Assessing Human Exposure to Animal Neurocarcinogens: A Pilot Study

Abstract

MAB4-O-04 Introduction: The assessment of multimedia and multipathway exposures to known and suspected animal neurocarcinogens (ANCs) in an epidemiologic investigation of brain cancer has not been attempted previously. We hypothesize that the poor associations or absence of causal links between exposure to a chemical agent and brain tumors may be due to inadequate exposure data underlying the analysis and/or exposure data nonspecific to chemicals, which have been demonstrated to cause neurocarcinogenicity in animal models. Methods: We present new human exposure assessment tools and methods used in support of a case-control study of brain tumors, with a focus on known and/or suspected animal neurocarcinogens. We initially reviewed the toxicity literature and compiled a list of 27 known ANCs and 15 suspected ANCs. Subsequently, we performed a comprehensive review of the physical, chemical, toxicological, environmental fate, and transport information for each compound to determine exposure media and pathway(s) of concern for each chemical of interest. Results: A neurocarcinogen-specific questionnaire was developed using occupational, environmental, and dietary exposure questions pertaining to specific exposure scenarios to assess overall human ANC exposure with consideration for the expected environmental media (air, water, and soil) and expected pathways of exposure (ingestion, inhalation, dermal). Data were obtained on approximately 200 cases from brain tumor clinics 180 friend and 180 sibling controls. Exposure specific indices created from these responses provide variation in human exposure for epidemiologic analysis. Preliminary results suggest exposures to selected ANCs in the breathing zone may increase the risk of brain tumors. Discussion and Conclusions: A neurocarcinogen questionnaire and detailed exposure matrix are essential for estimation of cumulative exposure index across pathway(s), across media, and across multiple chemicals. This exposure matrix links each compound to relevant questions in the questionnaire and allows calculation of an exposure score as a relative indicator of pathway-specific or cumulative exposure of an individual within the study population. These data, combined with biomarkers of exposure, will eventually provide a comprehensive assessment of ANCs and brain cancer.