Rat, inhalation LC50 < 5.1 mg/L/1 hour harmful Rabbit, skin irritation (3 studies) slightly irritating Rabbit, skin irritation moderately irritating (based on 24 hour exposure) Rabbit, eye irritation (4 studies) slightly irritating Guinea pig, skin sensitisation – adjuvant test. limited evidence of Guinea pig, skin sensitisation – adjuvant test (2 studies) no evidence of Rat, repeat toxicity – 91 days. NOEL = 500 mg/kg bw/day Genotoxicity – bacterial reverse mutation non mutagenic Genotoxicity – in vitro chromosomal aberrations in human lymphocytes non genotoxic Genotoxicity – in vitro mammalian cell gene mutation test equivocal Genotoxicity – in vivo mouse micronucleus test non genotoxic 7.1. Acute toxicity – oral 7.1.1 Analogue chemical 1 Analogue chemical 1 Regulation for the Enforcement of the Federal Hazardous Substance Act (16 CFR 1500). Species/Strain Rat/Sprague-Dawley derived, albino rats Vehicle Undiluted Remarks - Method The protocol was followed without deviation. Group Number and Sex of Animals Dose mg/kg bw Mortality 1 5 per sex 5000 0
Bio-Research Laboratories (1994) 7.4. Irritation – skin 7.4.1 Analogue chemical 1 Analogue chemical 1 US 16 CFR 1500 Hazardous Substances Labelling Act. Species/Strain Rabbit/New Zealand White Number of Animals 3 M, 3 F Vehicle None Observation Period 72 hours Type of Dressing Semi-occlusive. Remarks - Method Gauze patch was applied for 24 hours. Scoring was at 24 and 72 hours only. Lesion Mean Score* Maximum Value Maximum Duration of Any Effect Maximum Value at End of Observation Period Erythema/Eschar 0.42 2 > 24 0 Oedema 0 0 - - *Calculated on the basis of the scores at 24 and 72 hours for ALL animals. Remarks - Results The Primary Irritation Index was found to be 0.5 based on erythema and oedema. No evidence of tissue damage was found. The analogue chemical is slightly irritating to the skin. Hill Top Biolabs (1988e) 7.4.2 Analogue chemical 2 Analogue chemical 2 US 16 CFR 1500 Hazardous Substances Labelling Act. Species/Strain Rabbit/New Zealand White Number of Animals 6 F Vehicle None Observation Period 72 Type of Dressing Semi-occlusive. Remarks - Method Gauze patch was applied for 24 hours. Scoring was at 24 and 72 hours only. Lesion Mean Score* Maximum Value Maximum Duration of Any Effect Maximum Value at End of Observation Period Erythema/Eschar 0.67 3 > 72 hours 1 Oedema 0.42 2 > 24 hours 0 *Calculated on the of the scores at 24 and 72 hours for ALL animals. Remarks - Results The Primary Irritation Index was found to be 1.3 based on erythema and oedema. No evidence of tissue damage was found.
Under the study conditions, the mutagenic potential of the analogue chemical, was equivocal. Sitek Research Laboratories (2001) 7.11. Genotoxicity – in vivo Analogue chemical 6 OECD TG 474 Mammalian Erythrocyte Micronucleus Test. EC Directive 84/449/EC B.12 Mutagenicity - Mammalian Erythrocyte Micronucleus Test. Species/Strain Mouse/CD-1 Route of Administration Oral – gavage Vehicle Arachis oil Remarks - Method No deviations from protocol noted. Group Number and Sex of Animals for each sacrifice time Dose mg/kg bw Sacrifice Time hours I (vehicle control) 5/sex 0 24, 48, 72 hrs II (low dose) 5/sex 1250 24, 48, 72 hrs III (mid dose) 5/sex 2500 24, 48, 72 hrs IV (high dose) 5/sex 5000 24, 48, 72 hrs V (positive control, CP) 5/sex 50 24 hrs CP=cyclophosphamide. Doses Producing Toxicity No clinical signs noted. Genotoxic Effects was no indication of toxicity at any dose level. Remarks - Results There was no statistically significant increase in micronucleated PCEs in any test group when compared to vehicle control. There were no differences in the PCE/NCE ratio in any dose group as compared to the control. Positive control group showed a marked increase in the incidence of micronucleated polychromatic erythrocytes, confirming the system. The analogue chemical was not clastogenic under the conditions of this in vivo mouse micronucleus test.. Safepharm Laboratories Limited (1995b) 8. ENVIRONMENT 8.1. Environmental fate 8.1.1. biodegradability Notified chemical OECD TG 301 B Ready Biodegradability: CO2 Evolution Test. Inoculum Activated sludge Exposure Period 28 Days Auxiliary Solvent None specified Analytical Monitoring IC and TOC