxxx Xxxxx on the xx vivo Xxxxxxxxx Xxxx Marrow Chromozomal Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, R. X., Xxxxx, J. A., Xxxxxx, X. R., Xxxxxx, X. X., Xxx, J., Esdaile, X. X., Gatehouse, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx in In xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. P., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, G. X., Xxxxx, G., Xxxxxxxx, R., Xxxxxxx, X., Papworth, X. X., Savage, X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx vivo Cytogenetic Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

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

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


XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx OECD XX 474 — Test xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx vivo (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx, x xx xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x kostní dřeně x/xxxx buněk xxxxxxxxx xxxx, obvykle xxxxxxxx.

Xxxxxx xxxxx savčích erytrocytárních xxxxxxxxxx je identifikovat xxxxx, xxxxx způsobují xxxxxxxxxxxxx poškození, jehož xxxxxxxxx je tvorba xxxxxxxxxx xxxxxxxxxxxx nereplikující xx (lagging) xxxxxxxxxxxx xxxxxxxxx xxxx celé xxxxxxxxxx.

Xxxx xx erytroblast xxxxxx dřeně mění xx polychromatický xxxxxxxxx, xxxxxx xxxxx xx xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx xxxxxxxxx, zůstávají x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader je x xxxxxx buňkách xxxxxxxxx xxx, že xxxxxxxxxx xxxxxx jádro. Xxxxxx výskytu xxxxxxxxxxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x xxxxxxxxxxxx zvířatech xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx je rutinně xxxxxxxxx kostní dřeň xxxxxxxx, xxxxxxxx tato xxxx xxxxxxxxx polychromatické xxxxxxxxxx. Xxxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx v periferní xxxx je xxxxxxxxxx xxxxxxxxxx x kteréhokoli xxxxx, u xxxxx xxxx xxxxxxxxx neschopnost xxxxxxx odstraňovat erytrocyty x mikrojádry, xxxx xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx xxxxx xxxxxxxx. Ta xxxxxxxx xxxxxxxxxxxx přítomnosti xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX v xxxxxxxxxx. Xxxxxxxxx se xxxxxxx xxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x periferní xxxx, které obsahují xxxxxxxxxx, připadající na xxxxxx xxxxx zralých xxxxxxxxxx xxx xxxxxx xxxxxx xxxx konečný xxxxxxxx zkoušky, jestliže xxxx zvířata exponována xxxxx xxxxx nebo xxxx.

Xxxxx xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxx xxxxxx k xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx x procesy xxxxxxxx DNA, xxxxxxx xx xxxxx xxxxx x xxxxxxx xxxxx x xxxxx, jakož x x xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx je rovněž xxxxxxxx xxx xxxxx xxxxxx mutagenních xxxxxx xxxxxxxxxx x systémech xx xxxxx.

Xxxxxxxx existuje xxxxx o xxx, xx xx xxxxxxxx xxxxx xxxx reaktivní xxxxxxxxxx nedostanou xx xxxxxx xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx také Xxxxxx xxxx, část X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) chromozomu, x xxx (x xxxx) xx xxxxx xxxxxx xxxxx připojí xxxxxx vřeténko xxxxxxxxxx xxxxxxxxxx xxxxx dceřiných xxxxxxxxxx k pólům xxxxxxxxx xxxxx.

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

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx erytrocyt xxxxxxxxxxxx xxxxxxxx, xxxxx xxx xxxxxxxx xx xxxxxxxxx polychromatických erytrocytů xxxxxxxx selektivním xxx xxxxxxxx.

Xxxxxxxxxxxxxxx erytrocyt : xxxxxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx obsahuje xxxxxxxx, x xxxx být xxxx xxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx se xxxxxxx xxxxxxxx xxxxxxx zkoušené xxxxx. Při xxxxxxx xxxxxx xxxxx xx xxxxxxx xx xxxxxxx xxxxxxxx po xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx xxxx, připraví xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx použití periferní xxxx se xxxx xx xxxxxxx xxxxxxxx xx expozici xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx a xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx s periferní xxxx xx xxxx xxxx xxxxxxxx xxxxxxxx x sklizením xxxxx xxxxxxxx xx xxxxxxxxx xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx na přítomnost xxxxxxxxxx.

1.4 POPIS ZKUŠEBNÍ XXXXXX

1.4.1 Přípravky

1.4.1.1 Výběr xxxxx zvířete

Při xxxxxxx xxxxxx xxxxx xx xxxx xxxxxxxxx xxxxx xxxxxxxxxx xxx nebo xxxxxx, ačkoli xxx xxxxxx jakýkoli xxxxxx xxxxx druh. Xxx xxxxxxx xxxxxxxxx xxxx xx doporučuje xxx. Xxx však použít xxxxxxxx vhodný druh xxxxx za xxxxxxxxxxx, xx xxx o xxxx, x xxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, nebo xxxx xxxxxxxxxx dostatečnou xxxxxxxxx detekovat xxxxxxxx, xxxxx způsobují strukturní xxxx xxxxxxxxx chromozomové xxxxxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx zahájení xxxxxx xx měla být xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx by u xxxx xxxxxxx překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

Xxxxx obecné xxxxxxxx xxxxx xxxxxxxx úvodu x xxxxx B, xxxxxxx xx xxxx xxx dosaženo xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, x xxx se xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx. Xxxxx xx uspořádají xxx, xxx byl vliv xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx by xxxx xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx nebo vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx být podávány xxxxx xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx x jejich xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx účinky x xxxx by xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být jejich xxxxxxxx xxxxxxxxx údaji x jejich xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx zvážit xxxxxxx vodných rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx být xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly pro xxx xxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata xx xxxxxxxxx, x nichž xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, u xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx způsobem xxx zkoušená látka x aby byl xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx navíc xxxx xxx vzato x xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo podle XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx u xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx xxxxxxxxxx stejný xxxxxx xxxx exponované xxxxxxx, pokud nejsou x dosavadních xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx o xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li xx xxx xxxxxxxxx kontrolu xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx nebo xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx xxxx xxxx xxx jako negativní xxxxxxxx přijatelný xxxx xxxxxx krve xxxxxxxx xxxx expozicí, pouze xxxx x xxxxxxxx xxxxxx x xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, že xxxxxxxx xxxxx xxxxx x xxxxxxx, xxxxx xx na základě xxxxxxxxxxx xxxxxxx očekává.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx zvířat

Každá exponovaná x xxxxxxxxx xxxxxxx xx xxxx xxxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví (11). Xxxxxxxx xxxx x xxxx xxxxxx k xxxxxxxxx xxxxx ze xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx. Xx-xx expozice člověka xxxxxxxxxx pro určité xxxxxxx, xxxx xx xxxx například x xxxxxxxxx farmaceutických xxxxx, xxxx xx xxx xxxxxxx provedena se xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx aplikace

Nelze doporučit xxxxx xxxxxxxxxx xxxx (xx. jednu, xxx xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx xx xxxxxx s xxxxxxxxxxxx xxxxxxx xxxxxxxx jsou xxxxxxxxxx, pokud xx x xxxxxx studií xxxxxxx xxxxxxxxx výsledky, xxxx –v případě xxxxxxxxxxx xxxxxx — xxxxx byla prokázána xxxxxxxx nebo xxxx xxxxxxxxx xxxxxxx dávka x xxxxxxxx xxxxxxxxx xx do okamžiku xxxxxx. Xxxxxxxx látky xxxxx být xxxxxxxx xxxx xx dvou xxxxxxx, tzn. xxx xxxxx v týž xxx v xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx podávání xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx být xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx xxxxxx. Vzorky xxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 hodin xx xxxxxxxx x poslední xxxxxxxxxx 48 hodin xx aplikaci x x přiměřeným odstupem xxxx xxxxxx. Xxxxx xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx zdůvodněn. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 36 xxxxx xx aplikaci x xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x xx prvnímodběru xx dodrží xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx odběru xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx xxxxx;

x) xxxx-xx xxxxxxxx dvě xxxx xxxx xxxxx xxxxx (xxxx. xxx xxxx více xxxxx x xxxxxxxxx 24 xxxxx), xxxx xx xxx xxxxxx při xxxxxxx kostní xxxxx xxxxxxxx xxxxxx po 18 až 24 xxxxxxxx xx xxxxxxxx xxxxxxxx a xxx xxxxxxx xxxxxxxxx krve xxxxxx po 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx potřeby xxxxx xxx xxxxx xxxxxxx xxxx doby xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx studie pro xxxxxxxx xxxxxxx dávek, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx stejného xxxxxx xxxxxxxx, xxx xx xxxxxxx v xxxxxx studii (13). X případě xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx pokrývat rozpětí xxxx maximální xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx odběru stačí, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx dávkách (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx a xxxx xx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx být xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx některé xxxxxx xxxxxxxx (např. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx v kostní xxxxx nebo x xxxxxxxxx xxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx o xxxxxxx 2000 mg/kg xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách v xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx toxické xxxxxx a není-li xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. X déle xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx než 14xxxxx xxxxxxxx je xxxxxxx dávkou 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx xxxxxx x limitní xxxxxxx vyšší úroveň xxxxx.

1.5.5 Podávání dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx podávání jsou xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx je uvedený xxxxx, musí být xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx konstantní objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx nebo xxxx

Xxxxx xxxxxx xxxxx se xxxxxxx získávají x xxxxxx xxxx tibie xxxxx po xxxxxxxx. Xxxxx xx xxxxxxxx x femuru nebo xxxxx a xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x xxxxxx. Periferní xxxx xx získává x ocasní žíly xxxx jiné vhodné xxxxxx xxxx. Xxxxxx xxxxx xx ihned xxxxxxxxxxxx obarví (8, 9, 10), xxxx xx připraví preparáty xxxxxxxx x xxxx xx obarví. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) se xxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx x xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx DNA. Tato xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx barviv (např. Xxxxxx). Přídavné systémy (xxxx. xxxxxxxxxx xxxxxx x odstranění xxxxx xxxxxxxxxxxx jádra (16)) xxx xxxxxx za xxxxxxxxxxx, xx xx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxx v xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx každé xxxxx xx stanoví xxxxx xxxxxxxxx erytrocytů x celkového (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x xxxxxxx xxxxxx xxxxx xxxxxxx celkově xxxxxxx 200 erytrocytů x x případě xxxxxxxxx krve xxxxxxx 1000 erytrocytů (17). Xxxxxxx preparáty včetně xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxx xxxxxxx 2000 xxxxxxxxx erytrocytů xx xxxxxx mikrojader x xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx zralých xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx xxxxx být xxxxx xxxxxxxxx erytrocytů x celkového xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx xxxx xxxxxxxx xx výskyt xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx analýzu (xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxx) xxxx xx xxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxx přijatelnými xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx jednotlivá zvířata xx xxxx xxx xxxxxxxxxx ve formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx analyzované zvíře xx měl být xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx a xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxxx xx xxx xxxx uvedeny xxxxx x zralých erytrocytech, xxxx-xx xxxxxxxxxxxxx. Pro xxxxx xxxxx se xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx a xxxxxxxx xxxxxxxx erytrocytů x mikrojádry vyjádřené x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x odpovědi xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx analýzu xxxxx xxx xxx xxxxxxx zkombinována.

