News: Endocrine disruptor research planned by White House

Jun 7, 2011 - News: Endocrine disruptor research planned by White House, agencies, industry. Science. Jeff Johnson. Environ. Sci. Technol. , 1996, 30 ...
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sured levels with standards set by Environment Canada, because EPA has not set standards for pesticides on aquatic life. Atrazine and cyanazine concentrations in a few samples exceeded the Canadian guidelines, but what impressed the USGS scientists was the pervasiveness of pesticides in the Mississippi River water: the herbicides atrazine and metolachor were detected in more than 95% of the samples. In December 1995 EPA's Gulf of Mexico program looked into this issue and sponsored a conference of state and federal scientists, agencies, and citizens to discuss agricultural contamination in the Mississippi and the Gulf. "This conference represented the first effort to pull all of the data together," said Wilkins. "So far, EPA ha.s concentrated on a number of limited scientific issues but not tackled policy or management of the river as it relates to the Gulf " she said. "But as the scientific evidence accumulates citizens' grouDS are anxious to work with the federal and state governments to tackle these issues " REBECCA RENNER

R & D FUNDING EPA gets a budget Seven months into the fiscal year, Congress and the White House agreed to a 1996 EPA budget April 26. HR 3019 appropriated $6.5 billion to the agency, slightly less than last year's post-rescissions level of $6.6 billion. Congress maintained about the same level of science and research funding—$525 million— as it did in 1995. The account includes Office of Research and Development funding. In broad terms, the appropriation included $2.8 billion in grants to states for environmental programs and drinking water and clean water state revolving funds; $1.3 billion for Superfund; and most of the rest for EPA program management. A major stumbling block in reaching agreement was overcome when Republicans dropped several environmental riders and gave the president authority to suspend others.

Endocrine disruptor research planned by White House, agencies, industry Over the next year, federal agencies, industry associations, the White House, and the National Research Council will lay out extensive research strategies to help understand the threat from hormone-related toxic compounds in the environment. Triggering the search is growing concern about studies showing the potential of some 50 chemical compounds to disrupt the hormonal systems of wildlife and fears that these compounds may have similar effects on humans {ES&T,pril 1996 168A). A White House task force is taking the threat seriously and plans to complete an inventory this summer of all federally funded endocrine-disruptor-related research. The inventory will provide a research baseline and identify data gaps. Then the task force will move on to fashion a coordinated federal research strategy, according to officials with the National Science and Technology Council's Committee on Environmental and Natural Resources (CENR) who are organizing the effort Explaining the White House's interest in endocrine-disrupting chemicals, a staff member with CENR noted the "swirling controversy" over the veracity of the hypothesis in the scientific community. "There are clearly effects at high exposure from these chemicals and suggestive studies that low levels could be causing impacts. But there are also lots of confounders related to the observed impact. There is a serious research need to find out if the alleged decrease in sperm counts and quality as well as if the increases in testicular breast and prostate cancers are real or if they are reflective of our better abilities to detect these diseases " The inventory and plan are being put together by a working group of 26 government scientists who represent a half-dozen key agencies with an interest in the environment or health. White House officials estimate the federal government spends some $20 million to $30 million yearly on research directly focused on endocrine disruptors. But they

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note the amount could easily be as high as $500 million if research that indirectly examines endocrine disruption is figured in. In all, the federal government spends $5 billion to $6 billion on environmental and natural resource research, the officials said. The working group, chaired by Lawrence W. Reiter, director of EPA's National Health and Environmental Effects Research Laboratory, intends to have a national research plan completed by the

From the National Research Council to the chemical industry, researchers tailor multiyear agendas. end of the year. A White House official also opened the door to including industry research projects when setting a federal strategy but added, "Our first task is to get the federal house in order." The group is expected to closely consider recommendations from a soon-to-be published report from EPA national workshops (see box). EPA is also working on its own internal strategy to guide endocrine disruptor research over the next three to five years, according to Robert Kavlock, director of EPA's Reproductive Toxicology Department. The strategy will be completed this summer and then reviewed by EPA's Science Advisory Board. It will lay out how EPA will distribute its $3.5 million extramural and $1.5 million internal research grant program in this area Kavlock expects the amount to double next year as EPA gets a firmer handle on research needs The strategy has identified 14 major issues that must be explored, Kavlock said, particularly dose-response and exposure research. Key areas, according to Kavlock, include determining if mixed endocrine-disrupting chemicals are additive when working through the same cellular receptor; examination of mo-

