Biomonitoring equivalents: A screening approach for interpreting biomonitoring results from a public health risk perspective

Abstract

Advances in both sensitivity and specificity of analytical chemistry have made it possible to quantify substances in human biological specimens, such as blood, urine, and breast milk, in specimen volumes that are practical for collection from individuals. Research laboratories led by the Centers for Disease Control and Prevention (CDC) in its series National Report on Human Exposure to Environmental Chemicals [Centers for Disease Control and Prevention (CDC), 2005. Third National Report on Human Exposure to Environmental Chemicals. NCEH Pub. No. 05-0570.] are dedicating substantial resources to designing and conducting human biomonitoring studies and compiling biomonitoring data for the general population. However, the ability to quantitatively interpret the results of human biomonitoring in the context of a health risk assessment currently lags behind the analytical chemist's ability to make such measurements. The traditional paradigm for human health risk assessment of environmental chemicals involves comparing estimated daily doses to health-based criteria for acceptable, safe, or tolerable daily intakes (for example, reference doses [RfDs], tolerable daily intakes [TDIs], or minimal risk levels [MRLs]) to assess whether estimated doses exceed such health screening levels. However, biomonitoring efforts result in measured chemical concentrations in biological specimens (the result of absorption, distribution, metabolism and excretion of administered doses) rather than estimated intake doses. Quantitative benchmarks of acceptable or safe concentrations in biological specimens (analogous to RfDs, TDIs, or MRLs) needed to interpret these levels exist for very few chemicals of environmental interest. This paper discusses issues inherent in converting existing health screening benchmarks based on intake doses to screening levels for evaluating biomonitoring data, and presents methods and approaches that can be used to derive such screening levels (termed ''Biomonitoring Equivalents,'' or BEs) for a range of chemicals and biological media.

Reconstructing population exposures to environmental chemicals from biomarkers: Challenges and opportunities

“…Lack of specificity can lead to the problem of identifiability, whereas the lack of sensitivity may result in large uncertainties in the reconstruction results. Biochemical properties of absorption, distribution, metabolism, and elimination (ADME) impact the types of exposures that can be estimated from the biomarker data (Hays et al, 2007). Variability in ADME characteristics also results in a significant variation in the biological half-lives of different groups of environmental pollutants, such as volatile organics, organophosphate pesticides, and toxic metals.…”

“…However, simplifying assumptions such as linearity are known to produce erroneous exposure characterizations in the forward mode of analysis and therefore they should be considered with great caution in the inverse mode of analysis. An "interim" step in interpreting biomonitoring data is provided by biomonitoring equivalents, which employ forward modeling to determine exposure levels that correspond to the reference doses of the chemicals of concern (Hays et al, 2007). This indeed can provide useful insight in relating biomarker levels to regulatory requirements under the simplifying assumption of chronic, steady exposures.…”

“…This indeed can provide useful insight in relating biomarker levels to regulatory requirements under the simplifying assumption of chronic, steady exposures. However, as Hays et al (2007) also implicitly recognize, these techniques are not applicable to reconstructing realworld exposure scenarios, because such scenarios typically involve non-steady, transient exposures with variable frequencies, durations, and magnitudes.…”

Testing the coherence between occupational exposure limits for inhalation and their biological limit values with a generalized PBPK-model: The case of 2-propanol and acetone

“…Additionally, biological limit values (BLVs) such as biological exposure indices (BEI) and Biologische Arbeitsstoff-Toleranzwerten (BAT) have been derived as reference values for biological media, such as blood and urine. Another approach in which external dose-based guidance values, such as the tolerable daily intake (TDI) or reference dose (RfD), are translated into so-called biomonitoring equivalent (BE) values is increasingly being used in the public health context, but so far not in occupational settings (Hays et al, 2007(Hays et al, , 2008.…”

Creatinine corrections for estimating children's and adult's pesticide intake doses in equilibrium with urinary pesticide and creatinine concentrations

“…By physiologic-based pharmaco-kinetic modeling. One can estimate the equilibrium or ''biological equivalent'' blood serum contaminant concentration (mg/dl), which would result from a constant daily dietary intake at the RfD level (Timchalk et al, 2002;Hays et al, 2007). With a physiologic-based pharmaco-kinetic (PBPK) submodel of renal clearance and an assumption of the daily fluid intake (l/day), estimate the average daily urinary contaminant concentration, mg/l, which would be excreted in equilibrium with the calculated blood serum contaminant concentration.…”