A methodology for assessing developmental and reproductive hazards of chemicals

A method to evaluate developmental and reproductive toxicity for a wide variety of chemicals has been developed. The assessment includes all effects on male and female reproductive function as well as effects in the developing embryo or fetus. Effects are evaluated using primary literature. Studies are classified as adequate, supportive or inadequate. Only adequate studies are used in further assessment. Reproductive and developmental toxicity of each chemical is assessed using both qualitative and quantitative information. Three elements are used to describe developmental toxicity of chemicals: Lowest Observed Effect Level (LOEL), weight-of-evidence classification and a Risk Ratio (RR). For reproductive toxicity only two elements are used, LOEL and weight-of-evidence. LOEL is defined as the lowest dose at which statistically significant effects are found. A risk ratio is calculated using the levels of the chemical producing acute maternal lethality (LD50 or LC50) to the levels producing developmental toxicity in the same animal species and route of administration. The risk ratio is used to indicate the extent to which the developing embryo or fetus is more susceptible than the dam to the toxic effects of a chemical. A toxicity score (A through E) is assigned to each chemical from a two- or three-dimensional matrix based on the elements of assessment. The score reflects the degree of hazard associated with each chemical. To date, 110 chemicals have been evaluated using this system. From the selected databases, 188 articles were reviewed. Of these, 103 (55%) were judged to be adequate, 23 (12%) provide supportive information, and 62 (33%) were inadequate and excluded from the assessment methodology. Scores for 47 chemical with some adequate data available show that high hazard substances (28 A and B) outnumber those associated with lower hazards (a total of 19 C, D and E). This may reflect a selection process for testing which favors substances suspected of causing adverse reproductive and developmental effects.