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Neurotoxicol Teratol. 2017 Sep;63:24-45. doi: 10.1016/j.ntt.2017.07.001. Epub 2017 Jul 27.

Recommendations for harmonization of data collection and analysis of developmental neurotoxicity endpoints in regulatory guideline studies: Proceedings of workshops presented at Society of Toxicology and joint Teratology Society and Neurobehavioral Teratology Society meetings.

Author information

1
Exponent Health Science, Inc., USA. Electronic address: abbyli@exponent.com.
2
Bayer CropScience, USA. Electronic address: Larry.sheets@bayer.com.
3
US EPA Office of Land and Emergency Management, USA. Electronic address: Raffaele.kathleen@epa.gov.
4
US EPA National Health and Environmental Effects Research Laboratory, Office of Research and Development (NHEERL, ORD), USA.
5
Syngenta Canada, Canada. Electronic address: Angela.hofstra@syngenta.com.
6
Charles River Laboratories, Global Developmental, Reproductive and Juvenile Toxicology, USA. Electronic address: Alan.Hoberman@crl.com.
7
US EPA National Center for Environmental Assessment, Office of Research and Development (NCEA ORD), USA. Electronic address: Makris.Susan@epa.gov.
8
Consultants in Veterinary Pathology, Inc., USA. Electronic address: vetpathol@cs.com.
9
GEMpath Inc., USA. Electronic address: Bradgempath@aol.com.
10
Merck KGaA, Global Pathology & Reproductive Toxicology, Germany.
11
University of Saskatchewan, Department of Pathology, Canada. Electronic address: roland.auer@usask.ca.
12
Exponent Health Science, Inc., USA. Electronic address: Elau@exponent.com.
13
BioSTAT Consultants, USA. Electronic address: tomvidmar@biostat.com.
14
Department of Neuroscience, Carleton University, Ontario, Canada.

Abstract

The potential for developmental neurotoxicity (DNT) of environmental chemicals may be evaluated using specific test guidelines from the US Environmental Protection Agency or the Organisation for Economic Cooperation and Development (OECD). These guidelines generate neurobehavioral, neuropathological, and morphometric data that are evaluated by regulatory agencies globally. Data from these DNT guideline studies, or the more recent OECD extended one-generation reproductive toxicity guideline, play a pivotal role in children's health risk assessment in different world areas. Data from the same study may be interpreted differently by regulatory authorities in different countries resulting in inconsistent evaluations that may lead to inconsistencies in risk assessment decisions internationally, resulting in regional differences in public health protection or in commercial trade barriers. These issues of data interpretation and reporting are also relevant to juvenile and pre-postnatal studies conducted more routinely for pharmaceuticals and veterinary medicines. There is a need for development of recommendations geared toward the operational needs of the regulatory scientific reviewers who apply these studies in risk assessments, as well as the scientists who generate DNT data sets. The workshops summarized here draw upon the experience of the authors representing government, industry, contract research organizations, and academia to discuss the scientific issues that have emerged from diverse regulatory evaluations. Although various regulatory bodies have different risk management decisions and labeling requirements that are difficult to harmonize, the workshops provided an opportunity to work toward more harmonized scientific approaches for evaluating DNT data within the context of different regulatory frameworks. Five speakers and their coauthors with neurotoxicology, neuropathology, and regulatory toxicology expertise discussed issues of variability, data reporting and analysis, and expectations in DNT data that are encountered by regulatory authorities. In addition, principles for harmonized evaluation of data were suggested using guideline DNT data as case studies.

KEYWORDS:

Behavior; Developmental neurotoxicity testing; Extended one-generation reproductive toxicity; Learning and memory; Morphometry; Neuropathology

PMID:
28757310
DOI:
10.1016/j.ntt.2017.07.001
[Indexed for MEDLINE]

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