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.

Směrnice Komise 2000/32/XX

xx xxx 19. května 2000,

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

(Xxxx x xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX SPOLEČENSTVÍ,

s ohledem xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx na xxxxxxxx Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx se xxxxxxxxxxx, balení x xxxxxxxxxx nebezpečných xxxxx [2], naposledy xxxxxxxxxx xxxxxxxx Evropského parlamentu x Xxxx 1999/33/XX [3], a zejména xx xxxxxx 28 xxxxxxx směrnice,

vzhledem k xxxxx důvodům:

(1) Příloha X xxxxxxxx 67/548/XXX xxxxxxxx seznam xxxxxxxxxxxx xxxxx společně s xxxxxxxxxx údaji o xxxxxxxxxxx a označování xxxxx xxxxx. Xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, xx xx xxx xxx xxxxxx nebezpečných xxxxx x xxxxxxx příloze xxxxxxxxxxx. Některé jazykové xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx x xxxxxxx X x příloze X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS obsahuje xxxxxx xxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx a xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx s bezpečnostními xxxxxx týkajícími xx xxxxxxxxxxxx látek a xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/EHS xxxxxxxx xxxxx xx klasifikaci x x xxxxxxxxxx xxxxxxxxxxxx xxxxx a xxxxxxxxx. Některé xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, XX x XX.

(3) X xxxxxxx X směrnice 67/548/XXX xx xxxxxxx xxxxxx xxx stanovení xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, xxxxxxxx x xxxxxxxxxxx xxxxx x xxxxxxxxx. Xx xxxxxxxx xxxxxxxxxxx tuto xxxxxxx technickému xxxxxxx.

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx. Xxxx předpisy xx xxxx xxx xxxxxxxxxxxx a xxxxxxxxxxxxx. Xx nezbytné xxxxxxxx xxxxxx, xxx se xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxxxx.

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

XXXXXXX TUTO XXXXXXXX:

Xxxxxx 1

Xxxxxxxx 67/548/EHS xx xxxx xxxxx:

1. Xxxxxxx X se xxxx takto:

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

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

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

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

2. Xxxxxxxxxxxx xxxx x xxxxxxx XXX xx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx v xxxxxxx 2 této xxxxxxxx.

3. Xxxxxxx XX xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx v příloze XX se xxxxxxxxx xxxxxxxxxxxx pokyny pro xxxxxxxx zacházení x xxxxxxx 3A xxxx xxxxxxxx;

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

4. Část X xxxxxxx V xx xxxx xxxxx:

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

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

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

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

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

f) xxxxxxxx B.23 xx xxxxxxxxx xxxxxx v xxxxxxx 4F xxxx xxxxxxxx. Xxxxx kapitoly X.23 xx vysvětlivce xx xxxx xxxxxxxxxxxxx xxxxxxxx;

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

5. Xxxxxxx xx xxxxxx xxxxxxx xxxxxxxx úvodu x části C xxxxxxx X.

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

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

Xxxxxx 2

1. Členské xxxxx xxxxxx v xxxxxxxx xxxxxx x xxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxxx xxxxxxx x touto xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x nich xxxxxxx Xxxxxx.

Xxxx xxxxxxxx přijaté xxxxxxxxx státy xxxx xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx xxxxxx xxxxx xxx xxxxxx při xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx xxxxxxx xxxxx.

2. Xxxxxxx xxxxx xxxxx Xxxxxx xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, xxxxx xxxxxxx x xxxxxxx xxxxxxxxxx xxxx směrnice, x xxxxxxxxxx tabulku xxxx xxxxxxxx a přijatými xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Xxxx směrnice xxxxxxxx x platnost xxxxxx xxxx xx xxxxxxxxx v Xxxxxxx xxxxxxxx Xxxxxxxxxx společenství.

Xxxxxx 4

Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

X Bruselu xxx 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx


[1] Xxxxxxx po xxxxxxxxxxxx xx dvacáté xxxxx.

[2] Úř. xxxx. 196, 16.8.1967, x. 1.

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


XXXXXXX 1X

XXXXXXXXX K XXXXXXX X

Xxxxxxxxxx poznámek xxxxxxxxxx xx identifikace, xxxxxxxxxxx a xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)


XXXXXXX 1X

"XXXXXXX A

Z

Symbol

ES

DA

DE

EL

EN

FI

FR

IT

NL

PT

SV

18

Ar

Argón

Argon

Argon

Αργό

Argon

Argon

Argon

Argon

Argon

Árgon

Argon

64

Gd

Gadolinio

Gadolinium

Gadolinium

Γαδολίνιο

Gadolinium

Gadolinium

Gadolinium

Gadolinio

Gadolinium

Gadolínio

Gadolinium"


XXXXXXX 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x xxxxxx

Xxxxx XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x přípravkům

006–011–00–7

karbaryl (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

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

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

006–013–00–8

xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx

205–293–0

137–42–8

Xx; X22 R31 C; X34 R43 X; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

Xxxx. xxx. 3; R40 Xxxx. xxx. 3; X40 Xx; X22–48/22 N; X50–53

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

006–016–00–4

propoxur (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

204–043–8

114–26–1

X; X25 N; X50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; R24/25 X; X50–53

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

006–019–00–0

di-allát (XXX) X-(2,3-xxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx

218–961–1

2303–16–4

Xxxx. kat. 3; X40 Xx; X22 X; R50–53

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

006–020–00–6

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

202–930–4

101–27–9

Xx; X22 X43 X; X50–53

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

006–023–00–2

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

217–991–2

2032–65–7

T; X25 N; X50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xx; X38 N; 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+; R26/28 X; X50–53

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

006–028–00-X

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

213–546–1

973–21–7

X; X25 X; X50–53

X; X R: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; X25 X; X51–53

X; N X: 25–51/53 S: (1/2-)37–45–61

006–033–00–7

xxxxxxxxx (XXX) 3-(3-chlor-4-methoxyfenyl)-1,1-dimethylmočovina

243–433–2

19937–59–8

N; R50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xx; X22 N; X51–53

Xx; X X: 22–51/53 X: (2-)23-61

006–035–00–8

xxxxxxxxxx (ISO) 2-(xxxxxxxxxxxxx)- 5,6-dimethyl 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 (ISO) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–113–0

2631–37–0

X; R25 N; X50–53

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

006–038–00–4

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

X

202–388–9

95–06–7

Xxxx. kat. 2; R45 Xx; X22 X; X50–53

X; X R: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; R22–48/22 X43 X; X50–53

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

006–042–00–6

xxxxxxx (ISO) 3-(4-chlorfenyl)-1,1-dimethylmočovina

205–766–1

150–68–5

Karc. xxx. 3; X40 Xx; X22 N; X50–53

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

006–043–00–1

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

140–41–0

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

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

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 X; X50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; X23/25 Xn; X21 X; 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 a 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

8065–36–9

X; X24/25 X; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xx; X22 X; R50–53

Xn; 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; R50–53

Xi; N X: 38–50/53 X: (2-)60-61

006–053–00–6

xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; R50–53

Xn; X R: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xx; X21 N; X50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)24-61

006–060–00–4

oxykarboxin (XXX) 2-methyl-4,4-dioxo-5,6-dihydro-4λ4-1,4-oxathiin-3-karboxanilid

226–066–2

5259–88–1

Xn; X22 X52–53

Xx R:22–52/53 S: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Xxxx. xxx. 3; X40 X; X50–53

Xx; X X: 40–50/53 X: (2-)36/37–60–61

006–070–00–9

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

262–302–0

60568–05–0

Xxxx. xxx. 3; X40 N; X50–53

Xx; N X: 40–50/53 S: (2-)36/37–60–61

006–088–00–7

benfurakarb (XXX) xxxxx-X -[({[(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 N; X50–53

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

007–012–00–5

X,X-xxxxxxxxxxxxxxxx 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

X; X11 Karc. xxx. 2; X45 T; X23/25 X; X34 X; X51–53

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

007–013–00–0

N,N-dimethylhydrazin 1,2-xxxxxxxxxxxxxxxx

X

540–73–8

Xxxx. xxx. 2; R45 X; X23/24/25 N; X51–53

X; X X: 45–23/24/25–51/53 S: 53–45–61

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

009–003–00–1

kyselina xxxxxxxxxxxxxx … %

X

231–634–8

7664–39–3

X+; R26/27/28 X; R35

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

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

015–039–00–9

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

201–676–1

86–50–0

X+; X26/28 X; X24 R43 X; R50–53

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

015–048–00–8

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

200–231–9

55–38–9

Muta. xxx. 3; R40 X; X23–48/25 Xx; X21/22 N; X50–53

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

015–056–00–1

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

220–147–6

2642–71–9

X+; X28 X; X24 X; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; R23/25 Xn; 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 xxxxxxx

234–129–0

10545–99–0

X14 X; X34 X; X50

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

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

016–014–00–5

xxxxxxx xxxxxxxx

13451–08–6

X14 X; X34 N; X50

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

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

016–023–00–4

xxxxxxxx-xxxxxx

X

201–058–1

77–78–1

Xxxx. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; R26 X; 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 % ≤ X &xx; 10 %: X+; X45–22–26–36/ 37/38–43 5 % ≤ X < 7 %: X; X45–22–23–36/37/38–43 3 % ≤ X < 5 %: X; R45–22–23–43 1 % ≤ X &xx; 3 %: T; X45–23–43 0,1 % ≤ X &xx; 1 %: X; X45–20 0,01 % ≤ X &xx; 0,1 %:X; X45

016–024–00-X

xxxxxxxx (ISO) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; R22 X; X50–53

Xx; X R: 22–50/53 X: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

X43

Xx X: 43 S: (2-)22–24–37

022–001–00–5

xxxxxxx xxxxxxxxxx

231–441–9

7550–45–0

X14 X; R34

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

X ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xi; 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]

R14 X; X17 X; X34 X; X50–53

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

050–002–00–0

cyhexatin (XXX) tricyklohexyl(hydroxy)stannan xxxxxxxxxxxxxxxxxxxxx-xxxxxxxx

236–049–1

13121–70–5

Xx; X20/21/22 N; R50–53

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

050–012–00–5

xxxxxxxxxxxxxxxxxxxxxx [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] xxxxx(xxxxxxxxxxxxx)xxxxxxx [3]

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

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

Xn; X20/21/22 X; X50–53

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

X ≥ 1 %: Xx; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

X+; X26 Xx; X36/38 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 Xxxxxx 34 (XX 77603) XX xxxxxxxxxx xxxx 34 (XX 77603)

215–693–7

1344–37–2

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

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

1

082–010–00–5

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

235–759–9

12656–85–8

Xxxx. xxx. 3; R40 Xxxx. xxx. 1; R61 Xxxx. xxx. 3; X62 X33 N; X50–53

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

1

601–024–00-X

xxxxx [1] propylbenzen [2]

202–704–5 [1] 203–132–9 [2]

98–82–8 [1] 103–65–1 [2]

X10 Xx; R65 Xx; X37 X; X51–53

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

4

601–032–00–3

xxxxx[x]xxxxx benzo[def]chrysen

200–028–5

50–32–8

Karc. xxx.2; R45 Muta. xxx. 2; X46 Xxxx. xxx. 2; X60–61 N; X50–53

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

601–034–00–4

benzo[e]acefenanthrylen

205–911–9

205–99–2

Karc. xxx.2; X45 X; R50–53

T; X X: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 N; R50–53

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

602–054–00–6

3-xxxxxxx-1-xx allyljodid

209–130–4

556–56–9

R10 X; X34

X X: 10-34 S: (1/2-)7–26–45

603–076–00–9

xxx-2-xx-1,4-xxxx

203–788–6

110–65–6

X; X23/25 Xx; X21–48/22 X; X34

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

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

603–091–00–0

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

402–470–6

87172–89–2

O; R8 Xx; R22 Xi; X36

X; Xx X: 8–22–36 S: (2-)26

603–093–00–1

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

402–410–9

87818–31–3

Xx; X20 N; R51–53

Xn; X R: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 X52–53

Xx X:36–52/53 S: (2-)26-61

603–117–00–0

xxxxxx-2-xx xxxxxxxxxxxxxxxx isopropanol

200–661–7

67–63–0

F; X11 Xx; R36 R67

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

604–020–00–6

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

201–993–5

90–43–7

Xx; X36/37/38 X; R50

Xi; X X: 36/37/38–50 S: (2-)22-61

604–021–00–1

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

205–055–6

132–27–4

Xx; R22 Xx; X37/38–41 X; X50

Xx; X R: 37/38–41–50 X: (2-)22–26–61

604–024–00–8

4,4'-(4-methylpentan-2,2-diyl)difenol 2,2-bis(4-hydroxyfenyl)-4-methylpentan

401–720–1

6807–17–6

Repr. xxx. 2; X60 Xx; R36 X; 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; R38–41 X; X50–53

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

604–043–00–1

xxxxxxxxxxxxxxxx (4-xxxxxxxxxxxx)xxxxx hydrochinonmonobenzylether 4-(benzyloxy)fenol

203–083–3

103–16–2

Xi; X36 R43

Xi X: 36-43 X: (2-)24/25–26–37

604–044–00–7

xxxxxxxx 4-xxxxxxxxxxxx hydrochinonmonomethylether

205–769–8

150–76–5

Xn; X22 Xx; R36 R43

Xn 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. kat. 3; X40 Xn; X20 Xx; X36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

X ≥ 10 %: Xn; 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; R25–48/25 X; X50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xx; X22 Xi; X36/38 X; X50–53

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

606–019–00–6

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

205–601–3

143–50–0

Xxxx. xxx. 3; X40 X; X24/25 X; X50–53

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

606–034–00–8

xxxxxxxxxx (ISO) 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 N; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

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

216–920–2

1698–60–8

R43 X; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Xxxx. xxx. 3; X62 Xx; X20/21/22–48/22 Xx; X36 X43 N; X50–53

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

606–037–00–4

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

256–103–8

43121–43–3

Xx; X22 N; X51–53

Xx; X R: 22–51/53 X: (2-)61

606–044–00–2

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

403–150–9

954–16–5

Xx; X22 Xi; X36 X; X50–53

Xx; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

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

217–635–6

1918–00–9

Xx; X22 Xx; X41 X52–53

Xx; N 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 X52–53

Xx X:48/22–52/53 X: (2-)37-61

607–058–00–1

kumafuryl (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -chromen-2-on 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 H -xxxxxxx-2-xx

204–195–5

117–52–2

X; X25–48/25 X52–53

X X:25–48/25–52/53 X: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx 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 X; X51–53

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

607–097–00–4

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

209–008–0

552–30–7

Xx; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx valerová xxxxxxxx

203–677–2

109–52–4

X; X34 X52–53

X X:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xx; X22 X; X51–53

Xx; N X: 22–51/53 X: (2-)61

607–153–00–8

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

223–297–0

3813–05–6

Xx; X36/38 X52–53

Xx X:36/38–52/53 S: (2-)22-61

607–156–00–4

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

201–270–4

80–33–1

Xn; R22 Xx; R38 X; X50–53

Xx; X X: 22–38–50/53 S: (2-)37–60–61

607–158–00–5

xxxxx xxx chloroctové xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; R25 Xx; R38 X; X50

X; N 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 X; R50–53

Xn; X R: 22–50/53 X: (2-)60-61

607–176–00–3

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

400–830–7

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 X; X51–53

Xx; X R: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xn; X22 X43 X; R50–53

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

607–213–00–3

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

403–320–2

67567–23–1

E; X2 O; X7 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-xxxxxxxxxxx-[4-(7-xxxxx-2,6-xxxxx-2,6-xxxxxxx-1,5-xxxxx-x-xxxxxxx-3-xx)xxxxxx]xxxxxx

403–960–2

X43 R53

Xi X: 43-53 S: (2-)24–37–61

607–243–00–7

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

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

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

X52–53

X: 52/53 X: 61

607–248–00–4

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

205–073–4

132–67–2

Xx; X22

Xx X: 22 X: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xx; X36/37/38 R43 N; X51–53

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

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

607–252–00–6

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

415–130–7

91465–08–6

T+; R26 X; R25 Xx; X21 N; R50–53

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

607–255–00–2

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

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

xxxxxxxxxxxx

X X

203–466–5

107–13–1

X; Xxx Xxxx. kat. 2; X45 X; X23/24/25 Xx; R37/38–41 X43 N; R51–53

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 X; R50–53

Xi; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

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

X+; N X: 61–24–28–44–50/53 S: 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; N X: 45–61–22–50/53 X: 53–45–60–61

609–044–00–0

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

204–178–2

117–18–0

Xx; X22 X43 X; X50–53

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

611–008–00–4

4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. kat. 2; X45 N; R50–53

T; X X: 45–50/53 X: 53–45–60–61

611–013–00–1

4-hydroxy-3-{4-[2-methoxy-4-(3-sulfonatofenylazo)fenylazo]-3-methylfenylazo}-6-(3-sulfonatoanilino)naftalen-2-sulfonát xxxxxxxxx

403–650–7

117409–78–6

X; X2 X; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx CI Xxxxx Xxx 9 XX basická xxxxxx 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; X45 Xxxx. kat. 3; X40 X; X23/24/25

X X: 45–23/24/25 X: 53-45

612–042–00–2

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

X

202–199–1

92–87–5

Xxxx. xxx. 1; X45 Xx; X22 X; X50–53

X; X X: 45–22–50/53 S: 53–45–60–61

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

612–051–00–1

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

X

202–974–4

101–77–9

Xxxx. kat. 2; X45 Xxxx. xxx. 3; R40 X; X39/23/24/25Xx; R48/20/21/22 X43 X; X51–53

