OECD SIDS N-BUTYL ACRYLATE FOREWORD INTRODUCTION N-BUTYL ACRYLATE CAS N°:141-32-2 UNEP PUBLICATIONS 1 OECD SIDS N-BUTYL ACRYLATE SIDS Initial Assessment Report For SIAM 15 Boston, Massachusetts, October 22-25, 2002 1. Chemical Name: n-Butyl Acrylate 2. CAS Number: 141-32-2 3. Sponsor Country: United States National SIDS Contact Point in Sponsor Country: Oscar Hernandez Division Director RAD 7403 M 1200 Pennsylvania Avenue, NW Washington DC, 20460 (202) 564-7461 [email protected] 4. Shared Partnership with: ICCA 5. Roles/Responsibilities of the Partners: • Name of industry sponsor Industry Contact: Elizabeth Hunt /consortium Basic Acrylic Monomer Manufacturers, Inc. 941 Rhonda Place SE Leesburg, VA 20175 phone: 703-669-5688 e-mail: [email protected] Process used • 6. Sponsorship History How was the chemical or Documents were prepared and reviewed by industry prior to • category brought into the submission to sponsor country. Sponsor country conducted OECD HPV Chemicals reviews of submitted data and offered comments to industry. Programme ? Industry prepared and resubmitted documents for consideration at SIAM 15. Data searches consisted of searching available literature, databases and internal consortia files. 7. Review Process Prior to the SIAM: 8. Quality check process: 9. Date of Submission: 2 UNEP PUBLICATIONS OECD SIDS N-BUTYL ACRYLATE 10. Date of last Update: 11. Comments: Testing: No testing ( X ) Testing ( ) UNEP PUBLICATIONS 3 OECD SIDS N-BUTYL ACRYLATE SIDS INITIAL ASSESSMENT PROFILE CAS No. 141-32-2 Chemical Name n-Butyl Acrylate O Structural Formula O SUMMARY CONCLUSIONS OF THE SIAR Category/Analogue Rationale In some circumstances, available data on iso-butyl acrylate (CAS No. 106-63-8) may be presented to assist in the weight of evidence approach for n-butyl acrylate, based on structural similarities. Since sufficient data exists for n- butyl acrylate for the majority of SIDS endpoints, data on iso-butyl acrylate is only presented for those endpoints in which further supporting data may assist in adding to the characterization of a particular endpoint. This is done primarily for the aquatic toxicity endpoints. Human Health After oral administration, n-butyl acrylate is rapidly absorbed and metabolized in male rats (75% was eliminated as CO , approximately 10% via urine and 2% via feces). The major portion of n-butyl acrylate was hydrolyzed by 2 carboxyesterase to acrylic acid and butanol. Following acute exposure, n-butyl acrylate exhibits low toxicity. n-Butyl acrylate has oral LD50s of 3143 mg/kg bw (rats) and 9050 mg/kg bw (male rats), an inhalation LC50 (4-hour, rat) of 10.3 mg/L and a dermal LD50 (rabbit) of 2000 to 3024 mg/kg. n-Butyl acrylate is irritating to skin and eyes and showed a skin sensitizing potential in animals. In humans, skin sensitization to butyl acrylate was reported. In an oral (drinking water) 90-day study in rats, using a satellite group (gavage) at 150 mg/kg bw/day, the only effects reported were a slight reduction in water consumption in all dose groups and a decrease in weight gain in the highest dose group. The NOAEL (males) = 84 mg/kg/bw/day and NOAEL (females) = 111 mg/kg/bw/day. The NOAEL (gavage) (males and females) = 150 mg/kg/bw/day. In a 90-day inhalation study, rats were exposed to 0, 21, 108, 211, and 546 ppm (0, 0.11, 0.57, 1.12, 2.90 mg/L) n-butyl acrylate. The primary effects at 211 ppm (1.12 mg/L) were irritation of eyes and nasal mucosa, reduced body weights (13.3 percent in males and 3.76 percent in females compared with controls), decreased potassium values (females) and an increase in alkaline phosphatase activity (females.) At the highest dose of 546 ppm (2.90 mg/L) 31 of 40 animals died. The primary cause of death was due to the strong irritation of the substance on the respiratory tract. The NOAEL = 108 ppm (0.57 mg/L/day) and the LOAEL = 211 ppm (1.12 mg/L/day). In a two-year inhalation study, rats (male/female) received whole body exposures of 0, 15, 45, or 135 ppm (0, 0.086, 0.258, 0.773 mg/L). There was a slight decrease in food consumption and slightly lower relative heart, kidney, liver and thyroid weights at the highest dose. A NOAEL was determined to be 45 ppm (0.258 mg/L/day) based upon localized and diffuse stippling of the corneal epithelium, cloudiness of the cornea, and various degrees of vascularization. The severity of nasal mucosa effects