C-4

Group C-4 化学構造　(Chemical Structure)

● Carbomycin A 　(カルボマイシン　Ａ）　　　　　　　
　　 4564-87-8 　Medicine　 MW: 841.98

CA CHL/IU Max ( 1.0 mg/ml, -S9), 24-48h □ 1)

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

● Carbon disulfide 　（二硫化炭素）　（硫炭）　
　　　75-15-0　　Industry/Solvent　　 76.14

AM Sal. Max ( 2.0 mg/ml, ±S9), □ 1)

AM Sal. / E. coli Max ( 1.0 mg/ml, ±S9), □ 2)

CA CHL/IU Max ( 1.0 mg/ml, -S9), 24-48h □ 3)

CA Human Lym. Max ( 0.06mg/ml, -S9) □ 4)

SCE Human Lym. Min ( 0.06 mg/ml, +S9) ○ 4)

UDS Human, WI-38 Max ( 0.05 mg/ml, ±S9) □ 5)

CAv Rats Min ( LD50 x 0.1 mg/kg, or ), for >15 days ○ 6, 7)

SLRLv Drosophila Max ( 1,000 ppm, fed), for 24h □ 5)

DLv Rats Max ( 40 ppm, ih), 7h/day x 5 to male □ 5)

SPA Rats & Mice Max ( 40 ppm, ih), 7h/day x 5 □ 5)

1) Haworth S., et al., Environ. Mutagen. Suppl. 1, 3-142 (1983)
2) Donner M., et al., Mutation Res., 91, 163-166 (1981)
3) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test In Vitro, LIC, Tokyo (1998） (Tables in English)
4) Garry VF., et al., Teratog. Carcinog. Mutag., 10, 21-29 (1990)
5) Beliles RP., et al., Nat. Tech. Inform. Serv., 1-225 (1980)
6) Vesail' eva., Tsoitol. Gegnet., 16, 57-59, 1982)
7) US NISOH, 4-7, EPA (1985); IPCS/WHO; Environ. Health Criteria, 10 (1994)

US-NTP Genotoxicity Screening：
○　Ames Test：　□
○　CA Test with CHO Cells：　□
○　SCE Test with CHO Cells：　○

【Note】　(Cited from CICADS document, 37, 2002)

There is no clear evidence from in vitro studies that carbon disulfide is genotoxic (Environment Canada & Health Canada, 2000). In several studies in bacteria, carbon disulfide did not induce point mutations in Salmonella typhimurium or in Escherichia coli, both with and without metabolic activation. In studies of mammalian cells exposed to carbon disulfide in the presence of metabolic activation, there were small and/or equivocal increases in chromatid gaps in human lymphocytes, in unscheduled DNA synthesis in diploid WI-38 cells derived from human embryonic lung tissue, and in sister chromatid exchanges in human lymphocytes. In one study (Le & Fu, 1996), in human sperm exposed to carbon disulfide in vitro, there was a significant increase in the frequency of chromosomal aberrations and in the frequency of chromosomal breaks.
Available in vivo data on the genotoxicity of carbon disulfide are limited. In male and female rats inhaling 63 or 125 mg carbon disulfide/m³, 7 h/day for 1 or 5 days, there was no significant increase in the frequency of chromosomal aberrations in bone marrow cells (Belisles et al., 1980). In contrast, Vasil'eva (1982) reported that oral exposure to carbon disulfide induced chromosomal aberrations and polyploid cells in the bone marrow of female rats and in rat embryos exposed on days 10-13 of gestation. It is difficult to assess the validity of these findings, as the reporting was brief (e.g., the statistical significance was often not indicated) and the effective dose was not reported, except to indicate that it was one-tenth of the LD₅₀.
When male rats were exposed to 63-125 mg carbon disulfide/m³, 7 h/day for 5 days, there was no significant increase in dominant lethal mutations, nor was there a dose-related increase in sperm abnormalities in rats or mice exposed according to the same protocol (Belisles et al., 1980), although lack of an effect on sperm abnormalities in positive control rats undermines somewhat the significance of these observations.

References
・Le JY, Fu XM (1996) Human sperm chromosome analysis ? study on human sperm chromosome mutagens induced by carbon disulfide. Biomedical and Environmental Sciences, 9: 37-40.
・Belisles RP, Brusick DJ, Melcher FJ (1980) Teratogenic-mutagenic risk of workplace contaminants: trichloroethylene, perchloroethylene, and carbon disulphide. Report prepared by Litton Bionetics Inc. for the National Institute for Occupational Safety and Health, Cincinnati, OH, May (NTIS PB82-185075).
・Vasil'eva IA (1982) Investigation of the action of carbon disulfide on the chromosome apparatus of adult and embryonic rat cells. Tsitologiya i Genetica, 16(2): 57-59.

