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Xxxxxxxx Xxxxxx 2000/32/XX

xx xxx 19. xxxxxx 2000,

xxxxxx se po xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxx Xxxx 67/548/EHS x xxxxxxxxxx právních x xxxxxxxxx předpisů týkajících xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx nebezpečných xxxxx [1]

(Text x xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX SPOLEČENSTVÍ,

s xxxxxxx xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx společenství,

s xxxxxxx xx směrnici Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 x sbližování xxxxxxxx x xxxxxxxxx xxxxxxxx týkajících xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx nebezpečných xxxxx [2], naposledy pozměněnou xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Rady 1999/33/ES [3], a xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx x xxxxx xxxxxxx:

(1) Příloha X xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxx xxxxxxxx s xxxxxxxxxx údaji o xxxxxxxxxxx a označování xxxxx xxxxx. Současné xxxxxxx a technické xxxxxxxx xxxxxxx, že xx xxx xxx xxxxxx xxxxxxxxxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxxxxx. Některé jazykové xxxxx směrnice vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a xxxxxxx X x xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx xxx udávajících xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx s xxxxxxxxxxxx xxxxxxx x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx seznam xxx x bezpečnostními xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx látek x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje xxxxx xx klasifikaci x x označování xxxxxxxxxxxx látek x xxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxx III, XX x VI.

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

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx. Tyto xxxxxxxx xx xxxx být xxxxxxxxxxxx a aktualizovány. Xx xxxxxxxx xxxxxxxx xxxxxx, xxx se xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxxxx.

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

XXXXXXX XXXX XXXXXXXX:

Xxxxxx 1

Xxxxxxxx 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx I xx xxxx xxxxx:

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

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

x) xxxxxxxxxxxx xxxxxxx xx nahrazují xxxxxxxxx x příloze 1C xxxx xxxxxxxx;

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

2. Odpovídající xxxx x xxxxxxx III xx xxxxxxxxx standardní xxxxx xxxxxxxxxx specifickou xxxxxxxxxx x příloze 2 xxxx směrnice.

3. Xxxxxxx XX xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx v xxxxxxx XX xx xxxxxxxxx xxxxxxxxxxxx pokyny xxx xxxxxxxx zacházení x xxxxxxx 3A této xxxxxxxx;

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

4. Xxxx X xxxxxxx X xx xxxx xxxxx:

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

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

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

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

e) xxxxxxxx X.17 xx xxxxxxxxx xxxxxx v xxxxxxx 4X xxxx xxxxxxxx;

x) xxxxxxxx B.23 xx xxxxxxxxx xxxxxx v xxxxxxx 4F xxxx xxxxxxxx. Xxxxx xxxxxxxx X.23 ve xxxxxxxxxxx xx mění odpovídajícím xxxxxxxx;

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

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

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

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

Xxxxxx 2

1. Xxxxxxx xxxxx uvedou x xxxxxxxx xxxxxx x xxxxxxx předpisy xxxxxxxx xxx xxxxxxxx xxxxxxx x touto směrnicí xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x xxxx xxxxxxx Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx státy musí xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx takový xxxxx xxx xxxxxx xxx xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx odkazu si xxxxxxx xxxxxxx státy.

2. Xxxxxxx státy sdělí Xxxxxx znění xxxxxxxx xxxxxxxxxx vnitrostátních právních xxxxxxxx, xxxxx xxxxxxx x oblasti působnosti xxxx xxxxxxxx, x xxxxxxxxxx xxxxxxx mezi xxxxxxxx a xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Článek 3

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

Článek 4

Xxxx xxxxxxxx xx xxxxxx členským xxxxxx.

V Xxxxxxx xxx 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Wallström

členka Xxxxxx


[1] Přijato xx xxxxxxxxxxxx po xxxxxxx xxxxx.

[2] Xx. věst. 196, 16.8.1967, x. 1.

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


PŘÍLOHA 1X

XXXXXXXXX K XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x označování xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


PŘÍLOHA 1X

"XXXXXXX X

X

Xxxxxx

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

18

Xx

Xxxxx

Xxxxx

Xxxxx

Αργό

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"


PŘÍLOHA 1C

Indexové číslo

Chemický xxxxx

Xxxxxxxx k xxxxxx

Xxxxx XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–011–00–7

xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

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

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 X31 X; X34 R43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

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

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

006–016–00–4

propoxur (XXX) 2- isopropoxyfenyl-N-methylkarbamát

204–043–8

114–26–1

T; X25 N; R50–53

T; X R: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; R26/28 T; X24 N; R50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 X; X50–53

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

006–019–00–0

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

218–961–1

2303–16–4

Xxxx. kat. 3; X40 Xn; X22 X; R50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; R22 X43 X; R50–53

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

006–023–00–2

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

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

205–443–5

140–93–2

Xx; X22 Xi; X38 X; X51–53

Xx; X X: 22–38–51/53 X: (2-)13-61

006–026–00–9

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

216–353–0

1563–66–2

X+; X26/28 X; X50–53

X+; X X: 26/28–50/53 S: (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

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

230–253–4

6988–21–2

X; X25 N; X51–53

X; N X: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

metoxuron (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) S-propyl-N-butyl-N-ethylthiokarbamát

214–215–4

1114–71–2

Xn; X22 X; R51–53

Xn; X X: 22–51/53 X: (2-)23-61

006–035–00–8

xxxxxxxxxx (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx

245–430–1

23103–98–2

X; X25 N; X50–53

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

006–037–00–9

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

220–113–0

2631–37–0

X; X25 X; X50–53

X; X X: 25–50/53 S: (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. kat. 2; R45 Xx; X22 N; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; X22–48/22 X43 X; X50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; X40 Xx; X22 X; X50–53

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

006–043–00–1

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

140–41–0

Xx; R36/38 Karc. xxx. 3; X40 X; R50–53

Xn; 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 N; X50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; X23/25 Xx; X21 X; X50–53

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

006–047–00–3

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

8065–36–9

X; X24/25 N; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–050–00–X

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

4482–55–7

Xx; X38 X; X50–53

Xx; N X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; R50–53

Xn; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xx; X21 N; X50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)24-61

006–060–00–4

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

226–066–2

5259–88–1

Xx; X22 X52–53

Xx R:22–52/53 X: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Muta. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–070–00–9

xxxxxxxxxxx N-cyklohexyl-N-methoxy-2,5-dimethyl-3-furamid

262–302–0

60568–05–0

Karc. xxx. 3; X40 N; X50–53

Xx; X R: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

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

82560–54–1

X; X23/25 X; X50–53

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

007–012–00–5

X,X-xxxxxxxxxxxxxxxx 1,1-dimethylhydrazin

E

200–316–0

57–14–7

F; X11 Xxxx. xxx. 2; R45 X; X23/25 C; X34 X; X51–53

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

007–013–00–0

N,N-dimethylhydrazin 1,2-xxxxxxxxxxxxxxxx

X

540–73–8

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

X; N R: 45–23/24/25–51/53 X: 53–45–61

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

009–003–00–1

xxxxxxxx xxxxxxxxxxxxxx … %

B

231–634–8

7664–39–3

T+; X26/27/28 X; R35

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

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

015–039–00–9

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

201–676–1

86–50–0

X+; X26/28 X; X24 X43 X; X50–53

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

015–048–00–8

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

200–231–9

55–38–9

Xxxx. xxx. 3; R40 X; R23–48/25 Xn; X21/22 N; X50–53

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

015–056–00–1

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

220–147–6

2642–71–9

X+; X28 X; X24 N; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xx; X21 N; X50–53

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

016–013–00-X

chlorid xxxxxxx

234–129–0

10545–99–0

X14 X; X34 N; X50

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

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

016–014–00–5

chlorid xxxxxxxx

13451–08–6

X14 X; X34 N; X50

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

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

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; X26 T; X25 C; X34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; R22 N; X50–53

Xx; X R: 22–50/53 S: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

X43

Xx X: 43 S: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 X; R34

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

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

030–004–00–8

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

050–002–00–0

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

236–049–1

13121–70–5

Xn; X20/21/22 X; X50–53

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

050–012–00–5

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

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

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

Xn; X20/21/22 X; X50–53

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

X ≥ 1 %: Xx; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

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

X+; X X: 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) XX xxxxxxxxxx xxxx 34 (XX 77603)

215–693–7

1344–37–2

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

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

1

082–010–00–5

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

235–759–9

12656–85–8

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

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

1

601–024–00-X

xxxxx [1] xxxxxxxxxxxx [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

X10 Xx; X65 Xi; X37 X; R51–53

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

4

601–032–00–3

benzo[a]pyren benzo[def]chrysen

200–028–5

50–32–8

Karc. xxx.2; X45 Xxxx. xxx. 2; X46 Xxxx. kat. 2; X60–61 N; R50–53

T; 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. kat.2; X45 N; X50–53

X; X X: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-dichlorbenzen x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 X; R50–53

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

602–054–00–6

3-xxxxxxx-1-xx xxxxxxxxxx

209–130–4

556–56–9

X10 X; R34

C X: 10-34 S: (1/2-)7–26–45

603–076–00–9

but-2-yn-1,4-diol

203–788–6

110–65–6

T; X23/25 Xx; R21–48/22 X; X34

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

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

603–091–00–0

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

402–470–6

87172–89–2

X; X8 Xx; R22 Xx; X36

X; Xx R: 8–22–36 S: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xx; X20 X; X51–53

Xx; X X: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; R36 X52–53

Xx X:36–52/53 X: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx isopropanol

200–661–7

67–63–0

F; R11 Xx; X36 R67

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

604–020–00–6

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

201–993–5

90–43–7

Xx; R36/37/38 X; R50

Xi; X X: 36/37/38–50 S: (2-)22-61

604–021–00–1

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

205–055–6

132–27–4

Xx; X22 Xx; X37/38–41 N; X50

Xx; X X: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

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

401–720–1

6807–17–6

Xxxx. xxx. 2; X60 Xx; R36 N; X50–53

X; X X: 60–36–50/53 X: 53–45–60–61

604–041–00–0

xxxxxxxxxxx [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; R22 Xx; X38–41 X; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xx; X36 X43

Xx X: 36-43 X: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx

205–769–8

150–76–5

Xx; X22 Xx; X36 R43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

Xxxx. xxx. 3; X40 Xx; X20 Xx; R36/38 R43

Xn X: 20–36/38–40–43 S: (2-)36/37

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

606–016–00-X

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

201–462–8

83–26–1

X; X25–48/25 X; X50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xn; X22 Xx; R36/38 X; R50–53

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

606–019–00–6

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

205–601–3

143–50–0

Karc. xxx. 3; X40 T; X24/25 X; X50–53

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

606–034–00–8

xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx

244–209–7

21087–64–9

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

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

216–920–2

1698–60–8

R43 N; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

xxxxxxxxxxxxxx (XXX) 6-xxxxxx-2 H-[1,3]dithiolo[4,5-b]chinoxalin-2-on

219–455–3

2439–01–2

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

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

606–037–00–4

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

256–103–8

43121–43–3

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xx; R36 X; X50–53

Xx; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; R22 Xi; X41 X52–53

Xx; N X: 22–41–52/53 S: (2-)26-61

607–057–00–6

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

201–378–1

81–82–3

Xx; X48/22 R52–53

Xn X:48/22–52/53 X: (2-)37-61

607–058–00–1

kumafuryl (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -xxxxxxx-2-xx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-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 S: (1/2-)37–45–61

607–079–00–6

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

4234–79–1

X; R24 Xn; X22 X; X51–53

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

607–097–00–4

benzen-1,2,4-trikarbox-1,2-anhydrid 1,2-anhydrid xxxxxx-1,2,4-xxxxxxxxxxxxxx kyseliny xxxxxxxxxxxxxxxxx

209–008–0

552–30–7

Xx; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx

203–677–2

109–52–4

X; X34 R52–53

C X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xn; R22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; R36/38 R52–53

Xi X:36/38–52/53 X: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xn; X22 Xx; X38 N; X50–53

Xx; X X: 22–38–50/53 X: (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 X: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

chlorobenzilát (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; X51–53

Xx; X X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xn; X22 X43 X; X50–53

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

607–213–00–3

ethyl-3,3-bis(terc-pentylperoxy)butanoát

403–320–2

67567–23–1

E; X2 X; X7 X10 N; X51–53

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

607–217–00–5

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

403–960–2

X43 X53

Xx X: 43-53 X: (2-)24–37–61

607–243–00–7

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

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

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

X52–53

X: 52/53 X: 61

607–248–00–4

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

205–073–4

132–67–2

Xx; X22

Xx X: 22 X: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xx; X36/37/38 X43 X; X51–53

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

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

607–252–00–6

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

415–130–7

91465–08–6

X+; R26 X; X25 Xx; X21 X; X50–53

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

607–255–00–2

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 X

203–466–5

107–13–1

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

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

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 N; R50–53

Xi; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. xxx. 2; X61 X+; X28 X; X24 X44 X; R50–53

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

609–040–00–9

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

X

217–406–0

1836–75–5

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

X; X X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 X43 X; X50–53

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

611–008–00–4

4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. xxx. 2; X45 X; R50–53

T; X X: 45–50/53 X: 53–45–60–61

611–013–00–1

4-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; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

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

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X R: 45 X: 53-45

612–035–00–4

2-xxxxxxxxxxxxx x-xxxxxxxx

X

201–963–1

90–04–0

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

X X: 45–23/24/25 X: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; X22 X; X50–53

X; N X: 45–22–50/53 S: 53–45–60–61

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

612–051–00–1

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

E

202–974–4

101–77–9

Karc. xxx. 2; R45 Muta. xxx. 3; X40 X; X39/23/24/25Xx; X48/20/21/22 X43 N; X51–53

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

612–081–00–5

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

X E

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; X45 Xx; X22 X; X51–53

X; X R: 45–22–51/53 S: 53–45–61

612–099–00–3

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

X

202–453–1

95–80–7

Xxxx. xxx. 2; X45 T; X25 Xx; X21 Xi; X36 X43 N; X51–53

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

612–105–00–4

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

205–411–0

140–31–8

Xn; X21/22 X; X34 X43 X52–53

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

612–111–00–7

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

212–513–9

823–40–5

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

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

62924–70–3

Xx; X36/38 X4 3 N; X50–53

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

612–151–00–5

xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; R45 X; X25 Xn; X20/21 Xx; X36 X43 X; X51–53

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

613–018–00–4

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

7411–47–4

Xx; X22 Xx; R36/37/38 X52–53

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

613–031–00–5

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

201–782–8

87–90–1

O; R8 Xx; R22 X31 Xx; X36/37 X; X50–53

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

613–038–00–3

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

202–095–6

91–76–9

Xx; X22 R52–53

Xn X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

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

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xi; X41 N; R50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; R22 X; X50–53

Xx; N X: 22–50/53 X: (2-)60-61

613–091–00–2

xxxxxxxxxx-xxxxxxxxx [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]

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

613–130–00–3

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

79983–71–4

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

613–131–00–9

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

57369–32–1

Xx; R22 R52–53

Xn X:22–52/53 S: (2-)61

613–134–00–5

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

88671–89–0

Xxxx. xxx. 3; X63 Xx; X22 Xi; X36 X; 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 R: 50/53 S: 60-61

613–139–00–2

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

74223–64–6

X; X50–53

X X: 50/53 X: 60-61

614–001–00–4

xxxxxxx (XXX) 3-(1-methylpyrrolidin-2-yl)pyridin

200–193–3

54–11–5

T+; X27 T; 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-dimethoxystrychnidin-10-on

206–614–7

357–57–3

T+; R26/28 X52–53

X+ R:26/28–52/53 S: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; X26/28 X52–53

X+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

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

X

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

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

Xxxx. xxx. 3; X40 X+; X26 Xx; X36/37/38 R42/43 X52–53

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

X320 %: X+; R26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; X23–40–42/43 0,1 % ≤ C &xx; 1 %:Xx; X20–42

2

616–010–00–9

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

204–854–7

127–65–1

Xx; R22 X31 X; X34 R42

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

616–034–00-X

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

246–419–4

24691–76–7

R52–53

R: 52/53 X: 61

616–035–00–5

xxxxxxxxx X -[(xxxxxxxxxx)xxxxxxxx]-2-xxxx-2-(xxxxxxxxxxxx)xxxxxxxx 1-ethyl-3-[2-kyan-2-(methoxyimino)acetyl]močovina

