Use of the RISK21 roadmap and matrix: human health risk assessment of the use of a pyrethroid in bed netting

Abstract

The HESI-coordinated RISK21 roadmap and matrix are tools that provide a transparent method to compare exposure and toxicity information and assess whether additional refinement is required to obtain the necessary precision level for a decision regarding safety. A case study of the use of a pyrethroid, “pseudomethrin,” in bed netting to control malaria is presented to demonstrate the application of the roadmap and matrix. The evaluation began with a problem formulation step. The first assessment utilized existing information pertaining to the use and the class of chemistry. At each stage of the step-wise approach, the precision of the toxicity and exposure estimates were refined as necessary by obtaining key data which enabled a decision on safety to be made efficiently and with confidence. The evaluation demonstrated the concept of using existing information within the RISK21 matrix to drive the generation of additional data using a value-of-information approach. The use of the matrix highlighted whether exposure or toxicity required further investigation and emphasized the need to address the default uncertainty factor of 100 at the highest tier of the evaluation. It also showed how new methodology such as the use of in vitro studies and assays could be used to answer the specific questions which arise through the use of the matrix. The matrix also serves as a useful means to communicate progress to stakeholders during an assessment of chemical use.

Keywords:

• Integrated testing strategy
• pyrethroid
• risk assessment
• tiered approach

Acknowledgements

The authors gratefully acknowledge the government, academic, and industry scientists of the HESI RISK21 Technical Committee for their contributions to this work. (For a full list of RISK21 participants, see http://www.risk21.org.) The authors also gratefully acknowledge the comments of three anonymous reviewers who were selected by the Editor. These comments were very helpful in revising the manuscript.

Declaration of interest

This manuscript was prepared under the auspices of the International Life Sciences Institute Health and Environmental Sciences Institute (ILSI HESI), a non-profit organization aimed at engaging scientists from academia, government, industry, research institutes, and NGOs to identify and resolve global health and environmental issues. The authors’ affiliations are as shown on the cover page. The authors had sole responsibility for the writing and content of the paper. The views and opinions expressed in the paper are those of the authors, and do not necessarily reflect the views of the authors’ employers or the opinions or policies of the US EPA or NIH. Mention of trade names does not constitute endorsement. None of the authors has recently or is currently involved as an expert witness in litigation or formal government rule making on the subject of this paper. The authors employed by ILSI HESI participated as part of their normal employment. None of the authors received financial support or an honorarium in the preparation of this paper, with the exception of Dr. John Doe whose work was supported by Syngenta. The authors declare that there are no conflicts of interest.