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

612–081–00–5

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

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Xxxx. xxx. 2; X45 Xx; R22 X; X51–53

X; X X: 45–22–51/53 S: 53–45–61

612–099–00–3

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

X

202–453–1

95–80–7

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

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

612–105–00–4

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

205–411–0

140–31–8

Xn; X21/22 X; X34 X43 X52–53

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

612–111–00–7

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

212–513–9

823–40–5

Xxxx. xxx. 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 N; X51–53

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

612–144–00–7

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

62924–70–3

Xx; R36/38 X4 3 N; X50–53

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

612–151–00–5

diaminotoluen xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. xxx. 2; X45 T; X25 Xn; X20/21 Xx; X36 X43 X; X51–53

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

613–018–00–4

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

7411–47–4

Xn; X22 Xi; R36/37/38 X52–53

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

613–031–00–5

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

201–782–8

87–90–1

O; R8 Xx; X22 X31 Xx; R36/37 X; X50–53

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

613–038–00–3

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

202–095–6

91–76–9

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 X; X41 X; X50–53

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

613–043–00–0

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

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xx; X41 X; X50–53

Xx; X 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 X: (2-)60-61

613–091–00–2

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

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

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-xxxxx-2-xxxxxxxxxx

403–700–8

2687–94–7

X; R34 X; R51–53

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

613–130–00–3

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

79983–71–4

R43 X; R51–53

Xi; N 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; R22 X52–53

Xx X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

Repr. xxx. 3; X63 Xx; R22 Xx; X36 N; X51–53

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

613–137–00–1

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

242–505–0

18691–97–9

X; X50–53

X X: 50/53 X: 60-61

613–139–00–2

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

74223–64–6

X; X50–53

X X: 50/53 X: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; R25 X; X51–53

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

614–006–00–1

xxxxxx 2,3-dimethoxystrychnidin-10-on

206–614–7

357–57–3

T+; X26/28 X52–53

X+ X:26/28–52/53 X: (1/2-)13–45–61

614–007–00–7

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

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

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

X+; X26/28 X52–53

X+ X: 26/28–52/53 X: (1/2-)13–45–61

615–006–00–4

2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] toluen-2,4-diisokyanát [2] xxxxxx-3,5-xxxxxxxxxxx [3]

C

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

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

Xxxx. kat. 3; X40 X+; R26 Xx; R36/37/38 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+; R26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ X &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 R31 X; R34 X42

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

616–034–00-X

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

246–419–4

24691–76–7

X52–53

X: 52/53 X: 61

616–035–00–5

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

261–043–0

57966–95–7

Xx; X22 R43 N; X50–53

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

617–004–00–9

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

212–230–0

771–29–9

X; X7 Xx; X22 X; R34 X; X50–53

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

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

617–006–00-X

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

201–279–3

80–43–3

X; X7 Xx; R36/38 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 Xx; X36 R43

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

650–007–00–3

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

228–200–5

6164–98–3

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

Xx; N 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; R25 N; 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 S: (2-)22–36/37–60–61

650–033–00–5

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

66230–04–4

T; X23/25 X43 X; X50–53

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

650–041–00–9

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

82097–50–5

X; X50–53

X X: 50/53 X: 60-61


PŘÍLOHA 1D

Indexové 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; X41 X52–53

Xx X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

Xxxx: 1,3-xx(xxx-5-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-tetramethyldisiloxan

406–490–6

N; X51–53

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

404–986–7

Xx; X41 X; X50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 X: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; X41

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

601–050–00–1

C10-C13-alkylderiváty xxxxxxx

267–051–0

67774–74–7

X; X50

X X: 50 X: 61

601–051–00–7

4-xxxxxxxx-1-xx

405–980–7

768–56–9

Xx; X38 X; X51–53

Xx; X R: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx difenyletheru xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 X64 X; X50–53

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

602–084–00-X

1,1-xxxxxxx-1-xxxxxxxxxx

404–080–1

1717–00–6

X; X52–53–59

X X: 52/53–59 X: 59-61

603–128–00–0

2-(fenylmethoxy)naftalen

405–490–3

613–62–7

R53

R:53 X: 61

603–129–00–6

1-xxxx-xxxxxxxxxxxx-2-xx

406–180–0

57018–52–7

X10 Xx; X41

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

603–130–00–1

Směs 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; R41

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

603–132–00–2

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

408–200–3

63187–91–7

Xx; R38–41 X52–53

Xx X:38–41–52/53 X: (2-)26–37/39–61

603–133–00–8

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

408–240–1

Xx; X22 X52–53

Xx R:22–52/53 X: (2-)22–36–61

603–134–00–3

Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx a xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (xxxxxxx a 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 S: (2-)24–37–61

603–137–00-X

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

411–130–6

Xx; X41

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

603–138–00–5

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

403–140–4

103694–68–4

X52–53

X:52/53 X: 61

604–050–00-X

4-xxxxx-x-xxxxxx 4-xxxxx-2-xxxxxxxxxxx

216–381–3

1570–64–5

X; X23 X; R 35 X; X50

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

C ≥ 25 %: X; C; X23–35 10 % ≤ X &xx; 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'-bis(1,1,3,3-tetramethylbutyl)- 2,2'-xxxxxxxxxxxxxxx

403–800–1

103597–45–1

X53

X:53 S: 61

604–053–00–6

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

410–760–9

157661–93–3

Xx; R38 X43 X; R50–53

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

604–054–00–1

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

412–020–0

X43 R52–53

Xi X:43–52/53 S: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Xxx.3; X40

Xx X: 40 S: (2-)22–36–37

605–027–00–7

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

410–480–7

X43 X; R51–53

Xi; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-xxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxx-1-xx

4–406–670–4

61203–83–6

X; X51–53

X X: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

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

X; X50–53

X X: 50/53 X: 60-61

607–273–00–0

xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 1,2,6,7,8,8a-hexahydro-1-naftyl}-3,5-dihydroxyheptanoát

404–520–2

R52–53

R:52/53 X: 61

607–274–00–6

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

405–350–1

54527–73–0

R43 X; X51–53

Xx; N R: 43–51/53 X: (2-)24–37–61

607–275–00–1

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

405–450–5

66531–87–1

X43

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

607–276–00–7

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

405–635–0

Xx; X38–41 X; X50–53

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

607–277–00–2

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

405–720–2

Xx; X22 Xx; X41 X43 N; X51–53

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

607–278–00–8

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

405–760–0

Xx; X41 X43 X52–53

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

607–279–00–3

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

405–960–8

X43 X; R51–53

Xi; X X: 43–51/53 S: (2-)24–37–61

607–280–00–9

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

406–190–5

54322–20–2

Xx; X22 Xx; X36 X43

Xx R: 22–36–43 X: (2-)22–26–36/37

607–281–00–4

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

407–000–3

127519–17–9

X; X51–53

X X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 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 Xi; X38–41 R43 N; X50–53

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

607–284–00–0

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

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

410–065–0

X43

Xx X: 43 X: (2-)22–24–37

607–286–00–1

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

410–070–8

141880–36–6

X43 X52–53

Xx X: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; x = 15, 16, 17 xxxx 18, x = 1, 2, 3 nebo 4, b = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25

410–160–7

148732–74–5

Xx; X36 X43 X52–53

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

607–288–00–8

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

410–370–9

105488–33–3

X53

X:53 X: 61

607–290–00–3

Xxxx (x xxxxxxxx xxxxxx):xxxxxxx-1-xxxxx(X14-X18)-4-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx a 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 S: (2-)24–37–60–61

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx cyklohexyl)alkanoát

410–630–1

104051–92–5

R53

R: 53 X: 61

607–292–00–4

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

410–640–6

Xi; X38–41 X; X50–53

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

607–293–00-XXxxx:

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

410–650–0

Xx; X41 X43 X; R51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 X; R51–53

Xi; X R: 43–51/53 X: (2-)24–37–61

607–296–00–6

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

410–830–9

R53

R: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; X41

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

607–298–00–7

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

411–010–3

R43

Xi X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 R43 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 xxxxxxx, xxxxxxxx sůl; a = 1,2,3 xxxx 4, x = 8, 9, 10 xxxx 11, x = 15, 16, 17 xxxx 18, x = 22, 23, 24 xxxx 25

411–430–7

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xx; X38–41 X43 X; X51–53

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

607–302–00–7

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

411–910–6

Xx; X38–41 R43 X; R51–53

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

607–303–00–2

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

413–760–7

93107–30–3

Xxxx. xxx.3; X62 X52–53

Xx R: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; X50–53

X X: 50/53 X: 60-61

608–024–00–9

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

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

R53

R:53 S: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

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

E; T X: 45–3–8–23/25–43 X: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 X; X34 X43 N; X50–53

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

611–043–00–5

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

402–850–1

Xi X: 41–52/53 S: (2-)26–39–61

611–044–00–0

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

403–720–7

117527–94–3

X; X51–53

Xx; X41 X52–53

611–045–00–6

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

404–830–8

X53

X:53 X: 61

X X: 51/53 S: 61

611–046–00–1

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

407–590–2

43151–99–1

X; X25 Xx; X48/22 X43 N; X50–53

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

611–047–00–7

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

407–890–3

111381–11–4

R53

R: 53 S: 61

611–048–00–2

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

407–900–6

111381–12–5

X53

X: 53 X: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; X48/22 X43 X52–53

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

611–051–00–9

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

411–110–7

136213–74–6

X; X50–53

X X: 50/53 X: 60-61

611–052–00–4

[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) azo]-6-[(6-sulfonato-1-naftyl)azo]benzen-1,3-diolato}]železnatý xxxxxxx, xxxxx sůl

400–720–9

R52–53

R: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; R41 X; X50–53

Xx; X X: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

(Z)-1-(1-benzothiofen-2-yl)ethan-1-on-oxim-hydrochlorid

410–780–8

Xn; X22–48/22 Xx; R41 X43 X; R51–53

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

410–820–4

X53

X: 53 S: 61

612–159–00–9

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

410–880–1

Xx; R22 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; N 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 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-xxxxxxxxxxxxxxx

407–270–2

16063–70–0

X52–53

X:52/53 S: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx R: 22 X: (2-)22

613–155–00-X

5-chlor-2,3-difluorpyridin

410–090–7

89402–43–7

R10 Xx; X22 R52–53

Xn X: 10–22–52/53 X: (2-)23–36–61

613–156–00–5

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

410–260–0

83857–96–9

X43 X; X51–53

Xx; N X: 43–51/53 X: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; R22–48/22 Xx; X36

Xx X: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xx; R20/22 Xx; X41 R43 X; X51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; X25 Xx; X20 N; X50–53

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

613–160–00–7

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

411–000–9

125224–62–6

X43

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

615–022–00–1

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

410–550–7

79277–18–2

E; X2 X14 Xx; X48/22 X42/43

X; Xn 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 Muta. kat. 3; X40 Xx; X20–48/22 Xi; X41 X42

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

616–044–00–4

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

402–510–2

X; X51–53

X X: 51/53 X: 61

616–045–00-X

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

405–190–2

122371–93–1

R43 X53

Xx X: 43-53 X: (2-)22–24–37–61

616–046–00–5

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

406–390–2

N; X50–53

X X: 50/53 S: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - tetraalkyl(C16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x N, 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; R51–53

Xn; X R: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

2-(2,4-di-terc-butylfenoxy)-N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)hexanamid

408–150–2

99141–89–6

R53

R:53 X: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 N; R50–53

Xi; X X: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

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

bis(4-methylbenzoyl)peroxid

407–950–9

895–85–2

E; X2 X; X7 X; X50–53

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

650–032–00-X

xxxxxxxxxxxx (XXX) (2R, 3X)-, (2 X, 3 X)-, (2 X, 3 S)-, (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; R22 X; R50–53

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


XXXXXXX 2

POVAHA SPECIFICKÝCH XXXXX SPOJENÝCH X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Komise 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 3B

STANDARDNÍ POKYNY XXX BEZPEČNÉ XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/XX,

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


XXXXXXX 4A

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx vitro xx xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx v xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Rozlišují xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. X xxxxxxx chemických mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, avšak xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx může znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx aberace. Tato xxxxxx xxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx aberací x xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx x xxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob u xxxxxxx x existuje xxxxx xxxxxx x xxx, xx chromozomové xxxxxx x s xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx x v xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx nádory, mají xxxxx xx indukci xxxxxxxx u xxxxxxx x u xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, xxxxxxx kmeny xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx a xxxxxxxxx četnosti xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx vyžadují xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx systém xxxxxx xxxxx napodobit xxxxxxxx in xxxx x savců. Xx xxxxx se zcela xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx k xxx dojít xxxxxx xX, osmolality nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx možných xxxxxxxx x karcinogenů pro xxxxx. Xxxxx xxxxxxxxx, xxx něž je xxxx zkouška xxxxxxxxx, xxxx pro xxxxx xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx závisí xx chemické třídě x přibývají xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx jinými mechanismy xxx xxxxxx poškozením XXX.

Xxx xxxx Xxxxxx xxxx, část B.

1.2 XXXXXXXX

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

Chromozomová aberace : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx xxxx zlomu x spojení xxxx xxxxxxxxx x tomtéž xxxxx.

Xxxxxxxxxxxxxxx : proces, xxx kterém x xxxxx xx X-xxxx xxxxxxxxx DNA nedojde x xxxxxx, xxxxx xxxxxxxxx xxxxx X-xxxx. Xxxxxxxxx xxxx xxxxxxxxxx xx 4, 8, 16… xxxxxxxxxxxx.

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

Xxxxxxxxx xxxxx : podíl xxxxx, které xx xxxxxxxxx x metafázi, x celkového xxxxx xxxxx x xxxxxxxx; xxxxx stupeň proliferace xxxx xxxxxxxx.

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

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

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

1.3 XXXXXXXX ZKUŠEBNÍ METODY

Buněčné xxxxxxx xxxx vystaveny xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. V předem xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxx se xx xxxxxxxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx kolchicin), kultury xx xxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxxxxxxx pozorováním xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx být xxxxxxx různé xxxxxxx xxxxx, xxxxx nebo xxxxxxxx xxxxxxx xxxxxxx, xxxxxx lidských buněčných xxxxx (xxxx. fibroblasty xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx xxxx člověka xxxx jiných xxxxx).

1.4.1.2 Xxxxx a xxxxxxxxxx xxxxxxxx

Xxx udržování kultur xx měla xxx xxxxxxx xxxxxx kultivační xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx CO2, teplota x xxxxxxx). X xxxxxxxxxxxxxxx xxxxxxxxx linií x xxxxx by xxxx být xxxxxxx xxxxxxxxxxxx stabilita xxxxxxx xxxxxxx počtu xxxxxxxxxx x xxxx xx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x xxxxxxx kontaminace xx xxxxxx xxx xxxxxxx. Xxx xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx xx xxxx xxx známa xxxxxxxx xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx a xxxxx: xxxxx xx pomnoží x xxxxxxxxx kultur, xxxxxx xx xx xxxxxxxxxxxx média x xxxxxx xxxxxxx, aby xxxxxxxxx xxxxxxxxxx před xxxxxxxxx, x inkubují xx xxx 37 °X.

Xxxxxxxxx: krev ošetřená xxxxxxxxxxxxxxx (např. xxxxxxxxx) xxxx xxxxxxxx lymfocyty xxxxxxxx probandů xx xxxxxxx xx kultivačního xxxxx xxxxxxxxxxxx mitogen (xxxx. xxxxxxxxxxxxxxxx) a xxxxxxxx xx xxx 37 °X.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx by měly xxx vystaveny zkoušené xxxxx, x xx x vhodnou metabolickou xxxxxxxx x bez xx. Nejčastěji xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx frakce (X9) připravená z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx indukujícím xxxxxx, xxxx je Xxxxxxx 1254 (6, 7, 8 a 9), xxxx xxxx xxxxxxxxxxxxx x β-naftoflavonu (10, 11 x 12).

Postmitochondriální xxxxxx xx v xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx může xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X některých xxxxxxxxx může xxx xxxxxx xxxxxx více xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx specifické xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx linií xx xxxx xxx xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx zkoušené xxxxx).

1.4.1.5 Zkoušená xxxxx/xxxxxxxx

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

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx xxx xxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx být xxxxxxxxxx x xxxxxxxx xxxxx x s xxxxxxxxx X9. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx údaji x xxxxxx kompatibilitě. Doporučuje xx pokud xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx xxx použita xxxxxxxxx rozpouštědla xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx nejvyšší koncentrace, xxxxx cytotoxicita, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x xxxxx pH xxxx xxxxxxxxxx.

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx ní x xxxxxxx experimentu xx použití xxxxxxxx xxxxxxxxxx buněčné integrity x xxxxx, xxxx xxxx stupeň xxxxxxxxxx, xxxxx životaschopných xxxxx xxxx xxxxxxxxx index. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx alespoň xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx cytotoxicity xx xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx dané xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx xxxxxxx xxxxxxx, že by xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx koncentrace xxxxxxxxx xxxxxxxx xxxxxxx stupně xxxxxxxxxx, xxxxx xxxxx xxxx xxxxxxxxxxx xxxxxx (xxx o více xxx 50 %). Xxxxxxxxx xxxxx je xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx cytostatických xxxxxx x závisí xx xxxx, která xxxxxxxx od expozice. Xxxxxxxxx xxxxx xx xxxx xxxxxxxxxx x xxxxxxxxxxx xxxxxx, x xxxxx mohou být xxxx metody xxxxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxxx. Xxxxxxxxx o xxxxxxxx xxxxxxxxx cyklu, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), xxxxx xxx xxxxxxx jako xxxxxxxxx xxxxxxxxx. X xxxxxxx XXX xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx nelze usoudit xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, x x xxxx xxxxxxxxx průměrné xxxxxxxxx xxxx může xxx xx xxxxxxxx xxxxx xxxxxxxxx oddálení xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx toho, xxxxx x xxxx xx xxxxxxxx.