261–043–0

57966–95–7

Xn; X22 X43 X; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; X7 Xn; X22 C; X34 X; X50–53

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

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

617–006–00-X

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

201–279–3

80–43–3

O; X7 Xx; X36/38 X; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xi; X36 X43

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

650–007–00–3

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

228–200–5

6164–98–3

Xxxx. kat. 3; X40 Xx; R21/22 X; X50–53

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

650–008–00–9

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

227–197–8

5707–69–7

X; R25 X; X50–53

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

650–009–00–4

chlordimeform-hydrochlorid X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx 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; R40 Xx; R22 N; X50–53

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

650–033–00–5

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

66230–04–4

T; X23/25 X43 X; X50–53

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

650–041–00–9

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

82097–50–5

N; X50–53

X X: 50/53 S: 60-61


PŘÍLOHA 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x přípravkům

006–090–00–8

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

408–010–0

88558–41–2

Xn; R20 Xx; X41 X52–53

Xx X: 20–41–52/53 S: (2-)22–26–39–61

014–016–00–0

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

406–490–6

X; X51–53

X X: 51/53 X: 61

015–164–00–9

kalcium-dihydrogen-(1-hydroxyethylen)bisfosfonát xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

Směs: X, X, X', 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 S: (2-)15–26–39–60–61

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; X50

X X: 50 X: 61

601–051–00–7

4-xxxxxxxx-1-xx

405–980–7

768–56–9

Xx; X38 X; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx difenyletheru xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; R48/21/22 R64 X; X50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X R: 52/53–59 S: 59-61

603–128–00–0

2-(xxxxxxxxxxxx)xxxxxxxx

405–490–3

613–62–7

X53

X:53 X: 61

603–129–00–6

1-terc-butoxypropan-2-ol

406–180–0

57018–52–7

R10 Xx; X41

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

603–130–00–1

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

406–325–8

Xx; X22 R52–53

Xn X:22–52/53 X: (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; R38–41 X52–53

Xx X:38–41–52/53 S: (2-)26–37/39–61

603–133–00–8

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

408–240–1

Xn; R22 X52–53

Xx X:22–52/53 X: (2-)22–36–61

603–134–00–3

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

410–450–3

R53

R: 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; X41 X; X51–53

Xx; X X: 41–51/53 X: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

R43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

603–137–00-X

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

411–130–6

Xx; X41

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

603–138–00–5

3-(2,2-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 X; R 35 X; X50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 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 X: 61

604–053–00–6

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

410–760–9

157661–93–3

Xx; X38 X43 X; X50–53

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

604–054–00–1

Xxxx:2-xxxxxxx-4-(4-xxxxxxxxxxxxxxxxxxxxxxxxx-2-xx)xxxxx 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'-xxx[(2,3-xxxxxxxxxxx)xxx]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx

413–900–7

85954–11–6

Xxxx. Xxx.3; X40

Xx X: 40 X: (2-)22–36–37

605–027–00–7

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

410–480–7

X43 N; R51–53

Xi; X R: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx pentylcyklohexan-1-on

4–406–670–4

61203–83–6

N; X51–53

X X: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

X52–53

X:52/53 S: 61

607–272–00–5

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

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

X; X50–53

X R: 50/53 X: 60-61

607–273–00–0

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

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

X43 N; X51–53

Xx; X R: 43–51/53 S: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

X43

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

607–276–00–7

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

405–635–0

Xi; X38–41 X; 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 x xxxxxxx-xxxxxxxxx

405–720–2

Xx; X22 Xi; X41 R43 N; X51–53

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

607–278–00–8

Směs:alkyl(C7-C9 xxxxxxxxxx x nerozvětvené)-3-[3-(2 X - benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty

405–760–0

Xi; X41 X43 X52–53

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

607–279–00–3

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

405–960–8

X43 X; R51–53

Xi; X X: 43–51/53 S: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xn; X22 Xx; X36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

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

407–000–3

127519–17–9

N; R51–53

N X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 X: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xx; X38–41 X43 X; X50–53

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

607–284–00–0

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–070–8

141880–36–6

X43 X52–53

Xx R:43–52/53 X: (2-)22–24–37–61

607–287–00–7

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

410–140–8

X52–53

X:52/53 S: 61

607–288–00–2

[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 nebo 4, b = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25

410–160–7

148732–74–5

Xx; X36 X43 X52–53

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

607–288–00–8

3-[(3-{X —[4-(2,4-di-terc-pentylfenoxy)butyl]karbamoyl}-4-hydroxy-1-naftyl)sulfanyl]propanová xxxxxxxx

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

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

410–540–2

Xx; R38 R43 X; X50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

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

410–640–6

Xx; X38–41 N; R50–53

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

607–293–00-XSměs:

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

410–650–0

Xx; R41 R43 X; X51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

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

410–830–9

X53

X: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; X41

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

607–298–00–7

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

411–010–3

X43

Xx X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; R22 X43 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 komplex, xxxxxxxx xxx; x = 1,2,3 xxxx 4, x = 8, 9, 10 xxxx 11, c = 15, 16, 17 xxxx 18, x = 22, 23, 24 xxxx 25

411–430–7

X43

Xx R: 43 X: (2-)22–24–37

607–301–00–1

Směs:dodekanová kyselina x xxxxxxxxxxx xxxxx(1-7)xxxxxxx

411–860–5

Xx; X38–41 X43 X; X51–53

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

607–302–00–7

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

411–910–6

Xx; X38–41 X43 X; X51–53

Xx; X 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 kyselina

413–760–7

93107–30–3

Repr. xxx.3; X62 R52–53

Xn X: 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 S: 60-61

608–024–00–9

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

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

[2-nitro-4,5-bis(benzyloxy)fenyl]acetonitril

410–970–0

117568–27–1

R53

R:53 S: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; R3 O; X8 Xxxx. xxx. 2; X45 X; X23/25 R43

E; X X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 X; X34 R43 N; X50–53

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

611–043–00–5

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

402–850–1

Xi X: 41–52/53 S: (2-)26–39–61

611–044–00–0

Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx terc-alkyl(C12-C14)amonný, [(5-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-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx

403–720–7

117527–94–3

X; X51–53

Xx; X41 X52–53

611–045–00–6

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

404–830–8

X53

X:53 X: 61

N X: 51/53 X: 61

611–046–00–1

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

407–590–2

43151–99–1

X; R25 Xx; X48/22 X43 N; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 S: 61

611–048–00–2

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

407–900–6

111381–12–5

R53

R: 53 X: 61

611–049–00–8

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

405–620–9

Xx; X41 N; X50–53

Xx; X X: 41–50/53 S: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xx; X22–48/22 Xi; R41 X43 N; X51–53

Xx; 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 X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx komplex x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 X: 61

612–159–00–9

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

410–880–1

Xx; X22 X; X34 N; X50–53

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

613–149–00–7

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

405–700–3

96489–71–3

X; X23/25 X; X50–53

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

613–150–00–2

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

406–295–6

X53

X:53 X: 61

613–151–00–8

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

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-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 S: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 X52–53

Xx X: 10–22–52/53 S: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–157–00–0

2,4-diamino-5-(methoxymethyl)pyrimidin 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx

410–330–0

54236–98–5

Xx; R22–48/22 Xx; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xx; X20/22 Xx; X41 R43 X; X51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; X25 Xn; X20 X; R50–53

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

613–160–00–7

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

411–000–9

125224–62–6

X43

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

615–022–00–1

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

410–550–7

79277–18–2

X; X2 X14 Xn; X48/22 X42/43

X; Xn 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 Muta. xxx. 3; X40 Xn; X20–48/22 Xi; 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 S: 61

616–045–00-X

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

405–190–2

122371–93–1

X43 R53

Xi X: 43-53 X: (2-)22–24–37–61

616–046–00–5

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

406–390–2

X; X50–53

X X: 50/53 X: 60-61

616–047–00–0

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

406–640–0

X43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 X; X51–53

Xx; 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 X: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 N; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

Směs:3,3'-bis(4-methylfenyl)- 1,1'-(4-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx x 3,3'-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; X7 X; X50–53

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

650–032–00-X

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

94361–06–5

Xxxx. kat. 3; X63 Xn; R22 X; X50–53

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


XXXXXXX 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx směrnice Komise 2001/59/XX,

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


XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


PŘÍLOHA 3X

XXXXXXXXXX POKYNY XXX BEZPEČNÉ ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx na chromozomové xxxxxxx x xxxxx xx xxxxx má xxxxxxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx v xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, avšak xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx aberací x xxxx x tomuto xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx x existuje xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx x x xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx a v xxxxxx somatických buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x člověka x x pokusných xxxxxx.

Xx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxx xxx xxxxxxx stabilizované xxxxxxx xxxxx, buněčné xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx buňky xxxx xxxxxxx xx xxxxxxx schopnosti xxxxx x xxxxxxx, stálosti xxxxxxxxx, počtu xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx in xxxxx xxxxxx vyžadují xxxxxxx vnějšího xxxxxx xxxxxxxxxxx aktivace. Tento xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx napodobit xxxxxxxx xx vivo x xxxxx. Je xxxxx xx xxxxx xxxxxxxxx podmínek, které xx vedly x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx vlastní xxxxxxxxxx x xxxx x xxx xxxxx změnou xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx cytotoxicity (4, 5).

Xxxx xxxxxxx xx používá xx xxxxxxxx možných xxxxxxxx x xxxxxxxxxxx pro xxxxx. Xxxxx xxxxxxxxx, xxx něž xx xxxx zkouška xxxxxxxxx, xxxx pro savce xxxxxxxxxxx; mezi xxxxx xxxxxxxx x karcinogenitou xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx závisí xx xxxxxxxx třídě x xxxxxxxxx důkazy x tom, xx xxxxxxxx xxxxxxxxxxx, které xxxxxx zjištěny touto xxxxxxxx, xxxxx zřejmě xxxxxx jinými xxxxxxxxxx xxx xxxxxx xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx nebo xxxxx x xxxxxxx obou xxxxxxxxx v xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : proces, xxx xxxxxx x xxxxx po X-xxxx xxxxxxxxx XXX nedojde x xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx xxxx chromozomy xx 4, 8, 16… chromatidami.

Gap : xxxxxxxxxxxx xxxx menší xxx xxxxx xxxxx xxxxxxxxxx a s xxxxxxxxx xxxxxxxxx chromatid.

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

Numerická xxxxxxx : xxxxxxxx počtu xxxxxxxxxx od xxxxxxxxxx xxxxx xxxxxxxxx u xxxxxxxxx xxxx buněk.

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx xxxxxxxxxx při xxxxxxxx xxxxxx xx xxxxxx metafáze; xxxx xx xxxx xxxxxx x xxxxxxxxx, intrachromozomální xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x xx x metabolickou xxxxxxxx x xxx xx. X xxxxxx xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx látce se xx xxxxxxxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx xxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxxxxxxx pozorováním xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx různé xxxxxxx xxxxx, kmeny xxxx xxxxxxxx xxxxxxx kultury, xxxxxx lidských buněčných xxxxx (např. xxxxxxxxxxx xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx xxxx člověka xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x kultivační xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx být xxxxxxx xxxxxx kultivační xxxxx x inkubační xxxxxxxx (xxxxxxxxxx nádoby, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). U xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x kmenů by xxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx počtu xxxxxxxxxx x mělo xx xxx kontrolováno, xxx xxxxxx kontaminovány xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Xxx xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxx buněčného xxxxx.

1.4.1.3 Xxxxxxxx kultur

Stabilizované buněčné xxxxx a kmeny: xxxxx se pomnoží x xxxxxxxxx xxxxxx, xxxxxx xx xx xxxxxxxxxxxx xxxxx v xxxxxx xxxxxxx, xxx xxxxxxxxx konfluence xxxx xxxxxxxxx, a inkubují xx xxx 37 °X.

Xxxxxxxxx: krev xxxxxxxx xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx xxxxxxxx lymfocyty xxxxxxxx xxxxxxxx xx xxxxxxx xx xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. fytohemaglutinin) x xxxxxxxx xx xxx 37 °C.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx měly xxx xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx a xxx xx. Nejčastěji používaným xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx z xxxxx hlodavců xxxxxxxxxx xxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Xxxxxxx 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-naftoflavonu (10, 11 a 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx je v xxxxxxxx xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx metabolického xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, xxxxx je xxxxxxxx. X některých xxxxxxxxx xxxx xxx xxxxxx xxxxxx více xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, včetně přípravy xxxxxxxxx xxxxxxxxxxxxxx buněčných xxxxx exprimujících xxxxxxxxxx xxxxxxxxx xxxxxx, poskytuje xxxxxxxx xxx endogenní xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx linií xx xxxx být xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx P450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxx přímo x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx xxxxxxxx xxxxxxx. Xxxx by být xxxxxxx xxxxxxx připravené xxxxxxxx xxxxx, pokud xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx podezření, že xxxxxxx se xxxxxxxxx xxxxxx, a mělo xx xxx slučitelné x xxxxxxxx xxxxx x s xxxxxxxxx X9. Jsou-li xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Vodu xxx xxxxxxxxx přidáním molekulového xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Cytotoxicita xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx aktivací x bez xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx integrity x růstu, xxxx xxxx stupeň konfluence, xxxxx životaschopných xxxxx xxxx xxxxxxxxx xxxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx alespoň xxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx cytotoxicity xx xxxx tyto xxxxxxxxxxx xxxxxxxx rozmezí xxxx xxxxxxxxx až xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx xxxxxxx xxxxxxx, xx by xx koncentrace xxxxxx xxxxx xxxx nežli xxxxxxxx 2 až Ö10. X okamžiku xxxxxxx xx xxxx xxxxxxxx koncentrace xxxxxxxxx xxxxxxxx snížení xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx mitotického xxxxxx (xxx x více xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx nebo cytostatických xxxxxx x xxxxxx xx xxxx, xxxxx xxxxxxxx xx xxxxxxxx. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx x xxxxxxxxxxx kultur, u xxxxx xxxxx být xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx a xxxxxxxxxxx. Informace x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), xxxxx xxx xxxxxxx xxxx xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX xxxx xxx o celkovou xxxxxxxxx xxxxxxx, x xxx xxxxx xxxxxxx xx xxxxxxxxx zpožděných xxxxxxxxxxx, x x xxxx xxxxxxxxx průměrné xxxxxxxxx doby může xxx za xxxxxxxx xxxxx xxxxxxxxx oddálení xxxxxxxx xxxxxxxxxxx výtěžku xxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxxxx xxxxx xx xxxx xxx maximální xxxxxxxx koncentrace 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxx látek, které xxxxxx xxxxxxx xxx xxxxxxxxxxxxx xxxxxxx, xxx xx jejich rozpustnost, xx xxxx xxx xxxxxxx nejvyšší xxxxx x xxxxxxxxxxx, xxx xx xxx mezí xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxx xxxxxxxx. X určitých xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx pouze při xxxxxxx koncentracích, xxx xx xxxxxxxxxxx) se xxxxxxxxxx vyzkoušet xxxx xxxxxxxxxxx, xxx xxxxx xxxxxxx ke xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x xx xxxxx xxxxxxxx, neboť xxxxxxxxxxx x xxxxxxxxxx xxxxxxx xx xxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, xxxx X9 xxx. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx být xxxxxxxxx a negativní xxxxxxxx (kontroly xxxxxxxxxxxx xxxx xxxxxxxx). Při xxxxxxx metabolické xxxxxxxx xx měla být xxx xxxxxxxxx kontrolu xxxxxxx chemická xxxxx, xxxxx k mutagenní xxxxxx xxxxxxxx xxxxxxxx.

X xxxxxxxxx xxxxxxxx xx xxx být xxxxxx xxxxx elastogen x xxxxxxxxxxx koncentracích, xxxxx xxxxxxxx poskytnou xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxx, čímž xx xxxxxxx citlivost xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx nevyšla xxxxx najevo kódovaná xxxxxxxxxxxx preparátu. Příklady xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

Xxxx metabolické xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxx xxxxxx metabolické aktivace

methyl-methansulfonát

66–27–3

200–625–0

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Pro pozitivní xxxxxxxx xxxxx xxx xxxxxxx x xxxx xxxxxx látky. Xxx xxxxxxxxx kontrolu xx xxxx být xxxxx xxxxx vzato x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx xx xxxx xxx použity negativní xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx vehikula v xxxxxxxxxxx xxxxx x xxxxxxxxxx stejným xxxxxxxx xxxx kultury. Kromě xxxx xx xxxx xxx neexponované kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx dosud xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx se xxxxxxx zkoušené xxxxx xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx lymfocytů xx xxxx být zahájena xxx 48 hodin xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx každou koncentraci xx měly xxx xxxxxxx použity duplicitní xxxxxxx, x totéž xx xxxxxxx xxxxxxxxxx x xxxxxx xxx xxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx na xxxxxxx xxxxxxxxxxx údajů xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx xxxxxxxxx xx minimální rozdíl, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx kultury.

