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

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.