3-Methylphenol

3-メチルフェノール


[CAS No. 108-39-4]

m-Cresol

m-クレゾール

Molecular formula: C7H8O Molecular weight: 108.14

ABSTRACT

The single dose toxicity test of 3-methylphenol revealed LD50 values of 2241 mg/kg for males and 2007 mg/kg for females.

In a repeat dose toxicity test of 3-methylphenol, no adverse effects were observed in the 100 mg/kg group. In the 300 mg/kg group, females showed an increase in relative liver weights. In the 1000 mg/kg group, males and females showed tremors and or salivation throughout the administration period. Body weights and food consumption were low in these animals. Urinalysis showed low pH and negative protein in males and females, and increases in urinary volume and water consumption in males. An increase in serum total cholesterol was observed in males and females. Relative liver weights in males and females and relative kidney weights in females were increased. Histopathological examination revealed hypertrophy of centrilobular hepatocytes in one male. These changes were not observed at the end of the recovery period.

The NOELs for repeat dose toxicity are considered to be 300 mg/kg/day for males and 100 mg/kg/day for females.

Genotoxicity of 3-methylphenol was studied by reverse mutation test in bacteria and by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

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

3-Methylphenol induced structural chromosomal aberrations in CHL/IU cells after short-term treatment, with and without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:99.13 %
Test species/strains:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Doses:0(vehicle), 1430, 1640, 1890, 2170, 2500 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:Olive oil
GLP:Yes

　Test results:

Deaths occurred in males and females of all test substance-administered groups from 2 to 24 hours after the administration. Animals showed tremors and adoption of a prone or lateral position from a few minutes to 6 hours after the administration. Body weights of surviving animals were below the controls throughout the 14 day-observation period. Gross pathological examination of dead animals revealed detachment or thinning of the mucosa and dark red or brown patches in the glandular stomach.
The LD50 values were estimated to be 2241 mg/kg for males and 2007 mg/kg for females.

2. Repeat Dose Toxicity 1)

Purity:99.13 %
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)
　Doses:0(vehicle), 100, 300, 1000 mg/kg/day
　Number of animals/group:Males and females, 14, 7, 7 and 14/group for the 0, 100, 300 and 1000 mg/kg cases, respectively
　Vehicle:Olive oil
　Administration period:Males and females, 28 days
　Terminal kill:Days 29 and 43
GLP:Yes

　Test results:

No adverse effects were observed in the 100 mg/kg group. Females of the 300 mg/kg group showed an increase in relative liver weights. In the 1000 mg/kg group, tremors and/or salivation were observed in males and females throughout the administration period. Body weights of males and females were lowered throughout the administration and recovery periods. Food consumption was low in these animals. Urinalysis showed increases in the number of animals showing low pH and negative protein in males and females, and in urinary volume and water consumption in males. At the end of the administration period, an increase in serum total cholesterol was observed in males and females. Relative liver weights of males and females and relative kidney weights of females were increased. Histopathological examination revealed hypertrophy of centrilobular hepatocytes in one of 7 males. These changes were not observed at the end of the recovery period.
The NOELs are considered to be 300 mg/kg/day for males and 100 mg/kg/day for females.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:99.13 %
Test species/strains: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, 156, 313, 625, 1250, 2500, 5000 μg/plate
+S9 mix; 0, 156, 313, 625, 1250, 2500, 5000 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 2500 μg/plate (all strains) without S9 mix, and at more than 2500 μg/plate (TA100, TA1535, TA98, TA1537) and at 5000 μg/plate (WP2 uvrA) with S9 mix.

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98 and 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:99.13 %
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemical
(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, 300, 500, 700, 900, 1100 μg/mL
+S9 mix(6 hr short-term treatment); 0, 12.5, 25, 50, 100, 200, 400 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 700 and 900 μg/mL (20.0 and 27.5 %) without S9 mix, and at 25, 50, 100, 200 and 400 μg/mL (10.5, 21.5, 17.5, 24.0 and 30.5 %) with S9 mix, respectively. Polyploidy was not induced in any treatment group.
Cytotoxicity was observed at 1100 μg/mL after 6 hr short-term treatment without S9 mix.

Lowest concentration producing cytogenetic effects in vitro:
　With metabolic activation (6 hr short-term treatment):25 μg/mL(clastogenicity)

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

1)The tests were performed by the Safety Research Institute for Chemical Compounds Co., Ltd., 363-24, Shin-ei, Kiyota-ku, Sapporo, Hokkaido, 004-0839, Japan. Tel +81-11-885-5031 Fax +81-11-885-5313
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