1

7

* GLP

5.1 Xxxxx X 2006 14C-XXX 1111: Absorption, distribution, metabolism and excretion in male and female rats.Organics Inc. Report No: 20575GLP

( )

5.2.1 Xxxxx X 2001 XXX 1111 / Study for acute oral toxicity in rats – up –and –down procedure.Organics Inc. Report No: 19852GLP

( )

5.2.2 Xxxxx X 2001 XXX 1111 / Acute dermal study in rats.Organics Inc. Report No: 19854GLP

( )

5.2.3 Xxxxx X 2002 XXX 1111 / Study of the acute inhalation toxicity to rats using OECD guideline No. 403.Organics Inc. Report No: 15612GLP

( )

5.2.4/01 Xxxxx X 2002 XXX 1111 / Intracutaneous sensitisation test on guinea pigs (Draize-test).Organics Inc. Report No: 15622GLP

( )

5.2.4/02 Xxxxx X 2004 XXX 1111 maximization040105

GLP

( )

5.3.1/01 Xxxxx X 2003a XXX 1111 / Subchronic oral toxicity study on rats.Organics Inc. Report No: 9039GLP

( )

5.3.1/02 Xxxxx X 2003b XXX 1111 / Subchronic toxicity study on mice (three-month feeding experiment).Organics Inc. Report No: 9040GLP

( )

5.3.2 Xxxxx X 2004 XXX 1111 / 90-day dietary study in dogs.Organics Inc. Report No: 9065GLP

( )

5.3.4 Xxxxx X 2005 One month dermal study with XXX 1111 in CD rats.Organics Inc. Report No: 9115GLP

( )

5.4.1 Xxxxx X 2001 XXX 1111010012

GLP

( )

* a b c

1

8

5.4.2 Xxxxx X 2002 XXX 1111 in vitro

020024GLP

( )

5.4.3 Xxxxx X 2002 XXX 1111020025

GLP

( )

5.5.15.5.2

Xxxxx X 2006 XXX 1111 / Combined chronic toxicity/oncogenicity study –2-year feeding study in rats.Organics Inc. Report No: 9172GLP

( )

5.5.3 Xxxxx X 2006 XXX 1111 / Oncogenicity study – 18-month feeding study in mice.Organics Inc. Report No: 9173GLP

( )

5.6.1 Xxxxx X 2006 XXX 1111T06-0011

GLP

( )

5.6.2 Xxxxx X 2005 XXX 1111T05-0045

GLP

( )

5.6.3 Xxxxx X 2005 XXX 1111T05-0046

GLP

( )

5.7.1 Xxxxx X 2002 XXX 1111 / Acute neurotoxicity studies in rats.Organics Inc. Report No: 19953GLP

( )

5.7.2 Xxxxx X 2002 XXX 1111 / Neurotoxicity studies on hens.Organics Inc. Report No: 8753GLP

( )

5.8/01 Xxxxx X 2007 xxx070050

GLP

( )

5.8/02 Xxxxx X 2007 xxx070060

GLP

( )

5.9 Xxxxx X 2006 XXX 1111060120

( )

2 1

9

1 30 6278

1

1. 30 6278 1 5 (2) OECD IIA 5.2.2

2. 5.2.23. * X. Xxxxx

XXXX Study of acute dermal toxicity in the rat.

R eport No.20417 2007 7 5

4. * Organics Inc, Institute of Toxicology, Castlebar, Ireland,Report 10564

5. 2006 10 28 -2006 12 46. XXXX 17002/90 93.6 %

47. OECD 402 1987

305 g-320 g2,000 mg/kg

OECD402 2017** ………………….………………….

8. GLP

*

** OECD 2 3

2

1. 30 6278 1 5 (2) OECD IIA 5.3.290

2. 5.3.13. X. Xxxxx, X. Xxxxx

XXXX Subchronic toxicity study in wistar rats (thirteen-week administration in the diet with a four-week recovery period).

Report No. 21627 2008 8 184. Organics Inc, Institute of Toxicology, Castlebar, Ireland,

Report 11,2045. 2007 10 10 -2008 2 46. XXXX 17002/90 93.6 %

4

2 1

10

7. OECD 408 19986 25 ºC

OECD408 2018 …………………. ………………….

8. GLP

3

1. 30 6278 1 5 (2) OECD IIA 5.3.390

2. 5.3.23. X. Xxxxx, X. Xxxxx

XXXX 13- Week subchronic feeding study in beagle dogs.

Report No. MR7442 2008 12 74. Organics Inc, Institute of Toxicology, Castlebar, Ireland,

Report 13,2565. 2007 11 5 - 2008 2 66. XXXX 17002/90 93.5 %-94.9 %

47. OECD 409 1998

OECD409 1998

8. GLP

4

1. 30 6278 1 9 1 H OECD IIA 8.4

2. 8.2.33. X. Xxxxx

XXXX

XX-0612 2007 12 74.

XX-06125. 2006 11 5 - 2007 2 66. XXXX xx1002 94.9 %7. OECD 201

10 %100 mg/L

8. GLP

2 2

11

2 30 6278

1

1

1.1 30 6278 1 5 (2) OECD IIA 5.2.2

1.2

2 5.2.2

3

- 5.2.1 5.2.25.2.3 5.2.4 5.2.5

3.1 X.Xxxxxxx, X.Xxxxxxxxx

X.Xxxxxxxxxxx

3.2 XXX 1111 Acute Toxicity Studies

3.3 xxxxxxxx

3.4

3.5 xxxxx No.: 0000

3.6 1980 1 7

4

4.1 Xxxxxxxx, Xxxxxxxxxxxxx, Xxxxxxxxxxxxx, Xxxxxxxx

4.2 xxxxx

5

5.1 1979 2 -1979 8

5.2

6

6.1 XXX 1111 97.5 % xxx

6.2 5

6.3

6.4

6.5

6.6

6.7

6.8

7

7.1 X. Xxxxx (1969)

2 2

12

7.2 USEPA

(Proposed Guidelines for Registering Pesticides in the US, Federal Register, Vol 43, No. 163, August 22, 1978) OECD 402 2017*

…………………. ………………….

* OECD

7.3

7.4

7.5

8 GLP8.1 GLP

8.2 GLP

8.3 GLP

8.4 GLP

9 (TNO/W 74

Winkelmann, Borchen, Germany

10 15 5/10 per group

2500 mg/kg 5000 mg/kg

24

14

0 -14 0 7 14

10

11

11.1 X. Xxxxx, 1969

11.2

11.3

2

1

1.1 30 6278 1 5 (2) OECD IIA 5.3.2

1.2 90

2 5.3.1

3

3.1 X.Xxxxxxx, X.Xxxxxxxxx

X.Xxxxxxxxx

2 2

13

X.Xxxxxxxxxxx 3.2 XXX 1111 sub-chronic toxicity study on rats (three-month feeding experiment),

and histopathological addendum

3.3 xxx

3.4

3.5 xxxxxxx No.0000 0000

3.6 1980 6 4 1981 1 29

4

4.1 Xxxxxxxxxxxx,Xxxxxxxxxxxxx,Xxxxxxxxxxxxxxxxx,Xxxxxxxxx

4.2 xxxxxx

5

5.1 1979 11 -1980 2

5.2

6

6.1 XXX 1111 97.5 % xxx

6.2

6.3

6.4 2

6.5

6.6

6.7

6.8 Wessalon S CAS 7631-86-9 50 % Altromin®

7

7.1 9

7.2

USEPA Proposed

Guidelines for Registering Pesticides in the US Federal Register, Vol. 43, No. 163, August 22, 1978 OECD 408 2018*

.

NOAEL

* OECD

7.3

9

7.4

2 2

14

7.5

8 GLP8.1 GLP

8.2 GLP

8.3 GLP

8.4 GLP

9 TNO W. 74

Winkelmann, Borchen, Germany

120 120 1 30 5

2 7

28

0 50 100 500 ppm

1

3.24 8.39 28.52 mg/kg /

3.70 9.83 32.97 mg/kg /

3

RBC WBC Hb MCV MCH MCHC PLT Ht

APTT ( 1 3 1

5 )

ALP AST ALT

Bil TP 1 3

1 5

N- O-

P450 7 28 3 1 5

TP pH Bil 1

3 1 5

2 2

15

4

19 20 20 20

30 ppm 15 15 100 ppm

15 14

10 Wilcoxon-Mann-Whitney U-test

=5 % =1 %

11

3

1

1.1 30 6278 1 6 (1) OECD IIA 6.2.1

1.2

2 6.2.1

3

3.1 X.X. Xxxxxxx,X.X. Xxxxx

X. xxxxxxxxx 3.2 Metabolism of XXX 1111 in potatoes

3.3 xxxxxx

3.4

3.5 xxxxxxx No. 123456

3.6 1983 11 22 1986 12 1

4

4.1 Xxxxxxx Xxxxxxxxxx Xxxxx, Xxxxxxx, Xxxx

4.2

5

5.1 1982 9 -1983 4

5.2 XXX 1111

XXX 1111

6

6.1 XXX 1111 99.8 % xxxx

phenyl-UL-14C

6.2 99 % 23.65 mCi/mmo1e

4 cis/trans 00/00

2 2

16

cis/trans 00/00

6.3

6.4

6.5

6.6

6.7

6.8 / 200 EC

7

7.1

7.2 USEPA

OECD 501

7.3

7.4

7.5

8 GLP8.1

8.2

8.3 GLP

8.4 GLP

9 Solanum tuberosum

60

40 g ai/40 L/ha 200 EC 0.1 mL [14C] XXX

1111 20.1 mg 19 mL

100 g ai/100 L/ha

0 42 52 80 98

xxxx xxxx

TLC

UV

10

11

3 I.

17

I.

OECD

1.1.1 3 2 1

34 6IIIA 1.1

1.2 3 2 18

IIIA 1.2

1.3

1.3.1 3 2 234 6

IIIA 1.3

1.3.2 3. 4 IIIA 1.3

1.4 3 2 22 1 1

IIIA 1.4.1

30 62781 1 (2) 11

1.5 3 2 934 6

IIIA 1.4.5.1

30 62781 1 (2)

1.6 3 2 2 IIIA 1.5

2.2.1 3 2 2

2 1 2 11IIIA 2.1-2.6

30 62781 2 (2)

IIIA 2.8

2.2 30 62781 2 (2)

IIIA 2.7

3 I.

18

OECD

3.3.1 3 2 3

34 6IIIA 3.3-3.7

3.2 3 2 734 6

IIIA 3.9

4.4.1 2 1 10 2

30 62781 10 (2)

IIIA 5.2.1IIIA 5.2.2IIIA 5.2.4

5.5.1 2 1 3

30 62781 3 1

IIIA 6.1

5.2 2 1 430 6278

1 4 1

IIIA 6.2.1

5.3 2 1 430 6278

1 4 2

5.4 2 1 430 6278

1 4 3

6.6.1 2 1 5

30 62781 5 2

IIIA 7.1.1

6.2 2 1 530 6278

1 5 2

IIIA 7.1.2

6.3 2 1 530 6278

1 5 2

IIIA 7.1.3

6.4 2 1 530 6278

1 5 2

IIIA 7.1.4

6.5 2 1 530 6278

1 5 2

IIIA 7.1.5

3 I.

19

OECD

6.6 2 1 530 6278

1 5 2

IIIA 7.1.6

6.7 3 2 4 346

7

6.8 2 1 530 6278

1 5 2

IIIA 7.6

6.9 2 1 530 6278

1 5 2

IIIA 7.3.3

6.10 2 1 530 6278

1 5 2

IIIA 7.3.1IIIA 7.3.2

7.7.17.1.1 2 1 9

30 62781 9 1

IIIA 10.1.1

7.27.2.1 2 1 9

30 62781 9 1 J

7.2.2 2 1 930 6278

1 9 1 A

IIIA 10.2.2.1

7.2.3 2 1 930 6278

1 9 1 B

IIIA 10.2.2.2

7.2.4 2 1 930 6278

1 9 1 C

IIIA 10.2.2.3

7.2.5 3 2 534 6

7.37.3.17.3.1.1 2 1 9

30 62781 9 2

IIIA 10.4.1

3 I.

20

OECD

7.3.27.3.2.1 2 1 9

30 62781 9 2

IIIA 10.5

3 II.

21

II.

OECD

1.1.1 3 2 1 IIA 1.1

1.2 3 2 12 IIA 1.2

30 62781 1 1

1.3 3 2 2 IIA 1.3

30 62781 1 1

1.4 3 2 2 IIA 1.4

30 62781 1 1

1.5 30 62781 1 1

IIA 1.5.1

1.6 CAS 30 62781 1 1

IIA 1.6

1.7 30 62781 1 1

IIA 1.7

1.8 3 2 1334 6

IIA 1.8

2 1 130 6278

1 1 1

1.9 3 2 1134 6

2 1 1

IIA 1.9.1IIA 1.9.2

30 62781 1 1

3 II.

22

OECD

1.10 3 2 112 1 1

30 62781 1 1

IIA 1.10.1IIA 1.10.2

1.11 3 2 112 1 1

30 62781 1 1

IIA 1.11.1

1.12 2 1 130 6278

1 1 1

IIA 1.11.1

1.13 2 1 130 6278

1 1 1

IIA 1.11.1

2.2.1 2 1 2

30 62781 2 1

IIA 2.1.1

2.2 2 1 230 6278

1 2 1

IIA 2.1.2

2.3 2 1 230 6278

1 2 1

IIA 2.2

2.4 2 1 230 6278

1 2 1

IIA 2.3.1

2.5 2 1 230 6278

1 2 1

IIA 2.4.1

2.6 2 1 230 6278

1 2 1

IIA 2.4.2

2.72.7.1 UV 2 1 2

30 62781 2 1

IIA 2.5.1.1IIA 2.5.1.5

2.7.2 IR 2 1 230 6278

1 2 1

IIA 2.5.1.2

3 II.

23

OECD

2.7.3 NMR 2 1 230 6278

1 2 1

IIA 2.5.1.3

2.7.4 MS 2 1 230 6278

1 2 1

IIA 2.5.1.4

2.8 2 1 230 6278

1 2 1

IIA 2.6

2.9 2 1 230 6278

1 2 1

IIA 2.7

2.10 n- 2 1 230 6278

1 2 1 3 23

IIA 2.8.1

2.11 2 1 230 6278

1 2 1

IIA 2.9.1

2.12 2 1 230 6278

1 2 1

IIA 2.9.2

2.13 2 1 230 6278

1 2 1

IIA 2.9.5

2.14 2 1 230 6278

1 2 1

IIA 2.17.2

3.3.1 3 2 3 IIA 3.1

3.2 30 62781 3 2

IIA 3.2

3.3 3 2 3 IIA 3.3

3.4 30 62781 3 2

IIA 3.4

3.5 30 62781 3 2

IIA 3.5

3 II.

24

OECD

4.4.1 2 1 10

30 62781 10 1

IIA 4.2.1IIA 4.2.3IIA 4.2.4

4.2

4.2.1 2 1 1030 6278

1 10 1

IIA 4.3

4.2.2 2 1 1030 6278

1 10 1

IIA 4.3

4.3 2 1 1030 6278

1 10 1

IIA 4.4

4.4 2 1 1030 6278

1 10 1

IIA 4.5

4.5 2 1 1030 6278

1 5 2

IIIA 7.3.3

5.5.1 2 1 5

30 62781 5 1

IIA 5.1

5.2

5.2.1 2 1 530 6278

1 5 2

IIA 5.2.1

5.2.2 2 1 530 6278

1 5 2

IIA 5.2.2

5.2.3 2 1 530 6278

1 5 2

IIA 5.2.3

5.2.4 2 1 530 6278

1 5 2

IIA 5.2.6

3 II.

25

OECD

5.3

5.3.1 90 2 1 530 6278

1 5 2

IIA 5.3.2

5.3.2 90 2 1 530 6278

1 5 2

IIA 5.3.3

5.3.3 90 2 1 530 6278

1 5 2

IIA 5.3.6

5.3.4 21 2 1 530 6278

1 5 2

IIA 5.3.7

5.4

5.4.1 2 1 530 6278

1 5 2 A)

