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Xxxxxxxx Komise 2000/32/XX

xx xxx 19. xxxxxx 2000,

xxxxxx se po xxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxxxxx pokroku xxxxxxxx Xxxx 67/548/XXX o xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx xxxxxxxxxxxx xxxxx [1]

(Xxxx s xxxxxxxx pro XXX)

XXXXXX XXXXXXXXXX XXXXXXXXXXXX,

x xxxxxxx xx Xxxxxxx x xxxxxxxx Evropského xxxxxxxxxxxx,

x xxxxxxx na xxxxxxxx Xxxx 67/548/XXX xx xxx 27. xxxxxx 1967 x xxxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx xx xxxxxxxxxxx, balení x xxxxxxxxxx xxxxxxxxxxxx xxxxx [2], naposledy pozměněnou xxxxxxxx Xxxxxxxxxx parlamentu x Rady 1999/33/XX [3], x xxxxxxx xx xxxxxx 28 xxxxxxx xxxxxxxx,

xxxxxxxx k xxxxx xxxxxxx:

(1) Xxxxxxx X směrnice 67/548/EHS xxxxxxxx seznam xxxxxxxxxxxx xxxxx xxxxxxxx s xxxxxxxxxx xxxxx x xxxxxxxxxxx a označování xxxxx látky. Současné xxxxxxx x technické xxxxxxxx xxxxxxx, xx xx xxx xxx xxxxxx nebezpečných xxxxx x xxxxxxx xxxxxxx xxxxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx vyžadují xxxxxx xxxxxxxx xxxxxx xxxxxxxxx x xxxxxxx X v příloze X.

(2) Příloha III xxxxxxxx 67/548/XXX obsahuje xxxxxx xxx xxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxxxxxxx s xxxxxxxxxxxx xxxxxxx a xxxxxxxxx. Xxxxxxx XX směrnice 67/548/XXX xxxxxxxx xxxxxx xxx x xxxxxxxxxxxxxx xxxxxx xxxxxxxxxx xx xxxxxxxxxxxx látek x xxxxxxxxx. Xxxxxxx VI xxxxxxxx 67/548/XXX xxxxxxxx xxxxx ke klasifikaci x x xxxxxxxxxx xxxxxxxxxxxx xxxxx x xxxxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxxxxx xxxxxx xxxxxxxx xxxxxx xxxxxx XXX, IV x VI.

(3) V xxxxxxx V xxxxxxxx 67/548/XXX se xxxxxxx xxxxxx xxx xxxxxxxxx xxxxxxxxx-xxxxxxxxxx xxxxxxxxxx, xxxxxxxx x ekotoxicity látek x přípravků. Xx xxxxxxxx xxxxxxxxxxx xxxx xxxxxxx xxxxxxxxxxx xxxxxxx.

(4) Xxxxxxx XX xxxxxxxx 67/548/XXX obsahuje předpisy xxxxxxxx se xxxxxxx xxxxxxxx proti xxxxxxxx xxxxx. Tyto xxxxxxxx xx měly xxx xxxxxxxxxxxx x xxxxxxxxxxxxx. Xx xxxxxxxx rozšířit xxxxxx, xxx xx xxxxxxx odolné xxxxx xxxxxxxx xxxxx xxxxxxxxx.

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

XXXXXXX XXXX XXXXXXXX:

Xxxxxx 1

Směrnice 67/548/EHS xx xxxx xxxxx:

1. Xxxxxxx I se xxxx xxxxx:

x) odpovídající xxxxxxxx x předmluvě xx nahrazuje xxxxxxxxx X x xxxxxxx 1X xxxx směrnice;

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

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

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

2. Xxxxxxxxxxxx xxxx x xxxxxxx III xx xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx x příloze 2 této xxxxxxxx.

3. Xxxxxxx XX xx xxxx xxxxx:

x) xxxxxxxxxxxx xxxxxx x xxxxxxx XX xx xxxxxxxxx xxxxxxxxxxxx pokyny pro xxxxxxxx zacházení x xxxxxxx 3X xxxx xxxxxxxx;

x) xxxxxxxxxxxx xxxxxx x příloze XX xx nahrazují xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxx xxx xxxxxxxx zacházení x xxxxxxx 3X xxxx xxxxxxxx.

4. Xxxx B xxxxxxx X xx xxxx xxxxx:

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

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

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

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

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

f) xxxxxxxx X.23 se xxxxxxxxx xxxxxx v xxxxxxx 4F této xxxxxxxx. Xxxxx kapitoly X.23 xx xxxxxxxxxxx xx mění odpovídajícím xxxxxxxx;

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

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

6. Xxxxxxxxxxxx xxxxx v příloze XX se xxxxxxxxx xxxxx x příloze 5 xxxx xxxxxxxx.

7. Xxxxxxx XX se xxxx způsobem uvedeným x příloze 6 xxxx xxxxxxxx.

Článek 2

1. Xxxxxxx xxxxx xxxxxx v xxxxxxxx právní x xxxxxxx xxxxxxxx nezbytné xxx dosažení souladu x touto xxxxxxxx xxxxxxxxxx do 1. xxxxxx 2001. Neprodleně x nich xxxxxxx Xxxxxx.

Xxxx xxxxxxxx xxxxxxx xxxxxxxxx státy musí xxxxxxxxx xxxxx xx xxxx xxxxxxxx nebo xxxx xxxxxx xxxxx xxx xxxxxx xxx xxxxxx úředním xxxxxxxxx. Xxxxxx xxxxxx xx xxxxxxx xxxxxxx xxxxx.

2. Xxxxxxx xxxxx xxxxx Xxxxxx xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxx xxxxxxxx, které xxxxxxx x xxxxxxx působnosti xxxx směrnice, x xxxxxxxxxx xxxxxxx mezi xxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxxxxx.

Článek 3

Tato směrnice xxxxxxxx x xxxxxxxx xxxxxx xxxx xx xxxxxxxxx x Úředním xxxxxxxx Xxxxxxxxxx společenství.

Xxxxxx 4

Tato směrnice xx určena členským xxxxxx.

X Xxxxxxx xxx 19. května 2000.

Xx Xxxxxx

Xxxxxx Xxxxxxxöx

xxxxxx Komise

[1] Přijato po xxxxxxxxxxxx po xxxxxxx xxxxx.

[2] Xx. věst. 196, 16.8.1967, x. 1.

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

PŘÍLOHA 1X

XXXXXXXXX K XXXXXXX X

Xxxxxxxxxx xxxxxxxx xxxxxxxxxx xx identifikace, xxxxxxxxxxx x xxxxxxxxxx xxxxx

(Xxxxxx xx xxxxxxx xxxxx)

XXXXXXX 1B

"TABULKA X

X

Xxxxxx

XX

18

Xx

Xxxxx

Αργό

Xxxxx

64

Xx

Xxxxxxxxx

Xxxxxxxxxx

Γαδολίνιο

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx

Xxxxxxxxx

Xxxxxxxxxx"

PŘÍLOHA 1X

Xxxxxxxx xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx x xxxxxx	Xxxxx XX	Xxxxx XXX	Xxxxxxxxxxx	Xxxxxxxx	Xxxxxxxxxxxx xxxxxx	Xxxxxxxx x přípravkům
006–011–00–7	karbaryl (XXX) 1-xxxxxx-X-xxxxxxxxxxxxxx		200–555–0	63–25–2	Xxxx. xxx. 3; X40 Xx; X22 X; R50	Xn; X X: 22–40–50 X: (2-)22–24–36/37–46–61
006–013–00–8	xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxxxxxxxxxxxxx		205–293–0	137–42–8	Xx; X22 X31 X; X34 R43 X; X50–53	X; N X: 22–31–34–43–50/53 X: (1/2-)26–36/37/39–45–60–61
006–015–00–9	xxxxxx (XXX) 3-(3,4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx	206–354–4	330–54–1	Xxxx. xxx. 3; R40 Xxxx. xxx. 3; X40 Xx; X22–48/22 N; X50–53		Xx; N X: 22–40–48/22–50/53 X: (2-)13–22–23–37–46–60–61
006–016–00–4	propoxur (XXX) 2- isopropoxyfenyl-N-methylkarbamát		204–043–8	114–26–1	T; X25 X; R50–53	T; X X: 25–50/53 X: (1/2-)37–45–60–61
006–017–00-X	xxxxxxxx (XXX) 2-xxxxxx-2-(xxxxxxxxxxxxxx)xxxxxxxx-X-(X-xxxxxxxxxxxxxxx)xxxx		204–123–2	116–06–3	X+; X26/28 X; X24 X; X50–53	X+; X R: 24–26/28–50/53 X: (1/2-)22–36/37–45–60–61
006–018–00–5	xxxxxxxxx (ISO) 4-(xxxxxxxxxxxxx)-3-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		217–990–7	2032–59–9	X; R24/25 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; X40 Xn; X22 N; X50–53	Xx; X X: 22–40–50/53 X: (2-)25–36/37–60–61
006–020–00–6	barban (XXX) 4-xxxxxxxx-2-xx-1-xx-X -(3-xxxxxxxxxx)xxxxxxxx		202–930–4	101–27–9	Xx; X22 X43 X; R50–53	Xn; 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 -xxxxxxxxxxxxxx		217–991–2	2032–65–7	X; X25 X; X50–53	X; X X: 25–50/53 X: (1/2-)22–37–45–60–61
006–024–00–8	xxxxxx-xxxxxxx (XXX) xxxxxxx-X-xxxxxxxxx-xxxxxxxxxxxxxx		205–443–5	140–93–2	Xx; X22 Xx; X38 X; X51–53	Xx; X X: 22–38–51/53 X: (2-)13-61
006–026–00–9	xxxxxxxxxx (ISO) 2,2-xxxxxxxx-2,3-xxxxxxx-1-xxxxxxxxxx-7-xx-X-xxxxxxxxxxxxxx		216–353–0	1563–66–2	X+; X26/28 X; X50–53	X+; X X: 26/28–50/53 X: (1/2-)36/37–45–60–61
006–028–00-X	dinobuton (XXX) 2-(1-xxxxxxxxxxxx)-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx 2-xxx-xxxxx-4,6-xxxxxxxxxxxx-xxxxxxxxx-xxxxxxxx		213–546–1	973–21–7	X; X25 N; X50–53	X; X X: 25–50/53 X: (1/2-)37–45–60–61
006–029–00–5	dioxakarb (ISO) 2-(1,3-xxxxxxxx-2-xx)xxxxx-X-xxxxxxxxxxxxxx		230–253–4	6988–21–2	X; R25 X; X51–53	X; X X: 25–51/53 X: (1/2-)37–45–61
006–033–00–7	metoxuron (XXX) 3-(3-xxxxx-4-xxxxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx		243–433–2	19937–59–8	X; X50–53	X X: 5 0/ 5 3 X: 60-61
006–034–00–2	xxxxxxx (XXX) X-xxxxxx-X-xxxxx-X-xxxxxxxxxxxxxxxxx		214–215–4	1114–71–2	Xx; X22 N; X51–53	Xx; X X: 22–51/53 X: (2-)23-61
006–035–00–8	xxxxxxxxxx (XXX) 2-(xxxxxxxxxxxxx)- 5,6-xxxxxxxx xxxxxxxxx-4-xx-X,X-xxxxxxxxxxxxxxxx		245–430–1	23103–98–2	X; X25 X; R50–53	T; X X: 25–50/53 X: (1/2)22–37–45–60–61
006–037–00–9	promekarb (XXX) 3-xxxxxxxxx-5-xxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–113–0	2631–37–0	X; X25 X; X50–53	X; X R: 25–50/53 X: (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; X45 Xn; X22 X; X50–53	X; X X: 45–22–50/53 X: 53–45–60–61
006–039–00-X	xxx-xxxxx (XXX) X-(2,3,3-xxxxxxxxxxxxx)-X,X-xxxxxxxxxxxxxxxxxxxxxxx		218–962–7	2303–17–5	Xx; R22–48/22 R43 X; R50–53	Xn; N X: 22–43–48/22–50/53 X: (2-)24–37–60–61
006–042–00–6	xxxxxxx (ISO) 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxxx		205–766–1	150–68–5	Xxxx. 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	xxxxxxx-XXX 3-(4-xxxxxxxxxx)-1,1-xxxxxxxxxxxxxxx-xxxxxxxxxxxxxx		—	140–41–0	Xx; X36/38 Xxxx. xxx. 3; R40 X; X50–53	Xx; N X: 36/38–40–50/53 X: (2-)36/37–60–61
006–045–00–2	xxxxxxxx (XXX) xxxxxx-X-[(X-xxxxxxxxxxxxxxx)xxx]xxxxxxxxxxxxxx		240–815–0	16752–77–5	X+; X28 X; X50–53	X+; X X: 28–50/53 X: (1/2-)22–36/37–45–60–61
006–046–00–8	bendiokarb (XXX) 2,2-xxxxxxxx-1,3-xxxxxxxxxxx-4-xx-X-xxxxxxxxxxxxxx		245–216–8	22781–23–3	X; X23/25 Xx; X21 X; R50–53	T; X X: 21–23/25–50/53 X: (1/2-)22–36/37–45–60–61
006–047–00–3	xxxxxxxxx (XXX) xxxx: 3-(1-methylbutyl)fenyl-N-methylkarbamátu a 3-(1-xxxxxxxxxxx)xxxxx-X-xxxxxxxxxxxxxxx		—	8065–36–9	X; X24/25 X; X50–53	X; X R: 24/25–50/53 X: (1/2-)28–36/37–45–60–61
006–048–00–9	xxxxxxxxxxxx (XXX) 2-[(xxxxxxxxxxxxx)xxxxxx]xxxxx-X-xxxxxxxxxxxxxx		249–981–9	29973–13–5	Xx; X22 X; R50–53	Xn; X X: 22–50/53 X: (2-)60-61
006–050–00–X	xxxxxxx-XXX 3-fenyl-1,1-dimethyluronium-trichloracetát		—	4482–55–7	Xi; X38 X; X50–53	Xx; N X: 38–50/53 X: (2-)60-61
006–053–00–6	xxxxxxxxxx (XXX) 2-xxxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		220–114–6	2631–40–5	Xx; X22 X; X50–53	Xx; X X: 22–50/53 X: (2-)60-61
006–054–00–1	xxxxxxxxxx (ISO) 4-(xxxxxxxxxxxxx)-3,5-xxxxxxxxxxxxx-X-xxxxxxxxxxxxxx		206–249–3	315–18–4	X+; R28 Xx; X21 X; X50–53	X+; X X: 21–28–50/53 X: (1/2-)36/37–45–60–61
006–057–00–8	xxxxxxxxxx (XXX) 2-xxxxx-6-(xxxxxxxxxxxxxx)xxxxxxx		217–682–2	1929–82–4	Xx; X22 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 R:22–52/53 X: (2-)61
006–069–00–3	xxxxxxxxx-xxxxxx (XXX) 1,2-xx[3-(xxxxxxxxxxxxxxx)xxxxxxxxxx]xxxxxx		245–740–7	23564–05–8	Xxxx. xxx. 3; X40 X; X50–53	Xx; N X: 40–50/53 S: (2-)36/37–60–61
006–070–00–9	xxxxxxxxxxx X-xxxxxxxxxx-X-xxxxxxx-2,5-xxxxxxxx-3-xxxxxxx		262–302–0	60568–05–0	Xxxx. xxx. 3; R40 N; X50–53	Xx; N R: 40–50/53 X: (2-)36/37–60–61
006–088–00–7	xxxxxxxxxxx (XXX) ethyl-N -[({[(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 N; X50–53	X; X X: 23/25–50/53 X: (1/2-)36/37–45–60–61
007–012–00–5	N,N-dimethylhydrazin 1,1-dimethylhydrazin	E	200–316–0	57–14–7	F; X11 Xxxx. xxx. 2; X45 X; X23/25 X; R34 X; X51–53	X; T; X X: 45–11–23/25–34–51/53 X: 53–45–61
007–013–00–0	N,N-dimethylhydrazin 1,2-xxxxxxxxxxxxxxxx	X	—	540–73–8	Xxxx. xxx. 2; R45 X; X23/24/25 N; X51–53	X; X X: 45–23/24/25–51/53 S: 53–45–61	X ≥ 25 %: X; X45–23/24/25 3 % < C &xx; 25 %: X; X45–20/21/22 0,01 % &xx; X &xx; 3 %: X; R45
009–003–00–1	kyselina xxxxxxxxxxxxxx … %	B	231–634–8	7664–39–3	T+; R26/27/28 X; X35	X+; C X: 26/27/28–35 S: (1/2-)7/9–26–36/37–45	X ≥ 7 %: X+; X; X26/27/28–35 1 % ≤ C &xx; 7 %: X; X23/24/25–34 0,1 % ≤ C &xx; 1 %: Xx; X20/21/22–36/37/38
015–039–00–9	xxxxxxx-xxxxxx (ISO) X,X-xxxxxxxx-X -[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát		201–676–1	86–50–0	T+; X26/28 X; X24 X43 X; X50–53	X+; N X: 24–26/28–43–50/53 S: (1/2-)28–36/37–45–60–61
015–048–00–8	xxxxxxxx (XXX) O,O-dimethyl-O-[3-methyl-4-(methylsulfanyl)fenyl]-fosforothioát		200–231–9	55–38–9	Muta. xxx. 3; R40 X; R23–48/25 Xx; X21/22 X; X50–53	X; X R: 21/22–23–40–48/25–50/53 X: (1/2-)36/37–45–60–61
015–056–00–1	xxxxxxx-xxxxx (ISO) X,X-xxxxxxx-X-[(4(3 H)-oxo-1,2,3-benzotriazin-3-yl)methyl]-fosforodithioát		220–147–6	2642–71–9	T+; X28 X; X24 N; X50–53	X+; N X: 24–28–50/53 S: (1/2-)28–36/37–45–60–61
015–140–00–8	xxxxxxxxx (XXX) O,O-diethyl-O-(1-fenyl-1 X- 1,2,4-xxxxxxx-3-xx)-xxxxxxxxxxxxx		245–986–5	24017–47–8	X; R23/25 Xn; X21 X; R50–53	T; X X: 21–23/25–50/53 X: (1/2-)36/37–45–60–61
016–013–00-X	xxxxxxx xxxxxxx		234–129–0	10545–99–0	X14 X; X34 N; X50	X; X R: 14–34–50 S: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; X34 5 % ≤ C &xx; 10 %: Xx; X36/37/38
016–014–00–5	xxxxxxx xxxxxxxx		—	13451–08–6	X14 X; X34 X; X50	X; N X: 14–34–50 X: (1/2-)26–36/37/39–45–61	X ≥ 10 %: X; X34 5 % ≤ X &xx; 10 %: Xx; X36/37/38
016–023–00–4	xxxxxxxx-xxxxxx	X	201–058–1	77–78–1	Xxxx. kat. 2; R45 Xxxx. xxx. 3; X40 X+; X26 T; X25 X; R34 X43	X+ X: 45–25–26–34–43 X: 53-4 5	X ≥ 25 %: X+; X45–25–26–34–43 10 % ≤ X &xx; 25 %: X+; R45–22–26–34–43 7 % ≤ C &xx; 10 %: X+; R45–22–26–36/ 37/38–43 5 % ≤ X &xx; 7 %: T; 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; X45
016–024–00-X	xxxxxxxx (XXX) xxx(xxxxxxxxxxxxxxxxxxx)xxxxxxxx	X,X′-xxxxxxxx-xxxxxxxxxxx(xxxxxxxxxxx)215–993–8	1468–37–7	Xx; R22 N; X50–53	Xx; N R: 22–50/53 S: (2-)60-61
016–071–00–6	3-xxxxx-6,13-xxxxxxx-10-[(3-{[4-xxxxx-6-(2-xxxxxxxxxxxxxxxx)- 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; X34 5 % ≤ X < 10 %: Xx; 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 N; R50–53	F; X; N X: 14–17–34–50/53 S: (1/2-)16–43–45–60–61
050–002–00–0	xxxxxxxxx (XXX) tricyklohexyl(hydroxy)stannan xxxxxxxxxxxxxxxxxxxxx-xxxxxxxx		236–049–1	13121–70–5	Xx; X20/21/22 X; R50–53	Xn; X X: 20/21/22–50/53 X: (2-)13–60–61
050–012–00–5	xxxxxxxxxxxxxxxxxxxxxx [1] xxxxx(xxxxxxxxxxxxx)xxxxxxx [2] butyl(tricyklohexyl)stannan [3]		215–910–5 [1] 221–437–5 [2] 230–358–5 [3]	1449–55–4 [1] 3091–32–5 [2] 7067–44–9 [3]	Xx; X20/21/22 X; X50–53	Xx; X X: 20/21/22–50/53 X: (2-)26–28–60–61	X ≥ 1 %: Xx; X20/21/22	1
050–017–00–2	xxxxxxxxxxxxxx (XXX) 1,1,1,3,3,3-hexakis(2-fenyl-2-methylpropyl)distannoxan		236–407–7	13356–08–6	T+; R26 Xx; R36/38 N; X50/53	X+; X X: 26–36/38–50/53 X: (1/2-)28–36/37–45–60–61
082–009–00–X	xxxx (xxxxxxxxxxxx xxxxxxxx) XX Xxxxxxx Yellow 34 (XX 77603) CI xxxxxxxxxx xxxx 34 (XX 77603)		215–693–7	1344–37–2	Xxxx. xxx. 3; R40 Repr. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 N; X50–53	X; X X: 61–33–40–50/53–62 X: 53–45–60–61		1
082–010–00–5	červeň (xxxxxxx-xxxxxxxxxx-xxxxx xxxxxxxx) XX Xxxxxxx Xxx 104 (XX 77605) CI xxxxxxxxxx xxxxxx 104 (XX 77605)		235–759–9	12656–85–8	Xxxx. kat. 3; X40 Xxxx. xxx. 1; X61 Xxxx. xxx. 3; X62 X33 X; X50–53	X; X X: 61–33–40–50/53–62 X: 53–45–60–61		1
601–024–00-X	kumen [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	xxxxx[x]xxxxx xxxxx[xxx]xxxxxxx		200–028–5	50–32–8	Xxxx. xxx.2; X45 Muta. xxx. 2; X46 Xxxx. xxx. 2; X60–61 N; X50–53	X; X R: 45–46–60–61–50/53 X: 53–45–60–61
601–034–00–4	benzo[e]acefenanthrylen		205–911–9	205–99–2	Karc. xxx.2; X45 N; 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; X50–53	Xx; X X: 36–50/53 X: (2-)24/25–46–60–61
602–054–00–6	3-xxxxxxx-1-xx xxxxxxxxxx		209–130–4	556–56–9	X10 X; X34	X R: 10-34 X: (1/2-)7–26–45
603–076–00–9	but-2-yn-1,4-diol		203–788–6	110–65–6	T; X23/25 Xx; X21–48/22 X; X34	X X: 21–23/25–34–48/22 S: (1/2-)26–36/37/39–45	X ≥ 50 %: X; X21–23/25–34–48/22 25 % ≤ X &xx; 50 %: X; R21–23/25–36/38–48/22 10 % ≤ X &xx; 25 %: Xx; X20/22–48/22 3 % ≤ X &xx; 10 %: Xx; R20/22
603–091–00–0	exo-4-isopropyl-1-methyl-7-oxabicyklo[2.2.1]heptan-2-ol		402–470–6	87172–89–2	O; X8 Xx; X22 Xx; X36	X; Xx X: 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; X36 R52–53	Xi X:36–52/53 X: (2-)26-61
603–117–00–0	xxxxxx-2-xx xxxxxxxxxxxxxxxx xxxxxxxxxxx		200–661–7	67–63–0	X; X11 Xx; X36 R67	F; Xx X: 11–36–67 X: (2-)7–16–24/25–26
604–020–00–6	xxxxxxx-2-xx 2-hydroxybifenyl 2-xxxxxxxxxx (XXX)		201–993–5	90–43–7	Xx; X36/37/38 X; X50	Xx; X X: 36/37/38–50 X: (2-)22-61
604–021–00–1	2-xxxxxxxxxx, xxxxx sůl xxxxxxx-2-xxxxxxxxxxxx 2-xxxxxxxxx xxxxx xxxxxxx-xxxxxxx-2-xxxx		205–055–6	132–27–4	Xx; X22 Xx; X37/38–41 X; R50	Xn; X R: 37/38–41–50 X: (2-)22–26–61
604–024–00–8	4,4'-(4-methylpentan-2,2-diyl)difenol 2,2-xxx(4-xxxxxxxxxxxx)-4-xxxxxxxxxxxx		401–720–1	6807–17–6	Xxxx. xxx. 2; X60 Xx; R36 X; X50–53	X; X X: 60–36–50/53 X: 53–45–60–61
604–041–00–0	acifluorfen [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]	Xn; X22 Xx; X38–41 X; X50–53	Xx; X X: 22–38–41–50/53 X: (2-)24–39–60–61
604–043–00–1	monobenzonbenzyl (4-xxxxxxxxxxxx)xxxxx hydrochinonmonobenzylether 4-(xxxxxxxxx)xxxxx		203–083–3	103–16–2	Xx; X36 R43	Xi X: 36-43 X: (2-)24/25–26–37
604–044–00–7	xxxxxxxx 4-xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxxxxxxxx		205–769–8	150–76–5	Xx; R22 Xx; X36 R43	Xn X: 22–36–43 X: (2-)24/25–26–37/39–46
605–016–00–7	xxxxxxx… % xxxxxxxxx… %	X	203–474–9	107–22–2	Xxxx. kat. 3; X40 Xn; X20 Xx; X36/38 X43	Xx X: 20–36/38–40–43 X: (2-)36/37	X ≥ 10 %: Xx; X20–36/38–40–43 1 % ≤ X &xx; 10 %: Xx; R40–43
606–016–00-X	pindon (XXX) 2-(xxxxxxxxxxxxxxx)xxxxx-1,3-xxxx		201–462–8	83–26–1	X; X25–48/25 X; X50–53	X; X X: 25–48/25–50/53 X: (1/2-)37–45–60–61
606–018–00–0	xxxxxxx (ISO) 2,3-dichlor-1,4-naftochinon		204–210–5	117–80–6	Xn; X22 Xi; X36/38 X; X50–53	Xx; N X: 22–36/38–50/53 S: (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-dekachlorpentacyklo[5.3.0.02,6.04,10.05,9]dekan-3-on		205–601–3	143–50–0	Karc. kat. 3; X40 X; X24/25 X; X50–53	X; X X: 24/25–40–50/53 X: (1/2-)22–36/37–45–60–61
606–034–00–8	xxxxxxxxxx (XXX) 4-xxxxx-6-xxxx-xxxxx-3-(xxxxxxxxxxxxxx)-1,2,4-xxxxxxx-5(4 X)-xx 4-amino-6-terc-butyl-3-(methylsulfanyl)-4,5-dihydro-1,2,4-triazin-5-on		244–209–7	21087–64–9	Xn; X22 X; R50–53	Xn; X X: 22–50/53 X: (2-)60-61
606–035–00–3	xxxxxxxxxxx (XXX) 5-xxxxx-4-xxxxx-2-xxxxxxxxxxxxxx-3(2X)-xx xxxxxxx		216–920–2	1698–60–8	X43 N; X50–53	Xx; X X: 43–50/53 S: (2-)24–37–60–61
606–036–00–9	xxxxxxxxxxxxxx (XXX) 6-xxxxxx-2 X-[1,3]xxxxxxxx[4,5-x]xxxxxxxxxx-2-xx		219–455–3	2439–01–2	Xxxx. xxx. 3; X62 Xx; X20/21/22–48/22 Xx; X36 R43 X; X50–53	Xx; X R: 20/21/22–36–43–48/22–50/53–62 X: (2-)24–37–60–61
606–037–00–4	triadimefon (XXX) 1-(4-xxxxxxxxxxx)- 3,3-xxxxxxxx-1-(1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		256–103–8	43121–43–3	Xx; X22 N; X51–53	Xx; X R: 22–51/53 X: (2-)61
606–044–00–2	2,4,6-trimethylbenzofenon xxxxx(2,4,6-xxxxxxxxxxxxxx)xxxxxxxx		403–150–9	954–16–5	Xx; X22 Xi; X36 X; X50–53	Xx; N X: 22–36–50/53 X: (2-)26–60–61
607–043–00-X	xxxxxxx (XXX) 3,6-xxxxxxx-2-xxxxxxxxxxxxxxx xxxxxxxx		217–635–6	1918–00–9	Xx; R22 Xx; X41 X52–53	Xx; N X: 22–41–52/53 S: (2-)26-61
607–057–00–6	xxxxxxxxx (XXX) 3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx3-[1-(4-xxxxxxxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X-xxxxxxx-2-xx		201–378–1	81–82–3	Xx; R48/22 X52–53	Xx X:48/22–52/53 X: (2-)37-61
607–058–00–1	xxxxxxxxx (XXX) xxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxxxxxxxxx (XX)-3-[1-(2-xxxxx)-3-xxxxxxxx)]-4-xxxxxxx-2 X -xxxxxxx-2-xx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxxxxxxxxx 3-[1-(2-xxxxx)-3-xxxxxxxx]-4-xxxxxxx-2 X -xxxxxxx-2-xx		204–195–5	117–52–2	X; R25–48/25 R52–53	T X:25–48/25–52/53 X: (1/2-)37–45–61
607–079–00–6	kelevan (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 N; X51–53	X; X X: 22–24–51/53 X: (1/2-)36/37–45–61
607–097–00–4	xxxxxx-1,2,4-xxxxxxxxx-1,2-xxxxxxxx 1,2-xxxxxxxx xxxxxx-1,2,4-xxxxxxxxxxxxxx xxxxxxxx trimellitanhydrid		209–008–0	552–30–7	Xi; X37–41 X42/43	Xx R: 37–41–42/43 X: (2-)22–26–36/37/39
607–143–00–3	xxxxxxxxx xxxxxxxx xxxxxxxx kyselina		203–677–2	109–52–4	C; X34 X52–53	X X:34–52/53 X: (1/2-)26–36–45–61
607–152–00–2	2,3,6-XXX (XXX) 2,3,6-xxxxxxxxxxxxxxxx xxxxxxxx		200–026–4	50–31–7	Xx; R22 X; X51–53	Xx; X X: 22–51/53 X: (2-)61
607–153–00–8	xxxxxxxxx (XXX) (4-xxxxx-2-xxx-2,3-xxxxxxx-1,3-xxxxxxxxxxxx-3-xx)xxxxxx xxxxxxxx		223–297–0	3813–05–6	Xx; X36/38 X52–53	Xx X:36/38–52/53 X: (2-)22-61
607–156–00–4	xxxxxxxxxxx (XXX) 4-xxxxxxxxxx-4-xxxxxxxxxxx-1-xxxxxxxx		201–270–4	80–33–1	Xx; X22 Xx; R38 X; X50–53	Xx; N R: 22–38–50/53 S: (2-)37–60–61
607–158–00–5	xxxxx xxx chloroctové kyseliny xxxxxxxxxx xxxxx		223–498–3	3926–62–3	X; X25 Xx; X38 N; X50	X; N R: 25–38–50 S: (1/2-)22–37–45–61
607–159–00–0	xxxxxxxxxxxxxx (XXX) ethyl-2,2-bis(4-chlorfenyl)-2-hydroxyacetát ethyl-4,4'-dichlorbenzilát		208–110–2	510–15–6	Xn; X22 X; 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 H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propionyl}oxy)poly(oxyethylen)		400–830–7	—	R43 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 X: 43–51/53 X: (2-)24/37–61
607–209–00–1	Xxxx: X,X′-xxxxxxxxxxx-xxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx); X,X′-xxxxxxxxxxx-xxxxxxxxxxxxxx(xxxxxxxxxxx)		403–030–6	—	Xx; X22 X43 X; X50–53	Xx; X X: 22–43–50/ 53 X: (2-)36/37–60–61
607–213–00–3	xxxxx-3,3-xxx(xxxx-xxxxxxxxxxxx)xxxxxxxx		403–320–2	67567–23–1	X; X2 X; R7 X10 X; X51–53	X; X X: 2–7–10–51/53 X: (2-)3/7–14–33–36/37/39–61
607–217–00–5	2-xxxxxxxxxxx-[4-(7-xxxxx-2,6-xxxxx-2,6-xxxxxxx-1,5-xxxxx-x-xxxxxxx-3-xx)xxxxxx]xxxxxx		403–960–2	—	X43 X53	Xx X: 43-53 S: (2-)24–37–61
607–243–00–7	xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [1] xxxxxxx-3,6-xxxxxxx-x-xxxxxx [1] bis(2-hydroxyethyl)amonium-3,6-dichlor-2-methoxybenzoát [2] xxx(2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [2] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxx-2-xxxxxxxxxxxxxx [3] (2-xxxxxxxxxxxx)xxxxxxx-3,6-xxxxxxxxxxxxx [3]		217–846–3 [1] 246–590–5 [2] 258–527–9 [3]	1982–69–0 [1] 25059–78–3 [2] 53404–28–7 [3]	X52–53	X: 52/53 S: 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 xxxxxxxxxxxxxxxxx-xxxxxxxxx TPGDA		256–032–2	42978–66–5	Xi; X36/37/38 X43 X; X51–53	Xx; X R:36/37/38–43–51/53 X: (2-)24–37–61	C ≥ 10 %: Xx; X36/37/38–43 1 % ≤ X &xx; 10 %: Xx; X43
607–252–00–6	λ-xxxxxxxxxxx (XXX) Xxxx (1:1): (S)-[(3-fenoxyfenyl)kyanmethyl]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx x(X)-[(3-xxxxxxxxxxx)xxxxxxxxxx]-(1 X)-xxx-3-((X)-2-xxxxx-3,3,3-xxxxxxxxxxxx-1-xx-1-xx)-2,2-xxxxxxxxxxxxxxxxxxx-1-xxxxxxxxxx		415–130–7	91465–08–6	X+; R26 X; X25 Xx; X21 X; R50–53	T+; X X: 21–25–26–50/53 X: (1/2-)28–36/37/39–38–45–60–61
607–255–00–2	fluroxypyr (XXX) [(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx xxxxxxxx		—	69377–81–7	X52–53	X: 52/53 X: 61
608–003–00–4	xxxxxxxxxxxx	X X	203–466–5	107–13–1	X; Xxx Xxxx. xxx. 2; X45 T; X23/24/25 Xx; R37/38–41 X43 X; X51–53	X; X; N R: 45–11–23-/24/25–37/38–41–43–51/53 X: 9–16–53–45–61	X ≥ 20 %: X; R45–23/24/25–37/38–41–43 10 % ≤ X &xx; 20 %: X; X45–23/24/25–41–43 5 % ≤ X &xx; 10 %: X; X45–23/24/25–36–43 1 % ≤ X &xx; 5 %:T; X45–23/24/25–43 0,2 % ≤ X &xx; 1 %:X; X45–20/21/22 0,1 % ≤ X &xx; 0,2 %: X; R45	43
608–016–00–5	2,3,5,6-tetrachlor-1,4-dikyanbenzen xxxxxxxxxxxxxxxxxxxxxxxxx		401–550–8	1897–41–2	X43 N; X50–53	Xx; X R: 43–50/53 X: (2-)24–37–60–61
609–030–00–4	xxxxxxxx (XXX) 2-xxxx-xxxxx-4,6-xxxxxxxxxxxx	X	215–813–8	1420–07–1	Xxxx. kat. 2; X61 X+; X28 X; X24 X44 X; X50–53	X+; X X: 61–24–28–44–50/53 S: 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 Xn; X22 X; R50–53	T; X X: 45–61–22–50/53 S: 53–45–60–61
609–044–00–0	xxxxxxxx (XXX) 1,2,4,5-xxxxxxxxxx-3-xxxxxxxxxxx		204–178–2	117–18–0	Xx; X22 X43 X; X50–53	Xx; X R: 22–43–50/53 X: (2-)24–37–60–61
611–008–00–4	4-xxxxxxxxxxxxxx 4-(xxxxxxxx)xxxxxx		200–453–6	60–09–3	Xxxx. xxx. 2; X45 X; X50–53	X; X X: 45–50/53 X: 53–45–60–61
611–013–00–1	4-hydroxy-3-{4-[2-methoxy-4-(3-sulfonatofenylazo)fenylazo]-3-methylfenylazo}-6-(3-sulfonatoanilino)naftalen-2-sulfonát xxxxxxxxx		403–650–7	117409–78–6	X; X2 X; R51–53	E; X X: 2–51/53 X: (2-)35-61
611–031–00-X	4,4'-[(4-xxxxxxxxxxxxxx-2,5-xxxx-1-xxxxxx)xxxxxxxx]xxxxxxxx-xxxxxxxxxxxx XX Xxxxx Xxx 9 XX xxxxxxx červeň 9		209–321–2	569–61–9	Xxxx. kat. 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. xxx. 3; X40 X; X23/24/25	X X: 45–23/24/25 S: 53-45
612–042–00–2	xxxxxxxx bifenyl-4,4'-diamin 4,4'-diaminobifenyl xxxxxxx-4,4'-xxxxxxxxxx	X	202–199–1	92–87–5	Xxxx. xxx. 1; X45 Xx; X22 X; X50–53	X; N X: 45–22–50/53 X: 53–45–60–61	X ≥ 25 %: X; X45–22 0,01 % ≤ X &xx; 25 %: X; R45
612–051–00–1	4,4'-diaminodifenylmethan xxx(4-xxxxxxxxxx)xxxxxx 4,4'-xxxxxxxxxxxxxxxx	X	202–974–4	101–77–9	Xxxx. xxx. 2; X45 Xxxx. xxx. 3; R40 X; X39/23/24/25Xx; X48/20/21/22 X43 X; X51–53	X; X X: 45–39/23/24/25–43–48/20/21/22–51/53 X:53–45–61
612–081–00–5	3,3'-xxxxxxxxxxxxxxxx, xxxx o-tolidin, xxxx	X E	210–322–5 265–294–7 277–985–0	612–82–8 64969–36–4 74753–18–7	Karc. xxx. 2; X45 Xx; X22 X; X51–53	X; N X: 45–22–51/53 X: 53–45–61
612–099–00–3	4-methyl-m-fenylendiamin4-methyl-1,3-fenylendiamin4-methylbenzen-1,3-diamin 2,4-xxxxxxxxxxxx	X	202–453–1	95–80–7	Xxxx. xxx. 2; X45 T; X25 Xx; X21 Xi; X36 X43 X; X51–53	X; X R: 45–21–25–36–43–51/53 X: 53–45–61
612–105–00–4	2-(piperazin-1-yl)ethylamin2-(piperazin-1-yl)ethan-1-amin		205–411–0	140–31–8	Xn; X21/22 C; X34 X43 X52–53	X X: 21/22–34–43–52/53 X: (1/2-)26–36/37/39–45–61
612–111–00–7	2-methyl-m-fenylendiamin2-methyl-1,3-fenylendiamin2-methylbenzen-1,3-diamin 2,6-xxxxxxxxxxxx		212–513–9	823–40–5	Xxxx. kat. 3; X40 Xn; X21/22 X43 N; X51–53	Xx; X R: 21/22–40–43–51/53 X: (2-)24–36/37–61
612–125–00–3	2-methyl-p-fenylendiamin2-methyl-1,4-fenylendiamin2-methylbenzen-1,4-diamin 2,5-toluendiamin		202–442–1	95–70–5	T; X25 Xx; X20/21 X43 N; X51–53	X; X X: 20/21–25–43–51/53 X: (1/2-)24–37–45–61
612–144–00–7	flumetralin (XXX) X-(2-xxxxx-6-xxxxxxxxxxx)-X-xxxxx-2,6-xxxxxxx-4-(xxxxxxxxxxxxxx)xxxxxx		—	62924–70–3	Xx; X36/38 X4 3 X; X50–53	Xx; X X: 36/38–43–50/53 X: (2-)36/37–60–61
612–151–00–5	xxxxxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxxxxxxxxxxxxxx	X	246–910–3	25376–45–8	Xxxx. xxx. 2; X45 X; X25 Xx; X20/21 Xx; X36 X43 X; R51–53	T; X X: 45–20/21–25–36–43–51/53 X: 53–45–61
613–018–00–4	xxxxxxxxxx (XXX) 1,1'-xxx[(3,5-xxxxxxxxxxxxxxxx-4-xxxxxxxx)xxxxxx]-4,4'-xxxxxxxxx-1,1'-xxxxx		—	7411–47–4	Xx; X22 Xi; X36/37/38 X52–53	Xx X: 22–36/37/38–52/53 X: (2-)22–36–61
613–031–00–5	symklosen xxxxxxxxxxxxxxxxxxxx xxxxxxxx xxxxxxxx-1,3,5-xxxxxxxxxxxx 1,3,5-xxxxxxxx-1,3,5-xxxxxxx-2(1X), 4(3X), 6(5H)-trion		201–782–8	87–90–1	O; X8 Xx; X22 X31 Xx; R36/37 X; X50–53	X; Xn; X X: 8–22–31–36/37–50/53 X: (2-)8–26–41–60–61
613–038–00–3	6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxxxxxx 6-xxxxx-1,3,5-xxxxxxx-2,4-xxxxxx xxxxxxxxxxxxx		202–095–6	91–76–9	Xx; X22 X52–53	Xx R:22–52/53 X: (2-)61
613–042–00–5	xxxxxxxx (XXX) 1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]- 1 X-xxxxxxxx		252–615–0	35554–44–0	Xx; X20/22 X; X41 X; X50–53	Xx; X X: 20/22–41–50/53 S: (2-)26–39–60–61
613–043–00–0	xxxxxxxx-xxxxxx (XXX) 1-[2-(allyloxy)-2-(2,4-dichlorfenyl)ethyl]- 1X -xxxxxxxx-1-xxx-xxxxxxxxxxxxxx [1] (±)-1-[2-(xxxxxxxx)-2-(2,4-xxxxxxxxxxxx)xxxxx]-1X-xxxxxxxx-1-xxx-xxxxxxxxxxxxxx		261–351–5 [1] 281–291–3 [2]	58594–72–2 [1] 83918–57–4 [2]	Xx; X20/22 Xi; X41 N; X50–53	Xx; X X: 20/22–41–50/53 X: (2-)26–39–60–61
613–066–00–6	xxxxxxxxxx (XXX) 2-(xxxx-xxxxxxxxxx)-4-(xxxxxxxxxx)-6-xxxxxxx-1,3,5-xxxxxxx		251–637–8	33693–04–8	Xx; X22 X; X50–53	Xx; X X: 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; X36/37/38 X52–53	Xx; X: 22–36/37/38–52/53 X: (2-)22–36–61
613–098–00–0	1-xxxxxxxxxxxxxxx-2-xx 1-xxxxx-2-xxxxxxxxxx		403–700–8	2687–94–7	X; R34 X; X51–53	X; N X: 34–51/53 X: (1/2-)23–26–36/37/39–45–61
613–130–00–3	xxxxxxxxxxx (ISO) (XX)-2-(2,4-xxxxxxxxxxxx)-1-(1X-1,2,4-xxxxxxx-1-xx)xxxxx-2-xx		—	79983–71–4	X43 X; R51–53	Xi; X X: 43–51/53 X: (2-)24–37–61
613–131–00–9	xxxxxxxxxx (XXX) 1,2,5,6-xxxxxxxxxx-4 X-xxxxxxx[3,2,1-xx]xxxxxxxx-4-xx		—	57369–32–1	Xx; X22 R52–53	Xn X:22–52/53 S: (2-)61
613–134–00–5	xxxxxxxxxxxx (XXX) 2-(4-xxxxxxxxxx)-2-[(1 X-1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		—	88671–89–0	Xxxx. xxx. 3; X63 Xx; R22 Xx; X36 X; X51–53	Xx; X X: 22–36–51/53–63 X: (2-)36/37–46–61
613–137–00–1	xxxxxxxxxxxxxxxxxx (XXX) 1-(1,3-xxxxxxxxxxxx-2-xx)-1,3-xxxxxxxxxxxxxxxx		242–505–0	18691–97–9	X; X50–53	X X: 50/53 X: 60-61
613–139–00–2	xxxxxxxxxxx-xxxxxx xxxxxx-2-{X —[N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)karbamoyl]sulfamoyl}benzoát		—	74223–64–6	N; X50–53	X X: 50/53 S: 60-61
614–001–00–4	xxxxxxx (ISO) 3-(1-xxxxxxxxxxxxxxxx-2-xx)xxxxxxx		200–193–3	54–11–5	X+; X27 X; X25 X; R51–53	T+; X X: 25–27–51/53 S: (1/2-)36/37–45–61
614–006–00–1	xxxxxx 2,3-xxxxxxxxxxxxxxxxxxxx-10-xx		206–614–7	357–57–3	X+; X26/28 X52–53	X+ X:26/28–52/53 S: (1/2-)13–45–61
614–007–00–7	xxxxxx-xxxxxx [1] brucin-nitrát [2] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [3] xxxxxx-(X)-(1-xxxxxxxxxxxx)-xxxxxxxx-xxxxxx [4]		225–432–9 [1] 227–317–9 [2] 269–439–5 [3] 269–710–8 [4]	4845–99–2 [1] 5786–97–0 [2] 68239–26–9 [3] 68310–42–9 [4]	X+; X26/28 X52–53	X+ X: 26/28–52/53 S: (1/2-)13–45–61
615–006–00–4	2-xxxxxx-x-xxxxxxxxxxxxxxxxxx [1] 2-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [1] 4-xxxxxx-x-xxxxxxxxxxxxxxxxxx [2] 4-xxxxxx-1,3-xxxxxxxxxxxxxxxxxx [2] x-xxxxxxxxxxxxxxxxxxxx [3] 5-methyl-1,3-fenylendiisokyanát [3] xxxxxx-2,6-xxxxxxxxxxx [1] toluen-2,4-diisokyanát [2] toluen-3,5-diisokyanát [3]	C	202–039–0 [1] 209–544–5 [2] 247–722–4 [3]	91–08–7 [1] 584–84–9 [2] 26471–62–5 [3]	Xxxx. xxx. 3; X40 T+; 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 % ≤ C &xx; 20 %: X+; X26–40–42/43 1 % ≤ C &xx; 7 %: X; X23–40–42/43 0,1 % ≤ X &xx; 1 %:Xx; X20–42	2
616–010–00–9	xxxxxxx-xxxxxxxxxxxxxx N-chlor-4-methylbenzen-1-sulfonamid, sodná xxx		204–854–7	127–65–1	Xx; X22 X31 X; R34 X42	X X: 22–31–34–42 X: (1/2-)7–22–26–36/37/39–45
616–034–00-X	xxxxxxxxxxxx (XXX) 6-methyl-3,4-dihydro-2H-pyran-5-karboxanilid		246–419–4	24691–76–7	R52–53	R: 52/53 X: 61
616–035–00–5	xxxxxxxxx X -[(xxxxxxxxxx)xxxxxxxx]-2-xxxx-2-(xxxxxxxxxxxx)xxxxxxxx 1-xxxxx-3-[2-xxxx-2-(xxxxxxxxxxxx)xxxxxx]xxxxxxxx		261–043–0	57966–95–7	Xx; X22 R43 X; X50–53	Xx; X R: 22–43–50/53 S: (2-)36/37–60–61
617–004–00–9	(1,2,3,4-xxxxxxxxxx-1-xxxxxx)xxxxxxxxxxxx xxxxxxxxxxxxxxxxxxxx	212–230–0	771–29–9	X; X7 Xx; X22 X; X34 X; R50–53	O; 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 % ≤ X &xx; 10 %: Xx; X36/37/38
617–006–00-X	xxx(α, α-dimethylbenzyl)peroxid bis(2-fenylpropan-2-yl)peroxid xxx(1-xxxxx-1-xxxxxxxxxxx)xxxxxxx xxxxxxxxxxxxxx		201–279–3	80–43–3	X; X7 Xx; R36/38 X; X51–53	X; Xx; X X: 7–36/38–51/53 X: (2-)3/7–14–36/37/39–61
617–008–00–0	xxxxxxxxxxxxxxxx		202–327–6	94–36–0	X; X2 Xx; X36 R43	E; Xi; X: 2–36–43 S: (2-)3/7–14–36/37/39
650–007–00–3	xxxxxxxxxxxxx (XXX) X2-(4-xxxxx-2-xxxxxxxxxxx)-X1,X1-xxxxxxxxxxxxxxxxxxxx X2-(4-xxxxx-x-xxxxx)-X1,X1-xxxxxxxxxxxxxxxxxx		228–200–5	6164–98–3	Xxxx. xxx. 3; X40 Xx; X21/22 X; 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-xxxxxxxxxx)xxxxxxxxx]-3-xxxxxxxxxxxxxx-5(4 X)-xx		227–197–8	5707–69–7	X; R25 X; X50–53	X; N X: 25–50/53 S: (1/2-)22–24–36/37–45–60–61
650–009–00–4	xxxxxxxxxxxxx-xxxxxxxxxxxx X'-(4-xxxxx-x-xxxxx)-X,X-xxxxxxxxxxxxxxxxxx-xxxxxxxxxxxx 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 R: 22–40–50/53 X: (2-)22–36/37–60–61
650–033–00–5	esfenvalerát (XXX) [(X)-(3-xxxxxxxxxxx)xxxxxxxxxx]-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx (X)-3-xxxxxx-α-xxxxxxxxxx-(X)-2-(4-xxxxxxxxxx)-3-xxxxxxxxxxxxxx		—	66230–04–4	X; X23/25 R43 X; X50–53	X; N 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; R50–53	N X: 50/53 X: 60-61

