API TR 403:1995 pdf download.Closed-Patch Repeated Insult Dermal Sensitization Study of Tertiary AmyL MethyL Ether (TAME) in Guinea Pigs
A. Route of Administration: Dermal, to the clipped skin of the back and sides. B. Justification for Route of Administration: This study was intended to provide information on the hea lth haz ards 1ikely to arise from exposure to the test material by the derma 1 route; skin contact is a possible worker and consumer exposure route . The Buehler method is an acceptable method for evaluation of the potential of test materials to produce derma 1 sensitization. C. Range-Finding Study: Prior to initiation of the study, a range-finding study was performed in order to select a slightly irritating concentrat ion for topical induction and a non-i rritating concentration for the challenge app 1 ication. Six animals were treated topically with undiluted test material (100%) and with concentrations of 50%, 25% and 10% v/v of the test material in light minera1 oil (4 chambers per anima1). The test material mixtures were app 1 ied beneath a 25 mm Hilltop ChamberB in a volume of 0.3 m1. The chamber was then placed on the test site, occ1 uded with impermeable plastic and secured by an elastic adhesive bandage ( Elastoplast ) which was wound around the torso of the animal. The chambers were left in place for six hours, after which they were removed and the skin wiped free of any excess material with distilled water and gauze. Observations for irritation were made at 24 and 48 hours.
G. Induction Phase: The hair on the application sites (back and sides) was clipped short with an electric clipper on the day prior to each applica- tion. The test or contro1 materials were applied to saturation (approximately 0.3 mls) beneath a 25 Hilltop Chamber which was then placed directly on the test site. The test site was to one side of the midline, as close to the midline as possible. The chamber was covered by overl apping，impermeable plastic. This Was firmly secured by an elastic adhes ive bandage which was wound around the torso of the animal ●The chamber was 1 left in place for six hours after which it was removed and the skin Was wiped free of any excess material . This was performed once a week, for three weeks, for a total of three exposures. Note: Due to technician oversight, Female No. 8291’s (Group IIIA) second induction exposure was approximately 48 hours . Since no irritation was evident when the wrappings were removed, and there was no subsequent sensitization， this error did not affect the integrity of the study.