2-tert-Butylphenol

2-tert-ブチルフェノール


[CAS No. 88-18-6]

2-(1,1-Dimethylethyl)phenol

2-(1,1-ジメチルエチル)フェノール

Molecular formula: C10H14O　Molecular weight: 150.22

ABSTRACT

Single oral dose LD50 values of 2-tert-butylphenol were found to be 1231 mg/kg for males and 1414 mg/kg for females.

2-tert-Butylphenol was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at 0, 4, 20, 100, and 500 mg/kg.

Ataxic gait was observed in the 500 mg/kg group, and salivation was noted in the 100 and 500 mg/kg groups. Organ weight measurement revealed an increase in relative liver weight in the 500 mg/kg group. These changes disappeared after withdrawal. The NOEL is considered to be 20 mg/kg/day for both sexes.

Genotoxicity of 2-tert-butylphenol was studied by a reverse mutation test in bacteria and a chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

2-tert-Butylphenol was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

2-tert-Butylphenol induced structural and numerical chromosomal aberrations in CHL/IU cells after short-term treatment with an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Toxicity 1)

Purity:99.97 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral(gavage)
　Dosage:0(vehicle), 500, 1000, 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:Olive oil
GLP:Yes

　Test results:

Death occurred in the 1000 mg/kg and above dose groups for males and 2000 mg/kg for females.

Clinical signs observed were as follows: ataxic gait, abnormal gait, decrease in locomotor activity, tremor, irregular respiration, crouching, prone or lateral position, lacrimation, and hypothermia. Body weights were decreased in males of the 1000 and 2000 mg/kg groups on Day 4. Pathological changes were mainly observed in the forestomach and glandular stomach.

The LD50 values were 1231 mg/kg for males and 1414 mg/kg for females.

2. Repeat Dose Toxicity 1)

Purity:99.97 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:Guideline for 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
　Route:Oral(gavage)
　Dosage:0(vehicle), 4, 20, 100, 500 mg/kg/day
　Number of animals/group:Males, 6; females, 6
　Vehicle:Olive oil
　Administration period:Males and females, 28 days
　Sacrifice:Days 29 and 43
GLP:Yes

　Test results:

Ataxic gait was observed in both sexes of the 500 mg/kg group, and salivation was observed in both sexes of the 100 and 500 mg/kg groups. Organ weight measurement revealed an increase in relative liver weights in both sexes of the 500 mg/kg group. These changes disappeared after withdrawal. No changes attributable to the administration of 2-tert-butylphenol were observed in the body weight, food consumption, hematological examination, blood chemical examination, urinalysis, necropsy, and histopathological examination.

The NOEL is considered to be 20 mg/kg/day for both sexes.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:99.97 %
Test species/strain:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals(Chemical Substances Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent:DMSO
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98, WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine (TA1537)
+S9 mix; 2-Aminoanthracene (all strains)
　Doses:-S9 mix; 0, 6.25, 12.5, 25, 50, 100, 200 μg/plate
+S9 mix; 0, 6.25, 12.5, 25, 50, 100, 200 μg/plate
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:3
　Number of replicates:2
GLP:Yes

　Test results:

This chemical did not induce gene mutations in the S. typhimurium and E. coli strains. Toxicity was observed at more than 100 μg/plate (TA100, TA1535, TA98, TA1537) and at 200 μg/plate (WP2 uvrA) without S9 mix, and observed at more than 100 μg/plate (TA100, TA1535) and at 200 μg/plate (TA98, TA1537, WP2 uvrA) with S9 mix.

Genotoxic effects:
Salmonella typhimurium TA100, TA1535, TA98, TA1537
+?-
　Without metabolic activation:[ ][ ][*]
　With metabolic activation:[ ][ ][*]

Escherichia coli WP2 uvrA
+?-
　Without metabolic activation:[ ][ ][*]
　With metabolic activation:[ ][ ][*]

3-2. Non-bacterial in vitro test (chromosomal aberration test)2)

Purity:99.97 %
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals(Chemical Substances Control Law of Japan) and OECD Test Guideline 473
　Solvent:DMSO
　Positive controls:-S9 mix; 1-Methyl-3-nitro-1-nitrosoguanidine
+S9 mix; 3,4-Benzo[a]pyrene
　Doses:-S9 mix(6 hr short-term treatment); 0, 40, 60, 80, 100, 110, 120 μg/mL
+S9 mix(6 hr short-term treatment); 0, 1.25, 2.5, 5, 7.5, 10, 20 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

With 6 hr short-term treatment, structural chromosomal aberrations were induced at 7.5 and 10 μg/mL (5.5 and 11.0 %), respectively with S9 mix. Polyploidy was induced at 10 μg/mL (5.0 %) with S9 mix. Cytotoxicity was observed at more than 110 μg/mL without S9 mix, and at 20 μg/mL with S9 mix.

Lowest concentration producing cytogenetic effects in vitro:
With metabolic activation (6 hr short-term treatment):7.5 μg/mL(clastogenicity)

Genotoxic effects:
clastogenicitypolyploidy
+?-+?-
　Without metabolic activation:[ ][ ][*][ ][ ][*]
　With metabolic activation:[*][ ][ ][*][ ][ ]

1)The tests were performed by the Kashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki-machi, Kashima-gun, Ibaraki, 314-0255, Japan. Tel +81-479-46-2871 Fax +81-479-46-2874
2)The tests were performed by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa 229-1132, Japan. Tel +81-42-762-2775 Fax +81-42-762-7979