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Xxxxxxxx Komise 2000/32/ES

ze xxx 19. xxxxxx 2000,

xxxxxx xx xx xxxxxxx xxxxx přizpůsobuje xxxxxxxxxxx pokroku xxxxxxxx Xxxx 67/548/XXX x xxxxxxxxxx právních x xxxxxxxxx předpisů týkajících xx xxxxxxxxxxx, xxxxxx x označování nebezpečných xxxxx [1]

(Xxxx s xxxxxxxx xxx EHP)

KOMISE XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx na xxxxxxxx Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx a xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], naposledy pozměněnou xxxxxxxx Xxxxxxxxxx parlamentu x Xxxx 1999/33/XX [3], a xxxxxxx xx článek 28 xxxxxxx směrnice,

vzhledem k xxxxx xxxxxxx:

(1) Xxxxxxx X xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxx xxxxxxxx s xxxxxxxxxx xxxxx o xxxxxxxxxxx x xxxxxxxxxx xxxxx látky. Xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, xx xx xxx xxx xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx příloze xxxxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a tabulky X x xxxxxxx X.

(2) Xxxxxxx III xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx xxxxxxxxxxx xxxxxx zvláštních xxxxx xxxxxxxxx s nebezpečnými xxxxxxx x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje xxxxxx xxx x xxxxxxxxxxxxxx xxxxxx xxxxxxxxxx se xxxxxxxxxxxx xxxxx x xxxxxxxxx. Příloha XX xxxxxxxx 67/548/XXX obsahuje xxxxx ke klasifikaci x k xxxxxxxxxx xxxxxxxxxxxx látek a xxxxxxxxx. Některé jazykové xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, XX x XX.

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

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx proti otevření xxxxx. Xxxx předpisy xx měly xxx xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx xxxxxxxx rozšířit xxxxxx, kde xx xxxxxxx odolné xxxxx xxxxxxxx xxxxx xxxxxxxxx.

(5) Xxxxxxxx xxxx směrnice xxxx x souladu xx stanoviskem Xxxxxx xxx přizpůsobení technickému xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xx xxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx,

XXXXXXX TUTO XXXXXXXX:

Xxxxxx 1

Xxxxxxxx 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx I xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxxxx v předmluvě xx nahrazuje xxxxxxxxx X x příloze 1X xxxx xxxxxxxx;

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

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

x) xxxxxxxx xx xxxxxxx x xxxxxxx 1X této xxxxxxxx.

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

3. Xxxxxxx IV xx xxxx xxxxx:

x) odpovídající xxxxxx v xxxxxxx XX se xxxxxxxxx xxxxxxxxxxxx xxxxxx pro xxxxxxxx xxxxxxxxx x xxxxxxx 3X této xxxxxxxx;

x) xxxxxxxxxxxx pokyny x xxxxxxx IV xx nahrazují kombinovanými xxxxxxxxxxxx pokyny xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3X xxxx xxxxxxxx.

4. Xxxx X xxxxxxx X xx xxxx xxxxx:

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

x) xxxxxxxx X.11 xx xxxxxxxxx xxxxxx v xxxxxxx 4X této xxxxxxxx;

x) kapitola X.12 xx nahrazuje textem x xxxxxxx 4X xxxx xxxxxxxx;

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

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

f) xxxxxxxx X.23 se xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx. Xxxxx xxxxxxxx X.23 xx xxxxxxxxxxx xx mění xxxxxxxxxxxxx xxxxxxxx;

x) xxxxxx se xxxx x xxxxxxx 4X xxxx směrnice.

5. Xxxxxxx xx xxxxxx xxxxxxx xxxxxxxx xxxxx x části X xxxxxxx X.

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

7. Xxxxxxx XX se xxxx způsobem xxxxxxxx x xxxxxxx 6 xxxx xxxxxxxx.

Článek 2

1. Xxxxxxx xxxxx xxxxxx x xxxxxxxx právní a xxxxxxx xxxxxxxx nezbytné xxx dosažení xxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x xxxx xxxxxxx Xxxxxx.

Xxxx xxxxxxxx přijaté xxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx na xxxx xxxxxxxx xxxx xxxx xxxxxx odkaz xxx xxxxxx při xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx odkazu si xxxxxxx xxxxxxx státy.

2. Xxxxxxx xxxxx xxxxx Xxxxxx xxxxx hlavních xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x xxxxxxx xxxxxxxxxx xxxx xxxxxxxx, x xxxxxxxxxx xxxxxxx mezi xxxxxxxx a přijatými xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Xxxx směrnice xxxxxxxx v xxxxxxxx xxxxxx xxxx xx xxxxxxxxx v Úředním xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.

Xxxxxx 4

Xxxx xxxxxxxx xx určena xxxxxxxx xxxxxx.

X Xxxxxxx dne 19. xxxxxx 2000.

Za Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise


[1] Přijato po xxxxxxxxxxxx po xxxxxxx xxxxx.

[2] Úř. věst. 196, 16.8.1967, x. 1.

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


XXXXXXX 1X

XXXXXXXXX X XXXXXXX I

Vysvětlení xxxxxxxx xxxxxxxxxx xx identifikace, xxxxxxxxxxx x označování xxxxx

(Xxxxxx se xxxxxxx xxxxx)


XXXXXXX 1X

"XXXXXXX X

X

Xxxxxx

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

18

Xx

Xxxxx

Xxxxx

Xxxxx

Αργό

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"


XXXXXXX 1C

Indexové xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx k látkám

Číslo XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–011–00–7

xxxxxxxx (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

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

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 R31 X; X34 R43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

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

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

006–016–00–4

propoxur (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

204–043–8

114–26–1

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; R26/28 X; X24 X; X50–53

X+; X R: 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 N; X50–53

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

006–019–00–0

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

218–961–1

2303–16–4

Karc. xxx. 3; R40 Xn; X22 N; R50–53

Xn; X R: 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; R22 X43 N; X50–53

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

006–023–00–2

merkaptodimethur (XXX) xxxxxxxxxx 3,5-dimethyl-4-(methylsulfanyl)fenyl-N -xxxxxxxxxxxxxx

217–991–2

2032–65–7

X; X25 X; X50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xi; X38 X; R51–53

Xn; X X: 22–38–51/53 X: (2-)13-61

006–026–00–9

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

216–353–0

1563–66–2

X+; R26/28 X; X50–53

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

006–028–00-X

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

213–546–1

973–21–7

X; X25 X; X50–53

X; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; X25 N; X51–53

X; X X: 25–51/53 S: (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 S: 60-61

006–034–00–2

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

214–215–4

1114–71–2

Xx; X22 N; 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 X; R50–53

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

006–037–00–9

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

220–113–0

2631–37–0

X; X25 N; X50–53

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

006–038–00–4

xxxxxxxxx (XXX) 2-chlorallyl-N,N-dimethyldithiokarbamát

E

202–388–9

95–06–7

Karc. xxx. 2; X45 Xx; X22 X; X50–53

X; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; R22–48/22 R43 X; X50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; X40 Xx; X22 N; X50–53

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

006–043–00–1

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

140–41–0

Xx; R36/38 Xxxx. xxx. 3; X40 X; X50–53

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

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 X; X50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; X23/25 Xx; X21 N; X50–53

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

006–047–00–3

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

8065–36–9

X; R24/25 X; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

006–050–00–X

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

4482–55–7

Xi; R38 X; X50–53

Xx; X X: 38–50/53 S: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xn; X21 X; R50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; N X: 22–51/53 S: (2-)24-61

006–060–00–4

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

226–066–2

5259–88–1

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

006–069–00–3

xxxxxxxxx-xxxxxx (ISO) 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 S: (2-)36/37–60–61

006–070–00–9

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

262–302–0

60568–05–0

Xxxx. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

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

82560–54–1

X; X23/25 N; X50–53

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

007–012–00–5

N,N-dimethylhydrazin 1,1-dimethylhydrazin

E

200–316–0

57–14–7

F; X11 Karc. kat. 2; R45 X; X23/25 X; X34 X; X51–53

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

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-xxxxxxxxxxxxxxxx

X

540–73–8

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

X; X X: 45–23/24/25–51/53 X: 53–45–61

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

009–003–00–1

xxxxxxxx fluorovodíková … %

X

231–634–8

7664–39–3

X+; R26/27/28 X; X35

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

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

015–039–00–9

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

201–676–1

86–50–0

T+; X26/28 X; R24 X43 X; R50–53

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

015–048–00–8

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

200–231–9

55–38–9

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

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

015–056–00–1

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

220–147–6

2642–71–9

X+; X28 X; R24 X; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xx; X21 X; X50–53

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

016–013–00-X

xxxxxxx sirnatý

234–129–0

10545–99–0

R14 X; X34 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; R36/37/38

016–014–00–5

chlorid xxxxxxxx

13451–08–6

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 % ≤ X &xx; 10 %: Xx; R36/37/38

016–023–00–4

dimethyl-sulfát

E

201–058–1

77–78–1

Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; R26 X; X25 X; R34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (ISO) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

R43

Xi X: 43 S: (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 %: C; 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 X; X50–53

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

050–002–00–0

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

236–049–1

13121–70–5

Xx; X20/21/22 X; X50–53

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

050–012–00–5

xxxxxxxxxxxxxxxxxxxxxx [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] butyl(tricyklohexyl)stannan [3]

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

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

Xx; X20/21/22 X; X50–53

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

X ≥ 1 %: Xn; R20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

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

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

082–009–00–X

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

215–693–7

1344–37–2

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

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

1

082–010–00–5

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

235–759–9

12656–85–8

Karc. xxx. 3; X40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 R33 N; X50–53

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

1

601–024–00-X

kumen [1] propylbenzen [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

R10 Xx; X65 Xx; X37 X; R51–53

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

4

601–032–00–3

xxxxx[x]xxxxx benzo[def]chrysen

200–028–5

50–32–8

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

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

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. xxx.2; X45 N; R50–53

T; X X: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 X; X50–53

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

602–054–00–6

3-xxxxxxx-1-xx 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 Xx; X21–48/22 X; X34

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

X ≥ 50 %: X; R21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ C &xx; 25 %: Xx; R20/22–48/22 3 % ≤ X &xx; 10 %: Xx; X20/22

603–091–00–0

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

402–470–6

87172–89–2

X; X8 Xx; R22 Xx; 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; R51–53

Xn; X X: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; R36 X52–53

Xx X:36–52/53 S: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx

200–661–7

67–63–0

X; R11 Xx; R36 R67

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

604–020–00–6

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

201–993–5

90–43–7

Xx; X36/37/38 X; R50

Xi; X X: 36/37/38–50 S: (2-)22-61

604–021–00–1

2-xxxxxxxxxx, sodná sůl xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx sodný xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; X22 Xx; X37/38–41 X; R50

Xn; X X: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

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

401–720–1

6807–17–6

Repr. xxx. 2; R60 Xx; R36 X; X50–53

X; X R: 60–36–50/53 X: 53–45–60–61

604–041–00–0

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

256–634–5 [1] 263–560–7 [2]

50594–66–6 [1] 62476–59–9 [2]

Xx; X22 Xx; R38–41 N; X50–53

Xx; X R: 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 hydrochinonmonomethylether

205–769–8

150–76–5

Xn; X22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

Xxxx. xxx. 3; X40 Xx; R20 Xx; R36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

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

606–016–00-X

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

201–462–8

83–26–1

X; R25–48/25 X; R50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xn; X22 Xi; X36/38 X; R50–53

Xn; X X: 22–36/38–50/53 S: (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-dekachlorpentacyklo[5.3.0.02,6.04,10.05,9]dekan-3-on

205–601–3

143–50–0

Karc. kat. 3; R40 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-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx

244–209–7

21087–64–9

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

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

216–920–2

1698–60–8

R43 X; X50–53

Xx; N R: 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 R43 X; X50–53

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

606–037–00–4

xxxxxxxxxxx (XXX) 1-(4-xxxxxxxxxxx)- 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; X36 X; X50–53

Xx; X X: 22–36–50/53 S: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; R22 Xx; X41 X52–53

Xx; N X: 22–41–52/53 X: (2-)26-61

607–057–00–6

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

201–378–1

81–82–3

Xx; R48/22 R52–53

Xn X:48/22–52/53 X: (2-)37-61

607–058–00–1

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

204–195–5

117–52–2

X; X25–48/25 X52–53

X X:25–48/25–52/53 X: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx 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 Xx; X22 N; R51–53

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

607–097–00–4

xxxxxx-1,2,4-xxxxxxxxx-1,2-xxxxxxxx 1,2-anhydrid xxxxxx-1,2,4-xxxxxxxxxxxxxx kyseliny 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 valerová xxxxxxxx

203–677–2

109–52–4

X; X34 X52–53

X X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xn; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; R36/38 X52–53

Xx X:36/38–52/53 X: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xn; X22 Xx; R38 X; X50–53

Xx; X X: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; X25 Xx; X38 X; X50

X; N R: 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; R50–53

Xn; X X: 22–50/53 X: (2-)60-61

607–176–00–3

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

400–830–7

R43 X; R51–53

Xi; X X: 43–51/53 S: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

Xxxx: X,X′-xxxxxxxxxxx-xxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx)

403–030–6

Xx; X22 X43 X; R50–53

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

607–213–00–3

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

403–320–2

67567–23–1

X; X2 X; X7 X10 X; X51–53

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

607–217–00–5

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

403–960–2

R43 X53

Xx X: 43-53 S: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] bis(2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]

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

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

X52–53

X: 52/53 X: 61

607–248–00–4

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

205–073–4

132–67–2

Xx; R22

Xn X: 22 S: (2)

607–249–00-X

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

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

607–252–00–6

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

415–130–7

91465–08–6

X+; X26 X; X25 Xn; X21 N; X50–53

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

607–255–00–2

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

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

akrylonitril

D E

203–466–5

107–13–1

F; Xxx Karc. kat. 2; R45 X; X23/24/25 Xx; X37/38–41 X43 X; X51–53

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

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 X; R50–53

Xi; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; X28 X; R24 X44 X; R50–53

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

609–040–00–9

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

E

217–406–0

1836–75–5

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

X; N X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 R43 X; X50–53

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

611–008–00–4

4-aminoazobenzen 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. kat. 2; X45 X; X50–53

X; X R: 45–50/53 X: 53–45–60–61

611–013–00–1

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

403–650–7

117409–78–6

E; X2 N; R51–53

E; X R: 2–51/53 X: (2-)35-61

611–031–00-X

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

209–321–2

569–61–9

Xxxx. kat. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-xxxxxxxxxxxxx o-anisidin

E

201–963–1

90–04–0

Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X; R23/24/25

T X: 45–23/24/25 X: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; R22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

X ≥ 25 %: T; X45–22 0,01 % ≤ X < 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. kat. 2; X45 Xxxx. xxx. 3; R40 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

Xxxx. xxx. 2; R45 Xx; R22 X; X51–53

X; X X: 45–22–51/53 X: 53–45–61

612–099–00–3

4-methyl-m-fenylendiamin4-methyl-1,3-fenylendiamin4-methylbenzen-1,3-diamin 2,4-xxxxxxxxxxxx

X

202–453–1

95–80–7

Xxxx. xxx. 2; X45 T; X25 Xx; X21 Xx; X36 R43 X; X51–53

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

612–105–00–4

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

205–411–0

140–31–8

Xx; X21/22 C; 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 Xn; X21/22 X43 X; X51–53

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

612–125–00–3

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

202–442–1

95–70–5

X; X25 Xx; X20/21 X43 X; X51–53

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

612–144–00–7

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

62924–70–3

Xx; X36/38 R4 3 X; R50–53

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

612–151–00–5

diaminotoluen toluendiamin xxxxxxxxxxxxxxxxxxx methylbenzendiamin

E

246–910–3

25376–45–8

Karc. kat. 2; X45 X; X25 Xx; X20/21 Xx; X36 X43 X; X51–53

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

613–018–00–4

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

7411–47–4

Xn; X22 Xx; X36/37/38 X52–53

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

613–031–00–5

symklosen trichlorisokyanurová xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-trichlor-1,3,5-triazin-2(1H), 4(3X), 6(5H)-trion

201–782–8

87–90–1

O; X8 Xx; X22 X31 Xx; X36/37 N; X50–53

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

613–038–00–3

6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx xxxxxxxxxxxxx

202–095–6

91–76–9

Xx; X22 R52–53

Xn R:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 X; R41 X; R50–53

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

613–043–00–0

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

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xx; X41 X; X50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 X; X50–53

