A retrospective performance assessment of the developmental neurotoxicity study in support of OECD test guideline 426.
OBJECTIVE
We conducted a review of the history and performance of developmental neurotoxicity (DNT) testing in support of the finalization and implementation of Organisation of Economic Co-operation and Development (OECD) DNT test guideline 426 (TG 426).
In this review we summarize extensive scientific efforts that form the foundation for this testing paradigm, including basic neurotoxicology research, interlaboratory collaborative studies, expert workshops, and validation studies, and we address the relevance, applicability, and use of the DNT study in risk assessment.


CONCLUSIONS
The OECD DNT guideline represents the best available science for assessing the potential for DNT in human health risk assessment, and data generated with this protocol are relevant and reliable for the assessment of these end points. The test methods used have been subjected to an extensive history of international validation, peer review, and evaluation, which is contained in the public record. The reproducibility, reliability, and sensitivity of these methods have been demonstrated, using a wide variety of test substances, in accordance with OECD guidance on the validation and international acceptance of new or updated test methods for hazard characterization. Multiple independent, expert scientific peer reviews affirm these conclusions.
Makris
Susan L
SL
Office of Research and Development, National Center for Environmental Assessment, U.S Environmental Protection Agency, Washington, DC 20460-0001, USA. makris.susan@epa.gov
Raffaele
Kathleen
K
Allen
Sandra
S
Bowers
Wayne J
WJ
Hass
Ulla
U
Alleva
Enrico
E
Calamandrei
Gemma
G
Sheets
Larry
L
Amcoff
Patric
P
Delrue
Nathalie
N
Crofton
Kevin M
KM
D017408:Guidelines as Topic; D006801:Humans; D009420:Nervous System / Q000187:drug effects* / Q000254:growth & development; D012189:Retrospective Studies; D018570:Risk Assessment; D018675:Toxicity Tests