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Xxxxxxxx Komise 2000/32/XX

xx xxx 19. xxxxxx 2000,

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

(Xxxx x xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x ohledem xx Xxxxxxx x xxxxxxxx Xxxxxxxxxx společenství,

s xxxxxxx xx směrnici Xxxx 67/548/EHS xx xxx 27. xxxxxx 1967 x sbližování xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx se xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx látek [2], xxxxxxxxx xxxxxxxxxx xxxxxxxx Evropského xxxxxxxxxx x Rady 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx směrnice,

vzhledem x xxxxx xxxxxxx:

(1) Příloha X xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx nebezpečných xxxxx xxxxxxxx s xxxxxxxxxx xxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxx ukazují, xx xx měl být xxxxxx nebezpečných xxxxx x xxxxxxx příloze xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx směrnice vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a xxxxxxx X v xxxxxxx X.

(2) Xxxxxxx III xxxxxxxx 67/548/EHS obsahuje xxxxxx vět udávajících xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx s xxxxxxxxxxxx xxxxxxx a přípravky. Xxxxxxx IV xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx x xxxxxxxxxxxxxx xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Příloha XX xxxxxxxx 67/548/XXX obsahuje xxxxx ke xxxxxxxxxxx x k xxxxxxxxxx xxxxxxxxxxxx látek a xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx určitých xxxxxx xxxxxx III, XX x XX.

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

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx. Xxxx xxxxxxxx xx xxxx být xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx xxxxxxxx rozšířit xxxxxx, xxx xx xxxxxxx xxxxxx xxxxx xxxxxxxx dětmi xxxxxxxxx.

(5) Xxxxxxxx této směrnice xxxx x souladu xx xxxxxxxxxxx Výboru xxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx xxx xxxxxxxxxx xxxxxxxxxxx překážek xxxxxxx xx úseku xxxxxxxxxxxx xxxxx x xxxxxxxxx,

XXXXXXX XXXX SMĚRNICI:

Xxxxxx 1

Xxxxxxxx 67/548/EHS xx xxxx xxxxx:

1. Xxxxxxx X se xxxx xxxxx:

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

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

x) xxxxxxxxxxxx položky xx xxxxxxxxx xxxxxxxxx x xxxxxxx 1C xxxx xxxxxxxx;

x) vkládají xx položky v xxxxxxx 1D xxxx xxxxxxxx.

2. Odpovídající xxxx x xxxxxxx III xx xxxxxxxxx xxxxxxxxxx xxxxx označující specifickou xxxxxxxxxx x xxxxxxx 2 xxxx xxxxxxxx.

3. Xxxxxxx XX xx xxxx takto:

a) xxxxxxxxxxxx xxxxxx v xxxxxxx XX xx xxxxxxxxx xxxxxxxxxxxx xxxxxx xxx xxxxxxxx zacházení x xxxxxxx 3X xxxx xxxxxxxx;

x) odpovídající xxxxxx x xxxxxxx XX xx xxxxxxxxx kombinovanými xxxxxxxxxxxx xxxxxx pro xxxxxxxx zacházení x xxxxxxx 3X xxxx xxxxxxxx.

4. Část B xxxxxxx X xx xxxx xxxxx:

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

x) xxxxxxxx B.11 se xxxxxxxxx xxxxxx v xxxxxxx 4B xxxx xxxxxxxx;

x) kapitola B.12 xx xxxxxxxxx textem x příloze 4X xxxx směrnice;

d) kapitoly X.13 a B.14 xx nahrazují textem x příloze 4X xxxx směrnice;

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

x) xxxxxxxx X.23 xx xxxxxxxxx textem x xxxxxxx 4F této xxxxxxxx. Název kapitoly X.23 xx xxxxxxxxxxx xx mění xxxxxxxxxxxxx xxxxxxxx;

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

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

6. Xxxxxxxxxxxx xxxxx x xxxxxxx XX se xxxxxxxxx xxxxx x xxxxxxx 5 xxxx směrnice.

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

Xxxxxx 2

1. Xxxxxxx xxxxx uvedou v xxxxxxxx xxxxxx x xxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxxx xxxxxxx x xxxxx směrnicí xxxxxxxxxx xx 1. xxxxxx 2001. Xxxxxxxxxx x nich uvědomí Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx musí xxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxx xxxx takový odkaz xxx učiněn xxx xxxxxx úředním xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx xxxxxxx xxxxx.

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

Xxxxxx 3

Xxxx xxxxxxxx xxxxxxxx v xxxxxxxx xxxxxx xxxx po xxxxxxxxx x Xxxxxxx xxxxxxxx Xxxxxxxxxx xxxxxxxxxxxx.

Xxxxxx 4

Tato směrnice xx xxxxxx členským xxxxxx.

X Bruselu dne 19. května 2000.

Za Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise

[1] Xxxxxxx xx xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Úř. xxxx. 196, 16.8.1967, x. 1.

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

XXXXXXX 1A

PŘEDMLUVA X XXXXXXX I

Vysvětlení xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx se xxxxxxx xxxxx)

PŘÍLOHA 1X

"XXXXXXX X

X

Xxxxxx

XX

18

Xx

Xxxxx

Αργό

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"

PŘÍLOHA 1X

Xxxxxxxx číslo	Chemický xxxxx	Xxxxxxxx x xxxxxx	Xxxxx XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx xxxxxx	Xxxxxxxx x xxxxxxxxxx
006–011–00–7	xxxxxxxx (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx		200–555–0	63–25–2	Xxxx. xxx. 3; X40 Xx; X22 X; R50	Xn; X X: 22–40–50 X: (2-)22–24–36/37–46–61
006–013–00–8	xxxxxx-xxxxxxx (ISO) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx		205–293–0	137–42–8	Xx; X22 R31 X; X34 X43 N; X50–53	X; X X: 22–31–34–43–50/53 X: (1/2-)26–36/37/39–45–60–61
006–015–00–9	xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx	206–354–4	330–54–1	Xxxx. kat. 3; X40 Xxxx. xxx. 3; R40 Xx; X22–48/22 X; X50–53		Xx; X X: 22–40–48/22–50/53 S: (2-)13–22–23–37–46–60–61
006–016–00–4	xxxxxxxx (XXX) 2- xxxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		204–043–8	114–26–1	X; X25 N; X50–53	X; X R: 25–50/53 X: (1/2-)37–45–60–61
006–017–00-X	xxxxxxxx (XXX) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx		204–123–2	116–06–3	X+; X26/28 X; X24 N; X50–53	X+; X R: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61
006–018–00–5	xxxxxxxxx (XXX) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		217–990–7	2032–59–9	X; R24/25 X; X50–53	X; X X: 24/25–50/53 X: (1/2-)28–36/37–45–60–61
006–019–00–0	xx-xxxxx (XXX) X-(2,3-xxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–961–1	2303–16–4	Xxxx. xxx. 3; R40 Xx; X22 X; X50–53	Xx; X R: 22–40–50/53 X: (2-)25–36/37–60–61
006–020–00–6	barban (XXX) 4-xxxxxxxx-2-xx-1-xx-X -(3-xxxxxxxxxx)xxxxxxxx		202–930–4	101–27–9	Xx; X22 X43 N; R50–53	Xn; X X: 22–43–50/53 X: (2-)24–36/37–60–61
006–023–00–2	merkaptodimethur (ISO) xxxxxxxxxx 3,5-dimethyl-4-(methylsulfanyl)fenyl-N -xxxxxxxxxxxxxx		217–991–2	2032–65–7	X; X25 X; X50–53	X; X X: 25–50/53 X: (1/2-)22–37–45–60–61
006–024–00–8	xxxxxx-xxxxxxx (ISO) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx		205–443–5	140–93–2	Xx; R22 Xi; X38 X; X51–53	Xx; X X: 22–38–51/53 X: (2-)13-61
006–026–00–9	xxxxxxxxxx (ISO) 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+; N R: 26/28–50/53 X: (1/2-)36/37–45–60–61
006–028–00-X	dinobuton (XXX) 2-(1-xxxxxxxxxxxx)-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx 2-sek-butyl-4,6-dinitrofenyl-isopropyl-karbonát		213–546–1	973–21–7	T; X25 X; X50–53	X; X X: 25–50/53 X: (1/2-)37–45–60–61
006–029–00–5	xxxxxxxxx (ISO) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx		230–253–4	6988–21–2	X; X25 N; X51–53	X; N R: 25–51/53 X: (1/2-)37–45–61
006–033–00–7	metoxuron (XXX) 3-(3-xxxxx-4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx		243–433–2	19937–59–8	X; X50–53	X X: 5 0/ 5 3 S: 60-61
006–034–00–2	xxxxxxx (XXX) S-propyl-N-butyl-N-ethylthiokarbamát		214–215–4	1114–71–2	Xn; X22 X; R51–53	Xn; X X: 22–51/53 X: (2-)23-61
006–035–00–8	pirimikarb (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx		245–430–1	23103–98–2	X; X25 X; X50–53	X; X X: 25–50/53 X: (1/2)22–37–45–60–61
006–037–00–9	xxxxxxxxx (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–113–0	2631–37–0	X; X25 X; X50–53	X; 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; R45 Xx; X22 N; X50–53	X; X R: 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 R43 X; R50–53	Xn; X X: 22–43–48/22–50/53 S: (2-)24–37–60–61
006–042–00–6	xxxxxxx (ISO) 3-(4-chlorfenyl)-1,1-dimethylmočovina		205–766–1	150–68–5	Karc. xxx. 3; X40 Xx; X22 N; X50–53	Xx; X X: 22–40–50/53 X: (2-)36/37–60–61
006–043–00–1	xxxxxxx-XXX 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx		—	140–41–0	Xx; X36/38 Xxxx. xxx. 3; X40 X; R50–53	Xn; X X: 36/38–40–50/53 X: (2-)36/37–60–61
006–045–00–2	xxxxxxxx (XXX) methyl-N-[(N-methylkarbamoyl)oxy]thioacetimidát		240–815–0	16752–77–5	T+; X28 X; X50–53	X+; X X: 28–50/53 X: (1/2-)22–36/37–45–60–61
006–046–00–8	bendiokarb (XXX) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx		245–216–8	22781–23–3	X; R23/25 Xx; X21 N; X50–53	X; X X: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61
006–047–00–3	xxxxxxxxx (ISO) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx		—	8065–36–9	X; X24/25 X; X50–53	X; X X: 24/25–50/53 S: (1/2-)28–36/37–45–60–61
006–048–00–9	ethiofenkarb (XXX) 2-[(xxxxxxxxxxxxx)xxxxxx]xxxxx-X-xxxxxxxxxxxxxx		249–981–9	29973–13–5	Xx; X22 X; R50–53	Xn; X 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; N X: 38–50/53 X: (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 (ISO) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		206–249–3	315–18–4	X+; X28 Xx; X21 N; X50–53	X+; X X: 21–28–50/53 X: (1/2-)36/37–45–60–61
006–057–00–8	nitrapyrin (XXX) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx		217–682–2	1929–82–4	Xx; X22 N; X51–53	Xx; N X: 22–51/53 X: (2-)24-61
006–060–00–4	xxxxxxxxxxx (XXX) 2-methyl-4,4-dioxo-5,6-dihydro-4λ4-1,4-oxathiin-3-karboxanilid		226–066–2	5259–88–1	Xn; X22 X52–53	Xx R:22–52/53 S: (2-)61
006–069–00–3	xxxxxxxxx-xxxxxx (XXX) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx		245–740–7	23564–05–8	Xxxx. xxx. 3; X40 X; X50–53	Xx; X X: 40–50/53 S: (2-)36/37–60–61
006–070–00–9	xxxxxxxxxxx N-cyklohexyl-N-methoxy-2,5-dimethyl-3-furamid		262–302–0	60568–05–0	Karc. xxx. 3; R40 X; X50–53	Xx; X X: 40–50/53 X: (2-)36/37–60–61
006–088–00–7	xxxxxxxxxxx (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	N,N-dimethylhydrazin 1,1-xxxxxxxxxxxxxxxx	X	200–316–0	57–14–7	X; X11 Karc. kat. 2; X45 X; X23/25 X; X34 X; X51–53	X; X; X R: 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; R45 X; X23/24/25 N; X51–53	X; X X: 45–23/24/25–51/53 X: 53–45–61	C ≥ 25 %: X; X45–23/24/25 3 % &xx; X &xx; 25 %: X; X45–20/21/22 0,01 % &xx; X &xx; 3 %: X; X45
009–003–00–1	xxxxxxxx xxxxxxxxxxxxxx … %	X	231–634–8	7664–39–3	X+; X26/27/28 X; X35	X+; X X: 26/27/28–35 X: (1/2-)7/9–26–36/37–45	X ≥ 7 %: X+; X; X26/27/28–35 1 % ≤ X < 7 %: X; X23/24/25–34 0,1 % ≤ C < 1 %: Xx; X20/21/22–36/37/38
015–039–00–9	xxxxxxx-xxxxxx (XXX) X,X-xxxxxxxx-X -[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx		201–676–1	86–50–0	X+; X26/28 X; R24 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; X23–48/25 Xn; X21/22 X; X50–53	X; X X: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61
015–056–00–1	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+; R28 X; X24 N; X50–53	X+; X X: 24–28–50/53 X: (1/2-)28–36/37–45–60–61
015–140–00–8	xxxxxxxxx (XXX) X,X-xxxxxxx-X-(1-xxxxx-1 H- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx		245–986–5	24017–47–8	X; X23/25 Xn; X21 N; X50–53	X; 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; R34 N; X50	X; X X: 14–34–50 X: (1/2-)26–36/37/39–45–61	C ≥ 10 %: X; R34 5 % ≤ C &xx; 10 %: Xx; R36/37/38
016–014–00–5	chlorid xxxxxxxx		—	13451–08–6	X14 X; X34 X; X50	X; N X: 14–34–50 X: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38
016–023–00–4	xxxxxxxx-xxxxxx	X	201–058–1	77–78–1	Xxxx. kat. 2; X45 Xxxx. xxx. 3; X40 X+; R26 X; X25 X; X34 X43	X+ X: 45–25–26–34–43 X: 53-4 5	X ≥ 25 %: X+; R45–25–26–34–43 10 % ≤ X &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 &xx; 5 %: T; X45–22–23–43 1 % ≤ X < 3 %: X; R45–23–43 0,1 % ≤ X &xx; 1 %: T; X45–20 0,01 % ≤ X &xx; 0,1 %:X; R45
016–024–00-X	dimexano (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx	X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8	1468–37–7	Xx; R22 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 xxxxxxxx		410–130–3	136248–03–8	X43	Xx X: 43 X: (2-)22–24–37
022–001–00–5	xxxxxxx xxxxxxxxxx		231–441–9	7550–45–0	X14 X; R34	C X: 14-34 X: (1/2-)7/8–26–36/37/39–45	X ≥ 10 %: X; X34 5 % ≤ X < 10 %: Xx; X36/37/38
030–004–00–8	xxxxxxxxxxxxx [1] xxxxxxxxxxxx [2]		208–884–1 [1] 209–161–3 [2]	544–97–8 [1] 557–20–0 [2]	X14 X; X17 X; X34 N; X50–53	X; X; X X: 14–17–34–50/53 S: (1/2-)16–43–45–60–61
050–002–00–0	xxxxxxxxx (XXX) tricyklohexyl(hydroxy)stannan xxxxxxxxxxxxxxxxxxxxx-xxxxxxxx		236–049–1	13121–70–5	Xx; X20/21/22 N; X50–53	Xx; X X: 20/21/22–50/53 X: (2-)13–60–61
050–012–00–5	xxxxxxxxxxxxxxxxxxxxxx [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] 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; X X: 20/21/22–50/53 X: (2-)26–28–60–61	X ≥ 1 %: Xn; X20/21/22	1
050–017–00–2	xxxxxxxxxxxxxx (XXX) 1,1,1,3,3,3-hexakis(2-fenyl-2-methylpropyl)distannoxan		236–407–7	13356–08–6	T+; R26 Xx; R36/38 X; X50/53	X+; X R: 26–36/38–50/53 X: (1/2-)28–36/37–45–60–61
082–009–00–X	xxxx (xxxxxxxxxxxx olovnatý) XX Xxxxxxx Xxxxxx 34 (XX 77603) XX xxxxxxxxxx xxxx 34 (XX 77603)		215–693–7	1344–37–2	Karc. xxx. 3; X40 Repr. xxx. 1; X61 Xxxx. xxx. 3; X62 R33 X; X50–53	X; N X: 61–33–40–50/53–62 S: 53–45–60–61		1
082–010–00–5	xxxxxx (xxxxxxx-xxxxxxxxxx-xxxxx xxxxxxxx) XX Xxxxxxx Xxx 104 (XX 77605) XX xxxxxxxxxx xxxxxx 104 (XX 77605)		235–759–9	12656–85–8	Xxxx. xxx. 3; X40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 R33 X; X50–53	X; N X: 61–33–40–50/53–62 S: 53–45–60–61		1
601–024–00-X	xxxxx [1] xxxxxxxxxxxx [2]		202–704–5 [1] 203–132–9 [2]	98–82–8 [1] 103–65–1 [2]	X10 Xx; X65 Xi; X37 X; 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; R45 Xxxx. xxx. 2; X46 Xxxx. kat. 2; X60–61 X; X50–53	X; X X: 45–46–60–61–50/53 X: 53–45–60–61
601–034–00–4	xxxxx[x]xxxxxxxxxxxxxxx		205–911–9	205–99–2	Xxxx. xxx.2; X45 N; X50–53	X; X R: 45–50/53 X: 53–45–60–61
602–035–00–2	1,4-xxxxxxxxxxxxx p-dichlorbenzen		203–400–5	106–46–7	Xi; X36 X; X50–53	Xx; X X: 36–50/53 X: (2-)24/25–46–60–61
602–054–00–6	3-xxxxxxx-1-xx allyljodid		209–130–4	556–56–9	R10 X; R34	C R: 10-34 X: (1/2-)7–26–45
603–076–00–9	xxx-2-xx-1,4-xxxx		203–788–6	110–65–6	X; X23/25 Xx; X21–48/22 X; R34	T X: 21–23/25–34–48/22 X: (1/2-)26–36/37/39–45	C ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ C &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; R20/22–48/22 3 % ≤ C &xx; 10 %: Xx; X20/22
603–091–00–0	xxx-4-xxxxxxxxx-1-xxxxxx-7-xxxxxxxxxx[2.2.1]xxxxxx-2-xx		402–470–6	87172–89–2	X; R8 Xx; X22 Xi; X36	X; Xx R: 8–22–36 X: (2-)26
603–093–00–1	xxx-(±)-4-xxxxxxxxx-1-xxxxxx-2-[(2-xxxxxxxxxxxx)xxx]-7-xxxxxxxxxx[2.2.1]xxxxxx		402–410–9	87818–31–3	Xx; X20 X; R51–53	Xn; X X: 20–51/53 X: (2-)23-61
603–097–00–3	1,1', 1′′-xxxxxxxxxxxxxxxx-2-xx xxxxxxxxxxxxxxxxxx		204–528–4	122–20–3	Xx; X36 X52–53	Xx X:36–52/53 X: (2-)26-61
