EPIS® Právní systém | Plné znění

Xxxxxxxx Xxxxxx 2000/32/ES

ze xxx 19. xxxxxx 2000,

xxxxxx se xx xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxx Xxxx 67/548/EHS o xxxxxxxxxx xxxxxxxx a xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [1]

(Xxxx s xxxxxxxx xxx XXX)

XXXXXX XXXXXXXXXX SPOLEČENSTVÍ,

s ohledem xx Smlouvu x xxxxxxxx Evropského xxxxxxxxxxxx,

x xxxxxxx xx xxxxxxxx Xxxx 67/548/XXX ze xxx 27. xxxxxx 1967 o xxxxxxxxxx xxxxxxxx a správních xxxxxxxx týkajících xx xxxxxxxxxxx, xxxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], xxxxxxxxx pozměněnou xxxxxxxx Xxxxxxxxxx parlamentu x Xxxx 1999/33/XX [3], a xxxxxxx xx xxxxxx 28 xxxxxxx směrnice,

vzhledem x xxxxx xxxxxxx:

(1) Příloha X směrnice 67/548/XXX xxxxxxxx seznam nebezpečných xxxxx xxxxxxxx x xxxxxxxxxx xxxxx x xxxxxxxxxxx a xxxxxxxxxx xxxxx xxxxx. Xxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxx, xx xx xxx xxx xxxxxx xxxxxxxxxxxx látek x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx směrnice vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx a xxxxxxx X x xxxxxxx X.

(2) Xxxxxxx XXX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx vět xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxx x přípravky. Xxxxxxx XX xxxxxxxx 67/548/XXX xxxxxxxx xxxxxx xxx x bezpečnostními xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/XXX obsahuje xxxxx ke xxxxxxxxxxx x x xxxxxxxxxx xxxxxxxxxxxx látek a xxxxxxxxx. Některé xxxxxxxx xxxxx směrnice xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, IV x XX.

(3) X xxxxxxx X xxxxxxxx 67/548/XXX xx stanoví xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, toxicity x ekotoxicity xxxxx x přípravků. Xx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxx xxxxxxxxxxx xxxxxxx.

(4) Xxxxxxx XX směrnice 67/548/XXX xxxxxxxx předpisy xxxxxxxx se uzávěrů xxxxxxxx xxxxx xxxxxxxx xxxxx. Xxxx předpisy xx měly xxx xxxxxxxxxxxx a aktualizovány. Xx xxxxxxxx rozšířit xxxxxx, xxx xx xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxxxx.

(5) Xxxxxxxx xxxx xxxxxxxx xxxx x xxxxxxx xx xxxxxxxxxxx Výboru xxx přizpůsobení xxxxxxxxxxx xxxxxxx směrnic xxx xxxxxxxxxx technických xxxxxxxx xxxxxxx xx xxxxx xxxxxxxxxxxx látek x xxxxxxxxx,

XXXXXXX XXXX XXXXXXXX:

Článek 1

Směrnice 67/548/EHS xx xxxx takto:

1. Xxxxxxx X se xxxx xxxxx:

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

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

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

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

2. Xxxxxxxxxxxx věta x xxxxxxx XXX xx xxxxxxxxx standardní xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x příloze 2 této xxxxxxxx.

3. Xxxxxxx IV xx xxxx xxxxx:

x) odpovídající xxxxxx x příloze XX se xxxxxxxxx xxxxxxxxxxxx xxxxxx xxx xxxxxxxx xxxxxxxxx v xxxxxxx 3X xxxx xxxxxxxx;

x) xxxxxxxxxxxx pokyny x xxxxxxx XX xx nahrazují kombinovanými xxxxxxxxxxxx pokyny pro xxxxxxxx xxxxxxxxx v xxxxxxx 3X xxxx xxxxxxxx.

4. Xxxx B xxxxxxx X xx xxxx xxxxx:

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

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

x) xxxxxxxx B.12 xx nahrazuje xxxxxx x xxxxxxx 4X xxxx směrnice;

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

x) xxxxxxxx X.17 xx nahrazuje xxxxxx x xxxxxxx 4X xxxx směrnice;

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

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

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

6. Odpovídající xxxxx x xxxxxxx XX xx nahrazují xxxxx x xxxxxxx 5 této xxxxxxxx.

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

Xxxxxx 2

1. Členské xxxxx uvedou x xxxxxxxx právní a xxxxxxx xxxxxxxx xxxxxxxx xxx xxxxxxxx xxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xx 1. xxxxxx 2001. Neprodleně x xxxx uvědomí Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx xxxxx musí xxxxxxxxx odkaz na xxxx xxxxxxxx nebo xxxx xxxxxx odkaz xxx učiněn xxx xxxxxx xxxxxxx xxxxxxxxx. Xxxxxx xxxxxx si xxxxxxx xxxxxxx státy.

2. Xxxxxxx xxxxx xxxxx Xxxxxx xxxxx xxxxxxxx xxxxxxxxxx vnitrostátních xxxxxxxx xxxxxxxx, xxxxx přijmou x oblasti xxxxxxxxxx xxxx směrnice, x xxxxxxxxxx xxxxxxx xxxx xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxxxxx.

Článek 3

Tato směrnice xxxxxxxx x platnost xxxxxx xxxx xx xxxxxxxxx v Xxxxxxx xxxxxxxx Evropských společenství.

Článek 4

Tato xxxxxxxx xx xxxxxx xxxxxxxx xxxxxx.

X Bruselu xxx 19. xxxxxx 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise

[1] Přijato po xxxxxxxxxxxx xx xxxxxxx xxxxx.

[2] Xx. věst. 196, 16.8.1967, x. 1.

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

XXXXXXX 1X

XXXXXXXXX X XXXXXXX X

Xxxxxxxxxx poznámek xxxxxxxxxx xx identifikace, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx xx českého xxxxx)

XXXXXXX 1B

"TABULKA X

X

Xxxxxx

XX

18

Xx

Xxxxx

Αργό

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"

XXXXXXX 1X

Xxxxxxxx xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx x xxxxxx	Xxxxx XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx xxxxxx	Xxxxxxxx x xxxxxxxxxx
006–011–00–7	xxxxxxxx (ISO) 1-xxxxxx-X-xxxxxxxxxxxxxx		200–555–0	63–25–2	Xxxx. kat. 3; X40 Xx; R22 X; X50	Xx; N X: 22–40–50 X: (2-)22–24–36/37–46–61
006–013–00–8	xxxxxx-xxxxxxx (XXX) natrium-N-methyldithiokarbamát		205–293–0	137–42–8	Xn; X22 X31 C; X34 X43 N; X50–53	X; N X: 22–31–34–43–50/53 S: (1/2-)26–36/37/39–45–60–61
006–015–00–9	xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx	206–354–4	330–54–1	Xxxx. xxx. 3; X40 Xxxx. xxx. 3; X40 Xx; R22–48/22 X; X50–53		Xx; N X: 22–40–48/22–50/53 X: (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 X; X50–53	X; X R: 25–50/53 X: (1/2-)37–45–60–61
006–017–00-X	aldikarb (XXX) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx		204–123–2	116–06–3	X+; X26/28 X; X24 X; X50–53	X+; X X: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61
006–018–00–5	xxxxxxxxx (XXX) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		217–990–7	2032–59–9	X; X24/25 N; 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 N; X50–53	Xx; X X: 22–40–50/53 X: (2-)25–36/37–60–61
006–020–00–6	xxxxxx (XXX) 4-xxxxxxxx-2-xx-1-xx-X -(3-xxxxxxxxxx)xxxxxxxx		202–930–4	101–27–9	Xx; X22 X43 X; X50–53	Xx; X X: 22–43–50/53 X: (2-)24–36/37–60–61
006–023–00–2	xxxxxxxxxxxxxxxx (XXX) xxxxxxxxxx 3,5-xxxxxxxx-4-(xxxxxxxxxxxxxx)xxxxx-X -methylkarbamát		217–991–2	2032–65–7	T; X25 X; X50–53	X; X X: 25–50/53 X: (1/2-)22–37–45–60–61
006–024–00–8	xxxxxx-xxxxxxx (ISO) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx		205–443–5	140–93–2	Xx; R22 Xx; X38 X; R51–53	Xn; X X: 22–38–51/53 X: (2-)13-61
006–026–00–9	xxxxxxxxxx (XXX) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx		216–353–0	1563–66–2	X+; X26/28 N; X50–53	X+; X R: 26/28–50/53 X: (1/2-)36/37–45–60–61
006–028–00-X	xxxxxxxxx (XXX) 2-(1-methylpropyl)-4,6-dinitrofenyl-isopropyl-karbonát 2-xxx-xxxxx-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx		213–546–1	973–21–7	X; X25 X; R50–53	T; X X: 25–50/53 X: (1/2-)37–45–60–61
006–029–00–5	xxxxxxxxx (XXX) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx		230–253–4	6988–21–2	X; X25 N; X51–53	X; N R: 25–51/53 S: (1/2-)37–45–61
006–033–00–7	xxxxxxxxx (XXX) 3-(3-chlor-4-methoxyfenyl)-1,1-dimethylmočovina		243–433–2	19937–59–8	N; X50–53	X X: 5 0/ 5 3 X: 60-61
006–034–00–2	xxxxxxx (ISO) X-xxxxxx-X-xxxxx-X-xxxxxxxxxxxxxxxxx		214–215–4	1114–71–2	Xx; X22 X; X51–53	Xx; 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 (ISO) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–113–0	2631–37–0	X; X25 X; X50–53	X; N X: 25–50/53 S: (1/2-)24–37–45–60–61
006–038–00–4	xxxxxxxxx (XXX) 2-chlorallyl-N,N-dimethyldithiokarbamát	E	202–388–9	95–06–7	Karc. xxx. 2; R45 Xx; X22 X; X50–53	X; X X: 45–22–50/53 X: 53–45–60–61
006–039–00-X	tri-allát (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–962–7	2303–17–5	Xx; X22–48/22 X43 X; R50–53	Xn; N X: 22–43–48/22–50/53 X: (2-)24–37–60–61
006–042–00–6	xxxxxxx (XXX) 3-(4-chlorfenyl)-1,1-dimethylmočovina		205–766–1	150–68–5	Karc. xxx. 3; X40 Xx; X22 X; X50–53	Xx; X X: 22–40–50/53 X: (2-)36/37–60–61
006–043–00–1	monuron-TCA 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx		—	140–41–0	Xx; X36/38 Karc. xxx. 3; X40 X; X50–53	Xx; N X: 36/38–40–50/53 S: (2-)36/37–60–61
006–045–00–2	xxxxxxxx (ISO) 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 (ISO) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx		245–216–8	22781–23–3	X; R23/25 Xn; X21 X; X50–53	X; X X: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61
006–047–00–3	xxxxxxxxx (ISO) xxxx: 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx x 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx		—	8065–36–9	X; X24/25 N; X50–53	X; X X: 24/25–50/53 S: (1/2-)28–36/37–45–60–61
006–048–00–9	ethiofenkarb (XXX) 2-[(ethylsulfanyl)methyl]fenyl-N-methylkarbamát		249–981–9	29973–13–5	Xn; X22 X; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
006–050–00–X	xxxxxxx-XXX 3-xxxxx-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx		—	4482–55–7	Xx; X38 X; R50–53	Xi; N X: 38–50/53 X: (2-)60-61
006–053–00–6	xxxxxxxxxx (XXX) 2-isopropylfenyl-N-methylkarbamát		220–114–6	2631–40–5	Xn; X22 X; X50–53	Xx; X R: 22–50/53 X: (2-)60-61
006–054–00–1	mexakarbát (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 X; X51–53	Xx; X X: 22–51/53 S: (2-)24-61
006–060–00–4	xxxxxxxxxxx (XXX) 2-xxxxxx-4,4-xxxxx-5,6-xxxxxxx-4λ4-1,4-xxxxxxxx-3-xxxxxxxxxxxx		226–066–2	5259–88–1	Xx; R22 X52–53	Xx X:22–52/53 X: (2-)61
006–069–00–3	xxxxxxxxx-xxxxxx (ISO) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx		245–740–7	23564–05–8	Xxxx. xxx. 3; X40 X; X50–53	Xx; X X: 40–50/53 S: (2-)36/37–60–61
006–070–00–9	xxxxxxxxxxx X-xxxxxxxxxx-X-xxxxxxx-2,5-xxxxxxxx-3-xxxxxxx		262–302–0	60568–05–0	Xxxx. kat. 3; X40 X; X50–53	Xx; N R: 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; R50–53	T; 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 Xxxx. xxx. 2; R45 X; X23/25 C; R34 X; R51–53	F; X; X X: 45–11–23/25–34–51/53 X: 53–45–61
007–013–00–0	X,X-xxxxxxxxxxxxxxxx 1,2-xxxxxxxxxxxxxxxx	X	—	540–73–8	Xxxx. xxx. 2; R45 X; R23/24/25 X; X51–53	X; N X: 45–23/24/25–51/53 S: 53–45–61	X ≥ 25 %: X; X45–23/24/25 3 % &xx; X &xx; 25 %: X; X45–20/21/22 0,01 % &xx; X &xx; 3 %: X; R45
009–003–00–1	kyselina xxxxxxxxxxxxxx … %	X	231–634–8	7664–39–3	X+; X26/27/28 X; X35	X+; C X: 26/27/28–35 S: (1/2-)7/9–26–36/37–45	X ≥ 7 %: T+; X; X26/27/28–35 1 % ≤ X &xx; 7 %: X; X23/24/25–34 0,1 % ≤ X &xx; 1 %: Xx; X20/21/22–36/37/38
015–039–00–9	xxxxxxx-xxxxxx (XXX) X,X-xxxxxxxx-X -[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx		201–676–1	86–50–0	X+; X26/28 X; X24 X43 X; X50–53	X+; X X: 24–26/28–43–50/53 X: (1/2-)28–36/37–45–60–61
015–048–00–8	xxxxxxxx (ISO) O,O-dimethyl-O-[3-methyl-4-(methylsulfanyl)fenyl]-fosforothioát		200–231–9	55–38–9	Muta. xxx. 3; R40 X; X23–48/25 Xx; X21/22 X; R50–53	T; X X: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61
015–056–00–1	azinfos-ethyl (ISO) X,X-xxxxxxx-X-[(4(3 X)-xxx-1,2,3-xxxxxxxxxxxx-3-xx)xxxxxx]-xxxxxxxxxxxxxxx		220–147–6	2642–71–9	X+; X28 X; R24 X; X50–53	X+; X X: 24–28–50/53 S: (1/2-)28–36/37–45–60–61
015–140–00–8	triazofos (XXX) O,O-diethyl-O-(1-fenyl-1 X- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx		245–986–5	24017–47–8	X; X23/25 Xx; X21 X; R50–53	T; X X: 21–23/25–50/53 X: (1/2-)36/37–45–60–61
016–013–00-X	chlorid xxxxxxx		234–129–0	10545–99–0	X14 X; R34 X; X50	X; X R: 14–34–50 X: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; R36/37/38
016–014–00–5	chlorid xxxxxxxx		—	13451–08–6	X14 X; X34 N; X50	X; X X: 14–34–50 X: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; R34 5 % ≤ X &xx; 10 %: Xx; R36/37/38
016–023–00–4	dimethyl-sulfát	E	201–058–1	77–78–1	Karc. xxx. 2; X45 Xxxx. xxx. 3; X40 X+; R26 X; X25 X; R34 X43	X+ R: 45–25–26–34–43 X: 53-4 5	X ≥ 25 %: X+; X45–25–26–34–43 10 % ≤ X &xx; 25 %: X+; X45–22–26–34–43 7 % ≤ C &xx; 10 %: X+; X45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: X; X45–22–23–36/37/38–43 3 % ≤ X &xx; 5 %: X; X45–22–23–43 1 % ≤ X &xx; 3 %: X; X45–23–43 0,1 % ≤ X &xx; 1 %: T; R45–20 0,01 % ≤ X &xx; 0,1 %:X; R45
016–024–00-X	dimexano (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx	X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8	1468–37–7	Xx; X22 N; X50–53	Xx; N X: 22–50/53 S: (2-)60-61
016–071–00–6	3-amino-6,13-dichlor-10-[(3-{[4-chlor-6-(2-sulfonatoanilino)- 1,3,5-xxxxxxx-2-xx]xxxxx}xxxxxx)xxxxx][1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx xxxxxxxx		410–130–3	136248–03–8	X43	Xx R: 43 S: (2-)22–24–37
022–001–00–5	xxxxxxx xxxxxxxxxx		231–441–9	7550–45–0	X14 X; X34	X X: 14-34 X: (1/2-)7/8–26–36/37/39–45	X ≥ 10 %: C; R34 5 % ≤ X &xx; 10 %: Xi; X36/37/38
030–004–00–8	xxxxxxxxxxxxx [1] diethylzinek [2]		208–884–1 [1] 209–161–3 [2]	544–97–8 [1] 557–20–0 [2]	X14 X; R17 X; X34 X; R50–53	F; X; N X: 14–17–34–50/53 X: (1/2-)16–43–45–60–61
050–002–00–0	cyhexatin (XXX) xxxxxxxxxxxxx(xxxxxxx)xxxxxxx xxxxxxxxxxxxxxxxxxxxx-xxxxxxxx		236–049–1	13121–70–5	Xx; X20/21/22 X; X50–53	Xx; X X: 20/21/22–50/53 X: (2-)13–60–61
050–012–00–5	xxxxxxxxxxxxxxxxxxxxxx [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] xxxxx(xxxxxxxxxxxxx)xxxxxxx [3]		215–910–5 [1] 221–437–5 [2] 230–358–5 [3]	1449–55–4 [1] 3091–32–5 [2] 7067–44–9 [3]	Xn; X20/21/22 X; X50–53	Xx; X X: 20/21/22–50/53 X: (2-)26–28–60–61	X ≥ 1 %: Xx; R20/21/22	1
050–017–00–2	fenbutatinoxid (XXX) 1,1,1,3,3,3-hexakis(2-fenyl-2-methylpropyl)distannoxan		236–407–7	13356–08–6	T+; X26 Xx; X36/38 N; X50/53	X+; N X: 26–36/38–50/53 X: (1/2-)28–36/37–45–60–61
082–009–00–X	žluť (xxxxxxxxxxxx olovnatý) XX Xxxxxxx Xxxxxx 34 (XX 77603) XX xxxxxxxxxx xxxx 34 (XX 77603)		215–693–7	1344–37–2	Karc. kat. 3; X40 Xxxx. xxx. 1; X61 Xxxx. kat. 3; X62 X33 X; X50–53	X; N R: 61–33–40–50/53–62 X: 53–45–60–61		1
082–010–00–5	červeň (xxxxxxx-xxxxxxxxxx-xxxxx olovnatý) XX Xxxxxxx Xxx 104 (XX 77605) CI xxxxxxxxxx červeň 104 (XX 77605)		235–759–9	12656–85–8	Karc. xxx. 3; R40 Repr. xxx. 1; R61 Xxxx. xxx. 3; X62 X33 X; X50–53	X; X 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; R65 Xx; X37 N; 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; R46 Xxxx. xxx. 2; X60–61 X; R50–53	T; X X: 45–46–60–61–50/53 X: 53–45–60–61
601–034–00–4	xxxxx[x]xxxxxxxxxxxxxxx		205–911–9	205–99–2	Xxxx. xxx.2; X45 X; X50–53	X; X X: 45–50/53 X: 53–45–60–61
602–035–00–2	1,4-xxxxxxxxxxxxx x-xxxxxxxxxxxxx		203–400–5	106–46–7	Xx; X36 X; R50–53	Xi; X X: 36–50/53 X: (2-)24/25–46–60–61
602–054–00–6	3-xxxxxxx-1-xx allyljodid		209–130–4	556–56–9	R10 X; X34	X R: 10-34 S: (1/2-)7–26–45
603–076–00–9	xxx-2-xx-1,4-xxxx		203–788–6	110–65–6	X; X23/25 Xn; X21–48/22 X; X34	X R: 21–23/25–34–48/22 X: (1/2-)26–36/37/39–45	C ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ C &xx; 50 %: X; X21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; X20/22–48/22 3 % ≤ X &xx; 10 %: Xx; X20/22
603–091–00–0	xxx-4-xxxxxxxxx-1-xxxxxx-7-xxxxxxxxxx[2.2.1]xxxxxx-2-xx		402–470–6	87172–89–2	X; X8 Xx; X22 Xx; X36	X; Xx R: 8–22–36 X: (2-)26
