For decades, factory workers in the Russian city of Chapaevsk churned out chemical weapons as part of the Soviet military buildup. In the process they released high levels of dioxin into the air and soil of the small, industrial city on the banks of the Volga River. Today the Soviet Union is no more. The Volga Chemical Plant in Chapaevsk produces herbicides not poison gas. But the dioxin remains.

So when Russ Hauser, SD’94, assistant professor in the Department of Environmental Health, met Russian researcher Boris Revich at the International Society for Epidemiology meeting last summer, they had something to talk about. Revich was looking for someone to work with on a study of the effects of dioxin exposure on the people of Chapaevsk (pronounced Cha-PIE-esk); Hauser researches the effects of chemicals on the male reproductive system. The result is a $15,000 pilot project funded by the National Institute of Environmental Health Sciences to study the sexual development of the boys in Chapaevsk.

Dioxin is one of a group of chemicals that interacts with the endocrine system, so this project stands to put Hauser on some of the most contentious terrain in environmental health today. "With sperm counts and any reproductive endpoints, there is a lot of controversy and a lot of strong opinions," Hauser says. At a New York Academy of Medicine meeting last May on Hazardous Substances and Male Reproductive Health, he watched from the audience as scientists stood at the microphones shouting at each other.

In one camp are supporters of the arguments outlined in Our Stolen Future, a popular 1996 book that linked these hormone-like contaminants to sexual mutations and declining sperm counts in animals. In the other are researchers who say links between human health problems and these chemicals--which include PCBs, now banned, as well as some everyday plastics--remain unproven. Sperm count and breast cancer studies continue to come up with seemingly conflicting results. Professor David Hunter was the lead author of a key study published on October 30, 1997 in the New England Journal of Medicine that found no link between breast cancer and exposure to DDT and PCBs. Yet in December, a study was published in the Lancet that found high breast cancer rates among women with high blood levels of dieldrin, another banned pesticide. The zigs and zags of the research findings certainly feed the acrimony; Hauser hopes his study might begin to steer the science toward a consensus and lower the volume on the debate.

There is no quarrel about dioxin being a carcinogen, and Hauser says dioxin does, indeed, also have demonstrated anti-estrogenic properties. But what scientists don’t agree on are the biological mechanisms that might underlie its harmful effects on reproductive systems. Animal studies give some clues. "Testicular descent is testosterone dependent, and studies in rats show that dioxin decreases plasma testosterone levels, so this may be the mechanism, but it is still unclear," notes Hauser. Rat study findings have also picked up on an association between dioxin exposure and undescended testicles. Exposure in utero and through breast milk has altered spermatogenesis and delayed the descent of the testes, according to Hauser. Finally, a small human study also found lowered testosterone in workers exposed to dioxin, Hauser says.

Sadly, Chapaevsk offers a clear-cut case of human exposure to dioxin. Revich and others have found dioxin levels in the soil as high as those in parts of Vietnam doused with the dioxin-laden defoliant, Agent Orange. They’ve also found health problems. "The population of Chapaevsk displays a higher mortality rate for lung, throat, and digestive system cancer. Pregnant women have a higher number of spontaneous abortions, and children are more likely to develop anemia," Revich wrote recently via e-mail from Moscow, where he is on staff at the Russian Academy of Science.

Hauser’s study will look specifically at male sexual development. He and his team will go to the Chapaevsk schools and seek out 2,000 boys between the ages of 11 and 15 for screening. He will be looking for signs of delayed sexual maturation, including cryptorchidism, or undescended testicles. The team will also measure testicular volume and penis size.

Then, they will take blood samples to measure for dioxin. "What we’re really trying to do is look for whether dioxin levels are higher in individuals with delayed puberty," says Hauser, who hopes to finish collecting data by the fall.

Shanna Swan, an epidemiologist at the University of Missouri, Columbia, has argued for the endocrine disruptor—falling sperm count link. She notes that Hauser’s work could break new ground because "there is not a lot of data on male reproductive function that is directly correlated to exposure except in occupational settings." Yet Swan is also skeptical: she believes exposure to endocrine disruptors in utero is probably the most critical and doubts if a study like Hauser’s, which is measuring dioxin levels in the blood of teenagers, will nail down the answer to the key question.

Hauser acknowledges the criticism, but argues that since the half-life for dioxin is long, the blood samples taken when the children are 11 to 15 will represent early life exposure. His study also calls for getting information on breastfeeding, which can be a significant dioxin exposure for infants.

Hunter agrees that this method should suffice for dioxins. Because chemicals like dioxin bind to lipids, they do tend to have a longer half-life, he says. And while taking dioxin levels in boys might be a "suboptimal" way of measuring prenatal exposure, he notes, it may be the only way in studies like Hauser’s: "In many cases it is impossible to measure in utero exposure. You need a minimum 13- or 14-year study or banked samples from pregnant women or babies."

Hauser, a New York native who earned his medical degree at the Albert Einstein College of Medicine in New York City in 1985, has been an assistant professor at the School since 1997. He says his work in reproductive health grew from a "longstanding interest in endocrine disruptors such as PCBs, dioxins, and pesticides--compounds with widespread distribution and persistence. There were few human studies on the reproductive health effects of these compounds, and most studies focused on cancer endpoints." Hauser conducted a small study at a Massachusetts General Hospital infertility clinic last year looking for links between sperm count, motility, and morphology and blood levels of PCBs and DDE, a metabolite for exposure to the banned pesticide DDT. The study was "suggestive" of a link between exposure and sperm abnormalities, but Hauser decided the research only warranted an abstract for May’s meeting on Hazardous Substances and Male Reproductive Health, because it only included 29 men. Hauser says, "I’m hesitant for people to draw conclusions from such small numbers." He’s also seeking support for a study looking at the relationship between chemical and reproductive problems for women including endometriosis and menstrual cycle dysfunction.

-- Tinker Ready