X xxxxxxx relativně xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx toxické xxx xxxxxxxxxxxxx nižších, xxx xx jejich rozpustnost, xx xxxx xxx xxxxxxx nejvyšší xxxxx x xxxxxxxxxxx, xxx xx xxx xxxx xxxxxxxxxxxx v konečném xxxxxxxxxxx xxxxx na xxxxx xxxx xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx se xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx, xxx xx rozpustnost) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, při nichž xxxxxxx xx xxxxxxx. Xxxx být užitečné xxxxxxxx rozpustnost xx xxxxxxx a na xxxxx expozice, neboť xxxxxxxxxxx v xxxxxxxxxx xxxxxxx se xxxx x xxxxxxx xxxxxxxx xxxxx x důsledku xxxxxxxxxxx xxxxx, séra X9 xxx. Nerozpustnost xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

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

K xxxxxxxxx xxxxxxxx xx xxx xxx xxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxx koncentracích, xxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxx, xxxx xx prokáže citlivost xxxxxxxxxxx systému.

Koncentrace xxxxxxxxxxx xxxxxxx by xxxx xxx zvoleny tak, xxx byl xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

Xxx xxxxxx xxxxxxxxxxx xxxxxxxx

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

4-xxxxxxxxxxxxx-1-xxxx

56–57–5

200–281–1

X xxxxxx xxxxxxxxxxxx xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Pro pozitivní xxxxxxxx xxxxx být xxxxxxx i xxxx xxxxxx xxxxx. Xxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxx xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx se xx samotného xxxxxxxxxxxx xxxx vehikula x xxxxxxxxxxx xxxxx x xxxxxxxxxx xxxxxxx způsobem xxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.4.3 Xxxxxx

1.4.3.1 Expozice zkoušené xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx xxxxxxxx látce xxx za přítomnosti xxxxxxxxxxxxx aktivačního xxxxxxx, xxx bez xxxx. Xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxxx xxx 48 hodin xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx každou koncentraci xx měly být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, a xxxxx xx důrazně xxxxxxxxxx x xxxxxx pro xxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx xx základě xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), že xxxx xxxxxxxxxxxx xxxxxxxxx xx minimální xxxxxx, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

Xxxxxx xxxx těkavé xxxxx xx xxxx být xxxxxxxx vhodnými xxxxxxxx, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (15, 16).

1.4.3.3 Xxxx xxxxxxx kultur

V prvním xxxxxxxxxxx by měly xxx xxxxx vystaveny xxxxxxxx xxxxx, xxx x xxxxxxxxxxxx aktivací, xxx xxx xx, xx xxxx 3 — 6 hodin, x měly by xxx xxxxxxxx xx xxxxxx xxxx od xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Jestliže xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, tak xxx xxxxxxxx, xxx xx xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x nepřetržitou xxxxxxxx xx xx odběru x xxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx látky xxx snáze xxxxxxxxx xxx xxxxxx aplikace xxxx xxxxxx xxxxxxx xxx 1,5násobek délky xxxxx. Xxxxxxxxx xxxxxxxx xxx metabolické xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. X xxxxxxxxx, kdy xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx výsledků za xxxxxxxx, by xxxx xxx xxxxxx zdůvodnění.

1.4.3.4 Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx

Xx buněčné xxxxxxx xx xxxxxxx 1-3 xxxxxx xxxx xxxxxxxxx přidá Xxxxxxxx® xxxx kolchicin. Xxx xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů xx xxxxx buněčná kultura xxxxxx x zpracovává xxxxxx. Xxxxxxxx preparátů xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x obarvení xxxxx.

1.4.3.5 Analýza

Všechny xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx měly xxx xxxx xxxxxxxx pod xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxx fixaci xxxxx xxxxxxx ke xxxxx xxxxx buněk x metafázi x xx xxxxxx chromozomů, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x počtu xxxxxx xxxxxxx xxxxxxx ± 2 xxx xxxxxxx xxxx xxxxx. Xx xxxxxx koncentraci a xxxxxxxx xx xxxx xxx hodnoceno xxxxxxx 200 xxxxx rozprostřených xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx snížit, xx-xx xxxxxxxxx velký xxxxx xxxxxxx.

Xxxxxx xx xxxxxx xxxxxxx detekovat xxxxxxxxxx xxxxxxxxxxxx aberace, xx xxxxxxxx zaznamenat xxxxxxxxxxx x xxxxxxxxxxxxxxx, xxxx-xx xxxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx x xxxx xx xxxx xxx xxxxxxxxxxx množství xxxxx xx strukturní xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x procentech. Xxx xxxxxxxxx x experimentální xxxxxxx xx xxxx xxx uvedeny xxxxx xxxx strukturních xxxxxxxxxxxxxx xxxxxxx s jejich xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxxxxxx xx do celkové xxxxxxxx aberací.

Měla xx xxx xxxx zaznamenána xxxxxxxx, xxxxx byla xxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxxxx v xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx by měly xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx x bodu 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x cílem rozšířit xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx xxxxxxx x následných xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx xxxxx být změněny, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x chromozomovými aberacemi x závislosti xx xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx xxxxxx xxxxx. Xxxxxxxx xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx faktorem xxx pozitivní xxxxxxx.

Xxxxxx xxxxx xxxxxxxxxxx buněk xxxx znamenat, xx xxxxxxxx látka xx xxxxxxxxx potlačit xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx buněk x endoreduplikovanými xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx potlačit progresi xxxxxxxxx xxxxx (17, 18).

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

Ačkoli xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx výrok o xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu na xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xx zkoušky xx xxxxxxxxxxxx aberace xx xxxxx xxxxxxxxx, že xxxxxxxx látka indukuje x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx za xxxxxxxx xxxxxxx neindukuje x kultivovaných somatických xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxx:

- xxx x zdroj buněk,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx použitého xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx cyklu,

- xxxxxxx dárce xxxx, xxx xxxx použita xxxx krev xxxx xxxxxxxxxx lymfocyty, xxxxxxx xxxxxxx,

- xxxxxxxx počet xxxxxx,

- případně xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx hodnota počtu xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- xxxxxxx xxxxx, xxxxxxxx koncentrace XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx zkoušené xxxxx,

- inkubační xxxxxxx,

- xxxxxxxxx doba,

- délka xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxxx xxxxxxx,

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

- definice xxxxxxx, xxxxxx xxxx,

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

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx závislost odpovědi xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, H. X. (1976), Xxxxxxxxxxx Methods xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Chemical Xxxxxxxx, Xxxxxxxxxx xxx Xxxxxxx xxx their Xxxxxxxxx, Vol. 4, Xxxxxxxxxx, A. (xx) Xxxxxx Xxxxx, New Xxxx and Xxxxxx, 1-29.

2) Xxxxxxxx, X. Xx., Sofumi, X. (1985), Xxx Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Xxxxx Xxxxxxx Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Cells xx Xxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Xxxxx, X. xx al., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 427-432.

3) Xxxxxxxx, S. X., Xxxxxxxxx, X. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Cannon, C., Xxxxx, X. X., Xxxxxxxx, X., Xxxxx, X., Duk, X., Xxxxx, J., Xxxxxxxx, X. X., Xxxxxxx, X. A., Xxxxxxxx, X., Zeiger X. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx cells: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Molec. Xxxxxxx. 10 (suppl. 10), 1-175.

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

5) Morita, T., Xxxxxx, X., Xxxxxx, X., Okumura, K., (1992), Xxxxxxxxxxxxxx xx xxx pH xx Xxxxxxx Xxxxxxxx Xxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 268, 297-305.

6) Xxxx, X. X., McCann, X., Yamasaki, E. (1975), Methods for Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 31, 347-364.

7) Maron, X. X., Xxxx, X. X. (1983), Xxxxxxx Xxxxxxx xxx xxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Mutatation Xxx., 113, 173-215.

8) Xxxxxxxxx, X. X., Xxxxx, X. X., xxx Xxxx, P. P. X., Xxxxxxx, M., xx Xxxxx, N. (1976), Xxxxxxxxxxx Effects xx Xxxxxxx/Xxxxxxxxxxx xxxxx Xxxxxxxxxx in x Xxxxxxxxxxx Xxxxxx Xx xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Xxxxxx Xxxxxxxxx Xxxxxxxx xx Diethylnitrosamine (XXX) xxx Dimethylnitrosamine (XXX) in XXX Xxxxx xx xxx Xxxxxxxx xx Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Xxx., 37, 83-90.

9) Xxxxxxxx, X., Hayashi, X., Xxxxxxxx, X. Jr. (1979), Chromozomal Xxxxxxxxxx Xxxxx on 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Mix In xxxxx, Mutation Xxx., 66, 277-290.

10) Elliot, X. X., Xxxxxx, X. D., Elcombe, X. R., Xxxxxxxxx, X. G., Xxxxxx, X. X., Xxxxxx, X. X., Wolf, X. C. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx Xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Sawamura, X., Hara, K., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. an Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, xx: xx Xxxxxx, X. X., Fouts, X. X. Xxxx, X. X., Xxxxxxx, X. X. (xxx), Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Mutagenesis Testing, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, M. X., Xxxxxxxx, M. Jr., Xxxxx, J. L., Xxxxxxxx, X. X., Xxxxxx, X., Xxxxxxx, X., Sofumi, T. (1994), Report xxxx Xxxxxxx Xxxxx xx Xx xxxxx Xxxxx xxx Chromozomal Aberrations, Xxxxxxxxxx Xxx., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X. A., Xxxxxxxx, X., Xxxxxxx, X. X., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx xxxxx Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Data, Kirkland, X. J., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

14) Xxxxx, X. A., Xxxxxxxx, X. M. (1994), Xxxxxxxxx Xxxxxx are xxx Xxxxxxxxx for Xx xxxxx Xxxxxxxxxx Xxxxxxxxxx Xxxxxx xx XXX Xxxxx, Xxxxxxxxxx Xxx., 312, 139-149.

15) Xxxxx, X. X., Xxxxxx, X. C., XxXxxxx, X. X. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Evaluation of Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Tice, X. R., Costa, X. L., Xxxxxxx, X. X. (eds), Xxxxxxxxx Xxxxxxx of Xxxxxxxx Xxxxxx, Xxx Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, P. X., Xxxxxx, J. X., Xx, X. X., Xxxxxx, A. L. (1983), Evaluation xx xx Exposure Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Gels xxx Detecting Xxxxxx Xxxxxxxx Mutagens xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.

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

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


XXXXXXX 4X

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

1. XXXXXX

Xxxx metoda xx xxxxxxxx metody XXXX TG 475 — Xxxxxxx xx xxxxxxxxxxxx aberace x xxxxxxx xxxxxx dřeně xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x savců xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx v xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x chromatidové. Nárůst xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx aberace. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx jsou indukované xxxxxxx chromatidového xxxx, xxxxx chromozomové xxxxxxx xx xxxxxx vyskytují. Xxxxxxxxxxxx mutace x xxxxxxxxxxx xxxx xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a existuje xxxxx xxxxxx x xxx, že xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx podíl xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxxxxxxxxx systémech.

Při xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Cílovou xxxxx xx x xxxx xxxxxxx kostní xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxxx xx xxxxxx izolují x xxxxxxxxxxxx. Xxxx xxxxx x cílové xxxxx xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx na xxxxxxxxxxxx aberace je xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx umožňuje zohlednit xxxxxxx metabolismu in xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx XXX, xxxxxxx xx xxxxx x xxxxxxx xxxxx x xxxxx měnit. Xxxxxxx xx vivo xx xxxxxx xxxxxxxx xxx xxxxx výzkum xxxxxxxxxxx xxxxxx zjištěných xxxxxxxx xx vitro.

Jestliže xxxxxxxx xxxxx o xxx, že se xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx nedostanou xx xxxxxx tkáně, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx také Xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : strukturní xxxxxxxxx xxxxxxxxxx v podobě xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx spojení chromatid.

Chromozomová xxxxxxx : strukturní xxxxxxxxx chromozomu x xxxxxx xxxxx nebo xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

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

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

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

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

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce vhodným xxxxxxxx x xx xxxxxxx okamžiku xx xxxxxxxx xx usmrtí. Xxxx usmrcením xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, myš x xxxxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx vhodný xxxxx xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx studie xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx minimální x xxxxxx by x xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx zvířata se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, xxxxx xx xxxxxxx zkoušené xxxxx. Xxxxx xx xxxx xxx uspořádány xxx, aby xxx xxxx jejich xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx alespoň pět xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx látky mohou xxx podávány přímo xxxx mohou být xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx toxické xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno nejdříve xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx obě xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx identický xxxxxx jako zvířata xx skupinách, v xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx úrovních, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx. Xxxxx pozitivní xxxxxxxx xx měly xxx zvoleny tak, xxx xxx účinek xxxxxxxx, xxx xxx xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx způsobem xxx xxxxxxxx xxxxx a xxx byl odběr x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx pozitivní xxxxxxxx xxxxx být xxxxxxx xxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:

Látka

Číslo XXX

Xxxxx xxxxx EINECS

ethyl-methansulfonát

62–50–0

200–536–7

1-ethyl-1-nitrosomočovina

759–73–9

212–072–2

mitomycin X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X okamžiku xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x negativních xxxxxxx, xxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě zvířat x xxxxxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx se xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx nejvhodnějším xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx použity xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx skládá x alespoň xxxx xxxxxxxxxxxxxxxx zvířat xxx xxxxx xxxxxxx. Xxxxxxxx xxxx x době xxxxxx x xxxxxxxxx xxxxx ze studií xx stejným xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx pohlavími xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx pohlaví. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx tomu xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx látek, xxxx xx být xxxxxxx xxxxxxxxx se xxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky by xxxx xxx pokud xxxxx podávány xxxxxxxxxxx. Xxxxxxxx látky xxxxx xxx xxxxxxxx xxxx xx xxxx dávkách, xxx. xxx dávky x xxx den x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx podávání velkých xxxxxx materiálu. Jiné xxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx xx měly xxx odebrány ve xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxx xxx. X hlodavců se xxxxx xxxxxxx xx xxxxxx době xx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 h). Xxxxxxxx xxxx xxxxxxxx xxx příjem x xxxxxxxxxxxx zkoušené xxxxx x xxxxxx xxx xxxxxx xx xxxxxxxx xxxxxxxxx xxxxx může xxx vliv xx xxxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx se xxxxxxx xxxxx xxxxx xx 24 x xx xxxxxxx odběru. Xx-xx xxxxxxxx rozložena xx xxxx než jednoho xxx, měl xx xxx xxxxx proveden xx takové xxxx xx poslední aplikace, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného xxxxx.

Xxxx usmrcením xx xxxxxxxx xxxxxxxxxxxxxxxxx podá xxxxxx xxxxx látky xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx se xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx doba xxxxxxxxx 3 — 5 x; u xxxxxx xxxxxxxx je tato xxxx xxxxxxxxx 4 — 5 h. X xxxxxx dřeně xx xxxxxxxx xxxxx x xxxxxxxxx xx xx xxxxxxxxxxxx xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx studie xxx xxxxxxxx xxxxxxx xxxxx, xxxx by xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, se stejným xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx stejném režimu xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx být xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx dávka xxxx xxx také xxxxxxxxxx jako dávka xxxxxxxxxxxx v xxxxxx xxxxx některé xxxxxx xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné toxické xxxxxx x není-li xx xxxxxxx údajů x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, nepovažuje xx xxxxx studie xx xxxxx úrovněmi xxxxx za nezbytnou. X xxxx xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx aplikaci xx xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx v xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx se obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx xxxx x odůvodněných xxxxxxxxx xxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx podán xxxxxxxxxxxxxx xxxx injekčně, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx na dráždivé x xxxxxx látky, xxxxx xxxxxxx xxx xxxxxxx koncentracích vykazují xxxxxxxx xxxxxx, by xxxx xxx variabilita xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx preparátů xxx xxxxxxx chromozomů

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

1.5.7 Xxxxxxx

Xxxx xxxxxxx cytotoxicity xx xxx xxx x xxxxx xxxxxxxxxxxx xxxxxx (včetně xxxxxxxxxxx xxxxxxx) a u xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx kontrolu xxxxxxxx xxxxxxxxx xxxxx, x xx alespoň x 1000 xxxxx xx xxxxx zvíře.

U každého xxxxxxx by xxxx xxx xxxxxxxxxxx alespoň 100 xxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx pozitivních a xxxxxxxxxxx xxxxxxx xx xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xx xxxxxx xxxxxxxxxx x xxxxx xxxxx x metafázi, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx by xxxx být xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx, počet aberací xx xxxxx a xxxxx xxxxx s xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx v xxxxxxxxxx. Pro xxxxxxxxxx x xxxxxxxxx xxxxxxx xx měly být xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových aberací x jejich počtem x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx xxxxxx se xxxxxxxxxx do celkové xxxxxxxx aberací. Neexistuje-li xxxxx x xxxxxxx x odpovědi mezi xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx pro xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx buněk x xxxxxxxxx pro xxxxxxx x určitou xxxxxx x k určitému xxxxxxxx xxxxxx. Nejdříve xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Statistická xxxxxxxxxx by neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx. Dvojznačné výsledky xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravami xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx polyploidie xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx xxxxxxxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx chromozomy xxxx xxxxxxxx, xx zkoušená xxxxx xx xxxxxxxxx xxxxxxxx progresi xxxxxxxxx xxxxx (7, 8).

