Previous studies demonstrate that the effects of one chemical stressor on selected immunological parameters can be predicted on the basis of the area under the corticosterone concentration vs. time curve. However, it is not clear if this is applicable to other chemical stressors. The present study was conducted to determine if the stress-induced immunological effects of atrazine and ethanol could be predicted, and if it is feasible to use one immunological parameter as a biomarker of stress to predict the quantity of changes expected in other immunological parameters. The area under the corticosterone concentration-versus-time curve (AUC) was measured in mice treated with ethanol (EtOH, 4, 5, 6, or 7 g/kg by oral gavage) or atrazine (ATZ, 100, 200, or 300 mg/kg, ip). The effects of the same dosages of these chemicals on thymus and spleen cellularity, lymphocyte subpopulations in the thymus and spleen, expression of MHC class II protein on splenocytes, antibody responses to keyhole limpet hemocyanin, and natural killer-cell activity were determined. Models were derived describing the relationship between corticosterone AUC and immunological changes induced by these chemicals. The results for these chemical stressors were more similar to results obtained from mice subjected to restraint stress than from mice treated with exogenous corticosterone. Some effects were greater than predicted on the basis of the stress response alone, indicating other mechanisms of immunotoxicity. One of the parameters (MHC class II expression) was evaluated as a predictive biomarker for stress-related immunosuppression, and the results suggest it could be suitable for that purpose.

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One of the principal challenges facing a toxicologic pathologist is to determine and differentiate a true adverse effect from a non-adverse or an adaptive response. Recent publications from the Society of Toxicologic Pathology (STP) and the European STP provide guidance for determining and communicating adversity in nonclinical toxicology studies. In order to provide a forum to inform and engage in a discussion on this important topic, a continuing education (CE) course was held during the 2016 STP Annual meeting in San Diego, CA. The lectures at this course provided guidance on determining and communicating adversity using case studies involving both clinical pathology and anatomic pathology. In addition, one talk also focused on data quality, study design and interpretation of artifacts that could hinder the determination of adversity. The CE course ended with a talk on understanding adversity in preclinical studies and engaging the regulatory agencies in the decision making process. This manuscript is designed to provide brief summaries of all the talks in this well received CE course.

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