Norfolk, Va. - An original article by scientists at People for the Ethical Treatment of Animals (PETA) and the Humane Society of the United States (HSUS) evaluated acceptance of Other Scientifically Relevant Information (OSRI) by the United States Environmental Protection Agency (EPA) in the agency's Endocrine Disruptor Screening Program (EDSP) in lieu of requiring new testing on animals and found it to be low and at times inconsistent. The findings are published online in an "early view" edition of the journal Birth Defects Research Part B: Developmental and Reproductive Toxicology.
"The analysis we performed clearly suggests that the EPA did not utilize OSRI to the greatest extent possible to avoid duplicative data collection and reduce the number of animals," said Patricia Bishop, one of the authors and a research scientist at PETA's Regulatory Testing Division. "As there is extensive information available for the first chemicals to be tested--and for many that will be slated for future testing--the EPA must support and develop explicit guidance for the use of OSRI and standardize and clearly articulate its own evaluation procedures to avoid duplicative testing and the loss of thousands of animal lives."
The EDSP is a two-tiered testing program. Tier 1 consists of five in vitro and six in vivo tests that explore the potential of a chemical to interact with the estrogen, androgen, and thyroid hormone systems and uses 595 animals--at minimum--per chemical if the entire battery is performed. Positive chemicals from Tier 1 presumably proceed to Tier 2, consisting of multi-generation reproductive and developmental toxicity studies in mammals, fish, birds, and amphibians, for further testing. Tier 2 assays are extremely animal-intensive. For example, the bird assay requires hatching of a minimum of 800 birds while the fish and amphibian assays each use thousands of animals per test. The EPA indicated that, prior to requiring new Tier 1 testing, it would consider OSRI submitted by test order recipients and third parties and determine whether it satisfied data requirements of the EDSP. OSRI is existing data that is either functionally equivalent to information obtained from the Tier 1 assays (i.e., data from assays that perform the same function as EDSP Tier 1 assays) or provides evidence of a potential effect on the endocrine system.
Most of the 52 chemicals in the first round of Tier 1 testing under the EDSP were pesticides for which there is a wealth of existing toxicity data. This data includes results of guideline animal tests conducted under 40 CFR Part 158 data requirements to support pesticide registration as well as research studies published in the peer-reviewed literature. Guideline studies generally include two-generation reproduction toxicity studies in rodents; 28-day, 90-day, and 1-year chronic exposure studies in rodents and dogs; and reproduction and life-cycle studies in fish and birds. With so many of these chemicals already being extensively tested, acceptance of OSRI is a primary means for avoiding duplicative data collection and minimizing further animal use.
The authors found that, due to a lack of clear guidance from the EPA, OSRI submissions by test order recipients were quite variable in their length and content. Some respondents requested waivers based on OSRI for all Tier 1 tests while others did not seek any waivers at all. Of the 412 waivers sought, the EPA granted only 93--an overall OSRI acceptance rate of 23 percent. The 49 waivers for in vivo tests and 20 waivers for in vitro assays that use tissues collected from animals spared 3325 animals. However, at least 27,731 animals were estimated to have been used to perform the Tier 1 tests eventually required by the EPA after rejecting OSRI, with additional animals being used by laboratories in preparation for conducting the Tier 1 tests.
Despite language in the laws creating the EDSP that provides for the use of OSRI and direction by the Office of Management and Budget in approving the EPA's request to collect Tier 1 data that the agency accepts OSRI to the greatest extent possible, the study found that the EPA applied a rather narrow and limited approach to acceptance of OSRI. Most OSRI accepted in lieu of new testing either indicated a positive result or was produced using a study method that was identical or very similar to a Tier 1 or Tier 2 assay, even though the EPA said functionally equivalent studies would be considered. The OSRI analysis shows that results from Part 158 studies were accepted infrequently and that there were cases where literature studies were accepted for one chemical when the results were positive but rejected for another chemical evaluated in the study when the results were negative.
"Even with the EPA's planned integration of 21st -century toxicity-testing tools, such as computational toxicology methods and high throughput in vitro assays, into the EDSP for prioritization and screening purposes, OSRI will continue to play an important role in reducing the number of animals used in testing and in pretesting until such time when we can do away with animal testing completely," Bishop added.