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Untitled Document FOR IMMEDIATE RELEASE 1 February 2007 CONTACT: Kimberly Thigpen Tart, News Editor, EHP (919) 541-5377 Chelation therapy reduces lead-exposure problems but could create lasting effects for children treated for autism, CU researchers find By Krishna Ramanujan Lead chelation therapy -- a chemical treatment to remove lead from the body -- can significantly reduce learning and behavioral problems that result from lead exposure, a Cornell study of young rats finds. However, in a further finding that has implications for the treatment of autistic children, the researchers say that when rats with no lead in their systems were treated with the lead-removing chemical, they showed declines in their learning and behavior that were similar to the rats that were exposed to lead. Chelating drugs, which bind to lead and other metals in the blood, are increasingly being used for the treatment of autism in children. "Although these drugs are widely used to treat lead-exposed children, there is remarkably little research on whether or not they improve cognitive outcomes, the major area of concern in relation to childhood lead poisoning," said Barbara Strupp, Cornell associate professor of nutritional sciences and of psychology and the senior author of the study, which was published in a recent issue of Environmental Health Perspectives. Studies on the safety or effectiveness of the drugs for treating autism are similarly lacking, Strupp said. Strupp added that to her knowledge this is the first report that shows that chelation therapy can reduce behavioral and learning problems due to lead exposure as well as the first to show that this type of treatment can have lasting adverse effects when administered in the absence of elevated levels of heavy metals. The study used succimer (brand name, Chemet), the most widely prescribed drug for the treatment of lead poisoning. Doctors prefer succimer to other such drugs because it can be given orally on an outpatient basis, and it leaches less zinc, iron and other essential minerals out of the body. Although the Centers for Disease Control recommends chelation therapy only for children whose blood lead levels exceed 45 micrograms per deciliter, such drugs as succimer are commonly administered at much lower levels of exposure, due to concerns about lasting complications with even slightly elevated blood lead levels. It is important to remove lead from the body as quickly as possible to prevent or lessen lasting damage to the developing brain. High-lead exposure from peeling lead-based paint can lead to coma, convulsions and even death. At lower levels, lead exposure causes attention deficits, delinquency and difficulty regulating emotions and can lower IQ scores at a rate of about one IQ point per microgram/deciliter of exposure. The study used rats -- whose mental and behavioral responses to lead exposure are similar to humans' -- and exposed them to moderate- and high-lead levels (administered via mothers' milk). A third group -- the control -- was not exposed. Exposures were followed by a treatment with succimer or placebo. Immediately thereafter, the researchers conducted automated tests over six months on the rats' attention, memory and abilities to learn and regulate emotions. The rats with moderate-lead exposure benefited greatly from the succimer: Their test results were indistinguishable from the control test results. Rats exposed to higher lead levels showed benefits in the emotional domain: After succimer treatment, they behaved similarly to the control group. However, the treatment only slightly improved their learning deficit. In the group that had no lead exposure but were given succimer, "we found lasting cognition and emotion-regulation [deficits] that were as pervasive and large as rats with high lead exposure," said Strupp. She added that one possibility is that succimer, in the absence of lead, may disrupt the balance of such essential minerals as zinc and iron. "These findings raise concerns about the use of chelating agents in treating autistic children," she said. The study was funded by the National Institutes of Health. Among other colleagues, Diane Stangle, a psychology graduate student, and Stephane Beaudin, a research associate in nutritional sciences, contributed to this work.

