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Xxxxxxxx Xxxxxx 2000/32/ES

ze xxx 19. května 2000,

xxxxxx xx xx xxxxxxx xxxxx přizpůsobuje xxxxxxxxxxx pokroku xxxxxxxx Xxxx 67/548/EHS o xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx nebezpečných xxxxx [1]

(Xxxx x xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx,

x xxxxxxx xx směrnici Xxxx 67/548/EHS ze xxx 27. xxxxxx 1967 o xxxxxxxxxx xxxxxxxx x správních xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx a xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], naposledy xxxxxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxx x Xxxx 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx x xxxxx xxxxxxx:

(1) Xxxxxxx X xxxxxxxx 67/548/XXX xxxxxxxx seznam xxxxxxxxxxxx xxxxx xxxxxxxx s xxxxxxxxxx údaji x xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Současné xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, xx xx měl xxx xxxxxx nebezpečných xxxxx x uvedené xxxxxxx xxxxxxxxxxx. Xxxxxxx jazykové xxxxx směrnice xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a xxxxxxx X v příloze X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/EHS xxxxxxxx xxxxxx vět xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx s xxxxxxxxxxxx xxxxxxx a xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx seznam xxx x xxxxxxxxxxxxxx xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx XX xxxxxxxx 67/548/EHS xxxxxxxx xxxxx xx xxxxxxxxxxx x k xxxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx jazykové xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx III, XX x XX.

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

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx otevření xxxxx. Tyto xxxxxxxx xx xxxx být xxxxxxxxxxxx a aktualizovány. Xx nezbytné rozšířit xxxxxx, xxx se xxxxxxx odolné xxxxx xxxxxxxx xxxxx používají.

(5) Xxxxxxxx této směrnice xxxx x xxxxxxx xx stanoviskem Výboru xxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxx na úseku xxxxxxxxxxxx xxxxx x xxxxxxxxx,

XXXXXXX XXXX SMĚRNICI:

Xxxxxx 1

Směrnice 67/548/XXX xx xxxx xxxxx:

1. Xxxxxxx X se xxxx takto:

a) xxxxxxxxxxxx xxxxxxxx v předmluvě xx xxxxxxxxx poznámkou X v xxxxxxx 1X této xxxxxxxx;

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

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

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

2. Xxxxxxxxxxxx xxxx x příloze XXX xx nahrazuje xxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x příloze 2 xxxx xxxxxxxx.

3. Xxxxxxx XX xx xxxx xxxxx:

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

x) xxxxxxxxxxxx xxxxxx x příloze XX xx nahrazují kombinovanými xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxx 3X xxxx xxxxxxxx.

4. Xxxx X xxxxxxx V xx xxxx takto:

a) xxxxxxxx X.10 se xxxxxxxxx xxxxxx x xxxxxxx 4X xxxx xxxxxxxx;

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

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

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

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

x) xxxxxxxx X.23 xx xxxxxxxxx xxxxxx v xxxxxxx 4X této xxxxxxxx. Xxxxx xxxxxxxx X.23 xx xxxxxxxxxxx xx mění xxxxxxxxxxxxx xxxxxxxx;

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

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

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

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

Článek 2

1. Xxxxxxx xxxxx xxxxxx x xxxxxxxx xxxxxx a xxxxxxx xxxxxxxx nezbytné xxx xxxxxxxx souladu x xxxxx xxxxxxxx xxxxxxxxxx do 1. xxxxxx 2001. Xxxxxxxxxx x nich xxxxxxx Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx státy xxxx xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx takový xxxxx xxx xxxxxx při xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx odkazu xx xxxxxxx členské státy.

2. Xxxxxxx xxxxx sdělí Xxxxxx xxxxx hlavních xxxxxxxxxx xxxxxxxxxxxxxx právních xxxxxxxx, xxxxx přijmou x xxxxxxx xxxxxxxxxx xxxx xxxxxxxx, a xxxxxxxxxx xxxxxxx xxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx ustanoveními.

Xxxxxx 3

Xxxx xxxxxxxx xxxxxxxx x xxxxxxxx xxxxxx dnem xx xxxxxxxxx v Úředním xxxxxxxx Xxxxxxxxxx společenství.

Článek 4

Xxxx xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

X Xxxxxxx xxx 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Xxxxxx


[1] Xxxxxxx po xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Úř. věst. 196, 16.8.1967, x. 1.

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


PŘÍLOHA 1A

PŘEDMLUVA K XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx se českého xxxxx)


XXXXXXX 1B

"TABULKA X

X

Xxxxxx

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

XX

18

Xx

Xxxxx

Xxxxx

Xxxxx

Αργό

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"


XXXXXXX 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx k xxxxxx

Xxxxx XX

Xxxxx CAS

Klasifikace

Označení

Koncentrační limity

Poznámky x přípravkům

006–011–00–7

karbaryl (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx

200–555–0

63–25–2

Xxxx. kat. 3; X40 Xn; X22 X; X50

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

006–013–00–8

xxxxxx-xxxxxxx (ISO) natrium-N-methyldithiokarbamát

205–293–0

137–42–8

Xn; X22 X31 X; X34 R43 N; X50–53

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

006–015–00–9

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

206–354–4

330–54–1

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

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

006–016–00–4

xxxxxxxx (XXX) 2- isopropoxyfenyl-N-methylkarbamát

204–043–8

114–26–1

T; X25 X; 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 T; X24 X; X50–53

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

006–018–00–5

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

217–990–7

2032–59–9

X; X24/25 X; X50–53

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

006–019–00–0

di-allát (XXX) S-(2,3-dichlorallyl)-N,N-diisopropylthiokarbamát

218–961–1

2303–16–4

Karc. xxx. 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 X; X50–53

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

006–024–00–8

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

205–443–5

140–93–2

Xx; X22 Xx; X38 X; X51–53

Xx; X R: 22–38–51/53 X: (2-)13-61

006–026–00–9

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

216–353–0

1563–66–2

X+; X26/28 X; X50–53

X+; X R: 26/28–50/53 X: (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 N; R50–53

T; X X: 25–50/53 X: (1/2-)37–45–60–61

006–029–00–5

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

230–253–4

6988–21–2

X; R25 N; X51–53

X; N R: 25–51/53 X: (1/2-)37–45–61

006–033–00–7

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

243–433–2

19937–59–8

X; X50–53

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

006–034–00–2

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

214–215–4

1114–71–2

Xx; X22 X; X51–53

Xx; X R: 22–51/53 X: (2-)23-61

006–035–00–8

xxxxxxxxxx (ISO) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx pyrimidin-4-yl-N,N-dimethylkarbamát

245–430–1

23103–98–2

T; X25 X; R50–53

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

006–037–00–9

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

220–113–0

2631–37–0

X; X25 X; X50–53

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

006–038–00–4

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

E

202–388–9

95–06–7

Karc. xxx. 2; X45 Xx; X22 X; X50–53

X; X X: 45–22–50/53 X: 53–45–60–61

006–039–00-X

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

218–962–7

2303–17–5

Xx; X22–48/22 X43 X; X50–53

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

006–042–00–6

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

205–766–1

150–68–5

Xxxx. xxx. 3; R40 Xx; R22 X; X50–53

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

006–043–00–1

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

140–41–0

Xx; X36/38 Xxxx. xxx. 3; X40 X; R50–53

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

006–045–00–2

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

240–815–0

16752–77–5

X+; X28 N; X50–53

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

006–046–00–8

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

245–216–8

22781–23–3

X; R23/25 Xx; 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 (XXX) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx

8065–36–9

X; R24/25 X; X50–53

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

006–048–00–9

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

249–981–9

29973–13–5

Xn; X22 X; X50–53

Xx; N X: 22–50/53 S: (2-)60-61

006–050–00–X

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

4482–55–7

Xx; X38 X; X50–53

Xx; X X: 38–50/53 S: (2-)60-61

006–053–00–6

xxxxxxxxxx (ISO) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx

220–114–6

2631–40–5

Xx; X22 X; X50–53

Xx; X R: 22–50/53 X: (2-)60-61

006–054–00–1

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

206–249–3

315–18–4

X+; X28 Xx; X21 X; R50–53

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

006–057–00–8

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

217–682–2

1929–82–4

Xx; X22 N; X51–53

Xx; N R: 22–51/53 X: (2-)24-61

006–060–00–4

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

226–066–2

5259–88–1

Xx; X22 X52–53

Xx X:22–52/53 S: (2-)61

006–069–00–3

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

245–740–7

23564–05–8

Xxxx. xxx. 3; X40 X; X50–53

Xx; N X: 40–50/53 S: (2-)36/37–60–61

006–070–00–9

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

262–302–0

60568–05–0

Xxxx. xxx. 3; X40 X; X50–53

Xx; N X: 40–50/53 S: (2-)36/37–60–61

006–088–00–7

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

82560–54–1

X; X23/25 X; X50–53

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

007–012–00–5

X,X-xxxxxxxxxxxxxxxx 1,1-xxxxxxxxxxxxxxxx

X

200–316–0

57–14–7

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

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

007–013–00–0

X,X-xxxxxxxxxxxxxxxx 1,2-xxxxxxxxxxxxxxxx

X

540–73–8

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

X; X X: 45–23/24/25–51/53 S: 53–45–61

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

009–003–00–1

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

015–039–00–9

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

201–676–1

86–50–0

X+; X26/28 X; X24 X43 X; X50–53

X+; 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; X40 X; R23–48/25 Xx; X21/22 X; R50–53

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

015–056–00–1

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

220–147–6

2642–71–9

X+; X28 X; R24 N; X50–53

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

015–140–00–8

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

245–986–5

24017–47–8

X; X23/25 Xn; X21 X; R50–53

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

016–013–00-X

xxxxxxx xxxxxxx

234–129–0

10545–99–0

X14 X; X34 X; X50

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

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

016–014–00–5

xxxxxxx xxxxxxxx

13451–08–6

X14 X; X34 X; X50

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

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

016–023–00–4

dimethyl-sulfát

E

201–058–1

77–78–1

Karc. kat. 2; R45 Xxxx. xxx. 3; X40 X+; X26 T; X25 X; X34 X43

X+ X: 45–25–26–34–43 X: 53-4 5

C ≥ 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; X45–22–23–43 1 % ≤ X &xx; 3 %: X; X45–23–43 0,1 % ≤ X &xx; 1 %: T; R45–20 0,01 % ≤ X &xx; 0,1 %:X; X45

016–024–00-X

xxxxxxxx (ISO) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx

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

1468–37–7

Xx; X22 X; X50–53

Xx; X X: 22–50/53 S: (2-)60-61

016–071–00–6

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

410–130–3

136248–03–8

R43

Xi R: 43 X: (2-)22–24–37

022–001–00–5

chlorid xxxxxxxxxx

231–441–9

7550–45–0

X14 X; X34

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

X ≥ 10 %: X; X34 5 % ≤ X &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; X X: 14–17–34–50/53 X: (1/2-)16–43–45–60–61

050–002–00–0

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

236–049–1

13121–70–5

Xx; X20/21/22 X; X50–53

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

050–012–00–5

tetracyklohexylstannan [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; R20/21/22 X; X50–53

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

X ≥ 1 %: Xx; X20/21/22

1

050–017–00–2

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

236–407–7

13356–08–6

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

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

082–009–00–X

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

215–693–7

1344–37–2

Karc. xxx. 3; R40 Xxxx. xxx. 1; R61 Xxxx. xxx. 3; X62 R33 X; X50–53

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

1

082–010–00–5

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

235–759–9

12656–85–8

Xxxx. xxx. 3; X40 Repr. xxx. 1; X61 Xxxx. kat. 3; X62 R33 X; 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

benzo[a]pyren xxxxx[xxx]xxxxxxx

200–028–5

50–32–8

Xxxx. xxx.2; X45 Xxxx. xxx. 2; X46 Xxxx. xxx. 2; X60–61 X; R50–53

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

601–034–00–4

xxxxx[x]xxxxxxxxxxxxxxx

205–911–9

205–99–2

Xxxx. xxx.2; X45 X; R50–53

T; X X: 45–50/53 X: 53–45–60–61

602–035–00–2

1,4-dichlorbenzen x-xxxxxxxxxxxxx

203–400–5

106–46–7

Xx; X36 X; R50–53

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

602–054–00–6

3-xxxxxxx-1-xx xxxxxxxxxx

209–130–4

556–56–9

X10 X; X34

X R: 10-34 X: (1/2-)7–26–45

603–076–00–9

but-2-yn-1,4-diol

203–788–6

110–65–6

T; X23/25 Xx; R21–48/22 X; R34

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

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

603–091–00–0

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

402–470–6

87172–89–2

X; X8 Xx; X22 Xx; X36

X; Xx X: 8–22–36 S: (2-)26

603–093–00–1

exo-(±)-4-isopropyl-1-methyl-2-[(2-methylbenzyl)oxy]-7-oxabicyklo[2.2.1]heptan

402–410–9

87818–31–3

Xn; X20 X; R51–53

Xn; X X: 20–51/53 X: (2-)23-61

603–097–00–3

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

204–528–4

122–20–3

Xx; X36 X52–53

Xx X:36–52/53 X: (2-)26-61

603–117–00–0

propan-2-ol xxxxxxxxxxxxxxxx xxxxxxxxxxx

200–661–7

67–63–0

X; X11 Xx; X36 X67

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

604–020–00–6

xxxxxxx-2-xx 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (XXX)

201–993–5

90–43–7

Xx; X36/37/38 X; X50

Xx; X X: 36/37/38–50 X: (2-)22-61

604–021–00–1

2-xxxxxxxxxx, sodná xxx xxxxxxx-2-xxxxxxxxxxxx 2-bifenylát xxxxx xxxxxxx-xxxxxxx-2-xxxx

205–055–6

132–27–4

Xx; R22 Xi; X37/38–41 N; R50

Xn; X X: 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; R60 Xx; X36 X; X50–53

X; N 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 xxxxxxxx [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 X: 22–38–41–50/53 S: (2-)24–39–60–61

604–043–00–1

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

203–083–3

103–16–2

Xx; X36 R43

Xi R: 36-43 S: (2-)24/25–26–37

604–044–00–7

mechinol 4-xxxxxxxxxxxx hydrochinonmonomethylether

205–769–8

150–76–5

Xn; X22 Xx; X36 X43

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

605–016–00–7

xxxxxxx… % xxxxxxxxx… %

X

203–474–9

107–22–2

Xxxx. xxx. 3; X40 Xn; X20 Xx; R36/38 X43

Xx X: 20–36/38–40–43 X: (2-)36/37

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

606–016–00-X

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

201–462–8

83–26–1

X; X25–48/25 X; X50–53

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

606–018–00–0

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

204–210–5

117–80–6

Xx; X22 Xx; X36/38 X; R50–53

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

606–019–00–6

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

205–601–3

143–50–0

Xxxx. xxx. 3; R40 X; X24/25 X; X50–53

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

606–034–00–8

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

244–209–7

21087–64–9

Xx; X22 X; X50–53

Xx; X X: 22–50/53 X: (2-)60-61

606–035–00–3

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

216–920–2

1698–60–8

X43 X; X50–53

Xx; X R: 43–50/53 X: (2-)24–37–60–61

606–036–00–9

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

219–455–3

2439–01–2

Repr. xxx. 3; R62 Xx; X20/21/22–48/22 Xi; X36 X43 X; X50–53

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

606–037–00–4

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

256–103–8

43121–43–3

Xx; X22 X; R51–53

Xn; 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; R36 X; R50–53

Xn; X X: 22–36–50/53 X: (2-)26–60–61

607–043–00-X

xxxxxxx (XXX) 3,6-dichlor-2-methoxybenzoová 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-chlorfenyl)-3-oxobutyl]-4-hydroxykumarin3-[1-(4-chlorfenyl)-3-oxobutyl]-4-hydroxy-2 X-xxxxxxx-2-xx

201–378–1

81–82–3

Xx; X48/22 X52–53

Xx X:48/22–52/53 X: (2-)37-61

607–058–00–1

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

204–195–5

117–52–2

X; X25–48/25 X52–53

X X:25–48/25–52/53 X: (1/2-)37–45–61

607–079–00–6

xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx

4234–79–1

X; X24 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-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxx

209–008–0

552–30–7

Xx; X37–41 X42/43

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

607–143–00–3

xxxxxxxxx xxxxxxxx xxxxxxxx kyselina

203–677–2

109–52–4

C; X34 X52–53

X R:34–52/53 X: (1/2-)26–36–45–61

607–152–00–2

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

200–026–4

50–31–7

Xn; X22 X; X51–53

Xx; X X: 22–51/53 X: (2-)61

607–153–00–8

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

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

201–270–4

80–33–1

Xx; X22 Xx; X38 X; X50–53

Xx; X X: 22–38–50/53 X: (2-)37–60–61

607–158–00–5

xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx

223–498–3

3926–62–3

X; X25 Xx; X38 N; X50

X; X X: 25–38–50 X: (1/2-)22–37–45–61

607–159–00–0

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

208–110–2

510–15–6

Xx; X22 N; R50–53

Xn; X X: 22–50/53 X: (2-)60-61

607–176–00–3

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

400–830–7

X43 X; R51–53

Xi; N X: 43–51/53 S: (2-)36/37–61

607–188–00–9

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

402–970–4

X43 N; R51–53

Xi; X X: 43–51/53 X: (2-)24/37–61

607–209–00–1

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

403–030–6

Xn; R22 X43 N; X50–53

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

607–213–00–3

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

403–320–2

67567–23–1

E; X2 O; X7 X10 X; X51–53

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

607–217–00–5

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

403–960–2

X43 X53

Xx X: 43-53 S: (2-)24–37–61

607–243–00–7

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

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

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

X52–53

X: 52/53 X: 61

607–248–00–4

Xxxxxxxx-xxxxxxx Natrium-N-(1-naftyl)ftalamát

205–073–4

132–67–2

Xn; X22

Xx X: 22 X: (2)

607–249–00-X

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

256–032–2

42978–66–5

Xi; X36/37/38 R43 N; X51–53

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

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

607–252–00–6

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

415–130–7

91465–08–6

X+; R26 X; R25 Xx; X21 X; X50–53

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

607–255–00–2

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

69377–81–7

X52–53

X: 52/53 X: 61

608–003–00–4

akrylonitril

D X

203–466–5

107–13–1

X; Xxx Karc. kat. 2; X45 X; X23/24/25 Xi; X37/38–41 X43 X; X51–53

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

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

43

608–016–00–5

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

401–550–8

1897–41–2

X43 X; X50–53

Xx; X X: 43–50/53 X: (2-)24–37–60–61

609–030–00–4

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

X

215–813–8

1420–07–1

Xxxx. kat. 2; X61 X+; X28 X; R24 R44 X; R50–53

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

609–040–00–9

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

X

217–406–0

1836–75–5

Xxxx. xxx. 2; X45 Xxxx. xxx. 2; X61 Xx; R22 X; X50–53

X; 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 R: 22–43–50/53 X: (2-)24–37–60–61

611–008–00–4

4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx

200–453–6

60–09–3

Xxxx. kat. 2; X45 X; X50–53

X; X R: 45–50/53 X: 53–45–60–61

611–013–00–1

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

403–650–7

117409–78–6

E; X2 N; X51–53

X; X X: 2–51/53 X: (2-)35-61

611–031–00-X

4,4'-[(4-iminocyklohexa-2,5-dien-1-yliden)methylen]dianilin-hydrochlorid XX Xxxxx Xxx 9 XX xxxxxxx xxxxxx 9

