zilongwang/ReadingBank huggingface dataset:
Acute oral toxicity Rat LD50 > 4 168mg/kg bw Acute dermal toxicity Rat LD50 > 2 000 mg/kg bw Skin irritation Rabbit Mildly irritating Eye irritation Rabbit Mildly irritating Skin sensitisation – non adjuvant method Guineapig Non sensitising Bacterial Reverse Mutation S .typhimurium Non mutagenic 9.1 Acute Toxicity 9.1.1.1 Oral Toxicity (Safepharm Laboratories Limited Test Substance: Alkane 5 Species/strain: Rat/Sprague-Dawley Number/sex of animals: 5/sex Observation period: 14 days Method of administration: 5 000 mg/kg by gavage in a dose volume of 6.07 mL/kg Test method: OECD TG 401; EC Method B1 Mortality: Nil Clinical observations: There were no clinical signs of systemic toxicity. Morphological findings: No abnormalities were noted at necropsy. Estimated LD50: > 5 000 mg/kg Result: Alkane 5 was of very low acute oral toxicity to the rat. 9.1.1.2 Oral Toxicity (Hazelton Raltech Inc 1982b) Test Substance: Oronite Gulf Synfluid 8cSt Species/strain: Rat/Sprague-Dawley Number/sex of animals: 5/sex Observation period: 14 days Method of administration: 4 168 mg/kg by gavage in a dose volume of 5.0 mL/kg bw
Test method: Not stated Mortality: Nil Clinical observations: There were no clinical signs of systemic toxicity. Morphological findings: Moderate hydrometra was observed in one female. Clear, firm raised areas on all lobes of the lung were in one male. No other abnormalities were noted at necropsy. Estimated LD50: > 4 168 mg/kg Result: Oronite Gulf Synfluid 8cSt was of very low acute oral toxicity to the rat. 9.1.2.1 Dermal Toxicity (Safepharm Laboratories Limited 1995b) Test Substance: Alkane 5 Species/strain: Rat/Sprague-Dawley CD Number/sex of animals: 5/sex Observation period: 14 days Method of administration: A single, 24-hour semi occluded dermal application to intact skin at a dose of 2 000 mg/kg bw, dose volume of 2.43 mL/kg. Test method: OECD TG 402; EC Method B3. Mortality: Nil Clinical observations: No clinical signs of systemic toxicity were noted. Dermal response: No signs of dermal irritation were noted. Morphological findings: No abnormalities were noted at necropsy. LD50: > 2 000 mg/kg bw Result: Alkane 5 was of low dermal toxicity to the rat. 9.1.2.2 Dermal Toxicity (Hazelton Raltech Inc 1982a) Test Substance: Gulf Synfluid 8cSt Species/strain: Rabbit/New Zealand White
Number/sex of animals: 5 and 5 females per treatment and control group Method of administration: Orally by gavage. Dose/Study duration: 0, 50, 200 and 1000 mg/kg/day, in carboxymethyl-cellulose 0.5% with 0.1% Tween 80, for 28 consecutive days. Test method: OECD TG 407 Clinical observations: No deaths occurred. There were no significant differences in body weight gain and no signs of toxicity. Clinical chemistry/Haematology No treatment-related findings were observed. Histopathology: No treatment-related macro- or microscopic findings were observed. Result: A No Observed Effect level of 1000 mg/kg/day, the highest does tested was identified for the test chemical. 9.3 Genotoxicity 9.3.1 Bacterial Reverse Mutation Assay (Ciba-Geigy, 1992e) The test material used for this was TKK30009. Strains: Salmonella typhimurium: TA98, TA100, TA1535, TA1537; Escherichia coli: WP2 uvrA. Metabolic activation: Aroclor-induced rat S9 Concentration range: Without exogenous metabolic activation : Expt 1 : 156.25, 312.5, 625, 1250, and 2500 Expt 2 : 19.5, 39.1, 78.1, 125.25 and 312.5 g/plate. With exogenous metabolic activation : Expt 1: 312.5, 625, 1 250, 2500 and 5000 Cytotoxicity : 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 g/plate. Dimethylsulphoxide was used as vehicle throughout. Appropriate strain specific positive control reference substances were used. Test method: OECD TG 471
The Toxicology Research Laboratory Evaluation of the Acute Toxicity of Experimental Polyglycol XU-1348.01 to Daphnia magna Straus, Report #ES-3162. Michigan: The Dow Chemical Company. The Toxicology Research Laboratory (1997b): Evaluation of the Acute Toxicity of Experimental Polyglycol XU-13481.01 to the Fathead Minnow, Pimephales promelas Rafinesque, Report # 971052. Midland: The Dow Chemical Company. The Toxicology Research Laboratory (1997c): Experimental Polyglycol XU - 13481.01: Acute Dermal Toxicity Study in New Zealand White Rabbits, Report # DR-0353-5124-001D. Michigan: The Dow Chemical Company. The Toxicology Research Laboratory (1997d): Experimental Polyglycol XU - 13481.01: Acute Primary Eye Irritation Study in New Zealand White Rabbits, Report # Michigan: The Dow Chemical Company. The Toxicology Research Laboratory (1997e): Experimental Polyglycol XU - 13481.01: Primary Dermal Irritation Study in New Zealand White Rabbits, Report Michigan: The Dow Chemical Company. The Toxicology Research Laboratory (1997f): Experimental Polyglycol XU-13481.01: Acute Oral Toxicity Study in Fischer 344 Rats Report # DR-0353-5124-001A. Michigan: The Dow Chemical Company. The Toxicology Research Laboratory (1997g): Experimental Polyglycol XU-13481.01: Dermal Sensitization Potential in Hartley Albino Guinea Pigs, Report # DR-0353-5124-001E. Michigan: The Dow Chemical Company. Tupa RC (1987): Gasoline Port Fuel Injectors - Causes/Consequences/Cures, Society of Automotive Engineers Technical Paper No. 872113. Tupa RC Koehler DE (1986): Gasoline Port Fuel Injectors - Keep Clean/Clean Up with Additives, Society of Automotive Engineers Technical Paper No. 861536. Tupa RC Koehler DE (1988): Intake Valve Deposits - Effects of Engines, Fuel and Additives, Society of Automotive Engineers Technical Paper No. 881645. WIL Research Laboratories Inc. (1997): A Combined Four-Week Repeated-Dose Oral Toxicity, Reproduction and Neurotoxicity Screen in Rats with CP 2532 Study # Ashland.