● Carbon tetrachloride　（四塩化炭素）　(tetrachloromethane)　　
　　　 56-23-5　Solvent/ Dry-cleaning agent 　　 153.82

AM Sal. Max ( 10 mg/ml, ±S9) □ 1)

AM Sal. Max ( 2.8 mg/plate, ±S9) □ 9)

AM Sal./E. coli Min ( 0.5% vapor) spa=0.5% (TA98, ±S9) ○ 7)

AM Sal. Max ( 3.3 mg/plate, ±S9) □ 10)

YM S. cerev. Min ( 5.2 mg/ml, -S9) ○ 2)

CA A. Nidulans Min ( 7.9 mg/ml, -S9) ○ 3)

CA CHL/IU Max ( 0.5 mg/ml, ±S9), 6-18h □ 6, 8)

CA CHO Max ( 3.0 mg/ml, +S9) □ 12)

CA Rat/RL1 cells Max ( 0.032 mg/ml) □ 4)

CA Hum. Lym. Max ( 0.08 mg/ml, +S9) □ 13)

SCE CHO Min ( 0.15 mg/ml, -S9) ○ 14)

MLA L5178Y Max ( 0.63 mg/ml, +S9) □ 11)

CT Syr. ham. Min ( 3 μg/ml, -S9) ○w 15)

UDSv Rats, Liver Min ( 4 g/kg, po ), 17h ○ 5)

UDSv Rats, Liver Max ( 0.4 g/kg, or ) □ 19)

CAv Ret Liver Max ( 1.6 g/kg, or ) □ 16)

MNs Mice, BM Max ( 2 g/kg, or ) □ 17)

DNAv Mice, Liver Max ( 0.4 g/kg, or ) □ 18)

SPA Mice, Sperm Max ( 1.0 mg/kg, ip) □ 20)

１）McCann J., et al. : Proc. Natl Acad. Sci. (USA), 72, 51395-5
2) Callen DF., et al.: Mutation Res., 77, 55-63 (1980)
3) Gualandi G.: Mutation Res., 136, 109-114 (1984)
4) Dean, BJ. & Hudson-Walker G.: Mutation Res., 64, 329-337 (1979)
5) Craddock VM., et al.: Cancer Res., 38, 2135-2143 (1978)
6) Ishidate MJr.(Ed.): Data Book, Chromosomal Aberration Test In Vitro, LIC, Tokyo/Elsevier, Amsterdam (1988)
7) Ministry of Labour, Japan: Mutagenicity Test Data of Exist. Chem. Subst., JETOC (Ed.), Suppl. 3, pp. 155 (2005) (Tables in English)
8) Ministry of Labour, Japan: Mutagenicity Test Data of Exist. Chem. Subst., JETOC (Ed.), Suppl. 3, pp. 242 (2005) (Tables in English)
9) Barber ED et a;l., Mutation Res., 90, 31-48 (1981)
10) Zeiger E., et al., Envron. Mol. Mutagen., 12, 1-157 (1988)
11) Wangenheim J & Boscsfolds G, Mutagenesis, 3, 193-205 (1988)
12) Loveday KS et al., Environ. Mol. Mutagen., 16, 272-303 (1990)
13) Garry VF et al., Teratog. Carcinog. Mutag., 10, 21-29 (1990)
14) Athanasion K & Kyrlopoulos S., Nato Adv. Study. A. Life Sci., 41, 557-562 (1981)
15) Amacher DE & Zelljadt I., Carcinogenesis, 4, 291-295 (1983)
16) Sawada S., et al., Mutation Res., 251, 59-69 (1991)
17) Suzuki H., et al Mutation Res., 394, 77-80 (1997)
18 ) Bermudez E., et al., Environ. Mutag., 4, 667-679 (1982)
19) Mirsalis JC et al., Environ. Mutagen. 4, 553-562 (1982)
20) Topham JC, Mutation Res., 74, 379-387 (1980)

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

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

　　No data were available on teh genetic and related effects of carbon tetrachloride in humans.
　　This agent did not induce CAs, UDS or DNA strand breaks in cells of rodents treated in vivo. It did not induce CAs or SCEs in rat cells in vitro, but anaphase abnormalities were induced in cultured CHO cells. It induced mutation, gene conversion and mitotic recombination in Saccharomyces cerevissiae, under conditions in which edogenous levels of cytochrome P450 were enhanced; there was a weak induction of mitotic crossing-over and mutation in Asperigillus. It was not mutagenic to bacteria.

● Carboxymethylcellulose sodium salt 　(CMC sodium) 　
　　　9004-32-4　Food/Solvent　　

AM Sal./E. coli Max ( 5.0 mg/palte, ±S9) □ 1, 2)

CA CHL/IU Max ( 8.0 mg/ml, -S9), 24-48h □ 3)

1) Fujita H., et al. : Ann. Rep. Tokyo Metr. Res. Lab. P.H., 39, 343-350 (1988)
2) Ishidate MJr, et al: Fd. Chem. toxicol., 22, 623-636 (1984)
3) Sofuni T. (Ed): Data Book of Chromosomal Aberration Test In Vitro, LIC, Tokyo (1998) (Tables in English)

● Carnauba wax （カルナウバロウ）
8015-86-9　Industry/Natural　

CA CHL/IU Max ( 0.03 mg/ml, -S9), 24-48h □ 1)

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

● β-Carotene 　（Solatene; β-カロテン）
　　 7235-40-7　Food/Medicine 　 536.88

DNA Rec-assay Max (? ), (host-mediated) □ 1)