IIA 5.4.1

5.4.2 2 1 530 6278

1 5 2 B)

IIA 5.4.2

5.4.3 2 1 530 6278

1 5 2 C)

IIA 5.4.4

5.4.4 DNA 2 1 530 6278

1 5 2 D)

IIA 5.4.6

5.5

5.5.1 2 1 530 6278

1 5 2

IIA 5.5.1

5.5.2 2 1 530 6278

1 5 2

IIA 5.5.2

5.5.3 2 1 530 6278

1 5 2

IIA 5.5.3

5.5.4 2 1 5 IIA 5.5.4

3 II.

26

OECD

5.6

5.6.1 2 1 530 6278

1 5 2

IIA 5.6.1

5.6.2 2 1 530 6278

1 5 2

IIA 5.6.10

5.6.3 2 1 530 6278

1 5 2

IIA 5.6.11

5.7

5.7.1 2 1 530 6278

1 5 2

IIA 5.7.1

5.7.2 2 1 530 6278

1 5 2

IIA 5.7.2

5.7.3 28 2 1 530 6278

1 5 2

IIA 5.7.3

5.7.4 2 1 530 6278

1 5 2

IIA 5.7.4

5.7.5 2 1 530 6278

1 5 2

IIA 5.7.5

5.8 2 1 530 6278

3 2 3

IIA 5.8

5.9 2 1 530 6278

1 5 2

5.10

5.10.1 2 1 5 IIA 5.9.2

5.10.2 3 2 4 IIA 5.9.5

2 1 530 6278

1 5 2

IIA 5.9.6

3 II.

27

OECD

5.11 2 1 530 6278

1 5 2

IIIA 7.6

5.12 3. 4 IIA 5.11

6.6.1 2 1 6

30 62781 6 5

IIA 6.1

6.26.2.1 2 1 6

30 62781 6 1

IIA 6.2.1

6.2.2 2 1 730 6278

1 7 1

IIA 6.2.2IIA 6.2.3

6.3 GAP 3 2 3

6.4 2 1 630 6278

1 6 2

IIA 6.3

6.5 2 1 730 6278

1 7 2

IIA 6.4

6.6 2 1 630 6278

1 6 3

IIA 6.5

6.7 2 1 630 6278

1 6 4

IIA 6.6.3

6.86.8.1 2 1 9

30 62781 7 3 3 2 3

IIA 8.2.6

6.8.2 2 1 930 6278

1 9 1 J

6.8.3 3. 4

6.9

6.9.1 3. 4 IIA 6.7.1

3 II.

28

OECD

6.9.2 3. 4 IIA 6.7.2

6.9.3 3. 4

6.9.3.1 TMDI 1 3. 4 IIA 6.9.1

6.9.3.2 EDI 1 3. 4 IIA 6.9.2

6.9.3.3 ESTI 3. 4 IIA 6.9.3

6.9.4 3. 4 IIA 6.11

7.7.17.1.1 2 1 8

30 62781 8 1

7.1.2 2 1 830 6278

1 8 1

IIA 7.1.1

7.1.3 2 1 830 6278

1 8 1

IIA 7.1.2

7.2 2 1 830 6278

1 8 2

IIA 7.3.2

7.3 2 1 830 6278

1 8 3 3 2 3

IIA 7.4.1IIA 7.4.2

7.4 2 1 830 6278

1 8 4

IIA 7.5

7.5 2 1 830 6278

1 8 4

IIA 7.6

7.67.6.1 2 1 8

30 62781 8 5

7.6.2 2 1 830 6278

1 8 5

3 II.

29

OECD

7.6.3 2 1 830 6278

1 8 5

7.6.4 2 1 830 6278

1 8 5

7.6.5 2 1 830 6278

1 8 5

7.6.6 2 1 930 6278

1 9 1 J

7.6.7 2 1 830 6278

1 8 5

7.77.7.1 3. 4 IIA 7.11

7.7.2 3. 4

8.8.18.1.1 2 1 9

30 62781 9 1

IIA 8.1.1

8.28.2.18.2.1.1 2 1 9

30 62781 9 1 A

IIA 8.2.1

8.2.1.2 2 1 930 6278

1 9 1 D

8.2.1.3 2 1 930 6278

1 7 3

IIA 8.2.6

8.2.28.2.2.1 2 1 9

30 62781 9 1 B

IIA 8.3.1.1

3 II.

30

OECD

8.2.2.2 2 1 930 6278

1 9 1 C

8.2.2.3 2 1 930 6278

1 9 1 D

8.2.2.4 2 1 930 6278

1 9 1 E

IIA 8.3.1.2

8.2.2.5 2 1 930 6278

1 9 1 F

IIA 8.3.1.3

8.2.2.6 2 1 930 6278

1 9 1 G

IIA 8.3.2.1

8.2.38.2.3.1 2 1 9

30 62781 9 1 H

IIA 8.4

8.2.3.2 2 1 930 6278

1 9 1 I

IIA 8.6

8.38.3.18.3.1.1. 2 1 9

30 62781 9 2

IIA 8.7.2

8.3.1.2 2 1 930 6278

1 9 2

IIA 8.7.1

8.3.1.3 2 1 930 6278

1 9 2

8.3.1.4 2 1 930 6278

1 9 2

8.3.1.5 2 1 930 6278

1 9 2

3 II.

31

OECD

8.3.1.6 2 1 930 6278

1 9 2

1

2

3

4

32

OECD 8 1 2

1.

OEC 2222

1.4

chemx 80.0 % xxxxx xxxxxx 20.0 %

1.5

1.6

2.

2.1GLP

30 6278

4

33

CIPAC MT170

1,700 850-1,700

500-800300-500

45-300300

<0.1 %52.0 %47.7 %

0.1 %0.2 %

<0.1 %

Y

CIPAC MT53.3 1 min Y

CIPAC MT184xx %

15 Y

2.2

40 40.0 39.8 40.3

GLP

1 2 3

1 80.12 % 79.95 % 0.21 % 79.91 % 0.26 % 79.82 % 0.40 %

*1

300-1700 μm 99.8%298%*2

*1

300-1700 μm 98.5%396%*2

*1

300-1700 μm 99.5%299%*2

*1

300-1700 μm 99.0%397%*2

*1:*2:15

3.

3.1Chemx

-70 2.5 g/10 a 20-25 L/10a 1 1

4

34

3.2

4.

4.1

chemx C18 HPLC UV 250 nm

(r) 0.999

( (n=5)) 100.3 %

(RSD (n=5)) 0.2 %

5. 5.1

chem

x80%

OE

C 2

222

(

* (g

ai/L

))

H28

mm

/dd

mm

/dd

2.5g

/20L

/10a

0.10

mm

/dd

××30

mL/

100L

/10a

H29

mm

/dd

mm

/dd

2.5g

/20L

/10a

0.10

mm

/dd

××30

mL/

100L

/10a

61H

28m

m/d

dm

m/d

d2.

5g/2

0L/1

0a0.

10m

m/d

d××

40m

L/10

0L/1

0a

61H

29m

m/d

dm

m/d

d2.

5g/2

0L/1

0a0.

10m

m/d

d××

40m

L/10

0L/1

0a

5.2

chem

x80%

OE

C22

22

()

()

R2

mm

.dd

mm

.dd xx

2.5

g/20

L/1

0 a

61R

2 m

m.d

d

mm

.dd xx

2.5

g/20

L/1

0 a

mm

.dd

2.5

g/20

L/1

0 a

5.3

chem

x

(*

(g a

i/L))

H28

mm

/dd

2.5g

/20L

/10a

0.10

m

m/d

d

5.0g

/20L

/10a

0.20

1

4

37

6.

6.1

7

30 6278 1 5

GHS OEC 2222 GHS

6.2

7

30 6278 1 5

GHS OEC 2222 GHS

6.3

7

30 6278 1 5

GHS OEC 2222 GHS

6.4

6.4 Xxxx X 2006, 2006 Primary dermal irritation study in rabbits with OEC 2222.

CCC-95-193

OECD 404 2002

OECD404 2015* …………………. ………………….

4

38

* OECD

xxxxx Laboratory GLP

New Zealand white 3 0.5 g OEC 2222

79.3 % chemx 4 6 cm2 72 Draize

2 OEC 2222 4 1

48

OEC 2222 GHS

I.

A.

1. OEC 2222

80 % chemx

NPD-9501-6384-F

79.3 %

54°C 14

2.

3.

New Zealand

2.1 kg-2.4 kg

5

#5322

40 %-84 %

12

4

39

B. :

1. 2005 9 12 -22

2.

3

0.5 g

2 4

1 24 48 72

II.

A.

2 OEC 2222 4 1

48

3 1 3 24 48 72

xx, xx, 0 0, 0, 0 6.4-1

III.

OEC 2222

OEC 2222 GHS

6.4-1 OEC 222224 48 72

1 24 48 72

1 x x 0 0 xx0 0 0 0 0

2 x x 0 0 xx0 0 0 0 0

3 x 0 0 0 00 0 0 0 0

14

30 6278 1 5

GHS OEC 2222 GHS

4

40

6.5

6.5 Xxxx X 2006, Primary eye irritation study in rats with OEC 2222.

CCC-95-192

OECD 405 2002

OECD405 2017* …………………. ………………….

* OECD

xxxxx Laboratory GLP

New Zealand white 3 OEC 2222 79.3 %

chemx xx mg 7

1 3 2 48

3 72

24 OEC 2222 GHS

I.

A.

1. OEC 2222

80 % chemx

NPD-9501-6384-F

79.3 %

54 °C 14

2.

3.

New Zealand

2.4 kg-2.8 kg

5

4

41

#5322

35 %-84 %

12

B. :

1. 2005 10 11 -24

2.

3 1

xx mg 7 1 24 48

72 7 24

II.

A.

xx mg x.x mL OEC 2222

6.5-1

1 3 2 48

3 72

24 3 1 3

24 48 72

0, 0, 0 0, 0, 0 xx, xx, xxx 0, 0, 0

6.5-1 OEC 222224 48 72

1 24 48 72

1 0 0 0 0 0

0 0 0 0 0x 0 0 0 0x x 0 0 xx

2 0 0 0 0 00 0 0 0 0x 0 0 0 0x x 0 0 xx

3 0 0 0 0 00 0 0 0 0

4

42

x 0 0 0 0

x x x 0 xxx

21

III.

OEC 2222 GHS

30 6278 1 5

GHS OEC 2222 GHS

6.6

7

30 6278 1 5

GHS OEC 2222 GHS

6.7

30 6278 1 5

GHS

4

43

OEC 2222

GHS

OEC 2222SD

chemxSD

OEC 2222NZW

OEC 2222NZW

OEC 2222Hartley

LD50

>300 mg/kg 2000 mg/kg

LD50

>2000 mg/kg

LC50

>5.0 mg/L

4 chemx

6.8

10 50%

0.6%

8%

4

44

6.9

6.9 Xxxx X 2008,

XX-08-12

30 6278

GLP

I.

A.

1. OEC 2222

80 % chemx

NPD-9501-6384-F

79.3 %

54°C 14

2.

61

3.

10

70-90kg

4

45

B.

2007 7 -2008 4

1.

24

chemix 80 % 2.0-3.0 g/10 a 1.6-2.4 g ai/10a 20-25 L/10 a

10-30a 24 11 -12

-20 °C 8

24 HPLC

2.

chemx

chemx

chemx

II.

6.9-1 6.9-2

2 chemx

chemx

6.9-1

A x,xxx xx x,xxx

B x,xxx xx x,xxx

C x,xxx xx x,xxx

D x,xxx xx x,xxx

E x,xxx xx x,xxx

F x,xxx xx x,xxx

G x,xxx xx x,xxx

H x,xxx xx x,xxx

I x,xxx xx x,xxx

J x,xxx xx x,xxx

4

46

6.9-2

A x x xx xx xx xx xx xx x,xxx xx xx x,xxxB x x xx xx xx xx xx xx x,xxx xx xx x,xxxC x x xx xx xx xx xx xx x,xxx xx xx x,xxxD x x xx xx xx xx xx xx x,xxx xx xx x,xxxE x x xx xx xx xx xx xx x,xxx xx xx x,xxxF x x xx xx xx xx xx xx x,xxx xx xx x,xxxG x x xx xx xx xx xx xx x,xxx xx xx x,xxxH x x xx xx xx xx xx xx x,xxx xx xx x,xxxI x x xx xx xx xx xx xx x,xxx xx xx x,xxxJ x x xx xx xx xx xx xx x,xxx xx xx x,xxx

6.9-3

A x,xxx xxB x,xxx xxC x,xxx xxD x,xxx xxE x,xxx xxF x,xxx xxG x,xxx xxH x,xxx xxI x,xxx xxJ x,xxx xx

6.9-4

A x x,xxx xx xxB x x,xxx xx xxC x x,xxx xx xxD x x,xxx xx xxE x x,xxx xx xxF x x,xxx xx xxG x x,xxx xx xxH x x,xxx xx xxI x x,xxx xx xxJ x x,xxx xx xx

4

47

6.10chemx 80%

chemx

1 AOEL AAOEL 100

chemx AOEL AAOEL

6.10

6.10Chemx

-70

2.5 g/10 a

20-25 L/10a 1 1

6.9

chemx

10 %

chemx 8000 50 %

AOEL x.xx mg/kg /

AAOEL

80 %

( )

4

48

chem

x

%A

OEL 1)

%A

AO EL 2)

ai)

ai)

%A

OE L 1)

%A

AO EL 2)

1 -

702.

5g/1

0a20

L/10

a1

180

00/

/xx

.xxx

.xxx

.x(<

100)

1)A

OEL

/A

OEL

x.xx

mg/

kg/

×55

.1kg

×100

2)A

AO

EL/

AA

OEL

x.xx

mg/

kg×

55.1

kg×1

00

//

//

[/

/]

4

49

7.7.1

7.1.1

chemx

x

mg-ai/day kg-b.w. xx x

chemx…

10% 10% ……

(g-diet/day mL-diet/day)

4.4 g-diet/day 15 g-diet/day …

10% 5% …1.8 1.4 …

(mg-ai/kg-diet mg-ai/L-diet)

x x …

(kg-diet/g-diet L-diet/mL-diet)

0.001 0.001 …

(kg-b.w.) 0.022 0.022 …(mg-ai/day/kg-b.w.) x x …

…10% …

…(g-diet/day

mL-diet/day)15 g-diet/day …

5% …1.4 …

(mg-a.i./kg-diet mg-ai/L-diet)

x …

(kg-diet/g-diet L-diet/mL-diet)

0.001 …

(kg-b.w.) 0.022 …(mg-ai/day/kg-b.w.) x …

7.27.2.1.

9

7.2.210

4

50

7.2.3

10

7.2.4

10

7.2.5

7.2.6

( ) (hr)

Cyprinus carpio xx-xx 96 LC50 xxx mg/L

Daphnia magna xx-xx 48 EC50 xxx mg/L

Raphidocelis subcapitata xx-xx 72 ErC50 (0-72h) xxx g/L

7.3.7.3.17.3.1.1

4

51

ha

kg

a.i./

ha)

/ %

/

L/10

a

g/10

aμg

/g

P: ,N:

//

5000

150

0.06

40.

0043

6.3

P 0.

003

0.07

60.

023

0.09

720

270.

023

1000

0.2

0.18

P 0.

0022

0.00

066

0.60

0.

79

0.00

066

2000

700

0.35

0.00

50

34PN

0.00

356.

14.

20.

1117

0022

004.

2

1000

300

5000

150

ha

kg

a.i./

ha)

/ %

::

/

L/10

a

g/10

a

::

::

μg/g

P: ,N:

//

//

5000

150

0.06

420.

0042

86.

29P

0.00

30.

076

0.07

60.

023

0.09

720

270.

023

0.84

0.01

0 0.

0010

0.

0031

2.

7 0.

27

0.00

31

4

52

7.3.1.2LD50

LD50 LD50

………

………

LD50

LD50 LD50

………

………

ppm ppm ppm ppm

………

………

………………

10 8.3.1.1

7.3.2.2

4 1 502

%

2000

1 1030 40 60

1030

40

5

53

OECD 7 1

1.

