Observation period: 3 days Method of administration: 0.5 ml of MCP 1440 was applied to a 2.5 cm2 shaved area on the anterior and posterior flanks of each animal; the test sites were occluded with Webril patches followed by a rubber dam and surgical tape; anterior patches were removed after 1 hour (corrosion test) and posterior patches after 4 hours (irritation test); test sites were wiped clean after patch removal Corrosion evaluation: both 1 and 4 hour occluded test sites showed no ulceration or necrosis immediately after patch removal or at 48 hours Irritation evaluation - Draize scores (9): Animal Time after decontamination (4 hour occlusion) 30 min 1 day 2 days 3 days Erythema 1 1i 1 0 0 2 1 0 0 0 3 1 0 0 0 4 1 0 0 0 5 1 0 0 0 6 1 1 0 0 Oedema 1 0 0 0 0 2 0 0 0 0 3 0 0 0 0 4 0 0 0 0 5 0 0 0 0 6 1 0 0 0 i see Attachment 1 for Draize scales Test Method: based on USEPA Health Effects Testing Guidelines (8) Result: slightly irritating, non-corrosive to rabbit skin 9.1.5 Eye Irritation (6) Species/strain: New Zealand White rabbits
Test Method: based on USEPA Health Effects Testing Guidelines (8) Result: diffuse conjunctival redness, discharge and slight chemosis were observed at 1 and 24 hours; all animals were normal by 72 hours except one with slight redness of the conjunctivae; the total Draize scores were 9.7, 5.3, 1.7 and 0.3 at 1, 24, 48 and 72 hours, respectively; the mean score calculated from the 24, 48 and 72 hour readings was 0.7 for conjunctival redness and was 0.3 for chemosis; no effects on the cornea or iris were observed; the test substance was a slight eye irritant in rabbits 9.1.6 Skin Sensitisation (7) Species/strain: Dunkin Hartley albino guinea pig Number of animals: 4 range-finding animals (2/sex), 20 test animals (10/sex), 10 control animals (5/sex), 20 positive control animals (10/sex) Primary irritation: 4 animals were treated topically with 0.4 ml of 25, 50 or 75% test substance (w/w in Squibb Mineral Oil (SMO)) for 6 hours under occluded patches; skin reactions were assessed after 22 hours; the highest non-irritating concentration was determined to be 50%; 75% test substance produced slight irritation Induction procedure: 0.3 ml of test substance (75% w/w in SMO) was applied by occluded patch (6 hours) to the test guinea pigs once a week for 3 weeks; half the positive control animals were treated with 0.4 ml of 2,4-dinitrochlorobenzene (DNCB)(0.05% w/v in 80% ethanol); one test animal was found dead during induction phase, necropsy showed no treatment-related cause Challenge procedure: 16 days after the last induction dose 0.3 ml of test substance (50% w/w in SMO) was applied to the test and control animals; all positive control animals were treated with DNCB (0.05% w/v in acetone) Challenge outcome:
groups; the incidence and severity of the skin histological lesions were slightly reduced after 2 weeks recovery; diffuse hepatocellular hypertrophy was seen in both male and female rats administered 2000 mg/kg/day, but the liver lesions were not observed in the recovery group Test Method: based on OECD Guidelines for Testing Chemicals No: 410 (16); it was noted that individual animal data were not provided for any of the study parameters Result: the study showed that the target organ of toxicity in rats following repeated dermal exposure was the liver; because hepatocellular hypertrophy was not observed in the 500 mg/kg/day females, the increase in absolute liver weight was not considered to be treatment related 9.3 Genotoxicity 9.3.1 Salmonella typhimurium Reverse Mutation (17) Strains: Salmonella strains TA 98, TA 100, TA 1535, TA 1537 and TA 102 Concentration range: 95, 285, 950, 2850 or 9500 µg/plate Procedure: strains were cultured with MCP 1440 in the absence or presence of rat liver S9; DMSO was used as a solvent control, and 2nitrofluorene, and mitomycin C were used as positive controls Test Method: -incorporation method in accordance with OECD Guidelines for Testing Chemicals No: 471 (18) Result: there were no significant increases in the number of revertant colonies in the treated plates compared to controls; the positive controls produced marked increases in the number of revertant colonies in all the test strains; under the test condition, MCP 1440 was not mutagenic in the Salmonella typhimurium reverse mutation assay