XXXXXXX 1X

Xxxxxxxx xxxxx	Xxxxxxxx xxxxx	Xxxxxxxx k xxxxxx	Xxxxx XX	Xxxxx CAS	Klasifikace	Označení	Koncentrační limity	Poznámky 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-xxxxxxxxxxxxxxxxxxxx x 1,3-di(hex-x-en-1-yl)- 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 dihydrát		400–480–5	36669–85–9	R52–53	R:52/53 X: 61
015–165–00–4	Xxxx: S, X, S', S''-tetrafenyl-4,4'-sulfandiylbis(fenylsulfonium)-bis(hexafluorofosfát) x xxxxxxx[4-(xxxxxxxxxxxxx)xxxxx]xxxxxxxxx-xxxxxxxxxxxxxxxx		404–986–7	—	Xx; R41 X; X50–53	Xx; N X: 41–50/53 X: (2-)15–26–39–60–61
015–166–00-X	3,9-xxx(2,6-xx-xxxx-xxxxx-4-xxxxxxxxxxxx)-2,4,8,10-xxxxxxxx-3,9-xxxxxxxxxxxx[5.5]xxxxxxx		410–290–4	80693–00–1	X53	X:53 S: 61
015–167–00–5	3-[xxxxxxx(xxxxx)xxxxxxxxx]xxxxxxxxx xxxxxxxx		411–200–6	14657–64–8	Xx; X41	Xx X: 41 X: (2-)26-39
601–050–00–1	C10-C13-alkylderiváty xxxxxxx		267–051–0	67774–74–7	X; X50	X R: 50 X: 61
601–051–00–7	4-xxxxxxxx-1-xx		405–980–7	768–56–9	Xx; X38 X; X51–53	Xx; X X: 38–51/53 X: (2-)37-61
602–083–00–4	xxxxxxxxxxxxxxxx difenyletheru xxxxxxxxxxxxxxxxxxxxx		251–084–2	32534–81–9	Xx; R48/21/22 X64 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 X: 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 Xx; 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 R52–53	Xn X:22–52/53 X: (2-)39-61
603–131–00–7	Směs (3:1):1-xxxxx-1-[xxxxxx(1-xxxxxxxxxx)xxxxx]-X-xxxxxxxx; 1-deoxy-1-[methyl(1-oxotetradecyl)amino]-D-glucitol		407–290–1	—	Xi; R41	Xi X: 41 X: (2-)26-39
603–132–00–2	2-(xxxxxxxxxxxxx)-6-xxxxxxxxx-9-xxxxxx-1,4-xxxxxxxxxx[4.5]xxxxx		408–200–3	63187–91–7	Xx; X38–41 R52–53	Xi X:38–41–52/53 X: (2-)26–37/39–61
603–133–00–8	Xxxx:3-(4-xxxxx-2-xxxxx-5-xxxxxxxxxxxx)xxxxxx-1,2-xxxx x 3,3'-[(2-chlor-5-nitro-1,4-fenylen)diimino]di(propan-1,2-diol)		408–240–1	—	Xn; X22 X52–53	Xx X:22–52/53 S: (2-)22–36–61
603–134–00–3	Xxxx: xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxx x xxxxx(X1-X10)-xxxxxxxxxxxxxxxxxxxxxxx (xxxxxxx x xxxxxxxxxx nerozvětvené)		410–450–3	—	R53	R: 53 X: 61
603–135–00–9	xxx[2-(2-xxxxxxxxxxxxx)xxxxxxxxxx]xxx(2,2', 2-xxxxxxxxxxxxxxx-1-xxxxx-X,X)xxxxxxxxxx xxxxxxx		410–500–4	—	Xx; X41 N; X51–53	Xx; X X: 41–51/53 X: (2-)26–39–61
603–136–00–4	3-{4-[bis(2-hydroxyethyl)amino]-2-nitroanilino}propan-1-ol		410–910–3	104226–19–9	R43 X52–53	Xx X:43–52/53 S: (2-)24–37–61
603–137–00-X	Xxxx:1-xxxxx-1-[xxxxxx(1-xxxxxxxxxxxx)xxxxx]-X-xxxxxxxx x 1-deoxy-1-[methyl(1-oxooktadecyl)amino]-D-glucitol		411–130–6	—	Xi; X41	Xx X: 41 X: (2-)26-39
603–138–00–5	3-(2,2-dimethyl-3-hydroxypropyl)toluen 2,2-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-chlor-2-methylfenol		216–381–3	1570–64–5	T; X23 X; X 35 X; X50	X; X; X X: 23–35–50 X: (1/2-)26–36/37/39–45–61	X ≥ 25 %: X; X; X23–35 10 % ≤ X < 25 %: C;R20–35 5 % ≤ C &xx; 10 %: X;X20–34 3 % ≤ X &xx; 5 %: Xn;R20–36/37/38 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 S: 61
604–052–00–0	2,2'-methylenbis[6-(2 X - xxxxxxxxxxxx-2-xx)-4-(1,1,3,3-xxxxxxxxxxxxxxxx)xxxxx] 6,6'-xxx(2X -xxxxxxxxxxxx-2-xx)- 4,4'-xxx(1,1,3,3-xxxxxxxxxxxxxxxx)- 2,2'-xxxxxxxxxxxxxxx		403–800–1	103597–45–1	X53	X:53 S: 61
604–053–00–6	4-terc - butyl-2-methyl-6-(1-methylpentadecyl)fenol		410–760–9	157661–93–3	Xi; X38 X43 X; X50–53	Xx; X X: 38–43–50/53 X: (2-)24–37–60–61
604–054–00–1	Xxxx:2-xxxxxxx-4-(4-xxxxxxxxxxxxxxxxxxxxxxxxx-2-xx)xxxxx a 2-xxxxxxx-4-(4-xxxxxx-3,6-xxxxxxx-2X -xxxxx-2-xx)xxxxx		412–020–0	—	X43 X52–53	Xx X:43–52/53 S: (2-)24–37–61
604–055–00–7	4,4'-xxx[(2,3-xxxxxxxxxxx)xxx]-3,3', 5,5'-xxxxxxxxxxxxxxxxxx		413–900–7	85954–11–6	Xxxx. Xxx.3; X40	Xx X: 40 X: (2-)22–36–37
605–027–00–7	Xxxx:3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X-xxxxx-6-xxxxxxxxxxx a 3x, 4,5,6,7,7x-xxxxxxxxx-4,7-xxxxxxx-1X - xxxxx-5-xxxxxxxxxxx		410–480–7	—	X43 N; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
606–051–00–0	4-xxxxxxxxxxxxxxxxxx pentylcyklohexan-1-on		4–406–670–4	61203–83–6	N; X51–53	X R: 51/53 X: 61
606–052–00–6	4-(N, X-xxxxxxxxxxxx)-2-xxxxxxx-2'-xxxxxxxxxxxxxxxxx 2-[4-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxx]xxxxxxxx xxxxxxxx		410–410–5	54574–82–2	X52–53	X:52/53 X: 61
607–272–00–5	xxxxxxxxxxx-xxxxxx (ISO) [1] xxxxxxxxxx-xxxxxxxxx (XXX) [2] xxxxxxxxxxxx-[(4-xxxxx-3,5-xxxxxxx-6-xxxxx-2-xxxxxxx)xxx]xxxxxx [1] (2-butoxy-1-methylethyl)-[(4-amino-3,5-dichlor-6-fluor-2-pyridyl)oxy]acetát [2]		279–752–9 [1] —	81406–37–3 [1] 154486–27–8 [2]	X; X50–53	X X: 50/53 X: 60-61
607–273–00–0	xxxxxxx-7-{2,6-xxxxxxxx-8-[(2,2-xxxxxxxxxxxxxxxx)xxx]- 1,2,6,7,8,8a-hexahydro-1-naftyl}-3,5-dihydroxyheptanoát		404–520–2	—	R52–53	R:52/53 X: 61
607–274–00–6	{2-[benzyl(methyl)amino]ethyl}-3-aminobut-2-enoát		405–350–1	54527–73–0	R43 N; X51–53	Xx; N X: 43–51/53 X: (2-)24–37–61
607–275–00–1	natrium-4-(benzoyloxy)benzen-1-sulfonát		405–450–5	66531–87–1	R43	Xi X: 43 X: (2-)24-37
607–276–00–7	[xxx(2-xxxxxxxxxxxxxx) xxx(1-xxxxxxxxxxxxxx)]xxxxxxxxx komplex		405–635–0	—	Xi; X38–41 X; R50–53	Xi; X R: 38–41–50/53 X: (2-)26–37/39–60–61
607–277–00–2	Xxxx:2-(xxxxxxxxxxxxx)xxxxxxxxx-xxxxxxxxxxxx a xxxxxxx-xxxxxxxxx		405–720–2	—	Xx; X22 Xi; X41 X43 X; X51–53	Xx; N R: 22–41–43–51/53 X: (2-)24–26–37/39–61
607–278–00–8	Xxxx:xxxxx(X7-X9 xxxxxxxxxx a nerozvětvené)-3-[3-(2 X - xxxxxxxxxxxx-2-xx)-5-xxxx-xxxxx-4-xxxxxxxxxxxx]xxxxxxxxxx		405–760–0	—	Xx; X41 R43 X52–53	Xx X: 41–43–52/53 S: (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; R51–53	Xi; N X: 43–51/53 S: (2-)24–37–61
607–280–00–9	4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx xxxxx xxxxxxx-4-xxxxx-1-xxxxxxxxxxxx-1-xxxxxxxx		406–190–5	54322–20–2	Xx; X22 Xx; X36 X43	Xx R: 22–36–43 X: (2-)22–26–36/37
607–281–00–4	Xxxx:xxxxx(X7-X9 xxxxxxxxxx x lineární)-3-[3-(2H-benzotriazol-2-yl)-5-terc-butyl-4-hydroxyfenyl]propanoáty		407–000–3	127519–17–9	N; X51–53	X X: 51/53 X: 61
607–282–00-X	2-(xxxxxxxxxxxxx)-4-(xxxxxxxxx)xxxxx-xxxxxx		407–140–5	131266–10–9	X52–53	X: 52/53 X: 61
607–283–00–5	xxxxx-(X)-4-xxxxx-4-xxxxxx-2-xxxxxxxxxx-(X)-4-xxxxx-4-xxxxxxxxxxx		408–040–4	15121–89–8	Xx; R21/22 Xx; X38–41 R43 N; X50–53	Xx; X R: 21/22–38–41–43–50/53 S: (2-)26–36/37/39–60–61
607–284–00–0	Xxxx (9:1):xxxxxxx-3,3'-{(1,4-xxxxxxx)xxx[(xxxxxxxxxxxxx)(xxxxxx-3,1-xxxx)xxxxx]}xxx(10-xxxxx-6,13-xxxxxxx[1,4]xxxxxxxxxxx[2,3-x]xxxxxxxxx-4,11-xxxxxxxxxx) x lithium-3,3'-{(1,4-fenylen)bis[(karbonylimino)(propan-3,1-diyl)imino]}bis(10-amino-6,13-dichlor[1,4]benzoxazino[2,3-b]fenoxazin-4,11-disulfonát)		410–040–4	136213–76–8	N; X51–53	X X: 51/53 X: 61
607–285–00–6	Xxxx:7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxxx kyselina, xxxxxx-7-(3-xxxxxxxxxxxxxxxxxxxxxx)xxxxxxxx-1,3-xxxxxxxxxx x natrium-7-(3-aminobenzensulfonamido)naftalen-1,3-disulfonát		410–065–0	—	R43	Xi X: 43 S: (2-)22–24–37
607–286–00–1	Xxxx:xxxxxx- x xxxxxxx-7-[4-({4-[(2-xxxxxxx-1-xxxxxx)xxx]xxxxx}xxx)xxxxxxxxxxxxxxxxx]xxxxxxxx-1,3-xxxxxxxxxx		410–070–8	141880–36–6	X43 X52–53	Xx R:43–52/53 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 xxxxxxx, xxxxxxxxxx sůl; x = 15, 16, 17 nebo 18, x = 1, 2, 3 xxxx 4, x = 8, 9, 10 xxxx 11, x = 22, 23, 24 xxxx 25		410–160–7	148732–74–5	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-xx-xxxx-xxxxxxxxxxxx)xxxxx]xxxxxxxxx}-4-xxxxxxx-1-xxxxxx)xxxxxxxx]xxxxxxxxx xxxxxxxx		410–370–9	105488–33–3	X53	X:53 X: 61
607–290–00–3	Xxxx (o xxxxxxxx xxxxxx):xxxxxxx-1-xxxxx(X14-X18)-4-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx x xxxxxxx-4-xxxxx(X14-X18)-1-[3-(xxxxxxxx)-2-xxxxxxxxxxxxx]-2-xxxxxxxxxxxxxxxxxxx		410–540–2	—	Xx; X38 X43 X; X50–53	Xx; N X: 38–43–50/53 S: (2-)24–37–60–61
607–291–00–9	xxxxxxx-ω-xxxxxxxxxxx(xxxx cyklohexyl)alkanoát		410–630–1	104051–92–5	R53	R: 53 X: 61
607–292–00–4	Xxxx:[2-(xxxxx(X12)xxx)-1-(xxxxxxxxxxxxx)xxxxxx]xxxxxx xxxxxxxx x [2-(xxxxx(X14)xxx)-1-(xxxxxxxxxxxxx)]xxxxxx xxxxxxxx		410–640–6	—	Xx; X38–41 X; X50–53	Xx; X X: 38–41–50/53 X: (2-)26–37/39–60–61
607–293–00-XSměs:	1-(2-aminoethyl)piperazin-1,4-diium-[(2,4,6-trimethylnonyl)fenoxy]benzendisulfonát x 1-(2-xxxxxxxxxx)xxxxxxxxx-1,4-xxxxx-[xxx(2,4,6-xxxxxxxxxxxxxx)xxxxxx]xxxxxxxxxxxxxxxx		410–650–0	—	Xx; X41 X43 X; X51–53	Xx; N X: 41–43–51/53 X: (2-)26–36/37/39–61
607–294–00–5	xxxxxxx-2-(xxxxxxxxxx)-1-xxxxxxxxxxxx-1-xxxxxxxx		410–680–4	—	X43	Xx X: 43 X: (2-)24-37
607–295–00–0	Xxxx:xxxxxxxxxxxx-xxxxxxxxxxxxxxxxx x xxxxxxxxxxx-xxxxxxxxxxxx-1,2,3,4-xxxxxxxxxxxxxxx		410–800–5	—	X43 X; R51–53	Xi; X X: 43–51/53 X: (2-)24–37–61
607–296–00–6	Směs:tetraestery pentaerythritolu, xxxxxxxxx xxxxxxxx a 2-xxxxxxxxxxxxx xxxxxxxx		410–830–9	—	X53	X: 53 X: 61
607–297–00–1	3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(2-xxxxxxxxx-10-xxxxxxxxx xxxxxxxx)2,2'-xxxxx-3,3'-(1,4-xxxxxxxxxxxxxxxxxxx)xxx(1,7,7-xxxxxxxxxxxxxxxx[2.2.1]xxxxxx-1-xxxxxxxxxxxxxxx xxxxxxxx)		410–960–6	92761–26–7	Xx; X41	Xx X: 41 S: (2-)26-39
607–298–00–7	[2-(xxxxxxxxxxxxxxx)xxxxx]-4-xxxxxxxxxxxxxxxx		411–010–3	—	X43	Xx X: 43 S: (2-)22–36/37
607–299–00–2	xxxxxx-3-(xxxxxxxxxxxxxx)-2-xxxxxxxxxxxxxxx		411–040–7	97101–46–7	Xx; R22 X43 X; X50–53	Xx; X X: 22–43–50/53 X: (2-)24–37–60–61
607–300–00–6	[x-(X-{4-[(5-xxxxx-2,6-xxxxxxxxxxxxxxxx-4-xx)xxxxx]-3-xxxxxxxxxxxxxxxx}xxxxxxxxx)-x-xxxxxxxxx-x, x-xxxxxxxxxxxxxxxxxxxx]xxxxxxx xxxxxxx, xxxxxxxx sůl; x = 1,2,3 nebo 4, x = 8, 9, 10 xxxx 11, x = 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 dodekanoáty xxxxx(1-7)xxxxxxx		411–860–5	—	Xx; X38–41 X43 X; X51–53	Xx; N R: 38–41–43–51/53 S: (2-)24–26–37/39–61
607–302–00–7	Xxxx:xxxxxxxxxxxxx xxxxxxxx x xxxxxxxxxxxxxx xxxxx(1-7)xxxxxxx		411–910–6	—	Xx; R38–41 X43 X; X51–53	Xx; N X: 38–41–43–51/53 X: (2-)24–26–37/39–61
607–303–00–2	1-xxxxxxxxxxx-6,7-xxxxxxx-4-xxx-1,4-xxxxxxxxxxxxxxx-3-xxxxxxxxxxx kyselina		413–760–7	93107–30–3	Repr. kat.3; X62 X52–53	Xx X: 62–52/53 S: (2-)22–36/37–61
608–023–00–3	4-(4-xxxxxxxxxx)-2-xxxxx-2-[(1X- 1,2,4-xxxxxxx-1-xx)xxxxxx]xxxxxxxxxxx		406–140–2	114369–43–6	X; X50–53	X X: 50/53 X: 60-61
608–024–00–9	2-{4-[butyl(fenethyl)amino]fenyl}ethen-1,1,2-trikarbonitril		407–650–8	97460–76–9	R53	R:53 X: 61
608–025–00–4	[2-xxxxx-4,5-xxx(xxxxxxxxx)xxxxx]xxxxxxxxxxx		410–970–0	117568–27–1	X53	X:53 S: 61
609–053–00-X	xxxxxxxxxxx-xxxxxxxxxxxxxxxx		414–850–9	—	X; R3 X; X8 Karc. kat. 2; X45 X; X23/25 R43	E; T X: 45–3–8–23/25–43 S: 53-45
610–010–00–2	1-xxxx-2-(2-xxxxx)-1-xxxxxxxxxx		406–110–9	35950–52–8	Xx; X22–48/22 C; X34 X43 X; X50–53	X; X X: 22–34–43–48/22–50/53 X: (1/2-)22–26–36/37/39–45–60–61
611–043–00–5	Xxxx (2:1:1):[xxx(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx trisodný, [xxx{6-[(2-xxxxx-4-xxxxxxxxxxxx)xxx]- xxxx 6-[(2-xxxxx-6-xxxxxxxxxxxx)xxx]- xxxx 6-[(4-xxxxx-2-xxxxxxxxxxxx)xxx]-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx}]xxxxxxxxx xxxxxxxx a[{6-[(2-amino-4-hydroxyfenyl)azo]- 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}(6-{[1-(X-xxxxxxxxxxxxxx)-2-xxxxxxxxxxx-1-xx-1-xx]xxx}-5-xxxxxxxxx-3-xxxxxxxxxxxxxxxxx-2-xxx-1'-xxxxxx-1,2'-xxxxxxx)]xxxxxxxxx xxxxxxxx		402–850–1			Xx X: 41–52/53 S: (2-)26–39–61
611–044–00–0	Směs:[bis(5-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato)]chromitan xxxx-xxxxx(X12-X14)xxxxxx, [xxx(4-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [xxx(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx, [(5-xxxx-xxxxx-3-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)(5-xxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx a[(4(5)-nitrobenzen-1-azo-1'-naftalen-2,2'-diolato) (3-xxxxx-5-xxxxxxxxxxxx-1-xxx-1'-xxxxxxxx-2,2'-xxxxxxx)]xxxxxxxxx xxxx-xxxxx(X12-X14)xxxxxx		403–720–7	117527–94–3	X; 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	N X: 51/53 X: 61
611–046–00–1	4,4'-xxxxxxx-2-xxxxxxxxxxxxxxx2-xxxxxxxxxxxxxxx-4,4'-xxxxxx		407–590–2	43151–99–1	X; X25 Xx; X48/22 X43 X; X50–53	X; X R: 25–43–48/22–50/53 X: (1/2-)22–28–36/37–45–60–61
611–047–00–7	Směs (1:1):2-({4-[(2-xxxxxxxxxxxx)xxxxxxxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[(2-acetoxyethyl)ethylamino]fenyl}azo)-6,7-dichlorbenzothiazol		407–890–3	111381–11–4	R53	R: 53 S: 61
611–048–00–2	Xxxx (1:1):2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-5,6-xxxxxxxxxxxxxxxxxxx x 2-({4-[xxx(2-xxxxxxxxxxxx)xxxxx]xxxxx}xxx)-6,7-xxxxxxxxxxxxxxxxxxx	407–900–6	111381–12–5	X53	X: 53 S: 61
611–049–00–8	Směs (2:1:1)7-[(4-{[3-(xxxxxxxxxxxx)xxxxxx]xxxxx}-6-{[3-(xxxxxxxxxxxxx)xxxxxx]xxxxx}-1,3,5-xxxxxxx-2-xx)xxxxx]-3-{[4-(xxxxxxxx)xxxxx]xxx}-4-xxxxxxxxxxxxxxx-2-xxxxxxxx, xxxxxxxx xxxxxx x mléčná xxxxxxxx (2:1:1)	408–000–6	118658–98–3	Xx; R48/22 R43 X52–53	Xx X: 43–48/22–52/53 X: (2-(22–36/37–61
611–051–00–9	2-({4-[xxxxx(2-xxxxxxxxxxxx)xxxxx]-2-xxxxxxxxxxx}xxx)-6-xxxxxxx-3-xxxxxxxxxxxxxxxxxxxxx-xxxxxxx		411–110–7	136213–74–6	X; X50–53	X X: 50/53 X: 60-61
611–052–00–4	[xxxx{4-[(2-xxxxxxx-3,5-xxxxxxxxxxxx) xxx]-6-[(6-xxxxxxxxx-1-xxxxxx)xxx]xxxxxx-1,3-xxxxxxx}]xxxxxxxxx komplex, xxxxx xxx		400–720–9	—	X52–53	X: 52/53 X: 61
612–156–00–2	Xxxx:xxxxxxxxxxxx(xxxxxx)xxxxxxx-xxxxxxx x xxxxxxxxxxx(xxxxxxxx)xxxxxxx-xxxxxxx		405–620–9	—	Xx; R41 X; X50–53	Xx; N X: 41–50/53 X: (2-)26–39–60–61
612–157–00–8	(X)-1-(1-xxxxxxxxxxxx-2-xx)xxxxx-1-xx-xxxx-xxxxxxxxxxxx		410–780–8	—	Xx; X22–48/22 Xx; X41 X43 X; R51–53	Xn; X X: 22–41–43–48/22–51/53 X: (2-)22–26–36/37/39–61
612–158–00–3	Xxxx:[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxx-2-xxxxxxxxxxxxxxxxxx[xxx(5-xxxxx(xxxxxxxxxx X12))-2-xxxxxxxxxxxxxxxxxxxxx)]xxxxxxx xxxxxxx x 4-xxxxxxxxxxxxxxxxxxxxx		410–820–4	—	X53	X: 53 S: 61
612–159–00–9	xxxxxxx produkty xxxxx 2,2,4-xxxxxxxxx- x 2,4,4-xxxxxxxxxxxxxx-1,6-xxxxxxx (x xxxxxxx XXXXXX), xxxxxxxx [(xxxxx(X10-X16)xxx)xxxxxx]xxxxxxx (Epoxid 8) a 4-xxxxxxxxxxxx-1-xxxxxxxxx xxxxxxxx		410–880–1	—	Xx; R22 X; X34 N; 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; X X: 23/25–50/53 X: (1/2-)36/37–45–60–61
613–150–00–2	2,2'-[xxxxxxxxx-1,4-xxxxxx(xxxxxx-1,3-xxxx)]xxx(xxxxxxxxxxx[2,1-x]xxxxx[xxx][3,8]xxxxxxxxxxxx-1,3,6-xxxxx)		406–295–6	—	X53	X:53 X: 61
613–151–00–8	1-(2-xxxxx-3-X-xxxxx-5-X-xxxxxx-β-X-xxxxx-xxxxxxxxxxxxxx)-5-xxxxxxxxxxxxxxx-2(1X), 4(3 X)-xxxx		406–360–9	104218–44–2	X53	X:53 S: 61
613–152–00–3	xxxxx-X-(4,6-xxxxxxxxxxxxxxxxxx-2-xx)xxxxxxxx		406–600–2	89392–03–0	X43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
613–153–00–9	2,3,5-xxxxxxxxxxxxxxx		407–270–2	16063–70–0	X52–53	X:52/53 S: 61
613–154–00–4	2-xxxxx-4-xxxxx-6-xxxxxxxxxxxxxxxx		410–050–9	5734–64–5	Xx; X22	Xx X: 22 S: (2-)22
613–155–00-X	5-xxxxx-2,3-xxxxxxxxxxxxxx		410–090–7	89402–43–7	X10 Xx; X22 X52–53	Xx X: 10–22–52/53 X: (2-)23–36–61
613–156–00–5	2-xxxxx-4-xxxxx-5-xxxxxxxxxxxxxx 2-xxxxx-5-xxxxxxxxxxxxx-4-xxxxxxxxxxx		410–260–0	83857–96–9	X43 X; X51–53	Xx; X X: 43–51/53 X: (2-)24–37–61
613–157–00–0	2,4-xxxxxxx-5-(xxxxxxxxxxxxx)xxxxxxxxx 5-(xxxxxxxxxxxxx)xxxxxxxxx-2,4-xxxxxx		410–330–0	54236–98–5	Xx; X22–48/22 Xx; X36	Xx X: 22–36–48/22 X: (2-)22–26–36
613–158–00–6	2,3-xxxxxxx-5-(xxxxxxxxxxxxxx)xxxxxxx		410–340–5	69045–84–7	Xx; R20/22 Xx; X41 X43 X; X51–53	Xx; X X: 20/22–41–43–51/53 S: (2-)24–26–37/39–61
613–159–00–1	4-[2-(4-xxxx-xxxxxxxxxx)xxxxxx]xxxxxxxxxx		410–580–0	120928–09–8	X; X25 Xx; X20 N; R50–53	T; 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	methyl-3-(isokyanatosulfonyl)thiofen-2-karboxylát		410–550–7	79277–18–2	E; X2 X14 Xx; X48/22 X42/43	X; Xn X: 2–14–42/43–48/22 X: (2-)22–30–35–36/37
615–023–00–7	xxxxxxxxxxx 2-[(isokyanatosulfonyl)methyl]benzoové kyselinymethyl-2-[(isokyanatosulfonyl)methyl]benzoát		410–900–9	83056–32–0	R10 X14 Xxxx. xxx. 3; R40 Xn; X20–48/22 Xx; X41 X42	Xx X: 10–14–20–40–41–42–48/22 X: (2-)23–26–36/37/39
616–044–00–4	X-(3,5-xxxxxxx-4-xxxxx-2-xxxxxxxxxxxx)-2-(3-xxxxxxxxxxxxxxxx)xxxxxxxxx		402–510–2	—	X; X51–53	X X: 51/53 X: 61
616–045–00-X	2'-[(4-xxxxx-5-xxxxxx-3-xxxx-2-xxxxxxx)xxx]- 5'-(xxxxxxxxxxxx)-2-xxxxxxxxxxxxxxxxx		405–190–2	122371–93–1	X43 R53	Xi X: 43-53 S: (2-)22–24–37–61
616–046–00–5	X -[2-(6-xxxxx-7-xxxxxxxxxxxxxx[1,5-x][1,2,4]xxxxxxx-4-xx)xxxxxx]-2-(2,4-xx-xxxx-xxxxxxxxxxxx)xxxxxxxxx		406–390–2	—	X; X50–53	X X: 50/53 X: 60-61
616–047–00–0	Xxxx:X,X′,X″,X′′′ - tetraalkyl(C16)-2,2′, 2″, 2′′′ (ethylendinitrilo)tetraacetamid x N, N′,N″,N′′′ - tetraalkyl(C18)- 2,2′, 2′′, 2′′′-(xxxxxxxxxxxxxxxx)xxxxxxxxxxxxx		406–640–0	—	X43	Xx X: 43 S: (2-)24-37
616–048–00–6	3'-(trifluormethyl)isobutyranilid		406–740–4	1939–27–1	Xn; X48/22 N; 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 X: 61
616–050–00–7	1-[2,5-xxxxxxx-4-(1,1,2,3,3,3-xxxxxxxxxxxxxxxx)xxxxx]-3-(2,6-xxxxxxxxxxxx)xxxxxxxx		410–690–9	103055–07–8	X43 N; X50–53	Xx; X X: 43–50/53 X: (2-)24–37–60–61
616–051–00–2	Xxxx:3,3'-xxx(4-xxxxxxxxxxx)- 1,1'-(4-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx x 3,3'-xxx(4-xxxxxxxxxxx)-1,1'-(2-xxxxxx-1,3-xxxxxxx)xxxxxxxxxx Xxxx:2,4-xxx[3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx x 2,6-xxx[(3-(4-xxxxxxxxxxx)xxxxxx]xxxxxx		411–070–0	—	X53	X: 53 X: 61
617–015–00–9	bis(4-methylbenzoyl)peroxid		407–950–9	895–85–2	E; X2 X; X7 X; X50–53	X; X R: 2–7–50/53 X: (2-)7–14–36/37/39–47–60–61
650–032–00-X	xxxxxxxxxxxx (XXX) (2X, 3X)-, (2 X, 3 X)-, (2 R, 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 Xn; R22 X; R50–53	Xn; X X: 22–50/53–63 X: (2-)36/37–60–61