increased with dose and occurred at all doses in males and females. Effects ranged from slight atrophy of the neurogenic part of the olfactory epithelium at 15 ppm (0.086 mg/L) to partial loss of the columnar cell layer and stratified reserve-cell hyperplasia at 45 (0.258 mg/L) and 135 ppm (0.773 mg/L). n-Butyl acrylate was negative in the Ames test with Salmonella typhimurium TA98, TA100, TA1535 and TA1537 with and without metabolic activation tested up to 10,000 µg/plate. In a cytogenetic assay with Chinese Hamster Ovary Cells, n-butyl acrylate showed no clastogenic potential in concentrations where no cytotoxicity occurred. Without metabolic activation an increase of aberrant cells was observed at cytotoxic concentrations. No genotoxic effects were found in an in vitro micronucleus test and an UDS-test with Syrian hamster fibroblasts. In an in vivo 4 UNEP PUBLICATIONS OECD SIDS N-BUTYL ACRYLATE cytogenetic assay, n-butyl acrylate showed no clastogenic effect in rats and hamsters after inhalation exposure. n-Butyl acrylate was not carcinogenic to rats via inhalation up to 135 ppm (0.773 mg/L/day), the highest dose tested. No reproductive toxicity studies are available. However, in repeated-dose studies (noted above), no effects were seen in the reproductive organs. In developmental toxicity studies with rats via inhalation, n-butyl acrylate caused fetotoxic effects (resorptions and reduced number of live fetuses at >135 ppm) at maternally toxic concentrations. At exposures of 25, 135 and 250 ppm (0.13, 0.72 and 1.33 mg/L/day), the NOAEL (maternal) = 25 ppm (0.13 mg/L/day) based on reduced body weights and irritation to the eyes and nose. The NOAEL (developmental) = 25 ppm (0.13 mg/L/day), based on post-implantation loss and the NOAEL (teratogenicity) = 250 ppm. In a separate study, female rats were given 100, 200 and 300 ppm. A maternal NOAEL could not be determined based on a reduction of absolute body weight gain at all doses; the maternal LOAEL was set at 100 ppm. At 200 and 300 ppm there was a reduction in fetal body weights. Sporadic malformations occurred at 300 ppm and in the control group. The NOAEL (developmental) was 100 ppm and the NOAEL (teratogenicity) was 300 ppm (highest dose tested). Environment The water solubility of n-butyl acrylate is 2 g/L (25 °C) and specific gravity is 0.898 g/cm3 at 20 °C. The measured log Kow is 2.38. The vapor pressure (based on a regression analysis of measured values from several data sources) is 7.27 hPa at 25 °C. The melting point is - 64°C and the boiling point is 148 °C. The chemical is highly flammable and its flashpoint is approximately 36 0C. n-Butyl acrylate is photodegraded by reaction with hydroxyl radicals in the atmosphere with a half-life of 1.2 days (calculated). The hydrolysis rate of n-butyl acrylate is extremely low. At pH 7, the approximate half-life is calculated to be 1100 days. The Henry’s law constant is 4.7 x 10-4 atm/m3/mol, indicating the potential for moderate volatilization from water. Distribution modeling using Mackay Level I indicates that the main target compartment will be air (94%) with smaller amounts partitioning into water (5.73%) soil (0.11%), and sediment (0.11%). Fugacity model Level III gives comparable results; the levels are: 89.4% (air), 8.24% (water), 2.39% (soil) and 0.0963% (sediment). A BCF of 13 was determined, based on a log K of 2.38, ow indicating a low bioaccumulation potential. In a biodegradation assay according to OECD Guideline 301C (modified MITI-Test (I)) n-butyl acrylate was readily biodegradable (61% after 14 days). In another ready biodegradation test conducted according to OECD Guideline 301D, 57.8% of the chemical biodegraded after 28 days. In acute aquatic toxicity studies, n-butyl acrylate was determined to have toxic effects in the concentration range of 2.1 to 8.2 mg/L. A measured fish 96-hr LC50 of 2.1 mg/L was determined in a flow-through test in Cyprinodon variegates. A measured aquatic invertebrate 48-hr EC50 of 8.2 mg/L was determined in a flow-through test in Daphnia magna. Finally, in algae (Selenastrum capricornutum) a growth-rate study using measured concentrations resulted in a 96-hr EC50 of 2.6 mg/L (arithmetic mean). In addition, supporting data from iso-butyl acrylate indicate toxicity values with in the same ranges. For iso-butyl acrylate, the most sensitive species was the freshwater