NA851 FULL PUBLIC REPORT ALKANE 2 1. APPLICANT Chevron Oronite Australia of 22, 385 Bourke Street, MELBOURNE VIC 3000 (ARBN 001 010 037) has submitted a standard notification statement in support of their application for an assessment certificate for Alkane 2. 2. IDENTITY OF THE CHEMICAL The chemical name, CAS number, molecular and structural formulae, molecular weight, and spectral data have been exempted from publication in the Full Public Report and the Summary Report. 3. PHYSICAL AND CHEMICAL PROPERTIES Appearance at 20°C & 101.3 kPa: Clear, colourless liquid Boiling Range at 102 kPa:: (Safepharm Laboratories Limited 145-318°C Freezing Point: (Safepharm Laboratories Limited 1995j) <-20°C Relative Density at 20°C: (Safepharm Laboratories Limited 1995j) 0.80183 Vapour Pressure at 25°C: (Safepharm Laboratories Limited 3.0 x 10-7 kPa Solubility at 19.5°C: (Safepharm Laboratories Limited 1995j) <0.13 mg/L Particle Size: Viscous liquid, not likely to form aerosol under normal conditions Partition Co-efficient (n-octanol/water):
9.1.3 Inhalation Toxicity (Safepharm Laboratories Limited 1995d) Species/strain: CD Number/sex of animals: 5/sex/group Observation period: 14 days Test method: OECD TG 403; EC Method B2 Method of administration: A single nose only exposure to aerosolised test substance (dynamic exposure flow rate 16 L/minute). Atmosphere Concentration 1 Group 2 3 Nominal mg/L 19.1 9.9 4.5 Mean achieved atmosphere concentration, mg/L 5.06 2.57 1.19 Mean mass median aerodynamic diameter, m 1.7 1.8 1.7 Inspirable fraction % < 4 m 82.0 85.2 86.2 hour,
4-hour (estimated) Result: Alkane 2 was of moderate acute inhalation toxicity to the female rat. 9.1.4 Skin Irritation (Safepharm Laboratories Limited 1995b) Species/strain: Rabbit/New Zealand white Number/sex of animals: 4 females, 2 males Observation period: 3 days Method of administration: A single 4 semi occluded application of 0.5 mL of test substance to intact skin. Test method: OECD TG 404; EC Method B4. Dermal response: Grade 1 erythema (very slight erythema) was observed in 3 female and 1 male rabbit at the 30 minute observation period, persisting in one female and male at the 24 hour observation. No further skin reactions were observed for the remainder of the study. 24, 48 & 72 hour group mean score: Erythema/Eschar formation: 0.1; Oedema: 0.0. Result: Alkane 2 was very slightly irritating to rabbit skin. 9.1.5 Eye Irritation (Safepharm Laboratories Limited 1995o) Species/strain: Rabbit/New Zealand White Number/sex of animals: 6 males, 3 females Observation period: 1, 24, 48 and 72 hours post instillation Method of administration, Unirrigated eyes: A single instillation of 0.1 mL of the neat test substance into the conjunctival sac of the right eye of 6 rabbits. The left eye served as the control.