Plynné xxxx xxxxxx xxxxx xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. v xxxxx xxxxxxxxxx kultivačních nádobách (15, 16).

1.4.3.3 Doba xxxxxxx kultur

V xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, xxx x metabolickou xxxxxxxx, xxx xxx xx, xx dobu 3 — 6 xxxxx, x xxxx xx xxx odebrány xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, která xxxxxxxx 1,5násobku normální xxxxx xxxxxxxxx xxxxx (12). Jestliže xxxxx xxxxxx xxxx negativní xxxxxxxx xxx s xxxxxxxx, xxx xxx xxxxxxxx, xxx xx xxx xxxxxxxx dodatečný xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx do xxxxxx x xxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu. Xxxxxx chemické xxxxx xxx xxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx xxxx xxxxxx delších xxx 1,5násobek délky xxxxx. Negativní xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. X xxxxxxxxx, xxx xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx za xxxxxxxx, xx xxxx xxx podáno xxxxxxxxxx.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Do xxxxxxx xxxxxxx xx xxxxxxx 1-3 xxxxxx xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx xxxxxxxxx. Xxx xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů se xxxxx xxxxxxx xxxxxxx xxxxxx x zpracovává xxxxxx. Xxxxxxxx preparátů xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx a obarvení xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx pozitivních x negativních xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při fixaci xxxxx xxxxxxx xx xxxxx xxxxx xxxxx x xxxxxxxx x xx xxxxxx xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx xxxxxxx ± 2 pro všechny xxxx buněk. Xx xxxxxx xxxxxxxxxxx a xxxxxxxx xx xxxx xxx xxxxxxxxx alespoň 200 dobře rozprostřených xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx mezi duplicitní xxxxxxx. Xxxxx xxxxx xxx xxxxxx, je-li xxxxxxxxx xxxxx xxxxx xxxxxxx.

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

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx x xxxx xx tedy xxx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) vyjádřené x xxxxxxxxxx. Pro xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx by xxxx xxx uvedeny xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx s xxxxxx xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, ale xxxxxxxxxx xx xx celkové xxxxxxxx aberací.

Měla xx xxx také xxxxxxxxxxx xxxxxxxx, která byla xxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxx x xxxxx xxxxxxxxxxxx kultur x xxxxxxxxxxx xxxxxx x xxxxxxxx experimentech x xxxxxxxxx.

Xxxx xx xxx xxxxxxx údaje pro xxxxxxxxxx xxxxxxx. Xxxx xx měly xxx xxxxxxx xxxxx xxxxxxx xx xxxxx tabulky.

Ověření xxxxx xxxxxxxxx odpovědi xx nepožaduje. Dvojznačné xxxxxxxx by xxxx xxx vyjasněny xxxxxx xxxxxxxxx, nejlépe x xxxxxxxx experimentálních podmínek. Xxxxxxxxxx potvrdit xxxxxxxxx xxxxxxxx byla xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x cílem xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, které xx xxxxx xxx změněny, xxxxx xxxxxxx koncentrací x podmínky metabolické xxxxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX VÝSLEDKŮ

Pro stanovení xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x chromozomovými xxxxxxxxx x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx xxxxxx počtu. Xxxxxxxx by měla xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx výsledků zkoušky xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxxxx xxxxx, jejíž xxxxxxxx nesplňují xxxx xxxxxxx kritéria, xx x xxxxx systému xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx ohledu xx xx, kolikrát xx xxxxxxxxxx opakován.

Pozitivní výsledky xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx znamenají, že xxxxxxxx xxxxx indukuje x xxxxxxxxxxxxx somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje x xxxxxxxxxxxxx somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx musí obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxx:

- xxx x xxxxx buněk,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx použitého xxxx xxxxx,

- popřípadě xxxxxxxxxxxx xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx xxxxx,

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

- xxxxxxxx xxxxx xxxxxx,

- případně xxxxxx xxxxxxxxx buněčné xxxxxxx,

- xxxxxxx hodnota xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- složení xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- koncentrace zkoušené xxxxx,

- objem xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx hustota xxxxx xxx nasazení,

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

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity, xxxx. stupeň xxxxxxxxxx, xxxxx o buněčném xxxxx, xxxxx xxxxx, xxxxxxxxx xxxxx,

- xxxxxx xxxxxxx,

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

- definice xxxxxxx, včetně gapů,

- xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx a xxxx xxxxxxx xxxxxx xxx každou xxxxxxxxxxx x xxxxxxxxx kulturu,

- xxxxx xxxxxxx, pokud xxxx pozorovány,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X. (1976), Cytological Methods xxx Detecting Chemical Xxxxxxxx, in: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx and Xxxxxxx xxx xxxxx Xxxxxxxxx, Vol. 4, Xxxxxxxxxx, X. (xx) Xxxxxx Press, New Xxxx xxx London, 1-29.

2) Ishidate, M. Xx., Sofumi, T. (1985), Xxx Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Using Chinese Xxxxxxx Xxxx (CHL) Xxxxxxxxxx Cells in Xxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxx Research, Xxx. 5, Xxxxx, X. xx xx., (xxx) Elsevier Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, X. X., Armstrong, X. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Cannon, C., Xxxxx, X. X., Xxxxxxxx, X., Xxxxx, X., Xxx, X., Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X., Zeiger X. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx chromatic xxxxxxxxx xx Chinese xxxxxxx xxxxx xxxxx: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (suppl. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, S. X., Marshall, X. X., Xxxxxxxx, X. Xx., Xxxxxxx, D., Xxxxx, J., Myhr, X. C. (1991), Xxxxxxxxxxxx xxxxx Xxxxxxx Xxxxxxx Conditions. A xxxxxx from XXXXXX Xxxx Group 9, Xxxxxxxxxx Res., 257, 147-204.

5) Xxxxxx, X., Xxxxxx, X., Fukuda, X., Xxxxxxx, X., (1992), Clastogenicity of xxx xX to Xxxxxxx Xxxxxxxx Mammalian Xxxxx, Mutatation Res., 268, 297-305.

6) Xxxx, X. N., XxXxxx, X., Yamasaki, X. (1975), Methods xxx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Mutation Res., 31, 347-364.

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

8) Xxxxxxxxx, X. T., Tates, X. X., van Xxxx, X. X. X., Xxxxxxx, M., xx Vogel, N. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx in x Xxxxxxxxxxx Xxxxxx Xx xxxxx, X. Xxxxxxxxx xx Xxxxxxxxxx Aberrations xxx Xxxxxx Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) xx CHO Xxxxx in the Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Res., 37, 83-90.

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

10) Elliot, X. X., Xxxxxx, X. D., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Gibson, X. X., Xxxxxx, X. X., Xxxx, X. C. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx. Alternative xx Xxxxxxx 1254-xxxxxxx X9 in Xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, X., Xxxxxxxx, X. (1976), X. Safe Substitute xxx Xxxxxxxxxxxxxxx Biphenyls x. s. an Xxxxxxx of Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: xx Serres, F. X., Xxxxx, J. X. Xxxx, X. X., Xxxxxxx, R. X. (xxx), Xx xxxxx Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, M. X., Xxxxxxxx, X. Xx., Xxxxx, X. X., Xxxxxxxx, X. X., Xxxxxx, T., Xxxxxxx, X., Xxxxxx, X. (1994), Report xxxx Xxxxxxx Xxxxx on Xx xxxxx Tests xxx Chromozomal Xxxxxxxxxxx, Xxxxxxxxxx Res., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, X. A., Xxxxx, J. X., Xxxxxxxx, X., Chanter, X. X., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx vitro Xxxxxxxxxxx Xxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

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

15) Xxxxx, X. X., Xxxxxx, F. C., XxXxxxx, X. X. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Tice, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

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

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

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


XXXXXXX 4X

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

1. XXXXXX

Xxxx metoda xx replikou xxxxxx XXXX XX 475 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx v xxxxxxx xxxxxx xxxxx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx chromozomové aberace x xxxxx xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx látkou x xxxxxxx kostní dřeně xxxxx, xxxxxxx hlodavců (1, 2, 3, 4). Xxxxxxxxx se xxx xxxx xxxxxxxxxxxx xxxxxxx — chromozomové x xxxxxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx chemická látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx chemických xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx xx rovněž xxxxxxxxx. Xxxxxxxxxxxx mutace a xxxxxxxxxxx jevy xxxx xxxxxxxx xxxxx geneticky xxxxxxxxxxx chorob x xxxxxxx a existuje xxxxx xxxxxx x xxx, že xxxxxxxxxxxx xxxxxx x související xxxx xxxxxxxxxxx změny x xxxxxxxxxx x x genech xxxxxxxxxxx xxxxx tlumících xxxxxx, xxxx xxxxx na xxxxxxx rakoviny u xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx této xxxxxxx xxxx rutinně xxxxxxxxx hlodavci. Xxxxxxx xxxxx xx x xxxx xxxxxxx xxxxxx xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx populaci xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx izolují a xxxxxxxxxxxx. Xxxx xxxxx x xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx je xxxxxxx určená x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx umožňuje zohlednit xxxxxxx xxxxxxxxxxx xx xxxx, farmakokinetiku x xxxxxxx xxxxxxxx DNA, xxxxxxx se xxxxx x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx xx xxxx xx rovněž xxxxxxxx xxx další výzkum xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx xx vitro.

Jestliže xxxxxxxx důkaz x xxx, xx xx xxxxxxxx xxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v podobě xxxxx jednotlivých xxxxxxxxx xxxx zlomu x xxxxxxxx xxxxxxx xxxxxxxxx.

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

Endoreduplikace : xxxxxx, při kterém x xxxxx po X-xxxx xxxxxxxxx DNA xxxxxxx x xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Výsledkem xxxx xxxxxxxxxx xx 4, 8, 16,… xxxxxxxxxxxx.

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

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

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx xxxxxx xx xxxxxx metafáze; xxxx se jako xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

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

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxx x xxxxxx čínský, xxxxxx lze použít xxxxxxxx xxxxxx xxxxx xxxx. Měly by xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. V xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx x xxxx pohlaví překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx zvířata xx xxxxxxxx výběrem xxxxxxx xx kontrolní skupinu x skupinu, xxxxx xx xxxxxxx zkoušené xxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, aby byl xxxx xxxxxx polohy xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx zkoušené xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx xxxxxxxx přímo xxxx mohou být xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx toxické xxxxxx x mělo xx být vyloučeno xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx pohlaví. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx zvířata kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx jako zvířata xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx strukturní xxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx se xxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx byl odběr x jejím xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx xxx použity xxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx kontrolu:

Látka

Číslo CAS

Číslo xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

V xxxxxxxx xxxxxxx odběru xx xxx být xxxxxxxx xxxxx x negativních xxxxxxx, xxxx xx xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx x xxx xxxxx podstupují xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx údajů x xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx se pro xxxxxxxxx kontrolu xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx prvního xxxxxx. Xxxxx toho xx xxxx být xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx nebo mutagenní xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx a kontrolní xxxxxxx xx xxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví. Xxxxxxxx xxxx x xxxx xxxxxx k xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx druhem x xx xxxxxxx xxxxxxxx způsobu expozice, xxx prokazují, xx xxxxxxxxxx xxxx pohlavími xxxxxx x toxicitě, xxxx xxxxxxxxxxx zkoušení xxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxxxx specifická xxx určité xxxxxxx, xxxx xx xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx xxx zkouška xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx být pokud xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. dvě dávky x týž xxx x rozmezí ne xxxx xxx xxxxxxxx xxxxx, xxx bylo xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx xxxxxxxx xx xxxx různých intervalech xx xxxxxxxx xxxxxx x xxxxxx xxx. X hlodavců xx xxxxx provádí xx xxxxxx xxxx od xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx cyklu (jenž xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxx xxxxxx xx xxxxxxxx xxxxxxxxx cyklu xxxx xxx xxxx na xxxxxxxxx okamžik xxx xxxxxxxxx chromozomových aberací, xxxxxxxxxx xx xxxxxxx xxxxx xxxxx xx 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx rozložena do xxxx xxx jednoho xxx, xxx by xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného xxxxx.

Xxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx dávka látky xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx xxxx provede x xxxxxx xxxxx. X xxxx je xxxx xxxx přibližně 3 — 5 x; x xxxxxx xxxxxxxx je xxxx xxxx xxxxxxxxx 4 — 5 x. X xxxxxx dřeně xx xxxxxxxx xxxxx x xxxxxxxxx xx xx chromozomové xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, xxxxxxxx x xx stejného xxxxxx expozice, xxx xx použijí x xxxxxx studii (5). X xxxxxxx xxxxxxxx xx pro xxxxx xxxxx použijí xxx xxxxxx dávky. Tyto xxxxxx xxxxx by xxxx pokrývat xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx známky xxxxxxxx, xx vyšší xxxxx by xxxxx xxx stejném xxxxxx xxxxxxxxx xxxxx očekávání x xxxxxxxx. Xxxxx xx specifickou biologickou xxxxxxxxx při nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (např. více xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx dávkou xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx ve xxxx xxxxxxx v xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x xxxxxxx, které xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx xxxxx xxxxxx xx třemi xxxxxxxx xxxxx xx nezbytnou. X xxxx xxxxxxxxxx xxxxxx xx limitní xxxxxx pro 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx delší než 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx znamenat potřebu xxxxxx x limitní xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx obvykle xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx nebo vhodnou xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání jsou x xxxxxxxxxxxx případech xxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx najednou podán xxxxxxxxxxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Objem xx neměl xxxxxxxxx 2 xx/100 g xxxxxxx xxxxxxxxx. Použití xxxxxxx xxxxxx, xxx xx xxxxxxx objem, xxxx být xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx látky, xxxxx obvykle xxx xxxxxxx koncentracích vykazují xxxxxxxx xxxxxx, by xxxx xxx variabilita xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx se xxxxxxx xxxxxx dřeň, xxxxxxxxxxxx xx x xxxxxx. Xxxxx se nanesou xx xxxxxxxx sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx měřítko cytotoxicity xx xxx xxx x všech xxxxxxxxxxxx xxxxxx (xxxxxx pozitivních xxxxxxx) x x xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx xxxxxxxx stanoven xxxxxxxxx index, x xx xxxxxxx x 1000 xxxxx xx xxxxx zvíře.

U xxxxxxx xxxxxxx by xxxx xxx analyzováno xxxxxxx 100 xxxxx. Tento xxxxx xxx snížit, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx xx xxxx být před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx ke ztrátě xxxxxxxxxx x části xxxxx v metafázi, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxx xx xxx xxx vyhodnocen počet xxxxx, xxxxx aberací xx xxxxx x xxxxx xxxxx x xxxxxxxxxxxxx aberací (chromozomovými xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Pro xxxxxxxxxx x kontrolní xxxxxxx xx xxxx být xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx x jejich xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx odděleně x xxxxxxx se, xxx obecně se xxxxxxxxxx xx celkové xxxxxxxx aberací. Xxxxxxxxxx-xx xxxxx o xxxxxxx x xxxxxxxx mezi xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx zkombinovány.

2.2 HODNOCENÍ X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxxxxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx s xxxxxxxxx pro skupinu x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx odběru. Nejdříve xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx buněk s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx může xxxxxxxx, že xxxxxxxx xxxxx xx potenciál xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

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

Xxxxxx většina xxxxxxxxxxx poskytne jasně xxxxxxxxx xxxx negativní xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx xxxxxxxx konečný xxxxx o xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx na to, xxxxxxxx je experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx chromozomové aberace xx vivo xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx v xxxxxx xxxxx testovacího xxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx látka za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxx dřeni xxxxxxxxxxx druhu chromozomové xxxxxxx.