603–093–00–1	xxx-(±)-4-xxxxxxxxx-1-xxxxxx-2-[(2-xxxxxxxxxxxx)xxx]-7-xxxxxxxxxx[2.2.1]xxxxxx		402–410–9	87818–31–3	Xx; X20 N; X51–53	Xx; X X: 20–51/53 X: (2-)23-61
603–097–00–3	1,1', 1′′-xxxxxxxxxxxxxxxx-2-xx xxxxxxxxxxxxxxxxxx		204–528–4	122–20–3	Xx; R36 X52–53	Xx X:36–52/53 X: (2-)26-61
603–117–00–0	propan-2-ol xxxxxxxxxxxxxxxx xxxxxxxxxxx		200–661–7	67–63–0	X; X11 Xx; R36 R67	F; Xx X: 11–36–67 X: (2-)7–16–24/25–26
604–020–00–6	xxxxxxx-2-xx 2-xxxxxxxxxxxxxx 2-xxxxxxxxxx (XXX)		201–993–5	90–43–7	Xx; X36/37/38 X; X50	Xx; X X: 36/37/38–50 S: (2-)22-61
604–021–00–1	2-xxxxxxxxxx, xxxxx xxx xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx sodný xxxxxxx-xxxxxxx-2-xxxx		205–055–6	132–27–4	Xx; X22 Xx; X37/38–41 X; X50	Xx; X R: 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 N; X50–53	X; X R: 60–36–50/53 S: 53–45–60–61
604–041–00–0	xxxxxxxxxxx [1] acifluorfen-natrium [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; X38–41 X; X50–53	Xx; N R: 22–38–41–50/53 X: (2-)24–39–60–61
604–043–00–1	monobenzonbenzyl (4-xxxxxxxxxxxx)xxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx 4-(benzyloxy)fenol		203–083–3	103–16–2	Xi; X36 X43	Xx R: 36-43 X: (2-)24/25–26–37
604–044–00–7	mechinol 4-xxxxxxxxxxxx hydrochinonmonomethylether		205–769–8	150–76–5	Xn; X22 Xx; X36 X43	Xx X: 22–36–43 X: (2-)24/25–26–37/39–46
605–016–00–7	xxxxxxx… % ethandial… %	X	203–474–9	107–22–2	Xxxx. xxx. 3; X40 Xn; X20 Xx; X36/38 R43	Xn X: 20–36/38–40–43 X: (2-)36/37	X ≥ 10 %: Xx; R20–36/38–40–43 1 % ≤ X < 10 %: Xx; R40–43
606–016–00-X	pindon (XXX) 2-(trimethylacetyl)indan-1,3-dion		201–462–8	83–26–1	T; X25–48/25 X; X50–53	X; X X: 25–48/25–50/53 S: (1/2-)37–45–60–61
606–018–00–0	xxxxxxx (ISO) 2,3-xxxxxxx-1,4-xxxxxxxxxxx		204–210–5	117–80–6	Xx; X22 Xi; X36/38 X; R50–53	Xn; N X: 22–36/38–50/53 X: (2-)26–60–61
606–019–00–6	xxxxxxxxxx (XXX) xxxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx xxxxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx 1,2,4,5,6,7,8,8,9,10-xxxxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx		205–601–3	143–50–0	Xxxx. xxx. 3; R40 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 (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-4,5-xxxxxxx-1,2,4-xxxxxxx-5-xx		244–209–7	21087–64–9	Xx; X22 X; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
606–035–00–3	xxxxxxxxxxx (XXX) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx pyrazon		216–920–2	1698–60–8	R43 N; X50–53	Xx; X R: 43–50/53 X: (2-)24–37–60–61
606–036–00–9	chinomethionát (XXX) 6-xxxxxx-2 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx		219–455–3	2439–01–2	Xxxx. xxx. 3; X62 Xx; X20/21/22–48/22 Xx; X36 X43 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	triadimefon (XXX) 1-(4-chlorfenoxy)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		256–103–8	43121–43–3	Xx; X22 X; X51–53	Xx; X X: 22–51/53 X: (2-)61
606–044–00–2	2,4,6-xxxxxxxxxxxxxxxxxxx xxxxx(2,4,6-xxxxxxxxxxxxxx)xxxxxxxx		403–150–9	954–16–5	Xx; X22 Xx; R36 X; X50–53	Xx; X X: 22–36–50/53 X: (2-)26–60–61
607–043–00-X	xxxxxxx (ISO) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx		217–635–6	1918–00–9	Xx; R22 Xx; X41 R52–53	Xn; X 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 R52–53	Xn X:48/22–52/53 X: (2-)37-61
607–058–00–1	xxxxxxxxx (XXX) fumarin (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -chromen-2-on 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-furyl)-3-oxobutyl]-4-hydroxy-2 H -xxxxxxx-2-xx		204–195–5	117–52–2	X; X25–48/25 X52–53	X X:25–48/25–52/53 X: (1/2-)37–45–61
607–079–00–6	xxxxxxx (XXX) xxxxx-4-xxx-5-(xxxxxxxx-5-xxxxxxxxxxxxxxxxx[5.3.0.02,6.03,9.04,8]xxxxx-5-xx)xxxxxxxxx xxxxx-5-(1,2,3,5,6,7,8,9,10,10-xxxxxxxxx-4-xxxxxxxxxxxxxxxxx[5.2.1.02,6.03,9.05,8]xxxxx-4-xx)-4-xxxxxxxxxxxx xxxxx-5-(1,2,4,5,6,7,8,8,9,10-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx[5.3.0.02,6.04,10.05,9]xxxxx-3-xx)-4-xxxxxxxxxxxx		—	4234–79–1	X; X24 Xx; X22 X; X51–53	X; X X: 22–24–51/53 X: (1/2-)36/37–45–61
607–097–00–4	xxxxxx-1,2,4-xxxxxxxxx-1,2-xxxxxxxx 1,2-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx kyseliny xxxxxxxxxxxxxxxxx		209–008–0	552–30–7	Xx; X37–41 X42/43	Xx X: 37–41–42/43 X: (2-)22–26–36/37/39
607–143–00–3	xxxxxxxxx xxxxxxxx xxxxxxxx kyselina		203–677–2	109–52–4	C; X34 X52–53	X R:34–52/53 X: (1/2-)26–36–45–61
607–152–00–2	2,3,6-XXX (ISO) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx		200–026–4	50–31–7	Xx; X22 X; X51–53	Xx; X X: 22–51/53 S: (2-)61
607–153–00–8	xxxxxxxxx (ISO) (4-chlor-2-oxo-2,3-dihydro-1,3-benzothiazol-3-yl)octová xxxxxxxx		223–297–0	3813–05–6	Xx; R36/38 X52–53	Xx X:36/38–52/53 X: (2-)22-61
607–156–00–4	chlorfenson (XXX) 4-xxxxxxxxxx-4-xxxxxxxxxxx-1-xxxxxxxx		201–270–4	80–33–1	Xx; R22 Xx; X38 X; X50–53	Xx; N R: 22–38–50/53 S: (2-)37–60–61
607–158–00–5	xxxxx xxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx sodný		223–498–3	3926–62–3	T; X25 Xx; X38 X; X50	X; N X: 25–38–50 S: (1/2-)22–37–45–61
607–159–00–0	xxxxxxxxxxxxxx (XXX) ethyl-2,2-bis(4-chlorfenyl)-2-hydroxyacetát xxxxx-4,4'-xxxxxxxxxxxxxxx		208–110–2	510–15–6	Xx; X22 X; X50–53	Xx; X R: 22–50/53 X: (2-)60-61
607–176–00–3	Xxxx: α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-xxxxxxxxxxx(xxxxxxxxxx);α-{3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}-ω-({3-[3-(2 X-xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxx}xxx)xxxx(xxxxxxxxxx)		400–830–7	—	X43 X; X51–53	Xx; N X: 43–51/53 X: (2-)36/37–61
607–188–00–9	xxxxxxx-xxxxxxxx-X-(2-xxxxxxxxxxxx)-X-(xxxxxxx-9-xx-1-xx)xxxxxxxxxx		402–970–4	—	X43 X; X51–53	Xx; X R: 43–51/53 X: (2-)24/37–61
607–209–00–1	Xxxx: O,O′-diisopropyl-trisulfanbis(karbothioát); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx)		403–030–6	—	Xx; X22 X43 X; X50–53	Xx; X R: 22–43–50/ 53 S: (2-)36/37–60–61
607–213–00–3	xxxxx-3,3-xxx(xxxx-xxxxxxxxxxxx)xxxxxxxx		403–320–2	67567–23–1	X; X2 X; X7 X10 X; R51–53	E; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61
607–217–00–5	2-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 X: (2-)24–37–61
607–243–00–7	xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-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 S: (2)
607–249–00-X	(xxxxxxxxxxxxx)xxx[xxx(xxxxxxxxxxxxx)]-xxxxxxxxx tripropylenglykol-diakrylát XXXXX		256–032–2	42978–66–5	Xx; X36/37/38 X43 X; X51–53	Xx; X X:36/37/38–43–51/53 X: (2-)24–37–61	C ≥ 10 %: Xx; X36/37/38–43 1 % ≤ C < 10 %: Xx; 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+; X26 X; R25 Xx; X21 N; X50–53	X+; X R: 21–25–26–50/53 X: (1/2-)28–36/37/39–38–45–60–61
607–255–00–2	xxxxxxxxxx (ISO) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx xxxxxxxx		—	69377–81–7	X52–53	X: 52/53 X: 61
608–003–00–4	xxxxxxxxxxxx	X X	203–466–5	107–13–1	X; Xxx Xxxx. xxx. 2; R45 T; X23/24/25 Xx; R37/38–41 X43 X; X51–53	X; X; X R: 45–11–23-/24/25–37/38–41–43–51/53 S: 9–16–53–45–61	C ≥ 20 %: X; X45–23/24/25–37/38–41–43 10 % ≤ C &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ X &xx; 5 %:T; X45–23/24/25–43 0,2 % ≤ C &xx; 1 %:X; X45–20/21/22 0,1 % ≤ X < 0,2 %: X; X45	43
608–016–00–5	2,3,5,6-xxxxxxxxxx-1,4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxx		401–550–8	1897–41–2	X43 X; X50–53	Xx; X X: 43–50/53 X: (2-)24–37–60–61
609–030–00–4	xxxxxxxx (XXX) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx	X	215–813–8	1420–07–1	Xxxx. xxx. 2; X61 X+; X28 X; X24 X44 X; X50–53	X+; X X: 61–24–28–44–50/53 X: 53–45–60–61
609–040–00–9	xxxxxxxx (ISO) (2,4-xxxxxxxxxxxx)(4-xxxxxxxxxx)xxxxx	X	217–406–0	1836–75–5	Xxxx. xxx. 2; R45 Xxxx. xxx. 2; X61 Xx; R22 X; R50–53	T; X X: 45–61–22–50/53 S: 53–45–60–61
609–044–00–0	xxxxxxxx (XXX) 1,2,4,5-xxxxxxxxxx-3-xxxxxxxxxxx		204–178–2	117–18–0	Xx; X22 R43 X; X50–53	Xx; X X: 22–43–50/53 X: (2-)24–37–60–61
611–008–00–4	4-aminoazobenzen 4-(xxxxxxxx)xxxxxx		200–453–6	60–09–3	Xxxx. kat. 2; X45 N; X50–53	X; X X: 45–50/53 X: 53–45–60–61
611–013–00–1	4-xxxxxxx-3-{4-[2-xxxxxxx-4-(3-xxxxxxxxxxxxxxxxx)xxxxxxxx]-3-xxxxxxxxxxxxxx}-6-(3-xxxxxxxxxxxxxxxx)xxxxxxxx-2-xxxxxxxx trilithný		403–650–7	117409–78–6	E; X2 X; X51–53	X; X X: 2–51/53 X: (2-)35-61
611–031–00-X	4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx XX Xxxxx Xxx 9 XX xxxxxxx červeň 9		209–321–2	569–61–9	Xxxx. xxx. 2; X45	X X: 45 X: 53-45
612–035–00–4	2-xxxxxxxxxxxxx x-xxxxxxxx	X	201–963–1	90–04–0	Xxxx. xxx. 2; X45 Xxxx. kat. 3; X40 T; 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; X22 X; X50–53	X; X X: 45–22–50/53 X: 53–45–60–61	X ≥ 25 %: X; X45–22 0,01 % ≤ X &xx; 25 %: X; X45
612–051–00–1	4,4'-xxxxxxxxxxxxxxxxxxxx xxx(4-xxxxxxxxxx)xxxxxx 4,4'-methylendianilin	E	202–974–4	101–77–9	Karc. xxx. 2; R45 Muta. xxx. 3; R40 X; X39/23/24/25Xx; R48/20/21/22 X43 X; X51–53	X; X X: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61
612–081–00–5	3,3'-xxxxxxxxxxxxxxxx, soli x-xxxxxxx, xxxx	X E	210–322–5 265–294–7 277–985–0	612–82–8 64969–36–4 74753–18–7	Xxxx. xxx. 2; X45 Xx; R22 X; X51–53	X; N R: 45–22–51/53 X: 53–45–61
612–099–00–3	4-xxxxxx-x-xxxxxxxxxxxxx4-xxxxxx-1,3-xxxxxxxxxxxxx4-xxxxxxxxxxxx-1,3-xxxxxx 2,4-xxxxxxxxxxxx	X	202–453–1	95–80–7	Xxxx. xxx. 2; X45 X; X25 Xx; X21 Xx; X36 X43 X; X51–53	X; N X: 45–21–25–36–43–51/53 X: 53–45–61
612–105–00–4	2-(xxxxxxxxx-1-xx)xxxxxxxxx2-(xxxxxxxxx-1-xx)xxxxx-1-xxxx		205–411–0	140–31–8	Xx; X21/22 X; R34 X43 R52–53	C R: 21/22–34–43–52/53 S: (1/2-)26–36/37/39–45–61
612–111–00–7	2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,3-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,3-xxxxxx 2,6-xxxxxxxxxxxx		212–513–9	823–40–5	Xxxx. xxx. 3; X40 Xx; R21/22 X43 N; X51–53	Xx; X R: 21/22–40–43–51/53 X: (2-)24–36/37–61
612–125–00–3	2-xxxxxx-x-xxxxxxxxxxxxx2-xxxxxx-1,4-xxxxxxxxxxxxx2-xxxxxxxxxxxx-1,4-xxxxxx 2,5-toluendiamin		202–442–1	95–70–5	T; X25 Xx; X20/21 X43 N; R51–53	T; 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 R4 3 X; X50–53	Xx; X X: 36/38–43–50/53 X: (2-)36/37–60–61
612–151–00–5	diaminotoluen xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx	X	246–910–3	25376–45–8	Xxxx. xxx. 2; X45 T; X25 Xn; X20/21 Xx; X36 X43 X; X51–53	X; X X: 45–20/21–25–36–43–51/53 S: 53–45–61
613–018–00–4	xxxxxxxxxx (XXX) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx		—	7411–47–4	Xx; X22 Xx; R36/37/38 X52–53	Xx X: 22–36/37/38–52/53 X: (2-)22–36–61
613–031–00–5	xxxxxxxxx xxxxxxxxxxxxxxxxxxxx xxxxxxxx trichlor-1,3,5-triazintrion 1,3,5-trichlor-1,3,5-triazin-2(1H), 4(3X), 6(5X)-xxxxx		201–782–8	87–90–1	X; R8 Xx; X22 R31 Xx; X36/37 N; X50–53	X; Xx; N X: 8–22–31–36/37–50/53 X: (2-)8–26–41–60–61
613–038–00–3	6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx xxxxxxxxxxxxx		202–095–6	91–76–9	Xx; X22 X52–53	Xx X:22–52/53 X: (2-)61
613–042–00–5	xxxxxxxx (ISO) 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-(allyloxy)-2-(2,4-dichlorfenyl)ethyl]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx		261–351–5 [1] 281–291–3 [2]	58594–72–2 [1] 83918–57–4 [2]	Xx; X20/22 Xx; X41 N; R50–53	Xn; X R: 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; X22 X; X50–53	Xx; N R: 22–50/53 X: (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; X22 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-xxxxx-2-xxxxxxxxxx		403–700–8	2687–94–7	X; X34 X; X51–53	X; X X: 34–51/53 X: (1/2-)23–26–36/37/39–45–61
613–130–00–3	xxxxxxxxxxx (XXX) (XX)-2-(2,4-xxxxxxxxxxxx)-1-(1X-1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	79983–71–4	X43 X; R51–53	Xi; X X: 43–51/53 X: (2-)24–37–61
613–131–00–9	xxxxxxxxxx (ISO) 1,2,5,6-xxxxxxxxxx-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx		—	57369–32–1	Xx; R22 X52–53	Xx X:22–52/53 X: (2-)61
613–134–00–5	xxxxxxxxxxxx (XXX) 2-(4-chlorfenyl)-2-[(1 H-1,2,4-triazol-1-yl)methyl]hexannitril		—	88671–89–0	Repr. xxx. 3; X63 Xx; R22 Xi; X36 X; X51–53	Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61
613–137–00–1	methabenzthiazuron (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx		242–505–0	18691–97–9	X; X50–53	X R: 50/53 X: 60-61
613–139–00–2	metsulfuron-methyl xxxxxx-2-{X —[X-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxxx]xxxxxxxxx}xxxxxxx		—	74223–64–6	X; X50–53	X X: 50/53 S: 60-61
614–001–00–4	xxxxxxx (XXX) 3-(1-xxxxxxxxxxxxxxxx-2-xx)xxxxxxx		200–193–3	54–11–5	X+; X27 X; R25 X; X51–53	X+; N X: 25–27–51/53 X: (1/2-)36/37–45–61
614–006–00–1	xxxxxx 2,3-dimethoxystrychnidin-10-on		206–614–7	357–57–3	T+; X26/28 X52–53	X+ R: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+; X26/28 X52–53	X+ X: 26/28–52/53 X: (1/2-)13–45–61
615–006–00–4	2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-methyl-m-fenylendiisokyanát [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] m-tolylidendiisokyanát [3] 5-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [3] xxxxxx-2,6-xxxxxxxxxxx [1] xxxxxx-2,4-xxxxxxxxxxx [2] toluen-3,5-diisokyanát [3]	X	202–039–0 [1] 209–544–5 [2] 247–722–4 [3]	91–08–7 [1] 584–84–9 [2] 26471–62–5 [3]	Xxxx. xxx. 3; X40 X+; X26 Xx; X36/37/38 R42/43 X52–53	X+ X: 26–36/37/38–40–42/43–52/53 X: (1/2-)23–36/37–45–61	X320 %: X+; X26–36/37/38–40–42/43 7 % ≤ X &xx; 20 %: X+; X26–40–42/43 1 % ≤ C &xx; 7 %: X; X23–40–42/43 0,1 % ≤ C &xx; 1 %:Xx; X20–42	2
616–010–00–9	xxxxxxx-xxxxxxxxxxxxxx X-xxxxx-4-xxxxxxxxxxxx-1-xxxxxxxxxx, xxxxx xxx		204–854–7	127–65–1	Xx; X22 X31 X; R34 R42	C X: 22–31–34–42 S: (1/2-)7–22–26–36/37/39–45
616–034–00-X	xxxxxxxxxxxx (XXX) 6-xxxxxx-3,4-xxxxxxx-2X-xxxxx-5-xxxxxxxxxxxx		246–419–4	24691–76–7	X52–53	X: 52/53 X: 61
616–035–00–5	xxxxxxxxx X -[(ethylamino)karbonyl]-2-kyan-2-(methoxyimino)acetamid 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx		261–043–0	57966–95–7	Xx; X22 R43 N; X50–53	Xx; X X: 22–43–50/53 X: (2-)36/37–60–61
617–004–00–9	(1,2,3,4-tetrahydro-1-naftyl)hydroperoxid xxxxxxxxxxxxxxxxxxxx	212–230–0	771–29–9	X; X7 Xn; 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 %: X; X22–34 10 % ≤ X &xx; 25 %: X; X34 5 % ≤ C < 10 %: Xx; X36/37/38
617–006–00-X	xxx(α, α-xxxxxxxxxxxxxx)xxxxxxx bis(2-fenylpropan-2-yl)peroxid xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx dikumylperoxid		201–279–3	80–43–3	O; X7 Xx; X36/38 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; X2 Xi; X36 X43	X; Xx; X: 2–36–43 X: (2-)3/7–14–36/37/39
650–007–00–3	xxxxxxxxxxxxx (XXX) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx		228–200–5	6164–98–3	Xxxx. xxx. 3; X40 Xn; R21/22 X; R50–53	Xn; N 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; X25 X; X50–53	X; N R: 25–50/53 X: (1/2-)22–24–36/37–45–60–61
650–009–00–4	chlordimeform-hydrochlorid X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx		243–269–1	19750–95–9	Xxxx. xxx. 3; R40 Xx; R22 X; X50–53	Xx; X X: 22–40–50/53 X: (2-)22–36/37–60–61
650–033–00–5	xxxxxxxxxxxx (XXX) [(S)-(3-fenoxyfenyl)kyanmethyl]-(S)-2-(4-chlorfenyl)-3-methylbutanoát (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 S: (1/2-)24–36/37/39–45–60–61
650–041–00–9	xxxxxxxxxxxx (XXX) 1-[2-(2-xxxxxxxxxxx)xxxxxx-1-xxxxxxxx]-3-(4-xxxxxxx-6-xxxxxx-1,3,5-xxxxxxx-2-xx)xxxxxxxx		—	82097–50–5	X; X50–53	X X: 50/53 X: 60-61