Time Animal No. treatment (days) 1 2 3 4 5 6 7 8 Erythema 1 1 0 0 0 0 0 0 0 2 0 1 0 0 0 0 0 0 3 1 0 0 0 0 0 0 0 Oedema 1 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 3 0 0 0 0 0 0 0 0 a see Attachment 1 for Draize scales Comment: The experimental SS produced only marginal effects, and was similar in irritancy to analogues. Result: SS was slightly irritating to the skin of rabbits Eye Irritation Eye irritation with FA (Younger Laboratories, 1968b) Species/strain: New Zealand White rabbit Number/sex of animals: 3 (2 males, 1 female) Observation period: 1 to 7 days after treatment Method of administration: 100 mg of finely ground FA powder were placed into the conjunctival sac of the right eye of each rabbit. The eyes were examined for signs of irritation after 1, 24, 48, 72, 120 and 168 hours. The treated eyes were rinsed with warm isotonic saline 24 hours after treatment later. After the reading, fluorescein (concentration not stated) was instilled to detect corneal damage. Test method: Not stated Comment: Treated eyes were graded according to the severity of erythema, oedema, discharge, corneal opacity and iridial reactions on an arbitrary scale of 0 to 110. Moderate discharge and erythema, mild oedema and mild corneal cloudiness developed in all treated eyes after 1 hour. Iris clarity improved overnight and discharge had nearly ceased within 3 days. A slight degree of redness and oedema remained after 7 days.
Challenge Test animals Control animals Concentration 24 hours* 48 hours* 24 hours 48 Challenge 1 (33%) 0/10** 0/10 0/4 0/4 Challenge 2 (33%) 0/10 0/10 0/4 0/4 Challenge 3 (33%) 0/10 0/10 0/10 0/10 * time patch removal ** number of animals exhibiting erythema Comment: In the first challenge, the response was similar to that observed in treated controls. In the second challenge minimal erythema was observed and, under the conditions of the test, is not considered a positive response. Result: SS was not sensitising to the skin of guinea pigs. Skin Sensitisation test with SS (SEAC Toxicology, 1983) Species/strain: Guinea pigs/Albino Dunkin/Hartley Number of animals: 10 (6 males, 4 females) Induction procedure: Test day 0 day 7 Three pairs of intradermal injections (0.1 mL) were made on the shoulder region: FCA diluted 1:1 with physiological saline SS, 0.5% in physiological saline SS, 0.5% in a 1:1 mixture of FCA and saline A 2x4 cm filter patch was saturated with 25% SS and placed over the shaved area and covered by impermeable polythene adhesive tape. Control group: Treated controls: During the induction phase control animals (4/same sex) were treated in the same way as test animals except that the test substance was omitted from the intradermal injections and topical applications. Untreated controls: At challenge in the test, 4 previously untreated animals of the same sex and weighing approximately the same as the test animals at that challenge are treated in exactly the same way as the test animals. Challenge procedure:
Number of animals exhibiting positive responses at challenge: Challenge Test animals Control animals concentration 24 48 72 hours* 24 hours 48 hours 72 30% **3/10 3/10 3/10 0/5 0/5 0/5 10% 0/10 0/10 0/10 0/5 0/5 0/5 5% 0/10 0/10 0/10 0/5 0/5 0/5 0% 0/10 0/10 0/10 0/5 0/5 0/5 * time after patch removal ** number of animals exhibiting positive responses Challenge outcome: Challenge concentration of 30%: 2 animals had well defined erythema and one animal had very slight erythema, which persisted to the 72 hour observation time. Challenge concentrations of 0, 5, or 10% revealed no discernable reactions. Control group - no discernable reactions. Result: Magnol R was sensitising to guinea pig skin. Skin Sensitisation Buehler Method on Magnol (Magnol-R and Triethyl Citrate 50:50 w/w%) (Takahashai, 1996) Species/strain: guinea pig/Hartley Number of animals: 10 females (test group), 5 females (control group) Test substance: Magnol (Magnol-R and Triethyl Citrate 50:50 w/w%) Test method: Similar to OECD TG 406 Induction procedure: test animals: Days 1, 7 and 14: lint cloth soaked with 0.5 mL of 5% Magnol in vaseline was applied to the shorn left ventral skin and held under occlusive dressing for 6 hours; control animals: treated similarly to the test animals omitting the test substance from the topical application
Mortality: None Clinical observations: Hunched posture, piloerection, dyspnea; symptoms resolved within 5 days. Morphological findings: No deviations from normal morphology were observed. Comment: None LD50: > 2000mg/kg Result: The notified chemical was of very low oral toxicity in rats. 9.1.2 Dermal Toxicity (Hartmann, 1991b) Species/strain: Rats, Tif:RAIf Number/sex of animals: 5 males, 5 females Observation period: 14 days Method of administration: Test substance applied to shaved intact skin under semiocclusive dressing. Test method: OECD TG 402 Mortality: None Clinical observations: Piloerection; symptoms resolved within 2 days. Morphological findings: No deviations from normal morphology were observed. Comment: No assessments of skin irritation were provided. LD50: > 2000mg/kg Result: The notified chemical was of low dermal toxicity in rats. Inhalation toxicity No information was provided. 9.1.4 Skin Irritation (Hagemann, 1991a) Species/strain: Rabbits, New Zealand White Number/sex of animals: 3