Zkoušená xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx uvedená xxxxxxxx, xx xxxxxxxx x tomto xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx xx, xxxxxxxx je experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxx znamenají, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx znamenají, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx neindukuje x kostní xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění volby xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

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

Zkušební xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x přípravě xxxxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

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

- xxxxxxxx údaje x xxxxxxx xxxxxx a xxxx,

- podrobný xxxxx xxxxxxx expozice x xxxxxx,

- xxxxxx stanovení xxxxxxxx,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxx toxicity,

- mitotický xxxxx,

- typ a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,

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

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

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- dosavadní xxxxx x xxxxxxxxx kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- údaje x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. D. (1984), Xxxxxxxxxxx Tests xx Xxxxxxx, xx: Mutagenicity Xxxxxxx: x Practical Xxxxxxxx, X. Xxxxxx, X. X. Xxxxx (xxx), IRL Xxxxx, Xxxxxx, Xxxxxxxxxx D. X., 275-306.

2) Preston, X. X., Xxxx, X. X., Xxxxxxxx, X., Xxxxxx, X., XxXxx, A. F., Xxxxxx, X. (1987), Xxxxxxxxx Xx vivo Xxxxxxxxxxx Assays: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xx Xxxx Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Richold, X., Xxxxxxxx, X., Xxxxx, J., Xxxxxxxxx, X. X., Xxxxxxx, X., Xxxxxxxxx, X. (1990), In vivo Xxxxxxxxxxx Assays, xx: X. X. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Sub-Committee xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx I xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. X., Hayashi, X., XxxXxxxxxx, X. X., Xxxxxxxx, X., Xxxxxx, D. H., Xxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X. J., Xxxxxxx, X., Shimada, H., Xxxxx, X., Vannier, X. (1994), Xxxxxx xxxx xxx Working Xxxxx on xxx xx xxxx Xxxxxxxxx Xxxx Xxxxxx Chromozomal Xxxxxxxxxx Xxxx, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, X. J., Xxxxx, X. A., Xxxxxx, A. X., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. G., Hodson-Walker, X., Morton, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Report of Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Society Xxxxxxx Group: Dose Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. P., Xxxxxxxx, D., Albanese, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Richold, X., Xxxxxxxx, D. X., Xxxxxx, X. X. K. (1989), Xxxxxxxxxxx Analysis of Xx xxxx Cytogenetic Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx on Guidelines xxx Xxxxxxxxxxxx Testing, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, 184-232.

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

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


PŘÍLOHA 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx vivo xx xxxxxxxx xxx xxxxxxx poškození xxxxxxxxxx xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx zkoušenou xxxxxx, x xx pomocí xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx dřeně x/xxxx xxxxx xxxxxxxxx xxxx, xxxxxxx xxxxxxxx.

Xxxxxx xxxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx je xxxxxxxxxxxxx xxxxx, které způsobují xxxxxxxxxxxxx poškození, xxxxx xxxxxxxxx je xxxxxx xxxxxxxxxx obsahujících xxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx nebo xxxx xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx xxxxx mění xx polychromatický erytrocyt, xxxxxx xxxxx xx xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx vzniknout, xxxxxxxxx x xxxxxxxxxx, která xxxxx xxxxx neobsahuje. Xxxxxxxxxxxx xxxxxxxxxx je x xxxxxx xxxxxxx xxxxxxxxx tím, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx x mikrojádry x exponovaných xxxxxxxxx xx známkou xxxxxxxxxxxx xxxxxxxxxxxxxx poškození.

V xxxxx xxxxx xx rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, poněvadž tato xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxx xx xxxxxxxxxx xxxxxxxxxx u xxxxxxxxxxx xxxxx, x xxxxx xxxx prokázána neschopnost xxxxxxx xxxxxxxxxxx erytrocyty x xxxxxxxxxx, xxxx xxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxxx aberace. Mikrojádra xxx xxxxxxxx xxxxx xxxxxxxx. Ta zahrnují xxxxxxxxxxxx přítomnosti xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x mikrojádře. Xxxxxxxxx xx xxxxxxx xxxxxxx nezralých (polychromatických) xxxxxxxxxx s xxxxxxxxxx. Xxxxx zralých (normochromatických) xxxxxxxxxx x periferní xxxx, které xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx na xxxxxx xxxxx zralých xxxxxxxxxx xxx rovněž xxxxxx xxxx xxxxxxx xxxxxxxx xxxxxxx, jestliže xxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx xxxx.

Xxxxx test xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxx xxxxxx k xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x procesy xxxxxxxx XXX, třebaže xx xxxxx xxxxx x xxxxxxx xxxxx x tkání, jakož x x genetického xxxxxxxx. Zkouška in xxxx xx xxxxxx xxxxxxxx pro xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx x systémech xx xxxxx.

Xxxxxxxx existuje xxxxx x xxx, xx se zkoušená xxxxx nebo xxxxxxxxx xxxxxxxxxx nedostanou do xxxxxx xxxxx, není xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (kinetochor) : xxxxxx (oblasti) chromozomu, x xxx (x xxxx) se xxxxx xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx umožňující xxxxxxxxxx xxxxx dceřiných xxxxxxxxxx k xxxxx xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx jádra xxxxxxxxxx xxxxxxxx od xxxxxxxx xxxxx a vedle xxxx, vytvářená xxxxx xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxx xxxxxxxxxx.

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

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx erytrocyt ve xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx xxxxxxxx xxxxxxxx, x může být xxxx xxxxxxxx od xxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Xxx xxxxxxx xxxxxx xxxxx se xxxxxxx xx xxxxxxx xxxxxxxx xx expozici xxxxxx, xxxxxxx xx xxxxxx dřeň, xxxxxxxx xx xxxxxxxxx x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx použití periferní xxxx xx xxxx xx vhodném xxxxxxxx xx expozici odebere, xxxxxxxxxx xx xxxxxxxx xxxxxxxx a xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx s periferní xxxx xx xxxx xxxx poslední expozicí x xxxxxxxxx xxxxx xxxxxxxx xx nejkratší xxxx. Xxxxxxxxx jsou xxxxxxxxxxx xx xxxxxxxxxx xxxxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Při použití xxxxxx dřeně se xxxx testovací xxxxx xxxxxxxxxx myš xxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx druh. Xxx xxxxxxx xxxxxxxxx xxxx xx xxxxxxxxxx myš. Xxx však xxxxxx xxxxxxxx xxxxxx xxxx xxxxx xx předpokladu, xx xxx o xxxx, x xxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx detekovat činitele, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx být xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx xxxxx a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx xxxxxxx se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x skupinu, x xxx xx provede xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x laboratorních xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx. Xxxxx xx xxxxxxxxxx xxx, xxx xxx vliv xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx xxx xxx xxxxxxxxx úrovních xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx látkou. Xxxx-xx xxxxxxx jiná než xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx x jejich kompatibilitě. Xxxxxxxxxx se xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx pohlaví. X xxxxxxxx aplikace zkoušené xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx by měly xxxxxxxxxx xxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, x xxxxx xx očekává, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx by xxxx být xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale xxx při xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx přijatelné, xxx xxxxxxxxx kontrola byla xxxxxxxx xxxxx xxxxxxxx xxx zkoušená xxxxx x xxx xxx xxxxx x xxxxx xxxxxxx prováděn jen xxxxxx. Pro xxxxxxxxx xxxxxxxx xxxxx může xxx xxxxx x xxxxx xxxxxxx chemických xxxxx ze stejné xxxxxxxx xxxxx, jsou-li x xxxxxxxxx. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx X

50–07–7

200–008–6

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx odběru xx měl xxx xxxxxxxx xxxxx u xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx exponované xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx kontrolních xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx buněk s xxxxxxxxxx. Xxxxxxx-xx xx xxx negativní xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx nebo xxxxxx-xx publikovány kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx použití xxxxxxxxx xxxx xxxx xxx xxxx xxxxxxxxx xxxxxxxx přijatelný také xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx u xxxxxxxx xxxxxx s periferní xxxx (xxxx. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, xx xxxxxxxx xxxxx budou x xxxxxxx, xxxxx xx xx xxxxxxx xxxxxxxxxxx kontrol očekává.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní skupina xx xxxx xxxxxxx x alespoň pěti xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx (11). Xxxxxxxx jsou v xxxx xxxxxx x xxxxxxxxx údaje xx xxxxxx se xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx prokazují, xx neexistuje xxxx xxxxxxxxx rozdíl x xxxxxxxx, xxxx postačující xxxxxxxx jednoho xxxxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx určité xxxxxxx, xxxx xx xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx provedena xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx aplikace

Nelze xxxxxxxxx xxxxx xxxxxxxxxx xxxx (xx. xxxxx, dvě xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx ze xxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxx jsou xxxxxxxxxx, pokud se x xxxxxx xxxxxx xxxxxxx pozitivní výsledky, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx byla xxxxxxxxx xxxxxxxx nebo xxxx xxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxx xx xx xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. dvě xxxxx x xxx xxx x xxxxxxx xx xxxx než xxxxxxxx hodin, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu.

Test xxxx xxx xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx se aplikuje xxxxxxxx xxxxxx. Xxxxxx xxxxxx dřeně xx xxxxxxxx alespoň xxxxxxx, xxxxxxx xxxxx odběr xx xxxxxxx xxxxxxxx 24 hodin po xxxxxxxx a xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci x x xxxxxxxxxx xxxxxxxx xxxx odběry. Xxxxx xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx xxxxxxxxx. Xxxxxx xxxxxxxxx xxxx xx odeberou xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx se xxxxxxx xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx po xxxxxxxx x xx xxxxxxxxxxxx xx xxxxxx odpovídající xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx odpověď, xxxx xxxxx odběr xxxxx;

x) xxxx-xx podávány dvě xxxx xxxx xxxxx xxxxx (xxxx. dvě xxxx více dávek x intervalu 24 xxxxx), xxxx xx xxx xxxxxx při xxxxxxx xxxxxx xxxxx xxxxxxxx jednou xx 18 xx 24 xxxxxxxx po poslední xxxxxxxx x xxx xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx xxxxxxx mohou xxx xxxxx použity xxxx doby xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx xxxxx, xxxx by být xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, xxxxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx studii (13). X xxxxxxx xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx dávky. Xxxx xxxxxx xxxxx xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx xxxxxxx xxxxx nejvyšší dávka. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx dávka xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx vyšší xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x letalitě. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx x xxxx by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx x xxxxxx xxxxx některé xxxxxx xxxxxxxx (např. xxxxxxx xxxxxx nezralých erytrocytů x celkového množství xxxxxxxxxx x kostní xxxxx xxxx x xxxxxxxxx xxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx dávkou x xxxxxxx 2000 mg/kg xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné toxické xxxxxx x není-li xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, xxxx xxxxxxxxxx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx nezbytnou. X déle xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 mg/kg xxxxxxx hmotnosti/den x xxx xxxxx xxx 14xxxxx xxxxxxxx je xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx expozice xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Podávání dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx nitrožaludečně, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx x odůvodnitelných xxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx vyšších xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které obvykle xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx měla xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx kostní xxxxx nebo xxxx

Xxxxx xxxxxx xxxxx se xxxxxxx xxxxxxxxx z xxxxxx xxxx xxxxx xxxxx xx usmrcení. Xxxxx xx xxxxxxxx x xxxxxx nebo xxxxx x xxxxxxxxxx xxxxxxxx xx preparují x obarví. Xxxxxxxxx xxxx se xxxxxxx x ocasní žíly xxxx jiné xxxxxx xxxxxx cévy. Xxxxxx xxxxx xx xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), nebo xx připraví xxxxxxxxx xxxxxxxx x poté xx xxxxxx. Použitím xxxxxxx specifického xxx XXX (např. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx xxxxxxx některým xxxxxxxxxx xxxxxxxx s xxxxxxxx barviva xxxxxxxxxxxxxx xxx DNA. Tato xxxxxx xxxxxxx použití xxxxxxxxxxx barviv (např. Xxxxxx). Xxxxxxxx systémy (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, xx xx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx mikrojader x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx xx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového (nezralé + xxxxx) xxxxxxxx xxxxxxxxxx, přičemž se x xxxxxxx xxxxxx xxxxx xxxxxxx celkově xxxxxxx 200 xxxxxxxxxx x v xxxxxxx xxxxxxxxx xxxx xxxxxxx 1000 erytrocytů (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx kódovány. U xxxxxxx xxxxxxx se xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx na xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Další xxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx zralých xxxxxxxxxx xx xxxxxx mikrojader. Xxx xxxxxxxxxxxxx xxxxxxx xx neměl xxx xxxxx nezralých erytrocytů x celkového xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx týdny nebo xxxx, lze xxxx xxxxxxxx xx xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx na xxxxx zvíře. Systémy xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx xxxxxx x xxxxxxxxx cytometrická xxxxxxx xxxxxxx suspenze) xxxx xx xxxxxxxxxxxxx zdůvodnění x xxxxxxxx přijatelnými xxxxxxxxxxxxx xxxxxxxxxx hodnocení.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx měly být xxxxxxxxxx xx xxxxx xxxxxxx. Experimentální xxxxxxxxx xx zvíře. Xxx xxxxx analyzované xxxxx xx xxx xxx xxxxxx xxxxx vyšetřených xxxxxxxxx erytrocytů, počet xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx xxxx déle, xxxx xx xxx xxxx xxxxxxx xxxxx x zralých xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Pro xxxxx zvíře xx xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x procentech. Xxxxxxxxxx-xx xxxxx o rozdílu x xxxxxxxx xxxx xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx zkombinována.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxx x závislosti xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxxx xxx xxxxxxx x určitou xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx odpověď. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx látka, xxxxx xxxxxxxx nesplňují xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx x xxxxx xxxxxxx xx nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx mitotického xxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx erytrocytech testovacího xxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx zkoušená xxxxx xxxx její xxxxxxxxxx dostanou do xxxxxxxx oběhu, xxxx xxxxxxxxxx xx cílové xxxxx (xxxx. systémová xxxxxxxx).

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x zkoušce xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx zvířat,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx zkoušky, včetně xxxxxxx tělesné hmotnosti, xxxxxxx xxxxxxx a xxxxxxxxxx odchylka pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- zdůvodnění xxxxxxxxx xxxxxx dávek,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxxxxxx podávání,

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

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x vody,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- xxxxxxxx klasifikace xxxxxx xx pozitivní, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- podíl nezralých xxxxxxxxxx z xxxxxxxxx xxxxxxxx xxxxxxxxxx,

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxx,

- údaje x xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx kontrole.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

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

4) Xxxxxxxxx, K. X., Xxxxxx, X. H., Xxxxxx, X. C., Xxxxxxxx, X. F., Xxxxxx, X. X. (1990), The Xx xxxx Xxxxxxxxxxxx Xxxxx xx Mammalian Bone Xxxxxx xxx Xxxxxxxxxx Xxxxx. A report xx xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) XxxXxxxxx, J. X., Xxxxxxxx, R., Xxxx, X. X., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Erythrocytes: A Xxxxx Xxxxxx xxx Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Mice, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, ed. A. X. Hayes, X. X. Xxxxxxx, T. X. Xxxx. Elsevier, Xxxxxxxxx, 555-558.

6) MacGregor, X. X., Xxxxxx, X. A. Xxxx, X., Margolin, G. X., Ramel, X., Xxxxxxxx, M. F., Xxxx, X. R., Xxxx, X. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx of Micronucleus Xxxxxx in Xxxxxxxxx Xxxx Xxxxxx Erythrocytes, Xxxxxxxxxx Xxx., 189, 103-112.

7) MacGregor, X. X., Xxxx, X. X., Henika, X. X., Xxxxxx, M. X. (1990), Xxx xx vivo Erythrocyte Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Xxxxxx Xxxxx Xxxxxxxxx Xxxxx Efficiency xxx Xxxxxxx Integration xxxx Toxicity Studies, Xxxxxx. Xxxx. Toxicol. 14, 513-522.

8) Hayashi, X., Xxxxxx, T., Xxxxxx, X., Xxxxxx, X., Ishidate, X. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx with Xxxxx Peripheral Xxxxx Xxxxxxxxxxxxx Using Acridine Xxxxxx-Xxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 245, 245-249.

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

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx for xxx Xxxxxxxxxxxx Xxxx (XXXXX/XXXXX, XXX: Xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxx Group xx the Environmental Xxxxxxx Xxxxxxx of Xxxxx) (1995), Xxxxxxxx xxxxxxxxxxx xxx xxx xxxxx-xxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, M., Tice, X. R., XxxXxxxxx, X. X., Anderson, X., Xxxxxxx, D. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Xx. F. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Shimada, X., Xxxxx, S., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Micronucleus Xxxxx, Xxxxx. Res., 312, 293-304.

12) Xxxxxxxxxxx, X., Xxxxx, X. (1995), Xx optimal, xxxxxxxxxxx xxxxxxxx xxxx xx 30 ± 6 x xxxxx xxxxxx xxxxxx xx xxx xxxxx peripheral xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 313-319.

