Critical comparison of BMD and TD50 methods for the calculation of acceptable intakes for N-nitroso compounds -Pub

Guidance, Documents, Resources
1

Dear Nitrosamine Exchange Community,
I’m excited to share the latest research article, Critical Comparison of BMD and TD50 Methods for the Calculation of Acceptable Intakes for N-Nitroso Compounds by @schlinjo1975 @David et al. This work evaluates the strengths and limitations of the Benchmark Dose (BMD) and TD50 approaches for calculating acceptable intake (AI) limits for nitrosamines.

Open Access: Critical comparison of BMD and TD50 methods for the calculation of acceptable intakes for N-nitroso compounds | Archives of Toxicology

To facilitate a deeper understanding of this important research and spark engaging discussions, here are five thought-provoking questions for our community:

1. On Practical Implementation

The article demonstrates the feasibility of transitioning from TD50 to BMD-derived limits for nitrosamines.

  • Question: What practical challenges do you foresee in adopting BMD modeling within your organization or workflow? How might these challenges be addressed collaboratively?

2. Read-Across Implications

The study shows that potency estimates for nitrosamines relevant to read-across assessments differ by less than a factor of three between BMD and TD50 methods.

  • Question: How do you think the variability in potency estimates impacts the reliability of read-across approaches, particularly for less-studied nitrosamines?

3. Regulatory Adaptation

Despite individual differences, the study suggests that class-specific AI limits derived from BMD and TD50 are consistent.

  • Question: What would be the key considerations for regulators when transitioning to BMD-derived limits? How might this impact existing nitrosamine control strategies?

4. Data Convergence Challenges

The article highlights challenges with non-converging data in BMD modeling, resulting in the exclusion of some compounds from analysis.

  • Question: In your experience, what strategies or tools could improve data convergence in dose–response modeling to enhance the applicability of BMD methods?

5. Future Directions

The study emphasizes the flexibility of BMD modeling for diverse dose–response relationships.

  • Question: Beyond nitrosamines, how could the adoption of BMD methods enhance risk assessments for other impurity classes or broader pharmaceutical applications?

We encourage all members to share your thoughts, insights, and questions. Let’s make this a lively and insightful discussion!

:bookmark: Don’t forget to tag your colleagues who might have valuable perspectives to add.

3 Likes