Strains: Salmonella typhimurium TA98, 100, 1535, 1537; Escherischia coli WP2 uvrA Metabolic activation: Aroclor 1254-induced rat liver microsomal fraction S9 Concentration range: 312.5, 625, 1250, 2500, 5000g/plate Test method: OECD TG 471, 472 Comment: A finding toxicity test performed with and without microsomal activation determined a maximum test substance concentration without toxicity of 5000g/plate. In both initial and confirmatory experiments, no significant increase in the incidence of mutations was observed compared to negative controls. Result: The notified chemical was non mutagenic the conditions of the test. 9.3.2 Chromosomal Aberration Assay in Chinese Hamster Ovary Cells (Ogorek, 1992) Chinese hamster ovary CCL 61 Metabolic activation system: Aroclor 1254-induced rat microsomal fraction S9 Dosing schedule: Metabolic Activation Experiment/ Study Number Test concentration (g/mL) Controls -S9 Original study Confirmation study Treatment time = 18 hours 5.1*, 10.2*, 20.3*, 40.6, 81.3, 162.5, 325, 650 g/ml Treatment time = 42 hours 5.1*, 10.2*, 20.3*, 40.6, 81.3, 162.5, 325, 650 g/ml Positive: Mitomycin C Negative: Ethanol vehicle +S9 Original study Confirmation study Treatment time = 3 hours. Recovery time = 15 hours. 5.1*, 10.2, 20.3, 40.6, 81.3, 162.5*, 325*, 650* g/ml Treatment time = 3 hours. Recovery time = 15 or 39 hours. 5.1*, 10.2, 20.3, 40.6, 81.3, 162.5*, 325*, 650* g/ml Positive: Cyclophosphamide Negative: Ethanol vehicle * - cultures selected for metaphase analysis
Positive control: (without S9-mix) 2-nitrofluorene for TA98 and TA1538; sodium azide for TA100 and TA1535; 9-aminoacridine for TA1537; and methyl methanesulfonate for E. coli strains. Positive control: (with S9-mix) Sterigmatocystin for WP2 (pKM101); and 2-aminoanthracene for the remaining strains. Test method: OECD TG 471 Comment: Test article was soluble at 100 mg/mL, the maximum concentration tested. Toxicity was observed at 5 000 and 1800 g per plate, with and without S9-mix, respectively when using preincubation method. No appreciable toxicity was observed in the tests using plate incorporation method. were no significant increases in revertant colony numbers at any concentration, in the presence or absence of metabolic activation. Concurrent positive controls used in the tests induced marked increases in the frequency of revertant colonies and the activity of the S9 fraction was found to be satisfactory. Historic data were included to support the study findings. Result: The notified chemical was non mutagenic the conditions of the test. 9.3.2 Clonal Transformation Assay in Syrian Golden Hamster Embryo (SHE) Cells (Custer, 1999) Cells: Syrian golden hamster embryo (SHE) cells Dosing schedule: Each experiment consisted of 40 dishes per treatment group including at least one vehicle control and one positive control. Experiment Test concentration (g/mL) Controls treatment time = 24 hours 0, 15*, 35*, 40, 50*, 150*, 250*, 350 and 625 g/mL. Positive: Benzo(a)pyrene in DMSO Vehicle: DMEM culture medium treatment time = 7 days 0, 5*, 20*, 35*, (42*), 50*, (60*), 65, 80 and 100 g/mL. Vehicle: DMEM culture medium Positive: Benzo(a)pyrene in DMSO
Worker exposure is expected by the notifier to be 'minimal' when closed systems are used and recommendations for ventilation and protective gear are followed. PUBLIC EXPOSURE MDI is listed in the Australian Inventory of Chemical Substances and is covered by the Australian Code for the Transport of Dangerous Goods by Road and Rail (ADG code)(3). Since this compound is present in excess in the MDI-polyol prepolymer product, transport of the product is to be pursuant to the ADG code. Liquid waste is to be disposed of by a company licensed to incinerate MDI liquid. Solid waste will be sent to an approved landfill site for burial. Used container drums will be decontaminated by water prior to disposal (landfill or drum recycling) and rinse fluids will be disposed of according to state regulations (eg. treatment in an approved waste water facility). Public exposure to the raw material will therefore be low. During the production of manufactured goods, MDI-polyol prepolymer is further polymerised, forming polyurethane elastomers, resulting in negligible public exposure. ENVIRONMENTAL EXPOSURE . Release The notified product is stated to replace existing MDI prepolymer products currently used for this purpose. MDI-polyol prepolymer will be processed at the two sites utilising a closed system reaction injection moulding machine. This involves emptying the product drums into the machine's reservoirs, injecting liquid product and further polyol to an enclosed pressurised mould cavity where polymerisation occurs to endpoint/curing after a few minutes. When the moulded polyurethane elastomer components are removed from the mould, the notified substance is considered to be fully reacted. In the event of accidental spillage, the 1,1'-methylenebis (isocyanatobenzene) (MDI) component of MDI-polyol prepolymer could cause an immediate terrestrial or aquatic environmental hazard. Contamination of drains or water ways should be avoided by containing and absorbing the polymer mixture with wet sand or soil.
