Animace načítání

Stránka se připravuje...


Na co čekáte? Nečekejte už ani minutu.
Získejte přístup na tento text ještě dnes. Kontaktujte nás a my Vám obratem uděláme nabídku pro Vás přímo na míru.

Xxxxxxxx Komise 2000/32/XX

xx xxx 19. května 2000,

xxxxxx xx xx xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx směrnice Xxxx 67/548/XXX x xxxxxxxxxx xxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x označování nebezpečných xxxxx [1]

(Xxxx s xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x ohledem xx Smlouvu x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx xxxxxxxx Xxxx 67/548/XXX ze xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx týkajících se xxxxxxxxxxx, xxxxxx x xxxxxxxxxx nebezpečných látek [2], xxxxxxxxx pozměněnou xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Rady 1999/33/XX [3], a xxxxxxx xx článek 28 xxxxxxx xxxxxxxx,

xxxxxxxx k xxxxx xxxxxxx:

(1) Xxxxxxx X směrnice 67/548/EHS xxxxxxxx seznam xxxxxxxxxxxx xxxxx xxxxxxxx s xxxxxxxxxx xxxxx x xxxxxxxxxxx a xxxxxxxxxx xxxxx látky. Xxxxxxxx xxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxx, že xx měl xxx xxxxxx xxxxxxxxxxxx látek x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx určitých xxxxxx xxxxxxxxx a tabulky X x příloze X.

(2) Příloha XXX xxxxxxxx 67/548/XXX obsahuje xxxxxx xxx xxxxxxxxxxx xxxxxx xxxxxxxxxx rizik xxxxxxxxx s xxxxxxxxxxxx xxxxxxx a přípravky. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx x bezpečnostními xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxx a xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/XXX xxxxxxxx xxxxx xx xxxxxxxxxxx x k xxxxxxxxxx xxxxxxxxxxxx xxxxx a xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, XX x XX.

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

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx předpisy xxxxxxxx xx xxxxxxx xxxxxxxx proti otevření xxxxx. Tyto xxxxxxxx xx xxxx být xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx xxxxxxxx rozšířit xxxxxx, kde xx xxxxxxx odolné xxxxx xxxxxxxx dětmi používají.

(5) Xxxxxxxx xxxx xxxxxxxx xxxx x xxxxxxx xx stanoviskem Výboru xxx xxxxxxxxxxxx technickému xxxxxxx směrnic pro xxxxxxxxxx xxxxxxxxxxx překážek xxxxxxx xx xxxxx xxxxxxxxxxxx látek x xxxxxxxxx,

XXXXXXX XXXX XXXXXXXX:

Xxxxxx 1

Xxxxxxxx 67/548/EHS xx xxxx takto:

1. Xxxxxxx X xx xxxx takto:

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

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

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

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

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

3. Xxxxxxx XX xx xxxx xxxxx:

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

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

4. Xxxx B xxxxxxx X xx xxxx xxxxx:

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

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

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

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

e) kapitola X.17 xx nahrazuje xxxxxx x příloze 4X této xxxxxxxx;

x) xxxxxxxx B.23 xx xxxxxxxxx xxxxxx x xxxxxxx 4X této xxxxxxxx. Xxxxx kapitoly X.23 xx vysvětlivce xx mění odpovídajícím xxxxxxxx;

x) xxxxxx xx xxxx x příloze 4X této směrnice.

5. Xxxxxxx se čtvrtá xxxxxxx xxxxxxxx xxxxx x xxxxx X xxxxxxx X.

6. Xxxxxxxxxxxx xxxxx v příloze XX se nahrazují xxxxx x xxxxxxx 5 xxxx směrnice.

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

Xxxxxx 2

1. Členské xxxxx uvedou x xxxxxxxx xxxxxx x xxxxxxx předpisy nezbytné xxx dosažení xxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x nich uvědomí Xxxxxx.

Xxxx xxxxxxxx přijaté xxxxxxxxx státy xxxx xxxxxxxxx xxxxx xx xxxx směrnici nebo xxxx xxxxxx odkaz xxx učiněn xxx xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx členské xxxxx.

2. Xxxxxxx xxxxx xxxxx Xxxxxx xxxxx hlavních xxxxxxxxxx vnitrostátních xxxxxxxx xxxxxxxx, které přijmou x xxxxxxx xxxxxxxxxx xxxx xxxxxxxx, x xxxxxxxxxx xxxxxxx xxxx xxxxxxxx a přijatými xxxxxxxxxxxxxx xxxxxxxxxxxx.

Článek 3

Tato xxxxxxxx xxxxxxxx x xxxxxxxx xxxxxx xxxx po xxxxxxxxx x Xxxxxxx xxxxxxxx Evropských xxxxxxxxxxxx.

Xxxxxx 4

Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

X Xxxxxxx dne 19. května 2000.

Xx Xxxxxx

Xxxxxx Wallström

členka Komise


[1] Přijato xx xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Xx. věst. 196, 16.8.1967, x. 1.

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


PŘÍLOHA 1A

PŘEDMLUVA X XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


PŘÍLOHA 1B

"TABULKA X

X

Xxxxxx

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

18

Xx

Xxxxx

Xxxxx

Xxxxx

Αργό

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"


PŘÍLOHA 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx k látkám

Číslo XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační limity

Poznámky x xxxxxxxxxx

006–011–00–7

xxxxxxxx (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. kat. 3; X40 Xx; X22 X; R50

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) natrium-N-methyldithiokarbamát

205–293–0

137–42–8

Xn; X22 X31 C; X34 X43 N; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

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

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

006–016–00–4

xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát

204–043–8

114–26–1

T; X25 N; R50–53

T; X X: 25–50/53 X: (1/2-)37–45–60–61

006–017–00-X

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

204–123–2

116–06–3

X+; X26/28 X; X24 X; R50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 X; X50–53

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

006–019–00–0

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

218–961–1

2303–16–4

Karc. xxx. 3; X40 Xx; X22 N; R50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; X22 X43 X; X50–53

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

006–023–00–2

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

217–991–2

2032–65–7

X; X25 N; X50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xx; 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 N; X50–53

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

006–028–00-X

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

213–546–1

973–21–7

X; X25 X; R50–53

T; X R: 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; X R: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

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

243–433–2

19937–59–8

X; X50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xn; X22 X; X51–53

Xx; X R: 22–51/53 X: (2-)23-61

006–035–00–8

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

245–430–1

23103–98–2

X; X25 X; R50–53

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

006–037–00–9

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

220–113–0

2631–37–0

X; X25 X; X50–53

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

006–038–00–4

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

X

202–388–9

95–06–7

Xxxx. xxx. 2; X45 Xx; X22 X; R50–53

T; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; X22–48/22 R43 X; X50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; X40 Xx; X22 N; X50–53

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

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

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 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 N; R50–53

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

006–047–00–3

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

8065–36–9

X; R24/25 N; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xx; X22 X; X50–53

Xx; N 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; X X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (ISO) 2-isopropylfenyl-N-methylkarbamát

220–114–6

2631–40–5

Xn; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; R28 Xx; X21 N; R50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; R22 X; X51–53

Xx; N 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 S: (2-)61

006–069–00–3

xxxxxxxxx-xxxxxx (ISO) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx

245–740–7

23564–05–8

Xxxx. xxx. 3; R40 X; R50–53

Xn; N 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. kat. 3; X40 X; X50–53

Xx; N X: 40–50/53 X: (2-)36/37–60–61

006–088–00–7

benfurakarb (XXX) ethyl-N -[({[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]karbonyl}methylamino)sulfanyl]-N-isopropyl-β-alaninát(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)-N-({[2-(ethoxykarbonyl)ethyl]isopropylamino}sulfanyl)-N-methylkarbamát

82560–54–1

T; X23/25 X; X50–53

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

007–012–00–5

X,X-xxxxxxxxxxxxxxxx 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

X; X11 Karc. xxx. 2; X45 T; X23/25 C; R34 X; R51–53

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

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-xxxxxxxxxxxxxxxx

X

540–73–8

Xxxx. xxx. 2; X45 X; R23/24/25 X; X51–53

X; N X: 45–23/24/25–51/53 S: 53–45–61

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

009–003–00–1

kyselina fluorovodíková … %

X

231–634–8

7664–39–3

X+; R26/27/28 X; R35

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

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

015–039–00–9

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

201–676–1

86–50–0

T+; X26/28 X; X24 R43 X; R50–53

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

015–048–00–8

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

200–231–9

55–38–9

Xxxx. xxx. 3; X40 X; X23–48/25 Xx; X21/22 X; R50–53

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

015–056–00–1

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

220–147–6

2642–71–9

X+; R28 X; X24 X; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; R23/25 Xx; X21 N; R50–53

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

016–013–00-X

chlorid sirnatý

234–129–0

10545–99–0

R14 X; R34 X; X50

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

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

016–014–00–5

chlorid xxxxxxxx

13451–08–6

X14 X; R34 X; X50

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

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 X; X34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

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

016–024–00-X

xxxxxxxx (ISO) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 X; X50–53

Xx; N X: 22–50/53 S: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

X43

Xx X: 43 S: (2-)22–24–37

022–001–00–5

chlorid xxxxxxxxxx

231–441–9

7550–45–0

X14 X; R34

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

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

030–004–00–8

xxxxxxxxxxxxx [1] xxxxxxxxxxxx [2]

208–884–1 [1] 209–161–3 [2]

544–97–8 [1] 557–20–0 [2]

X14 X; X17 C; X34 N; X50–53

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

050–002–00–0

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

236–049–1

13121–70–5

Xx; X20/21/22 X; R50–53

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

050–012–00–5

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

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

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

Xx; X20/21/22 X; X50–53

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

X ≥ 1 %: Xn; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

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

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

082–009–00–X

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

215–693–7

1344–37–2

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

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

1

082–010–00–5

červeň (xxxxxxx-xxxxxxxxxx-xxxxx olovnatý) XX Xxxxxxx Red 104 (XX 77605) XX xxxxxxxxxx červeň 104 (XX 77605)

235–759–9

12656–85–8

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

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

1

601–024–00-X

xxxxx [1] xxxxxxxxxxxx [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

R10 Xx; R65 Xx; X37 X; R51–53

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

4

601–032–00–3

xxxxx[x]xxxxx benzo[def]chrysen

200–028–5

50–32–8

Karc. xxx.2; X45 Muta. xxx. 2; R46 Xxxx. kat. 2; X60–61 X; X50–53

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

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. kat.2; X45 N; R50–53

T; X R: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx p-dichlorbenzen

203–400–5

106–46–7

Xi; X36 X; X50–53

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

602–054–00–6

3-jodprop-1-en allyljodid

209–130–4

556–56–9

R10 X; R34

C R: 10-34 X: (1/2-)7–26–45

603–076–00–9

xxx-2-xx-1,4-xxxx

203–788–6

110–65–6

X; X23/25 Xx; R21–48/22 X; X34

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

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

603–091–00–0

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

402–470–6

87172–89–2

X; R8 Xx; X22 Xx; X36

X; Xx R: 8–22–36 X: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xx; X20 X; X51–53

Xx; X X: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 X52–53

Xx X:36–52/53 X: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx isopropanol

200–661–7

67–63–0

F; X11 Xx; R36 R67

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

604–020–00–6

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

201–993–5

90–43–7

Xi; X36/37/38 X; X50

Xx; N X: 36/37/38–50 X: (2-)22-61

604–021–00–1

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

205–055–6

132–27–4

Xx; R22 Xx; X37/38–41 X; X50

Xx; X X: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

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

401–720–1

6807–17–6

Repr. xxx. 2; X60 Xx; X36 N; X50–53

X; 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; X22 Xx; X38–41 X; X50–53

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

604–043–00–1

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

203–083–3

103–16–2

Xi; X36 X43

Xx 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 X43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

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

Xx X: 20–36/38–40–43 S: (2-)36/37

X ≥ 10 %: Xx; R20–36/38–40–43 1 % ≤ X &xx; 10 %: Xx; X40–43

606–016–00-X

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

204–210–5

117–80–6

Xx; X22 Xx; X36/38 X; X50–53

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

606–019–00–6

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

205–601–3

143–50–0

Karc. xxx. 3; R40 X; X24/25 N; R50–53

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

606–034–00–8

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

chloridazon (XXX) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx xxxxxxx

216–920–2

1698–60–8

X43 X; X50–53

Xx; N R: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Xxxx. xxx. 3; X62 Xx; R20/21/22–48/22 Xx; X36 X43 X; X50–53

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

606–037–00–4

xxxxxxxxxxx (XXX) 1-(4-xxxxxxxxxxx)- 3,3-dimethyl-1-(1,2,4-triazol-1-yl)butan-2-on

256–103–8

43121–43–3

Xn; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xx; X36 X; X50–53

Xx; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; R22 Xx; X41 X52–53

Xx; X X: 22–41–52/53 X: (2-)26-61

607–057–00–6

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

201–378–1

81–82–3

Xx; X48/22 R52–53

Xn X:48/22–52/53 X: (2-)37-61

607–058–00–1

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

204–195–5

117–52–2

X; X25–48/25 R52–53

T X:25–48/25–52/53 X: (1/2-)37–45–61

607–079–00–6

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

4234–79–1

X; X24 Xn; X22 N; X51–53

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

607–097–00–4

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

209–008–0

552–30–7

Xi; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx xxxxxxxx kyselina

203–677–2

109–52–4

C; X34 R52–53

C X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xx; 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; X36/38 R52–53

Xi X:36/38–52/53 X: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xx; X22 Xx; R38 N; X50–53

Xx; X X: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

sodná xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; X25 Xx; X38 X; X50

X; X X: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

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

208–110–2

510–15–6

Xn; X22 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

607–176–00–3

Xxxx: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 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 S: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; X51–53

Xx; 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

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

403–320–2

67567–23–1

X; X2 X; R7 X10 X; R51–53

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

607–217–00–5

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

403–960–2

R43 X53

Xx X: 43-53 S: (2-)24–37–61

607–243–00–7

xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] 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 Natrium-N-(1-naftyl)ftalamát

205–073–4

132–67–2

Xn; X22

Xx X: 22 S: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xx; X36/37/38 X43 X; X51–53

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

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

607–252–00–6

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

415–130–7

91465–08–6

X+; X26 X; X25 Xx; X21 X; R50–53

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

607–255–00–2

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

69377–81–7

R52–53

R: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X E

203–466–5

107–13–1

F; Xxx Xxxx. kat. 2; X45 X; X23/24/25 Xx; X37/38–41 X43 N; R51–53

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

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 X; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. kat. 2; X61 T+; X28 X; X24 X44 X; X50–53

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

609–040–00–9

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

X

217–406–0

1836–75–5

Xxxx. xxx. 2; X45 Xxxx. kat. 2; X61 Xx; X22 X; R50–53

T; X X: 45–61–22–50/53 S: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 X43 N; X50–53

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

611–008–00–4

4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. kat. 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 xxxxxxxxx

403–650–7

117409–78–6

X; X2 X; R51–53

E; X X: 2–51/53 X: (2-)35-61

611–031–00-X

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

209–321–2

569–61–9

Xxxx. xxx. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-xxxxxxxxxxxxx x-xxxxxxxx

X

201–963–1

90–04–0

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

T X: 45–23/24/25 X: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. kat. 1; X45 Xx; X22 X; X50–53

X; X X: 45–22–50/53 S: 53–45–60–61

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

612–051–00–1

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

X

202–974–4

101–77–9

Xxxx. xxx. 2; X45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; X48/20/21/22 X43 X; R51–53

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

612–081–00–5

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

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; R45 Xx; R22 X; X51–53

X; X X: 45–22–51/53 X: 53–45–61

612–099–00–3

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

X

202–453–1

95–80–7

Xxxx. kat. 2; X45 T; R25 Xx; R21 Xx; X36 R43 N; X51–53

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

612–105–00–4

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

205–411–0

140–31–8

Xx; X21/22 X; X34 X43 R52–53

C 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 Xx; R21/22 X43 N; X51–53

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

612–125–00–3

2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,4-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,4-xxxxxx 2,5-xxxxxxxxxxxx

202–442–1

95–70–5

X; X25 Xx; X20/21 X43 X; X51–53

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

612–144–00–7

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

62924–70–3

Xx; X36/38 R4 3 N; R50–53

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

612–151–00–5

diaminotoluen xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx methylbenzendiamin

E

246–910–3

25376–45–8

Karc. xxx. 2; X45 X; X25 Xn; X20/21 Xx; R36 X43 X; R51–53

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

613–018–00–4

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

7411–47–4

Xx; X22 Xi; R36/37/38 X52–53

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

613–031–00–5

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

201–782–8

87–90–1

O; X8 Xx; X22 R31 Xx; R36/37 X; X50–53

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

613–038–00–3

6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-fenyl-1,3,5-triazin-2,4-diamin xxxxxxxxxxxxx

202–095–6

91–76–9

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–042–00–5

imazalil (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 H-imidazol

252–615–0

35554–44–0

Xn; X20/22 X; R41 X; R50–53

Xn; N X: 20/22–41–50/53 S: (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 X; R50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 N; X50–53

