Toxicologic studies of four fluorescent whitening agents

Abstract

Studies have been conducted to define the toxicologic properties of sodium 2-(4-styryl-3-sulfophenyl)-2 H-naphtho-[1,2 d]triazole (I), disodium 4,4′-bis[(4-anilino-6-morpholino-1,3,5-triazin-2-yl)amino]stilbene-2,2′-disulfonate (II), disodium 4,4′-bis{[4-anilino-6-6-( N-methyl-2-hydroxyethylamino)-1,3,5-triazin-2-yl]amino}stilbene-2,2′-disulfonate (III) and disodium 4,4′-bis(2-sulfostyryl)biphenyl (IV). The following studies were performed on all the above materials: acute oral LD50, acute eye irritation, acute dust inhalation, acute fish toxicity, dominant lethal mutagenicity, teratogenicity, 90-day subacute oral toxicity in rats and dogs, and repeated insult patch tests in humans. Under the conditions of these studies the compounds were of low toxicity and were neither teratogenic nor mutagenic. Dose-related effects ranging from mild gastritis at 400 ppm to debilitation and peritonitis at 2000 ppm were observed in the 90-day dog feeding study with unbuffered compound I. Repetition of the study at 2000 ppm using compound I neutralized to pH 7 with hydrochloric acid showed no such effects. No adverse effects were observed with the unbuffered material in rats at levels up to 5000 ppm or in rhesus monkeys at a dose level of 50 mg/kg/day (approximately 2000 ppm). With compounds II, III and IV no effects were noted at levels up to 10,000 ppm in dogs or 5000 ppm in rats. No adverse effects have been observed at the end of 9 months of projected 2-year studies with compounds I, II, III and IV, at dietary levels up to 1000 ppm in rats and 2000 ppm in dogs, using neutralized material in the case of compound I in dogs. None of the materials exerted adverse effects in the first generation of a 3-generation rat reproduction study at dietary levels up to 1000 ppm. All were shown to be devoid of teratogenic activity in rabbits at dose levels of 10 and 30 mg/kg and of mutagenic activity in male mice. No evidence was obtained to indicate that any of the materials are sensitizing or phototoxic agents in either experimental animals or in man.