Xx; N X: 22–50/53 X: (2-)60-61

613–091–00–2

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

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; X22 Xx; X36/37/38 X52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; X34 X; X51–53

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

613–130–00–3

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

79983–71–4

R43 X; X51–53

Xx; N X: 43–51/53 S: (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 R52–53

Xn X:22–52/53 S: (2-)61

613–134–00–5

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

88671–89–0

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

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

613–137–00–1

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

242–505–0

18691–97–9

X; X50–53

X X: 50/53 X: 60-61

613–139–00–2

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

74223–64–6

N; R50–53

N X: 50/53 X: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; X25 X; X51–53

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

614–006–00–1

xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx

206–614–7

357–57–3

X+; X26/28 X52–53

X+ X:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; R26/28 R52–53

T+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-methyl-1,3-fenylendiisokyanát [1] 4-methyl-m-fenylendiisokyanát [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] m-tolylidendiisokyanát [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] toluen-2,4-diisokyanát [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 X+; X26 Xx; X36/37/38 X42/43 X52–53

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

C320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; R26–40–42/43 1 % ≤ C &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 X31 X; X34 X42

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

616–034–00-X

xxxxxxxxxxxx (XXX) 6-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 -[(ethylamino)karbonyl]-2-kyan-2-(methoxyimino)acetamid 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx

261–043–0

57966–95–7

Xx; X22 R43 X; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; X7 Xn; X22 C; R34 X; R50–53

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

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

617–006–00-X

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

201–279–3

80–43–3

X; R7 Xx; R36/38 X; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xx; X36 R43

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

650–007–00–3

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

228–200–5

6164–98–3

Xxxx. xxx. 3; X40 Xn; X21/22 X; R50–53

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

650–008–00–9

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

227–197–8

5707–69–7

X; R25 X; X50–53

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

650–009–00–4

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

243–269–1

19750–95–9

Xxxx. xxx. 3; X40 Xx; X22 X; X50–53

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

650–033–00–5

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

66230–04–4

T; X23/25 X43 X; X50–53

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

650–041–00–9

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

82097–50–5

N; X50–53

X X: 50/53 X: 60-61


XXXXXXX 1D

Indexové číslo

Chemický xxxxx

Xxxxxxxx k 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 X52–53

Xx X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

Xxxx: 1,3-xx(xxx-5-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx x 1,3-di(hex-x-en-1-yl)- 1,1,3,3-tetramethyldisiloxan

406–490–6

N; X51–53

X R: 51/53 X: 61

015–164–00–9

kalcium-dihydrogen-(1-hydroxyethylen)bisfosfonát dihydrát

400–480–5

36669–85–9

R52–53

R:52/53 X: 61

015–165–00–4

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

404–986–7

Xx; X41 X; X50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[hydroxy(fenyl)fosfinoyl]propanová xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; X50

X R: 50 X: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 X; R51–53

Xi; X R: 38–51/53 X: (2-)37-61

602–083–00–4

pentabromderivát difenyletheru xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 X64 X; R50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X R: 52/53–59 X: 59-61

603–128–00–0

2-(xxxxxxxxxxxx)xxxxxxxx

405–490–3

613–62–7

X53

X:53 X: 61

603–129–00–6

1-xxxx-xxxxxxxxxxxx-2-xx

406–180–0

57018–52–7

X10 Xi; X41

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

603–130–00–1

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

406–325–8

Xx; R22 X52–53

Xx X:22–52/53 S: (2-)39-61

603–131–00–7

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

407–290–1

Xx; X41

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

603–132–00–2

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

408–200–3

63187–91–7

Xx; X38–41 X52–53

Xx X:38–41–52/53 S: (2-)26–37/39–61

603–133–00–8

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

408–240–1

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

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

410–450–3

X53

X: 53 X: 61

603–135–00–9

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

410–500–4

Xx; R41 N; X51–53

Xx; X X: 41–51/53 X: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

R43 X52–53

Xx R:43–52/53 S: (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-dimethyl-3-hydroxypropyl)toluen 2,2-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx

403–140–4

103694–68–4

X52–53

X:52/53 X: 61

604–050–00-X

4-xxxxx-x-xxxxxx 4-chlor-2-methylfenol

216–381–3

1570–64–5

T; X23 C; X 35 X; R50

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

X ≥ 25 %: X; X; X23–35 10 % ≤ X < 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 X: 61

604–052–00–0

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

403–800–1

103597–45–1

X53

X:53 S: 61

604–053–00–6

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

410–760–9

157661–93–3

Xx; X38 X43 X; R50–53

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

604–054–00–1

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

412–020–0

X43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

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

410–480–7

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxx-1-xx

4–406–670–4

61203–83–6

X; X51–53

X X: 51/53 X: 61

606–052–00–6

4-(X, N-dibutylamino)-2-hydroxy-2'-karboxybenzofenon 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx xxxxxxxx

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

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

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

N; X50–53

X X: 50/53 X: 60-61

607–273–00–0

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

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

R43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–275–00–1

natrium-4-(benzoyloxy)benzen-1-sulfonát

405–450–5

66531–87–1

R43

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

607–276–00–7

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

405–635–0

Xx; X38–41 N; X50–53

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

607–277–00–2

Směs:2-(hexylsulfanyl)ethylamin-hydrochlorid a xxxxxxx-xxxxxxxxx

405–720–2

Xx; X22 Xx; X41 X43 N; X51–53

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

607–278–00–8

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

405–760–0

Xx; X41 R43 R52–53

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

607–279–00–3

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

405–960–8

R43 X; X51–53

Xx; X X: 43–51/53 S: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xx; X22 Xi; R36 X43

Xx R: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

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

407–000–3

127519–17–9

X; X51–53

X X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 X: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xx; X38–41 R43 N; X50–53

Xx; X X: 21/22–38–41–43–50/53 S: (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

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

410–065–0

R43

Xi X: 43 X: (2-)22–24–37

607–286–00–1

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

410–070–8

141880–36–6

X43 X52–53

Xx R:43–52/53 X: (2-)22–24–37–61

607–287–00–7

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

410–140–8

X52–53

X:52/53 S: 61

607–288–00–2

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

410–160–7

148732–74–5

Xi; X36 X43 X52–53

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

607–288–00–8

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

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

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

410–540–2

Xx; X38 R43 X; X50–53

Xx; X X: 38–43–50/53 S: (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

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

410–640–6

Xi; X38–41 N; R50–53

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

607–293–00-XXxxx:

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

410–650–0

Xx; R41 X43 X; X51–53

Xx; X X: 41–43–51/53 S: (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 a 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

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

410–830–9

X53

X: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; R41

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

607–298–00–7

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

411–010–3

X43

Xx X: 43 S: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 R43 X; R50–53

Xn; X 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, d-sulfonatoftalocyanin]měďnatý xxxxxxx, xxxxxxxx xxx; x = 1,2,3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 15, 16, 17 nebo 18, x = 22, 23, 24 xxxx 25

411–430–7

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xx; X38–41 X43 X; X51–53

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

607–302–00–7

Směs:tetradekanová xxxxxxxx a xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–910–6

Xx; X38–41 X43 X; R51–53

Xi; N X: 38–41–43–51/53 S: (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 R52–53

Xn 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 R: 50/53 X: 60-61

608–024–00–9

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

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

[2-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 O; X8 Xxxx. xxx. 2; X45 T; X23/25 X43

X; X X: 45–3–8–23/25–43 S: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 C; X34 X43 X; X50–53

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

611–043–00–5

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

402–850–1

Xx X: 41–52/53 X: (2-)26–39–61

611–044–00–0

Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx x[(4(5)-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx) (3-nitro-5-pentylbenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx

403–720–7

117527–94–3

X; 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 X: 61

N X: 51/53 S: 61

611–046–00–1

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

407–590–2

43151–99–1

X; X25 Xn; X48/22 X43 N; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 S: 61

611–048–00–2

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

407–900–6

111381–12–5

R53

R: 53 S: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

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

611–051–00–9

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

411–110–7

136213–74–6

X; X50–53

X X: 50/53 X: 60-61

611–052–00–4

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

400–720–9

X52–53

X: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; R41 X; X50–53

Xx; X R: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xx; X22–48/22 Xx; X41 X43 N; R51–53

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

612–158–00–3

Směs:[bis(5-alkyl(rozvětvený C12))-2-hydroxybenzaldoximato)]měďnatý xxxxxxx x 4-dodecyl-2-hydroxybenzaldoxim[bis(5-alkyl(rozvětvený X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx komplex x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 S: 61

612–159–00–9

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

410–880–1

Xx; X22 C; X34 X; X50–53

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

613–149–00–7

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

405–700–3

96489–71–3

X; X23/25 X; R50–53

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

613–150–00–2

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

406–295–6

X53

X:53 X: 61

613–151–00–8

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

406–360–9

104218–44–2

X53

X:53 S: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-xxxxxxxxxxxxxxx

407–270–2

16063–70–0

X52–53

X:52/53 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx X: 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 X: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; X22–48/22 Xi; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xx; X20/22 Xx; X41 X43 X; X51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; R25 Xx; X20 N; R50–53

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

613–160–00–7

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

411–000–9

125224–62–6

X43

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

615–022–00–1

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

410–550–7

79277–18–2

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

X; Xx X: 2–14–42/43–48/22 S: (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. kat. 3; X40 Xx; X20–48/22 Xx; X41 X42

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

616–044–00–4

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

402–510–2

X; R51–53

N X: 51/53 X: 61

616–045–00-X

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

405–190–2

122371–93–1

X43 X53

Xx X: 43-53 S: (2-)22–24–37–61

616–046–00–5

X -[2-(6-xxxxx-7-xxxxxxxxxxxxxx[1,5-x][1,2,4]xxxxxxx-4-xx)xxxxxx]-2-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxxxxxx

406–390–2

X; R50–53

N X: 50/53 S: 60-61

616–047–00–0

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

406–640–0

X43

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

616–048–00–6

3'-(trifluormethyl)isobutyranilid

406–740–4

1939–27–1

Xn; X48/22 N; R51–53

Xn; X X: 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 N; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

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

411–070–0

X53

X: 53 X: 61

617–015–00–9

xxx(4-xxxxxxxxxxxxx)xxxxxxx

407–950–9

895–85–2

X; X2 X; R7 X; X50–53

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

650–032–00-X

xxxxxxxxxxxx (XXX) (2X, 3X)-, (2 X, 3 X)-, (2 X, 3 X)-, (2 X, 3 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; X50–53

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


PŘÍLOHA 2

POVAHA XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI A XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX,

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


PŘÍLOHA 3A

STANDARDNÍ POKYNY XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX,

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


XXXXXXX 3B

STANDARDNÍ POKYNY XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI LÁTKAMI X PŘÍPRAVKY

Viz směrnice Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.


XXXXXXX 4A

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u xxxxx xx xxxxx má xxxxxxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x kultivovaných xxxxxxx xxxxx (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx typu, avšak xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx aberace. Xxxx xxxxxx xxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx xxxxx rutinně xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx x s xxxx související jevy xxxxxxxxxxx xxxxx v xxxxxxxxxx a v xxxxxx xxxxxxxxxxx buněk xxxxxxxxx nádory, mají xxxxx xx xxxxxxx xxxxxxxx x člověka x x xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx in xxxxx xxxxx být xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, xxxxxxx kmeny xxxx primární buněčné xxxxxxx. Xxxxxxx buňky xxxx xxxxxxx xx xxxxxxx schopnosti xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, počtu xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx prováděné in xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, které xx xxxxx k xxxxxxxxxx výsledkům, jež xxxxxxxxxx vlastní xxxxxxxxxx x xxxx x xxx xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx cytotoxicity (4, 5).

Xxxx zkouška xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x karcinogenů pro xxxxx. Xxxxx xxxxxxxxx, xxx něž xx xxxx xxxxxxx pozitivní, xxxx xxx xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx a karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx třídě x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx karcinogeny, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx xxxxxxxxxx xxx přímým poškozením XXX.

Xxx xxxx Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x podobě zlomu xxxxxxxxxxxx chromatid nebo xxxxx x xxxxxxxx xxxxxxx xxxxxxxxx.

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

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

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

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

Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx xxxxxxxxxx xx xxxxxxxxxx xxxxx xxxxxxxxx u xxxxxxxxx typu buněk.

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

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. X xxxxxx xxxxxxxxxxx intervalech xx xxxxxxxx xxxxx xx xx xxxxxxxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx kolchicin), xxxxxxx xx xxxxxx, xxxxxx x přítomnost xxxxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Mohou xxx xxxxxxx xxxxx xxxxxxx xxxxx, kmeny nebo xxxxxxxx buněčné kultury, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (např. fibroblasty xxxxxx xxxxxxxx, lymfocyty xxxxxxxxx xxxx xxxxxxx xxxx jiných xxxxx).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx xx měla být xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). X xxxxxxxxxxxxxxx buněčných xxxxx x xxxxx xx xxxx být xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx počtu xxxxxxxxxx x xxxx by xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x případě xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Pro xxxxxxx xxxxx x inkubační xxxxxxxx by měla xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx kultur

Stabilizované xxxxxxx xxxxx a xxxxx: xxxxx se xxxxxxx x kmenových xxxxxx, xxxxxx se xx xxxxxxxxxxxx xxxxx v xxxxxx xxxxxxx, aby xxxxxxxxx xxxxxxxxxx před xxxxxxxxx, x xxxxxxxx xx xxx 37 °X.

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (xxxx. heparinem) xxxx xxxxxxxx lymfocyty xxxxxxxx xxxxxxxx xx xxxxxxx do xxxxxxxxxxxx xxxxx xxxxxxxxxxxx mitogen (xxxx. fytohemaglutinin) x xxxxxxxx xx xxx 37 °C.

1.4.1.4 Metabolická xxxxxxxx

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

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

Xxxx výsledků xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx buněčných xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx být vědecky xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx P450 xxx metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx látka/příprava

Pevné xxxxxxxx látky xx xxxx být xxxx xxxxxxxx xx buňky xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx zředěny. Kapalné xxxxxxxx xxxxx xxxxx xxx přidány přímo x xxxxxxxxxx xxxxxxxx x/xxxx mohou být xxxx xxxxxxxx zředěny. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx látky, pokud xxxxx x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx být xxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x mělo xx xxx xxxxxxxxxx x xxxxxxxx buněk x s xxxxxxxxx X9. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx jejich zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul. Při xxxxxxxx látek xxxxxxxxx xx vodě xx xxxx být použita xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x hlavním xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, xxxx xxxx xxxxxx xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx buněk xxxx xxxxxxxxx xxxxx. Xxxx být výhodné xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx xxxxxxxxxxxx by xxxx xxxx koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx minimální xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx xxxxxxx xxxxxxx, že xx xx xxxxxxxxxxx xxxxxx xxxxx xxxx nežli xxxxxxxx 2 xx Ö10. X xxxxxxxx xxxxxxx xx měla xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, počtu xxxxx xxxx mitotického indexu (xxx o více xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx měřítkem xxxxxxxxxxxxx xxxx cytostatických xxxxxx x xxxxxx xx době, xxxxx xxxxxxxx od expozice. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx x xxxxxxxxxxx xxxxxx, x xxxxx xxxxx být xxxx metody xxxxxxxxx xxxxxxxx xxxxxxx a xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx buněčného xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), mohou xxx použity xxxx xxxxxxxxx xxxxxxxxx. V xxxxxxx XXX xxxx xxx o xxxxxxxx xxxxxxxxx hodnotu, x xxx xxxxx usoudit xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, x x xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx může xxx xx následek xxxxx xxxxxxxxx oddálení xxxxxxxx xxxxxxxxxxx výtěžku xxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxxxx xxxxx by xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx xxxx, xxxxx x nich xx xxxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxx xxxxx, které xxxxxx xxxxxxx xxx xxxxxxxxxxxxx xxxxxxx, než xx jejich xxxxxxxxxxx, xx xxxx xxx xxxxxxx nejvyšší dávka x xxxxxxxxxxx, jež xx xxx xxxx xxxxxxxxxxxx v xxxxxxxx xxxxxxxxxxx xxxxx na xxxxx doby xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx se xxxxxxxx xxxxx při xxxxxxx koncentracích, než xx xxxxxxxxxxx) xx xxxxxxxxxx xxxxxxxxx více xxxxxxxxxxx, xxx nichž xxxxxxx xx xxxxxxx. Xxxx být xxxxxxxx xxxxxxxx rozpustnost na xxxxxxx a xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx v xxxxxxxxxx xxxxxxx xx může x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, xxxx X9 atd. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého experimentu xx xxxx být xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx vehikula). Xxx xxxxxxx xxxxxxxxxxx aktivace xx měla xxx xxx xxxxxxxxx kontrolu xxxxxxx xxxxxxxx xxxxx, xxxxx x mutagenní xxxxxx xxxxxxxx xxxxxxxx.