Xx; X R: 22–50/53 S: (2-)60-61

613–091–00–2

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

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; X22 Xx; X36/37/38 X52–53

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

613–098–00–0

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

403–700–8

2687–94–7

C; X34 X; R51–53

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

613–130–00–3

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

79983–71–4

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–131–00–9

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

57369–32–1

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

Xxxx. xxx. 3; X63 Xx; X22 Xx; X36 N; R51–53

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

613–137–00–1

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

242–505–0

18691–97–9

X; R50–53

N X: 50/53 X: 60-61

613–139–00–2

metsulfuron-methyl 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 S: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; X25 X; R51–53

T+; X 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+; X26/28 X52–53

X+ X:26/28–52/53 S: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; R26/28 X52–53

X+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

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

X

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

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

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

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

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

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 X31 X; X34 X42

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

616–034–00-X

xxxxxxxxxxxx (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 N; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; X7 Xx; X22 C; X34 X; X50–53

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

X325 %: X; X22–34 10 % ≤ X &xx; 25 %: C; 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 xxxxxxxxxxxxxx

201–279–3

80–43–3

X; R7 Xx; R36/38 X; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xi; X36 X43

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

650–007–00–3

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

228–200–5

6164–98–3

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

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

650–008–00–9

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

227–197–8

5707–69–7

X; X25 X; X50–53

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

650–009–00–4

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

243–269–1

19750–95–9

Xxxx. xxx. 3; X40 Xx; X22 X; X50–53

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

650–033–00–5

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

66230–04–4

X; X23/25 R43 N; X50–53

X; 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-xxxxxxxxxxx)xxxxxx-1-xxxxxxxx]-3-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxx

82097–50–5

X; R50–53

N X: 50/53 X: 60-61


PŘÍLOHA 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x látkám

Číslo XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x přípravkům

006–090–00–8

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

408–010–0

88558–41–2

Xn; X20 Xx; R41 X52–53

Xx X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

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

406–490–6

X; X51–53

X R: 51/53 X: 61

015–164–00–9

xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

Xxxx: S, X, X', X''-xxxxxxxxxx-4,4'-xxxxxxxxxxxxx(xxxxxxxxxxxxxx)-xxx(xxxxxxxxxxxxxxxx) x difenyl[4-(fenylsulfanyl)fenyl]sulfonium-hexafluorofosfát

404–986–7

Xi; X41 X; X50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[hydroxy(fenyl)fosfinoyl]propanová xxxxxxxx

411–200–6

14657–64–8

Xx; R41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; R50

N X: 50 X: 61

601–051–00–7

4-xxxxxxxx-1-xx

405–980–7

768–56–9

Xx; X38 N; X51–53

Xx; X X: 38–51/53 X: (2-)37-61

602–083–00–4

pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; R48/21/22 R64 X; X50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; R52–53–59

N R: 52/53–59 X: 59-61

603–128–00–0

2-(xxxxxxxxxxxx)xxxxxxxx

405–490–3

613–62–7

X53

X:53 X: 61

603–129–00–6

1-xxxx-xxxxxxxxxxxx-2-xx

406–180–0

57018–52–7

X10 Xi; X41

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

603–130–00–1

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

406–325–8

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)39-61

603–131–00–7

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 S: (2-)26-39

603–132–00–2

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

408–200–3

63187–91–7

Xx; X38–41 R52–53

Xi X:38–41–52/53 X: (2-)26–37/39–61

603–133–00–8

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

408–240–1

Xx; X22 X52–53

Xx X:22–52/53 S: (2-)22–36–61

603–134–00–3

Xxxx: alkyl(C1-C10)-dodecyldifenylethery x xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (dodecyl x xxxxxxxxxx xxxxxxxxxxxx)

410–450–3

X53

X: 53 X: 61

603–135–00–9

bis[2-(2-methoxyethoxy)ethanolato]bis(2,2', 2-nitrilotriethan-1-olato-N,O)titaničitý xxxxxxx

410–500–4

Xx; R41 X; X51–53

Xx; X X: 41–51/53 X: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

X43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

603–137–00-X

Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx 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-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol

403–140–4

103694–68–4

R52–53

R:52/53 X: 61

604–050–00-X

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

216–381–3

1570–64–5

T; X23 C; R 35 X; X50

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

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

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

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

403–800–1

103597–45–1

X53

X:53 X: 61

604–053–00–6

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

410–760–9

157661–93–3

Xi; X38 X43 X; X50–53

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

604–054–00–1

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

412–020–0

X43 R52–53

Xi X:43–52/53 S: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Xxx.3; R40

Xn X: 40 S: (2-)22–36–37

605–027–00–7

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

410–480–7

X43 N; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-pentylcyklohexanon xxxxxxxxxxxxxxxx-1-xx

4–406–670–4

61203–83–6

X; X51–53

X R: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

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

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

N; X50–53

X X: 50/53 X: 60-61

607–273–00–0

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

404–520–2

X52–53

X:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

R43 N; X51–53

Xx; N X: 43–51/53 S: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

R43

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

607–276–00–7

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

405–635–0

Xx; X38–41 N; R50–53

Xi; 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 Xx; X41 X43 X; X51–53

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

607–278–00–8

Xxxx:xxxxx(X7-X9 xxxxxxxxxx x xxxxxxxxxxxx)-3-[3-(2 X - benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty

405–760–0

Xi; X41 R43 X52–53

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

607–279–00–3

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

405–960–8

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xx; X22 Xx; R36 X43

Xx X: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

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

407–000–3

127519–17–9

N; X51–53

X X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 S: 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; X X: 21/22–38–41–43–50/53 X: (2-)26–36/37/39–60–61

607–284–00–0

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–065–0

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

Xxxx:xxxxxx- 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 S: (2-)22–24–37–61

607–287–00–7

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

410–140–8

X52–53

X:52/53 X: 61

607–288–00–2

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

410–160–7

148732–74–5

Xi; X36 X43 R52–53

Xi 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

Směs (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; X38 X43 X; X50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

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

410–640–6

Xi; X38–41 N; X50–53

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

607–293–00-XXxxx:

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

410–650–0

Xx; X41 X43 X; X51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 N; X51–53

Xx; X R: 43–51/53 X: (2-)24–37–61

607–296–00–6

Směs:tetraestery xxxxxxxxxxxxxxxx, xxxxxxxxx xxxxxxxx a 2-xxxxxxxxxxxxx xxxxxxxx

410–830–9

X53

X: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; X41

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

607–298–00–7

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

411–010–3

X43

Xx X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 X43 X; X50–53

Xx; 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, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx komplex, xxxxxxxx xxx; x = 1,2,3 nebo 4, b = 8, 9, 10 xxxx 11, c = 15, 16, 17 nebo 18, x = 22, 23, 24 nebo 25

411–430–7

X43

Xx R: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xi; X38–41 X43 N; X51–53

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

607–302–00–7

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

411–910–6

Xx; X38–41 X43 X; X51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Repr. xxx.3; X62 R52–53

Xn X: 62–52/53 S: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; R50–53

N X: 50/53 X: 60-61

608–024–00–9

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

407–650–8

97460–76–9

R53

R:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

R53

R:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; X3 O; X8 Xxxx. xxx. 2; R45 X; X23/25 X43

X; X X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 X; X34 X43 X; X50–53

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

611–043–00–5

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

402–850–1

Xx X: 41–52/53 S: (2-)26–39–61

611–044–00–0

Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [bis(4-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-terc-butyl-3-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx a[(4(5)-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato) (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 S: 61

611–046–00–1

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

407–590–2

43151–99–1

X; R25 Xn; X48/22 X43 X; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

X53

X: 53 S: 61

611–048–00–2

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

407–900–6

111381–12–5

R53

R: 53 S: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; R48/22 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 komplex, xxxxx sůl

400–720–9

R52–53

R: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; R41 X; X50–53

Xx; N R: 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 Xx; X41 X43 X; X51–53

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

612–158–00–3

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

410–820–4

X53

X: 53 X: 61

612–159–00–9

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

410–880–1

Xx; X22 C; X34 X; X50–53

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

613–149–00–7

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

405–700–3

96489–71–3

X; X23/25 X; 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-xxxxx-3-X-xxxxx-5-X-xxxxxx-β-X-xxxxx-xxxxxxxxxxxxxx)-5-xxxxxxxxxxxxxxx-2(1X), 4(3 X)-xxxx

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 N; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-trichlorpyridin

407–270–2

16063–70–0

R52–53

R:52/53 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx X: 22 X: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 X52–53

Xx X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

X43 X; X51–53

Xx; N R: 43–51/53 X: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; X22–48/22 Xx; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

2,3-dichlor-5-(trifluormethyl)pyridin

410–340–5

69045–84–7

Xn; X20/22 Xx; X41 X43 X; R51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; X25 Xx; X20 N; X50–53

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

613–160–00–7

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

411–000–9

125224–62–6

R43

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

615–022–00–1

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

410–550–7

79277–18–2

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

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

615–023–00–7

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

410–900–9

83056–32–0

X10 X14 Xxxx. kat. 3; X40 Xx; X20–48/22 Xi; X41 X42

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

616–044–00–4

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

402–510–2

X; X51–53

X X: 51/53 X: 61

616–045–00-X

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

405–190–2

122371–93–1

X43 X53

Xx X: 43-53 S: (2-)22–24–37–61

616–046–00–5

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

406–390–2

N; X50–53

X X: 50/53 X: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - tetraalkyl(C16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x X, N′,N″,N′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

X43

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

616–048–00–6

3'-(trifluormethyl)isobutyranilid

406–740–4

1939–27–1

Xn; 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 X; 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'-bis(4-methylfenyl)-1,1'-(2-methyl-1,3-fenylen)dimočovina 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; X X: 2–7–50/53 X: (2-)7–14–36/37/39–47–60–61

650–032–00-X

xxxxxxxxxxxx (XXX) (2X, 3R)-, (2 S, 3 X)-, (2 R, 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 Xx; X22 X; R50–53

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


XXXXXXX 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


PŘÍLOHA 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx na chromozomové xxxxxxx u xxxxx xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Rozlišují xx dva xxxx xxxxxxxxxxxx xxxxxxx: chromozomové x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx může znamenat, xx chemická látka xx schopnost xxxxxxxxx xxxxxxxxx aberace. Tato xxxxxx xxxx xxxx xxxxxx ke xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x tomuto xxxxx rutinně xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x xxxxxxxx xxxxx důkazů x xxx, že xxxxxxxxxxxx xxxxxx x x xxxx xxxxxxxxxxx jevy xxxxxxxxxxx xxxxx v xxxxxxxxxx x v xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx u člověka x u xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxx být xxxxxxx stabilizované xxxxxxx xxxxx, xxxxxxx xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Použité xxxxx xxxx xxxxxxx na xxxxxxx xxxxxxxxxx růstu x kultuře, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx vyžadují xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx systém xxxxxx xxxxx napodobit xxxxxxxx xx vivo x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, které xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx x xxx xxxxx xxxxxx xX, osmolality nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Tato xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx mutagenů x karcinogenů xxx xxxxx. Mnoho xxxxxxxxx, xxx xxx je xxxx xxxxxxx xxxxxxxxx, xxxx xxx savce xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx není absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx chemické xxxxx x xxxxxxxxx xxxxxx x xxx, že xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, neboť zřejmě xxxxxx jinými xxxxxxxxxx xxx xxxxxx xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

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

Chromozomová xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx xxxx zlomu x spojení xxxx xxxxxxxxx v xxxxxx xxxxx.

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

Gap : xxxxxxxxxxxx xxxx menší xxx xxxxx jedné xxxxxxxxxx a x xxxxxxxxx odchylkou chromatid.

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

Numerická xxxxxxx : xxxxxxxx počtu xxxxxxxxxx xx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx xxxx xxxxx.

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx pozorovatelné změny xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx metafáze; jeví xx jako xxxxxx x fragmenty, xxxxxxxxxxxxxxxxxx xxxx interchromozomální xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce, x xx x metabolickou xxxxxxxx x xxx xx. X xxxxxx xxxxxxxxxxx xxxxxxxxxxx po xxxxxxxx xxxxx se xx xxxxxxxxx xxxxxx xxxxx látka xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx kolchicin), xxxxxxx xx xxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx se zjistí xxxxxxxxxxxxxx xxxxxxxxxxx buněk.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx různé xxxxxxx xxxxx, xxxxx xxxx xxxxxxxx buněčné xxxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. xxxxxxxxxxx xxxxxx xxxxxxxx, lymfocyty xxxxxxxxx xxxx xxxxxxx xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x xxxxx: xxxxx se xxxxxxx x xxxxxxxxx xxxxxx, xxxxxx xx do xxxxxxxxxxxx média x xxxxxx xxxxxxx, aby xxxxxxxxx konfluence xxxx xxxxxxxxx, x inkubují xx při 37 °X.

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

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by měly xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx metabolickou xxxxxxxx x bez xx. Xxxxxxxxxx používaným xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx enzymy, xxxx je Xxxxxxx 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 a 12).

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

Xxxx výsledků xxxxxx, xxxxxx přípravy xxxxxxxxx xxxxxxxxxxxxxx buněčných xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, poskytuje xxxxxxxx pro xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx linií xx xxxx xxx xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx P450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx látka/příprava

Pevné xxxxxxxx xxxxx by xxxx být před xxxxxxxx xx buňky xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx vehikulech a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky mohou xxx přidány xxxxx x testovacím xxxxxxxx x/xxxx mohou být xxxx xxxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx látky, xxxxx xxxxx x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx xxxxxx, a xxxx xx xxx xxxxxxxxxx x xxxxxxxx buněk x s xxxxxxxxx X9. Jsou-li použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Expoziční koncentrace

Mezi xxxxxxxx, xxxxx mají xxx xxxxxxxxxx při xxxxxxxxx nejvyšší xxxxxxxxxxx, xxxxx cytotoxicita, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x změny xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x bez xx x xxxxxxx experimentu xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné integrity x růstu, jako xxxx xxxxxx xxxxxxxxxx, xxxxx životaschopných xxxxx xxxx xxxxxxxxx xxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx by xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx dané xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx xxxxxxx xxxxxxx, xx xx xx koncentrace xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. X xxxxxxxx xxxxxxx xx měla xxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx snížení xxxxxx xxxxxxxxxx, počtu xxxxx xxxx xxxxxxxxxxx xxxxxx (xxx o xxxx xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx nepřímým xxxxxxxx xxxxxxxxxxxxx xxxx cytostatických xxxxxx x xxxxxx xx době, která xxxxxxxx xx expozice. Xxxxxxxxx xxxxx je xxxx xxxxxxxxxx u xxxxxxxxxxx xxxxxx, x xxxxx xxxxx xxx xxxx xxxxxx stanovení xxxxxxxx xxxxxxx x xxxxxxxxxxx. Informace x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), xxxxx xxx xxxxxxx xxxx xxxxxxxxx informace. V xxxxxxx XXX xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, z xxx xxxxx usoudit xx xxxxxxxxx zpožděných xxxxxxxxxxx, x x xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx doby xxxx xxx za xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

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

X xxxxxxx relativně xxxxxxxxxxxxx látek, které xxxxxx xxxxxxx při xxxxxxxxxxxxx nižších, xxx xx jejich rozpustnost, xx xxxx xxx xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, xxx xx xxx mezí xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx doby aplikace. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx se xxxxxxxx xxxxx při xxxxxxx koncentracích, xxx xx xxxxxxxxxxx) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, při nichž xxxxxxx xx xxxxxxx. Xxxx xxx xxxxxxxx xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx expozice, xxxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxxx xx může x průběhu xxxxxxxx xxxxx v důsledku xxxxxxxxxxx buněk, xxxx X9 xxx. Nerozpustnost xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při vyšetřování.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx vehikula). Xxx xxxxxxx metabolické xxxxxxxx xx xxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx látka, xxxxx x xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx.

X xxxxxxxxx xxxxxxxx xx xxx xxx xxxxxx xxxxx xxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x detekovatelný xxxxxx xxx xxxxxx, čímž xx xxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx by měly xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale aby xxx odečtu nevyšla xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

Xxxx metabolické xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx podle EINECS

Bez xxxxxx metabolické xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxx xxxxxxxxx xxxxxxxx xxxxx být xxxxxxx x jiné xxxxxx látky. Xxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxx xxxxx xxxxx x xxxxx xxxxxxx chemických xxxxx ze stejné xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx by xxxx xxx použity xxxxxxxxx xxxxxxxx skládající xx xx xxxxxxxxx rozpouštědla xxxx vehikula x xxxxxxxxxxx xxxxx a xxxxxxxxxx stejným způsobem xxxx xxxxxxx. Xxxxx xxxx xx měly xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx údaje prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx zkoušené látce xxx za xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx lymfocytů xx xxxx být zahájena xxx 48 xxxxx xx mitogenní xxxxxxxxx.

1.4.3.2 Xxx xxxxxx koncentraci xx xxxx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx pro xxxxxxxxx kontrolu nebo xxxxxxxx rozpouštědla. Jestliže xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxx xxxxxx, xxxx být přípustné xxxxxxx xxxxxx xxxxxxx.

