Thanks @sushantkamath - Good question!!
As per snapshot shared, it looks Forestomach is more sensitive than Oesophagus for NMPEA in rats for 33 weeks treatment. You may be correct. However, I have following observations:
- Forestomach tumors in rats might not be relevant to humans!
- If you pick lowest tested dose 0.4 mg/L for 104 weeks (the longest duration available), oesophagus looks more sensitive than forestomach with total incidence of with 8/20 for oesophagus and 5/20 for Forestomach.
- If you consider entire range of doses tested 0.4 to 115 mg/L- Oesophagus looks more sensitive than forestomach.
I am in opinion, that might have led to @jbercu and team to conclude like this in the recent article published. May be @jbercu and rest all could add more clarity and correct me if i am incorrect.
Regardless, of above discussion, I am in opinion still harmonic Lhasa TD50 value holds good because the way NMPEA has resulted tumors in wide organs when tested at wide dose range and pertinently the lowest tested dose for 104 weeks resulted fair amount of tumors in most of the organs. Additionally, if we considered labelled NMPEA treatment as separate studies and the resulting tumors of it, it would be worthy enough to select harmonic mean TD50. Hope Lhasa derived this TD50 considering all the data. @David - can add more clarity in this aspect. I am not the expert!
EMA used Harmonic mean TD50 to represent nitrosamines in descending order of potency
Just check- In our forum already a discussion came around same topic but this is of NMPA in Limits calculation a true mystery, help to understand NMPA?.
Despite of above discussion, I still respect the attempt by @jbercu and team on recent publication on 11 small nitrosamines and though process to think on choice of sensitive organ TD50. I agree to some extent with their attempts does really a nitrosamine like NMPEA should be controlled at level of 8 ng/day!!