XXXXXXX 1X

Xxxxxxxx číslo	Chemický 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 R52–53	Xn X: 20–41–52/53 X: (2-)22–26–39–61
014–016–00–0	Xxxx: 1,3-di(hex-5-en-1-yl)- 1,1,3,3-tetramethyldisiloxan x 1,3-xx(xxx-x-xx-1-xx)- 1,1,3,3-xxxxxxxxxxxxxxxxxxxx		406–490–6	—	X; X51–53	X X: 51/53 X: 61
015–164–00–9	xxxxxxx-xxxxxxxxxx-(1-xxxxxxxxxxxxxx)xxxxxxxxxxx xxxxxxxx		400–480–5	36669–85–9	X52–53	X:52/53 X: 61
015–165–00–4	Xxxx: S, X, X', S''-tetrafenyl-4,4'-sulfandiylbis(fenylsulfonium)-bis(hexafluorofosfát) x difenyl[4-(fenylsulfanyl)fenyl]sulfonium-hexafluorofosfát		404–986–7	—	Xi; X41 X; X50–53	Xx; N X: 41–50/53 S: (2-)15–26–39–60–61
015–166–00-X	3,9-xxx(2,6-xx-xxxx-xxxxx-4-xxxxxxxxxxxx)-2,4,8,10-xxxxxxxx-3,9-xxxxxxxxxxxx[5.5]xxxxxxx		410–290–4	80693–00–1	X53	X:53 S: 61
015–167–00–5	3-[hydroxy(fenyl)fosfinoyl]propanová xxxxxxxx		411–200–6	14657–64–8	Xx; R41	Xi R: 41 X: (2-)26-39
601–050–00–1	X10-X13-xxxxxxxxxxxxx xxxxxxx		267–051–0	67774–74–7	X; R50	N X: 50 X: 61
601–051–00–7	4-xxxxxxxx-1-xx		405–980–7	768–56–9	Xx; X38 X; X51–53	Xx; 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 R64 X; X50–53	Xx; X X: 48/21/22–50/53–64 X: (1/2-)36/37–45–60–61
602–084–00-X	1,1-xxxxxxx-1-xxxxxxxxxx		404–080–1	1717–00–6	X; X52–53–59	X R: 52/53–59 X: 59-61
603–128–00–0	2-(xxxxxxxxxxxx)xxxxxxxx		405–490–3	613–62–7	X53	X:53 X: 61
603–129–00–6	1-xxxx-xxxxxxxxxxxx-2-xx		406–180–0	57018–52–7	X10 Xi; X41	Xx X: 10-41 X: (2-)26-39
603–130–00–1	Xxxx isomerů: α-(xxxxxxxxxxxxxxxxx)-ω-xxxxxxxxxxx(xxxxxxxxxx)		406–325–8	—	Xx; X22 X52–53	Xx X:22–52/53 S: (2-)39-61
603–131–00–7	Xxxx (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-deoxy-1-[methyl(1-oxotetradecyl)amino]-D-glucitol		407–290–1	—	Xi; X41	Xx X: 41 S: (2-)26-39
603–132–00–2	2-(xxxxxxxxxxxxx)-6-xxxxxxxxx-9-xxxxxx-1,4-xxxxxxxxxx[4.5]xxxxx		408–200–3	63187–91–7	Xx; R38–41 R52–53	Xi X:38–41–52/53 X: (2-)26–37/39–61
603–133–00–8	Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-xxxxx-5-xxxxx-1,4-xxxxxxx)xxxxxxx]xx(xxxxxx-1,2-xxxx)		408–240–1	—	Xx; X22 X52–53	Xx 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-nitrilotriethan-1-olato-N,O)titaničitý xxxxxxx		410–500–4	—	Xx; X41 N; X51–53	Xx; X X: 41–51/53 X: (2-)26–39–61
603–136–00–4	3-{4-[xxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxxx}xxxxxx-1-xx		410–910–3	104226–19–9	X43 X52–53	Xx X:43–52/53 X: (2-)24–37–61
603–137–00-X	Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx		411–130–6	—	Xx; X41	Xx X: 41 X: (2-)26-39
603–138–00–5	3-(2,2-xxxxxxxx-3-xxxxxxxxxxxxx)xxxxxx 2,2-xxxxxxxx-3-(3-xxxxxxxxxxx)xxxxxx-1-xx		403–140–4	103694–68–4	X52–53	X:52/53 X: 61
604–050–00-X	4-xxxxx-x-xxxxxx 4-xxxxx-2-xxxxxxxxxxx		216–381–3	1570–64–5	X; X23 X; X 35 X; X50	X; X; X R: 23–35–50 X: (1/2-)26–36/37/39–45–61	C ≥ 25 %: X; C; X23–35 10 % ≤ X &xx; 25 %: C;R20–35 5 % ≤ X &xx; 10 %: X;X20–34 3 % ≤ X &xx; 5 %: Xx;X20–36/37/38 1 % ≤ X < 3 %:Xx;X36/37/38
604–051–00–5	3,5-xxx(3,5-xx-xxxx-xxxxx-4-xxxxxxxxxxxxx)-2,4,6-xxxxxxxxxxxxxx		401–110–5	87113–78–8	X52–53	X:52/53 X: 61
604–052–00–0	2,2'-xxxxxxxxxxx[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx		403–800–1	103597–45–1	X53	X:53 X: 61
604–053–00–6	4-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 a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx		412–020–0	—	X43 R52–53	Xi X:43–52/53 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; R40	Xn X: 40 S: (2-)22–36–37
605–027–00–7	Xxxx:3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X-xxxxx-6-xxxxxxxxxxx x 3x, 4,5,6,7,7a-hexahydro-4,7-methano-1H - xxxxx-5-xxxxxxxxxxx		410–480–7	—	X43 N; R51–53	Xi; X X: 43–51/53 X: (2-)24–37–61
606–051–00–0	4-pentylcyklohexanon xxxxxxxxxxxxxxxx-1-xx		4–406–670–4	61203–83–6	X; X51–53	X X: 51/53 X: 61
606–052–00–6	4-(X, N-dibutylamino)-2-hydroxy-2'-karboxybenzofenon 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx xxxxxxxx		410–410–5	54574–82–2	X52–53	X:52/53 X: 61
607–272–00–5	xxxxxxxxxxx-xxxxxx (ISO) [1] xxxxxxxxxx-xxxxxxxxx (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-xxxxxx-1-xxxxxxxxxxx)-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [2]		279–752–9 [1] —	81406–37–3 [1] 154486–27–8 [2]	X; X50–53	X X: 50/53 X: 60-61
607–273–00–0	xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 1,2,6,7,8,8x-xxxxxxxxx-1-xxxxxx}-3,5-xxxxxxxxxxxxxxxxxx		404–520–2	—	X52–53	X:52/53 X: 61
607–274–00–6	{2-[xxxxxx(xxxxxx)xxxxx]xxxxx}-3-xxxxxxxx-2-xxxxx		405–350–1	54527–73–0	X43 N; X51–53	Xx; X R: 43–51/53 X: (2-)24–37–61
607–275–00–1	xxxxxxx-4-(xxxxxxxxxx)xxxxxx-1-xxxxxxxx		405–450–5	66531–87–1	X43	Xx X: 43 X: (2-)24-37
607–276–00–7	[xxx(2-xxxxxxxxxxxxxx) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx xxxxxxx		405–635–0	—	Xx; X38–41 X; X50–53	Xx; X R: 38–41–50/53 X: (2-)26–37/39–60–61
607–277–00–2	Směs:2-(hexylsulfanyl)ethylamin-hydrochlorid x xxxxxxx-xxxxxxxxx		405–720–2	—	Xx; X22 Xx; X41 X43 N; X51–53	Xx; N X: 22–41–43–51/53 X: (2-)24–26–37/39–61
607–278–00–8	Směs:alkyl(C7-C9 xxxxxxxxxx x xxxxxxxxxxxx)-3-[3-(2 X - xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx		405–760–0	—	Xx; X41 X43 R52–53	Xi X: 41–43–52/53 X: (2-)24–26–37/39–61
607–279–00–3	Xxxx:(xxxxxxxxxxxxxx)xxxxxxxxx-xxx(xxxxxxxx-xxxxxxxx) a (oktadecylimino)diethylen-(hydrogen-ftalát)-(hydrogen-maleinát)		405–960–8	—	R43 X; X51–53	Xx; X X: 43–51/53 S: (2-)24–37–61
607–280–00–9	4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx xxxxx natrium-4-chlor-1-hydroxybutan-1-sulfonát		406–190–5	54322–20–2	Xn; X22 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; X51–53	X X: 51/53 X: 61
607–282–00-X	2-(xxxxxxxxxxxxx)-4-(xxxxxxxxx)xxxxx-xxxxxx		407–140–5	131266–10–9	X52–53	X: 52/53 X: 61
607–283–00–5	xxxxx-(X)-4-xxxxx-4-xxxxxx-2-xxxxxxxxxx-(X)-4-xxxxx-4-xxxxxxxxxxx		408–040–4	15121–89–8	Xx; X21/22 Xx; X38–41 R43 X; X50–53	Xx; N X: 21/22–38–41–43–50/53 X: (2-)26–36/37/39–60–61
607–284–00–0	Xxxx (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) 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 xxxxxxxx, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x natrium-7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonát		410–065–0	—	R43	Xi X: 43 X: (2-)22–24–37
607–286–00–1	Xxxx:xxxxxx- a xxxxxxx-7-[4-({4-[(2-xxxxxxx-1-xxxxxx)xxx]xxxxx}xxx)xxxxxxxxxxxxxxxxx]xxxxxxxx-1,3-xxxxxxxxxx		410–070–8	141880–36–6	X43 X52–53	Xx X:43–52/53 X: (2-)22–24–37–61
607–287–00–7	xxxxxx-[1-xxxxxx-2-(xxxxxxxxxxxxxxx)xxxxx]-1,2,3,6-xxxxxxxxxxxxxxxx		410–140–8	—	X52–53	X:52/53 X: 61
607–288–00–2	[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; c = 15, 16, 17 xxxx 18, x = 1, 2, 3 nebo 4, x = 8, 9, 10 xxxx 11, d = 22, 23, 24 xxxx 25		410–160–7	148732–74–5	Xx; X36 X43 R52–53	Xi X: 36–43–52/53 X: (2-)22–26–36/37–61
607–288–00–8	3-[(3-{X —[4-(2,4-di-terc-pentylfenoxy)butyl]karbamoyl}-4-hydroxy-1-naftyl)sulfanyl]propanová xxxxxxxx		410–370–9	105488–33–3	X53	X:53 X: 61
607–290–00–3	Xxxx (o xxxxxxxx xxxxxx):xxxxxxx-1-xxxxx(X14-X18)-4-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx a xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx		410–540–2	—	Xx; X38 X43 X; R50–53	Xi; X X: 38–43–50/53 S: (2-)24–37–60–61
607–291–00–9	xxxxxxx-ω-xxxxxxxxxxx(xxxx xxxxxxxxxx)xxxxxxxx		410–630–1	104051–92–5	X53	X: 53 X: 61
607–292–00–4	Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(alkyl(C14)oxy)-1-(methoxymethyl)]octová xxxxxxxx		410–640–6	—	Xx; X38–41 N; X50–53	Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61
607–293–00-XXxxx:	1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx		410–650–0	—	Xx; X41 R43 X; X51–53	Xx; X X: 41–43–51/53 X: (2-)26–36/37/39–61
607–294–00–5	xxxxxxx-2-(xxxxxxxxxx)-1-xxxxxxxxxxxx-1-xxxxxxxx		410–680–4	—	X43	Xx X: 43 X: (2-)24-37
607–295–00–0	Směs:tetranatrium-fosfonobutandioát x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx		410–800–5	—	X43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
607–296–00–6	Xxxx:xxxxxxxxxxx xxxxxxxxxxxxxxxx, xxxxxxxxx xxxxxxxx a 2-xxxxxxxxxxxxx kyselina		410–830–9	—	R53	R: 53 X: 61
607–297–00–1	3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(2-xxxxxxxxx-10-xxxxxxxxx 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 X: (2-)26-39
607–298–00–7	[2-(xxxxxxxxxxxxxxx)xxxxx]-4-xxxxxxxxxxxxxxxx		411–010–3	—	X43	Xx X: 43 S: (2-)22–36/37
607–299–00–2	xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx		411–040–7	97101–46–7	Xx; X22 R43 X; R50–53	Xn; X X: 22–43–50/53 S: (2-)24–37–60–61
607–300–00–6	[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, d-sulfonatoftalocyanin]měďnatý xxxxxxx, xxxxxxxx xxx; x = 1,2,3 xxxx 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 oligo(1-7)laktátů		411–860–5	—	Xi; X38–41 R43 X; X51–53	Xx; N X: 38–41–43–51/53 X: (2-)24–26–37/39–61
607–302–00–7	Směs:tetradekanová xxxxxxxx x tetradekanoáty xxxxx(1-7)xxxxxxx		411–910–6	—	Xx; X38–41 X43 X; X51–53	Xx; X X: 38–41–43–51/53 S: (2-)24–26–37/39–61
607–303–00–2	1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx kyselina		413–760–7	93107–30–3	Repr. xxx.3; X62 X52–53	Xx R: 62–52/53 X: (2-)22–36/37–61
608–023–00–3	4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		406–140–2	114369–43–6	X; R50–53	N X: 50/53 X: 60-61
608–024–00–9	2-{4-[xxxxx(xxxxxxxx)xxxxx]xxxxx}xxxxx-1,1,2-xxxxxxxxxxxxxx		407–650–8	97460–76–9	X53	X:53 X: 61
608–025–00–4	[2-nitro-4,5-bis(benzyloxy)fenyl]acetonitril		410–970–0	117568–27–1	R53	R:53 X: 61
609–053–00-X	xxxxxxxxxxx-xxxxxxxxxxxxxxxx		414–850–9	—	X; R3 X; X8 Karc. xxx. 2; X45 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 C; X34 R43 X; X50–53	X; N 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]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx trisodný x[{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-amino-6-hydroxyfenyl)azo]- nebo 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx		402–850–1			Xx X: 41–52/53 X: (2-)26–39–61
611–044–00–0	Xxxx:[xxx(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [bis(4-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx x[(4(5)-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx) (3-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx		403–720–7	117527–94–3	X; X51–53	Xx; R41 X52–53
611–045–00–6	2-({4-[(4-xxxxxxxxxxxx)xxxxxxxxxx]-2-xxxxxxxxxxx}xxx)-3-xxxxxx-5-xxxxxxxxxxxx		404–830–8	—	X53	X:53 X: 61	X X: 51/53 S: 61
611–046–00–1	4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx		407–590–2	43151–99–1	X; X25 Xn; X48/22 X43 X; X50–53	X; X R: 25–43–48/22–50/53 S: (1/2-)22–28–36/37–45–60–61
611–047–00–7	Xxxx (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[(2-acetoxyethyl)ethylamino]fenyl}azo)-6,7-dichlorbenzothiazol		407–890–3	111381–11–4	R53	R: 53 X: 61
611–048–00–2	Směs (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx a 2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx	407–900–6	111381–12–5	X53	X: 53 X: 61
611–049–00–8	Xxxx (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, xxxxxxxx xxxxxx x xxxxxx xxxxxxxx (2:1:1)	408–000–6	118658–98–3	Xx; R48/22 X43 X52–53	Xx R: 43–48/22–52/53 X: (2-(22–36/37–61
611–051–00–9	2-({4-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx		411–110–7	136213–74–6	X; R50–53	N X: 50/53 S: 60-61
611–052–00–4	[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx xxxxxxx, xxxxx xxx		400–720–9	—	X52–53	X: 52/53 X: 61
612–156–00–2	Směs:trihexadecyl(methyl)amonium-chlorid x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx		405–620–9	—	Xx; X41 X; X50–53	Xx; X X: 41–50/53 S: (2-)26–39–60–61
612–157–00–8	(Z)-1-(1-benzothiofen-2-yl)ethan-1-on-oxim-hydrochlorid		410–780–8	—	Xn; X22–48/22 Xx; R41 X43 X; X51–53	Xx; X R: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61
612–158–00–3	Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-dodecyl-2-hydroxybenzaldoxim[bis(5-alkyl(rozvětvený X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx komplex x 4-xxxxxxxxxxxxxxxxxxxxx		410–820–4	—	X53	X: 53 X: 61
612–159–00–9	xxxxxxx xxxxxxxx xxxxx 2,2,4-xxxxxxxxx- a 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Xxxxxx 8) x 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx		410–880–1	—	Xx; X22 X; X34 X; X50–53	X; X X: 22–34–50/53 X: (1/2-)23–26–36/37/39–45–60–61
613–149–00–7	2-xxxx-xxxxx-5-[(4-xxxx-xxxxxxxxxxx)xxxxxxxx]-4-xxxxxxxxxxxxxx-3(2X)-xx		405–700–3	96489–71–3	X; R23/25 X; X50–53	X; N X: 23/25–50/53 X: (1/2-)36/37–45–60–61
613–150–00–2	2,2'-[xxxxxxxxx-1,4-xxxxxx(xxxxxx-1,3-xxxx)]xxx(xxxxxxxxxxx[2,1-x]xxxxx[xxx][3,8]xxxxxxxxxxxx-1,3,6-xxxxx)		406–295–6	—	X53	X:53 X: 61
613–151–00–8	1-(2-xxxxx-3-X-xxxxx-5-X-xxxxxx-β-X-xxxxx-xxxxxxxxxxxxxx)-5-xxxxxxxxxxxxxxx-2(1X), 4(3 X)-xxxx		406–360–9	104218–44–2	X53	X:53 X: 61
613–152–00–3	xxxxx-X-(4,6-xxxxxxxxxxxxxxxxxx-2-xx)xxxxxxxx		406–600–2	89392–03–0	X43 N; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
613–153–00–9	2,3,5-trichlorpyridin		407–270–2	16063–70–0	R52–53	R:52/53 S: 61
613–154–00–4	2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx		410–050–9	5734–64–5	Xx; R22	Xn X: 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 S: (2-)23–36–61
613–156–00–5	2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-butyl-5-chlorimidazol-4-karbaldehyd		410–260–0	83857–96–9	R43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
613–157–00–0	2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx		410–330–0	54236–98–5	Xx; R22–48/22 Xx; X36	Xx X: 22–36–48/22 X: (2-)22–26–36
613–158–00–6	2,3-dichlor-5-(trifluormethyl)pyridin		410–340–5	69045–84–7	Xn; X20/22 Xx; R41 R43 X; X51–53	Xx; N X: 20/22–41–43–51/53 S: (2-)24–26–37/39–61
613–159–00–1	4-[2-(4-xxxx-xxxxxxxxxx)xxxxxx]xxxxxxxxxx		410–580–0	120928–09–8	X; R25 Xx; X20 X; X50–53	X; X X: 20–25–50/53 X: (1/2-)37–45–60–61
613–160–00–7	2-xxxxxx-2,5-xxxxxxxxxxxx[2.2.1]xxxxxx-xxxxxxxxxxxxx		411–000–9	125224–62–6	X43	Xx X: 43 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 R42/43	E; Xn X: 2–14–42/43–48/22 S: (2-)22–30–35–36/37
615–023–00–7	xxxxxxxxxxx 2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxxx xxxxxxxxxxxxxx-2-[(xxxxxxxxxxxxxxxxxx)xxxxxx]xxxxxxx		410–900–9	83056–32–0	X10 X14 Xxxx. kat. 3; X40 Xx; X20–48/22 Xx; R41 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 R53	Xi X: 43-53 S: (2-)22–24–37–61
616–046–00–5	X -[2-(6-chlor-7-methylpyrazolo[1,5-b][1,2,4]triazol-4-yl)propyl]-2-(2,4-di-terc-pentylfenoxy)oktanamid		406–390–2	—	N; X50–53	X X: 50/53 X: 60-61
616–047–00–0	Xxxx:X,X′,X″,X′′′ - xxxxxxxxxx(X16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x N, X′,X″,X′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(ethylendinitrilo)tetraacetamid		406–640–0	—	R43	Xi R: 43 S: (2-)24-37
616–048–00–6	3'-(xxxxxxxxxxxxxx)xxxxxxxxxxxxxx		406–740–4	1939–27–1	Xx; X48/22 X; X51–53	Xx; X X: 48/22–51/53 X: (2-)22–36–61
616–049–00–1	2-(2,4-di-terc-butylfenoxy)-N-(3,5-dichlor-4-ethyl-2-hydroxyfenyl)hexanamid		408–150–2	99141–89–6	R53	R:53 S: 61
616–050–00–7	1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx		410–690–9	103055–07–8	X43 X; R50–53	Xi; X R: 43–50/53 X: (2-)24–37–60–61
616–051–00–2	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	bis(4-methylbenzoyl)peroxid		407–950–9	895–85–2	E; X2 X; X7 N; X50–53	X; X X: 2–7–50/53 X: (2-)7–14–36/37/39–47–60–61
650–032–00-X	cyprokonazol (XXX) (2X, 3X)-, (2 X, 3 X)-, (2 X, 3 S)-, (2 X, 3 X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxx-1-(1X- 1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	94361–06–5	Xxxx. xxx. 3; X63 Xx; X22 X; R50–53	Xn; N X: 22–50/53–63 X: (2-)36/37–60–61

PŘÍLOHA 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI A XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX XXXXXXXX XXXXXXXXX X NEBEZPEČNÝMI LÁTKAMI X XXXXXXXXX

Xxx xxxxxxxx Xxxxxx 2001/59/XX,

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

XXXXXXX 3X

XXXXXXXXXX XXXXXX XXX BEZPEČNÉ ZACHÁZENÍ X XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX,

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

XXXXXXX 4A

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx na chromozomové xxxxxxx x xxxxx xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, které xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx x xxxxxxxxxxxxx xxxxxxx savců (1, 2, 3). Rozlišují xx dva xxxx xxxxxxxxxxxx aberací: chromozomové x xxxxxxxxxxxx. X xxxxxxx chemických mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx typu, xxxxx xxxxxxxxxxxx xxxxxxx xx xxxxxx vyskytují. Nárůst xxxxxxxxxxx může znamenat, xx xxxxxxxx xxxxx xx schopnost indukovat xxxxxxxxx xxxxxxx. Xxxx xxxxxx xxxx není xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x tomuto xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a xxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u xxxxxxx a xxxxxxxx xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx a s xxxx související jevy xxxxxxxxxxx xxxxx x xxxxxxxxxx x v xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx, mají xxxxx na xxxxxxx xxxxxxxx x xxxxxxx x u xxxxxxxxx xxxxxx.

Xx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, buněčné xxxxx xxxx primární xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxx x kultuře, stálosti xxxxxxxxx, počtu xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx chromozomových xxxxxxx.

Xxxxxxx prováděné xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxxxx aktivační systém xxxxxx xxxxx napodobit xxxxxxxx xx xxxx x xxxxx. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx vedly k xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x může k xxx dojít xxxxxx xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x karcinogenů pro xxxxx. Xxxxx xxxxxxxxx, xxx něž je xxxx zkouška pozitivní, xxxx xxx savce xxxxxxxxxxx; xxxx xxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxx není xxxxxxxxx xxxxxxxx. Korelace xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx důkazy x tom, že xxxxxxxx karcinogeny, které xxxxxx zjištěny touto xxxxxxxx, neboť zřejmě xxxxxx xxxxxx xxxxxxxxxx xxx přímým poškozením XXX.

Xxx také Obecný xxxx, xxxx X.

1.2 XXXXXXXX

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

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

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

Xxx : xxxxxxxxxxxx léze xxxxx xxx xxxxx jedné xxxxxxxxxx a s xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxx : xxxxx xxxxx, xxxxx xx xxxxxxxxx x metafázi, x xxxxxxxxx xxxxx xxxxx x populaci; xxxxx xxxxxx xxxxxxxxxxx xxxx populace.

Numerická aberace : odchylka xxxxx xxxxxxxxxx od xxxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxxx xxxx xxxxx.

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx, x xx x xxxxxxxxxxxx xxxxxxxx x bez xx. V xxxxxx xxxxxxxxxxx xxxxxxxxxxx po xxxxxxxx látce xx xx buněčných xxxxxx xxxxx látka zastavující xxxxxxxx (např. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx sklidí, xxxxxx x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxxxxxxx pozorováním buněk.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

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

1.4.1.2 Xxxxx x xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx kultur xx xxxx být xxxxxxx vhodná xxxxxxxxxx xxxxx a xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). U xxxxxxxxxxxxxxx xxxxxxxxx linií x kmenů by xxxx být xxxxxxx xxxxxxxxxxxx xxxxxxxxx modální xxxxxxx počtu xxxxxxxxxx x xxxx xx xxx xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x xxxxxxx xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Pro xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx by xxxx xxx známa xxxxxxxx xxxxx xxxxxxxxx cyklu.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x kmeny: xxxxx se xxxxxxx x xxxxxxxxx xxxxxx, xxxxxx xx do xxxxxxxxxxxx xxxxx v xxxxxx hustotě, aby xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx, x xxxxxxxx xx při 37 °X.

Xxxxxxxxx: xxxx ošetřená xxxxxxxxxxxxxxx (xxxx. xxxxxxxxx) xxxx xxxxxxxx lymfocyty xxxxxxxx probandů xx xxxxxxx xx xxxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx (xxxx. xxxxxxxxxxxxxxxx) x xxxxxxxx se xxx 37 °X.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx, a xx x xxxxxxx metabolickou xxxxxxxx x bez xx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx hlodavců zpracovaná xxxxxxxx indukujícím xxxxxx, xxxx je Aroclor 1254 (6, 7, 8 a 9), xxxx směs xxxxxxxxxxxxx x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx testovacím médiu xxxxxxx xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, xxxxx xx xxxxxxxx. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, včetně xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx exprimujících xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx být vědecky xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx cytochromu X450 xxx metabolismus xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx vehikulech x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxx přímo x testovacím xxxxxxxx x/xxxx mohou xxx xxxx xxxxxxxx zředěny. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx možnost skladování.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx mělo být xxxx podezření, že xxxxxxx se zkoušenou xxxxxx, a mělo xx být xxxxxxxxxx x xxxxxxxx buněk x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud možno xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx xxxxxxxxx xx xxxx xx xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

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

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

Xxxx by xxx xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx by xxxx tyto xxxxxxxxxxx xxxxxxxx xxxxxxx dané xxxxxxxxx až xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx obvykle xxxxxxx, že xx xx xxxxxxxxxxx neměly xxxxx xxxx nežli xxxxxxxx 2 xx Ö10. V xxxxxxxx xxxxxxx xx měla xxxxxxxx koncentrace xxxxxxxxx xxxxxxxx snížení xxxxxx xxxxxxxxxx, počtu xxxxx xxxx xxxxxxxxxxx xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx index xx xxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx a xxxxxx xx době, xxxxx xxxxxxxx od expozice. Xxxxxxxxx index je xxxx xxxxxxxxxx x xxxxxxxxxxx xxxxxx, x xxxxx xxxxx xxx xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx x xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxx, xxxxxxxxx xxxxxxxx xxxxxxxxx xxxx (XXX), xxxxx xxx použity xxxx xxxxxxxxx informace. X xxxxxxx XXX však xxx x xxxxxxxx xxxxxxxxx xxxxxxx, z xxx nelze xxxxxxx xx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxx, a i xxxx přírůstek xxxxxxxx xxxxxxxxx doby xxxx xxx xx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx optimálního výtěžku xxxxxxx.

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

X případě relativně xxxxxxxxxxxxx xxxxx, které xxxxxx xxxxxxx při xxxxxxxxxxxxx xxxxxxx, než xx xxxxxx xxxxxxxxxxx, xx xxxx xxx xxxxxxx xxxxxxxx xxxxx x koncentraci, xxx xx xxx xxxx xxxxxxxxxxxx v konečném xxxxxxxxxxx xxxxx na xxxxx doby xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. xxxxxxx-xx se xxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxxxxx, xxx xx rozpustnost) xx xxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxxxx, xxx xxxxx xxxxxxx xx xxxxxxx. Xxxx xxx užitečné xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx xxxxxxxx, neboť xxxxxxxxxxx v testovacím xxxxxxx xx xxxx x průběhu expozice xxxxx x důsledku xxxxxxxxxxx buněk, xxxx X9 atd. Xxxxxxxxxxxxx xxx xxxxxxx vizuálně. Xxxxxxxxx xx xxxxxx xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxxx a pozitivní xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly být xxxxxxxxx x negativní xxxxxxxx (kontroly rozpouštědla xxxx xxxxxxxx). Xxx xxxxxxx metabolické xxxxxxxx xx xxxx být xxx xxxxxxxxx xxxxxxxx xxxxxxx chemická látka, xxxxx x mutagenní xxxxxx vyžaduje xxxxxxxx.

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

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx xxxxxx nevyšla xxxxx xxxxxx kódovaná xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx x negativních xxxxxxx:

Xxxx xxxxxxxxxxx aktivace	Látka	Číslo XXX	Xxxxx podle XXXXXX
Xxx xxxxxx xxxxxxxxxxx xxxxxxxx	xxxxxx-xxxxxxxxxxxxxx	66–27–3	200–625–0
	xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
	1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
	xxxxxxxxx X	50–07–7	200–008–6
	4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1
X xxxxxx metabolickou 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 pozitivní xxxxxxxx xxxxx xxx xxxxxxx i xxxx xxxxxx xxxxx. Pro xxxxxxxxx kontrolu xx xxxx xxx xxxxx xxxxx vzato x xxxxx xxxxxxx xxxxxxxxxx xxxxx ze stejné xxxxxxxx xxxxx.

X xxxxxxxx xxxxxxxx by xxxx xxx použity xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx x xxxxxxxxxxx xxxxx x xxxxxxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx dosud žádné xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx buňky se xxxxxxx xxxxxxxx xxxxx xxx xx přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx, xxx xxx xxxx. Xxxxxxxx xxxxxxxxx xx xxxx xxx xxxxxxxx xxx 48 hodin xx xxxxxxxxx xxxxxxxxx.

1.4.3.2 Xxx každou xxxxxxxxxxx xx měly xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x xxxxx xx xxxxxxx xxxxxxxxxx x xxxxxx xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxx. Jestliže xxx na xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), xx xxxx xxxxxxxxxxxx xxxxxxxxx xx minimální xxxxxx, xxxx xxx přípustné xxxxxxx xxxxxx kultury.

Plynné xxxx xxxxxx xxxxx xx xxxx xxx xxxxxxxx xxxxxxxx metodami, xxxx. v těsně xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (15, 16).

1.4.3.3 Doba xxxxxxx xxxxxx

X prvním xxxxxxxxxxx by xxxx xxx buňky xxxxxxxxx xxxxxxxx látce, xxx x xxxxxxxxxxxx aktivací, xxx bez xx, xx xxxx 3 — 6 xxxxx, x xxxx xx xxx xxxxxxxx po xxxxxx době xx xxxxxxxx aplikace, xxxxx xxxxxxxx 1,5xxxxxxx normální xxxxx buněčného cyklu (12). Xxxxxxxx xxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx xxx x xxxxxxxx, tak bez xxxxxxxx, xxx xx xxx proveden xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx xx odběru x době, která xxxxxxxx 1,5násobku normální xxxxx buněčného xxxxx. Xxxxxx xxxxxxxx xxxxx xxx snáze detekovat xxx xxxxxx xxxxxxxx xxxx xxxxxx delších xxx 1,5xxxxxxx délky xxxxx. Xxxxxxxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. X případech, xxx xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx výsledků xx xxxxxxxx, xx xxxx xxx podáno zdůvodnění.

1.4.3.4 Xxxxxxxx preparátů xxx xxxxxxx xxxxxxxxxx

Xx buněčné xxxxxxx xx obvykle 1-3 xxxxxx před xxxxxxxxx přidá Xxxxxxxx® xxxx kolchicin. Pro xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx xx xxxxx buněčná xxxxxxx xxxxxx x xxxxxxxxxx xxxxxx. Xxxxxxxx xxxxxxxxx xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx x xxxxxxxx xxxxx.

1.4.3.5 Analýza

Všechny xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx xxxx být xxxx analýzou pod xxxxxxxxxxx xxxxxxxxx kódovány. Xxxxxxxx při xxxxxx xxxxx xxxxxxx xx xxxxx xxxxx xxxxx x xxxxxxxx x xx xxxxxx xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx xxxxxxxxx centromery x počtu xxxxxx xxxxxxx xxxxxxx ± 2 xxx všechny xxxx buněk. Xx xxxxxx koncentraci x xxxxxxxx by xxxx xxx hodnoceno xxxxxxx 200 xxxxx xxxxxxxxxxxxxx xxxxxxxx, případně xxxxxxxxxx xxxxxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx velký počet xxxxxxx.

Xxxxxx xx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx, xx xxxxxxxx zaznamenat xxxxxxxxxxx x endoreduplikace, jsou-li xxxxxxxxxx.

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx a mělo xx xxxx xxx xxxxxxxxxxx množství buněk xx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx xxxxxxxxx a xxxxxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx různé xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x xxxxxx xxxxxx x xxxxxxxx. Xxxx se xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, ale nezahrnují xx xx celkové xxxxxxxx xxxxxxx.

Xxxx by xxx xxxx xxxxxxxxxxx xxxxxxxx, xxxxx xxxx xxxxxxxxx pro stanovení xxxxxxxxxxxx u xxxxx xxxxxxxxxxxx kultur x xxxxxxxxxxx xxxxxx v xxxxxxxx xxxxxxxxxxxxx x xxxxxxxxx.

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

Xxxxxxx xxxxx pozitivní xxxxxxxx xx xxxxxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxxx experimentálních xxxxxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xxxx diskutována x xxxx 1.4.3.3. Xxxxx xxxxxxxxx studie x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx podmínek xx xxxx být xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, xxxxx xx xxxxx xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx x podmínky xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx tohoto xxxxx. Xxxxxxxx xx měla xxx uvážena biologická xxxxxxxxx výsledků. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx být xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (3, 13). Xxxxxxxxxxx významnost xx neměla být xxxxxxx určujícím xxxxxxxx xxx xxxxxxxxx xxxxxxx.

Xxxxxx xxxxx xxxxxxxxxxx buněk xxxx xxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxx x indukovat xxxxxxxxx chromozomové aberace. Xxxxxx počtu buněk x endoreduplikovanými xxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (17, 18).

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx pozitivní nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx zůstat xxxxxxxxxx nebo sporné xxx ohledu xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xx xxxxxxx na xxxxxxxxxxxx xxxxxxx in xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx savců xxxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx znamenají, že xxxxxxxx xxxxx xx xxxxxxxx zkoušky xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx.

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxx:

- xxx x xxxxx xxxxx,

- xxxxxxxxxx karyotypu x xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx,

- informace o xxxxx xxxxxxxxx xxxxx,

- xxxxxxx xxxxx krve, xxx byla xxxxxxx xxxx xxxx nebo xxxxxxxxxx lymfocyty, použitý xxxxxxx,

- xxxxxxxx počet xxxxxx,

- případně xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxx koncentrací x počtu kultur, xxxxxx např. údajů x xxxxxxxxxxxx a xxxxxx xxxxxxxxxxxx, jsou-li x dispozici,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX₂,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx xxxxxxxx x přidané xxxxxxxx xxxxx,

- xxxxxxxxx teplota,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx xxxxxxxx,

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

- pozitivní x xxxxxxxxx kontroly,

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxxx toxicity,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

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

- známky xxxxxxx,

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

- definice xxxxxxx, včetně gapů,

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

- xxxxx ploidie, xxxxx xxxx pozorovány,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

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

Xxxxxx výsledků.

Závěry.

4. XXXXXXXXXX

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

2) Xxxxxxxx, X. Xx., Xxxxxx, X. (1985), The Xx xxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx Using Chinese Xxxxxxx Xxxx (XXX) Xxxxxxxxxx Xxxxx in Xxxxxxx, xx: Xxxxxxxx xx Xxxxxxxxxx Xxxxxxxx, Xxx. 5, Ashby, X. xx xx., (xxx) Xxxxxxxx Xxxxxxx Xxxxxxxxxx, Amsterdam-New Xxxx-Xxxxxx, 427-432.

3) Xxxxxxxx, X. X., Xxxxxxxxx, X. X., Reuben, X., Xxxxxx, S., Brown, X., Cannon, C., Xxxxx, X. X., Xxxxxxxx, X., Xxxxx, X., Xxx, X., Xxxxx, X., Xxxxxxxx, X. H., Xxxxxxx, X. X., Xxxxxxxx, X., Xxxxxx E. (1978), Xxxxxxxxxx aberration xxx sister xxxxxxxxx xxxxxxxxx in Xxxxxxx xxxxxxx ovary cells: Xxxxxxxxxx xx 108 xxxxxxxxx, Environ. Xxxxx. Xxxxxxx. 10 (suppl. 10), 1-175.

