Eight compounds present in crude coal tar were tested for phototoxicity on guinea-pig skin. Four concentrations (5 p M to 5 mM) of each compound in ethanol were applied to the dorsal surface of 6 guinea-pigs. Each animal received 1.0 x lo5 JimZ of UVA radiation. The erythematous (phototoxic) response was evaluated after 20 h. Pyrene, anthracene and fluoranthene were strongly phototoxic. Acridine was markedly less phototoxic. Action spectra based on erythema as an endpoint were determined in guinea-pigs for anthracene, pyrene and fluoranthene. Each compound was applied to 5 animals which received irradiations from 274 to 5021 nm in 12 nm bands for 3, 6, 9, 12 and 15 min. The maximum erythema response to anthracene was observed between 346 and 382 nm, to fluoranthene between 322 and 382 nm and to pyrene between 322 and 358 nm. P A Y 36 I r
This study reports the induction of contact photodermatitis to musk ambrette, 2-methoxy-3,5-dinitro-4-methyl-t-butylbenzene, in guinea pigs. Photoallergic contact dermatitis was assayed using 2 alternative induction methods. Successful photosensitization was achieved only when the nuchal skin was stripped with scotch tape before application of musk ambrette and ultraviolet radiation. Induction methods utilizing nonstripped nuchal skin which induce photosensitivity to potent photoallergens were ineffective for musk ambrette. Phtotoxicity tests to musk ambrette at concentrations between 1 and 50% and a dose of 10.2 joules/cm2 from "Black Light" fluorescent tubes were all negative. Under identical irradiation conditions, anthracene at 0.9% and 8-methoxypsoralen at 1% were consistently positive. The mechanism of photosensitivity to musk ambrette appears to be photoallergic rather than phototoxic. The requirement for skin abrasion to induce photosensitization parallels the clinical reports of photosensitivity to musk ambrette in man.
The physiological mechanisms involved in anaphylaxis were further investigated by studies of drugs with adrenolytic, hypertensive, vasoconstrictive action, also tranquilizers and antihistaminics, diuretics, anti-inflammatory agents and newly available steroids. Mice were sensitized with normal horse serum. All drugs were administered prior to challenge and protection gauged by survival of sensitized mice compared with incidence of fatal anaphylaxis in untreated sensitized mice. Compounds exerting maximum protection were chlorpromazine, promazine, reserpine, lysergic acid diethylamide, prednisolone, prednisone, fluorohydrocortisone, hydrocortisone and cortisone. Inactive compounds were meprobamate, sedatives and antihistaminics, inflammatory agents, diuretics and predominantly sodium-retaining steroids.
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