EPA's Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC)
Davis Baltz / Commonweal 20 Apr 1999
Here's a report on the developments at EPA concerning their endocrine disruptor screening and testing program. There are three parts to this memo:
I. How to get on EPA's list if you would like to receive updates from EPA directly about the program and its implementation.
II. A summary of EPA's peer review of the Agency's proposed program.
III. A review of the funding constraints which are impacting implementation of the program.
Regards, Davis Baltz
Commonweal
PO Box 316
Bolinas CA 94924 USA
+1 415 868-0970 ext. 225 (office)
+1 415 868-2230 (fax)
dbaltz@igc.org
I. How to get on EPA's list if you would like to receive updates from EPA about the program and its implementation.
As EPA moves forward with implementing its program, the Agency plans to notify interested parties of significant developments. Primarily, this communication will happen electronically. A communication and outreach plan is not yet in place.
To request being added to the list, contact Susan Acree of EPA in Washington DC at:
Some of you may have been included on an earlier list generated during the life of the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC). This list is being retired, so anyone wishing to receive future communiqués from EPA should contact Ms. Acree directly.
II. A summary of EPA's peer review of the Agency's proposed program.
A joint EPA Science Advisory Board (SAB) and Scientific Advisory Panel (SAP) meeting was held in Washington (Crystal City) from 30 March-1 April, 1999 to provide input to the Agency on their proposed program.
EPA proposed their endocrine disruptor screening program in the Federal Register on 28 December 1998. It was based largely on the recommendations of the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), an advisory panel of experts which advised EPA about how to structure such a program. EDSTAC was chartered in October, 1996 and met frequently until submitting its final report to EPA in Aug98.
The Food Quality Protection Act and other statutes now require EPA to develop and implement a screening and testing program on chemicals to assess their endocrine-disrupting properties.
The EPA proposal was open to public comments until 26 February 1999, and some 60 set of comments were received. Public comments were heard in person on the first day of the SAB/SAP review.
Here were some key pieces of feedback from the SAB/SAP peer reviewers:
1. There was agreement that looking at androgen and thyroid effects, in addition to estrogen (which is the only one mentioned by name in the statute), is worthwhile and should be pursued.
2. There was agreement that wildlife effects as well as human health effects should be considered, although industry did ask for clarification of the statutory authority to test wildlife.
3. Mixtures should move to the "back burner" because of their complexity. Most reviewers felt that the program had to develop confidence in single compounds before tackling mixtures. EDSTAC had recommended that six mixtures be examined: 1) contaminants in human breast milk; 2) phytoestrogens in soy-based infant formulas; 3) mixtures of chemicals most commonly found at hazardous waste sites; 4) pesticide/ fertilizer mixtures; 5) disinfection byproducts; and 6) gasoline. In addition, there was significant interest in a proposal to test fish tissue as a mixture.
4. Low dose testing remained contentious. There was somewhat grudging acceptance from the peer reviewers that more than one dose should be utilized. One should be relatively high near the NOAEL (no observed adverse effect level), and it was put on the table that a second, lower dose be set somewhere about four times lower than the first.
There is clearly a great deal of industry resistance to comprehensive examination of very low doses, which have been shown to have effects with some compounds in laboratory rats at orders of magnitude below previously identified NOAELs. Industry representatives said it would be "arbitrary" to mandate more than one dose, so the program should retain "flexibility" to require only one dose if indicated by the existing data.
Public interest scientists believe that multiple doses must be mandatory, especially in integrative whole animal assays. Multiple doses are needed because it is the developing organism which is of concern rather than maternal toxicity.
EDSTAC had recommended that EPA undertake a research program within 4-6 months to resolve the low dose question. Since both the dose's level and timing of exposure can be critical events during developmental life stages, it is essential that EPA build in significant low dose testing or the screening and testing program will be flawed.
EPA said publicly that they remained committed to working on low dose. In summer/fall 1999, a peer reviewed workshop on low dose research is planned by the National Toxicology Program.
5. There was concern that the proposed tier one screening battery doesn't include an assay that looks at developmental life stages. Most thought working to develop one would be valuable, but nothing is on the immediate horizon.
Since irreversible effects from endocrine disruption may occur during the developmental life stages, the lack of an assay that examines prenatal or pre-hatch exposure is a shortcoming of the proposed screening battery and a compelling concern. Without such an assay in tier one screening, chemicals could be exonerated as false negatives without ever looking at effects during development (or low doses).
EDSTAC had recommended that EPA take "affirmative steps" in collaboration with stakeholders to develop a protocol for a full life cycle developmental exposure screening assay which would address embryonic exposure and the evaluation of adult offspring. It remains to be seen what kind of resources EPA will devote to this, but funding constraints seem to dictate that it won't be high on the priority list.
6. High Throughput Pre-Screening (HTPS) results from the demonstration project at a contract lab were mixed. This effort will need considerably more work before its results can be incorporated into the priority setting process at EPA.
There was agreement that EPA should invest more resources in the process, although this will mean EPA will have to issue a new RFP because of contracting laws which affect the federal government. Industry has not stepped forward and offered to help underwrite the costs of developing a viable HTPS program.
