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EVALUATION AND INTERPRETATION OF MATERNAL TOXICITY IN SEGMENT II STUDIES: ISSUES, SOME ANSWERS AND DATA NEEDS
Citation:
Rogers, J M. AND N Chernoff. EVALUATION AND INTERPRETATION OF MATERNAL TOXICITY IN SEGMENT II STUDIES: ISSUES, SOME ANSWERS AND DATA NEEDS. Presented at ICTX 10th International Congess of Toxicology, Tampere, Finland, July 11-15, 2004.
Description:
Rogers, J.M., and N. Chernoff. Reproductive Toxicology Division, NHEERL, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, U.S.A. Evaluation and interpretation of maternal toxicity in Segment II studies: Issues, some answers and data needs.
U.S. EPA guidelines for Segment II developmental toxicity stipulate that the highest maternal dosage used should induce significant maternal toxicity, measured as effects on weight gain or mortality. Often in such studies, developmental toxicity is observed only at the highest maternal dosage, thus requiring some interpretation of the relationship between the maternal and developmental toxicities observed. We and others have carried out studies and surveys of the literature to elucidate the links between maternal and developmental toxicity, including attempts to define spectral of developmental effects correlated with maternal toxicity in different laboratory species, to define specific ratios to quantify the relationship between maternal and developmental toxicity, and experiments carried out for specific toxicants demonstrating that a maternally toxic effect was responsible for the developmental toxicity observed. Despite the fact that the interpretation of the role of maternal toxicity in developmental toxicity studies has been a long-standing issue, there are still significant gaps in our understanding of this relationship. The limited maternal toxicity endpoints used (mortality, weight, clinical observations, food and water intake) do not inform one of the underlying physiological insult, so a biological link between maternal and developmental toxicities is difficult to make. Further, although maternal food intake is usually recorded, pair-fed controls are usually not included, making it impossible to determine the role of reduced food intake. This presentation will review the state of our understanding of the relationship between maternal and developmental toxicity and discuss research needs to improve our understanding of this relationship. This abstract does not reflect U.S. EPA policy.