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Relationships of maternal and fetal weight changes in developmental toxicology bioassays
Citation:
CHERNOFF, N. Relationships of maternal and fetal weight changes in developmental toxicology bioassays. Presented at 49th Annual Teratology Meeting, Rio Grande, PUERTO RICO, June 26 - July 01, 2009.
Impact/Purpose:
To be presented at the 49th Annual Teratology Meeting
Description:
Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects in the embryo/fetus. Guidelines require the inclusion of a dose level(s) that induces “overt maternal toxicity”. The common occurrence of dose levels at which both maternal and fetal toxicity has been observed has led to a number of attempts to characterize possible toxicological relationships between these endpoints. An analysis of 125 developmental toxicity bioassays in the mouse, rat, and rabbit conducted by the National Toxicology Program from 1982 to 2004 allows a number of general conclusions to be made: 1) most Lowest Observable Adverse Effect Levels (LOAELs) were determined by reduced maternal gestational weight gain or fetal weight at term, 2) maternal weight reductions are associated with reduced food intake for a variety of dissimilar test agents, 3) lower fetal weights were associated with reduced maternal weight gains late in gestation, and 4) the degree of fetal weight reduction is correlated with the extent of the maternal weight loss. In a substantial number of the studies, reduced term fetal weights may, therefore, be due to maternal undernutrition caused by general toxicity rather than direct developmental insult. Consequently, such test agents may be erroneously classified as primary developmental toxicants. There are experimental approaches that can test the hypothesis that maternal undernutrition in standard developmental toxicology bioassays may be responsible for significant term fetal weight decrements.