B-8

● N-sec-Butyl-N-(1-acetoxymethyl) nitrosamine
　 CAS: 56986-37-9 　Laboratory 　MW: 174.20
　

CA CHL/IU Min ( 0.03 mg/ml, -S9), 24h ○ 1)

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

● N-Butyl-N-(acetylaminomethyl) nitrosamine
　 64005-58-9　Laboratory　　 173.21

CA CHL/IU Max ( 4.0 mg/ml, -S9), 24-48h (No data for +S)) □ 1)

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

● n -Butyl acrylate （n-ブチルアクリレート）
　　 141-32-2　　Industrial 　　128.17

AM Sal Max ( 0.03-2.0 mg/plate, ±S9) □ 1, 2)

CAv CH/Rat/BM Max ( 820 ppm, 5-6h, ih, for 4d) □ 3)

1) Waegemaekers THJM & Bensink MPM: Mtation Res., 137, 95-102 (1984)
2) IARC Monograph, Vol 39, pp.67 (1986)
3) Engelhardt G & Klimisch HJ: Fundam. Appl. Toxicol.., 3, 640-641 (1983)

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

●n -Butylamine （n-ブチルアミン）
　　109-73-9　　Industry　 73.14

US-NTP Genotoxicity Screening:
○　Ames Test :　□

●tert-Butylamine （tert-ブチラミン）　(2-methyl-2-propanamine)
　 75-64-9　Industry　73.14

AM Sal/E.coli Max ( 2.5 mg/plate, ±S9) □ 1)

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

● Butylated hydroxyanisole (BHA)
　　25013-16-5　Industry/Food　 180.25

AM Sal Max (?) □ 1, 6)

REC B.subtilis Min (?) ○ 2)

CA CHL/IU Max ( 0.06 mg/ml, -S9), 24-48h □ 3)

CA DON Max ( 10^-4 M) □ 4)

SCE DON Max ( 10^-4 M) □ 4)

MNv Mice Max ( 250 mg/kg x 4, ip), 24h □ 5)

1) Ishidate MJr., et al., Mutagens & Toxicity, Vol. 12, 82-90 (1980) (in Japanese)
2) Kawachi T, et al: in IARC Sci. Pub., Lyon, 323-330 (1980)
3) Ishidate MJr. (Ed.): Data Book of ChromosomeAberration Test in vitro LIC/Tokyo & Elsevier/Amsterdam (1988)
4) Abe S & Sasaki M: J. Natl. Cancer Inst., 58, 1635-1641 (1977)
5) Hayashi M, et al: Fd. Chem. Toxicol., 26, 487-500 (1988)
6) Fujita H. et al., Ann. Rep. Tokyo Metr. Res., Lab. P.H. 36, 413-417 (1985) (in Japanese)

US-NTP Genotoxicity Screening：
○ Ames Test：　□
○ Mouse Lymphoma Assay (L-5178Y)；　○
○ CA Test with CHO Cells：　□
○ SCE Test with CHO Cells:：　□

●Butylated hydroxytoluene (BHT) (2,6 Dibutyl-p-cresol)
　 128-37-0　Industry/Food　 180.25

AM Sal Max (?) □ 1)

REC B. subtilis Max (?) □ 2)

CA CHL/IU Max ( 0.05 mg/ml, ±S9), 6-18h □ 3, 4)

CA DON Max （0.001M） □ 5)

MNv Mice Max (?) □ 6)

1) Ishidate MJr.(Ed.): Data Book of Mutagenicity Tests on Chemicals in Bacteria, LIC/Tokyo, pp.74 (1991) (Tables in English)
2) Kawachi T, et al,: In IARC Sci., Pub., Lyon, 323-330 (1980)
3) Ishidate MJr. & Odashima S.: Mtution Res., 48, 377-354 (1977
4) Sofuni T. (Ed.): Data Book of Chromosomal Aberration Test i In Vitro, LIC, Tokyo (1998) (Tables in English)
5) Abe S. & Sasaki M.: J. Natl Cancer Inst., 58, 1635-1641(1977)
6) Natl Inst. Hygien. Sci., Tokyo (?)

