Dr. Angela Hofstra from Syngenta Canada Inc. delivered a great introduction for the session. She began by saying that the study of potential chemical effects on neurodevelopment in children are guided by an Organisation for Economic Co-operation and Development (OECD) guideline published in 2012, and US Environmental Protection Agency (EPA) guidelines. She emphasized the need for a more harmonized scientific approach for evaluating developmental neurotoxicity (DNT) data across national boundaries. The goal of this workshop was to move closer towards providing an opportunity to develop a more harmonized scientific approach for evaluating DNT data.
Dr. Larry Sheets from Bayer CropSciences discussed how important measuring habituation is for analyzing motor activity. Managing extrinsic factors to reduce variability, controls, motor activity level, and habituation are important aspects of the research according to Dr. Sheets.
Dr. Wayne Bowers from Health Canada talked about how to analyze highly variable motor activity data as a case study. The importance of the activity measurement instrumentation (such as photocell-based systems or video-based systems) is clear in his presentation. In both types of software, they need to be customized, setting limits on comparisons between labs, between ages, and to historical controls. Dr. Bowers noted that non-associative learning is critical for adaptive behavior because habituation will affect total activity. He considers that total movement is not a good measurement endpoint, as it requires measurement of habituation through time blocks. He presented a couple of case studies to demonstrate how to solve these issues.
Dr. Kathleen Raffaele from the US EPA talked about hypothesis-driven testing, describing the typical protocol for Auditory Startle Habituation based on OECD guidelines 426 and 443. She remarked, as did previous speakers, about the change in response amplitude across trials. She also talked about how data generation and analysis should be done to evaluate the most biologically relevant outcomes.
Dr. Ginger Moser from the US EPA talked about standard operating procedures, reports, and evaluations, outlining the need for adequate study reports to allow defensible and consistent interpretation. She conveyed that accurate data interpretations requires a standardized presentation of data, especially for the non-standardized procedures.
Dr. Abby Li from Exponent ended the session by talking about non-cancer risk assessment frameworks, describing no observed adverse effect level (NOAEL), benchmark dose modeling, and others that have selective sensitivity. She recommended adding non-nervous system target organs to studies to link DNT studies with other toxicity studies.
Summarizing, Dr. Li mentioned the three issues that impact the assessment of qualitative and quantitative relative sensitivity that require further discussions: maternal toxicity, selection of levels and quality, and interpretation of morphometry data.
The goal of this session was to develop a straw proposal list of general guiding principles for reporting and evaluation of DNT endpoints based on input from speakers and their respective colleagues. Workshop attendees were invited to contribute to this open forum discussion.
This blog discusses highlights from the SOT Annual Meeting and ToxExpo Workshop "Regulatory Neurodevelopment Testing: New Guiding Principles for Harmonization of Data Collection and Analysis."