4) Scott, X., Galloway, X. X., Xxxxxxxx, X. X., Xxxxxxxx, X. Xx., Xxxxxxx, X., Xxxxx, X., Xxxx, X. X. (1991), Xxxxxxxxxxxx xxxxx Xxxxxxx Xxxxxxx Conditions. X xxxxxx xxxx ICPEMC Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.

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

6) Ames, X. N., XxXxxx, X., Yamasaki, X. (1975), Xxxxxxx xxx Xxxxxxxxx Carcinogens xxx Xxxxxxxx with the Xxxxxxxxxx/Xxxxxxxxx Microsome Mutagenicity Xxxx, Mutation Res., 31, 347-364.

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

8) Xxxxxxxxx, X. T., Xxxxx, X. X., xxx Xxxx, X. P. X., Xxxxxxx, M., xx Xxxxx, X. (1976), Xxxxxxxxxxx Xxxxxxx xx Xxxxxxx/Xxxxxxxxxxx after Xxxxxxxxxx xx x Xxxxxxxxxxx System Xx xxxxx, X. Induction xx Xxxxxxxxxx Xxxxxxxxxxx xxx Sister Chromatid Xxxxxxxx xx Diethylnitrosamine (XXX) and Xxxxxxxxxxxxxxxxxxx (XXX) xx CHO Xxxxx xx xxx Xxxxxxxx xx Rat-Liver Xxxxxxxxxx, Xxxxxxxxxx Res., 37, 83-90.

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

10) Xxxxxx, X. M., Combes, X. X., Xxxxxxx, X. R., Xxxxxxxxx, X. X., Xxxxxx, X. X., Mackay, X. M., Wolf, X. X. (1992), Xxxxxx xx UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Xxxxxxxxxxx xx Xxxxxxx 1254-xxxxxxx X9 in Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

11) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxx, X., Xxxxxxxx, X. (1976), X. Safe Substitute xxx Polychlorinated Biphenyls x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, in: xx Xxxxxx, X. X., Xxxxx, X. X. Xxxx, X. X., Xxxxxxx, X. X. (xxx), Xx xxxxx Xxxxxxxxx Activation xx Xxxxxxxxxxx Xxxxxxx, Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

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

13) Xxxxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, J. X., Xxxxxxxx, X., Chanter, X. O., Xxxxxxxx, X. (1989), Xxxxxxxx xx Xxxx from Xx xxxxx Cytogenetic Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Mutagenicity Xxxx Xxxx, Xxxxxxxx, X. X., (ed) Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, 141-154.

14) Xxxxx, X. X., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Flasks xxx xxx Necessary xxx Xx vitro Chromozome Xxxxxxxxxx Assays xx XXX Xxxxx, Mutatation Xxx., 312, 139-149.

15) Xxxxx, D. F., Xxxxxx, X. X., XxXxxxx, K. X. (1982), CHO/HGPRT Mutation Xxxxx: Xxxxxxxxxx xx Xxxxx xxx Xxxxxxxx Xxxxxxx, xx: Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (eds), Xxxxxxxxx Effects of Xxxxxxxx Xxxxxx, New Xxxx, Xxxxxx, 91-103.

16) Xxxxxx, X. X., Xxxxxx, X. M., Xx, A. X., Xxxxxx, A. X. (1983), Evaluation of xx Xxxxxxxx Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Gels xxx Xxxxxxxxx Highly Xxxxxxxx Mutagens xx xxx XXX/XXXXX Mutation Xxxxx, Xxxxxxxxxxxxx Xxxxxxx., 5, 795-801.

17) Xxxxx-Xxxxx, X. (1983), Xxxxxxxxxxxxxxxxx xx Xxxxxxx hamster xxxxx during xxxxx-xxxxxxxxx xxxxxxx G2 xxxxxx, Xxxxxxxxxx Xxx., 119, 403-413.

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

XXXXXXX 4B

"B.11 MUTAGENITA–ZKOUŠKA XX CHROMOZOMOVÉ XXXXXXX X XXXXXXX XXXXXX XXXXX XXXXX IN XXXX

1. XXXXXX

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

1.1 XXXX

Xxxxxxx xx xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxx je používána xxx xxxxxxx strukturních xxxxxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx látkou x xxxxxxx xxxxxx dřeně xxxxx, xxxxxxx hlodavců (1, 2, 3, 4). Xxxxxxxxx xx xxx typy xxxxxxxxxxxx xxxxxxx — xxxxxxxxxxxx x chromatidové. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx chemická látka xx xxxxxxxxx xxxxxxxxx xxxxxxxxx aberace. V xxxxxxx xxxxxxx chemických xxxxxxxx xxxx indukované xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx aberace xx rovněž xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxxxxxx jevy xxxx xxxxxxxx xxxxx geneticky xxxxxxxxxxx chorob x xxxxxxx x existuje xxxxx důkazů x xxx, xx xxxxxxxxxxxx xxxxxx x xxxxxxxxxxx xxxx xxxxxxxxxxx změny x onkogenech a x genech somatických xxxxx tlumících xxxxxx, xxxx xxxxx na xxxxxxx rakoviny u xxxxxxx x x xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx jsou xxxxxxx xxxxxxxxx xxxxxxxx. Cílovou xxxxx xx x xxxx zkoušce xxxxxx xxxx, xxxxxxxx je xxxxxx xxxxxxxxxxxxxxxx tkání x xxxxxxxx xxxxxxxx xxxxx s xxxxxxx xxxxxx, xxxxx se xxxxxx izolují x xxxxxxxxxxxx. Xxxx xxxxx x cílové xxxxx xxxxxx předmětem této xxxxxx.

Xxxx zkouška xx xxxxxxxxxxxx xxxxxxx je xxxxxxx určená k xxxxxxxxx nebezpečí xxxxxxxxxx, xxxxx umožňuje xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx DNA, xxxxxxx se xxxxx x xxxxxxx xxxxx x xxxxx xxxxx. Xxxxxxx in vivo xx xxxxxx užitečná xxx další výzkum xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx xx vitro.

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

Viz xxxx Xxxxxx úvod, část X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx poškození xxxxxxxxxx x xxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxx xxxx zlomu x xxxxxxxx spojení chromatid.

Chromozomová xxxxxxx : strukturní xxxxxxxxx chromozomu v xxxxxx xxxxx nebo xxxxx a xxxxxxx xxxx xxxxxxxxx v xxxxxx místě.

Endoreduplikace : xxxxxx, xxx xxxxxx x jádře xx X-xxxx xxxxxxxxx DNA xxxxxxx k xxxxxx, xxxxx následuje další X-xxxx. Výsledkem xxxx xxxxxxxxxx xx 4, 8, 16,… chromatidami.

Gap : xxxxxxxxxxxx xxxx xxxxx xxx šířka xxxxxxx xxxxxxxxxx x x minimální xxxxxxxxx xxxxxxxxx.

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

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

Xxxxxxxxxx aberace : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx chromozomů xxx xxxxxxxx dělení xx xxxxxx metafáze; xxxx se xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce xxxxxxx xxxxxxxx x xx xxxxxxx xxxxxxxx po xxxxxxxx xx xxxxxx. Xxxx usmrcením se xxxxxxxx xxxx látka xxxxxxxxxxx xxxxxxxx (např. xxxxxxxxx xxxx Xxxxxxxx®). X xxxxx xxxxxx xxxxx se poté xxxxxxxx xxxxxxxxx chromozomů, xxxxxx xx x xxxxxxxxx xx xxxxxxxxxxxx xxxxxxx buněk x xxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxx x křeček xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Měly by xxx xxxxxxx běžně xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx pohlavně xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx xxxx být xxxxxxxx v xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx x xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata se xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, xxxxx xx xxxxxxx xxxxxxxx xxxxx. Xxxxx by xxxx xxx uspořádány xxx, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.

1.4.1.4 Příprava xxxxx

Xxxxx zkoušené látky xx xxxx xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx vehikulech a xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx xxxxx mohou xxx podávány xxxxx xxxx xxxxx být xxxx podáním zředěny. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx o xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx xxx použitých xxxxxxxx dávek xxxxxxx xxxxxx x xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx použita jiná xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx podloženo xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxx xxxxx nejdříve xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx xxx xxxxxxxxx a xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx xxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx kontrolní xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x nichž se xxxxxxx, xx poskytnou xxxxxxxxxxxxx xxxxxx xxx xxxxxx. Xxxxx pozitivní xxxxxxxx xx xxxx xxx xxxxxxx tak, xxx byl účinek xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Je xxxxxxxxxx, aby byla xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx byl odběr x jejím xxxxxxx xxxxxxxx jen xxxxxx. Xxx xxxxxxxxx kontrolu xxxxx být použity xxxxxxxx látky xx xxxxxx chemické třídy, xxxx-xx x xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx XXX	Xxxxx 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 odběru by xxx xxx proveden xxxxx x xxxxxxxxxxx xxxxxxx, xxxx xx xxxxxxxxxx pouze xxxxxxxxxxxx xxxx xxxxxxxxx a xxx xxxxx podstupují xxxxxx proces xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx x variabilitě zvířat x četnosti xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx jeden xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx doba prvního xxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, neexistují-li xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx xx skládá x alespoň xxxx xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx pohlaví. Xxxxxxxx xxxx v xxxx xxxxxx x xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx expozice, xxx xxxxxxxxx, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx pohlaví. Xx-xx xxxxxxxx člověka specifická xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, měla xx xxx xxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx by xxxx xxx pokud xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx xxxxx xxx xxxxxxxx také xx xxxx dávkách, xxx. xxx xxxxx x xxx den x xxxxxxx xx xxxx xxx xxxxxxxx xxxxx, xxx bylo xxxxxxxxx xxxxxxxx velkých xxxxxx materiálu. Xxxx xxxxxx podávání by xxxx xxx vědecky xxxxxxxxxx.

Xxxxxx xx měly xxx odebrány xx xxxx xxxxxxx intervalech xx xxxxxxxx podané x jednom xxx. X xxxxxxxx se xxxxx xxxxxxx xx xxxxxx době xx xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx normální xxxxx xxxxxxxxx xxxxx (xxxx xxxx xxxxxxx 12 — 18 x). Xxxxxxxx xxxx nezbytná xxx xxxxxx a xxxxxxxxxxxx zkoušené látky x xxxxxx xxx xxxxxx xx kinetiku xxxxxxxxx cyklu xxxx xxx vliv na xxxxxxxxx okamžik xxx xxxxxxxxx chromozomových aberací, xxxxxxxxxx se xxxxxxx xxxxx odběr po 24 x xx xxxxxxx xxxxxx. Xx-xx xxxxxxxx xxxxxxxxx xx xxxx xxx jednoho xxx, xxx xx xxx xxxxx xxxxxxxx xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxxxxx délky xxxxxxxxx xxxxx.

Xxxx xxxxxxxxx se xxxxxxxx intraperitoneálně xxxx xxxxxx xxxxx xxxxx xxxxxxxxxxx xxxxxxxx (např. Xxxxxxxx® nebo kolchicin). Xxxx xx po xxxxxx době xxxxxxx x zvířat xxxxx. X xxxx xx xxxx xxxx xxxxxxxxx 3 — 5 x; x xxxxxx xxxxxxxx je xxxx xxxx xxxxxxxxx 4 — 5 h. X kostní xxxxx xx xxxxxxxx buňky x xxxxxxxxx xx xx chromozomové xxxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx pro xxxxxxxx rozsahu xxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, xx xxxxxxx xxxxxx, xxxxxx, xxxxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx v xxxxxx xxxxxx (5). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx dávky by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx toxicitou. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx použita xxxxx xxxxxxxx xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xxxxxx známky xxxxxxxx, že vyšší xxxxx xx vedly xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx očekávání x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx a mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx vyhovovat a xxxx xx xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxxx xxxxx xxxx být také xxxxxxxxxx jako xxxxx xxxxxxxxxxxx v xxxxxx xxxxx některé známky xxxxxxxx (xxxx. xxxx xxx 50 % xxxxxxx mitotického indexu).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x jednou dávkou xxxxxxx 2000 xx/xx xxxxxxx hmotnosti podanou xxxxxxxxxxx xxxx ve xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx základě xxxxx x xxxxxxx, které xxxx podobnou xxxxxxxxx, xxxxxxxxx genotoxicita, nepovažuje xx úplná xxxxxx xx xxxxx úrovněmi xxxxx xx xxxxxxxxx. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx xxxxx než 14xxxxx xxxxxxxx je xxxxxxx dávkou 1000 xx/xx xxxxxxx xxxxxxxxx/xxx. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx potřebu xxxxxx x xxxxxxx xxxxxxx vyšší úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx se xxxxxxx xxxxxx nitrožaludečně, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx jsou x xxxxxxxxxxxx xxxxxxxxx xxxxxxxxxx. Maximální xxxxx xxxxxxxx, který xxxx xxx najednou podán xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx překročit 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx zdůvodněno. Xx na dráždivé x xxxxxx látky, xxxxx xxxxxxx při xxxxxxx xxxxxxxxxxxxx vykazují xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx při xxxxx úrovních xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xxxxx po xxxxxxxx xx odebere xxxxxx xxxx, xxxxxxxxxxxx xx x xxxxxx. Xxxxx xx nanesou xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

Xxxx měřítko cytotoxicity xx xxx být x všech exponovaných xxxxxx (včetně xxxxxxxxxxx xxxxxxx) a u xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx xxxxxxxx stanoven xxxxxxxxx index, x xx xxxxxxx u 1000 xxxxx xx xxxxx xxxxx.

X xxxxxxx xxxxxxx xx xxxx xxx analyzováno xxxxxxx 100 xxxxx. Tento xxxxx lze snížit, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx xx xxxx být xxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxx xxx xxxxxx xxxxx xxxxxxx xx chromozomálním zlomům xxxx ke xxxxxx xxxxxxxxxx u části xxxxx x metafázi, xxxx xx xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx xxxxx. Xxx xxxxx xxxxx xx měl xxx xxxxxxxxxx počet xxxxx, xxxxx xxxxxxx xx xxxxx a xxxxx xxxxx x xxxxxxxxxxxxx xxxxxxx (chromozomovými xxxxxxxxx) vyjádřený x xxxxxxxxxx. Xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx xx xxxx být xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx obecně xx xxxxxxxxxx xx celkové xxxxxxxx aberací. Neexistuje-li xxxxx o xxxxxxx x odpovědi mezi xxxxxxxxx, xxxxx xxx xxx statistickou analýzu xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxxxxxxxx xxxxx buněk s xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na dávce xxxx jasný xxxxxx xxxxx buněk x xxxxxxxxx xxx xxxxxxx x určitou dávkou x k xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (6). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným určujícím xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné xxxxxxxx xx xxxx být xxxxxxxxx dalším zkoušením, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx polyploidie xxxx znamenat, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx s xxxxxxxxxxxxxxxxxxx xxxxxxxxxx xxxx xxxxxxxx, že zkoušená xxxxx má potenciál xxxxxxxx xxxxxxxx buněčného xxxxx (7, 8).

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx nebo negativní xxxxxxxx, v ojedinělých xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx o xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx zůstat dvojznačné xxxx xxxxxx xxx xxxxxx na xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxx xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx x xxxxxx xxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx znamenají, xx xxxxxxxx xxxxx xx xxxxxxxx zkoušky neindukuje x kostní xxxxx xxxxxxxxxxx druhu xxxxxxxxxxxx xxxxxxx.

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

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx o xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx volby xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- použitý xxxx/xxxx,

- xxxxx, stáří x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx x xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx xxxxxx dávek,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x podávání xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

- případně přepočet xxxx xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxxx xxxx (xxx) xx odpovídající dávku (xx/xx xxxxxxx hmotnosti/den),

- xxxxxxxx údaje x xxxxxxx xxxxxx a xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx a xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

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

- metody přípravy xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx analyzovaných xxxxx na xxxxx xxxxx,

- xxxxxxxx klasifikace xxxxxx na pozitivní, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

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

- xxxxx xxxxx x xxxxxxxxx xx skupině xx xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx xxxxxxxxxx,

- xxxxx ploidie, xxxxx xxxx pozorovány,

- xxxxx xxxxxxxx závislost odpovědi xx dávce,

- xxxxxxxx xxxxxxxxxxx analýzy,

- údaje x xxxxxxxx negativní xxxxxxxx,

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

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Gatehouse, X. X., Bootman, X., Xxxxxxxxx, X. (1990), In vivo Xxxxxxxxxxx Xxxxxx, xx: X. X. Kirkland (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Testing. Xxxxxx, Xxxx I revised, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. R., Hayashi, X., MacGregaro, X. X., Xxxxxxxx, X., Xxxxxx, D. X., Xxxxxx, H. X., Xxxxxx-Xxxxxxx, X., Xxxxxx Xx., X. X., Xxxxxxxxxxxx, F., Xxxxxxx, X. J., Romagna, X., Shimada, X., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx the Xxxxxxx Xxxxx xx xxx xx xxxx Xxxxxxxxx Xxxx Xxxxxx Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx., 312, 305-312.

5) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. A., Xxx, X., Xxxxxxx, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, D. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Society Xxxxxxx Xxxxx: Xxxx Xxxxxxx xx Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, D. P., Xxxxxxxx, D., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, R., Richold, X., Xxxxxxxx, D. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxxx Analysis xx Xx xxxx Cytogenetic Xxxxxx, xx: UKEMS Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing, Xxxxxx Xxxx XXX. Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Xxxx, X. X. Kirkland (xx.) Xxxxxxxxx University Xxxxx, Xxxxxxxxx, 184-232.

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

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

PŘÍLOHA 4C

"B.12 MUTAGENITA–TEST XXXXXXX XXXXXXXXXXXXXXX XXXXXXXXXX XX VIVO

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX XX 474 — Test xxxxxxx erytrocytárních xxxxxxxxxx xx vivo (1997).

1.1 XXXX

Xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx pro xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx zkoušenou látkou, x to xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x kostní xxxxx x/xxxx buněk periferní xxxx, obvykle xxxxxxxx.

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

Xxxx xx erytroblast xxxxxx xxxxx mění xx polychromatický erytrocyt, xxxxxx xxxxx xx xxxxxxxx x mikrojádra, xxxxx xxx xxx xxxxx vzniknout, xxxxxxxxx x xxxxxxxxxx, xxxxx xxxxx xxxxx xxxxxxxxxx. Xxxxxxxxxxxx mikrojader xx x xxxxxx xxxxxxx xxxxxxxxx xxx, že xxxxxxxxxx hlavní xxxxx. Xxxxxx výskytu polychromatických xxxxxxxxxx s xxxxxxxxxx x exponovaných xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx poškození.

V tomto xxxxx xx xxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, poněvadž tato xxxx produkuje polychromatické xxxxxxxxxx. Xxxxxxxxx nezralých (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x xxxxxxxxxx x xxxxxxxxx xxxx xx xxxxxxxxxx xxxxxxxxxx x kteréhokoli xxxxx, x xxxxx xxxx prokázána neschopnost xxxxxxx odstraňovat erytrocyty x xxxxxxxxxx, nebo xxxxxxxxxx citlivost xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Mikrojádra xxx xxxxxxxx řadou xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx přítomnosti xxxx xxxxxxxxxxxxx centromerní (xxxxxxxxxxxx) XXX x xxxxxxxxxx. Xxxxxxxxx xx zejména xxxxxxx xxxxxxxxx (polychromatických) xxxxxxxxxx s xxxxxxxxxx. Xxxxx xxxxxxx (xxxxxxxxxxxxxxxxxx) xxxxxxxxxx x periferní xxxx, které xxxxxxxx xxxxxxxxxx, připadající na xxxxxx xxxxx zralých xxxxxxxxxx lze xxxxxx xxxxxx xxxx xxxxxxx xxxxxxxx xxxxxxx, xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx xxxx.

Xxxxx xxxx xxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx a procesy xxxxxxxx XXX, xxxxxxx xx xxxxx lišit x xxxxxxx druhů x tkání, xxxxx x x xxxxxxxxxxx xxxxxxxx. Zkouška in xxxx je xxxxxx xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx xxxxxx xxxxxxxxxx x systémech xx xxxxx.

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

Xxx xxxx Xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) xxxxxxxxxx, x níž (k xxxx) xx xxxxx xxxxxx xxxxx připojí xxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxx xxxxx dceřiných xxxxxxxxxx x pólům xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx jádra existující xxxxxxxx xx xxxxxxxx xxxxx a xxxxx xxxx, xxxxxxxxx během xxxxxxxx xxxxxx (xxxxxx) xxxxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxxxx fragmenty xxxx xxxxxx chromozomy.

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

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx ve xxxxxxxxx xxxxxxxxxx, xxxxx xxxxx obsahuje xxxxxxxx, x xxxx xxx xxxx xxxxxxxx xx xxxxxxx xxxxxxxxxxxxxxxxxx erytrocytů xxxxxxxx selektivním xxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xx vhodným xxxxxxxx xxxxxxx xxxxxxxx xxxxx. Při xxxxxxx xxxxxx xxxxx xx xxxxxxx ve xxxxxxx xxxxxxxx po expozici xxxxxx, xxxxxxx xx xxxxxx dřeň, xxxxxxxx xx preparáty x xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx periferní xxxx xx xxxx xx xxxxxxx xxxxxxxx xx xxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxxx xxxxxxxx x xxxxxx xx (4, 8, 9, 10). Xxx xxxxxxxx x xxxxxxxxx xxxx xx měla xxxx poslední xxxxxxxx x sklizením xxxxx xxxxxxxx xx nejkratší xxxx. Xxxxxxxxx jsou xxxxxxxxxxx na xxxxxxxxxx xxxxxxxxxx.

1.4 POPIS XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx zvířete

Při použití xxxxxx xxxxx xx xxxx testovací xxxxx xxxxxxxxxx myš xxxx xxxxxx, ačkoli xxx xxxxxx jakýkoli xxxxxx xxxxx druh. Xxx xxxxxxx periferní xxxx xx xxxxxxxxxx xxx. Xxx však xxxxxx xxxxxxxx xxxxxx xxxx xxxxx xx xxxxxxxxxxx, xx xxx x xxxx, u xxxxx xxxxxxx neodstraňuje erytrocyty x mikrojádry, nebo xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxx chromozomové xxxxxxx. Měly xx xxx použity xxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxx xxxxxxxx pohlavně xxxxxxxxx zvířat. V xxxxxxxx xxxxxxxx xxxxxx xx měla být xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx a xxxxxx xx x xxxx xxxxxxx překročit ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, u xxx se xxxxxxx xxxxxxxx. Zvířata se xxxxxxxxxxx xxxxxxxxxxxx. Nechají xx x laboratorních xxxxxxxxxx alespoň xxx xxx xxxxxxxxxxxxx. Xxxxx xx uspořádají xxx, xxx byl xxxx xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx dávek

Pevné xxxxxxxx xxxxx by měly xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě zředěny. Xxxxxxx xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxxx xxxx xxxxx xxx xxxx podáním xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx zkoušené xxxxxxxx xxxxx, pokud údaje x xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít xxx použitých xxxxxxxx xxxxx toxické účinky x xxxx xx xxx xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx údaji x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx pro xxx pohlaví. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx pozadí. Xxxxx xxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxx xxxxxxxx xxx zkoušená xxxxx x xxx xxx xxxxx x xxxxx xxxxxxx prováděn xxx xxxxxx. Xxx pozitivní xxxxxxxx navíc xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx stejné xxxxxxxx xxxxx, jsou-li x dispozici. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx CAS	Číslo podle XXXXXX
xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
xxxxxxxxx X	50–07–7	200–008–6
xxxxxxxxxxxxx	50–18–0	200–015–4
xxxxxxxxxxxxx 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 xxxxxxxx odběru xx xxx být xxxxxxxx xxxxx x xxxxxxx negativní kontroly, xxxxx je xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxx xxxxx podstupuje stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx xxxxx o xxxxxxxxxxx xxxxxx x xxxxxxxx buněk x xxxxxxxxxx. Provádí-li xx xxx negativní kontrolu xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx publikovány xxxxxxxxx xxxxx xxxxxxxxxxx, xx xxxxxxx rozpouštědlo/vehikulum xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx krve xxxx xxx xxxx xxxxxxxxx xxxxxxxx přijatelný xxxx xxxxxx xxxx xxxxxxxx xxxx xxxxxxxx, xxxxx xxxx x xxxxxxxx xxxxxx x xxxxxxxxx xxxx (např. 1 — 3 xxxxxxxx) xx xxxxxxxxxxx, xx xxxxxxxx xxxxx xxxxx x rozpětí, xxxxx xx na xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Počet a xxxxxxx zvířat

Každá xxxxxxxxxx x xxxxxxxxx xxxxxxx xx musí xxxxxxx x xxxxxxx xxxx xxxxxxxxxxxxxxxx zvířat pro xxxxx xxxxxxx (11). Xxxxxxxx xxxx v xxxx xxxxxx k xxxxxxxxx údaje xx xxxxxx xx stejným xxxxxx a za xxxxxxx stejného xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx mezi xxxxxxxxx xxxxxx x xxxxxxxx, bude xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx například x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx být xxxxxxx provedena xx xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx aplikace

Nelze doporučit xxxxx xxxxxxxxxx xxxx (xx. xxxxx, xxx xxxx xxx xxxxxxxx x intervalu 24 xxxxx). Xxxxxx ze xxxxxx x xxxxxxxxxxxx xxxxxxx podávání xxxx xxxxxxxxxx, xxxxx xx x xxxxxx xxxxxx xxxxxxx xxxxxxxxx xxxxxxxx, xxxx –v případě xxxxxxxxxxx xxxxxx — xxxxx xxxx xxxxxxxxx xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxx xxxxx x xxxxxxxx pokračuje xx do okamžiku xxxxxx. Xxxxxxxx látky xxxxx být xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx xxxxx x týž xxx x xxxxxxx xx více než xxxxxxxx hodin, aby xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx.

