Trifluoromethylbenzene

(トリフルオロメチル)ベンゼン


[CAS No. 98-08-8]

Benzotrifluoride

ベンゾトリフルオリド

Molecular formula: C7H5F3  Molecular weight: 146.11

ABSTRACT

Trifluoromethylbenzene was studied for oral toxicity in Crj:CD (SD) rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 20, 100 and 500 mg/kg/day.

With regard to repeated dose toxicity, effects on liver and kidney were observed in both sexes given more than 100 mg/kg, indicating a NOEL is of 20 mg/kg/day for both sexes. In the reproductive/developmental toxicity study, there were no effects of the test article on the reproductive performance of the parents. Depression of body weight gain in offspring of all treatment groups was observed without any necropsy findings. The NOELs are considered to be 500 mg/kg/day for reproductive performance of the parents and less than 20 mg/kg/day for offspring development.

Trifluoromethylbenzene was not mutagenic to Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA, with or without an exogeneous metabolic activation system.

Trifluoromethylbenzene induced neither structural chromosomal aberrations nor polyploidy in CHL/IU cells, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose and Reproductive/Developmental Toxicity 1)

Purity:99.7%
Test species/strain:Rat/Crj:CD (SD)
Test method:OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test
 Route:Oral (gavage)
 Doses:0 (vehicle), 20, 100, 500 mg/kg/day
 Number of animals/group:Males, 12; females, 12
 Vehicle:Corn oil
 Administration period:Males, 49 days
Females, from 14 days before mating to day 3 of lactation
 Terminal kill:Males, day 50
Females, day 4 of lactation
GLP:Yes

  Test Results:

<Repeated dose toxicity>
No effects related to the test article were observed in terms of clinical signs, body weights, food consumption and hematological findings. Increases of total protein, albumin, total cholesterol, triglyceride and phospholipids, and decrease of glucose were observed on biochemical examination in the 500 mg/kg group. As necropsy findings, renal hypertrophy and discoloration were observed in males of the 500 mg/kg group. Increase kidney weights in males given more than 100 mg/kg and in females of the 500 mg/kg group, and increased liver weights in males given more than 100 mg/kg were observed. On histopathological examination, centrilobular hepatocyte hypertrophy in both sexes, and hyaline droplets, necrosis, basophilic change and dilatation of renal proximal tubules in males were noted in the 100 and 500 mg/kg groups. Therefore, the NOEL is considered to be 20 mg/kg/day for both sexes.

<Reproductive and developmental toxicity>
With regard to reproductive performance, no effects related to the test article were observed on the estrous cycle, copulation index and fertility indices for males or females. Examination of delivery and during the lactation period did not reveal any effects related to the test article in terms of the numbers of corpora lutea, implantations, litter and live newborns, gestational days, gestation index, stillborn index, birth index or the sex ratio. No external anomalies were observed. Depression of body weight gain in offspring was apparent in all treatment groups and decrease of the viability index on day 4 was also noted for the 500 mg/kg group. Therefore, the NOELs are considered to be 500 mg/kg/day for reproductive performance of parent and less than 20 mg/kg/day for offspring development.

2. Genetic Toxicity

2-1. Bacterial test 2)

Purity:above 98 %
Test species/strains:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test methods:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD (471 and 472)
 Procedures:Plate incorporation method
 Solvent:DMSO
 Positive controls:-S9 mix, 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, WP2, TA98), Sodium azide (TA1535)
and 9-Aminoacridine (TA1537),
+S9 mix, 2-Aminoanthracene (five strains)
 Doses:-S9 mix, 0, 31.3, 62.5, 125, 250, 500 and 1000 μg/plate (TA100, TA1535 and TA1537) and 0, 31.3 - 2000 μg/plate (WP2 and TA98),
+S9 mix, 0, 31.3 - 1000μg/plate (TA1535 and TA1537), 62.5 - 2000 μg/plate (TA100, WP2 and TA98)
 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 500 μg/plate (TA100, TA1535 and TA1537) and 1000 μg/plate (TA98 and WP2) without S9 mix and at 500 μg/plate (TA1535 and TA1537), 1000 μg/plate (TA98), 1500 μg/plate (TA100 and WP2) 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:[ ][ ][*]

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

Purity:more than 98%
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
 Solvent:Dimethyl sulfoxide
 Positive controls:-S9 mix, Mitomycin C
+S9 mix, Cyclophosphamide
 Doses:-S9 mix (continuous treatment): 0, 0.075, 0.15, 0.30 mg/ml
-S9 mix (short-term treatment): 0, 0.38, 0.75, 1.5 mg/ml
+S9 mix (short-term treatment): 0, 0.38, 0.75, 1.5 mg/ml
 S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
 Plates/test:2
GLP:Yes

  Test results:

Cytogenetic effects were not seen under the conditions of this experiment.

Genotoxic effects:

clastogenicity polyploidy 
+?- +?-
without metabolic activation:[ ][ ][*] [ ][ ][*]
with metabolic activation:[ ][ ][*] [ ][ ][*]

1)The tests were performed by Safety Assessment Laboratory, Panapharm Laboratories Co., Ltd. 1285 Kurisaki-machi, Uto-shi, Kumamoto, 869-04, Japan. Tel +81-964-23-5111 Fax +81-964-23-2282
2)The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627