Untitled Document FOR IMMEDIATE RELEASE 1 February 2007 CONTACT: Jim Tobin 919-653-2582 Report in Environmental Health Perspectives links prenatal alcohol exposure with increased risk of genital malformation in boys [Research Triangle Park, NC] Pregnant women who consume even moderate amounts of alcohol may be placing their sons' reproductive development at risk, according to a study published today in Environmental Health Perspectives (EHP). Researchers at the University of Copenhagen in Denmark have released findings suggesting that consumption of alcohol during pregnancy may increase the risk of cryptorchidism in sons. Cryptorchidism, or undescended testicles, is one of the most common genital malformations in males. Although its cause is still largely unknown, previous research has indicated several risk factors, including low birth weight, prematurity, and twinning. Recent studies have reported an increase in the prevalence of cryptorchidism in the last few generations, suggesting that environment and lifestyle factors such as smoking, caffeine intake, and alcohol consumption may play a part in its occurrence. The investigators in the current study analyzed lifestyle and medical data for 4,957 pregnant women collected in a joint prospective birth cohort in Denmark (1997-2001) and Finland (1997-1999). By the beginning of the third trimester, each woman had completed a questionnaire reporting how many alcoholic and caffeinated drinks they consumed per week as well as smoking habits. A total of 2,496 sons born to these women were examined at birth and at 3 months of age. At birth 128 boys (94 Danish, 34 Finnish) displayed varying degrees of cryptorchidism, and 33 boys remained cryptorchid at 3 months of age. Data analysis revealed that mothers who regularly consumed alcoholic beverages were more likely to give birth to sons with cryptorchidism, even after controlling for other confounding variables such as premature delivery, birth weight, and maternal smoking and caffeine intake. Results showed no statistically significant adverse effects in boys whose mothers consumed fewer than five drinks per week. However, the researchers caution that there is "no well-established safety level of drinking during pregnancy," and they say this new finding should be considered in counseling of pregnant women regarding alcohol consumption. The lead author of the study was Ida N. Damgaard of the University of Denmark Department of Growth and Reproduction. Other authors included Tina K. Jensen, the Nordic Cryptorchidism Study Group, Jorgen H. Petersen, Niels E. Skakkebaek, Jorma Toppari, and Katharina M. Main. The article is available free of charge at http://www.ehponline.org/members/2006/9608/9608.html. EHP is published by the National Institute of Environmental Health Sciences (NIEHS), part of the U.S. Department of Health and Human Services. EHP is an Open Access journal. More information is available online at http://www.ehponline.org/. Brogan Partners Convergence Marketing handles marketing and public relations for EHP, and is responsible for the creation and distribution of this press release. Editor s note: Working media can register to receive press releases via e-mail by visiting http://www.ehponline.org/press/, calling 919-653-2582, or e-mailing ehpmedia@brogan.com.

FOR IMMEDIATE RELEASE 3 January 2007 CONTACT: Jim Tobin 919-653-2582 Report in Environmental Health Perspectives says proposed heavy use of Tamiflu to combat pandemic avian flu could lead to resistant strains of the virus [Research Triangle Park, NC] Widespread use of the antiviral Tamiflu to fight pandemic avian flu in humans could actually lead to the development of what public health officials hope to avoid drug-resistant strains of the virus in wild birds. British researchers at the Centre for Ecology and Hydrology in Oxford have released findings in the January 2007 issue of Environmental Health Perspectives (EHP) that demonstrate how Tamiflu's persistence in wastewater and river water could affect the waterfowl that drink from those water sources. Since the World Health Organization's first warning of an avian flu pandemic two years ago, nations worldwide have been stockpiling Tamiflu for treatment and outbreak prevention. The drug, which minimizes flu symptoms and duration, inhibits the movement of the influenza virus from the cells it infects, and also helps uninfected people avoid contracting the flu. However, Tamiflu's active agent, the metabolite oseltamivir carboxylate (OC) would be excreted into sewers for several weeks during a pandemic and is expected to withstand biodegradation. According to the researchers in the current study, once birds drink OC-laced water from catchments receiving treated wastewater, they could produce Tamiflu-resistant strains and pass them on to other birds who share the same waters. The investigators analyzed 11 waterway catchments in the United States and 5 in England using a metabolic pathway prediction system to determine the potential biodegradability of OC. They also measured wastewater discharges into the catchments. They estimated the number of clinically infected people in each catchment area treated with a full 5-day course of Tamiflu with 100% compliance, assuming that 80% of the ingested Tamiflu was released into sewer systems as OC and that all of the OC entering each catchment was flushed out in one day. Their estimates showed a maximum concentration well above that required for development of resistance in vitro for 62 consecutive days in the arid Lower Colorado River catchment area. Overall, the