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DL-LACTONE CAS N°:79-50-5 - page 79 / 113





79 / 113



ID: 79-50-5 DATE: 18.01.2006

ascorbic acid (1000 mg/kg); (Charles River Breeding and Maintenance Diet for Guinea Pigs, Altromin, Lage, Germany). Certificates of analysis were examined and retained in the NOTOX archives. Hay (B.M.I., Helmond, The Netherlands) was provided at least twice a week. Water: Free access to tap water. Certificates of quarterly analysis for tap-water were examined and retained in the NOTOX archives. Results of analysis for ingredients and/or contaminants of diet, sawdust, and water were assessed and did not reveal any findings that were considered to have affected study integrity.

Preliminary irritation study A preliminary irritation study was conducted in order to select test substance concentrations to be used in the main Study. The selection of concentrations was based on the following criteria: The concentrations are well-tolerated systemically by the animals. For the induction exposures: the highest possible concentration that produced mild to moderate irritation (grades 2-3). For challenge exposure: the maximum non-irritant concentration. Series of test substance concentrations were tested. Practical feasibility of administration determined the highest starting concentration for each route. The starting and subsequent concentrations were taken from the series: 100% (undiluted), 50%, 20%, 10%, 5%, 2%, 1% and if needed, further lower concentrations using the same steps. The test system and procedures were identical to those used during the main study, unless otherwise specified. The four animals selected were between 4 and 9 weeks old. No body weights were determined. Intradermal injections: A series of four test substance concentrations was used, the highest concentration being the maximum concentration that could technically be injected. Each of two animals received two different concentrations in duplicate (0.1 ml/site) in the clipped scapular region. The injection sites were assessed for irritation 24 and 48 hours after treatment. Epidermal application: A series of four test substance concentrations was used, the highest concentration being the maximum concentration that could technically be applied. Two different concentrations were applied (0.5 ml each) per animal to the clipped flank, using Metalline patches (2x3 cm) mounted on Medical tape, which were held in place with Micropore tape and subsequently Coban elastic bandage. The animals receiving intradermal injections were treated with the lowest concentrations and two further animals with the highest concentrations. After 24 hours, the dressing was removed and the skin cleaned of residual test substance using water. Suppliers for materials: Lohmann GmbH, Neuwied, Germany (Metalline) and 3M, St. Paul, Minnesota, USA (Medical tape, Micropore and Coban).

Main study Induction - Experimental animals On day 1 the scapular region was clipped and three pairs of intradermal injections (0.1 ml/site) were made in this area as follows: A) A 1:1 w/w mixture of Freunds' Complete Adjuvant (Difco, Detroit, USA) with water for injection (Fresenius AG, Bad



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