Group C-7

化学構造　(Chemical Structure)

● m-Chloroaniline （m-クロロアニリン）　(3-Chloroaniline)
　　 　　CAS: 108-42-9　　Industry　　 MW: 127.57

AM	Sal./E. coli	Max ( 2.5 mg/plate, ±S9)	□	1)
CA	CHL/IU	Max ( 0.5 mg/ml, -S9), 6-18h; Poly	△	2)

1) Ishidate MJr. (Ed.); Data Book of Mutagenicity Tests in Bacteria, LIC/Tokyo, Japan (1991) (Tables in English)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test i In Vitro,, LIC, Tokyo (1998） (Tables in English)

● o-Chloroaniline （o-クロロアニリン） (2-Chloroaniline)
　　 　 95-51-2 　　Industry　　 127.57

AM	Sal./E. coli	Max ( 1.0 mg/plate, ±S9)	□	1)
CA	CHL/IU	Min ( 0.75 mg/ml, +S9); D20= 1.0; TR= 17 Poly (0.5 mg/ml, +S9), 6-18h	○w △	2, 14)
AM	Sal.	Max (0.25 mg/plate, ±S9)	□	3)
AM	Sal.	Max ( 1 mg/plate, ±S9)	□	4, 5,, 6)
AM	E. coli	Max ( 1 mg/plate, ±S9)	□	7)
BM	A. nidulans	Min ( 0.2 mg/plate, -S9)	○	8)
MLA	L5178Y	Max (?), ±S9)	□	9)
SM	V79	Min ( 0.6 μg/ml, -S9)	○	10)
DNA	E. coli	Min ( 0.02 mg/plate, ±S9)	○	7)
UDS	Rat hepatocytes	Max (0.127 mg/ml, ±S9)	□	11)
MY	S. cerevisiae	Max ( 0.2%, ±S9)	□	12)
MNv	Mice	Min ( 1g/kg)	○w	13)

1) Ishidate MJr. (Ed.); Data Book of Mutagenicity Tests in Bacteria, LIC/Tokyo, Japan (1991) (Tables in English)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro,, LIC, Tokyo (1998） (Tables in English)
3) Rozenkranz HS. & Poivier LA.,  J. Natl Cancer Inst., 62, 873-892 (1979)
4) Garner RC & Nutman CA., Mutation Res., 44, 9-19 (1977)
5) Thompson Ch.Z., et al., Environ. Mutagen. 5, 803-811 (1983)
6) Zeiger E et al., Environ. Mutagen, Suppl 9, 1-110 (1987)
7) Rozenkranz HS & Leifer Z, Mutagens, 6, 109-147 (1980)
8) Prasad I, Canad. J. Microbiol., 16, 369-372 (1970)
9) McGregor D. et al., Environ. Mutagen., 6, 545-557 (1984)
10) Kuroda Y, Basic Life Sci., 39, 359-373 (1986)
11) Yoshimi N., et al., Mutation Res., 206, 183-191 (1988)
12) Simmon VF, Nat.l Cancer Inst., 62, 901-909 (1979)
13) Herbold BA, Bayer Bericht, Nr. 177715, 43 Zeiten (1989)
14) Ishidate MJr., et al., Mutation Res., 95, 151-213 (1988)

● p-Chloroaniline （p-クロロアニリン） (4-Chloroaniline; 4-クロロベンゼンアミン）
　　 　 106-47-8　　Industry　　127.57

AM	Sal./E. coli	Max ( 2.5 mg/plate, ±S9)	□	1)
AM	Sal.	Max ( 2.0 mg/plate, ±S9)	□	3)
AM	Sal.	Min ( 5 mg/plate, +S9)	○	4)
AM	Sal.	Max ( 1 mg/plate, ±S9)	□	5)
AM	Sal.	Min ( 2 mg/plate, +S9)	○	6)
AM	E. coli	Max ( 2 mg/plate, +S9)	□	4, 5)
MLA	L5178Y	Max ( 0.5 mg/ml, ±S9)	□	7)
MLA	L5178Y	Min ( 0.4 mg/ml, -S9)	○w	8)
YM	S. cerevisiae	Max ( 2 mg/ml, ±S9)	□	9)
CA	CHO	Min ( 1 mg/ml, +S9)	○	10)
CA	CHL/IU	Min ( 0.4 mg/ml, +S9); D20= 0.38 mg/ml; TR= 33 Poly ( 0.5 mg/ml, -S9), 6-18h	○	2)
SCE	CHO	Min ( 0.5 mg/ml, ±S9);	○	10, 11)
UM	Sal.	Max ( 0.1 mg/ml, ±S9)	□	12)
UDS	Rat hepatocytes	Min ( 0.05 mg/ml)	○	13)
CT	C3H/10T1/2	Min ( 0.1 mg/ml)	○	14)
CT	Balb/C3T3	Max (?)	□	15)
SMv	Drosophila	(Spot-test) Min ( 1mg/ml)	○	16)
MNv	Mice, BM	Max ( 0.18 g/kg), or	□	17)