Metabolic Activation Number Test concentration (g/mL) Controls -S9 IA treatment time = 3 hours (20 hours harvest) 0, 5.73, 8.19*, 11.7*, 16.7* and 23.9* g/mL Positive: MMC Negative: vehicle II treatment time = 17.8 hours (20.3 hours harvest) 0, 1.25, 2.5*, 5*, 10*, 15*, 20 and 25 g/mL +S9 IA treatment time = 3 hours (20 hours harvest) 0, 8.19, 11.7*, 16.7*, 23.9* and 34.2* g/mL Positive: CP Negative: vehicle II treatment time = 3 (20 hours harvest) 0, 5, 10*, 15, 20*, 25*, 30* and 35 g/mL MMC - mitomycin C CP - cyclophosphamide DMSO – dimethylsulphoxide * - cultures selected for metaphase analysis Test method: OECD TG 473 Comment: No significant increase in with chromosomal aberrations, polyploidy, or endore-duplication was observed in the cultures analyzed in both the initial and confirmatory assays. The results of positive controls were not reported. Result: The notified chemical was non clastogenic under the conditions of the test. 9.3.3 Micronucleus in the Bone Marrow Cells of the Mouse No report of in vivo micronucleus assay was provided. 9.4 Overall Assessment of Toxicological Data The notified chemical was of very low acute oral toxicity (LD50>2 000 mg/kg) and low acute dermal toxicity (LD50>2 000 mg/kg) in rats. It was not an eye or skin irritant in rabbits, nor a skin sensitiser in guinea pigs. The notifier provided a report of using an Irritection Assay System to assess the potential ocular irritancy in vitro for the notified chemical. The results suggested that the notified chemical may have the potential to produce, at most, minimal eye irritation (Emmons, 2000), which was in consistent with the in vivo test results. In a repeat dose oral toxicity study in rats, a NOEL was established as 1 000 mg/kg/day, the highest dose tested. In genotoxicity studies, the notified chemical was not mutagenic in
acute oral toxicity rat LD50 > 5 000 mg/kg (Chevron, acute dermal toxicity rat LD50 > 5 000 mg/kg (Chevron, skin irritation rabbit slight irritant (Chevron, 1985c) eye irritation rabbit slight irritant (Chevron, skin sensitisation guinea pig sensitising (OLOA 224, OLOA 2990, OLOA 2000, XA 14328) or not sensitising (16.1% OLOA 2990) (Chevron, 1993; Hill Top Biolabs, 1991, 1995; Hill Top Research, 1996; TKL Research, 1992) 9.1.1 Oral Toxicity (Chevron, Species/strain: Rat/Sprague-Dawley. Number/sex of animals: 5/sex. Observation period: 14 days. Method of administration: Oral (gavage); vehicle: peanut oil; dose: 5 g/kg. Test method: OECD TG 401 Mortality: None. Clinical observations: The majority of animals exhibited pale or soft faeces on days 1 and/or 2. Morphological findings: None related to treatment. LD50: > 5 000 mg/kg Result: The notified chemical was of very low acute oral toxicity in rats. 9.1.2 Dermal Toxicity (Chevron, Species/strain: Rabbit/New Zealand White (NZW). Number/sex of animals: 4 females, 6 males initially and a fifth female 3 weeks later. Observation period: 14 days. Method of administration: Under occlusive dressing for 24 hours; dose 5g/kg. Test method: OECD TG 402
9.1.6.3 OLOA 2000 (15% OLOA 224) (Hill Top Research, 1996) Species/strain: Guinea pig/Dunkin-Hartley. Number of animals: 10 control/ 20 test. Induction procedure: test group: 3 treatments at intervals of 7 days 0.3 mL of the undiluted test substance placed in a 25 mm Hill Top Chamber applied to the left shoulder and occluded for 6 hours. control group: As for test group using mineral oil. Challenge procedure: Approximately 2 weeks after last induction exposure Same exposure procedure as for induction phase but at a different skin site; 1% in mineral oil. Test method: OECD TG 406 Challenge outcome: Challenge Test animals Control animals concentration 24 hours* 48 24 hours 48 hours 1% **0/20 2/20 0/10 0/10 * time after patch removal ** number of animals exhibiting positive response (ie Draize score 1) Result: OLOA 2000 was sensitising to the skin of guinea pigs. 9.1.6.4 XA 14328 (5.9% OLOA 224) (Hill Top Biolabs, 1995) Species/strain: Guinea pig/Dunkin-Hartley. Number of animals: 10 control/ 20 test. Induction procedure: test group: 3 treatments at intervals of 7 days 0.3 mL of the undiluted test substance placed in a 25 mm Hill Top Chamber applied to the left shoulder and occluded for 6 control group: As for test group using mineral oil. Challenge procedure:
Comment: No cytotoxicity was observed in Experiment 1. In both experiments the test substance did not cause any significant increases in the incidence of mutant colonies in the presence or absence of metabolic activation from that of the negative control. Positive controls used in the test caused marked increases in the incidence of mutant colonies and the activity of the S9 fraction was to be satisfactory. Result: The notified chemical did not induce gene mutations in CHO cells. 9.4.3 Chromosomal Aberration Assay (Health and Environmental Services 1989a) Cells: Rat lymphocytes Auxillary Metabolic activation system: Liver S9 fraction from Sprague-Dawley rats pre treated with Aroclor 1254 at 500 mg/kg. Dosing schedule: Each concentration was tested in duplicate, in two independent experiments for a treatment time of 4 hours in the presence or absence of metabolic activation at test concentrations of 0, 166.7, 500*, 1666.7*, 5000* g/mL. Appropriate clastogenic control substances were used. *cultures selected for metaphase analysis. Test method: OECD TG 473; EC Method B10. Comment: Cytotoxicity was not observed at any concentration. The test substance did not cause any significant increases in the incidence of cells with chromosomal aberrations, polyploidy or endoreplication, at the concentrations analysed in the presence or absence of metabolic activation. Positive controls used in the test caused marked increases in the incidence of aberrant cells and the activity of the S9 fraction was found to be satisfactory. Result: The notified chemical was not considered clastogenic the conditions of the test. 9.4.4 Micronucleus in the Bone Marrow Cells of the Mouse (Health and Environmental Services 1992) Species/strain: (ICR) BR Number and sex of animals: 5/sex/test group Study design: Test substance: 0, 200, 666, 2000 mg/kg. Positive control, cyclophosphamide (CP): 120 mg/kg.