2.2 HODNOCENÍ X INTERPRETACE VÝSLEDKŮ

Pro xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx počtu xxxxx s mikrojádry x závislosti na xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxxx xxx xxxxxxx x určitou xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx použity xxxx pomocný xxxxxxxxxx xxxxxxxxxxx metody (18, 19). Statistická významnost xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, jejíž xxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx x xxxxx xxxxxxx xx nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx zkoušené látky. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xxxxx na xxxxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx důsledkem xxxxxxxxxxxxxx poškození nebo xxxxxxxxx mitotického xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxxx mikrojádra x xxxxxxxxx erytrocytech xxxxxxxxxxx xxxxx.

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

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, stáří x pohlaví zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat na xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx odchylka xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

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

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx metody xxxxxxx, xxx xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx nebo xx cílové xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx nebo xxxx (xxx) na xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx hmotnosti/den),

- podrobné xxxxx o xxxxxxx xxxxxx x vody,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x odběru,

- xxxxxx xxxxxxxx preparátů,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx hodnocení xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx erytrocytů,

- xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx uvedený xxxxxxxxxx xxx xxxxx zvíře,

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

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy x xxxxxx,

- xxxxx x xxxxxxxx x xxxxxxxxx negativní xxxxxxxx,

- xxxxx x souběžné xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Schmid, X. (1975), Xxx Xxxxxxxxxxxx Test, Mutatation Xxx., 31, 9-15.

3) Xxxxxx, X. A., Xxxxxxxx, X. X., Xxxx, X., Kirkhart, X., Xxxxxxxxx, X., XxxXxxxxx, X. G., Xxxxxx, X. X. (1983), Xxx Xxxxxxxxx xx Xxxxxxxxxxx x. x. x Xxxxxxx xx Xxxxxxxxxxxx, Mutatation Xxx. 123, 61-118.

4) Xxxxxxxxx, K. H., Xxxxxx, X. X., Xxxxxx, M. C., Xxxxxxxx, X. X., Xxxxxx, J. A. (1990), Xxx In xxxx Xxxxxxxxxxxx Xxxxx xx Mammalian Bone Xxxxxx and Peripheral Xxxxx. X report xx xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Res., 239, 29-80.

5) XxxXxxxxx, X. X., Schlegel, X., Xxxx, X. N., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Xxxxxx xxx Xxxxxxxxxxx Xxxxxx During Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Xxxxxxx, X. X. Miya. Elsevier, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Xxxxxx, X. A. Xxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X. X., Xxxx, X. X., Xxxx, X. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx of Xxxxxxxxxxxx Xxxxxx in Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) MacGregor, X. X., Xxxx, X. X., Xxxxxx, X. X., Shelby, M. X. (1990), Xxx xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Xxxxxx Xxxxx Xxxxxxxxx Xxxxx Efficiency xxx Permits Xxxxxxxxxxx xxxx Xxxxxxxx Studies, Xxxxxx. Appl. Xxxxxxx. 14, 513-522.

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

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

10) Xxx Collaborative Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (CSGMT/JEMMS, XXX: Xxx Mammalian Xxxxxxxxxxx Study Xxxxx xx the Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx xx Xxxxx) (1995), Protocol xxxxxxxxxxx for the xxxxx-xxxx mouse xxxxxxxxxx xxxxx xxxxxxxxxxxx test, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Tice, X. X., MacGregor, X. T., Anderson, X., Xxxxxxx, X. X., Kirsch-Volders, X., Xxxxxx, Jr. X. X., Pacchicrotti, F., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, S., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Micronucleus Assay, Xxxxx. Xxx., 312, 293-304.

12) Higashikuni, N., Xxxxx, X. (1995), Xx optimal, xxxxxxxxxxx xxxxxxxx xxxx xx 30 ± 6 x xxxxx double xxxxxx xx xxx xxxxx xxxxxxxxxx micronucleus xxxx, Mutagenesis, 10, 313-319.

13) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, D. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Mutagenesis, 7, 313-319.

14) Hayashi, X., Xxxxxx, X., Ishidate, X. Jr. (1983), Xx Application xx Xxxxxxxx Orange Xxxxxxxxxxx Xxxxxxxx xx the Xxxxxxxxxxxx Test, Mutation Xxx., 120, 241-247.

15) XxxXxxxxx, X. X., Xxxx, C. X., Xxxxxxxx, R. X. (1983), A Simple Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Xxxxxxxxxxx xxx XXX xx Xxxxxxxxxxxx Xxxxx Xxxxxxx 33258 xxx Xxxxxxx X, Xxxxxxxx Xxx., 120, 269-275.

16) Xxxxxxx, F., Xxxxxxxxxx, X. X. (1989), The xxxxxxxxx xxxx xxxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxx Res., 213, 91-104.

17) Gollapudi, X., XxXxxxxx, X. X. (1995), Sample Xxxx xxx xxx Xxxxxxxxxx of Xxxxxxxxxxxxx xx Normochromatic Xxxxxxxxxxx Xxxxx in xxx Xxxx Marrow Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 347, 97-99.

18) Xxxxxxx, X., Ashby, X., Xxxxxxx, J., Chandley, X., Gatehouse, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxxx Xxxxx, xx: X. X. Kirkland (xx.), Basic Mutagenicity xxxxx, XXXXX Recommended Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx 1, xxxxxxx, Xxxxxxxxx University Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Melbourne, Xxxxxx, 115-141.

19) Xxxxxx, X. P., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, G. E., Xxxxx, G., Ferguson X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx of Xx xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Part XXX, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxx xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx používají xxxxxxxxxxx xxxxx závislé xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx coli, x detekci xxxxxxxx xxxxxx, které xxxxxxxx xxxxxxxxxx, xxxxx a xxxxxx xxxxxxx xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xxxxxxx x detekci xxxxxx, xxxxx revertují xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxx x xxxxxxxx tak funkční xxxxxxxxx bakterií syntetizovat xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx reverzi xxxx xxxxxxxxxx xxxx xxx xxxxxxxxxx růst x xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x xxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a xxxxxxxx mnoho důkazů x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx xxxxxx xxxx xxxxx xx tvorbě xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx. Zkouška na xxxxxxxx xxxxxx x xxxxxxxxxx je rychlá, xxxxxxxxxx x relativně xxxxxx. Xxxxx xxxxxxxxxxx xxxxx xx xxxx xxxxxxxxxx, díky nimž xxxx xxxxxxxxxx xx xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx reverzních xxxxxxx, xxxxxxx xxxxxxxxxxxx buněk xxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxx xxxxxxxx reparačních xxxxxxx XXX xxxxxxxxxx x xxxxxx. Specifičnost xxxxxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx užitečné xxxxxxxxx x xxxxxx xxxxxx, xxx jsou xxxxxxxxxx xxxxxxxxxxxxx činiteli. Xxx xxxxxxx na xxxxxxxx xxxxxx x bakteriemi xx x xxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx xxxxxxxx x xxxx xxxx xxxxxxxx xxxxx xxxxxxxxxx metody xxxxxxxx xxxxxxxxxx látek, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx také obecný xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx s bakteriemi Xxxxxxxxxx typhimurium xxxx Xxxxxxxxxxx coli xxxxxx x xxxxxxx mutací x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx xxxx. xxxxxxxxx), přičemž xxxxxx xxxx xxxxxxxxx na xxxxxxx přísunu xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx párů xxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx v xxxxxx XXX. Při xxxxxxx xxxxxxxxxx mutací xx xxxxx xxxx xxxxx xxxxxxxxxx xx xxxxx původní xxxxxx xxxx xxxxx místě xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx xxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxxx adici xxxx xxxxxx xxxxxxx nebo xxxx xxxx xxxx XXX x xxxxxxxx xxx čtecí xxxxx XXX.

1.3 XXXXXXX XXXXX

Xxx xxxxxxxxx na reverzní xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xx xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx a xxxxxxxxx xxxxxxx XXX. Xxxxxxx prováděné xx xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx in xxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x savců. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx látky xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx aktivity xxxxxxxxxxxx xxxxxx mutace. Z xxxxxxxx xxxxxxxx xxxxxxx, xx mnoho chemických xxxxx, xxxxx xxxx x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx mutagenní xxxxxxxx x x xxxxxx xxxxxxxxx. Existují xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx nejsou xxxxxxxxxx xxxxx xxxxxxxx. Xxxxxxx xxxxxx xxxxxxxxxxx xxx xxxxxxxxx ve xxxxxxxxxx xxxxxx detekovanéhokonečného jevu, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx nebo x xxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx faktory, xxxxx xxxxxxx citlivost xxxxxxx xx xxxxxxxx xxxxxx xx bakteriích, xxxxx xxxx k xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx xxxxxx xxx xxxxxx xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx vysoce xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) a xxx chemické xxxxx, x xxxxx xx xxxxxxxxxxx (nebo o xxxxx se ví), xx specificky xxxxxxxx xx replikačního systému xxxxx xxxxx (xxxx. xxxxxxx inhibitory xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). V xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, xxx něž xx xxxx zkouška xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, xxxx xxxxxxxx xxxxxxxxx. Xxxxxx xx xxxxxxxx třídě x xxxxxxxx xxxxx xxxxxxxxxxx, xxx nejsou xxxxxxxxxx xxxxx zkouškou, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, nebo xxxxxxxxxx, xxxxx v xxxxxxxxxxxxx buňkách xxxxxxxxxx.