1) Ishidate MJr. (Ed.); Data Book of Mutagenicity Tests in Bacteria, LIC/Tokyo, Japan (1991) (Tables in English)
2) Sofuni T. (Ed.): Data Book of Chromosomeal Aberration Test in vitro, LIC, Tokyo (1998） (Tables in English)
3) Gilbert P et al., Arch. Environ. Contam. Toxicol, 9, 533-541 (1980)
4) Dunkel VC.,et al., Environ. Mutagen., 7 (Suppl.  5, 1-248 (1985)
5) Thompson  CZ.,  et al, Environ. Mutagen., 5, 803-811 (1983)
6) Zeiger E., Environ. Mol. Mutagen., 16 (Suppl. 18) 32-54 (1990)
7) Caspary WJ., et al., Environ. Mol. Mutagen., 12 (Suppl. 13),  195-229 (1988)
8) Myhr BC & Caspary WJ, Environ. Mol. Mutagen., 12 (Suppl. 13),  103-194 (1988)
9) Simmon VF, J. Natl Cancer Inst., 62, 901-909 (1979)
10) Anderson BE., et al, Environ. Mol. Mutagen., 16 (Suppl. 18),  55-138 (1990)
11) US-NTP, NTP Tech. Rep. No. 351, Dept. of Health and Human Services (1989)
12) Ono Y., et al., Water Sci. Technol., 26, 61-69 (1992)
13) Williams GM., et al, Mutation Res., 97, 359-370 (1982)
14) Dunkel VC., et al., Environ. Mol. Mutagen., 12, 21-31 (1988)
15) US-NTP, NTP Tech. Bull., No.9 (1983)
16) Graf U., et al Environ. Mol. Mutagen., 16, 225-237 (1990)
17) TLL (1986)(GDCh BUA) (?)

【Note】　Cited from CICADs Documents, 48, 2003)

In vitro genotoxicity     The results of the many Salmonella mutagenicity tests were inconsistent. However, weak mutagenic activity was repeatedly shown in the presence of S9, presumably due to optimized test conditions. Single tests demonstrated the absence of mutagenic activity in the umu-test or in tests with Escherichia coli and the absence of mitotic recombination in Saccharomyces cerevisiae. PCA induced DNA damage in the Pol A test and gene mutations in Aspergillus nidulans. However, several mouse lymphoma assays uniformly found mutagenic activity of PCA in both the presence and absence of metabolic activation. In contrast, test results for the induction of chromosomal aberrations and sister chromatid exchange in Chinese hamster ovary cells as well as for the induction of DNA repair in primary rat hepatocytes again were conflicting for different laboratories. Overall, the screening tests indicate a possibility of mutagenicity.     PCA (14.5 and 19.0 μg/52 000 cells) was evaluated as positive in a cell transformation assay in Rauscher leukaemia virus-infected rat embryo cells measuring acquisition of attachment independence (Traul et al., 1981). Conflicting test results have been reported by one working group on the transforming activity of PCA in Syrian hamster embryo cells in identical test concentrations ranging from 0.01 to 100 μg/ml. In the first detailed publication of test results, no transformed colonies were identified at all (Pienta et al., 1977); in the later publication, however, test results were summarized as positive in the entire concentration range tested (Pienta & Kawalek, 1981). In an interlaboratory evaluation, both laboratories reported PCA as having transforming activity in the C3H/10T- cell transformation assay in non-cytotoxic concentrations ranging from 0.8 to 100 μg/ml (Dunkel et al., 1988). In vivo genotoxicity     In a wing somatic mutation and recombination test in Drosophila melanogaster, exposure was by 6-h feeding of 7.84 mmol PCA/litre. PCA was genotoxic in both repair-proficient and repair-defective larvae of the mei-9 cross, which indicates a potential to induce point mutations, chromosome breakages, and mitotic recombina-tions (Graf et al., 1990).    In a micronucleus test in the bone marrow of CFLP mice, the maximum tolerated dose of 180 mg PCA/kg body weight (single dose given by gavage as a suspension in tragacanth) caused no significant elevation of micronuclei in the time range 24-72 h post-administration (BUA, 1995). In another study, B6C3F1 mice were dosed with 0, 25, 50, 100, 200, or 300 mg PCA/kg body weight dissolved in phosphate-buffered saline 3 times at 24-h intervals, and bone marrow was collected 24 h after the third treatment. The micronucleus frequency at the highest dose (300 mg/kg body weight) was significantly increased (P < 0.001) over the corresponding control value. References ・Traul KA, Takayama K, Kachevsky V, Hink RJ, Wolff JS (1981) A rapid in vitro assay for carcinogenicity of chemical substances in mammalian cells utilizing an attachment-independence endpoint. Journal of Applied Toxicology, 1: 190-195. ・Pienta RJ, Poiley JA, Lebherz WB III (1977) Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens. International Journal of Cancer, 19: 642-655. ・Pienta RJ, Kawalek JC (1981) Transformation of hamster embryo cells by aromatic amines. National Cancer Institute Monographs, 58: 243-251. ・Dunkel VC, Schechtman LM, Tu AS, Sivak A, Lubet RA, Cameron TP (1988) Intralaboratory evaluation of the C3H/1OT1/2 cell transformation assay. Environmental and Molecular Mutagenesis, 12 :21-31. ・Graf U, Hall CB, van Schaik N (1990) On the use of excision repair defective cells in the wing somatic mutation and recombination test in Drosophila melanogaster. Environmental and Molecular Mutagenesis, 16: 225-237. ・BUA (1995) p-Chloroaniline. Beratergremium fur Umweltrelevante Altstoffe (BUA) der Gesellschaft Deutscher Chemiker. Weinheim, VCH, 171 pp. (BUA Report 153).

