Organ Weights in Toxicologic Pathology

In this issue of Toxicologic Pathology, there are two papers addressing organ weights in nonclinical toxicology studies. In the first, Michael et al. review the global regulatory guidance regarding collection of organ weights, while in the second Sellers et al. provide best practices recommendations for the collection of organ weights. The impetus of this work was the notice of the variability in guidances or the absence of coverage of organ weights in guidances by various regulatory bodies, as well as the notice of variability among different organization in actual practice. Because organ weights are evaluated in numerous study types and submitted globally to regulators, this topic was identified as one where a best practices type of position paper would be of benefit. The Scientific and Regulatory Policy Committee established a subcommittee. This organ weight subcommittee was charged with assessing organ weight practices in toxicology studies, reviewing, the literature and guidances, and surveying various members of industry on current practices. With those perspectives and much discussion and feedback from toxicologic pathology member groups globally, the committee developed the position paper. The papers published here are intended to provide a rationale for inclusion or exclusion of organs from routine organ weight collection. The position paper also highlights particular difficulties in interpretation, such as the frequent immaturity of male reproductive organs in nonhuman primate studies, or alternative methods that may be considered, such as weighing thyroids following fixation. These papers provide a baseline as to what organ weights your industry peers are collecting as well as a consideration of the value of various organ weights in toxicology studies. Notable is the recommendation that organ weights not be collected and evaluated at the terminal necropsy of carcinogenicity assays, parameters requested by some regulatory guidances. The position paper does not preclude the addition or exclusion of a particular organ from the organ weight list for any given study based on special needs: target organ toxicity, pharmacology, mechanism of action, or known toxicity for a particular compound or compound class. It also does not preclude consideration of regulatory guidances. Those designing toxicity studies should carefully consider all the information available and be able to provide satisfactory justification for inclusion or exclusion of given organ weight parameters, just as is done for clinical pathology parameters, organ selection for histologic evaluation, and special procedures performed in various studies.