Xxxx xx být xxxxxxxxxxx pravděpodobnost, s xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx xx xxxxxx xxxxx (např. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- použitý xxxx/xxxx,

- xxxxx, stáří x xxxxxxx zvířat,

- xxxxx, podmínky chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx odchylky pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x negativní (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- údaje xx studie pro xxxxxxxx rozsahu, xxxxx xxxx xxxxxxxxx,

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- popřípadě xxxxxx xxxxxxx, xxx xx xxxxxxxx xxxxx xxxxxxx xx krevního xxxxx xxxx xx xxxxxx xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx zkoušené xxxxx x xxxxxx xxxx xxxx (ppm) xx xxxxxxxxxxxx dávku (xx/xx xxxxxxx hmotnosti/den),

- xxxxxxxx údaje x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx metafázi, xxxx xxxxxxxxxxx a délka xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx hodnocení xxxxxxx,

- xxxxx analyzovaných xxxxx xx xxxxx xxxxx,

- xxxxxxxx klasifikace xxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxx x xxxxx xxxxxxx uvedený xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx ve skupině xx xxxxxxxxx hodnotami x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx buněk s xxxxxxxxx xx xxxxxxx xx xxxxxxxxx hodnotami x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxx, pokud xxxx pozorovány,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx o xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

2) Xxxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X., Xxxxxx, X., XxXxx, X. X., Xxxxxx, X. (1987), Xxxxxxxxx In xxxx Xxxxxxxxxxx Xxxxxx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Xxxx Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. X., Xxxxxxx, X., Henderson, X. (1990), Xx vivo Xxxxxxxxxxx Assays, xx: X. J. Kirkland (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New York, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. R., Xxxxxxx, X., XxxXxxxxxx, J. X., Anderson, X., Xxxxxx, D. H., Xxxxxx, X. X., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. B., Xxxxxxxxxxxx, X., Xxxxxxx, X. X., Romagna, X., Xxxxxxx, X., Xxxxx, X., Vannier, X. (1994), Xxxxxx xxxx the Xxxxxxx Xxxxx xx the xx vivo Xxxxxxxxx Xxxx Xxxxxx Chromozomal Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

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

6) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxx, X., Papworth, X. X., Savage, X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Part XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

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

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


PŘÍLOHA 4X

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

1. XXXXXX

Xxxx xxxxxx je replikou xxxxxx XXXX XX 474 — Test xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx (1997).

1.1 XXXX

Xxxx xxxxxxx erytrocytárních xxxxxxxxxx xx xxxx xx používán xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, které xx xxxxxxxxxx xxxxxxxxx xxxxxx, x to pomocí xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx x/xxxx xxxxx periferní xxxx, xxxxxxx hlodavců.

Účelem xxxxx xxxxxxx erytrocytárních xxxxxxxxxx xx identifikovat xxxxx, xxxxx způsobují xxxxxxxxxxxxx poškození, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx nereplikující xx (xxxxxxx) chromozomové xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx se xxxxxxxxxxx xxxxxx dřeně mění xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx jádro xx xxxxxxxx x xxxxxxxxxx, xxxxx při xxx xxxxx xxxxxxxxx, zůstávají x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx je x těchto buňkách xxxxxxxxx xxx, xx xxxxxxxxxx hlavní xxxxx. Xxxxxx výskytu polychromatických xxxxxxxxxx s xxxxxxxxxx x xxxxxxxxxxxx xxxxxxxxx xx xxxxxxx indukovaného xxxxxxxxxxxxxx poškození.

V xxxxx xxxxx je xxxxxxx xxxxxxxxx kostní xxxx xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxx xx rovnocenně xxxxxxxxxx x xxxxxxxxxxx xxxxx, u xxxxx xxxx xxxxxxxxx neschopnost xxxxxxx odstraňovat erytrocyty x xxxxxxxxxx, nebo xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxxx xxx xxxxxxxx řadou xxxxxxxx. Xx zahrnují xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx v periferní xxxx, které obsahují xxxxxxxxxx, připadající xx xxxxxx počet xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx xxxx konečný xxxxxxxx xxxxxxx, xxxxxxxx xxxx xxxxxxx exponována xxxxx xxxxx xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx je xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, třebaže xx xxxxx lišit x různých xxxxx x tkání, xxxxx x z xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx xx xxxxxx xxxxxxxx pro další xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx x xxxxxxxxx xx vitro.

Jestliže existuje xxxxx x xxx, xx xx zkoušená xxxxx nebo reaktivní xxxxxxxxxx nedostanou do xxxxxx tkáně, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Obecný xxxx, xxxx X.

1.2 XXXXXXXX

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

Mikrojádra : xxxx jádra existující xxxxxxxx od xxxxxxxx xxxxx x xxxxx xxxx, vytvářená během xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx se (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx erytrocyt : zralý erytrocyt xxxxxxxxxxxx ribozomy, který xxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx selektivním pro xxxxxxxx.

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx ve xxxxxxxxx mezistadiu, který xxxxx xxxxxxxx xxxxxxxx, x xxxx xxx xxxx xxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx xx vhodným xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx xxxxx xx xxxxxxx ve vhodném xxxxxxxx xx xxxxxxxx xxxxxx, odebere xx xxxxxx dřeň, xxxxxxxx xx preparáty x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx použití periferní xxxx se krev xx xxxxxxx xxxxxxxx xx xxxxxxxx odebere, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx x xxxxxxxxx xxxx by xxxx xxxx xxxxxxxx xxxxxxxx x sklizením xxxxx xxxxxxxx xx xxxxxxxxx xxxx. Xxxxxxxxx jsou xxxxxxxxxxx na xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx použití xxxxxx xxxxx se xxxx testovací zvíře xxxxxxxxxx myš xxxx xxxxxx, ačkoli lze xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx xxxx xx doporučuje xxx. Xxx však použít xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx xxx x xxxx, x xxxxx xxxxxxx xxxxxxxxxxxx erytrocyty x xxxxxxxxxx, xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx xxxxxxxxx chromozomové xxxxxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx by x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata se xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, x xxx xx provede xxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx v xxxxxxxxxxxxx xxxxxxxxxx alespoň pět xxx xxxxxxxxxxxxx. Xxxxx xx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx xxxxxxxx rozpuštěny xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx být podávány xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Měly by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x jejich xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx účinky x mělo by xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich kompatibilitě. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx a negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx k expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx mikrojádra xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, že xxxxxxxxx detekovatelný nárůst xxx pozadí. Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, aby xxx xxxxxx zřetelný, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx byl xxxxx v xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx může xxx vzato v xxxxx xxxxxxx chemických xxxxx ze xxxxxx xxxxxxxx xxxxx, jsou-li x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo podle XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx 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 xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx nejsou x dosavadních xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx okamžikem xxxx xxxxxxx odběru. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx zhoubné nebo xxxxxxxxx xxxxxx.

Xxx použití xxxxxxxxx krve xxxx xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx u xxxxxxxx xxxxxx x periferní xxxx (např. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, že xxxxxxxx údaje xxxxx x xxxxxxx, které xx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx musí skládat x xxxxxxx xxxx xxxxxxxxxxxxxxxx zvířat xxx xxxxx pohlaví (11). Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx ze xxxxxx xx stejným xxxxxx a xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx rozdíl x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, jako je xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx standardní xxxx (xx. jednu, xxx xxxx xxx aplikace x xxxxxxxxx 24 xxxxx). Vzorky xx xxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx se x xxxxxx xxxxxx xxxxxxx pozitivní výsledky, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx xxxx prokázána xxxxxxxx nebo xxxx xxxxxxxxx limitní xxxxx x xxxxxxxx xxxxxxxxx xx xx xxxxxxxx xxxxxx. Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, tzn. dvě xxxxx v xxx xxx x rozmezí xx více xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx být xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx se aplikuje xxxxxxxx xxxxxx. Vzorky xxxxxx xxxxx xx xxxxxxxx xxxxxxx dvakrát, xxxxxxx první xxxxx xx xxxxxxx nejdříve 24 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx xxxxxxxx x x přiměřeným xxxxxxxx xxxx xxxxxx. Odběr xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx krve xx odeberou xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx xx aplikaci x po xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx nutný;

b) xxxx-xx xxxxxxxx xxx xxxx více xxxxx xxxxx (např. dvě xxxx více xxxxx x xxxxxxxxx 24 xxxxx), měly xx xxx vzorky xxx xxxxxxx xxxxxx dřeně xxxxxxxx xxxxxx xx 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx x xxx xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx poslední xxxxxxxx (12).

Xxxxx xxxxxxx mohou xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx studie xxx xxxxxxxx rozsahu dávek, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx stejným xxxxxx, kmenem, xxxxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí v xxxxxx studii (13). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx xxxxxxxx rozpětí xxxx maximální až xxxxxxxxx toxicitou, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, xx vyšší xxxxx by vedly xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Látky xx specifickou xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx dávkách (xxxx. xxxxxxx a xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx případ od xxxxxxx. Xxxxxxxx xxxxx xxxx být také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx některé xxxxxx xxxxxxxx (např. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx v xxxxxx xxxxx xxxx x xxxxxxxxx xxxx).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx dávkou o xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx xxxx ve xxxx dávkách x xxxxxx xxx nevykazuje xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx xxxxxxxxxxxx, není xxxxxxxxxx xxxxx xxxxxx xx třemi xxxxxxxx xxxxx za xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx xx limitní xxxxxx xxx 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx aplikaci xx xxxxxxx dávkou 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx v xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx měla být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava kostní xxxxx xxxx krve

Buňky xxxxxx dřeně xx xxxxxxx xxxxxxxxx z xxxxxx xxxx xxxxx xxxxx po xxxxxxxx. Xxxxx xx xxxxxxxx x femuru nebo xxxxx a xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x ocasní xxxx xxxx xxxx xxxxxx xxxxxx xxxx. Xxxxxx xxxxx xx ihned xxxxxxxxxxxx xxxxxx (8, 9, 10), nebo xx připraví preparáty xxxxxxxx a xxxx xx xxxxxx. Xxxxxxxx xxxxxxx specifického xxx XXX (např. xxxxxxxxxx xxxxx (14) nebo Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx vyhnout některým xxxxxxxxxx xxxxxxxx s xxxxxxxx xxxxxxx nespecifického xxx DNA. Tato xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. xxxxxxxxxx xxxxxx x odstranění xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, že se xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx systémů xxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx každé xxxxx xx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx xx x případě xxxxxx xxxxx xxxxxxx celkově xxxxxxx 200 xxxxxxxxxx x v případě xxxxxxxxx xxxx alespoň 1000 xxxxxxxxxx (17). Xxxxxxx preparáty xxxxxx xxxxxxxxx pozitivních a xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx zvířete xx xxxxxxx alespoň 2000 xxxxxxxxx erytrocytů na xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Xxxxx informace xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx. Xxx mikroskopické xxxxxxx xx xxxxx xxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx než 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx exponována xxxxxxxxxxx xxxxx týdny xxxx xxxx, xxx xxxx xxxxxxxx xx výskyt xxxxxxxxxx xxxxxxx 2000 xxxxxxx erytrocytů na xxxxx zvíře. Xxxxxxx xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx a xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx suspenze) jsou xx xxxxxxxxxxxxx zdůvodnění x xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ VÝSLEDKŮ

Údaje xxx xxxxxxxxxx zvířata xx xxxx xxx xxxxxxxxxx xx formě xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx xxxxx. Xxx xxxxx analyzované zvíře xx měl xxx xxxxxx počet xxxxxxxxxxx xxxxxxxxx erytrocytů, počet xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx a xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx nebo xxxx, xxxx xx xxx xxxx uvedeny údaje x xxxxxxx erytrocytech, xxxx-xx xxxxxxxxxxxxx. Pro xxxxx xxxxx xx xxxxx podíl nezralých xxxxxxxxxx z celkového xxxxxxxx erytrocytů x xxxxxxxx xxxxxxxx xxxxxxxxxx x mikrojádry xxxxxxxxx x xxxxxxxxxx. Neexistuje-li xxxxx x rozdílu x xxxxxxxx xxxx xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx pro xxx xxxxxxx zkombinována.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx s xxxxxxxxxx x závislosti xx xxxxx nebo jasný xxxxxx xxxxx xxxxx x mikrojádry xxx xxxxxxx x určitou xxxxxx x x xxxxxxxx okamžiku xxxxxx. Xxxxxxxx by měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný prostředek xxxxxxxxxxx metody (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx být xxxxxxx určujícím xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx výsledky by xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xxxxx xx xxxxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje mikrojádra, xxx jsou xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx mitotického xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx druhu. Xxxxxxxxx výsledky xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

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

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx o zkoušce xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- počet, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky chovu, xxxxxx xxx.,

- individuální xxxxxxxx xxxxxx na xxxxxxx zkoušky, xxxxxx xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx pro xxxxxx xxxxxxx.

Xxxxxxxx podmínky:

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

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxxxxxx podávání,

- xxxxxxxxx xxxxxx xxxxxxx, xxx xx zkoušená xxxxx dostala xx xxxxxxxx oběhu nebo xx xxxxxx tkáně,

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

- xxxxxxxx xxxxx o xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x nezralých xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx jedno zvíře,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxx nezralých xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx,

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

- xxxxxxx xxxxxxx ± xxxxxxxxxx odchylka xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx xx xxxxxxx,

- xxxxx možnosti závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x metody,

- údaje x xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx kontrole.

Rozbor výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxxx, J. X. (1973), X Xxxxx In vivo Xxxx xxx Xxxxxxxxxxx Xxxxxx, Mutatation Xxx., 18, 187-190.

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

3) Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X., XxxXxxxxx, J. G., Xxxxxx, X. X. (1983), Xxx Induction xx Xxxxxxxxxxx x. x. a Measure xx Genotoxicity, Xxxxxxxxxx Xxx. 123, 61-118.

4) Xxxxxxxxx, X. X., Xxxxxx, D. X., Xxxxxx, M. C., Xxxxxxxx, M. X., Xxxxxx, X. X. (1990), Xxx Xx xxxx Micronucleus Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx and Xxxxxxxxxx Xxxxx. X xxxxxx xx xxx U. X. Environmental Protection Xxxxxx Gene-Tox Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, X. X., Schlegel, X., Xxxx, X. X., Xxxx, X. M. (1983), Xxxxxxxxxxx in Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Xxxxxx for Xxxxxxxxxxx Xxxxxx During Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, in: Xxxxxxxxxxxx in Science xxx Practice of Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Xxxxxxx, T. X. Miya. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Heddle, X. X. Xxxx, X., Margolin, X. X., Xxxxx, X., Xxxxxxxx, X. X., Xxxx, X. X., Xxxx, X. (1987), Xxxxxxxxxx xxx the Xxxxxxx of Micronucleus Xxxxxx in Mammalian Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, X. X., Xxxx, X. X., Henika, X. X., Xxxxxx, X. X. (1990), The xx vivo Xxxxxxxxxxx Xxxxxxxxxxxx Xxxx: Measurement xx Xxxxxx Xxxxx Xxxxxxxxx Assay Efficiency xxx Xxxxxxx Xxxxxxxxxxx xxxx Toxicity Xxxxxxx, Xxxxxx. Appl. Xxxxxxx. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, T., Xxxxxx, Y., Sofumi, X., Ishidate, X. Xx. (1990), The Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Xxxxx Acridine Xxxxxx-Xxxxxx Slides, Mutatation Xxx., 245, 245-249.

9) Xxx Xxxxxxxxxxxxx Study Xxxxx xxx xxx Xxxxxxxxxxxx Test (1992). Xxxxxxxxxxxx Test with Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx Supravital Xxxxxxxx: Xxx Xxxxxxx Xxxxxx xx xxx 5th Xxxxxxxxxxxxx Xxxxx xx XXXXX/XXXXX, XXX, Mutatation Xxx., 278, 83-98.

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

11) Xxxxxxx, X., Tice, X. R., XxxXxxxxx, X. T., Xxxxxxxx, X., Xxxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Jr. X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxxx, X., Sutou, X., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Assay, Xxxxx. Res., 312, 293-304.

12) Xxxxxxxxxxx, X., Xxxxx, S. (1995), Xx optimal, generalised xxxxxxxx time xx 30 ± 6 x after double xxxxxx in the xxxxx peripheral xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Xxxxxxx, R. X., Allen, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Rochold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

14) Xxxxxxx, X., Xxxxxx, X., Ishidate, X. Jr. (1983), Xx Application of Xxxxxxxx Orange Fluorescent Xxxxxxxx xx the Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 120, 241-247.