● Chlorobenzene （クロロベンゼン; 塩化フェニール）） (Benzenechloride; monochlorobenzene)
　　　 108-90-7　　Industry　112.56

AM	Sal./E. coli	Max ( 0.5 mg/plate, ±S9)	□	1)
AM	Sal.	Max ( 0.243 mg/plate, ±S9)	□	2)
AM	Sal.	Max ( 0.33 mg/plate, ±S9)	□	3)
MB	A.nidulans	Max ( 0.2 mg/plate, +S9)	□	4)
YM	Yeast	Max (?)	□	5)
YM	Yeast	Min ( 0.006 mg/plate, ±S9)	○	6)
MLA	L5178Y	Min ( 2.0mg/ml, ±S9)	○	7)
CA	CHO	Max (?)	△	8)
CA	CHL/IU	Max ( 0.5 mg/ml, -S); (No data for +S9)	□	9)
DNA	E. coli	Max ( 0.02 mg/plate, S), +S9	□	6)
UDS	Rat hepatocytes	Max (9.3 x 10-4M, +S9	□	10)
CT	ARL	Min(?)	○	11)
SCE	CHO	Max ( 1 mg/ml, -S9)	○	12)
SLRLv	Drosophila	Max ( 9000 ppm, ih), for 4h	□	13)
DLv	Mice	Max ( 0.4 g/kg, or)	□	14)
MNv	Mice	Min( 0.45 g/kg, ip x 2)	○	15)
SCEv	Mice	Max ( 0.4 g/kg, or)	□	14)

1) Litton Bionetics: Report Number 75-231 to Rohm and Haas, Bristol, PA (Jan. 16, 1976)
2) US-NTP,  MTP Tech. Rep. Series, No. 261, NIH Pub. No. 86-2517 (1985)
3) Haworth S., et al,  Environ. Mutagen., 1, 3-142 (1983)
4) Ishidate MJr. (Ed.); Data Book of Mutagenicity Tests in Bacteria, LIC/Tokyo, Japan (1991) (Tables in English)
5) Valencia R.: Report to Bioassay Systems Corporation, Woburn, MA. Univ of Wisconsin, Madison, WI (Feb. 5, 1982)
6) Simmon  VF., et al., Contract No. 68-02-2947, US-EPA, ORD, US-EPA (1984)
7) Mcgreger DB., et al., Environ Mol., Mutagen., 12, 85-154 (1988)
8) Loveday KS.: Report to US-EPA, Research Triangle Park, NC. Bioassay Systems Corporation, Woburn, MA.(Oct. 7, 1982)
9) Sofuni T. (Ed.): Data Book of Chromosomeal Aberration Test in vitro, LIC, Tokyo (1998） (Tables in English)
10)Williams GM., et al., Mutation Res., 221, 263-286 (1989)　
11) Shimada T., et al.: Naylor Dana Inst. for Disease Prevention, Am. Health Found., Balhalla, NY (Dec. 5, 1983)
12) Loveday KS., et al  Environ Mol. Mutagen., 13, 60-94 (1989)
13) Valencia ,R , Reprot prepared , Zool. Dept., Univ. of Wisconsin, Madison, USA (1982)
14) Fel'dt, EG., Bull. Environ. Contam. Toxicol., 54, 36-42 (1985)
15) Mohtashamipur, E., et al., Mutagenesis, 2, 111-113 (1987)
1
 US-NTP Genotoxicity Screening：
○ Ames Test (±S9): □
○ MLA　Test: 　○　　
○ CA Test with CHO Cells:　□
○ SCE Test with CHO Cells: 　□

● o-Chlorobenzoic acid　（o-クロル安息香酸）　
　　 　　 118-91-2　 Industry　　 156.57

AM

Sal./E. coli

Max ( 10.0 mg/plate, ±S9),

□

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (1996) (Tables in English)

● p-Chlorobenzoic acid　（p-クロル安息香酸）　
　　 　　 74-11-3　 Industry　　 156.57

AM

Sal./E. coli

Max ( 10.0 mg/plate, ±S9),

□

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (1996) (Tables in English)

