You are here:
DEVELOPMENTAL NEUROTOXICITY TESTING GUIDELINES: A QUALIFICATIVE RETROSPECTIVE ANALYSIS OF POSITIVE CONTROL DATA.
Citation:
Raffaele, K. C., S. L. Makris, W. F. Sette, AND K M. Crofton. DEVELOPMENTAL NEUROTOXICITY TESTING GUIDELINES: A QUALIFICATIVE RETROSPECTIVE ANALYSIS OF POSITIVE CONTROL DATA. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
The USEPA Developmental Neurotoxicity (DNT) Study Test Guideline calls for both functional and neuropathological assessments in offspring during and following maternal exposure. This guideline also requires data from positive control (PC) agents. Submission of these data permit evaluation of laboratory proficiency in the detection of changes in the structure and function of the developing nervous system and comparison of the sensitivity of assessments in different studies and labs. This project surveyed approaches taken in contract and industrial laboratories in generating and providing these data. Data from 24 DNT studies from 13 different laboratories were summarized by method, e.g., motor activity, for information on: age relevance, dose response, gender, group size, statistics, report quality, quality assurance, age of data relative to main study, and relevance of methods to the main study. Endpoints included: developmental landmarks, FOB, motor activity, startle response, learning and memory, standard histopathology and brain morphometry. Results ranged from no PC data for two laboratories, to one laboratory which submitted 16 different reports. The qualitative range was similarly broad, from excellent to extremely poor. Various quality problems were identified including: poor report structure (e.g., copies of poster presentations), lack of individual data, inadequate methodological details, differences in methods between the PC report and the main study, submission of very old data or data from completely different laboratories, significant variance in the submitted data, use of inappropriate PC chemicals or doses that were without effect, lack of statistical analysis, use of only one sex, and use of inappropriate age animals. Preliminary analyses suggest that there were only 4 out of 13 laboratories judged to have submitted adequate PC data. This abstract does not necessarily reflect the policy of the US EPA.