1.4 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxxx xxxxxxxxxxxxx buněk jsou xxxxxxxxx zkoušené xxxxx, x xx xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx systému a xxx něho. Xx xxxxxxxxxxx xxxxxxxx testu xx xxxxxxxx xxxxxxxx x xxxxxxx xxxxxx x xxxxx xx xxxxxxx xx xxxxxxxxx xxxx. X preinkubační xxxxxx xx xxxxxxxx xxxx xxxxxxxx x xxxx xx xxxx xxxxxxxxx na minimální xxxx xxxxxx x xxxxxxx xxxxxx. Xxx xxxx xxxxxxxxxx xx xx dvou nebo xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx revertantů x provede xx xxxxxxxx s xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx kontrolní misce x xxxxxxxxxxxxx.

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

Zde xxxxxxx xxxxxxx xx xxxxxx hlavně xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx xx xxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Některé xxxxx xxx účinněji xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx metody. Tyto xxxxx patří xx xxxxxxxxxx xxxx, do xxxxx patří xxxx xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxxx x nitrosloučeniny (3). Xxxxxx se připouští, xx určité xxxxx xxxxxxxx xxxxx vždy xxxxxxxxx standardními xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx test xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx xxx považovány xx "zvláštní případy" x x jejich xxxxxxx xx xxxxxxx xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (xxxxxxxx x xxxxxxxx postupů xxxxxx xxxxxxx): xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx a xxxxxx xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx od xxxxxxxxxxxx xxxxxxx xxxx xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX ZKUŠEBNÍ XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx by měly xxx xxxxxxxxxxx xx xxxxxx xxxxxxxxxxxxx fáze xxxx do xxxxx xxxxxxxxxxx fáze xxxxx (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Xx xxxxxxxx, aby xxxx xxxxxxx xxxxxxxx xxxxxx xxxx životaschopných xxxxxxxx. Xxxx může xxx xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x růstové xxxxxx, xxxx xxx xxxxxx zkoušku stanovením xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx xx xxx xxxxxxx alespoň xxx xxxxx bakterií. Xxxx xxxx xx xxxx xxx xxxxx xxxxx X. typhimurium (XX1535; XX1537 xxxx XX97x xxxx XX97; XX98 x TA100), xxxxxxx xxxxxxx xx xxxxxxx x různých xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx S. xxxxxxxxxxx xxxx pár xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx známo, xx xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx vláken XXX x xxxxxxxxx. Tyto xxxxx xxxxx být xxxxxxxxxx xxxxx X. xxxx XX2 nebo X. typhimurium TA102 (19), které mají xx primárním reverzním xxxxx xxx xxxx XX. Doporučená xxxxxxxxx xxxxx xx tedy xxxx:

- X. xxxxxxxxxxx XX1535 x

- X. xxxxxxxxxxx XX1537 nebo XX97x x

- S. xxxxxxxxxxx TA98 a

- X. typhimurium XX100 x

- E. xxxx XX2 xxxX, xxxx X. xxxx XX2 xxxX (pKM101), nebo X. typhimurium XX102.

Xxx xxxxxxx xxxxxxxx způsobujících xxxxxxxxxx xxxxxx XXX xxxx xxx xxxxxxxxx xxxxxxx XX102 xxxx xxxxxx kmen X. xxxx x xxxxxxx xxxxxxxxxx reparace XXX, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx xx xxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx kmenové xxxxxxx, verifikace xxxxxxx x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx xxx každou xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx pro kmeny X. xxxxxxxxxxx x xxxxxxxxx xxx E. xxxx). Xxxxxxx by xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx xxxxx potřeby xxxxxxxxxx nebo nepřítomnost X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx TA98, TA100 x TA97a xxxx XX97, XX2 uvrA x WP2 uvrA (xXX101) x ampicilinová x tetracyklinová xxxxxxxxxx x xxxxx TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. xxx xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx na xxxxxxxxxxx xxxxxx x xxxX xxxxxx u E. xxxx xxxx uvrB xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx na xxxxxxxxxxxx světlo) (2, 3). Kmeny by xxxx rovněž dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx misce x rozmezí xxxxxxxx xxxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx a xxxxxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) x glukosu) x xxxxxx agar xxxxxxxxxx histidin x xxxxxx xxxx tryptofan xxxxxxxxxx xxxxxxx buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx měly xxx xxxxxxxxx zkoušené xxxxx, x to s xxxxxxx systémem xxxxxxxxxxx xxxxxxxx a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Aroclor 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx v xxxxxxx 5 xx 30 % obj. xx xxxxx X9. Xxxxx x podmínky xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx záviset na xxxxx xxxxxxxx xxxxxxxx xxxxx. X některých xxxxxxxxx může xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce. U xxxxxxxxx a diazoniových xxxxxxxxx xxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx nebo xxxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx před xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx mohou xxx přidány přímo x xxxxxxxxxx systémům x/xxxx xxxxx být xxxx aplikací xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx mimo xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx nestálých ve xxxx by xxxx xxx použita organická xxxxxxxxxxxx xxxxxxxxxxxx vodu.

1.5.2 Xxxxxxxx podmínky

1.5.2.1 Zkušební xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Xxxx být užitečné xxxxxxxx toxicitu x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx může xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Cytotoxicita xxxxx xx může xxxxxx v přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx xx měla xxx posouzena xx xxxxxxx xxxxxxxxxxx srážení x xxxxxxx směsi xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx látky xx 5 xx/xxxxx xxxx 5 μx/xxxxx. U xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by xxxx xxx xxxxx xxxx xxxx zkušebních koncentrací xxxxxxxx, aby xxxxx xxxx x xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky, xxxxx jsou xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx než 5 xx/xxxxx nebo 5 μx/xxxxx, by xxxx xxx xxxxxxxx xx xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx při vyšetřování.

Mělo xx xxx xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx zkoušené xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx xxxx zkušebními xxxx xxxxx přibližně xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Menší xxxxxxxxx xxxx xxxxxx x xxxxxxx, kdy xx xxxxxxxxx křivka xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Xxxxxxxx koncentrací xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx být xxxxxxx xxx hodnocení xxxxx obsahujících významné xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

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

X xxxxxxx zkoušek x xxxxxxxx metabolického xxxxxxxxxxx systému xx xxxx být xxxxx (xxxxx) pro xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxx) xx xxxxxxx typu xxxxxxxxx xxxxx xxxxxxxx.

Xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx s xxxxxxxxxxxx xxxxxxxx xxxx xxxx xxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Direct Red 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx by xxxxx xxx použit xxxx xxxxxx xxxxxxxxx účinnosti xxxxx X9. Xxx xxxxxxx 2-xxxxxxxxxxxxxxx by xxxx xxx každá xxxxx X9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

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

Látka

Číslo CAS

Číslo xxxxx XXXXXX

Xxxx

xxxx sodný

26628–22–8

247–852–1

TA1535 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

TA1537, XX97 a TA97a

Kumenhydroperoxid

80–15–9

201–254–7

TA102

mitomycin X

50–07–7

200–008–6

XX2xxxX x XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 xxxX a XX2 xxxX (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX a XX2 xxxX (pKM101)

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

3688–53–7

xxxxx obsahující plasmidy

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

Měly by xxx použity xxxxxxxxx xxxxxxxx skládající xx xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, zpracované xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx by xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, neexistují-li dosud xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5.3 Xxxxxx

X xxxxxxxxxx xxxxxxx xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx xxxxxxxx se xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx kultury (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx sterilního xxxxx x 2,0 xx xxxxxxxx xxxxx. X xxxxxxx xxxxxxx x xxxxxxxxxxxx aktivací xx xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx aktivační xxxxx xxxxxxxxxx přiměřené xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x rozmezí 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx směsi) x xxxxxxx agarem (2,0 xx) x xxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx a xxxxxxx xxxx povrch xxxxxxxxxxx xxxxx xx misce. Xxxx inkubací xx xxxxx xxxxxx xxxx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx xxxxxxxxx x xxxxxxx xxxxxx x xxxxxxxx xxxx xxxxxx minimálního xxxxx xx misce xxxxxxx 20 xxxxx nebo xxxx xxxxxxxxxxx s xxxxxxxxxx xxxxxx (obsahujícím xxxxxxxxx 108 životaschopných xxxxx) a sterilním xxxxxx nebo metabolickým xxxxxxxxxx systémem (0,5 xx) xxx 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 xxxx 0,1 xx xxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx, 0,1 xx bakterií x 0,5 ml xxxxx S9 xxxx xxxxxxxxxx xxxxx x 2,0 xx vrchního xxxxx. Zkumavky xx xxxx být během xxxxxxxx provzdušňovány xx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx xxxxxxxx xx xxxx xxx xxx každé xxxxxx xxxxx použity 3 xxxxx. Použití xxxx xxxxx je xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx xxxxxx znamenat xxxxxxxxxxxx xxxxxxx.

Xxxxxx nebo xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx metodami, např. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

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

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Předloženými xxxxx xx měly xxx počty xxxxxxx xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Xxx xx xxx xxxxxx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xx miskách x xxxxxxxxx kontrolou (xxxxxxxx rozpouštědla x xxxxxxxx neexponovaná kontrola), xxx na xxxxxxx x xxxxxxxxx xxxxxxxxx. Xxxxx na xxxxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxx xxxxx kolonií revertantů xx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx xxx předloženy xxx zkoušenou xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx jasně xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx vyjasněny xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xx potvrzení xxxxxxxxxxx výsledků nepovažuje xx xxxxxxxx, xxxx xx xxx podáno xxxxxxxxxx. Změna parametrů xxxxxx s xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla xxx zvážena x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx studie, xxxxx xx xxxxx xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx, metoda zpracování (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) x xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx revertantů xx xxxxx xxx xxxxxxxxx rozsah u xxxxxxx xxxxxxx xxxxx x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxx bez xxxx, a xx x xxxxxxxxxx na xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx tohoto počtu xxx jednu nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Při xxxxxxxxx výsledků xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx jediným xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx.

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

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

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje x genomu kmenů Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx bodové xxxxxx xxxxxxxxxx xxxx xxxx posunem čtecího xxxxx. Negativní xxxxxxxx xxxxxxxxx, že zkoušená xxxxx xxxx za xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxx mutagenní.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce musí xxxxxxxxx tyto informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx volby xxxxxxxxxxxx/xxxxxxxx,

- xxxxxxxxxxx a stálost xxxxxxxx látky v xxxxxxxxxxxx/xxxxxxxx, je-li známa.

Kmeny:

- xxxxxxx xxxxx,

- počet xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx kmene.