US-NTP Genotoxicity Screening：
○ Ames Test：　□
○ Mouse Lymphoma Assay (L-5178Y)；　○
○ CA Test with CHO Cells：　□
○ SCE Test with CHO Cells:：　□
　　
IARC Carcinogenicity Criteria
　Group 3　（Not classifiable as to its carcinogenicity to humans）

● p-tert-Butylbenzoic acid （p-tert-ブチル安息香酸）
98-73-7　 Industry　 178.23

AM Sal Max ( 5.0 mg/plate, ±S9) □ 1)

1) Ministry of Labour, Japan; Mutagen. Test Data of Exist. Chem. Subst., JETOC (Ed.) Suppl. 3, pp. 144 (2005) (Tables in English)

●n-tert-Butyl-2-benzothiazolesulfenamide (N-(tert-ブチル）-2-ベンゾチアゾールスルフェンアミド）
　　 95-31-8　　Industry　 238.39

AM Sal. Max ( 2.5 mg/ml, ±S9) □ 1)

CA CHL/IU Max ( 0.4 mg/ml, +S9), 6-18h　 △ 1)

AM Sal./ E coli Max (　.5 mg/ml, ±S9) □ 2)

MLA L5178Y Min　( 40μｇ/ml, -S9), for 4h ○ 2)

MLA L5178Y Min ( 50 μｇ/ml, -S9), for 4h ○ 3)

CA CHO Max ( 10 μｇ/ml), for 2h □ 2)

CT Balb/3T3 Min　( 35μｇ/ml), for 3d ○ 2)

1) Ministry of Health, Labour & Welfare, Japan: Tox. Test. Rep. of Environ. Chem., Vol. 5, pp.157 (1997) (Tables in English)
2) Hinderer RK., et al., Environ. Mutagen., 5, 193-215 (1983)
3) Monsanto, EPA Doc. No. 88-920004696, NTIS OTSO543011 (1992)

●Butyl benzyl phthalate (ブチルベンジルフタレート）(フタル酸n-ブチルベンジル）
　　 85-68-7　Industry　 312.4

AM Sal. Max ( 10 mg/plate, ±S9) □ 1)

AM Sal. Max ( 1 mg/plate, ±S9) □ 2)

MLA L5178Y Max ( 1.2 μl/ml, ±S9), for 4h □ 3)

MLA L5178Y Max ( 100 nl/ml, ±S9), for 4h □ 4)

CA CHO Max ( 1.2 mg/ml, ±S9), for 12h □ 5)

SCE CHO Max ( 1.2 mg/ml, ±S9), for 26h □ 5)

DNA E. coli Max ( 30 mg/plate, -S9), for 26h □ 6)

CT Balb/C 3T3 Max ( 0.16μl/ml, -S9), for 3 days □ 3)

CAv Mice, BM Max ( 5g/kg, ip,), for 36h □ 7)

SCEv Rats, BM Max ( 5g/kg, ip,), for 36h □ 7)

MNv Rats, BM Max ( 5g/kg, ip,), for 36h □ 8)

SLRLv Drosophila Max ( 50000 ppm, fed,,) □ 9)

1) Zeiger E., et al., Environ. Mutagen., 7, 213-232 (1985)
2) Kozumbo WJ., et al., Environ. Health Perspect., 43, 103-109 (1982)
3) Barber ED., et al., J. App;. Toxicol., 20, 69-80 (2000)
4) Myhr BL & Caspary WJ, Environ. Mol. Mutagen., 18, 51-83 (1991)
5) Galloway EM., et al., Environ. Mol.. Mutagen., 10, 1-175 (1987)
6) Omori Y, Environ. Health. Perspect., 17, 203-209 (2000)
7) US NTP, TR 458, NIH Pub., No. 97-3374 (1997)
8) Ashby J., et al., Regul. Toxicol. Pharm., 56, 107-118 (1997)
9) Valencia R., et al., Environ. Mutagen., 7, 325-348 (1985)