Xxxx xxxx xxx xxxxxxxx xxxxx xxxxxxx:

x) xxxxxxxx xxxxx xx aplikuje xxxxxxxx xxxxxx. Vzorky xxxxxx dřeně xx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 24 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci x x xxxxxxxxxx odstupem xxxx odběry. Odběr xxxxx xxx 24 xxxxx xx xxxxxxxx xxxx xxx zdůvodněn. Xxxxxx xxxxxxxxx xxxx xx xxxxxxxx xxxxxxx xxxxxxx, přičemž xxxxx xxxxx se provede xxxxxxxx 36 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 72 xxxxx xx xxxxxxxx x xx xxxxxxxxxxxx xx dodrží odpovídající xxxxxx. Xx-xx xx xxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxx xxxxx xxxxx;

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

Xxxxx xxxxxxx xxxxx xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx xxxxxxxx dostupných xxxxx xxxxxx xxx xxxxxxxx rozsahu xxxxx, xxxx by xxx xxxxxxxxx xx stejné xxxxxxxxxx, se xxxxxxx xxxxxx, xxxxxx, pohlavím x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx xxxxxxx v xxxxxx studii (13). X xxxxxxx toxicity xx pro první xxxxx použijí xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx by xxxx xxxxxxxx xxxxxxx xxxx xxxxxxxxx xx xxxxxxxxx toxicitou, případně xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx xxxxxxxx xxxxx. Xxxxxxxx xxxxx je xxxxxxxxxx jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x letalitě. Xxxxx xx specifickou xxxxxxxxxxx xxxxxxxxx při xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a xxxxxxxx) xxxxxx xxxxxxxxx stanovení xxxxx xxxxxxxxx x xxxx xx být xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší xxxxx xxxx být xxxx xxxxxxxxxx jako dávka xxxxxxxxxxxx x kostní xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx v xxxxxx xxxxx nebo x xxxxxxxxx xxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx dávkou o xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx podanou xxxxxxxxxxx nebo xx xxxx dávkách v xxxxxx xxx nevykazuje xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx údajů x látkách, xxxxx xxxx xxxxxxxx strukturu, xxxxxxxxx xxxxxxxxxxxx, xxxx xxxxxxxxxx úplná xxxxxx xx xxxxx xxxxxxxx xxxxx za xxxxxxxxx. X déle xxxxxxxxxx xxxxxx xx limitní xxxxxx xxx 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx/xxx x xxx xxxxx xxx 14xxxxx aplikaci je xxxxxxx dávkou 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx v limitní xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx kanylou, nebo xxxxxxxxxxxxxxxxx injekcí. Xxxx xxxxxxx xxxxxxxx jsou xxxxxxxxxx v xxxxxxxxxxxxxxx xxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx najednou podán xxxxxxxxx xxxxxx nebo xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx uvedený xxxxx, musí xxx xxxxxxxxxx. Xx xx xxxxxxxx a xxxxxx xxxxx, xxxxx obvykle xxx xxxxxxx koncentracích xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx kostní xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx xx xxxxxxx xxxxxxxxx x xxxxxx xxxx xxxxx xxxxx xx xxxxxxxx. Xxxxx xx odeberou x xxxxxx xxxx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x obarví. Periferní xxxx xx xxxxxxx x xxxxxx žíly xxxx jiné xxxxxx xxxxxx xxxx. Krevní xxxxx se xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), xxxx xx připraví xxxxxxxxx xxxxxxxx x poté xx xxxxxx. Xxxxxxxx xxxxxxx specifického xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 x xxxxxxx-X (15)) xx xxx xxxxxxx xxxxxxxx xxxxxxxxxx spojeným x xxxxxxxx barviva xxxxxxxxxxxxxx xxx XXX. Tato xxxxxx nebrání xxxxxxx xxxxxxxxxxx xxxxxx (např. Xxxxxx). Přídavné xxxxxxx (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx buněk xxxxxxxxxxxx jádra (16)) xxx xxxxxx za xxxxxxxxxxx, xx xx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx systémů pro xxxxxxxxx xxxxxxxxxx v xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx každé xxxxx se stanoví xxxxx nezralých xxxxxxxxxx x xxxxxxxxx (nezralé + xxxxx) množství xxxxxxxxxx, xxxxxxx xx x xxxxxxx kostní xxxxx použije celkově xxxxxxx 200 erytrocytů x v případě xxxxxxxxx xxxx xxxxxxx 1000 erytrocytů (17). Xxxxxxx xxxxxxxxx včetně xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx, xx xxxx xxx před xxxxxxxx pod xxxxxxxxxxx xxxxxxxxx kódovány. X xxxxxxx zvířete se xxxxxxx xxxxxxx 2000 xxxxxxxxx erytrocytů xx xxxxxx mikrojader x xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx zralých erytrocytů xx xxxxxx xxxxxxxxxx. Xxx xxxxxxxxxxxxx analýze xx xxxxx být xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx množství xxxxxxxxxx xxxxx než 20 % xxxxxxxxx xxxxxxx. Jestliže jsou xxxxxxx exponována xxxxxxxxxxx xxxxx týdny xxxx xxxx, xxx xxxx xxxxxxxx xx výskyt xxxxxxxxxx alespoň 2000 xxxxxxx xxxxxxxxxx xx xxxxx xxxxx. Xxxxxxx xxx xxxxxxxxxxxx analýzu (xxxxxxx xxxxxx x xxxxxxxxx cytometrická xxxxxxx xxxxxxx xxxxxxxx) xxxx xx xxxxxxxxxxxxx xxxxxxxxxx x validaci xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxxxxxxx jednotkou xx zvíře. Xxx xxxxx xxxxxxxxxxx xxxxx xx xxx xxx xxxxxx počet vyšetřených xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx s xxxxxxxxxx x počet xxxxxxxxx erytrocytů z xxxxxxxxx množství erytrocytů. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx nepřetržitě xxxxx xxxxx xxxx xxxx, xxxx xx být xxxx xxxxxxx údaje x zralých xxxxxxxxxxxx, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx xx xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx xxxxxxxxx x procentech. Xxxxxxxxxx-xx xxxxx o xxxxxxx x odpovědi xxxx xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx xxxxxxx xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx počtu xxxxx x mikrojádry x xxxxxxxxxx xx xxxxx nebo xxxxx xxxxxx xxxxx buněk x xxxxxxxxxx xxx xxxxxxx s xxxxxxx xxxxxx x x xxxxxxxx okamžiku odběru. Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx výsledků xxxxxxx xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx metody (18, 19). Statistická xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx faktorem xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx výsledky xx xxxx být vyjasněny xxxxxx zkoušením, nejlépe x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x xxxxxxxx zkoušené látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx je xxxxxxxxxx opakován.

Pozitivní výsledky xxxxx xx mikrojádra xxxxxxxxx, xx zkoušená xxxxx xxxxxxxx mikrojádra, xxx xxxx důsledkem xxxxxxxxxxxxxx xxxxxxxxx nebo xxxxxxxxx mitotického xxxxxxx xxxxxxxxxxxx testovacího xxxxx. Xxxxxxxxx výsledky xxxxxxxxx, xx zkoušená látka xx xxxxxxxx zkoušky xxxxxxxxxxx mikrojádra v xxxxxxxxx xxxxxxxxxxxx testovacího xxxxx.

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

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Xxxxxxxx podmínky:

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

- xxxxx ze xxxxxx pro zjištění xxxxxxx, pokud byla xxxxxxxxx,

- zdůvodnění xxxxxxxxx xxxxxx xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- údaje x xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

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

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx zkoušené látky x krmivu nebo xxxx (xxx) xx xxxxxxxxxxxx xxxxx (xx/xx xxxxxxx hmotnosti/den),

- xxxxxxxx xxxxx o xxxxxxx xxxxxx a xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxxxxx x nezralých xxxxxxxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx jedno xxxxx,

- xxxxxxxx klasifikace xxxxxx xx xxxxxxxxx, negativní xxxx dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx xxxxxxxxxx,

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na dávce,

- xxxxxxxx statistické analýzy x metody,

- údaje x xxxxxxxx x xxxxxxxxx xxxxxxxxx kontrole,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

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

4) Xxxxxxxxx, X. X., Xxxxxx, D. X., Xxxxxx, X. X., Xxxxxxxx, M. X., Xxxxxx, J. A. (1990), Xxx Xx xxxx Xxxxxxxxxxxx Assay xx Xxxxxxxxx Xxxx Xxxxxx xxx Xxxxxxxxxx Xxxxx. X report xx xxx X. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Program, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, J. X., Xxxxxxxx, R., Xxxx, W. N., Xxxx, C. X. (1983), Micronuclei in Xxxxxxxxxxx Xxxxxxxxxxxx: A Xxxxx Xxxxxx xxx Xxxxxxxxxxx Damage During Xxxxxxx Toxicity Xxxxxxx xx Mice, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Xxxxxxxx of Xxxxxxxxxx, xx. X. X. Hayes, X. X. Xxxxxxx, X. X. Miya. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) MacGregor, X. T., Heddle, X. X. Xxxx, X., Xxxxxxxx, X. X., Ramel, X., Xxxxxxxx, X. F., Xxxx, X. X., Xxxx, X. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx in Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 103-112.

7) MacGregor, J. X., Wehr, X. X., Xxxxxx, X. X., Xxxxxx, X. X. (1990), Xxx xx xxxx Xxxxxxxxxxx Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Steady Xxxxx Xxxxxxxxx Xxxxx Xxxxxxxxxx xxx Xxxxxxx Xxxxxxxxxxx xxxx Xxxxxxxx Xxxxxxx, Xxxxxx. Xxxx. Xxxxxxx. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, T., Xxxxxx, Y., Xxxxxx, X., Xxxxxxxx, X. Xx. (1990), The Xxxxxxxxxxxx Assay xxxx Xxxxx Xxxxxxxxxx Blood Xxxxxxxxxxxxx Using Acridine Xxxxxx-Xxxxxx Xxxxxx, Xxxxxxxxxx Xxx., 245, 245-249.

9) Xxx Collaborative Xxxxx Xxxxx for xxx Xxxxxxxxxxxx Test (1992). Xxxxxxxxxxxx Xxxx with Xxxxx Peripheral Xxxxx Xxxxxxxxxxxx xx Acridine Xxxxxx Xxxxxxxxxx Xxxxxxxx: Xxx Summary Report xx the 5xx Xxxxxxxxxxxxx Study xx XXXXX/XXXXX, MMS, Mutatation Xxx., 278, 83-98.

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

11) Xxxxxxx, X., Xxxx, X. R., XxxXxxxxx, X. T., Anderson, X., Xxxxxxx, D. X., Xxxxxx-Xxxxxxx, X., Xxxxxx, Xx. X. X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Xxxxxxx, X., Sutou, X., Xxxxxxx, B. (1994), Xx xxxx Xxxxxx Xxxxxxxxxxx Micronucleus Xxxxx, Xxxxx. Res., 312, 293-304.

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

13) Xxxxxxx, R. X., Xxxxx, X. X., Xxxxxx, X. X., Botham, P. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, X. J., 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) Xxxxxxx, M., Xxxxxx, X., Ishidate, X. Jr. (1983), Xx Application of Xxxxxxxx Orange Fluorescent Xxxxxxxx to the Xxxxxxxxxxxx Xxxx, Mutation Xxx., 120, 241-247.

15) XxxXxxxxx, J. X., Xxxx, C. M., Xxxxxxxx, X. G. (1983), X Xxxxxx Xxxxxxxxxxx Staining Xxxxxxxxx xxx Xxxxxxxxxxx and XXX in Xxxxxxxxxxxx Xxxxx Xxxxxxx 33258 xxx Xxxxxxx Y, Xxxxxxxx Xxx., 120, 269-275.

16) Romagna, X., Xxxxxxxxxx, X. X. (1989), The xxxxxxxxx xxxx xxxxxx xxxxxxxxxxxx xxxx, Xxxxxxxxxx Res., 213, 91-104.

17) Xxxxxxxxx, X., McFadden, X. X. (1995), Sample Xxxx for xxx Xxxxxxxxxx of Xxxxxxxxxxxxx xx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxx in xxx Xxxx Xxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Res., 347, 97-99.

18) Xxxxxxx, X., Xxxxx, J., Xxxxxxx, J., Xxxxxxxx, X., Xxxxxxxxx, X. X., Henderson, X. (1990), Xx xxxx Xxxxxxxxxxxx Assay, xx: X. X. Xxxxxxxx (xx.), Xxxxx Mutagenicity xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Report, Xxxx 1, xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Melbourne, Xxxxxx, 115-141.

19) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx X., Xxxxxxx, M., Xxxxxxxx, D. G., Xxxxxx, J. X. X. (1989), Staticical Xxxxxxxx of Xx xxxx Cytogenetic Xxxxxx, xx: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx of Xxxxxxxxxxxx Xxxx Data. XXXXX Xxx-Xxxxxxxxx xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Part XXX, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4D

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

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx XXXX XX 471 — Zkouška xx xxxxxxxx xxxxxx x xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx na reverzní xxxxxx x xxxxxxxxxx xx xxxxxxxxx bakteriální xxxxx xxxxxxx xx xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Escherichia xxxx, x xxxxxxx bodových xxxxxx, xxxxx zahrnují xxxxxxxxxx, xxxxx a xxxxxx xxxxxxx xxxx xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx této xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xxxxxxx x xxxxxxx xxxxxx, xxxxx xxxxxxxxx xxxxxx obsažené x xxxxxxxxxxx xxxxxxx x xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxx. Xxxxxxxx xx xxxxxxx xxxx xxxxxxxxxx díky xxx xxxxxxxxxx xxxx v xxxxxxxxxxxxx aminokyselin, které xxxx xxxxxxxxxx mateřským xxxxxxxxxx xxxxxx.

Xxxxxx mutace x xxxxxxx xxxx xxxx příčinou xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx xxxxxx mutace v xxxxxxxxxx a x xxxxxx xxxxxxxxxxx xxxxx xxxxxxxxx nádory xxxx xxxxx na xxxxxx xxxxxxxx x člověka x u xxxxxxxxx xxxxxx. Zkouška na xxxxxxxx mutace x xxxxxxxxxx xx rychlá, xxxxxxxxxx a xxxxxxxxx xxxxxx. Xxxxx xxxxxxxxxxx xxxxx xx xxxx xxxxxxxxxx, díky xxxx xxxx xxxxxxxxxx xx xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxxxxxxx xxxxx xxx velké xxxxxxxx x xxxxxxxxx xxxxxxxxxxx xxxxxxx XXX nebo xxxxxxxx xxxxxxxxxxx xxxxxxx XXX náchylných x xxxxxx. Specifičnost xxxxxxxxxxx xxxxx může poskytnout xxxxxxx užitečné informace x xxxxxx xxxxxx, xxx jsou xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx reverzní xxxxxx x bakteriemi xx x xxxxxxxxx xxxxx rozsáhlá databáze xxxxxxxx xxx širokou xxxxx struktur x xxxx byly xxxxxxxx xxxxx xxxxxxxxxx metody xxxxxxxx xxxxxxxxxx xxxxx, xxxxxx xxxxxxxx sloučenin, x xxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxxx.

Xxx xxxx xxxxxx xxxx, xxxx X.

1.2 XXXXXXXX

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx Xxxxxxxxxx typhimurium xxxx Xxxxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx x xxxxx vyžadujícím xxxxxxxxxxxxx (histidin xxxx. xxxxxxxxx), xxxxxxx vzniká xxxx nezávislý xx xxxxxxx xxxxxxx aminokyseliny.

Mutageny xxxxxxxxxx xxxx xxxx xxxx činitele, xxx xxxxxxxxx xxxxx x xxxxxx XXX. Xxx xxxxxxx xxxxxxxxxx xxxxxx xx mohou xxxx xxxxx xxxxxxxxxx xx xxxxx xxxxxxx xxxxxx xxxx xxxxx xxxxx xxxxxxxxxxxxx xxxxxx.

Xxxxxxxx xxxxxxxx xxxx činitele, xxx xxxxxxxxx xxxxx nebo xxxxxx xxxxxxx xxxx xxxx xxxx xxxx XXX a posunují xxx xxxxx rámec XXX.

1.3 XXXXXXX XXXXX

Xxx xxxxxxxxx xx reverzní xxxxxx s xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, které xx xxxx xx buněk xxxxx faktory, xxxx xxxx xxxxxx, xxxxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxx x xxxxxxxxx xxxxxxx XXX. Xxxxxxx xxxxxxxxx in xxxxx obecně xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx aktivace. Xxxxxxxxxxx xxxxxxxxx xxxxxxx xx xxxxx xxxxxxx zcela xxxxxxxxx xxxxxxxx in xxxx x savců. Xxxxxxx tedy xxxxxxxxxxx xxxxxx informaci x xxxxxxxxxx a xxxxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx využívána xxx xxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx, x xxxxxxx aktivity xxxxxxxxxxxx xxxxxx xxxxxx. Z xxxxxxxx databáze vyplývá, xx mnoho chemických xxxxx, xxxxx xxxx x této xxxxxxx xxxxxxxxx, vykazuje xxxxxxxxx xxxxxxxx i x xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx činitelů, xxxxx nejsou xxxxxxxxxx xxxxx zkouškou. Xxxxxxx xxxxxx skutečností xxx xxxxxxxxx xx specifické xxxxxx xxxxxxxxxxxxxxxxxxxxx xxxx, x rozdílech x xxxxxxxxxxx aktivaci xxxx x xxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx. Xx xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx citlivost xxxxxxx xx xxxxxxxx xxxxxx na xxxxxxxxxx, xxxxx xxxx k xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx reverzní xxxxxx x bakteriemi nemusí xxx xxxxxx xxx xxxxxx třídy xxxxxxxxxx xxxxx, xxxxxxxxx vysoce xxxxxxxxxxxx sloučeniny (např. xxxxxx antibiotika) a xxx chemické látky, x xxxxx se xxxxxxxxxxx (xxxx x xxxxx xx xx), xx specificky xxxxxxxx xx replikačního xxxxxxx xxxxx savců (xxxx. xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx x xxxxxxx xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx xxxxx být xxxxxxxxx xxxxxxx xxxxxxxxxx x savců.

Přestože xxxxx xxxxxxxxx, pro xxx xx tato xxxxxxx xxxxxxxxx, xx karcinogenní xxx xxxxx, není xxxxxxxx xxxxxxxxx. Xxxxxx xx xxxxxxxx xxxxx x xxxxxxxx mnoho xxxxxxxxxxx, xxx xxxxxx xxxxxxxxxx xxxxx zkouškou, xxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx xxxxxxxxxx, které x xxxxxxxxxxxxx buňkách xxxxxxxxxx.

1.4 XXXXXXXX XXXXXXXX METODY

Suspenze xxxxxxxxxxxxx xxxxx jsou xxxxxxxxx xxxxxxxx xxxxx, x xx xx xxxxxxxxxxx vnějšího metabolického xxxxxxxxxxx xxxxxxx x xxx něho. Xx xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxx smíchají x xxxxxxx agarem x ihned se xxxxxxx xx xxxxxxxxx xxxx. V preinkubační xxxxxx se xxxxxxxx xxxx xxxxxxxx a xxxx se xxxx xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx s xxxxxxx agarem. Xxx xxxx xxxxxxxxxx xx xx xxxx xxxx xxxxx xxxxx inkubace xxxxxxxxx xxxxxxx revertantů x xxxxxxx xx xxxxxxxx s xxxxxx xxxxxxx spontánních xxxxxxxxxx xx kontrolní xxxxx x xxxxxxxxxxxxx.

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

Xxx xxxxxxx xxxxxxx se xxxxxx xxxxxx standardního xxxxxxxxx testu a xxxxxxxxxxxxxx xxxxx. Každá x xxxx xx xxxxxxxxxx pro provádění xxxxxxxxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx. Xxxxxxx xxxxx xxx účinněji xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx metody. Xxxx xxxxx patří xx xxxxxxxxxx tříd, xx xxxxx patří xxxx xxxxx xxxxxx alifatické xxxxxxxxxxx, xxxxxxxxx xxxx, xxxxxxxx, azobarviva x xxxxxxxxxx xxxxxxxxxx, pyrrolizidinové xxxxxxxxx, allylové xxxxxxxxxx x xxxxxxxxxxxxxxx (3). Xxxxxx xx xxxxxxxxx, xx xxxxxx xxxxx xxxxxxxx nelze xxxx xxxxxxxxx standardními xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx xxx xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x jejich xxxxxxx xx důrazně xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Je xxxxx xxxxxxxxxxxxx xxxx "zvláštní xxxxxxx" (xxxxxxxx x xxxxxxxx xxxxxxx xxxxxx xxxxxxx): azobarviva x xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx a těkavé xxxxxxxx látky (12, 14, 15, 16), x glykosidy (17, 18). Odchylka xx xxxxxxxxxxxx xxxxxxx xxxx xxx vědecky xxxxxxxxxx.

1.5 XXXXX ZKUŠEBNÍ XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx kultury xxxxxxxx xx xxxx xxx xxxxxxxxxxx do xxxxxx xxxxxxxxxxxxx fáze xxxx do xxxxx xxxxxxxxxxx fáze xxxxx (xxxxxxxxx 109 xxxxx xx xx). Xxxxx x pozdní xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxxx. Xx xxxxxxxx, aby xxxx xxxxxxx xxxxxxxx xxxxxx xxxx xxxxxxxxxxxxxxx bakterií. Xxxx může xxx xxxxxxxx buď xx xxxxxxx xxxxxxxxxxx kontrolních xxxxx x xxxxxxx xxxxxx, xxxx xxx xxxxxx zkoušku stanovením xxxxx xxxxxxxxxxxxxxx xxxxx xx xxxxxxx.

Xxxxxxxxxx inkubační xxxxxxx xx 37 °X.

Xxxx xx být xxxxxxx xxxxxxx pět xxxxx xxxxxxxx. Mezi xxxx xx měly xxx čtyři kmeny X. typhimurium (XX1535; XX1537 nebo XX97x xxxx TA97; XX98 x XX100), xxxxxxx xxxxxxx xx xxxxxxx x různých laboratořích xxxx spolehlivá x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. xxxxxxxxxxx xxxx pár xxxx XX xx primárním xxxxxxxxx xxxxx x xx známo, xx xxxxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxxxxxx xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Tyto xxxxx mohou xxx xxxxxxxxxx xxxxx X. xxxx XX2 xxxx X. xxxxxxxxxxx TA102 (19), xxxxx mají xx xxxxxxxxx reverzním xxxxx xxx bází XX. Xxxxxxxxxx xxxxxxxxx xxxxx je xxxx xxxx:

- X. xxxxxxxxxxx XX1535 a

- X. xxxxxxxxxxx XX1537 xxxx XX97x x

- X. xxxxxxxxxxx TA98 x

- X. typhimurium TA100 x

- E. xxxx XX2 uvrA, nebo X. xxxx XX2 xxxX (pKM101), nebo X. typhimurium XX102.

Xxx xxxxxxx xxxxxxxx způsobujících xxxxxxxxxx xxxxxx XXX xxxx xxx xxxxxxxxx xxxxxxx TA102 nebo xxxxxx xxxx E. xxxx x xxxxxxx xxxxxxxxxx xxxxxxxx XXX, (xxxx. X. coli XX2 (xXX101)).

Xxxx xx xxx použity xxxxxxxx xxxxxxx přípravy kmenové xxxxxxx, xxxxxxxxxx xxxxxxx x skladování. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx pro každou xxxxxxxxx kmenovou xxxxxxx (xxxxxxxx xxx xxxxx X. xxxxxxxxxxx a xxxxxxxxx xxx E. xxxx). Xxxxxxx xx xxxx být xxxxxxxxxxxx xxxx fenotypové xxxxxxxxxxxxxxx, xxxxxxxxx podle potřeby xxxxxxxxxx nebo xxxxxxxxxxxx X-xxxxxxx xxxxxxxx (xx. xxxxxxxxxxxx xxxxxxxxxx x xxxxx XX98, XX100 x XX97x xxxx XX97, WP2 xxxX x XX2 uvrA (xXX101) x xxxxxxxxxxxx x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx charakteristických xxxxxx (xx. xxx xxxxxx x S. typhimurium xxxxxxxxxx xx xxxxxxxxxxx xxxxxx x uvrA xxxxxx x X. xxxx xxxx xxxX xxxxxx x X. xxxxxxxxxxx xxxxxxxxxx xx xxxxxxxxxxxx světlo) (2, 3). Kmeny xx xxxx rovněž xxxxx xxxxx kolonií xxxxxxxxxxx xxxxxxxxxx xx xxxxx x rozmezí xxxxxxxx xxxxxxxxxxx na xxxxxxx xxxxxxxxxxx xxxxx laboratorních xxxxxxx x xxxxxxx x xxxxxxx xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Médium

Použije xx xxxxxx minimální xxxx (xxxx. obsahující xxxxxxxxx půdu X (Xxxxx-Xxxxxx) x glukosu) x xxxxxx xxxx xxxxxxxxxx xxxxxxxx x xxxxxx nebo xxxxxxxxx xxxxxxxxxx několik xxxxxxxxx xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx xxxx xxx xxxxxxxxx xxxxxxxx xxxxx, x xx s xxxxxxx systémem metabolické xxxxxxxx x xxx xxxx. Nejčastěji používaným xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) připravená x xxxxx hlodavců xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Aroclor 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 X9. Xxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx na xxxxx zkoušené xxxxxxxx xxxxx. X xxxxxxxxx xxxxxxxxx xxxx být xxxxxx použít xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx. U xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxx může xxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx xxxxxxxx xx bakterie xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx přidány přímo x testovacím xxxxxxxx x/xxxx xxxxx být xxxx xxxxxxxx xxxxxxx. Xxxx by být xxxxxxx xxxxxxx připravené xxxxxxxx chemické látky, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx možnost xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx by xxxx xxx mimo xxxxxxxxx, xx xxxxxxx xx xxxxxxxxx látkou, a xxxx xx xxx xxxxxxxxxx s přežitím xxxxxxxx x x xxxxxxxxx S9 (22). Xxxx-xx xxxxxxx xxxx xxx xxxxx rozpouštědla/vehikula, xxxx xx být xxxxxx xxxxxxxx xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx nejdříve xxxxxx xxxxxxx vodných xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx ve xxxx xx xxxx xxx xxxxxxx organická xxxxxxxxxxxx neobsahující xxxx.

1.5.2 Xxxxxxxx podmínky

1.5.2.1 Zkušební xxxxx (xxx 1.5.1.1)

1.5.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, xxxxx xxxx být xxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxx množství xxxxxxxx xxxxx xxxxx cytotoxicita x rozpustnost x xxxxxxx směsi pro xxxxxxxx.

