Use of the benchmark-dose (BMD) approach to derive occupational exposure limits (OELs) for genotoxic carcinogens: N-nitrosamines.
Détails
ID Serval
serval:BIB_D0B168147938
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Use of the benchmark-dose (BMD) approach to derive occupational exposure limits (OELs) for genotoxic carcinogens: N-nitrosamines.
Périodique
Journal of applied toxicology
ISSN
1099-1263 (Electronic)
ISSN-L
0260-437X
Statut éditorial
Publié
Date de publication
08/2023
Peer-reviewed
Oui
Volume
43
Numéro
8
Pages
1183-1200
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
N-Nitrosamines are potent carcinogens and considered non-threshold carcinogens in various regulatory domains. However, recent data indicate the existence of a threshold for genotoxicity, which can be adequately demonstrated. This aspect has a critical impact on selecting the methodology that is applied to derive occupational exposure limits (OELs). OELs are used to protect workers potentially exposed to various chemicals by supporting the selection of appropriate control measures and ultimately reducing the risk of occupational cancer. Occupational exposures to nitrosamines occur during manufacturing processes, mainly in the rubber and chemical industry. The present study derives OELs for inhaled N-nitrosamines, employing the benchmark dose (BMD) approach if data are adequate and read-across for nitrosamines without adequate data. Additionally, benchmark dose lower confidence limit (BMDL) is preferred and more suitable point-of-departure (PoD) to calculate human health guidance values, including OEL. The lowest OEL (0.2 μg/m <sup>3</sup> ) was derived for nitrosodiethylamine (NDEA), and nitrosopiperidine (NPIP) (OEL = 0.2 μg/m <sup>3</sup> ), followed by nitrosopyrrolidine (NPYR) (0.4 μg/m <sup>3</sup> ), nitrosodimethylamine (NDMA), nitrosodimethylamine (NMEA), and nitrosodipropylamine (NDPA) (0.5 μg/m <sup>3</sup> ), nitrosomorpholine (NMOR) (OEL = 1 μg/m <sup>3</sup> ), and nitrosodibutylamine (NDBA) (OEL = 2.5 μg/m <sup>3</sup> ). Limits based on "non-threshold" TD50 slope calculation were within a 10-fold range. These proposed OELs do not consider skin absorption of nitrosamines, which is also a possible route of entry into the body, nor oral or other environmental sources. Furthermore, we recommend setting a limit for total nitrosamines based on the occupational exposure scenario and potency of components.
Mots-clé
Humans, Carcinogens/toxicity, Dimethylnitrosamine, Benchmarking, Nitrosamines/toxicity, Diethylnitrosamine, Occupational Exposure/adverse effects, EHS, benchmark dose (BMD), cancer, carcinogens, nitrosamines, occupational exposure limit (OEL), occupational health hazard, occupational toxicology, safe workplace
Pubmed
Web of science
Création de la notice
03/03/2023 17:35
Dernière modification de la notice
14/12/2023 7:13