and haematocrit were noted in females at all tested doses; higher incidence of abnormal red cell morphology was also observed in all treated groups; a no-observed-effect-level (NOEL) could not be determined 9.3 Genotoxicity Salmonella typhimurium Reverse Mutation Assay (Lawlor TE, 1992) Strains: S. typhymurium TA98, TA100, TA1535, TA1537, TA 1538 Concentration range: 333, 667, 1 000, 3 300, 6 670, 10 000 g.plate-1 Test method: according to OECD guidelines (Organisation for Economic Co-operation and Development, Result: the notified chemical did not cause an increase in the number of revertants per plate in any of the bacterial strains tested in the presence and absence of microsomal enzyme from induced-rat liver S9 9.3.2 Chromosome Aberration Assay in Chinese Hamster Ovary (CHO) Cells (Barber ED, 1992) Species/strain: CHO Dose range: with metabolic activation: 2.5 – 80 g.mL-1 in 10 and 20 hours without metabolic activation: 2.5 – 10 g.mL-1 in 10 hours 7.5 – 20 g.mL-1 in 20 hours Test method: according to OECD guidelines (Organisation for Economic Co-operation and Development, Result: the notified chemical did not induce chromosomal aberrations in CHO cells in the presence or absence of metabolic activation 9.4 Overall Assessment of Toxicological Data CIN 10095204 shows low acute oral and dermal toxicity in rats with LD50 values greater than 2 000 mg.kg-1 for both administration routes. CIN 10096270 is not irritant to rabbit skin; however, it caused slight irritation to the rabbit eye. CIN was not considered to be a dermal sensitiser in guinea pigs.
Attachment 1 The Draize Scale for evaluation of skin reactions is as follows: Erythema Formation Rating Oedema Formation Rating No erythema 0 No oedema 0 Very slight erythema (barely perceptible) 1 Very slight oedema (barely perceptible) 1 Well-defined erythema 2 Slight oedema (edges of area by definite raising 2 Moderate to severe erythema 3 Moderate oedema (raised approx. 1 mm) 3 Severe erythema (beet redness) 4 Severe oedema (raised more than 1 mm and extending beyond area of exposure) 4 The Draize scale for evaluation of eye reactions is as follows: CORNEA Opacity Rating Area of Cornea involved Rating No opacity 0 none 25% or less (not zero) 1 Diffuse area, details of iris clearly visible 1 slight 25% to 50% 2 Easily visible translucent areas, details of iris slightly obscure 2 mild 50% to 75% 3 Opalescent no details of iris visible, size of pupil barely discernible 3 moderate Greater than 75% 4 Opaque, iris invisible 4 severe CONJUNCTIVAE Redness Rating Chemosis Rating Discharge Rating Vessels normal Vessels definitely injected above normal More diffuse, deeper crimson red with individual vessels not easily discernible Diffuse beefy red 0 none 1 slight 2 mod. 3 severe No swelling Any swelling above normal Obvious swelling with partial eversion of lids Swelling with lids half-closed Swelling with lids half-closed to completely closed 0 none 1 slight 2 mild 3 mod. 4 severe No discharge Any amount different from normal Discharge with moistening of lids and adjacent hairs Discharge with moistening of lids and hairs and considerable area around eye 0 none 1 slight 2 mod. 3 severe IRIS Values Rating Normal 0 none Folds above normal, congestion, swelling, circumcorneal injection, iris reacts to light 1 slight No reaction to light, haemorrhage, gross destruction 2 severe