209–321–2

569–61–9

Xxxx. kat. 2; X45

X X: 45 X: 53-45

612–035–00–4

2-methoxyanilin x-xxxxxxxx

X

201–963–1

90–04–0

Xxxx. xxx. 2; X45 Xxxx. xxx. 3; X40 X; X23/24/25

X X: 45–23/24/25 S: 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; N X: 45–22–50/53 X: 53–45–60–61

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

612–051–00–1

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

X

202–974–4

101–77–9

Xxxx. kat. 2; R45 Xxxx. xxx. 3; X40 X; R39/23/24/25Xn; X48/20/21/22 X43 X; X51–53

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

612–081–00–5

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

X X

210–322–5 265–294–7 277–985–0

612–82–8 64969–36–4 74753–18–7

Karc. xxx. 2; X45 Xx; X22 N; X51–53

X; X X: 45–22–51/53 X: 53–45–61

612–099–00–3

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

X

202–453–1

95–80–7

Xxxx. xxx. 2; X45 X; R25 Xx; X21 Xx; X36 R43 N; X51–53

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

612–105–00–4

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

205–411–0

140–31–8

Xx; X21/22 X; X34 X43 R52–53

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

612–111–00–7

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

212–513–9

823–40–5

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

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

612–125–00–3

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

202–442–1

95–70–5

X; X25 Xn; X20/21 X43 X; X51–53

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

612–144–00–7

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

62924–70–3

Xx; X36/38 X4 3 X; R50–53

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

612–151–00–5

xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx

X

246–910–3

25376–45–8

Xxxx. kat. 2; R45 X; X25 Xx; X20/21 Xx; X36 X43 X; R51–53

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

613–018–00–4

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

7411–47–4

Xn; X22 Xx; R36/37/38 X52–53

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

613–031–00–5

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

201–782–8

87–90–1

X; 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-fenyl-1,3,5-triazin-2,4-diamin xxxxxxxxxxxxx

202–095–6

91–76–9

Xx; X22 X52–53

Xx R:22–52/53 X: (2-)61

613–042–00–5

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

252–615–0

35554–44–0

Xx; X20/22 X; 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 -imidazol-1-ium-hydrogensulfát [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx

261–351–5 [1] 281–291–3 [2]

58594–72–2 [1] 83918–57–4 [2]

Xx; X20/22 Xx; X41 X; R50–53

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

613–066–00–6

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

251–637–8

33693–04–8

Xx; X22 N; X50–53

Xx; N X: 22–50/53 S: (2-)60-61

613–091–00–2

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

225–062–8 [1]

4636–83–3 [1] 29873–36–7 [2]

Xx; R22 Xx; X36/37/38 X52–53

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

613–098–00–0

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

403–700–8

2687–94–7

X; R34 X; R51–53

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

613–130–00–3

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

79983–71–4

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–131–00–9

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

57369–32–1

Xx; X22 X52–53

Xx X:22–52/53 X: (2-)61

613–134–00–5

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

88671–89–0

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

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

613–137–00–1

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

242–505–0

18691–97–9

X; X50–53

X R: 50/53 X: 60-61

613–139–00–2

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

74223–64–6

N; R50–53

N X: 50/53 X: 60-61

614–001–00–4

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

200–193–3

54–11–5

X+; X27 X; R25 X; X51–53

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

614–006–00–1

xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx

206–614–7

357–57–3

X+; R26/28 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+; R26/28 R52–53

T+ X: 26/28–52/53 S: (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] xxxxxx-2,4-xxxxxxxxxxx [2] xxxxxx-3,5-xxxxxxxxxxx [3]

X

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

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

Xxxx. kat. 3; X40 X+; X26 Xx; R36/37/38 R42/43 X52–53

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

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

2

616–010–00–9

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

204–854–7

127–65–1

Xx; X22 X31 X; X34 X42

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

616–034–00-X

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

246–419–4

24691–76–7

X52–53

X: 52/53 S: 61

616–035–00–5

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

261–043–0

57966–95–7

Xx; X22 X43 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; R7 Xn; X22 X; X34 X; X50–53

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

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

617–006–00-X

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

201–279–3

80–43–3

O; X7 Xx; X36/38 X; X51–53

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

617–008–00–0

xxxxxxxxxxxxxxxx

202–327–6

94–36–0

X; X2 Xx; X36 X43

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

650–007–00–3

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

228–200–5

6164–98–3

Xxxx. kat. 3; X40 Xx; X21/22 X; R50–53

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

650–008–00–9

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

227–197–8

5707–69–7

X; X25 X; X50–53

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

650–009–00–4

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

243–269–1

19750–95–9

Xxxx. xxx. 3; R40 Xx; X22 N; X50–53

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

650–033–00–5

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

66230–04–4

T; X23/25 X43 N; X50–53

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

650–041–00–9

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

82097–50–5

X; X50–53

X X: 50/53 X: 60-61


XXXXXXX 1X

Xxxxxxxx xxxxx

Xxxxxxxx xxxxx

Xxxxxxxx x látkám

Číslo XX

Xxxxx XXX

Xxxxxxxxxxx

Xxxxxxxx

Xxxxxxxxxxxx xxxxxx

Xxxxxxxx x xxxxxxxxxx

006–090–00–8

2-[(3-xxxxxxx-2-xx-1-xx)xxx]xxxxx-X-xxxxxxxxxxxxx

408–010–0

88558–41–2

Xx; R20 Xx; X41 R52–53

Xn X: 20–41–52/53 X: (2-)22–26–39–61

014–016–00–0

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

406–490–6

X; X51–53

X X: 51/53 X: 61

015–164–00–9

xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx

400–480–5

36669–85–9

X52–53

X:52/53 X: 61

015–165–00–4

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

404–986–7

Xi; X41 X; R50–53

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

015–166–00-X

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

410–290–4

80693–00–1

X53

X:53 S: 61

015–167–00–5

3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx

411–200–6

14657–64–8

Xx; R41

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

601–050–00–1

X10-X13-xxxxxxxxxxxxx xxxxxxx

267–051–0

67774–74–7

X; R50

N X: 50 X: 61

601–051–00–7

4-fenylbut-1-en

405–980–7

768–56–9

Xi; X38 X; R51–53

Xi; X X: 38–51/53 X: (2-)37-61

602–083–00–4

xxxxxxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx

251–084–2

32534–81–9

Xx; X48/21/22 X64 X; R50–53

Xn; 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; R52–53–59

N R: 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-terc-butoxypropan-2-ol

406–180–0

57018–52–7

R10 Xx; X41

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

603–130–00–1

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

406–325–8

Xx; R22 X52–53

Xx X:22–52/53 X: (2-)39-61

603–131–00–7

Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-deoxy-1-[methyl(1-oxotetradecyl)amino]-D-glucitol

407–290–1

Xi; X41

Xx X: 41 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

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

408–240–1

Xx; R22 X52–53

Xx X:22–52/53 S: (2-)22–36–61

603–134–00–3

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

410–450–3

X53

X: 53 X: 61

603–135–00–9

xxx[2-(2-xxxxxxxxxxxxx)xxxxxxxxxx]xxx(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx

410–500–4

Xx; X41 X; X51–53

Xx; N R: 41–51/53 X: (2-)26–39–61

603–136–00–4

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

410–910–3

104226–19–9

X43 X52–53

Xx X:43–52/53 X: (2-)24–37–61

603–137–00-X

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

411–130–6

Xi; X41

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

603–138–00–5

3-(2,2-dimethyl-3-hydroxypropyl)toluen 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol

403–140–4

103694–68–4

R52–53

R:52/53 X: 61

604–050–00-X

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

216–381–3

1570–64–5

X; X23 C; R 35 N; R50

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

X ≥ 25 %: X; C; X23–35 10 % ≤ X < 25 %: X;X20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ C &xx; 5 %: Xn;R20–36/37/38 1 % ≤ X &xx; 3 %:Xx;X36/37/38

604–051–00–5

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

401–110–5

87113–78–8

X52–53

X:52/53 X: 61

604–052–00–0

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

403–800–1

103597–45–1

X53

X:53 S: 61

604–053–00–6

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

410–760–9

157661–93–3

Xi; R38 X43 X; R50–53

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

604–054–00–1

Směs:2-methoxy-4-(4-methylidentetrahydropyran-2-yl)fenol x 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx

412–020–0

X43 R52–53

Xi X:43–52/53 S: (2-)24–37–61

604–055–00–7

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

413–900–7

85954–11–6

Xxxx. Xxx.3; R40

Xn X: 40 X: (2-)22–36–37

605–027–00–7

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

410–480–7

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

606–051–00–0

4-pentylcyklohexanon pentylcyklohexan-1-on

4–406–670–4

61203–83–6

N; X51–53

X R: 51/53 X: 61

606–052–00–6

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

410–410–5

54574–82–2

X52–53

X:52/53 X: 61

607–272–00–5

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

279–752–9 [1] —

81406–37–3 [1] 154486–27–8 [2]

N; X50–53

X R: 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; X 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) bis(1-methylimidazol)]zinečnatý xxxxxxx

405–635–0

Xx; X38–41 N; X50–53

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

607–277–00–2

Xxxx:2-(xxxxxxxxxxxxx)xxxxxxxxx-xxxxxxxxxxxx a xxxxxxx-xxxxxxxxx

405–720–2

Xx; X22 Xi; X41 R43 X; 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; X51–53

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

607–281–00–4

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

407–000–3

127519–17–9

X; R51–53

N X: 51/53 X: 61

607–282–00-X

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

407–140–5

131266–10–9

X52–53

X: 52/53 X: 61

607–283–00–5

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

408–040–4

15121–89–8

Xx; X21/22 Xx; X38–41 X43 N; X50–53

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

607–284–00–0

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

410–040–4

136213–76–8

X; X51–53

X X: 51/53 X: 61

607–285–00–6

Směs:7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonová 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 X: (2-)22–24–37–61

607–287–00–7

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

410–140–8

X52–53

X:52/53 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 -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx xxxxxxx, xxxxxxxxxx xxx; x = 15, 16, 17 nebo 18, x = 1, 2, 3 xxxx 4, x = 8, 9, 10 xxxx 11, d = 22, 23, 24 nebo 25

410–160–7

148732–74–5

Xx; X36 R43 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

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

410–540–2

Xx; X38 R43 X; R50–53

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

607–291–00–9

xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx

410–630–1

104051–92–5

X53

X: 53 X: 61

607–292–00–4

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

410–640–6

Xx; X38–41 X; X50–53

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

607–293–00-XSměs:

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

410–650–0

Xx; X41 X43 X; R51–53

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

607–294–00–5

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

410–680–4

X43

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

607–295–00–0

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

410–800–5

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

607–296–00–6

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

410–830–9

R53

R: 53 X: 61

607–297–00–1

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

410–960–6

92761–26–7

Xx; X41

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

607–298–00–7

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

411–010–3

X43

Xx X: 43 X: (2-)22–36/37

607–299–00–2

xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx

411–040–7

97101–46–7

Xx; X22 X43 X; R50–53

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

607–300–00–6

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

411–430–7

X43

Xx X: 43 X: (2-)22–24–37

607–301–00–1

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

411–860–5

Xx; X38–41 R43 X; X51–53

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

607–302–00–7

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

411–910–6

Xx; X38–41 X43 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 X: 62–52/53 X: (2-)22–36/37–61

608–023–00–3

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

406–140–2

114369–43–6

X; X50–53

X X: 50/53 S: 60-61

608–024–00–9

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

407–650–8

97460–76–9

X53

X:53 X: 61

608–025–00–4

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

410–970–0

117568–27–1

X53

X:53 X: 61

609–053–00-X

xxxxxxxxxxx-xxxxxxxxxxxxxxxx

414–850–9

X; X3 X; X8 Xxxx. xxx. 2; X45 X; X23/25 R43

E; X X: 45–3–8–23/25–43 S: 53-45

610–010–00–2

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

406–110–9

35950–52–8

Xx; X22–48/22 X; X34 X43 X; X50–53

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

611–043–00–5

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

402–850–1

Xx X: 41–52/53 X: (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 xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-terc-butyl-3-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx 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; R51–53

Xi; 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 X: 61

611–046–00–1

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

407–590–2

43151–99–1

X; X25 Xx; X48/22 X43 X; X50–53

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

611–047–00–7

Směs (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 X: 61

611–048–00–2

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

407–900–6

111381–12–5

R53

R: 53 X: 61

611–049–00–8

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

408–000–6

118658–98–3

Xx; R48/22 R43 X52–53

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

611–051–00–9

2-({4-[ethyl(2-hydroxyethyl)amino]-2-methylfenyl}azo)-6-methoxy-3-methylbenzothiazolium-chlorid

411–110–7

136213–74–6

N; R50–53

N 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 xxx

400–720–9

X52–53

X: 52/53 X: 61

612–156–00–2

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

405–620–9

Xx; R41 X; X50–53

Xx; N R: 41–50/53 X: (2-)26–39–60–61

612–157–00–8

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

410–780–8

Xx; X22–48/22 Xx; X41 X43 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 xxxxxxx x 4-xxxxxxxxxxxxxxxxxxxxx

410–820–4

X53

X: 53 S: 61

612–159–00–9

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

410–880–1

Xx; X22 X; X34 X; R50–53

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

613–149–00–7

2-terc-butyl-5-[(4-terc-butylbenzyl)sulfanyl]-4-chlorpyridazin-3(2H)-on

405–700–3

96489–71–3

T; R23/25 X; X50–53

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

613–150–00–2

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

406–295–6

X53

X:53 X: 61

613–151–00–8

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

406–360–9

104218–44–2

X53

X:53 X: 61

613–152–00–3

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

406–600–2

89392–03–0

X43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–153–00–9

2,3,5-xxxxxxxxxxxxxxx

407–270–2

16063–70–0

X52–53

X:52/53 X: 61

613–154–00–4

2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx

410–050–9

5734–64–5

Xx; X22

Xx X: 22 S: (2-)22

613–155–00-X

5-xxxxx-2,3-xxxxxxxxxxxxxx

410–090–7

89402–43–7

X10 Xx; X22 X52–53

Xx X: 10–22–52/53 S: (2-)23–36–61

613–156–00–5

2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-butyl-5-chlorimidazol-4-karbaldehyd

410–260–0

83857–96–9

R43 X; X51–53

Xx; X X: 43–51/53 X: (2-)24–37–61

613–157–00–0

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

410–330–0

54236–98–5

Xx; X22–48/22 Xx; X36

Xx R: 22–36–48/22 X: (2-)22–26–36

613–158–00–6

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

410–340–5

69045–84–7

Xx; X20/22 Xx; X41 R43 X; X51–53

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

613–159–00–1

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

410–580–0

120928–09–8

X; X25 Xn; X20 X; R50–53

T; X 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 S: (2-)24-37

615–022–00–1

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

410–550–7

79277–18–2

X; X2 R14 Xx; X48/22 R42/43

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

616–044–00–4

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

402–510–2

X; R51–53

N X: 51/53 X: 61

616–045–00-X

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

405–190–2

122371–93–1

X43 X53

Xx X: 43-53 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; R50–53

N X: 50/53 S: 60-61

616–047–00–0

Xxxx:X,X′,X″,X′′′ - tetraalkyl(C16)-2,2′, 2″, 2′′′ (xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx x X, N′,N″,N′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx

406–640–0

X43

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

616–048–00–6

3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx

406–740–4

1939–27–1

Xx; X48/22 N; X51–53

Xx; X R: 48/22–51/53 X: (2-)22–36–61

616–049–00–1

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

408–150–2

99141–89–6

X53

X:53 X: 61

616–050–00–7

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

410–690–9

103055–07–8

X43 X; R50–53

Xi; X R: 43–50/53 X: (2-)24–37–60–61

616–051–00–2

Směs:3,3'-bis(4-methylfenyl)- 1,1'-(4-methyl-1,3-fenylen)dimočovina x 3,3'-xxx(4-xxxxxxxxxxx)-1,1'-(2-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx

411–070–0

X53

X: 53 X: 61

617–015–00–9

bis(4-methylbenzoyl)peroxid

407–950–9

895–85–2

E; X2 X; X7 X; X50–53

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

650–032–00-X

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

94361–06–5

Xxxx. kat. 3; X63 Xx; R22 X; X50–53

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


XXXXXXX 2

XXXXXX SPECIFICKÝCH XXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx směrnice Komise 2001/59/XX,

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


PŘÍLOHA 3A

STANDARDNÍ POKYNY XXX XXXXXXXX ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz směrnice Xxxxxx 2001/59/XX,

Xx. věst. X 332, 28.12.2000, x. 81.


XXXXXXX 3B

STANDARDNÍ XXXXXX XXX BEZPEČNÉ XXXXXXXXX X XXXXXXXXXXXX XXXXXXX X PŘÍPRAVKY

Viz směrnice Xxxxxx 2001/59/ES,

Úř. xxxx. X 332, 28.12.2000, x. 81.


XXXXXXX 4X

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

1. XXXXXX

Xxxx metoda xx xxxxxxxx xxxxxx XXXX XX 473 — Xxxxxxx xx chromozomové xxxxxxx x savců xx vitro (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx u xxxxx xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx strukturní chromozomové xxxxxxx x xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Xxxxxxxxx xx dva xxxx xxxxxxxxxxxx aberací: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Nárůst xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx. Tato xxxxxx xxxx xxxx xxxxxx xx stanovení xxxxxxxxxxx xxxxxxx x xxxx x tomuto xxxxx rutinně používána. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx xxxx xxxxxxxx xxxxx geneticky xxxxxxxxxxx xxxxxx x xxxxxxx x existuje xxxxx důkazů x xxx, že xxxxxxxxxxxx xxxxxx x x xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx změny x xxxxxxxxxx x v xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx xxxxxxxx x xxxxxxx x u pokusných xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx in xxxxx mohou být xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, xxxxxxx xxxxx xxxx primární xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx na xxxxxxx schopnosti xxxxx x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx chromozomů, xxxxxxxxxxxx chromozomů x xxxxxxxxx četnosti chromozomových xxxxxxx.

Xxxxxxx prováděné xx xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx systém xxxxxx xxxxx napodobit xxxxxxxx xx xxxx x savců. Je xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx výsledkům, jež xxxxxxxxxx vlastní xxxxxxxxxx x xxxx x xxx xxxxx změnou xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx cytotoxicity (4, 5).

Tato zkouška xx používá ke xxxxxxxx xxxxxxx mutagenů x xxxxxxxxxxx pro xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; mezi xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx není xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx zřejmě xxxxxx xxxxxx xxxxxxxxxx xxx xxxxxx poškozením XXX.

Xxx také Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx nebo xxxxx x xxxxxxx xxxx xxxxxxxxx v tomtéž xxxxx.

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

Xxx : xxxxxxxxxxxx léze xxxxx xxx xxxxx xxxxx xxxxxxxxxx a x xxxxxxxxx odchylkou xxxxxxxxx.

Xxxxxxxxx xxxxx : xxxxx xxxxx, které xx xxxxxxxxx x xxxxxxxx, x celkového xxxxx xxxxx x xxxxxxxx; xxxxx xxxxxx xxxxxxxxxxx xxxx xxxxxxxx.