PŘÍLOHA 2

XXXXXX XXXXXXXXXXXX XXXXX XXXXXXXXX S XXXXXXXXXXXX XXXXXXX X XXXXXXXXX

Xxx směrnice Komise 2001/59/XX,

Xx. věst. X 332, 28.12.2000, s. 81.

PŘÍLOHA 3A

STANDARDNÍ XXXXXX XXX XXXXXXXX XXXXXXXXX X XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX,

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

PŘÍLOHA 3X

XXXXXXXXXX POKYNY XXX XXXXXXXX ZACHÁZENÍ X XXXXXXXXXXXX LÁTKAMI X XXXXXXXXX

Xxx směrnice Xxxxxx 2001/59/XX,

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

XXXXXXX 4X

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

1. XXXXXX

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

1.1 XXXX

Xxxxxxx na xxxxxxxxxxxx xxxxxxx x xxxxx xx xxxxx xx xxxxxxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx strukturní xxxxxxxxxxxx xxxxxxx v xxxxxxxxxxxxx xxxxxxx xxxxx (1, 2, 3). Rozlišují xx xxx xxxx xxxxxxxxxxxx xxxxxxx: xxxxxxxxxxxx x chromatidové. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxxxx xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx schopnost xxxxxxxxx xxxxxxxxx aberace. Xxxx xxxxxx xxxx xxxx xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x xxxxxx xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx mutace a xxxxxxx xxxx xxxx xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxxxx chorob x xxxxxxx x xxxxxxxx xxxxx xxxxxx x xxx, xx chromozomové xxxxxx x x xxxx xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx a x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx xxxxx xx indukci xxxxxxxx u xxxxxxx x x xxxxxxxxx xxxxxx.

Xx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxx mohou být xxxxxxx xxxxxxxxxxxxx xxxxxxx xxxxx, xxxxxxx xxxxx xxxx xxxxxxxx xxxxxxx xxxxxxx. Xxxxxxx xxxxx xxxx xxxxxxx xx xxxxxxx xxxxxxxxxx růstu x xxxxxxx, xxxxxxxx xxxxxxxxx, xxxxx xxxxxxxxxx, xxxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxx xxxxxxx.

Xxxxxxx xxxxxxxxx xx xxxxx obecně xxxxxxxx xxxxxxx xxxxxxxx zdroje xxxxxxxxxxx aktivace. Xxxxx xxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx xxxxx napodobit xxxxxxxx in xxxx x savců. Xx xxxxx xx xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx vedly k xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx x xxxx k xxx xxxxx změnou xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxxxxxxx (4, 5).

Xxxx xxxxxxx xx xxxxxxx xx xxxxxxxx xxxxxxx xxxxxxxx x karcinogenů pro xxxxx. Xxxxx sloučenin, xxx něž xx xxxx zkouška xxxxxxxxx, xxxx xxx xxxxx xxxxxxxxxxx; xxxx touto xxxxxxxx x xxxxxxxxxxxxxx xxxx xxxx absolutní xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx xxxxxx x xxx, že xxxxxxxx karcinogeny, xxxxx xxxxxx xxxxxxxx xxxxx xxxxxxxx, xxxxx zřejmě xxxxxx jinými xxxxxxxxxx xxx přímým poškozením XXX.

Xxx xxxx Xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

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

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

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

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

Xxxxxxxxx xxxxx : podíl xxxxx, které se xxxxxxxxx x xxxxxxxx, x xxxxxxxxx xxxxx xxxxx v populaci; xxxxx xxxxxx proliferace xxxx populace.

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

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

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

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx xxxxxxx xxxx xxxxxxxxx xxxxxxxx látce, x xx x xxxxxxxxxxxx xxxxxxxx x xxx xx. V předem xxxxxxxxxxx xxxxxxxxxxx xx xxxxxxxx látce xx xx xxxxxxxxx xxxxxx xxxxx látka zastavující xxxxxxxx (xxxx. Xxxxxxxx® xxxx xxxxxxxxx), kultury xx xxxxxx, obarví x xxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xx zjistí xxxxxxxxxxxxxx xxxxxxxxxxx xxxxx.

1.4 XXXXX XXXXXXXX METODY

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx

Xxxxx xxx xxxxxxx xxxxx xxxxxxx xxxxx, kmeny xxxx xxxxxxxx buněčné kultury, xxxxxx xxxxxxxx xxxxxxxxx xxxxx (např. xxxxxxxxxxx xxxxxx xxxxxxxx, xxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxx jiných savců).

1.4.1.2 Xxxxx x kultivační xxxxxxxx

Xxx xxxxxxxxx xxxxxx xx xxxx xxx xxxxxxx xxxxxx xxxxxxxxxx xxxxx a xxxxxxxxx xxxxxxxx (kultivační xxxxxx, xxxxxxxxxxx XX2, xxxxxxx x xxxxxxx). X xxxxxxxxxxxxxxx xxxxxxxxx xxxxx x kmenů xx xxxx xxx xxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx počtu xxxxxxxxxx x xxxx xx xxx kontrolováno, zda xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx; x případě xxxxxxxxxxx xx xxxxxx xxx xxxxxxx. Pro xxxxxxx xxxxx a xxxxxxxxx xxxxxxxx xx měla xxx xxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu.

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxxxxxxxxx xxxxxxx xxxxx x kmeny: xxxxx se xxxxxxx x xxxxxxxxx xxxxxx, xxxxxx xx xx xxxxxxxxxxxx média x xxxxxx xxxxxxx, xxx xxxxxxxxx xxxxxxxxxx před xxxxxxxxx, x xxxxxxxx xx při 37 °X.

Xxxxxxxxx: xxxx ošetřená xxxxxxxxxxxxxxx (xxxx. xxxxxxxxx) xxxx oddělené lymfocyty xxxxxxxx xxxxxxxx xx xxxxxxx xx kultivačního xxxxx xxxxxxxxxxxx mitogen (xxxx. xxxxxxxxxxxxxxxx) x xxxxxxxx xx při 37 °C.

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx xx měly xxx vystaveny xxxxxxxx xxxxx, x to x xxxxxxx metabolickou xxxxxxxx a bez xx. Nejčastěji xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx postmitochondriální frakce (X9) xxxxxxxxxx x xxxxx xxxxxxxx zpracovaná xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (6, 7, 8 x 9), xxxx směs fenobarbitonu x β-xxxxxxxxxxxx (10, 11 x 12).

Xxxxxxxxxxxxxxxxxxx xxxxxx xx x xxxxxxxx testovacím xxxxx xxxxxxx xxxxxxxxx v xxxxxxxxxxxxx 1 — 10 % xxx. Xxxx metabolického aktivačního xxxxxxx xxxx xxxxxxx xx třídě xxxxxxxx xxxxx, která xx xxxxxxxx. X xxxxxxxxx xxxxxxxxx xxxx být xxxxxx xxxxxx xxxx xxx xxxxx koncentraci xxxxxxxxxxxxxxxxxxx xxxxxx.

Xxxx xxxxxxxx xxxxxx, xxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxxxxx specifické xxxxxxxxx enzymy, xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxxxxxx xxxxxxxxx xxxxx xx xxxx být vědecky xxxxxxxxxx (xxxx. důležitostí xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxx/xxxxxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx být před xxxxxxxx na xxxxx xxxxxxxxxx xxxx suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky xxxxx xxx přidány xxxxx x xxxxxxxxxx xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Rozpouštědlo/vehikulum

Rozpouštědlo/vehikulum xx xxxx být xxxx xxxxxxxxx, xx xxxxxxx xx zkoušenou xxxxxx, a mělo xx xxx xxxxxxxxxx x přežitím xxxxx x s xxxxxxxxx X9. Xxxx-xx xxxxxxx xxxx než známá xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx. Při xxxxxxxx xxxxx nestálých xx vodě by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx xxx xxxxxxxxx přidáním xxxxxxxxxxxx xxxx.

1.4.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, která xxxx xxx zohledněna xxx xxxxxxxxx xxxxxxxx xxxxxxxxxxx, xxxxx xxxxxxxxxxxx, xxxxxxxxxxx x testovacím xxxxxxx x změny xX xxxx xxxxxxxxxx.

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x metabolickou xxxxxxxx x xxx xx x hlavním xxxxxxxxxxx xx xxxxxxx vhodných xxxxxxxxxx xxxxxxx xxxxxxxxx x xxxxx, xxxx xxxx xxxxxx xxxxxxxxxx, xxxxx xxxxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx xxxxx. Xxxx xxx výhodné xxxxxxxx cytotoxicitu a xxxxxxxxxxx v předběžném xxxxxxxxxxx.

Xxxx xx být xxxxxxx xxxxxxx xxx xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx xxxxxxxxxxxx xx xxxx tyto xxxxxxxxxxx xxxxxxxx rozmezí xxxx xxxxxxxxx až xxxxxxxxx xxxxxxxxx, xxxxxxxx žádnou xxxxxxxxx, xxx xxxxxxx xxxxxxx, xx xx xx xxxxxxxxxxx neměly xxxxx xxxx xxxxx xxxxxxxx 2 až Ö10. X okamžiku xxxxxxx xx měla xxxxxxxx xxxxxxxxxxx vykazovat xxxxxxxx xxxxxxx stupně xxxxxxxxxx, xxxxx buněk xxxx xxxxxxxxxxx xxxxxx (xxx x xxxx xxx 50 %). Xxxxxxxxx index je xxxxx xxxxxxxx měřítkem xxxxxxxxxxxxx xxxx xxxxxxxxxxxxxx xxxxxx x xxxxxx xx xxxx, xxxxx xxxxxxxx xx xxxxxxxx. Xxxxxxxxx index xx xxxx xxxxxxxxxx x xxxxxxxxxxx xxxxxx, x xxxxx xxxxx xxx xxxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx a xxxxxxxxxxx. Xxxxxxxxx x xxxxxxxx buněčného cyklu, xxxxxxxxx průměrná xxxxxxxxx xxxx (XXX), mohou xxx xxxxxxx jako xxxxxxxxx informace. V xxxxxxx XXX xxxx xxx x xxxxxxxx xxxxxxxxx xxxxxxx, x xxx nelze xxxxxxx xx xxxxxxxxx zpožděných xxxxxxxxxxx, a i xxxx přírůstek xxxxxxxx xxxxxxxxx xxxx může xxx za xxxxxxxx xxxxx xxxxxxxxx xxxxxxxx xxxxxxxx optimálního výtěžku xxxxxxx.

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

X případě xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xxxxxx toxické xxx xxxxxxxxxxxxx nižších, než xx jejich xxxxxxxxxxx, xx xxxx být xxxxxxx nejvyšší xxxxx x koncentraci, xxx xx xxx mezí xxxxxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxx xx xxxxx xxxx xxxxxxxx. X xxxxxxxx xxxxxxxxx (xxxx. projeví-li xx xxxxxxxx pouze při xxxxxxx koncentracích, xxx xx rozpustnost) xx xxxxxxxxxx xxxxxxxxx více xxxxxxxxxxx, při xxxxx xxxxxxx ke xxxxxxx. Xxxx být xxxxxxxx xxxxxxxx rozpustnost xx xxxxxxx x xx xxxxx expozice, xxxxx xxxxxxxxxxx x xxxxxxxxxx xxxxxxx xx xxxx x xxxxxxx xxxxxxxx xxxxx x xxxxxxxx xxxxxxxxxxx buněk, séra X9 xxx. Nerozpustnost xxx zjistit xxxxxxxx. Xxxxxxxxx xx xxxxxx xxxxx xxx vyšetřování.

1.4.2.3 Xxxxxxxxx a xxxxxxxxx xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x negativní xxxxxxxx (xxxxxxxx xxxxxxxxxxxx xxxx xxxxxxxx). Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx měla xxx xxx pozitivní kontrolu xxxxxxx chemická xxxxx, xxxxx x xxxxxxxxx xxxxxx vyžaduje aktivaci.

K xxxxxxxxx xxxxxxxx xx xxx být použit xxxxx xxxxxxxxx v xxxxxxxxxxx xxxxxxxxxxxxx, xxxxx xxxxxxxx xxxxxxxxx reprodukovatelný x detekovatelný nárůst xxx pozadí, xxxx xx prokáže xxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxxxxxxxx xxxxxxxxxxx xxxxxxx xx měly xxx xxxxxxx xxx, xxx byl účinek xxxxxxxx, xxx xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxxxxx a xxxxxxxxxxx xxxxxxx:

Xxxx xxxxxxxxxxx aktivace	Látka	Číslo XXX	Xxxxx xxxxx EINECS
Bez xxxxxx xxxxxxxxxxx xxxxxxxx	xxxxxx-xxxxxxxxxxxxxx	66–27–3	200–625–0
	xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
	1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
	xxxxxxxxx X	50–07–7	200–008–6
	4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1
X xxxxxx xxxxxxxxxxxx xxxxxxxx	xxxxx[x]xxxxx	50–32–8	200–028–5
	xxxxxxxxxxxxx	50–18–0	200–015–4
	xxxxxxxxxxxxx xxxxxxxxxx	6055–19–2	200–015–4

Xxx xxxxxxxxx xxxxxxxx xxxxx být xxxxxxx x jiné xxxxxx xxxxx. Pro xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxx xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx ze xxxxxx xxxxxxxx xxxxx.

X okamžiku xxxxxxxx xx xxxx xxx použity xxxxxxxxx xxxxxxxx skládající se xx samotného rozpouštědla xxxx xxxxxxxx x xxxxxxxxxxx xxxxx a xxxxxxxxxx xxxxxxx způsobem xxxx xxxxxxx. Xxxxx xxxx xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, xxxxxxxxxx-xx dosud xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx xxxxxxx rozpouštědlo xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.4.3 Xxxxxx

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

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

1.4.3.2 Xxx xxxxxx koncentraci xx měly xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx, x xxxxx xx důrazně doporučuje x kultur xxx xxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxx. Xxxxxxxx xxx xx základě xxxxxxxxxxx xxxxx xxxxxxxx (13, 14), že xxxx xxxxxxxxxxxx xxxxxxxxx xx xxxxxxxxx rozdíl, xxxx xxx xxxxxxxxx xxxxxxx xxxxxx xxxxxxx.

Xxxxxx xxxx xxxxxx látky xx měly xxx xxxxxxxx xxxxxxxx xxxxxxxx, xxxx. v xxxxx xxxxxxxxxx kultivačních xxxxxxxx (15, 16).

1.4.3.3 Xxxx xxxxxxx xxxxxx

X xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxx xxxxxxxxx xxxxxxxx xxxxx, jak x xxxxxxxxxxxx xxxxxxxx, xxx bez xx, xx dobu 3 — 6 hodin, x xxxx by xxx xxxxxxxx po xxxxxx xxxx xx xxxxxxxx xxxxxxxx, xxxxx xxxxxxxx 1,5násobku normální xxxxx xxxxxxxxx cyklu (12). Xxxxxxxx xxxxx xxxxxx dává xxxxxxxxx xxxxxxxx jak s xxxxxxxx, xxx bez xxxxxxxx, xxx by xxx xxxxxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx x xxxxxxxxxxxx xxxxxxxx xx do xxxxxx x době, xxxxx xxxxxxxx 1,5násobku normální xxxxx xxxxxxxxx xxxxx. Xxxxxx xxxxxxxx xxxxx xxx xxxxx xxxxxxxxx xxx dobách xxxxxxxx xxxx xxxxxx xxxxxxx xxx 1,5xxxxxxx xxxxx xxxxx. Negativní xxxxxxxx xxx metabolické aktivaci xxxx xxx potvrzeny xxxxxx od xxxxxxx. X xxxxxxxxx, kdy xx xxxxxxxxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xx xxxxxxxx, xx xxxx xxx podáno xxxxxxxxxx.

1.4.3.4 Xxxxxxxx preparátů pro xxxxxxx xxxxxxxxxx

Xx buněčné xxxxxxx se xxxxxxx 1-3 xxxxxx před xxxxxxxxx xxxxx Xxxxxxxx® xxxx xxxxxxxxx. Pro xxxxxxxx preparátů xxx xxxxxxx chromozomů se xxxxx xxxxxxx kultura xxxxxx x xxxxxxxxxx xxxxxx. Příprava xxxxxxxxx xxx xxxxxxx chromozomů xxxxxxxx xxxxxxxxxxxx xxxxx, xxxxxx a obarvení xxxxx.

1.4.3.5 Xxxxxxx

Xxxxxxx xxxxxxxxx, xxxxxx xxxxxxxxx xxxxxxxxxxx x negativních xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx nezávisle kódovány. Xxxxxxxx při fixaci xxxxx xxxxxxx xx xxxxx xxxxx xxxxx x xxxxxxxx x xx xxxxxx xxxxxxxxxx, xxxx xx xxxxxxxxxxx xxxxx obsahovat xxxxxxxxxx x xxxxx rovném xxxxxxx hodnotě ± 2 xxx xxxxxxx xxxx xxxxx. Xx xxxxxx xxxxxxxxxxx x xxxxxxxx by mělo xxx xxxxxxxxx xxxxxxx 200 dobře xxxxxxxxxxxxxx xxxxxxxx, xxxxxxxx rovnoměrně xxxxxxxxxxx mezi duplicitní xxxxxxx. Xxxxx xxxxx xxx xxxxxx, xx-xx xxxxxxxxx xxxxx xxxxx xxxxxxx.

Xxxxxx xx xxxxxx xxxxxxx detekovat xxxxxxxxxx xxxxxxxxxxxx xxxxxxx, xx xxxxxxxx xxxxxxxxxx xxxxxxxxxxx x endoreduplikace, xxxx-xx xxxxxxxxxx.

2. ÚDAJE

2.1 ZPRACOVÁNÍ XXXXXXXX

Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx a mělo xx tedy být xxxxxxxxxxx xxxxxxxx xxxxx xx xxxxxxxxxx chromozomovou xxxxxxx (xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Pro xxxxxxxxx a xxxxxxxxxxxxxx xxxxxxx by měly xxx uvedeny xxxxx xxxx strukturních xxxxxxxxxxxxxx xxxxxxx x jejich xxxxxx x četností. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x xxxxxxx xx, xxx nezahrnují xx xx celkové xxxxxxxx aberací.

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

Xxxx xx xxx xxxxxxx xxxxx xxx xxxxxxxxxx kultury. Xxxx xx xxxx xxx xxxxxxx xxxxx xxxxxxx xx formě xxxxxxx.

Xxxxxxx xxxxx xxxxxxxxx xxxxxxxx xx xxxxxxxxxx. Dvojznačné xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxxx xxxxxxxx negativní xxxxxxxx byla xxxxxxxxxxx x xxxx 1.4.3.3. Xxxxx parametrů xxxxxx x xxxxx xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx x xxxxxxxxxx xxxxxxxxxxxxx. X xxxxxxxxxx xxxxxx, které xx xxxxx být xxxxxxx, xxxxx xxxxxxx koncentrací x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 HODNOCENÍ X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx výsledku xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx aberacemi x závislosti xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx tohoto počtu. Xxxxxxxx by měla xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx použity xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (3, 13). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

Nárůst xxxxx polyploidie xxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx má xxxxxxxxx potlačit xxxxxxxxx xxxxxxx a xxxxxxxxx xxxxxxxxx xxxxxxxxxxxx aberace. Xxxxxx počtu xxxxx x endoreduplikovanými xxxxxxxxxx xxxx xxxxxxxx, že xxxxxxxx xxxxx xx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx cyklu (17, 18).

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

Ačkoli xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx nebo xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxx údajů vyslovit xxxxxxx xxxxx x xxxxxxxx zkoušené látky. Xxxxxxxx xxxxx xxxxxx xxxxxxxxxx nebo xxxxxx xxx ohledu na xx, kolikrát xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx zkoušky na xxxxxxxxxxxx aberace xx xxxxx xxxxxxxxx, že xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, že xxxxxxxx xxxxx za xxxxxxxx xxxxxxx xxxxxxxxxx x kultivovaných somatických xxxxxxx savců strukturní xxxxxxxxxxxx xxxxxxx.

3. ZPRÁVY

PROTOKOL X ZKOUŠCE

Protokol x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Buňky:

- typ x xxxxx buněk,

- xxxxxxxxxx xxxxxxxxx a xxxxxxxx xxxxxxxxx xxxx xxxxx,

- xxxxxxxxx nepřítomnost xxxxxxxxxxx,

- xxxxxxxxx o xxxxx xxxxxxxxx cyklu,

- xxxxxxx xxxxx xxxx, xxx xxxx použita xxxx xxxx xxxx xxxxxxxxxx lymfocyty, xxxxxxx xxxxxxx,

- xxxxxxxx xxxxx xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx kultury,

- xxxxxxx xxxxxxx xxxxx xxxxxxxxxx.

Xxxxxxxx xxxxxxxx:

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

- xxxxxxxxxx výběru xxxxxxxxxxx x xxxxx kultur, xxxxxx xxxx. xxxxx x cytotoxicitě x xxxxxx xxxxxxxxxxxx, xxxx-xx x dispozici,

- xxxxxxx xxxxx, xxxxxxxx koncentrace XX₂,

- xxxxxxxxxxx zkoušené xxxxx,

- xxxxx vehikula x xxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxx xxxxxxx,

- xxxxxxxxx xxxx,

- xxxxx xxxxxxxx,

- xxxxxxxx xxxxxxx xxxxx xxx xxxxxxxx,

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

- xxxxxxxxx x xxxxxxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria xxxxxxxxx aberací,

- xxxxx xxxxxxxxxxxxx metafází,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity, xxxx. xxxxxx konfluence, xxxxx x xxxxxxxx xxxxx, počty buněk, xxxxxxxxx xxxxx,

- xxxxxx xxxxxxx,

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

- definice xxxxxxx, včetně xxxx,

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

- xxxxx xxxxxxx, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx závislost xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

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

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

Xxxxxx výsledků.

Závěry.

4. LITERATURA

1) Xxxxx, H. X. (1976), Cytological Xxxxxxx xxx Xxxxxxxxx Xxxxxxxx Xxxxxxxx, in: Xxxxxxxx Xxxxxxxx, Xxxxxxxxxx and Xxxxxxx xxx xxxxx Xxxxxxxxx, Xxx. 4, Xxxxxxxxxx, X. (xx) Xxxxxx Xxxxx, Xxx Xxxx xxx London, 1-29.

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

3) Xxxxxxxx, X. X., Xxxxxxxxx, X. X., Xxxxxx, X., Xxxxxx, X., Xxxxx, X., Xxxxxx, X., Xxxxx, X. X., Xxxxxxxx, X., Ahmed, X., Duk, X., Xxxxx, J., Xxxxxxxx, X. X., Xxxxxxx, X. X., Xxxxxxxx, X., Xxxxxx E. (1978), Xxxxxxxxxx xxxxxxxxxx xxx xxxxxx chromatic xxxxxxxxx xx Xxxxxxx xxxxxxx xxxxx cells: Xxxxxxxxxx of 108 xxxxxxxxx, Environ. Xxxxx. Xxxxxxx. 10 (xxxxx. 10), 1-175.

4) Xxxxx, X., Xxxxxxxx, X. X., Marshall, X. X., Ishidate, X. Xx., Xxxxxxx, X., Xxxxx, J., Xxxx, X. X. (1991), Xxxxxxxxxxxx under Xxxxxxx Xxxxxxx Xxxxxxxxxx. X xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxxxx Res., 257, 147-204.

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

6) Xxxx, X. X., McCann, X., Xxxxxxxx, X. (1975), Methods for Xxxxxxxxx Xxxxxxxxxxx and Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx Microsome Xxxxxxxxxxxx Xxxx, Xxxxxxxx Xxx., 31, 347-364.

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

8) Natarajan, X. T., Xxxxx, X. X., xxx Xxxx, P. X. X., Xxxxxxx, M., xx Xxxxx, N. (1976), Cytogenetic Xxxxxxx xx Mutagen/Carcinogens after Xxxxxxxxxx in x Xxxxxxxxxxx Xxxxxx In xxxxx, I. Xxxxxxxxx xx Xxxxxxxxxx Xxxxxxxxxxx xxx Sister Xxxxxxxxx Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx (XXX) xxx Xxxxxxxxxxxxxxxxxxx (XXX) xx XXX Xxxxx in xxx Xxxxxxxx xx Xxx-Xxxxx Xxxxxxxxxx, Xxxxxxxxxx Res., 37, 83-90.

9) Xxxxxxxx, X., Xxxxxxx, M., Xxxxxxxx, X. Jr. (1979), Xxxxxxxxxxx Xxxxxxxxxx Xxxxx xx 29 Xxxxxxxxx Xxxxxxxx xxxx X9 Mix Xx xxxxx, Xxxxxxxx Xxx., 66, 277-290.

10) Xxxxxx, X. M., Xxxxxx, X. X., Elcombe, X. R., Xxxxxxxxx, X. G., Gibson, X. X., Xxxxxx, X. M., Xxxx, X. C. (1992), Xxxxxx xx XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx. Alternative xx Aroclor 1254-induced X9 xx Xx xxxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 175-177.

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

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

13) Richardson, X., Xxxxxxxx, X. X., Xxxxx, X. A., Xxxxxxxx, X., Chanter, X. X., Phillips, X. (1989), Xxxxxxxx xx Data from Xx xxxxx Xxxxxxxxxxx Xxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx of Mutagenicity Xxxx Xxxx, Kirkland, X. J., (ed) Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, 141-154.

14) Xxxxx, X. X., Xxxxxxxx, X. X. (1994), Xxxxxxxxx Xxxxxx xxx xxx Xxxxxxxxx xxx Xx xxxxx Xxxxxxxxxx Xxxxxxxxxx Assays in XXX Cells, Xxxxxxxxxx Xxx., 312, 139-149.

15) Xxxxx, X. X., Xxxxxx, X. X., XxXxxxx, K. X. (1982), XXX/XXXXX Mutation Xxxxx: Evaluation xx Xxxxx and Xxxxxxxx Xxxxxxx, xx: Tice, X. R., Costa, X. L., Xxxxxxx, X. X. (xxx), Xxxxxxxxx Xxxxxxx xx Xxxxxxxx Xxxxxx, Xxx Xxxx, Plenum, 91-103.

16) Xxxxxx, X. O., Xxxxxx, J. M., Xx, X. X., Xxxxxx, X. X. (1983), Xxxxxxxxxx of xx Exposure System Xxxxx Cells Xxxxx xx Xxxxxxxx Xxxx xxx Xxxxxxxxx Xxxxxx Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environmental Xxxxxxx., 5, 795-801.

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

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

XXXXXXX 4B

"B.11 MUTAGENITA–ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX X BUŇKÁCH XXXXXX XXXXX XXXXX XX XXXX

1. XXXXXX

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

1.1 ÚVOD

Zkouška xx xxxxxxxxxxxx aberace x xxxxx xx xxxx xx používána xxx detekci xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx indukovaných xxxxxxxxx látkou x xxxxxxx xxxxxx xxxxx xxxxx, xxxxxxx xxxxxxxx (1, 2, 3, 4). Rozlišují xx xxx xxxx strukturních xxxxxxx — xxxxxxxxxxxx x chromatidové. Nárůst xxxxxxxxxxx xxxx xxxxxxxx, xx xxxxxxxx xxxxx xx xxxxxxxxx indukovat xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx xxxx, xxxxx chromozomové aberace xx xxxxxx xxxxxxxxx. Xxxxxxxxxxxx mutace x xxxxxxxxxxx xxxx jsou xxxxxxxx xxxxx geneticky xxxxxxxxxxx xxxxxx x xxxxxxx x existuje xxxxx xxxxxx x xxx, že xxxxxxxxxxxx xxxxxx a xxxxxxxxxxx xxxx xxxxxxxxxxx xxxxx x xxxxxxxxxx x x xxxxxx somatických xxxxx xxxxxxxxx xxxxxx, xxxx podíl na xxxxxxx xxxxxxxx x xxxxxxx x v xxxxxxxxxxxxxxxx xxxxxxxxx.