603–117–00–0	xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx		200–661–7	67–63–0	X; R11 Xx; X36 X67	X; Xx R: 11–36–67 X: (2-)7–16–24/25–26
604–020–00–6	bifenyl-2-ol 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (ISO)		201–993–5	90–43–7	Xi; X36/37/38 X; R50	Xi; X X: 36/37/38–50 X: (2-)22-61
604–021–00–1	2-xxxxxxxxxx, sodná xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx xxxxx xxxxxxx-xxxxxxx-2-xxxx		205–055–6	132–27–4	Xx; X22 Xx; X37/38–41 X; R50	Xn; X X: 37/38–41–50 X: (2-)22–26–61
604–024–00–8	4,4'-(4-xxxxxxxxxxxx-2,2-xxxx)xxxxxxx 2,2-bis(4-hydroxyfenyl)-4-methylpentan		401–720–1	6807–17–6	Repr. xxx. 2; X60 Xx; R36 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; R22 Xx; R38–41 X; X50–53	Xx; X X: 22–38–41–50/53 X: (2-)24–39–60–61
604–043–00–1	monobenzonbenzyl (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(xxxxxxxxx)xxxxx		203–083–3	103–16–2	Xx; X36 X43	Xx X: 36-43 X: (2-)24/25–26–37
604–044–00–7	mechinol 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx		205–769–8	150–76–5	Xx; R22 Xx; X36 R43	Xn X: 22–36–43 X: (2-)24/25–26–37/39–46
605–016–00–7	xxxxxxx… % ethandial… %	X	203–474–9	107–22–2	Xxxx. kat. 3; X40 Xn; R20 Xx; R36/38 X43	Xx X: 20–36/38–40–43 S: (2-)36/37	X ≥ 10 %: Xn; X20–36/38–40–43 1 % ≤ X < 10 %: Xx; X40–43
606–016–00-X	xxxxxx (XXX) 2-(trimethylacetyl)indan-1,3-dion		201–462–8	83–26–1	T; R25–48/25 X; R50–53	T; X X: 25–48/25–50/53 X: (1/2-)37–45–60–61
606–018–00–0	xxxxxxx (XXX) 2,3-xxxxxxx-1,4-xxxxxxxxxxx		204–210–5	117–80–6	Xx; X22 Xi; X36/38 X; R50–53	Xn; X X: 22–36/38–50/53 S: (2-)26–60–61
606–019–00–6	xxxxxxxxxx (ISO) perchlorpentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-on xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-dekachlorpentacyklo[5.3.0.02,6.04,10.05,9]dekan-3-on		205–601–3	143–50–0	Karc. xxx. 3; X40 T; X24/25 N; R50–53	T; X R: 24/25–40–50/53 X: (1/2-)22–36/37–45–60–61
606–034–00–8	xxxxxxxxxx (ISO) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 H)-on 4-amino-6-terc-butyl-3-(methylsulfanyl)-4,5-dihydro-1,2,4-triazin-5-on		244–209–7	21087–64–9	Xn; X22 N; R50–53	Xn; X R: 22–50/53 X: (2-)60-61
606–035–00–3	xxxxxxxxxxx (XXX) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx pyrazon		216–920–2	1698–60–8	R43 X; X50–53	Xx; X R: 43–50/53 X: (2-)24–37–60–61
606–036–00–9	xxxxxxxxxxxxxx (XXX) 6-methyl-2 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx		219–455–3	2439–01–2	Xxxx. xxx. 3; R62 Xx; X20/21/22–48/22 Xx; X36 R43 X; X50–53	Xx; X R: 20/21/22–36–43–48/22–50/53–62 X: (2-)24–37–60–61
606–037–00–4	xxxxxxxxxxx (XXX) 1-(4-xxxxxxxxxxx)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		256–103–8	43121–43–3	Xx; X22 N; X51–53	Xx; X X: 22–51/53 X: (2-)61
606–044–00–2	2,4,6-xxxxxxxxxxxxxxxxxxx fenyl(2,4,6-trimethylfenyl)methanon		403–150–9	954–16–5	Xn; X22 Xx; R36 X; R50–53	Xn; X X: 22–36–50/53 X: (2-)26–60–61
607–043–00-X	xxxxxxx (XXX) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx		217–635–6	1918–00–9	Xx; R22 Xi; X41 X52–53	Xx; N X: 22–41–52/53 X: (2-)26-61
607–057–00–6	xxxxxxxxx (ISO) 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; R48/22 X52–53	Xx X:48/22–52/53 X: (2-)37-61
607–058–00–1	kumafuryl (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -chromen-2-on 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X -xxxxxxx-2-xx		204–195–5	117–52–2	X; X25–48/25 R52–53	T X:25–48/25–52/53 X: (1/2-)37–45–61
607–079–00–6	kelevan (XXX) ethyl-4-oxo-5-(perchlor-5-hydroxypentacyklo[5.3.0.02,6.03,9.04,8]dekan-5-yl)pentanoát xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx		—	4234–79–1	X; X24 Xn; X22 N; R51–53	T; X R: 22–24–51/53 X: (1/2-)36/37–45–61
607–097–00–4	xxxxxx-1,2,4-xxxxxxxxx-1,2-xxxxxxxx 1,2-anhydrid xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxx		209–008–0	552–30–7	Xx; X37–41 R42/43	Xn 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 X:34–52/53 X: (1/2-)26–36–45–61
607–152–00–2	2,3,6-XXX (XXX) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx		200–026–4	50–31–7	Xx; X22 X; R51–53	Xn; X X: 22–51/53 X: (2-)61
607–153–00–8	xxxxxxxxx (XXX) (4-xxxxx-2-xxx-2,3-xxxxxxx-1,3-xxxxxxxxxxxx-3-xx)xxxxxx xxxxxxxx		223–297–0	3813–05–6	Xx; X36/38 X52–53	Xx X:36/38–52/53 S: (2-)22-61
607–156–00–4	xxxxxxxxxxx (XXX) 4-chlorfenyl-4-chlorbenzen-1-sulfonát		201–270–4	80–33–1	Xn; X22 Xx; R38 X; X50–53	Xx; X X: 22–38–50/53 S: (2-)37–60–61
607–158–00–5	sodná xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx sodný		223–498–3	3926–62–3	T; X25 Xx; R38 X; X50	X; X R: 25–38–50 S: (1/2-)22–37–45–61
607–159–00–0	xxxxxxxxxxxxxx (XXX) xxxxx-2,2-xxx(4-xxxxxxxxxx)-2-xxxxxxxxxxxxx ethyl-4,4'-dichlorbenzilát		208–110–2	510–15–6	Xn; 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 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}oxy)poly(oxyethylen)		400–830–7	—	R43 X; R51–53	Xi; X X: 43–51/53 X: (2-)36/37–61
607–188–00–9	xxxxxxx-xxxxxxxx-X-(2-xxxxxxxxxxxx)-X-(xxxxxxx-9-xx-1-xx)xxxxxxxxxx		402–970–4	—	X43 X; R51–53	Xi; X X: 43–51/53 X: (2-)24/37–61
607–209–00–1	Xxxx: X,X′-xxxxxxxxxxx-xxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); O,O′-diisopropyl-pentasulfanbis(karbothioát)		403–030–6	—	Xn; X22 X43 X; X50–53	Xx; X X: 22–43–50/ 53 S: (2-)36/37–60–61
607–213–00–3	ethyl-3,3-bis(terc-pentylperoxy)butanoát		403–320–2	67567–23–1	E; X2 O; X7 X10 X; X51–53	X; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61
607–217–00–5	2-ethoxyethyl-[4-(7-fenyl-2,6-dioxo-2,6-dihydro-1,5-dioxa-s-indacen-3-yl)fenoxy]acetát		403–960–2	—	R43 X53	Xx X: 43-53 S: (2-)24–37–61
607–243–00–7	xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-hydroxyethyl)amonium-3,6-dichloranisát [3]		217–846–3 [1] 246–590–5 [2] 258–527–9 [3]	1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3]	X52–53	X: 52/53 X: 61
607–248–00–4	Xxxxxxxx-xxxxxxx Xxxxxxx-X-(1-xxxxxx)xxxxxxxx		205–073–4	132–67–2	Xx; X22	Xx X: 22 X: (2)
607–249–00-X	(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx tripropylenglykol-diakrylát XXXXX		256–032–2	42978–66–5	Xx; X36/37/38 R43 X; X51–53	Xx; N X:36/37/38–43–51/53 X: (2-)24–37–61	C ≥ 10 %: Xx; X36/37/38–43 1 % ≤ X < 10 %: Xi; X43
607–252–00–6	λ-xxxxxxxxxxx (XXX) Xxxx (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 Xn; X21 N; X50–53	X+; X X: 21–25–26–50/53 X: (1/2-)28–36/37/39–38–45–60–61
607–255–00–2	xxxxxxxxxx (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx kyselina		—	69377–81–7	R52–53	R: 52/53 X: 61
608–003–00–4	xxxxxxxxxxxx	X X	203–466–5	107–13–1	X; Xxx Xxxx. xxx. 2; R45 T; X23/24/25 Xx; X37/38–41 X43 X; R51–53	F; X; X X: 45–11–23-/24/25–37/38–41–43–51/53 X: 9–16–53–45–61	X ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; R45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ C &xx; 5 %:T; X45–23/24/25–43 0,2 % ≤ X &xx; 1 %:T; R45–20/21/22 0,1 % ≤ X &xx; 0,2 %: T; R45	43
608–016–00–5	2,3,5,6-tetrachlor-1,4-dikyanbenzen xxxxxxxxxxxxxxxxxxxxxxxxx		401–550–8	1897–41–2	X43 N; X50–53	Xx; X R: 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+; R28 X; R24 R44 X; R50–53	T+; N 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; X22 X; R50–53	T; X X: 45–61–22–50/53 X: 53–45–60–61
609–044–00–0	xxxxxxxx (ISO) 1,2,4,5-xxxxxxxxxx-3-xxxxxxxxxxx		204–178–2	117–18–0	Xx; X22 X43 X; X50–53	Xx; X R: 22–43–50/53 S: (2-)24–37–60–61
611–008–00–4	4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx		200–453–6	60–09–3	Xxxx. xxx. 2; X45 X; R50–53	T; X X: 45–50/53 X: 53–45–60–61
611–013–00–1	4-xxxxxxx-3-{4-[2-xxxxxxx-4-(3-xxxxxxxxxxxxxxxxx)xxxxxxxx]-3-xxxxxxxxxxxxxx}-6-(3-xxxxxxxxxxxxxxxx)xxxxxxxx-2-xxxxxxxx xxxxxxxxx		403–650–7	117409–78–6	X; X2 X; X51–53	X; X R: 2–51/53 X: (2-)35-61
611–031–00-X	4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx XX Xxxxx Xxx 9 XX basická červeň 9		209–321–2	569–61–9	Xxxx. xxx. 2; X45	X X: 45 X: 53-45
612–035–00–4	2-xxxxxxxxxxxxx x-xxxxxxxx	X	201–963–1	90–04–0	Xxxx. xxx. 2; R45 Xxxx. xxx. 3; X40 X; X23/24/25	X X: 45–23/24/25 X: 53-45
612–042–00–2	xxxxxxxx xxxxxxx-4,4'-xxxxxx 4,4'-xxxxxxxxxxxxxx xxxxxxx-4,4'-xxxxxxxxxx	X	202–199–1	92–87–5	Xxxx. xxx. 1; X45 Xn; R22 X; R50–53	T; 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. xxx. 2; X45 Xxxx. xxx. 3; X40 X; X39/23/24/25Xx; X48/20/21/22 X43 N; X51–53	X; X X: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61
612–081–00–5	3,3'-xxxxxxxxxxxxxxxx, xxxx x-xxxxxxx, xxxx	X X	210–322–5 265–294–7 277–985–0	612–82–8 64969–36–4 74753–18–7	Xxxx. xxx. 2; X45 Xx; X22 N; X51–53	X; X X: 45–22–51/53 S: 53–45–61
612–099–00–3	4-methyl-m-fenylendiamin4-methyl-1,3-fenylendiamin4-methylbenzen-1,3-diamin 2,4-xxxxxxxxxxxx	X	202–453–1	95–80–7	Xxxx. xxx. 2; X45 T; R25 Xx; X21 Xi; X36 R43 X; X51–53	X; X X: 45–21–25–36–43–51/53 X: 53–45–61
612–105–00–4	2-(piperazin-1-yl)ethylamin2-(piperazin-1-yl)ethan-1-amin		205–411–0	140–31–8	Xn; X21/22 X; R34 X43 R52–53	C X: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61
612–111–00–7	2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,3-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,3-xxxxxx 2,6-xxxxxxxxxxxx		212–513–9	823–40–5	Xxxx. xxx. 3; X40 Xn; 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-methyl-p-fenylendiamin2-methyl-1,4-fenylendiamin2-methylbenzen-1,4-diamin 2,5-xxxxxxxxxxxx		202–442–1	95–70–5	X; X25 Xx; R20/21 X43 N; X51–53	X; X X: 20/21–25–43–51/53 X: (1/2-)24–37–45–61
612–144–00–7	xxxxxxxxxxx (XXX) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx		—	62924–70–3	Xx; X36/38 X4 3 X; X50–53	Xx; X X: 36/38–43–50/53 X: (2-)36/37–60–61
612–151–00–5	xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx	X	246–910–3	25376–45–8	Xxxx. xxx. 2; X45 X; X25 Xn; R20/21 Xx; R36 X43 X; X51–53	X; N X: 45–20/21–25–36–43–51/53 X: 53–45–61
613–018–00–4	xxxxxxxxxx (ISO) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx		—	7411–47–4	Xx; X22 Xi; X36/37/38 X52–53	Xx X: 22–36/37/38–52/53 X: (2-)22–36–61
613–031–00–5	xxxxxxxxx trichlorisokyanurová xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5H)-trion		201–782–8	87–90–1	O; R8 Xx; X22 X31 Xx; X36/37 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 X:22–52/53 X: (2-)61
613–042–00–5	xxxxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 X-xxxxxxxx		252–615–0	35554–44–0	Xx; X20/22 N; X41 X; X50–53	Xx; X X: 20/22–41–50/53 S: (2-)26–39–60–61
613–043–00–0	xxxxxxxx-xxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx		261–351–5 [1] 281–291–3 [2]	58594–72–2 [1] 83918–57–4 [2]	Xx; X20/22 Xx; X41 X; R50–53	Xn; X X: 20/22–41–50/53 X: (2-)26–39–60–61
613–066–00–6	xxxxxxxxxx (ISO) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx		251–637–8	33693–04–8	Xx; R22 X; X50–53	Xx; N R: 22–50/53 S: (2-)60-61
613–091–00–2	xxxxxxxxxx-xxxxxxxxx [1] xxxxxxxxxx-xxxxxx [2] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx-xxxxxxxxx [1] 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxx-xxxxxxxx [2]		225–062–8 [1]	4636–83–3 [1] 29873–36–7 [2]	Xn; R22 Xx; R36/37/38 X52–53	Xx; X: 22–36/37/38–52/53 X: (2-)22–36–61
613–098–00–0	1-xxxxxxxxxxxxxxx-2-xx 1-oktyl-2-pyrrolidon		403–700–8	2687–94–7	C; X34 X; R51–53	C; X X: 34–51/53 X: (1/2-)23–26–36/37/39–45–61
613–130–00–3	xxxxxxxxxxx (ISO) (RS)-2-(2,4-dichlorfenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol		—	79983–71–4	R43 X; R51–53	Xi; 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; R22 X52–53	Xx X:22–52/53 X: (2-)61
613–134–00–5	xxxxxxxxxxxx (XXX) 2-(4-chlorfenyl)-2-[(1 X-1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		—	88671–89–0	Xxxx. xxx. 3; X63 Xx; X22 Xx; X36 X; X51–53	Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61
613–137–00–1	xxxxxxxxxxxxxxxxxx (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx		242–505–0	18691–97–9	X; X50–53	X X: 50/53 S: 60-61
613–139–00–2	xxxxxxxxxxx-xxxxxx xxxxxx-2-{X —[X-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxxx]xxxxxxxxx}xxxxxxx		—	74223–64–6	X; X50–53	X X: 50/53 X: 60-61
614–001–00–4	xxxxxxx (XXX) 3-(1-xxxxxxxxxxxxxxxx-2-xx)xxxxxxx		200–193–3	54–11–5	X+; X27 X; X25 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] xxxxxx-xxxxxx [2] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]		225–432–9 [1] 227–317–9 [2] 269–439–5 [3] 269–710–8 [4]	4845–99–2 [1] 5786–97–0 [2] 68239–26–9 [3] 68310–42–9 [4]	X+; R26/28 R52–53	T+ X: 26/28–52/53 X: (1/2-)13–45–61
615–006–00–4	2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] xxxxxx-3,5-xxxxxxxxxxx [3]	C	202–039–0 [1] 209–544–5 [2] 247–722–4 [3]	91–08–7 [1] 584–84–9 [2] 26471–62–5 [3]	Xxxx. kat. 3; X40 X+; X26 Xx; R36/37/38 X42/43 X52–53	X+ X: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61	X320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; R26–40–42/43 1 % ≤ X &xx; 7 %: X; R23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42	2
616–010–00–9	xxxxxxx-xxxxxxxxxxxxxx X-xxxxx-4-xxxxxxxxxxxx-1-xxxxxxxxxx, xxxxx xxx		204–854–7	127–65–1	Xx; R22 R31 X; X34 X42	X X: 22–31–34–42 S: (1/2-)7–22–26–36/37/39–45
616–034–00-X	xxxxxxxxxxxx (XXX) 6-methyl-3,4-dihydro-2H-pyran-5-karboxanilid		246–419–4	24691–76–7	R52–53	R: 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 R43 X; X50–53	Xx; N X: 22–43–50/53 S: (2-)36/37–60–61
617–004–00–9	(1,2,3,4-xxxxxxxxxx-1-xxxxxx)xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxx	212–230–0	771–29–9	X; X7 Xx; X22 X; X34 X; X50–53	X; X; X X: 7–22–34–50/53 X:(1/2-)3/7–14–26–36/37/39–45–60–61	X325 %: C; X22–34 10 % ≤ X &xx; 25 %: C; X34 5 % ≤ X < 10 %: Xi; X36/37/38
617–006–00-X	xxx(α, α-xxxxxxxxxxxxxx)xxxxxxx xxx(2-xxxxxxxxxxx-2-xx)xxxxxxx xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx xxxxxxxxxxxxxx		201–279–3	80–43–3	X; X7 Xx; R36/38 N; X51–53	X; Xi; X X: 7–36/38–51/53 X: (2-)3/7–14–36/37/39–61
617–008–00–0	xxxxxxxxxxxxxxxx		202–327–6	94–36–0	X; R2 Xx; X36 X43	X; Xx; X: 2–36–43 S: (2-)3/7–14–36/37/39
650–007–00–3	xxxxxxxxxxxxx (ISO) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx		228–200–5	6164–98–3	Xxxx. xxx. 3; X40 Xx; R21/22 X; X50–53	Xx; X X: 21/22–40–50/53 S: (2-)22–36/37–60–61
650–008–00–9	xxxxxxxxxx (XXX) 4-[(2-chlorfenyl)hydrazono]-3-methylisoxazol-5(4 X)-xx		227–197–8	5707–69–7	X; R25 N; X50–53	X; N X: 25–50/53 S: (1/2-)22–24–36/37–45–60–61
650–009–00–4	xxxxxxxxxxxxx-xxxxxxxxxxxx X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx 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; X40 Xx; R22 X; X50–53	Xx; N R: 22–40–50/53 X: (2-)22–36/37–60–61
650–033–00–5	esfenvalerát (XXX) [(S)-(3-fenoxyfenyl)kyanmethyl]-(S)-2-(4-chlorfenyl)-3-methylbutanoát (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx		—	66230–04–4	X; X23/25 X43 X; X50–53	X; X X: 23/25–43–50/53 X: (1/2-)24–36/37/39–45–60–61
650–041–00–9	xxxxxxxxxxxx (XXX) 1-[2-(2-chlorethoxy)benzen-1-sulfonyl]-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)močovina		—	82097–50–5	N; X50–53	X X: 50/53 S: 60-61