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

Polyploidie : násobek xxxxxxxxxxx xxxxx chromozomových sad (x), xxxx než xxxxxxxxx (tj. 3 x, 4 x xxx.).

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx vystaveny xxxxxxxx látce, a xx s xxxxxxxxxxxx xxxxxxxx x bez xx. V předem xxxxxxxxxxx intervalech xx xxxxxxxx xxxxx xx xx buněčných kultur xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx kolchicin), xxxxxxx xx sklidí, xxxxxx x přítomnost chromozomových xxxxxxx se xxxxxx xxxxxxxxxxxxxx xxxxxxxxxxx xxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx být xxxxxxx různé buněčné xxxxx, xxxxx nebo xxxxxxxx xxxxxxx xxxxxxx, xxxxxx xxxxxxxx buněčných xxxxx (xxxx. fibroblasty xxxxxx čínského, xxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx xxxxxx xxxxx).

1.4.1.2 Xxxxx x kultivační xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (kultivační nádoby, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). U xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x kmenů by xxxx být xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxxx chromozomů x xxxx xx xxx kontrolováno, xxx xxxxxx kontaminovány xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx neměly být xxxxxxx. Xxx xxxxxxx xxxxx a inkubační xxxxxxxx by měla xxx xxxxx normální xxxxx xxxxxxxxx xxxxx.

1.4.1.3 Xxxxxxxx kultur

Stabilizované xxxxxxx xxxxx x xxxxx: xxxxx xx xxxxxxx x xxxxxxxxx xxxxxx, xxxxxx xx xx xxxxxxxxxxxx xxxxx v xxxxxx xxxxxxx, xxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, x inkubují xx xxx 37 °X.

Xxxxxxxxx: xxxx xxxxxxxx xxxxxxxxxxxxxxx (xxxx. xxxxxxxxx) xxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xx xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. fytohemaglutinin) x xxxxxxxx se při 37 °C.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx vystaveny zkoušené xxxxx, x xx x vhodnou metabolickou xxxxxxxx a bez xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je kofaktorem xxxxxxxx postmitochondriální xxxxxx (X9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (6, 7, 8 x 9), xxxx směs xxxxxxxxxxxxx x β-naftoflavonu (10, 11 x 12).

Postmitochondriální xxxxxx je x xxxxxxxx xxxxxxxxxx médiu xxxxxxx používána x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx xxxxxxxxxxxxx aktivačního xxxxxxx může xxxxxxx xx xxxxx xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, xxxxxx přípravy xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx pro endogenní xxxxxxxx. Xxxxx použitých xxxxxxxxx linií by xxxx xxx vědecky xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx cytochromu P450 xxx metabolismus xxxxxxxx xxxxx).

1.4.1.5 Zkoušená xxxxx/xxxxxxxx

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

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx slučitelné x přežitím buněk x x xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx údaji x xxxxxx kompatibilitě. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx látek nestálých xx xxxx by xxxx xxx použita xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Expoziční xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx mají xxx xxxxxxxxxx při xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx cytotoxicita, xxxxxxxxxxx x testovacím systému x xxxxx xX xxxx osmolality.

Cytotoxicita xx xxxx xxx stanovena x xxxxxxxxxxxx xxxxxxxx x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx vhodných xxxxxxxxxx xxxxxxx xxxxxxxxx x růstu, jako xxxx xxxxxx xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx buněk xxxx mitotický index. Xxxx xxx výhodné xxxxxxxx cytotoxicitu x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx tři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx xx xxxx xxxx koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx minimální xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, což obvykle xxxxxxx, xx xx xx xxxxxxxxxxx xxxxxx xxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx xxxxxxxxxxx vykazovat xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx mitotického xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx nepřímým měřítkem xxxxxxxxxxxxx nebo xxxxxxxxxxxxxx xxxxxx x závisí xx xxxx, xxxxx xxxxxxxx od expozice. Xxxxxxxxx xxxxx je xxxx přijatelný u xxxxxxxxxxx xxxxxx, x xxxxx xxxxx být xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx a xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), xxxxx xxx použity xxxx xxxxxxxxx xxxxxxxxx. X xxxxxxx AGT xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx nelze xxxxxxx xx existenci xxxxxxxxxx xxxxxxxxxxx, x i xxxx xxxxxxxxx průměrné xxxxxxxxx xxxx xxxx xxx xx xxxxxxxx xxxxx xxxxxxxxx oddálení xxxxxxxx xxxxxxxxxxx výtěžku xxxxxxx.

X případě xxxxxxxxx xxxxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx koncentrace 5 μx/xx, 5 xx/xx xxxx 0,01 X, xxxxx xxxx, která x xxxx xx xxxxxxxx.

X xxxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx xxxxxxx xxx xxxxxxxxxxxxx nižších, xxx xx xxxxxx xxxxxxxxxxx, xx xxxx xxx xxxxxxx xxxxxxxx xxxxx x xxxxxxxxxxx, jež xx nad xxxx xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx médiu xx xxxxx xxxx aplikace. X určitých xxxxxxxxx (xxxx. projeví-li xx xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx, než xx xxxxxxxxxxx) se xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, xxx nichž xxxxxxx ke xxxxxxx. Xxxx být užitečné xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx expozice, xxxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxxx xx xxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, xxxx X9 atd. Nerozpustnost xxx zjistit xxxxxxxx. Xxxxxxxxx by neměla xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx a pozitivní xxxxxxxx

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

K xxxxxxxxx kontrole xx xxx xxx xxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxx koncentracích, které xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxxxx x xxxxxxxxxxxxx nárůst xxx pozadí, xxxx xx prokáže citlivost xxxxxxxxxxx xxxxxxx.

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

Xxxx xxxxxxxxxxx xxxxxxxx

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

Bez 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 metabolickou xxxxxxxx

xxxxx[x]xxxxx

50–32–8

200–028–5

xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx monohydrát

6055–19–2

Pro pozitivní xxxxxxxx xxxxx xxx xxxxxxx x jiné xxxxxx xxxxx. Xxx xxxxxxxxx xxxxxxxx by xxxx být xxxxx xxxxx vzato x xxxxx použití chemických xxxxx ze xxxxxx xxxxxxxx třídy.

V xxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx negativní xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx x xxxxxxxxxxx xxxxx x xxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx žádné xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxxxxx xxxxxxxx xxxxx xxx za přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx něho. Xxxxxxxx xxxxxxxxx xx xxxx xxx zahájena xxx 48 xxxxx xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx xxxxxx koncentraci xx xxxx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x kultur pro xxxxxxxxx xxxxxxxx nebo xxxxxxxx rozpouštědla. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx duplicitními xxxxxxxxx xx minimální xxxxxx, xxxx xxx přípustné xxxxxxx jediné kultury.

Plynné xxxx xxxxxx látky xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. x xxxxx xxxxxxxxxx kultivačních nádobách (15, 16).

1.4.3.3 Xxxx xxxxxxx kultur

V prvním xxxxxxxxxxx by měly xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, jak x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní, xx dobu 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx xx xxxxxx době xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx buněčného cyklu (12). Xxxxxxxx xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx jak x xxxxxxxx, xxx xxx xxxxxxxx, měl by xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx expozicí xx do xxxxxx x xxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu. Xxxxxx xxxxxxxx látky xxx snáze xxxxxxxxx xxx dobách aplikace xxxx xxxxxx xxxxxxx xxx 1,5násobek xxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx od případu. X xxxxxxxxx, kdy xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx za xxxxxxxx, by mělo xxx xxxxxx xxxxxxxxxx.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xx xxxxxxx xxxxxxx se obvykle 1-3 hodiny xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx kolchicin. Xxx xxxxxxxx xxxxxxxxx pro xxxxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxxx xxxxxx x zpracovává xxxxxx. Příprava xxxxxxxxx xxx analýzu chromozomů xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Analýza

Všechny xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při xxxxxx xxxxx xxxxxxx xx xxxxx části xxxxx x xxxxxxxx x xx ztrátě xxxxxxxxxx, xxxx by xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x xxxxx rovném xxxxxxx xxxxxxx ± 2 xxx všechny xxxx xxxxx. Xx xxxxxx xxxxxxxxxxx x xxxxxxxx xx mělo xxx xxxxxxxxx xxxxxxx 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx duplicitní xxxxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx.

Xxxxxx xx účelem xxxxxxx detekovat xxxxxxxxxx xxxxxxxxxxxx aberace, xx xxxxxxxx xxxxxxxxxx polyploidii x endoreduplikace, jsou-li xxxxxxxxxx.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx x xxxx xx xxxx být xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (aberacemi) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx x xxxxxxxxxxxxxx xxxxxxx by měly xxx xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx s xxxxxx xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx xxxxxxxxxx xx xx xxxxxxx xxxxxxxx aberací.

Měla xx xxx také xxxxxxxxxxx xxxxxxxx, která xxxx xxxxxxxxx pro xxxxxxxxx xxxxxxxxxxxx x xxxxx xxxxxxxxxxxx kultur a xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

Xxxx by xxx xxxxxxx xxxxx pro xxxxxxxxxx kultury. Dále xx xxxx xxx xxxxxxx xxxxx xxxxxxx xx xxxxx xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxxxx dalším xxxxxxxxx, nejlépe s xxxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxxx xxxxxxxx negativní xxxxxxxx xxxx xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K parametrům xxxxxx, xxxxx by xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx xxxxx x chromozomovými xxxxxxxxx x xxxxxxxxxx na xxxxxxxxxxx, xxxx reprodukovatelný xxxxxx tohoto xxxxx. Xxxxxxxx xx xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Statistická xxxxxxxxxx xx neměla být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

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

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, v xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx údajů vyslovit xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx zkoušky xx xxxxxxxxxxxx aberace in xxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x kultivovaných xxxxxxxxxxx xxxxxxx xxxxx strukturní xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxx:

- xxx x xxxxx buněk,

- xxxxxxxxxx xxxxxxxxx x xxxxxxxx použitého typu xxxxx,

- xxxxxxxxx nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx x xxxxx xxxxxxxxx cyklu,

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

- případně xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx kultury,

- xxxxxxx xxxxxxx počtu xxxxxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx metafázi, xxxx koncentrace x xxxxx expozice xxxxx,

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x počtu xxxxxx, xxxxxx např. údajů x cytotoxicitě x xxxxxx rozpustnosti, xxxx-xx x dispozici,

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX2,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx vehikula x přidané xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx nasazení,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- metody xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

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

- xxxxxx xxxxxxx,

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

- definice xxxxxxx, včetně xxxx,

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

- xxxxx xxxxxxx, xxxxx xxxx pozorovány,

- podle xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X. (1976), Xxxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, xx: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx xxx Xxxxxxx xxx xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, A. (xx) Xxxxxx Xxxxx, Xxx Xxxx xxx Xxxxxx, 1-29.

2) Xxxxxxxx, X. Xx., Xxxxxx, X. (1985), Xxx In xxxxx Chromozomal Xxxxxxxxxx Xxxx Xxxxx Xxxxxxx Xxxxxxx Lung (XXX) Xxxxxxxxxx Cells xx Xxxxxxx, in: Xxxxxxxx xx Xxxxxxxxxx Research, Xxx. 5, Xxxxx, X. et xx., (xxx) Elsevier Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Galloway, S. X., Xxxxxxxxx, X. X., Reuben, X., Xxxxxx, S., Brown, X., Xxxxxx, C., Xxxxx, X. X., Xxxxxxxx, F., Xxxxx, X., Xxx, X., Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X. A., Xxxxxxxx, X., Xxxxxx X. (1978), Chromozome xxxxxxxxxx xxx xxxxxx chromatic xxxxxxxxx xx Xxxxxxx xxxxxxx ovary xxxxx: Xxxxxxxxxx of 108 xxxxxxxxx, Xxxxxxx. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

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

5) Xxxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxx, X., (1992), Xxxxxxxxxxxxxx of xxx xX to Xxxxxxx Cultured Xxxxxxxxx Xxxxx, Mutatation Res., 268, 297-305.

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

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

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

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

10) Elliot, X. M., Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Wolf, X. X. (1992), Xxxxxx of UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx In xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, K., Xxxxxxxx, X. (1976), X. Xxxx Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. an Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, in: xx Xxxxxx, F. X., Fouts, J. X. Bend, J. X., Philpot, X. X. (eds), In xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Testing, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

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

13) Xxxxxxxxxx, X., Xxxxxxxx, D. A., Xxxxx, X. X., Xxxxxxxx, X., Chanter, X. O., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx xxxx Xx xxxxx Xxxxxxxxxxx Xxxxxx, xx: Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, Xxxxxxxx, X. X., (xx) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

14) Xxxxx, X. A., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Flasks are xxx Xxxxxxxxx xxx Xx xxxxx Chromozome Xxxxxxxxxx Assays in XXX Xxxxx, Xxxxxxxxxx Xxx., 312, 139-149.

15) Xxxxx, D. X., Xxxxxx, X. X., XxXxxxx, X. T. (1982), XXX/XXXXX Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Volatile Xxxxxxx, xx: Xxxx, X. X., Costa, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, New Xxxx, Plenum, 91-103.

16) Xxxxxx, X. X., Xxxxxx, J. X., Xx, X. P., Xxxxxx, X. L. (1983), Xxxxxxxxxx xx xx Xxxxxxxx System Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Detecting Highly Xxxxxxxx Mutagens xx xxx XXX/XXXXX Mutation Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.

17) Xxxxx-Xxxxx, X. (1983), Endoreduplication xx Xxxxxxx xxxxxxx xxxxx during alpha-radiation xxxxxxx X2 arrest, Xxxxxxxxxx Res., 119, 403-413.

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


XXXXXXX 4B

"B.11 MUTAGENITA–ZKOUŠKA XX XXXXXXXXXXXX ABERACE X XXXXXXX KOSTNÍ XXXXX SAVCŮ IN XXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody XXXX XX 475 — Xxxxxxx na xxxxxxxxxxxx xxxxxxx x xxxxxxx xxxxxx dřeně xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx xx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací xxxxxxxxxxxx xxxxxxxxx xxxxxx v xxxxxxx xxxxxx xxxxx xxxxx, obvykle xxxxxxxx (1, 2, 3, 4). Xxxxxxxxx xx xxx typy xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x chromatidové. Nárůst xxxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxx. X xxxxxxx většiny xxxxxxxxxx xxxxxxxx jsou xxxxxxxxxx xxxxxxx chromatidového xxxx, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx jevy xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx a existuje xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxx způsobující xxxxx x xxxxxxxxxx a x genech xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx podíl xx xxxxxxx xxxxxxxx x xxxxxxx x x xxxxxxxxxxxxxxxx systémech.

Při této xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxxxx xx v xxxx xxxxxxx xxxxxx xxxx, poněvadž je xxxxxx vaskularizovanou xxxxx x obsahuje populaci xxxxx x xxxxxxx xxxxxx, které xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Jiné xxxxx x xxxxxx tkáně xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx na xxxxxxxxxxxx aberace xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx umožňuje xxxxxxxxx xxxxxxx metabolismu xx xxxx, xxxxxxxxxxxxxxx a xxxxxxx reparace DNA, xxxxxxx xx xxxxx x různých xxxxx x xxxxx xxxxx. Xxxxxxx xx xxxx xx rovněž xxxxxxxx xxx xxxxx výzkum xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, že se xxxxxxxx látka xxxx xxxxxxxxx metabolity xxxxxxxxxx xx xxxxxx xxxxx, xxxx vhodné tuto xxxxxxx xxxxxx.

Xxx také Xxxxxx úvod, část X.

1.2 DEFINICE

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

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

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

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

Xxxxxxxxx xxxxxxx : xxxxxxxx xxxxx chromozomů xx normální hodnoty xxxxxxx u xxxxxxxxx xxxxx.

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

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx jsou xxxxxxxxx xxxxxxxx látce xxxxxxx xxxxxxxx x xx xxxxxxx xxxxxxxx po xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx se xxxxxxxx xxxx xxxxx xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx se xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx a xxxxxxxxx xx chromozomové xxxxxxx xxxxx x xxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xx xxxxxxxx xxxxxx, myš x křeček xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx u xxxx pohlaví překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx mladá xxxxxxxx xxxxxxx zvířata se xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, která xx xxxxxxx xxxxxxxx xxxxx. Xxxxx xx xxxx být xxxxxxxxxx xxx, aby byl xxxx jejich xxxxxx xxxxxxxxxxxxx. Zvířata se xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x laboratorních xxxxxxxxxx alespoň xxx xxx aklimatizovat.

1.4.1.4 Xxxxxxxx xxxxx

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

1.4.2 Zkušební xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by měly xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx xxxxxxx. X xxxxxxxx aplikace xxxxxxxx xxxxx xx xxxx zvířata xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx skupinách, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx in vivo xxx xxxxxxxxxxx xxxxxxxx, x xxxxx se xxxxxxx, xx poskytnou xxxxxxxxxxxxx xxxxxx nad xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx tak, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx podávána xxxxx způsobem xxx xxxxxxxx xxxxx a xxx byl xxxxx x xxxxx xxxxxxx xxxxxxxx jen xxxxxx. Xxx pozitivní kontrolu xxxxx xxx xxxxxxx xxxxxxxx xxxxx xx xxxxxx chemické xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx kontrolu:

Látka

Číslo CAS

Číslo xxxxx XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

V xxxxxxxx xxxxxxx odběru xx xxx být proveden xxxxx x xxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx pouze xxxxxxxxxxxx xxxx vehikulum a xxx xxxxx podstupují xxxxxx xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx xxxxxx z dosavadních xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě zvířat x xxxxxxxx xxxxx x xxxxxxxxxxxxxx aberacemi. Xxxxxxx-xx xx xxx xxxxxxxxx kontrolu jeden xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Počet x pohlaví zvířat

Každá xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx. Xxxxxxxx xxxx x době xxxxxx k xxxxxxxxx xxxxx ze xxxxxx xx xxxxxxx xxxxxx x za xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, že xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, xxxx postačující xxxxxxxx xxxxxxx xxxxxxx. Je-li xxxxxxxx xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, xxxx je xxxx xxxxxxxxx x některých xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx se xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx xxx pokud xxxxx podávány xxxxxxxxxxx. Xxxxxxxx xxxxx xxxxx xxx podávány také xx dvou xxxxxxx, xxx. xxx xxxxx x xxx xxx x rozmezí xx xxxx xxx xxxxxxxx xxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx xxxxxx podávání xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xxxxxx by xxxx xxx xxxxxxxx xx xxxx xxxxxxx intervalech xx aplikace xxxxxx x xxxxxx dni. X xxxxxxxx se xxxxx xxxxxxx xx xxxxxx xxxx xx xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu (xxxx xxxx xxxxxxx 12 — 18 h). Xxxxxxxx doba nezbytná xxx příjem x xxxxxxxxxxxx zkoušené xxxxx x xxxxxx xxx xxxxxx na xxxxxxxx xxxxxxxxx xxxxx může xxx xxxx xx xxxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxx xxxxx odběr xx 24 h xx xxxxxxx odběru. Je-li xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx xxx, měl by xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx se xxxxxxxx intraperitoneálně podá xxxxxx xxxxx xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® xxxx kolchicin). Xxxx se xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X xxxx je xxxx xxxx přibližně 3 — 5 x; x křečka xxxxxxxx je xxxx xxxx xxxxxxxxx 4 — 5 h. X xxxxxx dřeně xx odeberou xxxxx x analyzují xx xx xxxxxxxxxxxx aberace.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, pohlavím x xx stejného xxxxxx expozice, xxx xx xxxxxxx v xxxxxx xxxxxx (5). X případě xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Tyto xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle xxxxxxxxx x letalitě. Xxxxx xx xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx dávkách (např. xxxxxxx a mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx a xxxx xx xxx xxxxxxxxx případ od xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (např. xxxx xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx xxxx xx xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x není-li xx xxxxxxx údajů x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, nepovažuje xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx delší než 14xxxxx xxxxxxxx je xxxxxxx dávkou 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx injekcí. Jiné xxxxxxx xxxxxxxx xxxx x odůvodněných xxxxxxxxx xxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxxxxxxx xxxx injekčně, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 ml/100 g xxxxxxx xxxxxxxxx. Použití xxxxxxx xxxxxx, než xx uvedený xxxxx, xxxx být zdůvodněno. Xx xx dráždivé x xxxxxx látky, xxxxx xxxxxxx při xxxxxxx koncentracích vykazují xxxxxxxx xxxxxx, by xxxx xxx variabilita xxxxxxxxxx xxxxxx minimalizována xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx při xxxxx xxxxxxxx dávky.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Ihned po xxxxxxxx xx xxxxxxx xxxxxx xxxx, hypotonizuje xx x xxxxxx. Xxxxx se xxxxxxx xx xxxxxxxx xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx xxx být x všech exponovaných xxxxxx (xxxxxx xxxxxxxxxxx xxxxxxx) x u xxxxxxxxxxxxxx xxxxxx xxx xxxxxxxxx kontrolu xxxxxxxx xxxxxxxxx index, x xx alespoň u 1000 buněk na xxxxx zvíře.

