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Comparison of the short-term effects of di(2-ethylhexyl) phthalate, di(n-hexyl) phthalate, and di(n-octyl) phthalate in rats.

Abstract
This study compares changes in the livers of rats treated with di(2-ethylhexyl) phthalate (DEHP) and its straight-chain analogs di(n-hexyl) phthalate (DnHP) and di(n-octyl phthalate (DnOP). Groups of rats were fed diets containing 20,000 ppm of one of these compounds. Subgroups were killed after 3, 10, and 21 days, and the livers were examined by histological, cytological, and biochemical methods. The results show considerable differences between the effects of the branched-chain phthalate ester DEHP and its straight-chain analogs. The major effects on the liver following administration of diets containing DEHP were midzonal and periportal accumulation of small droplets of lipid, hepatomegaly accompanied by an initial burst of mitosis, proliferation of hepatic peroxisomes and of smooth endoplasmic reticulum accompanied by induction of peroxisomal fatty acid oxidation, damage to the peroxisomal membranes as evidenced by increased leakage of catalase to the cytosol, and centrilobular loss of glycogen and falls in glucose-6-phosphatase activity and in low-molecular-weight reducing agents. In contrast, diets containing DnHP or DnOP induced accumulation of large droplets of fat around central veins leading, by 10 days, to mild centrilobular necrosis and a very slight induction of one peroxisomal enzyme and an increase in liver weight, but no significant changes in any other parameters which were affected by DEHP.
AuthorsA H Mann, S C Price, F E Mitchell, P Grasso, R H Hinton, J W Bridges
JournalToxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 77 Issue 1 Pg. 116-32 (Jan 1985) ISSN: 0041-008X [Print] United States
PMID3966235 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Phthalic Acids
  • di-n-hexyl phthalate
  • di-n-octyl phthalate
  • Diethylhexyl Phthalate
Topics
  • Administration, Oral
  • Animals
  • Body Weight (drug effects)
  • Diethylhexyl Phthalate (pharmacology)
  • Eating (drug effects)
  • Liver (drug effects, enzymology, pathology)
  • Male
  • Organ Size (drug effects)
  • Phthalic Acids (pharmacology)
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship
  • Testis (drug effects)

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