ABSTRACT
BACKGROUND: Launched by the U.S. Environmental Protection Agency (EPA) in 1998, the High Production Volume (HPV) Challenge Program was developed to address the perceived gap in basic hazard information for the 2,800 chemicals produced or imported into the United States in quantities of ≥ 1 million pounds per year. Health and environmental effects data obtained from either existing information or through new vertebrate animal testing were voluntarily submitted by chemical companies (sponsors) to the U.S. EPA. Despite the potential for extensive animal testing, animal welfare guidelines were not provided until after the start of the program. OBJECTIVES: We evaluated compliance with the animal welfare principles that arose from an agreement reached between the U.S. EPA and animal protection organizations and tracked the HPV program's use of animals for testing. DISCUSSION: Under a worst-case scenario, the HPV program had the potential to consume 3.5 million animals in new testing. After application of animal-saving measures, approximately 127,000 were actually used. Categorization of chemicals based on similar structure-activity and application of read-across, along with use of existing test data, were the most effective means of reducing animal testing. However, animal-saving measures were inconsistently used by both sponsors and the U.S. EPA. CONCLUSIONS: Lessons learned from the HPV program can be applied to future programs to minimize animal testing and promote more human-relevant chemical risk assessment.