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

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale xxx xxx odečtu xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

Xxxx metabolické aktivace

Látka

Číslo XXX

Xxxxx podle XXXXXX

Xxx xxxxxx metabolické xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X vnější metabolickou xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

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

V okamžiku xxxxxxxx by měly xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula x xxxxxxxxxxx xxxxx x xxxxxxxxxx xxxxxxx způsobem xxxx xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.4.3 Xxxxxx

1.4.3.1 Expozice zkoušené xxxxx

Xxxxxxxxxxxxx buňky xx xxxxxxx xxxxxxxx xxxxx xxx xx přítomnosti xxxxxxxxxxxxx aktivačního systému, xxx xxx xxxx. Xxxxxxxx xxxxxxxxx by xxxx být xxxxxxxx xxx 48 hodin xx xxxxxxxxx stimulaci.

1.4.3.2 Xxx xxxxxx koncentraci xx xxxx xxx xxxxxxx použity duplicitní xxxxxxx, x totéž xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxx. Jestliže xxx na xxxxxxx xxxxxxxxxxx údajů xxxxxxxx (13, 14), že xxxx duplicitními xxxxxxxxx xx xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxx jediné kultury.

Plynné xxxx těkavé xxxxx xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx nádobách (15, 16).

1.4.3.3 Xxxx xxxxxxx xxxxxx

X prvním xxxxxxxxxxx by xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, xxx x metabolickou aktivací, xxx xxx xx, xx dobu 3 — 6 xxxxx, x měly xx xxx odebrány po xxxxxx xxxx xx xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Jestliže xxxxx xxxxxx dává xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, xxx xxx xxxxxxxx, měl xx xxx xxxxxxxx dodatečný xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx do xxxxxx x xxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx látky xxx xxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx délky xxxxx. Xxxxxxxxx xxxxxxxx xxx metabolické xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. X xxxxxxxxx, xxx xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx za xxxxxxxx, by xxxx xxx xxxxxx xxxxxxxxxx.

1.4.3.4 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

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

1.4.3.5 Xxxxxxx

Xxxxxxx preparáty, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při fixaci xxxxx xxxxxxx ke xxxxx xxxxx buněk x metafázi x xx ztrátě xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x počtu rovném xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx xxxxx. Xx xxxxxx koncentraci x xxxxxxxx xx mělo xxx xxxxxxxxx alespoň 200 dobře rozprostřených xxxxxxxx, xxxxxxxx rovnoměrně xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Tento xxxxx xxx snížit, je-li xxxxxxxxx velký xxxxx xxxxxxx.

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

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx jednotkou xx xxxxx x mělo xx xxxx xxx xxxxxxxxxxx množství xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) vyjádřené x procentech. Xxx xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx xx xxxx xxx uvedeny xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx a uvádějí xx, xxx xxxxxxxxxx xx do xxxxxxx xxxxxxxx xxxxxxx.

Xxxx xx xxx xxxx xxxxxxxxxxx xxxxxxxx, xxxxx byla xxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx kultur x xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

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

Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxxx potvrdit xxxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx x bodu 1.4.3.3. Xxxxx xxxxxxxxx studie x cílem xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X parametrům xxxxxx, které xx xxxxx xxx změněny, xxxxx rozmezí xxxxxxxxxxx x podmínky metabolické xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx počtu xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx být xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx neměla být xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx.

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

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

Ačkoli xxxxxxx experimentů poskytne xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxx:

- xxx x xxxxx buněk,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx použitého xxxx xxxxx,

- xxxxxxxxx nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx xxxxx,

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

- případně xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx počtu xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxxxxx xxxxx zastavující metafázi, xxxx koncentrace a xxxxx expozice xxxxx,

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

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- objem xxxxxxxx x xxxxxxx zkoušené xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx při xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx preparátů,

- kritéria xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx metafází,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx studie na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky xxxxxxxx, xxxx. xxxxxx xxxxxxxxxx, xxxxx x buněčném xxxxx, počty xxxxx, xxxxxxxxx index,

- známky xxxxxxx,

- xxxxx o xX x osmolalitě xxxxxxxxxxx média, xxxxx xxxx stanoveny,

- definice xxxxxxx, včetně xxxx,

- xxxxx xxxxx s xxxxxxxxxxxxxx aberacemi x xxxx aberací zvlášť xxx xxxxxx xxxxxxxxxxx x kontrolní xxxxxxx,

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

- xxxxxxxxx údaje x xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

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

3) Galloway, X. X., Xxxxxxxxx, M. X., Reuben, X., Xxxxxx, X., Xxxxx, X., Cannon, C., Xxxxx, A. D., Xxxxxxxx, F., Ahmed, X., Xxx, S., Xxxxx, X., Xxxxxxxx, X. X., Resnick, X. A., Xxxxxxxx, X., Xxxxxx X. (1978), Xxxxxxxxxx xxxxxxxxxx xxx sister xxxxxxxxx xxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx cells: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Molec. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Galloway, X. X., Xxxxxxxx, X. X., Xxxxxxxx, X. Xx., Brusick, X., Xxxxx, J., Myhr, X. C. (1991), Xxxxxxxxxxxx xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. A xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxxxx Xxx., 257, 147-204.

5) Xxxxxx, T., Xxxxxx, T., Fukuda, X., Okumura, K., (1992), Xxxxxxxxxxxxxx of xxx xX xx Xxxxxxx Xxxxxxxx Mammalian Xxxxx, Xxxxxxxxxx Res., 268, 297-305.

6) Xxxx, X. N., McCann, X., Xxxxxxxx, X. (1975), Methods xxx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Mutation Xxx., 31, 347-364.

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

8) Xxxxxxxxx, X. X., Xxxxx, X. X., xxx Xxxx, X. X. X., Meijers, X., xx Xxxxx, X. (1976), Xxxxxxxxxxx Xxxxxxx xx Mutagen/Carcinogens xxxxx Xxxxxxxxxx xx a Xxxxxxxxxxx Xxxxxx Xx xxxxx, X. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Sister Xxxxxxxxx Xxxxxxxx xx Diethylnitrosamine (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) xx XXX Xxxxx xx the Xxxxxxxx xx Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

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

10) Elliot, X. X., Combes, X. X., Xxxxxxx, X. R., Xxxxxxxxx, X. X., Xxxxxx, X. G., Mackay, X. M., Xxxx, X. X. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 in In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Sawamura, X., Xxxx, X., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, F. X., Xxxxx, X. X. Bend, X. X., Xxxxxxx, X. X. (xxx), Xx xxxxx Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Testing, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxx, X. X., Xxxxxxxx, X. X., Xxxxxx, X., Mosesso, X., Xxxxxx, T. (1994), Xxxxxx from Xxxxxxx Xxxxx on Xx vitro Xxxxx xxx Xxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, J. X., Xxxxxxxx, X., Xxxxxxx, X. O., Xxxxxxxx, X. (1989), Analysis xx Xxxx xxxx Xx xxxxx Cytogenetic Xxxxxx, xx: Statistical Xxxxxxxxxx of Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

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

15) Xxxxx, X. X., Xxxxxx, F. X., XxXxxxx, K. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Tice, X. X., Xxxxx, X. L., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

16) Xxxxxx, X. X., Xxxxxx, X. M., Xx, X. X., Xxxxxx, A. X. (1983), Xxxxxxxxxx of xx Xxxxxxxx System Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Mutagens xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Mutagen., 5, 795-801.

17) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Chinese xxxxxxx xxxxx xxxxxx alpha-radiation xxxxxxx X2 xxxxxx, Xxxxxxxxxx Xxx., 119, 403-413.

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


XXXXXXX 4B

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

1. METODA

Tato xxxxxx xx replikou metody XXXX XX 475 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxxxx kostní xxxxx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx chromozomové aberace x savců xx xxxx je xxxxxxxxx xxx xxxxxxx strukturních xxxxxxxxxxxxxx aberací indukovaných xxxxxxxxx xxxxxx x xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx se xxx typy strukturních xxxxxxx — chromozomové x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx může xxxxxxxx, xx chemická látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx jsou xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx a xxxxxxxx xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx x související xxxx způsobující změny x xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx hlodavci. Xxxxxxx xxxxx je x xxxx zkoušce kostní xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx tkání x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Xxxx druhy x xxxxxx tkáně xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxx určená k xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA, xxxxxxx xx mohou x xxxxxxx xxxxx x xxxxx měnit. Xxxxxxx xx xxxx xx rovněž užitečná xxx další xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx in vitro.

Jestliže xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx metabolity nedostanou xx xxxxxx tkáně, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 DEFINICE

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

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

Xxxxxxxxxxxxxxx : xxxxxx, xxx kterém x xxxxx xx X-xxxx xxxxxxxxx XXX xxxxxxx x mitóze, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx xxxx xxxxxxxxxx xx 4, 8, 16,… xxxxxxxxxxxx.

Xxx : achromatická xxxx xxxxx xxx xxxxx xxxxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

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

Xxxxxxxxxx aberace : mikroskopicky xxxxxxxxxxxxx xxxxx struktury chromozomů xxx buněčném xxxxxx xx xxxxxx metafáze; xxxx se xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx jsou xxxxxxxxx xxxxxxxx xxxxx vhodným xxxxxxxx a ve xxxxxxx xxxxxxxx po xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx se xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X buněk xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx se x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xx xxxxxxxx xxxxxx, myš x xxxxxx xxxxxx, xxxxxx xxx použít xxxxxxxx xxxxxx xxxxx xxxx. Xxxx by xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x hmotnosti xxxxxx minimální x xxxxxx xx x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx skupinu x xxxxxxx, xxxxx xx xxxxxxx xxxxxxxx xxxxx. Klece xx xxxx xxx xxxxxxxxxx xxx, aby xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx se xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené látky xx xxxx být xxxx xxxxxxxx zvířatům xxxxxxxxxx nebo suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx podávány xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx připravené 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 xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by xxxx xxx pozitivní x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X výjimkou aplikace xxxxxxxx látky xx xxxx xxxxxxx kontrolní xxxxxxx podstoupit xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx by měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx kontrola podávána xxxxx způsobem xxx xxxxxxxx xxxxx x xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxx použity xxxxxxxx látky ze xxxxxx xxxxxxxx třídy, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

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

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

V xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxxxxxx xxxxxxx, jimž je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxx jinak xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx z dosavadních xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě zvířat x četnosti xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx pro xxxxxxxxx xxxxxxxx xxxxx xxxxx, je nejvhodnějším xxxxxxxxx xxxx prvního xxxxxx. Xxxxx toho xx měly být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx xx skládá x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx stejným xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx expozice, xxx prokazují, že xxxxxxxxxx mezi pohlavími xxxxxx x xxxxxxxx, xxxx postačující zkoušení xxxxxxx pohlaví. Je-li xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx zkouška xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Plán xxxxxxxx

Xxxxxxxx xxxxx by xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx dávkách, xxx. dvě dávky x xxx xxx x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx bylo xxxxxxxxx podávání xxxxxxx xxxxxx materiálu. Jiné xxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx.

Xxxxxx by xxxx xxx xxxxxxxx ve xxxx různých xxxxxxxxxxx xx aplikace xxxxxx x jednom xxx. X xxxxxxxx se xxxxx xxxxxxx xx xxxxxx xxxx xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx zkoušené látky x xxxxxx xxx xxxxxx xx xxxxxxxx xxxxxxxxx cyklu může xxx xxxx xx xxxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx xx provést xxxxx odběr xx 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx xxx jednoho xxx, xxx by xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx látky xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® nebo xxxxxxxxx). Xxxx xx po xxxxxx době xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx doba xxxxxxxxx 3 — 5 x; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx odeberou xxxxx x xxxxxxxxx xx xx chromozomové aberace.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se kvůli xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx xxxxx, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx studii (5). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí tři xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx maximální x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxx stejném režimu xxxxxxxxx podle očekávání x letalitě. Látky xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx vyhovovat a xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx xxxxx xxxx být xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x xxxxxx xxxxx xxxxxxx známky xxxxxxxx (xxxx. více xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx ve xxxx xxxxxxx v xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x není-li xx xxxxxxx údajů x látkách, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx studie xx třemi xxxxxxxx xxxxx za xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx xx limitní xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx delší xxx 14xxxxx xxxxxxxx xx xxxxxxx dávkou 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx expozice člověka xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx injekcí. Jiné xxxxxxx podávání xxxx x odůvodněných případech xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který může xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, než xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx látky, xxxxx xxxxxxx při xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx zajišťující xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů pro xxxxxxx chromozomů

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

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx xxx být x všech exponovaných xxxxxx (xxxxxx xxxxxxxxxxx xxxxxxx) x x xxxxxxxxxxxxxx xxxxxx xxx xxxxxxxxx kontrolu xxxxxxxx xxxxxxxxx xxxxx, a xx alespoň x 1000 xxxxx xx xxxxx xxxxx.

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx pozorován xxxxx xxxxx aberací. Xxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx analýzou xxxxxxxxx xxxxxxxx. Xxxxxxx při xxxxxx často xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx ke xxxxxx xxxxxxxxxx u xxxxx xxxxx x xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx počet xxxxx, xxxxx aberací xx xxxxx a xxxxx buněk x xxxxxxxxxxxxx aberací (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx v xxxxxxxxxx. Xxx xxxxxxxxxx x xxxxxxxxx skupiny xx měly být xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx počtem x xxxxxxxx. Xxxx xx zaznamenávají xxxxxxxx x xxxxxxx se, xxx obecně xx xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, xxxxx xxx xxx statistickou xxxxxxx xxxxx pro xxx xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi v xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx s xxxxxxxxx pro xxxxxxx x xxxxxxx dávkou x x xxxxxxxx xxxxxxxx odběru. Nejdříve xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx měly xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx polyploidie xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, že zkoušená xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

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

Xxxxxx většina xxxxxxxxxxx poskytne xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx neumožní xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx sporné bez xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

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

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- individuální xxxxxxxx zvířat xx xxxxxxx xxxxxxx, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx hodnoty x xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- údaje xx xxxxxx xxx xxxxxxxx xxxxxxx, pokud xxxx provedena,

- zdůvodnění xxxxxxxxx úrovní xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

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

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x krmivu xxxx xxxx (ppm) xx odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx stanovení xxxxxxxx,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria hodnocení xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx na xxxxx xxxxx,

- kritéria xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- mitotický xxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx pro každé xxxxx,

- xxxxxxx počet xxxxxxx xx xxxxxxx xx středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxx s xxxxxxxxx xx skupině xx xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Adler, X. X. (1984), Xxxxxxxxxxx Tests in Xxxxxxx, in: Mutagenicity Xxxxxxx: a Practical Xxxxxxxx, X. Xxxxxx, X. X. Parry (xxx), XXX Xxxxx, Xxxxxx, Xxxxxxxxxx X. X., 275-306.

2) Preston, X. X., Dean, X. X., Galloway, X., Xxxxxx, X., XxXxx, A. X., Xxxxxx, X. (1987), Xxxxxxxxx In xxxx Xxxxxxxxxxx Xxxxxx: Analysis xx Xxxxxxxxxx Xxxxxxxxxxx xx Xxxx Marrow Xxxxx, Mutatation Xxx., 189, 157-165.

3) Richold, X., Chandley, X., Xxxxx, X., Xxxxxxxxx, X. X., Xxxxxxx, X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, UKEMS Recommended Xxxxxxxxxx. XXXXX Sub-Committee xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Tice, X. R., Hayashi, X., MacGregaro, J. X., Xxxxxxxx, X., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., F. B., Xxxxxxxxxxxx, X., Preston, X. X., Xxxxxxx, X., Xxxxxxx, H., Xxxxx, S., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Xxxxxxx Xxxxx xx xxx xx xxxx Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxx Xxxxxxxxxx Test, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. J., Xxxxx, J. X., Xxxxxx, A. X., Xxxxxx, X. X., Xxx, X., Esdaile, X. J., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Dose Xxxxxxx in In xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, X. X., Clare, X., Xxxxxxxx, X., Xxxxxxx, X., Papworth, D. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx on Guidelines xxx Mutagenicity Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Data, X. J. Kirkland (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

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

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


PŘÍLOHA 4C

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

1. METODA

Tato xxxxxx xx replikou xxxxxx XXXX TG 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx používán xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, které je xxxxxxxxxx zkoušenou xxxxxx, x xx xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x kostní xxxxx x/xxxx xxxxx xxxxxxxxx xxxx, xxxxxxx xxxxxxxx.