● p-Chlorobenzotrichloride　
　　 　　 5216-25-1　 Industry　　 229.92

AM	Sal./E. coli	Min ( 10 μg/plate, +S9)、Spe= 15000 (TA100)	○	1)
CA	CHL/IU	Min ( 0.1 mg/ml, -S9), 24h; D20= 0.13	○	1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (1996) (Tables in English)

● p-Chlorobenzoyl chloride　(p-クロルベンゾイルクロリド）
　　 　　 122-01-0　 Industry　　 175.02

AM

Sal./E. coli

Max ( 5.0 mg/plate, ±S9),

□

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (1996) (Tables in English)

●p-Chlorobenzylchloride　(p-クロルベンジルクロリド）
　　 　　 104-83-6　 Industry　　161.03

AM	Sal./E. coli	Max ( 200 μg/plate, ±S9),	□	1)
AM	CHL/IU	Min ( 0.08 mg/ml, -S9), 24h; D20= 0.011; TR= 1800	○	2)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (Ed.), pp. 352 (1996) (Tables in English)
2) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (Ed.) Suppl. 3, pp. 247 (2005) (Tables in English)

●p-Chlorobenzyl cyanide (p-chlorophenyl) acetontrile)
　　 　　140-53-4　 Industry　　 151.60

AM

Sal./E. coli

Max ( 625μg/plate, ±S9),

□

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. (1997) (Tables in English)

● o-Chlorobenzylidene malononitrile (o-クロロベンジリデンマロノニトリル;　CS)
　　　 　2698-41-1 　Incapacitating agent/Irritant　　　188.61

AM	Sal.	Max (?)	△	1,2)
SLRL	Drosophila	Max (?)	□	3)
MLA	L5178Y	Min (?)	○	4)
CA /SCE	CHO	Min (?)	○	4)
MNv	Mice/BM	Max (?) (ip/po)	□	3)

1) von Daeniken A., et al., Arch. Toxicol., 49, 15-27 (1981)
2) Zeiger E., et al.: Environ. Mutanen. , 9 (Suppl. 9), 1-110 (1987)
3) Wild D., et al.: Arch. Toxicol., 54, 167-170 (1983)
4) NTP: Technical Report, No.377, NIH, Research Triangle Park, NC (1990)

 US-NTP Genotoxicity Screening：
○ Ames Test:　△
○ MLA Test:　○
○ CA Test with CHO Cells (Analytical grade)：　○
○ SCE Test with CHO Cells (Analytical grade)： ○

● Chlorobromomethane （クロロブロモメタン）　
　　 74-97-5　(Fire-extingquishing agent)　　　129.39

AM

Sal.

Min (?)

○

1)

1) Osterman-Golkar S., et al.: Chem. Biol. Interact., 46, 121-130 (1983)
　　　　
US-NTP Genotoxicity Screening：
○ Ames Test: 　○

● 1-Chlorobutane （ 1-クロロブタン）

    109-69-3   Industry   92.58

AM	Sal./E. coli	Max ( 0.078 mg/pl,±S9)	□	1)
CA	CHL/IU	Max ( 0.93 mg/ml, ±S9 ), 6-18hr	□	1)

1) Ministry of Health & Welfare, Japan: Tox. Test. Reports of Environ. Chem., Vol. 2, 103 (1995) (Tables in English)

● α-Chlorobutyric acid 　　(α-クロロ酪酸）
　　 　　 4170-24-5 　Industry　　 122.1

CA

CHL/IU

Min ( 1.2 mg/plate, -S9),24h; D 20=2.1

○w

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (1996) (Tables in English)

● 4-Chloro-o-cresol （4-クロロ-o-クレゾール） 　
　　 　1570-64-5  Industry  142.59

AM	Sal./E. coli	Max ( 1.25 mg/plate, ±S9);	□	1)
CA	CHL/IU	Min ( 0.08 mg/ml, +S9), 6-18h; D20=0.12	○	1)

1) Ministry of Health & Welfare, Japan: Tox. Test. Reports of Environ. Chem., Vol. 4, 621 (1996) (Tables in English)

● 2'-(4-Chloro-3-cyano-5-formyl-2-thienylazo)-5'-diethylamino-2-acetanilide
　　 　　 104366-25-8　Industry　　403.88

CA

CHL/IU

Min ( 0.2 mg/ml -S9), 24h; D20= 0.21

○

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. (1997) (Tables in English)

● 2'-(4-Chloro-3-cyano-5-formyl-2-thienylazo)-5'-diethylamino-2-
　　　methoxyacetanilide
　　 　　 122371-93-1　Industry　　 433.92

CA

CHL/IU

Min ( 0.4 mg/ml -S9), 24h; Poly also; D20= 0.068

○

1)

1) Ministry of Labuor, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. (1997) (Tables in English)

● Chlorocyclohexane 　（Cyclohexyl chloride; クロロシクロヘキサン）
　　　 542-18-7　　Industry 　 118.61

