Xenobiotic and Metabolite Profiling in Skeletal Remains for Classification of Xenobiotic Exposure Patterns

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OBJECTIVESThe objective of this research program is to determine the extent to which the circumstances of exposure to a xenobiotic may be differentiated through modeling of quantitative relationships between concentrations of a xenobiotic and metabolites in decomposed skeletal tissues.SCIENTIFIC APPROACHThis work will develop quantitative, high throughput mass spectrometric methods to analyze model xenobiotics, their metabolites and endogenous metabolites in decomposed skeletal tissues. The hypothesis is that different patterns of xenobiotic exposure may be differentiated through relationships between relative levels of xenobiotic, toxin metabolites and endogenous metabolites measured in decomposed skeletal tissues. Rats will be exposed to xenobiotic(s) under different dosing patterns, with dose intervals based on the half-life of the xenobiotic in rats. Placebo exposed animals will serve as control groups for each toxin studied. For each pattern of exposure, various postmortem environments (e.g., temperature, humidity, soil conditions, entomological activity and/or degrees of decomposition) will be investigated. Xenobiotics and metabolites will be extracted from bone prior to analysis by chromatography and mass spectrometry. Mathematical relationships between toxin and metabolite levels will be investigated in order to determine if they may be used to predict different patterns of xenobiotic exposure.EXPECTED NOVELTY & SIGNIFICANCEToxicological analysis of skeletal remains is poorly understood. Discrimination between different patterns of xenobiotic exposure may be possible based on comparison of the mathematical relationship between levels of xenobiotic and metabolites in bone. This would provide an interpretive framework for toxicological measurements in skeletal tissues that is not currently possible, significantly impacting the forensic and environmental sciences.