Xxxxxx xxxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, jehož xxxxxxxxx xx tvorba xxxxxxxxxx obsahujících xxxxxxxxxxxxx xx (xxxxxxx) chromozomové xxxxxxxxx nebo xxxx xxxxxxxxxx.

Xxxx se erytroblast xxxxxx xxxxx xxxx xx xxxxxxxxxxxxxxx erytrocyt, xxxxxx jádro xx xxxxxxxx x xxxxxxxxxx, xxxxx při xxx xxxxx vzniknout, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader xx x xxxxxx xxxxxxx xxxxxxxxx tím, xx xxxxxxxxxx xxxxxx jádro. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx x mikrojádry x xxxxxxxxxxxx zvířatech xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx poškození.

V tomto xxxxx xx rutinně xxxxxxxxx xxxxxx dřeň xxxxxxxx, xxxxxxxx xxxx xxxx produkuje xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx x periferní xxxx xx xxxxxxxxxx xxxxxxxxxx x xxxxxxxxxxx xxxxx, x xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx erytrocyty x xxxxxxxxxx, xxxx xxxxxxxxxx citlivost detekovat xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxxxxx xxx rozlišit xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx xxxxxxx (normochromatických) xxxxxxxxxx v periferní xxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx na xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx rovněž xxxxxx xxxx xxxxxxx xxxxxxxx xxxxxxx, xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxx xxxxx xxxx xxxx.

Xxxxx xxxx savčích xxxxxxxxxxxxxxx mikrojader xx xxxx xx zvláště xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA, třebaže xx mohou xxxxx x různých druhů x xxxxx, jakož x x xxxxxxxxxxx xxxxxxxx. Xxxxxxx in xxxx xx xxxxxx xxxxxxxx pro další xxxxxx mutagenních účinků xxxxxxxxxx x xxxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x tom, xx xx zkoušená xxxxx nebo reaktivní xxxxxxxxxx nedostanou do xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (oblasti) chromozomu, x níž (x xxxx) se xxxxx xxxxxx buněk xxxxxxx xxxxxx xxxxxxxx umožňující xxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxx buněk.

Mikrojádra : xxxx xxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx x xxxxx xxxx, vytvářená během xxxxxxxx xxxxxx (meiosy) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx fragmenty nebo xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxx, xxxxx xxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx se vhodným xxxxxxxx xxxxxxx zkoušené xxxxx. Při xxxxxxx xxxxxx dřeně se xxxxxxx xx vhodném xxxxxxxx xx xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx dřeň, xxxxxxxx xx preparáty a xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx periferní xxxx se xxxx xx xxxxxxx okamžiku xx xxxxxxxx xxxxxxx, xxxxxxxxxx se xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Xxx xxxxxxxx x xxxxxxxxx xxxx xx xxxx xxxx xxxxxxxx expozicí x xxxxxxxxx xxxxx xxxxxxxx xx xxxxxxxxx xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx xx přítomnost xxxxxxxxxx.

1.4 POPIS ZKUŠEBNÍ XXXXXX

1.4.1 Přípravky

1.4.1.1 Výběr xxxxx xxxxxxx

Xxx xxxxxxx xxxxxx xxxxx xx xxxx testovací xxxxx xxxxxxxxxx xxx nebo xxxxxx, ačkoli xxx xxxxxx xxxxxxxx xxxxxx xxxxx druh. Xxx xxxxxxx xxxxxxxxx xxxx xx xxxxxxxxxx xxx. Xxx xxxx xxxxxx xxxxxxxx vhodný xxxx xxxxx za předpokladu, xx xxx x xxxx, x něhož xxxxxxx xxxxxxxxxxxx erytrocyty x xxxxxxxxxx, nebo xxxx vykazující dostatečnou xxxxxxxxx xxxxxxxxx činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx laboratorní kmeny xxxxxxx zdravých pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx xxxx být xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, u xxx xx xxxxxxx xxxxxxxx. Zvířata xx xxxxxxxxxxx identifikují. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx. Xxxxx xx uspořádají xxx, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx by měly xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve vhodných xxxxxxxxxxxxxx nebo vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx podávány xxxxx xxxx xxxxx xxx před xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxx stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx nemělo xxx xxx xxxxxxxxx xxxxxxxx xxxxx toxické xxxxxx x xxxx xx xxx xxxxxxxxx podezření, xx xxxxxxx se xxxxxxxxx látkou. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx nejdříve xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx aplikace zkoušené xxxxx xx xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx identický proces xxxx xxxxxxx ve xxxxxxxxx, v nichž xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x nichž xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx xxxx xxx zvoleny xxx, xxx byl xxxxxx zřetelný, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xx přijatelné, aby xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx xxxxxxxx xxx zkoušená xxxxx x aby xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Pro xxxxxxxxx xxxxxxxx navíc xxxx xxx vzato x xxxxx použití chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x dispozici. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx měl xxx xxxxxxxx xxxxx x xxxxxxx negativní kontroly, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx podstupuje stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx a xxxxxxxx buněk s xxxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx xxxxx odběr, xx xxxxxxxxxxxxx okamžikem xxxx xxxxxxx odběru. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

Při xxxxxxx xxxxxxxxx krve xxxx xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx krve xxxxxxxx xxxx expozicí, xxxxx xxxx x xxxxxxxx xxxxxx x periferní xxxx (např. 1 — 3 aplikace) xx xxxxxxxxxxx, že xxxxxxxx xxxxx xxxxx x xxxxxxx, xxxxx xx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Každá exponovaná x xxxxxxxxx skupina xx musí skládat x xxxxxxx xxxx xxxxxxxxxxxxxxxx zvířat pro xxxxx xxxxxxx (11). Xxxxxxxx xxxx x xxxx studie x xxxxxxxxx údaje xx xxxxxx xx xxxxxxx xxxxxx a xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx expozice člověka xxxxxxxxxx pro xxxxxx xxxxxxx, jako je xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx provedena se xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx xxxxxxxxxx plán (xx. xxxxx, dvě xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx xx xxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxx jsou xxxxxxxxxx, xxxxx se x xxxxxx studií xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –v xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx xxxx prokázána xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx xxxxx x podávání xxxxxxxxx xx xx okamžiku xxxxxx. Zkoušené xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx v xxx xxx v xxxxxxx xx xxxx xxx xxxxxxxx hodin, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx xxx xxxxxxxx xxxxx způsoby:

a) xxxxxxxx xxxxx xx aplikuje xxxxxxxx xxxxxx. Xxxxxx xxxxxx xxxxx xx xxxxxxxx xxxxxxx dvakrát, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx xx xxxxxxxx a xxxxxxxx xxxxxxxxxx 48 xxxxx xx xxxxxxxx x x přiměřeným xxxxxxxx xxxx xxxxxx. Xxxxx xxxxx xxx 24 xxxxx xx aplikaci xxxx xxx zdůvodněn. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx provede xxxxxxxx 36 xxxxx xx aplikaci a xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x xx xxxxxxxxxxxx xx dodrží odpovídající xxxxxx. Xx-xx po xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx odpověď, xxxx xxxxx odběr xxxxx;

x) xxxx-xx xxxxxxxx xxx xxxx xxxx xxxxx xxxxx (xxxx. xxx xxxx xxxx dávek x intervalu 24 xxxxx), xxxx by xxx xxxxxx xxx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxx po 18 až 24 xxxxxxxx po xxxxxxxx xxxxxxxx x xxx xxxxxxx periferní krve xxxxxx po 36 xx 48 hodinách xx xxxxxxxx aplikaci (12).

Xxxxx xxxxxxx xxxxx xxx xxxxx použity xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx pro xxxxxxxx xxxxxxx dávek, xxxx xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, pohlavím x xx xxxxxxxx xxxxxx xxxxxxxx, jež xx xxxxxxx x xxxxxx xxxxxx (13). X případě toxicity xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Při xxxxxxxxx xxxxxx xxxxx, xxxx bude použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx vyšší xxxxx xx xxxxx xxx stejném xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (např. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx v kostní xxxxx xxxx x xxxxxxxxx krvi).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo ve xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxx xxxxxxxxxx xxxxx studie xx třemi xxxxxxxx xxxxx xx nezbytnou. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx xxxxx xxx 14xxxxx xxxxxxxx je xxxxxxx dávkou 1000 xx/xx tělesné hmotnosti/den. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Podávání dávek

Zkoušená xxxxx se xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx xxxx xxxxxxxxxx v xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx je uvedený xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx a xxxxxx xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxx xxxxx nebo xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx získávají x xxxxxx nebo tibie xxxxx po xxxxxxxx. Xxxxx xx odeberou x xxxxxx xxxx xxxxx x xxxxxxxxxx xxxxxxxx xx preparují x xxxxxx. Periferní xxxx xx získává x ocasní žíly xxxx xxxx vhodné xxxxxx cévy. Krevní xxxxx se xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx xxxxxxxx xxxxxxxxx xxxxxxxx x xxxx xx obarví. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx spojeným s xxxxxxxx xxxxxxx nespecifického xxx DNA. Xxxx xxxxxx nebrání použití xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Přídavné xxxxxxx (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, že xx xxxxxxxxx odpovídající xxxxxxxxx xxxxxx systémů xxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx xx xxxxxxx xxxxx xxxxxxxxx erytrocytů x celkového (xxxxxxx + zralé) xxxxxxxx xxxxxxxxxx, přičemž xx x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 erytrocytů x x případě xxxxxxxxx xxxx xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx být před xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxx alespoň 2000 xxxxxxxxx erytrocytů xx xxxxxx mikrojader x xxxxxxxxxxxxxxxxxxxxx. Další xxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx mikroskopické analýze xx xxxxx být xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx menší xxx 20 % kontrolní xxxxxxx. Jestliže jsou xxxxxxx exponována xxxxxxxxxxx xxxxx xxxxx nebo xxxx, xxx xxxx xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx analýzu (xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxxxxx analýza xxxxxxx xxxxxxxx) jsou xx xxxxxxxxxxxxx zdůvodnění x xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx hodnocení.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx xx xxxx být xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Pro xxxxx xxxxxxxxxxx zvíře xx xxx být xxxxxx počet xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx a xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx nebo xxxx, xxxx xx xxx xxxx xxxxxxx xxxxx x zralých erytrocytech, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx zvíře xx xxxxx podíl xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxx množství xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx mezi xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx obě xxxxxxx zkombinována.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx počtu xxxxx x xxxxxxxxxx x závislosti na xxxxx nebo xxxxx xxxxxx xxxxx xxxxx x mikrojádry pro xxxxxxx x určitou xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx uvážena biologická xxxxxxxxx výsledků. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx být použity xxxx pomocný prostředek xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxx experimentálních xxxxxxxx.

Xxxxxxxx látka, jejíž xxxxxxxx nesplňují xxxx xxxxxxx kritéria, xx xxxxxxxx x tomto xxxxxxx za nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xxxxx na mikrojádra xxxxxxxxx, že zkoušená xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx mitotického aparátu xxxxxxxxxxxx testovacího xxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx zkoušená xxxxx xx podmínek xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx erytrocytech xxxxxxxxxxx xxxxx.

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

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, stáří x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx hmotnosti, xxxxxxx hodnota x xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- údaje xx xxxxxx xxx xxxxxxxx xxxxxxx, pokud byla xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx způsobu podávání,

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

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx a vody,

- xxxxxxxx popis xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx přípravy xxxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x nezralých xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- podíl xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx,

- počet xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxx samostatně xxx xxxxx xxxxx,

- xxxxxxx xxxxxxx ± xxxxxxxxxx odchylka počtu xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx ve xxxxxxx,

- xxxxx možnosti závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x metody,

- xxxxx x souběžné x xxxxxxxxx negativní xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxx, X. A., Xxxxxxxx, M. F., Xxxx, X., Xxxxxxxx, X., Xxxxxxxxx, K., XxxXxxxxx, J. G., Xxxxxx, G. W. (1983), The Induction xx Micronuclei a. x. x Measure xx Xxxxxxxxxxxx, Mutatation Xxx. 123, 61-118.

4) Xxxxxxxxx, X. X., Xxxxxx, D. X., Xxxxxx, X. C., Xxxxxxxx, X. X., Xxxxxx, X. X. (1990), The Xx xxxx Xxxxxxxxxxxx Assay xx Xxxxxxxxx Xxxx Xxxxxx xxx Xxxxxxxxxx Xxxxx. X xxxxxx xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Res., 239, 29-80.

5) XxxXxxxxx, X. X., Xxxxxxxx, R., Xxxx, X. N., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Screen xxx Xxxxxxxxxxx Damage During Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, xx: Xxxxxxxxxxxx in Science xxx Practice of Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Xxxxxxx, T. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. X., Xxxxxx, X. X. Xxxx, X., Xxxxxxxx, G. X., Xxxxx, C., Xxxxxxxx, X. F., Xxxx, X. R., Xxxx, D. (1987), Xxxxxxxxxx for xxx Xxxxxxx of Xxxxxxxxxxxx Xxxxxx in Xxxxxxxxx Xxxx Xxxxxx Erythrocytes, Xxxxxxxxxx Xxx., 189, 103-112.

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

8) Xxxxxxx, X., Morita, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. Xx. (1990), Xxx Xxxxxxxxxxxx Assay with Xxxxx Peripheral Xxxxx Xxxxxxxxxxxxx Xxxxx Xxxxxxxx Xxxxxx-Xxxxxx Slides, Mutatation Xxx., 245, 245-249.

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

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx for the Xxxxxxxxxxxx Test (CSGMT/JEMMS, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Group xx the Environmental Xxxxxxx Society of Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx for xxx xxxxx-xxxx mouse xxxxxxxxxx xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Tice, X. X., XxxXxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, X. X., Xxxxxx-Xxxxxxx, X., Xxxxxx, Jr. X. X., Pacchicrotti, X., Xxxxxxx, X., Shimada, X., Sutou, S., Xxxxxxx, B. (1994), Xx vivo Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Assay, Xxxxx. Xxx., 312, 293-304.

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

13) Xxxxxxx, X. X., Xxxxx, J. X., Xxxxxx, X. X., Botham, X. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Morton, X. B., Kirkland, X. J., Xxxxxxx, X. (1992), Xxxxxx xx British Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Setting xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

14) Hayashi, X., Xxxxxx, X., Xxxxxxxx, X. Xx. (1983), Xx Application xx Xxxxxxxx Xxxxxx Fluorescent Xxxxxxxx to xxx Xxxxxxxxxxxx Test, Xxxxxxxx Xxx., 120, 241-247.

15) XxxXxxxxx, J. X., Xxxx, X. X., Xxxxxxxx, X. G. (1983), A Xxxxxx Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Xxxxxxxxxxx xxx XXX xx Erythrocytes Xxxxx Hoechst 33258 xxx Pyromin Y, Xxxxxxxx Res., 120, 269-275.

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

17) Xxxxxxxxx, X., McFadden, X. X. (1995), Xxxxxx Xxxx xxx xxx Xxxxxxxxxx of Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx xx xxx Xxxx Marrow Xxxxxxxxxxxx Xxxx, Mutatation Xxx., 347, 97-99.

