Regulatory Rationale for Restricting LTL Application to Nitrosamines

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The topic of LTL is advancing, despite the fact that it doesn’t feel that way!!

We have a powerhouse in Dr. Joel Bercu (@jbercu) and Dr. Susan Felter (@SusanFelter), driving insightful engagements and leading a series of research to move the needle. Remember, this is one of the deliverables from the M7 revision working group. For now check the number of discussions related to Dr. Felter’s publications:

LTL or not LTL that's the question?

@SusanFelter Once again thank you for becoming part of our community. I had opportunity to read some of your published work (‘A proposed framework for assessing risk from less-than-lifetime exposure to carcinogens’. ICH M7(R1) defined a sub-class of MIs described as the Cohort of Concern (CoC), including N-nitroso compounds. However, there is still debate about the use or not of LTL for this family of compounds when defining acceptable limits. Do you think there is even room for debate on this?

Use of the TD50 99 % CI for single dose rodent carcinogenicity studies -Pub

The TD50 (tumor dose 50%) value is a crucial parameter in determining the acceptable intake limits (AIs) for nitrosamine impurities in pharmaceutical products. It represents the estimated daily dose of a substance that is expected to induce tumors in 50% of the exposed animal population over their lifetime. The TD50 value is primarily used in two approaches to calculate nitrosamine impurity AIs: Class-Specific Threshold of Toxicological Concern (TTC): For nitrosamines with limited or no avai…

Lifetime Cumulative Dose and Less Than Lifetime Approach

This was published just last week. I don’t have the full version to read yet but will purchase shortly. Evaluating the Lifetime Cumulative Dose as a Basis for Carcinogenic Potency of Nitrosamines – a Key Tenet Underpinning Less-than-Lifetime Approaches for Establishing Acceptable Intake limits - ScienceDirect [image] @David - thank you to you and all your colleagues for this. Something many of us have been waiting for.