researchers say that because of the lower population density for many of the U.S. catchments, peak concentrations of OC in a pandemic would be approximately 10 times less than the concentrations in British rivers. All but one of the American catchments studied are larger than those in Britain and, with the exception of the Lower Colorado River flow area, have more available dilution per person in each given population. There were no specific ecotoxicological risks from Tamiflu identified at the time the drug was submitted for approval to the European Medicines Agency. The authors, however, suggest that the ecotoxicological risk associated with Tamiflu use needs to be reassessed in light of the hundreds of millions of courses that would be consumed globally during a pandemic. The authors warn that, with the release of the uniquely structured, biochemically resistant OC antiviral into river water, "the range of OC concentrations predicted . . . will have uncharacterized ecotoxicological consequences." They call for more detailed water contamination modeling, especially in high-risk areas of the world such as Southeast Asian countries, where there is more frequent human-to-waterfowl contact and where future use of Tamiflu would be significant. They also recommend development of methods to minimize the release of OC into wastewater systems, such as biological and chemical pretreatment in the toilet. The lead author of the study was Andrew C. Singer. Other authors included Miles A. Nunn, Ernest A. Gould, and Andrew C. Johnson. The article is available free of charge at http://www.ehponline.org/docs/2006/9574/abstract.html. EHP is published by the National Institute of Environmental Health Sciences (NIEHS), part of the U.S. Department of Health and Human Services. EHP is an Open Access journal. More information is available online at http://www.ehponline.org/. Brogan Partners Convergence Marketing handles marketing and public relations for EHP, and is responsible for the distribution of this press release. -30- Editor's note: Working media can register to receive press releases via RSS feed or e-mail by visiting http://www.ehponline.org/press/, calling 919-653-2582, or e-mailing ehpmedia@brogan.com.

University of Iowa News Release Release: Nov. 17, 2006 p> A University of Iowa-sponsored international conference on concentrated animal feeding operations (CAFOs) has resulted in a series of published reports addressing major environmental health issues associated with large, industrialized livestock production facilities. The public conference and scientific workshop, "Environmental Health Impacts of CAFOs: Anticipating Hazards - Searching for Solutions," was held in March 2004 in Iowa City. It brought together UI researchers, stakeholders and national and international environmental health experts to discuss potential solutions to public health problems related to CAFOs. Five expert workgroups convened to consider the most relevant scientific challenges, including respiratory health effects, modeling and monitoring of air toxics, water quality issues, influenza pandemics and antibiotic resistance, and community health and socioeconomic issues. The workgroup reports published this week outline the state of the science in each of these areas and suggest opportunities to translate science to policy initiatives that would effect improvements in public and environmental health. The reports from these workgroups are available as a set of "mini-monographs" from Environmental Health Perspectives, a peer-reviewed journal published by the National Institute of Environmental Health Sciences. The reports can be accessed online for free at www.ehponline.org/docs/admin/minimono.html. " These publications represent a consensus view of the issues around the environmental health impacts of modern livestock production from 37 national and international experts," said Peter Thorne, UI professor of occupational and environmental health and director of the UI Environmental Health Sciences Research Center. Thorne contributed to each of the reports and served as chair of the 2004 conference. The reports discuss major emerging concerns, including health problems from air and water contamination, the rise of multidrug-resistant bacteria in livestock, and the specter of influenza outbreaks arising from placing poultry and swine production facilities in close proximity to each other and to humans. The 2004 conference was sponsored by the UI Environmental Health Sciences Research Center and the National Institute of Environmental Health Sciences, with additional support from the UI Center for Health Effects of Environmental Contamination and participation of the UI Hygienic Laboratory. STORY SOURCE: University of Iowa College of Public Health Office of Communications, 4257 Westlawn, Iowa City, Iowa 52242. MEDIA CONTACT: Debra Venzke, 319-335-9647, mailto:debra-venzke@uiowa.edu

