This analysis is only evaluating one chemical at a time and not considering the impacts of multiple chemical exposures. In many traditional risk assessment, exposure guidance values apply to a single substance, from a single route of exposure, and an associated BE also represents a substance-specific level, without consideration Seliciclib clinical trial of aggregate or cumulative exposure. In this sense, the approach presented here is consistent with the many current practise in regulatory risk assessment at this time.

Screening values such as BEs need to be regarded as interim values that can be updated as new data on toxicity become available, or replaced if more robust values such as human epidemiology-derived guidance values in blood or urine are adopted. In general, the urinary BE values were derived using assumptions regarding urinary flow and excretion fraction for people ages 6 and above (Hays et al., 2010). Therefore in this evaluation, urinary data for children under six were excluded due to the uncertainties in

extrapolation of the BE values for application to younger children. As for plasma there are no existing data for children since the survey population in the CHMS was limited to 20–79 years. Relevance of the various biomarkers to the critical effect varies for the different chemicals considered here and this is reflected in the measures of relevance in Table 1 In fact, some biomarkers are highly relevant while other are only moderately relevant for the critical dose ABT-199 in vitro metric (Hays et al., 2008a). Most biomarkers analysed in this manuscript were considered to have medium to high relevance. Biomarkers for inorganic arsenic however were considered to be of low relevance to the critical dose Thymidine kinase metric (Hays et al., 2010). The sampled medium may have been chosen on the basis of ease of collection rather than ease of interpretation in the toxic responses. For example, total BPA (free plus

conjugated) is measured in urine, although free BPA in blood would be a more relevant biomarker for the target organ (Krishnan et al., 2010). The more distant the sampled medium and measured biomarker is from the target organ, the more uncertainty may exist in the interpretation of the data in a risk-based context. Other times, the target organ or system is unknown, because the mode of action is not fully understood, as in the case of biomarkers of inorganic arsenic. The biomonitoring component of the CHMS provides a snapshot of population exposure integrated from all sources and when coupled with BE values, it offers a unique opportunity to screen population and prioritize environmental chemicals based on exposure. The results have the potential to be used by researchers, risk assessors, and risk managers. The CHMS biomonitoring program includes future cycles in which additional analytes will be added or rotated in.