Physiologically-based pharmacokinetic model for evaluating gender-specific exposures of N-nitrosodimethylamine (NDMA)

Kang, Dong Wook; Kim, Ju Hee; Choi, Go-Wun; Cho, Seok-jin; Cho, Hea-Young

doi:10.1007/s00204-023-03652-8

Cited by 2 publications

(1 citation statement)

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“…This would require to comprehensively take into account all sources of exposure, foremost the exposure of endogenous origin, which, according to the pioneering estimates presented above, may exceed by far the exposure from dietary intake. Nevertheless, the above-mentioned estimates require confirmation by state-of-the-art analytical methodology and advanced biokinetic modelling, such as recently proposed by (Kang et al 2024 ). The overarching aim is to provide a reliable database for a comprehensive risk assessment of human exposure to NOC.…”

Section: Exposure To N -Nitrosating Agents: the Co...mentioning

confidence: 99%

Commentary of the SKLM to the EFSA opinion on risk assessment of N-nitrosamines in food

Eisenbrand,

Buettner,

Diel

et al. 2024

Arch Toxicol

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Dietary exposure to N-nitrosamines has recently been assessed by the European Food Safety Authority (EFSA) to result in margins of exposure that are conceived to indicate concern with respect to human health risk. However, evidence from more than half a century of international research shows that N-nitroso compounds (NOC) can also be formed endogenously. In this commentary of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG), the complex metabolic and physiological biokinetics network of nitrate, nitrite and reactive nitrogen species is discussed with emphasis on its influence on endogenous NOC formation. Pioneering approaches to monitor endogenous NOC have been based on steady-state levels of N-nitrosodimethylamine (NDMA) in human blood and on DNA adduct levels in blood cells. Further NOC have not been considered yet to a comparable extent, although their generation from endogenous or exogenous precursors is to be expected. The evidence available to date indicates that endogenous NDMA exposure could exceed dietary exposure by about 2–3 orders of magnitude. These findings require consolidation by refined toxicokinetics and DNA adduct monitoring data to achieve a credible and comprehensive human health risk assessment.

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Section: Exposure To N -Nitrosating Agents: the Co...mentioning

confidence: 99%