582 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS II. TYPES OF N-NITROSO COMPOUNDS N-Nitroso compounds are formed by the interaction of a nitrogen-containing organic compound--such as an amine, amide, urea, guanidine, urethane or cyanamide--and a nitrosating agent, such as a nitrogen oxide. These compounds can be divided into two categories--nitrosamines and nitrosamides--which differ in their chemical stability, the mechanism of their carcino- genicity and their mutagenicity (2-4). N-Nitrosamines R N--N=O / R' R,R' = alkyloraryl N-Nitrosamides R N--N•O / z = alkyloraryl O O R',2NC-- NH II R',.,NC-- 0 R'OC-- NC l R'SO2-- nitrosamide nitrosourea nitrosoguanidine nitrosourethane nitrosocyanamide nitrososulfonamide The nitrosamines are very stable once they are formed. They require chemical modification in an enzyme-catalysed reaction before they exhibit carcinogenic and mutagenic activity (2, 3, 5). By comparison the nitrosamides can be hydrolysed, espe- cially in neutral and alkaline solution. They exhibit carcinogenic and mutagenic activities without modification and malignant tumors are produced at the site of their application (2-5). III. CARCINOGENICITY OF N-NITROSO COMPOUNDS The first report that nitrosamines cause cancer in laboratory animals was that rats fed low levels (50 ppm) of dimethylnitrosamine in their diet developed liver cancer (6, 7). Since then more than 120 nitrosamines and nitrosamides have been examined for

NITROSAMINE CHEMISTRY 5 83 Table I Varying Carcinogenic Activity of Nitrosamines Classification by Range of log (l/D5o) a Structure D5o a log (1/D•o) Highly Potent, 3.0 Potent, 2.1 to 3.0 Intermediate Activity, 1.1 to 2.0 Minimal Activity, • 1.0 (CHaCH2)2NNO CHaNCH2CHzC1 I NO CHaNCH2C6Hs I NO 0.00063 0.00061 0.00080 0.0010 CHaNCHzCHzNCHa 0.0039 NO NO (CHa)2NNO 0.0054 (n-CaH7)zNNO 0.0088 (NCCH2)2NNO NNO O NNO CHaCHzNCHzCHzOH I NO (n-CiH9)2NNO NO n-C4H9N(CH2)4OH NO I NO (i-CaHT)zNNO O II (CHaCOCHzCHz)zNNO (n-C•H•)2NNO CHaNCH2COzH I NO (HOCHzCHz)zNNO 0.012 0.012 0.011 0.016 O.O25 O.O25 0.031 O.O39 0.11 0.18 0.26 0.24 0.89 3.2 3.2 3.1 3.0 2.4 2.3 2.1 1.9 1.9 1.9 1.8 1.6 1.6 1.5 1.4 1.0 0.7 0.6 0.6 0.05 continued on p 584