Zkušební xxxxxxxx:

- xxxxxxxx xxxxxxxx látky xx xxxxx (xx/xxxxx xxxx μl/misku) x xxxxxxxxxxx xxxxxx xxxxx x xxxxx xxxxx xx koncentraci,

- použitá xxxxx,

- xxx a xxxxxxx metabolického aktivačního xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx miskách,

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx statistické analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Ames, X. X., McCann, X., Xxxxxxxx E. (1975), Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res., 31, 347-364.

2) Maron, X. X., Ames, X. X. (1983), Revised Xxxxxxx for xxx Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Xxx., 113, 173-215.

3) Gatehouse, X., Xxxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxx, L., Xxxxxxxxxx, X., Xxxxxxx, C., Xxxxx, X., Venitt, X., Xxxxxx, X. (1994), Xxxxxxxxxxxxxxx xxx xxx Performance xx Xxxxxxxxx Xxxxxxxx Assays, Xxxxxxxxxx Xxx., 312, 217-233.

4) Xxxx, X. X., Xxxxxxx X. X., Xxxxxxx, X. X., Xxx Xxxxx, X. X., Xxxxx, X. X., Simmon, X. X., Xxxxxx, X., XxXxxx, X., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Xxx X. (1986), Xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx xx xxx X. S. Xxxxxxxxxxxxx Xxxxxxxxxx Agency Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, T., Degawa, X., Xxxxx, Y. X., Xxxxxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Hashimoto, Y. (1975), Mutagenicity of Xxxxxxxxxx Xxx Xxxx xxx xxxxx Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Matsushima, X., Xxxxxxxx, T., Xxxxx, X., Xxxxxx, X., Xxxxxx, A., Sawamura, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Microbial Xxxxx, in: Xxxxx-xxxx Xxxx Systems for Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx X. X., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

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

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

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

10) Xxxxxxx, X. A., Xxxxx, X. H. L., Xxxxxxxxx, X., Xxxxxxx, X. X. (1984), Xxx Xxxxxxxxxxx Test xx Xxxxxxxx, xx: Xxxxxxxx of Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Kilbey, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Elsevier, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

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

12) Xxxxx, X., Xxxxxxx, T., Xxxx, X., Xxxxxxxxxx, X. (1994), Xxxxxxxx Xxxxxx xxx Mutagenicity Testing xx Xxxxxxx Compounds xx Using x Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Res., 307, 335-344.

13) Xxxxxx, X. X., Xxxx, X. X., Mitchell, V. X., Xxxxxxx, X. X., Xxxxxxx, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Dyes xxx Xxxxxxxx Xxxxxxx Xxxx xx a Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Anderson, X. X., Xxxxxxx, X., Xxxxxx, T., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Tests. X. Xxxxxxx from xxx Xxxxxxx xx 311 Chemicals, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

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

16) Xxxxxx, X. X., Xxxxxxx, X. X., Monteith, X. X., Xxxxxxx, X. D. (1987), Xxxxxxxxxxxx Technique to Xxxxxxx Mutagenic Xxxxxxxx xx Xxxxxxxx Organic Xxxxxxxxx in the Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

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

18) Xxxxxx, G., Gold, X., Xxxxx-Xxxxx, X., Xxxx, B. X. (1980), Xxxxxxxx: A Xxxxx xxx Xxxxxxxxxx xx Xxxxxxx Glycosides xx Xxxxxxxx xx Xxxxxxxxxx Xxxxx, Xxxx. Xxxx. Acad. Xxx. X. X. A, 77, 4961-4965.

19) Wilcox, X., Xxxxxx, X., Xxxx, X. X., Xxxxxxxxx, D. G. (1990), Xxxxxxxxxx xx Xxxxxxxxxx typhimurium TA 102 xxxx Xxxxxxxxxxx xxxx WP2 Tester xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Hara, X., Sugimura, T. (1976), X Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. xx Xxxxxxx or Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: Xx xxxxx Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, xxx. X. J. de Xxxxxx xx xx. Xxxxxxxx, Xxxxx Holland, 85-88.

21) Xxxxxx, X. X., Xxxxxx, X. X., Elcombe, X. X., Gatehouse, D. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, R. X. (1992), Alternatives xx Xxxxxxx 1254-xxxxxxx X9 xx xx xxxxx Genotoxicity Assays, Xxxxxxxxxxx, 7, 175-177.

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

23) Claxton, X. X., Xxxxx, X., Auletta, X., Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, E. (1987), Guide for xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Mutagenicity, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, X. X. X., Green, M. X. X., Xxxxxxxxx, X., Xxxxxxx, I., Xxxxxxxx, X. X., Xxxxxx, D. X. (1989), Xxxxxxxx of Xxxx from Xxxxxxxxx Xxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxx II. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, xx. Kirkland, X. X., Xxxxxxxxx University Xxxxx, 28-65."


XXXXXXX 4X

"X.17 XXXXXXXXXX — ZKOUŠKA NA XXXXXX MUTACE X XXXXXXX XXXXX XX XXXXX

1. XXXXXX

Xxxx metoda xx xxxxxxxx xxxxxx XXXX XX 476 — Xxxxxxx xx xxxxxx xxxxxx v xxxxxxx xxxxx xx xxxxx (1997).

1.1 ÚVOD

Zkoušku xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx lze xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx indukovaných xxxxxxxxxx xxxxxxx. Xxxx xxxxxx buněčné linie xxxxx xxxxx xxxxxxx X5178X xxxx, xxxxxxx xxxxx CHO, XXX-XX52 x X79 xxxxxx xxxxxxxx x xxxxxxxxxxxxxxx xxxxx XX6 xxxxxxx (1). X těchto xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace xxxx xxx thymidinkinasu (XX) x hypoxanthin-guaninfosforibosyltransferasu (HPRT) x xxxxxxxx xanthin-guaninfosforibosyltransferasy (XXXX). Xxxxxxx xx xxxxxx TK, XXXX x XXXX xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX a XPRT xxxx umožnit detekci xxxxxxxxxxx událostí (xxxx. xxxxxxxx delece), xxxxx xxxxx xxxxxxxxx x XXXX lokusu xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx lze xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx nebo buněčné xxxxx. Xxxxx se xxxxxxxx xxxxx schopnosti xxxxx x kultuře x xxxxxxxx četnosti xxxxxxxxxxx xxxxxx.

Xxxxxxx prováděné xx vitro obecně xxxxxxxx použití xxxxxxxx xxxxxx metabolické xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx nemůže xxxxx xxxxxxxxx xxxxxxxx in xxxx x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx vedly x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, jež neodrážejí xxxxxxx xxxxxxxxxx, může xxxxx změnou pH, xxxxxxxxxx xxxx xxxxxxxx xxxxxx cytotoxicity (7).

Xxxx xxxxxxx se xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx a karcinogenů xxxxx. Mnoho xxxxxxxxx, xxx xxx xx xxxx zkouška xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx zřejmě xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x bakteriálních buňkách xxxxxxxxxx (6).

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Přímá mutace : xxxxxx mutace xxxxxxxxx xxxx xxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx.

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

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

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

Xxxxxxx mutantů : xxxxx pozorovaných mutantních xxxxx xxxxxx počtem xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxx celkový xxxx : xxxxxx xxxxx buněk x xxxx xx srovnání x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx xx xxxx součin poměru xxxxxxxxx růstu v xxxxxxxx x x xxxxxxxxx kontrole a xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx k xxxxxxxxx xxxxxxxx.

Xxxxxxxxx růst x xxxxxxxx : xxxxxx xxxxx xxxxx v xxxxxxx exprese xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx na xxxxx xx xxxxxxxxxxxx podmínek xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx na xxxxx xx konci xxxxxx expozice; xxxxxxx xx obvykle xxxxxxxxx x xxxxxx x xxxxxxx kontrolní xxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) jsou xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (TFT). Xxxxx xxxxxxxxxxx thymidinkinasu xxxx xxxxxxx na TFT, xxx xxxxxxxxx inhibici xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx buňky xxxx xxxx schopny xxxxxxxxxxx za přítomnosti XXX, xxxxxxx xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxxxxxxx xxxx schopnost xxxxxx. Xxxxxxx lze x buněk x xxxxxxxxxxxx XXXX xxxx XXXX provést selekci xxxxxxxxxxxxxxx xxxxxxxxxx k 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (AG). Vlastnosti xxxxxxxx xxxxx xx xxxx xxx pečlivě xxxxxxx, jestliže je xx zkoušce xx xxxxxx mutace x xxxxxxx savců zkoušen xxxxxx báze nebo xxxxxxxxxx xxxxxxx selekčnímu xxxxxxx. Xxxx by xxx xxxxxxxxx vyšetřeno xxxxxxxx xxxxxxxxx xx xxxxxxxxxx xxxxxxxx zkoušené xxxxx pro xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx činidlo, xxxx xxxx být xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxx xxx selekci (8).

Xxxxx x xxxxxxxxx xxxx jednovrstevné kultuře xxxx vhodnou dobu xxxxxxxxx xxxxxxxx xxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx bez xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx exprese xxxxxxxx xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx kultur xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx x xxxxxxxx xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx pro xxxxx zvolený xxxxx x xxx buněk, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx xx xxxxxxx xxx, xx se xxxxxx xxxxx xxxxx xxxxx do xxxxx xxxxxxxxxxxx selekční xxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxx x xx xxxxx bez xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Četnost xxxxxxx se xxxxxxx x xxxxx xxxxxxxxxx xxxxxxx x selekčním xxxxx a xxxxx xxxxxxx x xxxxx xxx selekčního xxxxxxx.

1.4 XXXXX ZKUŠEBNÍ METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx použití x xxxx xxxxxxx xxxx x dispozici xxxxx xxxx buněk, xxxxxx subklonů xxxxx X5171X, XXX, XXX-XX52, X79 xxxx XX6. Xxxx xxxxx x xxxx zkoušce xx xxxx vykazovat citlivost x chemickým xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx frekvenci xxxxxxxxxxx mutací. Xxxxx xx měly xxx xxxxxxxxxxxx, zda nejsou xxxxxxxxxxxxx mykoplasmaty, x x xxxxxxx xxxxxxxxxxx xx xxxxxx být xxxxxxx.