Species/strain: rat/ Sprague-Dawley. Number/sex of animals: 5/sex Observation period: 14 days. Method of administration: Under semi-occluded gauze dressing for 24 hours, dose 2000 mg/kg. Test method: OECD TG 402 Mortality: None. Clinical observations: None. Morphological findings: None. Draize scores: All scores zero. LD50: > 2000 mg/kg. Result: The notified chemical was of low dermal toxicity in rats. Inhalation Toxicity Data not provided. 9.1.4 Skin Irritation (Safepharm Laboratories, Species/strain: rabbit/New Zealand White (NZW). Number/sex of animals: 3 males. Observation period: 7 days. Method of administration: 0.5 mL, single, 4-hour, semi-occluded application. Test method: OECD TG 404 Draize scores: Time after Animal treatment (days) 1 2 3 Erythema 1 hour 1a 1 1
Cells: CHL Metabolic activation system: Phenobarbitone/ -naphthoflavone-induced Sprague-Dawley rat liver S9 fraction. Dosing schedule: Activation Experiment Number Test concentration (g/mL) Controls -S9 1 treatment time = 6 hours, harvest time = 24 hours Positive: mitomycin C, 0.1 g/mL Negative: acetone vehicle Positive: mitomycin C, 0.05 g/mL Positive: mitomycin C, 0.025 g/mL Negative: acetone vehicle 0*, 1, 2*, 4*, 8*, 12*, 16 g/mL 2 treatment time = 24 hours = harvest time 0*, 2, 4*, 8*, 10*, 12, 16 g/mL treatment time = 48 hours = harvest time 0*, 1, 2, 4*, 8*, 10*, 12 g/mL +S9 1 treatment time = 6 hours, harvest time = 24 hours Positive: cyclophosphamide, 10 g/mL Negative: acetone vehicle Positive: cyclophosphamide, 10 g/mL 0*, 105, 210, 420, 840*, 1680*, 2100* g/mL 2 treatment time = 6 hours, harvest time = 24 hours 0*, 450, 900, 1800, 2100*, 2400*, 2700* g/mL Negative: acetone vehicle * selected for metaphase analysis Test method: OECD TG 473 Comment: The test substance was shown to be toxic and doses were selected accordingly. Statistically significant increases in
salivation was observed in two males and one female and waddling/unsteady gait was observed in one male and all females. One female was observed walking on toes and one female showed increased sensitivity to touch. Recovery as judged by external appearance and behaviour was complete in all animals by day 5. Morphological findings: No abnormalities were observed during macroscopic examinations. LD50: > 2000mg/kg Result: The notified chemical was of very low acute oral toxicity in rats. 9.1.2 Dermal Toxicity (Mason, 1999b) Species/strain: Rat, Sprague Dawley Number/sex of animals: 5 males, 5 females Observation period: 14 days Method of administration: 24 hour application to shaved skin via 50 x 50 cm porous gauze pad covered with waterproof dressing. Test method: OECD TG 402 Mortality: None Clinical observations: No mortalities occurred and all animals gained weight throughout the study. Vocalisation and hyperactivity were observed in one female on day 1. Slight to well-defined dermal irritation resolving by day 9 was seen in four males and three females. Additional desquamation was observed in two females with localised spots and/or scabbing in one female. These were resolved by day 13. Morphological findings: No abnormalities were observed during macroscopic examinations. Draize scores:
removing trapped film from the developer tank (one worker approximately 2 mm/day); removing exhausted developer from developer tank, replacing with working developer, and transfering exhausted working developer to holding tanks for neutralisation and further dilution before disposal (one worker approximately 45 min/2 months); mixing developer for the replenisher tank (one worker approximately 5 mm as required); and engineering service of reprographic (film processing) equipment containing diluted solution. The notifier states that during film processing, workers will not come into contact with the solution, however, fumes may be released to the atmosphere. The worker environment will vary for each user. Most film processors will be housed in airconditioned sites. Workers will be encouraged to use protective gloves and safety glasses when handling the material. PUBLIC EXPOSURE Lithographic film developer, (containing <1% w/w of the notified chemical FPC-156) will be imported to Australia in shipping bulk containers containing plastic containers on wooden pallets. These pallets (containing 51 ten litre containers of material) will be removed mechanically from the ship and loaded onto trucks for transportation to Collie Cooke. Covered transport will be used to transport units of film developer (in 10 litre lots) from Collie Cooke to each client. There is low potential for public exposure to the notified chemical during shipment and distribution. At the client’s premises, the film developing product is diluted with water (1 part product with 2 parts water), added to developing tanks and used in reprographic eqipment to fix photographic products. The exhausted, diluted product is removed from the equipment into a holding tank where it is further diluted with water before entry into the sewerage system or, when disposal by that method is not permitted, into holding tanks for removal to a waste treatment plant. The public should not be directly exposed to the chemical as the film developer will only be used by professionals in lithographic processing laboratories.
Work Category (number of workers) Nature of work Exposure Physical form of chemical Personal Protective Equipment used Transport (1) Transportation of imported drums to the plant. 4 hours/day, 12 days/year Cool liquid Safety glasses, neoprene or nitrile gloves, safety boots Storage (2) Forklift removal of drums from transport vehicle to storage site and from storage to processing areas. 1 hour/day, 36 days/year Cool liquid Safety eyewear, neoprene or nitrile gloves, safety cotton overalls Process workers (3 - 5) Pumping chemical into blending vessel, monitoring & adjusting blending conditions and component quantity, discharging blend to packaging. From 2 hours/day, 36 days/yeara to 4 hours/day, 210 days/yearb Cool liquid/gas Safety eyewear, neoprene or nitrile gloves, safety boots, cotton overalls, goggles, hard hats, organic vapour mask (where necessary) Maintenance (2) Routine maintenance of blending vessel, including opening charging and pumps, washing of blending vessel. From 4 hours per monthc over a 10 month periodb to 2 hours/day 3 days/yeara Cool liquid/gas Safety eyewear, neoprene or nitrile gloves, safety boots, cotton overalls, goggles, hard hats, organic vapour mask (where necessary) Quality assurance laboratory testing (3) Chemical and physical testing of plant sample, directing plant operators in component addition adjustments 2 hours/day, 36 days/year Liquid Safety eyewear, latex gloves, safety boots, cotton lab coat aHuntsman ICI Polyurethanes (Australia) Pty Ltd bAriel Industries Pty Ltd cMaximum exposure trial,
Observation period: 14 days. Method of administration: Semi-occluded 24-hour application to intact skin; dose 2000 mg/kg. Test method: OECD TG 402 Mortality: None. Clinical observations: No signs of toxicity. Erythema could not be evaluated due to black staining of the skin one day after dosing and at 8 treatment sites 2 days after dosing. No evidence of skin irritation was noted for the remainder of the observation period. Morphological findings: None. LD50: > 2000 mg/kg. Result: The notified chemical was of low dermal toxicity in rats. 9.1.3 Inhalation Toxicity No data provided. 9.1.3 Skin Irritation (Safepharm Laboratories Ltd, 2000f) Species/strain: rabbit/New Zealand (NZW). Number/sex of animals: 2 females/ 1 male. Observation period: 72 hours. Method of administration: 0.5 g test substance under semi-occluded dressing for 4 hours. Test method: OECD TG 404 Comment: Grey coloured staining was observed in all animals at 1 hour and in one animal at 24 hours post-treatment but this did not affect scoring of irritative effects. No erythema or oedema was observed in any animal at any time point. Result: The notified chemical was not irritating to the skin of rabbits. 9.1.5 Eye Irritation (Safepharm Laboratories Ltd, 2000g) Species/strain: rabbit/NZW.