PŘÍLOHA 1X

Xxxxxxxx xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx x xxxxxx	Xxxxx XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx xxxxxx	Xxxxxxxx x xxxxxxxxxx
006–090–00–8	2-[(3-xxxxxxx-2-xx-1-xx)xxx]xxxxx-X-xxxxxxxxxxxxx		408–010–0	88558–41–2	Xx; X20 Xx; X41 X52–53	Xx X: 20–41–52/53 S: (2-)22–26–39–61
014–016–00–0	Xxxx: 1,3-xx(xxx-5-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-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, X', S''-tetrafenyl-4,4'-sulfandiylbis(fenylsulfonium)-bis(hexafluorofosfát) x xxxxxxx[4-(xxxxxxxxxxxxx)xxxxx]xxxxxxxxx-xxxxxxxxxxxxxxxx		404–986–7	—	Xx; X41 X; X50–53	Xx; N 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; X41	Xx R: 41 S: (2-)26-39
601–050–00–1	X10-X13-xxxxxxxxxxxxx xxxxxxx		267–051–0	67774–74–7	X; R50	N X: 50 S: 61
601–051–00–7	4-fenylbut-1-en		405–980–7	768–56–9	Xi; X38 X; R51–53	Xi; X R: 38–51/53 X: (2-)37-61
602–083–00–4	pentabromderivát xxxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxx		251–084–2	32534–81–9	Xx; X48/21/22 X64 X; X50–53	Xx; N X: 48/21/22–50/53–64 S: (1/2-)36/37–45–60–61
602–084–00-X	1,1-xxxxxxx-1-xxxxxxxxxx		404–080–1	1717–00–6	X; R52–53–59	N X: 52/53–59 S: 59-61
603–128–00–0	2-(xxxxxxxxxxxx)xxxxxxxx		405–490–3	613–62–7	X53	X:53 X: 61
603–129–00–6	1-xxxx-xxxxxxxxxxxx-2-xx		406–180–0	57018–52–7	X10 Xi; X41	Xx R: 10-41 X: (2-)26-39
603–130–00–1	Směs xxxxxxx: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx)		406–325–8	—	Xx; R22 R52–53	Xn X:22–52/53 X: (2-)39-61
603–131–00–7	Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxxx)xxxxx]-X-xxxxxxxx		407–290–1	—	Xx; X41	Xx X: 41 X: (2-)26-39
603–132–00–2	2-(xxxxxxxxxxxxx)-6-xxxxxxxxx-9-xxxxxx-1,4-xxxxxxxxxx[4.5]xxxxx		408–200–3	63187–91–7	Xx; X38–41 X52–53	Xx X:38–41–52/53 X: (2-)26–37/39–61
603–133–00–8	Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)		408–240–1	—	Xx; X22 X52–53	Xx R:22–52/53 X: (2-)22–36–61
603–134–00–3	Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx x 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 N; X51–53	Xx; N X: 41–51/53 X: (2-)26–39–61
603–136–00–4	3-{4-[xxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxxx}xxxxxx-1-xx		410–910–3	104226–19–9	X43 X52–53	Xx X:43–52/53 X: (2-)24–37–61
603–137–00-X	Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-deoxy-1-[methyl(1-oxooktadecyl)amino]-D-glucitol		411–130–6	—	Xi; X41	Xx R: 41 X: (2-)26-39
603–138–00–5	3-(2,2-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-dimethyl-3-(3-methylfenyl)propan-1-ol		403–140–4	103694–68–4	R52–53	R:52/53 X: 61
604–050–00-X	4-xxxxx-x-xxxxxx 4-chlor-2-methylfenol		216–381–3	1570–64–5	T; X23 C; X 35 N; R50	T; X; X X: 23–35–50 S: (1/2-)26–36/37/39–45–61	X ≥ 25 %: X; C; X23–35 10 % ≤ X &xx; 25 %: X;X20–35 5 % ≤ C &xx; 10 %: X;X20–34 3 % ≤ C < 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 - benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)fenol] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx		403–800–1	103597–45–1	X53	X:53 X: 61
604–053–00–6	4-xxxx - xxxxx-2-xxxxxx-6-(1-xxxxxxxxxxxxxxxx)xxxxx		410–760–9	157661–93–3	Xx; X38 X43 X; X50–53	Xx; X X: 38–43–50/53 X: (2-)24–37–60–61
604–054–00–1	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 X: (2-)24–37–61
604–055–00–7	4,4'-xxx[(2,3-xxxxxxxxxxx)xxx]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx		413–900–7	85954–11–6	Xxxx. Kat.3; X40	Xx X: 40 X: (2-)22–36–37
605–027–00–7	Xxxx:3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X-xxxxx-6-xxxxxxxxxxx x 3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx		410–480–7	—	X43 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 X: 51/53 X: 61
606–052–00–6	4-(X, N-dibutylamino)-2-hydroxy-2'-karboxybenzofenon 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx kyselina		410–410–5	54574–82–2	R52–53	R:52/53 X: 61
607–272–00–5	xxxxxxxxxxx-xxxxxx (XXX) [1] xxxxxxxxxx-xxxxxxxxx (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-xxxxxx-1-xxxxxxxxxxx)-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [2]		279–752–9 [1] —	81406–37–3 [1] 154486–27–8 [2]	X; X50–53	X X: 50/53 X: 60-61
607–273–00–0	amonium-7-{2,6-dimethyl-8-[(2,2-dimethylbutanoyl)oxy]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx		404–520–2	—	X52–53	X:52/53 X: 61
607–274–00–6	{2-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx		405–350–1	54527–73–0	X43 N; X51–53	Xx; X X: 43–51/53 S: (2-)24–37–61
607–275–00–1	xxxxxxx-4-(xxxxxxxxxx)xxxxxx-1-xxxxxxxx		405–450–5	66531–87–1	X43	Xx X: 43 S: (2-)24-37
607–276–00–7	[xxx(2-xxxxxxxxxxxxxx) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx komplex		405–635–0	—	Xi; X38–41 N; R50–53	Xi; X X: 38–41–50/53 X: (2-)26–37/39–60–61
607–277–00–2	Směs:2-(hexylsulfanyl)ethylamin-hydrochlorid a xxxxxxx-xxxxxxxxx		405–720–2	—	Xx; R22 Xx; X41 X43 N; X51–53	Xx; X X: 22–41–43–51/53 X: (2-)24–26–37/39–61
607–278–00–8	Xxxx:xxxxx(X7-X9 xxxxxxxxxx x xxxxxxxxxxxx)-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) a (xxxxxxxxxxxxxx)xxxxxxxxx-(xxxxxxxx-xxxxxx)-(xxxxxxxx-xxxxxxxx)		405–960–8	—	X43 X; R51–53	Xi; X X: 43–51/53 X: (2-)24–37–61
607–280–00–9	4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx sodný natrium-4-chlor-1-hydroxybutan-1-sulfonát		406–190–5	54322–20–2	Xn; X22 Xi; R36 X43	Xx R: 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 S: 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; R21/22 Xi; 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	Xxxx (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) 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 R: 51/53 X: 61
607–285–00–6	Xxxx:7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxxx kyselina, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x xxxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx		410–065–0	—	X43	Xx X: 43 X: (2-)22–24–37
607–286–00–1	Xxxx:xxxxxx- x natrium-7-[4-({4-[(2-hydroxy-1-naftyl)azo]fenyl}azo)benzensulfonamido]naftalen-1,3-disulfonát		410–070–8	141880–36–6	R43 X52–53	Xx R:43–52/53 S: (2-)22–24–37–61
607–287–00–7	xxxxxx-[1-xxxxxx-2-(xxxxxxxxxxxxxxx)xxxxx]-1,2,3,6-xxxxxxxxxxxxxxxx		410–140–8	—	X52–53	X:52/53 S: 61
607–288–00–2	[x-(X -{3-[(1-{3-[(2,6(4,6)-xxxxxxx-5-xxxxxxxxxxxxx-4(2)-xx)xxxxxxxxxxx]xxxxxx}-2-xxxxxxx-4-xxxxxx-6-xxx-1,6-xxxxxxx-3-xxxxxxx)xxx]-4-xxxxxxxxxxxxxx}xxxxxxxxx)-x,x,x -xxxxxxxxxxxxxxxxxxxxxxx]xxxxxxxxx komplex, xxxxxxxxxx xxx; x = 15, 16, 17 xxxx 18, x = 1, 2, 3 xxxx 4, b = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25		410–160–7	148732–74–5	Xx; X36 X43 X52–53	Xx X: 36–43–52/53 X: (2-)22–26–36/37–61
607–288–00–8	3-[(3-{X —[4-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxx]xxxxxxxxx}-4-xxxxxxx-1-xxxxxx)xxxxxxxx]xxxxxxxxx xxxxxxxx		410–370–9	105488–33–3	X53	X:53 X: 61
607–290–00–3	Xxxx (o 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; R38 X43 X; X50–53	Xx; N X: 38–43–50/53 X: (2-)24–37–60–61
607–291–00–9	xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx		410–630–1	104051–92–5	X53	X: 53 X: 61
607–292–00–4	Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx xxxxxxxx		410–640–6	—	Xx; X38–41 X; X50–53	Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61
607–293–00-XXxxx:	1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx		410–650–0	—	Xx; X41 R43 X; R51–53	Xi; N X: 41–43–51/53 X: (2-)26–36/37/39–61
607–294–00–5	xxxxxxx-2-(xxxxxxxxxx)-1-xxxxxxxxxxxx-1-xxxxxxxx		410–680–4	—	X43	Xx X: 43 X: (2-)24-37
607–295–00–0	Xxxx:xxxxxxxxxxxx-xxxxxxxxxxxxxxxxx x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx		410–800–5	—	X43 N; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
607–296–00–6	Xxxx:xxxxxxxxxxx xxxxxxxxxxxxxxxx, xxxxxxxxx kyselina a 2-xxxxxxxxxxxxx kyselina		410–830–9	—	R53	R: 53 X: 61
607–297–00–1	3,3'-(1,4-fenylendimethyliden)bis(2-oxobornan-10-sulfonová kyselina)2,2'-dioxo-3,3'-(1,4-fenylendimethyliden)bis(1,7,7-trimethylbicyklo[2.2.1]heptan-1-methansulfonová xxxxxxxx)		410–960–6	92761–26–7	Xx; X41	Xx X: 41 S: (2-)26-39
607–298–00–7	[2-(trimethylamonio)ethyl]-4-sulfonatobenzoát		411–010–3	—	R43	Xi X: 43 X: (2-)22–36/37
607–299–00–2	xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx		411–040–7	97101–46–7	Xx; R22 X43 X; X50–53	Xx; X X: 22–43–50/53 X: (2-)24–37–60–61
607–300–00–6	[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx xxxxxxx, xxxxxxxx sůl; a = 1,2,3 nebo 4, x = 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 xxxxxxxx x xxxxxxxxxxx xxxxx(1-7)xxxxxxx		411–860–5	—	Xx; X38–41 X43 X; X51–53	Xx; N R: 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 R43 X; X51–53	Xx; X X: 38–41–43–51/53 X: (2-)24–26–37/39–61
607–303–00–2	1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx xxxxxxxx		413–760–7	93107–30–3	Xxxx. kat.3; X62 R52–53	Xn R: 62–52/53 X: (2-)22–36/37–61
608–023–00–3	4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		406–140–2	114369–43–6	X; X50–53	X X: 50/53 X: 60-61
608–024–00–9	2-{4-[xxxxx(xxxxxxxx)xxxxx]xxxxx}xxxxx-1,1,2-xxxxxxxxxxxxxx		407–650–8	97460–76–9	X53	X:53 X: 61
608–025–00–4	[2-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; R3 X; X8 Xxxx. xxx. 2; R45 X; X23/25 X43	X; T X: 45–3–8–23/25–43 X: 53-45
610–010–00–2	1-xxxx-2-(2-xxxxx)-1-xxxxxxxxxx		406–110–9	35950–52–8	Xx; X22–48/22 X; X34 R43 X; X50–53	X; X X: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61
611–043–00–5	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 xxxxxxxx x[{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný		402–850–1			Xi X: 41–52/53 S: (2-)26–39–61
611–044–00–0	Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx a[(4(5)-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato) (3-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx		403–720–7	117527–94–3	X; 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	N X: 51/53 S: 61
611–046–00–1	4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx		407–590–2	43151–99–1	X; X25 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	Xxxx (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[(2-acetoxyethyl)ethylamino]fenyl}azo)-6,7-dichlorbenzothiazol		407–890–3	111381–11–4	R53	R: 53 X: 61
611–048–00–2	Xxxx (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx a 2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx	407–900–6	111381–12–5	X53	X: 53 S: 61
611–049–00–8	Směs (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, xxxxxxxx xxxxxx x mléčná kyselina (2:1:1)	408–000–6	118658–98–3	Xx; X48/22 X43 X52–53	Xx X: 43–48/22–52/53 X: (2-(22–36/37–61
611–051–00–9	2-({4-[ethyl(2-hydroxyethyl)amino]-2-methylfenyl}azo)-6-methoxy-3-methylbenzothiazolium-chlorid		411–110–7	136213–74–6	N; X50–53	X X: 50/53 X: 60-61
611–052–00–4	[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx xxxxxxx, xxxxx sůl		400–720–9	—	R52–53	R: 52/53 X: 61
612–156–00–2	Xxxx:xxxxxxxxxxxx(xxxxxx)xxxxxxx-xxxxxxx a xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx		405–620–9	—	Xx; X41 X; X50–53	Xx; X X: 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 Xi; X41 X43 X; R51–53	Xn; X X: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61
612–158–00–3	Xxxx:[xxx(5-xxxxx(xxxxxxxxxx C12))-2-hydroxybenzaldoximato)]měďnatý xxxxxxx x 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxxxxxxxxxxxxxxxx		410–820–4	—	X53	X: 53 X: 61
612–159–00–9	xxxxxxx xxxxxxxx směsi 2,2,4-xxxxxxxxx- x 2,4,4-trimethylhexan-1,6-diaminu (x xxxxxxx XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Epoxid 8) a 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx		410–880–1	—	Xx; X22 X; X34 N; 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-xxxx-xxxxx-5-[(4-xxxx-xxxxxxxxxxx)xxxxxxxx]-4-xxxxxxxxxxxxxx-3(2X)-xx		405–700–3	96489–71–3	X; X23/25 X; X50–53	X; X X: 23/25–50/53 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 H)-dion		406–360–9	104218–44–2	R53	R:53 X: 61
613–152–00–3	xxxxx-X-(4,6-xxxxxxxxxxxxxxxxxx-2-xx)xxxxxxxx		406–600–2	89392–03–0	X43 N; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
613–153–00–9	2,3,5-xxxxxxxxxxxxxxx		407–270–2	16063–70–0	X52–53	X:52/53 X: 61
613–154–00–4	2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx		410–050–9	5734–64–5	Xx; R22	Xn R: 22 S: (2-)22
613–155–00-X	5-xxxxx-2,3-xxxxxxxxxxxxxx		410–090–7	89402–43–7	X10 Xx; R22 X52–53	Xx X: 10–22–52/53 X: (2-)23–36–61
613–156–00–5	2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-xxxxx-5-xxxxxxxxxxxxx-4-xxxxxxxxxxx		410–260–0	83857–96–9	X43 N; X51–53	Xx; N R: 43–51/53 X: (2-)24–37–61
613–157–00–0	2,4-diamino-5-(methoxymethyl)pyrimidin 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx		410–330–0	54236–98–5	Xx; X22–48/22 Xx; X36	Xx R: 22–36–48/22 X: (2-)22–26–36
613–158–00–6	2,3-dichlor-5-(trifluormethyl)pyridin		410–340–5	69045–84–7	Xn; R20/22 Xx; X41 R43 X; X51–53	Xx; X X: 20/22–41–43–51/53 X: (2-)24–26–37/39–61
613–159–00–1	4-[2-(4-xxxx-xxxxxxxxxx)xxxxxx]xxxxxxxxxx		410–580–0	120928–09–8	X; X25 Xx; X20 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 X: (2-)24-37
615–022–00–1	xxxxxx-3-(xxxxxxxxxxxxxxxxxx)xxxxxxx-2-xxxxxxxxxx		410–550–7	79277–18–2	X; X2 X14 Xx; X48/22 X42/43	X; Xn X: 2–14–42/43–48/22 X: (2-)22–30–35–36/37
615–023–00–7	xxxxxxxxxxx 2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxxx kyselinymethyl-2-[(isokyanatosulfonyl)methyl]benzoát		410–900–9	83056–32–0	R10 X14 Xxxx. xxx. 3; R40 Xx; X20–48/22 Xx; X41 X42	Xx X: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39
616–044–00–4	X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)-2-(3-xxxxxxxxxxxxxxxx)xxxxxxxxx		402–510–2	—	X; X51–53	X X: 51/53 S: 61
616–045–00-X	2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(diethylamino)-2-methoxyacetanilid		405–190–2	122371–93–1	R43 X53	Xx X: 43-53 X: (2-)22–24–37–61
616–046–00–5	X -[2-(6-chlor-7-methylpyrazolo[1,5-b][1,2,4]triazol-4-yl)propyl]-2-(2,4-di-terc-pentylfenoxy)oktanamid		406–390–2	—	N; R50–53	N X: 50/53 X: 60-61
616–047–00–0	Xxxx:X,X′,X″,X′′′ - tetraalkyl(C16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x X, N′,N″,N′′′ - xxxxxxxxxx(X18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx		406–640–0	—	X43	Xx R: 43 X: (2-)24-37
616–048–00–6	3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx		406–740–4	1939–27–1	Xx; X48/22 X; 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 N; R50–53	Xi; X X: 43–50/53 X: (2-)24–37–60–61
616–051–00–2	Xxxx:3,3'-xxx(4-xxxxxxxxxxx)- 1,1'-(4-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx x 3,3'-xxx(4-xxxxxxxxxxx)-1,1'-(2-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx		411–070–0	—	X53	X: 53 X: 61
617–015–00–9	xxx(4-xxxxxxxxxxxxx)xxxxxxx		407–950–9	895–85–2	X; R2 X; R7 X; X50–53	X; N X: 2–7–50/53 S: (2-)7–14–36/37/39–47–60–61
650–032–00-X	xxxxxxxxxxxx (XXX) (2X, 3R)-, (2 X, 3 X)-, (2 R, 3 X)-, (2 X, 3 R)-2-(4-chlorfenyl)-3-cyklopropyl-1-(1H- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	94361–06–5	Xxxx. kat. 3; X63 Xx; X22 X; X50–53	Xx; X X: 22–50/53–63 X: (2-)36/37–60–61

XXXXXXX 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX S XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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

XXXXXXX 3X

XXXXXXXXXX POKYNY XXX XXXXXXXX ZACHÁZENÍ X NEBEZPEČNÝMI LÁTKAMI X PŘÍPRAVKY

Viz xxxxxxxx Xxxxxx 2001/59/ES,

Úř. věst. X 332, 28.12.2000, x. 81.

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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

PŘÍLOHA 4A

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx na xxxxxxxxxxxx xxxxxxx u savců xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx v xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Rozlišují xx xxx typy xxxxxxxxxxxx aberací: chromozomové x xxxxxxxxxxxx. U xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx xxxxxx vyskytují. Xxxxxx xxxxxxxxxxx xxxx znamenat, xx xxxxxxxx xxxxx xx schopnost xxxxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxx však xxxx xxxxxx ke xxxxxxxxx xxxxxxxxxxx aberací x xxxx k xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxx xxxx xxxx xxxxxxxx xxxxx geneticky xxxxxxxxxxx chorob u xxxxxxx x existuje xxxxx xxxxxx x xxx, xx xxxxxxxxxxxx xxxxxx x x xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx v xxxxxxxxxx a x xxxxxx somatických buněk xxxxxxxxx xxxxxx, xxxx xxxxx xx indukci xxxxxxxx x xxxxxxx x x xxxxxxxxx xxxxxx.

Xx zkoušce xx xxxxxxxxxxxx xxxxxxx xx xxxxx mohou xxx xxxxxxx xxxxxxxxxxxxx buněčné xxxxx, xxxxxxx kmeny xxxx primární buněčné xxxxxxx. Použité xxxxx xxxx vybrány xx xxxxxxx xxxxxxxxxx růstu x kultuře, xxxxxxxx xxxxxxxxx, xxxxx chromozomů, xxxxxxxxxxxx chromozomů a xxxxxxxxx xxxxxxxx chromozomových xxxxxxx.

Xxxxxxx prováděné in xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační systém xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xx xxxxx se xxxxx xxxxxxxxx xxxxxxxx, které xx vedly x xxxxxxxxxx výsledkům, xxx xxxxxxxxxx xxxxxxx mutagenitu x xxxx x xxx xxxxx změnou xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx zkouška xx používá xx xxxxxxxx xxxxxxx mutagenů x xxxxxxxxxxx xxx xxxxx. Mnoho xxxxxxxxx, xxx něž je xxxx zkouška pozitivní, xxxx pro savce xxxxxxxxxxx; xxxx xxxxx xxxxxxxx a xxxxxxxxxxxxxx xxxx není xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx chemické třídě x xxxxxxxxx xxxxxx x tom, že xxxxxxxx xxxxxxxxxxx, které xxxxxx xxxxxxxx xxxxx xxxxxxxx, neboť xxxxxx xxxxxx xxxxxx xxxxxxxxxx xxx přímým xxxxxxxxxx XXX.

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx poškození xxxxxxxxxx x podobě xxxxx xxxx zlomu x xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxxxxxxxxxxxxxx : xxxxxx, xxx xxxxxx x xxxxx po S-fázi xxxxxxxxx XXX nedojde x xxxxxx, xxxxx xxxxxxxxx xxxxx S-fáze. Xxxxxxxxx xxxx chromozomy xx 4, 8, 16… xxxxxxxxxxxx.

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

Xxxxxxxxx xxxxx : xxxxx xxxxx, xxxxx xx xxxxxxxxx v xxxxxxxx, x xxxxxxxxx počtu xxxxx x xxxxxxxx; xxxxx xxxxxx xxxxxxxxxxx xxxx xxxxxxxx.

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

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx; xxxx xx jako xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. V xxxxxx xxxxxxxxxxx xxxxxxxxxxx po xxxxxxxx xxxxx xx xx xxxxxxxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx xxxxxx, obarví x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx se zjistí xxxxxxxxxxxxxx pozorováním xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx xxxxx xxxxxxx xxxxx, xxxxx nebo xxxxxxxx xxxxxxx kultury, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (xxxx. fibroblasty xxxxxx xxxxxxxx, lymfocyty xxxxxxxxx xxxx člověka xxxx xxxxxx savců).

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx nádoby, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). X xxxxxxxxxxxxxxx buněčných linií x xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxxx stabilita modální xxxxxxx xxxxx xxxxxxxxxx x xxxx xx xxx xxxxxxxxxxxx, zda xxxxxx xxxxxxxxxxxxx mykoplasmaty; x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Xxx xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu.

1.4.1.3 Xxxxxxxx kultur

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

Xxxxxxxxx: xxxx ošetřená xxxxxxxxxxxxxxx (xxxx. xxxxxxxxx) xxxx oddělené xxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx xx xxxxxxxxxxxx xxxxx obsahujícího mitogen (xxxx. xxxxxxxxxxxxxxxx) x xxxxxxxx xx xxx 37 °X.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx by měly xxx vystaveny xxxxxxxx xxxxx, a xx x xxxxxxx xxxxxxxxxxxx xxxxxxxx x bez xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx je kofaktorem xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx indukujícím xxxxxx, xxxx je Xxxxxxx 1254 (6, 7, 8 x 9), xxxx xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 x 12).

Postmitochondriální xxxxxx xx x xxxxxxxx xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx xxxxxxxxxxxxx aktivačního xxxxxxx xxxx xxxxxxx xx xxxxx chemické xxxxx, xxxxx xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx může být xxxxxx xxxxxx více xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx výsledků xxxxxx, včetně xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx buněčných xxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Volba použitých xxxxxxxxx xxxxx xx xxxx xxx vědecky xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx cytochromu P450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx látky xx xxxx xxx před xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech a xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx by být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx možnost skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx být xxxx podezření, že xxxxxxx se xxxxxxxxx xxxxxx, a xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx nestálých xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

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

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x metabolickou aktivací x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, xxxx xxxx xxxxxx konfluence, xxxxx xxxxxxxxxxxxxxx buněk xxxx mitotický index. Xxxx být xxxxxxx xxxxxxxx cytotoxicitu x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx alespoň xxx xxxxxxxxxxxxxx koncentrace. X xxxxxxx xxxxxxxxxxxx xx xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx dané xxxxxxxxx xx minimální xxxxxxxxx, případně xxxxxx xxxxxxxxx, což xxxxxxx xxxxxxx, xx xx xx xxxxxxxxxxx neměly xxxxx více xxxxx xxxxxxxx 2 xx Ö10. X xxxxxxxx xxxxxxx xx xxxx xxxxxxxx koncentrace xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxx, xxxxx xxxxx xxxx xxxxxxxxxxx xxxxxx (xxx o více xxx 50 %). Xxxxxxxxx xxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx době, xxxxx xxxxxxxx xx xxxxxxxx. Xxxxxxxxx index je xxxx přijatelný x xxxxxxxxxxx kultur, u xxxxx xxxxx xxx xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx a xxxxxxxxxxx. Informace x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (AGT), xxxxx xxx xxxxxxx xxxx xxxxxxxxx xxxxxxxxx. V xxxxxxx AGT však xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx nelze usoudit xx existenci zpožděných xxxxxxxxxxx, x x xxxx xxxxxxxxx průměrné xxxxxxxxx xxxx může xxx xx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx výtěžku xxxxxxx.

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

X xxxxxxx relativně xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx toxické xxx xxxxxxxxxxxxx nižších, xxx xx jejich xxxxxxxxxxx, xx xxxx xxx xxxxxxx nejvyšší xxxxx x xxxxxxxxxxx, jež xx xxx xxxx xxxxxxxxxxxx v xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxx aplikace. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx xx xxxxxxxx xxxxx xxx xxxxxxx koncentracích, xxx xx rozpustnost) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, xxx xxxxx xxxxxxx xx xxxxxxx. Xxxx být užitečné xxxxxxxx xxxxxxxxxxx xx xxxxxxx a na xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx x testovacím xxxxxxx se xxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, séra X9 atd. Xxxxxxxxxxxxx xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x negativní xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx). Xxx xxxxxxx metabolické xxxxxxxx xx xxxx být xxx pozitivní xxxxxxxx xxxxxxx xxxxxxxx látka, xxxxx k xxxxxxxxx xxxxxx vyžaduje xxxxxxxx.

X xxxxxxxxx xxxxxxxx xx xxx xxx použit xxxxx xxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx, xxxxx xxxxxxxx poskytnou reprodukovatelný x xxxxxxxxxxxxx xxxxxx xxx xxxxxx, čímž xx prokáže xxxxxxxxx xxxxxxxxxxx systému.

Koncentrace xxxxxxxxxxx xxxxxxx by měly xxx xxxxxxx tak, xxx byl účinek xxxxxxxx, ale xxx xxx odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Příklady xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx:

Xxxx metabolické aktivace	Látka	Číslo 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 xxxxxxxxxxxx xxxxxxxx	xxxxx[x]xxxxx	50–32–8	200–028–5
	xxxxxxxxxxxxx	50–18–0	200–015–4
	xxxxxxxxxxxxx xxxxxxxxxx	6055–19–2	200–015–4

Xxx xxxxxxxxx xxxxxxxx xxxxx být xxxxxxx x jiné xxxxxx látky. Xxx xxxxxxxxx kontrolu by xxxx být xxxxx xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx xx xxxx xxx použity xxxxxxxxx xxxxxxxx skládající xx xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx x xxxxxxxxxxx xxxxx a xxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx. Kromě xxxx xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx žádné xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo xxxxxxxxxx žádné xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx zkoušené xxxxx

Xxxxxxxxxxxxx buňky xx xxxxxxx xxxxxxxx látce xxx za xxxxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx, xxx bez xxxx. Xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxxx xxx 48 xxxxx xx xxxxxxxxx stimulaci.

1.4.3.2 Xxx každou xxxxxxxxxxx xx xxxx xxx xxxxxxx použity xxxxxxxxxx xxxxxxx, a xxxxx xx xxxxxxx doporučuje x xxxxxx xxx xxxxxxxxx kontrolu xxxx xxxxxxxx rozpouštědla. Xxxxxxxx xxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxx jediné kultury.

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

1.4.3.3 Xxxx xxxxxxx kultur

V prvním xxxxxxxxxxx by xxxx xxx xxxxx vystaveny xxxxxxxx xxxxx, jak x metabolickou aktivací, xxx bez xx, xx xxxx 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx (12). Jestliže tento xxxxxx xxxx negativní xxxxxxxx jak s xxxxxxxx, tak xxx xxxxxxxx, xxx xx xxx proveden dodatečný xxxxxxxxxx xxx xxxxxxxx x nepřetržitou xxxxxxxx xx do xxxxxx x době, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx xxxxx xxx snáze xxxxxxxxx xxx xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx xxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxx metabolické xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx xxxxxxx. X xxxxxxxxx, kdy xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx výsledků xx xxxxxxxx, xx mělo xxx podáno xxxxxxxxxx.

1.4.3.4 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xx xxxxxxx xxxxxxx se xxxxxxx 1-3 xxxxxx xxxx xxxxxxxxx xxxxx Xxxxxxxx® xxxx kolchicin. Xxx xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xx xxxxx xxxxxxx kultura xxxxxx x zpracovává xxxxxx. Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxx buněk, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Analýza

Všechny xxxxxxxxx, xxxxxx preparátů pozitivních x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx analýzou xxx xxxxxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx xx xxxxx xxxxx buněk x metafázi x xx xxxxxx xxxxxxxxxx, xxxx by xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x xxxxx xxxxxx xxxxxxx xxxxxxx ± 2 xxx všechny xxxx buněk. Xx xxxxxx koncentraci x xxxxxxxx xx mělo xxx xxxxxxxxx alespoň 200 dobře xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx xxxxxx, je-li xxxxxxxxx xxxxx xxxxx xxxxxxx.

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

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxxxx jednotkou je xxxxx x mělo xx xxxx xxx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Pro xxxxxxxxx a experimentální xxxxxxx by xxxx xxx xxxxxxx různé xxxx strukturních chromozomových xxxxxxx x jejich xxxxxx a xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx a uvádějí xx, ale xxxxxxxxxx xx do xxxxxxx xxxxxxxx xxxxxxx.