Xxxxxxx xx měly xxx xxxxxxxx xxx, xxx xxxx xxxxxx xxxxxxxxxx xxxxxxxxx x xxxx. Xxxxx xxxxxxxxx xxxxx, kultur a xxxxxxxxxxx zkoušené látky xx xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, které přežijí xxxxxxxx x xxxxx xxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx, xx xxx xxx xxxxxxx xx četnosti xxxxxxxxxxx mutací. Obecným xxxxxxxxx je, xxx xxx použit xxxxx xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx mutací. Xx však doporučeno, xxx xxxx použito xxxxxxx 106 xxxxx. Xxxx xx být x xxxxxxxxx xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx xxxxxxxx systému, xxx byla doložena xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx a xxxxxxxxx podmínky (kultivační xxxxxx, koncentrace CO2, xxxxxxx x xxxxxxx). Xxxxx xx xxxx xxx xxxxxxx podle xxxxxxxxxx xxxxxxx x xxxx xxxxx použitých xxx zkoušce. Xx xxxxxxx xxxxxxxx, xxx xxxxxxxxxx xxxxxxxx byly xxxxxxx xxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxx xxxxx během xxxxxx xxxxxxx x xxxxxxxxx xxx xxxxxxxxxx, xxx xxxxxxxxxxxx xxxxx xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx by xxxx xxx xxxxxxxxx z xxxxxxxxx xxxxxx, xxxxxxxx xx kultivačního xxxxx x xxxxxxxxxx xxx 37 °X. Před xxxxxxxx x xxxx xxxxxxx xxxx xxx xxxxxxxx odstranit x xxxxxxx již přítomné xxxxxxxx buňky.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx vystaveny xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx systémem xx xxxxxxxxxx dotovaná xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x jater xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (15, 16, 17 x 18), xxxx směs xxxxxxxxxxxxx x β-naftoflavonu (19, 20).

Xxxxxxxxxxxxxxxxxxx frakce xx x konečném xxxxxxxxxx xxxxx obvykle xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % obj. Xxxxx x xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx zkoušena. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx použít xxxx než xxxxx xxxxxxxxxxx postmitochondriální xxxxxx.

Xxxx xxxxxxxx vývoje, včetně xxxxxxxx geneticky modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií xx xxxx xxx xxxxxxx zdůvodněna (např. xxxxxxxxxxx isoenzymu xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by měly xxx xxxx xxxxxxxx xx buňky xxxxxxxxxx xxxx suspendovány ve xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx a/nebo xxxxx xxx xxxx xxxxxxxx zředěny. Měly xx xxx použity xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, x xxxx xx xxx xxxxxxxxxx x přežitím xxxxx x x xxxxxxxxx X9. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx být xxxxxxx xxxxxxxxx rozpouštědla neobsahující xxxx. Vodu lze xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx nejvyšší koncentrace, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx systému x změny pH xxxx osmolality.

Cytotoxicita by xxxx být xxxxxxxxx x xxxxxxxxxxxx aktivací x bez ní x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x růstu, xxxx xxxx relativní účinnost xxxxxxxxx (přežití) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx by být xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx xxxxxxxx by xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a minimální xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx xxxx xxxxxxx znamenat, xx xx xx koncentrace xxxx lišit faktorem 2 xx Ö10. Xx-xx maximální xxxxxxxxxxx xxxxxxxx xx cytotoxicity, xxxx by být xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) přežití (xxxxxxxxx xxxxxxxx klonování) xxxx xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx toho, xxxxx x nich xx xxxxxxxx.

Xxxxxxxxx nerozpustné látky xx měly xxx xxxxxxxx xx k xxxx rozpustnosti za xxxxxxxxxxxx xxxxxxxx, xxxx xx za xxxx xxx. Xxxx by xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx v xxxxxxxx xxxxx, ve kterému xxxx buňky exponovány. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx aplikace, xxxxx xxxxxxxxxxx xx může x xxxxxxx xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx buněk, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly být xxxxxxxxx a negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, tak xxx xx. Při xxxxxxx xxxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx pozitivní xxxxxxxx xxxxx být xxxx xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx podle Einecs

Bez 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 (xxxx a 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 xxxxxx úrovně X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx xxx xxxxxxx xxxx xxxx xxxxxxxxxx xxxxx pro pozitivní xxxxxxxx, xxxx. xx-xx xxxxxxxxx xxxxxxxx dosavadních xxxxx x 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, XXXXXX 200–415–9), xxxx xxx xxxx referenční látka xxxxxx xxxxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx vzato x xxxxx použití xxxxxxxxxx xxxxx xxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx tvořené xxxxxx xxxxxxxxxxx xxxxxxx rozpouštědlo xxxx xxxxxxxxx x xxxxxxxxxx jinak xxxxxxx xxxxxxxx jako xxxxxxxxxx xxxxxxx. Xxxxx toho xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Postup

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx zkoušené látce xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx bez něho. Xxxxxxxx xx xxxx xxxxx xxxxxxx xxxx (xxxxxxx xx xxxxxx xxxx 3 xx 6 xxxxx). Expoziční xxxx xxxx xxx xxxxxxxxxxx xx jeden xxxx xxxx xxxxxxxxx xxxxx.

Xxx každou zkušební xxxxxxxxxxx xxxxx xxx xxxxxxx duplicitní xxxxxxx xxxx xxxxx xxxxxxxxxx xxxxxxx. Xx-xx použita xxxxx xxxxxxx, měl xx xxx xxxxx xxxxxxxxxxx xxxxxx xxx, xxx byl xxxxxxxx xxxxxxxxxxxx xxxxx xxxxxx xxx analýzu (např. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx použity xxxxxxxxxx xxxxxxxxx xxxxxxxxx kultury (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx nebo xxxxxx látky xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx uzavřených xxxxxxxxxxxx nádobách (21, 22).

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx konci xxxxxxxxx xxxx xx buňky xxxxxxx a xxxxxxxxx xx účelem xxxxxxxxx xxxxxxx x xx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx se xxxxxxx xxxxxxx po expoziční xxxx.

Xxxxx lokus xx xxxxxxxxxx xxxxxxxxx časové xxxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx nově indukovaných xxxxxxx (XXXX x XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, XX xxxxxxx xxx dny). Xxxxx xxxx kultivovány x xxxxx se xxxxxxxxx xxxxxxxx (selekčními xxxxxxx) x xxx xxxx (xxx nich) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx a klonovací xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxx) xx xxxxxxx xx xxxxx xxxx xxxxxxx xxxxxxxxx na xxxxx xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx xxxxx xxxxxxxxx xx zkoušce X5178X XX+/-, mělo xx xxx xxxxxxxxx alespoň xx jedné xx xxxxxxxxxx xxxxxx (x xxxxxxxx pozitivní koncentrací) x xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx podle xxxxxxxxx kolonií. Xx-xx xxxxxxxx látka xx xxxxxxx L5178Y XX+/- xxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx kontrolách. Xxx studiích xx xxxxxxx XX6 XX+/- xxxx být xxxx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx velikosti xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx měly xxxxxxxxx xxxxxxxxx cytotoxicity a xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. X xxxxxxx pozitivní xxxxxxxx xx xxxxxxx X5178X XX+/- xx xxxxxxx xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx zkoušené xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x u xxxxxxxxx a xxxxxxxxx xxxxxxxx xx použití xxxxxxxx malá xxxxxxx — velká xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx jak xxxxxxx xxxxxxxxx xxxxx kolonie, xxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Ve xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx za xxxxxxx xxxxxxxx xxxxxxx s xxxxxxxxx xxxxxx (xxxxx) x kolonie x xxxxxxx xxxxxx (xxxx) (25). X mutantních xxxxx, které xxxxxxx xxxxxxxxxxxxxx genetické poškození, xx xxxxxxxxxxx doby xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx obvykle xxxxxx xx xxxxx xxxxxx xxxx xx xx xxxxxxxxxxxx viditelné xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx tvořících malé xxxxxxx se xxxxxxx x chemickými xxxxxxx, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx závažně postižené xxxxx xxxxxxx xxxxxx xxxxxxxx tempem xxxx xxxxxxxx xxxxx x xxxxx velké kolonie.

Mělo xx xxx xxxxx xxxxxxx (relativní xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Xxxxxxx xxxxxxx by měla xxx vyjádřena xxxx xxxxx xxxxxxx k xxxxx přeživších xxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Dvojznačné výsledky xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Tam, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxx, xx xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx xxxxxxxx rozsah xxxxxxxxxxxx podmínek by xxxx být xxxxxxx x xxxxxxxxxx experimentech xxx xxx xxxxxxxxxx xxxxxxxx, tak pro xxxxxxxxx výsledky. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx být xxxxxxx, patří xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. nárůst četností xxxxxxx x xxxxxxxxxx xx koncentraci, xxxx xxxxxxxxxxxxxxxx nárůst xxxx xxxxxxxx. Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx pomocný xxxxxxxxxx statistické metody. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx faktorem pro xxxxxxxxx odpověď.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx soubor xxxxx xxxxxxxx konečný xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx odpovědi xx xxxxxxxxxxx xx velmi xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx v xxxxxxxxx kultivovaných buňkách xxxxx genové xxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce musí xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Buňky:

- xxx a xxxxx xxxxx,

- počet xxxxxxxxx xxxxxx,

- případně počet xxxxxx,

- xxxxxxxx metody xxxxxxxxx buněčné xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- objem xxxxxxxx x přidané zkoušené xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx xxxxx expozice,

- xxx x složení xxxxxxxxx metabolického xxxxxxxxxxx xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxxxxxx,

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxx xxxx xxxxxxx (xxxxxxxx xxxxxx xxxxx nasazených xxxxx, xxxxxxxxx x xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx nebo dvojznačnou,

- xxxxxx xxxxxxx k xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx buněk,

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

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxx srážení,

- údaje x pH a xxxxxxxxxx xxxxx expozice xxxxxxxx látce, pokud xxxx xxxxxxxxx,

- xxxxxxxx xxxxxxx, xxxx-xx xxxxxxxxxxx, xxxxxxx pro xxxxxxxxx x pozitivní xxxxxxxx,

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

- podle xxxxxxxx závislost xxxxxxxx xx dávce,

- případné xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. M., XxXxxxxx, X. X., XxXxxxxx, X. X., Tindal, X. X. (eds.) (1987), Xxxxxxx Report 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Xxxx Xxxxxx Xxxxxx Xxxxxxxxxx, New Xxxx.

2) Chu, X. X. Y., Xxxxxxx X. X. (1968), Xxxxxxxxx Xxxx Xxxxxxxx. XX. Chemical Xxxxxxxxx xx Xxxxxxxx Locus Xxxxxxxxx xx Xxxxxxx Xxxxxxx Xxxxx Xx xxxxx, Proc. Natl. Xxxx. Sci. X. X. A, 61, 1306-1312.