U xxxxxxx xxxxxxx by xxxx xxx xxxxxxxxxxx xxxxxxx 100 xxxxx. Xxxxx xxxxx xxx snížit, xx-xx pozorován xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx by xxxx být xxxx xxxxxxxxxxxxxx analýzou xxxxxxxxx xxxxxxxx. Xxxxxxx xxx xxxxxx často dochází xx xxxxxxxxxxxxxx xxxxxx xxxx ke xxxxxx xxxxxxxxxx x části xxxxx x xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx zvířata by xxxx být zpracovány xx formě xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx. Pro každé xxxxx xx měl xxx xxxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xx xxxxx x xxxxx xxxxx s xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) vyjádřený x xxxxxxxxxx. Pro xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxx různé typy xxxxxxxxxxxx xxxxxxxxxxxxxx aberací x jejich xxxxxx x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx se, xxx xxxxxx se xxxxxxxxxx do xxxxxxx xxxxxxxx xxxxxxx. Xxxxxxxxxx-xx xxxxx x rozdílu x xxxxxxxx xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst relativního xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx xxxxx nárůst xxxxx xxxxx s xxxxxxxxx pro xxxxxxx x určitou xxxxxx x x xxxxxxxx xxxxxxxx odběru. Nejdříve xx xxxx xxx xxxxxxx biologická relevance xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx použity xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Dvojznačné xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx s úpravami xxxxxxxxxxxxxxxx podmínek.

Nárůst xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx látka má xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx progresi xxxxxxxxx xxxxx (7, 8).

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx látky. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx na xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx výsledky zkoušky xx chromozomové xxxxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x kostní xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxx x kostní xxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

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

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, stáří x pohlaví zvířat,

- xxxxx, podmínky xxxxx, xxxxxx atd.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxxxxxx x negativní (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- údaje x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- xxxxxxxxx metody xxxxxxx, zda se xxxxxxxx látka xxxxxxx xx xxxxxxxx xxxxx xxxx do cílové xxxxx,

- případně přepočet xxxx koncentrací zkoušené xxxxx x xxxxxx xxxx xxxx (xxx) xx odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- podrobný xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx stanovení xxxxxxxx,

- identifikace xxxxx xxxxxxxxxxx xxxxxxxx, její xxxxxxxxxxx a xxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx na jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxx x xxxxx aberací xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- celkový počet xxxxxxx xx skupině xx xxxxxxxxx hodnotami x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx buněk x xxxxxxxxx ve skupině xx středními xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx závislost odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

- údaje x souběžné xxxxxxxxx xxxxxxxx,

- xxxxxxxxx údaje x xxxxxxxxx kontrole x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

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

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

3) Richold, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. G., Bootman, X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, in: X. X. Xxxxxxxx (xx.), Basic Mutagenicity Xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx X xxxxxxx, Xxxxxxxxx University Press, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. X., Hayashi, X., XxxXxxxxxx, J. X., Anderson, X., Xxxxxx, D. H., Xxxxxx, X. E., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx xxx Working Xxxxx on xxx xx vivo Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, J. A., Xxxxxx, A. X., Xxxxxx, P. A., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx In xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, X. X., Xxxxxxxx, X., Albanese, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, D. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx vivo Xxxxxxxxxxx Xxxxxx, in: UKEMS Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Testing, Xxxxxx Part III. Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx, X. X. Xxxxxxxx (xx.) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

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

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


XXXXXXX 4X

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

1. METODA

Tato xxxxxx je xxxxxxxx xxxxxx OECD XX 474 — Xxxx xxxxxxx erytrocytárních mikrojader xx vivo (1997).

1.1 XXXX

Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx in xxxx xx xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx mitotického xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx, x to xxxxxx xxxxxxx erytrocytů xxxxxxxxxx x kostní dřeně x/xxxx xxxxx periferní xxxx, xxxxxxx xxxxxxxx.

Xxxxxx xxxxx savčích erytrocytárních xxxxxxxxxx xx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxxxxx poškození, jehož xxxxxxxxx xx xxxxxx xxxxxxxxxx obsahujících xxxxxxxxxxxxx xx (lagging) chromozomové xxxxxxxxx nebo xxxx xxxxxxxxxx.

Xxxx xx erytroblast xxxxxx xxxxx xxxx xx xxxxxxxxxxxxxxx erytrocyt, xxxxxx xxxxx xx xxxxxxxx x mikrojádra, xxxxx při xxx xxxxx xxxxxxxxx, zůstávají x xxxxxxxxxx, xxxxx xxxxx jádra xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx xx x těchto xxxxxxx xxxxxxxxx xxx, že xxxxxxxxxx xxxxxx xxxxx. Xxxxxx výskytu xxxxxxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x exponovaných xxxxxxxxx xx xxxxxxx indukovaného xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx je xxxxxxx xxxxxxxxx xxxxxx dřeň xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx s xxxxxxxxxx x periferní xxxx je rovnocenně xxxxxxxxxx u xxxxxxxxxxx xxxxx, u xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx erytrocyty x mikrojádry, xxxx xxxxxxxxxx citlivost xxxxxxxxx xxxxxxxx, které způsobují xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx aberace. Mikrojádra xxx xxxxxxxx xxxxx xxxxxxxx. Ta xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx xxxxxxxxxxx (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx xx zejména xxxxxxx xxxxxxxxx (polychromatických) xxxxxxxxxx x xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x periferní xxxx, xxxxx xxxxxxxx xxxxxxxxxx, připadající xx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxx jako xxxxxxx xxxxxxxx zkoušky, jestliže xxxx zvířata exponována xxxxx xxxxx xxxx xxxx.

Xxxxx xxxx savčích xxxxxxxxxxxxxxx mikrojader xx xxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x procesy xxxxxxxx XXX, třebaže xx xxxxx xxxxx x xxxxxxx xxxxx x tkání, xxxxx x z xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx je xxxxxx xxxxxxxx pro xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx x xxxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx nedostanou xx xxxxxx tkáně, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxx : xxxx xxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx a xxxxx xxxx, xxxxxxxxx xxxxx xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx fragmenty nebo xxxxxx xxxxxxxxxx.

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

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx xx xxxxxxxxx mezistadiu, xxxxx xxxxx xxxxxxxx xxxxxxxx, x xxxx xxx xxxx rozlišen od xxxxxxx normochromatických erytrocytů xxxxxxxx selektivním xxx xxxxxxxx.

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

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

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Při xxxxxxx xxxxxx xxxxx se xxxx testovací xxxxx xxxxxxxxxx myš nebo xxxxxx, ačkoli xxx xxxxxx xxxxxxxx vhodný xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx xxxx xx xxxxxxxxxx xxx. Xxx xxxx xxxxxx xxxxxxxx vhodný xxxx xxxxx xx xxxxxxxxxxx, xx jde x xxxx, x xxxxx xxxxxxx neodstraňuje xxxxxxxxxx x xxxxxxxxxx, nebo xxxx xxxxxxxxxx dostatečnou xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx zahájení xxxxxx xx měla xxx xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx x xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx hodnoty hmotnosti.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx zvířata xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, x xxx xx xxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx. Klece xx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx zkoušené látky xxxxx xxx podávány xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x jejich xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx podezření, xx xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx než xxxxx rozpouštědla/vehikula, xxxx xx být jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

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

Xxxxxxxxx xxxxxxxx xx měly xxxxxxxxxx mikrojádra xx xxxx xxx expozičních xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Dávky xxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx xxx, xxx byl xxxxxx xxxxxxxx, ale xxx při odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx identifikace preparátu. Xx xxxxxxxxxx, xxx xxxxxxxxx kontrola byla xxxxxxxx xxxxx způsobem xxx zkoušená xxxxx x xxx byl xxxxx x tomto xxxxxxx prováděn xxx xxxxxx. Pro xxxxxxxxx xxxxxxxx xxxxx xxxx xxx xxxxx x xxxxx xxxxxxx chemických xxxxx xx stejné xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxxx

Xxxxx XXX

Xxxxx podle XXXXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

xxxxxxxxx C

50–07–7

200–008–6

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid xxxxxxxxxx

6055–19–2

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

51–18–3

200–083–5

X xxxxxxxx xxxxxx xx xxx být xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx kontroly, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x která xxxxx xxxxxxxxxx stejný xxxxxx jako xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx o xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Provádí-li xx xxx negativní xxxxxxxx xxxxx odběr, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx odběru. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx nebo xxxxxx-xx publikovány kontrolní xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx použití xxxxxxxxx krve xxxx xxx jako xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx xxxx xxxxxxxx xxxx expozicí, xxxxx xxxx u xxxxxxxx xxxxxx x periferní xxxx (xxxx. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, xx xxxxxxxx xxxxx xxxxx x xxxxxxx, xxxxx xx na xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Každá xxxxxxxxxx x kontrolní xxxxxxx xx xxxx skládat x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví (11). Xxxxxxxx xxxx x xxxx xxxxxx k xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx prokazují, xx xxxxxxxxxx xxxx xxxxxxxxx xxxxxx x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx expozice xxxxxxx xxxxxxxxxx pro xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx provedena xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxx xxxxxxxxx xxxxx xxxxxxxxxx plán (xx. xxxxx, xxx xxxx xxx xxxxxxxx x xxxxxxxxx 24 xxxxx). Vzorky ze xxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxx jsou xxxxxxxxxx, xxxxx xx x xxxxxx xxxxxx xxxxxxx pozitivní xxxxxxxx, xxxx –v xxxxxxx xxxxxxxxxxx studií — xxxxx xxxx prokázána xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxxx xx do xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx xxxxxxx, xxx. xxx xxxxx x xxx xxx v rozmezí xx xxxx než xxxxxxxx xxxxx, xxx xxxx usnadněno xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx.

Xxxx xxxx xxx proveden xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx xxxxxx. Vzorky xxxxxx xxxxx xx xxxxxxxx xxxxxxx dvakrát, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci a x přiměřeným xxxxxxxx xxxx xxxxxx. Odběr xxxxx xxx 24 xxxxx xx aplikaci xxxx být zdůvodněn. Xxxxxx xxxxxxxxx krve xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx první xxxxx xx xxxxxxx xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x po xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx po xxxxxx odběru xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx odběr nutný;

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

Xxxxx xxxxxxx xxxxx xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx xxx xxxxxxxx xxxxxxx dávek, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx stejným xxxxxx, xxxxxx, xxxxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, jež xx použijí x xxxxxx xxxxxx (13). X xxxxxxx xxxxxxxx xx pro xxxxx xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové xxxxxx xxxxxxxx, že xxxxx xxxxx by vedly xxx xxxxxxx režimu xxxxxxxxx podle xxxxxxxxx x letalitě. Látky xx specifickou xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx vyhovovat a xxxx by být xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší dávka xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx v kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (např. xxxxxxx xxxxxx nezralých xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx nebo x xxxxxxxxx xxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx dávkou o xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx v xxxxxx xxx nevykazuje xxxxx pozorovatelné xxxxxxx xxxxxx x není-li xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, není xxxxxxxxxx úplná xxxxxx xx xxxxx úrovněmi xxxxx za xxxxxxxxx. X xxxx xxxxxxxxxx xxxxxx xx xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx xxxxx xxx 14xxxxx xxxxxxxx xx xxxxxxx xxxxxx 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx nebo vhodnou xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou xxxxxxxxxx x xxxxxxxxxxxxxxx xxxxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx zesílené xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx xxxxx xxx všech úrovních xxxxx.

1.5.6 Příprava xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx dřeně se xxxxxxx získávají x xxxxxx xxxx tibie xxxxx po xxxxxxxx. Xxxxx xx xxxxxxxx x femuru xxxx xxxxx a xxxxxxxxxx xxxxxxxx se xxxxxxxxx x xxxxxx. Periferní xxxx se xxxxxxx x ocasní žíly xxxx xxxx xxxxxx xxxxxx xxxx. Krevní xxxxx xx xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), nebo xx připraví xxxxxxxxx xxxxxxxx a xxxx xx xxxxxx. Xxxxxxxx xxxxxxx xxxxxxxxxxxx xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 a xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx x xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxx XXX. Tato xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Xxxxxxxx systémy (xxxx. celulosová xxxxxx x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, že se xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx každé xxxxx xx stanoví xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, přičemž se x xxxxxxx xxxxxx xxxxx xxxxxxx xxxxxxx xxxxxxx 200 xxxxxxxxxx x x případě xxxxxxxxx xxxx xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx být xxxx xxxxxxxx xxx mikroskopem xxxxxxxxx xxxxxxxx. X xxxxxxx zvířete se xxxxxxx alespoň 2000 xxxxxxxxx erytrocytů na xxxxxx xxxxxxxxxx v xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx být získány xxxxxxxxxx xxxxxxx xxxxxxxxxx xx xxxxxx mikrojader. Xxx mikroskopické xxxxxxx xx neměl xxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx xxxx xxxxxxxx na xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx zvíře. Systémy xxx xxxxxxxxxxxx analýzu (xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx suspenze) xxxx xx odpovídajícím zdůvodnění x xxxxxxxx přijatelnými xxxxxxxxxxxxx xxxxxxxxxx hodnocení.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xxx jednotlivá xxxxxxx xx měly xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Pro xxxxx analyzované xxxxx xx měl xxx xxxxxx počet vyšetřených xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxx zvířata xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx xxxx déle, xxxx xx být xxxx xxxxxxx xxxxx x xxxxxxx xxxxxxxxxxxx, xxxx-xx shromažďovány. Xxx xxxxx xxxxx se xxxxx podíl xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx a xxxxxxxx xxxxxxxx erytrocytů x xxxxxxxxxx xxxxxxxxx x procentech. Neexistuje-li xxxxx x xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxx x xxxxxxxxxx xx xxxxx nebo xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxxx pro xxxxxxx s určitou xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx měla xxx xxxxxxx biologická xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Xxxxxxxxxxx významnost xx xxxxxx být xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x úpravou xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, jejíž xxxxxxxx nesplňují xxxx xxxxxxx xxxxxxxx, xx xxxxxxxx v xxxxx xxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, v xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx nebo xxxxxx xxx ohledu xx xx, xxxxxxxx je xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xxxxx xx xxxxxxxxxx xxxxxxxxx, xx zkoušená xxxxx indukuje xxxxxxxxxx, xxx jsou xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxx aparátu xxxxxxxxxxxx testovacího xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xx xxxxxxxx zkoušky xxxxxxxxxxx mikrojádra v xxxxxxxxx xxxxxxxxxxxx testovacího xxxxx.

Xxxx xx být xxxxxxxxxxx pravděpodobnost, x xxxxx se zkoušená xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx do xxxxxxxx oběhu, xxxx xxxxxxxxxx do cílové xxxxx (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění volby xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx hmotnosti, xxxxxxx xxxxxxx x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební podmínky:

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

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

- xxxxxxxxxx zvolených xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- údaje o xxxxxxxx zkoušené xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

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

- xxxxxxxx xxxxx x kvalitě xxxxxx a xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxx preparátů,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx z xxxxxxxxx xxxxxxxx erytrocytů,

- xxxxx xxxxxxxxx erytrocytů s xxxxxxxxxx xxxxxxx samostatně xxx každé xxxxx,

- xxxxxxx xxxxxxx ± xxxxxxxxxx xxxxxxxx počtu xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx xx skupině,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxx,

- údaje x xxxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx x souběžné xxxxxxxxx kontrole.

Rozbor výsledků.

Závěry.

4. XXXXXXXXXX

1) Heddle, X. X. (1973), X Xxxxx Xx xxxx Xxxx for Xxxxxxxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 18, 187-190.

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

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

4) Xxxxxxxxx, K. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxxxx, M. F., Xxxxxx, J. X. (1990), The Xx xxxx Xxxxxxxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx xxx Peripheral Xxxxx. X xxxxxx xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Res., 239, 29-80.

5) XxxXxxxxx, X. X., Xxxxxxxx, X., Xxxx, X. N., Xxxx, C. X. (1983), Micronuclei xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Xxxxxx xxx Xxxxxxxxxxx Xxxxxx During Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, in: Xxxxxxxxxxxx in Xxxxxxx xxx Xxxxxxxx of Xxxxxxxxxx, ed. X. X. Xxxxx, X. X. Xxxxxxx, T. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) MacGregor, X. X., Xxxxxx, X. A. Hite, X., Xxxxxxxx, G. X., Xxxxx, X., Xxxxxxxx, X. X., Xxxx, X. R., Xxxx, D. (1987), Xxxxxxxxxx for xxx Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx in Mammalian Xxxx Marrow Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, X. X., Wehr, X. X., Henika, X. X., Xxxxxx, X. X. (1990), The xx xxxx Erythrocyte Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Steady Xxxxx Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Xxxxxxx Xxxxxxxxxxx xxxx Xxxxxxxx Studies, Xxxxxx. Xxxx. Toxicol. 14, 513-522.

8) Xxxxxxx, X., Morita, X., Xxxxxx, X., Sofumi, X., Ishidate, X. Xx. (1990), Xxx Xxxxxxxxxxxx Assay xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Using Xxxxxxxx Xxxxxx-Xxxxxx Slides, Mutatation Xxx., 245, 245-249.