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

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

Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx experimentálních podmínek. Xxxxxxxxxx potvrdit xxxxxxxxx xxxxxxxx byla xxxxxxxxxxx x bodu 1.4.3.3. Xxxxx xxxxxxxxx xxxxxx x cílem xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx měla být xxxxxxx v xxxxxxxxxx xxxxxxxxxxxxx. X parametrům xxxxxx, xxxxx by xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku existuje xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x chromozomovými aberacemi x závislosti xx xxxxxxxxxxx, nebo reprodukovatelný xxxxxx xxxxxx xxxxx. Xxxxxxxx by xxxx xxx uvážena xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx významnost xx xxxxxx xxx xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx odpověď.

Nárůst xxxxx xxxxxxxxxxx buněk xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx mitotické xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxx xxxxx xxxxx x endoreduplikovanými xxxxxxxxxx xxxx znamenat, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (17, 18).

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx vyslovit xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx ohledu xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xx xxxxxxx xx xxxxxxxxxxxx aberace in xxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x xxxxxxxxxxxxx somatických xxxxxxx xxxxx strukturní xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x xxxxxxxxxxxxx somatických xxxxxxx xxxxx strukturní xxxxxxxxxxxx aberace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx musí xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxx:

- xxx x zdroj xxxxx,

- xxxxxxxxxx karyotypu x xxxxxxxx použitého xxxx xxxxx,

- popřípadě nepřítomnost xxxxxxxxxxx,

- informace o xxxxx xxxxxxxxx cyklu,

- xxxxxxx xxxxx xxxx, xxx byla použita xxxx krev xxxx xxxxxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx,

- případně xxxxx xxxxxx,

- případně metody xxxxxxxxx xxxxxxx kultury,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx podmínky:

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

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

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX₂,

- xxxxxxxxxxx zkoušené xxxxx,

- objem xxxxxxxx x přidané zkoušené xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx doba,

- délka xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx xxxxxxxx,

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

- xxxxxxxxx a xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxxxxx,

- metody xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx studie xx xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx, xxxx. xxxxxx xxxxxxxxxx, xxxxx x buněčném xxxxx, xxxxx xxxxx, xxxxxxxxx xxxxx,

- xxxxxx xxxxxxx,

- xxxxx o xX x xxxxxxxxxx xxxxxxxxxxx média, pokud xxxx stanoveny,

- definice xxxxxxx, xxxxxx gapů,

- xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxx aberací zvlášť xxx xxxxxx exponovanou x xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- případné xxxxxxxxxxx analýzy,

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

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

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

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

2) Xxxxxxxx, X. Xx., Sofumi, X. (1985), The In xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Using Chinese Xxxxxxx Lung (CHL) Xxxxxxxxxx Xxxxx xx Xxxxxxx, xx: Progress xx Mutatation Research, Xxx. 5, Xxxxx, X. xx al., (xxx) Elsevier Xxxxxxx Xxxxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 427-432.

3) Galloway, S. X., Armstrong, X. X., Xxxxxx, X., Xxxxxx, X., Brown, X., Xxxxxx, X., Xxxxx, A. D., Xxxxxxxx, X., Ahmed, X., Xxx, X., Xxxxx, X., Xxxxxxxx, X. H., Resnick, X. A., Anderson, X., Xxxxxx E. (1978), Xxxxxxxxxx aberration xxx xxxxxx chromatic xxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx xxxxx: Xxxxxxxxxx xx 108 xxxxxxxxx, Xxxxxxx. Molec. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Scott, X., Galloway, S. X., Xxxxxxxx, R. X., Ishidate, X. Xx., Brusick, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx under Xxxxxxx Xxxxxxx Conditions. X xxxxxx from ICPEMC Xxxx Xxxxx 9, Xxxxxxxxxx Xxx., 257, 147-204.

5) Xxxxxx, T., Xxxxxx, X., Fukuda, X., Okumura, X., (1992), Xxxxxxxxxxxxxx xx xxx xX xx Xxxxxxx Cultured Xxxxxxxxx Xxxxx, Mutatation Xxx., 268, 297-305.

6) Ames, X. X., XxXxxx, X., Xxxxxxxx, X. (1975), Xxxxxxx for Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx xxxx the Xxxxxxxxxx/Xxxxxxxxx Microsome Mutagenicity Xxxx, Xxxxxxxx Res., 31, 347-364.

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

8) Xxxxxxxxx, X. X., Xxxxx, X. X., xxx Xxxx, X. X. X., Meijers, X., xx Vogel, N. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx after Xxxxxxxxxx xx x Xxxxxxxxxxx Xxxxxx In xxxxx, I. Xxxxxxxxx xx Chromozome Xxxxxxxxxxx xxx Sister Chromatid Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) xx CHO Xxxxx xx xxx Xxxxxxxx xx Rat-Liver Xxxxxxxxxx, Mutatation Xxx., 37, 83-90.

9) Xxxxxxxx, X., Hayashi, X., Xxxxxxxx, X. Xx. (1979), Chromozomal Aberration Xxxxx xx 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Xxx Xx xxxxx, Xxxxxxxx Xxx., 66, 277-290.

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

11) Xxxxxxxxxx, T., Sawamura, X., Hara, X., Xxxxxxxx, X. (1976), X. Xxxx Substitute xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. s. an Xxxxxxx xx Metabolic Xxxxxxxxxx Systems, xx: xx Xxxxxx, X. X., Xxxxx, X. X. Xxxx, J. X., Philpot, R. X. (xxx), Xx xxxxx Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, Xxxxxxxx, North-Holland, 85-88.

12) Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. Jr., Xxxxx, J. X., Xxxxxxxx, X. X., Xxxxxx, X., Xxxxxxx, X., Sofumi, T. (1994), Xxxxxx from Xxxxxxx Xxxxx xx Xx vitro Tests xxx Xxxxxxxxxxx Xxxxxxxxxxx, Xxxxxxxxxx Res., 312, 241-261.

13) Xxxxxxxxxx, X., Xxxxxxxx, D. A., Xxxxx, X. X., Xxxxxxxx, X., Chanter, X. X., Xxxxxxxx, X. (1989), Analysis xx Xxxx xxxx Xx vitro Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, Xxxxxxxx, X. X., (ed) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 141-154.

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

15) Xxxxx, D. X., Xxxxxx, X. C., XxXxxxx, X. T. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx of Xxxxx and Xxxxxxxx Xxxxxxx, in: Xxxx, X. X., Costa, X. L., Schaich, X. M. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Xxxxxx, New Xxxx, Plenum, 91-103.

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

17) Locke-Huhle, X. (1983), Endoreduplication xx Xxxxxxx xxxxxxx xxxxx xxxxxx alpha-radiation xxxxxxx G2 arrest, Xxxxxxxxxx Res., 119, 403-413.

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

PŘÍLOHA 4X

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

1. XXXXXX

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

1.1 ÚVOD

Zkouška xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx xx používána xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx aberací xxxxxxxxxxxx xxxxxxxxx xxxxxx x xxxxxxx kostní dřeně xxxxx, obvykle hlodavců (1, 2, 3, 4). Rozlišují se xxx typy strukturních xxxxxxx — xxxxxxxxxxxx x chromatidové. Nárůst xxxxxxxxxxx může xxxxxxxx, xx chemická xxxxx xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx jsou xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx aberace xx xxxxxx vyskytují. Xxxxxxxxxxxx mutace x xxxxxxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx x xxxxxxxx xxxxx důkazů x xxx, že xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx způsobující změny x xxxxxxxxxx x x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx xxxxxxx rakoviny x xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx této xxxxxxx xxxx rutinně xxxxxxxxx xxxxxxxx. Xxxxxxx xxxxx je v xxxx xxxxxxx xxxxxx xxxx, poněvadž xx xxxxxx xxxxxxxxxxxxxxxx xxxxx x obsahuje xxxxxxxx xxxxx x xxxxxxx xxxxxx, které se xxxxxx xxxxxxx x xxxxxxxxxxxx. Xxxx druhy x cílové tkáně xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx aberace je xxxxxxx určená x xxxxxxxxx nebezpečí xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx, farmakokinetiku x xxxxxxx reparace DNA, xxxxxxx xx xxxxx x xxxxxxx xxxxx x xxxxx měnit. Xxxxxxx in vivo xx xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxxxxx xx vitro.

Jestliže xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx nedostanou xx cílové tkáně, xxxx xxxxxx tuto xxxxxxx použít.

Viz xxxx Xxxxxx úvod, část X.

1.2 DEFINICE

Chromatidová aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x podobě xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx xxxxx x xxxxxxxx spojení chromatid.

Chromozomová xxxxxxx : strukturní xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx xxxxx a xxxxxxx xxxx chromatid v xxxxxx xxxxx.

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

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

Xxxxxxxxx aberace : xxxxxxxx xxxxx chromozomů xx xxxxxxxx hodnoty xxxxxxx u použitých xxxxx.

Xxxxxxxxxxx : násobek xxxxxxxxxxx xxxxx xxxxxxxxxxxxxx xxx (x), xxxx xxx diploidní (tj. 3 n, 4 x xxx.).

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx xxxxxxxxxx xxx buněčném dělení xx xxxxxx xxxxxxxx; xxxx xx jako xxxxxx a xxxxxxxxx, xxxxxxxxxxxxxxxxxx nebo interchromozomální xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xx xxxxxxx xxxxxxxx xx xxxxxxxx xx xxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx se xxxx xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx x xxxxxxxxx se xxxxxxxxxxxx xxxxxxx xxxxx x xxxxxxxx.

1.4 XXXXX ZKUŠEBNÍ XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx potkan, myš x xxxxxx xxxxxx, xxxxxx lze xxxxxx xxxxxxxx vhodný xxxxx xxxx. Xxxx by xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx xxxxxx. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x hmotnosti xxxxxx minimální x xxxxxx xx x 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 xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata se xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx skupinu x xxxxxxx, xxxxx xx xxxxxxx xxxxxxxx xxxxx. Xxxxx xx xxxx být uspořádány xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx v xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené látky xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx xxxxxxxxxx a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky mohou xxx xxxxxxxx přímo xxxx mohou xxx xxxx xxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx a mělo xx být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx použita jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Doporučuje se xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx by xxxx xxx pozitivní a xxxxxxxxx (rozpouštědlo/vehikulum) kontroly xxx xxx xxxxxxx. X xxxxxxxx aplikace xxxxxxxx látky xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx jako zvířata xx xxxxxxxxx, v xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx kontroly xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx vivo xxx expozičních xxxxxxxx, x nichž xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Xxxxx xxxxxxxxx xxxxxxxx xx měly xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, aby byla xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx xxx xxxxx x jejím případě xxxxxxxx xxx xxxxxx. Xxx pozitivní xxxxxxxx xxxxx xxx použity xxxxxxxx xxxxx ze xxxxxx xxxxxxxx třídy, xxxx-xx x dispozici. Xxxxxxxx látek xxx xxxxxxxxx kontrolu:

Látka	Číslo CAS	Číslo xxxxx EINECS
ethyl-methansulfonát	62–50–0	200–536–7
1-ethyl-1-nitrosomočovina	759–73–9	212–072–2
mitomycin C	50–07–7	200–008–6
cyklofosfamid	50–18–0	200–015–4
cyklofosfamid xxxxxxxxxx	6055–19–2	200–015–4
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx	51–18–3	200–083–5

X okamžiku xxxxxxx xxxxxx xx xxx být xxxxxxxx xxxxx u negativních xxxxxxx, jimž xx xxxxxxxxxx pouze xxxxxxxxxxxx xxxx xxxxxxxxx a xxx xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě xxxxxx x četnosti xxxxx x chromozomovými xxxxxxxxx. Xxxxxxx-xx se xxx xxxxxxxxx xxxxxxxx jeden xxxxx, xx nejvhodnějším xxxxxxxxx doba xxxxxxx xxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx kontroly použity xxxx tehdy, neexistují-li xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx a kontrolní xxxxxxx xx xxxxxx x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx pro xxxxx xxxxxxx. Xxxxxxxx xxxx x xxxx xxxxxx k xxxxxxxxx xxxxx ze xxxxxx xx stejným druhem x xx použití xxxxxxxx způsobu expozice, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx pohlavími xxxxxx x xxxxxxxx, xxxx postačující xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx zkouška xxxxxxxxx se xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx látky xx xxxx xxx xxxxx xxxxx xxxxxxxx jednorázově. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxx xx xxxx dávkách, xxx. dvě xxxxx x týž den x rozmezí ne xxxx xxx xxxxxxxx xxxxx, xxx bylo xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxxxxxx xx xxxx xxx vědecky xxxxxxxxxx.

Xxxxxx xx xxxx xxx xxxxxxxx ve xxxx xxxxxxx xxxxxxxxxxx xx aplikace xxxxxx x jednom dni. X hlodavců xx xxxxx xxxxxxx xx xxxxxx xxxx od xxxxxxxx, která xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx (jenž xxxx obvykle 12 — 18 x). Xxxxxxxx doba xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxx xxxxxx xx kinetiku xxxxxxxxx xxxxx xxxx xxx xxxx na xxxxxxxxx xxxxxxx pro xxxxxxxxx chromozomových aberací, xxxxxxxxxx xx provést xxxxx odběr xx 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx xxx jednoho xxx, xxx xx xxx odběr xxxxxxxx xx xxxxxx xxxx xx poslední xxxxxxxx, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx buněčného xxxxx.

Xxxx usmrcením se xxxxxxxx intraperitoneálně xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx metafázi (např. Xxxxxxxx® xxxx xxxxxxxxx). Xxxx se xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X xxxx xx xxxx xxxx přibližně 3 — 5 x; x xxxxxx xxxxxxxx xx tato xxxx xxxxxxxxx 4 — 5 x. X xxxxxx xxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xx xx xxxxxxxxxxxx xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se kvůli xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx xxx xxxxxxxx rozsahu xxxxx, xxxx xx být xxxxxxxxx xx stejné xxxxxxxxxx, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx stejného xxxxxx expozice, xxx xx xxxxxxx v xxxxxx studii (5). X xxxxxxx xxxxxxxx xx pro první xxxxx použijí xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx použita xxxxx nejvyšší xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, že xxxxx xxxxx by vedly xxx xxxxxxx xxxxxx xxxxxxxxx podle xxxxxxxxx x letalitě. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx dávkách (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx x xxxx xx xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx x kostní xxxxx některé xxxxxx xxxxxxxx (např. xxxx xxx 50 % xxxxxxx xxxxxxxxxxx xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x jednou dávkou xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo ve xxxx xxxxxxx v xxxxxx dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx nezbytnou. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx xxx 14denní xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx delší xxx 14xxxxx xxxxxxxx xx xxxxxxx dávkou 1000 xx/xx tělesné xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx nebo xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx xxxx x odůvodněných případech xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx podán xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx překročit 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, xxxx xxx zdůvodněno. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, by xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx koncentrace zajišťující xxxxxxxxxx objem při xxxxx úrovních dávky.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů

Ihned po xxxxxxxx xx xxxxxxx xxxxxx dřeň, hypotonizuje xx x fixuje. Xxxxx xx xxxxxxx xx podložní sklíčka x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx xxxxxxx xxxxxxxxxxxx xx měl xxx x xxxxx xxxxxxxxxxxx xxxxxx (xxxxxx xxxxxxxxxxx xxxxxxx) x x xxxxxxxxxxxxxx xxxxxx xxx xxxxxxxxx kontrolu xxxxxxxx xxxxxxxxx index, a xx xxxxxxx u 1000 buněk na xxxxx xxxxx.

X xxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx alespoň 100 buněk. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx by xxxx xxx xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx při xxxxxx často dochází xx xxxxxxxxxxxxxx zlomům xxxx xx xxxxxx xxxxxxxxxx x xxxxx xxxxx v xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x počtu xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx, xxxxx aberací xx xxxxx a xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Pro xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx být xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx odděleně x uvádějí xx, xxx xxxxxx xx xxxxxxxxxx do xxxxxxx xxxxxxxx aberací. Xxxxxxxxxx-xx xxxxx x xxxxxxx x xxxxxxxx mezi xxxxxxxxx, xxxxx být xxx statistickou analýzu xxxxx xxx xxx xxxxxxx zkombinovány.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik kritérií, xxxx. nárůst xxxxxxxxxxx xxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na dávce xxxx jasný nárůst xxxxx buněk x xxxxxxxxx xxx skupinu x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx prostředek xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx látka xx xxxxxxxxx xxxxxxxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx xxxxxxxxxx může xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx buněčného xxxxx (7, 8).

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx neumožní soubor xxxxx xxxxxxxx konečný xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx výsledky zkoušky xx xxxxxxxxxxxx aberace xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x kostní xxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky neindukuje x kostní xxxxx xxxxxxxxxxx xxxxx chromozomové xxxxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx atd.,

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

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

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

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx popis xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx stanovení xxxxxxxx,

- identifikace xxxxx xxxxxxxxxxx xxxxxxxx, její xxxxxxxxxxx x xxxxx xxxxxxxx,

- metody přípravy xxxxxxxxx,

- kritéria hodnocení xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- mitotický xxxxx,

- xxx x xxxxx xxxxxxx uvedený xxxxxxxxxx xxx každé xxxxx,

- xxxxxxx počet xxxxxxx ve xxxxxxx xx xxxxxxxxx hodnotami x xxxxxxxxxxxx xxxxxxxxxx,

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

- xxxxx ploidie, pokud xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- případné xxxxxxxxxxx xxxxxxx,

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxx x xxxxxxxx pozitivní xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. D. (1984), Xxxxxxxxxxx Tests xx Xxxxxxx, in: Xxxxxxxxxxxx Xxxxxxx: x Xxxxxxxxx Xxxxxxxx, X. Xxxxxx, X. M. Parry (xxx), IRL Press, Xxxxxx, Xxxxxxxxxx X. X., 275-306.

2) Xxxxxxx, X. X., Dean, X. X., Xxxxxxxx, X., Holden, X., XxXxx, A. X., Xxxxxx, X. (1987), Xxxxxxxxx Xx xxxx Xxxxxxxxxxx Xxxxxx: Analysis xx Xxxxxxxxxx Aberrations xx Xxxx Xxxxxx Xxxxx, Xxxxxxxxxx Xxx., 189, 157-165.

3) Richold, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxxxxx, X. X., Bootman, X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, in: X. X. Kirkland (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Recommended Xxxxxxxxxx. XXXXX Xxx-Xxxxxxxxx xx Guidelines for Xxxxxxxxxxxx Testing. Report, Xxxx I xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. X., Xxxxxxx, X., XxxXxxxxxx, J. X., Anderson, X., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxx-Xxxxxxx, M., Xxxxxx Xx., X. B., Xxxxxxxxxxxx, X., Xxxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, S., Vannier, X. (1994), Xxxxxx xxxx xxx Working Xxxxx xx xxx xx vivo Xxxxxxxxx Xxxx Xxxxxx Chromozomal Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. J., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, P. X., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, D. X., Xxxxxxx, X. (1992), Report of Xxxxxxx Toxicology Society/UK Xxxxxxxxxxxxx Mutagen Xxxxxxx Xxxxxxx Group: Xxxx Xxxxxxx in Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, D. P., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, X., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx vivo Xxxxxxxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Test Xxxx, X. J. Xxxxxxxx (xx.) Cambridge Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 184-232.

7) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx in Xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx-xxxxxxxxx-xxxxxxx G2 xxxxxx, Xxxxxxxxxx Res., 119, 403-413.

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

XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx vivo xx xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, které je xxxxxxxxxx zkoušenou xxxxxx, x xx xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx x/xxxx buněk xxxxxxxxx xxxx, xxxxxxx xxxxxxxx.

Xxxxxx xxxxx savčích erytrocytárních xxxxxxxxxx je xxxxxxxxxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, jehož xxxxxxxxx xx tvorba xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx xx xxxxxxxxxxx xxxxxx xxxxx xxxx xx xxxxxxxxxxxxxxx xxxxxxxxx, xxxxxx xxxxx je xxxxxxxx x mikrojádra, xxxxx při xxx xxxxx xxxxxxxxx, xxxxxxxxx x xxxxxxxxxx, která xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx xxxxxxxxxx je x xxxxxx xxxxxxx xxxxxxxxx tím, xx xxxxxxxxxx xxxxxx jádro. Xxxxxx xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x xxxxxxxxxxxx zvířatech xx známkou xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx.

X xxxxx xxxxx je rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxxxx tato xxxx produkuje xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x periferní xxxx xx xxxxxxxxxx xxxxxxxxxx u xxxxxxxxxxx xxxxx, x xxxxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxxx, xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Mikrojádra xxx xxxxxxxx řadou xxxxxxxx. Ta xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxxxxx centromerní (kinetochorní) XXX x xxxxxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx. Xxxxx zralých (normochromatických) xxxxxxxxxx x periferní xxxx, které xxxxxxxx xxxxxxxxxx, xxxxxxxxxxx xx xxxxxx xxxxx zralých xxxxxxxxxx xxx rovněž xxxxxx xxxx xxxxxxx xxxxxxxx zkoušky, xxxxxxxx xxxx xxxxxxx exponována xxxxx týdny xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, třebaže xx xxxxx xxxxx x různých xxxxx x xxxxx, xxxxx x z xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx je xxxxxx xxxxxxxx pro xxxxx xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx x xxxxxxxxx xx xxxxx.

Xxxxxxxx existuje xxxxx x tom, xx se zkoušená xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx do xxxxxx xxxxx, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxx xxxx Obecný xxxx, xxxx X.

1.2 XXXXXXXX

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

Xxxxxxxxxx : xxxx jádra xxxxxxxxxx xxxxxxxx xx hlavních xxxxx a vedle xxxx, xxxxxxxxx xxxxx xxxxxxxx mitosy (xxxxxx) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxx xxxxxxxxxx.

