Animal studies of methylmercury and PCBs: what do they tell us about expected effects in humans?

Abstract

Methylmercury and polychlorinated biphenyls (PCBs) exemplify the important interactions that should take place between epidemiological and laboratory investigations of developmental neurotoxicants. Often found in the same source, perhaps with multiplicative interactions, it is difficult to isolate specific profiles of effects without advanced behavioral procedures and controlled exposures using laboratory animals. The present review focuses on the effects of developmental exposure to methylmercury or PCBs as expressed in adult animals. The PCBs are subdivided into two structural classes, nonortho-substituted ("coplanar" or "dioxin-like") PCBs and ortho-substituted ("noncoplanar") PCBs, a distinction supported by different behavioral profiles and neural mechanisms of action. Methylmercury's profile is dominated by sensory effects with a likely cortical site of action. Some of these effects may be amplified with aging. Methylmercury's effects on functions generally termed cognitive can be understood by distinguishing between those reflecting the acquisition of a response-consequence relationship from those reflecting memory or contextual influences over behavior. Methylmercury does not appear to impair memory or discriminations, but retards acquisition of a response-reinforcer relationship. Like methylmercury, non-ortho-substituted PCBs do not appear to degrade memory and contextual control. Ortho-substituted PCBs impair performance on certain spatially-based discrimination and memory tasks. Methylmercury and non-ortho-substituted PCBs disturb the temporal pattern seen in fixed-interval schedules, but apparently without a significant change in the pattern of interresponse times. The ortho-substituted PCBs disrupted this pattern, but did so by increasing the number of short interresponse times.