Safety studies of pseudo-ceramide SLE66: Acute and short-term toxicity

Abstract Topical application of ceramides is reported to improve the structure and texture of the skin. Synthetic pseudo-cermaide, SLE66 has been shown to reduce dryness/scaling/itching of human skin. Although efficacy of topically applied ceramides and their analogs has been investigated to some extent, safety information is scarce. The objective of the present investigation was to evaluate potential adverse effects of SLE66. The oral LD 50 of SLE66 in rats and mice was >5000 mg/kg, while dermal LD 50 in rats was >2000 mg/kg. In animal and human studies, SLE66 did not cause skin irritation or sensitization. SLE66 does not possess phototoxicity or photosensitization potentials. Instillation of SLE66 into rabbit eye elicited transient conjunctival irritation. In 28 day repeat-dose studies, administration of SLE66 via gavage (daily) or by dermal application (five days/week) to Sprague Dawley rats at levels up to 1000 mg/kg/day did not cause mortality or morbidity. Compared to the controls, the clinical condition of the animals, body weights, feed consumption, hematology, clinical chemistry, organ weights, and gross necropsy findings were unaffected by oral or dermal administration of SLE66. The no-observed-adverse-effect level (NOAEL) for systemic toxicity following oral or dermal administration of SLE66 was 1000 mg/kg/day (the highest level tested).