By David N. Leff

From unbreakable baby bottles to flame-retarding pajamas to plastic food containers to bullet-proof vests to dental glue, pesticides and detergents, one chemical common denominator is bisphenol A.

This industrial compound was originally made as a synthetic estrogen, but now stars as a monomer in manufacturing many basic plastics, epoxies, polycarbonate and certain polyesters. Bisphenol A (BPA) is an environmental toxin, which in mammals mimics the potent effects of the estrogenic sex hormone, estradiol. Estradiol, a natural mammalian estrogen, gets the credit for many female traits. Pharmaceutically, it's a cornerstone of menstrual and menopausal therapeutics, and an ingredient of contraceptives.

Manufacturers of BPA-containing products claim that their plastics are nondegradable. However, this week in New Orleans, at a conference on Estrogens in the Environment, reproductive biologist Frederick vom Saal and his doctoral candidate, Kembra Howdeshell, presented evidence showing that BPA leaches into the environment from plastic products, with repeated use.

Vom Saal, professor of biological sciences at the University of Missouri in Columbia, is senior author of a brief communication in today's Nature, dated Oct. 21, 1999, titled: "Exposure to bisphenol A advances puberty." Howdeshell is a co-author.

BPA's suspected physiological threat to life in the wild, and to humans, has become a worldwide research undertaking, with 1,475 scientific papers currently displayed on the U.S. National Library of Medicine database. A random sampling records numerous tests of the compound's integrity in dental adhesives, its presumed cause of contact dermatitis from epoxy resins, damage to rainbow trout and carp in rivers, to its exposure in minute marine and freshwater crustaceans at the base of the food chain.

The Missouri scientists administered BPA to 21 pregnant mice "at a dose equivalent to that typically found in the environment, on days 11 to 17 of gestation," vom Saal told BioWorld Today. "Then on day 19," he recounted, "we delivered the litters of fully formed pups by Caesarian section.

Prenatal Litter Bundling Critical To Outcome

But while the future mice were still in the womb, the co-authors took careful note of their fetal positions relative to each other. "The intrauterine position," vom Saal explained, "determines fetal hormone levels, because endogenous sex steroids are transported from one fetus to another. Thus, mouse fetuses positioned between two males are exposed to the lowest levels of estradiol; those between females, to the highest.

"Then," he continued, "we gave the newborn mice for adoption and nursing to untreated foster mothers. Upon weaning them after 22 days of suckling mouse milk, we made a salient finding: Females, whose biological mothers had been treated with BPA, were heavier than control females. Those that had nestled between two other females while in utero had put on 22 percent more weight than controls; while females snuggling next to one male, added 9 percent to their avoirdupois.

"These findings," vom Saal added, "were virtually identical for male siblings," which suggests that although bisphenol A may not be immoral or illegal, it apparently is fattening.

But that's not all. At 26 days of post-natal life, the youthful females were housed in individual cages, but close enough to males so that the latter's' masculine pheromone sex signals reached the females. "Once their vaginas opened," vom Saal related, "which occurs early in puberty, our team took daily vaginal smears for cellular signs of estrus - readiness to receive male coital partners. This coming of reproductive age correlated markedly with first postpubertal ovulation in females who had passed their prenatal development under the influence of maternal BPA, while developing between two females, but not those who did so between two males."

From these outcomes, the co-authors concluded, "Very small increases in the level of endogenous (inborn) estradiol may substantially increase the sensitivity of fetuses to estrogenic endocrine-disrupting chemicals [such as bisphenol A] consumed by pregnant women, so some fetuses may be at particularly high risk for a wide array of abnormalities and diseases."

Add BPA To Overweight Suspect Lineup

This prognostication points squarely at disorders of childhood and maturity widespread in Western nations, notably obesity. Over recent decades, vom Saal pointed out, medical statisticians have reported a dramatic increase in the number of overweight Americans. This is commonly blamed on a sedentary lifestyle while pigging out on sweets and pizza. However, the co-authors suggest that "a chemical estrogen used to make plastics could be a contributing factor."

It could contribute as well, they point out, to the increasing incidence of precocious puberty in young girls, and sexual anomalies in boys. Vom Saal cited a 1997 report by the Centers for Disease Control "that for all male births in the U.S., the incidence of abnormal formation of the penis - hypospadias - has doubled over the last 20 years."

As for early puberty, he cited a presentation at the New Orleans meeting by a Puerto Rican investigator. "He reported that over the past 15 years in Puerto Rico - this is just stunning - we're talking about 2-year-old girls showing breast development. They suspect another plastics intermediate, phthalates.

"This," vom Saal said, "points to the need for research on humans, and emphasizes the role of underlying variability in the human population. We're not offering an answer concerning effects in humans with our findings," he observed. "Instead, the findings pose a question regarding human health. This study should serve as a guide for human research. We believe that the medical community ought to take a long look at this data, and consider bisphenol A as a possible cause for the changes in growth, sexual maturation and reproduction abnormalities that have been reported in humans in recent decades."

His research reported in today's Nature was conducted over a one-year period, funded by a $500,000 grant from the National Institutes of Health.