3) Xxxxx, X. X., Thilly, X. X. (1982), Xxxxxxxx Xxxxx xx the Xxxxxxxxx Kinase Xxxxx xx Xxxxxxx Xxxxx Xxxxxxxxxxxx, Xxxxxxxx Res. 94, 467-485.

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

5) Xxxxx, X. X., Xxxxxxxxxx, Xx. L. X., (1989), Xxxxxxxxxx xx xxx AS52/XPRT xxx xxx XXX/XXXX Xxxxxx: Xxxxxxxxxx xx Xxx Xxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx. 223, 121-128.

6) Xxxxx, X. X., Xxxxxxxxxx, G., Xxxxx, X. X., Xxxxx, X., Nishi, X., Xxxxxxxxxx, Xx. X. X., Xxxxxx, X., Xxxxxxxx, E. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Working Xxxxx Report. Xxxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxxx on Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, S. X., Marshall, X. X., Ishidate, X., Xxxxxxx, X., Ashby, X., Xxxx, X. X. (1991), Genotoxicity Xxxxx Extreme Culture Xxxxxxxxxx. A report xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, D., McCuen, X., Xxxxxxx, X. X. X., Piper, X., Xxxxxxxxx, X. X. (1983), Specific Xxxx Mutations in X5178X Xxxxx xx Xxxxxxx. X Xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 115, 225-251.

9) Xx, X. X., Xxxxx, R. X., Xxxxxxx, R. X., Xxxxxx, J. X. (1988), A Xxxxxx xxx Xxxxxxxx xx xxx Chinese Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Transferase System xx Determine xxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: A Report xx Xxxxx XXX xx xxx U. X. Environmental Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, A. X., Carver, X. X., Choy, X. X., Hsie, X. X., Gupta, X. X., Xxxxxxx, X. X., X'Νxxxx, X. X., Xxxxxx, X. X., Xxxxxxxxxx, X. X. Xx., Yang, X. X. (1987), X Xxxxx for xxx Performance of xxx Xxxxxxx Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Mutation Xxxxx, Mutatation Res., 189, 135-141.

11) Xxxxx, X. X., Yandell, X. X., Xxxxxx, X. X. (1989), X Comparison xx Xxxxxxxx Xxxxxxxxx at xxx XX xxx XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx xx xx Xxxxxxxxxx Xxxxx xx Xxxxxxxxx at xxx Xxxxxxxxx TK Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

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

13) Xxxxxx, X. T., Xxxxxx, X. X., Xxxxx, X. (1984), Xxxxxxxxx xxx the X5178X/XX+/--XX+/- Xxxxx Xxxxxxxx Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, B. X. xx xx (xxx.) Handbook xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Science Xxxxxxxxxx, Xxx Xxxx, 239-268.

14) Xxxxxx, C. X., Xxxxx, D. X., Xxxxxx, X. M., Xxxxx, X. H. X., Cole, X., XxXxxxxx, X. B., Xxxxxxx X. C. (1989), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxx upon Xxxxxx Xxxxxxxxx, xx: Statistical Xxxxxxxxxx xx Mutagenicity Xxxx Data, Kirkland, X. X., xx., Xxxxxxxxx Xxxxxxxxxx Press, 66-101.

15) Abbondandolo, X., Xxxxxxx, X., Xxxxx, X., Fiorio, R., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Xxxxxxxxx xx 6-Xxxxxxxxxxx-Xxxxxxxxx Xxxxxxx xx V79 Xxxxxxx Xxxxxxx Cells by Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Xxx. 46, 365-373.

16) Xxxx, X. X., XxXxxx, X., Xxxxxxxx, X. (1975), Xxxxxxx for Detecting Xxxxxxxxxxx and Xxxxxxxx xxxx xxx Salmonella/Mammalian-Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx. 31, 347-364.

17) Xxxxx, X., Xxxxxxx, X. X., Xxxxxxx, X. X. S., Xxxxxx X. X., Xxxxx X. X. X. (1979), Xxxxxxxxxx xxx Characterisation xx xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Assay Xxxxxx, Xxxxx. Xxx. 59, 61-108.

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

19) Elliott, B. X., Combes, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-Xxxxxxx X9 xx: In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Sawamura, X., Xxxx, X., Xxxxxxxx, X. (1976), X Xxxx Substitute xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxxxxx Xxxxxxx, de Xxxxxx, X. X., Fouts, X. R., Xxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, K. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Costa, X. X., Xxxxxxx, X. M. (eds), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, X. O., Xxxxxx, J. X., Xx, A. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Xxxxx Xxxxx xx Collagen Gels xxx Xxxxxxxxx Highly Xxxxxxxx Mutagens in xxx CHO/HGPRT Xxxxxxxx Xxxxx, Xxxxxxx. Mutagenesis, 5, 795-801.

23) Applegate, X. X., Moore, X. X., Xxxxxx, X. X., Burrell, X., Hozier, X. X. (1990), Xxxxxxxxx Xxxxxxxxxx of Xxxxxxxxx xx the Xxxxxxxxxxxx Xxxxxxxxx Kinase Xxxxx xx Mouse Xxxxxxxx Xxxxx, Xxxx. Xxxx. Xxxx. Xxx. U. X. A, 87, 51-55.

24) Moore, X. X., Xxxxx, X., Xxxxxx, X. C., Xxxxxx, X. E., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. (1985), Xxxxxxxx of Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Mutants xx X5178X/XX+/--Xxxxx Lymphoma Xxxxx, Mutatation Xxx. 151, 161-174.

25) Yandell, X. W., Xxxxx, X. X., Xxxxxx, X. B. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxx xx a Xxxxxxxxxxxx Xxxxxxxxx Locus xx Xxxxx Cells, Mutatation Xxx. 229, 89-102.

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


PŘÍLOHA 4F

"B.23 ZKOUŠKA XX CHROMOZOMOVÉ XXXXXXX XX XXXXXXXXXXXXXXX SAVCŮ

1. XXXXXX

Xxxx xxxxxx je xxxxxxxx metody OECD XX 483 — Xxxxxxx xx chromozomové xxxxxxx xx spermatogoniích xxxxx (1997).

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx in vivo xx xxxxxxxxxxxxx xxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Rozlišují xx xxx xxxx xxxxxxxxxxxx aberací: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Tato xxxxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x není x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx jsou příčinou xxxxx geneticky xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx se stanovují xxxxxxxxxxxx změny ve xxxxxxxxxxxxxxx a xxxxxxxxxxx xx tedy, že xxxx xxxxxxx xxxxxxxx xxxxxxxxx indukce xxxxxxxxx xxxxxx v germinálních xxxxxxx.

X této xxxxxxx xxxx rutinně xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx detekují chromozomové xxxxxxx xxx mitose xxxxxxxxxxxxx. Jiné xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx zkoušky.

Pro detekci xxxxxxx chromatidového typu xx spermatogoniích xx xxxx být — xxxxx xxx xxxxx xx ztrátě xxxx — xxxxxxxxx první xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Xxxxx informace x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx meiotickou xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx xxxxxxxx xxx vyšetření, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx aktivní xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx xx xxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx xx xxxxxxxx chemické látce. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx souhrnnou xxxxxxx xxxxxxxxxx populace xxxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X závislosti xx xxx poloze xx xxxxxxxxx, xxxxx xxxx nemusí být xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx krevnímu xxxxx v xxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxx Xxxxxxxxx buněk x xxxxxxx xxxx xxxxxxx xxxxxx x xxxxxxx.

Xxxxxxxx existuje důkaz x xxx, xx xx xxxxxxxx xxxxx xxxx reaktivní metabolity xxxxxxxxxx xx xxxxxx xxxxx, xxxx vhodné xxxx zkoušku použít.

Viz xxxx xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

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

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

Gap : xxxxxxxxxxxx xxxx xxxxx než xxxxx xxxxx xxxxxxxxxx x x xxxxxxxxx odchylkou xxxxxxxxx.

Xxxxxxxxx aberace : xxxxxxxx počtu xxxxxxxxxx xx xxxxxxxx hodnoty x xxxxxxxxx xxxxx.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx metafáze xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx x xxxxxxxxx, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx způsobem xxxxxxxxxx xxxxxxxx xxxxx x xx xxxxxx době xx expozici usmrcena. Xxxx xxxxxxxxx se xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx nebo Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx připraví xxxxxxxxx xxxxxxxxxx, obarví xx a xxxxxxxxx xx chromozomové xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xxxx xxxxxxxxx xxxxx xxxxxx čínského a xxxx; xxx xxxx xxxxxx samce xxxxxxxxxx xxxxxx xxxxxxxx xxxxx xxxxx. Měly xx xxx použity xxxxx xxxxxxx laboratorní kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx zahájení xxxxxx xx xxxx být xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu a xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx mladí pohlavně xxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, xxxxx xx xxxxxxxx. Xxxxx xx xxxx být xxxxxxxxxx tak, aby xxx xxxx xxxxxx xxxxxx minimalizován. Zvířata xx jednoznačně identifikují. Xxxx započetím xxxxxx xx xxxxxxx v xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx by xxxx xxx xxxx xxxxxxxx xxxxxxxx rozpuštěny xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo vehikulech x xxxxxxxxx zředěny. Xxxxxxx zkoušené xxxxx xxxxx být xxxxxxxx xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx mít při xxxxxxxxx xxxxxxxxx dávek xxxxxxx účinky a xxxx by být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu by xxxx být xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx aplikace xxxxxxxx xxxxx xx xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx identický proces xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xx xxxx xxx expozičních xxxxxxxx, x xxxxx xx xxxxxxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx xx xxxx xxx xxxxxxx tak, xxx byl účinek xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx xxx navíc xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek xx xxxxxx chemické xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:

Látka

Číslo XXX

Xxxxx podle Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxx (xxxxxxx)

79–06–1

201–173–7

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx odběru xx měl xxx xxxxxxxx xxxxx u xxxxxxx negativní xxxxxxxx, xxxxx je aplikováno xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a která xxxxx podstupuje xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 XXXXXX

1.5.1 Xxxxx zvířat

Každá exponovaná x kontrolní skupina xxxx xxxxxxxxx xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxx.

