In response to growing concerns about the human health effects of potential endocrine-disrupting chemicals in food and water sources, the US Congress in 1996 passed legislation requiring the EPA to set up an endocrine disruptor screening program (EDSP) that would evaluate chemicals – particularly pesticides – using “appropriate validated test systems and other scientifically relevant information” (OSRI). The EPA was also required to comply with instructions from the Office of Management and Budget (OMB), in keeping with the Federal Paperwork Reduction Act, to reduce unnecessary duplication and waste by promoting, encouraging, and accepting “to the greatest extent possible” the submission of OSRI in place of additional testing. The EPA spent nearly thirteen years developing the congressionally mandated program, and in 2009 finally issued its first EDSP test orders for 58 pesticide active ingredients and 9 high production volume (HPV) chemicals used as inert ingredients in pesticides. The recipients of these test orders – chosen because they either manufactured or imported the chemicals in question – were instructed to complete a battery of five in vitro and six in vivo tests (known as the “Tier 1” battery), or to submit existing data and/or a review of scientific literature that could be used to waive some or all of the Tier 1 test requirements. Chemicals exhibiting endocrine disrupting properties through this screening would advance to Tier 2 Testing, a battery of five multi-generation in vivo tests.
In a review of results for these first 67 chemicals evaluated in the EDSP, authors Patricia Bishop and Catherine Willett found that the agency only rarely and inconsistently admitted OSRI as evidence in lieu of additional testing. Among their findings:
- Respondents submitted OSRI data on 47 of the 67 targeted chemicals, out of which the EPA approved only 22% of in vitro assay waiver requests, and only 23% of in vivo assay waiver requests
- data from fish short-term reproduction assays (FSTR) had the lowest rate of acceptance (4%), followed by the amphibian metamorphosis assay (AMA) (13%); acceptance of data from mammalian assays ranged from 19-39%
- only 7% of literature review submissions were accepted to replace a Tier 1 assay (9%, when part of a weight-of-evidence approach), and more often to replace an in vitro assay than an in vivo assay
OSRI data indicating positive responses was more likely to be accepted than data indicating negative responses.
Contributing to the low acceptance rate for OSRI, the authors also found contradictions and lack of clarity in the guidance documents outlining EDSP data submission and evaluation – leading to variability in the quality of OSRI data submitted by respondents, and to inconsistent rulings by EPA staff. The authors note that there is a need for a “clear method of evaluating OSRI, one that determines the validity and applicability of a study based on a priori criteria, regardless of whether the chemical exhibited positive or negative effects,” and recommend the use of a decision tree that establishes a priori criteria and weights for different data types.
The EDSP Tier 1 test battery uses a minimum of 595 animals. Tier 2 testing is even more intensive, requiring potentially thousands of animals in a multi-generational design. Given a universe of more than 10,000 chemicals potentially subject to screening, the authors urge that “it is essential that OSRI be utilized to the greatest extent possible to avoid duplicative data collection and reduce the number of animals used in testing and in pretesting.”
Bishop P. and Willett C. (2013). “The Use and Acceptance of Other Scientifically Relevant Information (OSRI) in the US EPA Endocrine Disruptor Screening Program.” Birth Defects Research, Part B: Developmental and Reproductive Toxicology. Published online: 22 OCT 2013, DOI: 10.1002/bdrb.21077