Development of a 10-day chorioallantoic membrane vascular assay as an alternative to the Draize rabbit eye irritation test.

The chorioallantoic membrane (CAM) of a fertilized hen's egg has been studied extensively as a promising alternative model for predicting eye irritation potential. The specific methodology used with this model has varied among investigators but the basic premise of applying test material to the membrane surface and evaluating changes in the vasculature is relatively consistent. The CAM vascular assay (CAMVA) has shown high correlation with in vivo rabbit eye irritation data. This method uses the CAM of a 14-day-old egg and the response at 30 min after treatment as the endpoint. The primary CAM methods being evaluated in Europe use 9-10-day-old eggs because older eggs are considered 'live animals'; the possibility of using 10-day-old eggs to make the method more globally acceptable as a non-animal test was therefore investigated. By keeping the original CAMVA dosing and evaluation procedures the same, and only altering the age of the eggs from 14-day to 10-day, the results were found to be nearly identical for the two methods and both produce equivalent correlations to the in vivo eye irritation test results. Maintaining the original CAMVA methodology but using a younger egg, therefore, provides a good alternative method for predicting eye irritation potential that is more globally acceptable as a non-animal test.

Gingival absorption of triclosan following topical mouthrinse application.

This study assessed the gingival uptake and urinary excretion of triclosan in dogs following topical applications of a mouthrinse containing 0.03% of triclosan. Five different phases were conducted to define the time course of plasma concentration. The effect of plaque on gingival absorption was also measured. Phase I: Animals' teeth were cleaned of plaque via scraping. Blood sampling time was 0-2 hours. Phase II: Plaque was not removed from the animals' teeth. Blood sampling time was 0-2 hours. Phase III: Plaque was not removed from the animals' teeth. Blood sampling time was 0-6 hours. Phase IV: Plaque was not removed from the animals' teeth. Blood sampling time was 0-12 hours. Phase V: Animals' teeth were cleaned of plaque via scraping. Blood sampling time was 0-12 hours. The test substance was administered to 1 male and 1 female dog in Phases I, II, IV and V, and to 1 male dog in Phase III. The same animals were used in each phase. On the first day of each phase, the animals were treated with distilled water for a 15-minute period. The animals were exposed daily to the test material for a 15-minute period during the remaining 7 days of each phase. The test material was administered using custom-made acrylic applicator trays to enclose the maxillar premolars and molars and gingiva of one-half of the upper jaw. A leak-proof seal along the mucogingival junction and palatal mucosa was established and maintained during the exposure period.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety profile of Colgate Platinum Professional Toothwhitening System.

Colgate Platinum, a professional tooth-whitening paste containing 10% urea peroxide as the active ingredient, was evaluated for potential acute oral toxicity, genotoxicity, and irritation to oral mucosa. Oral administration to rats of a single dose of 5 g/kg of Colgate Platinum did not induce any adverse effects. Colgate Platinum was not mutagenic in Ames/Salmonella Plate Incorporation assay and did not induce primary DNA damage in the bone marrow hematopoietic cells of rats that were given oral doses of up to 1 g/kg for 5 consecutive days. Results of the oral mucosa irritation study in rats indicated that Colgate Platinum did not induce damage to soft and hard tissues of oral cavity after repeated applications for 28 days. Collectively, the data from these studies document the safety of the product for the intended use.

Safety profile of Colgate Platinum Professional Toothwhitening System.

Colgate Platinum, a professional tooth-whitening paste containing 10% urea peroxide as the active ingredient, was evaluated for potential acute oral toxicity, genotoxicity, and irritation to oral mucosa. Oral administration to rats of a single dose of 5 g/kg of Colgate Platinum did not induce any adverse effects. Colgate Platinum was not mutagenic in Ames/Salmonella Plate Incorporation assay and did not induce primary DNA damage in the bone marrow hematopoietic cells of rats that were given oral doses of up to 1 g/kg for 5 consecutive days. Results of the oral mucosa irritation study in rats indicated that Colgate Platinum did not induce damage to soft and hard tissues of oral cavity after repeated applications for 28 days. Collectively, the data from these studies document the safety of the product for the intended use.

Triclosan: a safety profile.

Triclosan (2, 4, 4'-trichloro-2'-hydroxydiphenyl ether), an antimicrobial agent, has been used extensively for 20 years in consumer products, principally in deodorants, soaps and other dermatological preparations. Recently, the use of triclosan has been extended to oral health care products such as dentifrices. This paper reviews safety information, both pre-clinical and clinical studies, from the literature, data submitted to the Antimicrobial I OTC Review Panel and unpublished work from the Pharmacology and Toxicology Department of the Colgate-Palmolive Company. The data spans acute, subacute, subchronic and chronic toxicity; mutagenicity, carcinogenicity, reproduction/teratology and pharmacokinetics. Results of these studies show that triclosan is well tolerated by a variety of species including man. In clinical studies with triclosan in solutions and dentifrices, a steady state was reached by day 7 with blood levels in the parts per billion (ppb) range and urine as the main route of excretion. Based on these studies, triclosan can be considered safe for use in dentifrice and mouthrinse products.

Surfactant-induced alteration of arachidonic acid metabolism of mammalian cells in culture.

Primary irritancy in human and animal skin is characterized by an inflammatory reaction mediated, in part, by membrane-derived arachidonate metabolites. One of the mechanisms of this reaction was investigated in cultured mammalian cells using three surfactants: linear alkyl benzene sulfonate (LAS), alkyl ethoxylate sulfate (AEOS), and TWEEN 20. These compounds listed in order in vivo irritancy are LAS greater than AEOS greater than TWEEN 20. Each of these compounds was studied in C3H-10T1/2 cells and human keratinocytes which had been prelabeled with 3H-labeled arachidonic acid (AA). After labeling, media were removed, cells were washed, and fresh media with or without surfactant were added. Cells were then incubated for 2 hr, media were removed and centrifuged, and an aliquot was assayed by liquid scintillation for release of label. In C3H-10T1/2 cells LAS and AEOS in 5-50 microM concentration stimulated 2 to 10 times the release of [3H]AA as compared to controls. In contrast, concentrations of 50-100 microM of TWEEN were required to release [3H]AA. With keratinocytes the same rank order of surfactant concentrations necessary for release was obtained as found with C3H-10T1/2 cells. High-performance liquid chromatography of media extracts of both cell systems revealed surfactant stimulation of the production of cyclooxygenase AA metabolites. These results confirm the induction of release by primary irritants of fatty acid groups from membrane phospholipids. Subsequent metabolism of these fatty acid groups are an integral part of the primary irritant response. Data presented with three known irritants in this in vitro model show a direct correlation with in vivo studies.

D & C Yellow Nos. 10 and 11: delayed contact hypersensitivity in the guinea pig.

D & C Yellow No. 11 was found to be a skin sensitizer in guinea pigs at an elicitation concentration of 10.0% in ethanol but not at 1.0 and 3.0%. Sensitization was induced with a 50% suspension in ethanol. D & C Yellow No. 10, the disodium salt of the mono- and disulfonic acids of D & C Yellow No. 11, was not a skin sensitizer nor was it capable of eliciting a response in the D & C Yellow No. 11-sensitized guinea pigs even at a challenge concentration of 10%. Two commercial products, a soap containing 0.015% D & C Yellow No. 11 and a shampoo containing 0.002% D & C Yellow No. 10 did not elicit a reaction in the D & C Yellow No. 11-sensitized guinea pigs.