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Toxicity Testing in Animals

Toxicity Testing in Animals

Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...

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Updated: May 7, 2026

Investigating Long-Distance Transport of Perfluoroalkyl Acids in Wheat via a Split-Root Exposure Technique

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Recommended Toxicity Reference Values for PFOS and PFHxS In Mammals and PFOS in Birds.

Christopher McCarthy¹, Jason Conder², Jeanmarie Zodrow³

¹Jacobs Engineering Inc., Bedford, New Hampshire, USA.

Integrated Environmental Assessment and Management

|May 5, 2026

Summary

This study establishes toxicity reference values (TRVs) for perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) in avian and mammalian wildlife. These TRVs are crucial for ecological risk assessments of PFAS contamination.

Keywords:

PFAS risk assessment Per- and polyfluoroalkyl substances perfluorohexane sulfonate perfluorooctane sulfonate toxicity reference values

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Last Updated: May 7, 2026

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Published on: February 10, 2023

Area of Science:

Environmental Toxicology
Wildlife Risk Assessment
Per- and Polyfluoroalkyl Substances (PFAS)

Background:

PFOS and PFHxS are persistent and bioaccumulative PFAS frequently found at contaminated sites.
These chemicals pose risks to avian and mammalian wildlife, necessitating ecological risk assessments (ERAs).
Toxicity reference values (TRVs) are essential for modeling wildlife exposure and effects in ERAs.

Purpose of the Study:

To review published toxicity data for PFOS and PFHxS in mammals and birds.
To recommend TRVs for use in site-specific ERAs and ecological screening value (ESV) derivation.
To identify the most sensitive endpoints for assessing PFAS toxicity in wildlife.

Main Methods:

Systematic review of published mammalian and avian laboratory toxicity studies.
Prioritization of oral exposure studies evaluating population-level apical endpoints (reproduction, growth, survival).
Derivation of no-effect and low-effect TRVs based on chronic dietary exposure data.

Main Results:

Reproductive effects were the most sensitive apical endpoint for both PFOS and PFHxS.
Avian TRVs for PFOS: 0.55 mg/kg-bw/d (no-effect), 1.1 mg/kg-bw/d (low-effect).
Mammalian TRVs for PFOS: 0.25 mg/kg-bw/d (no-effect), 0.5 mg/kg-bw/d (low-effect).
Mammalian TRVs for PFHxS were an order of magnitude higher than PFOS: 7 mg/kg-bw/d (no-effect), 14 mg/kg-bw/d (low-effect).

Conclusions:

The derived TRVs for PFOS and PFHxS are robust, based on chronic exposures and sensitive endpoints.
These TRVs will support accurate site-specific ERAs and ESV calculations for PFAS.
The findings highlight the differential toxicity between PFOS and PFHxS in wildlife.