lecular and cellular mechanisms to determine if observed effects are the result of endocrine disruptors or other causes; studies of ecological endpoints to see if observed changes in a single organism are transferred to the entire population; and analysis of chemical structures of suspected compounds to determine what makes chemicals active or inactive endocrine disruptors. Structural relationships are also being examined by the National Institute of Environmental Health Sciences (NIEHS), according to Kenneth Korach, chief of the NIEHS Laboratory of Reproductive and Development Toxicology. The lab is analyzing structures through molecular modeling, searching for the chemical keys that open a receptor's lock and trigger hormonal activities. Korach's group hopes to eventually develop a predictive, screening device. Of its $280 million budget, NIEHS spends about $30 million a year on endocrine-related research—$24 million in external grants, $5 million in-house—according to George Lucier, director of the NIEHS Environmental Toxicological Program. Lucier said NIEHS and the National Toxicology Program (NTP) are particularly interested in the dose-response relationship for endocrine disruptors. "We have little doubt that [endocrine disruptor chemicals] contribute to human disease to some extent but the big question is how much especially at low levels " Lucier also is responsible for NTP research, which is primarily funded by NIEHS, and conducts lexicological evaluations on specific agents. NTP researchers are beginning a multigenerational study of animals exposed to six or seven specific suspected endocrine disruptors. The $700,000per-year study will consider highand low-dose exposures cancer reproductive capacity (both male and female), neurological, and immunological endpoints. The chemicals include endosulfan (a pesticide) methoxychlor (a DDTlike pesticide with an estrogenic metabolite) vinclozolin (an antiandrogen fungicide) genistein (a natural phytoestrogen) and others that have not been selected

EPA report targets 10 key research areas Ten broad categories of endocrine disruptor research needs are identified in a report generated by EPA-sponsored workshops held last year. The report will serve as the basis of a national examination of this issue being conducted by a committee of the National Science and Technology Council, which advises the president on federal research efforts. The EPA workshop brought together some 90 invited participants representing government, academic, industry, and public interest groups as well as more than 200 observers to discuss the hypothesis that humans and wildlife have suffered adverse health effects from exposure to endocrine-disrupting chemicals. Generally the group believes the hypothesis warrants concerted research on the effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures, according to the report. The report identifies as the most important research area the potential effects on the "development of reproductive capability at multiple phylogenetic levels." It also identified 44 research needs spread among 10 areas: basic research, biomarkers, exposure determination, exposure follow-up, mixtures, multidisciplinary studies, risk assessment methods, hazard identification, and sentinel species. The report is scheduled to be published in the August issue of The National Institute of Environmental Health Sciences' Environmental Health Perspectives. —JEFF JOHNSON

Lucier also mentioned his personal interest in ongoing NIEHS research on dioxin, an endocrine disruptor, which is looking at human and animal dose-response relationships. Also being planned is a new NTP center, Lucier noted, which will be in partnership with industry. The center's role will be to generate peer-reviewed estimates of human risk from exposure to reproductive and developmental toxicants, including endocrine disrupters. At the request of EPA and the Department of Interior, a National Research Council committee is assessing the strengths and weaknesses of existing research in hormone-related toxicants and will present its report laying out research priorities in late spring of next year. The committee's charge is broad, and its members include scientists whose studies first brought the issue to national attention and researchers who have been most vocal in attacking its theoretical underpinnings. Industries that produce suspected endocrine disruptors have also initiated new research programs. In particular, the chemical industry is funding a $1.5 milliona-year endocrine disruptor research program at the Chemical Industry Institute of Toxicology. That program plans research on receptor-mediated mechanisms;

assessment of endocrine modulation in animals; metabolism, disposition, pharmacokinetics, and homeostasis of such chemicals; and biomathematical modeling of reproductive endocrine systems. Also the Endocrine Issues Coalition, formed early this year and made up of the Chemical Manufacturers Association (CMA), Chlorine Chemistry Council, National Crop Protection Association, Society of the Plastics Industry, American Forest and Paper Association, and American Petroleum Institute, meets every few months to share industry research, according to Sandra Tirey, CMA assistant vice president of regulatory affairs. "We take this issue seriously and understand the need for research people that the products we make safe " she said A coalition document summarized some 35 industry-funded research programs under way in this area at universities and contract laboratories. Of particular importance, Tirey said, is a study monitoring 30 rivers for levels of nonylphenol and nonylphenol ethoxylate (suspected estrogen mimics that break down from a class of commonly used chemicals), another study examining breast cancer epidemiology, and a research program looking into biodegradation of nonylphenol ethoxylate. JEFF JOHNSON

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