(Additional Ref.)
1) Hazardous Substances Data Bank (HSDS), U.S. Natl Lib. Med. (1996)
2) IARC, Monog. on the Evaluation of the Carcino. Risk of Chem. to Human, 29, 193-201 (1982)
3) J. American College of Toxicol., 11 (1), 1-23 (1992)

【Note】　(Cited from CICADS Document, 17, 1999)

In the (few) published reports of Ames assays with BBP, results have been negative (Litton Bionetics Inc., 1976; Rubin et al., 1979; Kozumbo et al., 1982; Zeiger et al., 1982, 1985). Negative results have also been reported for mouse lymphoma assays (Litton Bionetics Inc., 1977; Hazleton Biotechnologies Company, 1986), although equivocal findings have also been published (Myhr et al., 1986; Myhr & Caspary, 1991). In an assay for in vitro transformation of Balb/c-3T3 cells (Litton Bionetics Inc., 1985), results were negative. In an assay for chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary cells (Galloway et al., 1987), there was slight evidence for a trend in one sister chromatid exchange test without activation, but no convincing evidence for positive results for sister chromatid exchanges or aberrations. Conversion factor: 1 ppm in food = 0.13 mg/kg body weight per day (Health Canada, 1994).
The results from the mouse lymphoma (Myhr et al., 1986; Myhr & Caspary, 1991) and chromosomal aberration (Galloway et al., 1987) assays are equivocal. For the mouse lymphoma assay, the NTP concluded that "Increases in mutant colonies were observed in the absence of S9 in cultures treated with concentrations that produced precipitation, but such responses were not considered valid by experimental quality control parameters." However, it is difficult to dismiss the observed dose-response in several studies as spurious, although the repeat tests were negative, particularly in view of inconsistencies of results of the latter. In repeat studies ( n = 5) in the absence of S9, there was limited evidence of activity in only one case; however, although BBP was positive at 80 nl/ml in the second trial, it was toxic at concentrations above 30 nl/ml in the third. The inconsistently observed increase in small colony mutants and percent damaged Chinese hamster ovary cells may be indicative of weak clastogenic activity, which warrants proper confirmation in well-conducted assays.
A negative response was reported for an assay for the induction of sex-linked recessive lethals in Drosophila melanogaster (Valencia et al., 1985). Recently, the NTP (1997) published summary results of mouse bone marrow tests for sister chromatid exchanges and induction of chromosomal aberrations; responses were weak, and the sister chromatid exchange test was not repeated. Both of these responses, although statistically significant, were small and indicative of only weak clastogenic activity. Ashby et al. (1997) reported negative results in a micronucleus assay in rats.

