Display options
Share it on

J Toxicol. 2012;2012:376246. doi: 10.1155/2012/376246. Epub 2012 May 15.

Subchronic hepatotoxicity evaluation of 2,3,4,6-tetrachlorophenol in sprague dawley rats.

Journal of toxicology

Darol E Dodd, Linda J Pluta, Mark A Sochaski, Deborah A Banas, Russell S Thomas

Affiliations

  1. Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709-2137, USA.

PMID: 22666246 PMCID: PMC3362204 DOI: 10.1155/2012/376246

Abstract

Male Sprague Dawley rats were exposed to 2,3,4,6-tetrachlorophenol (TCP) for 5 days, 2 weeks, 4 weeks, or 13 weeks. TCP was administered by gavage at doses of 0, 10, 25, 50, 100, or 200 mg/kg/day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood TCP, gross pathology, and liver histopathology. There were no TCP exposure-related clinical signs of toxicity. Mean body weight decreased 12-22% compared to control in the 100 and 200 mg/kg/day groups. Serum ALT concentrations were increased in rats of the 200 mg/k/day. Liver weight increases were both dose- and exposure time-related and statistically significant at ≥25 mg/kg/day. Incidence and severity of centrilobular hepatocytic vacuolation, hepatocyte hypertrophy, and single cell hepatocytic necrosis were related to dose and exposure time. Following 13 weeks of exposure, bile duct hyperplasia and centrilobular and/or periportal fibrosis were observed in rats primarily of the highest TCP dose group. Blood TCP concentrations increased with dose and at 13 weeks ranged from 1.3 to 8.5 μg/mL (10 to 200 mg/kg/day). A NOAEL of 10 mg/kg/day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥25 mg/kg/day.

References

  1. Arch Environ Contam Toxicol. 1995 May;28(4):537-42 - PubMed
  2. IARC Sci Publ. 1990;(104):390-6 - PubMed
  3. Biochem Biophys Res Commun. 1989 Sep 29;163(3):1275-81 - PubMed
  4. Toxicol Lett. 2004 Feb 28;147(1):35-43 - PubMed
  5. Chem Biol Interact. 1977 Jul;18(1):35-46 - PubMed
  6. Toxicology. 1989 Oct 2;58(2):197-210 - PubMed
  7. Proc Soc Exp Biol Med. 1989 Jun;191(2):139-46 - PubMed
  8. Toxicol Appl Pharmacol. 1974 Apr;28(1):146-50 - PubMed
  9. J Biol Chem. 1965 Apr;240:1811-9 - PubMed
  10. Br J Pharmacol Chemother. 1958 Mar;13(1):20-4 - PubMed
  11. Arch Toxicol. 1978 Feb 21;40(1):63-74 - PubMed
  12. J Toxicol Clin Toxicol. 1983 Jun;20(4):343-52 - PubMed
  13. Exp Toxicol Pathol. 2002 Jul;54(1):9-14 - PubMed
  14. Chemosphere. 2007 Jan;66(2):234-42 - PubMed
  15. Xenobiotica. 1990 Jun;20(6):573-82 - PubMed
  16. Sci Total Environ. 1989 Jul 1;83(1-2):161-72 - PubMed
  17. Scand J Work Environ Health. 1976 Jun;2(2):71-81 - PubMed
  18. Bull Environ Contam Toxicol. 1981 Jun;26(6):795-800 - PubMed

Publication Types