Challenge procedure: Test and Control animals: Day 21: A 24 hour, semi occluded application of 100% w/v of test substance to the right flank of each animal, and 75% w/v test substance in dried arachis oil, to the left flank of each animal. Challenge Outcome: No skin reactions were observed in test animals at the 24 or 48-hour observation period. Grade 1 erythema (discrete or patchy erythema) was observed in one control animal at the 24 hour observation period. No other reactions were noted in control animals. Result: Alkane 2 was non-sensitising to guineapig skin. 9.1.6.2 Skin Sensitisation in Guineapigs [Hill Top Biolabs Inc, 1995 #18] Species/strain: Guineapig/Hartley Number of animals: 10/sex (test 5/sex (naïve control group) Test method: OECD TG 406 Buehler Technique Maximum Concentration not giving rise to irritating effects in irritation screen: Irritancy was observed at 0.5%, the lowest concentration tested. Induction procedure: test animals: Days 1, 7 and 14: 0.3 mL of neat test substance applied, via a Hill Top Chamber, to the clipped skin of the left shoulder for 6 hours; Challenge procedure: test and naïve control animals: Day 28: same procedure as induction phase, except test substance was applied to a previously non-treated site; Grading of dermal responses occurred 24 and 48 hours post exposure Number of animals exhibiting positive responses 1 or more) at challenge: Challenge Test Animals Naïve Control Animals concentration 24 hours* 48 hours* 24 hours* 48 hours* 100% 3/19** 7/19 1/10 3/10 * time after patch removal. ** one female was euthanised at induction because of uncertainity of pregnancy status. Challenge outcome: Following primary challenge the incidence and severity of the responses 1 – slight but confluent, or moderate
patchy erythema) in the test group (7 of 19) was comparable to those produced by the naïve control group (3/10) indicating that sensitisation had not been induced. All remaining test and control animals had Grade 0.5 responses, that is, slight, patchy erythema. Test method: OECD TG 406 Result: Alkane 2 was non sensitising to guineapig skin 9.2 Repeated Dose Toxicity – Test (Safepharm Laboratories Limited 1995a) Species/strain: Rat/Sprague-Dawley CD Number/sex of animals: Method of administration: Oral. Test substance administered by gavage as supplied. Dose/Study duration: Treatment 0, or 1 000 mg/kg/day for 28 consecutive days. Recovery phase: a treatment free period of 14 days. Recovery groups were separately provided for animals of the control and 1 000 mg/kg/day test groups. Test method: OECD TG 407; EC Method B7 Clinical observations There were no deaths or clinical signs of toxicity during the treatment or recovery phase. Food and water consumption and bodyweight gain were unremarkable. Clinical chemistry/Haematology/Urinalysis No findings considered related to treatment were observed for haematological indices or blood chemistry parameters. Weights & Necropsy Significantly increased absolute ovary weight, but not relative weight, in four treated females was not considered toxicologically significant. Significantly increased relative heart, brain and ovary weight for treated recovery females and increased relative testes weight for treated recovery males, were not observed in the animals of the treatment phase and therefore these effects were not considered to be related to treatment. No treatment related macroscopic abnormalities were detected. Histopathology No treatment related morphological findings were observed. Comment No adverse effects related to treatment at 1 000 mg/kg/day were observed in this 28-day study.
10. ASSESSMENT OF ENVIRONMENTAL EFFECTS Tests were performed according to EC and OECD test guidelines (European Commission 1992) at Safepharm Laboratories Limited UK. These facilities comply with the OECD principles of good laboratory practice (GLP) and full test reports were submitted. All tests were performed on Alkane 2. 10.1 Summary of Effects on Biotic Systems Test Species Results Acute Toxicity Semi-static WAF a 96 hour OECD TG 203 Rainbow trout (Oncorhynchus mykiss) b > 1 000 mg/L NOEC ≥ 1 000 mg/L Acute Immobilisation Static WAF a 48 hour OECD TG 202 Water Flea (Daphnia magna) ELR50 c > 1 000 mg/L NOEC ≥ 1 000 mg/L Growth Inhibition Static 96 hour OECD TG 201 Algae (Selenastrum capricornutum) EbLR50 d > 1 000 mg/L EµLR50 e > 1 000 mg/L NOEC ≥ 1 000 mg/L WAF: water accommodated fraction - see comments in text below. LLR: lethal loading rate. ELR: effective loading rate. EbLR50: effective loading rate that reduced biomass by 50%. EµLR 50: effective loading rate that reduced specific growth rate by 50% (24-48 hours). f) NOEC - no observable effect concentration. Based on the results of rangefinding studies, limit tests were conducted for the definitive studies. The toxicity of Alkane 2 on fish, water flea and algae was examined using a Water Accommodated Fraction (WAF) with a loading rate of 1 000 mg/L. The test media was stirred for 20 hours, with the mixture then allowed to stand for 4 hours prior to the removal of the aqueous phase or WAF. Analysis of the WAF was carried out by Total Organic Carbon (TOC) analysis. The results showed the concentrations of the carbon in the test vessels to be around the limit of detection of the analytical method. All exposures are expressed in of the original concentration of the chemical in water at the preparation of the WAF (the loading rate), irrespective of the actual concentration of the chemical in water. During all testing, the WAF was observed to be a clear, colourless solution. 10.2 Fish Acute Toxicity Test (Safepharm Laboratories Limited 1995g)