13) Xxxxxxx, X. X., Allen, X. X., Xxxxxx, X. X., Botham, X. X., Doe, X., Xxxxxxx, D. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Morton, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

15) XxxXxxxxx, X. X., Xxxx, X. X., Xxxxxxxx, X. X. (1983), X Simple Xxxxxxxxxxx Xxxxxxxx Procedure xxx Xxxxxxxxxxx and XXX in Erythrocytes Xxxxx Hoechst 33258 xxx Pyromin X, Xxxxxxxx Xxx., 120, 269-275.

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

17) Gollapudi, X., McFadden, X. X. (1995), Xxxxxx Xxxx for xxx Xxxxxxxxxx xx Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Erythrocyte Xxxxx in the Xxxx Marrow Micronucleus Xxxx, Xxxxxxxxxx Res., 347, 97-99.

18) Richold, X., Ashby, X., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, D. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxxx Xxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Mutagenicity xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx X., Richold, M., Xxxxxxxx, D. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx In xxxx Xxxxxxxxxxx Assays, xx: X. J. Xxxxxxxx (xx.), Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Xxx-Xxxxxxxxx on Guidelines xxx Mutagenicity Xxxxxxx. Xxxxxx, Xxxx XXX, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


PŘÍLOHA 4D

"B.13/14 XXXXXXXXXX — XXXXXXX NA XXXXXXXX MUTACE S XXXXXXXXXX

1. METODA

Tato metoda xx xxxxxxxx metody XXXX XX 471 — Xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx bakteriální xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Escherichia xxxx, x detekci xxxxxxxx xxxxxx, xxxxx zahrnují xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx xxxx xxxxxxxx párů bází XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx xxxxxxxx x xxxxxxxxxxx kmenech a xxxxxxxx tak xxxxxxx xxxxxxxxx xxxxxxxx syntetizovat xxxxxxxxxx xxxxxxxxxxxxx. Bakterie xx reverzi xxxx xxxxxxxxxx díky své xxxxxxxxxx xxxx x xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx kmenem.

Bodové xxxxxx x podobné xxxx xxxx příčinou mnoha xxxxxxxxx podmíněných xxxxxx x člověka x xxxxxxxx mnoho xxxxxx x xxx, xx xxxxxx mutace x xxxxxxxxxx a x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx nádory xxxx xxxxx na xxxxxx xxxxxxxx u xxxxxxx x u xxxxxxxxx xxxxxx. Zkouška na xxxxxxxx xxxxxx s xxxxxxxxxx xx rychlá, xxxxxxxxxx x xxxxxxxxx xxxxxx. Xxxxx xxxxxxxxxxx xxxxx má řadu xxxxxxxxxx, xxxx nimž xxxx xxxxxxxxxx na xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx permeability buněk xxx xxxxx xxxxxxxx x xxxxxxxxx reparačních xxxxxxx XXX xxxx xxxxxxxx reparačních xxxxxxx XXX náchylných k xxxxxx. Xxxxxxxxxxxx xxxxxxxxxxx xxxxx xxxx poskytnout xxxxxxx užitečné informace x typech xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx na xxxxxxxx xxxxxx x bakteriemi xx x xxxxxxxxx xxxxx rozsáhlá xxxxxxxx xxxxxxxx xxx xxxxxxx xxxxx xxxxxxxx a xxxx xxxx xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx těkavých xxxxxxxxx, x různými xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx slouží x xxxxxxx xxxxxx x xxxxx vyžadujícím xxxxxxxxxxxxx (xxxxxxxx resp. xxxxxxxxx), přičemž xxxxxx xxxx nezávislý xx xxxxxxx přísunu xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx reverzních xxxxxx xx mohou tyto xxxxx vyskytnout xx xxxxx xxxxxxx mutace xxxx jiném xxxxx xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx xxxxxxxx xxxx xxxxxxxx, jež xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx nebo xxxx párů xxxx XXX x xxxxxxxx xxx xxxxx rámec XXX.

1.3 XXXXXXX ÚVAHY

Při xxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xx xxxx od xxxxx xxxxx xxxxxxx, jako xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx struktura a xxxxxxxxx procesy DNA. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Metabolické xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx x savců. Xxxxxxx xxxx neposkytuje xxxxxx xxxxxxxxx x xxxxxxxxxx x karcinogenním xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx na reverzní xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxx xxx počáteční vyšetření xxxxxxxxxxx aktivity, x xxxxxxx xxxxxxxx vyvolávající xxxxxx mutace. X xxxxxxxx xxxxxxxx xxxxxxx, xx xxxxx xxxxxxxxxx xxxxx, xxxxx jsou x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx i v xxxxxx xxxxxxxxx. Existují xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx. Xxxxxxx xxxxxx xxxxxxxxxxx xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx xxxx x xxxxxxxxx v xxxxxxxxxx dostupnosti. Xx xxxxx xxxxxx xxxxxxx, xxxxx zvyšují citlivost xxxxxxx xx xxxxxxxx xxxxxx na xxxxxxxxxx, xxxxx xxxx k xxxxxxxxxxxx mutagenní xxxxxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx nemusí xxx vhodná xxx xxxxxx třídy xxxxxxxxxx xxxxx, například xxxxxx xxxxxxxxxxxx xxxxxxxxxx (např. xxxxxx xxxxxxxxxxx) x xxx chemické látky, x xxxxx xx xxxxxxxxxxx (xxxx o xxxxx xx xx), xx specificky zasahují xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). V takových xxxxxxxxx mohou xxx xxxxxxxxx xxxxxxx mutagenity x savců.

Přestože mnoho xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xx xxxxxxxxxxxx xxx savce, xxxx xxxxxxxx absolutní. Xxxxxx xx xxxxxxxx třídě x xxxxxxxx xxxxx xxxxxxxxxxx, jež xxxxxx xxxxxxxxxx xxxxx zkouškou, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, nebo xxxxxxxxxx, které x xxxxxxxxxxxxx xxxxxxx neexistují.

1.4 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx látce, x xx xx xxxxxxxxxxx vnějšího xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx x xxx xxxx. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx suspenze smíchají x xxxxxxx xxxxxx x ihned xx xxxxxxx xx minimální xxxx. V xxxxxxxxxxxx xxxxxx se xxxxxxxx xxxx xxxxxxxx x xxxx xx xxxx xxxxxxxxx na minimální xxxx smíchá x xxxxxxx xxxxxx. Xxx xxxx technikách xx xx xxxx xxxx xxxxx dnech inkubace xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxx xx xxxxxxxx s počtem xxxxxxx xxxxxxxxxxx revertantů xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

Xx xxxxxxx xxxxxxx xxxxxxx xxxxxxxxx xxxxxxx xx reverzní xxxxxx x bakteriemi. Xxxx xxxxx používané xxxxx xxxxxxxxxx miskový xxxx (1, 2, 3, 4), preinkubační xxxxxx (2, 3, 5, 6, 7, 8), fluktuační test (9, 10) a xxxxxxxxx xxxxxx (11). Xxxxxx pro xxxxxxxx xxxxx x xxx xxxx xxxxxxx (12).

Zde xxxxxxx postupy se xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxx. Každá x nich xx xxxxxxxxxx pro xxxxxxxxx xxxxxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxx za xxxxxxx xxxxxxxxxxxx xxxxxx. Tyto xxxxx xxxxx xx xxxxxxxxxx xxxx, xx xxxxx xxxxx xxxx xxxxx krátké xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, azobarviva x xxxxxxxxxx sloučeniny, pyrrolizidinové xxxxxxxxx, allylové sloučeniny x xxxxxxxxxxxxxxx (3). Xxxxxx xx připouští, xx xxxxxx xxxxx xxxxxxxx xxxxx xxxx xxxxxxxxx standardními xxxxxxx, xxxx xx standardní xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Měly xx xxx považovány xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Xx xxxxx xxxxxxxxxxxxx xxxx "zvláštní xxxxxxx" (xxxxxxxx x xxxxxxxx postupů jejich xxxxxxx): xxxxxxxxxx x xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx a těkavé xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Odchylka xx xxxxxxxxxxxx xxxxxxx musí xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Bakterie

Čerstvé xxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxx do xxxxxx xxxxxxxxxxxxx fáze xxxx xx xxxxx xxxxxxxxxxx xxxx růstu (xxxxxxxxx 109 xxxxx xx ml). Xxxxx x xxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Xx xxxxxxxx, xxx xxxx xxxxxxx bakterie vysoký xxxx xxxxxxxxxxxxxxx xxxxxxxx. Xxxx xxxx být xxxxxxxx xxx na xxxxxxx dosavadních xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxx pro xxxxxx xxxxxxx xxxxxxxxxx xxxxx životaschopných xxxxx xx xxxxxxx.

Xxxxxxxxxx inkubační xxxxxxx xx 37 °X.

Xxxx by být xxxxxxx xxxxxxx xxx xxxxx bakterií. Mezi xxxx xx xxxx xxx čtyři xxxxx X. typhimurium (XX1535; XX1537 xxxx XX97x xxxx XX97; XX98 x XX100), jejichž xxxxxxx xx xxxxxxx x různých laboratořích xxxx xxxxxxxxxx a xxxxxxxxxxxxxxxx. Xxxx čtyři xxxxx S. xxxxxxxxxxx xxxx xxx bází XX na primárním xxxxxxxxx xxxxx x xx xxxxx, xx xxxxxx prostřednictvím xxxxx xxxxxxxxx xxxxxx oxidační xxxxxxxx, xxxxxxxx způsobující xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Xxxx xxxxx mohou xxx xxxxxxxxxx xxxxx X. xxxx WP2 xxxx X. xxxxxxxxxxx XX102 (19), které xxxx xx xxxxxxxxx xxxxxxxxx xxxxx xxx xxxx XX. Doporučená kombinace xxxxx xx xxxx xxxx:

- X. typhimurium XX1535 a

- X. xxxxxxxxxxx TA1537 nebo XX97x a

- X. xxxxxxxxxxx TA98 x

- X. xxxxxxxxxxx TA100 x

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

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

Xxxx by xxx xxxxxxx xxxxxxxx xxxxxxx přípravy xxxxxxx xxxxxxx, verifikace xxxxxxx x skladování. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx kulturu (xxxxxxxx pro xxxxx X. xxxxxxxxxxx x xxxxxxxxx pro E. xxxx). Xxxxxxx xx xxxx xxx xxxxxxxxxxxx xxxx fenotypové xxxxxxxxxxxxxxx, xxxxxxxxx xxxxx xxxxxxx xxxxxxxxxx xxxx nepřítomnost X-xxxxxxx xxxxxxxx (tj. xxxxxxxxxxxx xxxxxxxxxx x xxxxx TA98, TA100 x TA97a xxxx XX97, WP2 xxxX x XX2 xxxX (xXX101) a xxxxxxxxxxxx x xxxxxxxxxxxxxx rezistence x kmene XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx mutací (xx. xxx xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x xxxX xxxxxx x E. xxxx nebo xxxX xxxxxx u S. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx světlo) (2, 3). Xxxxx xx xxxx rovněž dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxx četností xxxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx laboratorních xxxxxxx x nejlépe x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx xxxxxx minimální xxxx (např. xxxxxxxxxx xxxxxxxxx xxxx X (Xxxxx-Xxxxxx) x xxxxxxx) x vrchní xxxx xxxxxxxxxx xxxxxxxx x xxxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx xxxxxxxx

Xxxxxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx, x xx s xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x bez xxxx. Nejčastěji xxxxxxxxxx xxxxxxxx xx kofaktorem xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx z xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (1, 2) xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx v xxxxxxx 5 xx 30 % xxx. xx směsi X9. Xxxxx a xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx záviset na xxxxx zkoušené xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx xxxx být xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxx xxxx být xxxxxxxxx použití xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx látky by xxxx xxx před xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx mohou xxx přidány přímo x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx xxxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx mimo podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx by xxx xxxxxxxxxx x xxxxxxxx xxxxxxxx x s xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx podloženo xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx měla xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx vodu.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Xxxxxxxx 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 cytotoxicita x rozpustnost x xxxxxxx směsi pro xxxxxxxx.

Xxxx být užitečné xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxxxxxx může xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx stupně xxxxxxx xxxxxxxxxxxx kultur. Xxxxxxxxxxxx xxxxx xx xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systémů. Xxxxxxxxxxxxx xx měla xxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxxx xxxxx xx xxxxxxxxxx zkušebních xxxxxxxx.

Xxxxxxxxxx maximální xxxxxxxx xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx je 5 xx/xxxxx nebo 5 μx/xxxxx. X xxxxxxxxxxxxxxx látek xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by xxxx xxx xxxxx xxxx xxxx xxxxxxxxxx koncentrací xxxxxxxx, aby látky xxxx x xxxxxxx xxxxx xxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx cytotoxické xxx při xxxxxxxxxxxxx xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx xxxxxxxx xx xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

Mělo xx být xxxxxxx xxxxxxx pět xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx xx xxxx být intervaly xxxx zkušebními xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx logaritmické stupnice (xx. Ö10). Xxxxx xxxxxxxxx jsou vhodné x xxxxxxx, kdy xx xxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx na xxxxxxxxxxx. Xxxxxxxx koncentrací xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx být xxxxxxx při hodnocení xxxxx obsahujících xxxxxxxx xxxxxxxx potenciálně xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Negativní x xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx xx měly xxx kmenově specifické xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx a xxx xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx vybrány xxxxxxxxxxx xxxxxxxxxxx účinnost xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x použitím metabolického xxxxxxxxxxx xxxxxxx by xxxx xxx látka (xxxxx) pro xxxxxxxxx xxxxxxxx vybrána (xxxxxxx) xx xxxxxxx xxxx xxxxxxxxx xxxxx bakterií.

Příkladem xxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx x xxxxxxxxxxxx aktivací jsou 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 xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

XX Xxxxxx Xxx 28

573–58–0

209–358–4

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

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx u xxxxxxx xxx xxxxxx xxxxxxxxxxx aktivace jsou xxxx xxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx EINECS

Kmen

azid sodný

26628–22–8

247–852–1

TA1535 x XX100

2-xxxxxxxxxxxx

607–57–8

210–138–5

XX98

9-xxxxxxxxxxxx

90–45–9

201–995–6

XX1537, XX97 x TA97a

ICR 191

17070–45–0

241–129–4

TA1537, XX97 x XX97x

Xxxxxxxxxxxxxxxxx

80–15–9

201–254–7

XX102

xxxxxxxxx X

50–07–7

200–008–6

XX2xxxX a XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 xxxX x 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 obsahující xxxxxxxx

Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx jiné xxxxxx xxxxxxxxxx látky. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx chemické xxxxx, jsou li x xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx skládající se xx xxxxxxxxx rozpouštědla xxxx xxxxxxxx, bez xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx toho by xxxx xxx neexponované xxxxxxxx použity xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5.3 Xxxxxx

X standardní xxxxxxx xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx aktivace se xxxxxxx xxxxxx 0,05 xx xxxx 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx čerstvé xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx xxxxxxxxxx pufru x 2,0 ml xxxxxxxx xxxxx. X xxxxxxx xxxxxxx x xxxxxxxxxxxx aktivací xx xxxxxxx smíchá 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx obsahující xxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (x rozmezí 5 xx 30 % xxx. x metabolické xxxxxxxxx směsi) x xxxxxxx xxxxxx (2,0 xx) a xxxxxxx x bakteriemi x xxxxxxxxx xxxxxx xxxx xxxxxxxxx roztokem. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx a xxxxxxx xxxx xxxxxx minimálního xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X preinkubační xxxxxx (2, 3, 5, 6) xx zkoušená xxxxx xxxx zkoušený xxxxxx před xxxxxxxxx x xxxxxxx xxxxxx x xxxxxxxx přes xxxxxx xxxxxxxxxxx agaru xx xxxxx xxxxxxx 20 minut xxxx xxxx preinkubuje x xxxxxxxxxx kmenem (obsahujícím xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x xxxxxxxxx xxxxxx xxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °C. Xxxxxxx xx xxxxxx 0,05 nebo 0,1 xx xxxxxxxx látky xxxx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxxx x 0,5 xx xxxxx X9 nebo xxxxxxxxxx xxxxx s 2,0 xx vrchního xxxxx. Xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X dostatečnému odhadu xxxxxxxx xx měly xxx při xxxxx xxxxxx dávky použity 3 misky. Xxxxxxx xxxx xxxxx xx xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx xxxxxx znamenat xxxxxxxxxxxx xxxxxxx.

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

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx x xxxx xxxxxxx by xxxx xxx inkubovány xxx 37 °C xx 48 –72 xxxxxxxx. Xx uplynutí xxxxxxxxx doby xx xxxxxx počet xxxxxxx xxxxxxxxxx xx misku.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx xx měly xxx počty xxxxxxx xxxxxxxxxx připadající xx xxxxx. Měl xx xxx xxxxxx xxxxxx xxxxx kolonií revertantů xxx xx miskách x xxxxxxxxx xxxxxxxxx (xxxxxxxx xxxxxxxxxxxx a xxxxxxxx xxxxxxxxxxxx kontrola), xxx xx xxxxxxx x xxxxxxxxx kontrolou. Xxxxx xx jednotlivých xxxxxxx, xxxxxxx hodnoty xxxxx xxxxxxx xxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx zkoušenou xxxxx x pozitivní x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx xx xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx xxx potvrzeny xxxxxx xx případu. Xxxxxxxx se xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxx, xxxx xx xxx podáno xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla xxx xxxxxxx x xxxxxxxxxx experimentech. K xxxxxxxxxx studie, xxxxx xx xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, metoda xxxxxxxxxx (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx v xxxxxxxx xxxxx) x xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, např. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx rozsah x xxxxxxx jednoho xxxxx x xxxxxxxxxxxx aktivačním xxxxxxxx xxxx xxx xxxx, a xx x xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx xxx xxxxx xxxx xxxx koncentrací (23). Xxxxxxxx xx xxxx xxx uvážena biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků zkoušky xxxxx být použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (24). Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx negativní xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx znamenají, že xxxxxxxx xxxxx xxxxxxxx x genomu kmenů Xxxxxxxxxx typhimurium x/xxxx Xxxxxxxxxxx coli bodové xxxxxx xxxxxxxxxx bází xxxx posunem čtecího xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, že zkoušená xxxxx není xx xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxx xxxxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx v xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxx xxxxxxxx xxxxx xx xxxxx (xx/xxxxx xxxx μx/xxxxx) s xxxxxxxxxxx xxxxxx xxxxx x xxxxx misek xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

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

- xxxxxx expozice.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx miskách,

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

- xxxxx možnosti závislost xxxxxxxx na dávce,

- xxxxxxxx statistické xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Xxxxx, D. X., Ames, X. X. (1983), Xxxxxxx Xxxxxxx for xxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 113, 173-215.

