{"id":2539,"date":"2013-01-31T15:13:22","date_gmt":"2013-01-31T20:13:22","guid":{"rendered":"http:\/\/blogs.edf.org\/nanotechnology\/?p=2539"},"modified":"2016-03-23T14:19:40","modified_gmt":"2016-03-23T19:19:40","slug":"21st-century-on-the-horizon-for-endocrine-disruptor-screening","status":"publish","type":"post","link":"https:\/\/blogs.edf.org\/health\/2013\/01\/31\/21st-century-on-the-horizon-for-endocrine-disruptor-screening\/","title":{"rendered":"21st Century on the horizon for endocrine disruptor screening?"},"content":{"rendered":"

Rachel Shaffer<\/em> is a research assistant. Jennifer McPartland, Ph.D.<\/em><\/a>, <\/em>is a Health Scientist.<\/em><\/p>\n

BPA, DDT, PCBs, PBDEs, phthalates, PFOA \u2026 Forgive the alphabet soup, but chances are you\u2019ve heard of at least some of these <\/span>endocrine-disrupting chemicals<\/span><\/a> (EDCs)<\/span>, which have been the subject of a lot of public and media attention in the last several years. Research has begun to uncover the ways in which these chemicals can interact with the body\u2019s hormone \u2013 or endocrine \u2013 system to <\/span><\/span><\/span>disrupt various natural biological processes<\/span><\/a>, including metabolism, the reproductive system, and development of the brain and nervous systems. <\/span><\/span><\/span><\/p>\n

While the endocrine-disrupting properties of the chemicals named above have been confirmed, scientists suspect there may be many more such chemicals in our environment, in the products we use, and in our bodies.\u00a0 How can we identify them?<\/span><\/span><\/span><\/p>\n

Legislation enacted in 1996 required the U.S. Environmental Protection Agency (EPA) to develop a screening program to identify potential EDCs.\u00a0 More than 10 years later, EPA finally launched the <\/span>Endocrine Disruptor Screening Program (EDSP)<\/span><\/a>. \u00a0Testing is being conducted in two phases, or \u201ctiers.\u201d\u00a0 In \u201cTier 1,\u201d a screening battery of validated in vivo<\/em> and in vitro<\/em> assays is used to identify chemicals with potential to interfere with the endocrine system. Chemicals flagged in the first tier of testing are then subject to \u201cTier 2\u201d testing intended to determine the specific effect and the lowest dose at which it occurs. (We should note this program is very controversial and the subject of ongoing debate, but that is not the subject of this post.)<\/span><\/span><\/span><\/p>\n

EPA has identified an estimated 9,700 chemicals to be screened \u2013 a very daunting task given the time- and resource-intensive nature of the testing battery EPA has established. \u00a0Might there be a way to expedite the identification and testing of the more problematic chemicals? A <\/span>study<\/span><\/a> published earlier this year in Environmental Health Perspectives<\/em> (EHP) investigates a possible approach: using in vitro<\/em> <\/span>high-throughput (HT) assays<\/span><\/a> developed through EPA\u2019s <\/span>ToxCast<\/span><\/a> and <\/span>Tox21<\/span><\/a> programs to target and prioritize chemicals for further testing under the EDSP. While use of these assays poses its own <\/span>challenges<\/span><\/a>, might it at least help in determining an appropriate testing sequence?\u00a0 <\/span><\/span><\/span><\/p>\n

Incorporating in vitro<\/em> HT assays into EDSP is the centerpiece of EPA\u2019s <\/span>Endocrine Disruptor Screening Program for the 21st Century<\/span><\/a> (EDSP21), which aims to take advantage of advancements in chemical testing to \u201cmore quickly and cost-effectively complete chemical assessments.\u201d <\/span><\/span><\/span><\/p>\n

The EHP study referenced above focused on the initial phase of the EDSP and investigated whether available HT assays could sufficiently identify potential endocrine disruptors so as to prioritize chemicals for Tier 1 testing. <\/span><\/span><\/span><\/p>\n

The results were mixed. \u00a0For certain types of endocrine disrupting effects \u2013 those related to estrogenic and androgenic activity \u2013 the authors reported that the HT assays were fairly predictive, reaching the same conclusion for 90% of the chemicals as did the standardized tests EPA used as a benchmark.\u00a0 By contrast, assays for other types of endocrine disrupting effects \u2013 including those related to thyroid function \u2013 performed quite poorly, \u201ccorrectly\u201d categorizing only 50-60% of chemicals.<\/span><\/span><\/span>\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 <\/span><\/span><\/span><\/p>\n

What accounts for this stark difference? The explanation may lie in the manner by which chemicals perturb different parts of the endocrine system. \u00a0Many of the chemicals known to disrupt normal estrogen and androgen activity do so by binding to the same cell receptors that estrogen and androgen bind to.\u00a0 The current battery of HT assays is fairly effective in detecting this activity. \u00a0On the other hand, chemicals that interfere with the thyroid system, for example, act in many different ways, and the existing HT assays are unable to adequately detect these other types of interferences.<\/span><\/span><\/span><\/p>\n

This shortcoming reflects a broader challenge facing the use of this new approach to toxicity testing. If we are to have complete confidence in the results of these new techniques, then the assays used need to cover the full biological response landscape. In other words, they must be able to detect disruptions in any of the hundreds of biochemical processes that take place in our bodies (for more on this limitation, see <\/span>this EDF primer page<\/span><\/a>).\u00a0 \u00a0If not, then the tests may miss an effect (in the situation just described, an endocrine-disrupting effect) of a chemical not because there isn\u2019t one, but merely because an assay for the specific effect has not yet been developed.\u00a0 <\/span><\/span><\/span><\/p>\n

In the long term, such limitations may be addressed through research that yields new assays that increase coverage. In the interim, however, transparency and full disclosure about the capacity of these approaches are crucial. The authors of the EHP study did a good job in communicating clearly about the pros and cons of this potential application of HT assays to the EDSP: \u00a0based on the results, they concluded these assays can be used to effectively and efficiently prioritize estrogenic and androgenic chemicals, but not other types of EDCs.<\/span><\/span><\/span><\/p>\n

A new era for EDSP is peeking around the corner.\u00a0 In fact, EPA is holding a <\/span>meeting<\/span><\/a> on the development and application of EDSP21 this week. Further incorporating these 21<\/span>st<\/span><\/sup> century methods provides the potential to improve this chemical screening program, but, as demonstrated by this study, full transparency about the gaps and limitations is essential. <\/span><\/span><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Rachel Shaffer is a research assistant. Jennifer McPartland, Ph.D., is a Health Scientist. BPA, DDT, PCBs, PBDEs, phthalates, PFOA \u2026 Forgive the alphabet soup, but chances are you\u2019ve heard of at least some of these endocrine-disrupting chemicals (EDCs), which have been the subject of a lot of public and media attention in the last several …<\/p>\n","protected":false},"author":11089,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[56094,5009],"tags":[39187,39167,39986,5010,39169,39170,39163,91636,91637],"coauthors":[],"class_list":["post-2539","post","type-post","status-publish","format-standard","hentry","category-new-testing-methods","category-health-science","tag-bisphenol-a","tag-computational-toxicology","tag-endocrine-disruption","tag-flame-retardant","tag-in-vitro","tag-in-vivo","tag-phthalates","tag-tox21","tag-toxcast"],"acf":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/2539","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\/11089"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/comments?post=2539"}],"version-history":[{"count":0,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/2539\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/media?parent=2539"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/categories?post=2539"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/tags?post=2539"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/coauthors?post=2539"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}