Derivation of Biomonitoring Equivalent (BE) Values for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds: A Screening Tool for Interpretation of Biomonitoring Data in a Risk Assessment Context

Abstract

Recent efforts by the U.S. Centers for Disease Control and Prevention and other researchers have resulted in a growing database of measured concentrations of dioxins and related compounds in blood samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring equivalent (BE) values are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments This study reviews available health based exposure guidance values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds from a variety of agencies including the World Health Organization Joint Expert Committee on Food Additives (JECFA), the European Commission Scientific Committee on Foods (ECSCF), the United Kingdom Committee on Toxicology (UKCOT), and the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) to estimate corresponding BE values for dioxin-like compounds in blood on a serum lipid-adjusted basis. Based on data from the animal studies underlying the exposure guidance values, a serum lipid-adjusted dioxin toxicity equivalent (TEQ) concentration of approximately 15 ppt is consistent with the ATSDR minimal risk level (MRL) for dioxins. Serum lipid-adjusted TEQ concentrations of approximately 31 to 74 ppt are consistent with the tolerable intakes estimated by the other three agencies. These values may be used as screening tools for evaluation of biomonitoring data for dioxins in the context of existing risk assessments and for prioritization of the potential need for additional risk assessment efforts for dioxins.

Perspective on serum dioxin levels in the United States: an evaluation of the NHANES data

“…We briefly describe here the method used to develop BE values for the PCDDs/Fs and structurally related PCBs; detailed information is given in Aylward et al, 2008. Several agencies have conducted risk assessments for dioxin-like compounds and have established exposure guidance values in terms of daily, weekly, or monthly intake of these compounds.…”

“…Biomonitoring equivalents have been estimated corresponding to each of these exposure guidance values (Aylward et al, 2008). Each BE value is derived through consideration of the toxicological data underlying the respective exposure guidance value, understanding of the pharmacokinetics of dioxins in humans, and application of appropriate uncertainty factor components to the toxicological point of departure (Aylward et al, 2008).…”

“…Biomonitoring equivalents have been estimated corresponding to each of these exposure guidance values (Aylward et al, 2008). Each BE value is derived through consideration of the toxicological data underlying the respective exposure guidance value, understanding of the pharmacokinetics of dioxins in humans, and application of appropriate uncertainty factor components to the toxicological point of departure (Aylward et al, 2008). The BE values can be used as screening tools to identify whether the measured population concentrations are in the region of low, medium, or high priority for risk assessment follow-up (Hays et al, 2008;LaKind et al, 2008).…”

Polychlorinated Dibenzo-p-Dioxins, Polychlorinated Dibenzofurans, and Dioxin-Like Polychlorinated Biphenyls in Umbilical Cord Serum from Pregnant Women Living Near a Chemical Plant in Tianjin, China

“…BE values are designed to be used as screening tools to assess whether chemicals have a large, a small, or no margin of safety compared to existing health-based exposure guidelines [46]. Aylward et al reported that a serum lipid-adjusted TEQ of approximately 15 pg·g −1 lipid, on the basis of neurodevelopmental effects, is consistent with the minimal risk level (MRL) recommended by the Agency for Toxic Substances and Disease Registry [47]. Referring to the TEQs ∑(PCDDs/Fs + dl-PCBs) in our data, 42.7% of the participants exhibited levels higher than the BE value.…”

Evaluation of relative effect potencies (REPs) for dioxin-like compounds to derive systemic or human-specific TEFs to improve human risk assessment

“…The above systemic TEQ estimates that were calculated using the adjusted systemic TEF values can be further evaluated in a risk assessment context. Previously, Biomonitoring Equivalents (BEs), which are estimates of steady-state biomarker concentrations consistent with chronic exposure at a reference dose (RfD) or tolerable daily intake (TDI), have been estimated for TCDD (Aylward et al 2008 , 2013 ). The physiologically based pharmacokinetic (PBPK) model for TCDD selected by USEPA in their 2012 RfD evaluation was used to estimate steady-state serum TCDD concentrations consistent with chronic exposure at the USEPA reference dose (RfD) or the WHO JECFA TDI.…”