The common industrial chemical bisphenol A (BPA) has been linked to many ills, including reproductive abnormalities, cardiovascular disease and cancer. Much of the evidence for these associations, however, has been drawn from animal or in vitro research and has been somewhat controversial as to its precise implications for human health.

Now, a human study has found strong links between BPA levels and semen quality—and the findings are not looking good, especially for men frequently exposed to the compound on the job.

Researchers studied the urine (where BPA can be measured) and semen of 218 male factory workers in China, some of whom make BPA or put it into other products (such as plastics and epoxy resins that line cans), and the remainder, whose work did not put them in direct contact with the chemical.

Compared with the control group, the men who worked in the BPA-based factories had more than four times the chance of having lowered sperm counts and more than double the risk of having lower sperm motility (swimming ability). The results of the analysis, which controlled for potentially confounding factors (including age, heavy metal and other chemical exposures, chronic disease, smoking, alcohol use, sexual history, etcetera), were published online October 28 in Fertility and Sterility in a study led by De-Kun Li, a reproductive and perinatal epidemiologist at the Kaiser Permanente Division of Research in Oakland, Calif.

The men in the study group who had not been exposed to BPA in the workplace nonetheless had been subject to everyday environmental contact, such as with BPA-containing food or beverage containers. But even these men, whose levels were slightly lower than those found in a typical U.S. man, showed decreased semen quality that correlated with their relative BPA levels.

The precise mechanisms by which BPA might be affecting sexual function and semen quality are not yet well understood. The chemical is thought to be seen by the body as an estrogen and anti-androgen and likely disrupts hormones and hormone receptors, thus, possibly affecting hormone-dependent semen production and survival.

Previous studies by Li and his colleagues had linked environmental BPA exposure in U.S. men to sexual dysfunction. The new analysis, however, presents more objective data and implies "that BPA may have even more toxicity than we thought," Li says.

The new findings help corroborate results from another human study published earlier this year, which found that men who had the highest levels of BPA in their urine had about 23 percent lower sperm concentrations. This study, published online in July in Reproductive Toxicology, had recruited male subjects via a fertility clinic. John Meeker, an assistant professor of environmental health sciences at the University of Michigan School of Public Health, who led the July study and was not involved in the newest research, notes that the latest work from Li's group helps strengthen the case that BPA might not just be passing inertly through our bodies.

Li hopes that his team's work will help add to a growing body of literature that suggests current regulatory standards for BPA concentrations are outdated. "U.S. regulation is way out of whack," Li says. The men in his team's study who worked in the BPA-processing plants had median concentrations of about 38.7 micrograms of BPA per liter of urine, which was about 40 times higher than the control group (which had about 1.4 micrograms per liter—lower than average U.S. male levels, 2.3 micrograms per liter). Current U.S. regulatory standards, however, place daily intake limits at about 70 times the amount (2,687.5 micrograms per liter) that the BPA factory workers had. The U.S. Food and Drug Administration is in the process of reviewing current safety data on the chemical, and as of this March the U.S. Environmental Protection Agency had listed it as a "chemical of concern."

Both Li and Meeker emphasize the importance of consistent findings in human studies, which "gives you some more confidence in the existence of an association," Meeker says. And, says Li, "Our findings are consistent with animal studies," which can provide clues as to the biological processes behind the changes.

Just how much—and how often—people are exposed to BPA is still up for debate. But new tests, which continue to consistently find the compound in people's urine, suggest that either it is not cleared from the body as quickly as people have previously thought (in four to six hours) or, says Meeker, that "we're probably exposed on a daily basis—from a variety of sources."

New studies are looking to embryonic development, to see whether BPA exposure during pregnancy is having any deleterious effects on development. To Li, finding such striking differences in the quality of semen, the supply of which renews about every 90 days, is an indication that it might be having even more profound effects elsewhere in the body—of both males and females. "You have to wonder, if BPA does impact the semen, what else can it impact," he says.