1.5.2 Xxxx expozice

Zkoušené látky xx xxxx xxx xxxxx xxxxx podávány xxxxxxxxxxx xxxx xxxxxxxxx (xx. při xxxxx xxxxxxxx nebo dvou xxxxxxxxxx). Xxxxxxxx látky xxxxx být xxxxxxxx xxxx ve dvou xxxxxxx, xxx. xxx xxxxx x xxx xxx v xxxxxxx xx xxxx než xxxxxxxx hodin, xxx xxxx xxxxxxxxx podávání xxxxxxx xxxxxx materiálu. Xxxx xxxxxx podávání xx měly být xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x nejvyšší xxxxxx xx xxxx xxx xx xxxxxxxx provedeny xxx xxxxxx. Xxxxxxxx xxxxxxxx buněčného cyklu xxxx být xxxxxxxxx xxxxxx ovlivněna, xxxxxxx xx jeden časný xxxxx a xxxxx xxxxxxxx xxxxx přibližně 24 x 48 xxxxx xx expozici. X případě jiné xxx xxxxxxxx dávky xx xxx být xxxxx xxxxxxxx xx 24 hodin xxxx xx xxxxxx xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx xxxx xxxxx jiná vhodnější xxxx xxx xxxxxxx xxxxxx (6).

Xxxxx xxxxx xxx xxxxxx xxxxxxxxx xxxx v xxxx xxxx. Například x xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx indukovat xxxxxxxx xxxxxxxxx (xxxxxxx) xxxxxxxxxx xxxx mohou xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx být vhodnější xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx xxxxxxxxx expozice xxxx xxx určena xxxxxx xx xxxxxxx. X xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5násobek xxxxx xxxxx) po poslední xxxxxxxx. Podle xxxxxxx xxxxx xxx xxxxxxxxx xxxxx odběry v xxxx xxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx dávka xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Poté se xx xxxxxx době xxxxxxx x xxxxxx xxxxx. U xxxx xx xxxx doba xxxxxxxxx 3 — 5 hodin; x xxxxxx čínského xx xxxx doba xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li se xxxxx neexistenci vhodných xxxxxxxxxx údajů xxxxxx xxx xxxxxxxx xxxxxxx, xxxx by xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx expozice, který xx xxxxxxx x xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx pokrývat xxxxxxx xxxx maximální x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Při xxxxxxxxx odběru xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xx xxxxx dávky xxxxx xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx.

Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx nízkých netoxických xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx může xxx xxxx definována xxxx dávka vyvolávající xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx počtu spermatogonií x mitose xxxxxxxx x xxxxx x xxxxx meiotické xxxxxxxx; xxxx xxxxxxx by xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s jednou xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x jednom xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx dávky xx xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx použít x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx látka xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, musí být xxxxxxxxxx. Až na xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava preparátů xx xxxxxxx xxxxxxxxxx

Xxxxx xx usmrcení xx x xxxxxxx nebo xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxx xx xxxxxx xx podložní xxxxxxx x xxxxxx se.

1.5.7 Xxxxxxx

X xxxxxxx zvířete xx xxxx být xxxxxxxxxxx xxxxxxx 100 xxxxx x dobře xxxxxxxxxxxx metafázi (xx. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Xxxxx xxxxx xxx xxxxxx, xx-xx pozorován xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx dochází xx xxxxxxxxxxxxxx xxxxxx nebo xxxxxx chromozomů x xxxxx metafází, měly xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx v xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx zpracovány xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx počet xxxxx xx strukturními chromozomovými xxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx xxxxxxxxxx x kontrolní xxxxxxx xx xxxx xxx xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x četností. Xxxx xx zaznamenávají odděleně x xxxxxxx xx, xxx xxxxxx se xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, xxx xx xxx xxx stanovení xxxxxxx cytotoxických xxxxxx xxxx míra cytotoxicity xxxxxxxx x všech xxxxxxxxxxxx xxxxxx x xxxxxx sloužících xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx v xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx, a xx x xxxxxxxx xxxxxx 100 xxxxxxxx xx xxxxx xx xxxxx xxxxx. Pokud xx xxxxxxxxx pouze xxxxxx, xxxxxxx v 1000 xxxxxxx xx xxxxx xx xxx být xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. nárůst xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Nejdříve xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní výsledky, x xxxxxxxxxxx případech xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx to, kolikrát xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxxxxxxxx aberace ve xxxxxxxxxxxxxxx savců xx xxxx xxxxxxxxx, že xxxxxxxx látka indukuje x xxxxxxxxxxxx buňkách xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x germinálních xxxxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx se xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx do xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- počet x stáří xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx pro xxxxxx skupinu.

Zkušební xxxxxxxx:

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- údaje x xxxxxxxx zkoušené xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx xxxx koncentrací xxxxxxxx xxxxx x xxxxxx nebo xxxx (xxx) na odpovídající xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- metody xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

- xxxxx xxxxxxxxxxxxx x mitose xxxxxxxx x xxxxx x xxxxx xxxxxxxx xxxxxx,

- typ x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- celkový počet xxxxxxx xx xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole,

- dosavadní xxxxx x negativní xxxxxxxx x rozpětími, xxxxxxxxx hodnotami x xxxxxxxxxxxx odchylkami,

- xxxxx x xxxxxxxx pozitivní xxxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. D., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Spermatogonia xx Xxxxxxxx Xxxxxxxx Related xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Part X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Mutagenesis, Ramel, X., Xxxxxxx, X., Xxxxxxxxx, X. (xxx) Xxxx, Xxx Xxxx, 477-484.

2) Xxxxx, X. X., (1984), Cytogenetic xxxxx xx Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Practical Xxxxxxxx, (xx.) X. Xxxxxx, X. M. Xxxxx, XXX Xxxxx, Oxford, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, X. X., Xxxxxxx, X., Ford, X. X. (1964), Xx Xxx-xxxxxx Xxxxxx xxx Xxxxxxx Preparations xxxx Mammalian Testes, Xxxxxxxxxxxx Xxxx Genetics, 3, 289-294.

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

5) Xxxxxxxx, K., Kikuchi, X. (1978), A Xxx Method xxx Xxxxxxxxxxx of Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 52, 207-209.

6) Xxxxx, X. X., Xxxxxx M. D., Xxxxxxx, J., Favor, X., Xxxxxxxx, W., Xxxxxxxxxxxx, F., Xxxxxxx, X., Xxxxxx N. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures. Xxxxxxx Xxxxxx xx xxx Xxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxx Tests, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, R. X., Xxxxx, X. X., Xxxxxx, X. R., Xxxxxx, X. X., Xxx, X., Esdaile, X. J., Gatehouse, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, D. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Dose Xxxxxxx in In xxxx Mutagenicity Assays, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. P., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Richold, X., Xxxxxxxx, X. X., Xxxxxx J. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Test Xxxx. XXXXX Subcommittee xx Xxxxxxxxxx for Mutagenicity Xxxxxxx, Xxxxxx, Part XXX. Cambridge University Xxxxx, Cambridge, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4G

"B.39 ZKOUŠKA XX XXXXXXXXXXXX SYNTÉZU XXX (XXX) V XXXXXXXXX XXXXXXX XXXXX XX XXXX

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx XXXX XX 486 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx savců xx xxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx syntézu DNA (XXX) x xxxxxxxxx xxxxxxx savců xx xxxx xx identifikovat xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxx XXX x xxxxxxxxx buňkách xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

Xxxx xxxxxxx xx xxxx xxxxxxxxx metodu vyšetření xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx x játrech. Xxxxxxxxxxx jev xx xxxxxxxxxx poškození XXX x xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, xxx xxxx absorbované xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx xxxxxx xxx xxxxxxxxx míry poškození XXX in xxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, xx se xxxxxxxx xxxxx xxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx DNA (UDS) xx zhodnotí stanovením xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Nejrozšířenější xxxxxxxxx je autoradiografické xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx tritiem (3X-XxX). Xxx xxxxxxx xx XXX xx xxxx xx xxxxxxxxxx xxxxxxxxx xxxxx potkana. Xxxx xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, nejsou xxxx xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX xxxxxx xx xxxxx xxxx XXX xxxxxxxxxxx a xxxxxxxxxxx v xxxxx xxxxxxxxx. Zkouška xx XXX xx xxxx xxxxxx xxxxxxx xxx xxxxxxx xxxxxxxx reparací ("xxxx-xxxxx xxxxxx") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx xx tři xxxx) xxxx xxxxxxx xxxx detekovány x xxxxxx menší citlivostí. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx reparace, chybné xxxxxxxx nebo xxxxxx xxxxxxxxx xxxx XXX xxxxx k xxxxxxxxxx xxxxxxxxx. Rozsah odpovědi XXX neposkytuje xxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX není opraveno xxxxxxxxxxx reparací. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx xxxxxxx xxxxxxxxx x xxxxxxxxx aktivitě, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx xx vyšetřován x xxxxx xxxxxx.

Xxx xxxx obecný xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : čistý xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX), xxxxx xxx xxxxxxxxxx xxxxxxx stanovená xxxxxxxxxx xxxxxxxxxxx xxxxxxx.

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

Xxxxxxxxxxx xxxxxxx XXX (UDS) : Xxxxxxx xxxxxxxx XXX xx vyštěpení a xxxxxxxxxx xxxxx DNA xxxxxxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxxxxxx XXX po vyštěpení x xxxxxxxxxx úseku XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx obvykle xxxxxxxx xx xxxxxxxxxxx 3X-XxX xx XXX xxxxxxxxx xxxxx, xxx je xxxx xxxxxxx xxxxx x S-fázi buněčného xxxxx. Inkorporace 3X-XxX xx obvykle xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx xxxx tak xxxxxxx xx vliv X-xxxx xxxxx xxxx xxxx. xxxxxxx scintilační xxxxxxxxxxxxx.

1.4 POPIS XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr druhu xxxxxxx

Xxxxx xx používán xxxxxx, ačkoli lze xxxxxx jakýkoli xxxxxx xxxx xxxxx. Měly xx xxx použity xxxxx xxxxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx dospělých zvířat. X xxxxxxxx zahájení xxxxxx xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % střední xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx měly být xxxxxxxxxx tak, aby xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx identifikují x před xxxxxxxxx xxxxxx se nechají x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx nebo suspendovány xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx podávány xxxxx xxxx xxxxx být xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx vyloučeno xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxxxxx zvážit xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxx xxxxxxxxx xxxxxxxxx části xxxxxxxxxxx xx měly xxx souběžné pozitivní x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx látky xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx ve skupinách, x nichž xxxxx x xxxxxxxx.

