EPA Adopts Two New Nonanimal Methods for Chemical and Pesticide Safety Reviews

WASHINGTON — The Physicians Committee for Responsible Medicine welcomed the U.S. Environmental Protection Agency's (EPA) announcement of two scientific advancements that will reduce animal testing in chemical and pesticide safety reviews.

The updates allow the EPA to assess inhalation risk from surfactants using 3D human airway tissue models instead of animal tests and to predict the acute oral toxicity of certain pesticide mixtures using the internationally recognized Globally Harmonized System (GHS) mixtures equation rather than testing the final formulated product on animals.

"These are exactly the kinds of human-relevant, mechanistic approaches that produce more reliable safety data while sparing animals from suffering," said Dr. Shagun Krishna, director of toxicology at the Physicians Committee. "Replacing outdated animal tests with methods grounded in human biology is both good science and good policy."

The Physicians Committee has worked for years alongside the EPA and other regulatory scientists to advance nonanimal approaches to acute toxicity testing, including through collaborative research examining alternatives to traditional acute systemic toxicity studies and more recent work mapping the mechanistic pathways underlying acute oral toxicity using chemical structure and bioactivity data.

This work has also included efforts specifically aimed at reducing animal testing of pesticide formulations. In 2017, the Physicians Committee sponsored a stakeholder discussion on reducing and replacing the EPA’s pesticide “six-pack” animal tests, including a pilot effort to reduce formulation testing using the GHS Additivity Equation for acute systemic toxicity.

The Physicians Committee continued to advance nonanimal approaches to acute toxicity through scientific collaboration, stakeholder engagement, training, and peer-reviewed research. In 2020, the Physicians Committee again sponsored an acute toxicity stakeholder meeting at the Society of Toxicology Annual Meeting, where government, industry, and NGO scientists presented ongoing efforts toward the development, evaluation, and implementation of new approach methodologies for acute toxicity testing.

A subsequent peer-reviewed ALTEX publication led by Physicians Committee scientists also examined opportunities to replace acute systemic toxicity animal tests, including mathematical and other nonanimal approaches relevant to chemicals and mixtures.

The EPA established the GHS Mixtures Equation pilot in 2016 to evaluate this mathematical approach as an alternative to acute oral and inhalation animal toxicity studies for pesticide formulations. The EPA specifically describes the equation as a mathematical tool for estimating toxicity of pesticide formulations and evaluating whether it can substitute for animal oral and inhalation studies.

These efforts are part of the broader scientific shift reflected in the EPA’s adoption of the GHS mixtures equation: using existing data and computational methods, where appropriate, instead of conducting new acute oral toxicity tests. Today's announcement builds on the EPA's commitment to phase out mammalian testing requirements by 2035 and reflects continued progress toward that goal.

The Physicians Committee continues to partner with federal agencies, industry, and academic scientists to build the scientific foundation needed for regulators to confidently retire animal-based toxicity tests.