Xxx xxxx xxxxxxx xxxx rutinně xxxxxxxxx xxxxxxxx. Xxxxxxx xxxxx xx x xxxx xxxxxxx xxxxxx xxxx, xxxxxxxx xx xxxxxx xxxxxxxxxxxxxxxx tkání x xxxxxxxx xxxxxxxx xxxxx x rychlým xxxxxx, xxxxx xx xxxxxx xxxxxxx x xxxxxxxxxxxx. Jiné xxxxx x xxxxxx tkáně xxxxxx xxxxxxxxx xxxx xxxxxx.

Xxxx xxxxxxx xx xxxxxxxxxxxx aberace je xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxx zohlednit xxxxxxx xxxxxxxxxxx xx xxxx, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx se xxxxx x xxxxxxx druhů x xxxxx xxxxx. Xxxxxxx xx xxxx xx rovněž xxxxxxxx xxx xxxxx výzkum xxxxxxxxxxx účinků xxxxxxxxxx xxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx o xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx nedostanou xx cílové tkáně, xxxx vhodné xxxx xxxxxxx xxxxxx.

Xxx také Xxxxxx úvod, část X.

1.2 XXXXXXXX

Xxxxxxxxxxxx aberace : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx jednotlivých chromatid xxxx xxxxx a xxxxxxxx xxxxxxx xxxxxxxxx.

Xxxxxxxxxxxx xxxxxxx : xxxxxxxxxx xxxxxxxxx xxxxxxxxxx v xxxxxx xxxxx xxxx xxxxx x xxxxxxx xxxx chromatid x xxxxxx místě.

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

Xxx : xxxxxxxxxxxx xxxx xxxxx než xxxxx xxxxxxx xxxxxxxxxx a x xxxxxxxxx xxxxxxxxx xxxxxxxxx.

Xxxxxxxxx xxxxxxx : xxxxxxxx počtu xxxxxxxxxx xx xxxxxxxx xxxxxxx xxxxxxx x použitých xxxxx.

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

Xxxxxxxxxx xxxxxxx : xxxxxxxxxxxxx pozorovatelné xxxxx xxxxxxxxx xxxxxxxxxx xxx xxxxxxxx xxxxxx xx stadiu metafáze; xxxx se xxxx xxxxxx x fragmenty, xxxxxxxxxxxxxxxxxx nebo xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

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

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Přípravky

1.4.1.1 Výběr xxxxx xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, xxx x xxxxxx čínský, xxxxxx lze xxxxxx xxxxxxxx xxxxxx savčí xxxx. Xxxx xx xxx xxxxxxx xxxxx xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx studie xx měla být xxxxxxxx x hmotnosti xxxxxx xxxxxxxxx a xxxxxx by u xxxx pohlaví xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx chovu a xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxx xxxxxxxx xxxxxxx zvířata se xxxxxxxx výběrem rozdělí xx kontrolní xxxxxxx x xxxxxxx, která xx xxxxxxx xxxxxxxx xxxxx. Xxxxx xx xxxx být xxxxxxxxxx xxx, aby byl xxxx jejich polohy xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxxxxx xx x laboratorních xxxxxxxxxx xxxxxxx pět xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx xxxx aplikací zvířatům xxxxxxxxxx nebo xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx látky mohou xxx podávány xxxxx xxxx xxxxx xxx xxxx xxxxxxx zředěny. Xxxx xx být xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx údaje x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx při xxxxxxxxx xxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx xx xxx xxxxxxxxx xxxxxxxxx, že xxxxxxx xx zkoušenou xxxxxx. Xxxx-xx xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx podloženo xxxxx x jejich xxxxxxxxxxxxx. Xxxxxxxxxx xx xxxxx xxxxx nejdříve xxxxxx xxxxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx by měly xxx xxxxxxxxx x xxxxxxxxx (rozpouštědlo/vehikulum) xxxxxxxx xxx xxx pohlaví. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxx jako zvířata xx xxxxxxxxx, x xxxxx xxxxx k xxxxxxxx.

Xxxxxxxxx xxxxxxxx xx xxxx xxxxxxxxxx strukturní xxxxxxx xx xxxx xxx xxxxxxxxxxx xxxxxxxx, x xxxxx xx xxxxxxx, že xxxxxxxxx xxxxxxxxxxxxx xxxxxx nad xxxxxx. Xxxxx pozitivní xxxxxxxx xx xxxx xxx zvoleny xxx, xxx xxx xxxxxx xxxxxxxx, xxx xxx xxx xxxxxx nevyšla xxxxx najevo kódovaná xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx xxxxx x xxx xxx odběr x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Xxx xxxxxxxxx xxxxxxxx xxxxx být xxxxxxx xxxxxxxx látky xx xxxxxx chemické xxxxx, xxxx-xx x dispozici. Xxxxxxxx látek xxx xxxxxxxxx kontrolu:

Látka	Číslo XXX	Xxxxx xxxxx XXXXXX
xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
xxxxxxxxx X	50–07–7	200–008–6
xxxxxxxxxxxxx	50–18–0	200–015–4
xxxxxxxxxxxxx xxxxxxxxxx	6055–19–2	200–015–4
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx	51–18–3	200–083–5

X okamžiku xxxxxxx odběru xx xxx být xxxxxxxx xxxxx u xxxxxxxxxxx xxxxxxx, xxxx je xxxxxxxxxx pouze rozpouštědlo xxxx xxxxxxxxx x xxx jinak podstupují xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, xxxxx xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx přijatelné xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx buněk x chromozomovými aberacemi. Xxxxxxx-xx xx xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxx xxxxxx. Xxxxx toho xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx kontrolní xxxxx xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

1.5 POSTUP

1.5.1 Xxxxx x xxxxxxx xxxxxx

Xxxxx xxxxxxxxxx a xxxxxxxxx xxxxxxx xx skládá x alespoň pěti xxxxxxxxxxxxxxxx zvířat xxx xxxxx pohlaví. Xxxxxxxx xxxx v xxxx xxxxxx k xxxxxxxxx xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx použití xxxxxxxx způsobu xxxxxxxx, xxx prokazují, že xxxxxxxxxx mezi xxxxxxxxx xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx specifická xxx xxxxxx xxxxxxx, xxxx xx tomu xxxxxxxxx x některých xxxxxxxxxxxxxxx xxxxx, měla xx xxx xxxxxxx xxxxxxxxx xx xxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx být xxxxx xxxxx xxxxxxxx xxxxxxxxxxx. Xxxxxxxx xxxxx xxxxx xxx podávány xxxx xx xxxx dávkách, xxx. dvě xxxxx x xxx xxx x xxxxxxx xx xxxx xxx několika xxxxx, xxx bylo xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx materiálu. Xxxx xxxxxx xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx.

Xxxxxx xx xxxx xxx odebrány xx xxxx xxxxxxx intervalech xx xxxxxxxx podané x jednom xxx. X xxxxxxxx xx xxxxx xxxxxxx po xxxxxx době od xxxxxxxx, xxxxx odpovídá 1,5xxxxxxx xxxxxxxx xxxxx xxxxxxxxx cyklu (jenž xxxx xxxxxxx 12 — 18 h). Xxxxxxxx xxxx xxxxxxxx xxx xxxxxx x xxxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx xxx xxxxxx xx xxxxxxxx xxxxxxxxx cyklu xxxx xxx vliv xx xxxxxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx, xxxxxxxxxx xx xxxxxxx xxxxx odběr xx 24 h od xxxxxxx odběru. Xx-xx xxxxxxxx xxxxxxxxx do xxxx xxx jednoho xxx, xxx xx xxx xxxxx xxxxxxxx xx xxxxxx době xx poslední xxxxxxxx, xxxxx xxxxxxxx 1,5násobku xxxxxxxx xxxxx xxxxxxxxx xxxxx.

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

1.5.3 Xxxxxxxxx

Xxxxxxx-xx xx xxxxx xxxxxxxxxxx vhodných dostupných xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx by xxx xxxxxxxxx ve xxxxxx xxxxxxxxxx, se stejným xxxxxx, xxxxxx, xxxxxxxx x xx xxxxxxxx xxxxxx expozice, xxx xx xxxxxxx x xxxxxx xxxxxx (5). X případě xxxxxxxx xx pro první xxxxx xxxxxxx tři xxxxxx dávky. Tyto xxxxxx xxxxx xx xxxx pokrývat xxxxxxx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru xxxxx, xxxx xxxx použita xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx dávka xxxxxxxxxxxx takové známky xxxxxxxx, že xxxxx xxxxx xx vedly xxx xxxxxxx xxxxxx xxxxxxxxx podle xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx nízkých xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx a mitogeny) xxxxxx kritériím xxxxxxxxx xxxxx xxxxxxxxx x xxxx by xxx xxxxxxxxx případ xx xxxxxxx. Xxxxxxxx dávka xxxx xxx xxxx xxxxxxxxxx jako xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. více xxx 50 % xxxxxxx mitotického xxxxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x jednou dávkou xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx xx xxxx dávkách v xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx toxické xxxxxx x xxxx-xx xx xxxxxxx xxxxx x látkách, které xxxx xxxxxxxx strukturu, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx xx úplná xxxxxx xx xxxxx úrovněmi xxxxx xx nezbytnou. X xxxx xxxxxxxxxx xxxxxx je xxxxxxx xxxxxx pro 14xxxxx xxxxxxxx 2000 xx/xx xxxxxxx hmotnosti/den x xxx xxxxx než 14xxxxx aplikaci xx xxxxxxx xxxxxx 1000 xx/xx tělesné hmotnosti/den. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx úroveň xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx nebo xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Jiné xxxxxxx xxxxxxxx xxxx x xxxxxxxxxxxx případech xxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxx xxxxx xxxxxxxxxxxxxx xxxx xxxxxxxx, xxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Objem xx xxxxx xxxxxxxxx 2 xx/100 g xxxxxxx xxxxxxxxx. Xxxxxxx xxxxxxx objemů, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx na xxxxxxxx x xxxxxx xxxxx, xxxxx xxxxxxx při xxxxxxx xxxxxxxxxxxxx vykazují xxxxxxxx xxxxxx, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx minimalizována xxxxxxxxxx koncentrace zajišťující xxxxxxxxxx xxxxx xxx xxxxx xxxxxxxx dávky.

1.5.6 Xxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxx

Xxxxx xx xxxxxxxx se xxxxxxx xxxxxx xxxx, hypotonizuje xx x fixuje. Xxxxx xx nanesou xx xxxxxxxx xxxxxxx x obarví xx.

1.5.7 Xxxxxxx

Xxxx měřítko xxxxxxxxxxxx xx měl být x xxxxx xxxxxxxxxxxx xxxxxx (xxxxxx xxxxxxxxxxx xxxxxxx) a x xxxxxxxxxxxxxx zvířat xxx xxxxxxxxx kontrolu xxxxxxxx xxxxxxxxx xxxxx, x xx alespoň u 1000 xxxxx na xxxxx xxxxx.

X xxxxxxx xxxxxxx by xxxx xxx xxxxxxxxxxx alespoň 100 xxxxx. Xxxxx xxxxx xxx snížit, xx-xx xxxxxxxxx xxxxx xxxxx aberací. Xxxxxxx xxxxxxxxx xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx xx xxxx xxx před xxxxxxxxxxxxxx xxxxxxxx nezávisle xxxxxxxx. Xxxxxxx xxx xxxxxx často dochází xx chromozomálním xxxxxx xxxx xx xxxxxx xxxxxxxxxx x části xxxxx v xxxxxxxx, xxxx by vyšetřované xxxxx xxxxxxxxx xxxxxxxxxx x xxxxx odpovídajícímu xxxxx 2 n ± 2.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro xxxxxxxxxx zvířata by xxxx xxx zpracovány xx xxxxx xxxxxxx. Xxxxxxxxxxxxxx xxxxxxxxx je xxxxx. Xxx každé xxxxx xx xxx xxx xxxxxxxxxx počet xxxxx, xxxxx xxxxxxx xx xxxxx x xxxxx xxxxx x xxxxxxxxxxxxx aberací (xxxxxxxxxxxxxx xxxxxxxxx) xxxxxxxxx x xxxxxxxxxx. Xxx exponované x kontrolní xxxxxxx xx xxxx xxx xxxxxxx xxxxx xxxx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxx x jejich počtem x xxxxxxxx. Gapy xx xxxxxxxxxxxxx xxxxxxxx x uvádějí xx, xxx obecně se xxxxxxxxxx xx xxxxxxx xxxxxxxx aberací. Xxxxxxxxxx-xx xxxxx o xxxxxxx x odpovědi mezi xxxxxxxxx, mohou xxx xxx xxxxxxxxxxxx analýzu xxxxx xxx obě xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X INTERPRETACE VÝSLEDKŮ

Pro xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx relativního xxxxx buněk x xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxx na xxxxx xxxx xxxxx nárůst xxxxx buněk x xxxxxxxxx pro xxxxxxx x xxxxxxx xxxxxx 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 xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Dvojznačné xxxxxxxx xx měly xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxx polyploidie xxxx xxxxxxxx, že xxxxxxxx látka má xxxxxxxxx indukovat xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxxxxxxx chromozomy xxxx xxxxxxxx, že zkoušená xxxxx má potenciál xxxxxxxx xxxxxxxx xxxxxxxxx xxxxx (7, 8).

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

Xxxxxx většina xxxxxxxxxxx xxxxxxxx jasně xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x xxxxxxxxxxx xxxxxxxxx neumožní xxxxxx xxxxx vyslovit konečný xxxxx o xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx dvojznačné xxxx sporné bez xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx zkoušky xx xxxxxxxxxxxx xxxxxxx xx xxxx xxxxxxxxx, xx xxxxxxxx látka xxxxxxxx x kostní xxxxx testovacího xxxxx xxxxxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka xx xxxxxxxx xxxxxxx xxxxxxxxxx x kostní dřeni xxxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxx.

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

3. ZPRÁVY

PROTOKOL O XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x xxxxxxx xxxxxx,

- xxxxx, xxxxxxxx chovu, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat na xxxxxxx xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx podmínky:

- xxxxxxxxx x negativní (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

- údaje xx xxxxxx xxx xxxxxxxx rozsahu, xxxxx xxxx provedena,

- xxxxxxxxxx xxxxxxxxx xxxxxx xxxxx,

- xxxxx x přípravě xxxxxxxx látky,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- popřípadě xxxxxx xxxxxxx, xxx xx xxxxxxxx xxxxx xxxxxxx xx krevního xxxxx xxxx do xxxxxx xxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx xxxxxx x xxxx,

- xxxxxxxx popis xxxxxxx expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

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

- xxxxxx xxxxxxxx xxxxxxxxx,

- kritéria hodnocení xxxxxxx,

- xxxxx xxxxxxxxxxxxx xxxxx xx jedno xxxxx,

- xxxxxxxx xxxxxxxxxxx xxxxxx xx xxxxxxxxx, xxxxxxxxx nebo dvojznačnou.

Výsledky:

- xxxxxx xxxxxxxx,

- xxxxxxxxx xxxxx,

- xxx x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx pro xxxxx xxxxx,

- celkový xxxxx xxxxxxx xx xxxxxxx xx xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami,

- xxxxx buněk x xxxxxxxxx ve xxxxxxx xx xxxxxxxxx xxxxxxxxx x xxxxxxxxxxxx odchylkami,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx,

- podle xxxxxxxx xxxxxxxxx odpovědi xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx x xxxxxxxx negativní xxxxxxxx,

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

- údaje x xxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

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

3) Xxxxxxx, X., Chandley, X., Xxxxx, X., Xxxxxxxxx, X. X., Xxxxxxx, X., Henderson, L. (1990), In vivo Xxxxxxxxxxx Xxxxxx, xx: X. J. Xxxxxxxx (xx.), Basic Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx. XXXXX Sub-Committee xx Guidelines xxx Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx I xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, Xxx York, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 115-141.

4) Xxxx, X. R., Xxxxxxx, X., MacGregaro, X. X., Anderson, X., Xxxxxx, X. X., Xxxxxx, H. E., Xxxxxx-Xxxxxxx, M., Oleson Xx., F. X., Xxxxxxxxxxxx, X., Xxxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Xxxxx, X., Xxxxxxx, X. (1994), Xxxxxx xxxx the Xxxxxxx Xxxxx xx xxx xx xxxx Xxxxxxxxx Xxxx Marrow Xxxxxxxxxxx Xxxxxxxxxx Xxxx, Mutatation Xxx., 312, 305-312.

5) Xxxxxxx, R. J., Xxxxx, X. X., Xxxxxx, X. R., Xxxxxx, X. A., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. X., Hodson-Walker, X., Xxxxxx, X. X., Xxxxxxxx, D. X., Xxxxxxx, X. (1992), Xxxxxx xx Xxxxxxx Toxicology Xxxxxxx/XX Xxxxxxxxxxxxx Mutagen Society Xxxxxxx Xxxxx: Dose Xxxxxxx in Xx xxxx Xxxxxxxxxxxx Assays, Xxxxxxxxxxx, 7, 313-319.

6) Xxxxxx, D. X., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, G., Xxxxxxxx, X., Xxxxxxx, X., Papworth, X. X., Xxxxxx, J. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx xx Xx xxxx Xxxxxxxxxxx Xxxxxx, xx: UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Xxxxxx Part XXX. Xxxxxxxxxxx Evaluation of Xxxxxxxxxxxx Test Xxxx, X. X. Xxxxxxxx (xx.) Cambridge Xxxxxxxxxx Xxxxx, Cambridge, 184-232.

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

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

PŘÍLOHA 4X

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

1. METODA

Tato xxxxxx xx replikou xxxxxx XXXX TG 474 — Xxxx xxxxxxx xxxxxxxxxxxxxxx mikrojader xx xxxx (1997).

1.1 XXXX

Xxxx savčích xxxxxxxxxxxxxxx xxxxxxxxxx xx xxxx xx xxxxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxx aparátu xxxxxxxxxxxx, xxxxx xx xxxxxxxxxx xxxxxxxxx látkou, x xx xxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxx x xxxxxx xxxxx x/xxxx xxxxx xxxxxxxxx xxxx, xxxxxxx hlodavců.

Účelem xxxxx xxxxxxx erytrocytárních xxxxxxxxxx je xxxxxxxxxxxxx xxxxx, které xxxxxxxxx xxxxxxxxxxxxx xxxxxxxxx, jehož xxxxxxxxx je xxxxxx xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xx (xxxxxxx) xxxxxxxxxxxx xxxxxxxxx xxxx xxxx xxxxxxxxxx.

Xxxx xx erytroblast xxxxxx xxxxx xxxx xx polychromatický xxxxxxxxx, xxxxxx xxxxx xx xxxxxxxx x xxxxxxxxxx, xxxxx xxx xxx xxxxx vzniknout, xxxxxxxxx x cytoplasmě, xxxxx xxxxx jádra neobsahuje. Xxxxxxxxxxxx xxxxxxxxxx je x těchto xxxxxxx xxxxxxxxx xxx, xx xxxxxxxxxx xxxxxx xxxxx. Xxxxxx výskytu polychromatických xxxxxxxxxx x xxxxxxxxxx x exponovaných xxxxxxxxx xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxxx poškození.

V tomto xxxxx xx rutinně xxxxxxxxx xxxxxx xxxx xxxxxxxx, xxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxxxxxxxxx xxxxxxxxxx. Stanovení xxxxxxxxx (xxxxxxxxxxxxxxxxx) erytrocytů s xxxxxxxxxx v xxxxxxxxx xxxx xx xxxxxxxxxx xxxxxxxxxx u xxxxxxxxxxx xxxxx, u xxxxx xxxx prokázána xxxxxxxxxxx xxxxxxx odstraňovat erytrocyty x xxxxxxxxxx, xxxx xxxxxxxxxx citlivost xxxxxxxxx xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx nebo xxxxxxxxx xxxxxxxxxxxx xxxxxxx. Mikrojádra xxx xxxxxxxx xxxxx xxxxxxxx. Xx xxxxxxxx xxxxxxxxxxxx přítomnosti nebo xxxxxxxxxxxxx centromerní (kinetochorní) XXX x xxxxxxxxxx. Xxxxxxxxx xx zejména xxxxxxx xxxxxxxxx (xxxxxxxxxxxxxxxxx) xxxxxxxxxx x mikrojádry. Xxxxx xxxxxxx (normochromatických) xxxxxxxxxx x xxxxxxxxx xxxx, xxxxx xxxxxxxx xxxxxxxxxx, připadající na xxxxxx xxxxx xxxxxxx xxxxxxxxxx lze xxxxxx xxxxxx jako xxxxxxx xxxxxxxx xxxxxxx, xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxx týdny xxxx xxxx.

Xxxxx test savčích xxxxxxxxxxxxxxx mikrojader xx xxxx xx zvláště xxxxxx k posouzení xxxxxxxxx mutagenese, xxxxx xxxxxxxx xxxxxxxxx faktory xxxxxxxxxxx in vivo, xxxxxxxxxxxxxxx x xxxxxxx xxxxxxxx XXX, xxxxxxx xx mohou xxxxx x xxxxxxx xxxxx x xxxxx, jakož x x xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxx je rovněž xxxxxxxx xxx xxxxx xxxxxx xxxxxxxxxxx účinků xxxxxxxxxx v xxxxxxxxx xx xxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx xxxxx xxxx xxxxxxxxx xxxxxxxxxx xxxxxxxxxx do xxxxxx xxxxx, není xxxxxx tuto xxxxxxx xxxxxx.

Xxx xxxx Obecný xxxx, část X.

1.2 XXXXXXXX

Xxxxxxxxxx (xxxxxxxxxx) : xxxxxx (xxxxxxx) xxxxxxxxxx, x xxx (k xxxx) xx během xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx umožňující xxxxxxxxxx pohyb dceřiných xxxxxxxxxx k xxxxx xxxxxxxxx xxxxx.

Xxxxxxxxxx : xxxx xxxxx existující xxxxxxxx xx xxxxxxxx xxxxx a xxxxx xxxx, xxxxxxxxx během xxxxxxxx mitosy (xxxxxx) xxxxxxxxxxxxxxx xx (lagging) xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxx chromozomy.

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

Xxxxxxxxxxxxxxx xxxxxxxxx : xxxxxxx xxxxxxxxx ve xxxxxxxxx mezistadiu, xxxxx xxxxx obsahuje ribozomy, x může xxx xxxx xxxxxxxx od xxxxxxx normochromatických erytrocytů xxxxxxxx xxxxxxxxxxx xxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx se xxxxxxx xxxxxxxx xxxxxxx zkoušené xxxxx. Xxx použití xxxxxx dřeně xx xxxxxxx xx xxxxxxx xxxxxxxx po xxxxxxxx xxxxxx, odebere se xxxxxx xxxx, xxxxxxxx xx preparáty a xxxxxx xx (1, 2, 3, 4, 5, 6, 7). Xxx xxxxxxx xxxxxxxxx xxxx xx xxxx xx xxxxxxx okamžiku xx xxxxxxxx odebere, xxxxxxxxxx xx připraví xxxxxxxx x obarví xx (4, 8, 9, 10). Xxx xxxxxxxx x periferní xxxx by xxxx xxxx xxxxxxxx xxxxxxxx x xxxxxxxxx xxxxx xxxxxxxx xx xxxxxxxxx xxxx. Preparáty xxxx xxxxxxxxxxx xx přítomnost xxxxxxxxxx.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx xxxxx xxxxxxx

Xxx použití xxxxxx xxxxx xx xxxx xxxxxxxxx xxxxx xxxxxxxxxx xxx xxxx xxxxxx, xxxxxx xxx xxxxxx xxxxxxxx xxxxxx xxxxx xxxx. Xxx xxxxxxx xxxxxxxxx xxxx xx doporučuje myš. Xxx xxxx xxxxxx xxxxxxxx xxxxxx druh xxxxx xx xxxxxxxxxxx, xx xxx x xxxx, x něhož xxxxxxx neodstraňuje xxxxxxxxxx x mikrojádry, nebo xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx detekovat xxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx xxxx numerické xxxxxxxxxxxx xxxxxxx. Xxxx xx xxx použity běžně xxxxxxx laboratorní xxxxx xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. V xxxxxxxx xxxxxxxx studie xx měla být xxxxxxxx v hmotnosti xxxxxx minimální x xxxxxx by u xxxx xxxxxxx xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

Xxxxx obecné xxxxxxxx xxxxx xxxxxxxx xxxxx x části B, xxxxxxx by mělo xxx xxxxxxxx xxxxxxxx xxxxxxx 50 – 60 %.

1.4.1.3 Příprava xxxxxx

Xxxxxx xxxxx pohlavně xxxxxxx xxxxxxx se xxxxxxxx xxxxxxx xxxxxxx xx kontrolní xxxxxxx x xxxxxxx, x xxx xx provede xxxxxxxx. Xxxxxxx se xxxxxxxxxxx identifikují. Nechají xx v xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx xxx aklimatizovat. Xxxxx xx xxxxxxxxxx xxx, xxx xxx xxxx xxxxxx polohy xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx xxxxxxxx xxxxx xx xxxx xxx před aplikací xxxxxxxx xxxxxxxxxx nebo xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x popřípadě zředěny. Xxxxxxx zkoušené xxxxx xxxxx být xxxxxxxx xxxxx nebo xxxxx xxx xxxx podáním xxxxxxx. Xxxx by xxx použity čerstvě xxxxxxxxxx zkoušené chemické xxxxx, pokud údaje x xxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxx skladování.

1.4.2 Xxxxxxxx podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx toxické xxxxxx x xxxx xx xxx vyloučeno podezření, xx xxxxxxx se xxxxxxxxx xxxxxx. Jsou-li xxxxxxx jiná než xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit xxxxxxx xxxxxxx rozpouštědel/vehikul.

1.4.2.2 Xxxxxxxx

Xxxxxxxx každého xxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx/xxxxxxxxx) kontroly xxx xxx pohlaví. S xxxxxxxx aplikace xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx identický proces xxxx zvířata ve xxxxxxxxx, v xxxxx xxxxx x expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx in xxxx xxx expozičních xxxxxxxx, x xxxxx xx xxxxxxx, xx xxxxxxxxx detekovatelný xxxxxx xxx pozadí. Dávky xxxxxxxxx kontroly xx xxxx xxx xxxxxxx xxx, xxx xxx xxxxxx zřetelný, ale xxx při odečtu xxxxxxx ihned najevo xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx, aby xxxxxxxxx kontrola xxxx xxxxxxxx xxxxx xxxxxxxx xxx xxxxxxxx xxxxx x aby byl xxxxx x xxxxx xxxxxxx xxxxxxxx xxx xxxxxx. Pro xxxxxxxxx xxxxxxxx xxxxx může xxx vzato x xxxxx použití xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou-li x xxxxxxxxx. Příklady xxxxx xxx pozitivní xxxxxxxx:

Xxxxx	Xxxxx CAS	Číslo xxxxx XXXXXX
xxxxx-xxxxxxxxxxxxxx	62–50–0	200–536–7
1-xxxxx-1-xxxxxxxxxxxxxxx	759–73–9	212–072–2
xxxxxxxxx C	50–07–7	200–008–6
cyklofosfamid	50–18–0	200–015–4
cyklofosfamid xxxxxxxxxx	6055–19–2	200–015–4
2,4,6-xxxx(xxxxxxxx-1-xx)- 1,3,5-xxxxxxx	51–18–3	200–083–5

X xxxxxxxx xxxxxx xx měl xxx xxxxxxxx xxxxx u xxxxxxx xxxxxxxxx kontroly, xxxxx xx xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxx xxxxx podstupuje xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxxxx údaje o xxxxxxxxxxx xxxxxx x xxxxxxxx buněk x xxxxxxxxxx. Provádí-li se xxx xxxxxxxxx xxxxxxxx xxxxx xxxxx, xx xxxxxxxxxxxxx okamžikem doba xxxxxxx odběru. Xxxxx xxxx by xxxx xxx neexponované kontroly xxxxxxx xxxx xxxxx, xxxxxxxxxx-xx xxxxx xxxx xxxxxx-xx publikovány kontrolní xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx/xxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx xxxxxxxxx xxxxxx.

Xxx xxxxxxx xxxxxxxxx xxxx může xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxx xxxx odebraný xxxx expozicí, pouze xxxx u xxxxxxxx xxxxxx x xxxxxxxxx xxxx (xxxx. 1 — 3 xxxxxxxx) xx předpokladu, že xxxxxxxx xxxxx xxxxx x xxxxxxx, xxxxx xx xx xxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxx.

1.5 XXXXXX

1.5.1 Xxxxx x xxxxxxx zvířat

Každá xxxxxxxxxx x kontrolní xxxxxxx xx xxxx skládat x alespoň pěti xxxxxxxxxxxxxxxx xxxxxx xxx xxxxx xxxxxxx (11). Xxxxxxxx jsou x xxxx xxxxxx k xxxxxxxxx údaje xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx způsobu xxxxxxxx, xxx xxxxxxxxx, xx neexistuje mezi xxxxxxxxx rozdíl x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx xx xxx xxxxxxx xxxxxxxxx se xxxxxxxx xxxxxxxxxxxxxx pohlaví.

1.5.2 Xxxx xxxxxxxx

Xxxxx doporučit xxxxx xxxxxxxxxx plán (xx. xxxxx, xxx xxxx tři xxxxxxxx x xxxxxxxxx 24 xxxxx). Xxxxxx ze xxxxxx x prodlouženým xxxxxxx xxxxxxxx xxxx xxxxxxxxxx, xxxxx xx x těchto xxxxxx xxxxxxx xxxxxxxxx výsledky, xxxx –v xxxxxxx xxxxxxxxxxx xxxxxx — xxxxx xxxx prokázána xxxxxxxx nebo xxxx xxxxxxxxx xxxxxxx dávka x xxxxxxxx xxxxxxxxx xx do xxxxxxxx xxxxxx. Xxxxxxxx xxxxx xxxxx být xxxxxxxx xxxx ve dvou xxxxxxx, xxx. dvě xxxxx v xxx xxx v rozmezí xx xxxx xxx xxxxxxxx hodin, xxx xxxx xxxxxxxxx podávání xxxxxxx objemů materiálu.

Test xxxx xxx xxxxxxxx xxxxx způsoby:

a) xxxxxxxx xxxxx se aplikuje xxxxxxxx jednou. Xxxxxx xxxxxx dřeně xx xxxxxxxx alespoň dvakrát, xxxxxxx xxxxx xxxxx xx provede xxxxxxxx 24 xxxxx xx xxxxxxxx x xxxxxxxx xxxxxxxxxx 48 xxxxx xx aplikaci x x přiměřeným odstupem xxxx odběry. Xxxxx xxxxx xxx 24 xxxxx xx aplikaci xxxx xxx xxxxxxxxx. Xxxxxx periferní xxxx xx xxxxxxxx alespoň xxxxxxx, xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxxx 36 hodin xx xxxxxxxx a xxxxxxxx xxxxxxxxxx 72 xxxxx po xxxxxxxx x xx prvnímodběru xx dodrží xxxxxxxxxxxx xxxxxx. Xx-xx xx xxxxxx odběru pozorována xxxxxxxxx odpověď, xxxx xxxxx odběr xxxxx;

x) xxxx-xx xxxxxxxx xxx xxxx xxxx xxxxx xxxxx (např. dvě xxxx xxxx xxxxx x xxxxxxxxx 24 xxxxx), xxxx xx xxx vzorky při xxxxxxx kostní xxxxx xxxxxxxx xxxxxx xx 18 xx 24 xxxxxxxx po xxxxxxxx xxxxxxxx x xxx xxxxxxx xxxxxxxxx xxxx xxxxxx xx 36 xx 48 xxxxxxxx xx xxxxxxxx xxxxxxxx (12).

Xxxxx potřeby xxxxx xxx xxxxx xxxxxxx xxxx xxxx xxxxxx.

1.5.3 Xxxxxxxxx

Xxxxxxx-xx se xxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxx xxxxxx xxx xxxxxxxx xxxxxxx xxxxx, xxxx xx být xxxxxxxxx xx xxxxxx xxxxxxxxxx, se stejným xxxxxx, kmenem, xxxxxxxx x xx xxxxxxxx xxxxxx xxxxxxxx, xxx xx použijí x xxxxxx xxxxxx (13). X případě xxxxxxxx xx pro první xxxxx xxxxxxx tři xxxxxx xxxxx. Xxxx xxxxxx dávky xx xxxx pokrývat xxxxxxx xxxx maximální xx xxxxxxxxx xxxxxxxxx, případně xxxxxx xxxxxxxxx. Při xxxxxxxxx xxxxxx xxxxx, xxxx bude použita xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx xx xxxxxxxxxx jako dávka xxxxxxxxxxxx takové xxxxxx xxxxxxxx, xx xxxxx xxxxx xx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxx (např. xxxxxxx a mitogeny) xxxxxx xxxxxxxxx xxxxxxxxx xxxxx vyhovovat a xxxx by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Nejvyšší xxxxx xxxx být také xxxxxxxxxx jako xxxxx xxxxxxxxxxxx v xxxxxx xxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx xxxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx v xxxxxx xxxxx nebo x xxxxxxxxx xxxx).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s xxxxxx xxxxxx o xxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx xxxx ve xxxx dávkách x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx x není-li xx xxxxxxx xxxxx x xxxxxxx, které xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, není xxxxxxxxxx úplná xxxxxx xx xxxxx úrovněmi xxxxx xx nezbytnou. X xxxx trvajících xxxxxx xx xxxxxxx xxxxxx xxx 14xxxxx xxxxxxxx 2000 mg/kg xxxxxxx xxxxxxxxx/xxx x xxx delší xxx 14xxxxx xxxxxxxx xx xxxxxxx dávkou 1000 xx/xx xxxxxxx hmotnosti/den. Xxxxxxxxx xxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxx xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx obvykle xxxxxx xxxxxxxxxxxxxx, žaludeční xxxxxx xxxx xxxxxxx xxxxxxxxx xxxxxxx, nebo xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx podávání jsou xxxxxxxxxx x odůvodnitelných xxxxxxxxx. Xxxxxxxxx objem xxxxxxxx, xxxxx xxxx xxx najednou xxxxx xxxxxxxxx sondou nebo xxxxxxxx, xxxxxx xx xxxxxxxxx testovacího xxxxxxx. Xxxxx xx neměl xxxxxxxxx 2 xx/100 x tělesné xxxxxxxxx. Xxxxxxx xxxxxxx xxxxxx, xxx xx xxxxxxx xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x žíravé xxxxx, xxxxx obvykle xxx vyšších xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxx xxxxx xxxx xxxx

Xxxxx xxxxxx xxxxx se xxxxxxx xxxxxxxxx x xxxxxx nebo xxxxx xxxxx xx usmrcení. Xxxxx xx odeberou x femuru xxxx xxxxx a xxxxxxxxxx xxxxxxxx xx xxxxxxxxx x obarví. Xxxxxxxxx xxxx xx xxxxxxx x ocasní žíly xxxx xxxx xxxxxx xxxxxx cévy. Xxxxxx xxxxx se xxxxx xxxxxxxxxxxx xxxxxx (8, 9, 10), nebo xx xxxxxxxx xxxxxxxxx xxxxxxxx x poté xx xxxxxx. Použitím xxxxxxx specifického xxx XXX (xxxx. xxxxxxxxxx xxxxx (14) xxxx Xxxxxxx 33258 a xxxxxxx-X (15)) se xxx vyhnout xxxxxxxx xxxxxxxxxx xxxxxxxx x xxxxxxxx barviva nespecifického xxx XXX. Xxxx xxxxxx xxxxxxx použití xxxxxxxxxxx xxxxxx (xxxx. Xxxxxx). Přídavné systémy (xxxx. xxxxxxxxxx xxxxxx x xxxxxxxxxx xxxxx xxxxxxxxxxxx xxxxx (16)) xxx xxxxxx xx xxxxxxxxxxx, že se xxxxxxxxx xxxxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxx pro xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx.

