Teratogenicity of di(2-ethylhexyl) phthalate, 2-ethylhexanol, 2-ethylhexanoic acid, and valproic acid, and potentiation by caffeine

It is hypothesized that the teratogen di(2-ethylhexyl) phthalate (DEHP) acts by in vivo hydrolysis to 2-ethylhexanol (2-EHXO), which in turn is metabolized to 2-ethylhexanoic acid (2-EHXA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with administration of these a...

Full description

Saved in:
Bibliographic Details
Published inTeratology (Philadelphia) Vol. 35; no. 1; p. 41
Main Authors Ritter, E J, Scott, Jr, W J, Randall, J L, Ritter, J M
Format Journal Article
LanguageEnglish
Published United States 01.02.1987
Subjects
Abnormalities, Drug-Induced
Animals
Caffeine - toxicity
Caproates - metabolism
Caproates - toxicity
Diethylhexyl Phthalate - metabolism
Diethylhexyl Phthalate - toxicity
Drug Synergism
Female
Hexanols - metabolism
Hexanols - toxicity
Maternal-Fetal Exchange
Phthalic Acids - toxicity
Pregnancy
Rats
Rats, Inbred Strains
Valproic Acid - toxicity
Online AccessGet more information

Cover

More Information
Summary:It is hypothesized that the teratogen di(2-ethylhexyl) phthalate (DEHP) acts by in vivo hydrolysis to 2-ethylhexanol (2-EHXO), which in turn is metabolized to 2-ethylhexanoic acid (2-EHXA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with administration of these agents on day 12 of gestation. On an equimolar basis DEHP was least potent, 2-EHXO was intermediate, and 2-EXHA was the most potent of the three agents, which is consistent with the hypothesis. Similarity in the types of defects found with these agents also suggests a common mechanism, with 2-EHXA as the proximate teratogen. All three agents were potentiated by caffeine. Valproic acid, which is an isomer of 2-EXHA, also produced similar defects, and was approximately twice as potent as 2-EHXA.
ISSN:0040-3709
DOI:10.1002/tera.1420350107