Industry Bid For EPA Data May Aid Exclusion From Endocrine Program

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Date: October 20, 2009 -

Industry is seeking initial EPA research office data on testing for most of the chemicals on the initial list for review under the agency's pending endocrine screening program, which may help industry make the case to exclude certain chemicals from the program if the data indicate the substances do not disrupt human hormones.

In recently filed Freedom of Information Act (FOIA) requests, an attorney with the firm McKenna, Long & Aldridge and a senior scientist for pesticide manufacturer Cheminova separately ask for EPA Office of Research & Development (ORD) results of testing for various chemicals under the office's computational toxicology research program, ToxCast, operated by ORD's National Center for Computational Toxicology (NCCT).

Both requests seek data on chemicals that EPA's Office of Prevention, Pesticides and Toxic Substances (OPPTS) has proposed to require for screening in its long-pending endocrine disruption screening program (EDSP), a series of tests to determine whether chemicals interfere with human hormones.

John Connor Jr., the attorney handling the law firm's request, said in an interview that knowing what data EPA has is crucial for'responding to the forthcoming testing rule, which provides if there is available data you don?t need to [do] screening.? Industry is wary of subjecting chemicals to the EDSP, in part because the cost for running one chemical through the program's first 11 tests, or assays, could cost between $800,000 and $1.5 million, he said.

Connor's Sept. 21 FOIA request is for'all data and reports of in vitro studies of the 54 chemicals tested for or by? NCCT. He said that ToxCast data'may not address all? of the 11 assays in the first of EDSP's two tiers, but still might qualify as other scientifically relevant information the agency could accept on chemicals.

NCCT received a second FOIA request from Terri Spanogle, a scientist with pesticide manufacturer Cheminova, who sought ?all in vitro test results for malathion and dimethoate from EPA's ToxCast program,? according to the Sept. 17 request. Relevant documents are available on InsideEPA.com.

NCCT is performing pioneering research into in vitro or cell-based toxicology and computational toxicology. Its ToxCast high-throughput screening research program recently finished screening a first group of 320 chemicals through a series of 400 in vitro assays. The agency hopes the program can eventually be used to prioritize the toxicity of chemicals more effectively than using animal tests.

Among the chemicals are 54 pesticides that are also included on the toxics and pesticides office's list of the first 67 pesticides that will be required to submit data under the EDSP. The first tier of the program is meant to ascertain whether a chemical has the potential to interact with the human androgen, estrogen or thyroid hormones. If a chemical is flagged in the first tier, manufacturers will then have to submit that chemical for more costly testing in tier two, which is intended to provide the agency with data for hazard assessment.

The White House Office of Management and Budget (OMB) approved Oct. 2 EPA's information collection request and test orders for some 67 pesticides to undergo tier one testing. However, OMB said EPA must'to the greatest extent possible? accept existing data in lieu of results from the EDSP assays.

Industry, which has voiced concern with various aspects of the EDSP since Congress mandated EPA create the program in the Food Quality Protection Act of 1996, applauded OMB's signing notice (Risk Policy Report, Oct. 13).

If either of the FOIA requests are successful, industry may be able to use ORD's existing data on the safety or certain chemicals to argue that OPPTS must rely on that data rather than screen the chemicals through the EDSP.

But another pesticide industry source questions the usefulness of ORD's data in the EDSP, suggesting that ToxCast is just a research program and EPA is not using it for regulatory purposes.

The source does not expect EPA to give much weight to the ToxCast data in its decisions.'Computational data is still fairly preliminary and not getting the currency in the scientific community that I thought it would,? the source says, pointing to a recent National Academy of Sciences symposium on computational toxicology where federal scientists suggested the technology is not ready yet for regulatory purposes (Risk Policy Report, Sept. 29).

EPA did not response to a request for comment by press time.

EPA has yet to complete validation of the five assays slated for inclusion in the EDSP's second tier, or to publish guides of criteria for accepting other data in lieu of EDSP assay results, or how it will determine whether a chemical has to undergo tier two testing. Each of these points was raised at an International Society of Regulatory Toxicology and Pharmacology (ISRTP) conference on the EDSP Sept. 9-10, where attorneys and representatives questioned EPA staff and discussed legal challenges that could be brought against the program.

However, the agency's toxics office is preparing to issue two Federal Register notices providing additional information on the EDSP's'policies and procedures,? Steve Bradbury, EPA's deputy director for pesticide programs, said at an Oct. 14 pesticides stakeholder meeting in Arlington, VA.

One notice will provide an overview of the entire first tier testing scheme, while a second notice will include a schedule for the issuance of all 750 test orders, which will be staggered over several months, Bradbury said. The notice will also include information on how test order recipients -- as well as the general public -- should submit additional relevant scientific information to the agency. Further, the notice will include information on how to form consortia to facilitate data-sharing among companies responsible for the same chemical, he said.

During the ISRTP conference, NCCT scientist Keith Houck presented some of the center's initial results. His presentation was received with great interest among other presentations where industry representatives and consultants argued that existing data already exists that provides the same information that results of the tier one EDSP assays would provide EPA. Some speakers questioned the validity of the EDSP assays, arguing that the traditional animal-based assays are crude and that results from stressed animals could easily be misinterpreted. Some suggested that the program should wait until newer, in vitro or in silico assays have been validated for EDSP use (Risk Policy Report, Sept. 15).

Industry sources noted that Houck's results showed that only about half of the 54 chemicals interacted with a cell-based thyroid binding assay, results they interpreted as showing those chemicals of limited concern for hormone disruption. Houck, however, described his results as showing that 'several chemicals of concern for potential endocrine disruption had significant activity in the endocrine-related assays? in the ToxCast battery.

Meanwhile, EDSP critics are seeking a broad range of new information on the program, a likely prelude to a fresh Data Quality Act (DQA) challenge that if successful could stall the program until the agency addresses the critics? concerns about the adequacy of the assays and other elements of the EDSP.

The Center for Regulatory Effectiveness (CRE), an industry-funded regulatory watchdog group, sent an Oct. 13 letter to EPA toxics chief Steve Owens requesting a slew of documents relating to the agency's endocrine disruptor screening program (EDSP). CRE wants the agency to provide all comments on the EDSP and its information collection request (ICR), including all EPA responses to the OMB comments on the ICR, and the agency's responses to comments on the first tier of assays that will be used to screen chemicals under the two-tier program.

The group also wants all final test protocols for the first tier of assays, all EPA signed quality assurance project plans for the EDSP, and public disclosure of EPA's DQA pre-dissemination review process and record for development and validation of the second tier of assays, weight of evidence determinations on which chemicals must proceed to the second tier, and other information.

The current letter is'a lot broader? than an earlier CRE data challenge that the agency ultimately rejected, says a source with the group.'I?m not sure they?ve done the data quality checks. If they didn?t, we?ll start some kind of dialogue? on a new DQA challenge that -- if successful -- could significantly delay or block the EDSP from proceeding. -- Maria Hegstad

Source: Risk Policy Report via InsideEPA.com

Date: October 20, 2009

Issue: Vol. 16, No. 42

RISK-16-42-7