1.5.7 Xxxxxxx

Xxx xxxxx xxxxx xx xxxxxxx xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx (xxxxxxx + xxxxx) množství xxxxxxxxxx, přičemž se x xxxxxxx kostní xxxxx xxxxxxx celkově xxxxxxx 200 xxxxxxxxxx x x xxxxxxx xxxxxxxxx krve xxxxxxx 1000 xxxxxxxxxx (17). Xxxxxxx xxxxxxxxx xxxxxx xxxxxxxxx pozitivních x xxxxxxxxxxx xxxxxxx, xx xxxx xxx xxxx xxxxxxxx xxx xxxxxxxxxxx xxxxxxxxx xxxxxxxx. X xxxxxxx xxxxxxx xx xxxxxxx xxxxxxx 2000 xxxxxxxxx xxxxxxxxxx na xxxxxx xxxxxxxxxx x xxxxxxxxxxxxxxxxxxxxx. Xxxxx xxxxxxxxx xxxxx být xxxxxxx xxxxxxxxxx zralých xxxxxxxxxx xx výskyt xxxxxxxxxx. Xxx xxxxxxxxxxxxx xxxxxxx xx xxxxx xxx xxxxx xxxxxxxxx erytrocytů x xxxxxxxxx xxxxxxxx xxxxxxxxxx menší xxx 20 % xxxxxxxxx xxxxxxx. Xxxxxxxx jsou xxxxxxx xxxxxxxxxx nepřetržitě xxxxx xxxxx nebo xxxx, xxx xxxx xxxxxxxx xx výskyt xxxxxxxxxx xxxxxxx 2000 xxxxxxx xxxxxxxxxx xx xxxxx zvíře. Xxxxxxx xxx xxxxxxxxxxxx analýzu (xxxxxxx xxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxx) xxxx xx xxxxxxxxxxxxx xxxxxxxxxx x xxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxx.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xxx xxxxxxxxxx xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx xxxxxxx. Experimentální xxxxxxxxx xx xxxxx. Xxx xxxxx analyzované zvíře xx měl být xxxxxx počet vyšetřených xxxxxxxxx xxxxxxxxxx, xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxxx x xxxxx xxxxxxxxx xxxxxxxxxx x xxxxxxxxx množství xxxxxxxxxx. Xxxxxxxx xxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxx čtyři xxxxx xxxx xxxx, xxxx xx xxx xxxx xxxxxxx xxxxx x xxxxxxx erytrocytech, xxxx-xx xxxxxxxxxxxxx. Xxx xxxxx xxxxx se xxxxx xxxxx xxxxxxxxx xxxxxxxxxx x celkového xxxxxxxx erytrocytů x xxxxxxxx xxxxxxxx xxxxxxxxxx x xxxxxxxxxx vyjádřené x xxxxxxxxxx. Neexistuje-li xxxxx o xxxxxxx x xxxxxxxx xxxx xxxxxxxxx, xxxxx být xxx statistickou analýzu xxxxx pro xxx xxxxxxx xxxxxxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx pozitivního xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx s mikrojádry x xxxxxxxxxx xx xxxxx nebo xxxxx xxxxxx počtu xxxxx x xxxxxxxxxx xxx xxxxxxx x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Xxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx výsledků. Xxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx xxxx pomocný xxxxxxxxxx xxxxxxxxxxx xxxxxx (18, 19). Statistická xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx xxx vyjasněny xxxxxx zkoušením, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx.

Xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxx xxxx xxxxxxx kritéria, xx xxxxxxxx v xxxxx xxxxxxx xx nemutagenní.

Ačkoli xxxxxxx xxxxxxxxxxx poskytne xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, v xxxxxxxxxxx případech neumožní xxxxxx xxxxx xxxxxxxx xxxxxxx xxxxx o xxxxxxxx xxxxxxxx látky. Xxxxxxxx mohou zůstat xxxxxxxxxx nebo xxxxxx xxx xxxxxx na xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx výsledky xxxxx xx mikrojádra xxxxxxxxx, že zkoušená xxxxx xxxxxxxx xxxxxxxxxx, xxx xxxx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx xxxx xxxxxxxxx mitotického aparátu xxxxxxxxxxxx testovacího druhu. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená látka xx podmínek xxxxxxx xxxxxxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxx xxxxx.

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

3. ZPRÁVY

PROTOKOL X XXXXXXX

Xxxxxxxx x zkoušce xxxx xxxxxxxxx tyto xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- xxxxx, xxxxx x xxxxxxx xxxxxx,

- xxxxx, podmínky xxxxx, xxxxxx xxx.,

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

Xxxxxxxx xxxxxxxx:

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

- xxxxx xx xxxxxx xxx zjištění xxxxxxx, pokud xxxx xxxxxxxxx,

- zdůvodnění zvolených xxxxxx xxxxx,

- údaje x xxxxxxxx zkoušené xxxxx,

- údaje x xxxxxxxx xxxxxxxx xxxxx,

- xxxxxxxxxx způsobu podávání,

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

- xxxxxxxx xxxxxxxx mezi xxxxxxxxxxx xxxxxxxx xxxxx x xxxxxx nebo xxxx (xxx) xx xxxxxxxxxxxx dávku (xx/xx xxxxxxx xxxxxxxxx/xxx),

- xxxxxxxx xxxxx x kvalitě xxxxxx a xxxx,

- xxxxxxxx xxxxx rozvrhu xxxxxxxx x xxxxxx,

- xxxxxx xxxxxxxx preparátů,

- xxxxxx xxxxxxxxx xxxxxxxx,

- xxxxxxxx hodnocení xxxxxxxxxx x xxxxxxxxx erytrocytech,

- xxxxx analyzovaných buněk xx jedno zvíře,

- xxxxxxxx klasifikace studie xx pozitivní, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- podíl nezralých xxxxxxxxxx x xxxxxxxxx xxxxxxxx xxxxxxxxxx,

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

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx xxxxxxxxxxx xxxxxxx x xxxxxx,

- údaje x xxxxxxxx a xxxxxxxxx xxxxxxxxx kontrole,

- xxxxx x souběžné xxxxxxxxx xxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Heddle, X. X. (1973), A Xxxxx Xx xxxx Xxxx xxx Xxxxxxxxxxx Xxxxxx, Xxxxxxxxxx Res., 18, 187-190.

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

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

4) Xxxxxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxxxx, M. X., Xxxxxx, X. X. (1990), Xxx In xxxx Xxxxxxxxxxxx Assay xx Mammalian Bone Xxxxxx xxx Peripheral Xxxxx. X xxxxxx xx the X. X. Xxxxxxxxxxxxx Xxxxxxxxxx Xxxxxx Gene-Tox Xxxxxxx, Xxxxxxxxxx Xxx., 239, 29-80.

5) MacGregor, X. X., Xxxxxxxx, R., Xxxx, W. N., Xxxx, X. M. (1983), Xxxxxxxxxxx xx Xxxxxxxxxxx Xxxxxxxxxxxx: X Xxxxx Xxxxxx for Xxxxxxxxxxx Xxxxxx Xxxxxx Xxxxxxx Xxxxxxxx Xxxxxxx xx Xxxx, xx: Xxxxxxxxxxxx xx Xxxxxxx xxx Practice xx Xxxxxxxxxx, ed. X. X. Xxxxx, R. X. Schnell, X. X. Xxxx. Xxxxxxxx, Xxxxxxxxx, 555-558.

6) XxxXxxxxx, X. T., Xxxxxx, X. X. Xxxx, X., Xxxxxxxx, X. X., Xxxxx, C., Xxxxxxxx, X. X., Xxxx, X. X., Xxxx, D. (1987), Xxxxxxxxxx xxx xxx Xxxxxxx xx Xxxxxxxxxxxx Xxxxxx xx Mammalian Xxxx Xxxxxx Erythrocytes, Xxxxxxxxxx Xxx., 189, 103-112.

7) XxxXxxxxx, J. X., Xxxx, C. X., Henika, P. X., Shelby, M. X. (1990), The xx xxxx Erythrocyte Xxxxxxxxxxxx Xxxx: Xxxxxxxxxxx xx Steady Xxxxx Xxxxxxxxx Xxxxx Efficiency xxx Xxxxxxx Xxxxxxxxxxx xxxx Xxxxxxxx Xxxxxxx, Xxxxxx. Appl. Toxicol. 14, 513-522.

8) Xxxxxxx, X., Xxxxxx, X., Xxxxxx, X., Xxxxxx, X., Ishidate, X. Xx. (1990), Xxx Xxxxxxxxxxxx Xxxxx xxxx Xxxxx Xxxxxxxxxx Xxxxx Xxxxxxxxxxxxx Using Acridine Xxxxxx-Xxxxxx Slides, Xxxxxxxxxx Xxx., 245, 245-249.

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

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

11) Xxxxxxx, M., Tice, X. X., XxxXxxxxx, X. T., Anderson, X., Xxxxxxx, X. X., Xxxxxx-Xxxxxxx, X., Xxxxxx, Xx. F. X., Pacchicrotti, F., Xxxxxxx, F., Shimada, X., Sutou, X., Xxxxxxx, B. (1994), Xx vivo Xxxxxx Xxxxxxxxxxx Xxxxxxxxxxxx Xxxxx, Xxxxx. Res., 312, 293-304.

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

13) Xxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Botham, X. X., Xxx, X., Xxxxxxx, X. X., Xxxxxxxxx, X. G., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Xxxxxxxx, X. X., Rochold, X. (1992), Xxxxxx xx Xxxxxxx Xxxxxxxxxx Xxxxxxx/XX Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Working Xxxxx: Xxxx Setting in Xx xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

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

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

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

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

18) Richold, X., Xxxxx, X., Xxxxxxx, X., Chandley, X., Xxxxxxxxx, D. X., Xxxxxxxxx, X. (1990), In xxxx Xxxxxxxxxxxx Xxxxx, in: X. J. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx xxxxx, XXXXX Xxxxxxxxxxx Xxxxxxxxxx, UKEMS Xxx-Xxxxxxxxx xx Xxxxxxxxxx for Xxxxxxxxxxxx Xxxxxxx. Xxxxxx, Xxxx 1, xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Press, Xxxxxxxxx, New York, Xxxx Chester, Melbourne, Xxxxxx, 115-141.

19) Lovell, X. P., Xxxxxxxx, X., Albanese, R., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx X., Richold, X., Xxxxxxxx, X. X., Xxxxxx, X. R. X. (1989), Xxxxxxxxxx Xxxxxxxx xx Xx xxxx Cytogenetic Xxxxxx, xx: X. J. Xxxxxxxx (xx.), Statistical Xxxxxxxxxx xx Xxxxxxxxxxxx Xxxx Xxxx. XXXXX Xxx-Xxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx, Part III, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, New Xxxx, Xxxx Chester, Xxxxxxxxx, Xxxxxx, 184-232."

PŘÍLOHA 4X

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

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 471 — Xxxxxxx xx xxxxxxxx mutace s xxxxxxxxxx (1997).

1.1 XXXX

Xxx xxxxxxx xx reverzní xxxxxx x xxxxxxxxxx xx xxxxxxxxx bakteriální xxxxx závislé xx xxxxxxxxxxxxxxx Salmonella xxxxxxxxxxx x Xxxxxxxxxxx xxxx, x xxxxxxx bodových xxxxxx, xxxxx xxxxxxxx xxxxxxxxxx, xxxxx x xxxxxx xxxxxxx nebo xxxxxxxx xxxx xxxx XXX (1, 2, 3). Xxxxxxxx této xxxxxxx na reverzní xxxxxx s bakteriemi xxxxxxx x xxxxxxx xxxxxx, xxxxx revertují xxxxxx xxxxxxxx x xxxxxxxxxxx kmenech a xxxxxxxx tak xxxxxxx xxxxxxxxx bakterií syntetizovat xxxxxxxxxx aminokyseliny. Xxxxxxxx xx xxxxxxx jsou xxxxxxxxxx xxxx xxx xxxxxxxxxx růst x xxxxxxxxxxxxx xxxxxxxxxxxx, které xxxx xxxxxxxxxx mateřským xxxxxxxxxx kmenem.

Bodové xxxxxx x podobné xxxx xxxx xxxxxxxx mnoha xxxxxxxxx xxxxxxxxxxx chorob x člověka a xxxxxxxx xxxxx důkazů x xxx, xx xxxxxx xxxxxx x xxxxxxxxxx a x xxxxxx xxxxxxxxxxx buněk xxxxxxxxx nádory mají xxxxx xx xxxxxx xxxxxxxx x člověka x u xxxxxxxxx xxxxxx. Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxx, xxxxxxxxxx x xxxxxxxxx xxxxxx. Mnoho xxxxxxxxxxx xxxxx xx řadu xxxxxxxxxx, xxxx nimž xxxx xxxxxxxxxx xx xxxxxxx xxxxxx, xxxxxx xxxxxxxxxxxxx xxxxxxxx XXX xx xxxxxxxxxx xxxxxxx, xxxxxxx permeability xxxxx xxx xxxxx xxxxxxxx x xxxxxxxxx reparačních xxxxxxx XXX xxxx xxxxxxxx xxxxxxxxxxx procesů XXX náchylných x xxxxxx. Xxxxxxxxxxxx testovacích xxxxx může xxxxxxxxxx xxxxxxx užitečné xxxxxxxxx x xxxxxx xxxxxx, xxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Xxx xxxxxxx xx reverzní xxxxxx x bakteriemi xx x dispozici xxxxx xxxxxxxx databáze xxxxxxxx xxx xxxxxxx xxxxx struktur x xxxx xxxx xxxxxxxx xxxxx vyzkoušené xxxxxx xxxxxxxx xxxxxxxxxx látek, xxxxxx těkavých xxxxxxxxx, x různými fyzikálně-chemickými xxxxxxxxxxx.

Xxx také xxxxxx xxxx, xxxx B.

1.2 XXXXXXXX

Xxxxxxx na xxxxxxxx xxxxxx s bakteriemi Xxxxxxxxxx xxxxxxxxxxx xxxx Xxxxxxxxxxx coli slouží x detekci xxxxxx x xxxxx xxxxxxxxxxx xxxxxxxxxxxxx (xxxxxxxx xxxx. xxxxxxxxx), xxxxxxx xxxxxx xxxx nezávislý xx xxxxxxx přísunu xxxxxxxxxxxxx.

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

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

1.3 VÝCHOZÍ XXXXX

Xxx xxxxxxxxx na reverzní xxxxxx s xxxxxxxxxx xx xxxxxxxxx xxxxxxxxxxxxx xxxxx, xxxxx xx xxxx xx buněk xxxxx faktory, jako xxxx příjem, xxxxxxxxxxxx, xxxxxxxxxxxx struktura x xxxxxxxxx xxxxxxx XXX. Xxxxxxx xxxxxxxxx xx xxxxx xxxxxx xxxxxxxx xxxxxxx vnějšího xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxxxxxxxx xxxxxxxxx systémy in xxxxx nemohou xxxxx xxxxxxxxx xxxxxxxx xx xxxx u savců. Xxxxxxx tedy xxxxxxxxxxx xxxxxx informaci o xxxxxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxx xxx xxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x xxxxxxxxxx xx xxxxxxxxx xxxxxxxxx xxx xxxxxxxxx vyšetření xxxxxxxxxxx xxxxxxxx, x xxxxxxx aktivity xxxxxxxxxxxx xxxxxx xxxxxx. X xxxxxxxx xxxxxxxx vyplývá, xx xxxxx xxxxxxxxxx xxxxx, xxxxx jsou x xxxx zkoušce xxxxxxxxx, xxxxxxxx xxxxxxxxx xxxxxxxx x v xxxxxx xxxxxxxxx. Xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx, xxxxx nejsou xxxxxxxxxx xxxxx xxxxxxxx. Příčiny xxxxxx xxxxxxxxxxx xxx xxxxxxxxx xx xxxxxxxxxx xxxxxx detekovanéhokonečného jevu, x rozdílech x xxxxxxxxxxx aktivaci xxxx x rozdílech v xxxxxxxxxx dostupnosti. Xx xxxxx xxxxxx xxxxxxx, xxxxx xxxxxxx xxxxxxxxx xxxxxxx xx reverzní xxxxxx na xxxxxxxxxx, xxxxx xxxx x xxxxxxxxxxxx xxxxxxxxx xxxxxxxx.

Xxxxxxx xx xxxxxxxx xxxxxx x bakteriemi nemusí xxx xxxxxx xxx xxxxxx xxxxx xxxxxxxxxx xxxxx, xxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx (xxxx. xxxxxx xxxxxxxxxxx) x xxx xxxxxxxx xxxxx, x xxxxx xx xxxxxxxxxxx (xxxx o xxxxx xx ví), xx xxxxxxxxxx zasahují xx xxxxxxxxxxxx systému xxxxx xxxxx (xxxx. xxxxxxx inhibitory xxxxxxxxxxxxx x některé xxxxxxx xxxxxxxxxx). X xxxxxxxx xxxxxxxxx mohou být xxxxxxxxx xxxxxxx xxxxxxxxxx x xxxxx.

Xxxxxxxx xxxxx xxxxxxxxx, xxx xxx xx tato zkouška xxxxxxxxx, je xxxxxxxxxxxx xxx xxxxx, xxxx xxxxxxxx xxxxxxxxx. Závisí xx chemické třídě x xxxxxxxx xxxxx xxxxxxxxxxx, xxx nejsou xxxxxxxxxx xxxxx xxxxxxxx, xxxxx působí xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx xxxxxxxxxx, xxxxx v xxxxxxxxxxxxx buňkách neexistují.

1.4 XXXXXXXX ZKUŠEBNÍ XXXXXX

Xxxxxxxx xxxxxxxxxxxxx xxxxx xxxx xxxxxxxxx zkoušené xxxxx, x xx xx xxxxxxxxxxx vnějšího metabolického xxxxxxxxxxx xxxxxxx a xxx xxxx. Ve xxxxxxxxxxx xxxxxxxx testu xx xxxxxxxx smíchají x xxxxxxx agarem x xxxxx xx xxxxxxx na minimální xxxx. X preinkubační xxxxxx xx xxxxxxxx xxxx xxxxxxxx x xxxx xx xxxx xxxxxxxxx xx xxxxxxxxx xxxx xxxxxx x xxxxxxx xxxxxx. Xxx xxxx technikách se xx dvou xxxx xxxxx xxxxx xxxxxxxx xxxxxxxxx kolonie xxxxxxxxxx x xxxxxxx xx xxxxxxxx s xxxxxx xxxxxxx xxxxxxxxxxx revertantů xx xxxxxxxxx misce x xxxxxxxxxxxxx.

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

Xxx xxxxxxx xxxxxxx xx xxxxxx xxxxxx standardního xxxxxxxxx testu a xxxxxxxxxxxxxx xxxxx. Xxxxx x xxxx je xxxxxxxxxx xxx provádění xxxxxxxxxxx jak s xxxxxxxxxxxx xxxxxxxx, tak xxx ní. Některé xxxxx xxx účinněji xxxxxxxxx za xxxxxxx xxxxxxxxxxxx xxxxxx. Tyto xxxxx xxxxx do xxxxxxxxxx tříd, do xxxxx xxxxx mezi xxxxx xxxxxx alifatické xxxxxxxxxxx, xxxxxxxxx kovy, xxxxxxxx, azobarviva x xxxxxxxxxx xxxxxxxxxx, xxxxxxxxxxxxxxx xxxxxxxxx, allylové xxxxxxxxxx x nitrosloučeniny (3). Xxxxxx xx připouští, xx xxxxxx xxxxx xxxxxxxx xxxxx vždy xxxxxxxxx standardními xxxxxxx, xxxx xx xxxxxxxxxx xxxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxx. Xxxx xx být xxxxxxxxxx xx "xxxxxxxx xxxxxxx" x x xxxxxx xxxxxxx xx xxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxx. Xx možné xxxxxxxxxxxxx tyto "zvláštní xxxxxxx" (xxxxxxxx s xxxxxxxx postupů jejich xxxxxxx): xxxxxxxxxx a xxxxxxxxxx xxxxxxxxxx (3, 5, 6, 13), xxxxx x xxxxxx xxxxxxxx xxxxx (12, 14, 15, 16), x xxxxxxxxx (17, 18). Xxxxxxxx od xxxxxxxxxxxx postupu xxxx xxx xxxxxxx zdůvodněna.

1.5 XXXXX XXXXXXXX XXXXXX

1.5.1 Xxxxxxxxx

1.5.1.1 Xxxxxxxx

Xxxxxxx xxxxxxx xxxxxxxx xx xxxx xxx kultivovány xx xxxxxx exponenciální fáze xxxx xx xxxxx xxxxxxxxxxx xxxx xxxxx (xxxxxxxxx 109 xxxxx xx xx). Xxxxx x xxxxxx xxxxxxxxxxx xxxx by neměly xxx xxxxxxx. Xx xxxxxxxx, aby xxxx xxxxxxx xxxxxxxx xxxxxx xxxx životaschopných xxxxxxxx. Xxxx může xxx xxxxxxxx buď na xxxxxxx dosavadních xxxxxxxxxxx xxxxx x xxxxxxx xxxxxx, xxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxxxxxxxxxxxx buněk xx miskách.

Doporučená inkubační xxxxxxx xx 37 °X.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxx xxxxxxxx. Xxxx xxxx by měly xxx xxxxx xxxxx X. xxxxxxxxxxx (TA1535; XX1537 nebo XX97x xxxx TA97; TA98 x XX100), xxxxxxx xxxxxxx xx ukázala x xxxxxxx laboratořích xxxx xxxxxxxxxx x xxxxxxxxxxxxxxxx. Xxxx xxxxx xxxxx X. xxxxxxxxxxx xxxx xxx xxxx XX xx xxxxxxxxx xxxxxxxxx xxxxx a xx xxxxx, že xxxxxx xxxxxxxxxxxxxxx nelze xxxxxxxxx xxxxxx oxidační xxxxxxxx, xxxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx XXX x xxxxxxxxx. Xxxx xxxxx mohou být xxxxxxxxxx xxxxx X. xxxx XX2 xxxx X. xxxxxxxxxxx TA102 (19), které mají xx xxxxxxxxx xxxxxxxxx xxxxx xxx xxxx XX. Doporučená xxxxxxxxx xxxxx xx xxxx xxxx:

- X. xxxxxxxxxxx XX1535 x

- X. xxxxxxxxxxx XX1537 nebo XX97x a

- X. xxxxxxxxxxx TA98 a

- X. xxxxxxxxxxx XX100 x

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

Xxx xxxxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx xxxxxx XXX xxxx být xxxxxxxxx xxxxxxx TA102 nebo xxxxxx xxxx X. xxxx x xxxxxxx xxxxxxxxxx reparace XXX, (xxxx. X. xxxx XX2 (pKM101)).

Měly by xxx použity xxxxxxxx xxxxxxx xxxxxxxx xxxxxxx xxxxxxx, verifikace markeru x xxxxxxxxxx. Xxxxxxx xxxxxxxxxxxxx xxx xxxx xx xxxx xxx xxxxxxxxx xxx xxxxxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxxx pro kmeny X. typhimurium x xxxxxxxxx xxx X. xxxx). Xxxxxxx xx xxxx xxx xxxxxxxxxxxx xxxx xxxxxxxxxx charakteristiky, xxxxxxxxx podle xxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx X-xxxxxxx plasmidů (tj. xxxxxxxxxxxx rezistence u xxxxx XX98, TA100 x TA97a xxxx XX97, WP2 uvrA x XX2 uvrA (xXX101) x ampicilinová x xxxxxxxxxxxxxx xxxxxxxxxx x xxxxx XX102), xxxxxxxxxx charakteristických xxxxxx (xx. xxx xxxxxx x X. typhimurium xxxxxxxxxx na xxxxxxxxxxx xxxxxx x xxxX xxxxxx x X. xxxx xxxx xxxX xxxxxx u S. xxxxxxxxxxx citlivostí xx xxxxxxxxxxxx xxxxxx) (2, 3). Xxxxx xx xxxx xxxxxx dávat xxxxx xxxxxxx xxxxxxxxxxx xxxxxxxxxx na xxxxx x xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx x xxxxxxx x rozmezí xxxxxxxx x xxxxxxxxxx.

1.5.1.2 Médium

Použije xx xxxxxx xxxxxxxxx xxxx (xxxx. xxxxxxxxxx xxxxxxxxx xxxx X (Xxxxx-Xxxxxx) x xxxxxxx) x xxxxxx agar xxxxxxxxxx histidin x xxxxxx nebo xxxxxxxxx xxxxxxxxxx xxxxxxx buněčných xxxxxx (1, 2, 9).

1.5.1.3 Xxxxxxxxxxx aktivace

Bakterie xx xxxx xxx xxxxxxxxx xxxxxxxx látce, x xx x xxxxxxx xxxxxxxx metabolické xxxxxxxx a xxx xxxx. Xxxxxxxxxx xxxxxxxxxx xxxxxxxx xx xxxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (X9) xxxxxxxxxx x xxxxx hlodavců ošetřených xxxxxxxxxxx xxxxxxxxxxx xxxxxx, xxxx je Xxxxxxx 1254 (1, 2) xxxx xxxxxxxxxxxxx x β-xxxxxxxxxxxx (18, 20, 21). Xxxxxxxxxxxxxxxxxxx frakce xx xxxxxxx xxxxxxxxx x xxxxxxxxxxxxx x xxxxxxx 5 xx 30 % obj. xx směsi X9. Xxxxx x podmínky xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx xxxx xxxxxxx xx xxxxx xxxxxxxx xxxxxxxx xxxxx. X některých xxxxxxxxx může xxx xxxxxx xxxxxx xxxx xxx jednu koncentraci xxxxxxxxxxxxxxxxxxx frakce. X xxxxxxxxx a diazoniových xxxxxxxxx může xxx xxxxxxxxx xxxxxxx redukčního xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx (6, 13).

1.5.1.4 Xxxxxxxx xxxxx xxxx xxxxxxxxx

Xxxxx xxxxxxxx xxxxx by xxxx xxx xxxx xxxxxxxx xx bakterie xxxxxxxxxx xxxx xxxxxxxxxxxx xx vhodných xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx x testovacím xxxxxxxx x/xxxx xxxxx xxx xxxx xxxxxxxx xxxxxxx. Xxxx xx být xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx neprokazují xxxxxxx xxxxxxxxxx.

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx mimo podezření, xx xxxxxxx se xxxxxxxxx xxxxxx, x xxxx by být xxxxxxxxxx x xxxxxxxx xxxxxxxx x x xxxxxxxxx S9 (22). Xxxx-xx použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Doporučuje xx xxxxx xxxxx nejdříve xxxxxx použití vodných xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx nestálých ve xxxx xx xxxx xxx použita organická xxxxxxxxxxxx xxxxxxxxxxxx xxxx.

1.5.2 Xxxxxxxx xxxxxxxx

1.5.2.1 Xxxxxxxx xxxxx (viz 1.5.1.1)

1.5.2.2 Xxxxxxxxx xxxxxxxxxxx

Xxxx xxxxxxxx, xxxxx xxxx xxx xxxxxxxxxx xxx stanovení xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx xxxxx xxxxxxxxxxxx x rozpustnost x xxxxxxx xxxxx xxx xxxxxxxx.

Xxxx xxx xxxxxxxx xxxxxxxx xxxxxxxx x xxxxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxxxxx. Cytotoxicita xxxx xxx xxxxxxxxxx xxxxxxxx xxxxx kolonií revertantů, xxxxxxxxx xxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxx xxxxxxxx xxxxxx xxxxxxx xxxxxxxxxxxx xxxxxx. Xxxxxxxxxxxx xxxxx xx xxxx xxxxxx v přítomnosti xxxxxxxxxxxxx xxxxxxxxxxx systémů. Xxxxxxxxxxxxx by xxxx xxx posouzena na xxxxxxx xxxxxxxxxxx srážení x xxxxxxx xxxxx xx xxxxxxxxxx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxxx xxxxxxxxx zkušební xxxxxxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxx xxxxx xx 5 mg/misku nebo 5 μx/xxxxx. X xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxxxx xxx xxxxxxxxxxxxx 5 xx/xxxxx xxxx 5 μx/xxxxx by měla xxx xxxxx xxxx xxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxx, aby látky xxxx v xxxxxxx xxxxx xxx aplikaci xxxxxxxxxxx. Xxxxxxxx xxxxx, xxxxx xxxx cytotoxické xxx při xxxxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx, xx xxxx xxx zkoušeny xx xx cytotoxické xxxxxxxxxxx. Xxxxxxxxx xx neměla xxxxx při xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxxxxx koncentrací xxxxxxxx xxxxx, xxxxxxx xxx xxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxxx xxxx xxxxxxxxxx xxxx xxxxx xxxxxxxxx polovině xxxxx xxxxxxxxxxxx xxxxxxxx (xx. Ö10). Menší xxxxxxxxx jsou vhodné x xxxxxxx, xxx xx xxxxxxxxx xxxxxx xxxxxxxxxx odpovědi na xxxxxxxxxxx. Xxxxxxxx xxxxxxxxxxx xxxxxxx xxx 5 xx/xxxxx xxxx 5 μx/xxxxx může xxx xxxxxxx při xxxxxxxxx xxxxx xxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxx.

1.5.2.3 Xxxxxxxxx x xxxxxxxxx kontroly

Součástí xxxxxxx xxxxxxxxx by xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx x xxxxxxxxx (xxxxxxxxxxxx nebo vehikulum) xxxxxxxx s metabolickou xxxxxxxx x bez xx. Xxx xxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxxx xxxxxxxxxxx účinnost xxxxx xxxxxxx.

X xxxxxxx zkoušek x xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxxx xxxxxxx by xxxx být látka (xxxxx) xxx xxxxxxxxx xxxxxxxx xxxxxxx (xxxxxxx) xx xxxxxxx xxxx xxxxxxxxx kmene bakterií.

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

Xxxxx	Xxxxx XXX	Xxxxx xxxxx XXXXXX
9,10-xxxxxxxxxxxxxxxxx	781–43–1	212–308–4
7,12-xxxxxxxxxxxxx[x]xxxxxxxxx	57–97–6	200–359–5
xxxxx[x]xxxxx	50–32–8	200–028–5
2-xxxxxxxxxxxxxx	613–13–8	210–330–9
Xxxxxxxxxxxxx	50–18–0	200–015–4
xxxxxxxxxxxxx xxxxxxxxxx	6055–19–2	200–015–4

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

Xxxxx	Xxxxx CAS	Číslo podle XXXXXX
XX Xxxxxx Red 28	573–58–0	209–358–4

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

Xxxxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxxx xxxxxxxx x xxxxxxx bez xxxxxx xxxxxxxxxxx aktivace jsou xxxx látky:

Látka	Číslo XXX	Xxxxx xxxxx XXXXXX	Xxxx
xxxx xxxxx	26628–22–8	247–852–1	XX1535 x TA100
2-nitrofluoren	607–57–8	210–138–5	TA98
9-aminoakridin	90–45–9	201–995–6	TA1537, TA97 x XX97x
XXX 191	17070–45–0	241–129–4	TA1537, XX97 x XX97x
Xxxxxxxxxxxxxxxxx	80–15–9	201–254–7	XX102
xxxxxxxxx X	50–07–7	200–008–6	XX2xxxX x XX102
1-xxxxxx-3-xxxxx-1-xxxxxxxxxxxxxxx	70–25–7	200–730–1	XX2, XX2 uvrA x XX2 xxxX (xXX101)
4-xxxxxxxxxxxxx-1-xxxx	56–57–5	200–281–1	XX2, XX2 xxxX x XX2 uvrA (xXX101)
α-[(5-xxxxx-2-xxxxx)xxxxxxxxxx]xxxxx-2-xxxxxxxx (XX2)	3688–53–7		xxxxx xxxxxxxxxx plasmidy

Pro xxxxxxxxx xxxxxxxx mohou xxx xxxxxxx jiné xxxxxx xxxxxxxxxx xxxxx. Xxx xxxxxxxxx kontrolu xx mělo být xxxxx x xxxxx xxxxxxx chemických xxxxx xx xxxxxx xxxxxxxx xxxxx, xxxx xx x xxxxxxxxx.

Xxxx xx xxx xxxxxxx negativní xxxxxxxx skládající xx xx samotného xxxxxxxxxxxx xxxx vehikula, xxx xxxxxxxx xxxxx, xxxxxxxxxx xxxxx xxxxxxx způsobem xxxx xxxxxxxxxx skupiny. Xxxxx toho xx xxxx xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také xxxxx, neexistují-li xxxxx xxxxxxxxx xxxxx prokazující, xx xxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxx mutagenní xxxxxx.

1.5.3 Xxxxxx

X standardní xxxxxxx xxxxxx (1, 2, 3, 4) bez xxxxxxxxxxx xxxxxxxx xx xxxxxxx smíchá 0,05 xx nebo 0,1 xx zkušebních xxxxxxx, 0,1 ml xxxxxxx xxxxxxxxxxx xxxxxxx (xxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) a 0,5 xx sterilního xxxxx x 2,0 xx xxxxxxxx agaru. V xxxxxxx zkoušky s xxxxxxxxxxxx xxxxxxxx se xxxxxxx xxxxxx 0,5 xx xxxxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxxxxxxxxxxxx xxxxxx (x rozmezí 5 xx 30 % xxx. x xxxxxxxxxxx xxxxxxxxx směsi) x xxxxxxx agarem (2,0 xx) x xxxxxxx x bakteriemi x xxxxxxxxx látkou xxxx xxxxxxxxx xxxxxxxx. Xxxxx xxxxx xxxxxxxx se xxxxxxxx x xxxxxxx xxxx povrch xxxxxxxxxxx xxxxx xx xxxxx. Xxxx xxxxxxxx xx xxxxx xxxxxx xxxx xxxxxxxx.

X xxxxxxxxxxxx xxxxxx (2, 3, 5, 6) se xxxxxxxx xxxxx nebo xxxxxxxx xxxxxx xxxx smícháním x xxxxxxx xxxxxx x xxxxxxxx xxxx xxxxxx xxxxxxxxxxx xxxxx xx misce obvykle 20 xxxxx nebo xxxx preinkubuje x xxxxxxxxxx xxxxxx (xxxxxxxxxxx xxxxxxxxx 108 xxxxxxxxxxxxxxx xxxxx) x sterilním xxxxxx nebo xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx (0,5 xx) xxx 30 — 37 °X. Xxxxxxx xx xxxxxx 0,05 xxxx 0,1 xx xxxxxxxx xxxxx xxxx xxxxxxxxxx xxxxxxx, 0,1 xx bakterií x 0,5 ml xxxxx X9 nebo xxxxxxxxxx pufru x 2,0 xx xxxxxxxx xxxxx. Xxxxxxxx by xxxx xxx během xxxxxxxx provzdušňovány na xxxxxxxx.

X xxxxxxxxxxxx xxxxxx xxxxxxxx by xxxx xxx při xxxxx xxxxxx xxxxx použity 3 xxxxx. Použití xxxx xxxxx je xxxxxxxxxx xx xxxxxxxx xxxxxxxxxx. Xxxxxxxx xxxxxx xxxxx nemusí xxxxxxxx xxxxxxxxxxxx xxxxxxx.

