NTP technical report on the toxicology studies of indole-3-carbinol (CASRN 700-06-1) in F344/N rats and B6C3F1/N mice and toxicology and carcinogenesis studies of indole-3-carbinol in Harlan Sprague Dawley rats and B6C3F1/N mice gavage studies
There was clear evidence of carcinogenic activity of indole-3-carbinol in male B6C3F1/N mice based on increased incidences of liver neoplasms (hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma). There was no evidence of carcinogenic activity of indole-3-carbinol in female B6C3F1/N...
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| Format: | eBook |
| Language: | English |
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Research Triangle Park, North Carolina, USA
National Toxicology Program, Public Health Service, U.S. Department of Health and Human Services
July 2017, 2017
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| Series: | Technical report
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| Online Access: | |
| Collection: | National Center for Biotechnology Information - Collection details see MPG.ReNa |
| Summary: | There was clear evidence of carcinogenic activity of indole-3-carbinol in male B6C3F1/N mice based on increased incidences of liver neoplasms (hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma). There was no evidence of carcinogenic activity of indole-3-carbinol in female B6C3F1/N mice administered 62.5, 125, or 250\smg/kg. Administration of indole-3-carbinol caused increased incidences of nonneoplastic lesions in the small intestine, mesenteric lymph node, and liver of male and female rats, the thyroid gland of male rats, the uterus of female rats, and the liver, glandular stomach, and nose of male and female mice. Synonyms: 3-(Hydroxymethyl)indole; indole-3-methanol; 3-indolemethanol; 3-indolylcarbinol; 3-indolylmethanol In the mesenteric lymph node, significantly increased incidences of dilatation of the lymphatic vessels associated with lipidosis occurred in 150 and 300\smg/kg males and in 300\smg/kg females. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity (see Explanation of Levels of Evidence of Carcinogenic Activity; a summary of the Peer Review Panel comments and the public discussion on this Technical Report appears in Appendix\sM) of indole-3-carbinol in male Harlan Sprague Dawley rats administered 75, 150, or 300\smg/kg. There was some evidence of carcinogenic activity of indole-3-carbinol in female Harlan Sprague Dawley rats based on increased incidences of malignant uterine neoplasms (primarily adenocarcinoma). The occurrences of fibroma and fibrosarcoma in the skin may have been related to indole-3-carbinol administration. THREE-MONTH STUDY IN F344/N RATS: Groups of 10\smale and 10\sfemale core study rats were administered 0, 18.75, 37.5, 75, 150, or 300\smg indole-3-carbinol/kg\sbody weight in corn oil by gavage, 5\sdays per week for 14\sweeks. Groups of 10\smale and 10\sfemale clinical pathology study rats were administered the same dose for 25\sdays. All rats survived to the end of the study. The mean body weight gain of 300\smg/kg males was significantly less than that of the vehicle controls. The absolute and relative liver weights of all dosed groups of males and females were significantly increased compared to the vehicle controls. The relative kidney weights of 75\smg/kg or greater males and all dosed groups of females were significantly increased, as were the absolute kidney weights of 75\smg/kg males and 18.75, 37.5, and 300\smg/kg females. The absolute and relative thymus weights of 75\smg/kg or greater females were significantly decreased. There were significant and dose-dependent increases in CYP1A1-associated 7-ethoxyresorufin-O-deethylase (EROD) and CYP1A2-associated acetanilide-4-hydroxylase (A4H) activities in the liver of all dosed groups of male and females rats. Pulmonary EROD activity was significantly increased in males administered 75\smg/kg or greater and in all dosed groups of females. Indole-3-carbinol exhibited the potential to be a reproductive toxicant in female rats based on a significantly increased probability of extended diestrus and an increase in overall estrous cycle length (approximately 1\sday) observed at 300\smg/kg. In the small intestine, significantly increased incidences of lamina propria lipidosis and lymphatic ectasia occurred in the duodenum of 150 and 300\smg/kg males and females and in the jejunum of 75\smg/kg or greater males and females. |
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| Physical Description: | 1 PDF file (various pagings) illustrations |