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

Abstract

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.

Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health

“…Examples include the OECD defined approach for skin sensitization ( OECD, 2021a ), use of a WoE framework for chronic toxicity and cancer assessment ( Hilton et al, 2022 ), and PMRA’s “Guidance for Waiving or Bridging of Mammalian Acute Toxicity Tests for Pesticides” ( HC, 2013a ). In addition, PMRA no longer routinely requires the acute dermal toxicity assay ( HC, 2017 ), the one-year dog toxicity test ( Linke et al, 2017 ; HC, 2021d ), or the in vivo dermal absorption study ( Allen et al, 2021 ) in alignment with the US EPA. PMRA will consider these and other NAMs in lieu of animal testing for specific pesticides by applying a WoE approach to ensure that the available information is sufficient and appropriate for hazard characterization and the assessment of potential human health risks.…”

Canadian Regulatory Perspective on Next Generation Risk Assessments for Pest Control Products and Industrial Chemicals

“…This is consistent with the 2018 Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) strategic roadmap for establishing new approaches to evaluate the safety of chemicals and medical products in the United States ( ICCVAM, 2018 ). Individual project plans are also built upon the strategy noted in the CCA report by first focusing on retro-analysis and less complicated assays such as the acute toxicity studies ( Health Canada, 2017b ; Linke et al, 2017 ; Allen et al, 2021 ). The NAFTA TWG has also been used to develop science-policies, which are then brought for broader acceptance through OECD.…”

Rebooting the generally recognized as safe (GRAS) approach for food additive safety in the US

“…A number of analyses showed very convincingly that the test does not add to the 90-day-study in dogs (Appleman and Feron, 1986;Contrera et al, 1993;Gerbracht and Spielmann, 1998;Spielmann and Gerbracht, 2001;Box and Spielmann, 2005;Doe et al, 2006;Dellarco et al, 2010;Kobel et al, 2010Kobel et al, , 2014Linke et al, 2017). While this challenges the value of this animal test also for food additives, there is no similar analysis.…”