Result: The notified chemical was non mutagenic under the conditions of the test as no increases in the numbers of revertant colonies above background were observed. 9.3.2 Chromosomal Aberration Assay in human lymphocytes in vitro (Safepharm Laboratories Ltd, 2000k) Cells: Human lymphocytes. Metabolic activation system: Induced rat microsomal fraction. Dosing schedule: Activation Experiment Number Test concentration (g/mL) Controls -S9 1 Treatment time = 4 hours; expression time = 16 hours. Positive: EMS Negative: Vehicle = minimal essential medium Test concentration = 0*, 39.06, 78.13, 156.25, 312.5, 625*, 1250*, 2500* and 5000 microgram/mL. 2 Treatment time = 20 hours. Test concentration = 0, 78.13, 156.25, 312.5, 625*, 1250*, and 2500* microgram/mL. +S9 1 (S9 = 1%) Treatment time = 4 hours; expression time = 16 hours. Positive: CP Negative: Vehicle = minimal essential medium Test concentration = 0*, 39.06, 78.13, 156.25, 312.5*, 625*, 1250*, 2500 and 5000 microgram/mL. 2 (S9 = 2%) Treatment time = 4 hours; expression time = 16 hours. Test concentration = 0*, 78.13, 156.25, 312.5, 625*, 1250*, and 2500* microgram/mL. EMS = ethylmethanesulphonate; CP = cyclophosphamide * - cultures selected for metaphase analysis Test method: OECD TG 473 Comment: Positive controls demonstrated the sensitivity of the test and negative controls were within historical limits. Precipitation was observed at all dose levels and there was no reduction in mitotic index at any dose. No
and were all below the method detection limit. Accordingly, the bioconcentration factor was also below the limit of detection at <2.3 (Level 1) and <0.24 (Level 2). Therefore, the notified chemical is not expected to bioaccumulate in fish. This is not surprising, given the high water solubility of the notified chemical. 9. EVALUATION OF TOXICOLOGICAL DATA 9.1 Acute Toxicity Summary of the acute toxicity of the Dye for BJ Printer Ink 001 Test Species Outcome Reference acute oral toxicity rat LD50 >2000 mg/kg (Noakes, 1999c) acute dermal toxicity rat LD50 >2000 mg/kg (Noakes, skin irritation rabbit Non irritant (Noakes, 1999d) eye irritation rabbit Slight irritant (Noakes, 1999b) skin sensitisation guinea pig Non sensitiser (Noakes, 1999e) 9.1.1 Oral Toxicity (Noakes, Species/strain: Rat/Alpk:APfSD Number/sex of animals: 5/sex Observation period: 14 days Method of administration: A single oral dose of 2000 mg/kg notified chemical in deionised was given by gavage Test method: OECD TG 401 (limit test) Mortality: None Clinical observations: Blue urine, and blue or blue/black faeces. Fur and tail stained blue/black. Morphological findings: One male and one female had pelvic dilation of the kidney. Microscopic investigation was not conducted in the
Species/strain: Rabbits/New Zealand White Number/sex of animals: 3/female Observation period: 3 days Method of administration: A single dermal dose of 500 mg notified chemical (moistened with 0.5mL deionised water) was applied under an occlusive dressing for 4 hours. Test method: OECD TG 404 Comment: Histological examination was conducted on skin samples from the application sites of all animals due to black or black/green staining during the study. The staining prevented an accurate evaluation of irritation, as erythema could not be measured. There were no signs of oedema in any animals. Histological examination revealed no evidence of irritant effects. Result: the notified chemical was not irritating to the skin of rabbits 9.1.5 Eye Irritation (Noakes, 1999b) Species/strain: Rabbit/New Zealand White Number/sex of animals: 3/female Observation period: 3 days Method of administration: A single dose (approximately 100 mg notified chemical) was placed into the conjunctival sac of the left eye of each animal. The eyes remained unwashed. The untreated eye served as a control. Test method: OECD TG 405 Draize scores of unirrigated eyes:
Treatment Maximum average Number of animals with cornea involvement Days to normal 3 mg test substance, unrinsed eyes 16.7 2 of 3 2 in 3 days, 1 in 4 days 3 mg test substance, rinsed eyes 5.3 0 of 3 3 in 2 days 0.1 mL 10% test substance 28.0 3 of 3 2 in 4 days, 1 in 21 days The test substance was judged to be a slight to moderate eye irritant in rabbits. 9.1.6 Skin Sensitisation (Saitama Institute, 2000) Species/strain: guinea pig/Dunkin-Hartley. Number of animals: 10 test; 5 controls. Induction procedure: days 1 -14 test group: Twice weekly occluded applications of 10% BA-20 were applied for 24 hours twice per week for 2 weeks. An intradermal injection of 0.1 mL of Freund’s Complete Adjuvant was administered separately at 2 sites in the patched area of skin once before the 3rd treatment. control group: The control group received 50% ethanol in water under the same conditions as the test group. Challenge procedure: day 21 The flank was shaved and solutions (1, 5 and 10%) of the test substance applied. Sites were scored at 24, 48 and 72 hours. Test method: Cumulative enhancement protocol (Tsuchiya et. al, 1985) Challenge outcome: Challenge Test animals Control animals concentration 24 48 hours* 72 hours* 24 48 hours 72
-S9 0, 2, 5, 10, 20, 39, 78 0, 156, 313 625, 1250 2500, 5000 0, 39, 78 156, 313 625, 1250 0, 5, 10, 20, 39, 78, 156 +S9 0, 20, 39, 78, 156, 313, 625 0, 313, 625, 1250, 2500 5000 0, 20, 39, 78, 156, 313, 625 Test method: OECD TG 471 Comment: Solvent control: dimethylsulfoxide; Postive controls: (a) S9: 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2): TA 98, TA 100 and WP2uvrA; sodium azide, TA 1535; TA 1537; (b) + S9: benzo(a)pyrene, TA 100, TA 98 and TA 1537; 2-aminoanthracene, TA 1535, WP2uvrA. Similar numbers of back mutant colonies were observed regardless of the addition of the notified chemical to bacterial suspensions to plating with or without rat liver S9 fraction was included. Negative controls were within historical limits and positive controls demonstrated the sensitivity of the test system. Result: The notified chemical was non mutagenic under the conditions of the test. 9.3.2 Chromosomal Aberration Assay in Chinese Hamster Lung (CHL) Cells (Shin Nippon Biomedical Laboratories Ltd, 2001) Cells: CHL Metabolic activation system: S9 fraction from the livers of male Sprague-Dawley rats treated with phenobarbital/ 5,6-benzoflavone. Dosing schedule: Metabolic Activation Experiment Number Test concentration (microgram/mL) Controls -S9 1 treatment time = 6 hours, harvest time = 24 hours