References
・Litton Bionetics Inc. (1976) Mutagenicity evaluation of BIO-76-17Santicizer 160. NB 259784.Final report. Submitted by Monsanto Company, St. Louis, MO, to Office of Toxic Substances, US Environmental Protection Agency (Document Identification No. 87-7800282; Microfiche No. OTS200290).
・Litton Bionetics Inc. (1977) Mutagenicity evaluation of BIO-76-243CP731 (Santicizer 160) in the mouse lymphoma assay.Final report. Submitted by Monsanto Company, St. Louis, MO, to Office of Toxic Substances, US Environmental Protection Agency (Document Identification No. 87-7800282; Microfiche No. OTS200290).
・Litton Bionetics Inc. (1985) Evaluation of 1D in the in vitro transformation of BALB/3T3 cells assay. Final report. Submitted by Chemical Manufacturers Association, Washington, DC, to US Environmental Protection Agency (Document Identification No. 40+8526206; Microfiche No. OTS0509537).
;・Rubin RJ, Kozumbo W, Kroll R (1979) Ames mutagenic assay of a series of phthalic acid esters: positive response of the dimethyl and diethyl esters in TA100 [abstract]. Toxicology and applied pharmacology, 48 (1 Part 2):A133.
・Kozumbo WJ, Kroll R, Rubin RJ (1982) Assessment of the mutagenicity of phthalate esters. Environmental health perspectives, 45:103-109.
;・Zeiger E, Haworth S, Speck W, Mortelmans K (1982) Phthalate ester testing in the National Toxicology Program's Environmental Mutagenesis Test Development Program. Environmental health perspectives, 45:99-101.
・Zeiger E, Haworth S, Mortelmans K, Speck W (1985) Mutagenicity testing of di(2-ethylhexyl)phthalate and related chemicals in Salmonella.Environmental mutagenesis, 7(2):213-232.
・Hazleton Biotechnologies Company (1986) Mutagenicity of 1D in amouse lymphoma mutation assay.Final report. Submitted by Chemical Manufacturers Association, Washington, DC, to Office of Toxic Substances, US Environmental Protection Agency (Document Identification No. 40-8626225; Microfiche No. OTS0510527).
・Myhr BC, Bowers LR, Caspary WJ (1986) Results from the testing of coded chemicals in the L5178Y TK⁺/^- mouse lymphoma mutagenesis assay [abstract]. Environmental mutagenesis, 8 (Suppl. 6) :58.
・Myhr BC, Caspary WJ (1991) Chemical mutagenesis at the thymidine kinase locus in L1578Y mouse lymphoma cells: results for 31 coded compounds in the National Toxicology Program. Environmental andmolecular mutagenesis, 18(1): 51-83. .
・Galloway SM, Armstrong MJ, Reuben C, Colman S, Brown B, Cannon C, Bloom AD, Nakamura F, Ahmed M, Duk S, Rimpo J, Margolin BH, Resnick MA, Anderson B, Zeiger E (1987) Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals. Environmental and molecular mutagenesis, 10 (Suppl. 10): 1-175.
・Health Canada (1994) Human health risk assessment for PrioritySubstances. Canada Communications Group, Ottawa, Ontario.
・Valencia R, Mason JM, Woodruff RC, Zimmering S (1985) Chemical mutagenesis testing in Drosophila. III. Results of 48 coded compounds tested for the National Toxicology Program. Environmentalmutagenesis, 7(3): 325-348.
・NTP (1997a) Toxicology and carcinogenesis studies of butyl benzylphthalate (CAS No. 85-68-7) in F344/N rats (feed studies). Research Triangle Park, NC, National Institutes of Health, National Toxicology Program (NTP Technical Report No. 458; NIH Publication No. 97-3374).
・Ashby J, Tinwell H, Lefevre PA, Odum J, Paton D, Millward SW, Tittensor S, Brooks AN (1997a) Normal sexual development of rats exposed to butyl benzyl phthalate from conception to weaning. Regulatory toxicology and pharmacology, 26: 102-118.

● Butylbutanolamine （ブチルブタノールアミン）
　 4543-95-7　Laboratory　 145.24

AM Sal Max (?)　 □ 1)

CA CHL/IU Max ( 0.40 mg/ml, -9), 24-48h □ 3)

1) Natl Inst. Hygien. Sci., Tokyo (?)
2) Ishidate MJr. (Ed.): Data Book of ChromosomeAberration Test In Vitro, LIC/Tokyo & Elsevier/Amsterdam (1988)

● Butylbutanolnitrosoamine （ブチルブタノールニトロサアミン）
　 3817-11-6 　Laboratory　 174.24

AM Sal Min (?) ○ 1)

CA CHL/IU Min ( 0.9 mg/ml,+9), 3-12h ○ 2)

