April 12, 2010
Dr. John DeSesso and Dr. Abby Li’s paper, “Analysis and Integration of Developmental Neurotoxicity and Ancillary Data into Risk Assessment: A Case Study of Dimethoate,” was judged as the Outstanding Paper Demonstrating the Application of Risk Assessment Published in 2009, by the Risk Assessment Specialty Section of the Society of Toxicology.
A committee of scientists surveyed the papers dealing with applications of risk assessment that were published in 2009. Over 1,000 papers were considered. From this pool, after reviewing the abstracts, 83 papers were selected to be read in full by the entire committee.
About the Paper
An assessment was conducted on a complex data set to determine the critical effect to be used as the point of departure to set reference values for the organophosphate pesticide, dimethoate. The issue of concern was the occurrence of excess pup deaths during the early part of the lactation period, when dams had been exposed to dimethoate during gestation and throughout lactation as part of a developmental neurotoxicity study.
Intuition would lead many toxicologists to assume that such an exposure paradigm would lead to a direct impact of dimethoate on the health of the pups, leading to their demise. Our assessment, however, showed that the target organism was the lactating maternal animals, not the pups. An important element in the assessment was the examination of pup mortality data on a per litter basis. This examination led to a novel analysis that allowed us to identify certain maternal behaviors that were associated with those litters that experienced excess pup mortality. Analysis of cross-fostering data allowed us to demonstrate that exposure of maternal animals during lactation (regardless of whether pups had been borne of exposed or non-exposed dams) led to poor nurturing behavior and subsequent pup death. When we compared the BMDL10 for pup mortality in the reproductive and developmental toxicity studies to that of the previously calculated BMDL10 in cholinesterase sensitivity studies (which had been determined previously), the cholinesterase inhibition-derived level was greater than threefold more protective than the level derived from the set of reproductive studies.
DeSesso, J. M., R. E. Watson, C. L. Keen, K. P. Hazelden, L. C. Haws, and A. A. Li, (2009) “Analysis and Integration of Developmental Neurotoxicity and Ancillary Data into Risk Assessment: A Case Study of Dimethoate,” Journal of Toxicology and Environmental Health Part A: Current Issues, 72, pp. 94-109.