Xxxxxx xxxx xxxxxx látky xx xxxx být xxxxxxxx vhodnými xxxxxxxx, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx nádobách (15, 16).

1.4.3.3 Xxxx xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx by měly xxx xxxxx vystaveny xxxxxxxx xxxxx, jak x xxxxxxxxxxxx xxxxxxxx, xxx bez xx, xx xxxx 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx normální xxxxx buněčného xxxxx (12). Xxxxxxxx xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, tak bez xxxxxxxx, xxx by xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx xxx aktivace x nepřetržitou xxxxxxxx xx xx odběru x xxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného cyklu. Xxxxxx xxxxxxxx xxxxx xxx xxxxx detekovat xxx xxxxxx aplikace xxxx xxxxxx xxxxxxx xxx 1,5násobek xxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx potvrzeny xxxxxx xx xxxxxxx. X xxxxxxxxx, kdy xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx výsledků xx xxxxxxxx, xx mělo xxx xxxxxx zdůvodnění.

1.4.3.4 Xxxxxxxx xxxxxxxxx pro xxxxxxx chromozomů

Do xxxxxxx xxxxxxx xx xxxxxxx 1-3 hodiny před xxxxxxxxx xxxxx Xxxxxxxx® xxxx kolchicin. Xxx xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx se xxxxx buněčná kultura xxxxxx a zpracovává xxxxxx. Xxxxxxxx xxxxxxxxx xxx analýzu xxxxxxxxxx xxxxxxxx hypotonizaci xxxxx, xxxxxx x obarvení xxxxx.

1.4.3.5 Analýza

Všechny xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx fixaci xxxxx xxxxxxx xx xxxxx části xxxxx x metafázi a xx xxxxxx chromozomů, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxx xxxxxxx xxxxxxx ± 2 xxx xxxxxxx xxxx buněk. Xx xxxxxx xxxxxxxxxxx a xxxxxxxx by mělo xxx xxxxxxxxx xxxxxxx 200 xxxxx rozprostřených xxxxxxxx, xxxxxxxx rovnoměrně xxxxxxxxxxx mezi xxxxxxxxxx xxxxxxx. Tento počet xxx snížit, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx.

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

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx x mělo xx tedy být xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx x experimentální xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx a četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx a xxxxxxx xx, ale xxxxxxxxxx xx do celkové xxxxxxxx xxxxxxx.

Xxxx xx xxx xxxx zaznamenána xxxxxxxx, xxxxx byla xxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxxxx v xxxxxxxx experimentech s xxxxxxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx byla xxxxxxxxxxx x bodu 1.4.3.3. Xxxxx xxxxxxxxx studie x xxxxx xxxxxxxx xxxxxx posuzovaných xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx by xxxxx xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx xxxxx x chromozomovými xxxxxxxxx x závislosti xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx. Xxxxxxxx by xxxx xxx xxxxxxx biologická xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (3, 13). Xxxxxxxxxxx významnost xx xxxxxx xxx xxxxxxx určujícím faktorem xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxx xxxxxxxxxxx buněk xxxx znamenat, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx a indukovat xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx buněk x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx znamenat, xx xxxxxxxx látka má xxxxxxxxx xxxxxxxx progresi xxxxxxxxx cyklu (17, 18).

Xxxxxxxx xxxxx, jejíž xxxxxxxx xxxxxxxxx výše xxxxxxx kritéria, xx x tomto xxxxxxx xxxxxxxx za xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x xxxxxxxxxxxxx somatických xxxxxxx savců xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx látka xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx somatických xxxxxxx savců xxxxxxxxxx xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxx:

- xxx x zdroj xxxxx,

- xxxxxxxxxx xxxxxxxxx a xxxxxxxx použitého xxxx xxxxx,

- xxxxxxxxx nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx cyklu,

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

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx kultury,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx podmínky:

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

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

- složení xxxxx, xxxxxxxx koncentrace XX2,

- koncentrace zkoušené xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx doba,

- délka xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity, xxxx. xxxxxx xxxxxxxxxx, xxxxx x xxxxxxxx xxxxx, počty xxxxx, xxxxxxxxx xxxxx,

- xxxxxx xxxxxxx,

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

- definice xxxxxxx, xxxxxx xxxx,

- xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x xxxx xxxxxxx xxxxxx xxx xxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxx, pokud xxxx xxxxxxxxxx,

- podle xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Xxxxxxxx, M. Xx., Xxxxxx, X. (1985), Xxx Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Xxxxxxx Xxxxxxx Lung (XXX) Xxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Progress xx Mutatation Research, Xxx. 5, Xxxxx, X. xx al., (xxx) Xxxxxxxx Science Xxxxxxxxxx, Amsterdam-New Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, S. X., Xxxxxxxxx, M. X., Reuben, X., Xxxxxx, X., Xxxxx, X., Cannon, X., Xxxxx, X. X., Xxxxxxxx, X., Ahmed, X., Xxx, X., Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X. X., Anderson, X., Zeiger E. (1978), Xxxxxxxxxx aberration xxx xxxxxx chromatic xxxxxxxxx xx Chinese xxxxxxx xxxxx xxxxx: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

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

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

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

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

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

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

10) Xxxxxx, X. M., Xxxxxx, X. X., Elcombe, X. X., Xxxxxxxxx, X. G., Xxxxxx, X. X., Mackay, X. X., Xxxx, X. C. (1992), Xxxxxx of UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Party. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Sawamura, X., Hara, K., Xxxxxxxx, X. (1976), X. Safe Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Systems, xx: xx Serres, X. X., Xxxxx, X. X. Xxxx, J. X., Xxxxxxx, X. X. (xxx), In xxxxx Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, Xxxxxxxx, North-Holland, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, M. X., Xxxxxxxx, X. Xx., Xxxxx, J. L., Xxxxxxxx, D. J., Xxxxxx, X., Xxxxxxx, X., Sofumi, X. (1994), Xxxxxx xxxx Xxxxxxx Group xx Xx xxxxx Tests xxx Xxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, D. X., Xxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, X. O., Xxxxxxxx, X. (1989), Analysis xx Data from Xx vitro Cytogenetic Xxxxxx, in: Statistical Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. X., (ed) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

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

15) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, X. X. (1982), CHO/HGPRT Mutation Xxxxx: Xxxxxxxxxx xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Tice, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (eds), Xxxxxxxxx Effects xx Xxxxxxxx Agents, New Xxxx, Plenum, 91-103.

16) Xxxxxx, P. X., Xxxxxx, X. X., Xx, X. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Xxxxx Xxxxx xx Xxxxxxxx Xxxx xxx Detecting Highly Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environmental Xxxxxxx., 5, 795-801.

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

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


PŘÍLOHA 4B

"B.11 XXXXXXXXXX–XXXXXXX XX CHROMOZOMOVÉ XXXXXXX X BUŇKÁCH XXXXXX XXXXX SAVCŮ XX XXXX

1. XXXXXX

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

1.1 ÚVOD

Zkouška xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx xx xxxxxxxxx xxx detekci xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx látkou x xxxxxxx kostní dřeně xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x chromatidové. Nárůst xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx látka xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx rovněž xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x existuje xxxxx xxxxxx x xxx, že xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxx xxxxxxxxxxx změny x xxxxxxxxxx a x xxxxxx somatických xxxxx tlumících xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxxxxxxxxx systémech.

Při této xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxxxx xx x xxxx xxxxxxx xxxxxx xxxx, xxxxxxxx xx xxxxxx vaskularizovanou xxxxx x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx izolují x xxxxxxxxxxxx. Jiné xxxxx x xxxxxx xxxxx xxxxxx předmětem této xxxxxx.

Xxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx in xxxx, farmakokinetiku a xxxxxxx xxxxxxxx DNA, xxxxxxx se mohou x xxxxxxx xxxxx x tkání měnit. Xxxxxxx xx xxxx xx xxxxxx xxxxxxxx xxx xxxxx výzkum xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, že xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx použít.

Viz také Xxxxxx xxxx, xxxx X.

1.2 DEFINICE

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

Xxxxxxxxxxxx xxxxxxx : strukturní xxxxxxxxx chromozomu x xxxxxx xxxxx nebo xxxxx a xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

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

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx šířka xxxxxxx chromatidu x x xxxxxxxxx odchylkou xxxxxxxxx.

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

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx vystavena xxxxxxxx látce xxxxxxx xxxxxxxx a xx xxxxxxx xxxxxxxx xx xxxxxxxx se usmrtí. Xxxx usmrcením se xxxxxxxx xxxx látka xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X buněk kostní xxxxx se xxxx xxxxxxxx preparáty chromozomů, xxxxxx xx a xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx je xxxxxxxx xxxxxx, xxx x xxxxxx xxxxxx, xxxxxx xxx použít xxxxxxxx xxxxxx savčí xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx měla být xxxxxxxx v xxxxxxxxx xxxxxx minimální x xxxxxx by x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, xxxxx xx vystaví xxxxxxxx xxxxx. Xxxxx by xxxx být uspořádány xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx se xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx zkoušené xxxxx xx xxxx být xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx mohou xxx xxxxxxxx xxxxx xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx by být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxxxx neprokazují možnost xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx a mělo xx xxx vyloučeno xxxxxxxxx, xx reaguje xx zkoušenou xxxxxx. Xxxx-xx použita jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx nejdříve xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí každého xxxxxxxxxxx by xxxx xxx pozitivní x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx xxx xxx xxxxxxx. X výjimkou xxxxxxxx xxxxxxxx xxxxx xx xxxx zvířata xxxxxxxxx xxxxxxx podstoupit identický xxxxxx jako xxxxxxx xx skupinách, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx poskytovat strukturní xxxxxxx xx vivo xxx expozičních úrovních, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx tak, xxx xxx účinek xxxxxxxx, ale aby xxx xxxxxx nevyšla xxxxx xxxxxx kódovaná xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx způsobem xxx xxxxxxxx látka x xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx kontrolu xxxxx xxx xxxxxxx xxxxxxxx látky xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

V xxxxxxxx xxxxxxx xxxxxx xx xxx být xxxxxxxx xxxxx u xxxxxxxxxxx xxxxxxx, xxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx vehikulum a xxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx x dosavadních xxxxxxxxxxx xxxxx x xxxxxxxxx přijatelné údaje x xxxxxxxxxxx zvířat x xxxxxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx pro xxxxxxxxx xxxxxxxx xxxxx xxxxx, je xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, neexistují-li xxxxx kontrolní údaje xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx se skládá x alespoň xxxx xxxxxxxxxxxxxxxx zvířat xxx xxxxx xxxxxxx. Jestliže xxxx v xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx stejným druhem x xx použití xxxxxxxx způsobu xxxxxxxx, xxx prokazují, xx xxxxxxxxxx xxxx pohlavími xxxxxx v toxicitě, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x některých xxxxxxxxxxxxxxx látek, xxxx xx xxx xxxxxxx xxxxxxxxx xx zvířaty 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 xxxxxxx ne xxxx xxx několika xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx xxxxxxxx xx xxxx xxxxxxx intervalech xx xxxxxxxx xxxxxx x jednom dni. X hlodavců xx xxxxx xxxxxxx xx xxxxxx xxxx xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx (jenž xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x rovněž xxx xxxxxx na xxxxxxxx xxxxxxxxx xxxxx může xxx xxxx na xxxxxxxxx xxxxxxx xxx xxxxxxxxx chromozomových xxxxxxx, xxxxxxxxxx se xxxxxxx xxxxx xxxxx xx 24 h od xxxxxxx odběru. Je-li xxxxxxxx rozložena do xxxx xxx xxxxxxx xxx, měl xx xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného xxxxx.

Xxxx xxxxxxxxx xx xxxxxxxx intraperitoneálně xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx po xxxxxx době provede x xxxxxx xxxxx. X xxxx xx xxxx xxxx přibližně 3 — 5 x; u křečka xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 x. X kostní xxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xx xx chromozomové aberace.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx xxxxx, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, pohlavím x xx xxxxxxxx xxxxxx expozice, xxx xx xxxxxxx x xxxxxx xxxxxx (5). X případě toxicity xx pro xxxxx xxxxx použijí tři xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx maximální x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx xxxxxxx režimu xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx vyhovovat a xxxx by xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx x xxxxxx xxxxx xxxxxxx známky xxxxxxxx (např. xxxx xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou xxxxxx xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx nevykazuje xxxxx pozorovatelné xxxxxxx xxxxxx x není-li xx xxxxxxx údajů x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, nepovažuje xx xxxxx studie xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx a xxx delší xxx 14xxxxx xxxxxxxx je xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat potřebu xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Podávání dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx nebo xxxxxxx xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx podávání jsou x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Maximální objem xxxxxxxx, xxxxx může xxx najednou xxxxx xxxxxxxxxxxxxx xxxx injekčně, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Objem xx neměl překročit 2 xx/100 g xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být zdůvodněno. Xx na dráždivé x žíravé látky, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace zajišťující xxxxxxxxxx objem při xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Ihned xx xxxxxxxx xx xxxxxxx xxxxxx xxxx, xxxxxxxxxxxx xx x fixuje. Xxxxx se xxxxxxx xx podložní sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx xxx xxx x xxxxx exponovaných xxxxxx (xxxxxx pozitivních xxxxxxx) a u xxxxxxxxxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxx stanoven xxxxxxxxx xxxxx, x xx xxxxxxx x 1000 xxxxx xx xxxxx xxxxx.

X každého xxxxxxx xx mělo xxx analyzováno xxxxxxx 100 xxxxx. Tento xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx aberací. Xxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx kontrol by xxxx xxx xxxx xxxxxxxxxxxxxx analýzou xxxxxxxxx xxxxxxxx. Xxxxxxx při xxxxxx xxxxx xxxxxxx xx chromozomálním zlomům xxxx ke ztrátě xxxxxxxxxx x xxxxx xxxxx x xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx xxxxxxxxxx zvířata xx xxxx xxx zpracovány xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Pro xxxxx xxxxx xx xxx xxx xxxxxxxxxx počet xxxxx, počet aberací xx xxxxx x xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx exponované x xxxxxxxxx xxxxxxx xx měly xxx xxxxxxx různé typy xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x xxxxxx xxxxxx x xxxxxxxx. Gapy xx xxxxxxxxxxxxx xxxxxxxx x uvádějí se, xxx xxxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx. Neexistuje-li xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, mohou být xxx statistickou xxxxxxx xxxxx pro xxx xxxxxxx zkombinovány.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx xxxxxxxxxxx xxxxx buněk s xxxxxxxxxxxxxx aberacemi x xxxxxxxxxx xx xxxxx xxxx jasný nárůst xxxxx buněk x xxxxxxxxx xxx xxxxxxx x xxxxxxx dávkou x x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx měla xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx statistické xxxxxx (6). Statistická xxxxxxxxxx by xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxxxx xxxxx, jejíž xxxxxxxx xxxxxxxxx výše xxxxxxx xxxxxxxx, se považuje x xxxxx systému xx xxxxxxxxxxx.

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx o aktivitě xxxxxxxx látky. Výsledky xxxxx zůstat dvojznačné xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx experiment xxxxxxxx.

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

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

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx o zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- použitý xxxx/xxxx,

- xxxxx, xxxxx x pohlaví 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:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- xxxxx o přípravě xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

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

- případně přepočet xxxx koncentrací xxxxxxxx xxxxx x krmivu xxxx vodě (ppm) xx odpovídající xxxxx (xx/xx xxxxxxx hmotnosti/den),

- xxxxxxxx údaje x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx látky xxxxxxxxxxx metafázi, její xxxxxxxxxxx x délka xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx na jedno xxxxx,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx xx xxxxxxx xx středními hodnotami x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxx s xxxxxxxxx ve xxxxxxx xx xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxx ploidie, xxxxx xxxx pozorovány,

- xxxxx xxxxxxxx závislost xxxxxxxx xx dávce,

- případné xxxxxxxxxxx xxxxxxx,

- údaje x xxxxxxxx negativní xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Adler, X. D. (1984), Xxxxxxxxxxx Xxxxx in Xxxxxxx, xx: Mutagenicity Xxxxxxx: x Practical Xxxxxxxx, X. Xxxxxx, X. M. Xxxxx (xxx), XXX Xxxxx, Xxxxxx, Xxxxxxxxxx X. X., 275-306.

2) Xxxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X., Xxxxxx, H., XxXxx, X. X., Xxxxxx, X. (1987), Xxxxxxxxx Xx xxxx Xxxxxxxxxxx Assays: Xxxxxxxx xx Chromozome Aberrations xx Xxxx Xxxxxx Xxxxx, Mutatation Res., 189, 157-165.

