Ideally, a clear understanding of the quantitative linkages between exposure, dose, and biomarker levels will exist for any biomarker that is used in an epidemiological study. Considering see more the invasive nature of target tissue sampling, most biomarker-based epidemiological

studies utilize samples of blood, urine, hair, or other easily-accessible matrices. Elucidating quantitative relationships between biomarker measurements from these matrices and exposure/dose levels requires an understanding of chemical absorption, distribution, metabolism, and elimination (ADME); these processes are frequently described using pharmacokinetic (PK) models, or physiologically-based pharmacokinetic (PBPK) models. Prior to the use of biomarkers in an epidemiological study, a solid understanding of chemical ADME should exist, as well as the intrinsic (e.g., genetics, life-stage, pregnancy, gender) and extrinsic (e.g., diet, medication, medical conditions) factors that are likely to affect ADME. Furthermore, for short-lived biomarkers, it is important to know specific timing details (e.g., time of day, time since last meal for those chemicals associated with dietary exposure, time since last urine void) in relation to sample collection. Ideally, the

relationships between Anticancer Compound Library concentration biomarker concentration and exposure/dose levels, and the effects of intrinsic, extrinsic, and timing factors on these relationships, will be thoroughly evaluated before the biomarker is used in an epidemiological study. Critical information that is needed to properly interpret the biomarker (with respect to exposure/dose) should then be collected and carefully evaluated as part of the study. The costs and benefits of each biomarker of exposure should be carefully examined and interpreted as part of any epidemiological evaluation. cAMP It is important to note that matrix selection is an integral component of exposure and/or epidemiology research, and multiple

factors must be considered including measurement capability, contamination issues, and target analyte association with exposure or health outcome. BEES-C addresses each of these issues separately. Bisphenol A (BPA) is measured in urine in the free form (parent), as sulfate- or glucoronide-bound conjugates, or as a combination (total BPA) of the free and conjugated forms (Harthé et al., 2012, LaKind et al., 2012a, Völkel et al., 2008 and Ye et al., 2005). Several recent studies have examined endocrine-related health outcomes associated with BPA exposure. The most biologically-relevant biomarker is the free (parent) BPA, because only parent BPA is considered active in terms of estrogenicity (EPA (US Environmental Protection Agency), 2013 and WHO (World Health Organization), 2011).