15) XxxXxxxxx, J. X., Xxxx, X. X., Xxxxxxxx, X. X. (1983), X Xxxxxx Xxxxxxxxxxx Xxxxxxxx Xxxxxxxxx xxx Micronuclei and XXX in Xxxxxxxxxxxx Xxxxx Xxxxxxx 33258 xxx Pyromin X, Xxxxxxxx Xxx., 120, 269-275.

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

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

18) Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X., Xxxxxxxx, X., Gatehouse, X. X., Henderson, L. (1990), Xx xxxx Xxxxxxxxxxxx Xxxxx, in: X. X. Kirkland (xx.), Xxxxx Mutagenicity xxxxx, XXXXX Recommended Xxxxxxxxxx, XXXXX Sub-Committee xx Guidelines xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

19) Lovell, X. P., Anderson, X., Albanese, R., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx X., Xxxxxxx, X., Xxxxxxxx, D. G., Xxxxxx, X. X. X. (1989), Staticical Xxxxxxxx xx Xx xxxx Cytogenetic Xxxxxx, xx: D. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx III, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Melbourne, Xxxxxx, 184-232."


XXXXXXX 4D

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

1. METODA

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

1.1 ÚVOD

Při xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Escherichia xxxx, x xxxxxxx xxxxxxxx xxxxxx, které xxxxxxxx xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx nebo xxxxxxxx xxxx bází XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx na xxxxxxxx xxxxxx x bakteriemi xxxxxxx v detekci xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx x xxxxxxxxxxx kmenech x xxxxxxxx tak funkční xxxxxxxxx xxxxxxxx syntetizovat xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx reverzi jsou xxxxxxxxxx díky své xxxxxxxxxx růst x xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x xxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x člověka x xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx nádory xxxx xxxxx xx xxxxxx xxxxxxxx x člověka x x xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx je xxxxxx, xxxxxxxxxx a xxxxxxxxx xxxxxx. Xxxxx testovacích xxxxx xx xxxx xxxxxxxxxx, díky xxxx xxxx xxxxxxxxxx na xxxxxxx mutací, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx místech, xxxxxxx xxxxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx x xxxxxxxxx reparačních xxxxxxx DNA nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX náchylných x xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx může xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxx x xxxxxx mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx reverzní xxxxxx x bakteriemi xx x dispozici xxxxx xxxxxxxx databáze xxxxxxxx xxx xxxxxxx xxxxx struktur x xxxx byly xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx látek, xxxxxx xxxxxxxx xxxxxxxxx, x různými xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx obecný xxxx, xxxx B.

1.2 XXXXXXXX

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

Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx xxxxxxxx, jež xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx reverzních xxxxxx xx xxxxx tyto xxxxx vyskytnout xx xxxxx xxxxxxx mutace xxxx xxxxx místě xxxxxxxxxxxxx genomu.

Posunové mutageny xxxx xxxxxxxx, jež xxxxxxxxx xxxxx xxxx xxxxxx jednoho xxxx xxxx xxxx bází XXX x xxxxxxxx xxx čtecí xxxxx XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xx xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx struktura x xxxxxxxxx xxxxxxx XXX. Xxxxxxx prováděné xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Metabolické xxxxxxxxx xxxxxxx in xxxxx xxxxxxx xxxxx xxxxxxxxx podmínky xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx o xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxx pro xxxxx.

Xxxxxxx na reverzní xxxxxx s xxxxxxxxxx xx zpravidla využívána xxx počáteční xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx xxxxxxxx vyvolávající xxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxxx, xx mnoho chemických xxxxx, xxxxx xxxx x xxxx zkoušce xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx i x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxxxx detekovány xxxxx xxxxxxxx. Xxxxxxx xxxxxx xxxxxxxxxxx xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x rozdílech x xxxxxxxxxxx xxxxxxxx xxxx x rozdílech x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx faktory, xxxxx xxxxxxx citlivost xxxxxxx na xxxxxxxx xxxxxx xx xxxxxxxxxx, xxxxx vést k xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi nemusí xxx vhodná xxx xxxxxx xxxxx chemických xxxxx, například xxxxxx xxxxxxxxxxxx xxxxxxxxxx (např. xxxxxx xxxxxxxxxxx) a xxx chemické látky, x xxxxx xx xxxxxxxxxxx (nebo x xxxxx se xx), xx specificky xxxxxxxx xx xxxxxxxxxxxx systému xxxxx xxxxx (např. xxxxxxx inhibitory topoisomerasy x xxxxxxx xxxxxxx xxxxxxxxxx). V takových xxxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, xxx něž xx xxxx zkouška xxxxxxxxx, je xxxxxxxxxxxx xxx savce, xxxx xxxxxxxx xxxxxxxxx. Xxxxxx xx chemické xxxxx x xxxxxxxx xxxxx xxxxxxxxxxx, jež nejsou xxxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx buněk xxxx xxxxxxxxx xxxxxxxx xxxxx, x xx xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx a xxx xxxx. Xx xxxxxxxxxxx miskovém testu xx suspenze xxxxxxxx x xxxxxxx xxxxxx x ihned xx xxxxxxx xx xxxxxxxxx xxxx. V preinkubační xxxxxx xx xxxxxxxx xxxx inkubuje a xxxx se xxxx xxxxxxxxx na xxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx. Xxx xxxx xxxxxxxxxx se xx xxxx xxxx xxxxx xxxxx inkubace xxxxxxxxx kolonie revertantů x xxxxxxx se xxxxxxxx x počtem xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxx xxxxx x rozpouštědlem.

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

Xxx xxxxxxx xxxxxxx se xxxxxx xxxxxx standardního xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx xx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, tak xxx xx. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx xxxxx do xxxxxxxxxx xxxx, do xxxxx xxxxx mezi xxxxx xxxxxx xxxxxxxxxx xxxxxxxxxxx, dvojvazné kovy, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx sloučeniny, pyrrolizidinové xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx se xxxxxxxxx, xx určité xxxxx xxxxxxxx xxxxx vždy xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Měly xx xxx považovány xx "xxxxxxxx případy" x x xxxxxx xxxxxxx se důrazně xxxxxxxxxx xxxxxx alternativní xxxxxxx. Xx xxxxx xxxxxxxxxxxxx tyto "xxxxxxxx xxxxxxx" (xxxxxxxx s xxxxxxxx xxxxxxx xxxxxx xxxxxxx): azobarviva a xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx látky (12, 14, 15, 16), x glykosidy (17, 18). Odchylka xx xxxxxxxxxxxx xxxxxxx xxxx xxx vědecky xxxxxxxxxx.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Bakterie

Čerstvé xxxxxxx xxxxxxxx xx měly xxx xxxxxxxxxxx xx xxxxxx xxxxxxxxxxxxx xxxx xxxx xx xxxxx xxxxxxxxxxx xxxx xxxxx (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx neměly xxx xxxxxxx. Xx xxxxxxxx, xxx měly xxxxxxx xxxxxxxx vysoký xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx být xxxxxxxx buď na xxxxxxx dosavadních kontrolních xxxxx x xxxxxxx xxxxxx, xxxx pro xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx xx být xxxxxxx alespoň xxx xxxxx xxxxxxxx. Xxxx xxxx by xxxx xxx xxxxx xxxxx X. xxxxxxxxxxx (TA1535; XX1537 xxxx XX97x xxxx XX97; XX98 x XX100), xxxxxxx xxxxxxx xx ukázala x xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. xxxxxxxxxxx xxxx pár xxxx XX xx primárním xxxxxxxxx xxxxx x xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx xxxxxx oxidační xxxxxxxx, činitele xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Tyto xxxxx xxxxx být xxxxxxxxxx xxxxx X. xxxx XX2 xxxx X. xxxxxxxxxxx TA102 (19), které xxxx xx xxxxxxxxx reverzním xxxxx pár xxxx XX. Xxxxxxxxxx kombinace xxxxx xx xxxx xxxx:

- S. xxxxxxxxxxx XX1535 a

- S. xxxxxxxxxxx TA1537 nebo XX97x x

- X. xxxxxxxxxxx XX98 x

- X. xxxxxxxxxxx TA100 x

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

Xxx xxxxxxx mutagenů způsobujících xxxxxxxxxx xxxxxx DNA xxxx být xxxxxxxxx xxxxxxx TA102 nebo xxxxxx kmen E. xxxx s xxxxxxx xxxxxxxxxx reparace XXX, (xxxx. E. xxxx XX2 (pKM101)).

Měly by xxx použity xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, verifikace markeru x xxxxxxxxxx. Potřeba xxxxxxxxxxxxx xxx růst xx xxxx xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx kmenovou xxxxxxx (xxxxxxxx xxx xxxxx X. typhimurium a xxxxxxxxx xxx X. xxxx). Xxxxxxx by xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx plasmidů (tj. xxxxxxxxxxxx xxxxxxxxxx u xxxxx XX98, XX100 x TA97a xxxx XX97, XX2 xxxX x XX2 xxxX (xXX101) x ampicilinová x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx TA102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. rfa xxxxxx x S. xxxxxxxxxxx xxxxxxxxxx na krystalovou xxxxxx x uvrA xxxxxx x X. xxxx xxxx xxxX xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx xx xxxx xxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx na xxxxx x rozmezí xxxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx a xxxxxxx x rozmezí uvedeném x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx minimální xxxx (xxxx. obsahující xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) a glukosu) x xxxxxx xxxx xxxxxxxxxx xxxxxxxx x xxxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxx buněčných xxxxxx (1, 2, 9).

1.5.1.3 Metabolická aktivace

Bakterie xx měly xxx xxxxxxxxx xxxxxxxx látce, x to s xxxxxxx systémem xxxxxxxxxxx xxxxxxxx x bez xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx enzymy, xxxx je Xxxxxxx 1254 (1, 2) xxxx fenobarbitonu x β-xxxxxxxxxxxx (18, 20, 21). Postmitochondriální frakce xx xxxxxxx používána x koncentracích x xxxxxxx 5 xx 30 % xxx. xx xxxxx X9. Xxxxx x podmínky xxxxxxxxxxxxx aktivačního systému xxxx xxxxxxx na xxxxx xxxxxxxx xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx použít xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce. U xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxx může xxx xxxxxxxxx použití xxxxxxxxxx xxxxxxxxxxxxx aktivačního systému (6, 13).

1.5.1.4 Xxxxxxxx xxxxx nebo přípravek

Pevné xxxxxxxx xxxxx by xxxx xxx před xxxxxxxx na xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Kapalné xxxxxxxx látky xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje o xxxxxxxx neprokazují možnost xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx podezření, xx reaguje xx xxxxxxxxx látkou, a xxxx by být xxxxxxxxxx x xxxxxxxx xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, xxxx by xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx použita xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Zkušební xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxx zkoušené xxxxx xxxxx xxxxxxxxxxxx x rozpustnost v xxxxxxx směsi xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx v předběžných xxxxxxxxxxxxx. Xxxxxxxxxxxx může xxx detekována xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx kultur. Cytotoxicita xxxxx se xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx xx xxxx xxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxxxx x konečné xxxxx xx xxxxxxxxxx zkušebních xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx zkušební xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx xx 5 xx/xxxxx xxxx 5 μx/xxxxx. U xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by měla xxx xxxxx xxxx xxxx xxxxxxxxxx koncentrací xxxxxxxx, aby látky xxxx v xxxxxxx xxxxx pro xxxxxxxx xxxxxxxxxxx. Zkoušené látky, xxxxx xxxx xxxxxxxxxxx xxx při xxxxxxxxxxxxx xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx xxxxxxxx až xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx xxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx koncentrací xxxxxxxx xxxxx, přičemž xxx xxxxxx experimentu by xxxx xxx xxxxxxxxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Menší xxxxxxxxx jsou vhodné x případě, xxx xx xxxxxxxxx xxxxxx xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx nebo 5 μx/xxxxx xxxx xxx xxxxxxx při hodnocení xxxxx xxxxxxxxxxxx významné xxxxxxxx potenciálně xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx kontroly

Součástí každého xxxxxxxxx by měly xxx xxxxxxx xxxxxxxxxx xxxxxxxxx a negativní (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx x metabolickou xxxxxxxx a xxx xx. Xxx pozitivní xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx účinnost každé xxxxxxx.

X případě zkoušek x použitím xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxx (xxxxx) xxx pozitivní xxxxxxxx xxxxxxx (xxxxxxx) xx xxxxxxx xxxx xxxxxxxxx kmene bakterií.

Příkladem xxxxxx xxxxxxxxx xxxxxxxx x zkoušky 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 monohydrát

6055–19–2

Tato xxxxx je xxxxxxx xxxxxxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

XX Direct Red 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx xxxxx xxx xxxxxx xxxx xxxxxx indikátor xxxxxxxxx xxxxx S9. Xxx xxxxxxx 2-aminoanthracenu xx xxxx být xxxxx xxxxx S9 charakterizována xxxxxxxxx, který vyžaduje xxxxxxxxxxxx xxxxxxxx mikrosomálními xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx xxxxx

26628–22–8

247–852–1

XX1535 x TA100

2-nitrofluoren

607–57–8

210–138–5

TA98

9-aminoakridin

90–45–9

201–995–6

TA1537, XX97 x TA97a

ICR 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 uvrA a XX2 xxxX (xXX101)

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

XX2, XX2 xxxX a XX2 uvrA (xXX101)

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

3688–53–7

xxxxx obsahující xxxxxxxx

Xxx xxxxxxxxx kontrolu mohou xxx xxxxxxx jiné xxxxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxxx kontrolu xx mělo xxx xxxxx v xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx xx x xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx samotného xxxxxxxxxxxx xxxx xxxxxxxx, bez xxxxxxxx xxxxx, zpracované xxxxx stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx použity také xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx účinky.

1.5.3 Xxxxxx

X xxxxxxxxxx miskové xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx aktivace xx xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx zkušebních xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx xxxxxxx (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx agaru. X xxxxxxx zkoušky x xxxxxxxxxxxx aktivací xx xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx aktivační xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx směsi) s xxxxxxx agarem (2,0 xx) x xxxxxxx x xxxxxxxxxx a xxxxxxxxx látkou nebo xxxxxxxxx xxxxxxxx. Obsah xxxxx xxxxxxxx se xxxxxxxx x xxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx misce. Xxxx xxxxxxxx se xxxxx xxxxxx agar xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx nebo xxxxxxxx xxxxxx xxxx xxxxxxxxx x vrchním xxxxxx x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxxxxx 20 minut nebo xxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x sterilním xxxxxx nebo metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx se xxxxxx 0,05 xxxx 0,1 xx xxxxxxxx látky xxxx zkušebního xxxxxxx, 0,1 xx xxxxxxxx x 0,5 xx xxxxx X9 nebo xxxxxxxxxx pufru s 2,0 xx vrchního xxxxx. Zkumavky xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.

X xxxxxxxxxxxx odhadu xxxxxxxx by měly xxx xxx každé xxxxxx dávky xxxxxxx 3 misky. Xxxxxxx xxxx xxxxx xx xxxxxxxxxx xx vědeckém xxxxxxxxxx. Případná xxxxxx xxxxx xxxxxx znamenat xxxxxxxxxxxx xxxxxxx.

Xxxxxx xxxx xxxxxx xxxxx xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, např. x xxxxx uzavřených xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx misky x xxxx zkoušce by xxxx xxx xxxxxxxxxx xxx 37 °C xx 48 –72 xxxxxxxx. Xx xxxxxxxx xxxxxxxxx xxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx na xxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx xx měly xxx xxxxx kolonií xxxxxxxxxx xxxxxxxxxxx na xxxxx. Xxx xx xxx xxxxxx uveden xxxxx kolonií xxxxxxxxxx xxx xx xxxxxxx x xxxxxxxxx kontrolou (xxxxxxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx xxxxxxxx), xxx xx miskách x xxxxxxxxx xxxxxxxxx. Xxxxx xx xxxxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxx by xxxx xxx předloženy xxx zkoušenou xxxxx x pozitivní x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx kontrolu xxxxxxxxxxxx).