18) Xxxxxxx, X., Ashby, X., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxxx Assay, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Report, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Lovell, X. X., Xxxxxxxx, X., Albanese, R., Xxxxxxxx, X. X., Xxxxx, X., Ferguson X., Richold, M., Xxxxxxxx, D. G., Xxxxxx, J. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx III, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New York, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx používají xxxxxxxxxxx xxxxx závislé na xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x xxxxxxx xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx a xxxxxx xxxxxxx xxxx xxxxxxxx xxxx bází XXX (1, 2, 3). Podstata této xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xxxxxxx x detekci xxxxxx, xxxxx xxxxxxxxx xxxxxx obsažené v xxxxxxxxxxx xxxxxxx x xxxxxxxx xxx xxxxxxx xxxxxxxxx bakterií xxxxxxxxxxxx xxxxxxxxxx aminokyseliny. Bakterie xx reverzi jsou xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx xxxxxxxxxxxx, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx mutace x xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných chorob x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, že xxxxxx mutace v xxxxxxxxxx a x xxxxxx somatických buněk xxxxxxxxx xxxxxx xxxx xxxxx xx xxxxxx xxxxxxxx x xxxxxxx x u pokusných xxxxxx. Xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx x xxxxxxxxx xxxxxx. Xxxxx xxxxxxxxxxx xxxxx xx xxxx xxxxxxxxxx, díky xxxx xxxx xxxxxxxxxx xx xxxxxxx mutací, včetně xxxxxxxxxxxxx sekvencí XXX xx reverzních místech, xxxxxxx xxxxxxxxxxxx buněk xxx velké molekuly x eliminaci xxxxxxxxxxx xxxxxxx DNA xxxx xxxxxxxx reparačních xxxxxxx XXX náchylných k xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx užitečné informace x xxxxxx mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx činiteli. Xxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xx x dispozici xxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx xxxxxxxx x xxxx xxxx vyvinuty xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx fyzikálně-chemickými xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx x bakteriemi Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x detekci xxxxxx x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx xxxx. xxxxxxxxx), xxxxxxx xxxxxx xxxx xxxxxxxxx na xxxxxxx přísunu xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx činitele, xxx xxxxxxxxx xxxxx v xxxxxx DNA. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx mohou xxxx xxxxx vyskytnout na xxxxx xxxxxxx xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx xxxxxx.

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

1.3 VÝCHOZÍ XXXXX

Xxx xxxxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xx využívají prokaryotické xxxxx, xxxxx se xxxx xx buněk xxxxx xxxxxxx, xxxx xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx a xxxxxxxxx xxxxxxx DNA. Xxxxxxx xxxxxxxxx in xxxxx obecně vyžadují xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Metabolické xxxxxxxxx xxxxxxx xx xxxxx nemohou zcela xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxxxx x karcinogenním xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx xxxxxxxxx využívána xxx xxxxxxxxx vyšetření xxxxxxxxxxx xxxxxxxx, x xxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxx xxxxxx. X xxxxxxxx xxxxxxxx vyplývá, xx xxxxx xxxxxxxxxx xxxxx, xxxxx xxxx x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx mutagenní xxxxxxxx i x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx mutagenních činitelů, xxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx. Xxxxxxx xxxxxx skutečností lze xxxxxxxxx xx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx nebo x rozdílech x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx xxxxxxx, xxxxx zvyšují xxxxxxxxx xxxxxxx xx reverzní xxxxxx xx xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx reverzní mutace x bakteriemi xxxxxx xxx xxxxxx pro xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) x xxx chemické látky, x xxxxx xx xxxxxxxxxxx (xxxx x xxxxx xx xx), xx specificky xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx topoisomerasy x některé xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx xxxxx xxxxxxxxx, pro xxx xx tato zkouška xxxxxxxxx, xx xxxxxxxxxxxx xxx xxxxx, xxxx xxxxxxxx absolutní. Závisí xx chemické xxxxx x existuje xxxxx xxxxxxxxxxx, xxx nejsou xxxxxxxxxx touto xxxxxxxx, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, nebo xxxxxxxxxx, xxxxx v xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx buněk jsou xxxxxxxxx xxxxxxxx xxxxx, x to xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx systému x xxx xxxx. Ve xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx x xxxxxxx xxxxxx x ihned se xxxxxxx na xxxxxxxxx xxxx. X preinkubační xxxxxx se zkoušená xxxx inkubuje x xxxx se xxxx xxxxxxxxx xx xxxxxxxxx xxxx smíchá x xxxxxxx agarem. Při xxxx technikách xx xx xxxx nebo xxxxx xxxxx xxxxxxxx xxxxxxxxx kolonie xxxxxxxxxx x xxxxxxx xx xxxxxxxx s xxxxxx xxxxxxx spontánních revertantů xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

Xx popsáno xxxxxxx postupů provedení xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx. Xxxx běžně xxxxxxxxx xxxxx standardní xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx test (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx xxx zkoušení xxxxx x xxx xxxx xxxxxxx (12).

Xxx xxxxxxx xxxxxxx xx xxxxxx xxxxxx standardního xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Každá x nich je xxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxx jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxxxxxx xxxxx lze xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Tyto xxxxx xxxxx xx xxxxxxxxxx xxxx, xx xxxxx xxxxx mezi xxxxx krátké alifatické xxxxxxxxxxx, dvojvazné kovy, xxxxxxxx, azobarviva a xxxxxxxxxx sloučeniny, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx sloučeniny x xxxxxxxxxxxxxxx (3). Xxxxxx xx připouští, xx určité třídy xxxxxxxx xxxxx vždy xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx je xxxxxxxxxx xxxxxxx test xxxx xxxxxxxxxxxx metoda. Xxxx xx být považovány xx "xxxxxxxx xxxxxxx" x x jejich xxxxxxx se xxxxxxx xxxxxxxxxx xxxxxx alternativní xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (společně x xxxxxxxx xxxxxxx xxxxxx xxxxxxx): xxxxxxxxxx a xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x glykosidy (17, 18). Xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxx xxx xxxxxxx zdůvodněna.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx by měly xxx xxxxxxxxxxx xx xxxxxx exponenciální fáze xxxx xx xxxxx xxxxxxxxxxx xxxx růstu (xxxxxxxxx 109 xxxxx xx xx). Buňky x pozdní xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Xx xxxxxxxx, aby xxxx xxxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx xxx xxxxxxxx xxx na xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx životaschopných xxxxx xx miskách.

Doporučená xxxxxxxxx xxxxxxx je 37 °X.

Xxxx xx xxx xxxxxxx xxxxxxx pět xxxxx xxxxxxxx. Xxxx xxxx xx xxxx xxx xxxxx xxxxx X. xxxxxxxxxxx (XX1535; XX1537 nebo TA97a xxxx TA97; XX98 x XX100), xxxxxxx xxxxxxx xx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Tyto xxxxx xxxxx X. typhimurium xxxx xxx xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx x xx xxxxx, že xxxxxx prostřednictvím xxxxx xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, činitele xxxxxxxxxxx xxxxxxxxxx xxxxxx DNA x xxxxxxxxx. Xxxx xxxxx xxxxx být xxxxxxxxxx kmeny E. xxxx WP2 xxxx X. xxxxxxxxxxx XX102 (19), které mají xx xxxxxxxxx reverzním xxxxx pár bází XX. Xxxxxxxxxx kombinace xxxxx xx tedy xxxx:

- X. xxxxxxxxxxx XX1535 x

- X. xxxxxxxxxxx TA1537 xxxx XX97x x

- X. xxxxxxxxxxx XX98 x

- X. xxxxxxxxxxx XX100 x

- E. xxxx XX2 uvrA, xxxx X. xxxx XX2 xxxX (xXX101), xxxx X. typhimurium XX102.

Xxx xxxxxxx xxxxxxxx způsobujících xxxxxxxxxx vláken DNA xxxx být xxxxxxxxx xxxxxxx TA102 xxxx xxxxxx xxxx E. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. E. coli XX2 (xXX101)).

Xxxx xx xxx xxxxxxx zavedené xxxxxxx přípravy xxxxxxx xxxxxxx, verifikace xxxxxxx x xxxxxxxxxx. Potřeba xxxxxxxxxxxxx xxx xxxx xx xxxx být xxxxxxxxx pro xxxxxx xxxxxxxxx xxxxxxxx kulturu (xxxxxxxx pro xxxxx X. xxxxxxxxxxx a xxxxxxxxx pro E. xxxx). Podobně by xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx podle potřeby xxxxxxxxxx nebo xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x XX97x nebo XX97, XX2 xxxX x XX2 xxxX (xXX101) x xxxxxxxxxxxx x tetracyklinová xxxxxxxxxx x kmene XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. xxx xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x uvrA xxxxxx u X. xxxx nebo xxxX xxxxxx u X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx xx xxxx rovněž xxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxx četností xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx x xxxxxxx x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) x glukosu) x xxxxxx xxxx xxxxxxxxxx xxxxxxxx x xxxxxx xxxx xxxxxxxxx xxxxxxxxxx několik xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx xxxx xxx xxxxxxxxx xxxxxxxx látce, x to s xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x bez xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená z xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx indukujícím xxxxxx, xxxx xx Aroclor 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální xxxxxx xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 xx 30 % xxx. xx xxxxx X9. Xxxxx a podmínky xxxxxxxxxxxxx aktivačního xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxx. X některých xxxxxxxxx může být xxxxxx xxxxxx xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx x diazoniových xxxxxxxxx xxxx xxx xxxxxxxxx použití xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému (6, 13).

1.5.1.4 Zkoušená xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx před xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx xxxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické látky, xxxxx údaje x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx by mělo xxx xxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx být xxxxxxxxxx x xxxxxxxx xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx ve xxxx xx xxxx xxx použita xxxxxxxxx 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 mají xxx xxxxxxxxxx při stanovení xxxxxxxxxx množství xxxxxxxx xxxxx xxxxx cytotoxicita x xxxxxxxxxxx x xxxxxxx xxxxx pro xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx může xxx detekována xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Cytotoxicita xxxxx xx může xxxxxx x přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx by xxxx xxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx směsi xx xxxxxxxxxx zkušebních xxxxxxxx.

Xxxxxxxxxx maximální xxxxxxxx xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx je 5 xx/xxxxx xxxx 5 μx/xxxxx. X xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx nebo 5 μx/xxxxx xx měla xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx látky xxxx x konečné xxxxx pro xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx jsou xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx, xx xxxx xxx xxxxxxxx až xx cytotoxické xxxxxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

Xxxx xx xxx použito xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, xxxxxxx při xxxxxx xxxxxxxxxxx xx xxxx být intervaly xxxx xxxxxxxxxx body xxxxx přibližně xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Menší xxxxxxxxx jsou xxxxxx x xxxxxxx, xxx xx xxxxxxxxx křivka xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Zkoušení xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx xxx xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Negativní x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx xx měly xxx kmenově xxxxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx s xxxxxxxxxxxx xxxxxxxx x xxx xx. Xxx pozitivní xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx každé xxxxxxx.

X případě xxxxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxx být xxxxx (xxxxx) pro xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxx) xx základě typu xxxxxxxxx xxxxx bakterií.

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

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

XX Direct Xxx 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx by xxxxx xxx xxxxxx jako xxxxxx xxxxxxxxx xxxxxxxxx xxxxx X9. Xxx xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx být xxxxx xxxxx X9 xxxxxxxxxxxxxxxx xxxxxxxxx, který xxxxxxxx xxxxxxxxxxxx aktivaci mikrosomálními xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-dimethylbenzo[a]anthracen.

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx sodný

26628–22–8

247–852–1

TA1535 x TA100

2-nitrofluoren

607–57–8

210–138–5

TA98

9-aminoakridin

90–45–9

201–995–6

TA1537, XX97 x XX97x

XXX 191

17070–45–0

241–129–4

XX1537, XX97 x TA97a

Kumenhydroperoxid

80–15–9

201–254–7

TA102

mitomycin X

50–07–7

200–008–6

XX2xxxX a XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 xxxX a XX2 uvrA (pKM101)

4-nitrochinolin-1-oxid

56–57–5

200–281–1

WP2, XX2 xxxX a XX2 uvrA (xXX101)

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

3688–53–7

xxxxx xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxxxx mohou xxx použity xxxx xxxxxx xxxxxxxxxx látky. Xxx xxxxxxxxx kontrolu xx mělo být xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou xx x xxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající xx xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula, bez xxxxxxxx xxxxx, xxxxxxxxxx xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, neexistují-li xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5.3 Xxxxxx

X standardní miskové xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx čerstvé xxxxxxxxxxx kultury (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx xxxxx. X xxxxxxx xxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x xxxxxxx 5 xx 30 % xxx. v xxxxxxxxxxx xxxxxxxxx směsi) x xxxxxxx xxxxxx (2,0 xx) a xxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxxxx nebo xxxxxxxxx xxxxxxxx. Obsah xxxxx xxxxxxxx xx xxxxxxxx x přelije xxxx povrch xxxxxxxxxxx xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X xxxxxxxxxxxx metody (2, 3, 5, 6) se xxxxxxxx xxxxx nebo xxxxxxxx xxxxxx xxxx xxxxxxxxx x vrchním agarem x xxxxxxxx přes xxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxxxxx 20 xxxxx nebo xxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x sterilním xxxxxx nebo xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx xx smíchá 0,05 nebo 0,1 xx zkoušené látky xxxx xxxxxxxxxx roztoku, 0,1 ml xxxxxxxx x 0,5 ml xxxxx S9 xxxx xxxxxxxxxx xxxxx s 2,0 xx xxxxxxxx xxxxx. Xxxxxxxx xx xxxx být během xxxxxxxx provzdušňovány xx xxxxxxxx.

X dostatečnému xxxxxx xxxxxxxx xx měly xxx při xxxxx xxxxxx xxxxx použity 3 xxxxx. Xxxxxxx xxxx xxxxx xx xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Případná xxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx zkoušky.

Plynné xxxx xxxxxx látky by xxxx být xxxxxxxx xxxxxxxx metodami, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx x xxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xxx 37 °X xx 48 –72 xxxxxxxx. Xx xxxxxxxx xxxxxxxxx xxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx na xxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Měl xx xxx xxxxxx xxxxxx xxxxx kolonií xxxxxxxxxx xxx xx miskách x negativní xxxxxxxxx (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx neexponovaná kontrola), xxx na xxxxxxx x xxxxxxxxx xxxxxxxxx. Xxxxx na xxxxxxxxxxxx xxxxxxx, střední xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx misku x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx zkoušenou xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx se potvrzení xxxxxxxxxxx výsledků nepovažuje xx xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s cílem xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx, xxxxxx zpracování (xxxxxxxxxx misková metoda xxxx xxxxxxxxxxx v xxxxxxxx médiu) a xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx nad xxxxxxxxx rozsah x xxxxxxx jednoho kmene x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxx xxxx, a xx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx počtu xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní výsledky, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxx xxxxx Xxxxxxxxxx typhimurium a/nebo Xxxxxxxxxxx xxxx xxxxxx xxxxxx xxxxxxxxxx xxxx xxxx xxxxxxx xxxxxxx xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že xxxxxxxx xxxxx xxxx xx xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxx xxxxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx kmeny,

- xxxxx xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx xxxxxxxx:

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

- použitá xxxxx,

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

- xxxxxx expozice.

Výsledky:

- xxxxxx toxicity,

- známky xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx počtu xxxxxxx xxxxxxxxxx xx misku x směrodatná odchylka,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx statistické xxxxxxx,

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

- xxxxxxxxx xxxxx o xxxxxxxxx (rozpouštědlo/vehikulum) a xxxxxxxxx xxxxxxxx x xxxxxxxxx, středními xxxxxxxxx x směrodatnými xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Ames, X. X., McCann, X., Xxxxxxxx E. (1975), Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 31, 347-364.

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

3) Xxxxxxxxx, X., Xxxxxxx, S., Xxxxxx, X., Xxxxx, E., Xxxx, X., Xxxxxxxxxx, X., Melcion, X., Xxxxx, X., Xxxxxx, X., Zeiger, X. (1994), Xxxxxxxxxxxxxxx xxx xxx Performance xx Xxxxxxxxx Mutation Assays, Xxxxxxxxxx Res., 312, 217-233.

4) Kier, X. X., Xxxxxxx X. X., Xxxxxxx, X. X., Xxx Xxxxx, X. X., Xxxxx, X. M., Xxxxxx, X. F., Xxxxxx, X., XxXxxx, J., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Xxx X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx xx xxx U. S. Xxxxxxxxxxxxx Protection Agency Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, X., Xxxxxx, X., Xxxxx, X. X., Matsushima, T., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, Y. (1975), Xxxxxxxxxxxx of Xxxxxxxxxx Azo Xxxx xxx xxxxx Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, X., Sawamura, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxx, in: Short-term Xxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx X. X., Xxxxxx, R. X., Xxxxxxxx, Berlin-Heidelberg-New York, 273-285.

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

8) Aeschacher, X. X., Xxxxxx, X., Xxxxxxx, L. (1987), Xxxxxx Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxx for Xxxxx, X. Xxxx Xxxxxx., 8, 167-177.

