Is the 90-day dog study necessary for pesticide toxicity testing?

Area of Science:

• Toxicology
• Environmental Science
• Regulatory Science

Background:

• Standard pesticide registration includes 90-day oral toxicity studies in rodents (rats) and non-rodents (dogs).
• These animal tests are crucial for human health risk assessment (RA) globally.
• The necessity of the 90-day dog study in RA requires re-evaluation.

Purpose of the Study:

• To determine the necessity of the 90-day dog toxicity study in pesticide risk assessment.
• To review data from 195 pesticides evaluated by the US Environmental Protection Agency (USEPA).
• To assess if the dog study provides unique benefits over other available data.

Main Methods:

• Review of 195 pesticide evaluations by the USEPA (1998-2021).
• Analysis of the 90-day dog study's application in risk assessment.
• Comparison of no-observed-adverse-effect levels (NOAELs) between rats and dogs.
• Evaluation of dose normalization and allometric scaling effects.
• Identification of alternative studies for setting the point of departure (POD).

Main Results:

• The 90-day dog study was used in RA for only 42 out of 195 pesticides.
• Dog NOAELs were lower than rat NOAELs in 36/42 cases, initially suggesting greater sensitivity.
• Dose normalization explained lower dog NOAELs in 22/36 cases, indicating the rat study was comparable.
• Alternative studies could substitute for the dog study in 5/42 cases.
• Only 9/195 cases required the dog study for unique hazard identification or setting safe exposure levels.

Conclusions:

• The 90-day dog study offers limited additional benefit beyond rat studies or other available data for most pesticide risk assessments.
• Alternative data sources can often be used to establish the point of departure for non-dietary pesticide exposures.
• The use of the 90-day dog study in pesticide registration may be reduced without compromising human health risk assessment.