CA

CHL/IU

Max ( 0.5 mg/ml, ±S9)

□

1)

1) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test in vitro, LIC, Tokyo (1998） (Tables in English)

● Chlorodifluoromethane (Flon 22; Algeon 22)　
　　 　　75-45-6　 Industry　　 86.5

AM	Sal./E. coli	(Gas) Min ( 10%, ±S9); Spa= 10% (TA1535)	○	1)
AM	Sal..	Min (?), -S9	○	3, 4)
CA	CHL/IU	(Gas) Max ( 100%)l, -S9), 24、48h	□	2)
CT	Syr. ham.	Max (?)	□	3, 4)
CAv	Rat BM	Min ( 145,950 ppm, ih, for 2h)	○	3, 4)
CAv	Mice	Max ( 816 mg/kg, or )	□	3, 4)
DLv	Rats	Max ( 48,650 ppm,  ih, 5h/d, for 8 w)	□	3, 4)
MNv	Mice, BM	Max ( 145,950 ppm, ih, for 6h)	□	3, 4)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. 2 (2000)(Tables in English)
2) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (1996) (Tables in English)
3) IPCS/WHO; Environ. Health Criteria, 126 (1991)
4) SCETOC, Joint Assessment of Commondity Chemicals 9, Chlorodifluoromethane (1989)

● 2'-(2-Chloro-4,6-dinitrophenylazo)-5'-diethylamino-4'-methoxyacetanilide
　　 　　 79295-99-1 　Industry　　 464.86

CA

CHL/IU

Max ( 0.01 mg/ml ±S9), 6h; Poly (Weakly)

□

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. 2 (2000) (Tables in English)

● 2'-(2-Chloro-4,6-dinitrophenylazo)-5'-(diethylamino) acetanilide
　　 　　 66557-45-7 　Industry　　 434.84

CA

CHL/IU

Max ( 0.32 mg/ml ±S9), 6h

□

1)

1) Ministry of Labor, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. 2 (2000) (Tables in English)

● 2'-(2-Chloro-4,6-dinitrophenylazo)-5'-ethylamino-4'-methoxyacetanilide
　　 　　 170778-70-8　 Industry　　 436.81

CA

CHL/IU

Min ( 0.06 mg/ml -S9), 28-20h; Poly; D20= 0.13

○w

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. 2 (2000) (Tables in English)

● Chlorodiphenyl (54% Chlorine) （Aroclor 1254; PCB）
　　　 11097-69-1　Industry/Plasticizer 　　 328.4 (average)

DLv

Rat

Max ( 2.5 g/kg, po)

□

1)

1) Green S., et al., : Fd. Cosmet. Toxcicol., 13, 507,-510 (1975)
　　　　
US-NTP Genotoxicity Screening：
○ Ames Test: 　□
○ ＣＡ　Ｔｅｓｔ　ｗｉｔｈ　ＣＨＯ　Ｃｅｌｌｓ: □
○ SCE Test with CHO Cells:　○w

● 2-Chloroethyl ethylether (1-Chloro-2-ethoxyethane) 　
　　　628-34-2　　Industrial 　　 108.57

AM

Sal./E. coli

Min( 5.0 mg/plate, -S9); Spa= 60.0 (TA104)

○w

1)

1) Ministry of Labor, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. (1997) (Tables in English)

● 3-Chloro-2-fluoronitrobenzene 　
　　　2106-49-2　　Industrial 　　 175.55

CA

CHL/IU

Min ( 0.015 mg/ml -S9), 24h; D20= 0.0094

◎

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (1996) (Tables in English)

● Chloroform 　（クロロホルム）
　　　 67-66-3　　Industrial use/ Solvent　　 119.38

AM	Sal.	Max ( 5.0 mg/ml, ±S9)	□	1)
AM	Sal./ E.coli	Max ( 1.0 % ±S9, vapor)	□	9)
AM	E.. coli	Min ( 0.5%, +S9 with glutathion ( spa=0.5%)	○	10)
CA	Humn LY	Max ( 0.4 mg/ml, +S9), 2-22h	□	2)
YM	Yeast	Min ( 0.3 mg/ml)	○	3)
UDS	Hepatocytes	Max ( 1.0 mg/ml)	□	4)
SCE	CH cells	Max ( 0.01 mg/ml, +S9)	□	5)
SCE	Hum. Ly.	Max (15.0mg/ml, +S9)	□	2)
SM	V79	Max ( 0.12 mg/ml, -S9)	□	6)
CT	Sy .Ham.	Min ( 0.163 mg/ml, -S9)	○	7)
MNv	Mice/BM	Max ( 952 mg/kg )	□	8)

