Identification and interpretation of developmental neurotoxicity effects: a report from the ILSI Research Foundation/Risk Science Institute expert working group on neurodevelopmental endpoints.
The reliable detection, measurement, and interpretation of treatment-related developmental neurotoxicity (DNT) effects depend on appropriate study design and execution, using scientifically established methodologies, with appropriate controls to minimize confounding factors. Appropriate statistical approaches should be optimized for the specific endpoints in advance, analyzing effects across time and functional domains as far as possible. If available, biomarkers of exposure are useful to assess the bioavailability of toxicants to the dam and offspring in utero and after birth. Finally, "weight of evidence" principles are used to aid assessment of the biological significance of differences from concurrent controls. These effects should be interpreted in light of available information from historical controls, positive controls, maternal and offspring systemic toxicity, and other relevant toxicological data. This review provides a framework for the integration of all these types of information in the interpretation of DNT studies.
Tyl
Rochelle W
RW
RTI International, USA. rwt@rti.org
Crofton
Kevin
K
Moretto
Angelo
A
Moser
Virginia
V
Sheets
Larry P
LP
Sobotka
Thomas J
TJ
D000818:Animals; D035843:Biomedical Research / Q000379:methods* / Q000592:standards*; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018570:Risk Assessment