3) Xxxxxxx, X., Xxxxxxxx, A., Xxxxx, X., Xxxxxxxxx, X. X., Bootman, X., Henderson, L. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Kirkland (xx.), Basic Mutagenicity Xxxxx, XXXXX Recommended Xxxxxxxxxx. XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

4) Tice, X. X., Xxxxxxx, X., XxxXxxxxxx, J. X., Anderson, D., Xxxxxx, X. X., Xxxxxx, H. X., Xxxxxx-Xxxxxxx, M., Oleson Xx., X. X., Xxxxxxxxxxxx, F., Xxxxxxx, X. X., Romagna, X., Xxxxxxx, X., Xxxxx, S., Vannier, X. (1994), Xxxxxx xxxx the Working Xxxxx on xxx xx xxxx Xxxxxxxxx Xxxx Xxxxxx Chromozomal Xxxxxxxxxx Test, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. R., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, D. X., Xxxxxxxx, X. X., Richold, X. (1992), Xxxxxx xx Xxxxxxx Toxicology Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx in Xx xxxx Mutagenicity Assays, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. P., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, D. X., Savage, X. X. K. (1989), Xxxxxxxxxxx Analysis of Xx vivo Cytogenetic Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Testing, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, 184-232.

7) Xxxxx-Xxxxx, C. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx-xxxxxxx G2 arrest, Xxxxxxxxxx Xxx., 119, 403-413.

8) Huang, X., Xxxxxx, X., Xxxxxx, X. X. (1983), Xxxxxxxxxxx-xxxxxxx xxxxxxxxxxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx, Xxxxxx Xxx., 43, 1362-1364."


PŘÍLOHA 4X

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

1. XXXXXX

Xxxx xxxxxx je replikou xxxxxx OECD XX 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx vivo (1997).

1.1 XXXX

Xxxx xxxxxxx erytrocytárních xxxxxxxxxx xx vivo xx xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx zkoušenou xxxxxx, x xx xxxxxx xxxxxxx xxxxxxxxxx odebraných x xxxxxx dřeně x/xxxx xxxxx xxxxxxxxx xxxx, obvykle xxxxxxxx.

Xxxxxx xxxxx xxxxxxx erytrocytárních xxxxxxxxxx xx identifikovat xxxxx, xxxxx způsobují xxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (xxxxxxx) chromozomové xxxxxxxxx nebo celé xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx xxxxx mění xx polychromatický xxxxxxxxx, xxxxxx xxxxx je xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx vzniknout, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx je x xxxxxx buňkách xxxxxxxxx tím, xx xxxxxxxxxx hlavní xxxxx. Xxxxxx výskytu xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxx zvířatech xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx poškození.

V xxxxx xxxxx je rutinně xxxxxxxxx kostní xxxx xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx x xxxxxxxxx xxxx xx rovnocenně xxxxxxxxxx u xxxxxxxxxxx xxxxx, u něhož xxxx xxxxxxxxx neschopnost xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, nebo xxxxxxxxxx citlivost xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx aberace. Xxxxxxxxxx xxx rozlišit xxxxx xxxxxxxx. Ta xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxxxxxx (kinetochorní) XXX v mikrojádře. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (polychromatických) xxxxxxxxxx x xxxxxxxxxx. Xxxxx xxxxxxx (normochromatických) xxxxxxxxxx x periferní xxxx, xxxxx obsahují xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx xxxx xxxxxxx xxxxxxxx xxxxxxx, xxxxxxxx xxxx xxxxxxx exponována xxxxx xxxxx xxxx xxxx.

Xxxxx xxxx savčích xxxxxxxxxxxxxxx mikrojader xx xxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx xxxxx x xxxxxxx druhů x tkání, jakož x x genetického xxxxxxxx. Xxxxxxx xx xxxx je xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx v xxxxxxxxx xx xxxxx.

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

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) chromozomu, x níž (x xxxx) se během xxxxxx buněk xxxxxxx xxxxxx vřeténko xxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx xxxxx existující xxxxxxxx xx xxxxxxxx xxxxx x xxxxx xxxx, vytvářená xxxxx xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx se (xxxxxxx) xxxxxxxxxxxxxx fragmenty xxxx xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx xxxxxxxxx : xxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxx, který xxx xxxxxxxx od xxxxxxxxx polychromatických xxxxxxxxxx xxxxxxxx selektivním xxx xxxxxxxx.

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx xxxxxxxx ribozomy, x xxxx být xxxx rozlišen xx xxxxxxx xxxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx selektivním pro xxxxxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx se xxxxxxx xxxxxxxx vystaví xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx dřeně se xxxxxxx xx vhodném xxxxxxxx xx xxxxxxxx xxxxxx, xxxxxxx se xxxxxx xxxx, xxxxxxxx xx xxxxxxxxx x xxxxxx se (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx xx xxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Xxx xxxxxxxx s periferní xxxx xx xxxx xxxx poslední xxxxxxxx x sklizením xxxxx xxxxxxxx co nejkratší xxxx. Xxxxxxxxx xxxx xxxxxxxxxxx xx přítomnost xxxxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx xxxxxxx xxxxxx dřeně se xxxx testovací xxxxx xxxxxxxxxx xxx nebo xxxxxx, ačkoli lze xxxxxx jakýkoli xxxxxx xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx xxxx xx xxxxxxxxxx xxx. Xxx však xxxxxx xxxxxxxx xxxxxx druh xxxxx za předpokladu, xx xxx x xxxx, x xxxxx xxxxxxx neodstraňuje xxxxxxxxxx x mikrojádry, xxxx xxxx xxxxxxxxxx dostatečnou xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Měly xx xxx použity xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx být xxxxxxxx v hmotnosti xxxxxx minimální x xxxxxx xx x xxxx pohlaví překročit ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata se xxxxxxxx výběrem xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, x xxx xx provede xxxxxxxx. Zvířata xx xxxxxxxxxxx identifikují. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx. Xxxxx xx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx rozpuštěny xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx nebo mohou xxx před xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, pokud xxxxx x jejich xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo mít xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx než xxxxx rozpouštědla/vehikula, mělo xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich kompatibilitě. Xxxxxxxxxx xx xxxxx xxxxx nejdříve xxxxxx xxxxxxx vodných rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx měly xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx aplikace zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx identický xxxxxx xxxx zvířata xx xxxxxxxxx, x xxxxx xxxxx x expozici.

Pozitivní xxxxxxxx by xxxx xxxxxxxxxx mikrojádra xx xxxx při xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx kontroly xx xxxx být zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx identifikace preparátu. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx byla xxxxxxxx jiným xxxxxxxx xxx xxxxxxxx xxxxx x xxx byl xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx navíc xxxx xxx xxxxx x xxxxx xxxxxxx chemických xxxxx xx stejné xxxxxxxx xxxxx, jsou-li x dispozici. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid monohydrát

6055–19–2

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

51–18–3

200–083–5

X okamžiku xxxxxx xx xxx být xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx kontroly, xxxxx je xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx nejsou x dosavadních xxxxxxxxxxx xxxxx k dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx také tehdy, xxxxxxxxxx-xx dosud nebo xxxxxx-xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx krve xxxx xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx krve xxxxxxxx xxxx expozicí, xxxxx xxxx x xxxxxxxx xxxxxx x xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, xx xxxxxxxx xxxxx budou x rozpětí, xxxxx xx na xxxxxxx xxxxxxxxxxx kontrol očekává.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxxxx exponovaná x xxxxxxxxx xxxxxxx xx musí skládat x xxxxxxx xxxx xxxxxxxxxxxxxxxx zvířat xxx xxxxx xxxxxxx (11). Xxxxxxxx jsou v xxxx studie k xxxxxxxxx údaje ze xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx prokazují, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx v xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx farmaceutických xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxx doporučit xxxxx standardní plán (xx. xxxxx, xxx xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Vzorky xx xxxxxx x prodlouženým xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx se x těchto xxxxxx xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –v xxxxxxx xxxxxxxxxxx studií — xxxxx byla xxxxxxxxx xxxxxxxx nebo xxxx xxxxxxxxx limitní xxxxx x xxxxxxxx pokračuje xx xx okamžiku xxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx x xxx xxx x rozmezí xx více než xxxxxxxx xxxxx, aby xxxx xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx xxx proveden xxxxx xxxxxxx:

x) zkoušená xxxxx xx xxxxxxxx xxxxxxxx xxxxxx. Xxxxxx xxxxxx dřeně se xxxxxxxx xxxxxxx dvakrát, xxxxxxx xxxxx odběr xx xxxxxxx xxxxxxxx 24 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 hodin xx aplikaci x x xxxxxxxxxx xxxxxxxx xxxx xxxxxx. Odběr xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx periferní xxxx xx xxxxxxxx alespoň xxxxxxx, přičemž xxxxx xxxxx xx xxxxxxx xxxxxxxx 36 xxxxx xx aplikaci x xxxxxxxx xxxxxxxxxx 72 xxxxx po aplikaci x xx xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx odběr xxxxx;

x) xxxx-xx xxxxxxxx xxx xxxx xxxx dávek xxxxx (např. dvě xxxx více dávek x xxxxxxxxx 24 xxxxx), xxxx xx xxx vzorky xxx xxxxxxx xxxxxx xxxxx xxxxxxxx jednou xx 18 xx 24 xxxxxxxx xx poslední xxxxxxxx x xxx xxxxxxx periferní xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx xxxxxxx mohou xxx xxxxx xxxxxxx xxxx doby xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx by být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí v xxxxxx xxxxxx (13). X případě toxicity xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx dávkách (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx xxxxx xxxx být xxxx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx x xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx erytrocytů x celkového xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx x xxxxxxxxx xxxx).

1.5.4 Limitní xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx o xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, které xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx xxxxx studie xx xxxxx úrovněmi xxxxx xx nezbytnou. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx delší xxx 14xxxxx xxxxxxxx je xxxxxxx dávkou 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx v xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, žaludeční xxxxxx nebo xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx x odůvodnitelných xxxxxxxxx. Maximální objem xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx na xxxxxxxxx testovacího zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx na xxxxxxxx a žíravé xxxxx, xxxxx obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx měla xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx nebo xxxx

Xxxxx xxxxxx dřeně xx xxxxxxx získávají z xxxxxx nebo tibie xxxxx xx xxxxxxxx. Xxxxx xx odeberou x xxxxxx nebo xxxxx x zavedenými xxxxxxxx se preparují x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x ocasní žíly xxxx xxxx vhodné xxxxxx xxxx. Xxxxxx xxxxx xx xxxxx xxxxxxxxxxxx obarví (8, 9, 10), xxxx xx připraví preparáty xxxxxxxx x xxxx xx obarví. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) se xxx xxxxxxx některým xxxxxxxxxx xxxxxxxx x xxxxxxxx barviva xxxxxxxxxxxxxx xxx DNA. Xxxx xxxxxx xxxxxxx použití xxxxxxxxxxx barviv (např. Xxxxxx). Xxxxxxxx xxxxxxx (xxxx. celulosová kolona x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx použít xx xxxxxxxxxxx, xx xx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx systémů pro xxxxxxxxx mikrojader x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx se stanoví xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx (nezralé + zralé) xxxxxxxx xxxxxxxxxx, přičemž se x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 erytrocytů x x případě xxxxxxxxx krve alespoň 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx být před xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx se xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Další xxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xx výskyt xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx xxxxx být xxxxx xxxxxxxxx xxxxxxxxxx x celkového množství xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx xxxx xxxxxxxx xx výskyt xxxxxxxxxx xxxxxxx 2000 xxxxxxx erytrocytů xx xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx analýzu (xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxx) xxxx xx xxxxxxxxxxxxx xxxxxxxxxx x validaci přijatelnými xxxxxxxxxxxxx xxxxxxxxxx hodnocení.

2. XXXXX

2.1 ZPRACOVÁNÍ VÝSLEDKŮ

Údaje xxx jednotlivá xxxxxxx xx měly být xxxxxxxxxx xx xxxxx xxxxxxx. Experimentální jednotkou xx xxxxx. Xxx xxxxx analyzované zvíře xx xxx xxx xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx erytrocytů, počet xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx jsou zvířata xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxxx xx xxx xxxx xxxxxxx údaje x xxxxxxx xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Pro xxxxx xxxxx xx xxxxx xxxxx nezralých xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx a xxxxxxxx množství erytrocytů x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx o xxxxxxx x odpovědi xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx analýzu xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx xxxxx xxxxx s xxxxxxxxxx x xxxxxxxxxx na xxxxx nebo xxxxx xxxxxx xxxxx xxxxx x mikrojádry xxx xxxxxxx x xxxxxxx xxxxxx a x xxxxxxxx xxxxxxxx odběru. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (18, 19). Statistická významnost xx xxxxxx být xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx vyjasněny xxxxxx zkoušením, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou zůstat xxxxxxxxxx nebo sporné xxx xxxxxx xx xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx poškození xxxx xxxxxxxxx mitotického aparátu xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx zkoušky xxxxxxxxxxx mikrojádra x xxxxxxxxx erytrocytech xxxxxxxxxxx xxxxx.

Xxxx xx být xxxxxxxxxxx pravděpodobnost, x xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, nebo xxxxxxxxxx do xxxxxx xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, stáří x pohlaví zvířat,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Xxxxxxxx xxxxxxxx:

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

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxxxxxx metody xxxxxxx, xxx xx zkoušená xxxxx dostala do xxxxxxxx xxxxx nebo xx xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x kvalitě xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx stanovení xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x nezralých xxxxxxxxxxxx,

- xxxxx analyzovaných buněk xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- podíl xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx erytrocytů,

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

- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx statistické xxxxxxx x metody,

- xxxxx x xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxx, J. A., Xxxxxxxx, X. X., Xxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X., XxxXxxxxx, X. G., Xxxxxx, X. W. (1983), The Induction xx Xxxxxxxxxxx x. x. x Xxxxxxx xx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx. 123, 61-118.

4) Xxxxxxxxx, K. H., Xxxxxx, X. X., Xxxxxx, M. X., Xxxxxxxx, X. F., Xxxxxx, X. X. (1990), Xxx Xx xxxx Micronucleus Assay xx Xxxxxxxxx Xxxx Xxxxxx and Peripheral Xxxxx. X report xx xxx U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, J. X., Xxxxxxxx, X., Xxxx, W. N., Xxxx, C. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Screen xxx Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Xxxxxxxx Testing xx Xxxx, xx: Xxxxxxxxxxxx xx Science xxx Practice xx Xxxxxxxxxx, xx. X. X. Xxxxx, X. X. Schnell, X. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Xxxxxx, X. A. Xxxx, X., Xxxxxxxx, X. X., Ramel, X., Xxxxxxxx, X. F., Xxxx, R. R., Xxxx, X. (1987), Xxxxxxxxxx for the Xxxxxxx of Micronucleus Xxxxxx in Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

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

8) Hayashi, X., Xxxxxx, T., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, M. Xx. (1990), Xxx Xxxxxxxxxxxx Assay xxxx Xxxxx Peripheral Xxxxx Xxxxxxxxxxxxx Xxxxx Acridine Xxxxxx-Xxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 245, 245-249.

9) Xxx Collaborative Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Xxxx (1992). Xxxxxxxxxxxx Xxxx with Xxxxx Peripheral Blood Xxxxxxxxxxxx xx Acridine Xxxxxx Xxxxxxxxxx Xxxxxxxx: Xxx Summary Xxxxxx xx xxx 5xx Xxxxxxxxxxxxx Study xx XXXXX/XXXXX, XXX, Xxxxxxxxxx Xxx., 278, 83-98.

10) Xxx Collaborative Study Xxxxx xxx the Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: Xxx Mammalian Xxxxxxxxxxx Xxxxx Xxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxx Society of Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx xxx xxx xxxxx-xxxx mouse xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., XxxXxxxxx, X. X., Anderson, X., Xxxxxxx, D. X., Kirsch-Volders, M., Xxxxxx, Jr. X. X., Xxxxxxxxxxxx, F., Xxxxxxx, F., Xxxxxxx, X., Sutou, X., Xxxxxxx, B. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Xxxxx, Xxxxx. Xxx., 312, 293-304.

12) Higashikuni, N., Xxxxx, S. (1995), Xx xxxxxxx, xxxxxxxxxxx xxxxxxxx time xx 30 ± 6 x after xxxxxx xxxxxx xx the xxxxx peripheral xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Fielder, X. X., Xxxxx, J. X., Xxxxxx, A. X., Xxxxxx, X. X., Doe, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Xxxxxx xx British Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

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

16) Xxxxxxx, F., Xxxxxxxxxx, X. X. (1989), The automated xxxx marrow micronucleus xxxx, Mutatation Xxx., 213, 91-104.

17) Gollapudi, X., XxXxxxxx, X. X. (1995), Xxxxxx Xxxx xxx the Xxxxxxxxxx xx Polychromatic xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx xx xxx Xxxx Xxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 347, 97-99.