1) Van Abbe, NJ., et al.: Food Chem. Toxicol., 20, 557,-561 (1982)
2) Kirkland, DJ, et al,: Food Cosmet. Toxicol., 19, 651-656 (1981)
3) Sharp, DC & Parry JM; Prog. Mutat. Res., 1, 502-516 (1981)
4) Althaus, FR. et al.; Cancer Res., 42, 3010-3015 (1982)
5) Perry, PE & Thomson, EJ; Prog. Mutat. Res., 1, 560-569 (1981)
6) Sturrock, J.; Bri. J. Anaesthesiol., 49, 207-210 (1977)
7) Hatch, GG. et al.; Cancer Res., 43, 1945-1950 (1983)
8) Gocke, E. et al., Mutation Res., 90, 91-109 (1981)
9) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (Ed.) Suppl. 3, pp. 247 (2005) (Tables in English)
10)Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (Ed.) Suppl. 3, pp. 209 (2005) (Tables in English)
　　　　
 US-NTP Genotoxicity Screening：
 ○ MLA Test: ○
 ○ ＣＡ　Ｔｅｓｔ　ｗｉｔｈ　ＣＨＯ　Ｃｅｌｌｓ: △
 ○ SCE Test with CHO Cells:　□

 ＩARC Carcinogenicity Criteria：
Group 2B (Possibly carcinogenic in humans)

【Note】 (Cited from IARC Monograph, Suppl., 6 (1987)

No adequate data were available on the genetic and related effects of chloroform in humans. 　　This agent did not induce MNs in bone-marrow cells of mice or DNA damage in liver or kidney cells of rats treated in vivo. It did not induce CAs, SCEs or UDS in human Lym. in vitro.　 It enhanced virus-induced cell transformation of Syr. hamster embryo cells. It did not induce SCEs or mutation in Chinese hamster cells or DNA damage in rat hepatocytes in vitro.　 It did not induce SLRL mutation in Drosophila or aneuploidy, mutation or somatic segregation in Aspergillus. It induced DNA damage but not mutation, aneuploidy, mitotic recombination or gene conversion in Saccharomyces cerevisiae, whereas mutation, mitotic recomination and gene conversion were induced in S. cerevisiae under conditions in which edogenous levels of cytochrome P450 were enhanced. 　It did not induce mutation or DNA damage in bacteria.

【Note】 (Cited from CICADs Documents, 58, 2004)

