CHEMISTRY SUPPORT SERVICES TO THE ENVIRONMENAL TOXICOLOGY PROGRAM

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The goal of this project is to provide support of National Toxicology Program (NTP) hazard identification activities targeted toward the prevention of diseases or adverse effects caused by environmental exposure to chemical or physical agents. Toxicity testing is an important aspect of public health research in that it serves to identify chemicals that are hazardous to human health. Proper chemical analyses are required to ensure that, in toxicity studies, the test species are exposed to the prescribed chemicals at the specified dose concentrations. This contract contributes to the ability of toxicity studies to provide evidence of heightened cancer risk along with other toxicological outcomes, by providing characterization of the chemicals studied, confirmation of the dose levels administered, and internal dose determinations. This information is critical to evaluation of toxicity tests and development of sound, scientific conclusions about the potential toxicity of the study chemical in the test species and ultimately supports the risk assessment efforts of National Toxicology Program and other federal agencies. With internal dose information provided by this contract, extrapolations to humans can be made so that the public can be adequately informed about risk factors arising from exposure to studied chemicals. During FY10, more than 280 tasks were begun, performed, and/or completed in support of NTP and DIR research and testing protocols. In support of an NTP dietary zinc carcinogenesis study, an ICP-OES method was developed to analyze whole blood for Zn. 140 samples from the 2-year carcinogenesis study were analyzed for Zn, Cu, and Fe. Zn concentrations ranged from ~5.5 to ~9.0 regardless of Zn dose. In support of NTP reproductive toxicity studies, 15 phthalates were procured and comprehensively characterized using ultra high performance liquid chromatography (UPLC), gas chromatography, elemental analysis, and infrared spectroscopy. This year characterization efforts focused on the large, branched phthalates in the group. These substances are complex mixtures of branched phthalates, with chain length averages that reflect their nomenclature. Dose formulation and dose analysis methods were developed and validated for di-(2-ethylhexyl) phthalate in two different feed vehicles. In support of the carcinogenesis program, a low-level impurity screen was conducted on styrene acrylonitrile trimer looking for the presence of styrene and acrylonitrile mono- and dimers. Styrene monomer was found at a concentration of 230 ppm along with trace amounts of the dimer. Acrylonitrile was not detected (LOD = 80 ppm). In support of the NTP mold initiative, a source was identified to synthesize deoxynivalenol, a mycotoxin found on grain, which is a target test article for the NTP immunotoxicology program. In support of a DIR study, which is looking at diabetes in a population of Pima Indians, 350 serum samples, collected from the study, were analyzed for total and organic arsenic. In support of the NTP targeted testing program, 4 of 12 chemicals scheduled for liver toxicity testing were procured and characterized. A common dose vehicle was found and a formulation method was developed to administer each chemical. In support of a soy isoflavone study, formulations of the positive control, ethinyl estradiol, were prepared and analyzed for use in a uterotropic assay.