NITROSAMINE CHEMISTRY •93 Table II (continued) Amine (or Amide) System Investigated Effect of Ascorbic Acid Reference Aminopyrine Aminopyrine Chlordiazepoxide Chlordiazepoxide Dimethylamine Dimethylamine Ethylurea Morpholine Morpholine Morpholine Piperazine Proline Dimethylamine Pyrrolidine Proline Dimethylamine, Pyrrolidine, Piperidine Morpholine Piperazine Methylurea Morpholine, Oxytetracycline, Piperazine, N- Methylaniline, Methylurea, Dimethylamine Piperazine, Aminophenazone Hepatotoxicity, Rats Carcinogenesis, Rats In vitro Toxicity, Rats Acute tox., Rats In vitro Pregnant rats In vitro In vitro Nitrosomorpholine formation and tumor- genesis in rats In vitro, human gastric juice Fried, nitrite-cured bacon Model food systems Meat-curing mixtures Adenoma, lung, in mice In vitro In vitro, human gastric juice Inhibits elevation of GPT, Ala. aminotransferase, nitrosodi- methylamine serum levels. Greater incidence of cancer in rats in absence of ascorbic acid. Inhibits nitrosamine formation. Ascorbate protected against increases in liver and spleen wt. decrease in adrenal wt., increases in GPT, LDH. Hepatic necrosis inhibited. GOT, GPT elevation inhibited. Low conc. of ascorbate enhanced nitrosamine formation. High concentrations inhibited such formation. Formation and inhibition are a function ofpH. Prevents carcinoma in offspring. Amount ofascorbate required depends on the presence or absence of 02. Inhibits nitrosamine formation. Inhibits nitrosomorpholine for- mation and liver tumors. Enhanced forestomach papillomas and carcinoma. Inhibits nitrosamine formation. Formation of nitrosopyrrolidine from proline is inhibited. Inhibits nitrosamine formation. Inhibits nitrosamine formation. Ascorbate decreased adenoma frequency in some cases. In- creases adenoma frequency when given with the nitrosamines. Inhibits nitrosamine and nitrosamide formation. Inhibits nitrosarnine formation. Review 81, 82 83 84 85 86 87 88 90 91 92 93 94 78 96 97

594 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS Table III Effect of Phenols on Nitrosamine Formation In Vitro and In Vivo Phenol Amine System Effects of the Phenol Reference Phenol -- In vitro Phenol reacts with nitrite 104 X 98 as rapidly as dimethylamine. Adenoma strongly inhibited. 78 Gallic Acid Gallic Acid Gallic Acid Gallic Acid Propyl Gallate Propyl Gallate Propyl Gallate Morpholine Adenoma induction, Mice Diethylamine In vitro Diethylamine In vitro Piperazine In vitro, human Aminophenazone gastric juice Proline Oil/water system Proline Fried, nitrite-treated bacon Dimethylamine Hepatotoxicity, Rats Tannic Acid Dimethylamine In vitro Tannin Piperazine, In vitro, human Aminopherazone gastric juice o•-Tocopherol Dimethylamine In vitro o•-Tocopherol Dimethylamine Cigarettes t-Butyl- hydroquinone t-Butyl- hydroquinone 2,6-Di-t-butyl- p-cresol (BHT) Butylated Hydroxyani- sole (BHA) 4-Methyl- catechol Chlorogenic Acid Vanillin Hydroquinone Thymol Proline Bacon Aminopyrine Pyrrolidine Dimethylamine Dimethylamine Dimethylamine Piperidine Piperidine Dimethylamine Dimethylamine Dimethylamine Hepatotoxicity, Rats In vitro, Oil/Water Hepatotox., Rats Hepatotox., Rats Hepatotox., Rats In vitro In vitro In vitro In vitro In vitro Inhibited or catalysed de- 99 pending on pH and rel. conc. of reactants. Catalyses nitrosamine formation 100 (see text). Inhibited nitrosamine formation. 96 Inhibited nitrosamine formation. 93 Inhibited nitrosopyrrolidine 92 formation. Inhibited liver pathol. GOT, 101 GPT and ornithine carbamoyl transf erase. Inhibited nitrosamine formation. 93 Inhibited nitrosamine formation. 96 Inhibited nitrosamine formation. 93 Inhibited dimethylnitrosamine 102,103 formation. Inhibited nitrosopyrrolidine formation. Inhibited hepatotoxicity. Inhibited nitrosamine formation. 93 Inhibited hepatox. GOT, GPT, 101 ornithine carbamoyl trans- ferase. Relatively ineffective. 101 Relatively ineffective. 101 Catalysed nitrosamine formation. 104 Catalysed nitrosamine formation. 104 Inhibited nitrosamine formation. 93 Inhibited nitrosamine formation. 93 Inhibited nitrosamine formation. 93