9. EVALUATION OF TOXICOLOGICAL DATA 9.1 Summary of Toxicological Investigations Endpoint & Result Assessment Conclusion Rat, acute oral LD50 1 120.9 mg/kg bw Harmful Rabbit, skin irritation Slightly irritating Genotoxicity - bacterial reverse mutation Non mutagenic 9.1.1 Acute Oral Toxicity Test Substance 60% notified chemical Method OECD 401 Acute Oral Toxicity. Species/Strain Rat/Sprague-Dawkey Vehicle None. Remarks - Method GLP & QA. Results Group Number & Sex of Animals Dose mg/kg bw Mortality 1 5/sex 1 000 4/10 2 5/sex 1 130 5/10 3 5/sex 1 250 6/10 4 5/sex 1 400 7/10 5 5/sex 1 560 9/10 LD50 1 120.9 mg/kg bw Signs of Toxicity Most mortality occurred within the first 24 hours after dosing. Clinical signs included convulsions, tremors, dyspnoea, cyanosis, prostration, piloerection, apathy, passivity, distended abdomen and melena. These symptoms in some animals progressed into a coma-like state followed by death. Effects in Organs Necropsy showed that dead animals had stomach ulcers and haemorrhaging of the stomach and small intestines. Those survived animals had adhesions of the stomach to liver, spleen, small intestines and omentum. These findings were consistent and a consequence of perforated stomach ulcers and subsequent peritonitis. Remarks - Results The LD50 was found to be 721.1 and 1 234.9 mg/kg for the males and females, respectively. Conclusion The test material is harmful via the oral
Test method: OECD TG 404 Draize scores: Time Animal # treatment 1 2 3 Erythema 1 hour a1 0 1 24 hours 0 0 0 48 hours 0 0 0 72 hours 0 0 0 Oedema Draize scores for oedema were zero for all animals during the study. a see Attachment 1 for Draize scales Comment: Yellow coloured staining was noted at all treated skin sites throughout the study. This staining did not interfere with evaluation of skin reactions. Result: The notified chemical was slightly irritating to the skin of rabbits. 9.1.5 Eye Irritation (Safepharm Laboratories Ltd, 1998c) Species/strain: Rabbit/New Zealand Number/sex of animals: 3 Observation period: 72 hours Method of administration: A dose of 0.1 mL (65 mg notified chemical) was applied to conjunctival sac of one eye. The untreated eye served as the control. Test method: OECD TG 405 Draize scores of unirrigated eyes: Time after instillation
Main study: 0, 50, 150, 500, 1 500 and 5 000 g/plate in all strains. Positive controls: (without S9-mix) N-ethyl-N’-nitro-N-nitrosoguanidine (ENNG) for TA100, TA1535 and WP2uvrA; 9-aminoacridine (9AA) for TA1537; 4-nitroquinoline-1-oxide (4NQO) for TA98. (with S9-mix) 2-aminoanthracene (2AA) for all strains. Test method: OECD TG 471 Comment: No cytotoxicity was observed in the study. Under the conditions of the study, the notified chemical caused no substantial increases in revertant colony numbers over control counts at any concentration in either the presence or absence of the rat liver microsomal enzymes. All positive controls responded appropriately. Result: The notified chemical was non mutagenic under the conditions of the test. 9.3.2 Chromosomal Aberration Assay in Chinese Hamster Lung Cells (Safepharm Laboratories Ltd, 1998f) Chinese Hamster Lung (CHL) Cells Metabolic activation system: Liver fraction (S9 mix) from rats pretreated with Aroclor 1254. Dosing schedule: Duplicates were performed at each concentration. Metabolic Activation Experiment Number Test concentration (g/mL) Controls -S9 1 12 hr continuous treatment 0, 78.1, 156.25, 312.5*, 625*, 1 250* and 1875
3. PHYSICAL AND CHEMICAL PROPERTIES Appearance at 20°C & 101.3 kPa: Colourless to pale yellow viscous liquid Boiling Point: > 285°C Relative Density: 0.9503 ± 0.5% at 20C Vapour Pressure: Interpolated = 0.30 ± 0.03 Pa at 25C Upper limit = 25 Pa at 25°C Henry’s Law Constant: Using Interpolated VP = 3.41 x 10-2 Pa.m3/mol Using Upper limit VP = 2.84 Pa.m3/mol Solubility: 1.8 g/L at 22.5°C Partition Co-efficient (n-octanol/water): log Pow = 2.53 Hydrolysis as a Function of pH: T1/2 at pH 4.0, 7.0, 9.0 > 1 year Adsorption/Desorption: Not determined Dissociation Constant: Not determined Point: 152°C (closed cup) Flammability Limits: Not determined. The notified chemical is combustible. Autoignition Temperature: 250°C Explosive Properties: Not explosive Reactivity/Stability: Stable 3.1 Comments on Physico-Chemical Properties The vapour pressure (VP) of the notified chemical was determined using the Static Method according to the protocols and guidelines of OECD TG 104: Vapour Pressure Curve. Two series of measurements were performed. The first series of 80 measurements was determined at temperatures of 21.85 and 28.26ºC. During these measurements a continuous decrease in vapour pressure was observed. As a consequence, the sample vessel containing the test substance was evacuated for approximately 2 hours to remove volatile impurities. The second series of 115 measurements was determined at 3 different temperatures (23.74, 30.24 and 36.74ºC). A relatively small drop in vapour pressure was observed during the first 70 measurements taken at 23.74ºC. After the first 70 measurements, measurements were conducted at the 2 higher temperatures and the vapour pressure stabilised, indicating the vapour pressure shows ideal behaviour (RCC NOTOX, 1992).
