The authors Ponting et al., demonstrate that while the CPCA remains invaluable as a source of conservative default AIs, there are specific cases where existing toxicological data can support more refined AI calculations. This insight represents a significant opportunity to balance safety with practical implementation. 

The paper identifies several key factors that would drive this case: 

Compound-specific assessment 

The research supports utilising compound-specific toxicological data when available, rather than relying solely on conservative default values. They present evidence that this approach enables more precise risk characterisation while maintaining appropriate safety margins. 

Enhanced read-across applications 

The paper highlights advancements in read-across methodologies, demonstrating how these sophisticated analyses of structural analogues can provide a stronger scientific basis for establishing AIs when direct toxicological data is limited. 

Regulatory evolution 

They note recent regulatory shifts toward CPCA-based approaches, indicating increasing acceptance of more scientifically tailored assessments. Their analysis suggests that overly conservative limits may not always serve the best interests of public health, particularly when they impact drug availability. 

Practical implications 

A key conclusion from the paper stated that: 

“The consequences of highly conservative limits can lead to significant resource allocation and potential market withdrawals, underscoring the importance of a balanced approach to risk management.” 

Instead, the authors advocate for a more balanced approach, grounded in robust scientific data, while maintaining appropriate safety standards. 

Looking forward 

Based on the paper’s conclusions, the future of N-nitrosamine risk assessment lies in finding the optimal balance between protective measures and practical implementation. This requires: 

• Continued refinement of compound-specific assessment methods 

• Further development of read-across methodologies 

• Ongoing collaboration between industry stakeholders and regulatory bodies 

• Integration of new toxicological data as it becomes available 

You can access and read the publication via our website, or visit our nitrosamine risk assessment page for more information on read-across methodologies using in silico solutions. For more detailed insights into these developments or assistance with implementing these approaches, please contact our team.