3-Ethylphenol

3-エチルフェノール


[CAS No. 620-17-7]

m-Ethylphenol

m-エチルフェノール

Molecular formula: C8H10O　Molecular weight: 122.16

ABSTRACT

Single oral toxicity of 3-ethylphenol dissolved in olive oil was investigated using Crj:CD(SD)IGS rats at doses of 0, 1000, 1200, 1450, 1700, 2000 mg/kg and revealed LD50 values of 1709 mg/kg for males and 1691 mg/kg for females.

In a 28-day repeat dose toxicity test, the following behavior indicative of toxicity was observed in males and females given 1000 mg/kg; adoption of a lateral and/or prone position, staggering gait and soiling of perigenital fur. Males given 1000 mg/kg had decreased body weights and food consumption on Days 2 and 7. Males and females given 1000 mg/kg demonstrated increased water consumption and urine volume. Males and females given 1000 mg/kg had increased GPT, and females increased total cholesterol. Males and females given 1000 mg/kg demonstrated increase in liver weights with or without elevation in relative weights, and males increase in renal relative weights. Males and females given 1000 mg/kg showed hyperplasia of squamous cells in the forestomach. This change seemed to be caused by irritating effects of 3-ethylphenol. The NOELs are considered to be 300 mg/kg/day for males and females.

A reverse mutation test of 3-ethylphenol in 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 3-ethylphenol was studied by the chromosomal aberration test using cultured Chinese hamster lung (CHL/IU) cells.

3-Ethylphenol induced structural chromosomal aberrations at all three doses (0.050-0.20 mg/mL) tested with short-term treatment and metabolic activation.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:96.2 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral(Gavage)
　Doses:0(Vehicle), 1000, 1200, 1450, 1700, 2000 mg/kg
　Number of animals/group:Males, 5; Females, 5
　Vehicle:Olive oil
GLP:Yes

　Test results:

Deaths occurred in males and females given 1700 mg/kg or more. Behavior suggestive of acute toxicity included, staggering gait, and aportion of a prone and/or lateral position in both sexes given 1450 mg/kg or more from some minutes to 6 hours after administration. Body weight was suppressed continuously in males given 1200 mg/kg or more. The weights of females were decreased for only a day after administration of 1450 mg/kg or more. Edematous change and white discoloration of gastric mucosa were observed in the dead animals.

The LD50 values were estimated to be 1709 mg/kg for males and 1691 mg/kg for females.

2. Repeat Dose Oral Toxicity 1)

Purity:96.2 %
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 0, 100, 300 and 1000 mg/kg, respectively
　Vehicle:Olive oil
　Administration period:Males and females, 28 days
　Terminal kill:Days 29 and 43
GLP:Yes

　Test results:

Males and females given 1000 mg/kg demonstrated a lateral and/or prone position, staggering gait and soiling of perigenital fur. Males had decreased body weight and food consumption on Days 2 and 7. On urinalysis, males and females demonstrated increased water consumption and urine volume. On blood chemical examination, males and females had increased GPT, and females increased total cholesterol. Males and females showed increase in absolute and/or relative liver weights, and males increase in relative kidney weights. Histopathological examination revealed hyperplasia of squamous cells in the forestomach in males and females. This change seemed to be caused by irritating effects of 3-ethylphenol.

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

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:96.2 %
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 and above 1000 μg/plate (TA1537) and at 2000 μg/plate (TA100, TA1535, TA98 and 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:96.2 %
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, 0.063, 0.13, 0.25 mg/mL
+S9 mix(short-term treatment);0, 0.050, 0.10, 0.20 mg/mL
-S9 mix(continuous treatment for 24 hr); 0, 0.025, 0.050, 0.10 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 dose dependently with short-term treatment and metabolic activation (frequency:11.0-37.0 %).

Lowest concentration producing cytogenetic effects in vitro:
　With metabolic activation (short-term treatment):0.050 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