4-Ethylphenol

4-エチルフェノール


[CAS No. 123-07-9]

p-Ethylphenol

p-エチルフェノール

Molecular formula: C8H10O　Molecular weight: 122.16

ABSTRACT

A single dose toxicity test of 4-ethylphenol revealed an LD50 value of more than 2000 mg/kg for males and females.

In a 28-day repeat dose toxicity test, no adverse effects were observed in the 100 mg/kg group. In the 300 mg/kg group, males showed increases in absolute and relative liver weights. In the 1000 mg/kg group, males and females showed staggering gait and/or salivation. Body weight gain and food consumption were depressed in these animals. An increase in urinary volume was noted in females. Increases in GPT activity in males and in serum total cholesterol in females were observed. Relative liver weights of males and females and relative kidney weights of males were increased. Autopsy of males and females revealed thickening of the mucosa in the forestomach. Histopathology of the forestomach revealed hyperplasia of squamous cells. These changes were not observed at the end of the recovery period.

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

A reverse mutation test of 4-ethylphenol on bacteria was carried out. This substance was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Genotoxicity of 4-ethylphenol was studied by chromosomal aberration test using cultured Chinese hamster lung (CHL/IU) cells.

4-Ethylphenol induced structural chromosomal aberrations at the maximum dose of 0.075 mg/mL with short-term treatment and a metabolic activation system. With continuous treatment for 24 hr, structural chromosomal aberrations were also induced at two doses (0.038-0.075 mg/mL). Polyploidy was not induced with any treatment system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:98.3 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral(gavage)
　Doses:0(vehicle), 2000 mg/kg
　Number of animals/group:Males, 5; Females, 5
　Vehicle:Olive oil
GLP:Yes

　Test results:

No deaths occurred in either males or females of the 2000 mg/kg group. Animals showed staggering gait and adoption of a prone or lateral position from 10 minutes to 2 hours after the administration. Body weights of males were below the control values throughout the 14 day-observation period, and those of females were lowered on Days 1 and 3 after the administration. No gross pathological lesions were observed at autopsy on Day 14.

The LD50 values were estimated to be more than 2000 mg/kg for both sexes.

2. Repeat Dose Oral Toxicity 1)

Purity:98.3 %
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 abnormal findings were observed in the 100 mg/kg group. In the 300 mg/kg group, males showed increases in absolute and relative liver weights. In the 1000 mg/kg group, males and females showed staggering gait and/or salivation throughout the administration period. Body weight gain of males and females were depressed throughout the administration and recovery periods. Food consumption was low in these animals. An increase in urinary volume was noted in females. At the end of the administration period, increases in GPT activity in males and in serum total cholesterol in females were observed. Relative liver weights of males and females and relative kidney weights of males were increased. Autopsy of males and females revealed thickening of the mucosa in the forestomach. Histopathological examination of the forestomach revealed hyperplasia of squamous cells. These changes were not observed at the end of the recovery period.

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

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:98.328 %
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:Dimethyl sulfoxide
　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 (five strains)
　Doses:-S9 mix; 0, 62.5, 125, 250, 500, 1000, 2000 μg/plate(five strains)
+S9 mix; 0, 62.5, 125, 250, 500, 1000, 2000 μg/plate(five strains)
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavon
　Plates/test:3(1 for cytotoxicity test)
　Number of replicates:2(plus 1 cytotoxicity test)
GLP:Yes

　Test results:

This chemical did not induce gene mutations in S. typhimurium TA100, TA1535, TA98, TA1537 and E. coli WP2 uvrA strains, with or without S9 mix. Toxicity was observed at 1000 μg/plate and above (TA100, TA1535, TA98, TA1537) and at 2000 μg/plate (WP2 uvrA) without S9 mix and at 2000 μg/plate (five strains) with S9 mix.

Genetic 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:98.328 %
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:Dimethyl sulfoxide
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
　Doses:-S9 mix(short-term treatment); 0, 0.050, 0.10, 0.20 mg/mL
+S9 mix(short-term treatment); 0, 0.019, 0.038, 0.075 mg/mL
-S9 mix(continuous treatment for 24 hr); 0, 0.019, 0.038, 0.075 mg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Cells with structural chromosomal aberrations were increased with the maximum dose of 0.075 mg/mL after short-term treatment with metabolic activation (frequency:11.0 %). With continuous treatment for 24 hr, cells with structural chromosomal aberrations were increased at the doses of 0.038 and 0.075 mg/mL (frequencies:6.5 % and 21.0 %, respectively). Polyploidy was not induced with either treatment schedule.

Lowest concentration producing cytogenetic effects in vitro:
　With metabolic activation (short-term treatment):0.075 mg/mL(clastogenicity)
　Without metabolic activation (continuous treatment):0.038 mg/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 Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627