@@@@@@@@@@@@@@@@@@@@@@@@@@@@@
Group C-7 ‰»Šw\‘’@(Chemical Structure)  

œ m-Chloroaniline
im-ƒNƒƒƒAƒjƒŠƒ“j@(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j (Tables in English)

œ o-Chloroaniline io-ƒNƒƒƒAƒjƒŠƒ“j
(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 ƒΚg/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j (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)
œ p-Chloroaniline ip-ƒNƒƒƒAƒjƒŠƒ“j (4-Chloroaniline; 4-ƒNƒƒƒxƒ“ƒ[ƒ“ƒAƒ~ƒ“j
@@ @ 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j (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) (?)

yNotez@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 ƒΚg/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 ƒΚg/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 ƒΚg/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

ETraul 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.
EPienta 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.
EPienta RJ, Kawalek JC (1981) Transformation of hamster embryo cells by aromatic amines. National Cancer Institute Monographs, 58: 243-251.
EDunkel 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.
EGraf 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.
EBUA (1995) p-Chloroaniline. Beratergremium fur Umweltrelevante Altstoffe (BUA) der Gesellschaft Deutscher Chemiker. Weinheim, VCH, 171 pp. (BUA Report 153).


œ Chlorobenzene iƒNƒƒƒxƒ“ƒ[ƒ“; ‰–‰»ƒtƒFƒj[ƒ‹jj
(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j (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F
› Ames Test (}S9):
 
› MLA@Test: @›@@
› CA Test with CHO Cells:@ 
› SCE Test with CHO Cells: @
 

œ o-Chlorobenzoic acid
@io-ƒNƒƒ‹ˆΐ‘§Ž_j@
@@ @@ 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)

œ p-Chlorobenzoic acid@ip-ƒNƒƒ‹ˆΐ‘§Ž_j@
@@ @@ 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)

œ p-Chlorobenzotrichloride@
@@ @@ 5216-25-1@ Industry@@ 229.92

AM Sal./E. coli Min ( 10 ƒΚg/plate, +S9)ASpe= 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)

œ p-Chlorobenzoyl chloride@(p-ƒNƒƒ‹ƒxƒ“ƒ]ƒCƒ‹ƒNƒƒŠƒhj
@@ @@ 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)

œp-Chloroben
zylchloride@(p-ƒNƒƒ‹ƒxƒ“ƒWƒ‹ƒNƒƒŠƒhj
@@ @@ 104-83-6@ Industry@@161.03
AM Sal./E. coli Max ( 200 ƒΚg/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)

œp-Chloroben
zyl cyanide (p-chlorophenyl) acetontrile)
@@ @@140-53-4@ Industry@@ 151.60

AM Sal./E. coli Max ( 625ƒΚg/plate, }S9),
 
1)
1) Ministry of Labour, Japan; Mutagen. Test Data of Exixt. Chem. Subst.: JETOC, Suppl. (1997) (Tables in English)
œ o-Chlorobenzylidene malononitrile (o-ƒNƒƒƒxƒ“ƒWƒŠƒfƒ“ƒ}ƒƒmƒjƒgƒŠƒ‹;@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F
› Ames Test:@
’
› MLA Test:@›
›
CA Test with CHO Cells (Analytical grade)F@›
›
SCE Test with CHO Cells (Analytical grade)F ›

œ Chlorobromomethane iƒNƒƒƒuƒƒ‚ƒƒ^ƒ“j@
@@ 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F
› Ames Test: @›

œ 1-Chlorobutane i 1-ƒNƒƒƒuƒ^ƒ“j
    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)
œ ƒΏ-Chlorobutyric acid @@(ƒΏ-ƒNƒƒ—Ž_j
@@ @@ 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)
œ 4-Chloro-o-cresol i4-ƒNƒƒ-o-ƒNƒŒƒ][ƒ‹j @
@@ @
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)

œ 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)
œ 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)

œ Chlorocyclohexane @iCyclohexyl chloride; ƒNƒƒƒVƒNƒƒwƒLƒTƒ“j
@@@ 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j (Tables in English)

œ 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A48h   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)

œ 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)

œ 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)

œ 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)

œ Chlorodiphenyl (54% Chlorine) iAroclor 1254; PCBj
@@@ 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F
› Ames Test: @ 
› ‚b‚`@‚s‚…‚“‚”@‚—‚‰‚”‚ˆ@‚b‚g‚n@‚b‚…‚Œ‚Œ‚“:
 
› SCE Test with CHO Cells:@
›w

œ 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)

œ 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)

œ
Chloroform @iƒNƒƒƒzƒ‹ƒ€j
@@@ 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F
 › MLA Test:
›
 › ‚b‚`@‚s‚…‚“‚”@‚—‚‰‚”‚ˆ@‚b‚g‚n@‚b‚…‚Œ‚Œ‚“:
’
 › SCE Test with CHO Cells:@
 

 ‚hARC Carcinogenicity CriteriaF
Group 2B
(Possibly carcinogenic in humans)

yNotez
(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.
yNotez (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

EEnvironment 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.
EVarma 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.
EPegram 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].
EGocke E, King M-T, Eckhardt K, Wild D (1981) Mutagenicity of cosmetics ingredients licensed by the European Communities. Mutation Research, 90:91-109.
ESalamone 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).
ETsuchimoto 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).
EAgustin JS, Lim-Sylianco CY (1978) Mutagenic and clastogenic effects of chloroform. Bulletin: Philippine Biochemical Society, 1:17-23.
ERobbiano 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.
ESasaki 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).
EFujie 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.
EHoechst (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).
EPereira MA, Lin LC, Lippitt JM, Herren SL (1982) Trihalomethanes as initiators and promoters of carcinogenesis. Environmental Health Perspectives, 46:151-156.
EPereira 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).
EColacci 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.
ETopham JC (1980) Do induced sperm-head abnormalities in mice specifically identify mammalian mutagens rather than carcinogens? Mutation Research, 74:379-387.
ETopham 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).
ELand PC, Owen EL, Linde HW (1981) Morphologic changes in mouse spermatozoa after exposure to inhalational anaesthetics during early spermatogenesis. Anesthesiology, 54:53-56.

EColacci 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.
EPetzold GL, Swenberg JA (1978) Detection of DNA damage induced in vivo following exposure of rats to carcinogens. Cancer Research, 38:1589-1594
EDiaz-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.

EMirsalis 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.
EReitz RH, Fox TR, Quast JF (1982) Mechanistic considerations for carcinogenic risk estimations: Chloroform. Environmental Health Perspectives, 45:163-168.
ELarson 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.
EPotter 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.
EButterworth 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.


œ 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)

yNotez (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)

œ 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)

œ 5-Chloro-2-nitroaniline
@@@1635-61-6@Industry@@ 172.6
AM Sal./E. coli Min ( 78.1 ƒΚg /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)

œ 2-Chloronitrobenzene (o-chroronitrobenzene) (o-ƒNƒƒƒjƒgƒƒxƒ“ƒ[ƒ“
@@@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)  
œ 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)

œ p-Chlorophenol @ip-ƒNƒƒƒtƒFƒm[ƒ‹j@( 4-ƒNƒƒƒtƒFƒm[ƒ‹j
@@@106-48-9@@Industry/intermediate@ 128.56
AM Sal./E. coli Max ( 2.0 mg/plate, }S9)   ‚P)
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j (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)


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