Perspectives on reproductive and developmental toxicity.

Abstract

Human reproduction and development is a cycle of interdependent events. Virtually all of its phases have been shown to be the primary target of one or more non-mutagenic exogenous agents. Such agents interfere with certain of the countless epigenetic or ontogenic events essential for normal completion of the cycle. Mutagens disrupt this cycle at some points, but the overwhelming majority of reproductive and developmental toxins are not mutagenic. As in all aspects of toxicology, the reproductive and developmental effects of chemicals are determined by the intrinsic nature of the chemical, the quantity of the chemical exposure, the duration of exposure and the stage of the cycle at which it occurs. Signs of reproductive toxicity range from reduced fertility to spontaneous abortion. Adverse effects on the conceptus are categorized as functional deficits, developmental retardation, structural abnormality and death. One or more of these is anticipated to occur as a result of excess exposure to most chemicals. Although the degree of hazard and risk potential can be calculated in each instance, chemicals differ markedly in their ability to interfere with reproduction (Amann, 1982) and/or development (Johnson, 1984). Standardized methods for reproductive and developmental toxicity safety evaluation are available for detecting adverse effects upon any aspect of reproduction and development. Data currently available establish that these state-of-the-art tests conducted in laboratory animals are often highly predictive of the type of adverse effect a particular chemical will have in humans, as well as the exposure level at which it will occur. By adding a modest safety factor to the no-observed-effect-level of well-executed animal studies, safe human exposure levels can be established. Responsibility for determining the intrinsic hazard potential and the risk estimate of exposure rests with manufacturers and major users of occupational and other environmental chemicals. As public awareness of reproductive and developmental hazards has increased in recent years, it has come to be understood that some chemicals have a predilection for causing reproductive impairment and/or disrupting development in the absence of other toxicity. Such substances must be identified to establish safe exposure levels and to determine the types of effects to be expected, should excessive human exposure occur. The setting of safe exposure levels is necessary both from the standpoints of ensuring public safety and avoiding product liability.