Sexually dimorphic nonreproductive behaviors as indicators of endocrine disruption

Measures of cognitive and other behaviors not specifically related to reproduction are often sex-linked. Males and females perform differently on many tasks and often interact with members of their species in dissimilar ways. If such differences are diminished, reversed, or widened by prenatal chemical exposures, a reasonable inference is that exposure interfered with sexual differentiation of the brain, largely, but not exclusively, through interference with the actions of gonadal hormones. Explicit recognition of sex differences in performance is not a prominent feature of toxicity testing, however, except for reproduction studies, and is not a recognized criterion in developmental neurotoxicity testing. In contrast to the low visibility accorded sex differences in testing protocols for the assessment of developmental neurotoxicity, the literature is filled with examples showing that the developing male and female respond differently to many chemical agents, with subsequent expression in behavior. Quite often, even when such differences are reported, further analyses are not carried out nor are subsequent studies conducted for clarification. Moreover, many investigators include only male subjects. Both polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) studies provide several examples of striking differences between the behavioral responses of male and female offspring to developmental exposure. They offer examples, as well, of how to approach the study and analysis of such differences. Given the societal importance of risk assessments applied to potential developmental neurotoxicants, studies should be deemed questionable if they fail to include outcome measures based on sexual dimorphisms in nonreproductive behaviors.