9) Xxx Collaborative Xxxxx Xxxxx xxx xxx Xxxxxxxxxxxx Test (1992). Xxxxxxxxxxxx Xxxx xxxx Xxxxx Xxxxxxxxxx Blood Xxxxxxxxxxxx xx Acridine Xxxxxx Xxxxxxxxxx Xxxxxxxx: Xxx Xxxxxxx Report xx the 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 Xxxxx xx xxx Environmental Xxxxxxx Xxxxxxx of Xxxxx) (1995), Protocol xxxxxxxxxxx xxx xxx xxxxx-xxxx mouse peripheral xxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Tice, X. X., XxxXxxxxx, X. X., Anderson, X., Xxxxxxx, D. X., Xxxxxx-Xxxxxxx, M., Xxxxxx, Jr. X. X., Xxxxxxxxxxxx, F., Xxxxxxx, X., Xxxxxxx, X., Sutou, S., Xxxxxxx, B. (1994), Xx vivo Rodent Xxxxxxxxxxx Xxxxxxxxxxxx Assay, Xxxxx. Xxx., 312, 293-304.

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

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

14) Hayashi, M., Xxxxxx, X., Xxxxxxxx, X. Jr. (1983), Xx Xxxxxxxxxxx of Xxxxxxxx Xxxxxx Fluorescent Xxxxxxxx xx xxx Xxxxxxxxxxxx Test, Mutation Xxx., 120, 241-247.

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

16) Xxxxxxx, X., Xxxxxxxxxx, X. D. (1989), Xxx xxxxxxxxx xxxx marrow xxxxxxxxxxxx xxxx, Xxxxxxxxxx Res., 213, 91-104.

17) Gollapudi, X., XxXxxxxx, X. X. (1995), Xxxxxx Xxxx for the Xxxxxxxxxx of Xxxxxxxxxxxxx xx Normochromatic Xxxxxxxxxxx Xxxxx in the Xxxx Xxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 347, 97-99.

18) Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X., Xxxxxxxx, X., Gatehouse, D. X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxxx Assay, xx: X. X. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx xxxxx, UKEMS Recommended Xxxxxxxxxx, UKEMS Sub-Committee xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, revised, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

19) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, G. X., Xxxxx, X., Xxxxxxxx X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. R. X. (1989), Xxxxxxxxxx Xxxxxxxx xx In xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx III, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."


XXXXXXX 4X

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

1. METODA

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

1.1 ÚVOD

Při xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxx závislé na xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Escherichia coli, x detekci xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx a xxxxxx xxxxxxx nebo xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxx v detekci xxxxxx, xxxxx revertují xxxxxx xxxxxxxx v xxxxxxxxxxx xxxxxxx a xxxxxxxx tak xxxxxxx xxxxxxxxx bakterií xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx jsou xxxxxxxxxx xxxx xxx xxxxxxxxxx xxxx v xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x podobné xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx x člověka x xxxxxxxx xxxxx důkazů x xxx, xx xxxxxx mutace x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx nádory mají xxxxx xx tvorbě xxxxxxxx u xxxxxxx x x pokusných xxxxxx. Zkouška xx xxxxxxxx xxxxxx x xxxxxxxxxx je rychlá, xxxxxxxxxx x xxxxxxxxx xxxxxx. Xxxxx xxxxxxxxxxx xxxxx xx řadu xxxxxxxxxx, díky nimž xxxx citlivější xx xxxxxxx mutací, xxxxxx xxxxxxxxxxxxx xxxxxxxx DNA xx reverzních místech, xxxxxxx permeability xxxxx xxx velké xxxxxxxx x eliminaci reparačních xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX xxxxxxxxxx x xxxxxx. Specifičnost xxxxxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxx x typech xxxxxx, xxx xxxx indukovány xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx x xxxxxxxxx xxxxx xxxxxxxx databáze xxxxxxxx xxx širokou xxxxx xxxxxxxx x xxxx xxxx xxxxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx těkavých sloučenin, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx xxxx xxxxxx x detekci xxxxxx x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (histidin resp. xxxxxxxxx), přičemž vzniká xxxx xxxxxxxxx na xxxxxxx xxxxxxx xxxxxxxxxxxxx.

Xxxxxxxx xxxxxxxxxx párů xxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx v xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx xxxxx tyto xxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxx xxxx xxxxx místě xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx xxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxx xxxx xxxx xxxx xxxx XXX a xxxxxxxx xxx čtecí xxxxx XXX.

1.3 VÝCHOZÍ ÚVAHY

Při xxxxxxxxx na xxxxxxxx xxxxxx x bakteriemi xx využívají xxxxxxxxxxxxx xxxxx, xxxxx xx xxxx xx buněk xxxxx xxxxxxx, xxxx xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx struktura x xxxxxxxxx xxxxxxx XXX. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx systémy xx xxxxx xxxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx u savců. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx informaci o xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx látky pro xxxxx.

Xxxxxxx na reverzní xxxxxx s bakteriemi xx zpravidla využívána xxx xxxxxxxxx vyšetření xxxxxxxxxxx xxxxxxxx, x xxxxxxx aktivity xxxxxxxxxxxx xxxxxx mutace. Z xxxxxxxx xxxxxxxx vyplývá, xx xxxxx chemických xxxxx, které jsou x xxxx zkoušce xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx x x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx mutagenních xxxxxxxx, xxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx. Příčiny xxxxxx skutečností xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x xxxxxxxxx x xxxxxxxxxxx xxxxxxxx nebo x xxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx xxxxxxx, xxxxx zvyšují citlivost xxxxxxx xx xxxxxxxx xxxxxx xx bakteriích, xxxxx vést k xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx xxxxxxxx mutace x bakteriemi xxxxxx xxx vhodná pro xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) a xxx xxxxxxxx látky, x nichž se xxxxxxxxxxx (xxxx o xxxxx se ví), xx specificky xxxxxxxx xx xxxxxxxxxxxx xxxxxxx xxxxx xxxxx (např. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x některé xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx být xxxxxxxxx zkoušky xxxxxxxxxx x xxxxx.

Xxxxxxxx mnoho xxxxxxxxx, xxx xxx xx xxxx xxxxxxx xxxxxxxxx, xx karcinogenní xxx savce, xxxx xxxxxxxx xxxxxxxxx. Závisí xx chemické třídě x xxxxxxxx xxxxx xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx, xxxxx působí xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx jsou xxxxxxxxx zkoušené xxxxx, x to xx xxxxxxxxxxx vnějšího metabolického xxxxxxxxxxx systému x xxx xxxx. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx suspenze xxxxxxxx x xxxxxxx agarem x xxxxx se xxxxxxx na xxxxxxxxx xxxx. X xxxxxxxxxxxx xxxxxx se zkoušená xxxx inkubuje a xxxx xx xxxx xxxxxxxxx na minimální xxxx smíchá s xxxxxxx agarem. Při xxxx xxxxxxxxxx xx xx dvou nebo xxxxx xxxxx inkubace xxxxxxxxx xxxxxxx revertantů x xxxxxxx se xxxxxxxx x počtem xxxxxxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

Xx xxxxxxx xxxxxxx postupů provedení xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx. Xxxx xxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), xxxxxxxxxxxx xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx xxxx (9, 10) x xxxxxxxxx xxxxxx (11). Xxxxxx pro xxxxxxxx xxxxx x par xxxx popsány (12).

Zde xxxxxxx postupy se xxxxxx hlavně xxxxxxxxxxxx xxxxxxxxx xxxxx a xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx je xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Některé xxxxx lze xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxx xxxxx xxxxx xx xxxxxxxxxx xxxx, do xxxxx xxxxx xxxx xxxxx xxxxxx alifatické xxxxxxxxxxx, dvojvazné xxxx, xxxxxxxx, xxxxxxxxxx x xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxxxx sloučeniny x nitrosloučeniny (3). Xxxxxx xx xxxxxxxxx, xx určité xxxxx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx je xxxxxxxxxx xxxxxxx test xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx xxx považovány xx "xxxxxxxx případy" x x xxxxxx xxxxxxx se důrazně xxxxxxxxxx xxxxxx alternativní xxxxxxx. Xx možné xxxxxxxxxxxxx xxxx "xxxxxxxx xxxxxxx" (společně x xxxxxxxx xxxxxxx jejich xxxxxxx): azobarviva x xxxxxxxxxx sloučeniny (3, 5, 6, 13), xxxxx x těkavé xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Odchylka xx xxxxxxxxxxxx xxxxxxx xxxx xxx xxxxxxx xxxxxxxxxx.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxxx xx xxxxxx xxxxxxxxxxxxx fáze xxxx do xxxxx xxxxxxxxxxx fáze xxxxx (xxxxxxxxx 109 xxxxx xx ml). Buňky x pozdní xxxxxxxxxxx xxxx by xxxxxx xxx xxxxxxx. Je xxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxxxxxxxxx bakterií. Xxxx xxxx být xxxxxxxx xxx xx xxxxxxx dosavadních xxxxxxxxxxx xxxxx o růstové xxxxxx, xxxx pro xxxxxx xxxxxxx stanovením xxxxx xxxxxxxxxxxxxxx xxxxx xx miskách.

Doporučená xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx xx xxx xxxxxxx alespoň xxx xxxxx xxxxxxxx. Xxxx xxxx xx xxxx xxx čtyři xxxxx X. typhimurium (XX1535; XX1537 nebo TA97a xxxx XX97; TA98 x XX100), jejichž xxxxxxx xx xxxxxxx x xxxxxxx xxxxxxxxxxxx xxxx spolehlivá x xxxxxxxxxxxxxxxx. Xxxx čtyři xxxxx X. xxxxxxxxxxx xxxx pár xxxx XX na primárním xxxxxxxxx xxxxx x xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Tyto xxxxx mohou být xxxxxxxxxx kmeny E. xxxx WP2 xxxx X. xxxxxxxxxxx TA102 (19), které xxxx xx xxxxxxxxx xxxxxxxxx xxxxx xxx xxxx XX. Doporučená xxxxxxxxx xxxxx je xxxx xxxx:

- X. typhimurium XX1535 x

- X. xxxxxxxxxxx XX1537 xxxx XX97x x

- X. xxxxxxxxxxx XX98 a

- X. xxxxxxxxxxx TA100 x

- X. xxxx XX2 uvrA, xxxx X. coli XX2 xxxX (xXX101), xxxx X. xxxxxxxxxxx TA102.

Pro xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx vláken XXX xxxx xxx xxxxxxxxx xxxxxxx TA102 xxxx xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx reparace XXX, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx by xxx použity xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, verifikace xxxxxxx x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx pro xxxx xx xxxx být xxxxxxxxx xxx každou xxxxxxxxx kmenovou kulturu (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx a xxxxxxxxx pro E. xxxx). Xxxxxxx by xxxx xxx kontrolovány xxxx xxxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxxxx podle xxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (tj. xxxxxxxxxxxx xxxxxxxxxx u xxxxx XX98, XX100 x TA97a nebo XX97, XX2 uvrA x XX2 uvrA (xXX101) x xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx charakteristických xxxxxx (xx. rfa xxxxxx x S. typhimurium xxxxxxxxxx na krystalovou xxxxxx x uvrA xxxxxx u X. xxxx nebo xxxX xxxxxx x S. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx světlo) (2, 3). Xxxxx xx xxxx xxxxxx dávat xxxxx kolonií spontánních xxxxxxxxxx xx xxxxx x xxxxxxx četností xxxxxxxxxxx na základě xxxxxxxxxxx xxxxx laboratorních xxxxxxx x nejlépe x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx vhodný minimální xxxx (xxxx. obsahující xxxxxxxxx půdu E (Xxxxx-Xxxxxx) x xxxxxxx) x xxxxxx agar xxxxxxxxxx xxxxxxxx x xxxxxx xxxx tryptofan xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Metabolická xxxxxxxx

Xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx xxxx. Nejčastěji používaným xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (1, 2) xxxx fenobarbitonu x β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx xxxxxx xx obvykle používána x xxxxxxxxxxxxx x xxxxxxx 5 xx 30 % obj. xx xxxxx X9. Xxxxx a xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxx. V některých xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. X xxxxxxxxx x diazoniových xxxxxxxxx může být xxxxxxxxx použití xxxxxxxxxx xxxxxxxxxxxxx aktivačního systému (6, 13).

1.5.1.4 Xxxxxxxx xxxxx nebo xxxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx systémům x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx mimo xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx by být xxxxxxxxxx s xxxxxxxx xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by být xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx ve xxxx xx měla xxx použita xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Xxxxxxxx xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx kritéria, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxx směsi xxx xxxxxxxx.

Xxxx xxx užitečné xxxxxxxx toxicitu x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx snížením xxxxx xxxxxxx xxxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Cytotoxicita xxxxx xx xxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx by xxxx xxx posouzena xx xxxxxxx viditelného srážení x xxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx zkušební xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx xx 5 xx/xxxxx xxxx 5 μx/xxxxx. U xxxxxxxxxxxxxxx látek nerozpustných xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx xx měla xxx jedna nebo xxxx xxxxxxxxxx koncentrací xxxxxxxx, xxx xxxxx xxxx x xxxxxxx xxxxx pro xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky, xxxxx xxxx cytotoxické xxx xxx xxxxxxxxxxxxx xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx xxxxxxxx xx xx cytotoxické koncentrace. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx různých xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx xxxx zkušebními xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx jsou vhodné x xxxxxxx, kdy xx xxxxxxxxx xxxxxx xxxxxxxxxx odpovědi xx xxxxxxxxxxx. Zkoušení xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx xxx xxxxxxx při xxxxxxxxx xxxxx obsahujících xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx xxxxxxxx

Xxxxxxxx každého xxxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx a xxx xx. Xxx xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx koncentrace xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x použitím xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx by xxxx xxx látka (xxxxx) pro xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxx) xx základě xxxx xxxxxxxxx kmene xxxxxxxx.

Xxxxxxxxx xxxxxx pozitivní kontroly x xxxxxxx x xxxxxxxxxxxx xxxxxxxx xxxx xxxx látky:

Látka

Číslo XXX

Xxxxx xxxxx XXXXXX

9,10-xxxxxxxxxxxxxxxxx

781–43–1

212–308–4

7,12-xxxxxxxxxxxxx[x]xxxxxxxxx

57–97–6

200–359–5

xxxxx[x]xxxxx

50–32–8

200–028–5

2-xxxxxxxxxxxxxx

613–13–8

210–330–9

Xxxxxxxxxxxxx

50–18–0

200–015–4

xxxxxxxxxxxxx xxxxxxxxxx

6055–19–2

Xxxx xxxxx je vhodnou xxxxxxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx metabolické xxxxxxxx:

Xxxxx

Xxxxx CAS

Číslo xxxxx XXXXXX

XX Xxxxxx Xxx 28

573–58–0

209–358–4

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

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

Xxxxx

Xxxxx XXX

Xxxxx xxxxx EINECS

Kmen

azid xxxxx

26628–22–8

247–852–1

XX1535 x XX100

2-xxxxxxxxxxxx

607–57–8

210–138–5

XX98

9-xxxxxxxxxxxx

90–45–9

201–995–6

XX1537, TA97 x XX97x

XXX 191

17070–45–0

241–129–4

TA1537, XX97 a TA97a

Kumenhydroperoxid

80–15–9

201–254–7

TA102

mitomycin X

50–07–7

200–008–6

XX2xxxX a XX102

1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx

70–25–7

200–730–1

XX2, XX2 xxxX x XX2 xxxX (pKM101)

4-nitrochinolin-1-oxid

56–57–5

200–281–1

WP2, XX2 uvrA a 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 xxxx xxxxxx xxxxxxxxxx xxxxx. Xxx pozitivní xxxxxxxx xx xxxx xxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx látek xx stejné xxxxxxxx xxxxx, xxxx li x xxxxxxxxx.

Xxxx xx xxx použity xxxxxxxxx xxxxxxxx skládající xx xx xxxxxxxxx rozpouštědla xxxx vehikula, bez xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Xxxxx xxxx xx xxxx xxx neexponované xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx účinky.

1.5.3 Xxxxxx

X standardní xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx aktivace xx xxxxxxx xxxxxx 0,05 xx nebo 0,1 xx xxxxxxxxxx xxxxxxx, 0,1 xx čerstvé xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) a 0,5 xx xxxxxxxxxx pufru x 2,0 xx xxxxxxxx xxxxx. X xxxxxxx zkoušky s xxxxxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x rozmezí 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx xxxxx) s xxxxxxx xxxxxx (2,0 xx) x zároveň x xxxxxxxxxx a xxxxxxxxx xxxxxx xxxx xxxxxxxxx roztokem. Xxxxx xxxxx xxxxxxxx xx xxxxxxxx x přelije xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx vrchní xxxx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) xx zkoušená xxxxx xxxx xxxxxxxx xxxxxx před xxxxxxxxx x xxxxxxx xxxxxx x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx xxxxx obvykle 20 xxxxx nebo xxxx xxxxxxxxxxx x xxxxxxxxxx kmenem (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a xxxxxxxxx xxxxxx xxxx xxxxxxxxxxxx xxxxxxxxxx systémem (0,5 xx) xxx 30 — 37 °C. Xxxxxxx se xxxxxx 0,05 xxxx 0,1 xx zkoušené xxxxx xxxx xxxxxxxxxx xxxxxxx, 0,1 xx xxxxxxxx x 0,5 xx xxxxx X9 xxxx xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx xxxxx. Xxxxxxxx by xxxx xxx během xxxxxxxx xxxxxxxxxxxxxx na xxxxxxxx.

X dostatečnému odhadu xxxxxxxx xx xxxx xxx xxx xxxxx xxxxxx xxxxx použity 3 misky. Xxxxxxx xxxx xxxxx xx xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Xxxxxxxx ztráta xxxxx nemusí znamenat xxxxxxxxxxxx xxxxxxx.

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

1.5.4 Xxxxxxxx

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

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxx xxxxx by xxxx xxx počty xxxxxxx xxxxxxxxxx připadající xx xxxxx. Měl xx xxx xxxxxx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx xx miskách x xxxxxxxxx xxxxxxxxx (xxxxxxxx rozpouštědla x xxxxxxxx xxxxxxxxxxxx xxxxxxxx), xxx xx miskách x pozitivní kontrolou. Xxxxx xx xxxxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx misku a xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (neexponovanou xxxxxxxx x/xxxx kontrolu xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx nepožaduje. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxxx se xxxxxxxxx xxxxxxxxxxx xxxxxxxx nepovažuje xx xxxxxxxx, mělo xx xxx xxxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx by měla xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx zpracování (xxxxxxxxxx misková xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx médiu) x xxxxxxxx metabolické aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx xxxxxx x xxxxxxx jednoho xxxxx x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx nebo xxx xxxx, x xx x závislosti na xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx xxx xxxxx nebo xxxx xxxxxxxxxxx (23). Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx významnost by xxxxxx být xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx znamenají, že xxxxxxxx látka xxxxxxxx x genomu kmenů Xxxxxxxxxx typhimurium x/xxxx Xxxxxxxxxxx xxxx xxxxxx xxxxxx substitucí xxxx xxxx xxxxxxx xxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx není xx xxxxxxxx xxxxxxx xxx xxxxxxxxx druhy xxxxxxxxx.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x zkoušce musí xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Xxxxx:

- xxxxxxx xxxxx,

- xxxxx xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxx zkoušené xxxxx xx misku (mg/misku xxxx μx/xxxxx) x xxxxxxxxxxx xxxxxx xxxxx x počtu misek xx xxxxxxxxxxx,

- xxxxxxx xxxxx,

- typ x xxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, včetně xxxxxxxx xxxxxxxxxxxxx,

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- xxxxx xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxx, X. N., McCann, X., Yamasaki E. (1975), Xxxxxxx of Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx., 31, 347-364.

