Regulatory Forum Opinion Piece*: Effective Brain Trimming for Regulatory-type Nonclinical Toxicity Studies.

ABSTRACT

Regulatory guidances for nonclinical toxicity testing require brain evaluation but do not require a specific analytical strategy. The Society of Toxicologic Pathology (STP) has produced "best practice" recommendations for brain sampling and processing in general toxicity (GT) studies in adult rodents and nonrodents as well as developmental neurotoxicity (DNT) studies in rodents. This article explains acceptable brain trimming strategies as described in these 2 STP documents. Figures in the DNT and GT "best practices" illustrate coronal brain trimming at specific levels as defined by discrete external and internal anatomic landmarks. However, the text of both "best practice" papers states that institutions may choose different brain trimming levels or other planes (e.g., a longitudinal orientation) as long as key structures are sampled and trimming is consistent among individuals across the study. The STP-recommended number of brain levels to evaluate (7 or 8 coronal sections for GT and DNT studies, respectively) may need to be increased if neurotoxicity is considered possible or likely based on in-life clinical findings or other risk factors (chemical structure, known mode of action, etc.).