PILOT: Center for Appalachian Research in Environmental Sciences: Effects of Dietary Tris(1,3-Dichloro-2-Propyl) Phosphate (TDCPP) Exposure on Body Burden and Diabetes Risk

The usage of organophosphate flame retardants (OPFR) has been increasing over the past decade, since it was determined that another class of flame retardants (polybrominated diphenyl ethers) are potentially harmful to human health. However, these OPFR have not been thoroughly vetted as to whether they are a safe alternative. The OPFR tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is a high volume industrial chemical to which humans are ubiquitously exposed. TDCPP carcinogenicity has been investigated, but the ability of this chemical to disrupt metabolism and increase type 2 diabetes risk has yet to be determined. Moreover, TDCPP has been detected in seminal fluid, placenta, and breastmilk indicating developmental exposure. Whether TDCPP exposure during developmental windows of susceptibility increases chronic disease risk in adulthood also remains unexplored. Therefore, in order to begin filling these key knowledge gaps, the proposed studies will determine whether TDCPP disrupts metabolism associated with type 2 diabetes development and whether it impairs fetal growth at levels comparable to human exposure. The proposed studies in mice will incorporate a range of TDCPP concentrations into their chow. By putting the contaminant in food, the studies not only model a route of exposure in humans, but also the frequency of exposure. The metabolic consequences of subchronic TDCPP exposure will be evaluated by measuring changes in body weight, body composition, glucose tolerance and insulin sensitivity. Regarding developmental programming of adult metabolic disease, the proposed studies will test whether maternal TDCPP exposure results in reduced birth weight and/or disrupts the early postnatal proliferation rate of pancreatic â-cells, which together forecast later life type 2 diabetes risk. Finally, TDCPP metabolite concentration will be measured in the urine in order to determine what dietary concentration in mice reproduces the metabolite concentration found in humans and determine if metabolic or developmental disruption is observed at human exposure levels. Successful completion of the proposed studies fills key knowledge gaps related to the safety and hazards associated with exposure to this environmental contaminant.