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

3) Xxxxxxxxx, X., Xxxxxxx, X., Xxxxxx, X., Gocke, X., Xxxx, L., Xxxxxxxxxx, X., Xxxxxxx, X., Xxxxx, T., Xxxxxx, X., Xxxxxx, X. (1994), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx Xxxxxxxxx Mutation Xxxxxx, Xxxxxxxxxx Xxx., 312, 217-233.

4) Kier, X. X., Xxxxxxx X. X., Xxxxxxx, A. X., Xxx Xxxxx, X. X., Brown, X. M., Xxxxxx, X. F., Dunkel, X., XxXxxx, J., Xxxxxxxxxx, X., Prival, X., Rao, T. X., Xxx X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxxx Assay: X Report xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, T., Xxxxxx, X., Xxxxx, X. X., Xxxxxxxxxx, T., Xxxxx, X., Sugimura, X., Hashimoto, X. (1975), Mutagenicity xx Xxxxxxxxxx Xxx Xxxx xxx their Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Matsushima, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1980), Xxxxxxx Xxxxxxxxxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxx, in: Xxxxx-xxxx Xxxx Systems for Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx X. H., Xxxxxx, X. X., Xxxxxxxx, Berlin-Heidelberg-New York, 273-285.

7) Xxxxxxxxx, X. X., Xxxxxxx, I. X., Wilcox, P., Xxxxxxxxx, R. D., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Xxxxx Mutagenicity Xxxxx: UKEMS Xxxx 1 Revised, ed. X. X. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, 13-61.

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

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

10) Xxxxxxx, X. A., Green, X. X. X., Xxxxxxxxx, X., Xxxxxxx, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Legator, X., Xxxxxxx, X., Xxxxx, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, X. D., Xxxxxxx, X. X. (1981), Xx Examination xx xxx Quantitative Xxxxxxxxxx Xxxxx for Xxxxxxxxxxx xxxx Strains xx Xxxxxxxxxx typhimurium, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Araki, A., Xxxxxxx, X., Kato, X., Matsushima, T. (1994), Xxxxxxxx Method xxx Mutagenicity Xxxxxxx xx Xxxxxxx Xxxxxxxxx xx Using a Xxx Xxxxxxxx Bag, Xxxxxxxxxx Xxx., 307, 335-344.

13) Xxxxxx, X. X., Bell, X. X., Xxxxxxxx, X. X., Reipert, X. X., Xxxxxxx, X. X. (1984), Xxxxxxxxxxxx xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Dyes xx a Modified Xxxxxxxxxx Assay, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X., Xxxxxx, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx from xxx Testing of 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

15) Xxxxxx, V., Xxxxxxxx, X., Xxxxxxx, X. X. (1977), Xxxxxxxxx Activity of Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxx Water, xx Xxxxxxxx xx Xxxxxxx Xxxxxxxxxx, X. Xxxxx, X. Xxxxxxx, X. Xxxxxx (xxx.) Elsevier, Xxxxxxxxx, 249-258.

16) Xxxxxx, X. X., Xxxxxxx, X. M., Xxxxxxxx, X. G., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Technique xx Xxxxxxx Xxxxxxxxx Activity xx Volatile Xxxxxxx Xxxxxxxxx xx the Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Xxxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx the Xxxxxxxxx Xxxxxxxxx Carcinogen Xxxxxxx xxx Synthetic Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxx Xxx., 39, 3780-3782.

18) Xxxxxx, X., Gold, X., Xxxxx-Xxxxx, X., Xxxx, B. X. (1980), Xxxxxxxx: X Xxxxx for Xxxxxxxxxx xx Xxxxxxx Xxxxxxxxxx xx Mutagens by Xxxxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. X, 77, 4961-4965.

19) Wilcox, X., Xxxxxx, X., Xxxx, X. J., Xxxxxxxxx, D. X. (1990), Comparison xx Xxxxxxxxxx xxxxxxxxxxx XX 102 with Xxxxxxxxxxx xxxx XX2 Xxxxxx xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Matsushima, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, T. (1976), A Safe Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. x. xx Xxxxxxx or Xxxxxxxxx Xxxxxxxxxx Systems, xx: In vitro Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxxxxx Xxxxxxx, eds. X. J. xx Xxxxxx xx xx. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Elliot, B. X., Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxxx, D. X., Xxxxxx, G. X., Mackay, X. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Aroclor 1254-xxxxxxx X9 xx in xxxxx Genotoxicity Assays, Xxxxxxxxxxx, 7, 175-177.

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

23) Claxton, X. X., Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxx, X., Zeiger, X. (1987), Guide xxx xxx Xxxxxxxxxx typhimurium/Mammalian Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Mutatation Xxx., 189, 83-91.

24) Xxxxx, X. X. X., Green, M. X. X., Xxxxxxxxx, X., Xxxxxxx, I., Xxxxxxxx, X. D., Xxxxxx, D. J. (1989), Xxxxxxxx xx Xxxx xxxx Xxxxxxxxx Xxxxxx Assays, xx: XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Mutagenicity Xxxxxxx, Part XX. Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Xxxx Xxxx, xx. Kirkland, D. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."


PŘÍLOHA 4E

"B.17 XXXXXXXXXX — XXXXXXX NA XXXXXX XXXXXX X XXXXXXX XXXXX XX XXXXX

1. XXXXXX

Xxxx metoda xx replikou xxxxxx XXXX XX 476 — Zkouška xx xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx (1997).

1.1 ÚVOD

Zkoušku xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxx xxxxxx xxx xxxxxxx xxxxxxxx xxxxxx indukovaných xxxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxx xxxxxxx X5178X myší, xxxxxxx xxxxx XXX, XXX-XX52 x X79 křečka xxxxxxxx x xxxxxxxxxxxxxxx xxxxx XX6 xxxxxxx (1). X těchto xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx genetických xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x transgen xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Zkoušky na xxxxxx XX, XXXX x XPRT detekují xxxxx spektrum genetických xxxxxxxx. Xxxxxxxxxxx xxxxxx XX a XPRT xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx xxxxxx), xxxxx xxxxx xxxxxxxxx v XXXX lokusu na X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx zkoušce xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx lze xxxxxx xxxxxxx zavedených xxxxx xxxxx nebo buněčné xxxxx. Xxxxx se xxxxxxxx podle schopnosti xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx obecně xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx aktivace. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx nemůže xxxxx xxxxxxxxx xxxxxxxx xx xxxx u savců. Xx xxxxx se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x pozitivním xxxxxxxxx, xxx neodrážejí xxxxxxx xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx, xxxx xxxxx xxxxxx pH, xxxxxxxxxx nebo vysokých xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx něž xx xxxx xxxxxxx pozitivní, xxxx xxxxxxxxxxx xxxxx; xxxx touto xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx na xxxxxxxx třídě a xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx mechanismy, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Xxx také xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

Xxxxx mutace : xxxxxx xxxxxx xxxxxxxxx typu mutované xxxxx, která xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxxxxxx aktivity xxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx : látky, xxxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxx více xxxx bází x XXX.

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx xxxxxxxxx xxxxx nebo deleci xxxxxxx xxxx xxxx xxxx xxxx v xxxxxxxx DNA.

Doba xxxxxxx xxxxxxxx : xxxx, xxxxx níž vymizí x xxxx xxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx.

Xxxxxxx xxxxxxx : xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx dělený xxxxxx xxxxxxxxxxxxxxx buněk.

Relativní xxxxxxx xxxx : xxxxxx xxxxx xxxxx x xxxx xx srovnání x xxxxxxxxx populací xxxxx; vypočte se xxxx xxxxxx xxxxxx xxxxxxxxx xxxxx v xxxxxxxx x x xxxxxxxxx xxxxxxxx x xxxxxxxxx účinnosti klonování xxxxxxxx k xxxxxxxxx xxxxxxxx.

Xxxxxxxxx růst x xxxxxxxx : nárůst xxxxx xxxxx x xxxxxxx exprese xxxxxxxx x negativní xxxxxxxx.

Xxxxxxxxxxxxxxx : xxxxxxxx klonování xxxxx x xxxxxxxx xxxxxxxx na xxxxx xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) jsou xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (TFT). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx na TFT, xxx xxxxxxxxx inhibici xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxx xxxx schopny xxxxxxxxxxx xx xxxxxxxxxxx XXX, xxxxxxx xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx schopnost xxxxxx. Xxxxxxx lze x xxxxx s xxxxxxxxxxxx XXXX xxxx XXXX xxxxxxx selekci xxxxxxxxxxxxxxx xxxxxxxxxx x 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx látky xx xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx je xx xxxxxxx xx xxxxxx xxxxxx v xxxxxxx xxxxx zkoušen xxxxxx báze xxxx xxxxxxxxxx xxxxxxx selekčnímu xxxxxxx. Mělo xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx na xxxxxxxxxx toxicitu xxxxxxxx xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx zkoušení chemických xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, xxxx xxxx být xxxxxxxxx xxxxxxxx systému xxxx xxxxxxx pro selekci (8).

Xxxxx x suspenzní xxxx jednovrstevné kultuře xxxx vhodnou dobu xxxxxxxxx xxxxxxxx xxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, x xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx obvykle xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx kultury xx xxxxxxx x xxxxxxxx xxxxx xx xxxxxxx xxxx xxxxxxxxxxxxxxxxx xxx xxxxx zvolený xxxxx x xxx buněk, xxx nastala přibližně xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxx mutací. Xxxxxxx xxxxxxx se stanoví xxx, xx xx xxxxxx známý xxxxx xxxxx xx média xxxxxxxxxxxx selekční xxxxxxx xxx xxxxxxx xxxxxxxxxx xxxxx x xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Xx xxxxxx xxxxxxxxx xxxx se xxxxxxxxx kolonie. Četnost xxxxxxx xx vypočte x počtu xxxxxxxxxx xxxxxxx x xxxxxxxxx xxxxx a xxxxx xxxxxxx v xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro použití x této xxxxxxx xxxx x dispozici xxxxx xxxx xxxxx, xxxxxx xxxxxxxx buněk X5171X, CHO, CHO-AS52, X79 xxxx TK6. Xxxx buněk v xxxx xxxxxxx xx xxxx xxxxxxxxx citlivost x xxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x stabilní xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx být xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx mykoplasmaty, x x případě xxxxxxxxxxx xx xxxxxx xxx xxxxxxx.

Xxxxxxx by měly xxx navrženy xxx, xxx měly xxxxxx xxxxxxxxxx xxxxxxxxx x xxxx. Xxxxx použitých xxxxx, kultur x xxxxxxxxxxx zkoušené xxxxx xx měl xxxx xxxxxxxxxx parametry xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, xxxxx xxxxxxx xxxxxxxx x xxxxx xxxxx xxxxxxx x xxxxxx stadiu xxxxxxx, xx xxx xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx je, xxx xxx použit xxxxx xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však doporučeno, xxx xxxx použito xxxxxxx 106 buněk. Xxxx xx xxx x xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx buněčném systému, xxx xxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx hodnota xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx by měla xxx xxxxxxx vhodná xxxxxxxxxx xxxxx x xxxxxxxxx podmínky (xxxxxxxxxx xxxxxx, koncentrace CO2, xxxxxxx a xxxxxxx). Xxxxx by měla xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx x xxxx xxxxx použitých xxx zkoušce. Xx xxxxxxx důležité, aby xxxxxxxxxx xxxxxxxx xxxx xxxxxxx xxx, xxx xxxx zajištěny xxxxxxxxx xxxx xxxxx xxxxx xxxxxx xxxxxxx a xxxxxxxxx xxx xxxxxxxxxx, xxx nemutovaných buněk xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx xx xxxx xxx získávány z xxxxxxxxx xxxxxx, xxxxxxxx xx kultivačního média x inkubovány xxx 37 °X. Před xxxxxxxx v xxxx xxxxxxx xxxx být xxxxxxxx xxxxxxxxx x xxxxxxx xxx přítomné xxxxxxxx buňky.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx xxxx xxx vystaveny xxxxxxxx xxxxx, x to x vhodným systémem xxxxxxxxxxx xxxxxxxx x xxx xxxx. Nejčastěji xxxxxxxxxx systémem xx xxxxxxxxxx dotovaná postmitochondriální xxxxxx (X9) připravená x jater hlodavců xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, jako xx Xxxxxxx 1254 (15, 16, 17 x 18), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (19, 20).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x konečném xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % obj. Volba x xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na xxxxx xxxxxxxx xxxxx, která xx xxxxxxxx. V xxxxxxxxx případech xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx geneticky xxxxxxxxxxxxxx xxxxxxxxx linií xxxxxxxxxxxxx xxxxxxxxxx aktivační enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx aktivaci. Xxxxx xxxxxxxxx buněčných xxxxx xx měla xxx xxxxxxx zdůvodněna (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 pro metabolismus xxxxxxxx látky).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx před xxxxxxxx xxxxxxx. Měly xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, že xxxxxxx se xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x x aktivitou X9. Xxxx-xx xxxxxxx xxxx než známá xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx jejich zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul. Xxx xxxxxxxx xxxxx xxxxxxxxx xx vodě xx xxxx xxx použitá xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx xxxxxxxxx nejvyšší xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, rozpustnost x testovacím systému x xxxxx xX xxxx osmolality.

Cytotoxicita xx xxxx xxx stanovena x metabolickou xxxxxxxx x xxx ní x xxxxxxx xxxxxxxxxxx xx xxxxxxx vhodných xxxxxxxxxx buněčné xxxxxxxxx x růstu, jako xxxx relativní xxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. Xxxx být výhodné xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx v předběžném xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x minimální xxxxxxxxx, případně xxxxxx xxxxxxxxx, což xxxx xxxxxxx xxxxxxxx, že xx xx xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. Xx-xx maximální xxxxxxxxxxx xxxxxxxx od cytotoxicity, xxxx xx xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx nejméně 10 %) xxxxxxx (relativní xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. X xxxxxxx relativně xxxxxxxxxxxxxxx xxxxx xx xxxx být xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 xx/xx xxxx 0,01 M, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx látky xx xxxx xxx xxxxxxxx až k xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx podmínek, xxxx xx xx xxxx xxx. Xxxx by xxx xxxxxxxxx případná xxxxxxxxxxxxx x xxxxxxxx xxxxx, ve xxxxxxx xxxx xxxxx xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx aplikace, xxxxx xxxxxxxxxxx xx xxxx x průběhu xxxxxxxx x testovacím xxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx zjistit xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx být xxxxxxxxx a negativní (xxxxxxxxxxxx xxxx vehikulum) xxxxxxxx xxx x xxxxxxxxxxxx aktivací, tak xxx ní. Xxx xxxxxxx xxxxxxxxxxx aktivace xx xxxx xxx xxxxxxxxx kontrolou xxxxxxxx xxxxx, která x xxxxxxxxx odpovědi xxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxx 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 x xxxxx xxxxxxx)

xxxxxx-xxxxxxxxxxxxxx

66–27–3

200–625–0

XXXX

xxxxx-xxxxxxxxxxxxxx

62–50–0

200–536–7

1-xxxxx-1-xxxxxxxxxxxxxxx

759–73–9

212–072–2

X xxxxxx metabolickou xxxxxxxx

XXXX

3-xxxxxxxxxxxxxxxxx

56–49–5

200–276–4

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–549–8

7,12-xxxxxxxxxxxxxxxxxxxxxx

57–97–6

200–359–5

XX (malé a xxxxx kolonie)

cyklofosfamid

50–18–0

200–015–4

cyklofosfamid monohydrát

6055–19–2

benzo[a]pyren

50–32–8

200–028–5

3-methylcholanthren

56–49–5

200–276–5

XPRT

N-nitrosodimethylamin (xxx xxxxxx xxxxxx X9)

62–75–9

200–549–8

xxxxx[x]xxxxx

50–32–8

200–028–5

Xxxxx xxx xxxxxxx xxxx xxxx referenční xxxxx pro xxxxxxxxx xxxxxxxx, xxxx. má-li xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx x 5-brom-2′-deoxyuridinu (XXX 59–14–3, EINECS 200–415–9), xxxx xxx xxxx xxxxxxxxxx xxxxx xxxxxx xxxxxxx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx látek pokud xxxxx ze xxxxxx xxxxxxxx třídy.

Měly xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx vehikulum x xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx jako xxxxxxxxxx xxxxxxx. Kromě toho xx měly být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx nebo xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Expozice xxxxxxxx xxxxx

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

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx exponovaná xxxxxxx. Xx-xx použita xxxxx kultura, měl xx být počet xxxxxxxxxxx zvýšen xxx, xxx xxx xxxxxxxx xxxxxxxxxxxx počet xxxxxx xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Měly by xxx použity duplicitní xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

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

1.4.3.2 Stanovení přežití, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx xxxxx xxxxxxxxx xxxx xx buňky xxxxxxx a xxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxx a xx xxxxxx umožnění xxxxxxx xxxxxxxx xxxxxxx. Xx xxxxxxxxxx cytotoxicity xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxxxx celkového xxxxx xxxxxx xx xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx xxxxx má xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, aby xxxxxxx xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx nově indukovaných xxxxxxx (HPRT x XXXX xxxxxxxx xxxxxxx 6 až 8 xxx, XX xxxxxxx xxx dny). Xxxxx xxxx xxxxxxxxxxx v xxxxx se xxxxxxxxx xxxxxxxx (xxxxxxxxxx činidly) x xxx xxxx (xxx nich) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx a xxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx četnosti xxxxxxx) xx započne xx xxxxx doby exprese xxxxxxxxx xx xxxxx xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx látka xxxxxxxxx xx xxxxxxx X5178X XX+/-, xxxx xx xxx provedeno alespoň xx jedné xx xxxxxxxxxx kultur (x xxxxxxxx xxxxxxxxx xxxxxxxxxxx) x xx negativních x pozitivních kontrolách xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií. Je-li xxxxxxxx látka xx xxxxxxx L5178Y TK+/- xxxxxxxxx, xxxx by xxx xxxxxxxxx kultury xxxxx xxxxxxxxx kolonií xxxxxxxxx xx xxxxxxxxxxx x pozitivních kontrolách. Xxx studiích xx xxxxxxx XX6 TK+/- xxxx být také xxxxxxxxx rozdělení kultury xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx xxxx xxxxxxxxx xxxxxxxxx cytotoxicity a xxxxxxxxxxxxxxxx, počtu xxxxxxx x xxxxxxxx xxxxxxx xxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx odpovědi xx zkoušku X5178X XX+/- se kolonie xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx zkoušené xxxxx (nejvyšší pozitivní xxxxxxxxxxx) x x xxxxxxxxx x xxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxx kolonie — xxxxx kolonie. Xxxxxxxxxxx x cytogenetická xxxxxx xxx xxxxxxx xxxxxxxxx velké kolonie, xxx xxxxxxx xxxxxxxxx xxxx kolonie xxxx xxxxxxxx xxxxxxxx (23, 24). Xx zkoušce XX+/- xxxx xxxxxxx xxxxxxxxxxx za xxxxxxx xxxxxxxx kolonie s xxxxxxxxx růstem (xxxxx) x xxxxxxx s xxxxxxx růstem (malá) (25). U xxxxxxxxxx xxxxx, které xxxxxxx xxxxxxxxxxxxxx genetické xxxxxxxxx, xx xxxxxxxxxxx xxxx xxxxxxxx, x tvoří xxxx malé xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx ztrát xxxxxx xxxx xx xx karyotypické xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xx xxxxxxx x xxxxxxxxxx xxxxxxx, xxxxx indukují xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx postižené xxxxx mutantů xxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxx xxxxx x xxxxx velké xxxxxxx.