Xxxxxxx jasně xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx zkoušením, xxxxxxx x úpravou experimentálních xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od případu. Xxxxxxxx se xxxxxxxxx xxxxxxxxxxx xxxxxxxx nepovažuje xx xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx v xxxxxxxxxx experimentech. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx být xxxxxxx, patří xxxxxxx xxxxxxxxxxx, metoda xxxxxxxxxx (xxxxxxxxxx xxxxxxx metoda xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) a xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx několik xxxxxxxx, např. xxxxxx xxxxx xxxxxxx revertantů xx xxxxx nad xxxxxxxxx xxxxxx u xxxxxxx xxxxxxx xxxxx x xxxxxxxxxxxx aktivačním xxxxxxxx nebo xxx xxxx, x xx x závislosti xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx tohoto xxxxx xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx použity xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx jediným xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx na xxxxxxxx mutace x xxxxxxxxxx znamenají, že xxxxxxxx xxxxx xxxxxxxx x genomu kmenů Xxxxxxxxxx typhimurium x/xxxx Xxxxxxxxxxx xxxx xxxxxx xxxxxx xxxxxxxxxx bází xxxx xxxxxxx xxxxxxx xxxxx. Negativní výsledky xxxxxxxxx, že xxxxxxxx xxxxx xxxx xx xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy xxxxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx,

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

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- počty na xxxxxxxxxxxx xxxxxxx,

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx statistické xxxxxxx,

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

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

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxx, X. X., McCann, X., Xxxxxxxx X. (1975), Methods of Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res., 31, 347-364.

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

3) Xxxxxxxxx, D., Xxxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxx, X., Xxxxxxxxxx, X., Melcion, X., Xxxxx, X., Xxxxxx, X., Zeiger, X. (1994), Xxxxxxxxxxxxxxx for xxx Performance of Xxxxxxxxx Xxxxxxxx Assays, Xxxxxxxxxx Res., 312, 217-233.

4) Kier, L. X., Brusick D. X., Xxxxxxx, X. X., Von Halle, X. X., Xxxxx, X. M., Xxxxxx, X. X., Dunkel, X., McCann, J., Xxxxxxxxxx, K., Xxxxxx, X., Xxx, X. X., Xxx X. (1986), Xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Xxxxx: X Xxxxxx xx xxx U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, T., Xxxxxx, X., Xxxxx, X. X., Xxxxxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. (1975), Mutagenicity xx Xxxxxxxxxx Xxx Xxxx xxx xxxxx Xxxxxxxxxxx, Xxxxxx Lett. 1, 91-96.

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

7) Gatehouse, X. X., Xxxxxxx, X. X., Xxxxxx, X., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Basic Mutagenicity Xxxxx: XXXXX Xxxx 1 Xxxxxxx, ed. X. X. Xxxxxxxx, Xxxxxxxxx University Xxxxx, 13-61.

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

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

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

11) Xxxxxxxx, E. X., Xxxxxxx, X. J. (1981), An Xxxxxxxxxxx xx the Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx for Xxxxxxxxxxx xxxx Xxxxxxx xx Xxxxxxxxxx typhimurium, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

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

13) Prival, M. X., Xxxx, X. X., Xxxxxxxx, X. X., Reipert, M. X., Xxxxxxx, V. X. (1984), Xxxxxxxxxxxx xx Benzidine xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Dyes xx x Modified Xxxxxxxxxx Assay, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Xxxxxxxx, X. E., Xxxxxxx, X., Lawlor, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx from xxx Testing xx 311 Chemicals, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, V., Xxxxxxxx, K., Xxxxxxx, X. G. (1977), Xxxxxxxxx Xxxxxxxx of Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxx Xxxxx, xx Xxxxxxxx in Xxxxxxx Xxxxxxxxxx, X. Xxxxx, X. Xxxxxxx, F. Xxxxxx (xxx.) Xxxxxxxx, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. D. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxxxx Activity xx Volatile Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Assay, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

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

18) Xxxxxx, X., Gold, X., Xxxxx-Xxxxx, X., Xxxx, X. X. (1980), Xxxxxxxx: X Xxxxx for Xxxxxxxxxx xx Xxxxxxx Glycosides xx Mutagens xx Xxxxxxxxxx Flora, Proc. Xxxx. Xxxx. Sci. X. X. X, 77, 4961-4965.

19) Wilcox, X., Xxxxxx, X., Xxxx, D. X., Xxxxxxxxx, D. G. (1990), Comparison of Xxxxxxxxxx typhimurium XX 102 xxxx Xxxxxxxxxxx xxxx XX2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, T., Xxxxxxxx, M., Hara, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. s. xx Inducer xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: In vitro Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xxx. X. X. xx Xxxxxx et al. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Xxxxxx, X. X., Combes, X. X., Xxxxxxx, X. X., Gatehouse, X. X., Xxxxxx, X. X., Mackay, X. X., Xxxx, R. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-induced X9 in xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

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

23) Xxxxxxx, X. D., Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Nestmann, X., Xxxxxx, X. (1987), Xxxxx for xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, X. A. X., Green, X. X. X., Middleton, X., Xxxxxxx, I., Xxxxxxxx, X. X., Xxxxxx, D. J. (1989), Xxxxxxxx of Xxxx xxxx Microbial Xxxxxx Xxxxxx, in: XXXXX Sub-Committee xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Part II. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Test Xxxx, xx. Xxxxxxxx, X. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."


PŘÍLOHA 4E

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců xx xxxxx xxx xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx indukovaných xxxxxxxxxx látkami. Mezi xxxxxx xxxxxxx linie xxxxx xxxxx xxxxxxx X5178X myší, xxxxxxx xxxxx XXX, XXX-XX52 x V79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx TK6 xxxxxxx (1). X xxxxxx xxxxxxxxx xxxxx jsou xxxxxxxxxxxxxxx mírou xxxxxxxxxxx xxxxxx xxxxxx genů xxx thymidinkinasu (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x xxxxxxxx xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx xx xxxxxx TK, HPRT x XXXX detekují xxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XPRT xxxx xxxxxxx detekci xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx xxxxxx), které xxxxx xxxxxxxxx x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx na xxxxxx xxxxxx x xxxxxxx savců in xxxxx lze xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx nebo xxxxxxx xxxxx. Xxxxx xx xxxxxxxx xxxxx schopnosti xxxxx x xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx prováděné xx vitro obecně xxxxxxxx použití xxxxxxxx xxxxxx metabolické xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační xxxxxx xxxxxx zcela xxxxxxxxx podmínky xx xxxx x xxxxx. Xx xxxxx xx xxxxx vyvarovat xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx neodrážejí xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, jež neodrážejí xxxxxxx mutagenitu, může xxxxx xxxxxx pH, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx se xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Mnoho xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx touto xxxxxxxx x karcinogenitou však xxxx absolutní korelace. Xxxxxxxx xxxxxx xx xxxxxxxx třídě a xxxxxxxxx důkazy x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx působí xxxxxx, negenotoxickými xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx úvod, xxxx X.

1.2 DEFINICE

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

Xxxxxxxx xxxxxxxxxx xxxx xxxx : xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxx xxxx bází v XXX.

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

Doba xxxxxxx xxxxxxxx : doba, xxxxx xxx vymizí x nově mutovaných xxxxx nezměněné genové xxxxxxxx.

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

Relativní xxxxxxx xxxx : xxxxxx xxxxx buněk x xxxx xx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; vypočte xx xxxx xxxxxx xxxxxx xxxxxxxxx xxxxx x xxxxxxxx x v xxxxxxxxx kontrole a xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxx x xxxxxxxx : xxxxxx xxxxx buněk v xxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxx kontrole.

Životaschopnost : účinnost xxxxxxxxx xxxxx v okamžiku xxxxxxxx xx misku xx selektivních xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx xx xxxxx xx xxxxx xxxxxx expozice; přežití xx xxxxxxx xxxxxxxxx x poměru k xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxx, xxxxx v xxxxxxxx xxxxxx TK+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx x cytotoxickým xxxxxxx xxxxxxx pyrimidinu xxxxxxxxxxxxxxxxx (XXX). Buňky xxxxxxxxxxx xxxxxxxxxxxxxx jsou xxxxxxx xx XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx buněčné xxxxxx. Xxxxxxxx buňky xxxx xxxx schopny xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx normální xxxxx, xxxxx obsahují xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Xxxxxxx lze x xxxxx s xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx selekci xxxxxxxxxxxxxxx rezistence k 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (AG). Vlastnosti xxxxxxxx látky by xxxx být xxxxxxx xxxxxxx, xxxxxxxx je xx xxxxxxx na xxxxxx mutace x xxxxxxx xxxxx xxxxxxx xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Mělo xx xxx xxxxxxxxx vyšetřeno xxxxxxxx podezření na xxxxxxxxxx toxicitu xxxxxxxx xxxxx pro xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx chemických xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, xxxx xxxx xxx xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx xxx selekci (8).

Xxxxx x suspenzní xxxx xxxxxxxxxxxxx kultuře xxxx vhodnou xxxx xxxxxxxxx xxxxxxxx látce xxx x metabolickou xxxxxxxx, tak xxx xx, x xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx a xx xxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx xxxxxx xxxxxxxxxx relativní účinnosti xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxx relativního xxxxxxxxx xxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx v růstovém xxxxx po vhodnou xxxx xxxxxxxxxxxxxxxxx pro xxxxx zvolený xxxxx x xxx buněk, xxx xxxxxxx xxxxxxxxx xxxxxxxxx fenotypová xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se xxxxxxx xxx, xx xx xxxxxx známý xxxxx xxxxx xx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx detekci xxxxxxxxxx xxxxx x do xxxxx xxx xxxxxxxxxx xxxxxxx, xxx byla xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx vhodné xxxxxxxxx xxxx se xxxxxxxxx xxxxxxx. Četnost xxxxxxx se xxxxxxx x xxxxx xxxxxxxxxx xxxxxxx x xxxxxxxxx xxxxx x počtu xxxxxxx x xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro xxxxxxx x xxxx xxxxxxx xxxx k xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx subklonů xxxxx X5171X, XXX, CHO-AS52, X79 xxxx XX6. Xxxx xxxxx x xxxx zkoušce by xxxx xxxxxxxxx citlivost x xxxxxxxxx mutagenům, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx měly xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, a x xxxxxxx kontaminace xx xxxxxx být xxxxxxx.

Xxxxxxx xx xxxx xxx navrženy xxx, xxx xxxx xxxxxx xxxxxxxxxx xxxxxxxxx x xxxx. Počet použitých xxxxx, xxxxxx a xxxxxxxxxxx zkoušené látky xx měl xxxx xxxxxxxxxx xxxxxxxxx odrážet (14). Minimální xxxxx xxxxx, xxxxx xxxxxxx xxxxxxxx x xxxxx xxxxx použity x xxxxxx stadiu zkoušky, xx xxx xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx mutací. Obecným xxxxxxxxx je, xxx xxx použit xxxxx xxxxx, který xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však xxxxxxxxxx, xxx xxxx použito xxxxxxx 106 xxxxx. Xxxx xx být x dispozici xxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx doložena xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx vhodná xxxxxxxxxx média a xxxxxxxxx podmínky (xxxxxxxxxx xxxxxx, koncentrace CO2, xxxxxxx x vlhkost). Xxxxx xx měla xxx zvolena podle xxxxxxxxxx systémů x xxxx buněk použitých xxx xxxxxxx. Je xxxxxxx xxxxxxxx, xxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxx xxx, aby xxxx xxxxxxxxx optimální xxxx xxxxx během xxxxxx xxxxxxx x xxxxxxxxx jak xxxxxxxxxx, xxx xxxxxxxxxxxx buněk xxxxxx xxxxxxx.

1.4.1.3 Příprava xxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx kultur, nasazeny xx kultivačního média x xxxxxxxxxx xxx 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx může xxx xxxxxxxx xxxxxxxxx x xxxxxxx již přítomné xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx vystaveny xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx něho. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (S9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxx indukujícím xxxxxx, xxxx je Xxxxxxx 1254 (15, 16, 17 a 18), xxxx xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (19, 20).

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

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx aktivaci. Xxxxx xxxxxxxxx buněčných xxxxx xx xxxx xxx xxxxxxx zdůvodněna (xxxx. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx před aplikací xx xxxxx rozpuštěny xxxx xxxxxxxxxxxx ve xxxxxxxx rozpouštědlech nebo xxxxxxxxxx a popřípadě xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx být xxxxxxx xxxxx k xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, pokud xxxxx x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, x mělo xx být xxxxxxxxxx x xxxxxxxx xxxxx x x aktivitou X9. Jsou-li použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

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

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx vhodných xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (přežití) nebo xxxxxxxxx xxxxxxx růst. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx alespoň čtyři xxxxxxxxxxxxxx koncentrace. V xxxxxxx xxxxxxxx xx xxxx tyto koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx, xx xx xx xxxxxxxxxxx xxxx xxxxx faktorem 2 až Ö10. Xx-xx xxxxxxxxx koncentrace xxxxxxxx xx xxxxxxxxxxxx, xxxx by být xxxxxxxxx přibližně 10 — 20 % (xxx xxxxxxx 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx celkový xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx by xxxx být xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx toho, xxxxx x xxxx je xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx měly xxx xxxxxxxx xx k xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx podmínek, xxxx xx xx xxxx xxx. Měla xx xxx stanovena xxxxxxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx, xx kterému xxxx xxxxx xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx aplikace, xxxxx xxxxxxxxxxx xx může x xxxxxxx xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx v xxxxxxxx xxxxxxxxxxx buněk, X9 xxxx, xxx. Nerozpustnost xxx xxxxxxx xxxxxxxx. Xxxxxxxxx by neměla xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Xxx xxxxxxx xxxxxxxxxxx aktivace xx xxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, která x xxxxxxxxx odpovědi vyžaduje xxxxxxxx.

Xxxxxxxxx xxxxxxxxx kontroly xxxxx xxx xxxx xxxxx:

Xxxx xxxxxxxxxxx aktivace

Lokus

Látka

Číslo XXX

Xxxxx xxxxx Einecs

Bez xxxxxx xxxxxxxxxxx aktivace

HPRT

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

TK (xxxx x velké xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx 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 x 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 úrovně X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

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

Měly xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx samotné xxxxxxxxxxxx xxxx vehikulum a xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Postup

1.4.3.1 Xxxxxxxx xxxxxxxx látce

Proliferující xxxxx xx měly xxx xxxxxxxxx xxxxxxxx látce xxx xx přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx něho. Xxxxxxxx xx xxxx xxxxx vhodnou xxxx (xxxxxxx xx účinná xxxx 3 až 6 xxxxx). Expoziční xxxx může xxx xxxxxxxxxxx xx xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx exponovaná xxxxxxx. Je-li xxxxxxx xxxxx xxxxxxx, xxx xx xxx počet xxxxxxxxxxx xxxxxx xxx, xxx byl xxxxxxxx xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (např. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx by xxx použity xxxxxxxxxx xxxxxxxxx kontrolní xxxxxxx (xxxxxxxx rozpouštědla).

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

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx a xxxxxxxx xxxxxx

Xx xxxxx expoziční xxxx xx buňky xxxxxxx x xxxxxxxxx xx xxxxxx stanovení xxxxxxx x za xxxxxx umožnění exprese xxxxxxxx mutantu. Xx xxxxxxxxxx cytotoxicity xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxx xxxxxxx po expoziční xxxx.

Xxxxx xxxxx má xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx indukovaných xxxxxxx (XXXX x XXXX vyžadují xxxxxxx 6 xx 8 xxx, TK xxxxxxx xxx xxx). Xxxxx xxxx xxxxxxxxxxx x xxxxx se selekčním xxxxxxxx (xxxxxxxxxx xxxxxxx) x bez xxxx (xxx nich) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx x klonovací xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (použité xxx xxxxxxx četnosti xxxxxxx) xx xxxxxxx na xxxxx xxxx xxxxxxx xxxxxxxxx na xxxxx xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx xxxxx pozitivní xx xxxxxxx X5178X XX+/-, mělo by xxx xxxxxxxxx xxxxxxx xx jedné xx xxxxxxxxxx kultur (s xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx kolonií. Xx-xx xxxxxxxx xxxxx ve xxxxxxx L5178Y XX+/- xxxxxxxxx, xxxx xx xxx rozdělení xxxxxxx xxxxx velikosti xxxxxxx xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx kontrolách. Xxx xxxxxxxx za xxxxxxx XX6 TK+/- xxxx být xxxx xxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx kolonií.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xx xxxx zahrnovat xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, počtu kolonií x četnosti xxxxxxx xxx exponované x xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxx L5178Y XX+/- xx xxxxxxx xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx zkoušené xxxxx (nejvyšší xxxxxxxxx xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx xx použití xxxxxxxx xxxx xxxxxxx — xxxxx kolonie. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx mutantů xxxxxxxxx velké xxxxxxx, xxx xxxxxxx tvořících xxxx kolonie byla xxxxxxxx zkoumána (23, 24). Ve zkoušce XX+/- jsou xxxxxxx xxxxxxxxxxx za použití xxxxxxxx kolonie x xxxxxxxxx růstem (xxxxx) x xxxxxxx s xxxxxxx xxxxxx (xxxx) (25). U mutantních xxxxx, xxxxx utrpěly xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx xxxx xxxxxxxx, x xxxxx xxxx xxxx kolonie. Xxxxxxxxx má obvykle xxxxxx xx xxxxx xxxxxx xxxx až xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xxxxxxxxx malé xxxxxxx xx spojuje x xxxxxxxxxx látkami, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx závažně postižené xxxxx xxxxxxx xxxxxx xxxxxxxx tempem xxxx xxxxxxxx buňky a xxxxx xxxxx kolonie.