1) Natl Inst. Hygien. Sci., Tokyo (?)
2) Ishidate MJr. (Ed.): Data Book of Chromosomal Aberration Test In Vitro, LIC/Tokyo & Elsevier/Amsterdam (1988)

● N-Butyl-N-(3-carboxypropyl) nitrosamine
　 38252-74-3　Laboratory　 188.26

AM Sal Min (?) ○ 1)

CA CHL/IU Max ( 1.0 mg/ml, -S9), 24-48h　（No data for +S9) △ 2)

1)) Natl Inst. Hygien. Sci., Tokyo (?)
2) Ishidate MJr. (Ed.): Data Book of Chromosomal Aberration Test In Vitro, LIC/Tokyo & Elsevier/Amsterdam (1988)

● 6-tert-Butyl-m-cresol （6-tert-ブチル-m-クレゾール）
88-60-8 　Industry　　146.25

AM Sal Max ( 0.2 mg/plate, ±S9) □ 1),

CA CHL Max ( 0.015 mg/ml, +S9) 6-18h △ 1)

1) Ministry of Health, Labour & Welfare, Japan (Ed.) Tox. Test. Rep. of Environ. Chem., Vol. 7 (1999) (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 ( 0.03-2.0 mg/plate, ±S9)	□	1, 2)
CAv	CH/Rat/BM	Max ( 820 ppm, 5-6h, ih, for 4d)	□	3)

AM	Sal	Max (?)	□	1, 6)
REC	B.subtilis	Min (?)	○	2)
CA	CHL/IU	Max ( 0.06 mg/ml, -S9), 24-48h	□	3)
CA	DON	Max ( 10^-4 M)	□	4)
SCE	DON	Max ( 10^-4 M)	□	4)
MNv	Mice	Max ( 250 mg/kg x 4, ip), 24h	□	5)

AM	Sal.	Max ( 2.5 mg/ml, ±S9)	□	1)
CA	CHL/IU	Max ( 0.4 mg/ml, +S9), 6-18h	△	1)
AM	Sal./ E coli	Max (　.5 mg/ml, ±S9)	□	2)
MLA	L5178Y	Min　( 40μｇ/ml, -S9), for 4h	○	2)
MLA	L5178Y	Min ( 50 μｇ/ml, -S9), for 4h	○	3)
CA	CHO	Max ( 10 μｇ/ml), for 2h	□	2)
CT	Balb/3T3	Min　( 35μｇ/ml), for 3d	○	2)

AM	Sal.	Max ( 10 mg/plate, ±S9)	□	1)
AM	Sal.	Max ( 1 mg/plate, ±S9)	□	2)
MLA	L5178Y	Max ( 1.2 μl/ml, ±S9), for 4h	□	3)
MLA	L5178Y	Max ( 100 nl/ml, ±S9), for 4h	□	4)
CA	CHO	Max ( 1.2 mg/ml, ±S9), for 12h	□	5)
SCE	CHO	Max ( 1.2 mg/ml, ±S9), for 26h	□	5)
DNA	E. coli	Max ( 30 mg/plate, -S9), for 26h	□	6)
CT	Balb/C 3T3	Max ( 0.16μl/ml, -S9), for 3 days	□	3)
CAv	Mice, BM	Max ( 5g/kg, ip,), for 36h	□	7)
SCEv	Rats, BM	Max ( 5g/kg, ip,), for 36h	□	7)
MNv	Rats, BM	Max ( 5g/kg, ip,), for 36h	□	8)
SLRLv	Drosophila	Max ( 50000 ppm, fed,,)	□	9)

AM	Sal	Max (?)	□	1)
CA	CHL/IU	Max ( 0.40 mg/ml, -9), 24-48h	□	3)

AM	Sal	Max ( 0.2 mg/plate, ±S9)	□	1),
CA	CHL	Max ( 0.015 mg/ml, +S9) 6-18h	△	1)