NTP technical report on the toxicology and carcinogenesis studies of p-Chloro-α,α,α-trifluorotoluene (CASRN 98-56-6) in Sprague Dawley (Hsd: Sprague Dawley(r) sD(r)) rats and B6C3F1/N mice (Inhalation studies)
There was some evidence of carcinogenic activity of p-chloro-α,α,α-trifluorotoluene in female Hsd:Sprague Dawley(r) SD(r) rats based on increased incidences of C-cell adenoma in the thyroid gland, increased incidences of benign pheochromocytoma in the adrenal medulla, increased incidences of adenoca...
| Corporate Author: | |
|---|---|
| Format: | eBook |
| Language: | English |
| Published: |
Research Triangle Park, North Carolina, USA
National Toxicology Program, Public Health Service, U.S. Department of Health and Human Services
2018, June 2018
|
| Series: | Technical report
|
| Online Access: | |
| Collection: | National Center for Biotechnology Information - Collection details see MPG.ReNa |
| Summary: | There was some evidence of carcinogenic activity of p-chloro-α,α,α-trifluorotoluene in female Hsd:Sprague Dawley(r) SD(r) rats based on increased incidences of C-cell adenoma in the thyroid gland, increased incidences of benign pheochromocytoma in the adrenal medulla, increased incidences of adenocarcinoma in the uterus, and increased incidences of stromal polyp in the uterus. There was clear evidence of carcinogenic activity of p-chloro-α,α,α-trifluorotoluene in male B6C3F1/N mice based on increased incidences of hepatocellular carcinoma and hepatoblastoma in the liver. There was clear evidence of carcinogenic activity of p-chloro-α,α,α-trifluorotoluene in female B6C3F1/N mice based on increased incidences of hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma in the liver. The combined incidences of adenoma or adenocarcinoma in the Harderian gland of female mice were also considered to be related to treatment. In the Harderian gland, there were significantly increased incidences of degeneration in males and females exposed to 250\sppm or greater. There were significantly increased incidences of cytoplasmic vacuolization in the adrenal cortex of 2,000\sppm males and 1,000 and 2,000\sppm females. In the kidney of males, the severities of hyaline droplet accumulation and chronic nephropathy generally increased with increasing exposure concentration. There were significantly increased incidences of mammary gland hyperplasia in 1,000 and 2,000\sppm females. Males exposed to 2,000\sppm had significantly decreased left cauda and left epididymis weights and numbers of sperm per cauda epididymis. Sperm motility was also significantly decreased in 1,000 and 2,000\sppm males. These findings were associated with histopathologic changes in the testes and epididymides. THREE-MONTH STUDY IN RATS: Groups of 10\smale and 10\sfemale rats were exposed by whole body inhalation to p-chloro-α,α,α-trifluorotoluene vapor at concentrations of 0, 125, 250, 500, 1,000, or 2,000\sppm for 6\shours plus T90 (15\sminutes) per day, 5\sdays per week for 14\sweeks. There was no exposure-related effect on survival. The final mean body weights and mean body weight gains of females exposed to 500\sppm or greater were significantly greater than those of the chamber controls. Alanine aminotransferase and sorbitol dehydrogenase activities were significantly increased in 2,000\sppm males and females. Alkaline phosphatase activities were significantly increased in all exposed male groups and in females exposed to 250\sppm or greater, and bile salt concentrations were significantly increased in females exposed to 500\sppm or greater. Female rats exposed to 2,000\sppm had decreased frequency of estrus and increased frequency of diestrus, a significantly higher probability of extended diestrus, a fewer number of cycles, and a fewer number of rats exhibiting cycles. Based on these findings, p-chloro-α,α,α-trifluorotoluene exhibited the potential to be a reproductive toxicant in both male and female rats. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity of p-chloro-α,α,α-trifluorotoluene in male Hsd:Sprague Dawley(r) SD(r) rats based on increased incidences of C-cell adenoma in the thyroid gland (see Explanation of Levels of Evidence of Carcinogenic Activity; see summary of the Peer Review Panel comments and the public discussion on this Technical Report in Appendix M). The combined occurrences of alveolar/bronchiolar adenoma or carcinoma in the lung of male rats may have been related to treatment. Exposure to p-chloro-α,α,α-trifluorotoluene caused increased incidences of nonneoplastic lesions in the lung and liver of male and female rats and mice, in the nose of male rats, in the adrenal medulla and uterus of female rats, in the forestomach of male and female mice, and in the larynx in male mice. Exposure to p-chloro-α,α,α-trifluorotoluene caused increased severity of nonneoplastic lesions in the kidney of male rats. Synonyms: Benzene, 1-chloro-4-(trifluoromethyl)-; p-chlorobenzotrifluoride; 4-chlorobenzotrifluoride; 1-chloro-4-(trifluoromethyl)benzene; 4-trifluoromethylchlorobenzene There were significant exposure concentration-dependent increases in cholesterol and triglyceride concentrations in males exposed to 500\sppm or greater. In females, cholesterol concentrations were significantly increased in groups exposed to 250\sppm or greater and triglyceride concentrations were significantly increased in the 1,000 and 2,000\sppm groups. There were significant exposure concentration-related increases in the absolute and relative liver weights of males exposed to 250\sppm or greater and of females exposed to 500\sppm or greater. The absolute kidney weights were significantly increased in all exposed groups of males, and relative kidney weights were significantly increased in males exposed to 250\sppm or greater. In the liver, there were significantly increased incidences of centrilobular hepatocyte hypertrophy in males exposed to 250\sppm or greater and in females exposed to 1,000 or 2,000\sppm. |
|---|---|
| Physical Description: | 1 PDF file (various pageings) illustrations |