Xxxxxxxxxxxxxxxx erytrocyt : xxxxx xxxxxxxxx xxxxxxxxxxxx ribozomy, který xxx xxxxxxxx od xxxxxxxxx polychromatických xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

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

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xx xxxxxxx xxxxxxxx xxxxxxx zkoušené xxxxx. Xxx xxxxxxx xxxxxx xxxxx xx xxxxxxx xx vhodném xxxxxxxx xx xxxxxxxx xxxxxx, xxxxxxx xx xxxxxx xxxx, připraví xx xxxxxxxxx x xxxxxx se (1, 2, 3, 4, 5, 6, 7). Xxx použití xxxxxxxxx xxxx xx krev xx vhodném xxxxxxxx xx expozici xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x obarví xx (4, 8, 9, 10). Při xxxxxxxx x xxxxxxxxx xxxx xx měla xxxx poslední xxxxxxxx x xxxxxxxxx buněk xxxxxxxx xx xxxxxxxxx xxxx. Preparáty xxxx xxxxxxxxxxx xx přítomnost xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx použití xxxxxx dřeně xx xxxx testovací xxxxx xxxxxxxxxx xxx xxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx krve xx xxxxxxxxxx xxx. Xxx xxxx použít xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx jde x xxxx, x xxxxx xxxxxxx neodstraňuje xxxxxxxxxx x xxxxxxxxxx, nebo xxxx vykazující xxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx, xxxxx způsobují xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxx xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx u xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

Xxxxx obecné podmínky xxxxx xxxxxxxx xxxxx x xxxxx B, xxxxxxx by xxxx xxx dosaženo xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx rozdělí xx kontrolní skupinu x xxxxxxx, x xxx xx xxxxxxx xxxxxxxx. Zvířata xx xxxxxxxxxxx identifikují. Xxxxxxx xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx. Xxxxx xx xxxxxxxxxx tak, xxx byl xxxx xxxxxx xxxxxx minimalizován.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě zředěny. Xxxxxxx xxxxxxxx látky xxxxx být xxxxxxxx xxxxx xxxx xxxxx xxx před xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx údaje x jejich stálosti xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx toxické xxxxxx x mělo xx xxx xxxxxxxxx podezření, xx reaguje xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx rozpouštědla/vehikula, mělo xx xxx xxxxxx xxxxxxxx xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx nejdříve zvážit xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xx xxxx při expozičních xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx pozadí. Dávky xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx při odečtu xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxxxxxxx kontrola byla xxxxxxxx xxxxx způsobem xxx xxxxxxxx xxxxx x aby xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx může xxx vzato x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x dispozici. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx 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	200–015–4
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx	51–18–3	200–083–5

X okamžiku xxxxxx xx měl být xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx je aplikováno xxxxx rozpouštědlo nebo xxxxxxxxx x která xxxxx xxxxxxxxxx stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxx. Xxxxxxx-xx se xxx xxxxxxxxx xxxxxxxx xxxxx odběr, xx xxxxxxxxxxxxx xxxxxxxxx doba xxxxxxx odběru. Kromě xxxx by měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx xxxx xxxx xxx jako xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx krve xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx x krátkých xxxxxx x xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, xx xxxxxxxx xxxxx budou x rozpětí, které xx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx a xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx musí skládat x xxxxxxx xxxx xxxxxxxxxxxxxxxx xxxxxx pro xxxxx xxxxxxx (11). Xxxxxxxx xxxx x xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx se xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, jež xxxxxxxxx, xx neexistuje xxxx xxxxxxxxx rozdíl x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx jednoho pohlaví. Xx-xx expozice xxxxxxx xxxxxxxxxx xxx určité xxxxxxx, jako je xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by být xxxxxxx provedena xx xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx aplikace

Nelze xxxxxxxxx xxxxx xxxxxxxxxx xxxx (xx. jednu, dvě xxxx tři xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx xx xxxxxx x prodlouženým xxxxxxx podávání xxxx xxxxxxxxxx, xxxxx xx x xxxxxx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –x xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx byla xxxxxxxxx xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx dávka x xxxxxxxx xxxxxxxxx xx xx xxxxxxxx xxxxxx. Zkoušené xxxxx xxxxx být podávány xxxx ve dvou xxxxxxx, xxx. dvě xxxxx x xxx xxx v xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx být xxxxxxxx xxxxx způsoby:

a) xxxxxxxx xxxxx xx xxxxxxxx xxxxxxxx jednou. Xxxxxx xxxxxx dřeně xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx první xxxxx xx provede xxxxxxxx 24 xxxxx xx xxxxxxxx a poslední xxxxxxxxxx 48 xxxxx xx xxxxxxxx x x xxxxxxxxxx odstupem xxxx xxxxxx. Odběr xxxxx xxx 24 xxxxx po aplikaci xxxx být xxxxxxxxx. Xxxxxx periferní xxxx xx xxxxxxxx alespoň xxxxxxx, xxxxxxx první xxxxx se xxxxxxx xxxxxxxx 36 xxxxx xx xxxxxxxx a xxxxxxxx nejpozději 72 xxxxx xx xxxxxxxx x xx xxxxxxxxxxxx xx xxxxxx xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx odpověď, není xxxxx xxxxx xxxxx;

x) xxxx-xx xxxxxxxx dvě xxxx xxxx dávek xxxxx (např. dvě xxxx xxxx dávek x xxxxxxxxx 24 xxxxx), xxxx by xxx vzorky xxx xxxxxxx kostní dřeně xxxxxxxx xxxxxx xx 18 až 24 xxxxxxxx xx poslední xxxxxxxx x xxx xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 hodinách xx poslední xxxxxxxx (12).

Xxxxx potřeby xxxxx xxx navíc xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx rozsahu xxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, se stejným xxxxxx, xxxxxx, pohlavím x xx stejného xxxxxx xxxxxxxx, xxx xx xxxxxxx x xxxxxx xxxxxx (13). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx by xxxx pokrývat xxxxxxx xxxx maximální xx xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx takové známky xxxxxxxx, že xxxxx xxxxx by xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx kritériím xxxxxxxxx xxxxx vyhovovat a xxxx by xxx xxxxxxxxx případ od xxxxxxx. Xxxxxxxx xxxxx xxxx být xxxx xxxxxxxxxx jako dávka xxxxxxxxxxxx x xxxxxx xxxxx některé xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxx xxxxx xxxx v xxxxxxxxx xxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx o xxxxxxx 2000 mg/kg xxxxxxx hmotnosti podanou xxxxxxxxxxx xxxx xx xxxx dávkách v xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, není xxxxxxxxxx úplná studie xx třemi xxxxxxxx xxxxx xx xxxxxxxxx. X déle trvajících xxxxxx xx limitní xxxxxx xxx 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx hmotnosti/den x xxx xxxxx než 14xxxxx xxxxxxxx je xxxxxxx xxxxxx 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx vyšší úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx se xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání jsou xxxxxxxxxx x odůvodnitelných xxxxxxxxx. Maximální xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x xxxxxxx hmotnosti. Xxxxxxx vyšších objemů, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x žíravé xxxxx, xxxxx obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené xxxxxx, xx měla xxx xxxxxxxxxxx zkušebního xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx nebo krve

Buňky xxxxxx dřeně se xxxxxxx xxxxxxxxx x xxxxxx xxxx xxxxx xxxxx xx usmrcení. Xxxxx xx odeberou x xxxxxx nebo xxxxx x xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x xxxxxx. Xxxxxxxxx xxxx xx xxxxxxx x xxxxxx xxxx xxxx jiné xxxxxx xxxxxx xxxx. Krevní xxxxx se ihned xxxxxxxxxxxx obarví (8, 9, 10), xxxx xx xxxxxxxx xxxxxxxxx xxxxxxxx x xxxx xx xxxxxx. Použitím 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 DNA. Xxxx xxxxxx nebrání xxxxxxx xxxxxxxxxxx barviv (xxxx. Xxxxxx). Přídavné xxxxxxx (xxxx. celulosová xxxxxx x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx za xxxxxxxxxxx, že xx xxxxxxxxx xxxxxxxxxxxx funkčnost xxxxxx systémů pro xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx se stanoví xxxxx xxxxxxxxx erytrocytů x celkového (xxxxxxx + xxxxx) xxxxxxxx xxxxxxxxxx, xxxxxxx se x xxxxxxx kostní xxxxx xxxxxxx xxxxxxx xxxxxxx 200 erytrocytů x v xxxxxxx xxxxxxxxx xxxx xxxxxxx 1000 erytrocytů (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by xxxx xxx xxxx xxxxxxxx pod xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx se xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx xx xxxxxx mikrojader x xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx být získány xxxxxxxxxx xxxxxxx xxxxxxxxxx xx výskyt xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx neměl xxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx než 20 % kontrolní xxxxxxx. Jestliže xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxx xxxxx xxxx xxxx, xxx xxxx xxxxxxxx na xxxxxx xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx na xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx xxxxxxx (xxxxxxx obrazu x xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx suspenze) jsou xx odpovídajícím xxxxxxxxxx x validaci xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx měly xxx xxxxxxxxxx xx formě xxxxxxx. Experimentální xxxxxxxxx xx zvíře. Pro xxxxx analyzované xxxxx xx xxx xxx xxxxxx xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx erytrocytů x xxxxxxxxxx x xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx nepřetržitě xxxxx xxxxx nebo xxxx, xxxx xx xxx xxxx xxxxxxx xxxxx x xxxxxxx erytrocytech, xxxx-xx shromažďovány. Pro xxxxx xxxxx xx xxxxx xxxxx nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx a xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x xxxxxxxxxx. Xxxxxxxxxx-xx xxxxx x xxxxxxx x odpovědi mezi xxxxxxxxx, xxxxx xxx xxx xxxxxxxxxxxx analýzu xxxxx pro obě xxxxxxx zkombinována.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik kritérií, xxxx. xxxxxx xxxxx xxxxx x mikrojádry x xxxxxxxxxx na xxxxx xxxx xxxxx xxxxxx počtu buněk x xxxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx x k xxxxxxxx xxxxxxxx odběru. Xxxxxxxx by měla xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx výsledků zkoušky xxxxx xxx použity xxxx xxxxxxx prostředek xxxxxxxxxxx metody (18, 19). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx vyjasněny xxxxxx xxxxxxxxx, xxxxxxx x úpravou experimentálních xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx xxxx sporné xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxx xx mikrojádra xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx důsledkem xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx mitotického aparátu xxxxxxxxxxxx xxxxxxxxxxx druhu. Xxxxxxxxx výsledky xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxxx xxxxxxxxxx v xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

Xxxx xx xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, x xxxxx se xxxxxxxx xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxx xxxxx, xxxx xxxxxxxxxx do xxxxxx xxxxx (xxxx. systémová xxxxxxxx).

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

- xxxxxxxxxxx x xxxxxxx xxxxxxxx látky x rozpouštědle/vehikulu, xx-xx 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 xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx odchylka pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

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

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x přípravě zkoušené xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxxxxxx podávání,

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

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

- xxxxxxxx xxxxx x kvalitě xxxxxx a vody,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x nezralých xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx jedno zvíře,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx pozitivní, xxxxxxxxx xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx z celkového xxxxxxxx xxxxxxxxxx,

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

- xxxxxxx hodnota ± xxxxxxxxxx xxxxxxxx počtu xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx xx xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxx,

- xxxxx x xxxxxxxx x xxxxxxxxx xxxxxxxxx kontrole,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxx, J. X., Xxxxxxxx, M. X., Xxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X., XxxXxxxxx, J. X., Xxxxxx, X. W. (1983), Xxx Xxxxxxxxx xx Xxxxxxxxxxx x. x. x Measure xx Xxxxxxxxxxxx, Mutatation Xxx. 123, 61-118.

4) Xxxxxxxxx, X. X., Xxxxxx, D. H., Xxxxxx, X. C., Xxxxxxxx, X. X., Xxxxxx, X. A. (1990), Xxx Xx xxxx Micronucleus Xxxxx xx Xxxxxxxxx Xxxx Xxxxxx and Peripheral Xxxxx. X xxxxxx xx xxx U. X. Environmental Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Res., 239, 29-80.

5) XxxXxxxxx, J. X., Schlegel, X., Xxxx, X. N., Xxxx, X. X. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: A Xxxxx Screen xxx Xxxxxxxxxxx Damage Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Mice, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx xx Xxxxxxxxxx, xx. X. X. Hayes, R. X. Xxxxxxx, X. X. Miya. Elsevier, Xxxxxxxxx, 555-558.

6) MacGregor, X. X., Xxxxxx, X. X. Hite, X., Margolin, G. X., Ramel, X., Xxxxxxxx, M. X., Xxxx, R. R., Xxxx, D. (1987), Xxxxxxxxxx for the Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, X. X., Xxxx, X. X., Xxxxxx, X. X., Shelby, M. X. (1990), The xx xxxx Erythrocyte Xxxxxxxxxxxx Xxxx: Measurement xx Steady Xxxxx Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Xxxxxxx Integration xxxx Xxxxxxxx Studies, Xxxxxx. Appl. Xxxxxxx. 14, 513-522.

8) Hayashi, X., Xxxxxx, T., Xxxxxx, Y., Xxxxxx, X., Ishidate, X. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Peripheral Blood Xxxxxxxxxxxxx Xxxxx Xxxxxxxx Xxxxxx-Xxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 245, 245-249.

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

10) Xxx Xxxxxxxxxxxxx Xxxxx Xxxxx xxx the Xxxxxxxxxxxx Test (XXXXX/XXXXX, XXX: Xxx Mammalian Xxxxxxxxxxx Xxxxx Xxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx of Xxxxx) (1995), Protocol xxxxxxxxxxx for the xxxxx-xxxx xxxxx xxxxxxxxxx xxxxx micronucleus xxxx, Xxxxxxxxxxx, 10, 53-159.

11) Xxxxxxx, X., Xxxx, X. X., MacGregor, X. T., Anderson, X., Xxxxxxx, X. X., Kirsch-Volders, X., Xxxxxx, Xx. X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Shimada, X., Xxxxx, S., Xxxxxxx, X. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Micronucleus Xxxxx, Xxxxx. Xxx., 312, 293-304.

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

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

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

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

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

17) Xxxxxxxxx, X., XxXxxxxx, L. X. (1995), Xxxxxx Xxxx xxx xxx Xxxxxxxxxx of Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Erythrocyte Xxxxx xx xxx Xxxx Xxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 347, 97-99.

18) Richold, X., Xxxxx, J., Xxxxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, L. (1990), Xx vivo Xxxxxxxxxxxx Xxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, UKEMS Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx 1, revised, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

19) Lovell, X. P., Anderson, X., Xxxxxxxx, R., Xxxxxxxx, X. E., Xxxxx, X., Ferguson X., Richold, X., Xxxxxxxx, X. X., Xxxxxx, X. X. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Cytogenetic Xxxxxx, xx: D. X. Xxxxxxxx (ed.), Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data. XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx XXX, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx York, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 184-232."

XXXXXXX 4X

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

1. XXXXXX

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

1.1 ÚVOD

Při xxxxxxx xx xxxxxxxx xxxxxx s xxxxxxxxxx xx používají xxxxxxxxxxx xxxxx závislé xx xxxxxxxxxxxxxxx Xxxxxxxxxx xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x xxxxxxx xxxxxxxx xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx a xxxxxx jednoho xxxx xxxxxxxx xxxx bází XXX (1, 2, 3). Xxxxxxxx xxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxx x detekci xxxxxx, xxxxx revertují xxxxxx obsažené x xxxxxxxxxxx xxxxxxx x xxxxxxxx tak funkční xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx reverzi jsou xxxxxxxxxx díky xxx xxxxxxxxxx růst x xxxxxxxxxxxxx xxxxxxxxxxxx, xxxxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxx.

Xxxxxx xxxxxx x xxxxxxx jevy xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, že xxxxxx xxxxxx v xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx mají xxxxx xx xxxxxx xxxxxxxx x člověka x x pokusných xxxxxx. Xxxxxxx xx xxxxxxxx mutace x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx x relativně xxxxxx. Xxxxx testovacích xxxxx má řadu xxxxxxxxxx, díky xxxx xxxx xxxxxxxxxx xx xxxxxxx xxxxxx, včetně xxxxxxxxxxxxx sekvencí XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx DNA nebo xxxxxxxx xxxxxxxxxxx procesů XXX náchylných x xxxxxx. Specifičnost testovacích xxxxx xxxx xxxxxxxxxx xxxxxxx užitečné xxxxxxxxx x xxxxxx mutací, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx x dispozici xxxxx rozsáhlá databáze xxxxxxxx pro širokou xxxxx xxxxxxxx a xxxx xxxx vyvinuty xxxxx xxxxxxxxxx xxxxxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx xxxxxxxx sloučenin, x různými fyzikálně-chemickými xxxxxxxxxxx.

Xxx xxxx obecný xxxx, část X.

1.2 XXXXXXXX

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

Mutageny xxxxxxxxxx párů bází xxxx xxxxxxxx, xxx xxxxxxxxx xxxxx x xxxxxx DNA. Při xxxxxxx xxxxxxxxxx xxxxxx xx xxxxx tyto xxxxx xxxxxxxxxx na xxxxx původní xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx xxxxxx.

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

1.3 XXXXXXX XXXXX

Xxx xxxxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx prokaryotické xxxxx, xxxxx se xxxx xx xxxxx xxxxx xxxxxxx, xxxx xxxx xxxxxx, metabolismus, xxxxxxxxxxxx struktura a xxxxxxxxx procesy XXX. Xxxxxxx xxxxxxxxx in xxxxx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx xxxxxxx in xxxxx xxxxxxx zcela xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xxxxxxx xxxx xxxxxxxxxxx xxxxxx xxxxxxxxx o xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxx pro xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxx xxx počáteční vyšetření xxxxxxxxxxx aktivity, x xxxxxxx aktivity xxxxxxxxxxxx xxxxxx xxxxxx. X xxxxxxxx databáze xxxxxxx, xx mnoho xxxxxxxxxx xxxxx, xxxxx xxxx x xxxx xxxxxxx xxxxxxxxx, xxxxxxxx mutagenní xxxxxxxx x v xxxxxx xxxxxxxxx. Existují xxxxxxxx xxxxxxxxxxx činitelů, xxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxx. Příčiny xxxxxx skutečností lze xxxxxxxxx xx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxxxxxxxxx jevu, x xxxxxxxxx v xxxxxxxxxxx xxxxxxxx nebo x rozdílech x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx xxxxxxx, xxxxx zvyšují xxxxxxxxx xxxxxxx xx reverzní xxxxxx xx bakteriích, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx reverzní xxxxxx x bakteriemi nemusí xxx vhodná pro xxxxxx xxxxx chemických xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) x xxx chemické xxxxx, x nichž se xxxxxxxxxxx (xxxx x xxxxx xx xx), xx xxxxxxxxxx zasahují xx replikačního systému xxxxx xxxxx (xxxx. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx být xxxxxxxxx xxxxxxx mutagenity x savců.

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

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x to xx xxxxxxxxxxx vnějšího metabolického xxxxxxxxxxx xxxxxxx x xxx něho. Xx xxxxxxxxxxx miskovém testu xx xxxxxxxx xxxxxxxx x vrchním xxxxxx x ihned se xxxxxxx xx minimální xxxx. X xxxxxxxxxxxx xxxxxx xx xxxxxxxx xxxx inkubuje x xxxx se xxxx xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx. Xxx xxxx xxxxxxxxxx xx xx xxxx xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx x provede xx xxxxxxxx s xxxxxx xxxxxxx xxxxxxxxxxx revertantů xx xxxxxxxxx xxxxx x xxxxxxxxxxxxx.

Xx xxxxxxx xxxxxxx postupů xxxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi. Xxxx běžně xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxx xxxx (1, 2, 3, 4), preinkubační xxxxxx (2, 3, 5, 6, 7, 8), xxxxxxxxxx xxxx (9, 10) x xxxxxxxxx metoda (11). Xxxxxx xxx xxxxxxxx xxxxx x xxx xxxx xxxxxxx (12).

Xxx xxxxxxx postupy xx xxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxx testu x xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx xx xxxxxxxxxx pro provádění xxxxxxxxxxx jak s xxxxxxxxxxxx aktivací, tak xxx ní. Xxxxxxx xxxxx lze účinněji xxxxxxxxx xx použití xxxxxxxxxxxx metody. Tyto xxxxx xxxxx do xxxxxxxxxx xxxx, xx xxxxx patří mezi xxxxx krátké xxxxxxxxxx xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, azobarviva x xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, allylové sloučeniny x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx třídy xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx, xxxx xx standardní xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx být xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx použít xxxxxxxxxxxx xxxxxxx. Je xxxxx xxxxxxxxxxxxx xxxx "zvláštní xxxxxxx" (xxxxxxxx x xxxxxxxx xxxxxxx xxxxxx xxxxxxx): azobarviva a xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x xxxxxx xxxxxxxx látky (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx xx xxxxxxxxxxxx postupu musí xxx vědecky xxxxxxxxxx.

1.5 XXXXX XXXXXXXX METODY

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx kultury xxxxxxxx xx xxxx xxx kultivovány do xxxxxx exponenciální xxxx xxxx do xxxxx xxxxxxxxxxx xxxx xxxxx (xxxxxxxxx 109 buněk xx ml). Xxxxx x pozdní xxxxxxxxxxx xxxx xx neměly xxx xxxxxxx. Je xxxxxxxx, aby xxxx xxxxxxx bakterie xxxxxx xxxx životaschopných bakterií. Xxxx může být xxxxxxxx xxx xx xxxxxxx dosavadních xxxxxxxxxxx xxxxx o xxxxxxx xxxxxx, nebo xxx xxxxxx zkoušku xxxxxxxxxx xxxxx životaschopných xxxxx xx miskách.

Doporučená xxxxxxxxx xxxxxxx xx 37 °X.

Xxxx xx xxx xxxxxxx alespoň pět xxxxx xxxxxxxx. Xxxx xxxx by xxxx xxx xxxxx xxxxx X. xxxxxxxxxxx (TA1535; XX1537 xxxx TA97a xxxx TA97; TA98 x TA100), xxxxxxx xxxxxxx xx xxxxxxx x xxxxxxx laboratořích xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx čtyři xxxxx X. typhimurium xxxx pár bází XX xx primárním xxxxxxxxx xxxxx x xx xxxxx, xx xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx oxidační xxxxxxxx, xxxxxxxx způsobující xxxxxxxxxx xxxxxx XXX x hydraziny. Xxxx xxxxx xxxxx být xxxxxxxxxx xxxxx X. xxxx WP2 nebo X. xxxxxxxxxxx TA102 (19), xxxxx xxxx xx xxxxxxxxx reverzním xxxxx pár xxxx XX. Xxxxxxxxxx xxxxxxxxx xxxxx xx xxxx xxxx:

- X. xxxxxxxxxxx XX1535 x

- X. xxxxxxxxxxx XX1537 xxxx XX97x a

- X. xxxxxxxxxxx XX98 x

- X. xxxxxxxxxxx XX100 x

- X. xxxx XX2 xxxX, xxxx X. coli WP2 xxxX (xXX101), nebo X. typhimurium XX102.

Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx vláken XXX xxxx být xxxxxxxxx xxxxxxx TA102 nebo xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. X. xxxx XX2 (xXX101)).

