PCBs' legacy: fewer boys. (Endocrine Disruptions).

The world's worst polychlorinated biphenyl (PCB) contamination incident plagues male victims two decades later in their weakened ability to father boys. In 1979, 2,000 people in Yu-Cheng, Taiwan, were exposed to PCBs from contaminated cooking oil. Only 46% of children born to young men exposed in this oil disaster are male (compared to a world average of 51-52%), report a team of researchers from London and Taiwan in the 13 July 2002 issue of The Lancet. Women exposed in the same incident showed no abnormalities in the sex ratio of their offspring.

PCBs are synthetic organic chemicals used extensively for five decades to insulate electrical equipment. PCBs were used as a heat-transfer medium in processing the rice oil involved in the Yu-Cheng incident. PCBs accidentally leaked from a pipe into the oil, and polychlorinated dibenzofurans (PCDFs) were formed as a by-product during the oil processing as well as later during cooking.

PCBs were banned in the United States more than 25 years ago, but persist in the environment and accumulate in body fat. "Some PCBs are forever," says Walter Rogan, a senior epidemiologist at the NIEHS and a researcher in earlier Yu-Cheng studies. "They don't degrade or metabolize. They're very stable." PCB levels in Yu-Cheng victims remain about 20 times the U.S. average, according to Rogan, and their PCDF levels are 10,000 times the U.S. average.

The researchers don't understand how the chemicals alter sex ratios; they've had few exposed populations to study and are unable to replicate the phenomenon in animal models. But they suspect that PCBs somehow inhibit either sperm carrying the male Y chromosome or the XY-fertilized egg. Only men carry the sex-differentiating chromosome, which could explain why exposed women had children at normal sex ratios.

The researchers analyzed the sex of children born between 1979 and 1999 to 996 exposed mothers and 693 exposed fathers. (In a few couples, both parents had been exposed, but there were too few of these couples to be considered a study group.) For every exposed parent, the team enrolled three same-sex parents of similar age and neighborhood in a control group.

Exposed men of all ages fathered fewer boys than those in the control group. The effect was greatest in men exposed before age 20, who had a male birth rate of 46%. Men of the same generation in the control group had a male birth rate of 54%.

The lower ratio of male offspring in men exposed before age 20 suggests that men are most vulnerable to endocrine disruptors during their sexual development. "We see that developmental processes are at greater risk," says Iliana del Rio Gomez, a researcher from the London School of Hygiene & Tropical Medicine in England and coauthor of the Lancet report.

Del Rio Gomez suspects that the altered sex ratio of offspring is just one of a cluster of endocrine-disrupting effects that PCBs have on males. "When a population shows evidence of one [pathology], it is suggested that researchers should try to identify others, as they are more likely to be present, too," she says. "Sex ratios are being seen as a useful indicator of reproductive hazards in men and women."

Del Rio Gomez and her colleagues are studying fertility in Yu-Cheng men and women, and expect to publish their findings in the future.

In the January 2002 issue of the Journal of Occupational and Environmental Medicine, a team led by epidemiologist Wilfried Karmaus of Michigan State University reported skewed sex ratios in the children of Michigan men who ate PCB-contaminated fish from the Great Lakes. In this case, however, the men fathered fewer girls. "We don't know why [these PCBs had] the opposite effect," Rogan says.

A mass PCB poisoning on the magnitude of Yu-Cheng is unlikely in the United States. However, scientists warn that, although the contaminants have been banned for years, they remain in old transformers, appliances, and the food chain. Workers cleaning waste sites and people eating fish from contaminated lakes still face a risk. In 2001, eight states issued advisories against eating fish from PCB-contaminated waters.