Nitrosamine SAR resources by Dr. Kevin Cross

[Naiffer_Host]

Greetings. I wanted to pull together in a post the information that Kevin @kpcross has been sharing with us in the past few days related to Nitrosamine Impurities prediction and acceptable limits. I found it very educational and filled with great learnings.

• The toxicology forum Nitrosamine session description and slides

Q&A Nitrosamine SAR working group (23 companies and universities)

The latest from the Nitrosamine SAR workgroup is a Tox Forum Symposium on nitrosamines on August 2, 2021. Here is the symposium description.nitrosamine_toxforum_session_summer_2021_FINAL.pdf (143.2 KB) And there are the slides from my presentation. Tox Forum 2021 Cross Nitrosamines SAR no audio.pdf (849.0 KB) I have also recorded this presentation if people are interested I can make it available.

• Kevin’s presentation (recording) on Predicting N-Nitrosamine Activity from Structure-Activity relationships

Q&A Nitrosamine SAR working group (23 companies and universities)

If you desire to listen to me narrate my Tox Forum slides you can do so with this link:

• Case study on the use of less-than-lifetime duration limits for Nitrosamines

Why LTL approach is not been considered?

Since this FDA workshop in March a new paper by @jbercu Joel Bercu on LTL and NDEA has been published. It can be found here: ANVISA now considers LTL limits for nitrosamines acceptable based upon this paper. Other regulators are looking again at this issue. @kenyom01 @David @fernandaw

• We also learn that The Nitrosamine SAR group workgroup is developing monographs for NDMA and other popular nitrosamines that will help define clear TD50s

FDA / clinical trial Exposure to NDMA after taking ranitidine

Naiffer, the link you provided to the toxplanet CPDB web-site does provide TD50 values, a study data summary, and literature references to their carc studies. And yes this is a static database. The FDA has determined that the CPDB carc studies for NMPA were not robust enough so that a rat TD50 value could be used. Consequently, they defaulted to the TD50 value for NDEA. NDMA is the most widely studied nitrosamine. The Nitrosamine SAR workgroup is developing monographs for NDMA as well as other p…

[kpcross]

Thanks for the summarization Naiffer. There are new conferences on the horizon, some open to the public.

Among them is the American College of Toxicology annual meeting which includes a symposium, “Carcinogenic Nitrosamines in Food and Drugs” om Monday November 15^th 9 am-noon EDT. https://www.actox.org/am/am2021/index.asp

David Pointing @David from Lhasa LImited will be presenting the latest results from the Nitrosamine SAR workgroup entitled, “Predicting N-Nitrosamine Activity from Structure-Activity Relationships”. I will also be presenting a poster on nitrosamine research at this conference.

Kevin