3-Phenoxytoluene

3-フェノキシトルエン


[CAS No. 3586-14-9]

m-Phenoxytoluene

m-フェノキシトルエン

Molecular formula: C13H12O Molecular weight: 184.25

ABSTRACT

3-Phenoxytoluene was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 4, 20, 100 and 500 mg/kg.

Decreased food consumption and increased water intake were observed in the 500 mg/kg group. Hematological examination revealed shortening of APTT in males given 500 mg/kg and decreased platelet counts in females given 100 and 500 mg/kg. Blood chemical examination revealed increases in albumin, the A/G ratio, ALP and urea nitrogen and decreases in total cholesterol, triglyceride, inorganic phosphate and glucose in the 500 mg/kg group. Increased urine volumes were evident in the 500 mg/kg group. The liver weights were increased and histopathologically, hypertrophy of centrilobular hepatocytes was noted in the 500 mg/kg group.

The NOELs for the repeat dose toxicity are considered to be 100 mg/kg/day for males and 20 mg/kg/day for females.

3-Phenoxytoluene was not mutagenic in Salmonella typhimurium, TA100, TA1535, TA98, TA1537 and Escherichia coli WP2uvrA. Regardless of the presence or absence of exogenous metabolic activation system, this chemical substance did not induce structural chromosomal aberrations in CHL/IU cells. Polyploidy was not induced under the conditions of the present study.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose Toxicity1)

Purity:99.0%
Test species/strain:Rat/Crj:CD (SD)
Test method:Guidelines for 28-Day Repeat Dose Toxicity Testing for Chemicals (Japan)
 Route:Oral (gavage)
 Dosage:0 (vehicle), 4, 20, 100, 500 mg/kg/day
 Number of animals:Males, 6; females, 6/group
 Vehicle:0.1% Tween 80 solution
 Administration period:Males and females, 28 days
 Terminal kill:Days 29 or 43
GLP:Yes

 Test results:

Decreased food consumption was observed in females given 500 mg/kg and increased water intake in both sexes given 500 mg/kg. Hematological examination revealed shortening of APTT in males given 500 mg/kg and a decreased platelet counts in females given 100 and 500 mg/kg. Blood chemical examination revealed increases in albumin and the A/G ratio in both sexes given 500 mg/kg; decreases in total cholesterol, triglyceride and inorganic phosphate in males given 500 mg/kg; increases in ALP and urea nitrogen in females given 500 mg/kg; and a decrease in glucose in females given 500 mg/kg. Increased urine volume was evident in both sexes given 500 mg/kg. Absolute and relative liver weights were increased in both sexes given 500 mg/kg and histopathologically, centrilobular hypertrophy of hepatocytes was noted in both sexes given 500 mg/kg. These changes disappeared or tended to become reduced during the recovery period.

The NOELs for the repeat dose toxicity are considered to be 100 mg/kg/day for males and 20 mg/kg/day for females.

2. Genetic Toxicity

2-1. Bacterial test1)

Purity:99.0 %
Test species/strain:Salmonella typhimurium, TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:OECD Guidelines No. 471, 472 and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
 Procedures:Pre-incubation method
 Solvent:DMSO
 Positive controls:-S9 mix, AF-2 (TA100, TA98), Sodium azide (TA1535), ENNG (WP2 uvrA) and 9-Aminoacridine (TA1537)
+S9 mix, 2-Aminoanthracene (all strains)
 Doses:-S9 mix; 1.22, 2.44, 4.88, 9.77, 19.5, 39.1, 78.1 μg/plate (Salmonella strains)
313, 625, 1250, 2500, 5000 μg/plate (WP2 uvrA)
+S9 mix; 4.88, 9.77, 19.5, 39.1, 78.1, 156, 313 μg/plate (Salmonella strains)
39.1, 78.1, 156, 313, 625, 1250, 2500 μg/plate (WP2 uvrA)
 S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
 Plate/test:3
 Number of replicates:2
GLP:Yes

 Test results:

Toxicity was observed at a concentration of 39.1 μg/plate (TA100, TA1535, TA98 and TA1537) and 5000 μg/plate (WP2 uvrA) without metabolic activation, and 156 μg/plate (TA100, TA1535, TA98 and TA1537) and 625 μg/plate (WP2 uvrA) with metabolic activation.

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

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

2-2. Non-bacterial in vitro test (chromosomal aberration test)1)

Purity:99.0 %
Type of cell used:Chinese hamster lung CHL/IU cells
Test method:OECD Guidelines No. 473 and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
 Solvent:Dimethylsulfoxide
 Positive controls:-S9 mix, Mitomycin C
+S9 mix, Benzo[a]pyrene
 Doses:-S9 mix (24 hr continuous treatment): 0, 50, 100, 200, 400 μg/ml
-S9 mix (48 hr continuous treatment): 0, 25, 50, 100, 200 μg/ml
-S9 mix (short-term treatment): 0, 50, 100, 200, 400 μg/ml
+S9 mix (short-term treatment): 0, 25, 50, 100, 200 μg/ml
 S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
 Plate/test:2
GLP:Yes

 Test results :

This chemical did not induce structural chromosomal aberrations or polyploidy under the conditions of this experiment.

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

1)The tests were performed by the Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki-machi, Kashima-gun, Ibaraki, 314-02, Japan. Tel +81-479-46-2871 Fax +81-479-46-2874