The goal of this contract is to provide support of National Toxicology Program (NTP) or hazard assessment activities targeted toward the prevention of diseases or adverse effects caused by environmental exposure to chemical or physical agents. These studies will elucidate the developmental ontogeny of Peroxisome proliferorator receptor alpha (PPARα) in the rat and relationship to DEHP cancer (and other developmental toxicity) outcomes. In addition, the studies will provide the critical data to undertake mixture studies using various model approaches, to inform on potential cumulative and aggregate cancer and developmental toxicity risk. Recent data have indicated that because of similar modes of action in utero, phthalate esters do show dose addition when administered in combination and thus it would be appropriate to consider cumulative risk for the class, since human subjects (including fetuses) are typically exposed to multiple phthalates.
