Grant: Discovery Grants Program - Individual

OBJECTIVESThe objective of this research program is to determine the extent to which the circumstances of exposure to a toxin may be differentiated through modeling of quantitative relationships between concentrations of a toxin and metabolites in decomposed skeletal tissues.SCIENTIFIC APPROACHThis work will develop quantitative, high throughput mass spectrometric methods to analyze model toxins, their metabolites and endogenous metabolites in decomposed skeletal tissues. The hypothesis is that different patterns of toxin exposure may be differentiated through relationships between relative levels of toxin, toxin metabolites and endogenous metabolites measured in decomposed skeletal tissues. Rats will be exposed to toxin(s) under different dosing patterns, with dose intervals based on the half-life of the toxin 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. Toxins 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 toxin exposure.EXPECTED NOVELTY & SIGNIFICANCEToxicological analysis of skeletal remains is poorly understood. Discrimination between different patterns of toxin exposure may be possible based on comparison of the mathematical relationship between levels of toxin 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.