Chloroform has been extensively studied for genotoxic potential in a range of short-term screening assays. A more detailed, tabulated presentation of available data is given in the source document (Environment Canada & Health Canada, 2001).     Chloroform gave no evidence of mutagenic activity in the vast majority of a large number of assays in Salmonella typhimurium and Escherichia coli bacteria, although two papers report weak activity in, respectively, four Salmonella strains (Varma et al., 1988) and a single Salmonella strain (Pegram et al., 1997) at toxic/ lethal concentrations. Chloroform evidently did not cause chromosome aberrations in human lymphocytes in culture. Sister chromatid exchange (SCE) assays have given mixed results, but tests for unscheduled DNA synthesis (UDS) have consistently given no evidence of activity in a range of human and laboratory animal cells. In vivo, three of four bone marrow micronuclei studies in mice were clearly negative (Gocke et al., 1981; Salamone et al., 1981; Tsuchimoto & Matter, 1981), and the fourth (Agustin & Lim-Sylianco, 1978) was equivocal. Chloroform induced micronuclei formation in the kidney (Robbiano et al., 1998) and liver (Sasaki et al., 1998) of rats and chromosome damage (aberrations) in the bone marrow of rats (Fujie et al., 1990); a hamster bone marrow chromosome aberration study also gave evidence of a weak effect (Hoechst, 1987). Weak DNA binding has been reported in the rat liver and kidney (Pereira et al., 1982) and the mouse kidney, lung, liver, and stomach following intraperitoneal injection (Colacci et al., 1991), and there have been mixed results for sperm abnormalities in mice (Topham, 1980, 1981; Land et al., 1981) and a positive SCE result in mouse bone marrow (Morimoto & Koizumi, 1983). For other end-points (e.g., UDS in rat and mouse hepatocytes, DNA adducts, methylation, strand breaks and repair in mouse liver, DNA damage in rat liver and kidney), in vivo results have been negative (Petzold & Swenberg, 1978; Diaz-Gomez & Castro, 1980; Mirsalis et al., 1982; Reitz et al., 1982; Larson et al., 1994d; Potter et al., 1996; Butterworth et al., 1998; Pereira et al., 1998).     In conclusion, most studies did not identify genotoxic potential for chloroform. Results from a few, non-standard studies indicate the possibility of a weak positive response in rats. Overall, however, the weight of evidence indicates that chloroform does not have significant genotoxic potential. References ・Environment Canada, Health Canada (2001) Canadian Environmental Protection Act, 1999. Priority Substances List assessment report. Chloroform. Ottawa, Ontario, Minister of Public Works and Government Services Canada. ・Varma MM, Ampy FR, Verma K, Talbot WW (1988) In vitro mutagenicity of water contaminants in complex mixtures. Journal of Applied Toxicology, 8(4):243-248. ・Pegram RA, Andersen ME, Warren SH, Ross TM, Claxton LD (1997) Glutathione S-transferase-mediated mutagenicity of trihalomethanes in Salmonella typhimurium: contrasting results with bromodichloromethane and chloroform. Toxicology and Applied Pharmacology, 144:183-188 [cited in ILSI, 1997]. ・Gocke E, King M-T, Eckhardt K, Wild D (1981) Mutagenicity of cosmetics ingredients licensed by the European Communities. Mutation Research, 90:91-109. ・Salamone MF, Heddle JA, Katz M (1981) Mutagenic activity of 41 compounds in the in vivo micronucleus assay. In: De Serres FJ, Ashby J, eds. Evaluation of short-term tests for carcinogens: Report of the international collaborative study. Amsterdam, Elsevier/North-Holland, pp. 686-697 (Progress in Mutation Research, Vol. 1). ・Tsuchimoto T, Matter BE (1981) Activity of coded compounds in the micronucleus test. In: De Serres FJ, Ashby J, eds. Evaluation of short-term tests for carcinogens: Report of the international collaborative study. Amsterdam, Elsevier/North-Holland, pp. 705-711 (Progress in Mutation Research, Vol. 1). ・Agustin JS, Lim-Sylianco CY (1978) Mutagenic and clastogenic effects of chloroform. Bulletin: Philippine Biochemical Society, 1:17-23. ・Robbiano L, Mereto E, Morando AM, Pastore P, Brambilla G (1998) Increased frequency of micronucleated kidney cells in rats exposed to halogenated anaesthetics. Mutation Research, 413(1):1-6. ・Sasaki T, Suzuki M, Noda K, Noguchi T, Ishida R, Oda H, Araki A, Matsushima T (1998) Mutagenicity study of carbon tetrachloride and chloroform with microbial mutagenicity test and rat liver micronucleus test. Journal of Toxicological Sciences, 23(Suppl. II):305 (Abstract P-018). ・Fujie K, Aoki T, Wada M (1990) Acute and subacute cytogenetic effects of the trihalomethanes on rat bone marrow cells in vivo. Mutation Research, 242:111-119. ・Hoechst (1987) Chloroform. Detection of gene mutations in somatic cells in culture. HGPRT-test with V79 cells. Frankfurt, Pharma Research Toxicology and Pathology, Hoechst Aktiengesellschaft Laboratory (Project ID 86.1085; Hoechst Report No. 87.0692; TSCA Document No. FYI-OTS-0988-0635; Microfiche No. OTS0000635). ・Pereira MA, Lin LC, Lippitt JM, Herren SL (1982) Trihalomethanes as initiators and promoters of carcinogenesis. Environmental Health Perspectives, 46:151-156. ・Pereira MA, Kramer PM, Ge R, Tao L (1998) Effect of chloroform and haloacetic acids on DNA methylation in liver and tumors of female B6C3F1 mice. Environmental and Molecular Mutagenesis, 31(Suppl. 29):53 (Abstract P103). ・Colacci A, Bartoli S, Bonora B, Guidotti L, Lattanzi G, Mazzullo M, Niero A, Perocco P, Silingardi P, Grilli S (1991) Chloroform bioactivation leading to nucleic acids binding. Tumori, 77:285-290. ・Topham JC (1980) Do induced sperm-head abnormalities in mice specifically identify mammalian mutagens rather than carcinogens? Mutation Research, 74:379-387. ・Topham JC (1981) Evaluation of some chemicals by the sperm morphology assay. In: De Serres FJ, Ashby J, eds. Evaluation of short-term tests for carcinogens: Report of the international collaborative study. Amsterdam, Elsevier/North-Holland, pp. 718-720 (Progress in Mutation Research, Vol. 1). ・Land PC, Owen EL, Linde HW (1981) Morphologic changes in mouse spermatozoa after exposure to inhalational anaesthetics during early spermatogenesis. Anesthesiology, 54:53-56. ・Colacci A, Bartoli S, Bonora B, Guidotti L, Lattanzi G, Mazzullo M, Niero A, Perocco P, Silingardi P, Grilli S (1991) Chloroform bioactivation leading to nucleic acids binding. Tumori, 77:285-290. ・Petzold GL, Swenberg JA (1978) Detection of DNA damage induced in vivo following exposure of rats to carcinogens. Cancer Research, 38:1589-1594 ・Diaz-Gomez MI, Castro JA (1980) Covalent binding of chloroform metabolites to nuclear proteins: No evidence for binding to nucleic acids. Cancer Letters, 9:213-218. ・Mirsalis JC, Tyson CK, Butterworth BE (1982) Detection of genotoxic carcinogens in the in vivo-in vitro hepatocyte DNA repair assay. Environmental Mutagenesis, 4:553-562. ・Reitz RH, Fox TR, Quast JF (1982) Mechanistic considerations for carcinogenic risk estimations: Chloroform. Environmental Health Perspectives, 45:163-168. ・Larson JL, Sprankle CS, Butterworth BE (1994d) Lack of chloroform-induced DNA repair in vitro and in vivo in hepatocytes of female B6C3F1 mice. Environmental and Molecular Mutagenesis, 23:132-136. ・Potter CL, Chang LW, DeAngelo AB, Daniel FB (1996) Effects of four trihalomethanes on DNA strand breaks, renal hyaline droplet formation and serum testosterone in male F-344 rats. Cancer Letters, 106:235-242. ・Butterworth BE, Templin MV, Constan AA, Sprankle CS, Wong BA, Pluta LJ, Everitt JI, Recio L (1998) Long-term mutagenicity studies with chloroform and dimethylnitrosamine in female lacI transgenic B6C3F1 mice. Environmental and Molecular Mutagenesis, 31(3):248-256.