AM Sal Max ( 5 mg/plate, ±S9)　 □ 2)

CA CHL/IU Max ( 10..0 mg/ml, -S9), 24-48h □ 3)

1) kada T, et al..; Mutation Res., 16, 165 (1972)
2) Ishidate MJr (Ed.): Data Book of Mutagenicity Tests on Chemicals in Bacteria, LIC/Tokyo (1991)
3) Sofuni T. (Ed): Data Book of Chromosomal Aberration Test In Vitro, LIC, Tokyo (1998) (Tables in English)

● ι-Carrageenan (Ca-salt) （ι-カラギーナン・カルシウム塩）
　　　 9049-05-2　Natural/food/industry

CA CHL/IU Max ( 1.0 mg/ml, -S9), 24-48h □ 1)

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

● κ-Carrageenan (K-salt) （ι-カラギーナン・カリウム塩）
　　　 64366-24-1 　Natural/food/industry

CA CHL/IU Max ( 2.0 mg/ml, -S9), 24-48h □ 1)

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

● κ-Carrageenan (Na-salt) （ι-カラギーナン・ナトリウム塩）
　　　9000-07-1 　Natural/food/industry

CA CHL/IU Max ( 2.0 mg/ml, -S9), 24-48h □ 1)

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

● Carrot pigment （にんじん色素, ニンジンカロテン））　
　　　Natural/food

AM Sal Max ( 5 mg/plate, ±S9) □ 1)

CA CHL/IU Max ( 8.0 mg/ml, -S9), 24-48h □ 1)

1) Ishidate MJr., et al..: Toxicol. Forum, 11, 663-669 (1988) (in Japanese)
1) Sofuni T. (Ed): Data Book of Chromosomal Aberration Test In Vitro, LIC, Tokyo (1998) (Tables in English)

●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）

AM	Sal.	Max ( 2.0 mg/ml, ±S9),	□	1)
AM	Sal. / E. coli	Max ( 1.0 mg/ml, ±S9),	□	2)
CA	CHL/IU	Max ( 1.0 mg/ml, -S9), 24-48h	□	3)
CA	Human Lym.	Max ( 0.06mg/ml, -S9)	□	4)
SCE	Human Lym.	Min ( 0.06 mg/ml, +S9)	○	4)
UDS	Human, WI-38	Max ( 0.05 mg/ml, ±S9)	□	5)
CAv	Rats	Min ( LD50 x 0.1 mg/kg, or ), for >15 days	○	6, 7)
SLRLv	Drosophila	Max ( 1,000 ppm, fed), for 24h	□	5)
DLv	Rats	Max ( 40 ppm, ih), 7h/day x 5 to male	□	5)
SPA	Rats & Mice	Max ( 40 ppm, ih), 7h/day x 5	□	5)

AM	Sal.	Max ( 10 mg/ml, ±S9)	□	1)
AM	Sal.	Max ( 2.8 mg/plate, ±S9)	□	9)
AM	Sal./E. coli	Min ( 0.5% vapor) spa=0.5% (TA98, ±S9)	○	7)
AM	Sal.	Max ( 3.3 mg/plate, ±S9)	□	10)
YM	S. cerev.	Min ( 5.2 mg/ml, -S9)	○	2)
CA	A. Nidulans	Min ( 7.9 mg/ml, -S9)	○	3)
CA	CHL/IU	Max ( 0.5 mg/ml, ±S9), 6-18h	□	6, 8)
CA	CHO	Max ( 3.0 mg/ml, +S9)	□	12)
CA	Rat/RL1 cells	Max ( 0.032 mg/ml)	□	4)
CA	Hum. Lym.	Max ( 0.08 mg/ml, +S9)	□	13)
SCE	CHO	Min ( 0.15 mg/ml, -S9)	○	14)
MLA	L5178Y	Max ( 0.63 mg/ml, +S9)	□	11)
CT	Syr. ham.	Min ( 3 μg/ml, -S9)	○w	15)
UDSv	Rats, Liver	Min ( 4 g/kg, po ), 17h	○	5)
UDSv	Rats, Liver	Max ( 0.4 g/kg, or )	□	19)
CAv	Ret Liver	Max ( 1.6 g/kg, or )	□	16)
MNs	Mice, BM	Max ( 2 g/kg, or )	□	17)
DNAv	Mice, Liver	Max ( 0.4 g/kg, or )	□	18)
SPA	Mice, Sperm	Max ( 1.0 mg/kg, ip)	□	20)

AM	Sal./E. coli	Max ( 5.0 mg/palte, ±S9)	□	1, 2)
CA	CHL/IU	Max ( 8.0 mg/ml, -S9), 24-48h	□	3)

DNA	Rec-assay	Max (? ), (host-mediated)	□	1)
AM	Sal	Max ( 5 mg/plate, ±S9)	□	2)
CA	CHL/IU	Max ( 10..0 mg/ml, -S9), 24-48h	□	3)

AM	Sal	Max ( 5 mg/plate, ±S9)	□	1)
CA	CHL/IU	Max ( 8.0 mg/ml, -S9), 24-48h	□	1)