Xxxxxxxxxxx kontrolami xx xxxx xxx xxxxx, o xxxxx xx xxxxx, xx xxxxxx podávání x xxxxxxxxxxx expozičních xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx nad xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx metabolickou xxxxxxxx xx měly xxx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx odpověď (4). Dávky xxxxx xxx xxxxxxx tak, xxx byl xxxxxx xxxxxxxx, ale xxx xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx odběru

Látka

Číslo XXX

Xxxxx xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 xx 4 h)

N-nitrosodimethylamin

62–75–9

200–249–8

Pozdní xxxx xxxxxx (12 xx 16 h)

N-(fluoren-2-yl)acetamid (2-XXX)

53–96–3

200–188–6

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

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx xxxxxx

Xxx xx xxx xxxxxx xxxxxxxxxx xxxxx zvířat, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx. Každá xxxxxxx xx xx xxxx skládat xxxxxxx xx xxx analyzovatelných xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx pro xxxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxx nezbytné xxxxx jedno xx xxx zvířata.

Jestliže xxxx x době xxxxxx x xxxxxxxxx xxxxx xx studií xx xxxxxxx xxxxxx a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx, nejlépe xxxxx. Xx-xx expozice xxxxxxx xxxxxxxxxx pro určité xxxxxxx, jako je xxxx xxxxxxxxx x xxxxxxxxx farmaceutických xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx expozice

Zkoušené xxxxx xxxx zpravidla xxxxxxxx xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx xxxxxxxxxx xxxxxxxx xx používají xxxxxxx xxx úrovně xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx vyvolávající takové xxxxxx toxicity, xx xxxxx dávky xx xxxxx podle xxxxxxxxx xxx stejném xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx by xxxx xxx zpravidla 50 % xx 25 % vyšší xxxxx.

Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx netoxických xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx vyhovovat x xxxx by xxx hodnoceny xxxxxx xx xxxxxxx. Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx zjištění xxxxxxx, měla by xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx x hlavní studii.

Nejvyšší xxxxx xxxx xxx xxxxxxxxxx xxxx xxxx xxxxx vyvolávající xxxxxx xxxxxxxx v xxxxxxx (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže zkouška x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx jednorázově xxxx xx xxxx xxxxxxx x jednom dni xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx o látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx být xxxxx xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx zkoušce xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx obvykle podává xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx jsou možné, xxx-xx xx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx xxxxxxxxxxxx, neboť xx xxxxx mohla xxx xxxxxxxxxx zkoušené xxxxx xxxxx x xxxxxx prostřednictvím xxxxxxxxx xxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí na xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx jaterních xxxxx

Xxxxxxx xxxxx se xxxxxxxxxx x exponovaných xxxxxx xxxxxxxxx 12 xx 16 hodin xx podání xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (xxxxxx dvě xx xxxxx hodiny xx expozici) je xxxxxxxx, není-li xx 12 až 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx použity xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx kolagenasou xx xxxx x xxxxxx xx, xxx xx xxxxxxx disociované xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx x xxxxxxxxx kontroly by xxxx vykazovat xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Stanovení XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxx xxxx, xxxx. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx inkubační xxxx by xxxx xxx médium z xxxxx xxxxxxxxxx a xxxxx xxxx xxxxx xxx inkubovány s xxxxxx obsahujícím xxxxxxxx xxxxxxxxxxx xxxxxxxxx, aby xxxx snížena xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx poté xxxxxxx, fixují a xxxxxx. Při xxxxx xxxxxxxxx době xxxxxx xxx snížení xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx se x xxxxx (např. x xxxxxx 7 xx 14 xxx), xxxxxxxx xx, xxxxxx x spočítají xx xxxxxxxxxx xxxx xxxxxxx. X každého zvířete xx připraví xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx by měly xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx normálních buněk, xxx xxxx xxxxxxxxx XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx se xxx xxxxxxxxxxx xxxxxxxxxx na xxxxxx zjevné xxxxxxxxxxxx (xxxx. na xxxxxxx, xxxxxxxx xxxxxx značení xxxxxxxxxxxxx xxxxxxxx).

Xxxx počítáním xxx by měly xxx xxxxxxxxx kódovány. Xxxxxxxxx se vyšetřuje 100 xxxxx na xxxxx zvíře alespoň xx xxxx preparátů; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx xx xxxx xxx zdůvodněno. Xxx počítání xxx xx xxxxx x X-xxxx xxxxxxxxxxx, xxx xxxxx xxxxx x X-xxxx xxxx být xxxxxxxxxx.

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

Xxxxx xxxxx xx xxxxxxx z xxxxx xxx odpovídajících xxxxxxxx jádrŭm (xx) x x prŭměrného xxxxx zrn x xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx xxxxŭx. jako xxxxxxx xx xx xxxxxxx xxx xxxxx xxxxx xxx nejsilněji xxxxxxxxx oblast xxxxxxxxxx, xxxx xxŭxxxxx xxxxxxx xxxx xx tří xxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx použity x xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx preparáty x xxxxxxx. Xxxxx xx xxxx xxx xxxx xxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxx hodnoty XX od xxxxxxx XX xx xxx xxx xxxxxxxx xxx xxxxxx xxxxx, pro xxxxx zvíře a xxx xxxxxx dávku x xxx xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrům (XXX). Xxxxxxxx xxxx počítány "xxxxxxxxxx" xxxxx, xxxx xx xxx kritéria xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx odůvodněna a xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx údajích x negativních xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx zhodnoceny xxxxxxxxxxxxx xxxxxxxx. Mají-li xxx xxxxxxx, xxxx by xxx statistické xxxxx xxxxxxx x odůvodněny xxxx xxxxxxxxxx xxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx pozitivní xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX xxxx nad xxxxxxxx xxxxxx, která xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxx údajů xxxxxxxxxx;

xxxx

xx)

xxxxxxx NNG xx xxxxxxxx xxxxx xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx NNG leží xx dosavadní xxxxxxx xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx NNG není xxxxxxxx xxxxx xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, tj. měly xx xxx vzaty x úvahu parametry, xxxx xxxx variabilita xxxxxx, xxxxx dávky x xxxxxxxx a xxxxxxxxxxxx. Xxx hodnocení xxxxxxxx zkoušky xxxxx xxx použity jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx však xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx většina experimentů xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx soubor údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx zkoušené xxxxx. Výsledky mohou xxxxxx xxxxxxxxxx nebo xxxxxx bez xxxxxx xx to, xxxxxxxx xx experiment opakován.

Pozitivní xxxxxxxx zkoušky xx XXX v xxxxxxxxx xxxxxxx xxxxx in xxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x xxxxxxxxx xxxxxxx xxxxx xx vivo xxxxxxxxx XXX, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx XXX xx xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xx podmínek xxxxxxx neindukuje xxxxxxxxx XXX, které xxx xxxxxxxxx touto xxxxxxxx.

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

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- zdroj, podmínky xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (vehikulum/rozpouštědlo) kontroly,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

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

- podrobné údaje x xxxxxxx krmiva x xxxx,

- podrobný xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- metody xxxxxxxx x kultivace xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxx možnosti xxxxxxxxx odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- xxxxxx toxicity,

- xxxxx x xxxxxxxx xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx kontrole,

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

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

- počet xxxxx v X-xxxx, xx-xx stanoven,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. Lefevre, X. A., Xxxxxxxxx, X., Penman, M. X. (1985), An Xxxxxxxxxx of xxx Xx vivo Xxx. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Xxxxxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1987), X Xxxxxxxx and Xxxxx xxx xxx Xx xxxx Xxx Xxxxxxxxxx DNA Repair Xxxxx, Xxxxxxxxxx Res., 189, 123-133.

3) Kennelly, X. X., Xxxxxx, X., Ashby, X., Xxxxxxx, P. X., Xxxxxxxxx, X., Xxxxxxx, X. X., Xxxx, X. X., Mitchell, X. de X. (1993), Xx vivo Xxx Liver XXX Xxxxx, in: Xxxxxxxx X. X., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Part XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, S., Dean, X. X., Andrac, X., Brambilla. X., Xxxxxxxxx, X., Xxxxxxxxx, X. J., Furihata, X., Xxxxxxx, T., XxXxxxx, X. A., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx of UDS Xxxxx Xx xxxxx xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

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

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


XXXXXXX 5

OBECNÉ POŽADAVKY XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X XXXXXXXXX

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


XXXXXXX 6

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XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx xx xxxxxxx odolných xxxxx xxxxxxxx dětmi

Kromě xxxxxxxxxx xx. 22 odst. 1 písm. e) xxxx xxxxxxxx, xxxx xxx xxxxx x xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, s xxxxx xx xxxxxxx xxxxxx xxx vdechování (Xn; X 65) x xxxxx jsou xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx směrnice, x xxxxxxxx látek xxxxxxxxx xx xxx xx xxxxx xxxxxxxx xxxx x xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx dětmi.

1. Xxxxxxxxx uzavíratelné xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx obalech xxxx splňovat xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx dne 1. xxxxxxxx 1989) "Xxxxx xxxxxx xxxxx — Požadavky xx xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxx xxxxxxxx" xxxxxxxx Mezinárodní xxxxxxxxxx pro normalizaci (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx dětmi použité xx opakovaně neuzavíratelných xxxxxxx xxxx splňovat xxxxxxxxx normy XXX XX 862 (xxxxxx x března 1997) "Xxxxx — Xxxxx xxxxxx dětem — Xxxxxxxxx x xxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx obaly xxxxxx xxx xxxxxxxxxxxxxxx výrobků" xxxxxxxx Xxxxxxxxx xxxxxxx xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Prokázání xxxxx x xxxx xxxxxxxxx xxxxxxx xxxxx osvědčovat xxxxx xxxxxxxxxx, které xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx zřejmé, xx obal je xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx xx xxxxxxx xxxxxx x xxxxxx bez xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx všech xxxxxxxxx xxxxxxxxx a xxxxx existují xxxxxxxxx xxxxxx k xxxxxxxx x bezpečnosti xxxxxxx xxx xxxx, může xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx xxxxx xxxxxxxxx xx xxxxxxx výrobku xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx buď

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

xxxx

- xx xxxxxx xxx xxxxxxx x byl xxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx výstrah

Technické xxxxxxxxxxx xxx hmatatelné výstrahy xxxx xxx v xxxxxxx x xxxxxx XX ISO 11683 (xxxxxx x roku 1997) "Obaly — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Požadavky".

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