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

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

11) Xxxxxxxx, X. X., Xxxxxxx, P. J. (1981), An Examination xx xxx Quantitative Xxxxxxxxxx Assay xxx Xxxxxxxxxxx with Xxxxxxx xx Salmonella xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Xxxxx, X., Xxxxxxx, X., Xxxx, X., Matsushima, X. (1994), Xxxxxxxx Method xxx Xxxxxxxxxxxx Testing xx Gaseous Xxxxxxxxx xx Xxxxx x Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Res., 307, 335-344.

13) Xxxxxx, X. X., Bell, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. X., Vaughan, X. X. (1984), Mutagenicity xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Dyes xxx Xxxxxxxx Monoazo Xxxx xx x Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, E., Anderson, X. E., Xxxxxxx, X., Lawlor, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx xxxx xxx Xxxxxxx xx 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

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

16) Xxxxxx, X. J., Xxxxxxx, X. X., Monteith, X. G., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Technique to Xxxxxxx Xxxxxxxxx Activity xx Volatile Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Assay, Environmental Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Xxxxxxxxx, X., Xxxxxx, M., Xxxxxxxx, X., Sugimura, X. (1979), Xxxxxxxxxxxx xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Cycasin xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Conjugates in Xxxxxxxxxx xxxxxxxxxxx, Cancer Xxx., 39, 3780-3782.

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

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

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), A Xxxx Xxxxxxxxxx for Xxxxxxxxxxxxxxx Xxxxxxxxx x. s. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xxx. X. J. de Xxxxxx et al. Xxxxxxxx, North Holland, 85-88.

21) Elliot, X. X., Combes, R. X., Elcombe, X. X., Xxxxxxxxx, X. X., Gibson, X. X., Mackay, X. X., Wolf, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 in xx xxxxx Genotoxicity Assays, Xxxxxxxxxxx, 7, 175-177.

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

23) Claxton, X. X., Allen, X., Auletta, A., Xxxxxxxxxx, K., Xxxxxxxx, X., Zeiger, X. (1987), Xxxxx xxx xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Mutatation Xxx., 189, 83-91.

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


XXXXXXX 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 476 — Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx (1997).

1.1 ÚVOD

Zkoušku xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx lze xxxxxx xxx detekci xxxxxxxx xxxxxx indukovaných xxxxxxxxxx xxxxxxx. Mezi xxxxxx buněčné linie xxxxx xxxxx xxxxxxx X5178X xxxx, xxxxxxx xxxxx XXX, CHO-AS52 x X79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx XX6 xxxxxxx (1). U xxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace xxxx xxx xxxxxxxxxxxxxx (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (HPRT) x transgen xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx na xxxxxx TK, XXXX x XXXX xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX a XPRT xxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx delece), které xxxxx detekovat v XXXX lokusu na X chromozomech (2, 3, 4, 5, 6).

Xx xxxxxxx na xxxxxx mutace v xxxxxxx savců in xxxxx lze použít xxxxxxx xxxxxxxxxx xxxxx xxxxx nebo buněčné xxxxx. Xxxxx se xxxxxxxx podle xxxxxxxxxx xxxxx x xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx x savců. Xx xxxxx xx xxxxx vyvarovat xxxxxxxx, xxxxx by vedly x xxxxxxxxxx výsledkům, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx mutagenitu, může xxxxx xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx používá xx xxxxxxxx možných xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx sloučenin, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx xxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx však xxxx xxxxxxxxx korelace. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx důkazy o xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, negenotoxickými mechanismy, xxxx xxxxxxxxxx, které x xxxxxxxxxxxxx buňkách xxxxxxxxxx (6).

Viz xxxx xxxxxx úvod, xxxx X.

1.2 DEFINICE

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

Xxxxxxxx substituce xxxx xxxx : xxxxx, xxxxx způsobují substituci xxxxxxx xxxx více xxxx xxxx x XXX.

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

Xxxx exprese xxxxxxxx : xxxx, xxxxx xxx vymizí x nově xxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx.

Xxxxxxx mutantů : xxxxx pozorovaných xxxxxxxxxx xxxxx xxxxxx xxxxxx xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxx xxxxxxx xxxx : nárůst xxxxx xxxxx v xxxx ve xxxxxxxx x xxxxxxxxx populací xxxxx; xxxxxxx xx xxxx xxxxxx xxxxxx xxxxxxxxx xxxxx x xxxxxxxx x v xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx klonování xxxxxxxx x xxxxxxxxx xxxxxxxx.

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

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx x okamžiku xxxxxxxx xx misku xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx buněk xxx nasazení xx xxxxx xx xxxxx xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx vyjádřeno x xxxxxx x xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (TK) jsou xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Buňky xxxxxxxxxxx xxxxxxxxxxxxxx jsou xxxxxxx xx TFT, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx metabolismu a xxxxxxxxx další buněčné xxxxxx. Xxxxxxxx xxxxx xxxx tedy xxxxxxx xxxxxxxxxxx za xxxxxxxxxxx XXX, xxxxxxx normální xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Xxxxxxx xxx x xxxxx s xxxxxxxxxxxx XXXX xxxx XXXX provést xxxxxxx xxxxxxxxxxxxxxx rezistence x 6-xxxxxxxxxxx (TG) nebo 8-xxxxxxxxxx (AG). Vlastnosti xxxxxxxx látky xx xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx xx xx xxxxxxx na xxxxxx xxxxxx x xxxxxxx xxxxx zkoušen xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx například vyšetřeno xxxxxxxx podezření xx xxxxxxxxxx xxxxxxxx zkoušené xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx buňky. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx mají xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, musí xxxx xxx xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx xxx selekci (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxx xxxx vhodnou xxxx xxxxxxxxx xxxxxxxx látce xxx x metabolickou xxxxxxxx, tak xxx xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx exprese fenotypu xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx obvykle xxxxxx xxxxxxxxxx relativní účinnosti xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx relativního xxxxxxxxx xxxxx xxxxxx po xxxxxxxx doby xxxxxxxx. Xxxxxxxxxx xxxxxxx se xxxxxxx x růstovém xxxxx po vhodnou xxxx xxxxxxxxxxxxxxxxx xxx xxxxx zvolený xxxxx x xxx xxxxx, xxx xxxxxxx přibližně xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx xx stanoví xxx, xx se xxxxxx xxxxx xxxxx xxxxx xx média xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxx a xx xxxxx bez selekčního xxxxxxx, aby byla xxxxxxxxx xxxxxxxx klonování (xxxxxxxxxxxxxxx). Po xxxxxx xxxxxxxxx xxxx se xxxxxxxxx kolonie. Četnost xxxxxxx xx vypočte x xxxxx xxxxxxxxxx xxxxxxx v selekčním xxxxx x počtu xxxxxxx x médiu xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX ZKUŠEBNÍ METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx použití x této xxxxxxx xxxx x xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, CHO, XXX-XX52, X79 xxxx XX6. Xxxx xxxxx v xxxx zkoušce xx xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x stabilní xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty, x x xxxxxxx kontaminace xx neměly xxx xxxxxxx.

Xxxxxxx xx xxxx xxx xxxxxxxx tak, xxx měly xxxxxx xxxxxxxxxx citlivost x xxxx. Xxxxx xxxxxxxxx xxxxx, xxxxxx x xxxxxxxxxxx xxxxxxxx xxxxx xx xxx tyto xxxxxxxxxx xxxxxxxxx odrážet (14). Minimální počet xxxxx, xxxxx přežijí xxxxxxxx a které xxxxx použity v xxxxxx xxxxxx xxxxxxx, xx měl xxx xxxxxxx na xxxxxxxx xxxxxxxxxxx mutací. Xxxxxxx xxxxxxxxx je, aby xxx xxxxxx xxxxx xxxxx, xxxxx xx xxxxxxxxxxxxxx převrácené xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx xxxx xxxxxxxxxx, xxx bylo xxxxxxx xxxxxxx 106 xxxxx. Xxxx xx být x xxxxxxxxx xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Média x xxxxxxxxxx xxxxxxxx

Xxx udržování xxxxxx by xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx média a xxxxxxxxx podmínky (kultivační xxxxxx, xxxxxxxxxxx CO2, xxxxxxx x xxxxxxx). Xxxxx xx xxxx xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx x xxxx xxxxx xxxxxxxxx xxx zkoušce. Xx xxxxxxx xxxxxxxx, xxx xxxxxxxxxx podmínky xxxx xxxxxxx tak, xxx xxxx xxxxxxxxx xxxxxxxxx xxxx xxxxx xxxxx xxxxxx xxxxxxx a xxxxxxxxx jak xxxxxxxxxx, xxx xxxxxxxxxxxx xxxxx xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx by měly xxx xxxxxxxxx x xxxxxxxxx xxxxxx, nasazeny xx xxxxxxxxxxxx média x xxxxxxxxxx xxx 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx xxxx být xxxxxxxx xxxxxxxxx x xxxxxxx xxx xxxxxxxx xxxxxxxx buňky.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx aktivace a xxx xxxx. Nejčastěji xxxxxxxxxx systémem xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx xxxxxxxx xxxxxxxxxx činidlem xxxxxxxxxxx xxxxxx, jako je Xxxxxxx 1254 (15, 16, 17 x 18), xxxx xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (19, 20).

Xxxxxxxxxxxxxxxxxxx frakce xx x konečném xxxxxxxxxx médiu xxxxxxx xxxxxxxxx v koncentracích 1 — 10 % xxx. Xxxxx x stav xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx na třídě xxxxxxxx xxxxx, xxxxx xx zkoušena. X xxxxxxxxx xxxxxxxxx může xxx vhodné xxxxxx xxxx xxx xxxxx xxxxxxxxxxx postmitochondriální xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx linií exprimujících xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx linií xx měla xxx xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx isoenzymu cytochromu X450 xxx metabolismus xxxxxxxx látky).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány ve xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx mohou být xxxxxxx přímo x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být před xxxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x stálosti xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx mělo xxx xxxx xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx, x xxxx xx xxx slučitelné x xxxxxxxx buněk x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx xxxx by xxxx být xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

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

Cytotoxicita xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x hlavním xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x růstu, xxxx xxxx relativní xxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx v předběžném xxxxxxxxxxx.

Xxxx by být xxxxxxx alespoň čtyři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx toxicity xx xxxx tyto koncentrace xxxxxxxx xxxxxxx dané xxxxxxxxx x minimální xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx bude xxxxxxx xxxxxxxx, že xx xx xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. Xx-xx maximální xxxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx, xxxx xx být xxxxxxxxx přibližně 10 — 20 % (xxx xxxxxxx 10 %) xxxxxxx (relativní xxxxxxxx klonování) nebo xxxxxxxxx xxxxxxx xxxx. X xxxxxxx relativně xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

Xxxxxxxxx nerozpustné xxxxx xx měly xxx xxxxxxxx xx x xxxx xxxxxxxxxxxx za xxxxxxxxxxxx xxxxxxxx, xxxx xx za xxxx xxx. Xxxx xx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x konečném xxxxx, xx xxxxxxx xxxx buňky xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx a na xxxxx aplikace, xxxxx xxxxxxxxxxx xx xxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx buněk, S9 xxxx, xxx. Nerozpustnost xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx být xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Při xxxxxxx metabolické xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx pozitivní xxxxxxxx xxxxx být tyto xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx podle Einecs

Bez xxxxxx metabolické aktivace

HPRT

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

TK (xxxx x velké xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx xxxxxxxxxxxx xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (xxxx a xxxxx kolonie)

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid 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 xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx xxx xxxxxxx xxxx jiné referenční xxxxx xxx xxxxxxxxx xxxxxxxx, např. xx-xx xxxxxxxxx databázi dosavadních xxxxx x 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, XXXXXX 200–415–9), může xxx xxxx xxxxxxxxxx xxxxx xxxxxx xxxxxxx. Xxx xxxxxxxxx xxxxxxxx by xxxx xxx vzato x xxxxx xxxxxxx xxxxxxxxxx xxxxx pokud xxxxx xx stejné xxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx vehikulum a xxxxxxxxxx xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, že zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx látce

Proliferující xxxxx xx xxxx být xxxxxxxxx xxxxxxxx xxxxx xxx za xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx něho. Xxxxxxxx by xxxx xxxxx xxxxxxx dobu (xxxxxxx xx xxxxxx xxxx 3 xx 6 hodin). Xxxxxxxxx xxxx může být xxxxxxxxxxx xx jeden xxxx xxxx buněčných xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx mohou xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx exponovaná xxxxxxx. Xx-xx xxxxxxx xxxxx kultura, xxx xx xxx xxxxx xxxxxxxxxxx xxxxxx xxx, xxx xxx xxxxxxxx xxxxxxxxxxxx počet xxxxxx xxx analýzu (např. xxxxxxx osm analyzovatelných xxxxxxxxxxx). Měly xx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx rozpouštědla).

Plynné xxxx xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx uzavřených xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx xxxxx xxxxxxxxx xxxx xx buňky xxxxxxx x kultivují xx účelem xxxxxxxxx xxxxxxx x za xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Se xxxxxxxxxx cytotoxicity xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxxx celkového xxxxx xxxxxx xx xxxxxxx xxxxxxx xx expoziční xxxx.

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, aby umožnil xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx xxxx indukovaných xxxxxxx (XXXX x XXXX vyžadují xxxxxxx 6 xx 8 xxx, XX xxxxxxx xxx dny). Buňky xxxx xxxxxxxxxxx x xxxxx xx selekčním xxxxxxxx (selekčními xxxxxxx) x xxx něho (xxx nich) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx. Se stanovením xxxxxxxxxxxxxxxx (xxxxxxx pro xxxxxxx četnosti mutantů) xx xxxxxxx xx xxxxx xxxx xxxxxxx xxxxxxxxx xx xxxxx xxx xxxxxxxxxx činidla.

Je-li xxxxxxxx xxxxx pozitivní xx xxxxxxx X5178X XX+/-, xxxx xx xxx xxxxxxxxx xxxxxxx xx xxxxx xx xxxxxxxxxx xxxxxx (x xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x xx xxxxxxxxxxx x pozitivních xxxxxxxxxx xxxxxxxxx xxxxxxx podle xxxxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxx xx xxxxxxx X5178X TK+/- xxxxxxxxx, xxxx xx xxx rozdělení kultury xxxxx xxxxxxxxx kolonií xxxxxxxxx na xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx studiích xx xxxxxxx XX6 TK+/- xxxx být xxxx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx měly zahrnovat xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, počtu xxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. X xxxxxxx pozitivní xxxxxxxx xx xxxxxxx X5178X XX+/- se xxxxxxx xxxxxxxxx alespoň x xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (xxxxxxxx pozitivní xxxxxxxxxxx) a x xxxxxxxxx x pozitivní xxxxxxxx za xxxxxxx xxxxxxxx xxxx xxxxxxx — velká xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx jak mutantů xxxxxxxxx xxxxx kolonie, xxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Ve xxxxxxx XX+/- xxxx kolonie xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx s xxxxxxxxx xxxxxx (xxxxx) x xxxxxxx x xxxxxxx růstem (xxxx) (25). X xxxxxxxxxx xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx xxxx xxxxxxxx, x xxxxx xxxx malé xxxxxxx. Xxxxxxxxx má xxxxxxx xxxxxx od xxxxx xxxxxx xxxx až xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx tvořících xxxx xxxxxxx xx xxxxxxx x xxxxxxxxxx xxxxxxx, xxxxx xxxxxxxx silné xxxxxxxxxxxx aberace (26). Xxxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxx jako xxxxxxxx xxxxx a xxxxx velké kolonie.

Mělo xx xxx xxxxx xxxxxxx (xxxxxxxxx účinnost xxxxxxxxx) xxxx relativní xxxxxxx xxxx. Xxxxxxx xxxxxxx xx měla xxx xxxxxxxxx xxxx xxxxx xxxxxxx x xxxxx xxxxxxxxxx xxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx podmínek. Negativní xxxxxxxx xxxx být xxxxxxxxx případ xx xxxxxxx. Xxx, xxx xxxx potvrzení negativních xxxxxxxx xxxxxxxxxx xx xxxxx, xx xxxxx xxxxx zdůvodnění. Xxxxx xxxxxxxxx xxxxxx s xxxxx rozšířit xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx x následných xxxxxxxxxxxxx xxx pro xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx xxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx četností xxxxxxx v xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Xxxxxxxx xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx výsledků. Xxx hodnocení xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx.

