Phototoxic Agent Research Articles

Phototoxicity and photocarcinogenesis: Comparative effects of anthracene and 8-methoxypsoralen in the skin of mice

Erythema was produced in the skin of hairless mutant mice by a single exposure to a solar simulator ( λ > 290 nm). Topical pretreatment of the mice with either anthracene or 8-methoxypsoralen (8-MOP) intensified the reaction more than did pretreatment with the vehicle (methanol) alone. Skin tumours were produced in hairless mice during several months of daily topical treatment followed by exposure to the solar stimulator. Compared with the vehicle-treated group, the 8-MOP group developed more tumours and had a shorter tumour latent period. Tumour production in the anthracene group was not significantly different from that of the vehicle-treated group. Under the conditions of this test, enhanced photocarcinogenesis is not a necessary consequence of prolonged contact with the phototoxic agent anthracene.

A simple and rapid method for assaying cytotoxicity

A procedure has been developed in which fibroblasts are harvested from guinea-pig kidney and grown to confluency. Assay tubes containing graded concentrations of substances under examination are inoculated with portions of these fibroblasts and DNA synthesis is measured by means of [ 3H]thymidine uptake. Cytotoxicity is observed as an inhibition of DNA synthesis. This assay procedure was shown to be sensitive to three different cytotoxic agents, namely hydroxyurea, which is a metabolic inhibitor, sodium lauryl sulphate, a compound which lyses cells, and Rose Bengal, a phototoxic agent. It could be used to investigate the effect of a wide range of compounds that might come into contact with living cells.

Toxicologic studies of four fluorescent whitening agents

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.

Evaluation of the Phototoxic Potential of Topically Applied Agents Using Long-Wave Ultraviolet Light

A screening procedure for the detection of topically applied phototoxic agents is presented. Following application to the guinea pig ear, the significance of changes in ear thickness in irradiated and non-irradiated animals served as the determinant in establishing positive effects. Eight drugs reported to be phototoxic agents and hexachlorophene, which is suspected of being a photoallergen, were tested. Positive results were obtained with 8-methoxypsoralen, chlorpromazine, prochlorperazine and demethyl-chlortetracycline.

Evaluation Of The Phototoxic Potential Of Topically Applied Agents Using Long-Wave Ultraviolet Light

A screening procedure for the detection of topically applied phototoxic agents is presented. Following application to the guinea pig ear, the significance of changes in ear thickness in irradiated and non-irradiated animals served as the determinant in establishing positive effects. Eight drugs reported to be phototoxic agents and hexachlorophene, which is suspected of being a photoallergen, were tested. Positive results were obtained with 8-methoxypsoralen, chlorpromazine, prochlorperazine and demethyl-chlortetracycline.

Photoallergy to Methoxsalen

This paper describes three cases of photoallergy to the phototoxic agent methoxsalen (8-methoxypsoralen). Compared to the usual phototoxic response, less time and less ultraviolet energy were required to evoke this photoallergic reaction. Clinically and histologically, the picture mimicked contact allergy. Closed patch tests, using in vitro ultraviolet irradiated drugs, were positive. This indicates that photoallergy to methoxsalen is a variant of contact allergy. Similar mechanisms appear to explain photoallergy in general.

Photosensitivity Studies With Demethylchlortetracycline and Doxycycline

Of 30 volunteers, ten were given demethylchlortetracycline (600 mg/day), ten, doxycycline (200 mg/day), and ten, a placebo, for one week, and then all were taken on a voyage designed to maximize sun exposure. Nine out of ten receiving demethylchlortetracycline developed photosensitive eruptions, two of ten receiving doxycycline were also positive; while one volunteer on placebo was doubtful. These results support the concept of demethylchlortetracycline as a powerful phototoxic agent and suggest that doxycycline in the doses used will cause a lower incidence of this annoying side effect.