3) Gatehouse, X., Xxxxxxx, S., Cebula, X., Xxxxx, E., Xxxx, L., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxx, X., Zeiger, X. (1994), Recommendations xxx xxx Performance of Xxxxxxxxx Xxxxxxxx Assays, Xxxxxxxxxx Xxx., 312, 217-233.

4) Kier, X. X., Brusick D. X., Auletta, A. X., Von Halle, X. X., Xxxxx, X. X., Simmon, X. X., Dunkel, X., XxXxxx, J., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Ray X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Assay: X Xxxxxx of xxx U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

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

6) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Yahagi, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Mutagenicity Xxxxxxxxx Xxxxx, xx: Xxxxx-xxxx Xxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx K. H., Xxxxxx, X. C., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Gatehouse, D. X., Rowland, X. X., Wilcox, X., Xxxxxxxxx, X. X., Xxxxxx, R. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Xxxxx Mutagenicity Xxxxx: UKEMS Part 1 Xxxxxxx, xx. X. J. Kirkland, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.

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

9) Green, X. X. X., Xxxxxx, X. J., Xxxxxxx, X. X. (1976), Use xx x simplified xxxxxxxxxxx xxxx xx xxxxxx xxx levels xx xxxxxxxx, Mutatation Res., 38, 33-42.

10) Xxxxxxx, X. A., Xxxxx, X. X. X., Xxxxxxxxx, D., Xxxxxxx, X. X. (1984), Xxx Fluctuation Xxxx xx Xxxxxxxx, in: Xxxxxxxx xx Mutagenicity Xxxx Xxxxxxxxxx, 2. xxx., Kilbey, B. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X. (eds.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, E. X., Xxxxxxx, X. X. (1981), Xx Xxxxxxxxxxx xx the Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx xxx Xxxxxxxxxxx xxxx Strains xx Salmonella xxxxxxxxxxx, Xxxxxxxxxxxxx Mutagenesis, 3, 453-465.

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

13) Prival, X. X., Bell, S. X., Mitchell, X. X., Reipert, X. X., Xxxxxxx, X. X. (1984), Mutagenicity xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Xxxx xx x Xxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Anderson, X. X., Haworth, X., Xxxxxx, T., Xxxxxxxxxx, K. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Results from xxx Xxxxxxx xx 311 Xxxxxxxxx, Environ. Xxx. Xxxxxxx., 19, 2-141.

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

16) Hughes, X. J., Xxxxxxx, X. X., Xxxxxxxx, X. X., Claxton, X. D. (1987), Xxxxxxxxxxxx Technique to Xxxxxxx Xxxxxxxxx Activity xx Xxxxxxxx Xxxxxxx Xxxxxxxxx in xxx Xxxx/Xxxxxxxxxx Assay, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

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

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

19) Xxxxxx, X., Xxxxxx, X., Xxxx, X. X., Xxxxxxxxx, X. G. (1990), Xxxxxxxxxx of Xxxxxxxxxx xxxxxxxxxxx XX 102 xxxx Escherichia xxxx WP2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: Xx vitro Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, xxx. X. J. xx Xxxxxx et al. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Elliot, X. X., Xxxxxx, X. X., Xxxxxxx, C. X., Gatehouse, D. X., Gibson, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx in xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 175-177.

22) Xxxxx, X., Xxxxxxxxxxxxxxxx, X., Ames, X. X. (1981), Xxxxxxxxxxxxx xx Xxxxxxx Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 88, 343-350.

23) Claxton, X. X., Xxxxx, X., Auletta, A., Xxxxxxxxxx, X., Nestmann, X., Xxxxxx, X. (1987), Xxxxx xxx xxx Xxxxxxxxxx typhimurium/Mammalian Xxxxxxxxx Xxxxx for Xxxxxxxxx Mutagenicity, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, X. X. X., Xxxxx, X. X. X., Xxxxxxxxx, X., Xxxxxxx, I., Xxxxxxxx, X. D., Xxxxxx, D. X. (1989), Analysis of Xxxx xxxx Microbial Xxxxxx Xxxxxx, in: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Xxxx Xxxx, xx. Kirkland, X. X., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 28-65."


XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx vitro lze xxxxxx pro xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx látkami. Xxxx xxxxxx xxxxxxx linie xxxxx xxxxx lymfomu X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x X79 xxxxxx xxxxxxxx x lymfoblastoidní xxxxx TK6 člověka (1). U xxxxxx xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx mírou xxxxxxxxxxx xxxxxx mutace genů xxx thymidinkinasu (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x xxxxxxxx xanthin-guaninfosforibosyltransferasy (XXXX). Xxxxxxx na xxxxxx XX, HPRT x XXXX detekují xxxxx xxxxxxxx genetických xxxxxxxx. Xxxxxxxxxxx lokace XX x XPRT xxxx xxxxxxx detekci xxxxxxxxxxx událostí (xxxx. xxxxxxxx xxxxxx), které xxxxx xxxxxxxxx x XXXX xxxxxx xx X chromozomech (2, 3, 4, 5, 6).

Xx xxxxxxx xx xxxxxx xxxxxx v xxxxxxx xxxxx in xxxxx xxx použít xxxxxxx xxxxxxxxxx linií xxxxx xxxx xxxxxxx xxxxx. Xxxxx xx xxxxxxxx xxxxx xxxxxxxxxx xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.

Zkoušky xxxxxxxxx xx vitro xxxxxx xxxxxxxx použití vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační xxxxxx xxxxxx zcela xxxxxxxxx podmínky xx xxxx u xxxxx. Xx xxxxx xx xxxxx vyvarovat podmínek, xxxxx by xxxxx x pozitivním xxxxxxxxx, xxx neodrážejí vlastní xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx neodrážejí xxxxxxx xxxxxxxxxx, xxxx xxxxx změnou xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx cytotoxicity (7).

Xxxx xxxxxxx xx xxxxxxx xx zjištění xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx sloučenin, xxx něž xx xxxx xxxxxxx xxxxxxxxx, xxxx xxxxxxxxxxx savců; xxxx touto xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx na xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx nejsou xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x bakteriálních xxxxxxx xxxxxxxxxx (6).

Xxx také xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Přímá xxxxxx : xxxxxx xxxxxx xxxxxxxxx typu xxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxx nebo xxxxxx xxxxxxxxxxx xxxxxxxx kódovaných xxxxxxxx.

Xxxxxxxx substituce xxxx xxxx : látky, xxxxx způsobují xxxxxxxxxx xxxxxxx xxxx více xxxx bází v XXX.

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx způsobují xxxxx nebo xxxxxx xxxxxxx nebo xxxx xxxx xxxx x xxxxxxxx DNA.

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

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

Relativní xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx ve xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx se xxxx xxxxxx xxxxxx xxxxxxxxx růstu x xxxxxxxx a x xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx k negativní xxxxxxxx.

Xxxxxxxxx xxxx v xxxxxxxx : xxxxxx xxxxx xxxxx v xxxxxxx xxxxxxx vzhledem x xxxxxxxxx xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx klonování xxxxx x xxxxxxxx xxxxxxxx xx xxxxx xx selektivních xxxxxxxx xx expresi.

Přežití : xxxxxxxx xxxxxxxxx buněk xxx nasazení na xxxxx na xxxxx xxxxxx expozice; přežití xx xxxxxxx xxxxxxxxx x poměru x xxxxxxx kontrolní populace xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxx, které v xxxxxxxx xxxxxx TK+/-® XX— /- neobsahují xxxxxxxxxxxxxx (TK) jsou xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx analogu xxxxxxxxxx xxxxxxxxxxxxxxxxx (TFT). Xxxxx xxxxxxxxxxx thymidinkinasu xxxx xxxxxxx na XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx metabolismu x xxxxxxxxx další xxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxx tedy xxxxxxx xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx schopnost xxxxxx. Xxxxxxx lze x xxxxx s xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx xxxxxxx xxxxxxxxxxxxxxx rezistence k 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx látky xx xxxx být xxxxxxx xxxxxxx, xxxxxxxx xx xx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců xxxxxxx xxxxxx xxxx nebo xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx by xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx na xxxxxxxxxx toxicitu xxxxxxxx xxxxx xxx mutantní xxxx xxxxxxxxxx buňky. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, musí xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxx nebo xxxxxxx xxx xxxxxxx (8).

Xxxxx v xxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxx xxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxx x metabolickou xxxxxxxx, xxx xxx xx, x subkultivovány xx xxxxxx stanovení xxxxxxxxxxxx x xx xxxxxx exprese xxxxxxxx xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Cytotoxicita xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx po xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx se xxxxxxx x xxxxxxxx xxxxx po xxxxxxx xxxx charakteristickou pro xxxxx xxxxxxx xxxxx x xxx xxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx fenotypová xxxxxxx xxxxxxxxxxxx mutací. Četnost xxxxxxx xx stanoví xxx, xx xx xxxxxx známý xxxxx xxxxx xx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx xxxxxxx mutantních xxxxx a xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx účinnost klonování (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx xx xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx se xxxxxxx x xxxxx mutantních xxxxxxx x xxxxxxxxx xxxxx x xxxxx xxxxxxx v médiu xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx použití x této xxxxxxx xxxx x dispozici xxxxx xxxx buněk, xxxxxx xxxxxxxx xxxxx X5171X, CHO, CHO-AS52, X79 xxxx XX6. Xxxx buněk v xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxxxxx x chemickým mutagenům, xxxxxxx xxxxxxxxx schopnost x stabilní xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx měly být xxxxxxxxxxxx, xxx nejsou xxxxxxxxxxxxx mykoplasmaty, x x xxxxxxx kontaminace xx xxxxxx xxx xxxxxxx.

Xxxxxxx by xxxx xxx navrženy tak, xxx měly xxxxxx xxxxxxxxxx xxxxxxxxx x xxxx. Xxxxx xxxxxxxxx xxxxx, xxxxxx a xxxxxxxxxxx zkoušené xxxxx xx xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Minimální xxxxx xxxxx, xxxxx přežijí xxxxxxxx x které xxxxx xxxxxxx v xxxxxx stadiu xxxxxxx, xx měl xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx mutací. Xxxxxxx xxxxxxxxx xx, xxx xxx xxxxxx xxxxx xxxxx, který je xxxxxxxxxxxxxx převrácené xxxxxxx xxxxxxxx xxxxxxxxxxx mutací. Xx však xxxxxxxxxx, xxx bylo použito xxxxxxx 106 buněk. Xxxx xx xxx x dispozici xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx xxxxxxxx systému, xxx byla xxxxxxxx xxxxxxxxxxxx výpovědní xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx a xxxxxxxxxx podmínky

Pro udržování xxxxxx by xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx média x xxxxxxxxx podmínky (kultivační xxxxxx, xxxxxxxxxxx CO2, xxxxxxx x xxxxxxx). Xxxxx by měla xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx a xxxx xxxxx použitých xxx xxxxxxx. Xx xxxxxxx důležité, aby xxxxxxxxxx podmínky byly xxxxxxx tak, xxx xxxx xxxxxxxxx optimální xxxx buněk xxxxx xxxxxx xxxxxxx x xxxxxxxxx jak xxxxxxxxxx, xxx xxxxxxxxxxxx buněk xxxxxx xxxxxxx.

1.4.1.3 Příprava xxxxxx

Xxxxx xx měly xxx získávány z xxxxxxxxx kultur, xxxxxxxx xx kultivačního xxxxx x xxxxxxxxxx xxx 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx může xxx xxxxxxxx xxxxxxxxx z xxxxxxx xxx xxxxxxxx xxxxxxxx xxxxx.

1.4.1.4 Metabolická xxxxxxxx

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

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx xxxxxxxxxx médiu obvykle xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % obj. Xxxxx x xxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx případech xxxx xxx xxxxxx xxxxxx xxxx xxx jednu xxxxxxxxxxx postmitochondriální xxxxxx.

Xxxx xxxxxxxx vývoje, xxxxxx xxxxxxxx geneticky xxxxxxxxxxxxxx xxxxxxxxx linií xxxxxxxxxxxxx xxxxxxxxxx aktivační xxxxxx, xxxxxxxxx možnosti pro xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx (např. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx xxxxxxxxxxxx xxxxxxxx látky).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx před aplikací xx xxxxx rozpuštěny xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx být xxxxxxx přímo x xxxxxxxxxx systémům a/nebo xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, xxxxx xxxxx x stálosti xxxxxxxxxxx možnost skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx podezření, že xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x přežitím xxxxx x s aktivitou X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Doporučuje xx pokud xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx xxx použitá xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, xxxxx xxxx xxx zohledněna xxx xxxxxxxxx nejvyšší xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxxxx x změny xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x xxx ní x xxxxxxx xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, xxxx xxxx xxxxxxxxx účinnost xxxxxxxxx (přežití) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxx v xxxxxxxxxx xxxxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx toxicity xx xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a minimální xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, což xxxx xxxxxxx xxxxxxxx, xx xx xx koncentrace xxxx xxxxx xxxxxxxx 2 až Ö10. Xx-xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx od xxxxxxxxxxxx, xxxx by být xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx nejméně 10 %) přežití (relativní xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx celkový růst. X případě xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx xxxx, xxxxx x nich xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxx xx k xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx xxxxxxxx, nebo xx za tuto xxx. Měla xx xxx xxxxxxxxx případná xxxxxxxxxxxxx x xxxxxxxx xxxxx, ve kterému xxxx xxxxx xxxxxxxxxx. Xxxx xxx výhodné xxxxxxxx rozpustnost na xxxxxxx x xx xxxxx xxxxxxxx, neboť xxxxxxxxxxx xx xxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx xxxxxxx xxxxx x důsledku xxxxxxxxxxx buněk, X9 xxxx, xxx. Nerozpustnost xxx xxxxxxx vizuálně. Xxxxxxxxx xx neměla xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx jak s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Při xxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx kontrolou chemická xxxxx, xxxxx x xxxxxxxxx odpovědi vyžaduje xxxxxxxx.

Xxxxxxxxx pozitivní kontroly xxxxx být tyto xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx Xxxxxx

Xxx xxxxxx xxxxxxxxxxx xxxxxxxx

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

XX (xxxx a xxxxx xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx metabolickou xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (xxxx a xxxxx xxxxxxx)

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

xxxxx[x]xxxxx

50–32–8

200–028–5

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–5

XXXX

X-xxxxxxxxxxxxxxxxxxx (xxx vysoké xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx xxx použity xxxx jiné referenční xxxxx xxx xxxxxxxxx xxxxxxxx, např. má-li xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx o 5-brom-2′-deoxyuridinu (XXX 59–14–3, EINECS 200–415–9), xxxx být xxxx referenční xxxxx xxxxxx xxxxxxx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx vzato x xxxxx použití xxxxxxxxxx xxxxx pokud xxxxx xx xxxxxx xxxxxxxx xxxxx.

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx tvořené xxxxxx xxxxxxxxxxx xxxxxxx rozpouštědlo xxxx xxxxxxxxx x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx jako xxxxxxxxxx xxxxxxx. Xxxxx toho xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky xx měly xxx xxxxxxxxx zkoušené xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxx xxx xxxx. Xxxxxxxx by měla xxxxx vhodnou dobu (xxxxxxx xx xxxxxx xxxx 3 xx 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx xx jeden xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx zkušební xxxxxxxxxxx mohou xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx exponovaná xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, xxx xx xxx xxxxx xxxxxxxxxxx zvýšen xxx, xxx byl zajištěn xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx by xxx použity xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

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

1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx konci xxxxxxxxx xxxx se buňky xxxxxxx x xxxxxxxxx xx účelem xxxxxxxxx xxxxxxx x xx xxxxxx umožnění xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx účinnosti xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxxx xxxxxxxxx růstu xxxxxx xx xxxxxxx xxxxxxx xx expoziční xxxx.

Xxxxx xxxxx xx xxxxxxxxxx minimální xxxxxx xxxxxx, xxx umožnil xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx nově indukovaných xxxxxxx (XXXX x XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, XX xxxxxxx xxx xxx). Xxxxx xxxx kultivovány v xxxxx se selekčním xxxxxxxx (xxxxxxxxxx xxxxxxx) x xxx něho (xxx xxxx) xx xxxxxx xxxxxxxxx počtu xxxxxxx x xxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (použité xxx xxxxxxx xxxxxxxx mutantů) xx započne na xxxxx doby exprese xxxxxxxxx na misku xxx selekčního xxxxxxx.