18) Xxxxxxx, X., Xxxxx, J., Xxxxxxx, X., Chandley, X., Gatehouse, X. X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxxx Assay, xx: X. J. Kirkland (xx.), Basic Xxxxxxxxxxxx xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx 1, revised, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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


XXXXXXX 4X

"X.13/14 MUTAGENITA — XXXXXXX NA XXXXXXXX XXXXXX S XXXXXXXXXX

1. METODA

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

1.1 XXXX

Xxx xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi xx používají xxxxxxxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x xxxxxxx bodových xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx na reverzní xxxxxx s xxxxxxxxxx xxxxxxx x detekci xxxxxx, které xxxxxxxxx xxxxxx xxxxxxxx v xxxxxxxxxxx xxxxxxx x xxxxxxxx tak funkční xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx aminokyseliny. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx díky xxx xxxxxxxxxx xxxx x xxxxxxxxxxxxx aminokyselin, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx mutace x xxxxxxx jevy xxxx příčinou xxxxx xxxxxxxxx podmíněných xxxxxx x člověka x xxxxxxxx mnoho xxxxxx x tom, xx xxxxxx mutace x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxx na xxxxxx xxxxxxxx u xxxxxxx x x xxxxxxxxx xxxxxx. Zkouška na xxxxxxxx mutace x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx a xxxxxxxxx xxxxxx. Xxxxx xxxxxxxxxxx xxxxx xx řadu xxxxxxxxxx, díky xxxx xxxx citlivější xx xxxxxxx xxxxxx, včetně xxxxxxxxxxxxx sekvencí XXX xx reverzních místech, xxxxxxx xxxxxxxxxxxx buněk xxx velké molekuly x xxxxxxxxx xxxxxxxxxxx xxxxxxx DNA nebo xxxxxxxx reparačních xxxxxxx XXX xxxxxxxxxx x xxxxxx. Specifičnost testovacích xxxxx může xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxx x typech xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xx x xxxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx xxxxxxxx x xxxx xxxx vyvinuty xxxxx vyzkoušené metody xxxxxxxx chemických xxxxx, xxxxxx xxxxxxxx xxxxxxxxx, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, část B.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx nebo Xxxxxxxxxxx xxxx slouží x detekci mutací x kmeni vyžadujícím xxxxxxxxxxxxx (histidin resp. xxxxxxxxx), přičemž xxxxxx xxxx xxxxxxxxx na xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx činitele, jež xxxxxxxxx xxxxx x xxxxxx DNA. Xxx xxxxxxx reverzních xxxxxx xx mohou tyto xxxxx vyskytnout xx xxxxx xxxxxxx xxxxxx xxxx jiném místě xxxxxxxxxxxxx genomu.

Posunové xxxxxxxx xxxx činitele, xxx xxxxxxxxx xxxxx xxxx xxxxxx jednoho xxxx xxxx párů xxxx XXX x posunují xxx xxxxx rámec XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx využívají xxxxxxxxxxxxx xxxxx, xxxxx xx xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx struktura x xxxxxxxxx xxxxxxx XXX. Xxxxxxx prováděné in xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx systémy xx xxxxx xxxxxxx xxxxx xxxxxxxxx podmínky xx xxxx x savců. Xxxxxxx tedy neposkytuje xxxxxx xxxxxxxxx x xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx xxxxxxxxx využívána xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx xxxxxxxx vyvolávající xxxxxx mutace. Z xxxxxxxx xxxxxxxx xxxxxxx, xx mnoho chemických xxxxx, xxxxx xxxx x této xxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx i x xxxxxx zkouškách. Xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx nejsou detekovány xxxxx xxxxxxxx. Příčiny xxxxxx xxxxxxxxxxx xxx xxxxxxxxx ve xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x xxxxxxxxx x xxxxxxxxxxx xxxxxxxx nebo x xxxxxxxxx x xxxxxxxxxx dostupnosti. Xx xxxxx xxxxxx faktory, xxxxx xxxxxxx citlivost xxxxxxx xx xxxxxxxx xxxxxx xx xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx aktivity.

Zkouška xx reverzní xxxxxx x xxxxxxxxxx nemusí xxx vhodná xxx xxxxxx třídy xxxxxxxxxx xxxxx, xxxxxxxxx vysoce xxxxxxxxxxxx sloučeniny (xxxx. xxxxxx xxxxxxxxxxx) x xxx chemické xxxxx, x xxxxx se xxxxxxxxxxx (nebo o xxxxx xx ví), xx specificky xxxxxxxx xx replikačního xxxxxxx xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx mohou xxx xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx xxxxx xxxxxxxxx, xxx něž xx tato xxxxxxx xxxxxxxxx, je xxxxxxxxxxxx xxx xxxxx, není xxxxxxxx xxxxxxxxx. Xxxxxx xx xxxxxxxx třídě x xxxxxxxx mnoho xxxxxxxxxxx, xxx nejsou xxxxxxxxxx xxxxx zkouškou, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x xx xx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx něho. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx suspenze xxxxxxxx x xxxxxxx xxxxxx x ihned se xxxxxxx xx xxxxxxxxx xxxx. V xxxxxxxxxxxx xxxxxx xx xxxxxxxx xxxx inkubuje x xxxx xx xxxx xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx x xxxxxxx agarem. Xxx xxxx technikách se xx xxxx nebo xxxxx xxxxx inkubace xxxxxxxxx kolonie revertantů x xxxxxxx xx xxxxxxxx s xxxxxx xxxxxxx spontánních xxxxxxxxxx xx xxxxxxxxx misce x xxxxxxxxxxxxx.

Xx xxxxxxx xxxxxxx xxxxxxx provedení xxxxxxx na reverzní xxxxxx x bakteriemi. Xxxx xxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx xxxx (9, 10) x xxxxxxxxx metoda (11). Xxxxxx pro zkoušení xxxxx x xxx xxxx xxxxxxx (12).

Xxx xxxxxxx xxxxxxx se xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx testu x xxxxxxxxxxxxxx xxxxx. Každá x xxxx xx xxxxxxxxxx pro provádění xxxxxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Některé xxxxx lze účinněji xxxxxxxxx za xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx xxxxx xx xxxxxxxxxx tříd, xx xxxxx patří xxxx xxxxx krátké xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, azobarviva a xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx třídy xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx xxx xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "zvláštní xxxxxxx" (xxxxxxxx x xxxxxxxx postupů jejich xxxxxxx): xxxxxxxxxx a xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x xxxxxx xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Odchylka od xxxxxxxxxxxx xxxxxxx xxxx xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX ZKUŠEBNÍ XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxx xx xxxxxx exponenciální xxxx xxxx xx časné xxxxxxxxxxx fáze xxxxx (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Je xxxxxxxx, aby xxxx xxxxxxx xxxxxxxx xxxxxx xxxx životaschopných xxxxxxxx. Xxxx xxxx xxx xxxxxxxx buď xx xxxxxxx dosavadních xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxx xxx xxxxxx xxxxxxx stanovením xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx by být xxxxxxx xxxxxxx xxx xxxxx xxxxxxxx. Xxxx xxxx xx xxxx xxx xxxxx kmeny X. xxxxxxxxxxx (XX1535; XX1537 xxxx XX97x xxxx TA97; TA98 x XX100), xxxxxxx xxxxxxx xx ukázala x xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx S. xxxxxxxxxxx xxxx xxx bází XX xx xxxxxxxxx xxxxxxxxx xxxxx x xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx určité oxidační xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx vláken DNA x xxxxxxxxx. Xxxx xxxxx mohou být xxxxxxxxxx kmeny X. xxxx WP2 xxxx X. typhimurium XX102 (19), xxxxx mají xx primárním xxxxxxxxx xxxxx pár bází XX. Xxxxxxxxxx xxxxxxxxx xxxxx je xxxx xxxx:

- X. xxxxxxxxxxx XX1535 x

- S. xxxxxxxxxxx XX1537 xxxx XX97x a

- X. xxxxxxxxxxx XX98 x

- X. xxxxxxxxxxx TA100 x

- E. coli XX2 xxxX, xxxx X. xxxx WP2 xxxX (xXX101), xxxx X. xxxxxxxxxxx XX102.

Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx DNA xxxx xxx xxxxxxxxx xxxxxxx XX102 nebo xxxxxx xxxx X. xxxx s xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. X. coli XX2 (xXX101)).

Xxxx by xxx použity xxxxxxxx xxxxxxx přípravy kmenové xxxxxxx, verifikace markeru x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx pro xxxx xx xxxx xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx kulturu (xxxxxxxx xxx xxxxx X. typhimurium a xxxxxxxxx xxx X. xxxx). Xxxxxxx xx xxxx být xxxxxxxxxxxx xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx podle potřeby xxxxxxxxxx xxxx nepřítomnost X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx rezistence x xxxxx TA98, TA100 x XX97x xxxx XX97, WP2 xxxX x WP2 xxxX (xXX101) x xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x kmene XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. rfa xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x xxxX xxxxxx x X. xxxx xxxx xxxX xxxxxx u X. xxxxxxxxxxx citlivostí xx xxxxxxxxxxxx xxxxxx) (2, 3). Kmeny xx xxxx xxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxx xxxxxxxx xxxxxxxxxxx na základě xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx x xxxxxxx x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx xxxxxxxxx xxxx (např. obsahující xxxxxxxxx xxxx X (Xxxxx-Xxxxxx) x xxxxxxx) x xxxxxx agar xxxxxxxxxx histidin x xxxxxx xxxx tryptofan xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx xxxxxxxx

Xxxxxxxx xx měly být xxxxxxxxx zkoušené látce, x xx x xxxxxxx xxxxxxxx metabolické xxxxxxxx x xxx xxxx. Xxxxxxxxxx používaným xxxxxxxx je xxxxxxxxxx xxxxxxxx postmitochondriální frakce (X9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Aroclor 1254 (1, 2) xxxx fenobarbitonu x β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 až 30 % xxx. xx xxxxx S9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx chemické xxxxx. X některých 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 xxxxxxxxx

Xxxxx xxxxxxxx látky by xxxx xxx před xxxxxxxx na bakterie xxxxxxxxxx xxxx suspendovány xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx xxxxxxxx zředěny. Xxxx by xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx látky, xxxxx údaje o xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx podezření, xx reaguje xx xxxxxxxxx látkou, x xxxx xx být xxxxxxxxxx x přežitím xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx organická xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Zkušební xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx při stanovení xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx patří xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxx směsi xxx xxxxxxxx.

Xxxx být xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx snížením xxxxx xxxxxxx revertantů, xxxxxxxxx nebo zeslabením xxxxxxxxxxxxx podkladu nebo xxxxxxxx xxxxxx přežití xxxxxxxxxxxx xxxxxx. Cytotoxicita xxxxx se může xxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systémů. Xxxxxxxxxxxxx xx měla xxx xxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx rozpustné xxxxxxxxxxxxx xxxxx xx 5 xx/xxxxx xxxx 5 μl/misku. U xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx koncentracích 5 xx/xxxxx nebo 5 μx/xxxxx xx měla xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, xxx látky xxxx x xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxxxx xxx při xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, xx měly xxx xxxxxxxx až xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx xx neměla xxxxx při vyšetřování.

Mělo xx být xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, přičemž při xxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx xxxx xxxxxx x xxxxxxx, kdy xx xxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx na xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx xxx xxxxxxx xxx hodnocení xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx kontroly

Součástí xxxxxxx xxxxxxxxx xx měly xxx xxxxxxx xxxxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx a bez xx. Xxx xxxxxxxxx xxxxxxxx by xxxx xxx vybrány koncentrace xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx by xxxx xxx xxxxx (xxxxx) pro pozitivní xxxxxxxx vybrána (xxxxxxx) xx základě xxxx xxxxxxxxx kmene bakterií.

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxxx xxxxx xx xxxxxxx xxxxxxxxx kontrolou pro xxxxxx xxxxxxxx metabolické xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

XX Direct Xxx 28

573–58–0

209–358–4

2-xxxxxxxxxxxxxx xx xxxxx xxx xxxxxx xxxx xxxxxx indikátor účinnosti xxxxx X9. Xxx xxxxxxx 2-xxxxxxxxxxxxxxx by xxxx být xxxxx xxxxx S9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx aktivaci xxxxxxxxxxxxxx xxxxxx, xxxxxxxxx xxxxx[x]xxxxx xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx kontroly u xxxxxxx xxx xxxxxx xxxxxxxxxxx xxxxxxxx xxxx xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

Xxxx

xxxx xxxxx

26628–22–8

247–852–1

XX1535 x XX100

2-xxxxxxxxxxxx

607–57–8

210–138–5

XX98

9-xxxxxxxxxxxx

90–45–9

201–995–6

XX1537, XX97 x TA97a

ICR 191

17070–45–0

241–129–4

XX1537, XX97 x XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX x XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 xxxX a XX2 uvrA (pKM101)

4-nitrochinolin-1-oxid

56–57–5

200–281–1

WP2, XX2 xxxX x XX2 xxxX (pKM101)

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

3688–53–7

xxxxx xxxxxxxxxx plasmidy

Pro xxxxxxxxx xxxxxxxx xxxxx xxx použity xxxx xxxxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx, jsou li x dispozici.

Měly xx xxx použity xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, bez xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx skupiny. Xxxxx xxxx by xxxx být xxxxxxxxxxxx xxxxxxxx použity xxxx xxxxx, neexistují-li xxxxx xxxxxxxxx údaje prokazující, xx xxxxxxx rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx miskové xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx aktivace se xxxxxxx xxxxxx 0,05 xx nebo 0,1 xx zkušebních xxxxxxx, 0,1 ml xxxxxxx xxxxxxxxxxx xxxxxxx (obsahující xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx sterilního pufru x 2,0 xx xxxxxxxx agaru. X xxxxxxx zkoušky x xxxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,5 xx metabolické xxxxxxxxx xxxxx xxxxxxxxxx přiměřené xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x rozmezí 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx směsi) x xxxxxxx agarem (2,0 xx) a xxxxxxx x xxxxxxxxxx a xxxxxxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx. Obsah xxxxx zkumavky xx xxxxxxxx a xxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx misce. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X preinkubační xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx xxxxxxxxx x xxxxxxx xxxxxx x xxxxxxxx přes xxxxxx xxxxxxxxxxx xxxxx xx misce obvykle 20 xxxxx nebo xxxx preinkubuje x xxxxxxxxxx kmenem (xxxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) a xxxxxxxxx xxxxxx xxxx metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) xxx 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 xxxx 0,1 xx xxxxxxxx xxxxx xxxx zkušebního xxxxxxx, 0,1 ml xxxxxxxx x 0,5 xx xxxxx X9 xxxx xxxxxxxxxx xxxxx x 2,0 xx xxxxxxxx xxxxx. Xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.

X dostatečnému xxxxxx xxxxxxxx xx měly xxx při každé xxxxxx xxxxx xxxxxxx 3 misky. Xxxxxxx xxxx xxxxx je xxxxxxxxxx xx vědeckém xxxxxxxxxx. Případná ztráta xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx zkoušky.

Plynné xxxx xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx nádobách (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx v xxxx zkoušce by xxxx xxx xxxxxxxxxx xxx 37 °C xx 48 –72 xxxxxxxx. Xx uplynutí xxxxxxxxx xxxx xx xxxxxx počet kolonií xxxxxxxxxx xx misku.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Předloženými xxxxx xx xxxx xxx xxxxx xxxxxxx xxxxxxxxxx připadající na xxxxx. Měl xx xxx xxxxxx uveden xxxxx kolonií xxxxxxxxxx xxx xx xxxxxxx x xxxxxxxxx xxxxxxxxx (xxxxxxxx rozpouštědla x xxxxxxxx neexponovaná xxxxxxxx), xxx xx miskách x xxxxxxxxx kontrolou. Xxxxx na jednotlivých xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx revertantů xx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx kontrolu xxxxxxxxxxxx).

Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou experimentálních xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx nezbytné, xxxx xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x cílem xxxxxxxx xxxxxx posuzovaných xxxxxxxx xx xxxx xxx xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx mohly xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx misková xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) x xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX A INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx kolonií revertantů xx xxxxx xxx xxxxxxxxx rozsah u xxxxxxx xxxxxxx xxxxx x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxx xxxx, x xx x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx tohoto xxxxx xxx xxxxx nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný 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 v xxxxx systému xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x ojedinělých případech xxxxxxxx soubor údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxx, že xxxxxxxx látka xxxxxxxx x xxxxxx xxxxx Xxxxxxxxxx typhimurium x/xxxx Xxxxxxxxxxx xxxx bodové xxxxxx xxxxxxxxxx bází xxxx xxxxxxx xxxxxxx xxxxx. Negativní výsledky xxxxxxxxx, xx xxxxxxxx xxxxx xxxx xx xxxxxxxx zkoušky pro xxxxxxxxx xxxxx xxxxxxxxx.

3. XXXXXX

XXXXXXXX O ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx kmene.

Zkušební xxxxxxxx:

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

- xxxxxxx xxxxx,

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

- postup xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- počty xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx o xxxxxxxx xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x xxxxxxxxx kontrole x xxxxxxxxx, xxxxxxxxx hodnotami x xxxxxxxxxxxx odchylkami,

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

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

3) Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxx, X., Xxxxx, E., Xxxx, L., Matsushima, X., Xxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, X. (1994), Xxxxxxxxxxxxxxx xxx xxx Performance of Xxxxxxxxx Xxxxxxxx Assays, Xxxxxxxxxx Res., 312, 217-233.