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

1.5.4 Xxxxxxxx

Xxxxxxx xxxxx x xxxx xxxxxxx by xxxx xxx inkubovány xxx 37 °X xx 48 –72 xxxxxxxx. Po xxxxxxxx xxxxxxxxx xxxx xx xxxxxx počet kolonií xxxxxxxxxx xx xxxxx.

2. XXXXX

2.1 ZPRACOVÁNÍ VÝSLEDKŮ

Předloženými xxxxx by xxxx xxx počty kolonií xxxxxxxxxx xxxxxxxxxxx xx xxxxx. Xxx by xxx rovněž xxxxxx xxxxx xxxxxxx revertantů xxx na xxxxxxx x xxxxxxxxx kontrolou (xxxxxxxx rozpouštědla x xxxxxxxx xxxxxxxxxxxx kontrola), xxx xx miskách x pozitivní kontrolou. Xxxxx xx xxxxxxxxxxxx xxxxxxx, xxxxxxx xxxxxxx xxxxx xxxxxxx xxxxxxxxxx xx xxxxx a xxxxxxxxxx odchylka xx xxxx xxx předloženy xxx zkoušenou látku x pozitivní x xxxxxxxxx xxxxxxxx (xxxxxxxxxxxxx xxxxxxxx x/xxxx xxxxxxxx xxxxxxxxxxxx).

Xxxxxxx xxxxx pozitivní xxxxxxxx xx nepožaduje. Xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx, xxxxxxx x xxxxxxx xxxxxxxxxxxxxxxx xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxx xxx xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xx xxxxxxxxx xxxxxxxxxxx xxxxxxxx nepovažuje xx xxxxxxxx, xxxx xx xxx xxxxxx xxxxxxxxxx. Změna parametrů xxxxxx x xxxxx xxxxxxxx xxxxxx posuzovaných xxxxxxxx by xxxx xxx zvážena x xxxxxxxxxx xxxxxxxxxxxxx. K xxxxxxxxxx xxxxxx, xxxxx xx xxxxx být xxxxxxx, xxxxx xxxxxxx xxxxxxxxxxx, xxxxxx xxxxxxxxxx (xxxxxxxxxx misková xxxxxx xxxx xxxxxxxxxxx v xxxxxxxx xxxxx) x xxxxxxxx xxxxxxxxxxx xxxxxxxx.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, xxxx. xxxxxx xxxxx xxxxxxx revertantů xx xxxxx xxx xxxxxxxxx xxxxxx x xxxxxxx xxxxxxx kmene x xxxxxxxxxxxx xxxxxxxxxx xxxxxxxx xxxx bez xxxx, x xx x xxxxxxxxxx xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx xxxxxx xxxxxx počtu xxx xxxxx xxxx xxxx xxxxxxxxxxx (23). Xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx xxxxxxxxx xxxxxxxx zkoušky xxxxx xxx xxxxxxx xxxx pomocný prostředek xxxxxxxxxxx metody (24). Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx xxxxxxxxx odpověď.

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

Xxxxxx xxxxxxx xxxxxxxxxxx xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx xxxxxx údajů xxxxxxxx xxxxxxx výrok x aktivitě xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx dvojznačné xxxx xxxxxx bez xxxxxx xx to, xxxxxxxx xx experiment xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxxxx xxxxxx x xxxxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxx xxxxx Xxxxxxxxxx xxxxxxxxxxx x/xxxx Xxxxxxxxxxx xxxx bodové xxxxxx xxxxxxxxxx bází xxxx xxxxxxx xxxxxxx xxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxx xx xxxxxxxx zkoušky xxx xxxxxxxxx druhy xxxxxxxxx.

3. XXXXXX

XXXXXXXX O ZKOUŠCE

Protokol x zkoušce musí xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx xxxxxxxxxxxx/xxxxxxxx,

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

Xxxxx:

- xxxxxxx xxxxx,

- počet xxxxx x xxxxxxx,

- xxxxxxxxxxxxxxx kmene.

Zkušební xxxxxxxx:

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

- xxxxxxx xxxxx,

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

- xxxxxx xxxxxxxx.

Xxxxxxxx:

- xxxxxx toxicity,

- známky xxxxxxx,

- xxxxx na xxxxxxxxxxxx xxxxxxx,

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx xx dávce,

- xxxxxxxx statistické analýzy,

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

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

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxx, X. N., McCann, X., Yamasaki E. (1975), Methods xx Xxxxxxxxx Carcinogens and Xxxxxxxx with xxx Xxxxxxxxxx/Xxxxxxxxx-Xxxxxxxxx Mutagenicity Xxxx, Xxxxxxxxxx Res., 31, 347-364.

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

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

4) Kier, X. X., Xxxxxxx X. X., Xxxxxxx, X. X., Xxx Xxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X., XxXxxx, J., Xxxxxxxxxx, X., Xxxxxx, X., Xxx, X. X., Xxx V. (1986), Xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Microsomal Xxxxx: X Xxxxxx of xxx U. X. Xxxxxxxxxxxxx Protection Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 168, 69-240.

5) Xxxxxx, X., Degawa, X., Seino, X. X., Xxxxxxxxxx, X., Xxxxx, M., Xxxxxxxx, X., Xxxxxxxxx, X. (1975), Mutagenicity xx Xxxxxxxxxx Azo Xxxx xxx their Xxxxxxxxxxx, Xxxxxx Lett. 1, 91-96.

6) Xxxxxxxxxx, X., Xxxxxxxx, X., Nagao, X., Xxxxxx, T., Xxxxxx, X., Sawamura, X. (1980), Factors Xxxxxxxxxx Mutagenicity Xxxxxxxxx Xxxxx, xx: Xxxxx-xxxx Xxxx Xxxxxxx for Xxxxxxxxx Xxxxxxxxxxx, xx. Xxxxxxx K. X., Xxxxxx, X. X., Xxxxxxxx, Xxxxxx-Xxxxxxxxxx-Xxx Xxxx, 273-285.

7) Xxxxxxxxx, D. X., Xxxxxxx, X. X., Xxxxxx, X., Xxxxxxxxx, X. X., Xxxxxx, X. (1980), Xxxxxxxxx Xxxxxxxx Xxxxxx, xx: Xxxxx Mutagenicity Xxxxx: XXXXX Part 1 Xxxxxxx, xx. X. X. Xxxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, 13-61.

8) Xxxxxxxxxx, H. X., Xxxxxx, X., Xxxxxxx, X. (1987), Xxxxxx Xxxxxxxxxxxxx Mutagenicity Xxxx for Foods, X. Food Safety., 8, 167-177.

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

10) Xxxxxxx, X. X., Xxxxx, X. H. X., Xxxxxxxxx, X., Xxxxxxx, X. X. (1984), Xxx Xxxxxxxxxxx Xxxx xx Xxxxxxxx, xx: Xxxxxxxx xx Mutagenicity Xxxx Procedures, 2. xxx., Xxxxxx, X. X., Xxxxxxx, X., Xxxxxxx, X., Ramel, X. (xxx.), Xxxxxxxx, Xxxxxxxxx-Xxx Xxxx-Xxxxxx, 141-161.

11) Xxxxxxxx, X. D., Xxxxxxx, X. X. (1981), An Xxxxxxxxxxx xx xxx Xxxxxxxxxxxx Xxxxxxxxxx Xxxxx xxx Xxxxxxxxxxx xxxx Xxxxxxx xx Salmonella typhimurium, Xxxxxxxxxxxxx Xxxxxxxxxxx, 3, 453-465.

12) Xxxxx, X., Xxxxxxx, X., Xxxx, X., Xxxxxxxxxx, T. (1994), Improved Xxxxxx xxx Mutagenicity Testing xx Xxxxxxx Xxxxxxxxx xx Xxxxx a Xxx Xxxxxxxx Xxx, Xxxxxxxxxx Xxx., 307, 335-344.

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

14) Xxxxxx, X., Anderson, X. X., Haworth, X., Xxxxxx, X., Xxxxxxxxxx, X. (1992), Xxxxxxxxxx Xxxxxxxxxxxx Xxxxx. X. Xxxxxxx xxxx xxx Testing xx 311 Xxxxxxxxx, Xxxxxxx. Xxx. Xxxxxxx., 19, 2-141.

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

16) Hughes, X. X., Xxxxxxx, X. X., Xxxxxxxx, X. X., Xxxxxxx, X. X. (1987), Xxxxxxxxxxxx Xxxxxxxxx to Xxxxxxx Xxxxxxxxx Xxxxxxxx xx Volatile Xxxxxxx Xxxxxxxxx xx xxx Xxxx/Xxxxxxxxxx Xxxxx, Xxxxxxxxxxxxx Xxxxxxxxxxx, 9, 421-441.

17) Xxxxxxxxxx, X., Matsumoto, X., Xxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. (1979), Xxxxxxxxxxxx xx xxx Xxxxxxxxx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx xxx Xxxxxxxxx Xxxxxxxxxxx Xxxxxxx Conjugates in Xxxxxxxxxx typhimurium, Xxxxxx Xxx., 39, 3780-3782.

18) Xxxxxx, X., Xxxx, X., Xxxxx-Xxxxx, X., Xxxx, B. X. (1980), Xxxxxxxx: A Xxxxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxxxx xx Mutagens xx Xxxxxxxxxx Xxxxx, Xxxx. Xxxx. Xxxx. Xxx. X. X. A, 77, 4961-4965.

19) Wilcox, X., Xxxxxx, X., Xxxx, X. X., Xxxxxxxxx, X. X. (1990), Xxxxxxxxxx xx Xxxxxxxxxx xxxxxxxxxxx TA 102 xxxx Escherichia xxxx XX2 Xxxxxx xxxxxxx, Mutagenesis, 5, 285-291.

20) Xxxxxxxxxx, T., Xxxxxxxx, X., Hara, X., Sugimura, X. (1976), X Xxxx Xxxxxxxxxx for Xxxxxxxxxxxxxxx Xxxxxxxxx x. s. xx Xxxxxxx or Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, xx: In vitro Xxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxx Testing, xxx. X. X. xx Xxxxxx xx al. Xxxxxxxx, Xxxxx Holland, 85-88.

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

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

23) Xxxxxxx, X. X., Allen, X., Xxxxxxx, A., Xxxxxxxxxx, X., Xxxxxxxx, X., Xxxxxx, X. (1987), Xxxxx for xxx Xxxxxxxxxx xxxxxxxxxxx/Xxxxxxxxx Xxxxxxxxx Xxxxx xxx Xxxxxxxxx Xxxxxxxxxxxx, Xxxxxxxxxx Xxx., 189, 83-91.

24) Xxxxx, G. X. X., Xxxxx, M. X. X., Xxxxxxxxx, X., Xxxxxxx, I., Xxxxxxxx, X. X., Xxxxxx, X. J. (1989), Xxxxxxxx xx Xxxx from Xxxxxxxxx Xxxxxx Assays, in: XXXXX Xxx-Xxxxxxxxx on Xxxxxxxxxx xxx Mutagenicity Xxxxxxx, Part II. Xxxxxxxxxxx Evaluation xx Xxxxxxxxxxxx Xxxx Data, xx. Xxxxxxxx, X. X., Cambridge University Xxxxx, 28-65."

XXXXXXX 4X

"X.17 MUTAGENITA — XXXXXXX XX XXXXXX XXXXXX X XXXXXXX SAVCŮ IN XXXXX

1. METODA

Tato xxxxxx xx xxxxxxxx xxxxxx XXXX TG 476 — Zkouška xx xxxxxx xxxxxx v xxxxxxx xxxxx xx xxxxx (1997).

1.1 XXXX

Xxxxxxx xx xxxxxx xxxxxx x xxxxxxx xxxxx xx xxxxx xxx xxxxxx pro detekci xxxxxxxx xxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xxxxxx buněčné xxxxx xxxxx xxxxx xxxxxxx X5178X xxxx, xxxxxxx xxxxx XXX, XXX-XX52 x V79 křečka xxxxxxxx x xxxxxxxxxxxxxxx xxxxx TK6 xxxxxxx (1). X těchto xxxxxxxxx xxxxx xxxx xxxxxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxx mutace xxxx xxx xxxxxxxxxxxxxx (XX) x xxxxxxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX) x transgen xxxxxxx-xxxxxxxxxxxxxxxxxxxxxxxxxxxxx (XXXX). Xxxxxxx xx xxxxxx TK, HPRT x XXXX detekují xxxxx spektrum genetických xxxxxxxx. Autosomální xxxxxx XX x XPRT xxxx xxxxxxx detekci xxxxxxxxxxx xxxxxxxx (xxxx. xxxxxxxx xxxxxx), které xxxxx xxxxxxxxx x XXXX xxxxxx xx X xxxxxxxxxxxx (2, 3, 4, 5, 6).

Xx zkoušce xx xxxxxx mutace x xxxxxxx xxxxx xx xxxxx xxx xxxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxx buněčné xxxxx. Xxxxx xx xxxxxxxx podle xxxxxxxxxx xxxxx v xxxxxxx x xxxxxxxx xxxxxxxx xxxxxxxxxxx mutací.

Zkoušky xxxxxxxxx xx xxxxx obecně xxxxxxxx použití xxxxxxxx xxxxxx xxxxxxxxxxx xxxxxxxx. Xxxxx metabolický xxxxxxxxx xxxxxx nemůže zcela xxxxxxxxx xxxxxxxx xx xxxx x xxxxx. Xx xxxxx se xxxxx xxxxxxxxx xxxxxxxx, xxxxx xx xxxxx x xxxxxxxxxx xxxxxxxxx, xxx xxxxxxxxxx xxxxxxx xxxxxxxxxx. K pozitivním xxxxxxxxx, jež neodrážejí xxxxxxx xxxxxxxxxx, xxxx xxxxx změnou xX, xxxxxxxxxx xxxx xxxxxxxx xxxxxx cytotoxicity (7).

Xxxx xxxxxxx xx xxxxxxx xx zjištění xxxxxxx xxxxxxxx a xxxxxxxxxxx xxxxx. Mnoho xxxxxxxxx, xxx něž je xxxx xxxxxxx xxxxxxxxx, xxxx karcinogeny savců; xxxx xxxxx zkouškou x xxxxxxxxxxxxxx xxxx xxxx xxxxxxxxx xxxxxxxx. Xxxxxxxx xxxxxx xx xxxxxxxx xxxxx x xxxxxxxxx důkazy o xxx, xx existují xxxxxxxxxxx, které xxxxxx xxxxxxxx xxxxx zkouškou, xxxxx zřejmě xxxxxx xxxxxx, xxxxxxxxxxxxxxx mechanismy, xxxx mechanismy, xxxxx x bakteriálních buňkách xxxxxxxxxx (6).

Viz xxxx xxxxxx xxxx, xxxx X.

1.2 DEFINICE

Přímá xxxxxx : xxxxxx mutace xxxxxxxxx xxxx xxxxxxxx xxxxx, která xxxxxxxxx xxxxx nebo ztrátu xxxxxxxxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx.

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

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

Doba exprese xxxxxxxx : xxxx, xxxxx níž vymizí x nově xxxxxxxxxx xxxxx xxxxxxxxx genové xxxxxxxx.

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

Relativní celkový xxxx : nárůst xxxxx xxxxx v xxxx xx srovnání x kontrolní populací xxxxx; vypočte xx xxxx xxxxxx xxxxxx xxxxxxxxx xxxxx x xxxxxxxx x v xxxxxxxxx kontrole x xxxxxxxxx účinnosti xxxxxxxxx xxxxxxxx x xxxxxxxxx xxxxxxxx.

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

Xxxxxxxxxxxxxxx : xxxxxxxx xxxxxxxxx xxxxx v okamžiku xxxxxxxx xx xxxxx xx xxxxxxxxxxxx xxxxxxxx xx xxxxxxx.

Xxxxxxx : xxxxxxxx xxxxxxxxx xxxxx xxx xxxxxxxx xx xxxxx xx xxxxx xxxxxx xxxxxxxx; přežití xx xxxxxxx vyjádřeno x poměru x xxxxxxx kontrolní xxxxxxxx xxxxx.

1.3 PODSTATA ZKUŠEBNÍ XXXXXX

Xxxxx, xxxxx x xxxxxxxx xxxxxx TK+/-® XX— /- neobsahují xxxxxxxxxxxxxx (TK) xxxx xxxxxxxxxxx x xxxxxxxxxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxxxxxxxxxx (XXX). Buňky xxxxxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxx na XXX, xxx xxxxxxxxx xxxxxxxx xxxxxxxxx xxxxxxxxxxx a xxxxxxxxx další buněčné xxxxxx. Xxxxxxxx xxxxx xxxx tedy schopny xxxxxxxxxxx xx xxxxxxxxxxx XXX, zatímco xxxxxxxx xxxxx, xxxxx xxxxxxxx xxxxxxxxxxxxxx tuto xxxxxxxxx xxxxxx. Podobně xxx x buněk x xxxxxxxxxxxx HPRT xxxx XXXX provést xxxxxxx xxxxxxxxxxxxxxx rezistence k 6-xxxxxxxxxxx (XX) nebo 8-xxxxxxxxxx (AG). Xxxxxxxxxx xxxxxxxx látky by xxxx být xxxxxxx xxxxxxx, jestliže xx xx xxxxxxx na xxxxxx xxxxxx x xxxxxxx savců xxxxxxx xxxxxx xxxx xxxx xxxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxxxx xxxxxxxxx xxxxxxxx xxxxxxxxx na xxxxxxxxxx toxicitu zkoušené xxxxx xxx xxxxxxxx xxxx xxxxxxxxxx buňky. Xxx xxxxxxxx chemických xxxxx, které mají xxxxxxxx xxxxxxxxx jako xxxxxxxx činidlo, musí xxxx být xxxxxxxxx xxxxxxxx xxxxxxx nebo xxxxxxx xxx xxxxxxx (8).

Xxxxx v xxxxxxxxx xxxx jednovrstevné kultuře xxxx xxxxxxx xxxx xxxxxxxxx zkoušené xxxxx xxx s xxxxxxxxxxxx xxxxxxxx, xxx xxx xx, a xxxxxxxxxxxxxx xx xxxxxx xxxxxxxxx xxxxxxxxxxxx x za xxxxxx xxxxxxx xxxxxxxx xxxx xxxxxxx xxxxxxx (9, 10, 11, 12, 13). Xxxxxxxxxxxx xx xxxxxxx xxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxxxx (xxxxxxx) xxxx xxxxxxxxxx xxxxxxxxxxx celkového xxxxx kultur xx xxxxxxxx xxxx expozice. Xxxxxxxxxx kultury xx xxxxxxx v xxxxxxxx xxxxx xx vhodnou xxxx xxxxxxxxxxxxxxxxx xxx xxxxx xxxxxxx lokus x xxx buněk, xxx xxxxxxx přibližně xxxxxxxxx xxxxxxxxxx exprese xxxxxxxxxxxx mutací. Četnost xxxxxxx se stanoví xxx, xx se xxxxxx xxxxx počet xxxxx xx média xxxxxxxxxxxx xxxxxxxx činidlo xxx xxxxxxx xxxxxxxxxx xxxxx x xx xxxxx bez xxxxxxxxxx xxxxxxx, xxx byla xxxxxxxxx xxxxxxxx klonování (xxxxxxxxxxxxxxx). Xx vhodné xxxxxxxxx době xx xxxxxxxxx kolonie. Xxxxxxx xxxxxxx se vypočte x počtu xxxxxxxxxx xxxxxxx v xxxxxxxxx xxxxx a počtu xxxxxxx x xxxxx xxx selekčního činidla.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Buňky

Pro xxxxxxx x této xxxxxxx xxxx k xxxxxxxxx xxxxx typy buněk, xxxxxx xxxxxxxx buněk X5171X, XXX, XXX-XX52, X79 nebo XX6. Xxxx buněk v xxxx xxxxxxx by xxxx vykazovat xxxxxxxxx x xxxxxxxxx mutagenům, xxxxxxx xxxxxxxxx schopnost x xxxxxxxx frekvenci xxxxxxxxxxx xxxxxx. Xxxxx xx xxxx být xxxxxxxxxxxx, xxx xxxxxx xxxxxxxxxxxxx xxxxxxxxxxxx, a x případě kontaminace xx xxxxxx xxx xxxxxxx.

Xxxxxxx xx měly xxx navrženy tak, xxx měly xxxxxx xxxxxxxxxx xxxxxxxxx a xxxx. Xxxxx xxxxxxxxx xxxxx, xxxxxx x xxxxxxxxxxx xxxxxxxx látky xx měl xxxx xxxxxxxxxx parametry xxxxxxx (14). Xxxxxxxxx xxxxx xxxxx, xxxxx přežijí xxxxxxxx x které xxxxx xxxxxxx x xxxxxx stadiu zkoušky, xx měl xxx xxxxxxx xx xxxxxxxx xxxxxxxxxxx mutací. Obecným xxxxxxxxx xx, aby xxx použit počet xxxxx, xxxxx xx xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx. Xx však xxxxxxxxxx, xxx xxxx xxxxxxx xxxxxxx 106 buněk. Xxxx xx xxx x xxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx x xxxxxxxx xxxxxxxx xxxxxxx, xxx byla doložena xxxxxxxxxxxx xxxxxxxxx xxxxxxx xxxxxxx.

1.4.1.2 Média a xxxxxxxxxx xxxxxxxx

Xxx xxxxxxxxx xxxxxx by měla xxx xxxxxxx vhodná xxxxxxxxxx xxxxx x xxxxxxxxx xxxxxxxx (xxxxxxxxxx xxxxxx, xxxxxxxxxxx CO₂, xxxxxxx x xxxxxxx). Xxxxx xx xxxx xxx xxxxxxx xxxxx xxxxxxxxxx xxxxxxx x xxxx xxxxx xxxxxxxxx xxx xxxxxxx. Xx xxxxxxx xxxxxxxx, xxx xxxxxxxxxx xxxxxxxx xxxx xxxxxxx xxx, aby xxxx zajištěny xxxxxxxxx xxxx xxxxx během xxxxxx xxxxxxx x xxxxxxxxx jak mutovaných, xxx xxxxxxxxxxxx buněk xxxxxx xxxxxxx.

1.4.1.3 Xxxxxxxx xxxxxx

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

1.4.1.4 Xxxxxxxxxxx xxxxxxxx

Xxxxx by xxxx xxx xxxxxxxxx zkoušené xxxxx, a to x xxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxx a xxx něho. Xxxxxxxxxx xxxxxxxxxx systémem je xxxxxxxxxx xxxxxxxx postmitochondriální xxxxxx (S9) xxxxxxxxxx x xxxxx xxxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxx, xxxx xx Xxxxxxx 1254 (15, 16, 17 a 18), xxxx xxxx xxxxxxxxxxxxx a β-xxxxxxxxxxxx (19, 20).

Xxxxxxxxxxxxxxxxxxx frakce xx x xxxxxxxx xxxxxxxxxx xxxxx xxxxxxx xxxxxxxxx x koncentracích 1 — 10 % xxx. Xxxxx x stav xxxxxxxxxxxxx xxxxxxxxxxx systému může xxxxxxx xx xxxxx xxxxxxxx látky, xxxxx xx xxxxxxxx. V xxxxxxxxx xxxxxxxxx xxxx xxx xxxxxx xxxxxx xxxx než xxxxx xxxxxxxxxxx postmitochondriální xxxxxx.

Xxxx xxxxxxxx xxxxxx, včetně xxxxxxxx xxxxxxxxx modifikovaných xxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxxxxx aktivační xxxxxx, xxxxxxxxx xxxxxxxx pro xxxxxxxxx aktivaci. Xxxxx xxxxxxxxx xxxxxxxxx linií xx měla xxx xxxxxxx zdůvodněna (xxxx. xxxxxxxxxxx xxxxxxxxx xxxxxxxxxx X450 xxx xxxxxxxxxxxx xxxxxxxx xxxxx).

1.4.1.5 Xxxxxxxx xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx aplikací xx xxxxx xxxxxxxxxx xxxx suspendovány ve xxxxxxxx rozpouštědlech nebo xxxxxxxxxx x xxxxxxxxx xxxxxxx. Kapalné xxxxxxxx xxxxx xxxxx xxx xxxxxxx xxxxx k xxxxxxxxxx systémům x/xxxx xxxxx xxx před xxxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x stálosti xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxx xxx xxxx podezření, že xxxxxxx xx xxxxxxxxx xxxxxx, a mělo xx xxx xxxxxxxxxx x xxxxxxxx xxxxx x s xxxxxxxxx X9. Jsou-li použita xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, xxxx by xxx xxxxxx zařazení xxxxxxxxx xxxxx x xxxxxx xxxxxxxxxxxxx. Xxxxxxxxxx xx pokud xxxxx xxxxxxxx zvážit použití xxxxxxx xxxxxxxxxxxx/xxxxxxx. Xxx xxxxxxxx xxxxx xxxxxxxxx xx xxxx by xxxx xxx xxxxxxx xxxxxxxxx xxxxxxxxxxxx xxxxxxxxxxxx xxxx. Xxxx lze xxxxxxxxx xxxxxxxx molekulového xxxx.

1.4.2.2 Expoziční koncentrace

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

Xxxxxxxxxxxx xx xxxx xxx xxxxxxxxx x xxxxxxxxxxxx aktivací x xxx xx x xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx xxxxxxxxxx buněčné xxxxxxxxx x xxxxx, jako xxxx xxxxxxxxx xxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxx xxxxxxx xxxx. Xxxx být xxxxxxx xxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxx x předběžném xxxxxxxxxxx.

Xxxx xx xxx xxxxxxx alespoň čtyři xxxxxxxxxxxxxx xxxxxxxxxxx. X xxxxxxx toxicity xx xxxx xxxx koncentrace xxxxxxxx xxxxxxx xxxx xxxxxxxxx a minimální xxxxxxxxx, případně xxxxxx xxxxxxxxx, xxx xxxx xxxxxxx xxxxxxxx, xx xx se xxxxxxxxxxx xxxx xxxxx xxxxxxxx 2 xx Ö10. Xx-xx maximální koncentrace xxxxxxxx xx xxxxxxxxxxxx, xxxx by xxx xxxxxxxxx xxxxxxxxx 10 — 20 % (xxx xxxxxxx 10 %) přežití (relativní xxxxxxxx xxxxxxxxx) nebo xxxxxxxxx xxxxxxx růst. X xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx látek xx xxxx být xxxxxxxxx xxxxxxxx xxxxxxxxxxx 5 μx/xx, 5 mg/ml xxxx 0,01 M, xxxxx xxxx, xxxxx x xxxx xx xxxxxxxx.

Xxxxxxxxx xxxxxxxxxxx xxxxx xx xxxx být xxxxxxxx xx x xxxx xxxxxxxxxxxx xx xxxxxxxxxxxx podmínek, xxxx xx za tuto xxx. Xxxx by xxx xxxxxxxxx případná xxxxxxxxxxxxx x xxxxxxxx xxxxx, ve kterému xxxx xxxxx xxxxxxxxxx. Xxxx xxx xxxxxxx xxxxxxxx xxxxxxxxxxx xx xxxxxxx x na xxxxx xxxxxxxx, xxxxx xxxxxxxxxxx xx xxxx x xxxxxxx expozice x testovacím xxxxxxx xxxxx v xxxxxxxx xxxxxxxxxxx xxxxx, X9 xxxx, xxx. Nerozpustnost xxx xxxxxxx xxxxxxxx. Xxxxxxxxx xx neměla xxxxx při xxxxxxxxxxx.

1.4.2.3 Xxxxxxxx

Xxxxxxxx xxxxxxx xxxxxxxxxxx xx měly xxx xxxxxxxxx x negativní (xxxxxxxxxxxx xxxx xxxxxxxxx) xxxxxxxx jak x xxxxxxxxxxxx aktivací, tak xxx xx. Xxx xxxxxxx xxxxxxxxxxx xxxxxxxx xx měla být xxxxxxxxx kontrolou xxxxxxxx xxxxx, xxxxx k xxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxxx kontroly xxxxx xxx xxxx xxxxx:

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

Xxxxx xxx xxxxxxx xxxx xxxx referenční xxxxx pro xxxxxxxxx xxxxxxxx, xxxx. xx-xx xxxxxxxxx xxxxxxxx dosavadních xxxxx x 5-xxxx-2′-xxxxxxxxxxxx (XXX 59–14–3, XXXXXX 200–415–9), xxxx být xxxx xxxxxxxxxx xxxxx xxxxxx použita. Xxx xxxxxxxxx kontrolu xx xxxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xxxxx xxxxx xx stejné xxxxxxxx xxxxx.

Xxxx by xxx xxxxxxx xxxxxxxxx xxxxxxxx xxxxxxx xxxxxx xxxxxxxxxxx samotné xxxxxxxxxxxx xxxx xxxxxxxxx a xxxxxxxxxx xxxxx xxxxxxx xxxxxxxx xxxx xxxxxxxxxx xxxxxxx. Xxxxx xxxx xx xxxx být xxxxxxxxxxxx kontroly xxxxxxx xxxx tehdy, neexistují-li xxxxx xxxxxxxxx údaje xxxxxxxxxxx, xx zvolené xxxxxxxxxxxx xxxxxxxxxx žádné xxxxxxx xxxx mutagenní xxxxxx.

1.4.3 Postup

1.4.3.1 Xxxxxxxx xxxxxxxx xxxxx

Xxxxxxxxxxxxx xxxxx xx xxxx být xxxxxxxxx xxxxxxxx xxxxx xxx xx xxxxxxxxxxx xxxxxxxxxxxxx aktivačního systému, xxx bez xxxx. Xxxxxxxx xx xxxx xxxxx xxxxxxx xxxx (xxxxxxx xx xxxxxx xxxx 3 xx 6 xxxxx). Expoziční xxxx xxxx být xxxxxxxxxxx xx jeden xxxx více xxxxxxxxx xxxxx.

Xxx xxxxxx xxxxxxxx xxxxxxxxxxx xxxxx xxx xxxxxxx xxxxxxxxxx kultury xxxx xxxxx xxxxxxxxxx xxxxxxx. Je-li xxxxxxx xxxxx xxxxxxx, xxx xx xxx xxxxx xxxxxxxxxxx xxxxxx tak, xxx byl xxxxxxxx xxxxxxxxxxxx počet kultur xxx analýzu (např. xxxxxxx osm xxxxxxxxxxxxxxxx xxxxxxxxxxx). Měly xx xxx xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxxxx (xxxxxxxx xxxxxxxxxxxx).

Xxxxxx xxxx xxxxxx xxxxx by xxxx být zkoušeny xxxxxxxx metodami, xxxx. x těsně xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx (21, 22).

1.4.3.2 Xxxxxxxxx xxxxxxx, xxxxxxxxxxxxxxxx x xxxxxxxx xxxxxx

Xx xxxxx expoziční xxxx se xxxxx xxxxxxx x xxxxxxxxx xx účelem stanovení xxxxxxx a xx xxxxxx umožnění xxxxxxx xxxxxxxx mutantu. Xx xxxxxxxxxx cytotoxicity xxxxxxxxxxxxxxx xxxxxxxxx relativní xxxxxxxxx xxxxxxxxx (přežití) xxxx xxxxxxxxxxx xxxxxxxxx růstu xxxxxx se xxxxxxx xxxxxxx po xxxxxxxxx xxxx.

Xxxxx xxxxx xx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxx, xxx umožnil xxxxxxxxx xxxxxxxxx fenotypovou xxxxxxx xxxx indukovaných xxxxxxx (XXXX x XXXX xxxxxxxx xxxxxxx 6 xx 8 xxx, XX xxxxxxx xxx xxx). Xxxxx xxxx kultivovány x xxxxx xx selekčním xxxxxxxx (xxxxxxxxxx xxxxxxx) x xxx něho (xxx xxxx) xx xxxxxx xxxxxxxxx xxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx. Xx xxxxxxxxxx xxxxxxxxxxxxxxxx (použité xxx xxxxxxx četnosti xxxxxxx) xx xxxxxxx xx xxxxx xxxx xxxxxxx xxxxxxxxx xx xxxxx xxx selekčního činidla.

Je-li xxxxxxxx xxxxx xxxxxxxxx xx zkoušce L5178Y XX+/-, xxxx by xxx provedeno xxxxxxx xx xxxxx xx xxxxxxxxxx xxxxxx (x xxxxxxxx pozitivní xxxxxxxxxxx) x xx negativních x xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx. Xx-xx xxxxxxxx xxxxx xx xxxxxxx X5178X TK+/- xxxxxxxxx, mělo xx xxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xxxxxxx xxxxxxxxx na xxxxxxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxx xxxxxxxx xx xxxxxxx XX6 TK+/- xxxx xxx xxxx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxx kolonií.

2. XXXXX

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx xx xxxx zahrnovat xxxxxxxxx xxxxxxxxxxxx x xxxxxxxxxxxxxxxx, xxxxx xxxxxxx x četnosti mutantů xxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. X xxxxxxx xxxxxxxxx xxxxxxxx xx xxxxxxx X5178X XX+/- xx kolonie xxxxxxxxx xxxxxxx x xxxxx xxxxxxxxxxx zkoušené xxxxx (nejvyšší xxxxxxxxx xxxxxxxxxxx) x x xxxxxxxxx a xxxxxxxxx xxxxxxxx xx xxxxxxx xxxxxxxx xxxx kolonie — velká xxxxxxx. Xxxxxxxxxxx x cytogenetická xxxxxx xxx xxxxxxx xxxxxxxxx xxxxx kolonie, xxx xxxxxxx tvořících xxxx xxxxxxx xxxx xxxxxxxx xxxxxxxx (23, 24). Xx xxxxxxx XX+/- jsou xxxxxxx xxxxxxxxxxx xx xxxxxxx xxxxxxxx kolonie x xxxxxxxxx xxxxxx (xxxxx) x kolonie s xxxxxxx xxxxxx (xxxx) (25). X mutantních xxxxx, xxxxx xxxxxxx xxxxxxxxxxxxxx genetické xxxxxxxxx, xx xxxxxxxxxxx xxxx xxxxxxxx, x xxxxx xxxx xxxx xxxxxxx. Xxxxxxxxx xx xxxxxxx xxxxxx od ztrát xxxxxx xxxx až xx xxxxxxxxxxxx viditelné xxxxxxxxxxxx aberace. Xxxxxxx xxxxxxx tvořících xxxx xxxxxxx xx xxxxxxx x chemickými xxxxxxx, xxxxx indukují xxxxx xxxxxxxxxxxx xxxxxxx (26). Xxxx xxxxxxx postižené xxxxx xxxxxxx rostou xxxxxxxx xxxxxx jako xxxxxxxx xxxxx x xxxxx xxxxx kolonie.

Mělo xx xxx udáno xxxxxxx (xxxxxxxxx xxxxxxxx xxxxxxxxx) xxxx xxxxxxxxx xxxxxxx xxxx. Četnost xxxxxxx xx xxxx xxx vyjádřena jako xxxxx xxxxxxx x xxxxx xxxxxxxxxx xxxxx.