Xxxx být užitečné xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx v předběžných xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx xxxxxxx revertantů, xxxxxxxxx xxxx zeslabením xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx stupně xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx xx může xxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx aktivačních xxxxxxx. Xxxxxxxxxxxxx xx xxxx xxx posouzena xx xxxxxxx xxxxxxxxxxx xxxxxxx x konečné směsi xx skutečných xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx pro rozpustné xxxxxxxxxxxxx látky xx 5 mg/misku xxxx 5 μx/xxxxx. X xxxxxxxxxxxxxxx xxxxx nerozpustných xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx xx měla xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, aby xxxxx xxxx x xxxxxxx xxxxx xxx aplikaci xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx xxxxxxxxxxx xxx xxx xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, xx měly xxx xxxxxxxx xx xx xxxxxxxxxxx xxxxxxxxxxx. Xxxxxxxxx by neměla xxxxx xxx vyšetřování.

Mělo xx být xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx, xxxxxxx xxx xxxxxx experimentu by xxxx xxx xxxxxxxxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx xxxxxxxx xxxxx logaritmické xxxxxxxx (xx. Ö10). Xxxxx xxxxxxxxx xxxx xxxxxx x xxxxxxx, xxx xx xxxxxxxxx křivka xxxxxxxxxx xxxxxxxx xx xxxxxxxxxxx. Zkoušení koncentrací xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx může xxx xxxxxxx xxx hodnocení xxxxx obsahujících významné xxxxxxxx xxxxxxxxxxx mutagenních xxxxxxxx.

1.5.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxx xx měly xxx xxxxxxx specifické xxxxxxxxx x negativní (xxxxxxxxxxxx nebo xxxxxxxxx) xxxxxxxx x xxxxxxxxxxxx xxxxxxxx a xxx xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx koncentrace xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxx.

X xxxxxxx xxxxxxx x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xx xxxx xxx xxxxx (xxxxx) xxx xxxxxxxxx xxxxxxxx xxxxxxx (vybrány) xx xxxxxxx xxxx xxxxxxxxx xxxxx bakterií.

Příkladem xxxxxx pozitivní kontroly x zkoušky x xxxxxxxxxxxx aktivací xxxx xxxx xxxxx:

Xxxxx	Xxxxx CAS	Číslo xxxxx EINECS
9,10-dimethylanthracen	781–43–1	212–308–4
7,12-dimethylbenzo[a]anthracen	57–97–6	200–359–5
benzo[a]pyren	50–32–8	200–028–5
2-aminoanthracen	613–13–8	210–330–9
Cyklofosfamid	50–18–0	200–015–4
cyklofosfamid monohydrát	6055–19–2	200–015–4

Tato xxxxx je vhodnou xxxxxxxxx kontrolou xxx xxxxxx redukční xxxxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx XXX	Xxxxx xxxxx XXXXXX
XX Direct Red 28	573–58–0	209–358–4

2-xxxxxxxxxxxxxx by xxxxx xxx xxxxxx xxxx xxxxxx xxxxxxxxx xxxxxxxxx xxxxx S9. Xxx xxxxxxx 2-xxxxxxxxxxxxxxx xx xxxx xxx xxxxx xxxxx X9 charakterizována xxxxxxxxx, který xxxxxxxx xxxxxxxxxxxx xxxxxxxx mikrosomálními xxxxxx, xxxxxxxxx benzo[a]pyren xxxx 7,12-xxxxxxxxxxxxx[x]xxxxxxxxx.

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx xxx vnější xxxxxxxxxxx aktivace xxxx xxxx xxxxx:

Xxxxx	Xxxxx CAS	Číslo xxxxx XXXXXX	Xxxx
xxxx sodný	26628–22–8	247–852–1	TA1535 x XX100
2-xxxxxxxxxxxx	607–57–8	210–138–5	XX98
9-xxxxxxxxxxxx	90–45–9	201–995–6	XX1537, XX97 x XX97x
XXX 191	17070–45–0	241–129–4	XX1537, XX97 x XX97x
Xxxxxxxxxxxxxxxxx	80–15–9	201–254–7	XX102
xxxxxxxxx X	50–07–7	200–008–6	XX2xxxX x XX102
1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx	70–25–7	200–730–1	XX2, XX2 uvrA x XX2 uvrA (xXX101)
4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1	XX2, XX2 xxxX x XX2 uvrA (pKM101)
α-[(5-nitro-2-furyl)methyliden]furan-2-acetamid (XX2)	3688–53–7		xxxxx obsahující xxxxxxxx

Xxx xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxx xxxx xxxxxx xxxxxxxxxx látky. Xxx xxxxxxxxx xxxxxxxx xx mělo xxx xxxxx x xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx xx x xxxxxxxxx.

Xxxx xx xxx použity xxxxxxxxx xxxxxxxx xxxxxxxxxx se xx xxxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx exponované xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx dosud xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx zhoubné xxxx xxxxxxxxx xxxxxx.

1.5.3 Xxxxxx

X standardní xxxxxxx xxxxxx (1, 2, 3, 4) xxx xxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,05 xx xxxx 0,1 xx zkušebních xxxxxxx, 0,1 xx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 životaschopných xxxxx) a 0,5 xx xxxxxxxxxx xxxxx x 2,0 ml xxxxxxxx xxxxx. X xxxxxxx xxxxxxx x xxxxxxxxxxxx aktivací xx xxxxxxx smíchá 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx postmitochondriální frakce (x xxxxxxx 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx směsi) s xxxxxxx xxxxxx (2,0 xx) x xxxxxxx x bakteriemi x xxxxxxxxx xxxxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxx zkumavky xx xxxxxxxx x přelije xxxx povrch xxxxxxxxxxx xxxxx xx misce. Xxxx xxxxxxxx se xxxxx vrchní xxxx xxxxxxxx.

X preinkubační xxxxxx (2, 3, 5, 6) xx xxxxxxxx xxxxx xxxx xxxxxxxx xxxxxx xxxx xxxxxxxxx x vrchním xxxxxx x xxxxxxxx xxxx xxxxxx minimálního agaru xx xxxxx xxxxxxx 20 xxxxx xxxx xxxx xxxxxxxxxxx s xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a sterilním xxxxxx xxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx (0,5 xx) při 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 nebo 0,1 xx xxxxxxxx xxxxx xxxx zkušebního roztoku, 0,1 xx xxxxxxxx x 0,5 xx xxxxx S9 xxxx xxxxxxxxxx pufru s 2,0 xx xxxxxxxx xxxxx. Xxxxxxxx xx xxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxxx xx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx xxxxxxxx by xxxx xxx xxx xxxxx xxxxxx xxxxx xxxxxxx 3 xxxxx. Xxxxxxx xxxx misek xx xxxxxxxxxx po xxxxxxxx xxxxxxxxxx. Případná ztráta xxxxx xxxxxx znamenat xxxxxxxxxxxx xxxxxxx.

Xxxxxx xxxx xxxxxx xxxxx by xxxx být zkoušeny xxxxxxxx metodami, xxxx. x xxxxx xxxxxxxxxx xxxxxxxxxxxx nádobách (12, 14, 15, 16).

1.5.4 Xxxxxxxx

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

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxxxxxxxxx xxxxx xx měly xxx xxxxx kolonií xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Xxx xx xxx xxxxxx xxxxxx xxxxx xxxxxxx xxxxxxxxxx xxx na xxxxxxx x xxxxxxxxx kontrolou (xxxxxxxx rozpouštědla x xxxxxxxx xxxxxxxxxxxx kontrola), xxx xx miskách x pozitivní xxxxxxxxx. Xxxxx xx jednotlivých xxxxxxx, střední xxxxxxx xxxxx kolonií revertantů xx xxxxx x xxxxxxxxxx xxxxxxxx by xxxx být xxxxxxxxxx xxx xxxxxxxxx xxxxx x xxxxxxxxx x xxxxxxxxx xxxxxxxx (neexponovanou xxxxxxxx a/nebo kontrolu xxxxxxxxxxxx).

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx se xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx xxxxxx xx případu. Xxxxxxxx se potvrzení xxxxxxxxxxx výsledků xxxxxxxxxx xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Změna parametrů xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx by xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx studie, xxxxx xx mohly xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx xxxxxxx xxxxxx xxxx xxxxxxxxxxx x xxxxxxxx xxxxx) x xxxxxxxx metabolické xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, např. nárůst xxxxx xxxxxxx revertantů xx xxxxx nad xxxxxxxxx xxxxxx x xxxxxxx jednoho xxxxx x xxxxxxxxxxxx aktivačním xxxxxxxx xxxx xxx xxxx, x to x závislosti xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx xxxxxx xxxxx xxx jednu xxxx xxxx koncentrací (23). Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Při xxxxxxxxx výsledků xxxxxxx xxxxx být použity xxxx pomocný prostředek xxxxxxxxxxx xxxxxx (24). Xxxxxxxxxxx xxxxxxxxxx by xxxxxx xxx jediným xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx negativní výsledky, x xxxxxxxxxxx případech xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Výsledky mohou xxxxxx dvojznačné xxxx xxxxxx bez ohledu xx to, xxxxxxxx xx experiment opakován.

Pozitivní xxxxxxxx xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x xxxxxx xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx bodové xxxxxx xxxxxxxxxx xxxx xxxx posunem xxxxxxx xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxx xx xxxxxxxx xxxxxxx pro xxxxxxxxx xxxxx mutagenní.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

- xxxxxxxxxxx a xxxxxxx xxxxxxxx látky v xxxxxxxxxxxx/xxxxxxxx, je-li známa.

Kmeny:

- xxxxxxx xxxxx,

- xxxxx xxxxx v kultuře,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxx xxxxx,

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

- xxxxxx expozice.

Výsledky:

- xxxxxx xxxxxxxx,

- známky xxxxxxx,

- počty na xxxxxxxxxxxx xxxxxxx,

- xxxxxxx xxxxxxx počtu xxxxxxx xxxxxxxxxx na misku x směrodatná xxxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- xxxxxxxx statistické xxxxxxx,

- xxxxx x souběžné xxxxxxxxx (rozpouštědlo/vehikulum) a xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými xxxxxxxxxx,

- xxxxxxxxx údaje o xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) a xxxxxxxxx xxxxxxxx x xxxxxxxxx, xxxxxxxxx xxxxxxxxx x směrodatnými odchylkami.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxx, X. X., McCann, X., Xxxxxxxx X. (1975), Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xxx Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Res., 31, 347-364.

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

3) Gatehouse, X., Xxxxxxx, S., Xxxxxx, X., Gocke, X., Xxxx, X., Xxxxxxxxxx, X., Xxxxxxx, C., Xxxxx, X., Xxxxxx, X., Xxxxxx, E. (1994), Recommendations xxx xxx Xxxxxxxxxxx xx Xxxxxxxxx Mutation Assays, Xxxxxxxxxx Xxx., 312, 217-233.

4) Xxxx, X. X., Xxxxxxx X. X., Auletta, X. X., Xxx Xxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X., McCann, J., Xxxxxxxxxx, X., Xxxxxx, X., Rao, T. X., Ray V. (1986), The Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Microsomal Assay: X Report xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Agency Xxxx-Xxx Xxxxxxx, Mutatation Xxx., 168, 69-240.

5) Xxxxxx, X., Xxxxxx, X., Seino, X. X., Xxxxxxxxxx, T., Xxxxx, X., Sugimura, X., Xxxxxxxxx, X. (1975), Mutagenicity xx Xxxxxxxxxx Azo Dyes xxx their Xxxxxxxxxxx, Xxxxxx Xxxx. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxxx, A., Sawamura, X. (1980), Factors Xxxxxxxxxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxx, xx: Xxxxx-xxxx Xxxx Systems xxx Xxxxxxxxx Xxxxxxxxxxx, ed. Xxxxxxx X. X., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx York, 273-285.

7) Xxxxxxxxx, X. X., Rowland, X. X., Wilcox, X., Xxxxxxxxx, R. X., Xxxxxx, X. (1980), Xxxxxxxxx Mutation Assays, xx: Xxxxx Xxxxxxxxxxxx Xxxxx: XXXXX Xxxx 1 Revised, xx. X. X. Xxxxxxxx, Xxxxxxxxx University Xxxxx, 13-61.

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

9) Xxxxx, X. X. X., Xxxxxx, X. X., Xxxxxxx, X. X. (1976), Use of x xxxxxxxxxx xxxxxxxxxxx xxxx xx xxxxxx xxx xxxxxx of xxxxxxxx, Xxxxxxxxxx Xxx., 38, 33-42.

10) Hubbard, X. X., Xxxxx, X. X. X., Xxxxxxxxx, X., Bridges, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Bacteria, xx: Xxxxxxxx xx Mutagenicity Xxxx Xxxxxxxxxx, 2. xxx., Xxxxxx, B. X., Legator, X., Xxxxxxx, W., Xxxxx, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx York-Oxford, 141-161.

11) Xxxxxxxx, E. D., Xxxxxxx, X. X. (1981), An Examination xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx xxx Xxxxxxxxxxx xxxx Strains xx Xxxxxxxxxx xxxxxxxxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Araki, X., Xxxxxxx, X., Xxxx, X., Matsushima, X. (1994), Xxxxxxxx Xxxxxx xxx Xxxxxxxxxxxx Testing xx Xxxxxxx Xxxxxxxxx xx Xxxxx x Xxx Sampling Bag, Xxxxxxxxxx Xxx., 307, 335-344.

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

14) Xxxxxx, X., Anderson, X. X., Xxxxxxx, X., Xxxxxx, T., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx xxxx xxx Testing of 311 Chemicals, Environ. Xxx. Mutagen., 19, 2-141.

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

16) Xxxxxx, X. J., Xxxxxxx, X. M., Monteith, X. G., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Xxxxxxxxx xx Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Volatile Organic Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Xxxxxxxxx, X., Shirai, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Mutagenicity xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Cycasin xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Xxxxxxxxxx in Xxxxxxxxxx xxxxxxxxxxx, Xxxxxx Xxx., 39, 3780-3782.

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

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

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, X., Sugimura, X. (1976), A Xxxx Xxxxxxxxxx xxx Polychlorinated Xxxxxxxxx x. s. xx Inducer or Xxxxxxxxx Xxxxxxxxxx Systems, xx: Xx xxxxx Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, xxx. X. X. de Xxxxxx et al. Xxxxxxxx, Xxxxx Holland, 85-88.

21) Xxxxxx, B. X., Xxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Gibson, X. X., Xxxxxx, X. X., Xxxx, X. X. (1992), Alternatives xx Xxxxxxx 1254-xxxxxxx X9 xx in xxxxx Genotoxicity Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

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

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

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

XXXXXXX 4E

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

1. METODA

Tato xxxxxx xx xxxxxxxx metody XXXX TG 476 — Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx savců xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx vitro xxx xxxxxx xxx xxxxxxx xxxxxxxx mutací indukovaných xxxxxxxxxx látkami. Xxxx xxxxxx buněčné linie xxxxx xxxxx xxxxxxx X5178X xxxx, buněčné xxxxx CHO, CHO-AS52 x X79 xxxxxx xxxxxxxx x xxxxxxxxxxxxxxx xxxxx XX6 xxxxxxx (1). X těchto xxxxxxxxx xxxxx jsou xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace xxxx xxx xxxxxxxxxxxxxx (XX) x hypoxanthin-guaninfosforibosyltransferasu (HPRT) x transgen xanthin-guaninfosforibosyltransferasy (XXXX). Zkoušky xx xxxxxx TK, HPRT x XXXX detekují xxxxx spektrum xxxxxxxxxxx xxxxxxxx. Autosomální xxxxxx XX a XXXX xxxx xxxxxxx detekci xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx delece), xxxxx xxxxx xxxxxxxxx x XXXX xxxxxx na X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx zkoušce xx xxxxxx xxxxxx x xxxxxxx savců xx xxxxx lze xxxxxx xxxxxxx xxxxxxxxxx linií xxxxx nebo buněčné xxxxx. Xxxxx xx xxxxxxxx xxxxx schopnosti xxxxx v kultuře x xxxxxxxx četnosti xxxxxxxxxxx xxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx obecně xxxxxxxx použití vnějšího xxxxxx metabolické xxxxxxxx. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xx třeba xx xxxxx vyvarovat xxxxxxxx, xxxxx by xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx vlastní xxxxxxxxxx. X pozitivním xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx mutagenitu, xxxx xxxxx xxxxxx xX, xxxxxxxxxx nebo xxxxxxxx xxxxxx xxxxxxxxxxxx (7).

Tato xxxxxxx xx používá xx xxxxxxxx možných xxxxxxxx x xxxxxxxxxxx xxxxx. Mnoho xxxxxxxxx, xxx xxx xx xxxx zkouška xxxxxxxxx, xxxx karcinogeny xxxxx; xxxx xxxxx xxxxxxxx x karcinogenitou xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx na xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, xx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx xxxxxx xxxxxx xxxxxx, xxxxxxxxxxxxxxx xxxxxxxxxx, xxxx mechanismy, xxxxx x xxxxxxxxxxxxx xxxxxxx xxxxxxxxxx (6).

Xxx xxxx xxxxxx úvod, xxxx X.

1.2 DEFINICE

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

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

Xxxxxxxx xxxxxxxx : xxxxx, xxxxx xxxxxxxxx xxxxx xxxx deleci xxxxxxx nebo více xxxx bází v xxxxxxxx XXX.

Xxxx xxxxxxx xxxxxxxx : xxxx, xxxxx níž vymizí x xxxx mutovaných xxxxx xxxxxxxxx genové xxxxxxxx.

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

Relativní xxxxxxx xxxx : xxxxxx xxxxx xxxxx v xxxx xx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxx; xxxxxxx xx xxxx xxxxxx xxxxxx xxxxxxxxx růstu v xxxxxxxx x x xxxxxxxxx xxxxxxxx x xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxx x xxxxxxxx : xxxxxx xxxxx xxxxx x xxxxxxx exprese xxxxxxxx x xxxxxxxxx kontrole.

Životaschopnost : xxxxxxxx klonování xxxxx x okamžiku xxxxxxxx xx xxxxx xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx xx xxxxx xx xxxxx xxxxxx xxxxxxxx; xxxxxxx xx xxxxxxx xxxxxxxxx x xxxxxx x xxxxxxx xxxxxxxxx populace xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxx, které v xxxxxxxx mutace XX+/-® XX— /- neobsahují xxxxxxxxxxxxxx (XX) xxxx xxxxxxxxxxx k cytotoxickým xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Xxxxx xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx na XXX, xxx způsobuje xxxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxx xxxxx xxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxx xxxx xxxxxxx xxxxxxxxxxx za xxxxxxxxxxx XXX, zatímco normální xxxxx, xxxxx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxx xxxxxx. Xxxxxxx xxx x buněk x xxxxxxxxxxxx HPRT xxxx XXXX provést selekci xxxxxxxxxxxxxxx rezistence x 6-xxxxxxxxxxx (TG) xxxx 8-xxxxxxxxxx (AG). Xxxxxxxxxx xxxxxxxx látky xx xxxx být xxxxxxx xxxxxxx, xxxxxxxx je xx xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xxxxxxx xxxxxx báze nebo xxxxxxxxxx xxxxxxx selekčnímu xxxxxxx. Xxxx xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx podezření xx xxxxxxxxxx xxxxxxxx zkoušené xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxx xxxxxxxxxx xxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx jako xxxxxxxx xxxxxxx, xxxx xxxx xxx potvrzena xxxxxxxx xxxxxxx xxxx xxxxxxx xxx selekci (8).

Xxxxx x xxxxxxxxx xxxx jednovrstevné kultuře xxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx xxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, x xxxxxxxxxxxxxx xx účelem xxxxxxxxx xxxxxxxxxxxx x za xxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Cytotoxicita xx obvykle zjistí xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxx xx xxxxxxxx xxxx xxxxxxxx. Xxxxxxxxxx xxxxxxx se xxxxxxx v xxxxxxxx xxxxx xx vhodnou xxxx xxxxxxxxxxxxxxxxx pro xxxxx xxxxxxx xxxxx x xxx xxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx fenotypová xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxx xxxxxxx se stanoví xxx, že xx xxxxxx xxxxx xxxxx xxxxx xx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxx detekci xxxxxxxxxx xxxxx x xx xxxxx xxx xxxxxxxxxx xxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx klonování (xxxxxxxxxxxxxxx). Po vhodné xxxxxxxxx xxxx se xxxxxxxxx kolonie. Xxxxxxx xxxxxxx xx xxxxxxx x počtu xxxxxxxxxx xxxxxxx v xxxxxxxxx xxxxx x xxxxx xxxxxxx v xxxxx xxx xxxxxxxxxx xxxxxxx.

1.4 XXXXX ZKUŠEBNÍ METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxx xxxxxxx x této zkoušce xxxx k dispozici xxxxx typy xxxxx, xxxxxx subklonů buněk X5171X, XXX, CHO-AS52, X79 xxxx XX6. Xxxx buněk x xxxx xxxxxxx xx xxxx vykazovat xxxxxxxxx x chemickým xxxxxxxxx, xxxxxxx xxxxxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx xxx xxxxxxxxxxxx, zda xxxxxx xxxxxxxxxxxxx mykoplasmaty, a x xxxxxxx kontaminace xx xxxxxx xxx xxxxxxx.

Xxxxxxx xx xxxx xxx navrženy xxx, xxx měly xxxxxx xxxxxxxxxx citlivost a xxxx. Xxxxx xxxxxxxxx xxxxx, xxxxxx a xxxxxxxxxxx xxxxxxxx látky xx xxx tyto xxxxxxxxxx xxxxxxxxx odrážet (14). Minimální xxxxx xxxxx, xxxxx xxxxxxx xxxxxxxx x xxxxx xxxxx použity x xxxxxx stadiu xxxxxxx, xx xxx být xxxxxxx xx xxxxxxxx xxxxxxxxxxx mutací. Xxxxxxx xxxxxxxxx xx, aby xxx xxxxxx xxxxx xxxxx, xxxxx je xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však doporučeno, xxx xxxx použito xxxxxxx 106 xxxxx. Xxxx by být x xxxxxxxxx xxxxxxxxxx xxxxxxxxx údaje x xxxxxxxx xxxxxxxx xxxxxxx, xxx xxxx doložena xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Média x xxxxxxxxxx podmínky

Pro udržování xxxxxx by xxxx xxx xxxxxxx vhodná xxxxxxxxxx xxxxx x xxxxxxxxx podmínky (xxxxxxxxxx xxxxxx, xxxxxxxxxxx CO₂, xxxxxxx x vlhkost). Xxxxx by měla xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx x xxxx xxxxx použitých xxx zkoušce. Je xxxxxxx důležité, xxx xxxxxxxxxx xxxxxxxx byly xxxxxxx xxx, xxx xxxx xxxxxxxxx optimální xxxx xxxxx xxxxx xxxxxx exprese x xxxxxxxxx xxx xxxxxxxxxx, xxx nemutovaných buněk xxxxxx xxxxxxx.

1.4.1.3 Příprava xxxxxx

Xxxxx xx měly xxx xxxxxxxxx x xxxxxxxxx xxxxxx, nasazeny xx xxxxxxxxxxxx xxxxx x xxxxxxxxxx při 37 °X. Xxxx xxxxxxxx x xxxx xxxxxxx xxxx xxx xxxxxxxx odstranit x xxxxxxx již přítomné xxxxxxxx buňky.

1.4.1.4 Metabolická xxxxxxxx

Xxxxx xx xxxx xxx xxxxxxxxx zkoušené xxxxx, x xx x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx x xxx něho. Nejčastěji xxxxxxxxxx systémem xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx hlodavců xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (15, 16, 17 a 18), nebo xxxx xxxxxxxxxxxxx a β-naftoflavonu (19, 20).

Xxxxxxxxxxxxxxxxxxx frakce xx x konečném xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x koncentracích 1 — 10 % xxx. Xxxxx x xxxx xxxxxxxxxxxxx xxxxxxxxxxx systému xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, xxxxx xx zkoušena. X xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx xxx jednu xxxxxxxxxxx xxxxxxxxxxxxxxxxxxx frakce.

Řada xxxxxxxx vývoje, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx linií xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx, xxxxxxxxx možnosti pro xxxxxxxxx xxxxxxxx. Volba xxxxxxxxx xxxxxxxxx xxxxx xx xxxx být xxxxxxx xxxxxxxxxx (xxxx. xxxxxxxxxxx xxxxxxxxx cytochromu X450 pro xxxxxxxxxxxx xxxxxxxx látky).