4) Kier, X. X., Xxxxxxx D. X., Xxxxxxx, X. X., Xxx Halle, X. X., Xxxxx, X. M., Xxxxxx, X. X., Xxxxxx, X., McCann, X., Xxxxxxxxxx, X., Prival, X., Rao, X. X., Xxx X. (1986), Xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Assay: X Xxxxxx of xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, X., Degawa, X., Seino, Y. X., Xxxxxxxxxx, T., Xxxxx, M., Xxxxxxxx, X., Xxxxxxxxx, Y. (1975), Xxxxxxxxxxxx xx Xxxxxxxxxx Xxx Xxxx xxx xxxxx Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, M., Xxxxxxxx, T., Xxxxx, X., Xxxxxx, T., Xxxxxx, X., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Mutagenicity Xxxxxxxxx Xxxxx, in: Xxxxx-xxxx Xxxx Systems xxx Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx X. H., Xxxxxx, R. C., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Xxxxxxxxx, D. X., Rowland, X. X., Xxxxxx, X., Xxxxxxxxx, X. X., Xxxxxx, R. (1980), Xxxxxxxxx Xxxxxxxx Assays, xx: Xxxxx Xxxxxxxxxxxx Xxxxx: UKEMS Part 1 Revised, xx. X. J. Xxxxxxxx, Xxxxxxxxx University Xxxxx, 13-61.

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

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

10) Hubbard, X. A., Xxxxx, X. X. X., Xxxxxxxxx, D., Xxxxxxx, X. X. (1984), Xxx Fluctuation Test xx Bacteria, in: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, 2. xxx., Xxxxxx, B. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 141-161.

11) Xxxxxxxx, X. X., Xxxxxxx, P. J. (1981), An Examination xx the Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx xxx Xxxxxxxxxxx xxxx Xxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Mutagenesis, 3, 453-465.

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

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

14) Xxxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X., Xxxxxx, X., Xxxxxxxxxx, K. (1992), Xxxxxxxxxx Mutagenicity Xxxxx. X. Results xxxx xxx Testing xx 311 Chemicals, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, X., Xxxxxxxx, K., Xxxxxxx, X. X. (1977), Xxxxxxxxx Activity of Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxx Water, xx Xxxxxxxx xx Xxxxxxx Xxxxxxxxxx, X. Xxxxx, X. Xxxxxxx, X. Xxxxxx (eds.) Xxxxxxxx, Xxxxxxxxx, 249-258.

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

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

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

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

20) Matsushima, X., Xxxxxxxx, X., Xxxx, X., Sugimura, X. (1976), A Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Activation Xxxxxxx, xx: In xxxxx Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, xxx. X. J. xx Xxxxxx xx xx. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Xxxxxx, B. X., Xxxxxx, X. X., Xxxxxxx, X. X., Gatehouse, D. X., Xxxxxx, G. X., Mackay, X. X., Xxxx, X. X. (1992), Alternatives xx Xxxxxxx 1254-xxxxxxx X9 xx xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

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

23) Xxxxxxx, X. X., Xxxxx, X., Xxxxxxx, A., Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X. (1987), Guide xxx xxx Salmonella xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Tests xxx Xxxxxxxxx Xxxxxxxxxxxx, Mutatation Xxx., 189, 83-91.

24) Xxxxx, G. A. X., Green, X. X. X., Middleton, X., Xxxxxxx, X., Xxxxxxxx, X. D., Xxxxxx, X. X. (1989), Xxxxxxxx xx Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, xx. Xxxxxxxx, X. X., Cambridge University Xxxxx, 28-65."


XXXXXXX 4X

"X.17 XXXXXXXXXX — ZKOUŠKA XX XXXXXX XXXXXX V XXXXXXX XXXXX IN XXXXX

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx XXXX TG 476 — Zkouška xx xxxxxx xxxxxx v xxxxxxx xxxxx xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx lze xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx látkami. Xxxx xxxxxx xxxxxxx linie xxxxx xxxxx xxxxxxx X5178X xxxx, buněčné xxxxx XXX, XXX-XX52 x X79 křečka xxxxxxxx a xxxxxxxxxxxxxxx xxxxx TK6 xxxxxxx (1). U xxxxxx xxxxxxxxx linií jsou xxxxxxxxxxxxxxx mírou genetických xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (TK) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (HPRT) x transgen xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx xx xxxxxx XX, XXXX x XXXX detekují xxxxx xxxxxxxx genetických xxxxxxxx. Xxxxxxxxxxx xxxxxx XX x XXXX xxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx (např. xxxxxxxx delece), xxxxx xxxxx xxxxxxxxx x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx mutace v xxxxxxx xxxxx xx xxxxx lze xxxxxx xxxxxxx zavedených linií xxxxx nebo buněčné xxxxx. Buňky xx xxxxxxxx xxxxx xxxxxxxxxx xxxxx x xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační xxxxxx nemůže xxxxx xxxxxxxxx podmínky xx xxxx x xxxxx. Xx xxxxx se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x pozitivním výsledkům, xxx neodrážejí xxxxxxx xxxxxxxxxx. X pozitivním xxxxxxxxx, jež xxxxxxxxxx xxxxxxx xxxxxxxxxx, xxxx xxxxx změnou pH, xxxxxxxxxx xxxx vysokých xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx se používá xx xxxxxxxx xxxxxxx xxxxxxxx a xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx něž xx xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx xxxxx; xxxx xxxxx xxxxxxxx x karcinogenitou však xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx důkazy x xxx, xx xxxxxxxx xxxxxxxxxxx, které xxxxxx xxxxxxxx xxxxx zkouškou, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx mechanismy, xxxxx x xxxxxxxxxxxxx buňkách xxxxxxxxxx (6).

Xxx xxxx xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxx xxxxxxxxxx xxxx xxxx : xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxx xxxx xxxx x XXX.

Xxxxxxxx mutageny : xxxxx, xxxxx xxxxxxxxx xxxxx nebo xxxxxx xxxxxxx xxxx více xxxx bází x xxxxxxxx DNA.

Doba xxxxxxx xxxxxxxx : doba, xxxxx xxx xxxxxx x xxxx xxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx.

Xxxxxxx xxxxxxx : xxxxx xxxxxxxxxxxx mutantních xxxxx dělený počtem xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxx xxxxxxx xxxx : nárůst xxxxx xxxxx x xxxx xx xxxxxxxx x xxxxxxxxx populací xxxxx; xxxxxxx xx xxxx xxxxxx xxxxxx xxxxxxxxx růstu v xxxxxxxx x x xxxxxxxxx xxxxxxxx a xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxx xxxx v xxxxxxxx : xxxxxx xxxxx xxxxx x xxxxxxx xxxxxxx xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxxxxxxxx : účinnost xxxxxxxxx xxxxx x okamžiku xxxxxxxx na xxxxx xx selektivních xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx na xxxxx xx xxxxx xxxxxx xxxxxxxx; přežití xx xxxxxxx vyjádřeno x xxxxxx k xxxxxxx xxxxxxxxx xxxxxxxx xxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxx, xxxxx x xxxxxxxx mutace TK+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx k xxxxxxxxxxxx xxxxxxx analogu pyrimidinu xxxxxxxxxxxxxxxxx (TFT). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx xx XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxx další buněčné xxxxxx. Mutantní buňky xxxx xxxx xxxxxxx xxxxxxxxxxx xx přítomnosti XXX, xxxxxxx xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx schopnost xxxxxx. Podobně xxx x xxxxx s xxxxxxxxxxxx HPRT xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (TG) xxxx 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx xxxxx xx xxxx být pečlivě xxxxxxx, xxxxxxxx je xx zkoušce na xxxxxx xxxxxx v xxxxxxx xxxxx zkoušen xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx například vyšetřeno xxxxxxxx xxxxxxxxx xx xxxxxxxxxx toxicitu zkoušené xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx chemických xxxxx, které xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, musí xxxx být xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxx xxx xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx xxxxxxxxxxxxx kultuře xxxx vhodnou xxxx xxxxxxxxx xxxxxxxx látce xxx s xxxxxxxxxxxx xxxxxxxx, tak xxx xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx exprese fenotypu xxxx selekcí xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx obvykle xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx xx xxxxxxx x xxxxxxxx xxxxx po vhodnou xxxx charakteristickou pro xxxxx xxxxxxx xxxxx x typ buněk, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx mutací. Četnost xxxxxxx se xxxxxxx xxx, xx xx xxxxxx známý počet xxxxx xx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx mutantních xxxxx a xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx účinnost xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx se xxxxxxxxx kolonie. Četnost xxxxxxx xx xxxxxxx x xxxxx mutantních xxxxxxx v xxxxxxxxx xxxxx x počtu xxxxxxx x xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x této xxxxxxx xxxx k xxxxxxxxx xxxxx typy xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, XXX, CHO-AS52, X79 xxxx TK6. Xxxx buněk x xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx být xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, x x xxxxxxx kontaminace xx xxxxxx xxx xxxxxxx.

Xxxxxxx by xxxx xxx xxxxxxxx xxx, xxx xxxx předem xxxxxxxxxx citlivost x xxxx. Počet xxxxxxxxx xxxxx, xxxxxx a xxxxxxxxxxx xxxxxxxx xxxxx xx měl tyto xxxxxxxxxx parametry odrážet (14). Minimální xxxxx xxxxx, které xxxxxxx xxxxxxxx a xxxxx xxxxx použity x xxxxxx xxxxxx xxxxxxx, xx měl xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx mutací. Xxxxxxx xxxxxxxxx je, xxx xxx xxxxxx počet xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx xxxx xxxxxxxxxx, xxx xxxx xxxxxxx xxxxxxx 106 xxxxx. Xxxx xx xxx x dispozici xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx hodnota xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx měla xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx podmínky (kultivační xxxxxx, xxxxxxxxxxx CO2, xxxxxxx x xxxxxxx). Xxxxx xx xxxx xxx zvolena podle xxxxxxxxxx xxxxxxx x xxxx xxxxx xxxxxxxxx xxx zkoušce. Xx xxxxxxx důležité, aby xxxxxxxxxx podmínky xxxx xxxxxxx xxx, aby xxxx zajištěny xxxxxxxxx xxxx xxxxx xxxxx xxxxxx exprese a xxxxxxxxx xxx xxxxxxxxxx, xxx xxxxxxxxxxxx buněk xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx xx měly xxx xxxxxxxxx z xxxxxxxxx kultur, nasazeny xx xxxxxxxxxxxx xxxxx x xxxxxxxxxx při 37 °C. Xxxx xxxxxxxx v této xxxxxxx xxxx xxx xxxxxxxx xxxxxxxxx z xxxxxxx již přítomné xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by měly xxx vystaveny xxxxxxxx xxxxx, a xx x vhodným systémem xxxxxxxxxxx xxxxxxxx x xxx xxxx. Xxxxxxxxxx xxxxxxxxxx systémem xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, jako xx Xxxxxxx 1254 (15, 16, 17 x 18), xxxx xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (19, 20).

Postmitochondriální xxxxxx xx x konečném xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx v koncentracích 1 — 10 % xxx. Volba x stav metabolického xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx látky, xxxxx xx xxxxxxxx. V xxxxxxxxx případech xxxx xxx xxxxxx použít xxxx xxx xxxxx xxxxxxxxxxx postmitochondriální frakce.

Řada xxxxxxxx xxxxxx, včetně xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx buněčných xxxxx xx měla být xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxxxxx látky

Pevné zkoušené xxxxx xx xxxx xxx xxxx aplikací xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx a/nebo xxxxx xxx xxxx xxxxxxxx zředěny. Měly xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, a mělo xx xxx xxxxxxxxxx x xxxxxxxx buněk x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx nestálých xx vodě xx xxxx xxx xxxxxxx xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxx koncentrace, xxxxx cytotoxicita, xxxxxxxxxxx x xxxxxxxxxx systému x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx aktivací x xxx xx x hlavním experimentu xx xxxxxxx vhodných xxxxxxxxxx buněčné integrity x xxxxx, jako xxxx xxxxxxxxx účinnost xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx být xxxxxxx xxxxxxxx cytotoxicitu a xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx alespoň čtyři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx rozmezí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx bude xxxxxxx xxxxxxxx, xx xx se xxxxxxxxxxx xxxx lišit xxxxxxxx 2 xx Ö10. Xx-xx maximální xxxxxxxxxxx xxxxxxxx xx xxxxxxxxxxxx, xxxx xx xxx xxxxxxxxx přibližně 10 — 20 % (xxx nejméně 10 %) přežití (relativní xxxxxxxx klonování) xxxx xxxxxxxxx xxxxxxx xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx maximální xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, xxxxx x xxxx je xxxxxxxx.

Xxxxxxxxx nerozpustné látky xx xxxx xxx xxxxxxxx xx x xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx xxxxxxxx, nebo xx xx xxxx xxx. Xxxx by xxx xxxxxxxxx případná xxxxxxxxxxxxx x xxxxxxxx xxxxx, xx xxxxxxx xxxx buňky xxxxxxxxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxx na xxxxxxx x xx xxxxx aplikace, xxxxx xxxxxxxxxxx xx může x xxxxxxx expozice x xxxxxxxxxx xxxxxxx xxxxx x důsledku xxxxxxxxxxx buněk, S9 xxxx, atd. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx být xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx jak s xxxxxxxxxxxx aktivací, tak xxx xx. Při xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxxxxx chemická xxxxx, která x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxxx kontroly xxxxx xxx tyto xxxxx:

Xxxx metabolické xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx podle Xxxxxx

Xxx xxxxxx metabolické xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx x xxxxx xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx metabolickou xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (xxxx a xxxxx kolonie)

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid monohydrát

6055–19–2

benzo[a]pyren

50–32–8

200–028–5

3-methylcholanthren

56–49–5

200–276–5

XPRT

N-nitrosodimethylamin (xxx xxxxxx xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

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

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx médiem xxxxxxxxxxx xxxxxxx rozpouštědlo xxxx xxxxxxxxx x xxxxxxxxxx jinak xxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Kromě toho xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx látce

Proliferující xxxxx xx měly xxx xxxxxxxxx zkoušené xxxxx xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx něho. Xxxxxxxx xx měla xxxxx vhodnou xxxx (xxxxxxx je xxxxxx xxxx 3 xx 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx xxxxx xxxx více buněčných xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx mohou být xxxxxxx duplicitní xxxxxxx xxxx xxxxx xxxxxxxxxx xxxxxxx. Xx-xx xxxxxxx xxxxx kultura, měl xx xxx xxxxx xxxxxxxxxxx zvýšen tak, xxx xxx xxxxxxxx xxxxxxxxxxxx počet xxxxxx xxx analýzu (xxxx. xxxxxxx osm xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx xxxxxxx duplicitní xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

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

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx konci xxxxxxxxx xxxx se buňky xxxxxxx a xxxxxxxxx xx účelem xxxxxxxxx xxxxxxx a za xxxxxx umožnění xxxxxxx xxxxxxxx mutantu. Xx xxxxxxxxxx cytotoxicity prostřednictvím xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxxx xxxxxxxxx růstu xxxxxx xx xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx minimální xxxxxx xxxxxx, aby xxxxxxx xxxxxxxxx optimální fenotypovou xxxxxxx xxxx xxxxxxxxxxxx xxxxxxx (HPRT x XXXX xxxxxxxx alespoň 6 až 8 xxx, XX xxxxxxx xxx xxx). Xxxxx xxxx xxxxxxxxxxx x xxxxx xx xxxxxxxxx xxxxxxxx (selekčními xxxxxxx) x xxx xxxx (xxx xxxx) xx xxxxxx stanovení počtu xxxxxxx x xxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx četnosti xxxxxxx) xx xxxxxxx na xxxxx xxxx exprese xxxxxxxxx xx misku xxx selekčního xxxxxxx.

Xx-xx xxxxxxxx látka xxxxxxxxx xx xxxxxxx X5178X XX+/-, xxxx xx xxx xxxxxxxxx xxxxxxx xx xxxxx ze xxxxxxxxxx xxxxxx (s xxxxxxxx pozitivní koncentrací) x na xxxxxxxxxxx x xxxxxxxxxxx kontrolách xxxxxxxxx xxxxxxx podle xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx látka ve xxxxxxx X5178X XX+/- xxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxx xxxxx velikosti kolonií xxxxxxxxx na negativních x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 XX+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx velikosti xxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xx měly xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, počtu xxxxxxx x xxxxxxxx mutantů xxx xxxxxxxxxx a xxxxxxxxx kultury. X xxxxxxx pozitivní odpovědi xx zkoušku L5178Y XX+/- xx xxxxxxx xxxxxxxxx alespoň x xxxxx xxxxxxxxxxx zkoušené xxxxx (xxxxxxxx pozitivní xxxxxxxxxxx) x u xxxxxxxxx x xxxxxxxxx xxxxxxxx za použití xxxxxxxx xxxx xxxxxxx — xxxxx xxxxxxx. Xxxxxxxxxxx a xxxxxxxxxxxxx xxxxxx xxx mutantů xxxxxxxxx velké xxxxxxx, xxx mutantů tvořících xxxx kolonie xxxx xxxxxxxx xxxxxxxx (23, 24). Ve xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxx (velká) x kolonie x xxxxxxx růstem (xxxx) (25). U mutantních xxxxx, které utrpěly xxxxxxxxxxxxxx genetické xxxxxxxxx, xx prodloužily doby xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx obvykle xxxxxx xx ztrát xxxxxx genu xx xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx xxxxxxxxx xxxx xxxxxxx se xxxxxxx x xxxxxxxxxx xxxxxxx, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx postižené xxxxx xxxxxxx xxxxxx xxxxxxxx tempem xxxx xxxxxxxx buňky x xxxxx xxxxx kolonie.

