{"id":9515,"date":"2020-04-01T08:30:57","date_gmt":"2020-04-01T13:30:57","guid":{"rendered":"http:\/\/blogs.edf.org\/health\/?p=9515"},"modified":"2024-02-12T11:02:26","modified_gmt":"2024-02-12T16:02:26","slug":"peer-reviewers-of-epas-tce-report-must-affirm-that-the-key-risk-is-fetal-heart-damage","status":"publish","type":"post","link":"https:\/\/blogs.edf.org\/health\/2020\/04\/01\/peer-reviewers-of-epas-tce-report-must-affirm-that-the-key-risk-is-fetal-heart-damage\/","title":{"rendered":"Peer reviewers of EPA\u2019s TCE report must affirm that the key risk is fetal heart damage"},"content":{"rendered":"<p><em>Richard Denison, Ph.D.,\u00a0<\/em>is a Lead Senior Scientist.<\/p>\n<p>Last week, the EPA Science Advisory Committee on Chemicals (SACC) conducted a <a href=\"https:\/\/www.epa.gov\/tsca-peer-review\/peer-review-draft-risk-evaluation-trichloroethylene-tce\">virtual peer review meeting<\/a> for the Agency\u2019s <a href=\"https:\/\/www.epa.gov\/tsca-cbi\/draft-risk-evaluation-trichloroethylene\">draft risk evaluation of trichloroethylene (TCE)<\/a>. As expected, there was substantial discussion on the appropriateness of EPA\u2019s decision to make risk determinations based on immune endpoints rather than fetal cardiac malformations (FCMs). Unfortunately, the review panel lacked anyone with specific expertise in cardiac development.<\/p>\n<p>During the meeting, many of the peer review panelists signaled an initial inclination toward supporting EPA\u2019s decision to use immune endpoints for risk determinations. However, panel members also noted with serious concern the recent <a href=\"https:\/\/www.revealnews.org\/article\/epa-scientists-found-a-toxic-chemical-damages-fetal-hearts-the-trump-white-house-rewrote-their-assessment\/\">investigations that have uncovered political influence<\/a> exerted on EPA that led it to base the risk determinations in the draft risk evaluation on immune endpoints instead of FCMs.<\/p>\n<p>Stepping back from the specifics of the discussions last week, it is important to understand the longstanding basis and support for EPA\u2019s reliance on FCMs, the unprecedented nature of EPA\u2019s decision to now move away from it, and the adverse implications of the decision for EPA\u2019s ability to adequately manage the risks of TCE to all relevant subpopulations.<\/p>\n<p><strong>This decision is a major departure from thoroughly peer-reviewed science, fails to protect the most sensitive populations as mandated by TSCA, and deviates dramatically from existing Agency guidance. <\/strong>These concerns, discussed at length in <a href=\"https:\/\/www.regulations.gov\/document?D=EPA-HQ-OPPT-2019-0500-0056\">EDF\u2019s comments<\/a> in the TCE Docket, are briefly summarized below:\u00a0 <!--more--><\/p>\n<ul>\n<li><strong>Setting-aside of extensive peer-reviewed science<\/strong><\/li>\n<\/ul>\n<p>There is strong scientific support for TCE-induced FCMs not only from the Johnson et al. 2003 study but from epidemiological, <em>in vivo<\/em>, and <em>in vitro<\/em> studies.<\/p>\n<p>EPA and other scientific authorities \u2013 including the EPA Scientific Advisory Board (SAB) \u2013 have repeatedly examined and affirmed the importance of the FCM endpoint:<\/p>\n<ul>\n<li><a href=\"https:\/\/www.epa.gov\/iris\/supporting-documents-trichloroethylene\">EPA IRIS Assessment + SAB Peer Review<\/a> (2009-2011)<\/li>\n<li><a href=\"https:\/\/www.epa.gov\/assessing-and-managing-chemicals-under-tsca\/tsca-work-plan-chemical-risk-assessment-0\">EPA Work Plan Assessment + Peer Review<\/a> (2013-2014)<\/li>\n<li><a href=\"https:\/\/www.regulations.gov\/document?D=EPA-HQ-OPPT-2012-0723-0045\">TCE Developmental Cardiac Toxicity Update<\/a> (\u201cUpdate\u201d) (2014)<\/li>\n<li><a href=\"https:\/\/www.epa.gov\/sites\/production\/files\/2015-10\/documents\/14001-response.pdf\">Response to Halogenated Solvents Industry Association (HSIA) response for correction<\/a> (2015)<\/li>\n<li><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27575429\">EPA systematic evaluation of fetal cardiac effects published in peer-reviewed literature<\/a> (2016)<\/li>\n<li><a href=\"https:\/\/www.epa.gov\/sites\/production\/files\/2016-12\/documents\/epa_response_to_rfc_16001.pdf\">Response to HSIA response for correction<\/a> (2016)<\/li>\n<li><a href=\"https:\/\/www.epa.gov\/quality\/epa-response-rfr-14001a-issued-02262016-0\">Response to HSIA request for reconsideration<\/a> (2016)<\/li>\n<\/ul>\n<p>Any decision by the current peer review panel, lacking direct and specific expertise in cardiac development and based on discussions at a virtual meeting missing key members who could not participate, to discount years of robust scientific review that have upheld the database on fetal cardiac malformations must be made extremely carefully.<\/p>\n<ul>\n<li><strong>Failure to protect sensitive populations <\/strong><\/li>\n<\/ul>\n<p>EPA acknowledges that \u201ccongenital heart defects were the most sensitive endpoint for TCE\u201d (p. 377; Table 4-5 on p. 280). This endpoint is directly relevant to the potentially exposed or susceptible subpopulations of pregnant women, infants, and children identified under TSCA.