Interspecies scaling of toxicity reference values in human health versus ecological risk assessments: A critical review

Abstract

Risk assessments that focus on anthropogenic chemicals in environmental media—whether considering human health or ecological effects—often rely on toxicity data from experimentally studied species to estimate safe exposures for species that lack similar data. Current default extrapolation approaches used in both human health risk assessments (HHRAs) and ecological risk assessments (ERAs) account for differences in body weight between the test organisms and the species of interest, but the two default approaches differ in important ways. HHRAs currently employ a default based on body weight raised to the three‐quarters power. ERAs for wildlife (i.e., mammals and birds) are typically based directly on body weight, as measured in the test organism and receptor species. This review describes differences in the experimental data underlying these default practices and discusses the many factors that impact interspecies variability in chemical exposures. The interplay of these different factors can lead to substantial departures from default expectations. Alternative methodologies for conducting more accurate interspecies extrapolations in ERAs for wildlife are discussed, including tissue‐based toxicity reference values, physiologically based toxicokinetic/toxicodynamic modeling, chemical read‐across, and a system of categorical defaults based on route of exposure and toxic mode of action.

Methylmercury Effects on Birds: A Review, Meta‐Analysis, and Development of Toxicity Reference Values for Injury Assessment Based on Tissue Residues and Diet

“…For the dietary‐dosing analyses, we used dietary Hg concentrations in μg/g dry weight without scaling to body weight. Farrar & Kravitz (2021) and Clewell & Fuchsman (2023) recommended that for chronic, long‐term chemical exposures via the diet, such as MeHg contamination, toxicity reference values should be based on the concentration of the toxicant in the diet (feed; i.e., µg/g), without needing to determine a daily dose based on body weight (i.e., µg/g body wt per day), and can be applied across species without allometric scaling to body weight. It was still necessary to convert dietary‐dosed Hg concentrations into a common unit.…”

Toxicological effects assessment for wildlife in the 21st century: Review of current methods and recommendations for a path forward

“…Clearly, a greater understanding of toxicokinetics and toxicodynamics is needed if advancements are to be made in improving the extrapolation of data from laboratory animal models to freeranging wildlife. New approach methodologies that enable robust interspecies extrapolations with reduced uncertainty without further vertebrate testing should be a medium-to long-term priority (see also Fuchsman & Clewell, 2023;Rattner et al, 2023).…”

Wildlife ecological risk assessment in the 21st century: Promising technologies to assess toxicological effects

“…Interspecific differences also consider toxicodynamics that influence interactions between the contaminant and its target (e.g., differences in aryl hydrocarbon [AhR] binding and activation for dioxin-like compounds [DLC]). Clewell and Fuchsman (2023) discuss applications of NAMs for toxicokinetics and toxicodynamics in interspecies extrapolations in wildlife with a tiered approach depending on available data and resources.…”

“…Considering the complexity of toxicokinetics, tissue‐based TRVs are an appealing approach for retrospective assessments, allowing risk assessors to bypass translation from intake or absorption rates to internal exposures by evaluating internal exposures directly (Beyer & Meador, 2011; Clewell & Fuchsman, 2023; Mayfield et al, 2014). A limiting factor in tissue‐based risk analysis is the availability of toxic effect data paired with tissue concentrations.…”