The idea behind HTPS is to utilize robotics technology where possible and perform assays on thousands of chemicals which would otherwise have to be done at the bench at a much higher cost. The assays recommended for HTPS are designed to show whether or not a chemical binds to an estrogen, androgen, or thyroid receptor and causes transcriptional activation of genes.
It was initially hoped that HTPS could quickly generate reliable data on a large number of chemicals, in part because this data does not currently exist, and because of the substantial cost savings which could be realized. EDSTAC had recommended that all chemicals produced in excess of 10,000 pounds per year be subjected to HTPS. Currently, there are 15,000 chemicals which are produced at this level or greater.
The HTPS results would be used as additional information to consider in EPA's priority setting process (i.e., what will get tested first.) Given the unresolved questions with the feasibility of HTPS, it is clear
that EPA must move forward with priority setting without waiting for HTPS results.
7. The SAB/SAP felt the proposed assays in both tier one screening and tier two testing are about the best available now, but EPA must continue to look at alternatives.
It will be important for the Agency to formally re-assess the batteries at regular points in the future as science continues to evolve quickly. It was observed that many data that EPA will need to consider are only now being published and are not yet included in databases that EPA is proposing to utilize. States may have databases which EPA should explore.
A "super-apical" assay would be desirable which could replace more than one of the assays in the current battery, and reduce the number of lab animals needed.
Industry would like to see alternative assays used in some cases, especially in comprehensive multi-generational tests. The multi-generational tests are the most important for yielding crucial information. In general, the alternate proposals would generate less information for decision-making.
8. There was agreement that the "compartment" approach to priority setting was the best alternative, even though HTPS results will not be available in the short term. However, there are still many unresolved questions about the process of moving forward with priority setting.
Existing data on "exposure" and "effects" will be used, as well as a combination of the two: "effects and exposure." The actual "equation" which EPA ultimately proposes that generates a named list of chemicals to be tested first will be contentious. The results may be contested by industry, which could slow implementation considerably.
It was noted from a public interest point of view that EPA should give weight to chemicals that are persistent in the environment, bioaccumulate, and have POTENTIAL exposure. In addition, most chemicals have no information at all, so EPA must avoid giving "no weight to no evidence." Industry is saying that if there is no exposure, there is no reason for a chemical to even enter the process.
Industry would like to see exemptions granted to some chemicals by a rulemaking process. Such chemicals would never be prioritized.
A post-EDSTAC task force convened by EPA among stakeholders to further priority setting has met in 1999, and will tentatively convene again in August 1999.
9. The dataset for thyroid is much less developed than those for estrogen or androgen effects, and so the proposed assays may not catch all thyroid effects. But it is probably the best available now. This should be regularly reviewed by EPA. It was suggested that an assay examining TSH and T3 hormone be added to the tier one screening battery.
Industry asked whether looking at thyroid was premature, saying that some parties believe an investigation is being undertaken when there is not a demonstrated problem.
On the pubic interest side, it was noted that the brain is the key organ in development, and thyroid and insulin hormones are instrumental. Estrogen and androgen are likewise crucial for the gonads, which develop after the brain.
III. A review of the funding constraints which are impacting implementation of the program.
EPA is grossly under-budgeted for implementation activities for its endocrine disruptor screening program. It is now estimated that standardization and validation (S&V) of the proposed assays alone will cost in the neighborhood of $50 million.
But EPA has only $3.2 million for all endocrine disruptor work in Fiscal Year 1999, and the proposed figure for FY 2000 is $7.7 million. Industry has not expressed a willingness to contribute resources to the EPA S&V effort (although they have announced they will spend tens of millions on their own studies of endocrine disruption). Industry wants to see all screening and testing deferred until all S&V is completed at taxpayer expense.
EPA is prioritizing its activities based on the resources it has in its budget. Agency staff indicated at the SAB/SAP peer review that EPA would likely pursue S&V on assays which are in effect close to being ready to use. This raises the possibility that EPA may begin screening chemicals as soon as an assay is available, as opposed to waiting until all assays have completed S&V. Faced with the prospect of early test results, industry may decide to channel resources to speed S&V.
Once the screening and testing program begins, estimates are that it will cost $200,000 per chemical in tier one screening and up to $1,000,000 per chemical in tier two screening. One SAB/SAP peer reviewer stated publicly that the entire program is sufficiently cumbersome that it "realistically" will never get to tier two testing.
As with priority setting, a post-EDSTAC task force on standardization and validation has been convened by EPA to drive S&V implementation.
It was noted that the continuing absence of then National Academy of Sciences report on endocrine disruption is an obstacle to progress. It was said that EPA is trying to solve a problem that has not yet been clearly defined because the NAS has not yet spoken on the issue. Industry feels policy has gotten ahead of science because of the Food Quality Protection Act.
On the other hand, the NAS report has been delayed because of the same difference of opinion that affected EDSTAC and the SAB/SAP. The release of the NAS report, when it happens, will not likely radically re- establish parameters of the debate.
There is enough evidence that acting with precaution by beginning to generate screening and testing data as soon as possible is the sensible course to pursue. Endocrine disruption is not an emergent issue - it is a current issue.
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