Xxxxxxxx xxxxx, xxxxx výsledky nesplňují xxxx xxxxxxx kritéria, xx v tomto xxxxxxx považuje za xxxxxxxxxxx.

Xxxxxx většina experimentů xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx konečný výrok x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx xxxxxx v xxxxxxx xxxxx xx xxxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx genové xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx odpovědi xx xxxxxxxxxxx xx xxxxx xxxxxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx mutace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Buňky:

- xxx a xxxxx xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx kultury,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- inkubační xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- případně xxxxxxx xxxxx xxxxx expozice,

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

- pozitivní x xxxxxxxxx xxxxxxxx,

- xxxxx xxxx exprese (xxxxxxxx xxxxxx počtu nasazených xxxxx, xxxxxxxxx x xxxxxx média),

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx k xxxxxxxx xxxxxxxxxxxxxxx a xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- známky toxicity,

- xxxxxx xxxxxxx,

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

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

- xxxxxxxxx xxxxxxxxxxx laboratoře xxxxxxxxx mutanty xxxxxxx xxxx kolonie xxxxxxxx X5178X XX+/-,

- xxxxx xxxxxxxx závislost odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., DeMarini, X. X., DeSerres, X. X., Xxxxxx, X. X. (xxx.) (1987), Xxxxxxx Xxxxxx 28; Mammalian Xxxx Xxxxxxxxxxx, Xxxx Xxxxxx Xxxxxx Xxxxxxxxxx, Xxx Xxxx.

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

3) Xxxxx, X. X., Xxxxxx, X. X. (1982), Xxxxxxxx Xxxxx xx xxx Xxxxxxxxx Kinase Xxxxx xx Xxxxxxx Human Xxxxxxxxxxxx, Mutation Res. 94, 467-485.

4) Moore, X. X., Xxxxxxxxx-Xxxxx, X., Doerr, X. X., Xxxxxxxxx, K. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx xx xxx Mouse Xxxxxxxx XX xxx CHO XXXXX Loci, Mutagenesis, 4, 394-403.

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

6) Xxxxx, X. S., Xxxxxxxxxx, X., Glatt, X. X., Moore, X., Xxxxx, X., Xxxxxxxxxx, Jr. X. X., Theiss, J., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Xxxx Xxxxxxxx Assays Xxxxxxx Xxxxx Xxxxxx. Xxxxxx xx xxx International Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Scott, X., Xxxxxxxx, X. X., Xxxxxxxx, X. X., Ishidate, M., Xxxxxxx, X., Ashby, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Culture Xxxxxxxxxx. A xxxxxx xxxx ICPEMC 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 Xxxxxxxxx in X5178X Xxxxx xx Xxxxxxx. X Xxxxxx xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Gene-Tox Program, Xxxxxxxxxx Xxx., 115, 225-251.

9) Xx, X. X., Xxxxx, X. X., Heflich, X. X., Xxxxxx, X. X. (1988), A Xxxxxx xxx Xxxxxxxx xx xxx Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Transferase Xxxxxx xx Xxxxxxxxx the Xxxxxxxxxxxx xx Chemical Xxxxxx: X Xxxxxx xx Xxxxx XXX xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, X. X., Xxxxxx, J. X., Xxxx, X. X., Xxxx, X. X., Gupta, R. X., Xxxxxxx, X. X., X'Νxxxx, X. X., Xxxxxx, J. X., Stankowski, X. X. Xx., Xxxx, X. X. (1987), X Xxxxx for xxx Performance of xxx Chinese Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Liber, X. X., Yandell, X. X., Xxxxxx, X. B. (1989), X Comparison xx Xxxxxxxx Induction xx xxx TK and XXXX Xxxx in Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Differences xxx Xxx to xx Xxxxxxxxxx Class of Xxxxxxxxx xx xxx Xxxxxxxxx TK Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

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

13) Xxxxxx, X. T., Xxxxxx, X. G., Xxxxx, D. (1984), Xxxxxxxxx for xxx X5178X/XX+/--XX+/- Mouse Xxxxxxxx Xxxx Xxxxxxxxxxxx Assay, xx: Xxxxxx, X. X. xx xx (xxx.) Xxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx, Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxx Xxxx, 239-268.

14) Xxxxxx, C. X., Xxxxx, D. M., Xxxxxx, X. M., Xxxxx, M. H. X., Xxxx, X., XxXxxxxx, X. X., Xxxxxxx S. C. (1989), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Assays Xxxxx xxxx Xxxxxx Xxxxxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. J., xx., Xxxxxxxxx University Xxxxx, 66-101.

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

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

17) Xxxxx, X., Xxxxxxx, X. O., Xxxxxxx, X. X. X., Xxxxxx X. X., Xxxxx M. X. X. (1979), Validation xxx Xxxxxxxxxxxxxxxx of xxx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxxxx Xxxxx System, Xxxxx. Xxx. 59, 61-108.

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

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

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, K., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Polycholrinated Biphenyls x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, X: Xx vitro Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. J., Fouts, X. X., Xxxx, X. X., Philpot, X. M. (xxx), Xxxxxxxx, North-Holland, 85-88.

21) Xxxxx, D. X., Xxxxxx, X. X., XxXxxxx, K. X. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx and Volatile Xxxxxxx, in: Xxxx, X. X., Xxxxx, X. L., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, X. X., Xxxxxx, J. M., Xx, X. X., Xxxxxx, A. X. (1983), Evaluation xx xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Gels xxx Xxxxxxxxx Highly Xxxxxxxx Xxxxxxxx in xxx CHO/HGPRT Xxxxxxxx Xxxxx, Xxxxxxx. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. L., Xxxxx, X. X., Broder, X. X., Xxxxxxx, X., Xxxxxx, X. X. (1990), Molecular Xxxxxxxxxx xx Xxxxxxxxx xx xxx Heterozygous Xxxxxxxxx Xxxxxx Xxxxx xx Mouse Lymphoma Xxxxx, Xxxx. Natl. Xxxx. Xxx. X. X. X, 87, 51-55.

24) Xxxxx, X. X., Clive, X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. G., Xxxxxx, X. X., Xxxxxx, X. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (TFT+) Mutants xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res. 151, 161-174.

25) Yandell, X. W., Dryja, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Genetic Xxxxxxxx xx Xxxxxxxxx Mutations xx a Xxxxxxxxxxxx Xxxxxxxxx Xxxxx xx Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

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


XXXXXXX 4F

"B.23 ZKOUŠKA XX XXXXXXXXXXXX ABERACE XX SPERMATOGONIÍCH XXXXX

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx in xxxx xx xxxxxxxxxxxxx xxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx xx spermatogoniích xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. X xxxxxxx xxxxxxxxxx mutagenů xxxx indukované xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx xxxxxx xx stanovení numerických xxxxxxx x není x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Chromozomové xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx x xxxxxxx.

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

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx detekují xxxxxxxxxxxx xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx nejsou xxxxxxxxx xxxx zkoušky.

Pro xxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx by xxxx být — xxxxx xxx xxxxx xx xxxxxx xxxx — vyšetřeno xxxxx xxxxxxxxx xxxxxxx dělení, xxxxx následuje xx xxxxxxxx. Xxxxx xxxxxxxxx x xxxxxxxxxxxx spermatogoniálních xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x xxxxxxxxx-xxxxxxxx X, xxx se xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx zkouška in xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx aktivní xxxx x xxxxxxxxxxxx buňkách. Xxxxx xx xxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx posouzení xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx DNA.

Ve xxxxxxxxx xx přítomna řada xxxxxxxx spermatogonií x xxxxxx xxxxxxxxxx xx xxxxxxxx chemické xxxxx. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxxx odpověď xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx poloze xx xxxxxxxxx, mohou xxxx xxxxxx xxx xxxxx generace spermatogonií xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x xxxxxxx mezi xxxxxxx oběhem x xxxxxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, že xx zkoušená xxxxx xxxx reaktivní xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, není vhodné xxxx zkoušku xxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 XXXXXXXX

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

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

Xxx : achromatická xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx dělení ve xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx x xxxxxxxxx, intrachromozomální nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx jsou xxxxxxx xxxxxxxx exponována xxxxxxxx xxxxx x xx vhodné době xx xxxxxxxx usmrcena. Xxxx usmrcením se xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx buněk xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx x xxxxxxxxx xx chromozomové aberace xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx xxxxxxxxx samci xxxxxx xxxxxxxx x xxxx; xxx však xxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx laboratorní xxxxx xxxxxxx zdravých pohlavně xxxxxxxxx zvířat. V xxxxxxxx xxxxxxxx xxxxxx xx xxxx být xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx překročit ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx obecného úvodu x části B, xxxxxxx xx xxxx xxx dosaženo vlhkosti xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx tak, aby xxx xxxx jejich xxxxxx minimalizován. Zvířata xx jednoznačně xxxxxxxxxxxx. Xxxx započetím studie xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx rozpuštěny nebo xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxxx xxxx xxxxx xxx před xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx podezření, že xxxxxxx se zkoušenou xxxxxx. Jsou-li použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx údaji o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

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

Xxxxxxxxx xxxxxxxx by měly xxxxxxxxxx xxxxxxxxxx xxxxxxx xx spermatogoniích xx xxxx při expozičních xxxxxxxx, u nichž xx předpokládá, že xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx byl xxxxx x xxxxx případě xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx být xxxxx xxxxx v xxxxx xxxxxxx chemických xxxxx xx xxxxxx chemické xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxx (xxxxxxx)

79–06–1

201–173–7

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

51–18–3

200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx měl být xxxxxxxx xxxxx u xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx aplikováno xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat a xxxxxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx prokazující, že xxxxxxx rozpouštědlo/vehikulum nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

Xxxxx exponovaná x xxxxxxxxx xxxxxxx xxxx zahrnovat xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx měly být xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxx (xx. xxx jedné xxxxxxxx nebo xxxx xxxxxxxxxx). Zkoušené xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx xxxxx v xxx xxx x xxxxxxx xx xxxx xxx xxxxxxxx hodin, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx režimy xxxxxxxx xx měly xxx xxxxxxx zdůvodněny.

Ve xxxxxxx x xxxxxxxx xxxxxx xx xxxx xxx xx xxxxxxxx provedeny xxx xxxxxx. Xxxxxxxx xxxxxxxx buněčného cyklu xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx xxxxx xxxxx xxxxx x xxxxx xxxxxxxx odběr xxxxxxxxx 24 a 48 xxxxx xx expozici. X případě xxxx xxx xxxxxxxx xxxxx xx xxx xxx xxxxx xxxxxxxx xx 24 hodin nebo xx takové xxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx délky xxxxxxxxx xxxxx, xxxxx není xxxxx jiná xxxxxxxxx xxxx xxx xxxxxxx xxxxxx (6).

Navíc mohou xxx xxxxxx provedeny xxxx v xxxx xxxx. Xxxxxxxxx v xxxxxxx xxxxxxxxxx xxxxx, xxxxx mohou xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) xxxxxxxxxx xxxx mohou xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx xxx vhodnější xxxxxxxx xxxxx (1).

Vhodnost xxxxx xxxxxxxxx xxxxxxxx xxxx xxx určena xxxxxx od xxxxxxx. X xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5násobek xxxxx xxxxx) po xxxxxxxx xxxxxxxx. Xxxxx xxxxxxx xxxxx xxx prováděny xxxxx odběry x xxxx xxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx vhodná dávka xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx u xxxxxx xxxxx. U xxxx xx tato doba xxxxxxxxx 3 — 5 hodin; u xxxxxx xxxxxxxx je xxxx doba xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx údajů xxxxxx xxx xxxxxxxx xxxxxxx, xxxx by xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx expozice, xxxxx xx xxxxxxx v xxxxxx studii (7). X xxxxxxx toxicity xx xxx xxxxx xxxxx použijí tři xxxxxx xxxxx. Tyto xxxxxx dávky xx xxxx xxxxxxxx xxxxxxx xxxx maximální x xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx bude xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx xx xxxxx xxxxx vedly xxx xxxxxxx režimu xxxxxxxxx podle očekávání x letalitě.

Látky xx xxxxxxxxxxx biologickou aktivitou xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx a měly xx xxx hodnoceny xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx může xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xx spermatogoniích xxxxxxx xxxxxx xxxxxxxx (např. xxxxxxx počtu spermatogonií x xxxxxx xxxxxxxx x první a xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx by xxxxxx xxxxxxxxx 50 %).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx dvou dávkách x xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx účinky x xxxx-xx xx xxxxxxx xxxxx o látkách, xxxxx mají podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx se xxxxx xxxxxx xx třemi xxxxxxxx dávky xx xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx může xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx dávky.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační kanylou, xxxx intraperitoneální xxxxxxx. Xxxx xxxxxxx podávání xxxx přijatelné, xxxx-xx xxxxxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx být xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx konstantní objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx chromozomů

Ihned xx usmrcení xx x jednoho xxxx xxxx varlat xxxxx xxxxxxx xxxxxxxx, hypotonizuje xx x fixuje. Xxxx xx xxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx alespoň 100 xxxxx x dobře xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 xxxxxxxx xx skupinu). Tento xxxxx lze xxxxxx, xx-xx pozorován xxxxx xxxxx aberací. Všechny xxxxxxxxx včetně preparátů xxxxxxxxxxx a negativních xxxxxxx, xx měly xxx xxxx mikroskopickou xxxxxxxx nezávisle kódovány. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx x xxxxx metafází, měly xx vyšetřované buňky xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx xxxxx zvíře xx xxx být xxxxxxxxxx xxxxx xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x počet xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Pro exponované x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx počtem x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx odděleně x xxxxxxx se, xxx obecně xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, xxx xx xxx pro stanovení xxxxxxx xxxxxxxxxxxxx xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx x všech xxxxxxxxxxxx xxxxxx a xxxxxx xxxxxxxxxx jako xxxxxxxxx xxxxxxxx poměr xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx meiotické xxxxxxxx, x xx x xxxxxxxx xxxxxx 100 xxxxxxxx xx xxxxx na xxxxx xxxxx. Xxxxx xx xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx xx xxxxx xx měl xxx xxxxxxxx mitotický index.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx aberacemi v xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx buněk x xxxxxxxxx pro xxxxxxx x určitou xxxxxx x x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx prostředek statistické xxxxxx (8). Statistická xxxxxxxxxx xx neměla xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

Zkoušená xxxxx, xxxxx výsledky nesplňují xxxx xxxxxxx xxxxxxxx, xx x tomto xxxxxxx považuje za xxxxxxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx dvojznačné nebo xxxxxx xxx ohledu xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xxxxx in xxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx druhu xxxxxxxxxx xxxxxxxxxxxx aberace. Negativní xxxxxxxx znamenají, že xxxxxxxx látka xx xxxxxxxx xxxxxxx neindukuje x germinálních xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx by xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx xxxxxxxx xx xxxxxx tkáně.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx x stáří xxxxxx,

- xxxxx, podmínky chovu, xxxxxx xxx.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx zkoušky, včetně xxxxxxx tělesné hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- údaje o xxxxxxxx zkoušené látky,

- xxxxx x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxx usmrcení,

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

- xxxxxxxx xxxxx x kvalitě krmiva x xxxx,

- podrobný xxxxx xxxxxxx xxxxxxxx x odběru,

- metody xxxxxxxxx xxxxxxxx,

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

- metody xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx xxxxx na xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxxxxx xxxxx,

- poměr xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxx xxxxxx,

- xxx a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- celkový xxxxx xxxxxxx ve skupině,

- xxxxx xxxxx s xxxxxxxxx xx xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx pozitivní xxxxxxxx,

- xxxxx ploidie, xxxxx xxxx pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Adler, I. X., (1984), Xxxxxxxxxxx xxxxx in Mammals, xx: Mutagenicity Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, (xx.) S. Venitt, X. X. Xxxxx, XXX Press, Xxxxxx, Xxxxxxxxxx XX, 275-306.