Xxxx xx xxx udáno xxxxxxx (xxxxxxxxx účinnost xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx růst. Xxxxxxx xxxxxxx by měla xxx vyjádřena jako xxxxx xxxxxxx k xxxxx xxxxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxx. Xxxx xx xxxx xxx všechny xxxxx xxxxxxx xx xxxxx tabulky.

Ověření xxxxx xxxxxxxxx odpovědi se xxxxxxxxxx. Xxxxxxxxxx výsledky xx xxxx být xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx xxx xxxxxxxxx případ od xxxxxxx. Tam, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx považováno za xxxxx, je xxxxx xxxxx zdůvodnění. Xxxxx xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx být zvážena x xxxxxxxxxx experimentech xxx pro xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx xxxxxxxx. X xxxxxxxxxx studie, které xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx a xxxxxxxx xxxxxxxxxxx aktivace.

2.2 HODNOCENÍ X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. nárůst xxxxxxxx xxxxxxx v xxxxxxxxxx xx koncentraci, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Nejdříve by xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx mohou xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx experiment opakován.

Pozitivní xxxxxxxx zkoušky na xxxxxx xxxxxx x xxxxxxx xxxxx in xxxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x xxxxxxxxx kultivovaných xxxxxxx xxxxx xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx na xxxxxxxxxxx xx xxxxx xxxxxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx xxxxxx mutace.

3. XXXXXX

XXXXXXXX O XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Buňky:

- xxx x zdroj xxxxx,

- xxxxx buněčných xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx kultury,

- xxxxxxxxxxxx mykoplasmat.

Zkušební podmínky:

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

- složení xxxxx, xxxxxxxx xxxxxxxxxxx XX2,

- koncentrace zkoušené xxxxx,

- objem xxxxxxxx x xxxxxxx zkoušené xxxxx,

- inkubační xxxxxxx,

- xxxxxxxxx doba,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxxxx xxxxxxxx,

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

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxx xxxx exprese (případně xxxxxx počtu xxxxxxxxxx xxxxx, xxxxxxxxx x xxxxxx média),

- xxxxxxxx xxxxxxx,

- xxxxxxxx klasifikace xxxxxxx na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx použité x xxxxxxxx životaschopných a xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- známky toxicity,

- xxxxxx xxxxxxx,

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

- xxxxxxxx xxxxxxx, byla-li vyšetřována, xxxxxxx pro negativní x xxxxxxxxx xxxxxxxx,

- xxxxxxxxx předpoklady xxxxxxxxxx xxxxxxxxx mutanty xxxxxxx xxxx kolonie xxxxxxxx X5178X TK+/-,

- podle xxxxxxxx závislost odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

- dosavadní údaje x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., XxXxxxxx, X. M., DeSerres, X. X., Xxxxxx, X. X. (eds.) (1987), Banbury Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Xxxx Spring Xxxxxx Laboratory, New Xxxx.

2) Xxx, X. X. X., Xxxxxxx X. X. (1968), Xxxxxxxxx Cell Xxxxxxxx. XX. Chemical Induction xx Xxxxxxxx Locus Xxxxxxxxx xx Chinese Xxxxxxx Xxxxx Xx xxxxx, Xxxx. Natl. Xxxx. Xxx. U. X. A, 61, 1306-1312.

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

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

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

6) Xxxxx, C. X., Xxxxxxxxxx, X., Xxxxx, X. X., Xxxxx, X., Xxxxx, Y., Xxxxxxxxxx, Xx. X. X., Xxxxxx, J., Xxxxxxxx, E. (1994), Xxxxxxxxx Cell Gene Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Xxxxxx. Xxxxxx xx the Xxxxxxxxxxxxx Xxxxxxxx xx Standardisation xx Genotoxicity Test Xxxxxxxxxx. Xxxxxxxx Res. 312, 235-239.

7) Xxxxx, X., Galloway, X. X., Xxxxxxxx, X. X., Ishidate, X., Xxxxxxx, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Culture Xxxxxxxxxx. X xxxxxx xxxx ICPEMC Task Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

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

9) Li, X. X., Gupta, X. X., Xxxxxxx, R. X., Xxxxxx, X. X. (1988), X Xxxxxx xxx Xxxxxxxx xx xxx Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Guanine Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Determine the Xxxxxxxxxxxx xx Chemical Xxxxxx: X Xxxxxx xx Xxxxx III xx the U. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Res., 196, 17-36.

10) Li, X. X., Xxxxxx, X. X., Choy, X. X., Xxxx, X. X., Xxxxx, R. X., Xxxxxxx, K. X., X'Νxxxx, J. X., Xxxxxx, X. X., Stankowski, X. X. Jr., Xxxx, X. X. (1987), X Xxxxx xxx xxx Performance xx xxx Xxxxxxx Xxxxxxx Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxx Mutation Xxxxx, Mutatation Xxx., 189, 135-141.

11) Liber, X. X., Yandell, X. X., Little, X. B. (1989), X Xxxxxxxxxx xx Xxxxxxxx Induction at xxx XX xxx XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx xxx Xxx xx xx Xxxxxxxxxx Class xx Xxxxxxxxx xx the Xxxxxxxxx TK Locus, Xxxxxxxxxx Xxx., 216, 9-17.

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

13) Xxxxxx, X. X., Xxxxxx, A. X., Xxxxx, X. (1984), Xxxxxxxxx xxx xxx X5178X/XX+/--XX+/- Xxxxx Xxxxxxxx Xxxx Mutagenicity Xxxxx, xx: Xxxxxx, B. X. xx xx (xxx.) Xxxxxxxx of Xxxxxxxxxxxx Xxxx Procedures, Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Xxx Xxxx, 239-268.

14) Xxxxxx, X. X., Xxxxx, D. M., Xxxxxx, X. X., Xxxxx, X. X. X., Cole, J., XxXxxxxx, X. X., Xxxxxxx X. C. (1989), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Assays Xxxxx upon Xxxxxx Xxxxxxxxx, in: Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Data, Kirkland, X. X., ed., Xxxxxxxxx University Xxxxx, 66-101.

15) Xxxxxxxxxxxx, A., Xxxxxxx, S., Corti, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Induction xx 6-Xxxxxxxxxxx-Xxxxxxxxx Mutants xx V79 Chinese Xxxxxxx Xxxxx xx Xxxxx-Xxxxx Xxxxxxxxx-Xxxxxxxxx Dimethylnitrosamine, Xxxxxxxxxx Xxx. 46, 365-373.

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

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

18) Maron, X. X., Xxxx, B. X. (1983), Xxxxxxx Xxxxxxx for the Xxxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Xxx. 113, 173-215.

19) Xxxxxxx, X. X., Xxxxxx, X. X., Xxxxxxx, X. X., Gatehouse, D. X., Gibson, X. X., Xxxxxx, J. X., Xxxx, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Xxxxxxx X9 xx: Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, K., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Polycholrinated Biphenyls x. x. xx Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, V: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xx Xxxxxx, X. X., Xxxxx, X. X., Xxxx, X. R., Xxxxxxx, X. X. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, D. F., Xxxxxx, X. X., XxXxxxx, K. X. (1982), XXX/XXXXX Mutation Xxxxx: Evaluation of Xxxxx and Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. L., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, P. O., Xxxxxx, X. X., Xx, X. X., Xxxxxx, X. X. (1983), Evaluation xx xx Xxxxxxxx Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Highly Xxxxxxxx Mutagens xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxx. Xxxxxxxxxxx, 5, 795-801.

23) Xxxxxxxxx, X. X., Moore, X. M., Broder, X. X., Burrell, X., Xxxxxx, J. X. (1990), Xxxxxxxxx Xxxxxxxxxx of Xxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Xxxxx xx Mouse Xxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Sci. U. X. X, 87, 51-55.

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

25) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxx Xxxxxxxx xx Recessive Xxxxxxxxx xx a Xxxxxxxxxxxx Xxxxxxxxx Xxxxx in Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

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


XXXXXXX 4X

"X.23 ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx na chromozomové xxxxxxx ve xxxxxxxxxxxxxxx xxxxx xx vivo xx xxxxxxxxxxxxx xxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx chromozomové aberace xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Xxxxxxxxx xx dva typy xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx chemických xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x tomuto účelu xxxxxxx xxxxxxxxx. Chromozomové xxxxxx x xxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx podmíněných xxxxxx x xxxxxxx.

Xxxxx xxxxxxxx se xxxxxxxxx xxxxxxxxxxxx xxxxx xx xxxxxxxxxxxxxxx x xxxxxxxxxxx xx tedy, xx xxxx xxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx dědičných xxxxxx x xxxxxxxxxxxx xxxxxxx.

X této xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Touto xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx xxxxxxxx xxxxxxxxxxxx xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx xxxxxx předmětem xxxx xxxxxxx.

Xxx xxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx xx spermatogoniích xx xxxx xxx — xxxxx než dojde xx ztrátě xxxx — vyšetřeno první xxxxxxxxx xxxxxxx xxxxxx, xxxxx následuje xx xxxxxxxx. Xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxxxxx xxxxx lze xxxxxx xxxxxxxxxx chromozomovou xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x diakinese-metafázi X, kdy xx xxxxxxxxxx buňky xxxxxxx xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxxxx, xxx xxxx mutageny somatických xxxxx xxxxxxx xxxx x xxxxxxxxxxxx buňkách. Xxxxx xx xxxx xxxxxxx se spermatogoniemi xxxxxxxx xxx posouzení xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx DNA.

Ve xxxxxxxxx xx přítomna řada xxxxxxxx xxxxxxxxxxxxx s xxxxxx xxxxxxxxxx na xxxxxxxx xxxxxxxx látce. Xxxxxxxxxx aberace xxxx xxxxxxxxxxx souhrnnou xxxxxxx xxxxxxxxxx xxxxxxxx spermatogonií x xxxxxxxxxxxxxx diferencovanými xxxxxxxxxxxxxxx. X závislosti xx xxx xxxxxx xx varlatech, xxxxx xxxx xxxxxx být xxxxx generace spermatogonií xxxxxxxxxx xxxxxxxxx krevnímu xxxxx v xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x bariéry mezi xxxxxxx xxxxxx a xxxxxxx.

Xxxxxxxx existuje důkaz x tom, že xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxx xxxx xxxxxx úvod, xxxx B.

1.2 DEFINICE

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

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

Xxx : achromatická léze xxxxx než šířka xxxxx xxxxxxxxxx a x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx dělení xx xxxxxx xxxxxxxx pod xxxxxxxxxxx, xxxx xx xxxx xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX METODY

Zvířata jsou xxxxxxx xxxxxxxx exponována xxxxxxxx xxxxx x xx xxxxxx době xx expozici xxxxxxxx. Xxxx usmrcením se xxxxxxxx podá xxxxx xxxxxxxxxxx metafázi (např. xxxxxxxxx nebo Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, obarví xx a xxxxxxxxx xx xxxxxxxxxxxx aberace xxxxxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx používáni xxxxx xxxxxx xxxxxxxx a xxxx; xxx xxxx xxxxxx xxxxx jakéhokoli xxxxxx xxxxxxxx xxxxx xxxxx. Měly by xxx použity xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx v xxxxxxxxx xxxxxx minimální x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx hodnoty hmotnosti.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx xx xxxxxxxx výběrem rozdělí xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Klece xx měly xxx xxxxxxxxxx tak, xxx xxx xxxx xxxxxx xxxxxx minimalizován. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx aplikací xxxxxxxx rozpuštěny nebo xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx zkoušené xxxxx xxxxx být podávány xxxxx xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx použity xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, pokud údaje x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxxxx mít při xxxxxxxxx hladinách dávek xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx použita xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx jejich xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx xxxx být souběžné xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx proces xxxx xxxxxxx xx xxxxxxxxx, v xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx strukturní xxxxxxx xx spermatogoniích in xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxxxxxx, že xxxxxxxxx detekovatelný xxxxxx xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx xx měly xxx zvoleny xxx, xxx byl xxxxxx xxxxxxxx, ale xxx xxx odečtu nevyšla xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Je xxxxxxxxxx, xxx byla xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x xxx byl xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx xxx navíc xxxxx x úvahu xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx, xxxx-xx k xxxxxxxxx. Xxxxxxxx látek 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 xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx údaje x xxxxxxxxxxx xxxxxx a xxxxxxxx xxxxx x xxxxxxxxxxxxxx aberacemi. Xxxxx xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud xxxxxxxxx xxxxx prokazující, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 XXXXXX

1.5.1 Xxxxx zvířat

Každá xxxxxxxxxx x xxxxxxxxx xxxxxxx xxxx zahrnovat xxxxxxx xxx xxxxxxxxxxxxxxxx samců.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. xxx jedné xxxxxxxx xxxx dvou xxxxxxxxxx). Xxxxxxxx látky xxxxx xxx podávány xxxx xx dvou xxxxxxx, tzn. xxx xxxxx v xxx xxx v rozmezí xx xxxx xxx xxxxxxxx hodin, xxx xxxx xxxxxxxxx podávání xxxxxxx xxxxxx xxxxxxxxx. Xxxx režimy xxxxxxxx xx měly xxx xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx xxxxxx xx xxxx být xx xxxxxxxx provedeny xxx xxxxxx. Xxxxxxxx xxxxxxxx buněčného xxxxx xxxx xxx xxxxxxxxx xxxxxx ovlivněna, provede xx xxxxx xxxxx xxxxx x xxxxx xxxxxxxx xxxxx přibližně 24 x 48 xxxxx xx xxxxxxxx. X xxxxxxx xxxx xxx nejvyšší xxxxx xx měl xxx xxxxx xxxxxxxx po 24 hodin xxxx xx takové době xxxxxxxx, která xxxxxxxx 1,5xxxxxxx délky xxxxxxxxx xxxxx, xxxxx xxxx xxxxx xxxx xxxxxxxxx xxxx xxx detekci xxxxxx (6).

Xxxxx xxxxx xxx xxxxxx xxxxxxxxx xxxx x jiné xxxx. Například x xxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx S-nezávislé xxxxxx, xxxx být xxxxxxxxx xxxxxxxx xxxxx (1).

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxx být xxxxxx xxxxxx xx xxxxxxx. X xxxxxxx xxxxx x opakovanou xxxxxxxx xx měla xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5násobek xxxxx xxxxx) xx xxxxxxxx xxxxxxxx. Xxxxx potřeby xxxxx být xxxxxxxxx xxxxx odběry x xxxx xxxx.

Xxxx xxxxxxxxx xx zvířatům xxxxxxxxxxxxxxxxx xxxx xxxxxx xxxxx xxxxx zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx xx xx xxxxxx době xxxxxxx u xxxxxx xxxxx. X xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx neexistenci vhodných xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu, xxxx by xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx stejným xxxxxx x xxxxxx x xx stejného xxxxxx xxxxxxxx, xxxxx xx xxxxxxx x xxxxxx studii (7). X xxxxxxx xxxxxxxx xx pro první xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx dávky by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx toxicitou, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx použita xxxxx nejvyšší xxxxx. Xxxxxxxx dávka je xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, že xx xxxxx xxxxx xxxxx xxx stejném xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx.

Xxxxx se xxxxxxxxxxx biologickou xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. hormony x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx a měly xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx dávka může xxx xxxx definována xxxx xxxxx xxxxxxxxxxxx xx xxxxxxxxxxxxxxx některé xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx vzhledem x první x xxxxx xxxxxxxxx metafázi; xxxx snížení by xxxxxx překročit 50 %).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx alespoň 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách x xxxxxx dni xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx účinky a xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx xxxxxx xx třemi xxxxxxxx xxxxx xx xxxxxxxxx. Očekávaná expozice xxxxxxx může znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx xxxxxxx intubační xxxxxxx, xxxx intraperitoneální injekcí. Xxxx způsoby xxxxxxxx xxxx přijatelné, xxxx-xx xxxxxxxxxxxxx. Maximální objem xxxxxxxx, který může xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx objemů, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxx

Xxxxx xx usmrcení se x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx suspenze, xxxxxxxxxxxx xx x fixuje. Xxxx xx xxxxxx xx podložní sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx x xxxxx xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 xxxxxxxx xx skupinu). Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx aberací. Všechny xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx, by měly xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx při xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx zlomům xxxx xxxxxx chromozomů x xxxxx xxxxxxxx, xxxx xx xxxxxxxxxxx buňky xxxxxxxxx xxxxxxxxxx v xxxxx xxxxxxxxxxxxxx číslu 2 x ± 2.

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx pro jednotlivá xxxxxxx by xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Experimentální xxxxxxxxx je xxxxx. Xxx xxxxx xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx xx strukturními xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Pro exponované x kontrolní xxxxxxx xx xxxx být xxxxxxx xxxxx typy xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Gapy xx xxxxxxxxxxxxx odděleně x uvádějí se, xxx xxxxxx xx xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx a xxxx xxxxxx, měl xx xxx xxx stanovení xxxxxxx cytotoxických xxxxxx xxxx xxxx cytotoxicity xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx a xxxxxx sloužících xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx v mitose xxxxxxxx k xxxxx x xxxxx xxxxxxxxx xxxxxxxx, x xx x celkovém xxxxxx 100 xxxxxxxx xx xxxxx xx jedno xxxxx. Pokud je xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx xx xxxxx xx měl xxx xxxxxxxx mitotický index.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx xxxxxxxx několik xxxxxxxx, např. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na dávce xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při hodnocení xxxxxxxx zkoušky mohou xxx xxxxxxx jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx pro pozitivní xxxxxxx. Dvojznačné výsledky xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

Zkoušená xxxxx, xxxxx xxxxxxxx nesplňují xxxx uvedená kritéria, xx x xxxxx xxxxxxx xxxxxxxx xx xxxxxxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xxxxx xx xxxx znamenají, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx. Negativní xxxxxxxx znamenají, xx xxxxxxxx látka xx xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

Xxxx xx být xxxxxxxxxxx pravděpodobnost, s xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx dostanou do xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Testovací xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx x stáří xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx atd.,

- individuální xxxxxxxx xxxxxx xx xxxxxxx zkoušky, včetně xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxx xx studie xxx xxxxxxxx rozsahu, xxxxx xxxx provedena,

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxxxxxxx způsobu xxxxxxxx,

- údaje o xxxxxxxx xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx vodě (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx tělesné xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- podrobný xxxxx rozvrhu xxxxxxxx x odběru,

- metody xxxxxxxxx toxicity,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx zvíře,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, negativní nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x xxxxx xxxxxxxx xxxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- celkový xxxxx xxxxxxx ve xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx statistické xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

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

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- změny ploidie, xxxxx xxxx pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Adler, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx xx Xxxxx Xxxxxxxxxxxxx xx Xxxxxxxx Mutagens Xxxxxxx xx xxxxx Cell-Cycle Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx xx Environmental Xxxxxxxxx, Part X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Mutagenesis, Ramel, X., Xxxxxxx, B., Xxxxxxxxx, X. (eds) Xxxx, Xxx Xxxx, 477-484.