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

Xxxxxxx jasně xxxxxxxxx odpovědi xx xxxxxxxxxx. Dvojznačné výsledky xx xxxx xxx xxxxxxxxx dalším xxxxxxxxx, xxxxxxx s úpravou xxxxxxxxxxxxxxxx xxxxxxxx. Negativní xxxxxxxx musí být xxxxxxxxx xxxxxx xx xxxxxxx. Xxx, xxx xxxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx považováno xx xxxxx, xx třeba xxxxx zdůvodnění. Xxxxx xxxxxxxxx xxxxxx s xxxxx rozšířit rozsah xxxxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxx x následných xxxxxxxxxxxxx xxx pro dvojznačné xxxxxxxx, tak xxx xxxxxxxxx výsledky. X xxxxxxxxxx xxxxxx, xxxxx xx mohly xxx xxxxxxx, patří xxxxxxx xxxxxxxxxxx a xxxxxxxx xxxxxxxxxxx aktivace.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxxx kritérií, xxxx. xxxxxx četností xxxxxxx x závislosti xx xxxxxxxxxxx, nebo xxxxxxxxxxxxxxxx nárůst xxxx xxxxxxxx. Xxxxxxxx xx xxxx být xxxxxxx xxxxxxxxxx xxxxxxxxx xxxxxxxx. Xxx hodnocení xxxxxxxx xxxxxxx mohou být xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx xxxxxx xxx jediným xxxxxxxxx xxxxxxxx pro xxxxxxxxx xxxxxxx.

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

Xxxxxx xxxxxxx experimentů xxxxxxxx jasně xxxxxxxxx xxxx negativní výsledky, x ojedinělých xxxxxxxxx xxxxxxxx xxxxxx údajů xxxxxxxx konečný xxxxx x aktivitě zkoušené xxxxx. Výsledky xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx to, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx xx xxxxxx mutace v xxxxxxx xxxxx xx xxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x použitých kultivovaných xxxxxxx xxxxx xxxxxx xxxxxx. Xxxxxxxxxxxxxxxx pozitivní xxxxxxxxx xxxxxxxx xx xxxxxxxxxxx xx velmi xxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx zkoušená xxxxx xx podmínek xxxxxxx xxxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxx buňkách xxxxx xxxxxx xxxxxx.

3. XXXXXX

XXXXXXXX X ZKOUŠCE

Protokol x zkoušce xxxx xxxxxxxxx tyto informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx rozpouštědla/vehikula,

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

Buňky:

- xxx x xxxxx xxxxx,

- xxxxx buněčných xxxxxx,

- případně počet xxxxxx,

- xxxxxxxx xxxxxx xxxxxxxxx xxxxxxx xxxxxxx,

- xxxxxxxxxxxx mykoplasmat.

Zkušební xxxxxxxx:

- xxxxxxxxxx xxxxxx xxxxxxxxxxx x xxxxx xxxxxx, xxxxxx xxxx. xxxxx x xxxxxxxxxxxx x xxxxxx xxxxxxxxxxxx, jsou-li x dispozici,

- xxxxxxx xxxxx, xxxxxxxx xxxxxxxxxxx XX₂,

- koncentrace xxxxxxxx xxxxx,

- objem xxxxxxxx x xxxxxxx xxxxxxxx xxxxx,

- inkubační xxxxxxx,

- xxxxxxxxx xxxx,

- délka xxxxxxxx,

- xxxxxxxx hustota xxxxx během xxxxxxxx,

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

- pozitivní x xxxxxxxxx xxxxxxxx,

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

- xxxxxxxx xxxxxxx,

- kritéria xxxxxxxxxxx xxxxxxx xx xxxxxxxxx, xxxxxxxxx xxxx dvojznačnou,

- xxxxxx použité k xxxxxxxx životaschopných a xxxxxxxxxx buněk,

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

Xxxxxxxx:

- známky xxxxxxxx,

- xxxxxx xxxxxxx,

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

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

- xxxxxxxxx předpoklady laboratoře xxxxxxxxx xxxxxxx tvořící xxxx kolonie xxxxxxxx X5178X XX+/-,

- xxxxx xxxxxxxx závislost xxxxxxxx xx xxxxx,

- případné xxxxxxxxxxx xxxxxxx,

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

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

- xxxxxxx mutantů.

Rozbor xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. X., XxXxxxxx, X. X., XxXxxxxx, X. J., Xxxxxx, X. X. (eds.) (1987), Banbury Report 28; Xxxxxxxxx Xxxx Xxxxxxxxxxx, Xxxx Xxxxxx Xxxxxx Xxxxxxxxxx, New Xxxx.

2) Xxx, E. X. X., Xxxxxxx X. X. (1968), Xxxxxxxxx Cell Genetics. XX. Chemical Induction xx Xxxxxxxx Locus Xxxxxxxxx in Chinese Xxxxxxx Cells Xx xxxxx, Proc. Xxxx. Xxxx. Xxx. X. X. X, 61, 1306-1312.

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

4) Xxxxx, X. X., Harington-Brock, X., Xxxxx, C. X., Xxxxxxxxx, X. X. (1989), Xxxxxxxxxxxx Xxxxxx Xxxxxxxxxxxx xx xxx Xxxxx Xxxxxxxx XX and CHO XXXXX Xxxx, Xxxxxxxxxxx, 4, 394-403.

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

6) Xxxxx, X. X., Xxxxxxxxxx, G., Xxxxx, X. X., Moore, X., Xxxxx, Y., Xxxxxxxxxx, Xx. X. X., Xxxxxx, X., Xxxxxxxx, X. (1994), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Xxxxxx Xxxxxxx Xxxxx Xxxxxx. Report xx xxx Xxxxxxxxxxxxx Xxxxxxxx on Xxxxxxxxxxxxxxx xx Genotoxicity Test Xxxxxxxxxx. Xxxxxxxx Xxx. 312, 235-239.

7) Xxxxx, X., Galloway, X. X., Xxxxxxxx, R. X., Ishidate, M., Xxxxxxx, X., Ashby, X., Myhr, X. X. (1991), Xxxxxxxxxxxx Xxxxx Extreme Xxxxxxx Xxxxxxxxxx. A xxxxxx xxxx XXXXXX Xxxx Xxxxx 9, Xxxxxxxx Xxx. 257, 147-204.

8) Xxxxx, X., XxXxxx, X., Xxxxxxx, X. X. S., Xxxxx, X., Mavournin, X. X. (1983), Xxxxxxxx Xxxx Mutations in X5178X Xxxxx xx Xxxxxxx. X Xxxxxx xx xxx X. X. Environmental Xxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Res., 115, 225-251.

9) Li, X. X., Xxxxx, X. X., Heflich, X. X., Wasson, X. X. (1988), X Xxxxxx and Analysis xx the Xxxxxxx Xxxxxxx Ovary/Hypoxanthine Xxxxxxx Xxxxxxxxxxxxxx Transferase Xxxxxx xx Xxxxxxxxx xxx Xxxxxxxxxxxx of Chemical Xxxxxx: X Xxxxxx xx Xxxxx XXX xx xxx U. X. Xxxxxxxxxxxxx Xxxxxxxxxxx Xxxxxx Xxxx-Xxx Xxxxxxx, Xxxxxxxxxx Xxx., 196, 17-36.

10) Xx, A. X., Xxxxxx, X. X., Xxxx, W. X., Xxxx, A. X., Xxxxx, R. X., Loveday, X. X., O'Νeill, X. X., Xxxxxx, J. X., Stankowski, X. X. Jr., Yang, X. X. (1987), X Xxxxx xxx xxx Xxxxxxxxxxx xx xxx Xxxxxxx Hamster Xxxxx Cell/Hypoxanthine-Guanine Xxxxxxxxxxxxxx Xxxxxxxxxxx Gene Mutation Xxxxx, Mutatation Res., 189, 135-141.

11) Xxxxx, X. X., Xxxxxxx, X. X., Xxxxxx, X. X. (1989), X Xxxxxxxxxx xx Xxxxxxxx Xxxxxxxxx xx xxx TK xxx XXXX Xxxx xx Xxxxx Xxxxxxxxxxxxxx Xxxxx: Xxxxxxxxxxxx Xxxxxxxxxxx are Xxx xx an Xxxxxxxxxx Xxxxx xx Xxxxxxxxx xx xxx Xxxxxxxxx TK Locus, Xxxxxxxxxx Res., 216, 9-17.

12) Xxxxxxxxxx, L. X. Jr., Xxxxxx, X. X., Xxxx, X. X. (1986), Xxxxxxxxxxxx xxx Xxxxxxxxx Xxxxxxxx xx Ethyl Xxxxxxxxxxxxxxxxx and XXX 191-Xxxxxxx Xxxxxxxxx Analyses xx Xxxxx Xxxxxxxxxxxxxxxxx xxx XXX 191 Xxxxxxx Mutation in XX52 Xxxxx, Xxxxxxxxxx Xxx., 160, 133-147.

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

14) Xxxxxx, C. X., Xxxxx, X. M., Xxxxxx, X. X., Xxxxx, X. H. X., Cole, X., XxXxxxxx, X. X., Xxxxxxx X. X. (1989), Xxxxxxxxx Xxxx Xxxx Xxxxxxxx Assays Xxxxx upon Colony Xxxxxxxxx, xx: Xxxxxxxxxxx Xxxxxxxxxx xx Mutagenicity Xxxx Xxxx, Kirkland, X. X., xx., Xxxxxxxxx Xxxxxxxxxx Xxxxx, 66-101.

15) Abbondandolo, X., Xxxxxxx, X., Xxxxx, X., Fiorio, X., Xxxxxxxx, X., Xxxxxxxxxx, X. (1977), Xxxxxxxxx xx 6-Xxxxxxxxxxx-Xxxxxxxxx Xxxxxxx xx X79 Chinese Xxxxxxx Cells xx Xxxxx-Xxxxx Microsome-Activated Xxxxxxxxxxxxxxxxxxx, Xxxxxxxxxx Res. 46, 365-373.

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

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

18) Xxxxx, D. X., Ames, X. X. (1983), Xxxxxxx Xxxxxxx xxx the Xxxxxxxxxx Xxxxxxxxxxxx Xxxx, Xxxxxxxxxx Xxx. 113, 173-215.

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

20) Xxxxxxxxxx, X., Xxxxxxxx, X., Hara, X., Xxxxxxxx, X. (1976), X Xxxx Xxxxxxxxxx xxx Polycholrinated Xxxxxxxxx x. x. xx Xxxxxxx xx Xxxxxxxxx Xxxxxxxxxx Xxxxxxx, X: Xx xxxxx Metabolic Xxxxxxxxxx in Mutagenesis Xxxxxxx, de Xxxxxx, X. X., Xxxxx, X. X., Bend, X. X., Xxxxxxx, X. X. (eds), Xxxxxxxx, Xxxxx-Xxxxxxx, 85-88.

21) Xxxxx, X. X., Xxxxxx, F. X., XxXxxxx, X. T. (1982), CHO/HGPRT Mutation Xxxxx: Evaluation of Xxxxx and Xxxxxxxx Xxxxxxx, xx: Ticc, X. R., Xxxxx, X. L., Schaich, X. M. (eds), Xxxxxxxxx Effects of Xxxxxxxx Agents, Xxx Xxxx, Plenum, 91-103.

22) Xxxxxx, X. O., Xxxxxx, J. X., Xx, X. X., Xxxxxx, A. L. (1983), Evaluation xx xx Exposure Xxxxxx Xxxxx Cells Xxxxx xx Xxxxxxxx Gels xxx Detecting Highly Xxxxxxxx Xxxxxxxx xx xxx XXX/XXXXX Xxxxxxxx Xxxxx, Environ. Mutagenesis, 5, 795-801.

23) Xxxxxxxxx, X. X., Xxxxx, X. X., Xxxxxx, X. X., Burrell, X., Xxxxxx, J. X. (1990), Molecular Xxxxxxxxxx of Mutations xx xxx Xxxxxxxxxxxx Xxxxxxxxx Xxxxxx Locus xx Xxxxx Lymphoma Xxxxx, Xxxx. Xxxx. Xxxx. Xxx. X. X. A, 87, 51-55.

24) Moore, X. X., Clive, X., Xxxxxx, X. C., Xxxxxx, X. E., Xxxxxx, X. X., Xxxxxx, X. X., Xxxxxx, X. (1985), Xxxxxxxx xx Xxxxxxxxxxxxxxxxxx, Xxxxxxxxx (TFT+) Xxxxxxx xx X5178X/XX+/--Xxxxx Xxxxxxxx Xxxxx, Xxxxxxxxxx Res. 151, 161-174.

25) Yandell, X. X., Dryja, X. X., Xxxxxx, X. X. (1990), Xxxxxxxxx Xxxxxxx Analysis xx Xxxxxxxxx Mutations xx x Xxxxxxxxxxxx Xxxxxxxxx Locus xx Xxxxx Xxxxx, Xxxxxxxxxx Xxx. 229, 89-102.

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

PŘÍLOHA 4X

"X.23 ZKOUŠKA XX XXXXXXXXXXXX XXXXXXX XX XXXXXXXXXXXXXXX SAVCŮ

1. XXXXXX

Xxxx xxxxxx xx xxxxxxxx metody OECD XX 483 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx spermatogoniích xxxxx (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx xxxxx in xxxx xx identifikovat xxxxxx xxxxx, xxxxx xxxxxxxxx xxxxxxxxxx chromozomové aberace xx xxxxxxxxxxxxxxx xxxxx (1, 2, 3, 4, 5). Rozlišují xx dva xxxx xxxxxxxxxxxx xxxxxxx: chromozomové x xxxxxxxxxxxx. X xxxxxxx xxxxxxxxxx mutagenů xxxx xxxxxxxxxx aberace xxxxxxxxxxxxxx xxxx, xxxxx xxxxxxxxxxxx xxxxxxx se xxxxxx xxxxxxxxx. Xxxx xxxxxx xxxx určena xx xxxxxxxxx xxxxxxxxxxx xxxxxxx a xxxx x tomuto xxxxx xxxxxxx xxxxxxxxx. Xxxxxxxxxxxx xxxxxx a podobné xxxx xxxx xxxxxxxx xxxxx geneticky podmíněných xxxxxx x člověka.

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

X xxxx xxxxxxx xxxx rutinně xxxxxxxxx xxxxxxxx. Touto xxxxxxxxxxxxxx xxxxxxxx xx xxxx xx xxxxxxxx chromozomové xxxxxxx xxx xxxxxx xxxxxxxxxxxxx. Xxxx xxxxxx xxxxx nejsou xxxxxxxxx xxxx xxxxxxx.

Xxx detekci xxxxxxx xxxxxxxxxxxxxx xxxx xx spermatogoniích by xxxx xxx — xxxxx než xxxxx xx xxxxxx xxxx — vyšetřeno xxxxx xxxxxxxxx xxxxxxx xxxxxx, xxxxx xxxxxxxxx po xxxxxxxx. Další informace x exponovaných xxxxxxxxxxxxxxxxxx xxxxxxxxx buněk xxx xxxxxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx aberací xxxxxxxxxxxxxx xxxx x xxxxxxxxx-xxxxxxxx X, kdy se xxxxxxxxxx buňky stávají xxxxxxxxxxxx.

Xxxx xxxxxxx in xxxx je xxxxxxxx xxx xxxxxxxxx, xxx xxxx xxxxxxxx xxxxxxxxxxx xxxxx xxxxxxx také x xxxxxxxxxxxx xxxxxxx. Xxxxx xx tato xxxxxxx se xxxxxxxxxxxxxxx xxxxxxxx pro posouzení xxxxxxxxx xxxxxxxxxx, neboť xxxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx in xxxx, xxxxxxxxxxxxxxx a procesy xxxxxxxx XXX.

Xx xxxxxxxxx xx xxxxxxxx xxxx xxxxxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxxxx xx xxxxxxxx chemické xxxxx. Xxxxxxxxxx aberace xxxx xxxxxxxxxxx souhrnnou xxxxxxx xxxxxxxxxx xxxxxxxx spermatogonií x převládajícími xxxxxxxxxxxxxxx xxxxxxxxxxxxxxx. V xxxxxxxxxx xx xxx xxxxxx xx xxxxxxxxx, mohou xxxx xxxxxx xxx xxxxx xxxxxxxx xxxxxxxxxxxxx xxxxxxxxxx celkovému xxxxxxxx xxxxx x důsledku xxxxxxxxx x xxxxxxxxxxxx xxxxxxx Xxxxxxxxx buněk x xxxxxxx mezi xxxxxxx oběhem a xxxxxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, xx xx xxxxxxxx látka xxxx reaktivní metabolity xxxxxxxxxx do xxxxxx xxxxx, xxxx xxxxxx xxxx zkoušku xxxxxx.

Xxx xxxx obecný xxxx, xxxx X.

1.2 DEFINICE

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

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

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

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

Xxxxxxxxxxx : násobek xxxxxxxxxxx xxxxx chromozomových sad (x), xxxx xxx xxxxxxxxx (xx. 3 x, 4 x xxx.).

Xxxxxxxxxx aberace : xxxxxxxxxxxxx xxxxxxxxxxxxx změny xxxxxxxxx xxxxxxxxxx při xxxxxxxx dělení xx xxxxxx xxxxxxxx pod xxxxxxxxxxx, jeví xx xxxx delece x xxxxxxxxx, xxxxxxxxxxxxxxxxxx xxxx xxxxxxxxxxxxxxxxxx xxxxx.

1.3 PODSTATA XXXXXXXX XXXXXX

Xxxxxxx xxxx xxxxxxx způsobem xxxxxxxxxx xxxxxxxx xxxxx x xx xxxxxx xxxx xx xxxxxxxx xxxxxxxx. Xxxx xxxxxxxxx se xxxxxxxx xxxx látka xxxxxxxxxxx metafázi (xxxx. xxxxxxxxx nebo Colcemid®). X xxxxxxxxxxxx xxxxx xx xxxx připraví xxxxxxxxx xxxxxxxxxx, xxxxxx xx a analyzují xx xxxxxxxxxxxx xxxxxxx xxxxxxxxxxxxxx buněk.

1.4 XXXXX XXXXXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xxxx používáni xxxxx xxxxxx čínského a xxxx; xxx xxxx xxxxxx xxxxx xxxxxxxxxx xxxxxx xxxxxxxx druhu xxxxx. Xxxx by xxx použity xxxxx xxxxxxx xxxxxxxxxxx kmeny xxxxxxx xxxxxxxx xxxxxxxx xxxxxxxxx xxxxxx. X xxxxxxxx zahájení studie xx měla být xxxxxxxx x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx by xxxxxxxxx ± 20 % xxxxxxx xxxxxxx xxxxxxxxx.

1.4.1.2 Xxxxxxxx xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx mladí xxxxxxxx xxxxxxx samci xx xxxxxxxx výběrem xxxxxxx xx xxxxxxxxx xxxxxxx x xxxxxxx, která xx xxxxxxxx. Klece xx xxxx být xxxxxxxxxx xxx, xxx xxx vliv jejich xxxxxx xxxxxxxxxxxxx. Xxxxxxx xx xxxxxxxxxxx xxxxxxxxxxxx. Xxxx xxxxxxxxx xxxxxx xx xxxxxxx x xxxxxxxxxxxxx podmínkách xxxxxxx xxx xxx xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx xxxxx

Xxxxx zkoušené xxxxx by xxxx xxx xxxx xxxxxxxx xxxxxxxx xxxxxxxxxx xxxx xxxxxxxxxxxx ve xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx xxxxxxx. Xxxxxxx xxxxxxxx xxxxx xxxxx xxx xxxxxxxx xxxxx nebo xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx by xxx xxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, pokud xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Xxxxxxxx xxxxxxxx

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx mít při xxxxxxxxx hladinách xxxxx xxxxxxx účinky x xxxx by být xxxxxxxxx xxxxxxxxx, že xxxxxxx se xxxxxxxxx xxxxxx. Jsou-li xxxxxxx xxxx xxx xxxxx xxxxxxxxxxxx/xxxxxxxx, mělo by xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx x xxxxxx kompatibilitě. Doporučuje xx xxxxx možno xxxxxxxx xxxxxx použití xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Kontroly

Součástí xxxxxxx xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx a negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. S xxxxxxxx xxxxxxxx xxxxxxxx xxxxx by xxxx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxx xxxxxxxxx proces xxxx xxxxxxx xx xxxxxxxxx, x xxxxx xxxxx x expozici.

Pozitivní xxxxxxxx xx xxxx xxxxxxxxxx xxxxxxxxxx aberace xx xxxxxxxxxxxxxxx xx xxxx při xxxxxxxxxxx xxxxxxxx, x xxxxx xx předpokládá, xx xxxxxxxxx xxxxxxxxxxxxx xxxxxx xxx xxxxxx.

Xxxxx xxxxxxxxx xxxxxxxx xx měly xxx xxxxxxx xxx, xxx xxx xxxxxx xxxxxxxx, xxx aby xxx xxxxxx xxxxxxx xxxxx najevo xxxxxxxx xxxxxxxxxxxx preparátu. Xx xxxxxxxxxx, xxx xxxx xxxxxxxxx kontrola xxxxxxxx xxxxx xxxxxxxx než xxxxxxxx látka x xxx xxx xxxxx x xxxxx xxxxxxx xxxxxxxx xxx jednou. Xxx pozitivní kontrolu xxxx xxx xxxxx xxxxx x xxxxx xxxxxxx xxxxxxxxxx xxxxx xx xxxxxx xxxxxxxx xxxxx, jsou-li x xxxxxxxxx. Xxxxxxxx látek xxx xxxxxxxxx kontrolu:

Látka	Číslo 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 xxxxxxx xxxxxx xx xxx xxx xxxxxxxx xxxxx x xxxxxxx negativní xxxxxxxx, xxxxx xx aplikováno xxxxx xxxxxxxxxxxx nebo xxxxxxxxx x která xxxxx xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxxxxx xxxxxxx, pokud xxxxxx x xxxxxxxxxxx xxxxxxxxxxx xxxxx k dispozici xxxxxxxxxx xxxxx x xxxxxxxxxxx xxxxxx x xxxxxxxx xxxxx x xxxxxxxxxxxxxx aberacemi. Kromě xxxx xx měly xxx xxxxxxxxxxxx xxxxxxxx xxxxxxx také tehdy, xxxxxxxxxx-xx xxxxx xxxxxxxxx xxxxx prokazující, že xxxxxxx xxxxxxxxxxxx/xxxxxxxxx nevyvolává xxxxx xxxxxxx xxxx xxxxxxxxx účinky.

1.5 XXXXXX

1.5.1 Xxxxx xxxxxx

Xxxxx xxxxxxxxxx x kontrolní xxxxxxx xxxx xxxxxxxxx xxxxxxx xxx xxxxxxxxxxxxxxxx samců.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xx xxxx být xxxxx xxxxx podávány xxxxxxxxxxx xxxx xxxxxxxxx (xx. při xxxxx xxxxxxxx nebo xxxx xxxxxxxxxx). Zkoušené xxxxx xxxxx xxx xxxxxxxx xxxx xx dvou xxxxxxx, xxx. xxx xxxxx x xxx xxx x rozmezí xx více xxx xxxxxxxx xxxxx, xxx xxxx xxxxxxxxx xxxxxxxx xxxxxxx objemů xxxxxxxxx. Xxxx režimy xxxxxxxx xx měly xxx xxxxxxx xxxxxxxxxx.

Xx xxxxxxx x xxxxxxxx xxxxxx xx xxxx být xx xxxxxxxx xxxxxxxxx xxx xxxxxx. Poněvadž xxxxxxxx buněčného xxxxx xxxx xxx zkoušenou xxxxxx ovlivněna, provede xx xxxxx xxxxx xxxxx a xxxxx xxxxxxxx xxxxx přibližně 24 x 48 xxxxx xx xxxxxxxx. X případě jiné xxx xxxxxxxx xxxxx xx xxx být xxxxx xxxxxxxx xx 24 xxxxx nebo xx xxxxxx xxxx xxxxxxxx, xxxxx xxxxxxxx 1,5xxxxxxx xxxxx xxxxxxxxx xxxxx, xxxxx není xxxxx xxxx xxxxxxxxx xxxx xxx detekci xxxxxx (6).

Navíc xxxxx xxx xxxxxx xxxxxxxxx xxxx x xxxx xxxx. Například x xxxxxxx chemických xxxxx, xxxxx xxxxx indukovat xxxxxxxx xxxxxxxxx (lagging) xxxxxxxxxx xxxx xxxxx xxxxxxxxxx X-xxxxxxxxx xxxxxx, xxxx být xxxxxxxxx xxxxxxxx xxxxx (1).

Vhodnost xxxxx xxxxxxxxx xxxxxxxx xxxx být xxxxxx xxxxxx od xxxxxxx. X xxxxxxx xxxxx x xxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx xxxxxxxx 24 xxxxx (1,5násobek délky xxxxx) po poslední xxxxxxxx. Xxxxx potřeby xxxxx být xxxxxxxxx xxxxx xxxxxx x xxxx xxxx.

Xxxx xxxxxxxxx xx xxxxxxxx xxxxxxxxxxxxxxxxx xxxx xxxxxx dávka xxxxx xxxxxxxxxxx metafázi (xxxx. Xxxxxxxx® nebo xxxxxxxxx). Xxxx se xx xxxxxx xxxx xxxxxxx x xxxxxx xxxxx. U xxxx xx xxxx doba xxxxxxxxx 3 — 5 xxxxx; x xxxxxx xxxxxxxx je xxxx xxxx přibližně 4 — 5 xxxxx.

1.5.3 Dávkování

Provádí-li xx xxxxx xxxxxxxxxxx vhodných xxxxxxxxxx xxxxx xxxxxx xxx zjištění xxxxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx xxxxxxxxxx, se stejným xxxxxx x xxxxxx x za xxxxxxxx xxxxxx xxxxxxxx, který xx použije v xxxxxx xxxxxx (7). X xxxxxxx toxicity xx xxx první xxxxx xxxxxxx xxx xxxxxx xxxxx. Xxxx xxxxxx xxxxx xx xxxx xxxxxxxx xxxxxxx xxxx maximální x xxxxxxxxx xxxxxxxxx, xxxxxxxx xxxxxx xxxxxxxxx. Xxx xxxxxxxxx odběru stačí, xxxx xxxx xxxxxxx xxxxx xxxxxxxx dávka. Xxxxxxxx xxxxx je xxxxxxxxxx xxxx dávka xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xx xxxxx xxxxx xxxxx xxx xxxxxxx xxxxxx xxxxxxxxx podle očekávání x xxxxxxxx.

Xxxxx se xxxxxxxxxxx xxxxxxxxxxx aktivitou xxx xxxxxxx xxxxxxxxxxx xxxxxxx (xxxx. xxxxxxx x mitogeny) nemusí xxxxxxxxx stanovení xxxxx xxxxxxxxx a měly xx být xxxxxxxxx xxxxxx xx případu. Xxxxxxxx xxxxx může xxx xxxx xxxxxxxxxx xxxx xxxxx vyvolávající xx xxxxxxxxxxxxxxx xxxxxxx xxxxxx xxxxxxxx (xxxx. xxxxxxx počtu xxxxxxxxxxxxx x xxxxxx vzhledem x první x xxxxx meiotické xxxxxxxx; xxxx xxxxxxx by xxxxxx překročit 50 %).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx s jednou xxxxxx xxxxxxx 2000 xx/xx xxxxxxx hmotnosti xxxxxxx xxxxxxxxxxx nebo xx xxxx dávkách x xxxxxx dni xxxxxxxxxx xxxxx pozorovatelné xxxxxxx xxxxxx a xxxx-xx na základě xxxxx x xxxxxxx, xxxxx xxxx xxxxxxxx xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxxxxxx se xxxxx xxxxxx se třemi xxxxxxxx xxxxx xx xxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxxxx může znamenat xxxxxxx xxxxxx x xxxxxxx xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Podávání xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx sondou xxxx xxxxxxx xxxxxxxxx xxxxxxx, xxxx xxxxxxxxxxxxxxxxx xxxxxxx. Xxxx xxxxxxx xxxxxxxx xxxx přijatelné, xxxx-xx xxxxxxxxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, který xxxx xxx najednou xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx xxxxxxxxx 2 xx/100 x xxxxxxx xxxxxxxxx. Xxxxxxx vyšších xxxxxx, xxx xx uvedený xxxxx, xxxx xxx xxxxxxxxxx. Xx xx xxxxxxxx x žíravé xxxxx, xxxxx xxxxxxx xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx účinky, xx xxxx být xxxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxxxxxx nastavením xxxxxxxxxxx xxxxxxxxxxx konstantní xxxxx xxx všech xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx preparátů xx xxxxxxx chromozomů

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

1.5.7 Xxxxxxx

X xxxxxxx xxxxxxx xx mělo xxx xxxxxxxxxxx xxxxxxx 100 xxxxx v xxxxx xxxxxxxxxxxx xxxxxxxx (xx. xxxxxxxxx 500 xxxxxxxx xx skupinu). Xxxxx xxxxx xxx snížit, xx-xx pozorován velký xxxxx xxxxxxx. Xxxxxxx xxxxxxxxx xxxxxx preparátů xxxxxxxxxxx x xxxxxxxxxxx xxxxxxx, by měly xxx xxxx mikroskopickou xxxxxxxx nezávisle xxxxxxxx. Xxxxxxxx při xxxxxx xxxxx xxxxxxx xx xxxxxxxxxxxxxx xxxxxx xxxx xxxxxx xxxxxxxxxx x xxxxx xxxxxxxx, měly xx xxxxxxxxxxx buňky xxxxxxxxx xxxxxxxxxx x xxxxx xxxxxxxxxxxxxx xxxxx 2 n ± 2.

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxxx pro jednotlivá xxxxxxx xx xxxx xxx xxxxxxxxxx xx xxxxx tabulky. Xxxxxxxxxxxxxx xxxxxxxxx xx zvíře. Xxx xxxxx zvíře xx xxx xxx xxxxxxxxxx xxxxx xxxxx xx xxxxxxxxxxxx xxxxxxxxxxxxxx xxxxxxxxx x xxxxx xxxxxxxxxxxxxx aberací xx xxxxx. Pro xxxxxxxxxx x xxxxxxxxx skupiny xx xxxx být xxxxxxx xxxxx typy xxxxxxxxxxxx chromozomových xxxxxxx x xxxxxx počtem x xxxxxxxx. Xxxx xx xxxxxxxxxxxxx xxxxxxxx x uvádějí se, xxx xxxxxx se xxxxxxxxxx xx celkové xxxxxxxx xxxxxxx.

Xx-xx xxxxxxxxxx xxxxxx x xxxx xxxxxx, měl xx xxx xxx xxxxxxxxx xxxxxxx xxxxxxxxxxxxx xxxxxx xxxx xxxx xxxxxxxxxxxx xxxxxxxx u xxxxx xxxxxxxxxxxx xxxxxx x xxxxxx xxxxxxxxxx jako xxxxxxxxx xxxxxxxx xxxxx xxxxxxxxxxxxx x xxxxxx xxxxxxxx k první x xxxxx xxxxxxxxx xxxxxxxx, x xx x xxxxxxxx xxxxxx 100 xxxxxxxx se xxxxx xx xxxxx xxxxx. Xxxxx je xxxxxxxxx xxxxx xxxxxx, xxxxxxx x 1000 xxxxxxx xx zvíře xx xxx být xxxxxxxx xxxxxxxxx index.

2.2 XXXXXXXXX X XXXXXXXXXXXX XXXXXXXX

Xxx xxxxxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxx několik xxxxxxxx, xxxx. xxxxxx xxxxx xxxxx x xxxxxxxxxxxxxx xxxxxxxxx v xxxxxxxxxx xx xxxxx xxxx xxxxx xxxxxx xxxxx xxxxx x xxxxxxxxx xxx skupinu x xxxxxxx xxxxxx x x xxxxxxxx xxxxxxxx xxxxxx. Nejdříve xx xxxx xxx xxxxxxx biologická xxxxxxxxx xxxxxxxx. Při hodnocení xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxx (8). Xxxxxxxxxxx xxxxxxxxxx xx neměla xxx xxxxxxx xxxxxxxxx xxxxxxxx xxx pozitivní xxxxxxx. Xxxxxxxxxx xxxxxxxx xx xxxx být xxxxxxxxx xxxxxx zkoušením, xxxxxxx x xxxxxxxx xxxxxxxxxxxxxxxx podmínek.

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

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx výsledky, x xxxxxxxxxxx případech xxxxxxxx soubor xxxxx xxxxxxxx xxxxxxx výrok x xxxxxxxx xxxxxxxx xxxxx. Výsledky xxxxx xxxxxx dvojznačné xxxx xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx xxxxxxxx.

Xxxxxxxxx xxxxxxxx xxxxxxx na xxxxxxxxxxxx xxxxxxx xx xxxxxxxxxxxxxxx savců xx xxxx xxxxxxxxx, xx xxxxxxxx xxxxx xxxxxxxx x xxxxxxxxxxxx buňkách xxxxxxxxxxx druhu strukturní xxxxxxxxxxxx aberace. Xxxxxxxxx xxxxxxxx xxxxxxxxx, xx xxxxxxxx látka za xxxxxxxx zkoušky neindukuje x xxxxxxxxxxxx buňkách xxxxxxxxxxx druhu chromozomové xxxxxxx.

Xxxx xx xxx xxxxxxxxxxx pravděpodobnost, x xxxxx se zkoušená xxxxx xxxx její xxxxxxxxxx dostanou do xxxxxx tkáně.

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx xxxxxxxxx xxxx informace:

Rozpouštědlo/vehikulum:

- xxxxxxxxxx xxxxx vehikula,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet x xxxxx xxxxxx,

- xxxxx, xxxxxxxx xxxxx, xxxxxx xxx.,

- xxxxxxxxxxxx xxxxxxxx zvířat na xxxxxxx xxxxxxx, xxxxxx xxxxxxx tělesné xxxxxxxxx, xxxxxxx xxxxxxx a xxxxxxxxxx xxxxxxxx xxx xxxxxx xxxxxxx.

Xxxxxxxx podmínky:

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- zdůvodnění způsobu xxxxxxxx,

- xxxxx x xxxxxxxx xxxxxxxx xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx xxxxx,

- zdůvodnění xxx xxxxxxxx,

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

- xxxxxxxx xxxxx x xxxxxxx krmiva x vody,

- podrobný xxxxx rozvrhu expozice x xxxxxx,

- metody xxxxxxxxx xxxxxxxx,

- xxxxxxxxxxxx xxxxx xxxxxxxxxxx xxxxxxxx, xxxx koncentrace a xxxxx xxxxxxxx,

- xxxxxx xxxxxxxx xxxxxxxxx,

- xxxxxxxx xxxxxxxxx aberací,

- počet xxxxxxxxxxxxx buněk xx xxxxx xxxxx,

- kritéria xxxxxxxxxxx xxxxxx na xxxxxxxxx, negativní xxxx xxxxxxxxxxx.

Xxxxxxxx:

- xxxxxx xxxxxxxx,

- xxxxxxxxx index,

- xxxxx xxxxxxxxxxxxx x mitose xxxxxxxx k xxxxx x xxxxx xxxxxxxx xxxxxx,

- typ x xxxxx xxxxxxx xxxxxxx xxxxxxxxxx xxx xxxxx xxxxx,

- xxxxxxx počet xxxxxxx xx xxxxxxx,

- xxxxx xxxxx s xxxxxxxxx xx xxxxxxx,

- xxxxx možnosti xxxxxxxxx xxxxxxxx xx xxxxx,

- xxxxxxxx xxxxxxxxxxx analýzy,

- xxxxx x souběžné xxxxxxxxx kontrole,

- xxxxxxxxx xxxxx o xxxxxxxxx xxxxxxxx s xxxxxxxxx, xxxxxxxxx hodnotami a xxxxxxxxxxxx odchylkami,

- údaje x xxxxxxxx pozitivní xxxxxxxx,

- xxxxx ploidie, xxxxx xxxx xxxxxxxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

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

2) Adler, X. X., (1984), Xxxxxxxxxxx xxxxx in Xxxxxxx, xx: Xxxxxxxxxxxx Xxxxxxx: x Practical Approach, (xx.) S. Xxxxxx, X. X. Xxxxx, XXX Xxxxx, Oxford, Xxxxxxxxxx XX, 275-306.

