Regulatory developmental neurotoxicology testing: data evaluation for risk assessment purposes

Abstract

The recent emphasis on children's health has led to new requirements in developmental neurotoxicity testing and evolving new approaches to children's risk assessment. As more regulatory DNT studies are being submitted and used for children's risk assessment, appropriate data interpretation of developmental neurotoxicity studies is an important step to improving the scientific basis for children's risk assessments. Preweaning motor activity testing is used to illustrate the types of issues important to appropriate data analysis and evaluation. The EPA guidelines require that motor activity be tested at PND 13, 17, 21 and 60. Total activity at each time point and activity levels at each intrasession interval must be reported. Consequently, one common method for analyzing this data is to evaluate total activity levels at each time point or activity level in each intrasession time interval as independent measurements. Review of the scientific literature indicates that data evaluation for motor activity during development should focus primarily on the overall inverted U-shaped pattern of total activity over PND 13, 17 and 21 and secondarily on the development of intrasession response decrement. The interpretation of the data for risk assessment purposes needs to be guided by our understanding of the strengths and limitations of our knowledge of the biologic basis for these tests.