A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): non-monotonic dose-response and low dose effects on rat brain aromatase activity.

Full Abstract

Di-(2-ethylhexyl)-phthalate (DEHP) is a commonly used plasticizer which can act as an endocrine disruptor. It has been suggested that in addition to its antiandrogenic effects, DEHP may interfere with estrogen metabolism through suppression of aromatase enzyme activity. This enzyme catalyzes the conversion of testosterone to estradiol and plays a critical role in brain sexual differentiation. We investigated the effects of two wide ranges of DEHP doses on brain aromatase activity of male and female rat offspring. Wistar rat dams were treated daily with DEHP and peanut oil (control) by gavage from gestation day 6 to lactation day 21 at doses of 0.015, 0.045, 0.135, 0.405 and 1.215mgDEHP/kgbodyweight(bw)/day (low doses) and at 5, 15, 45, 135 and 405mgDEHP/kgbw/day (high doses). Aromatase activity was determined in hypothalamic/preoptic area (HPOA) brain sections from male and female pups on postnatal days (PNDs) 1 and 22. In males on PND 1, aromatase activity was inhibited at low doses and increased at high doses resulting in a non-monotonic dose-response profile which resembled a J-shaped curve. Inhibition was statistically significant at 0.135 and 0.405mgDEHP/kg/day, while increased activity was observed at 15, 45 and 405mg/kg/day. In contrast to findings on PND 1, aromatase activity at weaning (PND 22) was more affected in females than in males. An increase in aromatase activity was observed at only one dose in males (0.405mg/kg/day) while an increase in activity was observed at all doses in the females except for 0.045 and 5mgDEHP/kg/day. Overall, these results indicate that males and females respond differently to DEHP not only in regard to the age at which effects are manifested, but also in the shape of the dose-response curve. To our knowledge, this is the first study to report biological effects of DEHP at doses that overlap with the estimated exposure of the general human population.

Learn Faster Today Improve your study skills

Author information

Author/s: Andrade, Anderson J M (AJ); Grande, Simone W (SW); Talsness, Chris E (CE); Grote, Konstanze (K); Chahoud, Ibrahim (I);

Affiliation: Charité University Medical School Berlin, Campus Benjamin Franklin, Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Garystrasse 5, 14195 Berlin, Germany.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Toxicology (Toxicology), published in Ireland. (Language: eng)

Reference: 2006-Oct; vol 227 (issue 3) : pp 185-92

Dates: Created 2006/09/25; Completed 2006/11/13; Revised 2006/11/15;

PMID: 16949715, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article (including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Age Factors
Animals
Aromatase - metabolism
Brain - drug effects; enzymology
Diethylhexyl Phthalate - pharmacokinetics; toxicity
Dose-Response Relationship, Drug
Endocrine Disruptors - pharmacokinetics; toxicity

Female
Lactation
Male
Pregnancy
Prenatal Exposure Delayed Effects - chemically induced; enzymology; physiopathology
Rats
Sex Differentiation - drug effects

Associated Chemicals: Endocrine Disruptors (0) ; Diethylhexyl Phthalate (117-81-7) ; Aromatase (EC 1.14.14.1)

These are the highest related articles currently in the database:

See 100+ related articles.