ToxSci Advance Access originally published online on August 24, 2005
Toxicological Sciences 2005 88(1):24-29; doi:10.1093/toxsci/kfi299
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Developmental Toxicology Evaluations—Issues with Including Neurotoxicology and Immunotoxicology Assessments in Reproductive Toxicology Studies
* The DuPont Company., Haskell Laboratory, Newark, Delaware 19714; Worldwide Safety Sciences, Pfizer Global Research and Development, Groton, Connecticut 06340; United States Food and Drug Administration, Center for Drug Evaluation Research, Office of New Drugs, Rockville, Maryland 20857; ILSI Health and Environmental Sciences Institute, Washington, DC 20005–5802; ¶ United States Environmental Protection Agency, National Center for Environmental Assessment, Washington, DC 20460–0001; || Bayer CropScience LP, Stilwell, Kansas 66085–9104; ||| The Dow Chemical Company, Toxicology & Environmental Research and Consulting, Midland, Michigan 48674; and |||| Worldwide Safety Sciences, Pfizer Global Research and Development, San Diego, CA 92064, leighann.burns{at}pfizer.com
Received June 30, 2005; accepted August 21, 2005
Developmental and reproductive toxicology (DART) has routinely been a part of safety assessment. Attention is now focused on the effects of chemicals on the developing nervous and immune systems. This focus on developmental neurotoxicology (DNT) and developmental immunotoxicology (DIT) is based on the premise that children differ from adults in some aspects of their biology and, thus, may also differ in their responses to chemicals. This session's objective was to discuss issues common to DNT and DIT as they relate to DART protocols, including high dose selection and maternal toxicity, adequacy of pup exposure during lactation, use of a different dosing paradigm for DART versus DNT or DIT studies, and whether DIT and DNT endpoints can be incorporated into a single DART study for hazard identification purposes. Consensus was achieved on all topics except the adequacy for risk assessment purposes of the use of a limited number of endpoints for DIT and DNT, with the DNT endpoints being the primary focus of disagreement. Panelists indicated that a combination study design for hazard identification was feasible, though flexibility to meet the scientific needs of the project was emphasized. The adequacy of existing triggers for additional developmental studies was also questioned. Panelists iterated the importance of understanding pup exposure during the various life stages and the use of toxicokinetic data in designing these studies. The group agreed to consider the HESI ACSA Life Stages Task Force recommendations as a next step to address some of the issues and challenges raised during this session.
Key Words: developmental immunotoxicology; DIT; developmental neurotoxicology; DNT; developmental and reproductive toxicology; DART; study design; combination study; hazard identification; panel discussion.
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