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Extending the threshold of regulation concept: de minimis limits for carcinogens and mutagens
Janice M Fiori1, Roger D Meyerhoff
1Toxicology and Drug Disposition, Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, IN 46140, USA.
Abstract:
Risk assessment processes for carcinogens are highly developed but risk assessment processes for mutagens are not well established. In the pharmaceutical industry, risk associated with exposure to carcinogens is tightly controlled. It is desirable to control risk associated with exposure to mutagens also, in spite of the greater uncertainty associated with the risk. In this paper, a published cancer potency database is used to frame the risk and to support risk management decisions. A de minimis exposure for mutagens is proposed and a decision matrix is presented to align available data with risk assessment approaches for carcinogens and mutagens.
Insights
Establishing risk assessment for mutagens is crucial, mirroring established carcinogen processes. This study proposes a de minimis exposure level and a decision matrix to manage mutagenic risks in the pharmaceutical industry.
Area of Science:
- Toxicology and Risk Assessment
- Pharmaceutical Safety
- Genotoxicity Studies
Background:
- Carcinogen risk assessment is well-established, but mutagen risk assessment lacks standardized processes.
- The pharmaceutical industry requires robust methods to control exposure risks from mutagens, despite inherent uncertainties.
- Existing cancer potency databases can inform mutagen risk management strategies.
Purpose of the Study:
- To address the need for established risk assessment processes for mutagens.
- To propose a framework for managing mutagenic risks in the pharmaceutical sector.
- To adapt existing methodologies for carcinogen risk assessment to mutagens.
Main Methods:
- Utilized a published cancer potency database to frame mutagen risk.
- Developed a proposed de minimis exposure level for mutagens.
- Presented a decision matrix to align data with risk assessment approaches.
Main Results:
- A framework for mutagen risk assessment has been proposed.
- A de minimis exposure level for mutagens is suggested.
- A decision matrix facilitates the integration of available data for risk assessment.
Conclusions:
- Standardized risk assessment for mutagens is achievable and necessary.
- The proposed de minimis exposure and decision matrix offer practical tools for risk management.
- This approach supports safer pharmaceutical development by addressing mutagenic risks effectively.