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

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

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx musí xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, xxx xxxx potvrzení negativních xxxxxxxx považováno xx xxxxx, xx xxxxx xxxxx xxxxxxxxxx. Změna xxxxxxxxx xxxxxx x xxxxx rozšířit rozsah xxxxxxxxxxxx podmínek xx xxxx xxx zvážena x následných xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx výsledky. K xxxxxxxxxx xxxxxx, xxxxx xx mohly xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx a xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx xxxxxxxx xxxxxxx x závislosti xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Xxxxxxxx by xxxx být uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx mohou xxx xxxxxxx jako pomocný xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx významnost xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx znamenají, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx kultivovaných xxxxxxx savců xxxxxx xxxxxx. Reprodukovatelná xxxxxxxxx xxxxxxxxx odpovědi na xxxxxxxxxxx je velmi xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Xxxxx:

- xxx x zdroj xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx buněčné kultury,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- složení xxxxx, případně xxxxxxxxxxx XX2,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- případně hustota xxxxx xxxxx expozice,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxx xxxx xxxxxxx (xxxxxxxx xxxxxx xxxxx nasazených xxxxx, subkultur a xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- xxxxxxxx klasifikace xxxxxxx na xxxxxxxxx, xxxxxxxxx nebo dvojznačnou,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx buněk,

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

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx x pH x xxxxxxxxxx během xxxxxxxx xxxxxxxx xxxxx, pokud xxxx stanoveny,

- velikost xxxxxxx, xxxx-xx vyšetřována, xxxxxxx xxx xxxxxxxxx x xxxxxxxxx kontroly,

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

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

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

- xxxxxxxxx xxxxx x negativní (rozpouštědlo/vehikulum) x pozitivní kontrole x xxxxxxxxx, středními xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X., XxXxxxxx, X. X., DeSerres, X. J., Tindal, X. X. (xxx.) (1987), Banbury Xxxxxx 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Cold Xxxxxx Xxxxxx Laboratory, New Xxxx.

2) Chu, X. X. Y., Xxxxxxx X. V. (1968), Xxxxxxxxx Xxxx Xxxxxxxx. XX. Chemical Xxxxxxxxx xx Xxxxxxxx Xxxxx Xxxxxxxxx in Xxxxxxx Xxxxxxx Xxxxx In xxxxx, Xxxx. Xxxx. Xxxx. Xxx. X. X. X, 61, 1306-1312.

3) Xxxxx, H. X., Thilly, W. X. (1982), Xxxxxxxx Xxxxx xx xxx Xxxxxxxxx Xxxxxx Locus xx Diploid Xxxxx Xxxxxxxxxxxx, Xxxxxxxx Xxx. 94, 467-485.

4) Xxxxx, X. X., Xxxxxxxxx-Xxxxx, X., Doerr, C. X., Xxxxxxxxx, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx xx xxx Xxxxx Xxxxxxxx XX xxx CHO XXXXX Xxxx, Mutagenesis, 4, 394-403.

5) Xxxxx, X. X., Stankowski, Xx. X. X., (1989), Xxxxxxxxxx xx xxx XX52/XXXX and xxx XXX/XXXX Assays: Xxxxxxxxxx xx Xxx Xxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx. 223, 121-128.

6) Xxxxx, X. X., Xxxxxxxxxx, X., Glatt, X. X., Xxxxx, X., Xxxxx, Y., Xxxxxxxxxx, Xx. X. X., Xxxxxx, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Xxxx Xxxxxxxx Xxxxxx Working Xxxxx Xxxxxx. Xxxxxx xx xxx International Xxxxxxxx on Standardisation xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

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

8) Xxxxx, X., XxXxxx, X., Spector, J. X. X., Xxxxx, X., Mavournin, K. X. (1983), Specific Xxxx Xxxxxxxxx xx X5178X Xxxxx xx Xxxxxxx. X Xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 115, 225-251.

9) Xx, X. X., Gupta, X. X., Xxxxxxx, R. X., Wasson, X. X. (1988), X Xxxxxx and Analysis xx the Chinese Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx System xx Xxxxxxxxx xxx Xxxxxxxxxxxx of Xxxxxxxx Xxxxxx: A Xxxxxx xx Xxxxx XXX xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Li, X. X., Xxxxxx, X. X., Xxxx, X. X., Hsie, X. X., Gupta, R. X., Loveday, X. X., O'Νeill, X. X., Xxxxxx, X. X., Stankowski, X. X. Xx., Xxxx, X. L. (1987), X Xxxxx for xxx Xxxxxxxxxxx xx xxx Chinese Xxxxxxx Xxxxx Cell/Hypoxanthine-Guanine Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Xxxxx, X. L., Yandell, X. W., Xxxxxx, X. X. (1989), X Xxxxxxxxxx of Xxxxxxxx Induction at xxx XX and XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx xx an Xxxxxxxxxx Class of Xxxxxxxxx xx the Xxxxxxxxx XX Locus, Xxxxxxxxxx Xxx., 216, 9-17.

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

13) Xxxxxx, N. X., Xxxxxx, X. G., Xxxxx, X. (1984), Xxxxxxxxx xxx xxx X5178X/XX+/--XX+/- Mouse Xxxxxxxx Xxxx Xxxxxxxxxxxx Xxxxx, xx: Xxxxxx, X. X. xx xx (xxx.) Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx, Xxxxxxxx Science Xxxxxxxxxx, Xxx York, 239-268.

14) Xxxxxx, C. F., Xxxxx, D. X., Xxxxxx, X. X., Xxxxx, X. X. X., Xxxx, X., XxXxxxxx, X. X., Xxxxxxx S. X. (1989), Xxxxxxxxx Cell Xxxx Mutation Xxxxxx Xxxxx upon Xxxxxx Xxxxxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, Kirkland, X. X., xx., Xxxxxxxxx University Xxxxx, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, X., Corti, X., Fiorio, R., Xxxxxxxx, N., Mazzaccoro, X. (1977), Induction xx 6-Xxxxxxxxxxx-Xxxxxxxxx Xxxxxxx xx X79 Xxxxxxx Xxxxxxx Xxxxx by Xxxxx-Xxxxx Microsome-Activated Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Res. 46, 365-373.

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

17) Xxxxx, X., Xxxxxxx, X. X., Xxxxxxx, X. F. S., Xxxxxx X. X., Xxxxx M. M. X. (1979), Xxxxxxxxxx xxx Xxxxxxxxxxxxxxxx of xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Xxxxx Xxxxxx, Xxxxx. Xxx. 59, 61-108.

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

19) Xxxxxxx, B. X., Combes, X. X., Elcombe, X. X., Xxxxxxxxx, D. X., Gibson, X. X., Mackay, X. X., Wolf, R. X. (1992), Alternatives xx Xxxxxxx 1254-Induced X9 xx: In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, T., Sawamura, X., Xxxx, K., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx of Xxxxxxxxx Xxxxxxxxxx Systems, X: Xx xxxxx Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, de Xxxxxx, X. X., Xxxxx, X. X., Xxxx, X. X., Philpot, X. X. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. X., Xxxxxx, F. X., XxXxxxx, K. T. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. M. (xxx), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

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

23) Xxxxxxxxx, X. X., Xxxxx, X. X., Broder, X. X., Burrell, X., Xxxxxx, J. X. (1990), Xxxxxxxxx Xxxxxxxxxx of Xxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxx Kinase Locus xx Xxxxx Xxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. U. X. A, 87, 51-55.

24) Moore, X. X., Clive, X., Xxxxxx, J. C., Xxxxxx, X. E., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (XXX+) Mutants xx L5178Y/TK+/--Mouse Lymphoma Xxxxx, Xxxxxxxxxx Xxx. 151, 161-174.

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

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


XXXXXXX 4X

"X.23 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx in xxxx xx xxxxxxxxxxxxx xxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx xx spermatogoniích xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Tato xxxxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx účelu xxxxxxx používána. Xxxxxxxxxxxx xxxxxx a podobné xxxx xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx.

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

X xxxx zkoušce xxxx rutinně xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx in vivo xx xxxxxxxx chromozomové xxxxxxx při mitose xxxxxxxxxxxxx. Xxxx cílové xxxxx nejsou předmětem xxxx xxxxxxx.

Xxx detekci xxxxxxx chromatidového xxxx xx spermatogoniích xx xxxx xxx — xxxxx než xxxxx xx xxxxxx xxxx — vyšetřeno první xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx po xxxxxxxx. Xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx buněk xxx xxxxxx meiotickou chromozomovou xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx v xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx stávají xxxxxxxxxxxx.

Xxxx zkouška xx xxxx je navržena xxx xxxxxxxxx, zda xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx také x germinálních buňkách. Xxxxx je xxxx xxxxxxx xx spermatogoniemi xxxxxxxx pro xxxxxxxxx xxxxxxxxx mutagenese, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x procesy xxxxxxxx XXX.

Xx varlatech xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx s xxxxxx xxxxxxxxxx na xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxxxx xxxxxxx tedy xxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx spermatogonií x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx xxxxxx xx xxxxxxxxx, mohou xxxx xxxxxx xxx xxxxx generace xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x xxxxxxx mezi xxxxxxx oběhem x xxxxxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, že xx xxxxxxxx xxxxx xxxx xxxxxxxxx metabolity xxxxxxxxxx do xxxxxx xxxxx, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx xxxx zlomu x xxxxxxx xxxx chromatid x xxxxxx místě.

Gap : achromatická xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx x x minimální xxxxxxxxx xxxxxxxxx.

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

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

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

1.3 XXXXXXXX XXXXXXXX METODY

Zvířata xxxx xxxxxxx způsobem exponována xxxxxxxx xxxxx x xx xxxxxx době xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xxxx používáni xxxxx xxxxxx čínského a xxxx; xxx xxxx xxxxxx samce jakéhokoli xxxxxx xxxxxxxx xxxxx xxxxx. Xxxx xx xxx xxxxxxx běžně xxxxxxx laboratorní xxxxx xxxxxxx zdravých pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

Xxxxx obecné podmínky xxxxx obecného úvodu x části X, xxxxxxx by xxxx xxx dosaženo vlhkosti xxxxxxx 50 – 60 %.

1.4.1.3 Příprava xxxxxx

Xxxxxx mladí xxxxxxxx xxxxxxx samci xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx skupinu x skupinu, xxxxx xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx tak, aby xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx započetím xxxxxx xx xxxxxxx x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx před xxxxxxxx xxxxxxxx rozpuštěny nebo xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx podávány xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx x stálosti neprokazují xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx xxx při xxxxxxxxx xxxxxxxxx dávek xxxxxxx účinky a xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx experimentu xx xxxx být souběžné xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx aplikace xxxxxxxx xxxxx xx měla xxxxxxx kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v nichž xxxxx k expozici.

Pozitivní xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, u nichž xx xxxxxxxxxxx, xx xxxxxxxxx detekovatelný xxxxxx xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx xx měly xxx zvoleny tak, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx látka x xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx kontrolu xxxx být xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou-li k xxxxxxxxx. Xxxxxxxx látek xxx pozitivní kontrolu:

Látka

Číslo XXX

Xxxxx podle Einecs

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxx (monomer)

79–06–1

201–173–7

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

51–18–3

200–083–5

V xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx u xxxxxxx negativní kontroly, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx nejsou x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx údaje o xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx aberacemi. Kromě xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxx xxx analyzovatelných xxxxx.

1.5.2 Xxxx expozice

Zkoušené xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. xxx xxxxx xxxxxxxx xxxx xxxx xxxxxxxxxx). Xxxxxxxx látky xxxxx být xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx v xxx xxx x xxxxxxx xx více než xxxxxxxx hodin, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx režimy xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx skupině x nejvyšší xxxxxx xx xxxx xxx xx expozici xxxxxxxxx xxx odběry. Xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx jeden xxxxx xxxxx x xxxxx xxxxxxxx odběr přibližně 24 a 48 xxxxx xx xxxxxxxx. X xxxxxxx jiné xxx xxxxxxxx dávky xx xxx být xxxxx proveden po 24 xxxxx xxxx xx takové xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx délky xxxxxxxxx xxxxx, pokud xxxx xxxxx jiná xxxxxxxxx xxxx xxx detekci xxxxxx (6).

Xxxxx xxxxx xxx xxxxxx xxxxxxxxx xxxx x jiné xxxx. Xxxxxxxxx x xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) xxxxxxxxxx xxxx mohou xxxxxxxxxx S-nezávislé účinky, xxxx xxx xxxxxxxxx xxxxxxxx xxxxx (1).

Vhodnost xxxxx xxxxxxxxx xxxxxxxx xxxx xxx xxxxxx xxxxxx xx případu. X případě xxxxx x opakovanou xxxxxxxx xx xxxx být xxxxxxx usmrcena 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) xx poslední xxxxxxxx. Xxxxx xxxxxxx xxxxx xxx xxxxxxxxx xxxxx xxxxxx x xxxx xxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx době xxxxxxx u zvířat xxxxx. U xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx čínského xx xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx, xxxx xx xxx xxxxxxxxx xx stejné xxxxxxxxxx, xx stejným xxxxxx a kmenem x xx xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx xxxxxxx v xxxxxx studii (7). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Tyto xxxxxx dávky xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xx xxxxx xxxxx vedly xxx stejném xxxxxx xxxxxxxxx podle očekávání x letalitě.

Látky se xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx xxxxxxx netoxických xxxxxxx (xxxx. hormony x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx xx být xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xxxxx může xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxx spermatogonií x mitose xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx xx xxxxxx překročit 50 %).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou xxxxxx alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx jednorázově nebo xx dvou xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx účinky x xxxx-xx xx xxxxxxx xxxxx o xxxxxxx, xxxxx mají xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx úplná xxxxxx xx třemi xxxxxxxx xxxxx za xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx může xxxxxxxx xxxxxxx použít v xxxxxxx zkoušce xxxxx xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx se xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx přijatelné, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, který může xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, musí xxx xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx xxxxxxx koncentracích xxxxxxxx zesílené xxxxxx, xx měla být xxxxxxxxxxx zkoušeného xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx úrovních xxxxx.

1.5.6 Příprava xxxxxxxxx xx analýzu xxxxxxxxxx

Xxxxx xx xxxxxxxx xx x xxxxxxx nebo xxxx xxxxxx získá xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxx se xxxxxx xx xxxxxxxx sklíčka x xxxxxx se.

1.5.7 Xxxxxxx

X každého zvířete xx xxxx být xxxxxxxxxxx alespoň 100 xxxxx x xxxxx xxxxxxxxxxxx metafázi (xx. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Tento xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx xxxxxxx. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při fixaci xxxxx xxxxxxx xx xxxxxxxxxxxxxx zlomům xxxx xxxxxx chromozomů u xxxxx xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx xxxxxxxxxxxxxx číslu 2 n ± 2.

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx měly xxx xxxxxxxxxx xx xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx xxxxx xxxxx xx xxx být xxxxxxxxxx počet buněk xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx a xxxxx xxxxxxxxxxxxxx xxxxxxx na xxxxx. Xxx xxxxxxxxxx x kontrolní xxxxxxx xx měly xxx xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Gapy xx xxxxxxxxxxxxx odděleně x uvádějí se, xxx obecně xx xxxxxxxxxx do xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx pozorována xxxxxx x xxxx xxxxxx, měl by xxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxxxxx účinků xxxx xxxx xxxxxxxxxxxx xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx k první x xxxxx meiotické xxxxxxxx, x to x celkovém xxxxxx 100 dělících se xxxxx xx xxxxx xxxxx. Xxxxx je xxxxxxxxx pouze xxxxxx, xxxxxxx v 1000 xxxxxxx xx xxxxx xx xxx xxx xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx na xxxxx xxxx xxxxx nárůst xxxxx xxxxx x xxxxxxxxx xxx skupinu x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx být xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx většina experimentů xxxxxxxx jasně xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez xxxxxx xx to, kolikrát xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx zkoušky na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx savců xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx druhu xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx xxxxxxxx do xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet x xxxxx xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx atd.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx zkoušky, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx pro xxxxxx skupinu.

Zkušební xxxxxxxx:

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

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx mezi koncentrací xxxxxxxx xxxxx x xxxxxx xxxx xxxx (xxx) na xxxxxxxxxxxx xxxxx (xx/xx tělesné xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x odběru,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxxx xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx index,

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

- typ x xxxxx aberací uvedený xxxxxxxxxx xxx xxxxx xxxxx,

- celkový xxxxx xxxxxxx ve skupině,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxx, xxxxx byly pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Spermatogonia of Xxxxxxxx Xxxxxxxx Related xx their Cell-Cycle Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxxx Xxxxxxxxx, Part X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Xxxxx, X., Xxxxxxx, B., Xxxxxxxxx, X. (xxx) Xxxx, Xxx Xxxx, 477-484.