1.1

1.2

1.3 chemx ISO

1.4

IUPAC

CAS

1.5

OEC 1000 BJC 14

1.6 CAS 16335-17-2

1.7

440.37

1.8

1.9

g/kg

5

54

1.10

1.11

1.12

1.13

2.

2-1 chemx

GLP

2.1 OECD102 99 %GHQ-9209-4531-A

201.1-201.7 ºC(n=3; ±0.1 ºC)

Y

2.2( )

2.3 CIPAC MT3.( )

99.5 %30016916

1.518 g/cm3 ( 20.0 ºC) Y

2.4 OECD104( )

99.5 %30016916

7.22 10-7 Pa (35 ºC)1.87 10-6 Pa (40 ºC)

3.05 10-8 Pa (20 ºC ) 8.81 10-8 Pa (25 ºC )

Y

2.5 99.5 %30016919

2.6 99.5 %30016919

2.7 UVIRH-NMRC-NMRMS

99.5 %30016919

2.1-2.4

UV : ( pH >10)

max=208 nm,=187,150 L. mol -1. cm-1

Y

2.8 EEC A.8( )

99 %GHQ-9209-4531-A

pH 5: 17.60±2.71 ppm (20 ºC)pH 7: 1626.8±39.8 ppm (20 ºC) pH 9: 482.44±8.35 ppm (20 ºC)

(n=3 95% )

Y

2.9 OECD 105( )

99.5 %30016916

n- : <0.001 g/L (20 ºC): 0.16 g/L (20 ºC)

1,2- : 4.35 g/L (20 ºC): 0.33 g/L (20 ºC)

: 0.71 g/L (20 ºC): 1.01 g/L (20 ºC)

Y

5

55

GLP

2.10n- /

OECD 107( )

99 %GHQ-9209-4531-A

pH 5: log Pow<1pH 7: log Pow<1 pH 9: log Pow<1

Y

2.11 OECD 111 [14C]-chem2-chemx[14C]-chem3-chemx

99 %

x.xx MBq/mg

pH 4: =7.0 (25 ºC) 0.83 (40 ºC)pH 5: =48 (25 ºC) 6.0 (40 ºC) pH 7: =168 (25 ºC) 16 (40 ºC)pH 9: =156 (25 ºC) 15 (40 ºC)

Y

2.12 FIFRA 162-2 [14C]-chem2-chemx[14C]-chem3-chemx

99 %

x.xx MBq/mg

(pH 7.0 25 ºC)

( 12 ): chem2: 3.2chem3: 2.8

Y

2.13 OECD 112 99.5 %30016916

pKa=3.51 (20 ºC) Y

2.14 OECD 113( )

Y

2-1 UV

UV

2-2 IR

IR

2-3 NMR

NMR

2-4 MS

MS

2-2

2-1

5

56

3.

3.1

3.2

3.3

3.4

(Avena fatua) (Bromus) (Galium Aparine)

chemx

3.5

chemx

3 6

6

57

OECD 7 2

44.14.1.1

4.1 Xxxx X 2005, chemx

XX-xxxx

GLP

chemx HPLC

chemx

chemx 50 %-150 % 5

r 0.999

chemx 5 RSDr 0.6 %

r 0.999 500 1500 g/kgRSDr % n=5 0.6*

* 945 g/kg RSDr % 2 1-0.5logC ×0.67 2 1-0.5log0.945 ×0.67 1.4

4.1.2

6

58

4.24.2.1

4.2.1 Xxxx X 2008,

XX-08-12GLP

/ x:x v:v chemx

7 HPLC

7 7 mg/kg chemx

4.2.1-1 chemx

(mg/kg) (%) SD %RSD

0.01 5 104 6 6 0.02 5 98 4 4 0.05 5 93 10 11

(a) chemx(b) chemx 7 7

30 6278 70 %-120 %

7 0.0025 g/mL -0.1 g/mL r 0.998

chemx 7

7 10%

chemx

7 chemx

0.01 mg/kg

RSD 30 6278 RSD 20 %

6

59

chemx chemx 7 HPLC

7 chemx 0.01 mg/kg

4.2.2

0.01 mg/kg

4.3

4.3 Xxxx X 2010,

XX-10-05GLP

chemx

x:x v:v

chemx 7

7 HPLC

7 mg/kg chemx

30 6278 70 %-120 %

7 0.001 g/mL -0.05 g/mL r 0.999

chemx 7

chemx 7

7 chemx

0.0005 mg/kg

6

60

RSD 30 6278 RSD 20%

4.3-1 chemx

(mg/kg) (%) SD %RSD

0.0005 4 93 12 130.001 1 88 na na0.002 1 77 na na0.005 3 75 2 3 0.015 1 89 na na

(a) chemx

chemx

x:x v:v chemx

7

7 HPLC

7 mg/kg chemx chemx

30 6278 70 %-120 %

7 0.001 g/mL -0.05 g/mL r 0.999

chemx 7

7.1.2 7

desmethyl chemx 1 xxxxxxx 2

7 chemx

0.0005 mg/kg

RSD chemx 0.0005 mg/kg 30 6278

RSD 20 % chemx 0.0005 mg/kg RSD

24% 0.0005 mg/kg

6

61

4.3-2 chemx

(mg/kg) (%) SD %RSD

0.0005(a) 6 108 26 240.001(a) 4 84 11 130.01(a) 3 89 4 4 0.05(a) 3 77 3 4

0.0005(b) 3 90 8 100.0005(c) 3 88 10 12

(a) chemx(b) desmethyl chemx 1(c) xxxxxxx 2

chemx chemx

chemx 7 HPLC

chemx chemx 7 mg/kg chemx

chemx chemx

4.4

chemx

4.1 4.3

4.5

4.1 4.3

7

62

OECD 7 3

5.

5.1

5.1 Xxxx X 1996, The absorption, distribution, elimination and metabolism of

chemx in Sprague-Dawley rats following oral and intravenous administration.

CCC-14300

US EPA FIFRA 85-1

OECD417 2010* …………………. ………………….

* OECD

xxxxx Laboratory GLP

chem2 C-3 chem3 C-5 14C 2 chemx

98 % x xx xxx mg/kg Sprague-Dawley 4

4 1 xx mg/kg

2 xx mg/kg 3 xxx mg/kg

chemx 14 14C chemx

4 xx mg/kg /

chemx

77 %-87 % 4.8 %-13 %

59 % 32 %-33 % CO2

24 14CO2 0.04 % 90 %

38 % chemx

<0.13 %

0.01 % 90 % 3

chemx

chemx chem2

7

63

chemx xxx chem2 chem3

chemx 5.1-1

I.

A.

1. chemx

chem2 C-3 14C

0.76 MBq/mg 9 mCi/mmol

chem3 C-5 14C

0.76 MBq/mg 9 mCi/mmol

chem2 chem3

NPD-9307-5386-T

chem2

chem3

98 %

98 %

CAS 16335-17-2

7

2. Emulphor®

3.

Sprague-Dawley CD

46 -68 50 -70

245 g-386 g 162 g-384 g

10

24

Purina

USPHS-NIH

7

64

20 C -24 C

45 %-65 %

16-20 /

12

4.

chem2 -chemx 14C- 12-chemx 1 1

chemx

Emulphor® 1 1 8

B.

1.

2 14C-chemx chem2 -chemx chem3 -chemx

2 P1 chem3 -chemx )

P3 chem2 -chemx xx mg/kg P2 chem3 -chemx

P4 chem3 -chemx xxx mg/kg

2.

4 1 xx mg/kg

2 xx mg/kg 3 xxx mg/kg 14

chemx 14C chemx

4 xx mg/kg / 5.1-1

5.1-1

mg/kg

1 xx 4 4 2 xx 4 4 3 xxx 4 4 4 xx 4 4

II.

1.

24 0.04 % 14CO2

chemx xxx

2.

chemx -20 ºC 4

7

65

12

3.

5.1-2

1

5.1-2xx mg/kg xxx mg/kg

Cmax g eq/gTmax hrT1/2 hrAUC hr* g eq/g

95 % 91 %

93 % 90 % 36 % 39 %

5

<0.13 %

0.01 %

0.02 %-0.36 %

5.1-3 g eq/gxxx mg/kg

xx * xx ** 120

* Tmax ** Tmax/2

7

66

77 %-87 %

4.8 %-13 %

59 % 32 %-33 %

2.2 -5.8 21 -57

90 % 3

97 %-101 %

5.1-4 %

mg/kg +

1 xx 82.5 87.0 10.2 97.4xx 77.5 88.7 9.4 98.3

2 xx 87.3 89.7 9.0 98.7xx 84.9 94.6 4.8 99.4

3 xxx 31.8 38.2 62.6 100.8xxx 33.4 43.2 54.7 98.0

4 xx 81.2 85.1 13.2 98.4xx 77.0 90.3 8.4 98.7

chemx HPLC

LC-MS HPLC

95 %

chemx

4 desmethyl-chemx 5-hydroxy-chemx chem3ide

chem4-sulphate 5 %

chemx 77 %-89 % 35 %

40 % 1.5 %-3.2 %

53 % 51 %

Chemx 1 chem2 5- 2 chem2

4- 6- desmethyl-chemx

5-hydroxy-chemx chem2 4- 6-

7

67

chem2 chem3 xxx

5.1-5 %Desmethyl-chemx chem3ide 5-hydroxy-chemx chemx

1 1.41 0.58 0.66 78.56 81.211.60 0.16 0.26 1.96 7.18

1 0.80 2.62 0.32 79.85 83.581.13 0.26 0.50 2.67 7.09

2 1.76 0.84 1.13 82.39 86.111.28 ND 0.30 1.57 5.90

2 1.12 1.77 0.48 88.85 92.220.51 0.09 0.10 1.49 3.38

3 0.35 0.27 0.13 34.76 35.513.59 ND 1.26 52.89 60.00

3 0.17 0.33 ND 40.03 40.531.33 0.53 0.31 50.71 53.26

4 1.74 1.68 0.57 76.55 80.541.56 0.15 0.41 3.22 9.21

4 0.72 ND 1.88 87.18 89.780.84 ND 0.84 2.65 5.79

ND

5.1-1 chemx

III.

Chemx

Chemx

0.2 %

90 %

38 % chemx chem2

chem2 chem3 xxx

CO2

7

68

5.2.5.2.1

5.2.1 Xxxx X 2003, chemx: Acute oral toxicity study in rats - acute toxic class method.

CCC-13156

OECD 423 2001

OECD423 2001*

* OECD

xxxxx Laboratory GLP

Sprague-Dawley 3

chemx 98.9 % 2,000 mg/kg 14

2 2,000 mg/kg

LD50 >2,000 mg/kg

chemx 2

1 7 14 1 7

14

I.

A.

1. chemx

NPD-9209-4523-T

98.9 %

CAS 16335-17-2

2.

3.

Crl:CD(SD)BR, albino

8 2 10

7

69

155 g-65 g 2 190 g-215 g

7

#5001

35 %-84 %

12

B. :

1. 2003 1 15 -2 15

2.

17 - 22 chemx 2,000 mg/kg

10 mL/kg 0.5 1

2.5 4 14 1 1

7 14 14

2 2,000 mg/kg

II.

A.

5.2.1-1 2,000 mg/kg

5.2.1-1mg/kg 22,000 0/3 0/3

B.

chemx 2

C.

1 7 14 1

7 14

7

70

D.

III.

chemx LD50

LD50 >2,000 mg/kg

5.2.2

5.2.2 Xxxx X 2003, Acute dermal toxicity study in rats chemx

SB-92-480

OECD 402 1987

OECD402 2017* …………………. ………………….

* OECD

xxxxx Laboratory GLP

Sprague-Dawley 5 chemx

98.9 % 2,000 mg/kg

10 % 24 15

LD50 >2,000 mg/kg

>2,000 mg/kg

chemx

2 4

I.

A.

1. chemx

NPD-9209-4523-T

98.9 %

CAS 16335-17-2

7

71

2.

3.

Crl:CD(SD)BR, albino

240 g-260 g 230 g-245 g

5

#5002

35 %-84 %

12

B.

1. 2003 10 28 -12 16

2.

5.2.2-1

10 % 24

3 1 1

1 2 1 8 15

15

II.

A.

5.2.2-1 2,000 mg/kg

5.2.2-1mg/kg

0 0/5 0/52,000 0/5 0/5

7

72

B.

2

4

C.

D.

III.

chemx LD50

LD50 >2,000 mg/kg

>2,000 mg/kg

5.2.3

5.2.3 Xxxx X 2004, Acute inhalation study of chemx herbicide.

CCC-13880

OECD 403 1981

OECD403 2009* …………………. ………………….

* OECD

xxxxx Laboratory GLP

Sprague-Dawley 5 chemx

98.5 % 5.0 mg/L 4 14

LC50 >5.0 mg/L

>5.0 mg/L

chemx

1

7

73

14 2 3

7

2

I.

A.

1. chemx

GHQ-9307-5385-T

98.5 %

CAS 16335-17-2

4

2. chemx

3.

Crl:CD(SD)BR, albino

315 g-340 g 235 g-255 g

8

#5002

35 %-84 %

12

B. :

1. 2004 2 13 -3 7

2.

5.2.3-1 4 1

1 2

2 7 14 14

7

74

3.

80-L 4

2

JET-O-MIZER®

20 80 140 223 HPLC

HPLC x 2 % UV xx nm

chemx LOD x g/L LOQ xx g/L

5.0 0.2 mg/L

2

1 1

2.7 m

1.5

xx m 65 %

x m 1.8 %

II.

A.

5.2.3-1 5.0 mg/L

5.2.3-1mg/L

0 0/5 0/55.0 0/5 0/5

B.

1 14

C.

2 3 7

D.

2

III.

7

75

chemx LC50

LC50 >5.0 mg/L

>5.0 mg/L

4

5.2.4

5.2.4 Xxxx X 2005, Guinea pig maximization test with chemx (Method of

Magnusson and Kligman).

PL-04-047

OECD 406 1992

OECD406 1992*

* OECD

xxxxx Laboratory GLP

Dunkin Hartley 10

FCA chemx 98.8 % 1

8 22

22 1

chemx

I.

A.

1. chemx

GHQ-0307-5385-T

98.8 %

CAS 16335-17-2

2. FCA

9 %

7

76

3.

Dunkin Hartley Haz DH FBR

5 -7

345 g-420 g 270 g-435 g

GTP

14

Agway Prolab Purina

18 ºC -24 ºC

30 %-60 %

12

B. :

1. 2004 11 11 -12 16

2.

1 8 22

10 %

chemx 5 % w/v

FCA 50 % v/v chemx

5 % w/v 0.9 %

chemx Dunkin Hartley

10 5 % 100 %

II.

22 1

2004 9

III.

chemx chemx

7

77

5.2.5 chemx

LD50 >2,000 mg/kg

LD50 >2,000 mg/kg

4 LC50 >5.0 mg/L

maximization

5.35.3.1 90

5.3.1 Xxxx X and Xxxx X 2005, 90-day feeding study with chemx administered in

feed to Sprague-Dawley rats.

CCC-14049

OECD 408 1998

OECD408 2018* …………………. ………………….

* OECD

xxxxx Laboratory GLP

90 Sprague-Dawley 1 10 0 20

200 2,000 6,000 xx,xxx ppm 1.2 12.1 123 370 x,xxx mg/kg /day

1.5 14.6 144 448 x,xxx mg/kg /

chemx

chemx

NOAEL

xxx mg/kg / xxx mg/kg /

I.

A.

1. chemx

NPD-9209-4523-T

99.3 %

7

78

CAS 16335-17-2

7

2.

3.

Crl CD (SD) BR, albino

7

215.4 g-286.7 g 102.9 g-147.0 g

27

Purina Mills #5002

20 °C -24 °C

45 %-65 %

16-20 /

12

B.

1.

2003 2 22

2003 5 30

2003 6 30 4

2.

