American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV): Exposure by all routes should be carefully controlled to levels as low as possible; Skin; Appendix A3 - Confirmed Animal Carcinogen with Unknown Relevance to Humans
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Limit (REL):Appendix A - NIOSH Potential Occupational
Health Effects: Cancer (HE1); Liver cirrhosis (HE3); Suspect teratogen (HE5)
Affected Organs: Liver, kidneys, lungs
N-Nitrosodimethylamine is an OSHA Regulated Carcinogen without a PEL (29 CFR 1910.1003).
It undergoes activation by cytochrome P450 2E1 to reactive metabolites that result in the chemical modification of DNA and consequent apoptotic cell death.
The main chemical modification of DNA involves the methylation of guanine residues to form N7-methylguanine (major adduct) and O6-methylguanine, which are thought to be involved in the mutagenicity of N-nitrosodimethylamine.
In addition to worker exposure in the rubber industry and wide exposure to users of tobacco products, recent research has focused on the formation of N-nitrosodimethylamine during water disinfection using chlorination or chloramination processes.
In April 1998, the California Department of Health Services established an "action level" (now termed notification level) for N-nitrosodimethylamine of 10 nanograms per liter of drinking water.
Biological monitoring of worker exposure may be facilitated by the recent development of a sensitive ELISA assay for DNA adducts in peripheral blood lymphocytes.
Choi, J. and Valentine, R.L.: Formation of N-nitrosodimethylamine (NDMA) from reaction of monochloramine: a new disinfection by-product. Water Res. 36(4): 817,824, 2002.
Lin, H.L., Parsels, L.A., Maybaum, J. and Hollenberg, P.F.: N-Nitrosodimethylamine-mediated cytotoxicity in a cell line expressing P450 2E1: evidence for apoptic cell death. Toxicol. Appl. Pharmacol. 157(2): 117-124, 1999.
Mitch, W.A., Gerecke, A.C. and Sedlak, D.L.: A N-nitrosodimethylamine precursor analysis for chlorination of water and wastewater. Water Res. 37(15): 3733-3741, 2003.
Niot-Mansart, V., Muhamedi, A. and Arnould, J.P.: A competitive ELISA detecting 7-methylguanosine adduct induced by N-nitrosodimethylamine exposure. Hum. Exp. Toxicol. 24(2): 89-94, 2005.
No Author: Nitrosamines, 15 Listings.Report on Carcinogens (latest edition); U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program.
Oury, B., Limasset, J.C. and Protois, J.C.: Assessment of exposure to carcinogenic N-nitrosamines in the rubber industry. Int. Arch. Occup. Environ. Health70(4): 261-271, 1997.
Pohanish, R.P. (editor): N-Nitrosodimethylamine. In, Sittig's Handbook of Toxic and Hazardous Chemicals and Carcinogens, Fourth Ed., Vol. 2. Norwich, NY: Noyes Publications, William Andrew Publishing, 2002, pp. 1731-1733.
Siddiqui, M. and Atasi, K.Z.: N-Nitrosodimethylamine: a disinfectant byproduct and its occurrence in wastewater. Water Environ. Res. 76(4): 316-326, 2004.
Straif, K., et al.: Exposure to high concentrations of nitrosamines and cancer mortality among a cohort of rubber workers. Occup. Environ. Med. 57(3): 180-187, 2000.
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