December 1998 - Questions to the SAP
A Retrospective Analysis of
Twelve Developmental Neurotoxicity Studies:
Submitted to the USEPA Office of Prevention, Pesticides, and Toxic
Questions to the Scientific Advisory Panel
1.) Does the Panel agree with the conclusions, that based upon these data:
- That the data show a variety of effects on functional development of behavior and the structural development of the nervous system, as currently assessed by the methods in the DNT guideline, and that these methods constitute a reasonable set of general methods for assessment of toxicity to the offspring;
- that effects on neurological development, as currently assessed in the DNT, can be a sensitive indicator of toxicity to offspring in comparison to effects found in either developmental or reproduction studies, or in comparison to adult neurotoxicity studies;
- that effects on brain weight, histopathology, and morphometric assessments also can be sensitive indicators of toxicity to the offspring;
- that these functional and morphological effects both seem to occur with similar frequency, i.e., appear to be correlated; and
- that neurobehavioral effects in dams as assessed by detailed clinical observations in the DNT can be sensitive indicators of toxicity in adults.
2.) Does the Panel have comments on any of the specific issues raised in this paper?
- Route of administration
- Duration of treatment
- The use of combined protocols
- Biochemical measures, including cholinesterase inhibition
- Pharmacokinetic data
- Simple morphometric analysis
- Age-related susceptibility
3.) Does the Panel agree with the Agency proposal to include the use of the developmental neurotoxicity study, when available, for the selection of endpoints for risk assessment of pesticides and, if so, for revision of the document: Hazard Identification: Toxicology Endpoint Selection Process to reflect this addition?
- in acute dietary risk assessment
- in short-term and intermediate-term occupational and residential risk assessment
- in chronic dietary risk assessment