1 10 5.3.1-1 10

4

5.3.1-1

(ppm)(mg/kg / ) (mg/kg / )

1 0 0 0 20 202 20 1.22 1.47 10 103 200 12.1 14.6 10 10

7

79

4 2,000 123.2 144.3 10 105 6,000 370 448 10 106 xx,xxx x,xxx x,xxx 20 20

5.3.1-2%

20mg/kg T=22 110M=22 110B=22 113

S=19.7 89xx,xxx mg/kg T=xx,xxx 102

M=xx,xxx 104B=xx,xxx 98S=xx,xxx 94

T = M = B = S = 35

3.

Hobart HCM-450

20 ppm xx,xxx ppm

35

5.3.1-2

4.

APTT Dunnett Fisher

Barrette Dunnett

C.

1.

1 1

2.

1

3.

1

4.

12

7

80

5.

6.

RBC WBC PLT Hb

Ht MCV MCH

MCHC PT

APTT

TP Alb Glob A/G

Glu T-Cho TG

T-Bil BUN CREA

AST ALT -

-GPT ALP Na

K Cl Ca P

7.

13 pH

8.

7

81

II.

A.

1.

2.

3.

B.

6,000 ppm

5.3.1-3 xx,xxx ppm 31 -92

15 % 31 79

xx,xxx ppm 10 %

5.3.1-4

5.3.1-3 g

(ppm)3 31 79 92

0 23.16 250.14 395.28 412.4620 21.48 254.42 388.07 409.63

200 29.22 253.87 386.66 411.072,000 30.08 245.13 386.97 411.916,000 29.73 231.17 366.69 387.09xx,xxx 28.20 219.79* 332.13* 349.29

* p 0.05

5.3.1-4 gppm

0 20 200 2,000 6,000 xx,xxx630.01 628.9 629.2 626.5 602.1 575.8280.5 298.5 283.2 299.9 304.2 283.2

C.

1.

0 20 200 2,000 6,000

xx,xxx ppm 1.2 12.1 123.2 370 x,xxx mg/kg

7

82

/ 1.5 14.6 144.3 448 x,xxx mg/kg /

2.

D.

E.

F.

1.

2.

xx,xxx ppm ALT

GLU

TP Ca

Cl

6,000 ppm xx,xxx ppm

4

5.3.1-5ppm

0 20 200 2,000 6,000 xx,xxxALT (IU/L) 40.0 36.3 33.4 34.6 50.0 31.9*

GLU (mg/dL) 227.0 228.4 218.0 252.7 230.0 229.6TP (g/dL) 6.58 6.82 6.87 6.77 6.78 6.55

ALP (g/dL) 4.27 4.17 4.38 4.31 4.42 4.13Ca (mg/dL) 11.46 11.68 11.60 11.71 11.61 11.51Cl (meQ/L) 100.3 101.4 101.8 102.4 103.9** 104.4**ALT (IU/L) 42.8 46.7 38.2 35.1 37.2 28.5

GLU (mg/dL) 160.7 214.2* 188.8 205.0 227.7** 181.9TP (g/dL) 6.91 7.61** 7.06 7.34 7.26 7.01

ALP (g/dL) 4.72 5.47** 5.00 4.99 4.90 4.61Ca (mg/dL) 11.22 11.90* 11.44 11.76 11.52 11.34Cl (meQ/L) 100.9 100.5 101.8 101.2 101.9 101.9

* p 0.05 ** p 0.01

7

83

G.

H. :

1.

2.

5.3.1-6

(ppm)0 20 200 2,000 6,000 xx,xxx 0 20 200 2,000 6,000 xx,xxx

0 0 0 0 0 1 0 0 0 0 0 2 ( ) 2 0 2 0 0 0 0 0 0 0 0 2

0 0 0 0 0 1 0 0 0 0 0 1 1 0 4 2 4 4 3 0 4 3 2 2

0 0 0 0 0 1 0 0 0 0 0 2 0 0 0 0 0 1 0 0 0 0 0 1 0 0 0 0 0 1 - - - - - -

III.

NOAEL x,xxx ppm

xxx mg/kg / xxx mg/kg /

90

90 5.3.1

5.3.1 90

5.3.1.1

7

84

5.3.1.2

5.3.2 90

90 5.3.1

5.3.3 90

5.2.3

5.2.3 90

5.3.1

5.3.4 21

5.2.2

90 5.3.1

5.3.5

(mg/kg / ) NOAEL

(mg/kg / ) LOAEL

(mg/kg / )

90 0 20 200 2,000 6,000xx,xxx ppm

xxxxxx

x,xxxx,xxx

0 1.2 12.1 123 370 x,xxx0 1.5 14.6 144 448 x,xxx

90 0, 30, 100, 300, x,xxx xxxxxx

x,xxxx,xxx

5.4

5.4.1

5.4.1 Xxxx X 2005, Ames / Salmonella mutagenicity assay of chemx.

CC-94002

OECD471 1997

OECD471 1997*

* OECD

xxxxx Laboratory GLP

7

85

Salmonella typhimurium TA98 TA100 TA102 TA1535

TA1537 chemx 98.5 % 5 15 50 150 500 1,500 x,xxx μg/plate

DMSO S9 mix

1 1 3

x,xxx μg/plate

S9

x,xxx μg/plate

S9mix 1,500 μg/plate

S9mix

/ p 0.01

chemx

I.

A.

1. chemx

NPD-9307-5385-T

98.5 %

CAS 16335-17-2

1

DMSO

2.

DMSO 0.1mL/

4-nitroquinoline-N-oxide 0.1 g/plate TA98 TA100

sodium nitrite 2.5 mg/plate TA1535

9-aminoacridine 50 g/plate TA1537

Cumene hydroperoxide 50 g /plate TA1022-acetylaminofluorene 15 g/plate TA98

benzo(a)pyrene 1 g/plate TA100

2-aminoanthracene 5 g/plate TA1535, TA1537

Dantron 25 g/plate TA102

7

86

3. Sprague-Dawley S9 Aroclor 1254

MolTox 0339

39.2 mg/mL

Molecular Toxicology Inc.

S9

S9mix

sodium phosphate (pH7.4) 100 moles

glucose 6-phosphate 5 moles

NADP 4 moles

KCl 33 moles

MgCl2 8 moles

S9 10 %(v/v)

4. S. typhimurium TA98 TA100 TA102 TA1535 TA153

rfa R

5.

(a) 2

TA100 50 150 500 1,500 x,xxx g/plate S9mix

1

TA100 50 150 500 1,500 x,xxx g/plate S9mix

1

(b)

5 15 50 150 500 1,500 x,xxx g/plate S9mix

3

5 15 50 150 500 1,500 x,xxx g/plate S9mix

3

B.

2004 10 30 -11 28

1.

0.1 mL 0.1 mL

2.0 mL S9 S9mix 0.5 mL

37 1 ºC 48

3

7

87

2.

0.5 mL

37 1 ºC 20 2

3.

log10 Bartlett

t Grubbs

p 0.01

4.

3 p 0.01

II.

A.

1 78 %

87 %-119 % 9

-1.76 %

B.

50 g/plate-x,xxx g/plate S9mix 5

x,xxx g/plate

S9mix

1 1 p.18

x,xxx μg/plate S9mix

C.

1,500 μg/plate S9mix

chemix

DMSO 5.4.1-1

5.4.1-2 5.4.1-3

5 -50 p 0.01

III.

7

88

5.4.1-1

( plate) S9mixplate

TA98 TA100 TA102 TA1535 TA1537

Chemx

0 xx±x xxx±x xx±x xx±x xx±x

5 xx±x xxx±x xx±x xx±x xx±x

15 xx±x xxx±x xx±x xx±x xx±x

50 xx±x xxx±x xx±x xx±x xx±x

150 xx±x xxx±x xx±x xx±x xx±x

500 xx±x xxx±x xx±x xx±x xx±x

1,500 xx±x* xx±x* xx±x* xx±x* xx±x*

x,xxx x±x* xx±x* x±x* x±x* x±x*

0 xx±x xxx±x xx±x xx±x xx±x

5 xx±x xxx±x xx±x xx±x xx±x

15 xx±x xxx±x xx±x xx±x xx±x

50 xx±x xxx±x xx±x xx±x xx±x

150 xx±x xxx±x xx±x xx±x xx±x

500 xx±x xxx±x xx±x xx±x xx±x

1,500 xx±x* xx±x* xx±x* xx±x* xx±x*

x,xxx x±x* xx±x* x±x* x±x* x±x*

4NQO 0.1 xxx±x xxx±x ne ne ne

NaNO2 2,500 ne ne ne xxx±x Ne

9AA 50 ne ne ne ne xxx±x

CHP 50 ne ne xxx±x ne ne

2AAF 15 xxx±x ne ne ne ne

BP 1 ne xxx±x ne ne ne

2AA 5 ne ne ne xxx±x xxx±x Dantron 25 ne ne xxx±x ne ne

4NQO 4-nitroquinoline-N-oxide NaNO2 sodium nitrite 9AA 9-aminoacridine CHP cumene hydroperoxide

2AAF 2-acetylaminofluorene BP benzo(a)pyrene 2AA 2-aminoanthracene

ne Not evaluated *

5.4.1-2 1

5.4.1-1

5.4.1-3 2

7

89

5.4.1-1

5.4.2

5.4.2 Xxxx X 2006, Chromosome aberration study in human whole blood

lymphocytes with chemx and a confirmatory assay with multiple harvests.

CC-95-201

OECD 473 1997

OECD473 2016* …………………. ………………….

* OECD

xxxxx Laboratory GLP

in vitro

DMSO chemx 98.5 % 100 250 500 750 x,xxx μg/mL

chemx 500 750 x,xxx μg/mL

100 250 500 750 x,xxx μg/mL 3

19.5 43.4

22.3 46 500

750 x,xxx μg/mL

chemx

I.

A.

1. chemx

NPD-9503-6466-T

98.5 %

CAS 16335-17-2

DMSO 24

7

90

DMSO

2.

DMSO 1 %

-S9 mitomycin C MMC 0.2 2 10 g/mL

+S9 cyclophosphamide CP 30 40 g/mL

3.

S9mix

Sprague-Dawley S9 Aroclor 1254

S9 15 L/mL NADP 1.5 mg/mL 2.7 mg/mL

4.

5. RPMI 1640 15 % phytohaemaglutinin 1 %

penicillin 1 % streptomycin 1 % L-glutamine 1 %

6.

1 100 250 500 750 x,xxx g/mL

2 100 250 500 750 x,xxx g/mL

1 100 250 500 750 x,xxx g/mL

2 100 250 500 750 x,xxx g/mL

B.

2005 9 10 -11 5

1.

S9 33.3 g/mL-x,xxx g/mL 3

S9 3.33 g/mL-x,xxx g/mL 19.3

MI 1,000

2.

3 1 19.5 43.4 2

3 1 2

7

91

0.1 g/mL 2

19

1 2 2 22

5 %

2 100 1 200

2

8

3.

p 0.01

Armitage

II.

A.

x,xxx g/mL

3 10 g/mL 333 g/mL MI >50 %

x,xxx g/mL MI 15 % 19.3

333 g/mL x,xxx g/mL 39 % 61 %

100 g/mL 333 g/mL x,xxx g/mL MI 14 % 33 % 19 %

B.

7

92

1 3 100 g/mL

chemx MI 13 %-33 %

5.4.2-1 MI 69 %

5.4.2-1 22.3 46

2 MI 54 %

500 750 x,xxx g/mL

5.4.2-2

5.4.2-1 1

( mL) (h) (h)

S9mix(%)

MI

(%)G B E G B E

RPMI1640

3 22

200 18 1 0 4 5 1 0 2.5 0.0 3.1

DMSO 10 200 13 2 0 2 0 1 0 1.5 0.5 3.0

chemx500 200 11 0 0 1 0 0 0 0.0 0.0 2.5750 200 13 1 0 4 0 0 0 0.5 0.0 4.2

x,xxx 200 21 3 0 0 1 0 0 2.0 0.0 2.1

MMC 2.0 200 50 53 48 14 16 3 0 39.5* 0.0 0.6

RPMI1640

3 22

200 5 0 0 1 0 0 0 0.0 0.0 2.4

DMSO 10 200 5 0 0 1 0 0 0 0.0 0.0 2.6

chemx500 200 7 2 0 1 1 0 0 1.5 0.0 2.0750 200 6 1 0 2 0 0 0 0.5 0.0 2.3

x,xxx 200 10 1 0 1 0 0 0 0.5 0.0 0.8

CP 40 200 50 47 13 12 8 1 0 32.0* 0.0 0.3

G (%)BE 3 4

10MI* p 0.01

5.4.2-2 2

5.4.2-1

III.

chemx

7

93

5.4.3

5.4.3 Xxxx X 2005, Mouse bone marrow micronucleus assay of chemx.

CCC-14073

OECD 474 1997

OECD474 2016* …………………. ………………….

* OECD

xxxxx Laboratory GLP

CD-1 1,000 mg/kg 5

x,xxx mg/kg 10 1,250 2,500 x,xxx mg/kg

1 5 -10 chemx

10 mL/kg

40 mg/kg chemx 24 48 72

24

5

MN PCE /

chemx 2,500 mg/kg

1 1 2

chemx

chemx /

MN PCE 24 2,500 mg/kg

p 0.01

chemx MN

PCE MN PCE 2.7 MN

PCE/1000 PCE 0.0-7.4 MN PCE/1000

PCE MN PCE

chemx in vivo

I.

A.

7

94

1. chemx

NPD-9307-5385-T

98.5 %

CAS 16335-17-2

7

1,2,3-trioctanoylglycerol

2.

1,2,3-trioctanoylglycerol 10 mL/kg

Cyclophosphamide monohydrate 40 mg/kg

3.

CD-1

8 -10

29.6 g-38.3 g 18.8 g-29.0 g

1 5 -10

1 5

4. 1,000 x,xxx mg/kg

0 1,250 2,500 x,xxx mg/kg

B.

2004 2 10 -8 2

1.

1,250 2,500 x,xxx mg/kg 24 48

24

2.

2,000 PCE 2 1,000 PCE

1,000 PCE NCE

3.

24 48 72

24

7

95

2,000 PCE 2 1,000 PCE

NCE PCE

4.

MN PCE

(a)

(b)

5.

MN PCE MN PCE/

MN PCE PCE/

Dunnett

p 0.05

II.A.

5 1,000 mg/kg 10 x,xxx mg/kg 72chemx

B.1.