Xxxx by xxx xxxxxxx zavedené xxxxxxx xxxxxxxx kmenové xxxxxxx, xxxxxxxxxx xxxxxxx x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx být xxxxxxxxx pro xxxxxx xxxxxxxxx xxxxxxxx kulturu (xxxxxxxx xxx kmeny X. typhimurium a xxxxxxxxx xxx E. xxxx). Xxxxxxx xx xxxx xxx xxxxxxxxxxxx xxxx fenotypové xxxxxxxxxxxxxxx, xxxxxxxxx xxxxx potřeby xxxxxxxxxx nebo xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (tj. xxxxxxxxxxxx rezistence u xxxxx XX98, XX100 x TA97a xxxx XX97, XX2 xxxX x WP2 uvrA (xXX101) x xxxxxxxxxxxx x tetracyklinová xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx xxxxxxxxxxxxxxxxxx xxxxxx (xx. xxx mutací x X. typhimurium xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x xxxX xxxxxx x X. xxxx xxxx xxxX xxxxxx u S. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxxx) (2, 3). Kmeny xx xxxx rovněž xxxxx xxxxx kolonií xxxxxxxxxxx xxxxxxxxxx xx misce x rozmezí xxxxxxxx xxxxxxxxxxx xx základě xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx a xxxxxxx x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Xxxxxx

Xxxxxxx xx vhodný xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx E (Xxxxx-Xxxxxx) x xxxxxxx) x vrchní xxxx xxxxxxxxxx xxxxxxxx x xxxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Metabolická xxxxxxxx

Xxxxxxxx xx xxxx být xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a bez xxxx. Nejčastěji xxxxxxxxxx xxxxxxxx je xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx z xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx enzymy, xxxx xx Xxxxxxx 1254 (1, 2) xxxx fenobarbitonu a β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx xxxxxx xx obvykle xxxxxxxxx x koncentracích v xxxxxxx 5 xx 30 % xxx. xx xxxxx S9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx na xxxxx zkoušené chemické xxxxx. X xxxxxxxxx xxxxxxxxx xxxx být xxxxxx xxxxxx více xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx frakce. X xxxxxxxxx x diazoniových xxxxxxxxx xxxx xxx xxxxxxxxx použití xxxxxxxxxx xxxxxxxxxxxxx aktivačního xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx nebo xxxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před xxxxxxxx xx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx mohou xxx xxxx xxxxxxxx zředěny. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx xxxxxxxx x x xxxxxxxxx X9 (22). Xxxx-xx xxxxxxx jiná xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx zařazení xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx zkoušení xxxxx nestálých xx xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx podmínky

1.5.2.1 Xxxxxxxx xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx kritéria, xxxxx mají xxx xxxxxxxxxx při stanovení xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx patří xxxxxxxxxxxx x xxxxxxxxxxx v xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx toxicitu x xxxxxxxxxxxxx x předběžných xxxxxxxxxxxxx. Cytotoxicita může xxx xxxxxxxxxx snížením xxxxx xxxxxxx revertantů, xxxxxxxxx nebo zeslabením xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx stupně přežití xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx se může xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxxxxxxxxxx by měla xxx posouzena xx xxxxxxx xxxxxxxxxxx srážení x konečné směsi xx xxxxxxxxxx zkušebních xxxxxxxx.

Xxxxxxxxxx maximální zkušební xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx xx 5 xx/xxxxx xxxx 5 μx/xxxxx. U xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by měla xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, aby xxxxx xxxx v xxxxxxx xxxxx pro xxxxxxxx xxxxxxxxxxx. Xxxxxxxx látky, xxxxx jsou xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx než 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx xxxxxxxx xx xx cytotoxické xxxxxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx xxxxxxxxxxx.

Xxxx xx být použito xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx zkoušené xxxxx, přičemž při xxxxxx xxxxxxxxxxx by xxxx xxx xxxxxxxxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx xxxx xxxxxx x xxxxxxx, xxx xx vyšetřuje xxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx xxxx xxx xxxxxxx při xxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx kontroly

Součástí xxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxx specifické xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx x metabolickou xxxxxxxx x xxx xx. Xxx pozitivní xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x použitím xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx by xxxx xxx látka (xxxxx) xxx xxxxxxxxx xxxxxxxx vybrána (vybrány) xx xxxxxxx typu xxxxxxxxx kmene xxxxxxxx.

Xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx x xxxxxxxxxxxx xxxxxxxx xxxx xxxx látky:

Látka	Číslo CAS	Číslo 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	200–015–4

Xxxx xxxxx xx xxxxxxx xxxxxxxxx xxxxxxxxx xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx XXX	Xxxxx podle XXXXXX
XX Direct Xxx 28	573–58–0	209–358–4

2-xxxxxxxxxxxxxx by neměl xxx xxxxxx xxxx xxxxxx xxxxxxxxx xxxxxxxxx xxxxx X9. Při xxxxxxx 2-xxxxxxxxxxxxxxx by xxxx být xxxxx xxxxx X9 xxxxxxxxxxxxxxxx xxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxx, například xxxxx[x]xxxxx xxxx 7,12-dimethylbenzo[a]anthracen.

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

Xxxxx	Xxxxx XXX	Xxxxx xxxxx XXXXXX	Xxxx
xxxx 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 XX97x
Xxxxxxxxxxxxxxxxx	80–15–9	201–254–7	XX102
xxxxxxxxx X	50–07–7	200–008–6	XX2xxxX a XX102
1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx	70–25–7	200–730–1	XX2, XX2 uvrA a XX2 xxxX (xXX101)
4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1	XX2, XX2 xxxX x XX2 xxxX (xXX101)
α-[(5-xxxxx-2-xxxxx)xxxxxxxxxx]xxxxx-2-xxxxxxxx (XX2)	3688–53–7		xxxxx obsahující xxxxxxxx

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

Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, zpracované xxxxx xxxxxxx způsobem xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5.3 Xxxxxx

X xxxxxxxxxx miskové xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx aktivace xx xxxxxxx xxxxxx 0,05 xx nebo 0,1 xx zkušebních xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) x 0,5 xx sterilního xxxxx x 2,0 xx xxxxxxxx agaru. X xxxxxxx zkoušky s xxxxxxxxxxxx xxxxxxxx se xxxxxxx xxxxxx 0,5 xx metabolické aktivační xxxxx xxxxxxxxxx přiměřené xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x rozmezí 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx směsi) x xxxxxxx xxxxxx (2,0 xx) x xxxxxxx x bakteriemi a xxxxxxxxx látkou xxxx xxxxxxxxx roztokem. Xxxxx xxxxx zkumavky se xxxxxxxx x přelije xxxx xxxxxx minimálního xxxxx na xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) xx zkoušená xxxxx xxxx zkoušený xxxxxx xxxx xxxxxxxxx x vrchním agarem x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx agaru xx xxxxx xxxxxxx 20 minut nebo xxxx xxxxxxxxxxx x xxxxxxxxxx kmenem (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x sterilním xxxxxx nebo metabolickým xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx se smíchá 0,05 xxxx 0,1 xx zkoušené látky xxxx xxxxxxxxxx roztoku, 0,1 xx xxxxxxxx x 0,5 xx xxxxx S9 nebo xxxxxxxxxx xxxxx x 2,0 ml vrchního xxxxx. Xxxxxxxx xx xxxx být xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx xxxxxxxx xx xxxx xxx xxx xxxxx xxxxxx dávky xxxxxxx 3 xxxxx. Použití xxxx xxxxx xx xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Případná xxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxx.

Xxxxxx nebo xxxxxx látky by xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx uzavřených xxxxxxxxxxxx xxxxxxxx (12, 14, 15, 16).

1.5.4 Xxxxxxxx

Xxxxxxx misky x xxxx xxxxxxx xx xxxx xxx inkubovány xxx 37 °X xx 48 –72 xxxxxxxx. Xx xxxxxxxx xxxxxxxxx xxxx xx xxxxxx xxxxx kolonií xxxxxxxxxx xx misku.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxx xxxxx xx xxxx xxx xxxxx xxxxxxx xxxxxxxxxx připadající xx xxxxx. Xxx xx xxx rovněž uveden xxxxx xxxxxxx revertantů xxx na xxxxxxx x xxxxxxxxx xxxxxxxxx (xxxxxxxx rozpouštědla x xxxxxxxx xxxxxxxxxxxx xxxxxxxx), xxx xx miskách x xxxxxxxxx xxxxxxxxx. Xxxxx na xxxxxxxxxxxx xxxxxxx, xxxxxxx hodnoty xxxxx kolonií revertantů xx xxxxx x xxxxxxxxxx odchylka by xxxx xxx xxxxxxxxxx xxx xxxxxxxxx xxxxx x xxxxxxxxx a xxxxxxxxx kontrolu (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Xxxxxxxxxx výsledky xx xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx xxxx xxx potvrzeny xxxxxx od xxxxxxx. Xxxxxxxx se potvrzení xxxxxxxxxxx xxxxxxxx nepovažuje xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Změna xxxxxxxxx xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx x xxxxxxxxxx experimentech. K xxxxxxxxxx xxxxxx, které xx xxxxx xxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx zpracování (xxxxxxxxxx xxxxxxx metoda xxxx xxxxxxxxxxx v xxxxxxxx xxxxx) a xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx stanovení pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx xxx xxxxxxxxx xxxxxx x xxxxxxx jednoho kmene x metabolickým aktivačním xxxxxxxx xxxx bez xxxx, x xx x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx xxx xxxxx nebo xxxx koncentrací (23). Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx výsledků xxxxxxx xxxxx xxx použity xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx zkoušené xxxxx. Výsledky xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxxxx xxxxxx s xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx látka indukuje x xxxxxx xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx bodové xxxxxx xxxxxxxxxx xxxx xxxx posunem xxxxxxx xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxx za xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxx xxxxxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx kmeny,

- xxxxx xxxxx x kultuře,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx,

- xxx x xxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxxxxx kritérií xxxxxxxxxxxxx,

- postup xxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxx xxxxxxx,

- počty xx xxxxxxxxxxxx xxxxxxx,

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

- xxxxx xxxxxxxx závislost xxxxxxxx na xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxx, X. X., McCann, X., Xxxxxxxx X. (1975), Xxxxxxx of Xxxxxxxxx Carcinogens xxx Xxxxxxxx xxxx xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 31, 347-364.

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

3) Xxxxxxxxx, X., Xxxxxxx, X., Cebula, X., Xxxxx, X., Xxxx, X., Xxxxxxxxxx, X., Xxxxxxx, C., Xxxxx, X., Xxxxxx, X., Xxxxxx, E. (1994), Xxxxxxxxxxxxxxx for xxx Xxxxxxxxxxx xx Xxxxxxxxx Xxxxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 312, 217-233.

4) Kier, X. X., Xxxxxxx X. X., Xxxxxxx, A. X., Xxx Xxxxx, X. X., Xxxxx, X. M., Xxxxxx, X. X., Dunkel, X., McCann, X., Xxxxxxxxxx, X., Prival, X., Rao, X. X., Ray X. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Microsomal Assay: X Report xx xxx U. X. Xxxxxxxxxxxxx Protection Agency Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, X., Xxxxxx, X., Xxxxx, X. X., Matsushima, X., Xxxxx, M., Sugimura, X., Xxxxxxxxx, X. (1975), Mutagenicity xx Xxxxxxxxxx Xxx Xxxx xxx xxxxx Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

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

7) Xxxxxxxxx, D. X., Rowland, X. X., Xxxxxx, P., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Assays, xx: Xxxxx Mutagenicity Xxxxx: UKEMS Xxxx 1 Xxxxxxx, ed. X. X. Xxxxxxxx, Xxxxxxxxx University Xxxxx, 13-61.

8) Aeschacher, X. X., Wolleb, X., Xxxxxxx, L. (1987), Xxxxxx Preincubation Xxxxxxxxxxxx Xxxx xxx Foods, X. Xxxx Xxxxxx., 8, 167-177.

9) Green, X. X. L., Xxxxxx, W. X., Xxxxxxx, B. A. (1976), Use of x simplified xxxxxxxxxxx xxxx to xxxxxx xxx levels xx xxxxxxxx, Xxxxxxxxxx Xxx., 38, 33-42.

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

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

12) Araki, X., Xxxxxxx, X., Xxxx, X., Matsushima, T. (1994), Improved Xxxxxx xxx Xxxxxxxxxxxx Xxxxxxx xx Xxxxxxx Xxxxxxxxx xx Using x Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

13) Xxxxxx, M. X., Xxxx, S. X., Xxxxxxxx, X. X., Reipert, M. X., Xxxxxxx, X. X. (1984), Mutagenicity xx Xxxxxxxxx xxx Xxxxxxxxx-Xxxxxxxx Xxxx xxx Xxxxxxxx Xxxxxxx Xxxx xx x Xxxxxxxx Xxxxxxxxxx Assay, Xxxxxxxxxx Xxx., 136, 33-47.

14) Xxxxxx, X., Xxxxxxxx, X. X., Xxxxxxx, X., Xxxxxx, T., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Mutagenicity Xxxxx. X. Xxxxxxx xxxx xxx Testing xx 311 Xxxxxxxxx, Xxxxxxx. Xxx. Mutagen., 19, 2-141.

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

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

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

18) Xxxxxx, G., Xxxx, X., Ferro-Luzzi, X., Xxxx, X. X. (1980), Fecalase: A Xxxxx xxx Activation xx Dietary Glycosides xx Xxxxxxxx xx Xxxxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. X, 77, 4961-4965.

19) Xxxxxx, X., Xxxxxx, X., Xxxx, X. X., Xxxxxxxxx, X. X. (1990), Comparison xx Xxxxxxxxxx typhimurium XX 102 with Xxxxxxxxxxx xxxx WP2 Tester xxxxxxx, Xxxxxxxxxxx, 5, 285-291.

20) Matsushima, X., Xxxxxxxx, X., Hara, X., Xxxxxxxx, X. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Xxxxxxxxx x. x. xx Xxxxxxx or Xxxxxxxxx Xxxxxxxxxx Systems, xx: In xxxxx Xxxxxxxxx Xxxxxxxxxx in Xxxxxxxxxxx Testing, eds. X. J. de Xxxxxx et al. Xxxxxxxx, Xxxxx Xxxxxxx, 85-88.

21) Xxxxxx, X. X., Combes, R. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Mackay, J. X., Wolf, X. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 xx xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

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

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

24) Xxxxx, G. A. X., Xxxxx, M. X. X., Xxxxxxxxx, X., Xxxxxxx, I., Xxxxxxxx, X. X., Xxxxxx, D. X. (1989), Xxxxxxxx xx Xxxx xxxx Xxxxxxxxx Xxxxxx Xxxxxx, xx: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx for Mutagenicity Xxxxxxx, Xxxx XX. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Xxxx Data, xx. Kirkland, X. X., Cambridge Xxxxxxxxxx Xxxxx, 28-65."

PŘÍLOHA 4E

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

1. METODA

Tato metoda xx xxxxxxxx xxxxxx XXXX XX 476 — Xxxxxxx na xxxxxx mutace v xxxxxxx xxxxx xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců xx xxxxx lze xxxxxx xxx detekci xxxxxxxx xxxxxx indukovaných xxxxxxxxxx látkami. Xxxx xxxxxx xxxxxxx xxxxx xxxxx buňky xxxxxxx X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x X79 křečka xxxxxxxx x xxxxxxxxxxxxxxx xxxxx XX6 člověka (1). X těchto xxxxxxxxx linií jsou xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx xxxxxx xxxx xxx xxxxxxxxxxxxxx (TK) x hypoxanthin-guaninfosforibosyltransferasu (HPRT) x xxxxxxxx xanthin-guaninfosforibosyltransferasy (XXXX). Xxxxxxx xx xxxxxx XX, XXXX x XXXX xxxxxxxx xxxxx spektrum xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxx XX a XXXX xxxx umožnit xxxxxxx xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx xxxxxx), xxxxx xxxxx xxxxxxxxx x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx xxxxxxx na xxxxxx xxxxxx v xxxxxxx savců in xxxxx lze xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx buněčné xxxxx. Buňky xx xxxxxxxx podle schopnosti xxxxx v xxxxxxx x xxxxxxxx četnosti xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx obecně xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx metabolický aktivační xxxxxx xxxxxx zcela xxxxxxxxx xxxxxxxx in xxxx x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx podmínek, xxxxx by xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx vlastní xxxxxxxxxx. X xxxxxxxxxx xxxxxxxxx, xxx neodrážejí xxxxxxx xxxxxxxxxx, xxxx xxxxx změnou xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx a xxxxxxxxxxx xxxxx. Xxxxx xxxxxxxxx, xxx xxx xx xxxx zkouška xxxxxxxxx, xxxx xxxxxxxxxxx xxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx závisí na xxxxxxxx třídě x xxxxxxxxx důkazy o xxx, xx existují xxxxxxxxxxx, které xxxxxx xxxxxxxx xxxxx zkouškou, xxxxx xxxxxx působí xxxxxx, negenotoxickými xxxxxxxxxx, xxxx xxxxxxxxxx, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx úvod, část X.

1.2 XXXXXXXX

Xxxxx mutace : genová xxxxxx xxxxxxxxx xxxx mutované xxxxx, xxxxx xxxxxxxxx xxxxx xxxx xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxxxxxxx xxxx xxxx : látky, xxxxx způsobují substituci xxxxxxx nebo xxxx xxxx xxxx v XXX.

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx xxxxxxxxx xxxxx nebo xxxxxx xxxxxxx nebo xxxx xxxx bází x xxxxxxxx XXX.

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

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

Xxxxxxxxx celkový xxxx : xxxxxx xxxxx xxxxx v xxxx xx srovnání x xxxxxxxxx populací xxxxx; xxxxxxx se xxxx xxxxxx xxxxxx xxxxxxxxx růstu x xxxxxxxx a x xxxxxxxxx xxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx růst x xxxxxxxx : xxxxxx xxxxx xxxxx x xxxxxxx xxxxxxx vzhledem x xxxxxxxxx xxxxxxxx.

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

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx XX+/-® XX— /- xxxxxxxxxx xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxx pyrimidinu xxxxxxxxxxxxxxxxx (TFT). Buňky xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx xx XXX, xxx způsobuje xxxxxxxx xxxxxxxxx metabolismu a xxxxxxxxx xxxxx xxxxxxx xxxxxx. Mutantní xxxxx xxxx xxxx xxxxxxx xxxxxxxxxxx xx přítomnosti XXX, xxxxxxx xxxxxxxx xxxxx, které xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Podobně xxx x xxxxx x xxxxxxxxxxxx XXXX nebo XXXX xxxxxxx selekci xxxxxxxxxxxxxxx xxxxxxxxxx k 6-xxxxxxxxxxx (XX) xxxx 8-xxxxxxxxxx (XX). Xxxxxxxxxx xxxxxxxx látky by xxxx xxx xxxxxxx xxxxxxx, xxxxxxxx je xx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xxxxxxx xxxxxx báze xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx například xxxxxxxxx xxxxxxxx xxxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx pro xxxxxxxx xxxx nemutantní buňky. Xxx xxxxxxxx xxxxxxxxxx xxxxx, které mají xxxxxxxx xxxxxxxxx xxxx xxxxxxxx xxxxxxx, musí xxxx být xxxxxxxxx xxxxxxxx xxxxxxx nebo xxxxxxx xxx xxxxxxx (8).

Xxxxx x xxxxxxxxx xxxx jednovrstevné xxxxxxx xxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxx x xxxxxxxxxxxx xxxxxxxx, tak xxx xx, x xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx x xx xxxxxx exprese fenotypu xxxx xxxxxxx mutantů (9, 10, 11, 12, 13). Cytotoxicita xx obvykle xxxxxx xxxxxxxxxx relativní xxxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx kultur xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx kultury se xxxxxxx v růstovém xxxxx po vhodnou xxxx xxxxxxxxxxxxxxxxx xxx xxxxx xxxxxxx xxxxx x xxx buněk, xxx xxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxxx exprese xxxxxxxxxxxx xxxxxx. Četnost xxxxxxx se xxxxxxx xxx, xx se xxxxxx xxxxx xxxxx xxxxx xx xxxxx xxxxxxxxxxxx selekční činidlo xxx detekci mutantních xxxxx a xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx byla xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxx). Po xxxxxx xxxxxxxxx xxxx se xxxxxxxxx kolonie. Četnost xxxxxxx se xxxxxxx x počtu xxxxxxxxxx xxxxxxx x xxxxxxxxx xxxxx x počtu xxxxxxx v xxxxx xxx selekčního xxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x této xxxxxxx xxxx x xxxxxxxxx xxxxx xxxx xxxxx, xxxxxx xxxxxxxx xxxxx X5171X, XXX, XXX-XX52, X79 nebo TK6. Xxxx xxxxx x xxxx xxxxxxx xx xxxx vykazovat citlivost x chemickým xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxxxx, xxx nejsou xxxxxxxxxxxxx xxxxxxxxxxxx, a x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx.

Xxxxxxx by měly xxx xxxxxxxx tak, xxx xxxx předem xxxxxxxxxx citlivost x xxxx. Počet xxxxxxxxx xxxxx, kultur x xxxxxxxxxxx xxxxxxxx xxxxx xx xxx tyto xxxxxxxxxx xxxxxxxxx xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, které přežijí xxxxxxxx x xxxxx xxxxx použity x xxxxxx xxxxxx xxxxxxx, xx xxx xxx xxxxxxx na xxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxxxx je, xxx xxx použit xxxxx xxxxx, xxxxx je xxxxxxxxxxxxxx xxxxxxxxxx hodnoty xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však doporučeno, xxx xxxx xxxxxxx xxxxxxx 106 buněk. Xxxx by xxx x xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx o xxxxxxxx xxxxxxxx systému, xxx xxxx doložena xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx použita xxxxxx xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (kultivační xxxxxx, xxxxxxxxxxx XX₂, xxxxxxx a xxxxxxx). Xxxxx xx xxxx xxx zvolena podle xxxxxxxxxx systémů a xxxx xxxxx xxxxxxxxx xxx xxxxxxx. Xx xxxxxxx xxxxxxxx, xxx xxxxxxxxxx xxxxxxxx byly xxxxxxx tak, aby xxxx xxxxxxxxx xxxxxxxxx xxxx buněk xxxxx xxxxxx xxxxxxx x xxxxxxxxx xxx mutovaných, xxx nemutovaných buněk xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxx by měly xxx získávány x xxxxxxxxx kultur, nasazeny xx xxxxxxxxxxxx xxxxx x xxxxxxxxxx při 37 °C. Před xxxxxxxx x této xxxxxxx xxxx xxx xxxxxxxx odstranit x xxxxxxx již přítomné xxxxxxxx xxxxx.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

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

Xxxxxxxxxxxxxxxxxxx xxxxxx xx v konečném xxxxxxxxxx médiu xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx 1 — 10 % xxx. Xxxxx x xxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, která xx xxxxxxxx. X xxxxxxxxx případech xxxx xxx vhodné xxxxxx xxxx xxx xxxxx xxxxxxxxxxx postmitochondriální xxxxxx.

Xxxx xxxxxxxx vývoje, včetně xxxxxxxx geneticky xxxxxxxxxxxxxx xxxxxxxxx xxxxx exprimujících xxxxxxxxxx aktivační enzymy, xxxxxxxxx možnosti xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx buněčných xxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx metabolismus xxxxxxxx látky).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx být xxxxxxx přímo k xxxxxxxxxx systémům x/xxxx xxxxx být xxxx xxxxxxxx zředěny. Měly xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx mělo xxx xxxx xxxxxxxxx, xx xxxxxxx se zkoušenou xxxxxx, x mělo xx být xxxxxxxxxx x xxxxxxxx xxxxx x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx než xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo xx xxx jejich xxxxxxxx xxxxxxxxx údaji o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud možno xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx látek nestálých xx xxxx by xxxx být použitá xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

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

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxx x bez ní x hlavním experimentu xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x růstu, xxxx xxxx relativní účinnost xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx by být xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. V xxxxxxx toxicity by xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx, případně žádnou xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx, xx xx xx xxxxxxxxxxx xxxx xxxxx faktorem 2 xx Ö10. Xx-xx maximální koncentrace xxxxxxxx od xxxxxxxxxxxx, xxxx xx xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx nejméně 10 %) xxxxxxx (relativní xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx celkový xxxx. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx látek by xxxx xxx maximální xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 X, xxxxx toho, xxxxx x xxxx xx xxxxxxxx.

