title: Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.
abstract: The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.
authors.affiliation: Centre de recherche en infectiologie, Laval University, Quebec, Quebec, Canada, G1V 4G2.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Piret
authors.forename: Geneviève
authors.initials: G
authors.lastname: Laforest
authors.forename: Martin
authors.initials: M
authors.lastname: Bussières
authors.forename: Michel G
authors.initials: MG
authors.lastname: Bergeron
mesh_terms: D000278:Administration, Buccal; D000282:Administration, Intravaginal; D000285:Administration, Rectal; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D002626:Chemistry, Pharmaceutical; D006224:Cricetinae; D004334:Drug Administration Schedule; D004339:Drug Compounding; D004852:Epoxy Compounds / Q000737:chemistry / Q000633:toxicity*; D005027:Ethylene Oxide / Q000737:chemistry / Q000633:toxicity*; D005123:Eye / Q000187:drug effects / Q000473:pathology; D005260:Female; D005782:Gels; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D010413:Penis / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000187:drug effects / Q000473:pathology; D018570:Risk Assessment; D012867:Skin / Q000187:drug effects / Q000473:pathology; D023422:Skin Irritancy Tests; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D013997:Time Factors; D018675:Toxicity Tests; D014621:Vagina / Q000187:drug effects / Q000473:pathology
chemical_list: D000891:Anti-Infective Agents, Local; D004852:Epoxy Compounds; D005782:Gels; D012967:Sodium Dodecyl Sulfate; D005027:Ethylene Oxide; C009068:propylene oxide