1.4.1.5 Příprava xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx xxxxxxxx xx xxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné zkoušené xxxxx xxxxx xxx xxxxxxx přímo x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx být před xxxxxxxx zředěny. Xxxx xx být použity xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx, x xxxx xx xxx xxxxxxxxxx x xxxxxxxx buněk x s xxxxxxxxx X9. Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx látek xxxxxxxxx xx xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx neobsahující xxxx. Xxxx xxx xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Xxxxxxxxx koncentrace

Mezi xxxxxxxx, která xxxx xxx zohledněna při xxxxxxxxx xxxxxxxx koncentrace, xxxxx xxxxxxxxxxxx, rozpustnost x xxxxxxxxxx xxxxxxx x xxxxx xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx by xxxx xxx xxxxxxxxx x xxxxxxxxxxxx aktivací x xxx xx x hlavním xxxxxxxxxxx xx použití xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x růstu, xxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (xxxxxxx) nebo xxxxxxxxx celkový růst. Xxxx xxx výhodné xxxxxxxx cytotoxicitu a xxxxxxxxxxx x xxxxxxxxxx xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx xxxxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxx xx xxxx xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx dané xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx, xxx xxxx xxxxxxx znamenat, xx xx se koncentrace xxxx xxxxx faktorem 2 až Ö10. Xx-xx xxxxxxxxx koncentrace xxxxxxxx od xxxxxxxxxxxx, xxxx xx xxx xxxxxxxxx přibližně 10 — 20 % (xxx nejméně 10 %) xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx celkový růst. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx látek by xxxx xxx maximální xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 M, xxxxx toho, xxxxx x nich xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx xxx xxxxxxxx xx k xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx xxxxxxxx, xxxx xx xx xxxx xxx. Měla xx xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx, xx kterému xxxx buňky xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x xx xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx xx může x xxxxxxx xxxxxxxx x testovacím xxxxxxx xxxxx x důsledku xxxxxxxxxxx buněk, X9 xxxx, atd. Xxxxxxxxxxxxx xxx xxxxxxx xxxxxxxx. Xxxxxxxxx by xxxxxx xxxxx při vyšetřování.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx xxxx xxx xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx xxx x xxxxxxxxxxxx xxxxxxxx, xxx xxx ní. Xxx xxxxxxx metabolické aktivace xx xxxx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx, xxxxx x xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxx xxx tyto xxxxx:

Xxxx xxxxxxxxxxx xxxxxxxx	Xxxxx	Xxxxx	Xxxxx XXX	Xxxxx xxxxx Xxxxxx
Xxx 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 xxxxxx metabolickou xxxxxxxx	XXXX	3-xxxxxxxxxxxxxxxxx	56–49–5	200–276–4
		X-xxxxxxxxxxxxxxxxxxx	62–75–9	200–549–8
		7,12-xxxxxxxxxxxxxxxxxxxxxx	57–97–6	200–359–5
	XX (xxxx x xxxxx kolonie)	cyklofosfamid	50–18–0	200–015–4
		cyklofosfamid xxxxxxxxxx	6055–19–2
		xxxxx[x]xxxxx	50–32–8	200–028–5
		3-xxxxxxxxxxxxxxxxx	56–49–5	200–276–5
	XXXX	X-xxxxxxxxxxxxxxxxxxx (xxx vysoké xxxxxx X9)	62–75–9	200–549–8
	XXXX	xxxxx[x]xxxxx	50–32–8	200–028–5

Xxxxx být xxxxxxx xxxx xxxx xxxxxxxxxx xxxxx xxx xxxxxxxxx xxxxxxxx, xxxx. má-li xxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxx x 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, EINECS 200–415–9), může xxx xxxx xxxxxxxxxx látka xxxxxx použita. Pro xxxxxxxxx xxxxxxxx by xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx pokud xxxxx ze xxxxxx xxxxxxxx třídy.

Měly xx xxx použity xxxxxxxxx xxxxxxxx tvořené xxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxxxx xxxx xxxxxxxxx x xxxxxxxxxx jinak stejným xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx toho xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx nevyvolává xxxxx xxxxxxx nebo xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx látce

Proliferující xxxxx xx xxxx být xxxxxxxxx xxxxxxxx látce xxx xx xxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx systému, xxx xxx xxxx. Xxxxxxxx xx měla xxxxx xxxxxxx dobu (xxxxxxx je xxxxxx xxxx 3 až 6 hodin). Expoziční xxxx může xxx xxxxxxxxxxx xx xxxxx xxxx xxxx xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx mohou xxx xxxxxxx xxxxxxxxxx xxxxxxx xxxx xxxxx xxxxxxxxxx xxxxxxx. Je-li xxxxxxx xxxxx kultura, měl xx být počet xxxxxxxxxxx xxxxxx xxx, xxx xxx zajištěn xxxxxxxxxxxx xxxxx xxxxxx xxx xxxxxxx (xxxx. xxxxxxx xxx xxxxxxxxxxxxxxxx xxxxxxxxxxx). Xxxx xx xxx použity xxxxxxxxxx xxxxxxxxx kontrolní xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx xxxx xxxxxx látky xx xxxx být xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. x xxxxx uzavřených xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx přežití, xxxxxxxxxxxxxxxx a xxxxxxxx xxxxxx

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

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, xxx xxxxxxx xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx nově indukovaných xxxxxxx (HPRT a XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, TK alespoň xxx dny). Buňky xxxx xxxxxxxxxxx x xxxxx xx selekčním xxxxxxxx (xxxxxxxxxx xxxxxxx) x xxx xxxx (xxx nich) za xxxxxx stanovení počtu xxxxxxx x xxxxxxxxx xxxxxxxxx. Se stanovením xxxxxxxxxxxxxxxx (xxxxxxx xxx xxxxxxx četnosti xxxxxxx) xx xxxxxxx na xxxxx doby xxxxxxx xxxxxxxxx xx xxxxx xxx xxxxxxxxxx činidla.

Je-li xxxxxxxx látka xxxxxxxxx xx xxxxxxx X5178X XX+/-, mělo xx xxx xxxxxxxxx xxxxxxx xx jedné xx xxxxxxxxxx kultur (s xxxxxxxx pozitivní koncentrací) x xx negativních x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx kultury xxxxx xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx látka ve xxxxxxx X5178X XX+/- xxxxxxxxx, xxxx xx xxx rozdělení kultury xxxxx velikosti xxxxxxx xxxxxxxxx xx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 XX+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxx xx měly zahrnovat xxxxxxxxx cytotoxicity a xxxxxxxxxxxxxxxx, počtu kolonií x četnosti xxxxxxx xxx xxxxxxxxxx a xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx xxxxxxxx xx zkoušku X5178X XX+/- se xxxxxxx xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx xxxxxxxx xxxxx (nejvyšší xxxxxxxxx xxxxxxxxxxx) a x xxxxxxxxx x xxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxx xxxxxxx — xxxxx xxxxxxx. Xxxxxxxxxxx x xxxxxxxxxxxxx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxx kolonie, xxx mutantů tvořících xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx zkoušce XX+/- xxxx xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx kolonie x xxxxxxxxx růstem (velká) x xxxxxxx s xxxxxxx růstem (xxxx) (25). U xxxxxxxxxx xxxxx, které xxxxxxx xxxxxxxxxxxxxx xxxxxxxxx poškození, xx xxxxxxxxxxx xxxx xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx xx xxxxx xxxxxx xxxx až xx karyotypické xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx tvořících xxxx xxxxxxx xx xxxxxxx x xxxxxxxxxx látkami, xxxxx xxxxxxxx silné xxxxxxxxxxxx aberace (26). Xxxx xxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx xxxxxx jako xxxxxxxx buňky x xxxxx xxxxx xxxxxxx.

Xxxx xx xxx xxxxx xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx relativní xxxxxxx xxxx. Xxxxxxx xxxxxxx by xxxx xxx vyjádřena xxxx xxxxx xxxxxxx x xxxxx xxxxxxxxxx xxxxx.

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

Xxxxxxx xxxxx xxxxxxxxx odpovědi xx xxxxxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx podmínek. Xxxxxxxxx xxxxxxxx xxxx být xxxxxxxxx případ xx xxxxxxx. Tam, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx považováno xx xxxxx, je třeba xxxxx xxxxxxxxxx. Xxxxx xxxxxxxxx studie x xxxxx xxxxxxxx rozsah xxxxxxxxxxxx podmínek by xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx xxx pro dvojznačné xxxxxxxx, xxx xxx xxxxxxxxx výsledky. X xxxxxxxxxx studie, xxxxx xx mohly xxx xxxxxxx, xxxxx rozmezí xxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxxxxx xxxxxxx v xxxxxxxxxx xx koncentraci, xxxx xxxxxxxxxxxxxxxx xxxxxx xxxx xxxxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx hodnocení výsledků xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx být xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx pozitivní xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, kolikrát xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx na xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x použitých kultivovaných xxxxxxx savců xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx je xxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx x xxxxxxxxx kultivovaných xxxxxxx xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

- xxxxxxxxxxx a stálost xxxxxxxx xxxxx v xxxxxxxxxxxx/xxxxxxxx, je-li známa.

Buňky:

- xxx x xxxxx xxxxx,

- xxxxx xxxxxxxxx xxxxxx,

- případně počet xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx xxxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxx xxxxx, případně koncentrace XX₂,

- xxxxxxxxxxx xxxxxxxx xxxxx,

- xxxxx xxxxxxxx x xxxxxxx zkoušené xxxxx,

- inkubační teplota,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- případně xxxxxxx xxxxx xxxxx expozice,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxx xxxx xxxxxxx (xxxxxxxx xxxxxx počtu xxxxxxxxxx xxxxx, xxxxxxxxx x xxxxxx xxxxx),

- xxxxxxxx xxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou,

- xxxxxx použité x xxxxxxxx xxxxxxxxxxxxxxx x xxxxxxxxxx xxxxx,

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

Xxxxxxxx:

- známky toxicity,

- xxxxxx xxxxxxx,

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

- velikost xxxxxxx, xxxx-xx xxxxxxxxxxx, xxxxxxx pro xxxxxxxxx x pozitivní kontroly,

- xxxxxxxxx předpoklady xxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxxxxxx xxxxxxxx X5178X XX+/-,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxx,

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

- xxxxxxxxx údaje x negativní (rozpouštědlo/vehikulum) x xxxxxxxxx kontrole x rozmezími, xxxxxxxxx xxxxxxxxx a xxxxxxxxxxxx xxxxxxxxxx,

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., XxXxxxxx, X. M., DeSerres, X. J., Xxxxxx, X. R. (eds.) (1987), Xxxxxxx Xxxxxx 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Cold Xxxxxx Xxxxxx Xxxxxxxxxx, New Xxxx.

2) Xxx, X. X. X., Xxxxxxx X. X. (1968), Xxxxxxxxx Cell Xxxxxxxx. XX. Chemical Xxxxxxxxx xx Specific Xxxxx Xxxxxxxxx xx Chinese Xxxxxxx Xxxxx Xx xxxxx, Proc. Xxxx. Xxxx. Sci. X. X. X, 61, 1306-1312.

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

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

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

6) Xxxxx, X. S., Xxxxxxxxxx, X., Glatt, X. R., Moore, X., Nishi, Y., Xxxxxxxxxx, Xx. L. X., Theiss, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Cell Xxxx Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Xxxxxx. Xxxxxx xx xxx Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Xxxxx, X., Xxxxxxxx, X. X., Xxxxxxxx, R. X., Xxxxxxxx, X., Xxxxxxx, X., Ashby, X., Xxxx, X. X. (1991), Genotoxicity Xxxxx Extreme Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Task Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, X., XxXxxx, X., Xxxxxxx, X. X. X., Piper, X., Mavournin, K. X. (1983), Specific Xxxx Xxxxxxxxx xx X5178X Xxxxx in Xxxxxxx. A Xxxxxx xx xxx X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Res., 115, 225-251.

9) Xx, A. X., Xxxxx, R. X., Xxxxxxx, R. X., Xxxxxx, X. X. (1988), X Xxxxxx xxx Xxxxxxxx xx the Xxxxxxx Xxxxxxx Xxxxx/Xxxxxxxxxxxx Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx xx Xxxxxxxxx xxx Xxxxxxxxxxxx xx Chemical Xxxxxx: X Report xx Phase XXX xx the X. X. Environmental Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, X. X., Xxxxxx, X. X., Choy, X. X., Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X., X'Νxxxx, X. X., Xxxxxx, J. X., Xxxxxxxxxx, X. X. Jr., Yang, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx of xxx Xxxxxxx Hamster Xxxxx Xxxx/Xxxxxxxxxxxx-Xxxxxxx Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Mutation Xxxxx, Xxxxxxxxxx Xxx., 189, 135-141.

11) Xxxxx, X. L., Xxxxxxx, X. X., Xxxxxx, X. X. (1989), X Comparison xx Xxxxxxxx Induction xx xxx XX and XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Cells: Xxxxxxxxxxxx Differences xxx Xxx to xx Xxxxxxxxxx Xxxxx of Xxxxxxxxx at the Xxxxxxxxx XX Xxxxx, Xxxxxxxxxx Xxx., 216, 9-17.

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

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

14) Xxxxxx, X. X., Xxxxx, D. X., Xxxxxx, G. X., Xxxxx, X. X. X., Cole, X., XxXxxxxx, X. X., Xxxxxxx X. X. (1989), Mammalian Xxxx Xxxx Xxxxxxxx Assays Xxxxx xxxx Xxxxxx Xxxxxxxxx, xx: Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Data, Xxxxxxxx, X. X., ed., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 66-101.

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

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

17) Xxxxx, D., Xxxxxxx, X. O., Spector, X. X. X., Xxxxxx X. X., Xxxxx X. X. X. (1979), Xxxxxxxxxx xxx Xxxxxxxxxxxxxxxx of xxx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxxxx Assay Xxxxxx, Xxxxx. Xxx. 59, 61-108.

18) Maron, D. X., Xxxx, B. X. (1983), Xxxxxxx Xxxxxxx for xxx Xxxxxxxxxx Xxxxxxxxxxxx Test, Xxxxxxxxxx Xxx. 113, 173-215.

19) Elliott, X. X., Xxxxxx, X. X., Xxxxxxx, C. X., Xxxxxxxxx, X. X., Xxxxxx, X. X., Mackay, X. X., Xxxx, R. X. (1992), Xxxxxxxxxxxx xx Xxxxxxx 1254-Xxxxxxx X9 in: Xx xxxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx 7, 175-177.

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, X., Xxxxxxxx, T. (1976), X Xxxx Substitute xxx Polycholrinated Biphenyls x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Systems, V: Xx vitro Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxx, de Serres, X. X., Xxxxx, X. X., Xxxx, X. R., Xxxxxxx, X. X. (xxx), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. X., Xxxxxx, X. C., XxXxxxx, K. T. (1982), XXX/XXXXX Mutation Xxxxx: Evaluation of Xxxxx xxx Volatile Xxxxxxx, in: Xxxx, X. X., Xxxxx, X. X., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Effects xx Xxxxxxxx Agents, New Xxxx, Xxxxxx, 91-103.

22) Xxxxxx, X. X., Xxxxxx, J. M., Xx, X. P., Xxxxxx, A. L. (1983), Xxxxxxxxxx of xx Exposure Xxxxxx Xxxxx Xxxxx Grown xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environ. Mutagenesis, 5, 795-801.

23) Xxxxxxxxx, X. X., Moore, X. X., Broder, X. B., Burrell, X., Hozier, J. X. (1990), Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxx xx xxx Heterozygous Xxxxxxxxx Kinase Xxxxx xx Xxxxx Lymphoma Xxxxx, Proc. Natl. Xxxx. Xxx. X. X. X, 87, 51-55.

24) Xxxxx, M. X., Xxxxx, X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. T., Xxxxxx, J. (1985), Xxxxxxxx of Trifluorothymidine, Xxxxxxxxx (XXX+) Mutants xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Mutatation Xxx. 151, 161-174.

25) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Genetic Analysis xx Xxxxxxxxx Mutations xx a Xxxxxxxxxxxx Xxxxxxxxx Xxxxx xx Xxxxx Cells, Xxxxxxxxxx Xxx. 229, 89-102.

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

XXXXXXX 4F

"B.23 XXXXXXX XX CHROMOZOMOVÉ XXXXXXX XX XXXXXXXXXXXXXXX SAVCŮ

1. XXXXXX

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

1.1 ÚVOD

Účelem xxxxxxx na xxxxxxxxxxxx xxxxxxx ve xxxxxxxxxxxxxxx xxxxx in xxxx xx xxxxxxxxxxxxx takové xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx chromozomové xxxxxxx xx xxxxxxxxxxxxxxx savců (1, 2, 3, 4, 5). Xxxxxxxxx xx xxx typy xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx x xxxx x tomuto xxxxx xxxxxxx používána. Xxxxxxxxxxxx xxxxxx x xxxxxxx xxxx jsou xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx xxxxxx u člověka.

Touto xxxxxxxx xx xxxxxxxxx xxxxxxxxxxxx xxxxx ve xxxxxxxxxxxxxxx x xxxxxxxxxxx xx tedy, xx xxxx zkouška xxxxxxxx xxxxxxxxx indukce xxxxxxxxx xxxxxx x xxxxxxxxxxxx xxxxxxx.

X xxxx xxxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxxx. Touto xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx detekují chromozomové xxxxxxx při xxxxxx xxxxxxxxxxxxx. Xxxx cílové xxxxx xxxxxx předmětem xxxx zkoušky.

Pro detekci xxxxxxx chromatidového typu xx xxxxxxxxxxxxxxx xx xxxx xxx — xxxxx xxx xxxxx xx ztrátě léze — xxxxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx následuje xx xxxxxxxx. Xxxxx informace x xxxxxxxxxxxx spermatogoniálních xxxxxxxxx xxxxx xxx xxxxxx xxxxxxxxxx chromozomovou xxxxxxxx xxxxxxx chromozomového xxxx x xxxxxxxxx-xxxxxxxx X, xxx xx xxxxxxxxxx xxxxx stávají xxxxxxxxxxxx.

Xxxx xxxxxxx xx xxxx xx navržena xxx xxxxxxxxx, zda xxxx xxxxxxxx xxxxxxxxxxx xxxxx aktivní také x xxxxxxxxxxxx buňkách. Xxxxx xx tato xxxxxxx xx xxxxxxxxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xx vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX.

Xx xxxxxxxxx xx přítomna xxxx xxxxxxxx spermatogonií x xxxxxx xxxxxxxxxx na xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxxxx xxxxxxx tedy xxxxxxxxxxx souhrnnou odpověď xxxxxxxxxx xxxxxxxx spermatogonií x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. X xxxxxxxxxx xx xxx poloze xx xxxxxxxxx, xxxxx xxxx nemusí xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx celkovému krevnímu xxxxx v xxxxxxxx xxxxxxxxx x fyziologické xxxxxxx Sertoliho xxxxx x bariéry mezi xxxxxxx xxxxxx a xxxxxxx.

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

Xxx xxxx xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxxxxxxx xxxxxxx : strukturní xxxxxxxxx xxxxxxxxxx x xxxxxx zlomu xxxxxxxxxxxx xxxxxxxxx nebo xxxxx x opětného xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x podobě xxxxx xxxx xxxxx x xxxxxxx xxxx xxxxxxxxx x xxxxxx xxxxx.

Xxx : achromatická xxxx xxxxx xxx xxxxx xxxxx xxxxxxxxxx a x minimální odchylkou xxxxxxxxx.

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

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx xxxxxxxxxxxxx xxxxx xxxxxxxxx chromozomů při xxxxxxxx xxxxxx xx xxxxxx xxxxxxxx xxx xxxxxxxxxxx, xxxx se xxxx xxxxxx x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 XXXXXXXX XXXXXXXX METODY

Zvířata xxxx xxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxx a xx xxxxxx době xx expozici xxxxxxxx. Xxxx xxxxxxxxx xx xxxxxxxx xxxx xxxxx xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx nebo Xxxxxxxx®). X xxxxxxxxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxxxx xxxxxxxxxx, obarví xx a xxxxxxxxx xx chromozomové xxxxxxx xxxxxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxxxx xxxx xxxxxxxxx samci xxxxxx čínského a xxxx; xxx xxxx xxxxxx samce xxxxxxxxxx xxxxxx xxxxxxxx xxxxx xxxxx. Měly xx xxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx zdravých xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx xxxxxx xx xxxx xxx xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx a xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx hmotnosti.

1.4.1.2 Xxxxxxxx chovu x xxxxxx

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

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx xx xxxxxxxx výběrem rozdělí xx kontrolní xxxxxxx x skupinu, která xx xxxxxxxx. Klece xx měly xxx xxxxxxxxxx tak, xxx xxx xxxx xxxxxx xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx započetím xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před aplikací xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx mohou xxx před xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx by xxxxxx xxx při xxxxxxxxx xxxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx xx xxx xxxxxxxxx podezření, že xxxxxxx se xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx xxxx xxx známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx jejich zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx experimentu xx xxxx být xxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx zkoušené xxxxx xx xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxx zvířata ve xxxxxxxxx, v xxxxx xxxxx k expozici.

Pozitivní xxxxxxxx xx měly xxxxxxxxxx xxxxxxxxxx aberace xx spermatogoniích xx xxxx při expozičních xxxxxxxx, x xxxxx xx xxxxxxxxxxx, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx pozitivní xxxxxxxx by měly xxx xxxxxxx xxx, xxx xxx účinek xxxxxxxx, xxx aby xxx xxxxxx nevyšla xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx látka x xxx byl xxxxx x jejím případě xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxx být navíc xxxxx x úvahu xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx-xx x xxxxxxxxx. Příklady xxxxx xxx xxxxxxxxx xxxxxxxx:

Xxxxx	Xxxxx XXX	Xxxxx xxxxx Einecs
cyklofosfamid	50–18–0	200–015–4
cyklofosfamid 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 každého odběru xx xxx xxx xxxxxxxx xxxxx x xxxxxxx negativní xxxxxxxx, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxx xxxxx podstupuje stejný xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x dosavadních xxxxxxxxxxx xxxxx x dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx. Xxxxx xxxx by xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx dosud kontrolní xxxxx xxxxxxxxxxx, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 POSTUP

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x xxxxxxxxx skupina xxxx zahrnovat alespoň xxx xxxxxxxxxxxxxxxx xxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx měly xxx xxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxxx nadvakrát (xx. při jedné xxxxxxxx nebo dvou xxxxxxxxxx). Xxxxxxxx látky xxxxx být xxxxxxxx xxxx ve xxxx xxxxxxx, xxx. dvě xxxxx x týž xxx x rozmezí xx více xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx xxxxxx xx xxxx xxx xx expozici xxxxxxxxx xxx xxxxxx. Xxxxxxxx xxxxxxxx buněčného cyklu xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, provede xx xxxxx xxxxx xxxxx a xxxxx xxxxxxxx odběr xxxxxxxxx 24 a 48 xxxxx po expozici. X xxxxxxx jiné xxx xxxxxxxx xxxxx xx xxx xxx xxxxx xxxxxxxx po 24 hodin xxxx xx xxxxxx xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx není xxxxx jiná xxxxxxxxx xxxx xxx xxxxxxx xxxxxx (6).

Xxxxx xxxxx xxx odběry xxxxxxxxx xxxx v jiné xxxx. Xxxxxxxxx x xxxxxxx chemických xxxxx, xxxxx xxxxx indukovat xxxxxxxx xxxxxxxxx (xxxxxxx) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxxx odběr (1).

Vhodnost xxxxx xxxxxxxxx xxxxxxxx xxxx xxx xxxxxx xxxxxx xx případu. X případě plánu x opakovanou xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5xxxxxxx xxxxx xxxxx) po poslední xxxxxxxx. Xxxxx potřeby xxxxx xxx xxxxxxxxx xxxxx odběry x xxxx xxxx.

Xxxx xxxxxxxxx xx zvířatům xxxxxxxxxxxxxxxxx xxxx vhodná xxxxx xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Xxxx xx xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. X myši xx tato xxxx xxxxxxxxx 3 — 5 xxxxx; x xxxxxx čínského je xxxx xxxx xxxxxxxxx 4 — 5 xxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx xxxxxxxxxx xxxxx studie xxx zjištění xxxxxxx, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, se xxxxxxx xxxxxx x xxxxxx x za stejného xxxxxx expozice, xxxxx xx použije v xxxxxx xxxxxx (7). X xxxxxxx xxxxxxxx xx xxx první xxxxx xxxxxxx xxx xxxxxx dávky. Xxxx xxxxxx dávky xx xxxx pokrývat rozmezí xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx xxxxxx xxxxx, xxxx xxxx xxxxxxx xxxxx nejvyšší dávka. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx by xxxxx xxxxx xxxxx xxx xxxxxxx režimu xxxxxxxxx xxxxx xxxxxxxxx x letalitě.

Látky se xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. hormony x xxxxxxxx) xxxxxx xxxxxxxxx xxxxxxxxx dávky xxxxxxxxx a xxxx xx xxx xxxxxxxxx xxxxxx od xxxxxxx. Xxxxxxxx xxxxx může xxx xxxx definována xxxx dávka vyvolávající xx xxxxxxxxxxxxxxx některé xxxxxx xxxxxxxx (např. xxxxxxx xxxxx spermatogonií x mitose xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx; xxxx xxxxxxx xx xxxxxx překročit 50 %).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x xxxxxx xxxxxx xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x jednom xxx xxxxxxxxxx žádné xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx na xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx genotoxicita, xxxxxxxxxx se xxxxx xxxxxx xx xxxxx xxxxxxxx xxxxx xx xxxxxxxxx. Očekávaná expozice xxxxxxx xxxx znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx podává xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, jsou-li xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx na xxxxxxxxx testovacího xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 ml/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx xxxxxxx xxxxx, xxxx být xxxxxxxxxx. Xx xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx zkoušeného xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xx xxxxxxx chromozomů

Ihned xx xxxxxxxx xx x xxxxxxx xxxx xxxx xxxxxx získá xxxxxxx xxxxxxxx, xxxxxxxxxxxx xx a fixuje. Xxxx se xxxxxx xx xxxxxxxx xxxxxxx x xxxxxx xx.

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx xxxx být xxxxxxxxxxx xxxxxxx 100 xxxxx x xxxxx xxxxxxxxxxxx xxxxxxxx (tj. xxxxxxxxx 500 xxxxxxxx xx xxxxxxx). Tento xxxxx xxx snížit, xx-xx pozorován xxxxx xxxxx aberací. Všechny xxxxxxxxx xxxxxx preparátů xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, xx měly xxx před xxxxxxxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx při xxxxxx xxxxx dochází xx xxxxxxxxxxxxxx xxxxxx nebo xxxxxx xxxxxxxxxx u xxxxx xxxxxxxx, měly xx vyšetřované buňky xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx xxxxxxx by xxxx xxx xxxxxxxxxx ve xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx každé xxxxx xx xxx být xxxxxxxxxx xxxxx xxxxx xx strukturními chromozomovými xxxxxxxxx x počet xxxxxxxxxxxxxx aberací xx xxxxx. Xxx xxxxxxxxxx x xxxxxxxxx skupiny xx měly xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx počtem x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí se, xxx xxxxxx xx xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx.

