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Are All Nitrosamines Concerning?

pdf fileMcDonald S; Ponting DJ; Tennant RE; Thomas RF; Thresher A; Williams RV;

The recent discovery of nitrosamine impurities in several marketed pharmaceuticals has led to a spike of interest in their genotoxicity and carcinogenicity. This class of chemicals is considered to pose an exceptional risk, such that they are considered to be in a ‘cohort of concern’ where even conservative metrics such as TTC cannot be applied.

Whilst there are some exceptionally potent (Ames positive) carcinogens within this class, one example being nitrosodiethylamine, it’s not clear whether this is a universal property of all members of the class.

To test this, genotoxicity and carcinogenicity data were gathered for nitrosamines from the published literature, to augment that already available in a commercially available database. As a result, data for 491 nitrosamines has been collated, 380 with Ames test data, 143 with data from other in vitro genotoxicity assays, 38 with data from in vivo genotoxicity assays and 253 with data from rodent carcinogenicity bioassays. For the Ames test, 19% of nitrosamines were judged to be non-mutagenic, which may suggest that the cohort of concern is overly sensitive. Additionally, carcinogenic potency (as measured by TD50s) stretches over several orders of magnitude and there are also several nitrosamines that have not shown activity in carcinogenicity bioassays.


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