Xx-xx xxxxxxxx xxxxx pozitivní xx zkoušce L5178Y XX+/-, xxxx xx xxx xxxxxxxxx alespoň xx xxxxx xx xxxxxxxxxx xxxxxx (x xxxxxxxx xxxxxxxxx koncentrací) x xx negativních x pozitivních kontrolách xxxxxxxxx xxxxxxx podle xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxx ve xxxxxxx L5178Y TK+/- xxxxxxxxx, xxxx xx xxx rozdělení xxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx kontrolách. Xxx studiích xx xxxxxxx XX6 TK+/- xxxx xxx také xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx velikosti xxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xx xxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx a xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx xxxxxxxx xx zkoušku X5178X XX+/- xx xxxxxxx xxxxxxxxx xxxxxxx u xxxxx koncentrace xxxxxxxx xxxxx (nejvyšší pozitivní xxxxxxxxxxx) x u xxxxxxxxx x xxxxxxxxx xxxxxxxx za použití xxxxxxxx malá xxxxxxx — velká xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxx kolonie, xxx xxxxxxx tvořících xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx s xxxxxxxxx xxxxxx (xxxxx) x kolonie s xxxxxxx xxxxxx (xxxx) (25). X xxxxxxxxxx xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx prodloužily xxxx xxxxxxxx, a xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx xx xx karyotypické viditelné xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xx xxxxxxx x chemickými xxxxxxx, xxxxx xxxxxxxx silné xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx xxxxxxxxx xxxxx mutantů xxxxxx xxxxxxxx tempem xxxx xxxxxxxx xxxxx x xxxxx xxxxx kolonie.

Mělo xx xxx xxxxx xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. Xxxxxxx xxxxxxx by xxxx xxx xxxxxxxxx jako xxxxx mutantů x xxxxx přeživších xxxxx.

Xxxx xx xxx uvedeny xxxxx xxx xxxxxxxxxx xxxxxxx. Dále xx xxxx xxx xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx případ xx xxxxxxx. Xxx, kde xxxx potvrzení xxxxxxxxxxx xxxxxxxx považováno xx xxxxx, je xxxxx xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx s xxxxx xxxxxxxx rozsah xxxxxxxxxxxx xxxxxxxx by xxxx xxx zvážena x následných experimentech xxx xxx xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx xxxxxxxx. X xxxxxxxxxx xxxxxx, které xx xxxxx být xxxxxxx, patří rozmezí xxxxxxxxxxx a xxxxxxxx xxxxxxxxxxx aktivace.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx četností xxxxxxx x xxxxxxxxxx xx koncentraci, xxxx xxxxxxxxxxxxxxxx xxxxxx této xxxxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxx mutace x xxxxxxx savců xx xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx savců xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx je xxxxx xxxxxxxx. Negativní výsledky xxxxxxxxx, xx zkoušená xxxxx xx xxxxxxxx xxxxxxx neindukuje v xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxx a zdroj xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x počtu xxxxxx, xxxxxx např. xxxxx x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, xxxx-xx x xxxxxxxxx,

- složení xxxxx, případně koncentrace XX2,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx doba,

- délka xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx během xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- délka xxxx exprese (případně xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx a xxxxxx xxxxx),

- selekční xxxxxxx,

- xxxxxxxx klasifikace xxxxxxx na pozitivní, xxxxxxxxx nebo xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx a xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx srážení,

- xxxxx x xX x xxxxxxxxxx během xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxx,

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

- xxxxxxxxx předpoklady xxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxxxxxx systémem X5178X TK+/-,

- xxxxx xxxxxxxx závislost xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx xxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

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

4) Moore, X. X., Xxxxxxxxx-Xxxxx, X., Xxxxx, C. X., Xxxxxxxxx, K. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx xx xxx Xxxxx Xxxxxxxx XX and CHO XXXXX Loci, Xxxxxxxxxxx, 4, 394-403.

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

6) Xxxxx, X. S., Xxxxxxxxxx, X., Glatt, X. X., Xxxxx, X., Xxxxx, X., Xxxxxxxxxx, Xx. X. X., Xxxxxx, X., Xxxxxxxx, E. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Report. Xxxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxxx on Standardisation xx Genotoxicity Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Scott, X., Galloway, S. X., Xxxxxxxx, R. X., Ishidate, M., Xxxxxxx, D., Xxxxx, X., Myhr, X. X. (1991), Genotoxicity Xxxxx Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Task Xxxxx 9, Mutation Xxx. 257, 147-204.

8) Xxxxx, D., McCuen, X., Xxxxxxx, J. X. X., Piper, X., Mavournin, X. X. (1983), Specific Xxxx Xxxxxxxxx xx X5178X Xxxxx xx Xxxxxxx. X Report xx xxx X. X. Environmental Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 115, 225-251.

9) Xx, X. X., Xxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, J. X. (1988), A Xxxxxx xxx Xxxxxxxx xx xxx Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Xxxxxxxxx the Xxxxxxxxxxxx of Xxxxxxxx Xxxxxx: X Xxxxxx xx Xxxxx III xx xxx X. X. Environmental Xxxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Res., 196, 17-36.

10) Li, X. X., Carver, J. X., Choy, W. X., Hsie, X. X., Xxxxx, R. X., Xxxxxxx, K. X., X'Νxxxx, J. X., Riddle, J. X., Xxxxxxxxxx, L. X. Xx., Xxxx, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx of xxx Xxxxxxx Hamster Xxxxx Cell/Hypoxanthine-Guanine Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Xxxxxxxx Xxxxx, Mutatation Res., 189, 135-141.

11) Liber, X. X., Yandell, X. W., Xxxxxx, X. B. (1989), X Xxxxxxxxxx xx Xxxxxxxx Xxxxxxxxx xx xxx XX xxx XXXX Xxxx xx Xxxxx Lymphoblastoid Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx to an Xxxxxxxxxx Class xx Xxxxxxxxx at the Xxxxxxxxx XX Locus, Xxxxxxxxxx Xxx., 216, 9-17.

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

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

14) Xxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxx, X. X. X., Cole, X., XxXxxxxx, D. B., Xxxxxxx X. C. (1989), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxx xxxx Xxxxxx Xxxxxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Kirkland, X. X., xx., Xxxxxxxxx University Xxxxx, 66-101.

15) Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxxxx, N., Xxxxxxxxxx, X. (1977), Xxxxxxxxx xx 6-Xxxxxxxxxxx-Xxxxxxxxx Xxxxxxx xx X79 Xxxxxxx Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Dimethylnitrosamine, Xxxxxxxxxx Res. 46, 365-373.

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

17) Xxxxx, D., Johnson, X. X., Spector, X. X. X., Xxxxxx X. X., Xxxxx X. M. X. (1979), Xxxxxxxxxx xxx Xxxxxxxxxxxxxxxx xx xxx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxxxx Xxxxx Xxxxxx, Xxxxx. Xxx. 59, 61-108.

18) Xxxxx, X. X., Ames, B. X. (1983), Revised Xxxxxxx xxx xxx Xxxxxxxxxx Mutagenicity Test, Xxxxxxxxxx Res. 113, 173-215.

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

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Biphenyls x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, X: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Serres, X. X., Xxxxx, X. X., Bend, X. X., Xxxxxxx, X. M. (xxx), Xxxxxxxx, North-Holland, 85-88.

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

22) Xxxxxx, X. X., Xxxxxx, X. X., Xx, X. P., Xxxxxx, A. L. (1983), Xxxxxxxxxx of xx Xxxxxxxx System Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx CHO/HGPRT Xxxxxxxx Xxxxx, Xxxxxxx. Mutagenesis, 5, 795-801.

23) Xxxxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxxxxx of Xxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Xxxxx xx Mouse Lymphoma Xxxxx, Proc. Xxxx. Xxxx. Sci. U. X. A, 87, 51-55.

24) Xxxxx, X. X., Xxxxx, X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, N. X., Xxxxxx, X. (1985), Xxxxxxxx of Trifluorothymidine, Xxxxxxxxx (XXX+) Mutants xx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxx, Mutatation Xxx. 151, 161-174.

25) Xxxxxxx, X. W., Dryja, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Xxxxxxxxx Xxxxxxxxx xx a Heterozygous Xxxxxxxxx Xxxxx xx Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

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


XXXXXXX 4X

"X.23 ZKOUŠKA XX CHROMOZOMOVÉ XXXXXXX XX SPERMATOGONIÍCH XXXXX

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx xx chromozomové xxxxxxx ve spermatogoniích xxxxx xx xxxx xx identifikovat xxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx indukované aberace xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx aberace se xxxxxx xxxxxxxxx. Xxxx xxxxxx není určena xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x xxxxxx účelu xxxxxxx používána. Xxxxxxxxxxxx xxxxxx a xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx x člověka.

Touto xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx xx xxxxxxxxxxxxxxx x předpokládá xx xxxx, že xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx x germinálních xxxxxxx.

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

Pro detekci xxxxxxx xxxxxxxxxxxxxx xxxx xx xxxxxxxxxxxxxxx xx xxxx xxx — xxxxx než dojde xx xxxxxx xxxx — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx následuje po xxxxxxxx. Xxxxx xxxxxxxxx x exponovaných xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx xxx xxxxxx meiotickou xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx in xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx xx xxxx xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx řada xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx na xxxxxxxx chemické látce. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx xxxxxxxxx odpověď xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxxxxxxx diferencovanými xxxxxxxxxxxxxxx. V závislosti xx xxx xxxxxx xx varlatech, xxxxx xxxx xxxxxx xxx xxxxx generace xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx krevnímu xxxxx x xxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxx Sertoliho xxxxx x xxxxxxx xxxx xxxxxxx xxxxxx x xxxxxxx.

Xxxxxxxx xxxxxxxx důkaz x tom, xx xx xxxxxxxx látka xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx cílové xxxxx, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 DEFINICE

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

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx chromozomu x xxxxxx xxxxx xxxx zlomu x xxxxxxx obou xxxxxxxxx x xxxxxx xxxxx.

Xxx : xxxxxxxxxxxx xxxx xxxxx xxx šířka xxxxx chromatidy x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

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

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

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx jsou xxxxxxx xxxxxxxx exponována xxxxxxxx xxxxx a xx xxxxxx xxxx xx xxxxxxxx usmrcena. Xxxx xxxxxxxxx xx xxxxxxxx xxxx látka xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx buněk xx poté xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx x analyzují xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xxxx používáni xxxxx xxxxxx xxxxxxxx a xxxx; xxx xxxx xxxxxx samce xxxxxxxxxx xxxxxx xxxxxxxx druhu xxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x hmotnosti xxxxxx minimální a xxxxxx by xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx samci se xxxxxxxx výběrem rozdělí xx xxxxxxxxx skupinu x xxxxxxx, xxxxx xx exponuje. Xxxxx xx měly xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx jednoznačně xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx nechají x xxxxxxxxxxxxx podmínkách xxxxxxx xxx dní aklimatizovat.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx by xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx být xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx xxx při xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx účinky x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by xxxx xxx xxxxxxxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx skupiny xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v nichž xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx měly xxxxxxxxxx strukturní xxxxxxx xx xxxxxxxxxxxxxxx in xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx byla xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx a xxx byl xxxxx x jejím xxxxxxx xxxxxxxx xxx jednou. Xxx pozitivní xxxxxxxx xxxx xxx xxxxx xxxxx x xxxxx xxxxxxx chemických látek xx stejné chemické xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx kontrolu:

Látka

Číslo XXX

Xxxxx xxxxx Einecs

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

xxxxxxxxxxxxxx

108–91–8

203–629–0

xxxxxxxxx C

50–07–7

200–008–6

akrylamid (xxxxxxx)

79–06–1

201–173–7

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

51–18–3

200–083–5

X xxxxxxxx každého xxxxxx xx xxx xxx xxxxxxxx xxxxx u xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx rozpouštědlo xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx stejný xxxxxx jako xxxxxxxxxx xxxxxxx, pokud nejsou x dosavadních xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx zvířat x xxxxxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx. Kromě xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

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

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx nebo nadvakrát (xx. xxx xxxxx xxxxxxxx nebo dvou xxxxxxxxxx). Xxxxxxxx látky xxxxx xxx podávány xxxx ve xxxx xxxxxxx, xxx. xxx xxxxx x týž xxx x xxxxxxx xx xxxx než xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx podávání xxxxxxx objemů materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx dávkou xx xxxx xxx xx expozici xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx buněčného xxxxx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx xxxxx xxxxx xxxxx x xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 a 48 xxxxx po xxxxxxxx. X případě xxxx xxx xxxxxxxx xxxxx xx xxx xxx xxxxx xxxxxxxx po 24 xxxxx xxxx xx takové době xxxxxxxx, která odpovídá 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, pokud není xxxxx xxxx vhodnější xxxx xxx xxxxxxx xxxxxx (6).

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

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxx být určena xxxxxx xx případu. X případě plánu x opakovanou xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5násobek xxxxx xxxxx) xx xxxxxxxx xxxxxxxx. Xxxxx xxxxxxx xxxxx xxx xxxxxxxxx xxxxx xxxxxx x xxxx době.

Před usmrcením xx xxxxxxxx intraperitoneálně xxxx vhodná xxxxx xxxxx xxxxxxxxxxx metafázi (xxxx. Colcemid® xxxx xxxxxxxxx). Xxxx se xx vhodné xxxx xxxxxxx x xxxxxx xxxxx. X myši xx tato xxxx xxxxxxxxx 3 — 5 hodin; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxxxx xx xxxxxxx x xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx pro první xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx rozmezí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx toxicitou. Xxx xxxxxxxxx odběru stačí, xxxx xxxx xxxxxxx xxxxx nejvyšší xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx by xxxxx xxxxx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x letalitě.

Látky xx xxxxxxxxxxx biologickou xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (např. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx být hodnoceny xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx toxicity (xxxx. xxxxxxx počtu spermatogonií x xxxxxx xxxxxxxx x první a xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx xx xxxxxx překročit 50 %).

1.5.4 Limitní zkouška

Jestliže xxxxxxx s xxxxxx xxxxxx xxxxxxx 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx pozorovatelné xxxxxxx účinky x xxxx-xx xx xxxxxxx xxxxx o látkách, xxxxx mají podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx xx třemi xxxxxxxx xxxxx xx xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx může znamenat xxxxxxx použít v xxxxxxx zkoušce xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační xxxxxxx, xxxx xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxx sondou nebo xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx a žíravé xxxxx, které obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Příprava preparátů xx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx xx x xxxxxxx xxxx xxxx xxxxxx získá xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx a fixuje. Xxxx xx nanese xx podložní sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

X každého zvířete xx xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v xxxxx xxxxxxxxxxxx metafázi (xx. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Xxxxx xxxxx lze xxxxxx, xx-xx pozorován velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx při fixaci xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx chromozomů u xxxxx metafází, xxxx xx vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx jednotlivá xxxxxxx xx xxxx xxx xxxxxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx zvíře xx xxx xxx xxxxxxxxxx xxxxx xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx a xxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx exponované x xxxxxxxxx skupiny xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových aberací x xxxxxx xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx se, xxx obecně se xxxxxxxxxx do xxxxxxx xxxxxxxx xxxxxxx.

Xx-xx pozorována xxxxxx a také xxxxxx, xxx xx xxx pro stanovení xxxxxxx xxxxxxxxxxxxx xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx x všech xxxxxxxxxxxx zvířat x xxxxxx xxxxxxxxxx xxxx xxxxxxxxx kontrola poměr xxxxxxxxxxxxx v xxxxxx xxxxxxxx k první x druhé xxxxxxxxx xxxxxxxx, x xx x celkovém xxxxxx 100 xxxxxxxx xx xxxxx xx xxxxx xxxxx. Xxxxx xx xxxxxxxxx pouze mitosa, xxxxxxx v 1000 xxxxxxx na xxxxx xx měl xxx xxxxxxxx xxxxxxxxx xxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx xxxxx s xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx buněk s xxxxxxxxx pro xxxxxxx x xxxxxxx dávkou x k určitému xxxxxxxx odběru. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx mohou xxx xxxxxxx jako xxxxxxx xxxxxxxxxx statistické xxxxxx (8). Statistická xxxxxxxxxx xx neměla xxx jediným určujícím xxxxxxxx pro pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx dalším zkoušením, xxxxxxx x úpravami xxxxxxxxxxxxxxxx podmínek.

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx opakován.

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

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx se xxxxxxxx xxxxx nebo její xxxxxxxxxx xxxxxxxx do xxxxxx xxxxx.

3. ZPRÁVY

PROTOKOL X ZKOUŠCE

Protokol x xxxxxxx xxxx obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx x stáří xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

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

- xxxxxxxxxx zvolených úrovní xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- xxxxx x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxx xxxxxxxx,

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

- podrobné údaje x xxxxxxx krmiva x vody,

- podrobný xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxxx xxxxxxxx preparátů,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx index,

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

- xxx x xxxxx xxxxxxx uvedený xxxxxxxxxx pro každé xxxxx,

- xxxxxxx xxxxx xxxxxxx xx skupině,

- xxxxx xxxxx s xxxxxxxxx ve skupině,

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx pozitivní xxxxxxxx,

- xxxxx xxxxxxx, xxxxx byly pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Adler, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx in Xxxxx Spermatogonia of Xxxxxxxx Xxxxxxxx Related xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, in: Genetic Xxxxxxxxxx of Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxxxx, Ramel, X., Lambert, X., Xxxxxxxxx, J. (xxx) Xxxx, New York, 477-484.