3) Xxxxx, X. P., Xxxxxxx, G., Ford, X. E. (1964), Xx Air-drying Method xxx Xxxxxxx Xxxxxxxxxxxx xxxx Xxxxxxxxx Testes, Xxxxxxxxxxxx Cell Genetics, 3, 289-294.

4) Xxxxxxx, X., Xxxxx, X., Xxxxxxxx, X., Xxxxxxxxx, X. X., Xxxxxxxxx, X. (1990), In xxxx Cytogenetic Assays, xx: X. X. Xxxxxxxx (xx.), Xxxxx Xxxxxxxxxxxx Xxxxx, XXXXX Xxxxxxxxxxx Procedures. XXXXX Xxxxxxxxxxxx xx Guidelines xxx Mutagenicity Xxxxxxx. Xxxxxx. Part I xxxxxxx, Xxxxxxxxx University Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 115-141.

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

6) Xxxxx, X. D., Xxxxxx X. D., Xxxxxxx, X., Favor, X., Generoso, X., Xxxxxxxxxxxx, X., Xxxxxxx, X., Tanaka X. (1994), International Workshop xx Xxxxxxxxxxxxxxx of Xxxxxxxxxxxx Xxxx Procedures. Xxxxxxx Xxxxxx xx xxx Xxxxxxx Xxxxx xx Xxxxxxxxx Xxxx Xxxx Tests, Xxxxxxxxxx Xxx., 312, 313-318.

7) Xxxxxxx, X. X., Xxxxx, J. X., Xxxxxx, X. X., Xxxxxx, P. A., Xxx, J., Esdaile, X. J., Xxxxxxxxx, X. X., Xxxxxx-Xxxxxx, X., Xxxxxx, X. X., Kirkland, D. X., Xxxxxxx, X. (1992), Xxxxxx of Xxxxxxx Toxicology Society/UK Xxxxxxxxxxxxx Xxxxxxx Xxxxxxx Xxxxxxx Xxxxx: Dose Xxxxxxx xx In xxxx Xxxxxxxxxxxx Xxxxxx, Xxxxxxxxxxx, 7, 313-319.

8) Xxxxxx, X. P., Xxxxxxxx, X., Xxxxxxxx, X., Xxxxxxxx, X. X., Xxxxx, X., Xxxxxxxx, R., Xxxxxxx, X., Xxxxxxxx, X. X., Xxxxxx X. X. X. (1989), Xxxxxxxxxxx Xxxxxxxx of Xx vivo Xxxxxxxxxxx Xxxxxx, in: X. X. Xxxxxxxx (xx.), Xxxxxxxxxxx Xxxxxxxxxx xx Xxxxxxxxxxxx Test Xxxx. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Xxxxxxx, Xxxxxx, Part XXX. Xxxxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxxxx, Xxx Xxxx, Xxxx Xxxxxxx, Xxxxxxxxx, Xxxxxx, 184-232."

XXXXXXX 4G

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

1. XXXXXX

Xxxx xxxxxx xx replikou xxxxxx XXXX TG 486 — Xxxxxxx xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x xxxxxxxxx xxxxxxx savců xx vivo (1997).

1.1 XXXX

Xxxxxx xxxxxxx xx xxxxxxxxxxxx xxxxxxx XXX (XXX) x jaterních xxxxxxx xxxxx xx xxxx xx identifikovat xxxxxxxx látky, xxxxx xxxxxxxx xxxxxxxx DNA x jaterních buňkách xxxxxxxxxxxx xxxxxx (1, 2, 3, 4).

Xxxx xxxxxxx in xxxx xxxxxxxxx xxxxxx vyšetření xxxxxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx v játrech. Xxxxxxxxxxx jev je xxxxxxxxxx xxxxxxxxx DNA x následné xxxxxxxx x xxxxxxxxx buňkách. Xxxxx xxxx xxxxxxx xxxxxxx xxxxxx, kde xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxxxxx. Xxxx tedy xxxxxxx xxxxxx xxx xxxxxxxxx xxxx xxxxxxxxx XXX in xxxx.

Xxxxxxxx xxxxxxxx xxxxx x xxx, že xx xxxxxxxx látka nedostane xx cílové xxxxx, xxxx xxxxxx xxxx xxxxxxx xxxxxx.

Xxxxxx neplánované xxxxxxx XXX (UDS) xx zhodnotí xxxxxxxxxx xxxxxxxxxxx xxxxxxxxx nukleosidů xx xxxxx, které xxxxxxxx xxxxxxxxxx xxxxxxxx XXX (S-fází). Nejrozšířenější xxxxxxxxx xx autoradiografické xxxxxxxxx xxxxxxxxxxx thymidinu xxxxxxxxx xxxxxxx (3X-XxX). Xxx xxxxxxx na XXX xx xxxx xx xxxxxxxxxx používají xxxxx xxxxxxx. Xxxx xxxxx xxx xxxxx xxxxx být rovněž xxxxxxx, xxxxxx však xxxxxxxxx této metody.

Detekce xxxxxxxx XXX xxxxxx xx xxxxx xxxx XXX xxxxxxxxxxx x xxxxxxxxxxx x místě xxxxxxxxx. Xxxxxxx na XXX xx xxxx xxxxxx zvláště pro xxxxxxx xxxxxxxx reparací ("xxxx-xxxxx repair") (20 xx 30 bází) xxxxxxxxxxxx látkou. Xxxxxx xxxxxx ("xxxxx-xxxxx repair") (xxxxx až xxx xxxx) jsou xxxxxxx xxxx detekovány x xxxxxx menší xxxxxxxxxx. Xxxxx xxxx důsledkem xxxxxxxxxxxxx xxxxxxxx, xxxxxx xxxxxxxx nebo xxxxxx xxxxxxxxx xxxx XXX xxxxx x xxxxxxxxxx xxxxxxxxx. Rozsah odpovědi XXX neposkytuje xxxxxx xxxxxxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx. Xxxxx xx xxxxx, xx xxxxxxx reaguje x XXX, xxx poškození XXX xxxx opraveno xxxxxxxxxxx xxxxxxxx. Nedostatek xxxxxxxxxxxx informací, xxxxx xxxx zkouška poskytuje x mutagenní xxxxxxxx, xx xxxxxxx xxxxxxxxxxx xxxxxxxxxx xxxxxx jevu, xxxxx xx vyšetřován x celém genomu.

Viz xxxx xxxxxx úvod, xxxx X.

1.2 XXXXXXXX

Xxxxxxxxxx xxxxx : xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (NNG), xxxxx xxx xxxxxxxxxx xxxxxxx stanovená xxxxxxxxxx xxxxxxxxxxx xxxxxxx.

Xxxxx xxxxx xxx odpovídajících xxxxxxxx xxxxxx (NNG) : xxxxxxxxxxxxx xxxx UDS xxxxxxxx xxxxx x xxxxxxxxxxxxxxxxx xxxxxxx xx XXX, xxxxxxxxx odečtením xxxxxxxxxx xxxxx xxx x cytoplasmatických oblastech (XX) xxxxxxxxxxxxxx jádrům xx počtu xxx xxxxxxxxxxxxxx xxxxxxxx xxxxxx (XX): NNG = XX — XX. Xxxxxxx XXX xx xxxxxxx xxx xxxxxxxxxx xxxxx, poté společně xxx xxxxx x xxxxxxx, v xxxxxxxxxxx xxxxxxxxx xxx.

Xxxxxxxxxxx xxxxxxx XXX (UDS) : Xxxxxxx xxxxxxxx XXX xx xxxxxxxxx x xxxxxxxxxx úseku XXX xxxxxxxxxxxx xxxxxx s xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx.

1.3 XXXXXXXX XXXXXXXX XXXXXX

Xxxxxxx na XXX x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxx syntézu xxxxxxxx XXX xx vyštěpení x xxxxxxxxxx úseku XXX obsahujícího xxxxxx x xxxxxxxxxx indukovaným xxxxxxxxxx xxxxxxx nebo xxxxxxxxxxx xxxxxxxx. Xxxxxxx xx xxxxxxx xxxxxxxx xx inkorporaci 3X-XxX xx XXX xxxxxxxxx xxxxx, xxx je xxxx xxxxxxx xxxxx x X-xxxx xxxxxxxxx xxxxx. Xxxxxxxxxxx 3X-XxX xx xxxxxxx xxxxxxxxx xxxxxxxxxxxxxxx, xxxxxxx xxxx xxxxxxxx xxxx xxx xxxxxxx xx vliv X-xxxx buněk xxxx xxxx. xxxxxxx scintilační xxxxxxxxxxxxx.

1.4 XXXXX XXXXXX

1.4.1 Xxxxxxxxx

1.4.1.1 Xxxxx druhu xxxxxxx

Xxxxx xx xxxxxxxx xxxxxx, ačkoli lze xxxxxx xxxxxxxx vhodný xxxx xxxxx. Xxxx xx xxx xxxxxxx xxxxx používané laboratorní xxxxx xxxxxxx zdravých xxxxxxxx xxxxxxxxx zvířat. X xxxxxxxx xxxxxxxx xxxxxx xx měla xxx odchylka x xxxxxxxxx xxxxxx xxxxxxxxx x xxxxxx xx xxxxxxxxx ± 20 % xxxxxxx hodnoty xxxxxxxxx xxx obě xxxxxxx.

1.4.1.2 Podmínky xxxxx x xxxxxx

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

1.4.1.3 Xxxxxxxx xxxxxx

Xxxxxx xxxxxxxx xxxxxxx xxxxxxx se xxxxxxxx xxxxxxx rozdělí xx xxxxxxxxx skupinu x skupinu, která xx exponuje. Xxxxx xx měly být xxxxxxxxxx tak, aby xxx vliv jejich xxxxxx xxxxxxxxxxxxx. Zvířata xx xxxxxxxxxxx xxxxxxxxxxxx x před započetím xxxxxx xx xxxxxxx x xxxxxxxxxxxxx xxxxxxxxxx xxxxxxx xxx dní xxxxxxxxxxxxx.

1.4.1.4 Xxxxxxxx zkoušené xxxxx

Xxxxx zkoušené xxxxx xx xxxx xxx xxxx xxxxxxxx zvířatům xxxxxxxxxx nebo suspendovány xx xxxxxxxx xxxxxxxxxxxxxx xxxx xxxxxxxxxx x xxxxxxxxx zředěny. Xxxxxxx xxxxxxxx látky xxxxx xxx xxxxxxxx přímo xxxx xxxxx xxx xxxx xxxxxxx xxxxxxx. Xxxx xx xxx xxxxxxx čerstvě xxxxxxxxxx xxxxxxxx xxxxxxxx xxxxx, xxxxx xxxxx x xxxxxxxx xxxxxxxxxxx xxxxxxx xxxxxxxxxx.

1.4.2 Zkušební podmínky

1.4.2.1 Xxxxxxxxxxxx/xxxxxxxxx

Xxxxxxxxxxxx/xxxxxxxxx xx xxxxxx xxx xxx použitých xxxxxxxx xxxxx xxxxxxx xxxxxx a xxxx xx být xxxxxxxxx xxxxxxxxx, že xxxxxxx xx xxxxxxxxx xxxxxx. Xxxx-xx xxxxxxx jiná xxx xxxxx rozpouštědla/vehikula, xxxx xx xxx xxxxxx xxxxxxxx xxxxxxxxx xxxxx o jejich xxxxxxxxxxxxx. Doporučuje xx xxxxxxxx xxxxxx použití xxxxx xxxxx xxxxxxx xxxxxxxxxxxx/xxxxxxx.

1.4.2.2 Xxxxxxxx

Xxxxxxxx xxxxx xxxxxxxxx xxxxxxxxx části xxxxxxxxxxx xx xxxx xxx xxxxxxxx xxxxxxxxx x negativní (xxxxxxxxxxxx/xxxxxxxxx) xxxxxxxx. X xxxxxxxx xxxxxxxx xxxxxxxx xxxxx xx měla zvířata xxxxxxxxx skupiny xxxxxxxxxx xxxxxx xxxxxx xxxx xxxxxxx ve xxxxxxxxx, x xxxxx xxxxx x expozici.

Pozitivními xxxxxxxxxx xx měly xxx xxxxx, x xxxxx xx známo, xx xxxxxx xxxxxxxx x xxxxxxxxxxx expozičních koncentracích xxxx x nárůstu XXX detekovatelnému xxx xxxxxxx. Xxxxxxxxx kontroly xxxxxxxxxx xxxxxxxxxxxx xxxxxxxx xx xxxx xxx xxxxxxx v xxxxxxx xxxxxxxxxxxx xxxxxx xxxxxxx (4). Xxxxx xxxxx xxx xxxxxxx tak, xxx xxx účinek xxxxxxxx, ale xxx xxx xxxxxx xxxxxxx xxxxx xxxxxx xxxxxxxx xxxxxxxxxxxx xxxxxxxxx. Xxxxxxxx xxxxx pro xxxxxxxxx xxxxxxxx:

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

Xxxxx xxx xxxxxxx také xxxx xxxxx pro xxxxxxxxx xxxxxxxx. Je xxxxxxxxx, xxx byla xxxxxxxxx kontrolní xxxxx xxxxxxxx xxxxx způsobem, xxx zkoušená xxxxx.

1.5 XXXXXX

1.5.1 Počet x xxxxxxx xxxxxx

Xxx xx xxx použit xxxxxxxxxx xxxxx zvířat, xxx xxxx zohledněno xxxxxxxxx xxxxxxxxxx kolísání odpovědi xx xxxxxxx. Každá xxxxxxx by se xxxx xxxxxxx xxxxxxx xx tří xxxxxxxxxxxxxxxx xxxxxx. Jestliže xxxx xxxxxxxxxxx xxxxxxxxxx xxxxxxxxx xxxxx, xx xxx xxxxxxxxx x pozitivní xxxxxxxxx xxxxxxx nezbytné xxxxx xxxxx xx xxx xxxxxxx.

Xxxxxxxx xxxx x xxxx studie x dispozici xxxxx xx xxxxxx xx xxxxxxx xxxxxx x xx xxxxxxx xxxxxxxx xxxxxxx xxxxxxxx, jež xxxxxxxxx, xx xxxxxxxxxx xxxx pohlavími xxxxxx x xxxxxxxx, xxxx xxxxxxxxxxx xxxxxxxx xxxxxxx xxxxxxx, nejlépe xxxxx. Xx-xx expozice xxxxxxx xxxxxxxxxx xxx xxxxxx xxxxxxx, xxxx xx xxxx xxxxxxxxx x xxxxxxxxx xxxxxxxxxxxxxxx xxxxx, xxxx by být xxxxxxx provedena xx xxxxxxxx odpovídajícího xxxxxxx.

1.5.2 Xxxx xxxxxxxx

Xxxxxxxx xxxxx xxxx xxxxxxxxx podávány xxxxxxxxxxx.

1.5.3 Dávkování

Za normálních xxxxxxxx xx xxxxxxxxx xxxxxxx xxx úrovně xxxxx. Xxxxxxxx dávka xx xxxxxxxxxx xxxx xxxxx xxxxxxxxxxxx xxxxxx xxxxxx xxxxxxxx, xx xxxxx xxxxx by xxxxx xxxxx xxxxxxxxx xxx xxxxxxx xxxxxx xxxxxxxxx x xxxxxxxx. Xxxxx xxxxx by xxxx xxx xxxxxxxxx 50 % xx 25 % vyšší xxxxx.

Xxxxx xx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxx při xxxxxxx netoxických xxxxxxx (xxxx. xxxxxxx x xxxxxxxx) nemusí xxxxxxxxx xxxxxxxxx xxxxx xxxxxxxxx x xxxx by xxx xxxxxxxxx xxxxxx xx xxxxxxx. Xxxxxxx-xx xx kvůli xxxxxxxxxxx xxxxxxxx xxxxxxxxxx údajů xxxxxx xxx xxxxxxxx xxxxxxx, xxxx xx xxx xxxxxxxxx xx xxxxxx laboratoři, se xxxxxxx xxxxxx, xxxxxx, xxxxxxxx a za xxxxxxxx xxxxxx expozice, xxx se xxxxxxx x xxxxxx studii.

Nejvyšší xxxxx xxxx xxx xxxxxxxxxx xxxx xxxx xxxxx xxxxxxxxxxxx známky xxxxxxxx x játrech (xxxx. xxxxxxxxxx jádra).

1.5.4 Xxxxxxx xxxxxxx

Xxxxxxxx xxxxxxx x jednou xxxxxx x xxxxxxx 2000 xx/xx xxxxxxx xxxxxxxxx xxxxxxx xxxxxxxxxxx nebo xx xxxx xxxxxxx x xxxxxx xxx xxxxxxxxxx xxxxx xxxxxxxxxxxxx xxxxxxx xxxxxx a xxxx-xx na xxxxxxx xxxxx o xxxxxxx, xxxxx xxxx podobnou xxxxxxxxx, xxxxxxxxx xxxxxxxxxxxx, xxxxxx xxx xxxxx xxxxxx nezbytná. Očekávaná xxxxxxxx xxxxxxx může xxxxxxxx potřebu xxxxxx x limitní xxxxxxx xxxxx xxxxxx xxxxx.

1.5.5 Xxxxxxxx xxxxx

Xxxxxxxx xxxxx xx xxxxxxx xxxxxx xxxxxxxxxxxxxx, xxxxxxxxx xxxxxx xxxx vhodnou xxxxxxxxx xxxxxxx. Xxxx způsoby xxxxxxxx xxxx možné, xxx-xx je zdůvodnit. Xxxxxxxx xxxxxxxxxxxxxxxxx xx xxxx nedoporučuje, xxxxx xx játra mohla xxx xxxxxxxxxx zkoušené xxxxx přímo x xxxxxx xxxxxxxxxxxxxxx xxxxxxxxx xxxxxxx. Xxxxxxxxx xxxxx xxxxxxxx, xxxxx může xxx xxxxxxxx xxxxx xxxxxxxxx xxxxxx xxxx xxxxxxxx, závisí xx xxxxxxxxx xxxxxxxxxxx zvířete. Xxxxx by neměl xxxxxxxxx 2 xx/100 x xxxxxxx hmotnosti. Xxxxxxx xxxxxxx xxxxxx, xxx je uvedený xxxxx, xxxx xxx xxxxxxxxxx. Až xx xxxxxxxx x žíravé xxxxx, xxxxx obvykle xxx xxxxxxx xxxxxxxxxxxxx xxxxxxxx xxxxxxxx xxxxxx, xx xxxx xxx xxxxxxxxxxx xxxxxxxxxx objemu xxxxxxxxxxxxxx xxxxxxxxxx xxxxxxxxxxx xxxxxxxxxxx xxxxxxxxxx objem xxx xxxxx xxxxxxxx xxxxx.

1.5.6 Xxxxxxxx xxxxxxxxx xxxxx

Xxxxxxx buňky xx xxxxxxxxxx x xxxxxxxxxxxx xxxxxx zpravidla 12 xx 16 xxxxx xx xxxxxx xxxxx. Xxxxxxxxxx dřívější odebrání xxxxxx (xxxxxx xxx xx xxxxx hodiny xx xxxxxxxx) xx xxxxxxxx, xxxx-xx po 12 xx 16 xxxxxxxx jasná pozitivní xxxxxxx. Xxxxx xxxx xxx xxxxxxx xxxx xxxx xxxxxx, xxxx-xx xxxxxxxxxx na xxxxxxx xxxxxxxxxxxxxxxxx údajů.

Krátkodobé xxxxxxx xxxxxxxxx buněk savců xx xxxxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxxxxxxxx xx situ x xxxxxx xx, aby xx čerstvě xxxxxxxxxxx xxxxxxx xxxxx xxxxxxxxx xx vhodném xxxxxxx. Xxxxxxx xxxxx x xxxxxxxxx xxxxxxxx by xxxx xxxxxxxxx životaschopnost (5) xxxxxxx 50 %.

1.5.7 Xxxxxxxxx XXX

Xxxxxxx xxxxxxxxx xxxxxxx xxxxx xxxxx xx xxxxxxx xxxxxxx xxxx, xxxx. xxx xx osm xxxxx, inkubují s xxxxxx xxxxxxxxxxx 3X-XxX. Xx xxxxx xxxxxxxxx xxxx by mělo xxx xxxxxx x xxxxx xxxxxxxxxx x xxxxx poté xxxxx xxx xxxxxxxxxx x xxxxxx xxxxxxxxxxx xxxxxxxx xxxxxxxxxxx xxxxxxxxx, xxx xxxx xxxxxxx neinkorporovaná xxxxxxxxxxxxx ("cold xxxxx"). Xxxxx xx poté xxxxxxx, xxxxxx x xxxxxx. Xxx delší xxxxxxxxx době xxxxxx xxx xxxxxxx radioaktivity xxxxxxxx. Xxxxxxxxx xx xxxxxx xx xxxxxxxxxxxxxxxxx xxxxxx, exponují xx x xxxxx (xxxx. x xxxxxx 7 xx 14 xxx), xxxxxxxx xx, xxxxxx x xxxxxxxxx xx xxxxxxxxxx xxxx stříbra. X xxxxxxx xxxxxxx xx xxxxxxxx xxx xx xxx xxxxxxxxx.

1.5.8 Xxxxxxx

Xxxxxxxxx xx xxxx xxxxxxxxx dostatečný xxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx, xxx mělo xxxxxxxxx XXX výpovědní xxxxxxx. Xxxxxxxxx xx xxx xxxxxxxxxxx prohlédnou xx xxxxxx xxxxxx xxxxxxxxxxxx (xxxx. xx xxxxxxx, xxxxxxxx úroveň xxxxxxx xxxxxxxxxxxxx xxxxxxxx).

Xxxx xxxxxxxxx xxx xx měly xxx xxxxxxxxx xxxxxxxx. Xxxxxxxxx se xxxxxxxxx 100 xxxxx xx xxxxx xxxxx xxxxxxx xx xxxx xxxxxxxxx; xxxxxxxxx méně xxx 100 xxxxx/xxxxx by xxxx xxx xxxxxxxxxx. Xxx xxxxxxxx xxx xx xxxxx x X-xxxx nevyšetřují, xxx xxxxx xxxxx x X-xxxx xxxx být xxxxxxxxxx.

Xxxxxxxx 3X-XxX inkorporovaného xx xxxxx x xxxxxxxxxx xxxxxxxxxxxx xxxxxxxxxx xxxxx xxxxxxxx xxxxxxxxxxx xxx stříbra xx xxxx být stanoveno xxxxxxx metodou.

Počet xxxxx xx xxxxxxx x xxxxx zrn xxxxxxxxxxxxxx xxxxxxxx jádrŭm (ng) x z prŭměrného xxxxx zrn x xxxxxxxxxxxxxxxxx xxxxxxxxx (cg) xxxxxxxxxxxxxx jádrŭm. xxxx xxxxxxx xx se xxxxxxx xxx xxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxx xxxxxx xxxxxxxxxx, xxxx prŭměrná xxxxxxx xxxx xx tří xxxxxxx xxxxxxxxx xxxxxxx x xxxxxxxxx xxxxxxxxx xxxxxxxxx xxxxx. po xxxxxxxxxxxxx xxXxxxxxxx xxxxx xxx použity i xxxx xxxxxxx stanovení xxxxx xxxxx (xxxx. xxxxxxxx celých xxxxx) (6).

2. ÚDAJE

2.1 XXXXXXXXXX XXXXXXXX

Xxxx by xxx xxxxxxx xxxxx pro xxxxxxxxxx xxxxxxxxx a xxxxxxx. Údaje xx xxxx být dále xxxxxxx xx xxxxx xxxxxxx. Xxxxxxxxx xxxxxxx XX xx xxxxxxx XX xx xxx xxx vypočten pro xxxxxx xxxxx, pro xxxxx xxxxx x xxx každou xxxxx x čas čistý xxxxx zrn odpovídajících xxxxxxxx xxxxxx (NNG). Xxxxxxxx jsou xxxxxxxx "xxxxxxxxxx" xxxxx, xxxx xx být xxxxxxxx xxx xxxxxxxxxx "opravovaných" xxxxx odůvodněna a xxxxxxxx na dosavadních xxxx souběžných xxxxxxx x xxxxxxxxxxx xxxxxxxxxx. Xxxxxxxxx xxxxxxxx xxxxx xxx xxxxxxxxxx xxxxxxxxxxxxx xxxxxxxx. Mají-li xxx xxxxxxx, xxxx xx xxx xxxxxxxxxxx xxxxx xxxxxxx x xxxxxxxxxx xxxx xxxxxxxxxx xxxxxx.

2.2 XXXXXXXXX A XXXXXXXXXXXX XXXXXXXX

Xxxx příklady kritérií xxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxx xxxxx:

xxxxxxxxx	x)	xxxxxxx XXX xxxx xxx xxxxxxxx úrovní, xxxxx xx xxxxxxxxxx xx xxxxxxx dosavadních xxxxx xxxxxxxxxx;
xxxx	xx)	xxxxxxx NNG je xxxxxxxx xxxxx než xxxxxxx xxx souběžnou xxxxxxxx;
xxxxxxxxx	x)	xxxxxxx NNG leží xx dosavadní prahové xxxxxxx xxxx xxx xx;
xxxx	xx)	xxxxxxx XXX xxxx xxxxxxxx xxxxx než xxxxxxx pro xxxxxxxxx xxxxxxxx.

Xxxx xx být xxxxxxxxx xxxxxxxxxx relevance xxxxx, xx. xxxx xx xxx xxxxx x úvahu xxxxxxxxx, xxxx jsou variabilita xxxxxx, xxxxx xxxxx x odpovědi a xxxxxxxxxxxx. Při xxxxxxxxx xxxxxxxx xxxxxxx xxxxx xxx xxxxxxx jako xxxxxxx xxxxxxxxxx statistické xxxxxx. Xxxxxxxxxxx xxxxxxxxxx xx však neměla xxx jediným určujícím xxxxxxxx xxx pozitivní xxxxxxx.

Xxxxxx xxxxxxx experimentů xxxxxxxx xxxxx xxxxxxxxx xxxx xxxxxxxxx xxxxxxxx, x ojedinělých případech xxxxxxxx xxxxxx xxxxx xxxxxxxx konečný xxxxx x xxxxxxxx xxxxxxxx xxxxx. Xxxxxxxx mohou xxxxxx dvojznačné nebo xxxxxx xxx xxxxxx xx xx, xxxxxxxx xx xxxxxxxxxx opakován.

Pozitivní xxxxxxxx xxxxxxx xx XXX x jaterních xxxxxxx xxxxx xx xxxx xxxxxxxxx, že xxxxxxxx xxxxx indukuje x xxxxxxxxx xxxxxxx xxxxx xx xxxx xxxxxxxxx XXX, xxxxx xxx opravit xxxxxxxxxxxx xxxxxxxx XXX in xxxxx. Negativní xxxxxxxx xxxxxxxxx, xx xxxxxxxx xxxxx xx podmínek xxxxxxx neindukuje xxxxxxxxx XXX, které xxx xxxxxxxxx touto zkouškou.

Měla xx být xxxxxxxxxxx xxxxxxxxxxxxxxx, x jakou xx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxx xxxxx xxxx. xx xxxxxx tkáně (např. xxxxxxxxx xxxxxxxx).

3. XXXXXX

XXXXXXXX X XXXXXXX

Xxxxxxxx x xxxxxxx xxxx obsahovat xxxx xxxxxxxxx:

Xxxxxxxxxxxx/xxxxxxxxx:

- xxxxxxxxxx xxxxx xxxxxxxx,

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

Xxxxxxxxx xxxxxxx:

- xxxxxxx xxxx/xxxx,

- počet, xxxxx x pohlaví xxxxxx,

- xxxxx, podmínky xxxxx, strava xxx.,

- xxxxxxxxxxxx xxxxxxxx xxxxxx xx počátku xxxxxxx, xxxxxx xxxxxxx xxxxxxx xxxxxxxxx, xxxxxxx xxxxxxx x směrodatné odchylky xxx xxxxxx skupinu.

Zkušební xxxxxxxx:

- xxxxxxxxx a xxxxxxxxx (xxxxxxxxx/xxxxxxxxxxxx) xxxxxxxx,

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

- xxxxxxxxxx xxxxxxxxx úrovní xxxxx,

- údaje o xxxxxxxx zkoušené xxxxx,

- xxxxx o xxxxxxxx xxxxxxxx látky,

- xxxxxxxxxx xxxxxxx xxxxxxxx,

- xxxxxxxxx xxxxxx ověření, xxx xx zkoušená xxxxx xxxxxxx do krevního xxxxx nebo do xxxxxx xxxxx,

- xxxxxxxx xxxxxxxx xxxx xxxxxxxxxxx xxxxxxxx látky x xxxxxx nebo vodě (xxx) na xxxxxxxxxxxx xxxxx (mg/kg tělesné xxxxxxxxx/xxx),

- xxxxxxxx údaje x xxxxxxx krmiva x xxxx,

- podrobný xxxxx xxxxxxx expozice x odběru,

- xxxxxx xxxxxxxxx xxxxxxxx,

- metody xxxxxxxx x xxxxxxxxx xxxxxxxxx buněk,

- xxxxxxx xxxxxxxxxxxxxxxxx xxxxxxxx,

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

- xxxxx xxxxxxxx xxxxxxxxx xxxxxxxx na xxxxx,

- případné xxxxxxxxxxx xxxxxxxxx,

- známky xxxxxxxx,

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

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

- xxxxx xxxxx "opravovaných" buněk, xx-xx xxxxxxxx,

- xxxxx xxxxx x S-fázi, xx-xx xxxxxxxx,

- xxxxxxxxxxxxxxx xxxxx.

Xxxxxx xxxxxxxx.

Xxxxxx.

4. XXXXXXXXXX

1) Xxxxx, X. Lefevre, X. X., Burlinson, X., Xxxxxx, X. X. (1985), Xx Xxxxxxxxxx xx the Xx vivo Xxx. Xxxxxxxxxx XXX Repair Xxxxx, Mutatation Xxx., 156, 1-18.

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

3) Xxxxxxxx, X. X., Xxxxxx, X., Xxxxx, J., Xxxxxxx, X. X., Xxxxxxxxx, B., Benford, X. X., Xxxx, X. X., Xxxxxxxx, X. de X. (1993), Xx xxxx Xxx Liver UDS Xxxxx, in: Xxxxxxxx X. X., Xxx X., (xxx), Xxxxxxxxxxxxx Xxxxxxxxxxxx Tests: XXXX Xxxxxxxxxxx Procedures. XXXXX Xxxxxxxxxxxx xx Xxxxxxxxxx xxx Xxxxxxxxxxxx Testing. Xxxxxx. Xxxx XX xxxxxxx, Xxxxxxxxx Xxxxxxxxxx Xxxxx, Cambridge, Xxx Xxxx, Port Chester, Xxxxxxxxx, Xxxxxx, 52-77.

4) Xxxxx, X., Dean, X. W., Andrac, X., Xxxxxxxxx. X., Xxxxxxxxx, X., Xxxxxxxxx, X. J., Xxxxxxxx, X., Xxxxxxx, X., XxXxxxx, C. X., Xxxx, H. (1993), Xxxxxxxxxxxxxxx xxx xxx Xxxxxxxxxxx xx XXX Xxxxx Xx vitro xxx In vivo, Xxxxx. Res., 312, 263-285.

5) Xxxxx, X., Xxxxxxx, X., Xxxxxxxxxx, X., Xxxxxxxxxxxx-Xxxxxx, C. (1993), Assessment of xxx Xxxxxxxx Xxxxxxx xxx Xxxxxxx Viability xxx xxx Xxxxxxxxxx xx Xxxxxxx Xxxxxxxx Xxx Xxxxxxxxxxx Xxxx xxx xxx In xxxx/Xx xxxxx XXX Xxxxxx Assay (XXX), Xxxxxxxxxx Xxx., 291, 21-27.

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

XXXXXXX 5

OBECNÉ XXXXXXXXX XX XXXXXXXXXXX A XXXXXXXXXX XXXXXXXXXXXX XXXXX X PŘÍPRAVKŮ

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

XXXXXXX 6

"

XXXXXXX XX

XXXX X

xxxxxxxx xxxxxxxx se xxxxxxx xxxxxxxx xxxxx xxxxxxxx xxxxx

Xxxxx xxxxxxxxxx xx. 22 xxxx. 1 xxxx. x) xxxx xxxxxxxx, musí xxx xxxxx x xxxxxxxxx objemu xxxxxxxxxx xxxxx, x xxxxx xx xxxxxxx xxxxxx xxx vdechování (Xn; X 65) a xxxxx xxxx xxxxxxxxxxxxx x xxxxxxxx xxxxx xxxx 3.2.3 xxxxxxx XX xxxx xxxxxxxx, x výjimkou xxxxx xxxxxxxxx xx xxx xx xxxxx xxxxxxxx xxxx v xxxxxxxx xxxxxxxxxx aerosolovým xxxxxxxxxxxxx, xxxxxxxx uzávěry xxxxxxxx xxxxx xxxxxxxx xxxxx.

1. Xxxxxxxxx uzavíratelné obaly

Uzávěry xxxxxx proti xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX 8317 (xxxxxx xx dne 1. xxxxxxxx 1989) "Xxxxx xxxxxx xxxxx — Požadavky xx xxxxxxxxx uzavíratelné xxxxx x metody jejich xxxxxxxx" přijatou Xxxxxxxxxxx xxxxxxxxxx xxx xxxxxxxxxxx (XXX).

2. Opakovaně neuzavíratelné xxxxx

Xxxxxxx odolné xxxxx xxxxxxxx xxxxx xxxxxxx xx xxxxxxxxx xxxxxxxxxxxxxxxx xxxxxxx xxxx xxxxxxxx xxxxxxxxx xxxxx XXX XX 862 (xxxxxx x xxxxxx 1997) "Xxxxx — Obaly xxxxxx xxxxx — Xxxxxxxxx x zkušební xxxxxxx xxx xxxxxxxxx xxxxxxxxxxxxxx obaly xxxxxx xxx xxxxxxxxxxxxxxx xxxxxxx" xxxxxxxx Evropským výborem xxx normalizaci (XXX).

3. Xxxxxxxx

1. Xxxxxxxxx xxxxx x xxxx xxxxxxxxx xxxxxxx mohou xxxxxxxxxx xxxxx xxxxxxxxxx, které xxxxxxx xxxxxxxx xxxxx xxxx XX 45000.

2. Xxxxxxxxxx případy

Je-li xxxxxx, xx xxxx xx xxxxxxxxxx xxxxxxxx xxx xxxx, neboť se xxxxxxx xxxxxx x xxxxxx xxx pomoci xxxxxxxx, xxxxxx xxx xxxxxxx xxxxxxxxx.

Xx xxxxx xxxxxxxxx případech a xxxxx xxxxxxxx xxxxxxxxx xxxxxx x xxxxxxxx x xxxxxxxxxxx uzávěru xxx xxxx, může xxxxxxxxxxxx xxxxx xxxxxxxxx, xxx xxxxx xxxxxxxxx xx xxxxxxx výrobku xx xxx xxxxxxxxxx xxxxxxxxxx xxxxxx xxxxxxxxxx xxxxx xxxx. 3 xxxx 1 xxxxxxxxxxxx, xx xxx

- xxx xxxxxxx xx xxxxxx, xx jej xxxx xxxxxxxx zkoušet xxxxx xxxx xxxxxxxxx norem XXX x XXX,

xxxx

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

XXXX X

Xxxxxxxx xxxxxxxx xx xxxxxxxxxxxx xxxxxxx

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

"

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