Development of Screening Tools for the Interpretation of Chemical Biomonitoring Data

Abstract

Evaluation of a larger number of chemicals in commerce from the perspective of potential human health risk has become a focus of attention in North America and Europe. Screening-level chemical risk assessment evaluations consider both exposure and hazard. Exposures are increasingly being evaluated through biomonitoring studies in humans. Interpreting human biomonitoring results requires comparison to toxicity guidance values. However, conventional chemical-specific risk assessments result in identification of toxicity-based exposure guidance values such as tolerable daily intakes (TDIs) as applied doses that cannot directly be used to evaluate exposure information provided by biomonitoring data in a health risk context. This paper describes a variety of approaches for development of screening-level exposure guidance values with translation from an external dose to a biomarker concentration framework for interpreting biomonitoring data in a risk context. Applications of tools and concepts including biomonitoring equivalents (BEs), the threshold of toxicologic concern (TTC), and generic toxicokinetic and physiologically based toxicokinetic models are described. These approaches employ varying levels of existing chemical-specific data, chemical class-specific assessments, and generic modeling tools in response to varying levels of available data in order to allow assessment and prioritization of chemical exposures for refined assessment in a risk management context.

Thresholds of Toxicological Concern for cosmetics-related substances: New database, thresholds, and enrichment of chemical space

“…It has also been used as a first-level screening tool to prioritize for review a large number of substances identified as needing an assessment under the Canadian Environmental Protection Act (Health Canada, 2016). Consideration has also been given to whether the TTC approach could be applied to human biomonitoring data (Becker et al, 2012) and to human exposures by non-oral routes (Carthew et al, 2009;Escher et al, 2010;Hennes, 2012;Kroes et al, 2007;Partosch et al, 2015).…”

The role of human biological monitoring in health risk assessment

“…For many chemicals health-based guidance values developed by government agencies using transparent, peer-reviewed methods are unavailable. In such cases, if sufficient animal toxicity data are available, provisional (screening level) guidance values can be derived using the POD values from the key study, after applying adjustment factors (Sand et al, 2011;Becker et al, 2012). Based on the robustness of the toxicity data (e.g., whether the critical data are based on chronic versus acute animal studies), additional UF may need to be considered.…”

“…Based on the robustness of the toxicity data (e.g., whether the critical data are based on chronic versus acute animal studies), additional UF may need to be considered. For several high production volume chemicals, the lowest observable adverse effect level (LOAEL) and NOAEL values could be used as the starting point to derive screening level health-based exposure guidance values (Becker et al, 2012). Chemicals that lack robust toxicity data pose a major challenge for deriving health-based guidance values.…”

“…Chemicals that lack robust toxicity data pose a major challenge for deriving health-based guidance values. In such cases, the threshold of toxicological concern (TTC) method may be used to determine provisional tolerable dose levels from historic data and a distribution of NOAEL values (Kroes et al, 2005;Becker et al, 2012).…”

Hazard quotient profiles used as a risk assessment tool for PFOS and PFOA serum levels in three distinctive European populations

“…Numerous biomonitoring studies have measured concentrations of these chemicals in biological specimens like blood, urine, adipose tissue, and breast milk. To assess the biological relevance of these findings, different approaches have been extensively discussed by Hays et al (2008) and Becker et al (2012). Normally, for a biomonitoring-based risk assessment, the actual exposures to chemicals are compared with the exposure at the relevant PoD which, for the purpose of interpretation of biomonitoring results, can be defined as an internal exposure-response point that marks the threshold above which the incidence begins to increase, thus allowing biomonitoring data to be placed within a public health risk context (Hays et al, 2008).…”