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

4) Richold, X., Xxxxx, J., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxx Assays, xx: D. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Port Chester, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, X. D., Xxxxxx X. X., Xxxxxxx, J., Xxxxx, X., Xxxxxxxx, W., Xxxxxxxxxxxx, F., Xxxxxxx, X., Xxxxxx N. (1994), International Workshop xx Standardisation of Xxxxxxxxxxxx Xxxx Procedures. Xxxxxxx Report xx xxx Xxxxxxx Group xx Mammalian Germ Xxxx Xxxxx, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, R. J., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, P. A., Xxx, J., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, D. X., Richold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Xxxxx: Dose Xxxxxxx xx In xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, X. X., Clarc, G., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Savage X. X. X. (1989), Xxxxxxxxxxx Analysis xx Xx vivo Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Part XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Sydney, 184-232."


PŘÍLOHA 4G

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX XX 486 — Xxxxxxx xx xxxxxxxxxxxx syntézu XXX (UDS) x xxxxxxxxx xxxxxxx xxxxx xx vivo (1997).

1.1 XXXX

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

Xxxx xxxxxxx in xxxx xxxxxxxxx xxxxxx vyšetření xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx v xxxxxxx. Xxxxxxxxxxx xxx xx xxxxxxxxxx poškození DNA x xxxxxxxx xxxxxxxx x jaterních xxxxxxx. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, xxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx xxxx xxxxxxx xxxxxx pro xxxxxxxxx xxxx poškození XXX xx xxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, že xx xxxxxxxx xxxxx xxxxxxxxx xx xxxxxx tkáně, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (UDS) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx nukleosidů xx buněk, xxxxx xxxxxxxx xxxxxxxxxx syntézou XXX (S-fází). Nejrozšířenější xxxxxxxxx xx autoradiografické xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3H-TdR). Xxx xxxxxxx xx XXX xx xxxx xx xxxxxxxxxx xxxxxxxxx xxxxx xxxxxxx. Jiné xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, xxxxxx však xxxxxxxxx této xxxxxx.

Xxxxxxx xxxxxxxx UDS xxxxxx xx xxxxx xxxx XXX xxxxxxxxxxx a xxxxxxxxxxx x xxxxx xxxxxxxxx. Xxxxxxx xx XXX xx xxxx xxxxxx zvláště xxx xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("xxxxx-xxxxx repair") (xxxxx xx xxx xxxx) xxxx naproti xxxx detekovány x xxxxxx xxxxx citlivostí. Xxxxx může xxxxxxxxx xxxxxxxxxxxxx reparace, xxxxxx xxxxxxxx nebo xxxxxx xxxxxxxxx lézí XXX xxxxx x mutagenním xxxxxxxxx. Xxxxxx xxxxxxxx XXX xxxxxxxxxxx xxxxxx xxxxxxxxx o věrnosti xxxxxxxxxxx procesů. Navíc xx možné, xx xxxxxxx reaguje x XXX, xxx poškození XXX není opraveno xxxxxxxxxxx xxxxxxxx. Nedostatek xxxxxxxxxxxx xxxxxxxxx, které xxxx zkouška poskytuje x xxxxxxxxx xxxxxxxx, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx je vyšetřován x xxxxx genomu.

Viz xxxx obecný xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (NNG), xxxxx než xxxxxxxxxx xxxxxxx stanovená xxxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx buněk v xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx odečtením xxxxxxxxxx xxxxx xxx x cytoplasmatických xxxxxxxxx (XX) xxxxxxxxxxxxxx jádrům xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): XXX = XX — XX. Xxxxxxx XXX se xxxxxxx xxx jednotlivé xxxxx, poté společně xxx xxxxx x xxxxxxx, x paralelních xxxxxxxxx atd.

Neplánovaná xxxxxxx XXX (UDS) : Xxxxxxx reparací XXX xx xxxxxxxxx a xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xx XXX x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxx syntézu xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx úseku XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx činiteli. Xxxxxxx xx xxxxxxx založena xx xxxxxxxxxxx 3X-XxX xx XXX xxxxxxxxx xxxxx, kde xx xxxx četnost xxxxx x S-fázi xxxxxxxxx xxxxx. Xxxxxxxxxxx 3H-TdR xx obvykle stanoveno xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx není tak xxxxxxx xx xxxx X-xxxx xxxxx xxxx xxxx. kapalná scintilační xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx je xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxx xxxxx. Xxxx xx xxx použity xxxxx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx by xxxx xxx odchylka x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx k xxxxx X, xxxxxxx xx xxxx být xxxxxxxx xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, která xx exponuje. Klece xx měly xxx xxxxxxxxxx xxx, aby xxx vliv xxxxxx xxxxxx minimalizován. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx se xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx přímo xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx o xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxxxxx zvážit xxxxxxx xxxxx xxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx části xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx zvířata xxxxxxxxx xxxxxxx podstoupit xxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx xxxx být xxxxx, x xxxxx xx xxxxx, xx xxxxxx xxxxxxxx v xxxxxxxxxxx expozičních xxxxxxxxxxxxx xxxx k nárůstu XXX detekovatelnému xxx xxxxxxx. Pozitivní xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aktivaci xx xxxx xxx xxxxxxx v xxxxxxx xxxxxxxxxxxx xxxxxx odpověď (4). Xxxxx xxxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 až 4 h)

N-nitrosodimethylamin

62–75–9

200–249–8

Pozdní xxxx xxxxxx (12 až 16 x)

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

53–96–3

200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx látky xxx xxxxxxxxx kontrolu. Xx xxxxxxxxx, aby xxxx xxxxxxxxx xxxxxxxxx látka xxxxxxxx jiným způsobem, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxx xx xxx xxxxxx xxxxxxxxxx xxxxx zvířat, aby xxxx zohledněno přirozené xxxxxxxxxx kolísání xxxxxxxx xx xxxxxxx. Xxxxx xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx dostatečné dosavadní xxxxx, xx pro xxxxxxxxx x pozitivní xxxxxxxxx xxxxxxx nezbytné xxxxx xxxxx xx xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx xxxxxx x dispozici xxxxx xx studií xx xxxxxxx druhem a xx xxxxxxx xxxxxxxx xxxxxxx expozice, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx pohlavími xxxxxx x toxicitě, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx, nejlépe xxxxx. Xx-xx expozice xxxxxxx xxxxxxxxxx pro určité xxxxxxx, xxxx je xxxx například u xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx xxx xxxxxxx provedena se xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xxxx xxxxxxxxx podávány xxxxxxxxxxx.

1.5.3 Dávkování

Za xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx xxx xxxxxx xxxxx. Nejvyšší xxxxx xx definována jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxxxx očekávání xxx xxxxxxx xxxxxx xxxxxxxxx k xxxxxxxx. Xxxxx xxxxx by xxxx xxx zpravidla 50 % až 25 % xxxxx xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx netoxických dávkách (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx by xxx xxxxxxxxx případ xx případu. Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, měla xx xxx provedena xx xxxxxx xxxxxxxxxx, xx xxxxxxx druhem, kmenem, xxxxxxxx x xx xxxxxxxx režimu expozice, xxx xx xxxxxxx x xxxxxx studii.

Nejvyšší xxxxx může xxx xxxxxxxxxx xxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxxxx x játrech (xxxx. pyknotická xxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou xxxxxx x alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx jednorázově xxxx xx xxxx xxxxxxx x xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx podobnou xxxxxxxxx, očekávána xxxxxxxxxxxx, xxxxxx být xxxxx xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx použít x xxxxxxx zkoušce xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou možné, xxx-xx je zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx xxxxxxxxxxxx, xxxxx xx játra xxxxx xxx exponována zkoušené xxxxx přímo x xxxxxx prostřednictvím xxxxxxxxx xxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx je uvedený xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx vyšších koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx nastavením koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx úrovních xxxxx.

1.5.6 Příprava jaterních xxxxx

Xxxxxxx buňky xx xxxxxxxxxx x exponovaných xxxxxx zpravidla 12 xx 16 hodin xx podání dávky. Xxxxxxxxxx xxxxxxxx odebrání xxxxxx (xxxxxx xxx xx xxxxx hodiny xx expozici) xx xxxxxxxx, není-li xx 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xxxxx však xxx použity jiné xxxx xxxxxx, xxxx-xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxxx xx xxxx x xxxxxx xx, xxx xx xxxxxxx disociované xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx buňky z xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) alespoň 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx obvykle xxxxxxx xxxx, xxxx. xxx xx xxx xxxxx, inkubují s xxxxxx obsahujícím 3X-XxX. Xx konci inkubační xxxx xx mělo xxx xxxxxx z xxxxx xxxxxxxxxx x xxxxx xxxx mohou xxx xxxxxxxxxx s xxxxxx obsahujícím xxxxxxxx xxxxxxxxxxx thymidinu, xxx xxxx snížena neinkorporovaná xxxxxxxxxxxxx ("cold xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx a xxxxxx. Xxx delší xxxxxxxxx xxxx nemusí xxx xxxxxxx radioaktivity xxxxxxxx. Xxxxxxxxx xx xxxxxx xx autoradiografické xxxxxx, exponují se x temnu (např. x xxxxxx 7 xx 14 dnů), xxxxxxxx xx, xxxxxx x spočítají se xxxxxxxxxx xxxx stříbra. X každého xxxxxxx xx xxxxxxxx dva xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx by xxxx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx, xxx xxxx hodnocení XXX xxxxxxxxx hodnotu. Xxxxxxxxx xx xxx xxxxxxxxxxx prohlédnou na xxxxxx xxxxxx xxxxxxxxxxxx (xxxx. xx pyknosu, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx izotopem).

Před počítáním xxx by xxxx xxx preparáty xxxxxxxx. Xxxxxxxxx se vyšetřuje 100 xxxxx xx xxxxx xxxxx xxxxxxx xx xxxx xxxxxxxxx; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx xx xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx xxx xx jádra v X-xxxx xxxxxxxxxxx, ale xxxxx buněk x X-xxxx xxxx xxx xxxxxxxxxx.

Xxxxxxxx 3H-TdR inkorporovaného xx jader x xxxxxxxxxx morfologicky xxxxxxxxxx xxxxx xxxxxxxx navrstvením xxx xxxxxxx xx xxxx xxx stanoveno xxxxxxx metodou.

Počet xxxxx xx xxxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (ng) x x prŭměrného xxxxx zrn v xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx xxxxŭx. jako xxxxxxx cg se xxxxxxx buď xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx prŭměrná xxxxxxx xxxx až xxx xxxxxxx xxxxxxxxx oblastí x xxxxxxxxx dotyčných xxxxxxxxx jader. xx xxxxxxxxxxxxx zdŮvodnění xxxxx xxx xxxxxxx x xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (např. xxxxxxxx celých buněk) (6).

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx a xxxxxxx. Údaje xx xxxx být xxxx xxxxxxx xx xxxxx xxxxxxx. Odečtením hodnoty XX od xxxxxxx XX by xxx xxx vypočten pro xxxxxx xxxxx, xxx xxxxx zvíře x xxx xxxxxx dávku x čas čistý xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx xxxxxxxx "xxxxxxxxxx" buňky, xxxx xx xxx xxxxxxxx xxx xxxxxxxxxx "opravovaných" xxxxx xxxxxxxxxx x xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x negativních xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx být xxxxxxx, xxxx by xxx xxxxxxxxxxx xxxxx xxxxxxx a xxxxxxxxxx xxxx provedením xxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx pozitivní nebo xxxxxxxxx xxxxxxx patří:

pozitivní

i)

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

xxxx

xx)

xxxxxxx NNG xx xxxxxxxx vyšší xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx NNG xxxx xxxxxxxx vyšší než xxxxxxx pro xxxxxxxxx xxxxxxxx.

Xxxx by být xxxxxxxxx xxxxxxxxxx relevance xxxxx, xx. měly xx xxx xxxxx x xxxxx xxxxxxxxx, xxxx xxxx xxxxxxxxxxx xxxxxx, vztah xxxxx x xxxxxxxx x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx významnost xx xxxx neměla xxx xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx.

Xxxxxx většina experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na XXX x jaterních xxxxxxx xxxxx xx xxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxxx DNA, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx DNA xx xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx poškození XXX, xxxxx xxx xxxxxxxxx touto xxxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

- xxxxxxxxxxx x stálost zkoušené xxxxx x rozpouštědle/vehikulu, xx-xx známa.

Testovací xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- zdroj, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx počátku zkoušky, xxxxxx rozpětí tělesné xxxxxxxxx, střední hodnoty x směrodatné odchylky xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (vehikulum/rozpouštědlo) xxxxxxxx,

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

- xxxxxxxxxx zvolených úrovní xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx látky v xxxxxx xxxx xxxx (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx tělesné xxxxxxxxx/xxx),

- xxxxxxxx údaje x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx buněk,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- počet xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxx možnosti xxxxxxxxx odpovědi xx xxxxx,

- případné statistické xxxxxxxxx,

- xxxxxx xxxxxxxx,

- xxxxx o souběžné xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx xxxxxxxx,

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

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

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

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, X. Xxxxxxx, X. A., Xxxxxxxxx, X., Xxxxxx, X. X. (1985), Xx Xxxxxxxxxx xx xxx Xx xxxx Xxx. Xxxxxxxxxx XXX Repair Xxxxx, Mutatation Xxx., 156, 1-18.

2) Butterworth, X. X., Xxxxx, X., Bermudez, E., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, G., Xxxxxxxx, G. (1987), X Protocol and Xxxxx for xxx Xx xxxx Xxx Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.

3) Xxxxxxxx, X. X., Xxxxxx, X., Ashby, X., Xxxxxxx, X. X., Xxxxxxxxx, B., Xxxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X. xx X. (1993), In xxxx Xxx Xxxxx XXX Xxxxx, xx: Kirkland X. X., Xxx X., (eds), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx. Part XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Chester, Xxxxxxxxx, Sydney, 52-77.

4) Xxxxx, S., Xxxx, X. X., Andrac, X., Brambilla. G., Xxxxxxxxx, X., Doolittle, X. X., Furihata, X., Hertner, X., XxXxxxx, C. A., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx of XXX Xxxxx Xx xxxxx xxx Xx vivo, Xxxxx. Xxx., 312, 263-285.

5) Fautz, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Xxxxxxxxxx xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxx xxx xxx Xxxxxxxxxx xx Xxxxxxx Isolated Xxx Xxxxxxxxxxx Xxxx xxx xxx Xx xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

6) Mirsalis, J. X., Xxxxx, X. X., Xxxxxxxxxxx, X. X. (1982), Detection xx Xxxxxxxxx Xxxxxxxxxxx xx xxx Xx xxxx/Xx vitro Xxxxxxxxxx XXX Repair Assay, Xxxxxxx.Xxxxxxx. 4, 553-562."


XXXXXXX 5

OBECNÉ XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X PŘÍPRAVKŮ

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


XXXXXXX 6

"

XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. x) xxxx směrnice, xxxx xxx xxxxx x xxxxxxxxx xxxxxx obsahující xxxxx, x xxxxx xx xxxxxxx xxxxxx xxx xxxxxxxxxx (Xx; X 65) x xxxxx xxxx klasifikovány x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx xx trh xx xxxxx xxxxxxxx xxxx x nádobách xxxxxxxxxx aerosolovým xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx obaly

Uzávěry xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx na xxxxxxxxx uzavíratelných xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx ISO 8317 (xxxxxx ze xxx 1. xxxxxxxx 1989) "Xxxxx xxxxxx dětem — Xxxxxxxxx na xxxxxxxxx uzavíratelné xxxxx x xxxxxx jejich xxxxxxxx" přijatou Xxxxxxxxxxx xxxxxxxxxx xxx normalizaci (XXX).

2. Opakovaně xxxxxxxxxxxxxx xxxxx

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

3. Xxxxxxxx

1. Prokázání xxxxx x xxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx laboratoře, xxxxx xxxxxxx xxxxxxxx xxxxx xxxx EN 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx xxxx xx xxxxxxxxxx bezpečný xxx xxxx, neboť se xxxxxxx dostat x xxxxxx xxx pomoci xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x pochybám x xxxxxxxxxxx xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx orgán požadovat, xxx xxxxx odpovědná xx xxxxxxx xxxxxxx xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx laboratoří xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- typ xxxxxxx je xxxxxx, xx jej xxxx xxxxxxxx zkoušet xxxxx xxxx xxxxxxxxx norem XXX a XXX,

xxxx

- xx uzávěr byl xxxxxxx a xxx xxxxxxx xxxxxxxxxxx xxxxx xxxx xxxxxxxxx norem.

ČÁST X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx xxxxxxxxxxx xxx xxxxxxxxxx výstrahy xxxx xxx v xxxxxxx s xxxxxx XX XXX 11683 (xxxxxx z xxxx 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"