EVALUATING ENDOCRINE DISRUPTION BY PESTICIDES AND OTHER CONTAMINANTS OF THE FOOD SUPPLY

There is a great need for high throughput assessment of endocrine disrupting activity, e.g. chemicals targeting the activity of receptors for estrogen, androgen, thyroid, and insulin. This will contribute to hazard assessment of chemicals of concern, namely those that are generated by agriculture, that have high production or waste volume, and that are found in the Californian food and drinking water supply. This project proposes to address that need. The goal of this project is two fold: 1) to develop an understanding of the endocrine disrupting properties of data-sparse chemicals in the environment (herein "chemicals of concern") and 2) to develop mechanistic insights into the hazards identified in the first goal.First, potential chemicals of concern will be screened in silico for their molecular docking to endocrine receptors. Second, candidate chemicals of concern will be examined for their dose-dependent effects on molecular and cellular receptor activities, such as receptor mediated- transcription and cell proliferation respectively. Third, a data-rich chemical of concern that was biologically active will be evaluated in vivo for endocrine disrupting effects on rodents, such as reproduction, puberty, metabolism, and mammary cancer. Lastly, molecular analyses will be conducted on chemicals of concern that produce endocrine disrupting effects on rodents to develop mechanistic insights into disease.