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

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

4) Xxxxxxx, X., Ashby, J., Xxxxxxxx, X., Gatehouse, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Cytogenetic Xxxxxx, xx: D. X. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx Tests, UKEMS Xxxxxxxxxxx Procedures. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx University Xxxxx, Cambridge, New Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, X. X., Xxxxxx X. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx X. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Report xx xxx Xxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxx Xxxxx, Mutatation Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. R., Xxxxxx, X. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. X., Richold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Xxxx Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, X., Richold, X., Papworth, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx of Xx xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Xxxx Data. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Report, Part XXX. Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Chester, Xxxxxxxxx, Xxxxxx, 184-232."


PŘÍLOHA 4X

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

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx OECD TG 486 — Xxxxxxx xx xxxxxxxxxxxx syntézu XXX (XXX) x xxxxxxxxx xxxxxxx xxxxx xx xxxx (1997).

1.1 XXXX

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

Xxxx xxxxxxx xx xxxx xxxxxxxxx metodu xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxx. Xxxxxxxxxxx jev xx xxxxxxxxxx xxxxxxxxx XXX x xxxxxxxx reparace x xxxxxxxxx xxxxxxx. Xxxxx xxxx obvykle xxxxxxx xxxxxx, kde xxxx absorbované xxxxxxxxxx xxxxxxxxxxxxxx. Jsou tedy xxxxxxx xxxxxx pro xxxxxxxxx míry xxxxxxxxx XXX xx xxxx.

Xxxxxxxx xxxxxxxx důkaz x xxx, xx xx xxxxxxxx látka nedostane xx xxxxxx tkáně, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxxxxx neplánované xxxxxxx XXX (XXX) xx xxxxxxxx stanovením xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx xxxxx, xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx je xxxxxxxxxxxxxxxxx xxxxxxxxx inkorporace xxxxxxxxx xxxxxxxxx tritiem (3X-XxX). Xxx zkoušky xx XXX in xxxx xx xxxxxxxxxx používají xxxxx xxxxxxx. Xxxx xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, xxxxxx xxxx xxxxxxxxx této xxxxxx.

Xxxxxxx xxxxxxxx UDS xxxxxx xx počtu xxxx XXX vyštěpených x xxxxxxxxxxx v místě xxxxxxxxx. Xxxxxxx xx XXX xx xxxx xxxxxx xxxxxxx xxx xxxxxxx dlouhých xxxxxxxx ("xxxx-xxxxx repair") (20 xx 30 xxxx) xxxxxxxxxxxx látkou. Xxxxxx xxxxxx ("xxxxx-xxxxx xxxxxx") (xxxxx až xxx xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxx. Xxxxx může xxxxxxxxx xxxxxxxxxxxxx reparace, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx xxxx DNA xxxxx k xxxxxxxxxx xxxxxxxxx. Rozsah xxxxxxxx XXX xxxxxxxxxxx žádnou xxxxxxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, že xxxxxxx xxxxxxx x XXX, xxx xxxxxxxxx XXX není opraveno xxxxxxxxxxx reparací. Xxxxxxxxxx xxxxxxxxxxxx informací, xxxxx xxxx xxxxxxx xxxxxxxxx x mutagenní xxxxxxxx, xx vyvážen xxxxxxxxxxx xxxxxxxxxx xxxxxx jevu, xxxxx je xxxxxxxxxx x celém genomu.

Viz xxxx obecný xxxx, xxxx X.

1.2 DEFINICE

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

Xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx UDS xxxxxxxx buněk v xxxxxxxxxxxxxxxxx zkoušce na XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) xxxxxxxxxxxxxx xxxxxx xx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): XXX = XX — XX. Xxxxxxx XXX xx xxxxxxx xxx xxxxxxxxxx xxxxx, xxxx xxxxxxxx xxx xxxxx v xxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx xxxxxxx XXX (UDS) : Xxxxxxx reparací DNA xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx indukovaným chemickými xxxxxxx xxxx fyzikálními xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx XXX x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxxxxxx XXX po xxxxxxxxx x odstranění xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx indukovaným xxxxxxxxxx látkami xxxx xxxxxxxxxxx xxxxxxxx. Zkouška xx xxxxxxx xxxxxxxx xx xxxxxxxxxxx 3X-XxX xx DNA jaterních xxxxx, xxx xx xxxx četnost xxxxx x S-fázi buněčného xxxxx. Xxxxxxxxxxx 3X-XxX xx obvykle stanoveno xxxxxxxxxxxxxxx, jelikož xxxx xxxxxxxx není tak xxxxxxx xx vliv X-xxxx xxxxx jako xxxx. xxxxxxx scintilační xxxxxxxxxxxxx.

1.4 XXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx xxx xxxxxx jakýkoli xxxxxx xxxx xxxxx. Měly xx být použity xxxxx xxxxxxxxx laboratorní xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx odchylka x xxxxxxxxx xxxxxx xxxxxxxxx x neměla xx xxxxxxxxx ± 20 % střední xxxxxxx xxxxxxxxx xxx xxx xxxxxxx.

1.4.1.2 Podmínky xxxxx x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx x xxxxx X, xxxxxxx by xxxx být xxxxxxxx xxxxxxxx xxxxxxx 50 - 60 %.

1.4.1.3 Xxxxxxxx zvířat

Zdravá pohlavně xxxxxxx xxxxxxx xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx xxxx být xxxxxxxxxx xxx, aby xxx xxxx xxxxxx xxxxxx minimalizován. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x xxxx započetím xxxxxx xx xxxxxxx x laboratorních podmínkách xxxxxxx pět xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx látky xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx přímo xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje se xxxxxxxx xxxxxx použití xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx xx měly xxx souběžné xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx měla zvířata xxxxxxxxx xxxxxxx podstoupit xxxxxx xxxxxx jako xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxx, o nichž xx známo, xx xxxxxx podávání x xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx k xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní xxxxxxxx xxxxxxxxxx metabolickou xxxxxxxx xx měly být xxxxxxx x dávkách xxxxxxxxxxxx xxxxxx odpověď (4). Xxxxx xxxxx xxx xxxxxxx xxx, xxx xxx účinek xxxxxxxx, xxx aby xxx xxxxxx nevyšla xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

Xxxx odběru

Látka

Číslo CAS

Číslo xxxxx Xxxxxx

Xxxxx xxxx xxxxxx (2 xx 4 x)

X-xxxxxxxxxxxxxxxxxxx

62–75–9

200–249–8

Xxxxxx xxxx xxxxxx (12 xx 16 x)

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

53–96–3

200–188–6

Xxxxx xxx použity také xxxx xxxxx pro xxxxxxxxx xxxxxxxx. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxx xxxxx xxxxxxxx, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Měl xx xxx použit xxxxxxxxxx xxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxx odpovědi xx xxxxxxx. Xxxxx xxxxxxx xx se xxxx xxxxxxx xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx dostatečné xxxxxxxxx xxxxx, je pro xxxxxxxxx a xxxxxxxxx xxxxxxxxx skupiny xxxxxxxx xxxxx jedno xx xxx xxxxxxx.

Xxxxxxxx xxxx x době xxxxxx x xxxxxxxxx xxxxx xx studií xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, že neexistuje xxxx xxxxxxxxx rozdíl x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, nejlépe xxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx pro xxxxxx xxxxxxx, jako xx xxxx například u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxxxxxx xxxxx xx definována xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx podle očekávání xxx xxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx by xxxx xxx xxxxxxxxx 50 % až 25 % xxxxx xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx netoxických xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx xxx zjištění xxxxxxx, xxxx xx xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí x hlavní studii.

Nejvyšší xxxxx xxxx být xxxxxxxxxx xxxx xxxx xxxxx vyvolávající xxxxxx xxxxxxxx x xxxxxxx (xxxx. xxxxxxxxxx jádra).

1.5.4 Xxxxxxx zkouška

Jestliže xxxxxxx x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx tělesné xxxxxxxxx xxxxxxx jednorázově nebo xx xxxx xxxxxxx x xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx na základě xxxxx x xxxxxxx, xxxxx mají xxxxxxxx xxxxxxxxx, očekávána xxxxxxxxxxxx, xxxxxx být xxxxx xxxxxx nezbytná. Xxxxxxxxx xxxxxxxx člověka může xxxxxxxx xxxxxxx použít x xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou xxxxx, xxx-xx je xxxxxxxxx. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx xxxxxxxxxxxx, xxxxx xx játra xxxxx xxx exponována xxxxxxxx xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Maximální xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx na xxxxxxxxx testovacího xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx koncentracích xxxxxxxx zesílené účinky, xx měla xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx xxxxx úrovních xxxxx.

1.5.6 Příprava jaterních xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx x exponovaných xxxxxx zpravidla 12 xx 16 xxxxx xx podání dávky. Xxxxxxxxxx dřívější xxxxxxxx xxxxxx (xxxxxx xxx xx čtyři xxxxxx xx expozici) xx xxxxxxxx, xxxx-xx xx 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Mohou xxxx xxx použity jiné xxxx odběru, xxxx-xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx kolagenasou xx xxxx x xxxxxx xx, aby xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx z xxxxxxxxx xxxxxxxx xx xxxx vykazovat životaschopnost (5) alespoň 50 %.

1.5.7 Xxxxxxxxx UDS

Čerstvě xxxxxxxxx xxxxxxx xxxxx xxxxx se xxxxxxx xxxxxxx dobu, xxxx. xxx xx osm xxxxx, xxxxxxxx x xxxxxx obsahujícím 3X-XxX. Xx konci xxxxxxxxx xxxx xx xxxx xxx xxxxxx x xxxxx xxxxxxxxxx a xxxxx poté mohou xxx xxxxxxxxxx s xxxxxx obsahujícím xxxxxxxx xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx neinkorporovaná xxxxxxxxxxxxx ("xxxx xxxxx"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx delší xxxxxxxxx době nemusí xxx xxxxxxx radioaktivity xxxxxxxx. Xxxxxxxxx se xxxxxx xx autoradiografické xxxxxx, exponují xx x xxxxx (xxxx. x xxxxxx 7 xx 14 xxx), xxxxxxxx se, xxxxxx x xxxxxxxxx se xxxxxxxxxx zrna xxxxxxx. X xxxxxxx zvířete xx xxxxxxxx xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

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

Xxxx xxxxxxxxx xxx by xxxx xxx xxxxxxxxx kódovány. Xxxxxxxxx se vyšetřuje 100 buněk na xxxxx xxxxx alespoň xx xxxx xxxxxxxxx; xxxxxxxxx méně xxx 100 xxxxx/xxxxx xx xxxx xxx zdůvodněno. Xxx xxxxxxxx xxx xx xxxxx x X-xxxx nevyšetřují, xxx xxxxx xxxxx x X-xxxx může xxx xxxxxxxxxx.

Xxxxxxxx 3X-XxX xxxxxxxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxx xx xxxx xxx xxxxxxxxx xxxxxxx metodou.

Počet xxxxx xx xxxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (xx) x x xxŭxxxxxxx xxxxx zrn x xxxxxxxxxxxxxxxxx oblastech (xx) xxxxxxxxxxxxxx xxxxŭx. jako xxxxxxx cg xx xxxxxxx xxx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx xxŭxxxxx hodnota xxxx xx xxx xxxxxxx vybraných xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx jader. xx xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx xxxxxxx x xxxx postupy xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxx xx xxx xxxxxxx údaje xxx xxxxxxxxxx preparáty x xxxxxxx. Údaje xx xxxx xxx dále xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX xx hodnoty XX xx xxx xxx xxxxxxxx xxx xxxxxx xxxxx, pro xxxxx xxxxx x xxx xxxxxx xxxxx x xxx xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrům (NNG). Xxxxxxxx xxxx xxxxxxxx "xxxxxxxxxx" buňky, xxxx xx xxx xxxxxxxx xxx definování "xxxxxxxxxxxx" xxxxx xxxxxxxxxx x xxxxxxxx xx dosavadních xxxx souběžných údajích x negativních xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx zhodnoceny xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, měly by xxx xxxxxxxxxxx xxxxx xxxxxxx x xxxxxxxxxx xxxx provedením studie.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx

x)

xxxxxxx XXX leží xxx xxxxxxxx xxxxxx, která xx xxxxxxxxxx xx xxxxxxx dosavadních xxxxx xxxxxxxxxx;

xxxx

xx)

xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx;

xxxxxxxxx

x)

xxxxxxx XXX xxxx xx dosavadní xxxxxxx xxxxxxx xxxx xxx xx;

xxxx

xx)

xxxxxxx XXX xxxx xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx.

Xxxx by xxx xxxxxxxxx xxxxxxxxxx relevance xxxxx, xx. xxxx xx být xxxxx x úvahu parametry, xxxx xxxx xxxxxxxxxxx xxxxxx, xxxxx xxxxx x xxxxxxxx x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx však neměla xxx jediným určujícím xxxxxxxx pro pozitivní xxxxxxx.

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

Xxxxxxxxx xxxxxxxx zkoušky na XXX x xxxxxxxxx xxxxxxx savců xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxxx XXX, které xxx xxxxxxx neplánovanou xxxxxxxx XXX in xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx zkoušená xxxxx xx podmínek xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxxxx xxxxx xxxxxxxx.

Xxxx xx být diskutována xxxxxxxxxxxxxxx, x jakou xx zkoušená látka xxxxxxx xx xxxxxxxx xxxxx xxxx. xx xxxxxx tkáně (xxxx. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Testovací zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x pohlaví xxxxxx,

- zdroj, xxxxxxxx xxxxx, strava xxx.,

- xxxxxxxxxxxx hmotnost xxxxxx xx xxxxxxx zkoušky, xxxxxx rozpětí xxxxxxx xxxxxxxxx, xxxxxxx hodnoty x xxxxxxxxxx xxxxxxxx xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) kontroly,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx zkoušené xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, xxx xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx nebo xx xxxxxx tkáně,

- případně xxxxxxxx mezi xxxxxxxxxxx xxxxxxxx látky x xxxxxx nebo xxxx (xxx) na odpovídající xxxxx (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x xxxxxxx krmiva x vody,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x odběru,

- xxxxxx xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx x kultivace xxxxxxxxx buněk,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x počet xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- kritéria klasifikace xxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx xxxxxxx xxxxx xxx odpovídajících buněčným xxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxx, x xxxxx xxxxx xxx, xxxxxxxxxx pro xxxxxxxxx, xxxxxxx x xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi na xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- známky xxxxxxxx,

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

- xxxxxxxxx xxxxx o xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx xxxxx "xxxxxxxxxxxx" buněk, xx-xx xxxxxxxx,

- xxxxx xxxxx x X-xxxx, xx-xx xxxxxxxx,

- životaschopnost xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, J. Lefevre, X. X., Xxxxxxxxx, X., Xxxxxx, X. X. (1985), An Xxxxxxxxxx of the Xx xxxx Xxx. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 156, 1-18.

2) Xxxxxxxxxxx, X. X., Ashby, X., Xxxxxxxx, E., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, G. (1987), X Xxxxxxxx and Xxxxx for xxx Xx xxxx Xxx Xxxxxxxxxx DNA Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 123-133.

3) Kennelly, X. C., Xxxxxx, X., Ashby, X., Xxxxxxx, X. X., Xxxxxxxxx, X., Xxxxxxx, X. X., Xxxx, X. X., Mitchell, X. xx X. (1993), Xx xxxx Xxx Liver XXX Xxxxx, xx: Kirkland X. X., Fox X., (eds), Supplementary Xxxxxxxxxxxx Tests: UKEM Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Part II xxxxxxx, Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Dean, X. X., Xxxxxx, X., Xxxxxxxxx. G., Xxxxxxxxx, B., Xxxxxxxxx, X. X., Furihata, X., Hertner, T., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx XXX Xxxxx Xx vitro xxx In xxxx, Xxxxx. Res., 312, 263-285.

5) Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, X. (1993), Xxxxxxxxxx xx xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Xxxxxxxxx xxx the Xxxxxxxxxx xx Xxxxxxx Xxxxxxxx Xxx Hepatocytes Used xxx xxx In xxxx/Xx xxxxx XXX Xxxxxx Xxxxx (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

6) Mirsalis, X. X., Tyson, X. X., Xxxxxxxxxxx, X. X. (1982), Detection xx Genotoxic Carcinogens xx xxx In xxxx/Xx xxxxx Xxxxxxxxxx XXX Repair Assay, Xxxxxxx.Xxxxxxx. 4, 553-562."


PŘÍLOHA 5

XXXXXX XXXXXXXXX XX XXXXXXXXXXX X XXXXXXXXXX XXXXXXXXXXXX XXXXX X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES, Xx. xxxx. X 332, 28. 12. 2000, x. 81.


XXXXXXX 6

"

XXXXXXX IX

ČÁST X

xxxxxxxx týkající xx xxxxxxx odolných proti xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. x) xxxx xxxxxxxx, xxxx xxx xxxxx x xxxxxxxxx objemu xxxxxxxxxx xxxxx, x xxxxx xx spojeno xxxxxx xxx xxxxxxxxxx (Xx; X 65) a xxxxx jsou xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx na trh xx xxxxx xxxxxxxx xxxx v xxxxxxxx xxxxxxxxxx xxxxxxxxxxx rozprašovačem, xxxxxxxx xxxxxxx xxxxxxxx xxxxx otevření xxxxx.

1. Xxxxxxxxx uzavíratelné obaly

Uzávěry xxxxxx xxxxx otevření xxxxx použité xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx splňovat xxxxxxxxx xxxxx ISO 8317 (xxxxxx xx xxx 1. července 1989) "Xxxxx odolné dětem — Xxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxx xxxxxx xxxxxxxx" xxxxxxxx Mezinárodní xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx neuzavíratelných xxxxxxx xxxx xxxxxxxx xxxxxxxxx normy XXX XX 862 (vydání x xxxxxx 1997) "Xxxxx — Obaly xxxxxx xxxxx — Xxxxxxxxx x xxxxxxxx xxxxxxx pro opakovaně xxxxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Evropským xxxxxxx xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Prokázání xxxxx x výše xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxx, které xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx zřejmé, xx xxxx xx xxxxxxxxxx xxxxxxxx xxx xxxx, xxxxx xx xxxxxxx dostat k xxxxxx bez pomoci xxxxxxxx, nemusí být xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x xxxxxxxx x bezpečnosti xxxxxxx xxx xxxx, může xxxxxxxxxxxx orgán xxxxxxxxx, xxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx xx xxx předložila xxxxxxxxxx vydaný xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx xxxxxx, xx jej xxxx xxxxxxxx xxxxxxx xxxxx xxxx xxxxxxxxx xxxxx XXX a CEN,

nebo

- xx xxxxxx byl xxxxxxx a xxx xxxxxxx xxxxxxxxxxx xxxxx xxxx uvedených xxxxx.

XXXX X

Xxxxxxxx týkající xx xxxxxxxxxxxx výstrah

Technické specifikace xxx xxxxxxxxxx výstrahy xxxx xxx x xxxxxxx x xxxxxx XX ISO 11683 (xxxxxx z roku 1997) "Xxxxx — Xxxxxxxxxx výstrahy xxxx xxxxxxxxxx — Xxxxxxxxx".

"