Mammary Gland Development as a Sensitive End Point after Acute Prenatal Exposure to an Atrazine Metabolite Mixture in Female Long-Evans Rats
Open Access
- 1 April 2007
- journal article
- Published by American Chemical Society (ACS) in Environmental Health Perspectives
- Vol. 115 (4) , 541-547
Abstract
Background: Atrazine (ATR), a widely used chlorotriazine herbicide, inhibits a number of endocrine-dependent processes, including gonadotrophin surges and mammary gland development in rats. Chlorotriazine herbicides are rapidly metabolized in plants and animals to form a group of metabolites that are detected both in the environment and in exposed animals. The extent to which these metabolites are responsible directly for the observed health effects is not understood. Objectives: Our goal was to determine if a mixture of ATR metabolites, in proportions found in the environment, might produce developmental effects in Long-Evans rats following exposure late in pregnancy. Methods: We administered an ATR metabolite mixture (AMM) containing ATR, hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine orally to pregnant Long-Evans rats at 0.09, 0.87, or 8.73 mg/kg body weight (bw)/day, on gestation days 15–19, using 0 and 100 mg ATR/kg bw/day as negative and positive controls, respectively. Results: We observed no significant effect of acute AMM exposure on body weight gain in dams during the dosing period, weight loss in pups on postnatal day (PND)4, or pubertal timing, as is seen with ATR alone. However, as with ATR, we detected delayed mammary gland development, evaluated by whole mount analysis, as early as PND4 in all treatment groups. Conclusions: Our data suggest that acute exposure to AMM at levels as low as 0.09 mg/kg bw during late pregnancy causes persistent alterations in mammary gland development of female offspring, and that these effects do not appear to be related to bw or associated with pubertal timing.Keywords
This publication has 33 references indexed in Scilit:
- Identification of a Novel Hemoglobin Adduct in Sprague Dawley Rats Exposed to AtrazineChemical Research in Toxicology, 2006
- Pubertal Development in Female Wistar Rats following Exposure to Propazine and Atrazine Biotransformation By-Products, Diamino-S-Chlorotriazine and HydroxyatrazineToxicological Sciences, 2003
- Strain comparisons of atrazine-induced pregnancy loss in the rat☆11☆Disclaimer: The information in this document has been funded wholly by the US Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.Reproductive Toxicology, 2000
- Neuroendocrine and reproductive effects of contemporary-use pesticidesToxicology and Industrial Health, 1999
- Appearance of Mammary Tumors in Atrazine-Treated Female Rats: Probable Mode of Action Involving Strain-Related Control of Ovulation and Estrous Cycling1998
- Effect of atrazine on ovarian function in the ratReproductive Toxicology, 1996
- Factors affecting mammary tumor incidence in chlorotriazine-treated female rats: hormonal properties, dosage, and animal strain.Environmental Health Perspectives, 1994
- Chloro‐s‐triazine antagonism of estrogen action: Limited interaction with estrogen receptor bindingJournal of Toxicology and Environmental Health, 1994
- Chronic effects of atrazine on estrus and mammary tumor formation in female Sprague‐Dawley and Fischer 344 ratsJournal of Toxicology and Environmental Health, 1994
- Short‐term effects of chlorotriazines on estrus in female Sprague‐Dawley and Fischer 344 ratsJournal of Toxicology and Environmental Health, 1994