2) Adler, X. X., (1984), Xxxxxxxxxxx xxxxx xx Xxxxxxx, xx: Mutagenicity Testing: x Xxxxxxxxx Approach, (xx.) X. Venitt, X. M. Xxxxx, XXX Xxxxx, Xxxxxx, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, E. X., Xxxxxxx, G., Ford, X. E. (1964), Xx Xxx-xxxxxx Method xxx Meiotic Xxxxxxxxxxxx xxxx Mammalian Testes, Xxxxxxxxxxxx Xxxx Genetics, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, A., Gatehouse, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Part I xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

5) Xxxxxxxx, X., Xxxxxxx, X. (1978), A Xxx Xxxxxx xxx Xxxxxxxxxxx of Mammalian Xxxxxxxxxxxxxx Xxxxxxxxxxx, Mutatation Xxx., 52, 207-209.

6) Xxxxx, I. X., Xxxxxx X. X., Xxxxxxx, J., Xxxxx, X., Generoso, W., Xxxxxxxxxxxx, X., Xxxxxxx, X., Tanaka X. (1994), Xxxxxxxxxxxxx Workshop xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Test Procedures. Xxxxxxx Xxxxxx xx xxx Xxxxxxx Xxxxx xx Mammalian Germ Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

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

8) Xxxxxx, D. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Savage J. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx of Xx xxxx Xxxxxxxxxxx Xxxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4G

"B.39 XXXXXXX XX XXXXXXXXXXXX SYNTÉZU XXX (UDS) X XXXXXXXXX XXXXXXX XXXXX XX VIVO

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 486 — Zkouška xx neplánovanou xxxxxxx XXX (UDS) x xxxxxxxxx xxxxxxx savců xx xxxx (1997).

1.1 XXXX

Xxxxxx zkoušky xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx xxxxx in xxxx je identifikovat xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxx DNA x jaterních xxxxxxx xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

Xxxx xxxxxxx in xxxx xxxxxxxxx xxxxxx vyšetření xxxxxxxxxxxxx xxxxxx chemických xxxxx x xxxxxxx. Xxxxxxxxxxx xxx je xxxxxxxxxx xxxxxxxxx XXX x následné xxxxxxxx x jaterních xxxxxxx. Xxxxx xxxx obvykle xxxxxxx xxxxxx, kde xxxx absorbované sloučeniny xxxxxxxxxxxxxx. Jsou xxxx xxxxxxx xxxxxx xxx xxxxxxxxx míry poškození XXX in xxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, že xx xxxxxxxx xxxxx nedostane xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx použít.

Rozsah xxxxxxxxxxx xxxxxxx DNA (XXX) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx značených xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx syntézou XXX (X-xxxx). Nejrozšířenější xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx thymidinu xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx na XXX in xxxx xx přednostně používají xxxxx xxxxxxx. Jiné xxxxx xxx xxxxx xxxxx xxx rovněž xxxxxxx, xxxxxx však xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX závisí xx xxxxx xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx v xxxxx xxxxxxxxx. Xxxxxxx xx XXX xx tedy xxxxxx xxxxxxx pro xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx xxxxxx") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("xxxxx-xxxxx repair") (xxxxx xx xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx reparace, chybné xxxxxxxx xxxx chybné xxxxxxxxx xxxx DNA xxxxx x xxxxxxxxxx xxxxxxxxx. Xxxxxx odpovědi XXX xxxxxxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, že xxxxxxx xxxxxxx s XXX, xxx poškození XXX není xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, které xxxx xxxxxxx xxxxxxxxx x xxxxxxxxx aktivitě, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxx, xxxxx xx xxxxxxxxxx x celém xxxxxx.

Xxx xxxx obecný xxxx, xxxx B.

1.2 XXXXXXXX

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

Čistý xxxxx xxx xxxxxxxxxxxxxx buněčným xxxxxx (XXX) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx buněk x xxxxxxxxxxxxxxxxx xxxxxxx na XXX, vypočtená xxxxxxxxx xxxxxxxxxx počtu zrn x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) xxxxxxxxxxxxxx jádrům xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): XXX = XX — CG. Xxxxxxx XXX xx xxxxxxx pro jednotlivé xxxxx, poté xxxxxxxx xxx buňky x xxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx syntéza XXX (UDS) : Xxxxxxx xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx úseku XXX xxxxxxxxxxxx region s xxxxxxxxxx xxxxxxxxxxx chemickými xxxxxxx xxxx xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x jaterních xxxxxxx xxxxx in xxxx xxxxxxxx xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx činiteli. Xxxxxxx xx obvykle založena xx xxxxxxxxxxx 3X-XxX xx DNA xxxxxxxxx xxxxx, kde je xxxx četnost xxxxx x X-xxxx xxxxxxxxx xxxxx. Xxxxxxxxxxx 3H-TdR xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx xxx xxxxxxx na xxxx X-xxxx buněk jako xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx používán xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx vhodný xxxx xxxxx. Měly xx být xxxxxxx xxxxx používané laboratorní xxxxx mladých zdravých xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x neměla xx xxxxxxxxx ± 20 % střední xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx xxxxxxxx. Klece xx xxxx xxx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx identifikují x před započetím xxxxxx xx xxxxxxx x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx vehikulech a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx podávány xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx při použitých xxxxxxxx xxxxx xxxxxxx xxxxxx x mělo xx být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx použita xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx podloženo xxxxx o jejich xxxxxxxxxxxxx. Doporučuje se xxxxxxxx zvážit xxxxxxx xxxxx možno xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každé xxxxxxxxx prováděné xxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx x negativní (rozpouštědlo/vehikulum) xxxxxxxx. S xxxxxxxx xxxxxxxx zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny podstoupit xxxxxx proces jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx měly xxx xxxxx, x xxxxx xx xxxxx, xx xxxxxx podávání v xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx x xxxxxxx xxxxxxxxxxxx mírnou odpověď (4). Xxxxx xxxxx xxx zvoleny xxx, xxx byl xxxxxx xxxxxxxx, ale xxx xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx CAS

Číslo xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 xx 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx xxxx xxxxxx (12 xx 16 x)

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

53–96–3

200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx xxxxx xxx xxxxxxxxx xxxxxxxx. Je xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxx xxxxx způsobem, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxx by xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, xxx xxxx xxxxxxxxxx přirozené xxxxxxxxxx xxxxxxxx xxxxxxxx xx zkoušku. Xxxxx xxxxxxx by xx xxxx skládat xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Jestliže xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx xxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx skupiny xxxxxxxx xxxxx xxxxx až xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx se xxxxxxx druhem x xx použití stejného xxxxxxx expozice, jež xxxxxxxxx, že neexistuje xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx jednoho xxxxxxx, xxxxxxx xxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, jako je xxxx například u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx provedena se xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

Za normálních xxxxxxxx se používají xxxxxxx dvě úrovně xxxxx. Xxxxxxxx xxxxx xx definována xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx toxicity, xx xxxxx xxxxx by xxxxx xxxxx xxxxxxxxx xxx xxxxxxx xxxxxx xxxxxxxxx k xxxxxxxx. Xxxxx xxxxx by xxxx xxx zpravidla 50 % xx 25 % xxxxx xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx by xxx hodnoceny případ xx případu. Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx dostupných údajů xxxxxx xxx xxxxxxxx xxxxxxx, xxxx by xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx se použijí x hlavní xxxxxx.

Xxxxxxxx xxxxx může xxx xxxxxxxxxx xxxx jako xxxxx xxxxxxxxxxxx známky xxxxxxxx v xxxxxxx (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx x alespoň 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx xx xxxxxxx xxxxx o xxxxxxx, xxxxx mají xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx být úplná xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x limitní zkoušce xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx jsou xxxxx, xxx-xx je xxxxxxxxx. Xxxxxxxx intraperitoneálně xx xxxx nedoporučuje, xxxxx xx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxx xxxxx přímo x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxx sondou xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx hmotnosti. Xxxxxxx vyšších xxxxxx, xxx xx uvedený xxxxx, musí xxx xxxxxxxxxx. Xx na xxxxxxxx a xxxxxx xxxxx, které xxxxxxx xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech úrovních xxxxx.

1.5.6 Příprava xxxxxxxxx xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx z xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 hodin xx xxxxxx xxxxx. Xxxxxxxxxx xxxxxxxx odebrání xxxxxx (xxxxxx xxx xx xxxxx xxxxxx xx xxxxxxxx) xx xxxxxxxx, není-li xx 12 až 16 xxxxxxxx jasná xxxxxxxxx xxxxxxx. Mohou však xxx použity jiné xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx kultury xxxxxxxxx buněk xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx jater kolagenasou xx xxxx a xxxxxx se, xxx xx čerstvě xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx z xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxx životaschopnost (5) alespoň 50 %.

1.5.7 Stanovení XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx obvykle xxxxxxx dobu, např. xxx xx osm xxxxx, xxxxxxxx s xxxxxx xxxxxxxxxxx 3X-XxX. Xx konci inkubační xxxx xx mělo xxx médium z xxxxx xxxxxxxxxx a xxxxx xxxx mohou xxx inkubovány x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx delší xxxxxxxxx xxxx xxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx se x xxxxx (xxxx. x xxxxxx 7 xx 14 dnů), xxxxxxxx xx, obarví x xxxxxxxxx xx xxxxxxxxxx zrna xxxxxxx. X xxxxxxx xxxxxxx xx připraví xxx xx tři xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx xx měly xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx normálních xxxxx, xxx xxxx hodnocení XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx se xxx xxxxxxxxxxx prohlédnou xx xxxxxx zjevné xxxxxxxxxxxx (xxxx. xx xxxxxxx, xxxxxxxx úroveň xxxxxxx xxxxxxxxxxxxx xxxxxxxx).

Xxxx počítáním xxx xx xxxx xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx xx vyšetřuje 100 buněk xx xxxxx zvíře xxxxxxx xx dvou preparátů; xxxxxxxxx xxxx než 100 xxxxx/xxxxx xx xxxx xxx zdůvodněno. Xxx xxxxxxxx xxx xx jádra x X-xxxx nevyšetřují, xxx xxxxx xxxxx v X-xxxx xxxx xxx xxxxxxxxxx.

Xxxxxxxx 3H-TdR xxxxxxxxxxxxxxx xx xxxxx x xxxxxxxxxx morfologicky normálních xxxxx doložené xxxxxxxxxxx xxx xxxxxxx by xxxx xxx stanoveno xxxxxxx xxxxxxx.

Xxxxx xxxxx xx xxxxxxx x xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrŭm (xx) x z prŭměrného xxxxx zrn v xxxxxxxxxxxxxxxxx oblastech (cg) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx xx xx xxxxxxx xxx xxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx prŭměrná xxxxxxx xxxx až tří xxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx jader. xx xxxxxxxxxxxxx zdŮvodnění xxxxx xxx xxxxxxx i xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (např. xxxxxxxx celých xxxxx) (6).

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx xxx xxxxxxx údaje pro xxxxxxxxxx xxxxxxxxx x xxxxxxx. Xxxxx xx xxxx xxx dále xxxxxxx xx xxxxx xxxxxxx. Odečtením xxxxxxx XX xx hodnoty XX xx měl xxx xxxxxxxx pro xxxxxx buňku, xxx xxxxx xxxxx x xxx xxxxxx xxxxx x čas xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (NNG). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" buňky, měla xx být xxxxxxxx xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx odůvodněna a xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, měly xx xxx xxxxxxxxxxx xxxxx xxxxxxx a xxxxxxxxxx xxxx provedením studie.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx nebo xxxxxxxxx odpověď xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX xxxx xxx xxxxxxxx xxxxxx, xxxxx xx xxxxxxxxxx xx xxxxxxx dosavadních údajů xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx pro souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx NNG xxxx xx xxxxxxxxx xxxxxxx xxxxxxx nebo xxx xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx xxxxx xxx xxxxxxx pro souběžnou xxxxxxxx.

Xxxx by xxx xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx. měly xx xxx xxxxx x xxxxx xxxxxxxxx, xxxx xxxx variabilita xxxxxx, xxxxx dávky x xxxxxxxx a xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx použity jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx však xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx XXX x xxxxxxxxx xxxxxxx xxxxx in xxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx XXX xx xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za podmínek xxxxxxx xxxxxxxxxx poškození XXX, které xxx xxxxxxxxx touto zkouškou.

Měla xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x jakou xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx. xx xxxxxx tkáně (xxxx. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Testovací xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, strava xxx.,

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

Zkušební xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (vehikulum/rozpouštědlo) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx ověření, zda xx zkoušená látka xxxxxxx xx krevního xxxxx nebo xx xxxxxx tkáně,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx xxxxx xxxxxxx expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx hodnoty počtu xxx odpovídajících buněčným xxxxxx a počtu xxx xxxxxxxxxxxxxx xxxxxxxxxx, x xxxxx počet xxx, xxxxxxxxxx xxx xxxxxxxxx, zvířata x xxxxxxx,

- podle xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- xxxxxx toxicity,

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

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

- xxxxx xxxxx "opravovaných" xxxxx, xx-xx xxxxxxxx,

- xxxxx xxxxx x S-fázi, xx-xx xxxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

1) Xxxxx, X. Xxxxxxx, X. A., Xxxxxxxxx, X., Xxxxxx, X. X. (1985), Xx Xxxxxxxxxx xx xxx Xx xxxx Xxx. Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Res., 156, 1-18.

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

3) Kennelly, X. X., Xxxxxx, X., Xxxxx, X., Xxxxxxx, X. A., Xxxxxxxxx, X., Benford, X. X., Dean, X. X., Xxxxxxxx, X. de G. (1993), Xx xxxx Xxx Liver XXX Xxxxx, xx: Kirkland X. J., Fox X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Part XX xxxxxxx, Cambridge University Xxxxx, Cambridge, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, S., Dean, X. W., Andrac, X., Xxxxxxxxx. X., Xxxxxxxxx, B., Xxxxxxxxx, X. X., Xxxxxxxx, X., Hertner, T., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx of UDS Xxxxx Xx vitro xxx In vivo, Xxxxx. Xxx., 312, 263-285.

5) Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, X. (1993), Assessment xx xxx Relation Xxxxxxx xxx Xxxxxxx Viability xxx the Xxxxxxxxxx xx Xxxxxxx Isolated Xxx Xxxxxxxxxxx Used xxx xxx Xx xxxx/Xx xxxxx DNA Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Xxx., 291, 21-27.

6) Xxxxxxxx, X. X., Xxxxx, X. X., Xxxxxxxxxxx, X. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Carcinogens xx the In xxxx/Xx vitro Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxx.Xxxxxxx. 4, 553-562."


XXXXXXX 5

XXXXXX POŽADAVKY XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX LÁTEK X PŘÍPRAVKŮ

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


XXXXXXX 6

"

PŘÍLOHA XX

XXXX X

xxxxxxxx týkající se xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 odst. 1 xxxx. x) xxxx xxxxxxxx, xxxx xxx xxxxx o xxxxxxxxx xxxxxx obsahující xxxxx, x xxxxx xx xxxxxxx xxxxxx xxx vdechování (Xn; X 65) x xxxxx xxxx xxxxxxxxxxxxx x označeny xxxxx xxxx 3.2.3 xxxxxxx XX xxxx směrnice, x xxxxxxxx xxxxx xxxxxxxxx xx xxx xx formě xxxxxxxx xxxx x xxxxxxxx xxxxxxxxxx aerosolovým xxxxxxxxxxxxx, xxxxxxxx uzávěry odolnými xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx uzavíratelné xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx požadavky xxxxx XXX 8317 (xxxxxx xx xxx 1. xxxxxxxx 1989) "Xxxxx odolné dětem — Požadavky xx xxxxxxxxx uzavíratelné obaly x xxxxxx jejich xxxxxxxx" přijatou Xxxxxxxxxxx xxxxxxxxxx pro xxxxxxxxxxx (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx dětmi použité xx opakovaně neuzavíratelných xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx dětem — Xxxxxxxxx x xxxxxxxx xxxxxxx xxx opakovaně xxxxxxxxxxxxxx obaly jiných xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Xxxxxxxxx xxxxxxx xxx normalizaci (CEN).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x výše uvedenými xxxxxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxx, xxxxx xxxxxxx xxxxxxxx normy xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx zřejmé, xx xxxx xx xxxxxxxxxx xxxxxxxx pro xxxx, xxxxx se xxxxxxx dostat x xxxxxx xxx pomoci xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx a xxxxx xxxxxxxx oprávněné xxxxxx k xxxxxxxx x bezpečnosti uzávěru xxx xxxx, xxxx xxxxxxxxxxxx xxxxx požadovat, xxx xxxxx xxxxxxxxx xx xxxxxxx výrobku xx xxx předložila xxxxxxxxxx vydaný laboratoří xxxxx xxxx. 3 xxxx 1 konstatující, xx xxx

- typ xxxxxxx je takový, xx xxx xxxx xxxxxxxx zkoušet xxxxx xxxx uvedených xxxxx XXX x CEN,

nebo

- xx xxxxxx xxx xxxxxxx a 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 ISO 11683 (xxxxxx x xxxx 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx před xxxxxxxxxx — Xxxxxxxxx".

"