DALLAS Nov. 16, 2006 A dioxin toxin contained in the herbicide Agent Orange affects male reproductive health by limiting the growth of the prostate gland and lowering testosterone levels, researchers at UT Southwestern Medical Center have found in a cohort study of more than 2,000 Air Force veterans who served during the Vietnam War. The study, published in the November issue of the journal Environmental Health Perspectives, indicates that exposure to TCDD, the most toxic dioxin contained in Agent Orange, may disturb the male endocrine and reproductive systems in several ways. "Until now, we did not have very good evidence whether or not dioxins affect the human reproductive system," said Dr. Amit Gupta, a urologist at UT Southwestern and the study s lead author. "Now we know that there is a link between dioxins and the human prostate leading us to speculate that dioxins might be decreasing the growth of the prostate in humans like they do in animals." The researchers found that veterans exposed to dioxin had lower incidence rates of benign prostate hyperplasia (BPH), better known as enlarged-prostate disease. BPH is a disease in humans that is caused by an enlargement of the prostate. Patients must strain to pass urine and they also must urinate frequently. BPH can lead to complications such as an inability to urinate and urinary tract infection. Surgery is sometimes needed. Dr. Claus Roehrborn, professor and chairman of urology at UT Southwestern and a study author, said, "We know that dioxin causes many endocrine disturbances in the human body. The study indirectly proves that BPH is an endocrine disorder." Regarding the decreased risk for BPH found in the veterans groups, Dr. Gupta cautioned that the finding should not be interpreted as a positive result. "It may be construed that a decrease in the risk of BPH is not a harmful effect, but the larger picture is that dioxins are affecting the normal growth and development of the reproductive system. Moreover, several effective treatments are available for BPH and thus reduction of BPH by a toxic compound is not a desirable effect." The study was based on data from the Air Force Health Study (AFHS). The AFHS is an epidemiologic study of more than 2,000 Air Force veterans who were responsible for spraying herbicides including Agent Orange during the Vietnam War. This group is called the Ranch Hand group because the spray program was called Operation Ranch Hand. Agent Orange was contaminated by a dioxin called 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). This study also involved a comparison group comprising veterans who served in Southeast Asia during the same time period, 1962-1971, but were not involved in the spraying program and thus were exposed to dioxins at levels equivalent to the general population. The veterans were interviewed and underwent physical examinations and lab tests during six examination cycles. The first cycle was conducted in 1982, so the veterans were followed for more than 20 years. "We found that the risk of developing BPH decreased with increasing exposure to dioxins in the comparison group," said Dr. Arnold Schecter, professor of environmental sciences at the UT School of Public Health Regional Campus at Dallas and a study author. "The risk of developing BPH was 24 percent lower in the group with the highest dioxin levels compared to the group with the lowest levels. In the Ranch Hand group, the risk of BPH tended to decrease with increased exposure to dioxins, but at extremely high exposure levels there was a tendency for the risk to increase." In addition, the study shows that higher dioxin exposure is associated with decreased testosterone levels, Dr. Gupta said. "It is known that lower testosterone levels are associated with decreased sexual function, decreased muscle mass and strength, infertility, increased fatigue, depression and reduced bone density," Dr. Gupta said. "However, we could not conclude from this study that dioxin exposure did lead to any of these adverse affects in the veterans in the study." The study points out the necessity to conduct additional environmental studies of the impact of dioxins and other toxins on the male reproductive system. Previous research was largely based on animal models, Dr. Gupta said, noting that the urgency of further research is underlined by a rise in disorders of the male reproductive tract over the past several decades. These include a decrease in sperm production by almost 50 percent, a three- to four-fold increase in testicular cancer, an increase in the incidence of cryptorchidism (undescended testes, a condition where the testes are not in their normal location in the scrotum) and hypospadias (abnormality of the urethra). The reason for this increase is not known, but it is thought that these disorders might be caused by environmental chemicals that are estrogenic and have endocrine-disrupting effects, Dr. Gupta said. Dioxins are among the most toxic substances known and are thought to be partially responsible for this increase in male reproductive tract disorders. They are formed as byproducts of processes such as incineration, smelting, paper and pulp manufacturing and pesticide and herbicide production. Humans are exposed to these chemicals primarily through consumption of animal fat and dairy products. Babies are exposed to the highest levels of dioxins through breast milk. Dioxins are eliminated extremely slowly from the body and they tend to stay in the body for several years to several decades after exposure. Other researchers contributing to the study came from the UT Health Science Center at San Antonio and the Air Force Research Laboratory, Brooks City-Base, Texas. ### About UT Southwestern Medical Center UT Southwestern Medical Center, one of the premier medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. Its more than 1,400 full-time faculty members including four active Nobel Prize winners, more than any other medical school in the world are responsible for groundbreaking medical advances and are committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 89,000 hospitalized patients and oversee 2.1 million outpatient visits a year. ### Media Contact: Toni Heinzl 214-648-3404 Toni.Heinzl@utsouthwestern.edu