2000 Progress Report: Endocrine Disruption in AdolescenceEPA Grant Number: R827404
Title: Endocrine Disruption in Adolescence
Investigators: Golub, Mari S. , Gershwin, M. Eric , Hendrickx, Andrew G.
Institution: University of California - Davis
EPA Project Officer: Fields, Nigel
Project Period: September 1, 1999 through August 31, 2002 (Extended to August 31, 2003)
Project Period Covered by this Report: September 1, 1999 through August 31, 2000
Project Amount: $670,805
RFA: Endocrine Disruptors (1999) RFA Text | Recipients Lists
Research Category: Economics and Decision Sciences , Health , Safer Chemicals , Endocrine Disruptors
Objective:The objective of the research project is to determine whether administration of estrogenic agents disrupts the timeline of female adolescent development and leads to long-term effects on reproductive, skeletal, immune, and nervous system function in a nonhuman primate.
Progress Summary:This project is designed as a single longitudinal experiment covering the 2-year period of peripubertal development in rhesus monkeys. Although the funding date was designated as September 1, 1999, the coordination of puberty in monkeys with the annual breeding season required that experimental work begin in January 2000. A pilot dose-finding study was conducted using methoxychlor (MXC) and endpoints of vaginal cytology and disruption of ovarian cyclicity as determined by urinary hormone assays. As a result of the study two doses of MXC, 25 and 50 mg/kg body weight, were selected for use in the study. The positive control for the study is diethylstilbestrol at a dose of 0.5 mg/kg. Dosing of the pre-menarchal monkeys began May 2000 and is in its 8th month. We have devised a dosing method based on a feeding syringe that obviates the need for daily nasogastric lavage. DES has proved to be effective as a positive control, with a variety of effects on endpoints of interest. The young monkeys have been successfully trained in the automated behavioral task and are being tested regularly. Several adjustments needed to made in the markers used for the bimonthly FACS assessments for immune system effects. In addition, chemistry panels were added to the longitudinal assessment. The health of the monkeys is being closely monitored by veterinary staff and no clinically important effects of the treatments have been detected to date. Although the main endpoints of the study (completion of adolescent maturation) have not yet been evaluated, some effects have been detected on the adolescent growth spurt, hematology, clinical chemistry, and manifestations of sex skin swelling. Because rhesus monkeys typically achieve menarche from October to January of their third year of life, data on abnormal timing of menarche will be available shortly.
Future Activities:The project will proceed according to the original timeline. Assessment of maturation at the conclusion of the adolescent period will be conducted in the coming year. In addition, we hope to design and obtain funding for a pharmacokinetic study that will enable a comparison of estrogenic effects across species and extrapolation to humans. Another additional small study is planned varying the timing of daily dosing relative to behavioral testing to look for short-term effects of the estrogenic treatments on cognitive function.
Journal Articles:No journal articles submitted with this report: View all 16 publications for this project
Supplemental Keywords:health effects, human health, sensitive populations, dose response, mammalian, children, sex, chemicals, biology., RFA, Health, Scientific Discipline, Health Risk Assessment, Environmental Chemistry, Endocrine Disruptors - Environmental Exposure & Risk, Epidemiology, Risk Assessments, endocrine disruptors, Susceptibility/Sensitive Population/Genetic Susceptibility, Children's Health, genetic susceptability, Biology, Endocrine Disruptors - Human Health, puberty, sensitive populations, adolescence, cytotoxic, endocrine disrupting chemicals, steroid, Human Health Risk Assessment, Lymphocytes, Methoxychlor, children, assessment of exposure, human exposure, immune system response, environmental toxicant, harmful environmental agents, hypothalamus, reproductive processes, environmentally caused disease, estrogen receptors, hormone production, diethyl stilbestrol, age dependent response, environmental hazard exposures, toxics
Progress and Final Reports:Original Abstract