Xxxxxxxxx nerozpustné xxxxx xx xxxx xxx xxxxxxxx až x xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx podmínek, xxxx xx xx xxxx xxx. Měla xx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx, ve kterému xxxx buňky xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx se xxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx systému xxxxx x xxxxxxxx xxxxxxxxxxx xxxxx, X9 xxxx, xxx. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx by neměla xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxx

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

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx být xxxx xxxxx:

Xxxx metabolické xxxxxxxx	Xxxxx	Xxxxx	Xxxxx XXX	Xxxxx podle Einecs
Bez xxxxxx xxxxxxxxxxx aktivace	HPRT	ethyl-methansulfonát	62–50–0	200–536–7
	HPRT	1-ethyl-1-nitrosomočovina	759–73–9	212–072–2
	TK (xxxx x velké xxxxxxx)	xxxxxx-xxxxxxxxxxxxxx	66–27–3	200–625–0
	XXXX	xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
	XXXX	1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
X vnější xxxxxxxxxxxx xxxxxxxx	XXXX	3-xxxxxxxxxxxxxxxxx	56–49–5	200–276–4
		X-xxxxxxxxxxxxxxxxxxx	62–75–9	200–549–8
		7,12-xxxxxxxxxxxxxxxxxxxxxx	57–97–6	200–359–5
	XX (xxxx a xxxxx kolonie)	cyklofosfamid	50–18–0	200–015–4
		cyklofosfamid xxxxxxxxxx	6055–19–2
		xxxxx[x]xxxxx	50–32–8	200–028–5
		3-xxxxxxxxxxxxxxxxx	56–49–5	200–276–5
	XXXX	X-xxxxxxxxxxxxxxxxxxx (xxx xxxxxx úrovně X9)	62–75–9	200–549–8
	XXXX	xxxxx[x]xxxxx	50–32–8	200–028–5

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

Xxxx xx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxxxxxxx xxxxx stejným xxxxxxxx jako xxxxxxxxxx xxxxxxx. Xxxxx toho xx xxxx xxx xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, neexistují-li xxxxx kontrolní xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Postup

1.4.3.1 Expozice xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx xxx za xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx xx měla xxxxx xxxxxxx xxxx (xxxxxxx xx xxxxxx xxxx 3 až 6 xxxxx). Xxxxxxxxx xxxx xxxx xxx xxxxxxxxxxx na xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx mohou být xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx exponovaná xxxxxxx. Xx-xx xxxxxxx xxxxx xxxxxxx, měl xx xxx počet xxxxxxxxxxx xxxxxx xxx, xxx xxx zajištěn xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (xxxx. xxxxxxx osm xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx xxxxxxx duplicitní xxxxxxxxx kontrolní kultury (xxxxxxxx xxxxxxxxxxxx).

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

1.4.3.2 Stanovení xxxxxxx, xxxxxxxxxxxxxxxx x četnosti xxxxxx

Xx konci expoziční xxxx se buňky xxxxxxx a xxxxxxxxx xx účelem xxxxxxxxx xxxxxxx x xx xxxxxx xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx. Se xxxxxxxxxx xxxxxxxxxxxx prostřednictvím xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (přežití) nebo xxxxxxxxxxx celkového xxxxx xxxxxx se xxxxxxx xxxxxxx xx xxxxxxxxx xxxx.

Xxxxx lokus má xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, xxx umožnil xxxxxxxxx optimální xxxxxxxxxxx xxxxxxx nově xxxxxxxxxxxx xxxxxxx (HPRT x XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, XX alespoň xxx xxx). Xxxxx xxxx xxxxxxxxxxx x xxxxx xx xxxxxxxxx xxxxxxxx (selekčními xxxxxxx) x xxx něho (xxx xxxx) za xxxxxx stanovení xxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx. Se stanovením xxxxxxxxxxxxxxxx (použité xxx xxxxxxx xxxxxxxx mutantů) xx započne xx xxxxx xxxx xxxxxxx xxxxxxxxx xx xxxxx xxx xxxxxxxxxx xxxxxxx.

Xx-xx xxxxxxxx xxxxx xxxxxxxxx xx zkoušce L5178Y XX+/-, xxxx xx xxx xxxxxxxxx alespoň xx xxxxx xx xxxxxxxxxx xxxxxx (s xxxxxxxx pozitivní koncentrací) x xx xxxxxxxxxxx x pozitivních kontrolách xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx. Je-li xxxxxxxx látka xx xxxxxxx X5178X TK+/- xxxxxxxxx, mělo xx xxx xxxxxxxxx kultury xxxxx velikosti xxxxxxx xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 XX+/- xxxx být také xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií.

2. XXXXX

2.1 XXXXXXXXXX VÝSLEDKŮ

Údaje xx měly zahrnovat xxxxxxxxx cytotoxicity x xxxxxxxxxxxxxxxx, xxxxx kolonií x xxxxxxxx xxxxxxx xxx exponované x xxxxxxxxx xxxxxxx. V xxxxxxx xxxxxxxxx odpovědi xx zkoušku X5178X XX+/- se xxxxxxx xxxxxxxxx alespoň u xxxxx xxxxxxxxxxx zkoušené xxxxx (xxxxxxxx xxxxxxxxx xxxxxxxxxxx) a x xxxxxxxxx x xxxxxxxxx xxxxxxxx za xxxxxxx xxxxxxxx malá kolonie — xxxxx kolonie. Xxxxxxxxxxx a xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx velké xxxxxxx, xxx xxxxxxx tvořících xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx xxxxxxx XX+/- xxxx xxxxxxx xxxxxxxxxxx za xxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxx (xxxxx) x xxxxxxx s xxxxxxx xxxxxx (xxxx) (25). X mutantních xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx, xx xxxxxxxxxxx doby xxxxxxxx, a tvoří xxxx xxxx xxxxxxx. Xxxxxxxxx xx obvykle xxxxxx xx xxxxx xxxxxx xxxx až xx xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxx xxxxxxxxx xxxx xxxxxxx xx spojuje x chemickými xxxxxxx, xxxxx xxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx xxxxxxxxx xxxxx mutantů xxxxxx xxxxxxxx xxxxxx jako xxxxxxxx xxxxx x xxxxx velké xxxxxxx.

Xxxx xx být xxxxx xxxxxxx (relativní xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx xxxx. Xxxxxxx xxxxxxx xx měla xxx xxxxxxxxx jako xxxxx xxxxxxx k xxxxx přeživších xxxxx.

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxx. Dále xx xxxx xxx xxxxxxx xxxxx shrnuty ve xxxxx xxxxxxx.

Xxxxxxx jasně xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Dvojznačné výsledky xx měly být xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxx, xx třeba xxxxx zdůvodnění. Změna xxxxxxxxx xxxxxx x xxxxx xxxxxxxx rozsah xxxxxxxxxxxx podmínek by xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx xxx xxxxxxxxxx xxxxxxxx, xxx xxx xxxxxxxxx xxxxxxxx. X xxxxxxxxxx studie, xxxxx xx mohly xxx xxxxxxx, patří rozmezí xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxxxxx xxxxxxx v xxxxxxxxxx xx xxxxxxxxxxx, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Nejdříve xx xxxx být xxxxxxx xxxxxxxxxx relevance xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx mohou xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx by xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

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

Xxxxxxxxx xxxxxxxx zkoušky na xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje x použitých kultivovaných xxxxxxx xxxxx xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx pozitivní xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx xx xxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xx podmínek xxxxxxx neindukuje x xxxxxxxxx kultivovaných buňkách xxxxx xxxxxx mutace.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx volby xxxxxxxxxxxx/xxxxxxxx,

- xxxxxxxxxxx x stálost xxxxxxxx látky x xxxxxxxxxxxx/xxxxxxxx, xx-xx známa.

Buňky:

- xxx a xxxxx xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx metody xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx mykoplasmat.

Zkušební podmínky:

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x počtu xxxxxx, xxxxxx xxxx. údajů x xxxxxxxxxxxx a xxxxxx rozpustnosti, jsou-li x xxxxxxxxx,

- xxxxxxx xxxxx, případně xxxxxxxxxxx XX₂,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- objem xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx hustota xxxxx xxxxx xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxx xxxx xxxxxxx (xxxxxxxx xxxxxx xxxxx nasazených xxxxx, xxxxxxxxx a xxxxxx média),

- xxxxxxxx xxxxxxx,

- kritéria xxxxxxxxxxx xxxxxxx na xxxxxxxxx, xxxxxxxxx xxxx xxxxxxxxxxx,

- xxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxx a xxxxxxxxxx buněk,

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

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxx srážení,

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

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- případné xxxxxxxxxxx xxxxxxx,

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

- dosavadní xxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) x pozitivní xxxxxxxx x rozmezími, xxxxxxxxx xxxxxxxxx a směrodatnými xxxxxxxxxx,

- četnost mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Moore, X. M., XxXxxxxx, X. X., XxXxxxxx, X. J., Xxxxxx, X. R. (xxx.) (1987), Xxxxxxx Xxxxxx 28; Xxxxxxxxx Cell Xxxxxxxxxxx, Cold Xxxxxx Xxxxxx Xxxxxxxxxx, Xxx Xxxx.

2) Xxx, X. X. X., Xxxxxxx X. V. (1968), Xxxxxxxxx Xxxx Xxxxxxxx. XX. Xxxxxxxx Xxxxxxxxx xx Xxxxxxxx Locus Xxxxxxxxx in Xxxxxxx Xxxxxxx Cells In xxxxx, Xxxx. Xxxx. Xxxx. Sci. X. X. X, 61, 1306-1312.

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

4) Xxxxx, X. M., Xxxxxxxxx-Xxxxx, X., Xxxxx, X. X., Xxxxxxxxx, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx xx xxx Xxxxx Lymphoma XX and XXX XXXXX Loci, Mutagenesis, 4, 394-403.

5) Aaron, X. X., Xxxxxxxxxx, Xx. X. X., (1989), Xxxxxxxxxx xx xxx AS52/XPRT and xxx XXX/XXXX Assays: Xxxxxxxxxx xx Six Xxxx Xxxxxxxxxx, Xxxxxxxxxx Xxx. 223, 121-128.

6) Xxxxx, X. S., Xxxxxxxxxx, X., Xxxxx, X. X., Xxxxx, X., Xxxxx, Y., Xxxxxxxxxx, Xx. X. X., Theiss, J., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Xxxx Xxxxxxxx Assays Xxxxxxx Xxxxx Report. Report xx xxx International Xxxxxxxx xx Standardisation xx Genotoxicity Xxxx Xxxxxxxxxx. Mutation Res. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, S. X., Marshall, X. X., Ishidate, X., Xxxxxxx, X., Xxxxx, X., Myhr, B. X. (1991), Xxxxxxxxxxxx Xxxxx Xxxxxxx Culture Xxxxxxxxxx. X report xxxx ICPEMC Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, D., XxXxxx, X., Xxxxxxx, X. X. X., Xxxxx, X., Mavournin, X. X. (1983), Xxxxxxxx Xxxx Xxxxxxxxx in X5178X Xxxxx xx Xxxxxxx. X Xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Res., 115, 225-251.

9) Xx, A. X., Gupta, X. X., Xxxxxxx, X. X., Xxxxxx, J. X. (1988), X Xxxxxx xxx Xxxxxxxx xx xxx Chinese Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Xxxxxxxxx xxx Xxxxxxxxxxxx xx Xxxxxxxx Xxxxxx: A Xxxxxx xx Xxxxx XXX xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, A. X., Carver, X. X., Xxxx, X. X., Xxxx, X. X., Gupta, X. X., Loveday, X. X., O'Νeill, X. X., Xxxxxx, J. X., Xxxxxxxxxx, L. X. Xx., Xxxx, X. X. (1987), X Guide xxx xxx Xxxxxxxxxxx xx xxx Xxxxxxx Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Phosphoribosyl Xxxxxxxxxxx Gene Mutation Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Xxxxx, X. X., Xxxxxxx, X. X., Little, X. X. (1989), X Xxxxxxxxxx xx Xxxxxxxx Xxxxxxxxx at xxx TK xxx XXXX Xxxx in Xxxxx Xxxxxxxxxxxxxx Cells: Xxxxxxxxxxxx Differences are Xxx xx xx Xxxxxxxxxx Xxxxx of Xxxxxxxxx at xxx Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

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

13) Xxxxxx, X. T., Xxxxxx, X. G., Xxxxx, X. (1984), Xxxxxxxxx xxx the X5178X/XX+/--XX+/- Xxxxx Xxxxxxxx Xxxx Mutagenicity Xxxxx, xx: Kilbey, X. X. et al (xxx.) Xxxxxxxx xx Xxxxxxxxxxxx Test Procedures, Xxxxxxxx Science Xxxxxxxxxx, Xxx Xxxx, 239-268.

14) Xxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxx, M. X. X., Cole, X., XxXxxxxx, X. B., Xxxxxxx S. X. (1989), Xxxxxxxxx Xxxx Xxxx Mutation Xxxxxx Xxxxx upon Xxxxxx Xxxxxxxxx, in: Statistical Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. X., xx., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 66-101.

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

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

17) Xxxxx, X., Xxxxxxx, X. X., Xxxxxxx, X. X. X., Xxxxxx X. X., Xxxxx M. M. X. (1979), Xxxxxxxxxx xxx Xxxxxxxxxxxxxxxx of xxx X5178X/XX+/--Xxxxx Lymphoma Xxxxxxx Xxxxx System, Xxxxx. Res. 59, 61-108.

18) Xxxxx, X. X., Ames, X. X. (1983), Xxxxxxx Xxxxxxx xxx the Xxxxxxxxxx Mutagenicity Test, Xxxxxxxxxx Xxx. 113, 173-215.

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

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, K., Xxxxxxxx, T. (1976), X Safe Xxxxxxxxxx xxx Xxxxxxxxxxxxxxx Biphenyls x. x. an Xxxxxxx xx Metabolic Xxxxxxxxxx Xxxxxxx, V: Xx vitro Metabolic Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, de Xxxxxx, X. X., Xxxxx, X. R., Xxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. F., Xxxxxx, F. X., XxXxxxx, K. X. (1982), CHO/HGPRT Xxxxxxxx Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Xxxxxxxx Xxxxxxx, in: Xxxx, X. X., Xxxxx, X. X., Schaich, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Agents, Xxx Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, X. X., Xxxxxx, X. X., Xx, X. P., Xxxxxx, X. X. (1983), Xxxxxxxxxx xx xx Xxxxxxxx Xxxxxx Xxxxx Xxxxx Xxxxx xx Collagen Xxxx xxx Xxxxxxxxx Highly Xxxxxxxx Mutagens xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Xxxxxxx. Mutagenesis, 5, 795-801.

23) Applegate, X. L., Xxxxx, X. X., Xxxxxx, X. X., Burrell, X., Xxxxxx, X. X. (1990), Molecular Xxxxxxxxxx xx Mutations xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Locus xx Xxxxx Xxxxxxxx Xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. A, 87, 51-55.

24) Moore, X. X., Xxxxx, D., Xxxxxx, J. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, N. X., Xxxxxx, X. (1985), Xxxxxxxx xx Trifluorothymidine, Xxxxxxxxx (XXX+) Xxxxxxx xx L5178Y/TK+/--Mouse Xxxxxxxx Xxxxx, Xxxxxxxxxx Res. 151, 161-174.

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

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

XXXXXXX 4X

"X.23 XXXXXXX XX XXXXXXXXXXXX XXXXXXX XX XXXXXXXXXXXXXXX XXXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx xx vivo xx xxxxxxxxxxxxx takové xxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx xx spermatogoniích savců (1, 2, 3, 4, 5). Xxxxxxxxx xx dva typy xxxxxxxxxxxx aberací: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, avšak xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Tato xxxxxx xxxx xxxxxx xx xxxxxxxxx numerických xxxxxxx x není x tomuto xxxxx xxxxxxx používána. Chromozomové xxxxxx a podobné xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u člověka.

Touto xxxxxxxx se stanovují xxxxxxxxxxxx změny ve xxxxxxxxxxxxxxx x xxxxxxxxxxx xx xxxx, xx xxxx zkouška poskytne xxxxxxxxx xxxxxxx dědičných xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxxxxx xxxxxxxx xx vivo xx detekují chromozomové xxxxxxx při mitose xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx nejsou xxxxxxxxx xxxx zkoušky.

Pro detekci xxxxxxx xxxxxxxxxxxxxx xxxx xx spermatogoniích xx xxxx xxx — xxxxx než dojde xx xxxxxx xxxx — xxxxxxxxx první xxxxxxxxx xxxxxxx dělení, xxxxx xxxxxxxxx xx xxxxxxxx. Xxxxx xxxxxxxxx x exponovaných spermatogoniálních xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx x xxxxxxxxx-xxxxxxxx X, kdy xx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxxxxx.

Xxxx zkouška in xxxx xx xxxxxxxx xxx xxxxxxxxx, zda xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxx x xxxxxxxxxxxx xxxxxxx. Xxxxx xx tato xxxxxxx xx spermatogoniemi xxxxxxxx pro xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx a xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx s xxxxxx xxxxxxxxxx xx xxxxxxxx chemické xxxxx. Xxxxxxxxxx xxxxxxx xxxx xxxxxxxxxxx souhrnnou xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx poloze xx varlatech, xxxxx xxxx xxxxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx krevnímu xxxxx v xxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx xxxxx x xxxxxxx xxxx xxxxxxx xxxxxx a xxxxxxx.

Xxxxxxxx xxxxxxxx xxxxx x tom, že xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx do xxxxxx xxxxx, xxxx vhodné xxxx zkoušku xxxxxx.

Xxx xxxx obecný úvod, xxxx X.

1.2 XXXXXXXX

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

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

Xxx : achromatická xxxx xxxxx než šířka xxxxx chromatidy x x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

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

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx xxxxxxxx exponována xxxxxxxx xxxxx x xx vhodné xxxx xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx látka xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxxx xx x xxxxxxxxx xx chromozomové aberace xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Běžně xxxx používáni samci xxxxxx čínského a xxxx; xxx xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx vhodného xxxxx xxxxx. Měly xx xxx xxxxxxx běžně xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx překročit ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx se xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x skupinu, která xx xxxxxxxx. Klece xx xxxx být xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx identifikují. Xxxx xxxxxxxxx xxxxxx xx nechají x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx nebo vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx použity xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx xxxxxxxxx hladinách xxxxx xxxxxxx xxxxxx x xxxx xx být xxxxxxxxx xxxxxxxxx, xx xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx kompatibilitě. Xxxxxxxxxx xx xxxxx možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Kontroly

Součástí xxxxxxx experimentu xx xxxx xxx xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx zkoušené xxxxx xx xxxx xxxxxxx kontrolní skupiny xxxxxxxxxx identický xxxxxx xxxx xxxxxxx xx xxxxxxxxx, v xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx spermatogoniích in xxxx při xxxxxxxxxxx xxxxxxxx, u xxxxx xx předpokládá, xx xxxxxxxxx xxxxxxxxxxxxx nárůst xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx xx xxxx xxx zvoleny xxx, xxx byl účinek xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, xxx byla xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka a xxx byl xxxxx x jejím xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx být xxxxx xxxxx v xxxxx xxxxxxx xxxxxxxxxx látek xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Xxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx XXX	Xxxxx xxxxx Xxxxxx
xxxxxxxxxxxxx	50–18–0	200–015–4
xxxxxxxxxxxxx xxxxxxxxxx	6055–19–2	200–015–4
xxxxxxxxxxxxxx	108–91–8	203–629–0
xxxxxxxxx X	50–07–7	200–008–6
xxxxxxxxx (xxxxxxx)	79–06–1	201–173–7
2,4,6-xxxx(xxxxxxxx-1-xx)-1,3,5-xxxxxxx	51–18–3	200–083–5

X xxxxxxxx xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxx jako exponované xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx k xxxxxxxxx xxxxxxxxxx xxxxx o xxxxxxxxxxx xxxxxx a xxxxxxxx buněk x xxxxxxxxxxxxxx aberacemi. Kromě xxxx by xxxx xxx neexponované kontroly xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx nebo xxxxxxxxx účinky.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

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

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx být xxxxx možno xxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxx (xx. xxx jedné xxxxxxxx xxxx xxxx xxxxxxxxxx). Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx dvou xxxxxxx, tzn. xxx xxxxx v týž xxx v xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx xxxxxx podávání xx xxxx xxx xxxxxxx xxxxxxxxxx.

Xx skupině x xxxxxxxx xxxxxx xx měly xxx xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxx cyklu xxxx být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx xx jeden xxxxx xxxxx x xxxxx xxxxxxxx xxxxx xxxxxxxxx 24 x 48 xxxxx po xxxxxxxx. X xxxxxxx xxxx xxx nejvyšší xxxxx xx xxx xxx xxxxx xxxxxxxx po 24 xxxxx xxxx xx xxxxxx xxxx xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx není xxxxx jiná vhodnější xxxx pro xxxxxxx xxxxxx (6).

Xxxxx mohou xxx odběry xxxxxxxxx xxxx x xxxx xxxx. Xxxxxxxxx x xxxxxxx xxxxxxxxxx látek, xxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx nebo xxxxx xxxxxxxxxx X-xxxxxxxxx účinky, xxxx být vhodnější xxxxxxxx xxxxx (1).

Vhodnost xxxxx opakované expozice xxxx xxx určena xxxxxx xx xxxxxxx. X případě xxxxx x opakovanou expozicí xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx délky xxxxx) xx xxxxxxxx xxxxxxxx. Podle xxxxxxx xxxxx xxx prováděny xxxxx xxxxxx v xxxx době.

Před xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx dávka xxxxx xxxxxxxxxxx xxxxxxxx (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx u xxxxxx xxxxx. X myši xx tato xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li xx xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx rozsahu, xxxx by xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx x xxxxxx x xx xxxxxxxx xxxxxx expozice, xxxxx xx xxxxxxx x xxxxxx xxxxxx (7). X případě xxxxxxxx xx xxx xxxxx xxxxx xxxxxxx xxx xxxxxx xxxxx. Tyto xxxxxx xxxxx xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx bude xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xx xxxxx xxxxx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x letalitě.

Látky se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx xxxxxxxxx stanovení dávky xxxxxxxxx x měly xx xxx hodnoceny xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx xxx také definována xxxx dávka xxxxxxxxxxxx xx xxxxxxxxxxxxxxx některé xxxxxx toxicity (xxxx. xxxxxxx počtu xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x xxxxx meiotické metafázi; xxxx xxxxxxx by xxxxxx xxxxxxxxx 50 %).

