Dermal absorption for pesticide health risk assessment: Harmonization of study design and data reporting for North American Regulatory submissions

- In North America, the dermal absorption potential of pesticides is assessed with an in vivo rat study.
- There is an interest in in vitro human skin methods to improve human relevance and reduce animal use.
- A barrier to acceptance of in vitro approaches is the consistency of data submitted to regulatory agencies.
- A multi-stakeholder workshop harmonized protocol elements and created a reporting template for regulatory submissions.
- Improving study quality and consistency will facilitate the acceptance of stand-alone in vitro test methods.

Although an internationally-adopted in vitro dermal absorption test guideline is available (OECD Test Guideline 428), the replacement of the in vivo approach in North America for pesticide formulations has not occurred due to concern over the reliability and consistency of the in vitro results. A 2012 workshop convened a panel of experts in the conduct of in vitro studies used for pesticide risk assessment, together with North American regulators, to examine techniques for in vitro dermal absorption testing. Discussions led to the recommended “best practices” for the conduct of in vitro dermal absorption studies provided herein. The workshop participants also developed recommendations for reporting study results in order to improve the quality and consistency of the data submitted to regulatory agencies in North America. Finally, a case study is presented that illustrates the use of the “triple-pack” approach; the studies, conducted for the registration of sulfoxaflor, follow the standardized recommendations provided at the workshop. In addressing the concerns of these regulators and of the regulated community, and providing harmonized recommendations to facilitate comparative data analyses, it is anticipated that wider acceptance of in vitro dermal absorption studies alone can be achieved for pesticide risk assessment.