Undertaking positive control studies as part of developmental neurotoxicity testing: a report from the ILSI Research Foundation/Risk Science Institute expert working group on neurodevelopmental endpoints.
Developmental neurotoxicity testing involves functional and neurohistological assessments in offspring during and following maternal and/or neonatal exposure. Data from positive control studies are an integral component in developmental neurotoxicity risk assessments. Positive control data are crucial for evaluating a laboratory's capability to detect chemical-induced changes in measured endpoints. Positive control data are also valuable in a weight-of-evidence approach to help determine the biological significance of results and provide confidence in negative results from developmental neurotoxicity (DNT) studies. This review is a practical guide for the selection and use of positive control agents in developmental neurotoxicology. The advantages and disadvantages of various positive control agents are discussed for the endpoints in developmental neurotoxicity studies. Design issues specific to positive control studies in developmental neurotoxicity are considered and recommendations on how to interpret and report positive control data are made. Positive control studies should be conducted as an integral component of the incorporation and use of developmental neurotoxicity testing methods in laboratories that generate data used in risk decisions.
Crofton
Kevin M
KM
Neurotoxicology Division, NHEERL, ORD, US EPA, Research Triangle Park, NC, USA. crofton.kevin@epa.gov
Foss
John A
JA
Hass
Ulla
U
Jensen
Karl F
KF
Levin
Edward D
ED
Parker
Sherry P
SP
D000818:Animals; D035843:Biomedical Research / Q000379:methods / Q000592:standards*; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011786:Quality Control; D012107:Research Design; D018570:Risk Assessment / Q000379:methods* / Q000592:standards*; D012680:Sensitivity and Specificity