2,500 mg/kg 1 1 -2 x,xxx mg/kg1 1

2. PCEPCE/

5.4.3-1

5.4.3-1 PCEPCE/ SD

1,250 mg/kg 2,500 mg/kg x,xxx mg/kg24 5 0.26 0.07 0.34 0.10 0.30 0.07 0.28 0.06 0.37 0.1248 5 0.28 0.06 0.39 0.08 0.28 0.12 0.29 0.0972 5 0.36 0.05 0.31 0.08 0.37 0.03 0.33 0.1124 5 0.35 0.06 0.40 0.11 0.41 0.09 0.43 0.09 0.44 0.0348 5 0.37 0.05 0.46 0.06 0.45 0.09 0.43 0.0572 5 0.50 0.08 0.44 0.09 0.43 0.06 0.51 0.06

1,2,3-trioctanolglycerol 10 mL/kg cyclophosphamide 40 mg/kg

7

96

3. MN PCE

24 2,500 mg/kg p 0.01 MN PCE

5.4.3-2 2.7/1,000 PCE

0.0-7.4/1000 PCE - 5.4.3-3

24 1.0/1,000 PCE 48 1.3/1,000 PCE 72

1.6/1,000 PCE 24 x,xxx mg/kg

1.4/1,000 PCE

5.4.3-2 MN PCEMN PCE/1,000PCE SD

1,250 mg/kg 2,500 mg/kg x,xxx mg/kg24 5 0.6 04 1.5 1.9 1.5 1.0 1.3 1.2 13.1 5.1**48 5 0.8 0.4 0.7 0.6 0.7 0.3 1.5 0.672 5 1.5 1.1 1.7 1.2 1.5 0.4 1.6 1.0

5 1.0 0.8 1.5 0.6 2.7 0.8** 1.4 0.4 8.8 3.0**5 1.3 1.0 2.5 1.4 1.8 0.8 1.7 1.75 1.6 1.0 2.1 0.8 1.4 1.8 2.0 1.5

*p 0.05 **p 0.01 Dunnett1,2,3-trioctanolglycerol 10 mL/kg cyclophosphamide 40 mg/kg

5.4.3-3 CD-1 10 mL/kg * h SD SD %

MN PCE/1,000 PCE48 70 1.200 1.431 0.20-2.40 130.3% 55.5%72 45 1.022 1.469 0.20-2.20 143.8% 51.5%

180 0.954 1.303 0.00-2.40 140.0% 55.4%MN PCE/1,000 PCE

48 50 1.880 4.074 0.20-7.40 132.5% 61.5%72 45 1.356 1.569 0.20-2.40 108.8% 53.7%

180 1.421 2.676 0.00-7.40 123.1% 54.1%* 13 10

III.

chemx x,xxx mg/kg

5.4.4 DNA5.4.1 DNA

7

97

5.4.5

AmesS. typhimurium

TA98 TA100 TA102 TA1535 TA15375-x,xxx g/plate S9mix

500-x,xxx g/mL3 S9mix19.5 43.4 S9mix

1,250-x,xxx mg/kg

5.5

5.5.1

90 5.3.1

5.5.2

90 5.3.1

5.5.1 5.5.2

5.5.1

5.5.3

90 5.3.1

5.5.4

90 5.3.1

5.5.5

(mg/kg / ) NOAEL

(mg/kg / ) LOAEL

(mg/kg / )

0 20 xxx x,xxx ppm

0 xx xxx x,xxx0 xx xxx x,xxx

xxxxxx

x,xxxx,xxx

18 0 20 xxx x,xxx ppm

0 xx xxx x,xxx0 xx xxx x,xxx

xxxxxx

x,xxxx,xxx

5.6

5.6.1

90 5.3.1

7

98

P

101

83 1 1

03 1

0

3 4 48

0 4 7 14 214

F1

F1 241 2

F1

10P

3 P P3 P

P3 P

F1 F1

7

99

P F1

ppm0 20 200 2,000 0 20 200 2,000

g

g

g

g

g

021021

g

0-210-21

g

0-210-21

g

0-210-21

P F1

ppm0 20 200 2,000 0 20 200 2,000

%%%

7

100

P F1

ppm0 20 200 2,000 0 20 200 2,000

106/g

%%

P F1

ppm0 20 200 2,000 0 20 200 2,000

g%

g%

g%

P F1

ppm0 20 200 2,000 0 20 200 2,000

2/24 1/24 3/24 8/24

7

101

F1 F2

ppm0 20 200 2,000 0 20 200 2,000

%0 4 71421

0 4 71421

5.6.2

90 5.3.1

ppm0 100 300 1,000

g21

g6-21

g0-21

ppm0 100 300 1,000

g

7

102

ppm0 100 300 1,000

270 24 275 24 265 24 272 24

135 24 138 24 133 24 136 24

135 24 137 24 132 24 136 24

5.6.3

90 5.3.1 5.6.2

5.6.4

(mg/kg / ) NOAEL

(mg/kg / ) LOAEL

(mg/kg / )

2 0 20 xxx x,xxx ppm

P 0 xx xxx x,xxxP 0 xx xxx x,xxxF1 0 xx xxx x,xxxF1 0 xx xxx x,xxx

P 0 xx xxx x,xxxF1 0 xx xxx x,xxx

P 0 xx xxx x,xxxF1 0 xx xxx x,xxx

P xxxP xxxF1 xxxF1 xxx

P x,xxxF1 x,xxx

P xxxF1 xxx

P x,xxxP x,xxxF1 x,xxxF1 x,xxx

PF1

P x,xxxF1 x,xxx

0, 30, 100, 300, x,xxx x,xxxx,xxx

0, 30, 100, 300, x,xxx x,xxxx,xxx

7

103

5.7

5.7.1

5.2.1 90 5.3.1

chemx

90 5.3.1

5.7.2

90 5.3.1

90 5.3.1

5.7.3 28

90 5.3.1

28

90 5.3.1

5.7.4

90 5.3.1

chemx

90 5.3.1

5.7.5

90 5.3.1 5.6.1

90 5.3.1

7

104

5.85.8.1 desmethyl chemx 1

5.9

5.10

5.10.1

5.10.2

5.11

5.12

chemx 90 % 3

77 %-87 %

59 % 90 %

38 % <0.13 %

0.01 %

chemx chemx chem2

chemx

90 xx,xxx ppm

xx,xxx ppm

NOAEL x,xxx ppm xxx mg/kg

/ xxx mg/kg /

7

105

90 xx,xxx mg/kg /

NOAEL xxx mg/kg / xxx mg/kg /

chemx

xxx ppm x,xxx ppm

NOAEL xxx ppm

xxx mg/kg / xxx mg/kg /

x,xxx ppm

NOAEL xxx ppm xxx mg/kg / xxx mg/kg

/

2 xxx ppm x,xxx ppm

P F1

x,xxx ppm F1 F2

NOAEL xxx ppm P xxx mg/kg / xxx mg/kg / F1

xxx mg/kg / xxx mg/kg / x,xxx ppm P x,xxx mg/kg / x,xxx

mg/kg / F1 x,xxx mg/kg / x,xxx mg/kg / xxx ppm P

xxx mg/kg / F1 xxx mg/kg /

NOAEL x,xxx mg/kg /

NOAEL x,xxx mg/kg /

ADI

NOAEL 1

xxx mg/kg / 100

x.xx mg/kg / ADI

ARfD

ARfD

ARfD ADI

7

106

AOEL

NOAEL 90

xxx mg/kg / xxx

100 x.xx mg/kg / AOEL

AAOEL

AAOEL

AAOEL AOEL

5.11-1

LD50 >2,000 mg/kg

LD50 >2,000 mg/kg

4 LC50 >5.0 mg/L

maximization

(mg/kg / )NOAEL

(mg/kg / ) LOAEL

(mg/kg / ) 90 0 20 200 2,000 6,000

xx,xxx ppm

0 1.2 12.1 123 370x,xxx

0 1.5 14.6 144 448x,xxx

xxxxxx

x,xxxx,xxx

90 0, 30, 100, 300, x,xxx xxxxxx

x,xxxx,xxx

7

107

AmesS. typhimurium

TA98 TA100 TA102 TA1535 TA15375-x,xxx g/

S9mix500-x,xxx g/mL

3 S9mix19.5 43.4 S9mix

1,250-x,xxx mg/kg

(mg/kg / )NOAEL

(mg/kg / ) LOAEL

(mg/kg / ) 0 20 xxx x,xxx ppm

0 xx xxx x,xxx0 xx xxx x,xxx

xxxxxx

x,xxxx,xxx

18 0 20 xxx x,xxx ppm

0 xx xxx x,xxx0 xx xxx x,xxx

xxxxxx

x,xxxx,xxx

(mg/kg / )NOAEL

(mg/kg / ) LOAEL

(mg/kg / ) 2 0 20 xxx x,xxx ppm

P 0 xx xxx x,xxxP 0 xx xxx x,xxxF1 0 xx xxx x,xxxF1 0 xx xxx x,xxx

P 0 xx xxx x,xxxF1 0 xx xxx x,xxx

P 0 xx xxx x,xxxF1 0 xx xxx x,xxx

P xxxP xxxF1 xxxF1 xxx

P x,xxxF1 x,xxx

P xxxF1 xxx

P x,xxxP x,xxxF1 x,xxxF1 x,xxx

PF1

P x,xxxF1 x,xxx

0, 30, 100, 300, x,xxx x,xxxx,xxx

0, 30, 100, 300, x,xxx x,xxxx,xxx

8

108

OECD 7 4

6.

6.1

6.4.1/01 Xxxx X 2008,

XX-08-12

12 8147

30 6278

GLP GLP

chemx 99 % 0.2 mg/kg

-20 C 250 8 chemx

chemx

10 % chemx

-20 C 250 8

I.

A.

1. chemx

NPD-9211-4628-T

99 %

CAS 16335-17-2

CR 48500

0.2 mg / kg

2.

8

109

61

Triticum aestivum

10.0 ± 1 g

B.

2007 7 -2008 4

1.

chemx 99 % 0.2 mg/kg -20 C 250

8 2

chemx 4.2.1 chemx

2.

chemx

chemx

chemx

II.

250

6.1-1

III.

chemx -20ºC 250 >70 %

6.1-1 -20ºC chemx

(mg/kg) ( )*

(%) (%)chemx 0.2 250 90 102

*

8

110

6.26.2.16.2.1.1

6.2.1 Xxxx X 2004, Metabolism of chemx in wheat.

XX-13043

OECD 501

xxxxx Laboratory GLP

chemx WG chem2 C-3 14C

98 % 99.7 % chem3 C-5 14C

99.4 % 99.9 % 70 g ai/ha 200 g ai/ha 3.5 10

chemx Feekes scale stage 3

2 10

chemx 61 % 37 %

<0.01 mg/kg

6 10 %

13 % 14 %

I.

A.

1. chemx

chem2 C-3 14C

2.40 MBq/mg 28.6 mCi/mmol

chem3 C-5 14C

2.47 MBq/mg 29.4 mCi/mmol

2.44 MBq/mg 29.1 mCi/mmol

chem2 chem3

chem2 99.7 % 98.0 %

chem3 99.9 % 99.4 %

8

111

CAS 16335-17-2

7

2. Elder

6.2.1.1-1

pH OM% % % % (1/3 )

CECmeg / 100 g

Elder 6.6* 1.1** 78 10 12 9.92 10.7* 1 2.5** 1.72

B.

2003 3 2004 5

1.

chemx 76 cm 91 cm 30 cm

chemx WG

Feekes scale stage 3

70 g ai/ha 3.5 200 g ai/ha 10

2.

2 10

2003 6

II.

A. TRR

chemx 70 g ai/ha 200 g ai/ha PHI-104 PHI-8314C TRR 6.2.1-2

14C

chemx 20 g ai/ha GS 13-39

chemx 0.01 mg/kg

chem2 chemx chem3 chemx

chem2

8

112

chemx 13 %

6.2.1.1-2 TRR (mg/kg)*

chem2 chemx chem3 chemx

** 70 g ai/ha 200 g ai/ha 70 g ai/ha 200 g ai/ha

0.0027 0.0076 0.005 0.013

0.32 1.1 0.31 1.1

0.89 2.9 0.77 1.6

0.0021 0.0044 0.0047 0.0095

0.065 0.21 0.031 0.066

0.012 0.025 0.0046 0.01* 0.00086 mg/kg 0.0014 mg/kg 0.0018 mg/kg** 200g ai/ha 164.5 g ai/ha chem2 chemx 185.2g ai/ha chem3 chemx

197.6 g ai/ha chem2 chemx 171.9 g ai/ha chem3 chemx66 70.6 g ai/ha

B.14C 25/75 v/v

6.2.1.1-3

6.2.1.1-3 / 25/75 chemx

%14C %14C %14C %14C %14C %14C

chem2 chemx,70 g ai/ha n.e. 102.3 6.9 84.2 12

chem2 chemx,197.6 g ai/ha 39.8 59.6 93.7 6.3 86.7 10.3

[6.2*] chem3 chemx,

70 g ai/ha n.e. 98.9 7.3 81.4 16.5[11.8*]

chem3 chemx,171.9 g ai/ha 38.4 61.5 93.2 6.8 76.8 14.7

[10.8*]chem2 chemx,

70 g ai/ha n.e. n.e. 78.8 15.8

chem2 chemx,164.5 g ai/ha 61.1 37.6 77.5 15.6 73.2 13.9

chem3 chemx,70 g ai/ha n.e. n.e. 63.6 24.7

chem3 chemx,185.2 g ai/ha 26.2 77.4 73.6 29.3 62.5 24.9

n.e.* 14C [ ] %

1.

6.2.1-2

200 g ai/ha

chem2 chemx chem3 chemx 0.0024-0.005 mg/kg

8

113

pH 1 pH 7 pH 1

74 %-100 % pH 7 70 %-80 %

chem2 pH 1 150 ºC 14C

11 % 33 % chem2 chem3

chemx 14C14C 68 %-85 %

14C14C

2.14C

5 -17 6.2.1-2 HPLC-LSC

chemx chemx

chem2-4

chem2-7 chem3-1 chem3-4 chem3-6 chem2

chem3 chemx

chem214C pH 7 pH 1

39.6 %-65.2 %

60.4 %-96.9 %

3.14C 40 HPLC

14C 170 33414C chem2 chemx

chem3 chemx

HPLC 2 30 168

43 9814C HPLC

2

4.

chemx

8

114

6.2.1-4 chemx GAP

14C

chem2 chemx 200 g ai/ha chem3 chemx

200 g ai/ha14C 60 %-74 % chem3 54 %

HPLC 27 %-29 % chem3ide

chem3ide

1 N 1 N 6 N14C 86 % 61 %

6.2.1.1-4 chemx mg/kg TRRchem2 chemx

70 g ai/hachem2 chemx

200 g ai/hachem3 chemx

70 g ai/hachem3 chemx

200 g ai/haTRR 0.32 1.1 0.31 1.1Chemx[chem2-9=chemx3-9] 0.13 (41.0) 0.50 (45.1) 0.10 (33.4) 0.44 (39.6)

Desmethyl chemx[chem2-8=chemx3-8] 0.009 (2.9) 0.034 (3.1) 0.013 (4.1) 0.045 (4.1)

xxxxxxx[chemx2-7] 0.010 (3.5) 0.037 (3.4)xxxxxx[chemx2-4] 0.022 (6.7) 0.078 (7.1)xxx[chemx3-7] 0.018 (5.7) 0.046 (4.2)xxxx[chemx3-5] 0.011 (3.5) 0.034 (3.1)xxyx[chemx2-3] a 0.003 (1.0) 0.011 (1.0)chemx2-6 b 0.0xx (4.3) 0.0xx (4.4)chem2-5 c 0.0xx (2.1) 0.0xx (2.3)chem2-1/2 d 0.0xx (5.0) 0.0xx (5.9)chem3-6 e 0.0xx (4.4) 0.0xx (4.8)chem3-4 f 0.0xx (4.7) 0.0xx (5.2)chem3-3 g 0.0xx (4.8) 0.0xx (5.2)chem3-1 h 0.0xx (7.5) 0.0xx (7.9)

0.xx (72.2) 0.xx (77.6) 0.xx (68.9) 0.xx (73.4)i 0.0xx (12.4) 0.0xx (10.6) 0.0xx (16.9) 0.0xx (16.1)

0.xx (84.6) 0.xx (88.2) 0.xx (85.9) 0.xx (89.5)a xxyx chem2-3 15 % xxyxb chem2 33 %

chem2c chem2 53 %d

chem2 chem2e chem3 12.9 % chem3idef chem3g chem3 36 % chem3ideh chem3 chem3ide chem3

i chem3 14C 73.7 % 0.027 mg/kg chem3ide

8

115

5.

HPLC

70 g ai/ha chemx

chem3 55.4 %TRR chem2 65.7 %TRR desmethyl chemx chem3

6.4 %TRR chem2 4.3 %TRR chem2-1-chem2-7

chem3-1-chem3-7 0.05 mg/kg

6.

chemx

1 N 95 ºC 55 chemx chem3ide chem3ide

xxxxxxx chem2-7

1 N 150 ºC 70 chemx chem2

chemx

4.2.1

7.