Method OECD 404 Acute Dermal Irritation/Corrosion. EC Directive 92/69/EEC B.4 Acute Toxicity (Skin Irritation). Species/Strain Rabbit/New Zealand White. Number of Animals 6 females. Observation Period 72 hours. Vehicle Distilled water. Type of Dressing Semi-occlusive. Remarks - Method GLP & QA. Results Lesion Mean Score* Maximum Value Maximum Duration of Any Effect Maximum at End of Observation Period Erythema/Eschar 0 1 30-60 min 0 Oedema 0 0 - 0 *Calculated on the basis of the scores at 24, 48, & 72 hours for ALL animals. Remarks - Results Two animals had Draize scores of 1 during 30-60 minutes after treatment. Conclusion The notified chemical is non-irritating to skin. Test Facility MB Research Labs (1997c) 9.2.5 Eye Irritation Test Substance TKA 45009 Method OECD 405 Acute Eye Irritation/Corrosion. EC Directive 92/69/EEC B.5 Acute Toxicity (Eye Irritation). Species/Strain Rabbit/New Zealand White Number of Animals 3/sex Observation Period 72 hours Remarks - Method GLP & QA. Vehicle was not stated. Results Lesion Mean Score* Maximum Value Maximum Duration of Any Effect Maximum Value at End of Observation Period Conjunctiva: redness 0.39 2 48 hours 0 Conjunctiva: chemosis 0.17 2 24 hours 0 Conjunctiva: discharge 0.22 2 24 hours 0
PUBLIC EXPOSURE There is low potential for public exposure to the notified chemical during its storage and distribution. Public exposure to the polymer in Airflex 4530 in anticipated to be minimal since the polymer will be bound to the inner surface of the laminate and the laminate will be available to the public only once the adhesive is cured. The end use of the adhesive containing Airflex 4500 appears to be similar to that containing Airflex 4530. Disposal of the polymer is expected to relate in minimal public exposure. ENVIRONMENTAL EXPOSURE . Release The potential for release of polymer to the environment occurs through spillage in the storage and application areas or during transport to and from storage. This release would be in the form of a liquid which can be treated by containment and adsorption in sand or similar material which can then be disposed of in compliance with local, state or federal disposal regulations, probably to landfill. Manufacturing plant wash water during use of Airflex 4530 will be collected and reused in following batches. For Airflex 4500 wash water containing the notified polymer will be collected and treated prior to release to the waste stream. Spillages and container residues are likely to be disposed of in landfill, where the polymer may persist but is expected to remain immobile. Losses to the environment of the adhesive containing the polymer in the fabrication of the end use product are expected to be low. Closed system application technology is utilised to protect the integrity of the adhesive until applied and allowed to set. Release may also be expected via disposal of articles fabricated the adhesive, probably to landfill or by incineration. Both applications are long lifetime products with disposal on demolition of the building in which the products were integrated. . Fate The main environmental exposure to notified chemical will occur via disposal of waste polymer to landfill, where it is expected to remain immobile. Articles fabricated using adhesive containing the polymer are expected to be incinerated or be consigned to landfill at the end of their useful life. The polymer exhibits characteristics that render it non-reactive and non (or only slowly)- biodegradable when exposed to the environment. In landfill the polymer would likely remain undegraded and if as part of a finished article, attached to the substrate to which it is adhered. ASSESSMENT OF ENVIRONMENTAL EFFECTS No ecotoxicological data were provided, which is acceptable for polymers of NAMW > 1000 according to the Act.
NAA-NT Newsletter National Autism Association of North Texas newsletter The Advocate The Newsletter of the Autism Society of America -must be a member of the ASA - membership fees (individual $25.00 and family $35.00) FEAT-NT Newsletter -sign up to receive (no fee) -membership is free Books: Autism: Effective Biomedical Treatments by Jon B. Pangborn, Ph.D. and Sidney M. Baker, M.D. Recovering Autistic Children Edited by Stephen M. Edelson, Ph.D. and Bernard Rimland, Ph.D “Unraveling the Mystery of Autism and PDD” (A Mother’s of Research and Recovery) by Seroussi “Let Me Hear Your Voice” by Catherine Maurice “Special Diets for Special Kids” by Lisa “Autism: Handle with Care” by Gail Gillingham “Thinking in Pictures” by Temple Grandin “Is This Your Child?” Allergies, Intolerances & Sensitivities by Dr. Rapp “An Anthropologist on Mars” by Temple Grandin College Guide For Students with Learning Disabilities Children with Autism A Parent’s Guide by Michael D. Powers Understanding and Teaching Children with Autism by Rita Jordan and Stuart Powell