2) Xxxxx, X. X., (1984), Xxxxxxxxxxx xxxxx in Mammals, xx: Xxxxxxxxxxxx Xxxxxxx: x Practical Xxxxxxxx, (xx.) X. Venitt, X. X. Xxxxx, XXX Press, Oxford, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, X. X., Xxxxxxx, G., Ford, X. E. (1964), Xx Xxx-xxxxxx Xxxxxx xxx Xxxxxxx Preparations xxxx Xxxxxxxxx Testes, Xxxxxxxxxxxx Cell Genetics, 3, 289-294.

4) Richold, X., Xxxxx, X., Xxxxxxxx, A., Xxxxxxxxx, X. G., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Tests, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Testing. Xxxxxx. Xxxx I xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

5) Xxxxxxxx, K., Xxxxxxx, X. (1978), A Xxx Xxxxxx xxx Xxxxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Xxx., 52, 207-209.

6) Xxxxx, X. X., Xxxxxx M. X., Xxxxxxx, X., Favor, X., Generoso, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx X. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxx Xxxxxx of xxx Working Xxxxx xx Xxxxxxxxx Germ Xxxx Tests, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. A., Xxxxxx, X. X., Xxxxxx, X. A., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Xxxxxxx, X. (1992), Report of Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Amphlett, X. X., Clarc, X., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Savage J. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Test Data. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Xxxx XXX. Xxxxxxxxx University Xxxxx, Cambridge, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4G

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

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx OECD TG 486 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx XXX (XXX) v xxxxxxxxx buňkách xxxxx xx vivo (1997).

1.1 XXXX

Xxxxxx xxxxxxx na xxxxxxxxxxxx syntézu XXX (XXX) v jaterních xxxxxxx xxxxx in xxxx xx xxxxxxxxxxxxx xxxxxxxx látky, xxxxx xxxxxxxx xxxxxxxx DNA x xxxxxxxxx xxxxxxx xxxxxxxxxxxx zvířat (1, 2, 3, 4).

Tato xxxxxxx xx xxxx xxxxxxxxx metodu xxxxxxxxx xxxxxxxxxxxxx xxxxxx chemických xxxxx x xxxxxxx. Xxxxxxxxxxx xxx je xxxxxxxxxx xxxxxxxxx XXX x xxxxxxxx reparace x xxxxxxxxx xxxxxxx. Xxxxx xxxx obvykle xxxxxxx xxxxxx, xxx xxxx absorbované xxxxxxxxxx xxxxxxxxxxxxxx. Jsou xxxx xxxxxxx xxxxxx xxx xxxxxxxxx míry poškození XXX in xxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, xx xx xxxxxxxx látka xxxxxxxxx xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (XXX) xx zhodnotí xxxxxxxxxx xxxxxxxxxxx značených xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx plánovanou xxxxxxxx XXX (S-fází). Xxxxxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (3X-XxX). Xxx zkoušky na XXX xx xxxx xx přednostně používají xxxxx xxxxxxx. Jiné xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, nejsou xxxx xxxxxxxxx xxxx metody.

Detekce xxxxxxxx XXX xxxxxx xx xxxxx bází XXX xxxxxxxxxxx a xxxxxxxxxxx v xxxxx xxxxxxxxx. Xxxxxxx na XXX je xxxx xxxxxx xxxxxxx xxx xxxxxxx xxxxxxxx xxxxxxxx ("xxxx-xxxxx repair") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("short-patch repair") (xxxxx xx xxx xxxx) xxxx naproti xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx důsledkem xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx lézí XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Rozsah xxxxxxxx XXX xxxxxxxxxxx žádnou xxxxxxxxx x xxxxxxxx xxxxxxxxxxx procesů. Xxxxx xx xxxxx, že xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX xxxx opraveno xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx informací, xxxxx xxxx xxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxxx, xx vyvážen potenciální xxxxxxxxxx xxxxxx jevu, xxxxx xx vyšetřován x xxxxx xxxxxx.

Xxx xxxx xxxxxx úvod, xxxx B.

1.2 DEFINICE

Opravované xxxxx : čistý xxxxx xxx odpovídajících xxxxxxxx xxxxxx (XXX), xxxxx než xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxx.

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

Neplánovaná syntéza XXX (XXX) : Xxxxxxx xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx na UDS x xxxxxxxxx buňkách xxxxx xx vivo xxxxxxxx xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX obsahujícího xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx látkami xxxx xxxxxxxxxxx xxxxxxxx. Zkouška xx obvykle založena xx xxxxxxxxxxx 3X-XxX xx XXX xxxxxxxxx xxxxx, xxx xx xxxx xxxxxxx xxxxx x X-xxxx xxxxxxxxx xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx xxxx xxx xxxxxxx xx vliv X-xxxx buněk xxxx xxxx. xxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr druhu xxxxxxx

Xxxxx je používán xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxx savce. Xxxx xx xxx xxxxxxx xxxxx používané laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X okamžiku xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx v xxxxxxxxx zvířat xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % střední xxxxxxx xxxxxxxxx pro xxx xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx zvířat

Zdravá xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx minimalizován. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x před xxxxxxxxx xxxxxx se xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx.

1.4.1.4 Příprava zkoušené xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxxx přímo xxxx mohou být xxxx xxxxxxx zředěny. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x mělo xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí každé xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx xx měly xxx souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx zkoušené látky xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx proces xxxx xxxxxxx xx skupinách, x xxxxx xxxxx x expozici.

Pozitivními xxxxxxxxxx xx měly xxx xxxxx, x xxxxx xx známo, xx xxxxxx xxxxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x nárůstu XXX detekovatelnému nad xxxxxxx. Pozitivní kontroly xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Dávky mohou xxx xxxxxxx tak, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxx xxxxxx

Xxxxx

Xxxxx CAS

Číslo xxxxx Xxxxxx

Xxxxx doby xxxxxx (2 xx 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx xxxx xxxxxx (12 xx 16 h)

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

53–96–3

200–188–6

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

1.5 XXXXXX

1.5.1 Počet x xxxxxxx zvířat

Měl xx xxx použit xxxxxxxxxx xxxxx xxxxxx, xxx xxxx zohledněno přirozené xxxxxxxxxx xxxxxxxx odpovědi xx zkoušku. Každá xxxxxxx xx xx xxxx skládat alespoň xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx jsou xxxxxxxxxxx xxxxxxxxxx dosavadní xxxxx, je xxx xxxxxxxxx x pozitivní xxxxxxxxx skupiny nezbytné xxxxx xxxxx xx xxx zvířata.

Jestliže xxxx x době xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx stejného xxxxxxx xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx xxxxxxxxx rozdíl x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx samců. Xx-xx xxxxxxxx člověka xxxxxxxxxx pro xxxxxx xxxxxxx, xxxx je xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx se xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx normálních xxxxxxxx xx xxxxxxxxx xxxxxxx xxx úrovně xxxxx. Xxxxxxxx dávka xx definována xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx dávky by xxxxx podle xxxxxxxxx xxx stejném xxxxxx xxxxxxxxx k xxxxxxxx. Xxxxx xxxxx by xxxx být xxxxxxxxx 50 % až 25 % xxxxx xxxxx.

Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx při xxxxxxx netoxických dávkách (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx x xxxx by xxx hodnoceny xxxxxx xx xxxxxxx. Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx údajů xxxxxx xxx xxxxxxxx xxxxxxx, xxxx xx xxx provedena xx xxxxxx xxxxxxxxxx, se xxxxxxx druhem, xxxxxx, xxxxxxxx a xx xxxxxxxx režimu xxxxxxxx, xxx se xxxxxxx x hlavní xxxxxx.

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

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x jednou xxxxxx x xxxxxxx 2000 xx/xx tělesné xxxxxxxxx xxxxxxx jednorázově xxxx xx xxxx xxxxxxx x jednom xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx o látkách, xxxxx mají podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxx xxx úplná xxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx použít x xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle podává xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx jsou xxxxx, xxx-xx je zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx se xxxx xxxxxxxxxxxx, xxxxx xx xxxxx xxxxx xxx exponována xxxxxxxx xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx může xxx najednou podán xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by neměl xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, které obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx všech xxxxxxxx xxxxx.

1.5.6 Příprava xxxxxxxxx xxxxx

Xxxxxxx xxxxx se xxxxxxxxxx x exponovaných xxxxxx zpravidla 12 xx 16 hodin xx podání xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (xxxxxx dvě xx xxxxx hodiny xx xxxxxxxx) xx xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx xxxxx pozitivní xxxxxxx. Xxxxx však xxx xxxxxxx xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

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

1.5.7 Xxxxxxxxx UDS

Čerstvě xxxxxxxxx xxxxxxx xxxxx xxxxx se xxxxxxx xxxxxxx xxxx, xxxx. xxx xx osm xxxxx, xxxxxxxx s xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx xxxxxxxxx xxxx xx xxxx xxx xxxxxx z xxxxx odstraněno x xxxxx xxxx xxxxx xxx xxxxxxxxxx x xxxxxx obsahujícím xxxxxxxx xxxxxxxxxxx xxxxxxxxx, aby xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("cold xxxxx"). Xxxxx se poté xxxxxxx, xxxxxx x xxxxxx. Při xxxxx xxxxxxxxx době xxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xx xxxxxx xx autoradiografické xxxxxx, xxxxxxxx se x xxxxx (xxxx. x xxxxxx 7 xx 14 xxx), xxxxxxxx xx, xxxxxx x spočítají xx xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx zvířete xx xxxxxxxx xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx by měly xxxxxxxxx dostatečný počet xxxxxxxxxxxx xxxxxxxxxx xxxxx, xxx xxxx xxxxxxxxx XXX xxxxxxxxx xxxxxxx. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxx xxxxxxxxxxxx (xxxx. na pyknosu, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx izotopem).

Před xxxxxxxxx xxx xx měly xxx preparáty xxxxxxxx. Xxxxxxxxx xx xxxxxxxxx 100 xxxxx xx xxxxx xxxxx xxxxxxx xx dvou preparátů; xxxxxxxxx méně xxx 100 xxxxx/xxxxx xx xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx zrn xx xxxxx x X-xxxx xxxxxxxxxxx, ale xxxxx xxxxx x X-xxxx xxxx xxx xxxxxxxxxx.

Xxxxxxxx 3H-TdR xxxxxxxxxxxxxxx xx xxxxx a xxxxxxxxxx xxxxxxxxxxxx normálních xxxxx xxxxxxxx xxxxxxxxxxx xxx stříbra xx xxxx být stanoveno xxxxxxx xxxxxxx.

Xxxxx xxxxx xx xxxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx jádrŭm (xx) x x xxŭxxxxxxx xxxxx xxx v xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx xxxxŭx. jako xxxxxxx cg se xxxxxxx xxx xxxxx xxxxx pro nejsilněji xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx prŭměrná xxxxxxx xxxx až tří xxxxxxx vybraných xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx xxxxxxx i xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxx by xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx x xxxxxxx. Xxxxx xx xxxx být xxxx xxxxxxx ve formě xxxxxxx. Odečtením hodnoty XX xx xxxxxxx XX xx xxx xxx vypočten xxx xxxxxx xxxxx, xxx xxxxx zvíře x xxx každou xxxxx x xxx čistý xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx xxxxxxxx "xxxxxxxxxx" xxxxx, měla xx xxx xxxxxxxx xxx definování "xxxxxxxxxxxx" xxxxx xxxxxxxxxx a xxxxxxxx xx xxxxxxxxxxx xxxx souběžných xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx výsledky xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, měly xx xxx statistické testy xxxxxxx a odůvodněny xxxx xxxxxxxxxx studie.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxxx příklady kritérií xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx patří:

pozitivní

i)

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

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx NNG xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx NNG xxxx xxxxxxxx vyšší xxx xxxxxxx xxx souběžnou xxxxxxxx.

Xxxx by xxx xxxxxxxxx biologická xxxxxxxxx xxxxx, xx. měly xx xxx xxxxx x úvahu xxxxxxxxx, xxxx xxxx xxxxxxxxxxx xxxxxx, vztah xxxxx x xxxxxxxx x xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx významnost xx xxxx neměla xxx jediným xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx bez xxxxxx xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na XXX v xxxxxxxxx xxxxxxx savců in xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxx buňkách xxxxx xx xxxx xxxxxxxxx XXX, které xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx XXX in xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že zkoušená xxxxx xx xxxxxxxx xxxxxxx neindukuje poškození XXX, xxxxx lze xxxxxxxxx touto xxxxxxxx.

Xxxx xx xxx diskutována xxxxxxxxxxxxxxx, s jakou xx xxxxxxxx xxxxx xxxxxxx do xxxxxxxx xxxxx xxxx. do xxxxxx xxxxx (např. xxxxxxxxx xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x pohlaví xxxxxx,

- zdroj, xxxxxxxx xxxxx, xxxxxx atd.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx počátku xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx hodnoty x směrodatné xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

- případně xxxxxxxx mezi xxxxxxxxxxx xxxxxxxx látky x xxxxxx nebo xxxx (xxx) xx odpovídající xxxxx (mg/kg tělesné xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x kvalitě krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx expozice x odběru,

- xxxxxx xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- počet xxxxxxxxx x počet xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx hodnoty xxxxx xxx xxxxxxxxxxxxxx buněčným xxxxxx a počtu xxx xxxxxxxxxxxxxx xxxxxxxxxx, x čistý xxxxx xxx, xxxxxxxxxx pro xxxxxxxxx, zvířata x xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxx,

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

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

- počet xxxxx "xxxxxxxxxxxx" xxxxx, xx-xx stanoven,

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

- životaschopnost xxxxx.

Xxxxxx výsledků.

Závěry.

4. LITERATURA

1) Xxxxx, J. Xxxxxxx, X. X., Xxxxxxxxx, X., Penman, M. X. (1985), Xx Xxxxxxxxxx of xxx Xx vivo Xxx. Xxxxxxxxxx DNA Xxxxxx Xxxxx, Mutatation Xxx., 156, 1-18.

2) Xxxxxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1987), X Xxxxxxxx xxx Xxxxx xxx xxx Xx vivo Xxx Xxxxxxxxxx XXX Repair Xxxxx, Xxxxxxxxxx Res., 189, 123-133.

3) Xxxxxxxx, X. X., Waters, X., Ashby, X., Xxxxxxx, X. X., Xxxxxxxxx, X., Xxxxxxx, X. J., Xxxx, X. X., Xxxxxxxx, X. de X. (1993), Xx xxxx Xxx Xxxxx XXX Xxxxx, xx: Xxxxxxxx X. J., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Tests: XXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx II xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Xxxx, X. X., Xxxxxx, X., Xxxxxxxxx. G., Xxxxxxxxx, X., Xxxxxxxxx, X. J., Furihata, X., Xxxxxxx, T., XxXxxxx, C. A., Xxxx, H. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx XXX Xxxxx Xx xxxxx xxx Xx xxxx, Xxxxx. Xxx., 312, 263-285.

5) Fautz, X., Xxxxxxx, X., Efstathiou, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Assessment of xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxx xxx the Xxxxxxxxxx xx Xxxxxxx Xxxxxxxx Xxx Xxxxxxxxxxx Used xxx the In xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (UDS), Xxxxxxxxxx Res., 291, 21-27.

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


XXXXXXX 5

OBECNÉ XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX NEBEZPEČNÝCH XXXXX X PŘÍPRAVKŮ

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


PŘÍLOHA 6

"

XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. e) xxxx xxxxxxxx, xxxx xxx xxxxx x xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, x nimiž xx spojeno riziko xxx vdechování (Xn; X 65) x xxxxx xxxx klasifikovány x xxxxxxxx podle xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx látek xxxxxxxxx na xxx xx xxxxx xxxxxxxx xxxx v xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx uzavíratelné xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxx na xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx splňovat xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx odolné xxxxx — Xxxxxxxxx na xxxxxxxxx xxxxxxxxxxxx xxxxx x metody xxxxxx xxxxxxxx" xxxxxxxx Mezinárodní xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Opakovaně neuzavíratelné xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx použité xx xxxxxxxxx neuzavíratelných xxxxxxx xxxx splňovat xxxxxxxxx xxxxx CEN XX 862 (vydání x xxxxxx 1997) "Xxxxx — Xxxxx xxxxxx xxxxx — Xxxxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx výrobků" xxxxxxxx Xxxxxxxxx xxxxxxx xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Prokázání xxxxx x výše xxxxxxxxx xxxxxxx mohou xxxxxxxxxx xxxxx laboratoře, které xxxxxxx evropské xxxxx xxxx EN 45000.

2. Xxxxxxxxxx případy

Je-li xxxxxx, xx xxxx xx xxxxxxxxxx xxxxxxxx pro xxxx, xxxxx se xxxxxxx dostat k xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x xxxxxxxx x xxxxxxxxxxx xxxxxxx xxx dítě, může xxxxxxxxxxxx orgán xxxxxxxxx, xxx xxxxx xxxxxxxxx xx xxxxxxx výrobku xx xxx předložila xxxxxxxxxx vydaný xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx takový, xx xxx xxxx xxxxxxxx xxxxxxx xxxxx xxxx xxxxxxxxx norem XXX a CEN,

nebo

- xx uzávěr xxx xxxxxxx a xxx xxxxxxx vyhovujícím xxxxx xxxx xxxxxxxxx xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx se xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx xxxxxxxxxxx xxx hmatatelné výstrahy xxxx xxx x xxxxxxx x xxxxxx XX XXX 11683 (xxxxxx z roku 1997) "Xxxxx — Xxxxxxxxxx výstrahy xxxx xxxxxxxxxx — Požadavky".

"