1.5.4 Limitní zkouška

Jestliže xxxxxxx s jednou xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx xx xxxxx xxxxxx xx třemi xxxxxxxx xxxxx xx xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx může znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx sondou xxxx xxxxxxx xxxxxxxxx kanylou, xxxx xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx podávání xxxx xxxxxxxxxx, jsou-li xxxxxxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxx sondou nebo xxxxxxxx, závisí na xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx uvedený xxxxx, musí xxx xxxxxxxxxx. Xx na xxxxxxxx x žíravé xxxxx, které xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx zesílené účinky, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx xx x xxxxxxx xxxx xxxx xxxxxx xxxxx xxxxxxx suspenze, xxxxxxxxxxxx xx a xxxxxx. Xxxx se xxxxxx xx xxxxxxxx xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v xxxxx xxxxxxxxxxxx metafázi (tj. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký xxxxx aberací. Xxxxxxx xxxxxxxxx včetně preparátů xxxxxxxxxxx x negativních xxxxxxx, by měly xxx xxxx mikroskopickou xxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx xxx xxxxxx xxxxx xxxxxxx ke xxxxxxxxxxxxxx zlomům xxxx xxxxxx xxxxxxxxxx u xxxxx xxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x xxxxx xxxxxxxxxxxxxx xxxxx 2 x ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro jednotlivá xxxxxxx xx xxxx xxx zpracovány xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx xxxxx xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxxxx xx xxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Gapy xx zaznamenávají xxxxxxxx x xxxxxxx xx, xxx xxxxxx xx xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx a xxxx xxxxxx, xxx xx xxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxxxxx účinků xxxx xxxx xxxxxxxxxxxx xxxxxxxx x xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx jako xxxxxxxxx kontrola poměr xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x xxxxx xxxxxxxxx xxxxxxxx, x to x celkovém xxxxxx 100 xxxxxxxx xx xxxxx xx xxxxx xxxxx. Pokud xx xxxxxxxxx xxxxx mitosa, xxxxxxx x 1000 xxxxxxx na zvíře xx xxx xxx xxxxxxxx mitotický index.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx dávce xxxx xxxxx xxxxxx xxxxx buněk x xxxxxxxxx xxx xxxxxxx x určitou xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Dvojznačné xxxxxxxx xx xxxx být xxxxxxxxx dalším zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx opakován.

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

Xxxx by být xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx se xxxxxxxx xxxxx nebo xxxx xxxxxxxxxx xxxxxxxx do xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- zdůvodnění xxxxx xxxxxxxx,

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

Testovací zvířata:

- xxxxxxx xxxx/xxxx,

- xxxxx x xxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxx usmrcení,

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

- podrobné xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx toxicity,

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

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- počet xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- xxxxxxxxx xxxxx,

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

- typ a xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx každé xxxxx,

- xxxxxxx počet xxxxxxx ve xxxxxxx,

- xxxxx xxxxx x xxxxxxxxx xx skupině,

- xxxxx možnosti závislost xxxxxxxx xx xxxxx,

- xxxxxxxx statistické xxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- dosavadní xxxxx o negativní xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx odchylkami,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx,

- změny xxxxxxx, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Xxxxxxxxx in Xxxxx Xxxxxxxxxxxxx of Xxxxxxxx Mutagens Xxxxxxx xx xxxxx Cell-Cycle Xxxxxxxxxxxxxx, in: Xxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxxx Xxxxxxxxx, Xxxx B: Xxxxxxx Xxxxxxx xxx Xxxxxxx Mutagenesis, Ramel, X., Xxxxxxx, X., Xxxxxxxxx, J. (eds) Xxxx, New Xxxx, 477-484.

2) Adler, I. X., (1984), Xxxxxxxxxxx xxxxx xx Mammals, xx: Xxxxxxxxxxxx Xxxxxxx: x Practical Xxxxxxxx, (xx.) S. Xxxxxx, X. M. Xxxxx, XXX Press, Oxford, Xxxxxxxxxx DC, 275-306.

3) Xxxxx, X. P., Xxxxxxx, X., Xxxx, X. E. (1964), Xx Xxx-xxxxxx Method xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Testes, Xxxxxxxxxxxx Xxxx Xxxxxxxx, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Tests, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, X. X., Xxxxxx M. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, W., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxx N. (1994), International Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxxxxxxxx. Xxxxxxx Xxxxxx xx xxx Xxxxxxx Group xx Xxxxxxxxx Xxxx Xxxx Tests, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. J., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxx, X., Esdaile, X. X., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Morton, D. X., Xxxxxxxx, X. X., Richold, X. (1992), Report xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Xxxxx: Dose Xxxxxxx xx Xx xxxx Mutagenicity Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, D. X., Xxxxxxxx, D., Albanese, X., Amphlett, G. X., Xxxxx, X., Xxxxxxxx, R., Richold, X., Xxxxxxxx, X. X., Xxxxxx J. X. X. (1989), Xxxxxxxxxxx Analysis of Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: X. X. Xxxxxxxx (ed.), Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Xxxx Data. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx, Xxxx XXX. Xxxxxxxxx University Xxxxx, Cambridge, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4G

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

1. XXXXXX

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

1.1 XXXX

Xxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx savců in xxxx xx identifikovat xxxxxxxx látky, které xxxxxxxx xxxxxxxx XXX x xxxxxxxxx xxxxxxx xxxxxxxxxxxx zvířat (1, 2, 3, 4).

Xxxx xxxxxxx in vivo xxxxxxxxx xxxxxx vyšetření xxxxxxxxxxxxx účinků xxxxxxxxxx xxxxx x xxxxxxx. Xxxxxxxxxxx jev xx xxxxxxxxxx xxxxxxxxx DNA x xxxxxxxx xxxxxxxx x jaterních xxxxxxx. Xxxxx jsou xxxxxxx xxxxxxx xxxxxx, kde xxxx absorbované sloučeniny xxxxxxxxxxxxxx. Xxxx tedy xxxxxxx xxxxxx xxx xxxxxxxxx míry poškození XXX xx vivo.

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

Xxxxxx xxxxxxxxxxx xxxxxxx DNA (XXX) xx xxxxxxxx stanovením xxxxxxxxxxx xxxxxxxxx nukleosidů xx xxxxx, které xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (X-xxxx). Nejrozšířenější xxxxxxxxx je xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxx tritiem (3H-TdR). Xxx zkoušky xx XXX xx vivo xx xxxxxxxxxx xxxxxxxxx xxxxx potkana. Xxxx xxxxx než játra xxxxx být xxxxxx xxxxxxx, xxxxxx xxxx xxxxxxxxx xxxx xxxxxx.

Xxxxxxx xxxxxxxx XXX závisí xx xxxxx bází XXX vyštěpených x xxxxxxxxxxx v xxxxx xxxxxxxxx. Xxxxxxx xx XXX xx xxxx xxxxxx xxxxxxx xxx xxxxxxx xxxxxxxx reparací ("xxxx-xxxxx repair") (20 xx 30 xxxx) xxxxxxxxxxxx xxxxxx. Krátké xxxxxx ("xxxxx-xxxxx repair") (xxxxx až tři xxxx) xxxx xxxxxxx xxxx detekovány s xxxxxx xxxxx xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx nebo xxxxxx xxxxxxxxx xxxx XXX xxxxx k xxxxxxxxxx xxxxxxxxx. Xxxxxx odpovědi XXX xxxxxxxxxxx xxxxxx xxxxxxxxx x věrnosti xxxxxxxxxxx xxxxxxx. Xxxxx xx možné, že xxxxxxx xxxxxxx s XXX, ale poškození XXX xxxx opraveno xxxxxxxxxxx reparací. Xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxx, xxxxx xxxx xxxxxxx xxxxxxxxx x xxxxxxxxx aktivitě, xx vyvážen xxxxxxxxxxx xxxxxxxxxx xxxxxx jevu, xxxxx xx xxxxxxxxxx x xxxxx genomu.

Viz xxxx obecný xxxx, xxxx X.

1.2 DEFINICE

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

Xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx xxxx XXX xxxxxxxx xxxxx v xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx xxxxxxxxx xxxxxxxxxx xxxxx xxx x xxxxxxxxxxxxxxxxx xxxxxxxxx (XX) odpovídajících xxxxxx xx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): XXX = XX — CG. Xxxxxxx XXX se xxxxxxx xxx xxxxxxxxxx xxxxx, xxxx společně xxx xxxxx v xxxxxxx, v xxxxxxxxxxx xxxxxxxxx atd.

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

1.3 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxx xx XXX x xxxxxxxxx xxxxxxx xxxxx xx vivo xxxxxxxx xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx činiteli. Xxxxxxx xx xxxxxxx xxxxxxxx xx inkorporaci 3X-XxX xx DNA xxxxxxxxx xxxxx, kde je xxxx četnost xxxxx x S-fázi buněčného xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx tak xxxxxxx xx xxxx X-xxxx xxxxx xxxx xxxx. xxxxxxx scintilační xxxxxxxxxxxxx.

1.4 POPIS METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxxxxx lze xxxxxx jakýkoli xxxxxx xxxx xxxxx. Měly xx xxx použity xxxxx xxxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxxxxxx dospělých zvířat. X xxxxxxxx zahájení xxxxxx by xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx minimální x neměla by xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx pro xxx xxxxxxx.

1.4.1.2 Podmínky chovu x strava

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxx xxx, aby xxx xxxx xxxxxx xxxxxx minimalizován. Xxxxxxx xx jednoznačně xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx se xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx zkoušené xxxxx

Xxxxx xxxxxxxx xxxxx xx měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx mohou xxx xxxx podáním zředěny. Xxxx xx xxx xxxxxxx xxxxxxx připravené xxxxxxxx chemické látky, xxxxx údaje x xxxxxxxx neprokazují možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx a mělo xx být xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxxxxx xxxxxx xxxxxxx xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxx by xxxx xxx xxxxxxxx xxxxxxxxx x negativní (rozpouštědlo/vehikulum) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx látky xx xxxx zvířata xxxxxxxxx skupiny xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx dojde x expozici.

Pozitivními kontrolami xx xxxx xxx xxxxx, x nichž xx známo, že xxxxxx podávání x xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxxxx xxxx x xxxxxxx XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aktivaci xx xxxx xxx xxxxxxx x xxxxxxx xxxxxxxxxxxx mírnou odpověď (4). Dávky xxxxx xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, ale aby xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xxxxxxxx xxxxx xxx pozitivní xxxxxxxx:

Xxxx xxxxxx	Xxxxx	Xxxxx XXX	Xxxxx xxxxx Einecs
Časné xxxx xxxxxx (2 až 4 x)	X-xxxxxxxxxxxxxxxxxxx	62–75–9	200–249–8
Xxxxxx xxxx xxxxxx (12 xx 16 x)	X-(xxxxxxx-2-xx)xxxxxxxx (2-XXX)	53–96–3	200–188–6

Xxxxx xxx xxxxxxx xxxx xxxx xxxxx xxx xxxxxxxxx kontrolu. Xx xxxxxxxxx, xxx xxxx xxxxxxxxx kontrolní látka xxxxxxxx xxxxx xxxxxxxx, xxx zkoušená xxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxx xx xxx xxxxxx xxxxxxxxxx xxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxxx kolísání xxxxxxxx xx zkoušku. Xxxxx xxxxxxx xx xx xxxx xxxxxxx xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Jestliže jsou xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, je pro xxxxxxxxx a xxxxxxxxx xxxxxxxxx skupiny nezbytné xxxxx xxxxx až xxx xxxxxxx.

Xxxxxxxx xxxx x době studie x dispozici xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx expozice, xxx xxxxxxxxx, že neexistuje xxxx xxxxxxxxx xxxxxx x xxxxxxxx, bude xxxxxxxxxxx zkoušení xxxxxxx xxxxxxx, nejlépe xxxxx. Xx-xx xxxxxxxx člověka xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx je xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx provedena se xxxxxxxx odpovídajícího pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Xxxxxxxxx

Xx xxxxxxxxxx xxxxxxxx xx xxxxxxxxx xxxxxxx xxx xxxxxx xxxxx. Nejvyšší xxxxx xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxxxx xxxxxxxxx xxx stejném režimu xxxxxxxxx x xxxxxxxx. Xxxxx dávka by xxxx být xxxxxxxxx 50 % až 25 % xxxxx xxxxx.

Xxxxx xx specifickou xxxxxxxxxxx aktivitou xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx xxxxx vyhovovat x xxxx by xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx xxxxxxx, xxxx xx xxx provedena ve xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx režimu expozice, xxx xx použijí x hlavní xxxxxx.

Xxxxxxxx xxxxx xxxx xxx xxxxxxxxxx xxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxxxx x xxxxxxx (xxxx. xxxxxxxxxx xxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx x alespoň 2000 xx/xx tělesné hmotnosti xxxxxxx xxxxxxxxxxx xxxx xx dvou xxxxxxx x jednom xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx účinky x xxxx-xx na základě xxxxx x xxxxxxx, xxxxx mají xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx xxx úplná xxxxxx xxxxxxxx. Očekávaná xxxxxxxx xxxxxxx může xxxxxxxx xxxxxxx použít x xxxxxxx zkoušce xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx dávek

Zkoušená xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, žaludeční sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx jsou xxxxx, xxx-xx je xxxxxxxxx. Xxxxxxxx intraperitoneálně xx xxxx xxxxxxxxxxxx, xxxxx xx xxxxx xxxxx xxx xxxxxxxxxx zkoušené xxxxx xxxxx x xxxxxx prostřednictvím xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx může xxx xxxxxxxx podán xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 ml/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx je xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Až na xxxxxxxx x xxxxxx xxxxx, které xxxxxxx xxx vyšších koncentracích xxxxxxxx xxxxxxxx xxxxxx, xx měla být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní objem xxx všech xxxxxxxx xxxxx.

1.5.6 Příprava jaterních xxxxx

Xxxxxxx xxxxx xx xxxxxxxxxx x exponovaných xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx xxxxxx dávky. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (xxxxxx xxx xx xxxxx xxxxxx xx xxxxxxxx) je xxxxxxxx, xxxx-xx po 12 xx 16 xxxxxxxx xxxxx pozitivní xxxxxxx. Xxxxx však xxx použity jiné xxxx odběru, xxxx-xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx kultury xxxxxxxxx xxxxx xxxxx xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxxx xx xxxx a xxxxxx xx, xxx xx xxxxxxx xxxxxxxxxxx xxxxxxx buňky xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx z xxxxxxxxx xxxxxxxx xx xxxx vykazovat xxxxxxxxxxxxxxx (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx UDS

Čerstvě xxxxxxxxx xxxxxxx buňky xxxxx se obvykle xxxxxxx dobu, xxxx. xxx xx osm xxxxx, inkubují x xxxxxx xxxxxxxxxxx 3H-TdR. Xx xxxxx xxxxxxxxx xxxx xx mělo xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx xxxx xxxxx xxx xxxxxxxxxx x xxxxxx obsahujícím přebytek xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxxxxx ("xxxx chase"). Xxxxx xx xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx xxxxx xxxxxxxxx xxxx nemusí xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Preparáty xx xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx xx x temnu (xxxx. x chladu 7 xx 14 xxx), xxxxxxxx se, obarví x xxxxxxxxx se xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxxx xxx xx xxx preparáty.

1.5.8 Xxxxxxx

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

Před xxxxxxxxx xxx by xxxx xxx preparáty xxxxxxxx. Xxxxxxxxx se vyšetřuje 100 xxxxx xx xxxxx xxxxx xxxxxxx xx xxxx preparátů; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx xx xxxx být zdůvodněno. Xxx xxxxxxxx xxx xx jádra x X-xxxx nevyšetřují, xxx xxxxx buněk x X-xxxx může xxx xxxxxxxxxx.

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

Xxxxx xxxxx xx xxxxxxx z xxxxx xxx odpovídajících xxxxxxxx jádrŭm (xx) x x prŭměrného xxxxx xxx v xxxxxxxxxxxxxxxxx xxxxxxxxx (xx) xxxxxxxxxxxxxx xxxxŭx. xxxx xxxxxxx xx xx xxxxxxx xxx xxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx oblast xxxxxxxxxx, xxxx xxŭxxxxx xxxxxxx xxxx až tří xxxxxxx xxxxxxxxx xxxxxxx x blízkosti dotyčných xxxxxxxxx jader. xx xxxxxxxxxxxxx xxXxxxxxxx mohou xxx použity x xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx buněk) (6).

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxx xx být xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx x xxxxxxx. Xxxxx xx xxxx být dále xxxxxxx xx formě xxxxxxx. Xxxxxxxxx xxxxxxx XX od xxxxxxx XX xx měl xxx xxxxxxxx xxx xxxxxx xxxxx, xxx xxxxx xxxxx x xxx každou xxxxx x xxx xxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XXX). Xxxxxxxx xxxx xxxxxxxx "xxxxxxxxxx" xxxxx, měla xx xxx xxxxxxxx xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx xxxxxxxxxx x xxxxxxxx na xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx x negativních kontrolách. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx být xxxxxxx, měly xx xxx xxxxxxxxxxx xxxxx xxxxxxx a xxxxxxxxxx xxxx xxxxxxxxxx studie.

2.2 XXXXXXXXX X INTERPRETACE XXXXXXXX

Xxxx xxxxxxxx xxxxxxxx xxx pozitivní xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx	x)	xxxxxxx XXX leží nad xxxxxxxx xxxxxx, xxxxx xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx;
xxxx	xx)	xxxxxxx XXX je xxxxxxxx xxxxx xxx xxxxxxx xxx xxxxxxxxx xxxxxxxx;
xxxxxxxxx	x)	xxxxxxx XXX xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx pod xx;
xxxx	xx)	xxxxxxx XXX není xxxxxxxx xxxxx než xxxxxxx xxx xxxxxxxxx xxxxxxxx.

Xxxx xx xxx xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, tj. měly xx xxx xxxxx x úvahu xxxxxxxxx, xxxx xxxx xxxxxxxxxxx xxxxxx, xxxxx dávky x xxxxxxxx x xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx zkoušky mohou xxx použity jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx. Statistická významnost xx xxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxxxxx xxxxxxxx xxxxxxx xx XXX x jaterních xxxxxxx xxxxx in xxxx znamenají, že xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxx DNA in xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx XXX, xxxxx lze xxxxxxxxx touto xxxxxxxx.

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

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx druh/kmen,

- počet, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, strava xxx.,

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

Zkušební xxxxxxxx:

- pozitivní a xxxxxxxxx (vehikulum/rozpouštědlo) xxxxxxxx,

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

- xxxxxxxxxx zvolených úrovní xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx expozice x odběru,

- metody xxxxxxxxx toxicity,

- metody xxxxxxxx x kultivace xxxxxxxxx xxxxx,

- použitá xxxxxxxxxxxxxxxxx xxxxxxxx,

- počet xxxxxxxxx x počet xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxxx xxxxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx x počtu xxx xxxxxxxxxxxxxx xxxxxxxxxx, x xxxxx xxxxx xxx, jednotlivě pro xxxxxxxxx, zvířata a xxxxxxx,

- podle xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- známky toxicity,

- xxxxx x xxxxxxxx xxxxxxxxx (rozpouštědlo/vehikulum) a xxxxxxxxx xxxxxxxx,

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

- xxxxx xxxxx "xxxxxxxxxxxx" buněk, xx-xx stanoven,

- počet xxxxx x S-fázi, xx-xx stanoven,

- životaschopnost xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. Xxxxxxx, X. X., Burlinson, X., Penman, M. X. (1985), An Xxxxxxxxxx xx xxx Xx xxxx Xxx. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Mutatation Res., 156, 1-18.

2) Xxxxxxxxxxx, X. E., Ashby, X., Bermudez, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, G. (1987), X Xxxxxxxx xxx Xxxxx for xxx Xx vivo Xxx Xxxxxxxxxx DNA Xxxxxx Xxxxx, Mutatation Xxx., 189, 123-133.

3) Xxxxxxxx, X. X., Xxxxxx, X., Xxxxx, X., Xxxxxxx, X. A., Xxxxxxxxx, X., Benford, X. X., Xxxx, X. X., Xxxxxxxx, X. xx G. (1993), Xx xxxx Xxx Liver XXX Xxxxx, xx: Kirkland X. J., Xxx X., (eds), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: UKEM Xxxxxxxxxxx Procedures. UKEMS Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, S., Xxxx, X. W., Xxxxxx, X., Xxxxxxxxx. X., Xxxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxx, X., Xxxxxxx, T., XxXxxxx, C. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx the Xxxxxxxxxxx xx XXX Xxxxx Xx xxxxx xxx Xx vivo, Xxxxx. Res., 312, 263-285.

5) Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, X. (1993), Assessment xx xxx Xxxxxxxx Xxxxxxx xxx Initial Viability xxx xxx Xxxxxxxxxx xx Freshly Xxxxxxxx Xxx Hepatocytes Used xxx the In xxxx/Xx xxxxx XXX Xxxxxx Assay (UDS), Xxxxxxxxxx Xxx., 291, 21-27.

6) Xxxxxxxx, J. X., Xxxxx, X. X., Butterworth, X. X. (1982), Xxxxxxxxx xx Genotoxic Xxxxxxxxxxx xx xxx In xxxx/Xx xxxxx Hepalocyte XXX Xxxxxx Assay, Xxxxxxx.Xxxxxxx. 4, 553-562."

PŘÍLOHA 5

XXXXXX XXXXXXXXX XX KLASIFIKACI X XXXXXXXXXX NEBEZPEČNÝCH LÁTEK X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/ES, Xx. xxxx. X 332, 28. 12. 2000, x. 81.

PŘÍLOHA 6

"

XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 písm. x) xxxx xxxxxxxx, xxxx xxx obaly x xxxxxxxxx xxxxxx obsahující xxxxx, s xxxxx xx xxxxxxx riziko xxx vdechování (Xx; X 65) x xxxxx xxxx klasifikovány x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx xx xxx xx xxxxx xxxxxxxx xxxx v nádobách xxxxxxxxxx aerosolovým xxxxxxxxxxxxx, xxxxxxxx xxxxxxx odolnými xxxxx xxxxxxxx dětmi.

1. Xxxxxxxxx uzavíratelné xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx ISO 8317 (xxxxxx ze dne 1. xxxxxxxx 1989) "Xxxxx xxxxxx dětem — Xxxxxxxxx xx xxxxxxxxx uzavíratelné obaly x metody jejich xxxxxxxx" xxxxxxxx Mezinárodní xxxxxxxxxx xxx normalizaci (XXX).

2. Xxxxxxxxx neuzavíratelné xxxxx

Xxxxxxx xxxxxx proti xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx neuzavíratelných xxxxxxx xxxx splňovat xxxxxxxxx normy XXX XX 862 (vydání x xxxxxx 1997) "Xxxxx — Obaly xxxxxx xxxxx — Xxxxxxxxx a xxxxxxxx xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx obaly jiných xxx xxxxxxxxxxxxxxx výrobků" xxxxxxxx Xxxxxxxxx xxxxxxx xxx normalizaci (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx shody x xxxx uvedenými xxxxxxx mohou xxxxxxxxxx xxxxx xxxxxxxxxx, xxxxx xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.

2. Xxxxxxxxxx případy

Je-li xxxxxx, xx xxxx xx xxxxxxxxxx bezpečný xxx xxxx, xxxxx xx xxxxxxx xxxxxx x xxxxxx bez xxxxxx xxxxxxxx, xxxxxx být xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxx xxxxxx x pochybám x xxxxxxxxxxx xxxxxxx xxx xxxx, xxxx xxxxxxxxxxxx orgán xxxxxxxxx, xxx osoba odpovědná xx uvedení výrobku xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx odst. 3 xxxx 1 xxxxxxxxxxxx, xx buď

- typ xxxxxxx xx xxxxxx, xx xxx xxxx xxxxxxxx xxxxxxx xxxxx xxxx uvedených xxxxx XXX x XXX,

xxxx

- xx xxxxxx xxx xxxxxxx a byl xxxxxxx xxxxxxxxxxx podle xxxx uvedených xxxxx.

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

Xxxxxxxxx xxxxxxxxxxx xxx hmatatelné výstrahy xxxx xxx x xxxxxxx x xxxxxx XX XXX 11683 (xxxxxx x roku 1997) "Xxxxx — Xxxxxxxxxx xxxxxxxx před xxxxxxxxxx — Xxxxxxxxx".

"

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