12

LSC HPLC 9

chemx 6

6.2.1-4 6.2.1-1 desmethyl chemx chem2-8 chem3-8

chem3ide

HPLC HPLC HPLC14C

pH 1 pH 7

HPLC chem2-6 chem2-5 chem2-1/2 chem3-6 chem3-3 chem3-114C 2.1 %-7.9 % 6.2.1-4

TRR 6.5 % chem2-3 15 % xxyx

chem3ide

chem3ide

chem3ide

12

8

116

chemx chem2-9 / chem3-9 desmethyl chemx chem2-8 / chem3-8

xxxx chemx3-5 xxx chemx3-7

chem3ide chem3ide-N-glucoside

monohydroxychem3ide xxxxxxx chem2-7

Yyyyy xxyyxxxxxxx chem2-4 xxyx chem2-3

chemx chem2-9 / chem3-9 desmethyl chemx chem2-8 / chem3-8 HPLC

HPLC LC/FAB/MS HPLC

desmethyl chemx chem2-8 / chem3-8 MS

xxxxxxx chem2-7 HPLC 2 HPLC

HPLC/FAB/MS

HPLC

HPLC HPLC14C % chem3ide

chem3 chem2

8.

chemx 6.2.1-1

6.2.1.1-1 chemx

III.

chemx 20 g ai/ha

0.01 mg/kg

chemx chemx

33 %-45 % chemx 20 g ai/ha

0.1 mg/kg

chemx 20 g ai/ha 0.05 mg/kg

8

117

10% chem2-7 chem2-4 25 %

chemx chemx

chemx chemx

chemx

chemx chemx

6.2.1.2

6.2.2

6.2.2.1

6.2.2.2

6.2.2.2

6.2.2/02 Xxxx X 2006, Metabolism of chemx in lactating goats.

XX-11713

OECD 503

GLP

chem2 C-2 chem3 C-5 14C

chemx 98 % xxx mg/kg / xx mg/kg

5

TAR 85 % 5 chem2 chem3

TAR 0.2 %

TRR 0.18 mg/kg 0.14 mg/kg 0.18 mg/kg 0.14 mg/kg 0.008 mg/kg

0.021 mg/kg 0.002 mg/kg 0.008 mg/kg TRR 0.027 mg/kg

0.030 mg/kg

chemx TRR 13 %-89 %

0.002-0.15 mg/kg 73 %-98 % 81 %-86 % 72 %-89 %

19 %-37 % 2 TRR 6 %-25% 0.002-

0.032 mg/kg 1 TRR 1.1 %-11 % 0.002 mg/kg -0.015 mg/kg 11 TRR

8

118

1.5 %-19 % 0.002-0.006 mg/kg TRR

I.

A.

1. chemx

chem2 C-2 14C

0.95 MBq/mg 11.4 mCi/mmol

chem3 C-5 14C

0.88 MBq/mg 10.5 mCi/mmol

NPD-9307-5386-T

chem2 98 %

chem3 98 %

CAS 16335-17-2

7

2.

30 -42

xx.x kg -xx.x kg

1 1

10 24

USPHS-NIH

20 °C -24 °C

45 %-65 %

16-20 /

12

B.

1.

xxx mg/kg / chem2 chem3

8

119

xx kg/

1 /

5

2.

2 /

1 /

xx

3.

chem2 chemx chem3 chemx -20 ºC

14 -15 1/1 v/v

HPLC/RAD 95 %

1

chemx 14 -15 chemx

chem2 chem3 4 -6

II.

A. TRR

IIA 6.2.2.2-1

TAR chem2 chem3 86 %

99.9 %

TRR chem2 chem3

0.18 mg/kg 0.14 mg/kg 0.18 mg/kg 0.14 mg/kg 0.008 mg/kg 0.021 mg/kg

0.002 mg/kg 0.008 mg/kg TAR 0.1 % 0.2 %

TRR chem2 chem3 0.027 mg/kg 0.030 mg/kg

8

120

6.2.2.2-1 TRRchem2 chem3

mg/kg %TAR mg/kg %TAR

0.18 0.010 0.14 0.008

0.18 0.051 0.14 0.040

0.008 0.045 0.021 0.11

<0.002 <0.002 0.008 0.013

0.027 0.027 0.030 0.040

9.5 29 8.5 38

28 46 26 40

1.1 4 0.92 2.6

5.6 6.9 4.1 5.1

- 86 - 86

B.

3/1 v/v

1/1 v/v

LSC

LSC

HPLC/LSC Beckman Ultraspere Cyano

HPLC Beckman Ultraspere ODS C18

UV

chem2 chem2

1N

chemx 7 HPLC/LSC

C.

chem2 chem3

3/1 v/v 0.1N 0.1N HPLC/LSC

chem3 chem2

HPLC

HPLC chem2 chemx 2

FAB/MS

11 HPLC HPLC/ESI/MS

11

8

121

chemx 6.2.2.2-2

1.

chem2 chem3 TRR 98 %

0.18 mg/kg 95 % 0.13 mg/kg TRR 5.1 % 0.01 mg/kg

TRR 93 % 0.13 mg/kg chemx

chem2 chem3 TRR 75 %

0.13 mg/kg 89 % 0.13 mg/kg 3 chem2

1 TRR 1.1 % 2 TRR 18 % 0.03 mg/kg

chem3 1 TRR 2.9 % 11 TRR 1.5 %

TRR 1.5 % 2 chem2

chem3

2.

chem2 chem3 TRR 97 %

0.17 mg/kg TRR 83 % 0.12 mg/kg TRR

3.4 % 0.01 mg/kg TRR 16 % 0.02 mg/kg

chem2 chem3 TRR 93 %

0.17 mg/kg 80 % 0.11 mg/kg chemx

TRR 85 % 0.15 mg/kg 69 % 0.09 mg/kg 2

chem2 chem3 1 TRR 2.6 %

11 % 0.02 mg/kg chem2 2 TRR 6.0 %

0.01 mg/kg TRR 1.3 %

3.

TRR 65 % 0.01 mg/kg TRR

35 % 3/1 v/v

chem3 2 chem3-4 chem3-6 TRR

11 % 38 %

chem2 chem3 TRR

48 % 13 % chemx TRR 13 % 0.002 mg/kg

TRR 24 % 0.003 mg/kg chem2 2 TRR

25 % 0.002 mg/kg

8

122

6.2.2.2-2 chemxchem2

mg/kg %TRR mg/kg %TRR mg/kg %TRR mg/kg %TRR

Chemx 0.128 74.6 0.147 84.8 0.002 23.5 0.024 88.8

1 <0.002 1.1 0.005 2.6 ND ND ND ND

2 0.032 17.7 0.011 6.0 0.002 25.0 0.002 8.9

Chem2-1 0.002 1.5 <0.002 0.4 ND ND ND ND

Chem2-2 <0.002 0.9 0.002 1.3 ND ND ND ND

( ) 0.164 93.4 0.166 93.4 0.004 48.5 0.026 97.7

( ) 0.003 2.4 0.003 1.7 ND ND ND ND

0.177 98.3 0.174 96.6 0.005 64.6 0.027 99.7

0.002 1.7 0.006 3.4 0.003 35.4 <0.002 0.3

chem3

mg/kg %TRR mg/kg %TRR mg/kg %TRR mg/kg %TRR

Chemx 0.130 89.4 0.094 69 0.003 13.0 0.021 68.3

1 0.004 2.9 0.015 10.7 ND ND 0.002 3.3

11 0.002 1.5 ND ND ND ND 0.006 18.9

Chem3-1 ND ND <0.002 0.7 ND ND <0.002 2.0

Chem3-4 ND ND ND ND 0.002 11.4 ND ND

Chem3-6 ND ND ND ND 0.008 38.0 ND ND

( ) 0.136 93.8 0.109 79.7 0.003 13.0 0.028 90.4

( ) ND ND <0.002 0.7 0.010 49.4 <0.002 2.0

0.133 94.9 0.116 82.9 0.014 65.1 0.029 97.4

0.007 5.1 0.023 16.4 0.007 34.9 <0.002 2.6

4.

TRR 97 % 0.03 mg/kg TRR

2.6 %

chem2 chem3 TRR

90 % 0.03 mg/kg 98 % 0.03 mg/kg chemx

TRR 89 % 0.02 mg/kg 68 % 0.02 mg/kg 3

chem2 2 TRR 8.9 % chem3

11 1 TRR 19 % 3.3 %

8

123

5.

chemx 1 2

chem2 chem3 11 chem3

chemx

6.

chemx 6.2.2.1-1 chemx chem2 5

1 2

6.2.2.1-1 chemx

III.

chemx

99.9 % TAR

0.1 %-0.2 % 0.14-0.18 mg/kg

0.008-0.021 mg/kg 0.002 mg/kg -0.008 mg/kg 0.027-

0.030 mg/kg

chemx TRR 13 %-89 % 0.002-0.15 mg/kg

2 TRR 6 %-25 % 0.002-0.032 mg/kg

1 TRR 1.1 %-11 % 0.002 mg/kg -0.015 mg/kg 11 TRR 1.5 %-19 % 0.002-

0.006 mg/kg chemx chem2 5

1 2

chem2 chem3 chemx chem2

chemx

chemx

chemx 1 2 chem2

chemx 7 chemx

chemx

chemx

8

124

6.3 GAP

chemx 6.3-1

6.3-1 chemx GAP

(g ai/10 a) (L/10 a) ( )

80% 2 20-25 1 -( 70 )

6.4

6.4.1

6.4.1/01 Xxxx X 2008,

XX-08-12

6.4.1/02 Xxxx X 2012,

XX-12-004

12 8147

30 6278

6.4.1/01 6.4.1/02

GLP 6.4.1/01 GLP 6.4.1/02

I.

20

chemix 60 % 2.5-3.0 g/10 a 1.5-

1.8 ai/10 a 25-30 L/10 a 2 20

11

24

chemix 80 % 2.0-3.0 g/10 a 1.6-2.4 g ai/10a

20-25 L/10 a 24 11 -12

chemx chemx 4.2.1

-20 °C 8

24 HPLC

II.

6.4-1 2

2 2

chemx

chemx <0.01 mg/kg

8

125

6 GAP 2 g ai/10 a 1 70

chemx chemx

chemx <0.01 mg/kg

6.4-1

( ) ( )

DAT ( )

1)

(mg/kg)(g ai/10 a) ( )

( ) ( ) H20 60 % 1.5 1

42

56

70

<0.01<0.01<0.01<0.01<0.01<0.01

( 61 ) ( ) H20 60 % 1.8 1

42

56

70

<0.01<0.01<0.01<0.01<0.01<0.01

( ) ( ) H24 80 % 2.0 1

506075

<0.01<0.01<0.01

( ) ( ) H24 80 % 2.4 1

425670

<0.01<0.01<0.01

( 61 )( ) H24 80 % 2.0 1 60 <0.01

( )( ) H24 80 % 1.6 1 70 <0.01

1) 2 2

( ) ( )

PHI( )

(mg/kg)2)

( )

1)

(kg ai/hL) (L/10 a) ( )chemx

B ( )

( ) ( )

H2620.0 %

2,000 0.0100

250250250

3

1 6.78 <0.013 4.00 <0.017 3.76 <0.01

240240250

21 0.55 <0.01

( ) ( )

H2620.0 %

2,000 0.0100

265265250

3

1 0.98 <0.013 0.70 <0.017 0.55 <0.01

200250250

21 0.02 <0.01

1) 2) chemx

8

126

2

( ) ( )

PHI( )

(mg/kg)2)

( )1)

(kg ai/hL) (L/10a) ( ) chemx Bchemx

B C

(90)

( )

H26

18.0% 400 0.045 0.5 L/1

()

4

1 3 7 14

0.500.100.070.02

0.130.220.100.02

0.630.320.170.04

<0.011<0.011<0.011<0.01110.0 % 2,000 0.005

300300300

3

()

( )

H26

18.0% 400 0.045 0.5 L/1

()

4

1 3 7 14

0.340.300.140.05

0.050.080.120.06

0.390.380.260.11

<0.011<0.011<0.011<0.01110.0 % 2,000 0.005

200200200

3

1) 2) chemx

3

( ) ( )

DAT( )

(mg/kg)3)

1)

(g ai/10a) ( ) ( )2)

chemxA

+A B

( ) ( )

H26

1.5 % 15.0 1

3

0

607590

<0.01<0.01<0.01

<0.013<0.013<0.013

<0.023<0.023<0.023

<0.013<0.013<0.013

607590

0.22<0.01<0.01

0.055<0.013<0.013

0.275<0.023<0.023

<0.013<0.013<0.013

12.0 % 5.0 2

45 60

30 45 607590

2.731.460.34

0.720.810.38

3.442.270.72

<0.013<0.013<0.01315 30

1) 2) 3) chemx

III.

GAP chemx chemx

<0.01 mg/kg

8

127

6.56.5.1

6.5.2

6.5.2

6.5/02 Xxxx X 2006, chemx residue in lactating dairy cattle.

XX-11865

OECD 505

GLP

chemx 3

28 8.1 mg/kg 23.5 mg/kg 81.7 mg/kg

8.1 mg/kg chemx chem2 chemx

0.004 mg/kg

0.005 mg/kg 0.004 mg/kg 0.12 mg/kg 0.096

mg/kg 0.10 mg/kg 0.076 mg/kg 81.7 mg/kg 0.73

mg/kg 0.52 mg/kg 0.1 mg/kg

4

0.01 mg/kg 8.1 mg/kg

chemx

0.004 mg/kg

I.

A.

1. chemx

NPD-9503-6466-T

98.5 %

CAS 16335-17-2

7

2.

8

128

30 -42

xxx.xx kg-xxx.xx kg

1 3

28 24

USPHS-NIH

20 °C -24 °C

45 %-65 %

16-20 /

12

B.

1.

1 8.1 mg/kg AM

2 23.5 mg/kg AM

3 81.7 mg/kg AM

4 AM

xx kg/

1 /

28

2.

28

18

3.

-10°C 159

chemx -12 °C 169

4.

RES-095-96 v.0

8

129

3/1 v/v

chemx chem2 7 HPLC

0.004 mg/kg 0.001 mg/kg

chemx chemx

6.5.2-1

6.5.2-1(mg/kg) (%) RSDr(%)

0.0030.52.0

55 5

809096

108.56.5

II.

6.4.1

6.5.2-2 6.5.2-3

8.1 mg/kg chemx chem2 chemx

0.004 mg/kg 6.5.2-4

0.005 mg/kg 0.004 mg/kg 0.12 mg/kg

0.096 mg/kg 0.10 mg/kg 0.076 mg/kg 81.7 mg/kg

0.73 mg/kg 0.52 mg/kg 0.1 mg/kg

4

6.5.2-2

(mg/kg) (%) (%) (mg/kg)

Xxx HR 80 80

Xxxx STMR 90 10

(mg/kg)

8

130

6.5.2-3

(mg/kg) (%) (%) (mg/kg)

Xxx HR 90 55

Xxxx STMR 90 25

(mg/kg)

6.5.2-4 chemx chem2 chemx

(mg/kg )* ** **

<0.004 [3] <0.004 [3] <0.004 [3] <0.004 [3] <0.004 [3] <0.004 [3] <0.004 [3]

8.1

<0.004 [3]

Av <0.004

<0.004 [3]

Av <0.004

<0.0040.0040.005Av <0.004

<0.004 [3]

Av <0.004

<0.004 [3]

Av <0.004

0.0840.0890.115Av 0.096

0.0950.0640.069Av 0.076

23.5

0.0080.0090.008Av 0.008

0.0060.0080.009Av 0.008

<0.0040.0040.006Av 0.004

<0.004 [2]0.007

Av 0.004

0.0050.0060.005Av 0.006

0.1990.2230.163Av 0.195

0.1360.2760.257Av 0.223

81.7

0.0150.0240.023Av 0.021

0.0130.0240.021Av 0.019

0.0060.0120.009Av 0.009

0.0440.0050.070Av 0.040

0.0180.0170.024Av 0.020

0.7660.4121.006Av 0.728

0.5220.4780.556Av 0.519

* 27 ** 14

III.

chemx

0.004 mg/kg

6.6

6.7

chemx 7.2 50% DT50 xx

xx 100

6.4.1

6.8

6.8.1

chemx log Pow 1

BCF 1

log10BCF 0.80 log 10Pow 0.52 1.9

8

131

9

6.8.2

chemx 80 %

PECtier1 7.9 × 10-5 g/L 7.6.7

6.8.3

chemx 7.5 × 10-7 mg/kg

PECtier1 BCF

7.9 × 10-5 g/L 1.9 5 7.5 × 10-7 mg/kg

6.9

6.9.1

chemx 6.2.1

chemx

chemx

chemx chemx

6.9.2

chemx 0.01 mg/kg

0.02 mg/

6.9.3

6.9.3.1 TMDI 1

chemx 17 19

chemx 1 6

65 TMDI ADI 0.24 mg/kg /

TMDI/ADI 0.02 0.04 0.01 0.02 % 6.9.3-1

8

132

6.9.3-1 chemx TMDI /day

(ppm) TMDI(1 6 )

TMDITMDI

(65 )

TMDI

0.02 2.3 1.6 2.5 1.7

2.3 1.6 2.5 1.7

ADI % 0.02 0.04 0.01 0.02TMDI

6.9.3.2 EDI 1

EDI

chemx

17 19 chemx 1 6

65 EDI ADI 0.24 mg/kg

/ EDI/ADI % 6.9.3-2

6.9.3-2 chemx EDI /day

(ppm) EDI(1 6 )

EMDIEDI

(65 )

EDI

ADI %

6.9.3.3 ESTI

chemx ARfD ESTI

ESTI

chemx

17 19 22

chemx 1 1 6 ESTI

ARfD ESTI/ARfD 100% 6.9.3-3

8

133

6.9.3-3 chemx ESTI /day

(1 ) (1 6 )

(ppm)

ESTI/ARfD

(%) (ppm)

ESTI/ARfD

(%)

6.9.4

chemx

desmethyl chemx 1 xxxxxxx 2 xxxxxx 6 xxyx 8 xxx

5 xxxx 10 33 % 45 %

chemx

chemx chemx

HPLC

mg/kg chemx

0.01 mg/kg

GAP chemx

0.01 mg/kg

0.02 mg/kg

chemx

1 TMDI ADI 0.24 mg/kg / 0.1 %

9

134

OECD 7 5

7.