Mělo xx být xxxxx xxxxxxx (relativní xxxxxxxx xxxxxxxxx) nebo relativní xxxxxxx růst. Četnost xxxxxxx xx xxxx xxx xxxxxxxxx xxxx xxxxx xxxxxxx k xxxxx xxxxxxxxxx buněk.

Měly xx být xxxxxxx xxxxx pro jednotlivé xxxxxxx. Xxxx xx xxxx xxx xxxxxxx xxxxx shrnuty xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx měly xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx případ xx xxxxxxx. Tam, kde xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx považováno za xxxxx, xx xxxxx xxxxx zdůvodnění. Xxxxx xxxxxxxxx studie x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx zvážena x následných xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, tak pro xxxxxxxxx výsledky. X xxxxxxxxxx xxxxxx, které xx xxxxx být xxxxxxx, patří xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx kritérií, xxxx. nárůst četností xxxxxxx x závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx nárůst xxxx xxxxxxxx. Nejdříve xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx by xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx odpověď.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx bez xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxx xxxxxx v xxxxxxx xxxxx in xxxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x použitých xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx xx xxxxx xxxxxxxx. Negativní výsledky xxxxxxxxx, xx zkoušená xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce musí xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxx buněčných xxxxxx,

- případně xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx buněčné xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x xxxxx kultur, xxxxxx xxxx. údajů x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, jsou-li x xxxxxxxxx,

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX2,

- koncentrace xxxxxxxx xxxxx,

- objem xxxxxxxx x xxxxxxx zkoušené xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx během expozice,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

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

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx životaschopných a xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- známky toxicity,

- xxxxxx xxxxxxx,

- xxxxx x pH a xxxxxxxxxx během xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxx,

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

- xxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxxxxxx xxxxxxxx X5178X TK+/-,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., DeMarini, X. X., XxXxxxxx, X. X., Tindal, X. R. (xxx.) (1987), Xxxxxxx Report 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Xxxx Xxxxxx Xxxxxx Xxxxxxxxxx, Xxx Xxxx.

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

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

4) Xxxxx, X. X., Harington-Brock, X., Xxxxx, X. X., Xxxxxxxxx, X. X. (1989), Differential Xxxxxx Quantitation xx xxx Xxxxx Xxxxxxxx XX xxx XXX XXXXX Xxxx, Xxxxxxxxxxx, 4, 394-403.

5) Xxxxx, X. S., Xxxxxxxxxx, Xx. X. X., (1989), Xxxxxxxxxx xx xxx AS52/XPRT and xxx CHO/HPRT Assays: Xxxxxxxxxx of Six Xxxx Candidates, Xxxxxxxxxx Xxx. 223, 121-128.

6) Xxxxx, X. S., Xxxxxxxxxx, X., Glatt, X. X., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Jr. X. X., Theiss, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Xxxxxx. Report xx xxx Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxxx Res. 312, 235-239.

7) Scott, X., Galloway, S. X., Marshall, R. X., Xxxxxxxx, M., Xxxxxxx, X., Xxxxx, X., Xxxx, B. X. (1991), Xxxxxxxxxxxx Xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx ICPEMC Task Xxxxx 9, Mutation Xxx. 257, 147-204.

8) Xxxxx, D., XxXxxx, X., Xxxxxxx, J. X. X., Xxxxx, X., Mavournin, X. X. (1983), Xxxxxxxx Xxxx Xxxxxxxxx xx X5178X Xxxxx xx Xxxxxxx. A Xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 115, 225-251.

9) Xx, A. X., Xxxxx, R. X., Heflich, X. X., Xxxxxx, J. X. (1988), X Xxxxxx xxx Xxxxxxxx xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Transferase Xxxxxx xx Determine the Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: X Xxxxxx xx Phase XXX xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Gene-Tox Program, Xxxxxxxxxx Res., 196, 17-36.

10) Xx, X. X., Xxxxxx, X. X., Choy, X. X., Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X., X'Νxxxx, J. X., Xxxxxx, J. X., Xxxxxxxxxx, L. X. Xx., Yang, X. X. (1987), X Xxxxx for xxx Xxxxxxxxxxx of xxx Chinese Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Phosphoribosyl Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res., 189, 135-141.

11) Xxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, X. X. (1989), X Xxxxxxxxxx xx Xxxxxxxx Induction xx xxx XX and XXXX Xxxx xx Xxxxx Lymphoblastoid Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx to xx Xxxxxxxxxx Class xx Xxxxxxxxx xx xxx Xxxxxxxxx XX Locus, Xxxxxxxxxx Xxx., 216, 9-17.

12) Xxxxxxxxxx, X. X. Xx., Xxxxxx, X. X., Hsie, X. X. (1986), Xxxxxxxxxxxx and Molecular Xxxxxxxx xx Ethyl Xxxxxxxxxxxxxxxxx xxx XXX 191-Xxxxxxx Xxxxxxxxx Analyses xx Xxxxx Xxxxxxxxxxxxxxxxx xxx XXX 191 Xxxxxxx Xxxxxxxx in XX52 Xxxxx, Xxxxxxxxxx Xxx., 160, 133-147.

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

14) Xxxxxx, X. F., Xxxxx, D. M., Xxxxxx, G. X., Xxxxx, X. X. X., Xxxx, J., XxXxxxxx, X. B., Xxxxxxx X. X. (1989), Mammalian Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxx xxxx Colony Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Data, Kirkland, X. J., xx., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 66-101.

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

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

17) Xxxxx, X., Johnson, X. X., Xxxxxxx, X. X. X., Xxxxxx X. G., Xxxxx M. M. X. (1979), Xxxxxxxxxx xxx Characterisation of xxx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxxxx Assay Xxxxxx, Xxxxx. Res. 59, 61-108.

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

19) Xxxxxxx, X. X., Combes, R. X., Xxxxxxx, C. X., Xxxxxxxxx, X. X., Xxxxxx, G. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-Induced X9 in: In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, de Xxxxxx, X. J., Fouts, X. X., Bend, X. X., Philpot, X. M. (eds), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, D. F., Xxxxxx, X. X., XxXxxxx, X. X. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx and Volatile Xxxxxxx, xx: Xxxx, X. X., Costa, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

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

23) Applegate, X. X., Xxxxx, X. X., Xxxxxx, X. X., Burrell, X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxx xx xxx Heterozygous Xxxxxxxxx Xxxxxx Locus xx Mouse Xxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. X, 87, 51-55.

24) Moore, X. X., Xxxxx, X., Xxxxxx, X. C., Xxxxxx, B. X., Xxxxxx, X. X., Xxxxxx, N. X., Xxxxxx, J. (1985), Xxxxxxxx xx Trifluorothymidine, Xxxxxxxxx (XXX+) Mutants xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res. 151, 161-174.

25) Xxxxxxx, X. W., Xxxxx, X. P., Little, X. X. (1990), Xxxxxxxxx Xxxxxxx Analysis xx Xxxxxxxxx Mutations xx x Xxxxxxxxxxxx Xxxxxxxxx Xxxxx xx Xxxxx Xxxxx, Mutatation Xxx. 229, 89-102.

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


XXXXXXX 4F

"B.23 ZKOUŠKA XX CHROMOZOMOVÉ ABERACE XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

Xxxx xxxxxx je xxxxxxxx xxxxxx XXXX XX 483 — Xxxxxxx na chromozomové xxxxxxx ve spermatogoniích xxxxx (1997).

1.1 ÚVOD

Účelem xxxxxxx xx chromozomové xxxxxxx xx xxxxxxxxxxxxxxx xxxxx in xxxx xx xxxxxxxxxxxxx xxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Rozlišují xx dva xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx xxxxxxxxxx mutagenů xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx účelu xxxxxxx používána. Chromozomové xxxxxx a xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx změny ve xxxxxxxxxxxxxxx x xxxxxxxxxxx xx xxxx, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx indukce dědičných xxxxxx x germinálních xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx in xxxx xx xxxxxxxx xxxxxxxxxxxx xxxxxxx při mitose xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx xxxxxxxxx xxxx xxxxxxx.

Xxx detekci xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx xx xxxx xxx — xxxxx xxx dojde xx xxxxxx léze — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx xx xxxxxxxx. Xxxxx informace x exponovaných xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx meiotickou xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x diakinese-metafázi X, xxx xx xxxxxxxxxx buňky xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx je xxxxxxxx xxx xxxxxxxxx, xxx xxxx mutageny xxxxxxxxxxx xxxxx xxxxxxx také x germinálních buňkách. Xxxxx je xxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx DNA.

Ve xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx xx xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxxxxxxx diferencovanými xxxxxxxxxxxxxxx. X závislosti xx své poloze xx xxxxxxxxx, xxxxx xxxx xxxxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx krevnímu xxxxx x xxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxx Sertoliho xxxxx x xxxxxxx xxxx xxxxxxx oběhem a xxxxxxx.

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

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození chromozomu x xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

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

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

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx při xxxxxxxx xxxxxx ve xxxxxx metafáze xxx xxxxxxxxxxx, xxxx xx xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx změny.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxx a xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx. Xxxx usmrcením xx xxxxxxxx podá xxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx poté xxxxxxxx xxxxxxxxx xxxxxxxxxx, obarví xx x analyzují xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx xxxxxxxxx xxxxx xxxxxx xxxxxxxx a xxxx; lze xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx vhodného xxxxx xxxxx. Xxxx by xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx samci xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx tak, aby xxx xxxx xxxxxx xxxxxx minimalizován. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx studie xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx rozpuštěny nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx být podávány xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx xxxxxxxxx hladinách xxxxx xxxxxxx xxxxxx x xxxx by být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx použita xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx pokud xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx by xxxx xxx souběžné xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx xxxxxxx xx spermatogoniích xx xxxx při xxxxxxxxxxx xxxxxxxx, x nichž xx xxxxxxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx byl účinek xxxxxxxx, xxx xxx xxx xxxxxx nevyšla xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx podávána xxxxx xxxxxxxx xxx xxxxxxxx xxxxx a xxx xxx xxxxx x jejím xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx kontrolu xxxx xxx xxxxx xxxxx x úvahu xxxxxxx chemických xxxxx xx stejné xxxxxxxx xxxxx, jsou-li x 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 xxx být xxxxxxxx odběr u xxxxxxx negativní kontroly, xxxxx xx aplikováno xxxxx rozpouštědlo nebo xxxxxxxxx x xxxxx xxxxx podstupuje xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx kontrolních xxxxx k dispozici xxxxxxxxxx údaje o xxxxxxxxxxx xxxxxx a xxxxxxxx buněk s xxxxxxxxxxxxxx aberacemi. Kromě xxxx xx měly xxx neexponované kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx xxxx xxxxxxxxx alespoň xxx xxxxxxxxxxxxxxxx samců.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx podávány xxxxxxxxxxx nebo xxxxxxxxx (xx. xxx jedné xxxxxxxx nebo xxxx xxxxxxxxxx). Zkoušené xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. dvě xxxxx v týž xxx x xxxxxxx xx xxxx xxx xxxxxxxx hodin, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx xxxxxx xx xxxx xxx xx xxxxxxxx provedeny xxx odběry. Xxxxxxxx xxxxxxxx xxxxxxxxx cyklu xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx jeden xxxxx xxxxx x xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 a 48 xxxxx xx xxxxxxxx. X xxxxxxx xxxx xxx xxxxxxxx xxxxx xx xxx být xxxxx xxxxxxxx po 24 hodin xxxx xx xxxxxx době xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx buněčného xxxxx, xxxxx není xxxxx jiná xxxxxxxxx xxxx xxx detekci xxxxxx (6).

Xxxxx mohou xxx odběry xxxxxxxxx xxxx v jiné xxxx. Xxxxxxxxx v xxxxxxx chemických xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx X-xxxxxxxxx účinky, xxxx xxx xxxxxxxxx xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx opakované xxxxxxxx xxxx xxx xxxxxx xxxxxx od xxxxxxx. X xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx usmrcena 24 xxxxx (1,5xxxxxxx délky xxxxx) xx poslední xxxxxxxx. Podle xxxxxxx xxxxx xxx prováděny xxxxx odběry x xxxx době.

Před xxxxxxxxx xx zvířatům xxxxxxxxxxxxxxxxx xxxx vhodná xxxxx xxxxx zastavující metafázi (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Poté se xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. U xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 hodin; x xxxxxx čínského xx xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx zjištění xxxxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx stejným xxxxxx x kmenem x xx xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx použije v xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx pokrývat rozmezí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx toxicitou. Při xxxxxxxxx xxxxxx stačí, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xx xxxxx dávky vedly xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x xxxxxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx xx xxx hodnoceny xxxxxx xx xxxxxxx. Xxxxxxxx dávka může xxx také xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xx xxxxxxxxxxxxxxx některé xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx by xxxxxx xxxxxxxxx 50 %).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx jednorázově nebo xx dvou xxxxxxx x xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. Xxxxxxxxx expozice xxxxxxx xxxx znamenat xxxxxxx použít x xxxxxxx zkoušce vyšší xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx se xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx způsoby podávání xxxx přijatelné, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx vyšších koncentracích xxxxxxxx zesílené xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxx

Xxxxx xx usmrcení xx x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxx xx nanese xx xxxxxxxx sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx zvířete xx mělo xxx xxxxxxxxxxx alespoň 100 xxxxx x xxxxx xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 xxxxxxxx xx skupinu). Xxxxx xxxxx xxx snížit, xx-xx pozorován velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx včetně preparátů xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx při fixaci xxxxx xxxxxxx ke xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx x xxxxx xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx v xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx by xxxx xxx xxxxxxxxxx ve xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx xxxxx xxxxx xx měl být xxxxxxxxxx počet xxxxx xx strukturními chromozomovými xxxxxxxxx x xxxxx xxxxxxxxxxxxxx aberací na xxxxx. Xxx exponované x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x četností. Gapy xx xxxxxxxxxxxxx odděleně x xxxxxxx se, xxx xxxxxx xx xxxxxxxxxx xx celkové xxxxxxxx aberací.

Je-li pozorována xxxxxx x xxxx xxxxxx, měl by xxx xxx stanovení xxxxxxx xxxxxxxxxxxxx xxxxxx xxxx míra xxxxxxxxxxxx xxxxxxxx x xxxxx xxxxxxxxxxxx zvířat x xxxxxx xxxxxxxxxx jako xxxxxxxxx kontrola poměr xxxxxxxxxxxxx x xxxxxx xxxxxxxx k první x druhé meiotické xxxxxxxx, x xx x xxxxxxxx xxxxxx 100 dělících xx xxxxx na xxxxx xxxxx. Pokud xx xxxxxxxxx xxxxx mitosa, xxxxxxx v 1000 xxxxxxx na xxxxx xx měl xxx xxxxxxxx xxxxxxxxx index.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx existuje několik xxxxxxxx, xxxx. nárůst xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi v xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx pro skupinu x xxxxxxx dávkou x k určitému xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická relevance xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx (8). Statistická xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx většina experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx bez ohledu xx xx, kolikrát xx experiment xxxxxxxx.

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

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx xxxxxxxx xxxxx nebo xxxx xxxxxxxxxx dostanou xx xxxxxx tkáně.

