Utilisation of parametric methods to improve percentile-based estimates for the carcinogenic potency of nitrosamines

• Published in: Regulatory toxicology and pharmacology Vol. 121; p. 104875
• Main Authors: Thomas, Robert, Thresher, Andrew, Ponting, David J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.04.2021
• Subjects: Carcinogenicity; N-Nitrosamine; Percentile; TD50; Percentile; TD50; Carcinogenicity; N-Nitrosamine; TD
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2021.104875

N-Nitrosamines have recently been the subject of intense regulatory scrutiny, including the setting of low exposure limits (18 ng/day) (European Medicines Agency (EMA), 2020). This paper evaluates different methodologies to determine statistically robust bounds on the carcinogenic potency of chemical classes, using historic TD50 data (Peto et al., 1984; Thresher et al., 2019) and exemplified for N-nitrosamines. Initially, the distribution of TD50 values (TD50s) for N-nitrosamines of known potency was characterised. From this, it is possible to compare parametric and non-parametric methods to obtain percentiles of interest from the distribution of TD50s, which are shown to be robust to uncertainty in the initial TD50 estimates. These methods may then be applied to different chemical subclasses. The values obtained may be of use in refining acceptable intakes for N-nitrosamines and their subclasses. •The distribution of N-nitrosamine carcinogenic potencies is log-normal.•Parametric methods allow for increased statistical power when estimating features of interest.•Structure based subclasses of N-nitrosamines show different potencies.