<\/p>\n<p>By instead using the immune endpoint for risk determinations, EPA fails to ensure that it is protecting <em>\u201cpotentially exposed or susceptible subpopulations,<\/em>\u201d as called for under TSCA. \u00a0EPA cannot adequately identify or protect against risks specific to pregnant women and their developing fetuses by selecting immune effects as the basis for its risk determinations.<\/p>\n<p>In other words, it is not simply a matter of choosing between two endpoints for the same population; these endpoints are relevant to distinct, if overlapping, subpopulations. The SACC should ensure that its advice to EPA is consistent with EPA\u2019s mandate to protect the most sensitive subpopulations.<\/p>\n<ul>\n<li><strong>Deviation from Agency policies <\/strong><\/li>\n<\/ul>\n<p>EPA\u2019s choice to dismiss FCMs contradicts previous agency assessments of TCE and existing agency guidance to use the most sensitive endpoint and protect the most sensitive group, including:<\/p>\n<ul>\n<li>EPA, <a href=\"https:\/\/www.epa.gov\/sites\/production\/files\/2014-11\/documents\/dev_tox.pdf\"><em>Guidelines for Developmental Toxicity Risk Assessment<\/em><\/a> (p. 48)<\/li>\n<li>EPA Risk Assessment Task Force, <a href=\"https:\/\/www.worldcat.org\/title\/examination-of-epa-risk-assessment-principles-and-practices-staff-paper-prepared-for-the-us-environmental-protection-agency-by-members-of-the-risk-assessment-task-force\/oclc\/55850621\"><em>Staff Paper on Risk Assessment Principles and Practices<\/em><\/a> (pp. 57-58)<\/li>\n<li>EPA, <a href=\"https:\/\/www.epa.gov\/sites\/production\/files\/2014-12\/documents\/rfd-final.pdf\"><em>A Review of the Reference Dose and Reference Concentration Processes<\/em><\/a> (p. 4-22)<\/li>\n<li>EPA, <a href=\"https:\/\/www.epa.gov\/children\/epas-policy-evaluating-risk-children\"><em>Policy on Evaluating Risk to Children<\/em><\/a> (p. 1)<\/li>\n<\/ul>\n<p>The National Academy of Sciences (NAS) has also reiterated the need to protect the most sensitive subpopulations and to protect against the most sensitive endpoints:<\/p>\n<ul>\n<li>NAS, <a href=\"https:\/\/www.nap.edu\/catalog\/12209\/science-and-decisions-advancing-risk-assessment\"><em>Science and Decisions: Advancing Risk Assessment<\/em><\/a> (p. 120)<\/li>\n<li>NAS, <a href=\"https:\/\/www.nap.edu\/catalog\/2125\/science-and-judgment-in-risk-assessment\"><em>Science and Judgment<\/em><\/a> (pp. 142, 145)<\/li>\n<\/ul>\n<p>These documents make clear that if EPA protects against the most sensitive endpoint, it will also generally protect against other effects.\u00a0 In contrast, EPA asserts without providing supporting evidence that \u201cit is expected that addressing risks for these [immune system] effects would address other identified risks.\u201d (p. 377)\u00a0 EPA\u2019s \u201cexpectation\u201d contravenes its own scientific guidance.<\/p>\n<p><strong>In summary, a recommendation by the SACC supporting EPA\u2019s profoundly problematic decision to use immune rather than fetal cardiac endpoints for risk determinations on TCE is directly counter to the weight of evidence and years of peer review; ignores TSCA\u2019s mandate to protect sensitive subpopulations; and disregards extensive Agency policies on the selection of the most sensitive endpoints for risk modeling. <\/strong><\/p>\n<p><strong>The public health consequences of this choice will be substantial<\/strong>. Risk determinations based on immune endpoints rather than fetal cardiac malformations would allow EPA to develop regulations that are on the order of 500-fold less protective of acute risks and 10-fold less protective of chronic risks.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Richard Denison, Ph.D.,\u00a0is a Lead Senior Scientist. Last week, the EPA Science Advisory Committee on Chemicals (SACC) conducted a virtual peer review meeting for the Agency\u2019s draft risk evaluation of trichloroethylene (TCE). As expected, there was substantial discussion on the appropriateness of EPA\u2019s decision to make risk determinations based on immune endpoints rather than fetal &#8230;<\/p>\n","protected":false},"author":100,"featured_media":8326,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[44,5009,56093,56096,114108],"tags":[68,91722,39179],"coauthors":[],"class_list":["post-9515","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-policy","category-health-science","category-industry-influence","category-omboira","category-tsca","tag-epa","tag-risk-evaluation","tag-trichloroethylene-tce"],"acf":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/9515","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/users\/100"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/comments?post=9515"}],"version-history":[{"count":1,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/9515\/revisions"}],"predecessor-version":[{"id":12907,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/9515\/revisions\/12907"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/media\/8326"}],"wp:attachment":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/media?parent=9515"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/categories?post=9515"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/tags?post=9515"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/coauthors?post=9515"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}