United States regulatory requirements for skin and eye irritation testing.

PURPOSE: Eye and skin irritation test data are required or considered by chemical regulation authorities in the United States to develop product hazard labelling and/or to assess risks for exposure to skin- and eye-irritating chemicals. The combination of animal welfare concerns and interest in implementing methods with greater human relevance has led to the development of non-animal skin- and eye-irritation test methods. To identify opportunities for regulatory uses of non-animal replacements for skin and eye irritation tests, the needs and uses for these types of test data at U.S. regulatory and research agencies must first be clarified. METHODS: We surveyed regulatory and non-regulatory testing needs of U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) agencies for skin and eye irritation testing data. Information reviewed includes the type of skin and eye irritation data required by each agency and the associated decision context: hazard classification, potency classification, or risk assessment; the preferred tests; and whether alternative or non-animal tests are acceptable. Information on the specific information needed from non-animal test methods also was collected. RESULTS: A common theme across U.S. agencies is the willingness to consider non-animal or alternative test methods. Sponsors are encouraged to consult with the relevant agency in designing their testing program to discuss the use and acceptance of alternative methods for local skin and eye irritation testing. CONCLUSIONS: To advance the implementation of alternative testing methods, a dialog on the confidence of these methods to protect public health and the environment must be undertaken at all levels.

A retrospective analysis of the added value of 1-year dog studies in pesticide human health risk assessments.

The 1-year dog toxicity study is no longer required by certain pesticide regulatory jurisdictions, including the United States and the European Union. Health Canada's Pest Management Regulatory Agency (PMRA) examined its current requirement for this study to determine if it could be refined or eliminated. A retrospective analysis was conducted to examine the impact of the 1-year dog study on human health risk assessment. The Acceptable Daily Intake (ADI), a measure of the amount of a pesticide in food that can be ingested on a daily basis over a lifetime without an appreciable health risk, was the metric for this analysis. For 143 pesticides evaluated by the PMRA between 2008 and 2015, the supporting toxicology databases were examined to determine if other toxicology studies were protective of the findings in the 1-year dog study. When this criterion was not met, further investigation was undertaken to determine the potential impact of not having the 1-year dog study. For most of the pesticides, effect levels in the 1-year dog study were not substantially different from those in other toxicology studies, when considering factors such as dose-spacing and known experimental variability. The results of this analysis suggest that absence of the 1-year dog study would have minimal impact on the assessment of human health risk. Therefore, Health Canada's PMRA has removed the routine requirement for the 1-year dog study from its pesticide data requirements.