● p-Chloromethyl methylether (Chlorodimethyl ether)
　　　107-30-2　　Industry　　 80.5

CA

CHL/IU

Min ( 0.012 mg/ml -S9), 24h; D20= 0.015; (Poly also)

◎

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, (1996) (Tables in English)

【Note】 (Cited from IARC Monograph, Suppl., 6 (1987)

A slight increase in the incidence of CAs was observed in peripheral Ly. of workers exposed to this agent in the preparation of ion-exchange resins. 　It enhanced virus-induced transformation of Syrian hamster embryo cells and was mutagenic to bacteria. (IARC Monographs, 4, 239, 1974; Suppl. 4, 64, 1982)

● 2-Chloro-4-nitroaniline
　　　121-87-9　Industry　　172.6

CA

CHL/IU

Min ( 0.25 mg/ml -S9), 6h; D20= 0.16; (Poly also)

○

1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, (1996) (Tables in English)

● 5-Chloro-2-nitroaniline
　　　1635-61-6　Industry　　 172.6

AM	Sal./E. coli	Min ( 78.1 μg /plate, +S9); Spa=320 (TA98)	○	1)
CA	CHL/IU	Min ( 0.012 mg/ml, -S9), 24h; D20= 0.015; (Poly also)	◎	1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, (1996) (Tables in English)

● 2-Chloronitrobenzene (o-chroronitrobenzene) (o-クロロニトロベンゼン
　　　88-73-3　　Industry　　157.56

AM	Sal./E. coli	Max ( 0.5 mg/plate, S9)	□	1, 3, 4)
AM	Sal.	Min (?),  -S9	○	3-6)
CA	CHL/IU	Min ( 0.2 mg/ml, -S9), 48h; Poly	○w	2)
CA	CHO	Min ( 0.46 mg/ml, -S9)	○	4)
SCE	CHO	Min ( 0.05 mg/ml, -S9)	○	4)
SLRLv	Drosophila	Max ( 10 g /kg,)	□	4)
DNAv	Mice	Min ( 60 mg/kg, ip)	○	3, 4)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (Ed.), pp. 188 (1996) (Tables in English)
2) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC (Ed.), Suppl. 3,  pp. 218 (2005) (Tables in English)
3) BUA Report, 41 (1985)
4) IARC Monog. on the Evaluation of the Carcinog. Risk of Chemicals to Humans, 65 (1996)
5) Registory of Toxic Effects of Chemical Substances (RTECS, US NIOSH (1996)
6) Hazardous Substances Data Bank (HSDB), US Natl Library Medicine (1997)
7)  
● 4-(2-Chloro-4-nitrophenylazo)-N-(2-cyanoethyl)-N-phenethylaniline
　　　 19649-68-4　　　　Industry　　433.5

CA

CHL/IU

Min ( 3.5 mg/ml -S9), 48h; D20= 5.5

○w

1)

1) Ministry of Labor, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, (1996) (Tables in English)

● p-Chlorophenol 　（p-クロロフェノール）　( 4-クロロフェノール）
　　　106-48-9　　Industry/intermediate　 128.56

AM	Sal./E. coli	Max ( 2.0 mg/plate, ±S9)	□	１)
CA	CHL/IU	Max ( 0.4 mg/ml, ±S9), 6-18h (with Poly)	△	2)
CA	CHL/IU	Min ( 0.4 mg/ml, ±S9)	○	3)
UM	Sal.	Min (?)	○	4)

1) Ministry of Health & Welfare, Labor, Japan. Toxicol. Tests on Chemicals, Rep. 8, 444-448 (2001) (Tables in English)
2) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro,, LIC, Tokyo (1998） (Tables in English)
3) Ministry of Health & Welfare, Labor, Toxicol. Tests on Chemicals, Rep. 8, 449-452 (2001) (Tables in English)
4) Degirmenci E., et al., Water Sci., Technol., 42, 125-131 (2000)

●Top Page　（トップページ）

●Abbreviation 　（省略記号）

●Mutagenicity 　（変異原性）

●Test Systems　(試験法の種類）

●Technical Problems　（技術的問題点）

●List of　Compounds（化合物リスト）

●Evaluation of Results　（試験結果の評価）