Xx-xx pozorována xxxxxx x také xxxxxx, xxx xx xxx pro xxxxxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxx xxxx míra xxxxxxxxxxxx xxxxxxxx u všech xxxxxxxxxxxx xxxxxx x xxxxxx sloužících jako xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx x xxxxx x xxxxx xxxxxxxxx xxxxxxxx, a xx x xxxxxxxx xxxxxx 100 xxxxxxxx xx xxxxx xx xxxxx xxxxx. Pokud xx xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx xx xxxxx xx měl xxx xxxxxxxx xxxxxxxxx index.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx xx xxxxx xxxx jasný xxxxxx xxxxx xxxxx x xxxxxxxxx xxx skupinu x xxxxxxx dávkou x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx měly být xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx s xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x ojedinělých xxxxxxxxx xxxxxxxx soubor xxxxx xxxxxxxx konečný xxxxx x aktivitě zkoušené xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx xxx ohledu xx xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxxxxxxxx aberace xx xxxxxxxxxxxxxxx savců in xxxx znamenají, že xxxxxxxx xxxxx indukuje x xxxxxxxxxxxx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx látka xx xxxxxxxx zkoušky neindukuje x germinálních buňkách xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

Xxxx by xxx xxxxxxxxxxx xxxxxxxxxxxxxxx, s xxxxx xx xxxxxxxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxx xx xxxxxx xxxxx.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Testovací xxxxxxx:

- xxxxxxx druh/kmen,

- počet x xxxxx xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx na xxxxxxx xxxxxxx, včetně xxxxxxx tělesné hmotnosti, xxxxxxx xxxxxxx a xxxxxxxxxx odchylky pro xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- zdůvodnění xxxxxxx xxxxxxxx,

- údaje o xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o podávání xxxxxxxx xxxxx,

- zdůvodnění xxx xxxxxxxx,

- xxxxxxxx xxxxxxxx xxxx koncentrací xxxxxxxx látky x xxxxxx xxxx xxxx (xxx) na odpovídající xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- podrobné xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- identifikace xxxxx xxxxxxxxxxx metafázi, xxxx koncentrace a xxxxx xxxxxxxx,

- metody xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx xxxxx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx na xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- poměr xxxxxxxxxxxxx x xxxxxx xxxxxxxx x první x druhé xxxxxxxx xxxxxx,

- typ x xxxxx aberací xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- xxxxxxx xxxxx xxxxxxx xx skupině,

- xxxxx xxxxx s xxxxxxxxx ve xxxxxxx,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx o xxxxxxxx xxxxxxxxx kontrole,

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

- xxxxx x xxxxxxxx xxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxx, xxxxx xxxx pozorovány.

Rozbor xxxxxxxx.

Xxxxxx.

4. LITERATURA

1) Xxxxx, X. X., (1986), Xxxxxxxxxxx Potential in Xxxxx Xxxxxxxxxxxxx of Xxxxxxxx Xxxxxxxx Related xx xxxxx Xxxx-Xxxxx Xxxxxxxxxxxxxx, xx: Xxxxxxx Xxxxxxxxxx of Environmental Xxxxxxxxx, Part X: Xxxxxxx Xxxxxxx xxx Xxxxxxx Mutagenesis, Xxxxx, X., Xxxxxxx, B., Xxxxxxxxx, X. (xxx) Xxxx, Xxx Xxxx, 477-484.

2) Xxxxx, X. X., (1984), Cytogenetic xxxxx in Xxxxxxx, xx: Mutagenicity Xxxxxxx: x Xxxxxxxxx Approach, (xx.) S. Xxxxxx, X. X. Xxxxx, XXX Press, Xxxxxx, Xxxxxxxxxx XX, 275-306.

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

4) Richold, X., Ashby, J., Xxxxxxxx, X., Xxxxxxxxx, X. G., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxx Xxxxxx, xx: D. X. Xxxxxxxx (ed.), Xxxxx Xxxxxxxxxxxx Tests, UKEMS Xxxxxxxxxxx Procedures. XXXXX Xxxxxxxxxxxx on Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx. Xxxx X xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Port Xxxxxxx, Xxxxxxxxx, Sydney, 115-141.

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

6) Xxxxx, X. D., Xxxxxx X. X., Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, W., Xxxxxxxxxxxx, X., Shibuya, X., Xxxxxx N. (1994), Xxxxxxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Procedures. Xxxxxxx Xxxxxx xx xxx Working Xxxxx xx Xxxxxxxxx Germ Xxxx Xxxxx, Xxxxxxxxxx Xxx., 312, 313-318.

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

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

XXXXXXX 4X

"X.39 XXXXXXX XX NEPLÁNOVANOU XXXXXXX XXX (XXX) X XXXXXXXXX BUŇKÁCH SAVCŮ XX XXXX

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx xxxxxx XXXX TG 486 — Xxxxxxx xx xxxxxxxxxxxx syntézu XXX (XXX) x xxxxxxxxx buňkách savců xx vivo (1997).

1.1 XXXX

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

Xxxx xxxxxxx xx xxxx xxxxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxx chemických xxxxx v játrech. Xxxxxxxxxxx jev xx xxxxxxxxxx xxxxxxxxx XXX x xxxxxxxx reparace x jaterních buňkách. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, kde xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Jsou xxxx xxxxxxx xxxxxx pro xxxxxxxxx xxxx poškození XXX xx xxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, že xx xxxxxxxx xxxxx xxxxxxxxx xx cílové tkáně, xxxx xxxxxx tuto xxxxxxx xxxxxx.

Xxxxxx xxxxxxxxxxx xxxxxxx XXX (UDS) xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx xx xxxxx, které xxxxxxxx plánovanou xxxxxxxx XXX (X-xxxx). Xxxxxxxxxxxxxxx xxxxxxxxx je xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxxxxx thymidinu xxxxxxxxx tritiem (3X-XxX). Xxx xxxxxxx xx XXX xx xxxx xx xxxxxxxxxx používají xxxxx potkana. Xxxx xxxxx xxx xxxxx xxxxx xxx xxxxxx xxxxxxx, xxxxxx xxxx xxxxxxxxx této xxxxxx.

Xxxxxxx xxxxxxxx XXX xxxxxx xx xxxxx xxxx XXX vyštěpených x xxxxxxxxxxx x místě xxxxxxxxx. Xxxxxxx na XXX je tedy xxxxxx zvláště xxx xxxxxxx dlouhých reparací ("xxxx-xxxxx xxxxxx") (20 xx 30 bází) xxxxxxxxxxxx xxxxxx. Xxxxxx xxxxxx ("short-patch repair") (xxxxx xx tři xxxx) xxxx xxxxxxx xxxx xxxxxxxxxx s xxxxxx menší xxxxxxxxxx. Xxxxx xxxx xxxxxxxxx xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx xxxx xxxxxx xxxxxxxxx xxxx XXX xxxxx k mutagenním xxxxxxxxx. Xxxxxx odpovědi XXX xxxxxxxxxxx xxxxxx xxxxxxxxx x věrnosti xxxxxxxxxxx procesů. Xxxxx xx možné, že xxxxxxx reaguje x XXX, xxx xxxxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxxxxxx informací, xxxxx xxxx xxxxxxx poskytuje x mutagenní xxxxxxxx, xx vyvážen potenciální xxxxxxxxxx xxxxxx xxxx, xxxxx je xxxxxxxxxx x xxxxx xxxxxx.

Xxx xxxx xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

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

Čistý počet xxx odpovídajících xxxxxxxx xxxxxx (XXX) : xxxxxxxxxxxxx míra XXX xxxxxxxx xxxxx v xxxxxxxxxxxxxxxxx zkoušce na XXX, vypočtená xxxxxxxxx xxxxxxxxxx xxxxx xxx x cytoplasmatických oblastech (XX) xxxxxxxxxxxxxx xxxxxx xx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): XXX = XX — XX. Xxxxxxx XXX xx xxxxxxx xxx xxxxxxxxxx xxxxx, xxxx xxxxxxxx xxx xxxxx x xxxxxxx, x xxxxxxxxxxx xxxxxxxxx atd.

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

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxxxx na XXX x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxx syntézu xxxxxxxx XXX po vyštěpení x xxxxxxxxxx xxxxx XXX xxxxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx činiteli. Xxxxxxx xx obvykle xxxxxxxx xx inkorporaci 3X-XxX xx XXX xxxxxxxxx xxxxx, xxx xx xxxx xxxxxxx xxxxx x X-xxxx xxxxxxxxx xxxxx. Inkorporace 3X-XxX xx obvykle stanoveno xxxxxxxxxxxxxxx, xxxxxxx tato xxxxxxxx xxxx xxx xxxxxxx xx xxxx X-xxxx xxxxx xxxx xxxx. kapalná xxxxxxxxxxx xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, ačkoli xxx xxxxxx xxxxxxxx vhodný xxxx savce. Xxxx xx xxx xxxxxxx xxxxx používané xxxxxxxxxxx xxxxx mladých xxxxxxxx xxxxxxxx dospělých xxxxxx. X xxxxxxxx zahájení xxxxxx by xxxx xxx odchylka x xxxxxxxxx zvířat xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx xxx obě xxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx k xxxxx X, xxxxxxx by xxxx být dosaženo xxxxxxxx vzduchu 50 - 60 %.

1.4.1.3 Xxxxxxxx zvířat

Zdravá pohlavně xxxxxxx zvířata xx xxxxxxxx xxxxxxx xxxxxxx xx kontrolní skupinu x xxxxxxx, xxxxx xx exponuje. Xxxxx xx xxxx být xxxxxxxxxx tak, aby xxx xxxx xxxxxx xxxxxx minimalizován. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx x xxxx xxxxxxxxx xxxxxx se xxxxxxx x laboratorních xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx xx xxxxxxxx rozpouštědlech xxxx vehikulech x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx xxxx xxxxx být xxxx podáním xxxxxxx. Xxxx xx být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx chemické xxxxx, xxxxx xxxxx o xxxxxxxx neprokazují možnost xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx nemělo xxx při xxxxxxxxx xxxxxxxx dávek xxxxxxx xxxxxx x xxxx xx být xxxxxxxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by být xxxxxx xxxxxxxx xxxxxxxxx xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx se xxxxxxxx zvážit použití xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každé xxxxxxxxx xxxxxxxxx části xxxxxxxxxxx by xxxx xxx xxxxxxxx pozitivní x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx měla xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxx xxxxxx jako xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x xxxxxxxx.

Xxxxxxxxxxx kontrolami xx xxxx xxx xxxxx, x xxxxx xx xxxxx, že xxxxxx podávání x xxxxxxxxxxx expozičních xxxxxxxxxxxxx xxxx x nárůstu XXX xxxxxxxxxxxxxxx xxx xxxxxxx. Pozitivní xxxxxxxx xxxxxxxxxx xxxxxxxxxxxx aktivaci xx měly xxx xxxxxxx v xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Xxxxx xxxxx xxx xxxxxxx xxx, xxx xxx účinek xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Příklady xxxxx xxx pozitivní xxxxxxxx:

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

Xxxxx xxx použity také xxxx xxxxx xxx xxxxxxxxx xxxxxxxx. Xx xxxxxxxxx, aby xxxx xxxxxxxxx xxxxxxxxx látka xxxxxxxx jiným xxxxxxxx, xxx xxxxxxxx xxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxx by xxx xxxxxx xxxxxxxxxx xxxxx zvířat, xxx xxxx xxxxxxxxxx přirozené xxxxxxxxxx xxxxxxxx xxxxxxxx xx xxxxxxx. Každá xxxxxxx by xx xxxx xxxxxxx xxxxxxx xx xxx xxxxxxxxxxxxxxxx xxxxxx. Xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxxxx dosavadní xxxxx, xx xxx xxxxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxx xx xxx zvířata.

Jestliže xxxx x xxxx xxxxxx x dispozici údaje xx xxxxxx xx xxxxxxx xxxxxx x xx použití xxxxxxxx xxxxxxx xxxxxxxx, xxx xxxxxxxxx, xx xxxxxxxxxx xxxx pohlavími rozdíl x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, xxxxxxx samců. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx u xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by xxx xxxxxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx.

1.5.3 Dávkování

Za xxxxxxxxxx xxxxxxxx xx používají xxxxxxx dvě úrovně xxxxx. Xxxxxxxx xxxxx xx definována jako xxxxx xxxxxxxxxxxx xxxxxx xxxxxx toxicity, že xxxxx xxxxx xx xxxxx xxxxx xxxxxxxxx xxx xxxxxxx režimu xxxxxxxxx k xxxxxxxx. Xxxxx xxxxx by xxxx xxx zpravidla 50 % xx 25 % vyšší xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx netoxických xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) xxxxxx kritériím xxxxxxxxx dávky xxxxxxxxx x xxxx xx xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxx-xx xx xxxxx neexistenci xxxxxxxx dostupných xxxxx xxxxxx pro zjištění xxxxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx laboratoři, xx xxxxxxx xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx režimu xxxxxxxx, xxx xx xxxxxxx x hlavní studii.

Nejvyšší xxxxx xxxx být xxxxxxxxxx xxxx xxxx xxxxx vyvolávající xxxxxx xxxxxxxx v játrech (xxxx. xxxxxxxxxx jádra).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx zkouška x xxxxxx xxxxxx x xxxxxxx 2000 xx/xx tělesné xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx xxxxxxx x jednom dni xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x xxxx-xx xx xxxxxxx xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, očekávána genotoxicita, xxxxxx xxx xxxxx xxxxxx xxxxxxxx. Očekávaná xxxxxxxx člověka xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx dávky.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx. Jiné způsoby xxxxxxxx xxxx xxxxx, xxx-xx xx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx xxxxxxxxxxxx, xxxxx xx xxxxx mohla xxx exponována xxxxxxxx xxxxx xxxxx x xxxxxx xxxxxxxxxxxxxxx oběhového xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který může xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx by xxxxx xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx je xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech úrovních xxxxx.

1.5.6 Příprava xxxxxxxxx xxxxx

Xxxxxxx xxxxx se xxxxxxxxxx x xxxxxxxxxxxx xxxxxx xxxxxxxxx 12 xx 16 xxxxx xx podání xxxxx. Xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx (xxxxxx xxx xx čtyři hodiny xx xxxxxxxx) je xxxxxxxx, není-li xx 12 xx 16 xxxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xxxxx xxxx xxx použity xxxx xxxx odběru, xxxx-xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxxxxxxxx xxxxx.

Xxxxxxxxxx kultury xxxxxxxxx buněk xxxxx xx zpravidla xxxxxxxxx xxxxxxx xxxxx kolagenasou xx situ x xxxxxx se, xxx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx xxxxxxx xxxxxxx. Xxxxxxx xxxxx z xxxxxxxxx kontroly xx xxxx xxxxxxxxx xxxxxxxxxxxxxxx (5) alespoň 50 %.

1.5.7 Stanovení UDS

Čerstvě xxxxxxxxx jaterní buňky xxxxx xx obvykle xxxxxxx xxxx, např. xxx xx xxx xxxxx, xxxxxxxx x xxxxxx xxxxxxxxxxx 3H-TdR. Xx konci inkubační xxxx xx xxxx xxx xxxxxx z xxxxx odstraněno a xxxxx poté xxxxx xxx xxxxxxxxxx x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, aby xxxx xxxxxxx neinkorporovaná xxxxxxxxxxxxx ("cold xxxxx"). Xxxxx se xxxx xxxxxxx, xxxxxx x xxxxxx. Xxx xxxxx xxxxxxxxx xxxx nemusí xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx se xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, xxxxxxxx xx x xxxxx (xxxx. x chladu 7 xx 14 xxx), xxxxxxxx xx, xxxxxx x spočítají xx xxxxxxxxxx xxxx xxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxxx xxx xx xxx preparáty.

1.5.8 Xxxxxxx

Xxxxxxxxx xx xxxx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxx normálních xxxxx, xxx xxxx hodnocení XXX výpovědní xxxxxxx. Xxxxxxxxx xx xxx xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxxxxx xxxxxxxxxxxx (xxxx. na xxxxxxx, xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx).

Xxxx xxxxxxxxx xxx xx měly xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx xx vyšetřuje 100 xxxxx na xxxxx xxxxx alespoň xx dvou xxxxxxxxx; xxxxxxxxx xxxx xxx 100 xxxxx/xxxxx xx xxxx být xxxxxxxxxx. Xxx xxxxxxxx xxx xx xxxxx v X-xxxx nevyšetřují, xxx xxxxx xxxxx x X-xxxx xxxx být xxxxxxxxxx.

Xxxxxxxx 3H-TdR xxxxxxxxxxxxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx doložené xxxxxxxxxxx xxx xxxxxxx xx xxxx být stanoveno xxxxxxx xxxxxxx.

Xxxxx xxxxx xx xxxxxxx x xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxŭx (ng) x z xxŭxxxxxxx xxxxx zrn v xxxxxxxxxxxxxxxxx oblastech (xx) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx xx xx xxxxxxx buď xxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx xxxxxx cytoplasmy, xxxx xxŭxxxxx hodnota xxxx xx xxx xxxxxxx vybraných xxxxxxx x blízkosti dotyčných xxxxxxxxx xxxxx. xx xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx xxxxxxx i xxxx xxxxxxx xxxxxxxxx xxxxx xxxxx (xxxx. xxxxxxxx xxxxxx xxxxx) (6).

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxx by být xxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx x xxxxxxx. Xxxxx by xxxx xxx xxxx xxxxxxx xx formě xxxxxxx. Xxxxxxxxx xxxxxxx XX xx xxxxxxx XX xx xxx xxx vypočten pro xxxxxx xxxxx, pro xxxxx zvíře x xxx xxxxxx dávku x čas xxxxx xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrům (NNG). Xxxxxxxx xxxx počítány "xxxxxxxxxx" buňky, xxxx xx xxx xxxxxxxx xxx xxxxxxxxxx "xxxxxxxxxxxx" xxxxx xxxxxxxxxx x xxxxxxxx xx xxxxxxxxxxx xxxx xxxxxxxxxx údajích x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxxx-xx xxx xxxxxxx, xxxx xx xxx statistické xxxxx xxxxxxx x odůvodněny xxxx xxxxxxxxxx xxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxxx xxxxxxxx kritérií xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx	x)	xxxxxxx XXX leží xxx xxxxxxxx xxxxxx, xxxxx xx xxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxx;
xxxx	xx)	xxxxxxx XXX xx xxxxxxxx xxxxx xxx xxxxxxx xxx souběžnou xxxxxxxx;
xxxxxxxxx	x)	xxxxxxx NNG xxxx xx xxxxxxxxx xxxxxxx xxxxxxx xxxx xxx xx;
xxxx	xx)	xxxxxxx XXX xxxx xxxxxxxx vyšší než xxxxxxx xxx xxxxxxxxx xxxxxxxx.

Xxxx xx být xxxxxxxxx xxxxxxxxxx relevance xxxxx, xx. xxxx xx xxx xxxxx x xxxxx xxxxxxxxx, xxxx xxxx xxxxxxxxxxx xxxxxx, xxxxx dávky x odpovědi x xxxxxxxxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx prostředek xxxxxxxxxxx xxxxxx. Statistická xxxxxxxxxx xx však xxxxxx xxx jediným určujícím xxxxxxxx pro pozitivní xxxxxxx.

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých případech xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx xxxxx x aktivitě xxxxxxxx xxxxx. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx xxxx xxxxxx bez xxxxxx xx xx, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx XXX v jaterních xxxxxxx xxxxx xx xxxx xxxxxxxxx, že xxxxxxxx látka indukuje x jaterních buňkách xxxxx xx xxxx xxxxxxxxx XXX, které xxx opravit xxxxxxxxxxxx xxxxxxxx XXX xx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx podmínek xxxxxxx xxxxxxxxxx poškození XXX, xxxxx xxx xxxxxxxxx xxxxx xxxxxxxx.

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

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x xxxxxxx xxxx obsahovat xxxx informace:

Rozpouštědlo/vehikulum:

- zdůvodnění xxxxx vehikula,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x pohlaví xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, střední xxxxxxx x směrodatné xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- xxxxx xx xxxxxx xxx zjištění rozsahu, xxxxx byla xxxxxxxxx,

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx x podávání xxxxxxxx látky,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx xxxxxxx, zda xx zkoušená xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx xx xxxxxx xxxxx,

- případně xxxxxxxx xxxx koncentrací xxxxxxxx xxxxx v xxxxxx xxxx vodě (xxx) xx odpovídající xxxxx (mg/kg xxxxxxx xxxxxxxxx/xxx),

- podrobné xxxxx x xxxxxxx krmiva x xxxx,

- xxxxxxxx xxxxx xxxxxxx xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx a kultivace xxxxxxxxx buněk,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

- xxxxx xxxxxxxxx x xxxxx xxxxxxxxxxx xxxxx,

- xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxxx xxxxxxx xxxxx xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx x xxxxx xxx xxxxxxxxxxxxxx cytoplasmě, x xxxxx počet xxx, jednotlivě xxx xxxxxxxxx, xxxxxxx x xxxxxxx,

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxxxxx,

- xxxxxx toxicity,

- xxxxx o souběžné xxxxxxxxx (rozpouštědlo/vehikulum) x xxxxxxxxx xxxxxxxx,

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

- počet xxxxx "opravovaných" xxxxx, xx-xx xxxxxxxx,

- xxxxx xxxxx v S-fázi, xx-xx xxxxxxxx,

- životaschopnost xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. Lefevre, X. A., Burlinson, X., Xxxxxx, X. X. (1985), An Xxxxxxxxxx xx xxx Xx xxxx Xxx. Xxxxxxxxxx XXX Xxxxxx Xxxxx, Xxxxxxxxxx Res., 156, 1-18.

2) Xxxxxxxxxxx, X. E., Xxxxx, X., Bermudez, X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X., Xxxxxxxx, X. (1987), X Xxxxxxxx xxx Xxxxx xxx xxx Xx xxxx Xxx Xxxxxxxxxx DNA Repair Xxxxx, Xxxxxxxxxx Res., 189, 123-133.

3) Kennelly, X. X., Xxxxxx, X., Ashby, J., Xxxxxxx, P. X., Xxxxxxxxx, X., Benford, X. J., Xxxx, X. X., Xxxxxxxx, X. xx X. (1993), Xx xxxx Xxx Xxxxx XXX Xxxxx, xx: Kirkland X. X., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Xxxxx: XXXX Xxxxxxxxxxx Xxxxxxxxxx. UKEMS Xxxxxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx. Xxxxxx. Part XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Xxxx, X. X., Xxxxxx, X., Xxxxxxxxx. X., Xxxxxxxxx, B., Xxxxxxxxx, X. X., Xxxxxxxx, X., Hertner, X., XxXxxxx, X. X., Xxxx, X. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx XXX Xxxxx Xx xxxxx xxx Xx vivo, Xxxxx. Xxx., 312, 263-285.

5) Fautz, X., Xxxxxxx, X., Xxxxxxxxxx, X., Hechenberger-Freudl, X. (1993), Xxxxxxxxxx xx xxx Relation Xxxxxxx xxx Initial Xxxxxxxxx xxx xxx Xxxxxxxxxx xx Xxxxxxx Isolated Xxx Xxxxxxxxxxx Used xxx xxx In xxxx/Xx xxxxx DNA Xxxxxx Assay (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

6) Mirsalis, J. X., Tyson, X. X., Xxxxxxxxxxx, X. X. (1982), Xxxxxxxxx xx Xxxxxxxxx Xxxxxxxxxxx xx the In xxxx/Xx xxxxx Hepalocyte XXX Xxxxxx Xxxxx, Xxxxxxx.Xxxxxxx. 4, 553-562."

XXXXXXX 5

XXXXXX XXXXXXXXX XX KLASIFIKACI X XXXXXXXXXX XXXXXXXXXXXX XXXXX X PŘÍPRAVKŮ

Viz směrnice Xxxxxx 2001/59/XX, Xx. xxxx. X 332, 28. 12. 2000, x. 81.

PŘÍLOHA 6

"

PŘÍLOHA XX

XXXX X

xxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx ustanovení xx. 22 xxxx. 1 písm. x) xxxx xxxxxxxx, xxxx xxx obaly x xxxxxxxxx xxxxxx xxxxxxxxxx xxxxx, x xxxxx xx xxxxxxx riziko xxx xxxxxxxxxx (Xx; X 65) x xxxxx xxxx xxxxxxxxxxxxx x označeny xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x xxxxxxxx xxxxx xxxxxxxxx na xxx xx formě xxxxxxxx xxxx v nádobách xxxxxxxxxx xxxxxxxxxxx rozprašovačem, xxxxxxxx xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx xxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx obalech xxxx xxxxxxxx požadavky xxxxx XXX 8317 (xxxxxx xx xxx 1. xxxxxxxx 1989) "Xxxxx odolné dětem — Xxxxxxxxx xx xxxxxxxxx uzavíratelné xxxxx x metody xxxxxx xxxxxxxx" xxxxxxxx Xxxxxxxxxxx xxxxxxxxxx xxx normalizaci (XXX).

2. Xxxxxxxxx xxxxxxxxxxxxxx xxxxx

Xxxxxxx xxxxxx xxxxx xxxxxxxx xxxxx xxxxxxx xx opakovaně xxxxxxxxxxxxxxxx xxxxxxx xxxx splňovat xxxxxxxxx xxxxx XXX XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Obaly xxxxxx dětem — Xxxxxxxxx x zkušební xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx obaly jiných xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Evropským výborem xxx xxxxxxxxxxx (XXX).

3. Xxxxxxxx

1. Prokázání shody x výše xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxx xxxxxxxxxx, xxxxx xxxxxxx evropské xxxxx xxxx EN 45000.

2. Xxxxxxxxxx xxxxxxx

Xx-xx xxxxxx, xx obal je xxxxxxxxxx xxxxxxxx pro xxxx, xxxxx se xxxxxxx xxxxxx k xxxxxx xxx xxxxxx xxxxxxxx, xxxxxx xxx xxxxxxx provedena.

Ve xxxxx xxxxxxxxx xxxxxxxxx x xxxxx existují oprávněné xxxxxx x xxxxxxxx x xxxxxxxxxxx xxxxxxx xxx dítě, může xxxxxxxxxxxx orgán xxxxxxxxx, xxx xxxxx xxxxxxxxx xx uvedení výrobku xx xxx předložila xxxxxxxxxx vydaný laboratoří xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx xxxxxx, xx xxx xxxx xxxxxxxx xxxxxxx xxxxx xxxx uvedených norem XXX a XXX,

xxxx

- xx xxxxxx xxx xxxxxxx x byl xxxxxxx vyhovujícím podle xxxx uvedených norem.

ČÁST X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx výstrah

Technické specifikace xxx xxxxxxxxxx výstrahy xxxx xxx x xxxxxxx s xxxxxx XX XXX 11683 (xxxxxx x xxxx 1997) "Xxxxx — Xxxxxxxxxx výstrahy xxxx xxxxxxxxxx — Xxxxxxxxx".

"

Plné znění - 32000L0032

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

Plné znění - 32000L0032

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

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