Bisphenol aggression: effects shown in mice. (Science Selections).

Although many studies have documented the adverse effects of endocrine disruptors on reproductive organs, until recently little research has been done on the influence of these chemicals on behavioral development. A new study led by Keisuke Kawai of Kyushu University evaluates the effect of fetal exposure to the estrogen mimic bisphenol A on aggression and serum testosterone concentrations in male mice [EHP 111:175-178]. Bisphenol A is a monomer used to manufacture polycarbonate plastic and the resin used to line food and drink cans. It also is a component of the plastic used in dental fillings. The Japanese team found that bisphenol A, administered to pregnant mice during the early period of gestation, temporarily exaggerated aggressive behavior in male offspring. Low-dose bisphenol A also interfered with the normal development of the offspring's reproductive organs.

From gestation days 11 to 17, pregnant CD-1 mice were fed bisphenol A at doses of either 2 ng/g or 20 ng/g body weight. Their male offspring underwent aggression rating and blood sampling for testosterone at 8, 12, and 16 weeks of age. (Mice are considered to have just reached sexual maturity at age 8 weeks.) The team rated aggression according to how a male mouse acted toward an age-matched control "opponent" introduced into its cage. The scientists assessed the amount of time each test mouse spent sniffing or attacking its opponent over a 7-minute period.

At 8 weeks, males whose mothers were exposed to either concentration of bisphenol A were rated as significantly more aggressive than the control group, and the increase in aggression was comparable in both dose groups. At 12 and 16 weeks, however, no difference was found between the treated and control mice.

For the low-dose mice, the relative testis weight per gram of body weight at 8 and 12 weeks was significantly lower than that of the controls. The same effect was noted for the high-dose mice at 12 weeks only. Both dose groups had normal testis weight at 16 weeks. Testosterone concentration was never significantly different in treated mice compared to the controls.

Whether bisphenol A also affected reproductive organ function is unclear. However, neither relative testis weight nor testosterone concentration appeared to be related to aggressive behavior.

Perhaps more interesting is the observation that the low dose of bisphenol A seemed to have a greater effect than the higher dose on relative testis weight. Some researchers have suggested that indeed, low doses of endocrine disruptors might cause unique outcomes that will not be observed at higher doses. The mechanisms of the low-dose effects of endocrine disruptors such as bisphenol A remain unclear, and their pathway has yet to be determined.