A new approach methodology using kinetically-derived maximum dose levels in risk assessment - A case study with
Anne E Loccisano1, Elaine Freeman2, Adriana Doi3
1Exponent Inc, Alexandria, VA, 22314, USA.
This study introduces a new method using the kinetically-derived maximum dose (KMD) to assess chronic dietary human health risks from insecticides like afidopyropen. This approach reduces animal testing while reliably identifying health-protective levels.
Area of Science:
- Environmental toxicology
- Risk assessment methodologies
- Insecticide safety evaluation
Background:
- Traditional chronic dietary human health risk assessments (HHRA) rely on extensive toxicological data.
- Current HHRA practices often prioritize hazard characterization over exposure information.
- Existing methodologies may generate more data than necessary for defining health-protective endpoints.
Purpose of the Study:
- To present a case study of afidopyropen (AF) using a Risk 21-based approach for chronic dietary HHRA.
- To demonstrate a New Approach Methodology (NAM) utilizing the kinetically-derived maximum dose (KMD) for identifying a health-protective point of departure (PoD).
- To show how NAM can reduce animal testing requirements in HHRA.
Main Methods:
- Application of a Risk 21-based framework for case study analysis.
- Determination of the kinetically-derived maximum dose (KMD) through metabolic pathway saturation.
- Utilizing KMD as an alternative PoD in HHRA.
Main Results:
- The NAM, using KMD, effectively identified a health-protective PoD for afidopyropen.
- This approach significantly reduces the need for extensive toxicological testing.
- Demonstrated that non-genotoxicity and KMD protection in 90-day rat and developmental studies suffice for alternative PoD use.
Conclusions:
- The kinetically-derived maximum dose (KMD) offers a viable alternative PoD for chronic dietary HHRA.
- New Approach Methodologies (NAM) can streamline risk assessment processes, minimizing animal use.
- Afidopyropen's chronic dietary risk can be characterized using NAM, supporting regulatory efficiency.
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