Result: the notified chemical was not a skin irritant in rabbits Eye Irritation (Jackson & Ogilvie, 1993b) Species/strain: rabbit/New Zealand White Number/sex of animals: 3/male Observation period: 6 days Method of administration: 0.1 g of the notified chemical into the conjunctival sac of the right eye of each rabbit Draizea scores (Draize, 1959): Cornea no corneal effects (all Draize scores zero) except for dulling of corneal lustre in animal #1 and #2 at 1 hour, animals #1 and #3 at 48 hours and animal #3 at 72 hours Iris slight iridal effects (Draize score of 1) up to and including 72 hours in all animals except that animal #2 had no iridal effects at 72 hours but constriction of the pupil; no effects on days 4 - 6 Time after instillation Animal 1 hour 1 day 2 days 3 days 4 days 5 days 6 days a see Attachment 1 for Draize scales r = redness c = chemosis d = discharge, s = slight, m = moderate, t = Test method: OECD TG 405 Result: the notified chemical was a moderate eye irritant in rabbits
Test method: OECD TG 406 Result: the notified chemical was a not a skin sensitiser in guinea pigs Repeated Dose Toxicity (Lea & Spurgeon, 1994) Species/strain: rat/SD Number/sex of animals: 5/sex/dose group Method of administration: gavage in corn oil Dose/Study duration:: 0, 15, 150 or 1 000 mg/kg/day (control, low, mid or high respectively) for 28 days Clinical observations: no deaths occurred during the study; non- treatment-related and/or ocular discharge was observed in all groups; no treatment-related changes in body weight at week 4 or in body weight gain were observed during the study Clinical chemistry/Haematology Haematology: no statistically significant differences between control and treatment groups Clinical chemistry: 7% increase in magnesium levels in high dose 10% increase in aspartate transaminase, 68% increase in alanine transaminase, 32% increase in alkaline phosphatase levels in high dose males Macroscopic findings: no statistically significant differences in weights were observed; moderate fluid distension of the uterus was observed in 1 mid dose and 4 high dose females; enlargement of the mesenteric lymph nodes was observed in 1 high dose male
Histopathology: rats killed following 28 days of dosing treatment-related findings in the ovary, liver and mesenteric lymph node were observed ovaries: vacuolated cells were present in the corpora lutea of 6/10 treated rats; granulomata were present in the corpora lutea of 4/10 treated rats; in total, 9/10 rats showed a histological change in the ovary liver: granulomata in the liver of a single treated rat corresponding with the pale foci noted macroscopically in this animal; for this reason the tissue was processed as an abnormality mesenteric lymph node: marked histiocytosis in the mesenteric lymph node of a single treated rat, corresponding with the enlargement noted macroscopically incidental findings: there was a higher incidence of luminal dilatation of the uterus in treated, but this was consistent with the stage of the oestrous cycle that they were in and is not considered likely to be related to treatment; treated rats were in a variety of different stages of the oestrous cycle, such as would normally be expected in rats of this age rats killed on day 20 of gestation ovaries: there were vacuolated cells in the corpora lutea and granulomata in the ovaries of the majority of treated rats liver: there were granulomata in the livers of two treated rats (these livers were processed due to the presence of macroscopic abnormalities). all findings were of a nature and incidence commonly found in rats of this age and strain, and were considered of no toxicological importance; there were no histological findings in tissues from the pair of rats that did not breed successfully to suggest any infertility Foetal observations: external observations at dissection, narrow and flattened heads were seen in 15/113 foetuses from 7/9 litters treated with the notified chemical; 27/113 treated foetuses were observed to have narrow heads and 13/113 flattened heads; this finding was not seen in the 125 control