Kikugawa K, Kato T
Tokyo College of Pharmacy, Japan.
Food Chem Toxicol. 1988 Mar;26(3):209-14. doi: 10.1016/0278-6915(88)90121-4.
Reaction of phenol with nitrite under mildly acidic conditions produced p-nitrosophenol, p-diazoquinone and o-diazoquinone. p-Diazoquinone showed mutagenicity in Salmonella typhimurium strains TA98 and TA100 without metabolic activation; the number of his+ revertant colonies in strain TA98 was 85 with a dose of 20 nmol (after deduction of the background (control) number of about 20). Higher doses of the compound were bactericidal. While the reaction of phenol with an equivalent amount of nitrite at pH 3 produced p-nitrosophenol in high yield, reaction with excess nitrite produced a high yield of p-diazoquinone. p-Nitrosophenol was converted to p-diazoquinone by reaction with nitrite. Formation of o-diazoquinone also increased with increasing amounts of nitrite. The formation of these compounds was not greatly affected by the presence of dimethylamine. Nitrosation of dimethylamine with nitrite was stimulated by phenol because of the formation of p-nitrosophenol and its stimulatory effect. Thus, the reaction of phenol with nitrite can produce mutagenic p-diazoquinone, and can also stimulate nitrosation of secondary amines by production of p-nitrosophenol.
在温和酸性条件下，苯酚与亚硝酸盐反应生成对亚硝基苯酚、对重氮醌和邻重氮醌。对重氮醌在无代谢活化的情况下，对鼠伤寒沙门氏菌TA98和TA100菌株显示出致突变性；在菌株TA98中，剂量为20 nmol时（扣除约20的背景（对照）数量后），his+回复突变菌落数为85。更高剂量的该化合物具有杀菌作用。虽然在pH 3时，苯酚与等量亚硝酸盐反应可高产率生成对亚硝基苯酚，但与过量亚硝酸盐反应则可高产率生成对重氮醌。对亚硝基苯酚通过与亚硝酸盐反应转化为对重氮醌。随着亚硝酸盐量的增加，邻重氮醌的形成也增加。二甲胺的存在对这些化合物的形成影响不大。由于对亚硝基苯酚的形成及其刺激作用，苯酚可促进亚硝酸盐对二甲胺的亚硝化作用。因此，苯酚与亚硝酸盐反应可产生致突变性的对重氮醌，还可通过生成对亚硝基苯酚促进仲胺的亚硝化作用。
