The proposed study is a competing continuation of R01 ES09718, 'Environmental Organochlorines and semen quality'. There is scientific and public concern about whether several families of chemicals considered endocrinologically active, such as PCBs and phthalates, have adverse male reproductive health effects. Concern stems from studies showing that a majority of the U.S. general population are exposed to PCBs and phthalates, as well as animal and limited human studies suggesting possible associations of PCBs and phthalates with adverse reproductive health effects. In the proposed competing continuation, we will build upon our earlier work and more precisely define the exposure-response relationships we found between estrogenic and anti-estrogenic PCBs and alterations in semen parameters and reproductive hormones. We will extend our investigation to include measurements for hydroxylated metabolites of PCBs (OH-PCBs) since studies report that OH-PCBs are prevalent in human serum and may be more biologically active than the parent PCBs. The proposed new research direction on phthalates and male reproductive health evolved from a pilot study conducted in collaboration with the CDC. Long-standing toxicological data consistently shows that select phthalatesare male reproductive toxins. Leveraging the ongoing study on organochlorines and semen quality, we analyzed urine samples for phthalate monoesters from a sub-group of men. The results were suggestive of an association between select phthalates and alterations in semen parameters and reproductive hormones, as well as increased sperm DNA damage measured with the comet assay. The apoptosis DNA diffusion assay will be incorporated into the proposed study since the measurement of apoptosis is a necessary counterpart to the assessment of sperm DNA damage, as many cells with significant DNA damage are eliminated by apoptosis. To determine the optimal design for assessing exposure to phthalates, we conducted an exposure study on a sub-sample of men from the organochlorine and semen quality study. Each subject collected nine urine samples over three months. Variance components for between-subject and with-in subject, consisting of monthly and daily variances, were calculated. Based on our results, the optimal exposure assessment strategy for the proposed study is to collect three urine samples from all subjects on day 1, 2 and 31 of their study participation.
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