7.1

7.1.1

chemx

7.1.2

7.1.2

7.1.2 Xxxx X 2006, The aerobic soil metabolism of 14C-chemx.

XX-14019

ISBN No. 90-5607-002-9 SETAC-Europe 1995

30 6278

xxxxx Laboratory GLP

2003 8 -2004 12

Speyer 2.2 14C-chemx

0.08 mg ai/kg 80 g ai/ha 4 19 °C-22 °C

225 pH 5.8 40 %

chem2-14C 2.2 % chem3-14C 13%

chem2-14C chem3-14C chemx DT50

51 54 DT90 175 181

93 %

desmethyl chemx TAR 29 %

chem2 chemx xxx

xxxxxxx 2 9.0 %TAR xxxx 10 5.0 %TAR chem3

3 3.4 %TAR

9

135

chem2-14C chem3-14C chemx 0

99 %TAR 98 %TAR 100 79 %TAR 70 %TAR 225 72 %TAR 50 %TAR

100 14 %TAR

15 %TAR 225 41 %TAR 33 %TAR

I.

A.

1. chemx

chem2 C-3 14C

4.92 GBq/mg 58.6 mCi/mmol

chem3 C-5 14C

5.34 GBq/mg 64.2 mCi/mmol

chem2 chem3

NPD-9307-5385-T

chem2 97 %

chem3 97 %

CAS 16335-17-2

7

2.

Speyer 2.2 5

7.1.2-1

pH OM% % % % %

CECmeg/100g gC/g

Speyer 2.2 5.8* 3.94** 82 13 5 55.2 9.7 316 (0 )316 (312 )

* 1 2.5** 1.72

B.

1.

chemx chem2 chem3 chemx 0.08 mg/kg

80 g ai/ha 4

60 g 40 %

9

136

1

0.08 mg/kg 2

19 °C -22 °C 100

4.4 mg/kg chemx

220 225

2.

0 312 Anderson & Domsch 1978

0 8 16 32 64 100 181 225

3.

2

a 0.5 % 65:35 V:V 80 mL 3

b 2 M 50:50 V:V 100 mL 1

10 100

20 1,500 rpm 10

b

14C LSC

LSC HPLC Spherisorb S5 ODS1, 25 cm 10 mm id

1 % 1.35 %

UV 254 nm

TLC GC-MS

chemx desmethyl chemx

1 x mg ai/kg x mg ai/kg x mg ai/kg

x mg ai/kg

9

137

II.

A.

7.1.2-2 Speyer 2.2 225 20 %TAR

0 8 16 32 64 100 181 225

chem2 14C chemx

Chemx 93 84 74 63 39 26 16 18

xxxxxxx ( 2) 2.2 2.5 5.2 5.7 9.1 9.0 8.7 7.5

desmethyl chemx ( 1) 1.0 3.7 11 20 21 28 23 19

xxxx ( 10) <0.2 0.4 0.7 1.4 1.6 2.6 5.0 3.2

* <2.7 2.2 <1.7 <3.9 5.8 10 <6.4 8.7

** ns 1.0 1.0 2.0 3.0 4.0 7.0 9.0

5.5 6.7 <2.2 5.1 17 14 28 41

CO2 ns 0.8 0.8 0.9 1.2 1.6 1.9 2.2

105 101 93 101 97 95 94 110

chem3 14C chemx

Chemx 94 89 79 60 43 24 25 23

3 0.9 0.6 0.7 3.0 1.2 3.4 0.9 1.8

desmethyl chemx ( 1) 0.9 4.6 10 29 26 29 18 19

* <2.6 <1.8 <1.6 <4.2 <5.4 <8.7 <2.7 <3.5

** ns 1.0 1.0 2.0 3.0 5.0 6.0 8.0

3.2 2.7 2.4 4.5 18 15 38 33

CO2 ns 2.6 3.2 4.0 5.8 8.1 12 13

101 100 98 105 102 93 102 101ns* 4 2 %-4 %TAR** 2 M

B.

Speyer 2.2 93 % 93 %-115 %

C.

chem2-14C chem3-14C chemx 0

99 %TAR 98 %TAR 100 79 %TAR 70 % 225 72 %TAR 50 %TAR

100 14 %TAR

15 %TAR 225 41 %TAR 33 %TAR

9

138

D.

chem2-14C chem3-14C chemx 14CO2

100 1.6 %TAR 8.1 %TAR 225 2.2 %TAR 13 %TAR

E.

chem2-14C chem3-14C chemx chemx

100 26 %TAR 24 %TAR 225 18 %TAR 23 %TAR

chem2-14C chem3-14C chemx 0 -100

DT50 51 54 DT90 170 181

2 M 50:50

chemx

lnC = -Kt + lnC0

K =

C = t 0 %

C0 = t0 %

t =

7.1.2-3r2 K (x10-4) DT50 DT90

chem2-14C chemxchem3-14C chemx

66

0.9960.988

135.5127.4

5154

170181

desmethyl chemx 1 desmethyl chemx

chem2-14C chem3-14C chemx 100 28 %TAR 29 %TAR

225 19 %TAR chem2-14C chemx xxxxxxx

2 100 9 %TAR 225 7.5 %TAR

xxxx 10 5 %TAR chem3-14C chemx

3 100 3.4 %TAR 225 1.8 %TAR

4 4 %TAR

III.

chemx Speyer 2.2 desmethyl chemx

29 %TAR chem2 chemx xxx

9

139

xxxxxxx 2 9.0 %TAR xxxx 10 5.0 %TAR

chem3 3 3.4 %TAR

DT50 DT90 51 -54 170 -181

7.1.2-1

7.1.2-1 chemx

7.1.3

chemx DT50 51 -54 100

7.1.2

7.2

7.2 Xxxx X 2010,

XX-10-05

30 6278

I.

1. chemx 80 %

NPD-9403-5772-F

2. pH 6.0 KCl 8.5 %

pH 5.0 KCl 12.0 %

3. 2.0 g ai/10a 2.5 g/10a 1

22 4 20

4. - 180 8

8 5cm 10cm

5.

chemx chemx chemx chemx 7

chemx 4.3

chemx chemx

9

140

7.2-1 chemx 80%mg/kg

chemx chmex

0 0.0140 0.0005 0.0145

7 0.0120 0.0010 0.0130

14 0.0108 0.0014 0.0122

30 0.0082 0.0030 0.0112

60 0.0072 0.0036 0.0108

90 0.0046 0.0050 0.0096

120 0.0026 0.0046 0.0072

180 0.0018 0.0036 0.0054

0 0.0106 0.0005 0.0111

7 0.0110 0.0012 0.0122

14 0.0080 0.0036 0.0116

30 0.0088 0.0016 0.0104

60 0.0054 0.0030 0.0084

90 0.0032 0.0044 0.0076

120 0.0018 0.0040 0.0058

180 0.0014 0.0030 0.0044

7.2-2 chemx

(mg/kg) ( ) (%) (%)

chemx

0.0010 200

90 102

desmethyl chemx 1 86 95

xxxxxxx 2 85 92

chemx 82 100

desmethyl chemx 1 90 103

xxxxxxx 2 88 99

II.

7.2.1 chemx 0 0.014 mg/kg

7 0.011 mg/kg

0.005 mg/kg 0.004 mg/kg

DT50 SFO Single First-Order Kinetics Model

chemx 56 55 chemx 141

124

-20 °C chemx desmethyl chemx 1 xxxxxxx 2

9

141

7 7.2-2

190 chemx >70 %

III.

chemx 0.011 mg/kg-0.014 mg/kg

SFO DT50 55 -56

0.005 mg/kg

7.3

7.3.1 chemx

7.3/01 Xxxx X 2005, 14C-chemx, adsorption and desorption.

XX-13701

OECD106

xxxxx Laboratory GLP

2004 8 -2004 11

2 3 pH 5.3- pH 7.9

chemx KadsFoc

5.3-89 33 chemx KdesFoc

= 400 chemx

87 %-99 %

I.

A.

1. chemx

chem2 C-3 14C

2.40 GBq/mg 28.6 mCi/mmol

NPD-9307-5385-T

98 %

CAS 16335-17-2

7

9

142

2.

5 3 2

3 0-15 cm

x 7.3.1-1

Soil Survey of England and Wales SSEW

7.3.1-1Elder Hanford Evesham Sandiacre Wick

USA USA UK UK UK

/

(%) 70 82 35 42 67

(%) 16 15 34 38 21

(%) 14 3 31 20 12

OC(%)* 0.9 0.3 1.2 4.3 0.8

CEC meq/100g 13.5 6.4 18.9 21.1 14.2

pH# 6.8 7.3 7.9 7.1 5.3

*OM/1.72=OC # 1:2.5

B.

1.

pH x.x chem2 14C chemx

0.04 0.08 1.05 4.7 μg/mL 0.01 M

0.1 % v/v

2:1 10 % 10 mL

5 g 25 °C 24 x rpm

x

0.01 M 20 mL 25 °C 24

15 mL 2 chemx

2.

LSC 4.7 μg/mL

HPLC TLC GC-MS

chemx 1 x mg ai/kg x mg ai/kg

chemx 1 x mg ai/kg x mg ai/kg

9

143

II.

A.

87 %-99 %

101 %-114 %

B.

24 chemx

xxxxxxx 2 0.1 % Hanford

0.6 % Sandiacre/Elder 0.8% Evesham 8 % Wick

1 %

C.

Freundlich

Freundlich 1

Freundlich

KadsF 5 0.076-0.71 chemx

KadsFoc 5.3-89 33

Freundlich KdesF 1.9-4.7 KdesFoc 66-630

400

7.3.1-2 25 chemx

OC%1/nads KadsF r KadsFoc 1/ndes KdesF r KdesFoc

Elder 0.9 x.xxx 0.359 0.985 40 x.xxx 4.42 0.986 490

Hanford 0.3 x.xxx 0.076 0.895 25 x.xxx 1.90 0.926 630

Evesham 1.2 x.xxx 0.079 0.982 6.6 x.xxx 2.59 0.996 220

Sandiacre / 4.3 x.xxx 0.230 0.937 5.3 x.xxx 2.82 0.940 66

Wick 0.8 x.xxx 0.710 0.991 89 x.xxx 4.69 0.997 590

III.

KadsFoc 5.3-89 33

9

144

7.3.2 desmethyl chemx 1

7.3/02 Xxxx X 2006, Soil adsorption/desorption of 14C-desmethyl chemx (metabolite

1), by the batch equilibrium method.

XX-14410

OECD106

xxxxx Laboratory GLP

2005 10

2 2

24 xxxxxxx 2 pH 5.5-pH 8.1

4 14C-desmethyl chemx KadsF 0.326-0.732

KadsFoc 36.7-116 KdesF 2.20-5.25

KdesFoc 255-820 486

17 % Wick - 32 % Evesham

23 % Evesham - 40 % Wick

KdesFoc KadsFoc 100±3 %

I.

7.3.1

7.4

7.4 Xxxx X 2005, The hydrolysis of 14C-chemx.

XX-13700

BBA IV 4-3 1990 2

30 6278

xxxxx Laboratory GLP

2005 4 -6

25 °C 40 °C pH 4 pH 5 pH 7 pH 9

chemx chemx pH 4

0.5 mg ai/L pH 5 7 9 3 mg ai/L 0.1 %

95 %-105 %

9

145

xxxxxxx 2 3 xxxxxxx 2

25°C 30

pH 4 93 % pH 5 34 % pH 7 13 % pH 9 15 %

chemx pH 4 7 pH 5 48 pH 7 168 pH 9

156

I.

A.

1. chemx

chem2 chem3 1 1

chem2 C-3 14C

4.90 GBq/mg 58.5mCi/mmol

chem3 C-5 14C

2.55 GBq/mg 30.5 mCi/mmol

chem2 chem3

C-1872.1

chem2 98.9 %

chem3 99.4 %

CAS 16335-17-2

7

2.

pH 4 pH 5 pH 7

pH 9 HPLC

0.1 M

B.

1.

25 °C pH 4 pH 5 pH 7

pH 9 chem2 chem3 chemx

40 °C pH chem2 chemx

x mL 100 mL

chemx pH 4 0.5 mg ai/L pH 5 pH 7 pH 9

3 mg ai/L 0.1 % x mL 0

9

146

x xx xxx xn 3014C LSC HPLC x 2 % UV xx nm

chemx chemx

1 x μg ai/L x μg ai/L chemx 1

xx μg ai/L xx μg ai/L

II.

A.

95 %-105 %

B.

chemx pH 4-pH 9 pH

40 °C pH 4 25 °C

TAR 0 97 % 30 5 % pH

4 40 °C 0 98 %TAR 14 0.2 %TAR

1 chemx 25 °C pH 4 7 pH 5 48 pH 7

168 pH 9 156

7.4-1 chemx25 ºC 40 ºC

pH ( ) r2 ( ) r2

45 7 9

7.048

168156

1.0000.9970.9250.790

0.836.01615

0.9980.9980.9960.998

7.4-2 pH 4 chemx %TAR

0 t1 t2 t3 t4 t5 t6 tn

chem2 14C-chemx

Chemx

desmethyl chemx ( 1)

xxxxxxx ( 2)

n

chem3 14C-chemx

Chemx

desmethyl chemx ( 1)

3

9

147

7.4-3 pH 5 chemx %TAR

7.4-2

chem2 14C-chemx xxxxxxx

2 25 °C 30 pH 4 93 %TAR pH 5

34 %TAR pH 7 13 %TAR pH 9 15 %TAR 40 ºC

chem3 14C-chemx 25 ºC 30

1 3 pH 4 92 %TAR pH 5 31 %TAR pH 7

12 %TAR pH 9 15 %TAR 1 %TAR

III.

25 °C pH 4 pH 5 pH 7 pH 9

chemx 7 48 168 156 chemx

xxxxxxx 2 3

7.5

7.5.1

7.5/01 Xxxx X 2006, Aqueous photolysis studies of chemx.

XX-12898

US EPA FIFRA 161-2

30 6278

xxxxx Laboratory GLP

2006 2 -4

144 25 ºC pH 7

12.64 mg/L 17.98 mg/L chemx chemx

12 pH 7

DT50 chem2 14C-chemx 36 3.2 chem3 14C-chemx 33

2.8 chem2 96.8 % 98.2 % chem3

96.5 % 104.7 %

chem2 14C-chemx TAR 6.2 % chem314C-chemx 1.3 % 1 %TAR

6 3 10 %TAR 7

9

148

chem2 14C-chemx 3 chem3 14C-chemx 4

10 %TAR 144 8.7 %TAR

I.

A.