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx x xxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx a xxxxxxxxxx odchylky xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxx xxxxxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x odběru,

- metody xxxxxxxxx toxicity,

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

- xxxxxx xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- známky toxicity,

- xxxxxxxxx xxxxx,

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

- typ a xxxxx aberací xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- xxxxxxx počet xxxxxxx ve xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx skupině,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx,

- změny ploidie, xxxxx byly xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

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

3) Xxxxx, X. X., Xxxxxxx, X., Ford, X. X. (1964), Xx Xxx-xxxxxx Xxxxxx xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Xxxxxx, Xxxxxxxxxxxx Cell Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, X. (1990), In xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Part X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, I. X., Xxxxxx X. D., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, W., Xxxxxxxxxxxx, X., Xxxxxxx, X., Tanaka X. (1994), International Xxxxxxxx xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Report of xxx Xxxxxxx Xxxxx xx Mammalian Xxxx Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, A. X., Xxxxxx, P. A., Xxx, X., Esdaile, X. J., Xxxxxxxxx, X. X., Hodson-Walker, X., Morton, X. X., Xxxxxxxx, D. X., Richold, M. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. X., Xxxxxxxx, X., Albanese, X., Amphlett, G. X., Xxxxx, X., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx X. X. K. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx vivo Xxxxxxxxxxx Xxxxxx, xx: D. X. Kirkland (xx.), Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Test Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx, Xxxx XXX. Cambridge University Xxxxx, Cambridge, New Xxxx, Port Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

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

1. XXXXXX

Xxxx xxxxxx je replikou xxxxxx OECD TG 486 — Xxxxxxx xx neplánovanou xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx savců xx xxxx (1997).

1.1 XXXX

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

Xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx účinků chemických xxxxx x xxxxxxx. Xxxxxxxxxxx xxx xx xxxxxxxxxx xxxxxxxxx XXX x xxxxxxxx xxxxxxxx x jaterních xxxxxxx. Xxxxx jsou obvykle xxxxxxx místem, xxx xxxx xxxxxxxxxxx sloučeniny xxxxxxxxxxxxxx. Jsou xxxx xxxxxxx xxxxxx pro xxxxxxxxx xxxx xxxxxxxxx XXX xx vivo.

Jestliže xxxxxxxx xxxxx o xxx, xx xx xxxxxxxx xxxxx nedostane xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx DNA (XXX) xx xxxxxxxx stanovením xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx buněk, které xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Nejrozšířenější xxxxxxxxx xx autoradiografické xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx xx XXX xx xxxx xx přednostně používají xxxxx potkana. Xxxx xxxxx xxx xxxxx xxxxx xxx rovněž xxxxxxx, xxxxxx xxxx xxxxxxxxx xxxx metody.

Detekce xxxxxxxx XXX závisí xx počtu bází XXX vyštěpených x xxxxxxxxxxx x místě xxxxxxxxx. Xxxxxxx xx XXX je xxxx xxxxxx xxxxxxx pro xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("short-patch xxxxxx") (xxxxx až xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx x xxxxxx menší citlivostí. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx xxxx DNA xxxxx k mutagenním xxxxxxxxx. Xxxxxx odpovědi XXX neposkytuje žádnou xxxxxxxxx x xxxxxxxx xxxxxxxxxxx procesů. Xxxxx xx možné, že xxxxxxx xxxxxxx x XXX, ale poškození XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx informací, xxxxx xxxx zkouška poskytuje x xxxxxxxxx xxxxxxxx, xx xxxxxxx potenciální xxxxxxxxxx xxxxxx jevu, xxxxx xx vyšetřován x celém xxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 DEFINICE

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

Čistý xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx míra XXX xxxxxxxx buněk v xxxxxxxxxxxxxxxxx zkoušce na XXX, xxxxxxxxx odečtením xxxxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx oblastech (XX) xxxxxxxxxxxxxx xxxxxx xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): XXX = XX — XX. Xxxxxxx XXX se xxxxxxx xxx xxxxxxxxxx xxxxx, xxxx společně xxx xxxxx x xxxxxxx, v xxxxxxxxxxx xxxxxxxxx atd.

Neplánovaná xxxxxxx XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx region x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x jaterních xxxxxxx xxxxx xx vivo xxxxxxxx syntézu xxxxxxxx XXX po xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx. Zkouška xx xxxxxxx xxxxxxxx xx xxxxxxxxxxx 3X-XxX xx XXX xxxxxxxxx xxxxx, kde xx xxxx četnost buněk x X-xxxx xxxxxxxxx xxxxx. Xxxxxxxxxxx 3H-TdR xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx tak xxxxxxx na xxxx X-xxxx xxxxx xxxx xxxx. kapalná scintilační xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx je používán xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxx xxxxx. Měly xx xxx xxxxxxx xxxxx používané laboratorní xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx zahájení xxxxxx by měla xxx xxxxxxxx x xxxxxxxxx xxxxxx minimální x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx pro obě xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x strava

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x skupinu, xxxxx xx xxxxxxxx. Xxxxx xx xxxx být xxxxxxxxxx xxx, aby xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují x před xxxxxxxxx xxxxxx se xxxxxxx x laboratorních xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx zkoušené xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx nebo suspendovány xx vhodných rozpouštědlech xxxx vehikulech a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx podávány přímo xxxx xxxxx být xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by nemělo xxx xxx použitých xxxxxxxx dávek toxické xxxxxx x mělo xx xxx xxxxxxxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení podloženo xxxxx x jejich xxxxxxxxxxxxx. Doporučuje se xxxxxxxx zvážit xxxxxxx xxxxx možno xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx by měly xxx souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx zkoušené xxxxx xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x xxxxx dojde x expozici.

Pozitivními kontrolami xx xxxx xxx xxxxx, x nichž xx xxxxx, xx xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx k xxxxxxx XXX xxxxxxxxxxxxxxx nad xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aktivaci xx měly xxx xxxxxxx x xxxxxxx xxxxxxxxxxxx mírnou xxxxxxx (4). Dávky xxxxx xxx xxxxxxx tak, xxx byl xxxxxx xxxxxxxx, xxx aby xxx odečtu xxxxxxx xxxxx najevo kódovaná xxxxxxxxxxxx preparátu. Příklady xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxx odběru

Látka

Číslo XXX

Xxxxx xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 xx 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx doby xxxxxx (12 xx 16 x)

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

53–96–3

200–188–6

Mohou xxx použity xxxx xxxx xxxxx xxx xxxxxxxxx kontrolu. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx látka xxxxxxxx jiným způsobem, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxx xx xxx použit xxxxxxxxxx xxxxx zvířat, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxx odpovědi xx xxxxxxx. Xxxxx xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx tří xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx xxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxx nezbytné xxxxx jedno až xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx xx studií se xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, že neexistuje xxxx pohlavími xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx, nejlépe samců. Xx-xx expozice xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx by být xxxxxxx xxxxxxxxx xx xxxxxxxx odpovídajícího pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xxxx zpravidla xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

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

Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx netoxických dávkách (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Provádí-li xx kvůli neexistenci xxxxxxxx dostupných údajů xxxxxx xxx xxxxxxxx xxxxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx laboratoři, se xxxxxxx druhem, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx xx xxxxxxx x hlavní xxxxxx.

Xxxxxxxx xxxxx xxxx být xxxxxxxxxx xxxx xxxx xxxxx vyvolávající známky xxxxxxxx x xxxxxxx (xxxx. xxxxxxxxxx jádra).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx na základě xxxxx o látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána xxxxxxxxxxxx, xxxxxx xxx úplná xxxxxx nezbytná. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx. Jiné způsoby xxxxxxxx xxxx možné, xxx-xx je xxxxxxxxx. Xxxxxxxx intraperitoneálně xx xxxx xxxxxxxxxxxx, neboť xx játra xxxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx je xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx měla být xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx xxxxx se xxxxxxxxxx x xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx xxxxxx xxxxx. Xxxxxxxxxx dřívější odebrání xxxxxx (xxxxxx dvě xx xxxxx hodiny xx xxxxxxxx) xx xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx použity xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx údajů.

Krátkodobé kultury xxxxxxxxx xxxxx savců xx xxxxxxxxx zakládají xxxxxxx jater xxxxxxxxxxx xx situ x xxxxxx xx, aby xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx vhodném xxxxxxx. Xxxxxxx xxxxx x 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, xxxxxxxx x xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx xxxxxxxxx xxxx by xxxx xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx poté xxxxx xxx inkubovány x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx thymidinu, aby xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("cold chase"). Xxxxx xx poté xxxxxxx, xxxxxx x xxxxxx. Xxx delší xxxxxxxxx xxxx xxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xx autoradiografické xxxxxx, exponují xx x temnu (např. x xxxxxx 7 xx 14 xxx), xxxxxxxx xx, xxxxxx x xxxxxxxxx se xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxxx xxx xx tři preparáty.

1.5.8 Xxxxxxx

Xxxxxxxxx by měly xxxxxxxxx dostatečný xxxxx xxxxxxxxxxxx xxxxxxxxxx buněk, xxx xxxx xxxxxxxxx XXX xxxxxxxxx hodnotu. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxx cytotoxicity (xxxx. xx xxxxxxx, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx izotopem).

Před xxxxxxxxx xxx xx xxxx xxx preparáty kódovány. Xxxxxxxxx se vyšetřuje 100 xxxxx xx xxxxx xxxxx xxxxxxx xx xxxx preparátů; xxxxxxxxx xxxx než 100 xxxxx/xxxxx xx xxxx xxx zdůvodněno. Xxx xxxxxxxx xxx xx jádra v X-xxxx nevyšetřují, ale xxxxx xxxxx v X-xxxx xxxx být xxxxxxxxxx.

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

Počet buněk xx xxxxxxx x xxxxx xxx odpovídajících xxxxxxxx xxxxŭx (xx) x x xxŭxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx xx xx xxxxxxx buď xxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx oblast xxxxxxxxxx, xxxx xxŭxxxxx hodnota xxxx xx xxx xxxxxxx vybraných oblastí x xxxxxxxxx xxxxxxxxx xxxxxxxxx jader. po xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx použity i xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx xx xxx xxxxxxx údaje pro xxxxxxxxxx xxxxxxxxx x xxxxxxx. Xxxxx xx xxxx xxx xxxx xxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX od xxxxxxx XX xx xxx xxx xxxxxxxx xxx xxxxxx xxxxx, xxx xxxxx xxxxx x xxx xxxxxx xxxxx x xxx xxxxx xxxxx xxx odpovídajících xxxxxxxx jádrům (NNG). Xxxxxxxx xxxx xxxxxxxx "xxxxxxxxxx" xxxxx, xxxx xx xxx kritéria xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx xxxxxxxxxx a xxxxxxxx na xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx být xxxxxxx, měly xx xxx xxxxxxxxxxx xxxxx xxxxxxx x odůvodněny xxxx provedením xxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx pozitivní nebo xxxxxxxxx odpověď xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX leží xxx xxxxxxxx úrovní, xxxxx xx xxxxxxxxxx xx xxxxxxx dosavadních údajů xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX je xxxxxxxx xxxxx než xxxxxxx xxx souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX xxxx xx xxxxxxxxx prahové xxxxxxx xxxx pod xx;

xxxx

xx)

xxxxxxx NNG není xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx.

Xxxx xx xxx xxxxxxxxx biologická xxxxxxxxx xxxxx, xx. měly xx být xxxxx x úvahu xxxxxxxxx, xxxx jsou xxxxxxxxxxx xxxxxx, xxxxx dávky x xxxxxxxx x xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx xxxx neměla xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx bez xxxxxx xx xx, kolikrát xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx XXX v xxxxxxxxx xxxxxxx xxxxx xx xxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxx xxxxx in vivo xxxxxxxxx XXX, které xxx xxxxxxx neplánovanou xxxxxxxx DNA xx xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s jakou xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx. xx xxxxxx xxxxx (např. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx rozpětí xxxxxxx xxxxxxxxx, střední xxxxxxx x směrodatné xxxxxxxx xxx každou xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx o xxxxxxxx zkoušené látky,

- xxxxx x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- popřípadě xxxxxx xxxxxxx, zda xx zkoušená látka xxxxxxx do xxxxxxxx xxxxx xxxx do xxxxxx xxxxx,

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

- podrobné údaje x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxx,

- použitá xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx a xxxxx xxx odpovídajících cytoplasmě, x čistý xxxxx xxx, jednotlivě xxx xxxxxxxxx, zvířata x xxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné statistické xxxxxxxxx,

- známky toxicity,

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

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

- xxxxx xxxxx "xxxxxxxxxxxx" xxxxx, xx-xx stanoven,

- xxxxx xxxxx x S-fázi, xx-xx xxxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Xxxxxxxxxxx, X. E., Xxxxx, X., Xxxxxxxx, E., Xxxxxxxx, X., Xxxxxxxx, X., Probst, X., Xxxxxxxx, X. (1987), X Xxxxxxxx xxx Xxxxx for xxx Xx xxxx Xxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Mutatation Xxx., 189, 123-133.

3) Kennelly, X. X., Xxxxxx, X., Ashby, J., Xxxxxxx, X. A., Xxxxxxxxx, B., Xxxxxxx, X. X., Dean, X. X., Xxxxxxxx, X. de X. (1993), In xxxx Xxx Xxxxx XXX Xxxxx, xx: Xxxxxxxx X. X., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Testing. Xxxxxx. Part II xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Dean, X. X., Xxxxxx, X., Xxxxxxxxx. X., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Furihata, X., Xxxxxxx, T., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx XXX Xxxxx In vitro xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

5) Fautz, X., Xxxxxxx, X., Efstathiou, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Xxxxxxxxxx of xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Viability xxx xxx Xxxxxxxxxx xx Xxxxxxx Isolated Xxx Xxxxxxxxxxx Xxxx xxx the In xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Res., 291, 21-27.

6) Xxxxxxxx, J. X., Tyson, X. X., Xxxxxxxxxxx, B. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xx xxx Xx xxxx/Xx xxxxx Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxx.Xxxxxxx. 4, 553-562."


XXXXXXX 5

OBECNÉ POŽADAVKY XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX XXXXX X XXXXXXXXX

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


XXXXXXX 6

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PŘÍLOHA XX

XXXX X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx ustanovení xx. 22 xxxx. 1 xxxx. x) xxxx xxxxxxxx, xxxx xxx obaly o xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, x xxxxx xx spojeno riziko xxx xxxxxxxxxx (Xx; X 65) x xxxxx xxxx klasifikovány x označeny xxxxx xxxx 3.2.3 přílohy XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx na xxx xx formě aerosolů xxxx x xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx otevření xxxxx.

1. Xxxxxxxxx uzavíratelné xxxxx

Xxxxxxx xxxxxx xxxxx otevření xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx splňovat xxxxxxxxx xxxxx XXX 8317 (xxxxxx ze xxx 1. července 1989) "Xxxxx xxxxxx xxxxx — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxx xxxxxxxx" xxxxxxxx Mezinárodní xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx xxxxx použité xx xxxxxxxxx neuzavíratelných xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx CEN XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Obaly xxxxxx dětem — Xxxxxxxxx a xxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx výrobků" xxxxxxxx Xxxxxxxxx xxxxxxx xxx normalizaci (CEN).

3. Xxxxxxxx

1. Prokázání shody x výše uvedenými xxxxxxx xxxxx xxxxxxxxxx xxxxx laboratoře, xxxxx xxxxxxx xxxxxxxx normy xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx xxxx xx xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx xx xxxxxxx xxxxxx k xxxxxx bez pomoci xxxxxxxx, nemusí xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx případech a xxxxx xxxxxxxx xxxxxxxxx xxxxxx x pochybám x xxxxxxxxxxx xxxxxxx xxx dítě, xxxx xxxxxxxxxxxx xxxxx požadovat, xxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx xx xxx předložila xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx odst. 3 xxxx 1 xxxxxxxxxxxx, xx buď

- xxx xxxxxxx xx xxxxxx, xx xxx není xxxxxxxx xxxxxxx xxxxx xxxx uvedených xxxxx XXX a CEN,

nebo

- xx xxxxxx xxx xxxxxxx x xxx xxxxxxx vyhovujícím xxxxx xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx xxxxxxxxxxx xxx xxxxxxxxxx výstrahy xxxx xxx x xxxxxxx x xxxxxx XX XXX 11683 (xxxxxx x roku 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx — Xxxxxxxxx".

"