1. chemx

chem2 C-3 14C

4.90 GBq/mg 58.5mCi/mmol

chem3 C-5 14C

2.55 GBq/mg 30.5 mCi/mmol

chem2 chem3

C-1872.1

chem2 98.9 %

chem3 99.4 %

CAS 16335-17-2

7

2.

HPLC pH 7

0.1 M

B.

1.

2 12.64 mg/L 17.98 mg/L

0.05 M <1 %

60 % 290 nm

7.5 cm 10.5 cm

25 1 ºC

25 ºC

xx.x W/m2 300 nm-400 nm 300 nm-750 nm

CO2

CO2 0.01N

9

149

144 chemx

12 x mL x

4 °C 2

2.

LSC

HPLC/RAD

chemx 5 %

HPLC X Y x %/y % chemx 1

LOD x μg ai/L x μg ai/L chemx 1 LOQ

x μg ai/L x μg ai/L

II.

A.

TAR chem2 14C-chemx 96.8 %

98.2 % chem3 14C-chemx 96.5 % 104.7 %

B.

CO2 chem2 6.2 %TAR chem3 1.3 %TAR

1 %TAR chemx

7.5-1

7.5-1 chemx1

(h-1)DT50

( )DT50

(12 / ) r2

chem2 14C-chemx 0.01907 36.3 3.2 0.9969

chem3 14C-chemx 0.02101 33.0 2.8 0.9992

7.5-2 chemx14C (%) ( ) mg/kg

3 chem3 28.31 144 4.99

xxxx ( 9) chem3 20.95 144 3.69

N-hydroxy ( 12) chem3 14.98 48 2.69

zzzz ( 11) chem3 5.09 96 0.91

xxx ( 7) chem3 8.96 144 1.58

xxxyx ( 10) chem2 15.62 144 1.74

xxxx ( 5) chem2 14.59 96 1.69

8 chem2 28.34 96 3.28

9

150

6 3 10 %TAR 7

chem2 14C-chemx 3 chem3 14C-chemx 4

10 %TAR 144 8.74 %TAR

7.5-1

7.5-1 chemx

7.5-3 chemx TAR

0 t1 t2 t3 t4 t5 t6 144

chem2 14C-chemx

Chemx

xxxyx 10

xyxx 5

8

Chem3 14C-chemx

Chemx

3

xxxx 9

N- 12

xx 7

III.

chemx

DT50 3 12 13

6 10 %TAR 7.5-2

22 -346

9

151

chemx

7.5.2

7.5/02 Xxxx X 2006, Aqueous photolysis studies of chemx.

7.5/01 DT50

7.5.3

7.5.1

7.6

7.6.1

chemx

7.2

7.6.2

7.6.1

7.6.3

7.6.1

7.6.4

7.6.1

7.6.5

chemix

7.6.1

9

152

7.6.6

chemx 80 % PECtier1

7.6.6-1

PECtier1 7.9 × 10-5 g/L

7.6.6-1 80 % PECtier1

80 %

2.5 g/10 a

20 g/ha

0.1 %

1

PEC

7.6.7

chemx 80% PECtier1

7.6.7-1

PECtier1 4.4 × 10-4 g/L

7.6.7-1 chemx PECtier1

80 %

2.5 g/10 a

1

20 g/ha

0.2 %

1

7.77.7.1

7.7.1.1

desmethyl chemx 1 29 %TAR

0.005 mg/kg

9

153

chemx

7.7.1.2

chemx chemx 1

7.7.2

desmethyl chemx 1 29 %TAR

chemx xxx xxxxxxx 2 9.0 %TAR

xxxx 10 5.0 %TAR 3 3.4 %TAR

chemx 0.011 mg/kg -0.014 mg/kg

0.005 mg/kg

chemx chemx DT50

55 -56

pH 4 pH 5 pH 7 pH 9 chemx DT50 7 48

168 156 xxxxxxx 2 3

pH 7 pH x.x chemx DT50

xx xx 6

3 x n

chemx PECtier1

PECtier1 7.9 × 10-5 g/L 4.4 × 10-4 g/L

xx g/L 0.63 mg/L

10

154

OECD 7 3

8.8.1

8.1.1

8.1.1 Xxxx X 2008, chemx technical - the acute oral toxicity of chemx with the

northern bobwhite.

XXX-11111

US EPA OPPTS 850.2100

xxxxx Laboratory GLP

2

chemx 0 292 486 810 1,350 2,250 mg-ai/kg-b.w. 6 mL/kg-b.w.

14

chmix LD50 720 mg-ai/kg-b.w.

I.

A.

1. chemx

NPD-9209-4523-T

98.9 %

CAS 16335-17-2

2.

3.

10

155

Colinus virginianus

34

170 g-250 g

xxx Laboratory

17

80 50 cm 25 cm

24 °C -26 °C

15 %-35 %

8

B. :

1. 2008 2 15 -2 29

2.

2 chemx 0 29 486

810 1,350 2,250 mg-ai/kg-b.w. 6 mL/kg-b.w.

2

3.

14

0 -3 4 -7 8

-14

II.

III.

chemx LD50 720 mg-ai/kg-b.w.

8.1.2 1

2 0 292 486 810

1,350 2,250 mg ai/kg-b.w. LD50 720 mg-ai/kg-b.w.

10

156

LD50 720 mg-ai/kg-b.w.

LD50Adj. xx mg-ai/kg-b.w. xx mg-ai/day kg-b.w.

chemx

8.28.2.1

8.2.1.1

8.2.1.1 Xxxx X 2006, chemx

XXX-0011

OECD 203

GLP

100 mg/L

xx mg/L

96 LC50 >xx mg/L

I.

A.

1. chemx

NPD-9209-4523-T

98.9 %

CAS 16335-17-2

2.

3.

Cyprinus carpio

4.5 cm (4.2 cm-5.8 cm)

1.10 g (0.85 g-1.20 g)

10

157

17

(L30 cm W30 cm H30 cm) 20 L (

22.5 cm)

10

21.9 °C -22.1 °C

16 8 xxx-yyy lx

24

6.6 mg/L -8.2 mg/L 77 %-96 %

pH 7.7-7.8

B. :

1. 2006 2 15 -2 19

2.

1 10 100 mg/L

chemx 96

3.

24

48 pH

24

II.

xx mg/L xx %

96 LC50 xx mg/L

2005 12 xx ± x mg/L n=xx

III.

chemx 96 LC50 >xx mg/L

8.2.1.2

8.2.1.2 Xxxx X 2006, chemx

XXX-0020

OECD305

GLP

10

158

10 g/L 100 g/L

9.7 g/L 94.5 g/L

0.01 mg/kg 3

0.08 mg/kg 1

0.01 mg/kg BCFss 0.8

I.

A.

8.2.1.1

9

B. :

1. 2006 2 9 -2 19

2.

1 50 10 g/L 100 g/L

chemx 7 3

3.

1 2 3

5 7 1 3 1 4

1 0 1 2 3 5 7 1

3 pH

II.

A.

B.

9.7 g/L 94.5 g/L

0.01 mg/kg 3

3 -7 0.08 mg/kg

BCFss 1 0.8

C.

1 0.01 mg/kg

10

159

III.

chemx BCFss 0.8

8.2.28.2.2.1

8.2.2.1 Xxxx X 2006, chemx

XXX-0021

OECD 202

GLP

0 5.0 10 20 40 80 mg/L

4.0 8.2 16 32 xx mg/L

48 EC50 xx mg/L 95 % xx mg/L -xx mg/L

I.

A.

1. chemx

NPD-9209-4523-T

98.9 %

CAS 16335-17-2

2. Elendt M4

3.

Daphnia magna

24

100 mL 50 m L ( 4.0 cm)

5 4

20.0 °C -20.5 °C

10

160

16 8 xxx-yyy lx

8.2 mg/L -8.5 mg/L

pH 7.5-7.6

B. :

1. 2006 3 28 -3 30

2.

24 1 20 5 4

0 5.0 10 20 40 xx mg/L chemx 48

3.

24

pH

4.

Fisher EC50

II.

4.0 8.2 16 32 xx mg/L 80 %-xx %

8.2.2.1-1

48 EC50 xx mg/L

2006 2 xx±x mg/L n=xx

8.2.2.1-1 chemx

Chemx

(mg/L)24 48

I II III IV I II III IV

0.0 0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5

4.0 0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5

8.2 0/5 0/5 0/5 0/5 0/5 0/5 0/5 0/5

16a 2/5 1/5 2/5 1/5 3/5 2/5 3/5 3/5

32a 3/5 3/5 3/5 4/5 5/5 4/5 3/5 4/5

xxa 5/5 4/5 3/5 5./5 5/5 5/5 4/5 5/5I-IV 4 a 0.0 mg/L p 0.05

10

161

III.

48 EC50 xx mg/L 95 % xx mg/L-xx mg/L

8.2.38.2.3.1

8.2.3.1 Xxxx X 2006, chemx

XXX-0031

OECD 201

GLP

Raphidocelis subcapitata

0 2.5 5.0 10 20 40 80 g/L 72

1.6 3.3 6.8 12 25 xx g/L

ErC50 (0-72 h) NOECr xx g/L 95 %

xx g/L -xx g/L 6.8 g/L

I.

A.

1. chemx

NPD-9209-4523-T

98.9 %

CAS 16335-17-2

2. OECD

3.

Raphidocelis subcapitata ATCC 22662

1 104 cells/mL

250 mL 100 mL

22.5 °C -23.5 °C

10

162

xxx lx -xxx lx

pH 7.5-7.9

100 rpm

B. :

1. 2006 7 2 -7 10

2.

1 3 6 0 2.5 5.0 10 20 40 80 g/L chemx

72

3.

24

pH

4.

Dunnett EC50

II.

1.6 3.3 6.8 12 25 xx g/L 60 %-xx %

72 24

12.5 % 0 72 3.0 %

72 8.2.3.1-1

48 EC50 xx mg/L 2006 6

xx±x mg/L n=xx

8.2.3.1-1 72 %Chemx ( g/L)

0

1.6 8 3

3.3 5 2

6.8 10 3

12 40 a 10 a

25 xx a xx a

xx xx a xx a

a 0.0 mg/L p 0.05

10

163

III.

Raphidocelis subcapitata chemx

ErC50 (0-72h) = xx g/L 95 % xx g/L-xx g/L

NOECr = 6.8 g/L

8.2.4

( ) (hr)

Cyprinus carpio 21.9-22.1 96 LC50 >xx mg ai/L

Daphnia magna 20.0-20.5 48 EC50 xx mg ai/L

Raphidocelis subcapitata 22.5-23.5 72 ErC50 (0-72h) xx g ai/L

96h LC50

48h LC50

Raphidocelis subcapitata 72h ErC50

AECf LC50/10

AECd EC50/10

AECa ErC50/10

7.9

× 10-5 chemx

8.38.3.1

8.3.1.1

8.3.1.1 Xxxx X 2005, chemx

XXX-0051

OECD 214

GLP

10

164

100 g/

LD50 >100 g/

I.

A.

1. chemx

NPD-9209-4523-T

98.9 %

CAS 16335-17-2

2.

3.

Apis mellifera

50 %

(L10 cm W8.5 cm H5.5 cm)

23.0 °C-25.0 °C

38 %-70 %

B. :

1. 2005 2 14 -2 16

2.

1 10 3 1 30

chemx 3

3.

4 24 48

10

165

II.

III.

chemx 48 LD50 >100 g/

8.3.1.2

8.3.1.1

8.3.1.3

8.3.1.1

8.3.1.4

8.3.1.1

8.3.1.5

8.3.1.1

8.3.1.6

6.4

8.3.2

Apis mellifera1 10

3 (98.9 %)LD50 (48h) >

Apis mellifera1 10

3 (98.9 %)LD50 (48h)

Apis mellifera1 10

5 (98.9 %)LDD50 (10d) /

Apis mellifera1 12

3 (98.9 %)LD50 (72h)

11

166

I.

1.4

1.5

6.1 GHS

6.2 GHS

6.3 GHS

6.4 GHS

6.5 GHS

6.6 GHS

1.

1.4

(%)*

chemx

100.0

* % %

1.5

6.

6.1 GHS

7 chemx >2000mg/kg >300 2000mg/kg

GHS

6.1

11

167

6.1 GHS

(%) (ATE )GHS

chemx80.0 LD50

>300 2000mg/kg

GLP

4 (500)

GHS 3.1.3.6

= 100÷(80.0/500+15.0/2500)= 602

4 (>3002000mg/kgbw)

1 xxxx

15.0 LD 50>2000 mg/kg

1

GLP

(2500)

2 xxxx

3.5 LD 50>2000 mg/kg

GLP)

3 xxxx

0.6 * -

4 xxxx

0.9 * -

100

3 41.0%3 4

LD50 602 mgkg/ 4 >300 2000 mg/kg GHS 4

6.2 GHSGHS 6.1

6.3 GHSGHS 6.1

6.4 GHS7 chemx

GHS6.4

11

168

6.4 GHS

(%)

GHS

chemx80.0 3

24 48 72/

0,x,0 0,0,xGLP

GHS 3.2.3.3 ( 3.2.3)

11 5%

1

21 <5 1%

2 10%

2

1 xxxx

15.0 324 48 72

/0,0,0 0,0,0

GLP

2 xxxx

3.5 3 214

GLP

2

3 xxxx

0.6 -

4 xxxx

0.9 -

100

GHS3.2.3.3 3.2.3

pH 2 11 GHS3.2.3.3 3.2.3 GHS3.2.3.3 3.2.4)

chemx 1 3 41.0%

2 22 1 <5 1% 2

10% GHS

6.5 GHS7 chemx

GHS6.5

11

169

6.5 GHS

(%)

GHS

chemx80.0 1 21

GLP

GHS 3.3.3.3 ( 3.3.3)

11 13%

1

21 1

<3 1% 210%

2

1 xxxx

15.0 324 48

<2 72

GLP2

xxxx3.5 3 2

24 48 72 >1

7

GLP

2

3 xxxx

0.6 -

4 xxxx

0.9 -

100

GHS3.3.3.3 3.3.3

pH 2 11 GHS3.3.3.3 3.3.3 GHS3.3.3.3 3.3.4)

chemx 1 3 41.0%

2 22 1 <3 1% 2

10% GHS

6.6 GHSGHS

6.6

11

170

6.6 GHS

(%)GHS

chemx80.0 maximization

GLP

GHS 3.4.3.3 ( 3.4.5)

11 1.0

1 xxxx

15.0 LLNA:DASI = 1.2

GLP2

xxxx3.5 LLNA:BrdU-ELISA

SI = 1.4GLP

3 xxxx

0.6 -

4 xxxx

0.9 -

100

3 41.0%

3 4GHS 1 1

1.0 % GHS

11

171

II.

chemx

1.2

1.8

1.

1.2

1.8

pH

1.10

*

g/kg

g/kg

* IUPAC

11

172

1.11

(g/kg)SD

Lot.123

chemix

3SD 3SD

1.12

(g/kg)

Lot.123

PCDDs 2,3,7,8-TeCDD

1.13

(g/kg)

Lot.0401 Lot.0503 Lot.0604

chemix

11

173

4.4.14.1.2

HPLC-UV

g/kg % g/kgRSDr %

n=5)2 1-0.5logC

×0.67

ABC0.999

0.110 g/kg

0.5 991.2 0.5 3.7

5 100

DEF0.999

0.110 g/kg

0.5 1013.4 0.6 3.2

5 102

5 .9

12

174

I.

chemx xxxx

xxxx

* xxxx chemx

chemx

xxxx chemx80 % OEC 2222

xxxx

* xxxx xxxx

xxxx

MRL

MRL 0.01 mg/kg

12

175

II.

*

Chemx

1 desmethyl chemx1

2 xxxxxxx2

3 3

* IUPAC

III.

chemx

A P S W chemx S W L

P S W

P S W desmethyl chemx xxxxxxx 3

A P S W L

13

176

1

xx xx xx

xxxxx

chemx

13

177

13

178

2

xx xx xx

xxxxx

chemx

chemx

UVIR

NMRMS

n-

13

179

90

9021

in vitroin vitro

in vitroDNA in vivo

28

13

180