fish Pimephales promelas (fathead minnow) with a 96-hour LC50 of 2.09 mg/L (measured). The 48-hour EC50 for Daphnia magna is 9.7 mg/L (nominal), and for algae (Desmodesmus subspicatus) the 72-hour EC50s were 3.18 mg/L (measured) for biomass and 5.28 mg/L (measured) for growth rate. Exposure n-Butyl acrylate is manufactured as a chemical intermediate in a closed system. Its major use is in the production of homo- and co-polymers with other monomers (i.e. acrylic acid and its salts, esters, amides, etc.) to produce emulsion polymers. The three major uses of acrylate esters are: surface coatings, adhesives/sealants and textiles. In 2000, production volumes were 250,000 – 400,000 tonnes for Europe, 581,000 tonnes for the US and 130,000 tonnes for Japan. In 2000, US TRI reporting indicates that the majority of n-butyl acrylate is released to the air compartment (94%, 233,013 pounds) where it is subject to photolysis. However, a small percentage is released to the water compartment (6%, 14,566 pounds). Impact on the environment is expected to be low due to photolysis and biodegraditive properties. Extensive occupational exposure monitoring records are available which indicate that 8 hr TWAs for a variety of operations are below the regulatory/guideline values of 2 ppm (8hr TWA) . However, peak exposures were reported above the 2 ppm value and in some circumstances exceeded the NIOSH REL of 10 ppm (TWA) during sampling, cleaning, change of pump filter, check of detonation arrestors, inhibitor preparation, drumming and waste disposal. Records indicate that personnel performing these tasks wear the appropriate personal protective equipment and therefore, exposures to pesonnel are estimated to be lower depending upon protection factors of the personal protective equipment. End-use consumer products contain only trace levels of acrylic acid and esters (as a result of polymerization). Therefore, consumer exposure to acrylate monomers is likely to be low. UNEP PUBLICATIONS 5 OECD SIDS N-BUTYL ACRYLATE RECOMMENDATION The chemical is currently of low priority for further work. RATIONALE FOR THE RECOMMENDATION AND NATURE OF FURTHER WORK RECOMMENDED The chemical possesses properties indicating a hazard for human health and the environment. Based on data presented by the Sponsor country, exposure to humans and the environment is anticipated to be low, and therefore this chemical is currently a low priority for further work. Countries may desire to investigate any exposure scenarios that were not presented by the Sponsor country. 6 UNEP PUBLICATIONS OECD SIDS N-BUTYL ACRYLATE FULL SIDS SUMMARY TABLE CAS NO: 141-32-2 SPECIES PROTOCOL RESULTS PHYSICAL-CHEMICAL 2.1 Melting Point Measured -64 °C 2.2 Boiling Point DIN 51751 148 °C 2.3 Density DIN 51757 0.898 g/m³ at 20 °C 2.4 Vapour Pressure Regression calculation 7.27 hPa at 25 °C 2.5 Partition Coefficient OECD 107 2.38 at 25 °C (log Kow) 2.6 Water Solubility Measured 2 g/l at 25 °C 2.7 Henry’ Law Constant calculated 46.59 Pa m³ mol-1 (at 25 °C) 2.8 Flammability - flammable 2.9 Explosive properties LEL 1.1 vol% (35 °C), UEL 7.8 vol% (73.4 °C) 2.10 Flash point DIN 51755 36.5 °C 2.11 Ignition point - 267 °C 2.11 Stability - Polymerises easily on standing, accelerated by heat, light and peroxides, polymerisation inhibitors are added to commercial product ENVIRONMENTAL FATE AND PATHWAY 3.1.1 Photodegradation Calculated t : 1.2 days 1/2;air (AOP, V 1.87) 3.1.2 Stability in Water measured / calculated t pH 3: 2800 days 1/2 t pH 7: 1100 days 1/2 t pH 11: 243 minutes 1/2 3.3 Transport and calculated Air: 94 % Distribution (Mackay, Level I) Water: 5.73 % Soil: 0.11 % Sediment : 0.11 % Calculated Air: 89.4 % (Level III Fugacity Water: 8.24 % Model) Soil: 2.39 % Sediment: 0.00963 % Biodegradation Activated OECD 301 C 61 % after 14 d sludge (Modified MITI Test (readily biodegradable) (domestic) (I)) Secondary effluent of a OECD 301 D (Closed 57.8 % after 28 days WWTP Bottle Test) UNEP PUBLICATIONS 7 OECD SIDS N-BUTYL ACRYLATE ECOTOXICOLOGY 4.1 Acute/Prolonged Cyprinodon OECD 203 LC : 2.1 mg/l/96 h (measured) 50 Toxicity to Fish variegatus Salmo gairdneri OECD 203 LC : 5.2 mg/l/96 h (measured) 50 Fish ECOSAR calculation LC : 1.786 mg/l/96 h (calculated) 50 *iso-butyl acrylate Pimephales OECD 203 LC : 2..09 mg/l/96 h (measured) 50 promelas *iso-butyl acrylate Fish ECOSAR calculation LC : 1.838 mg/l/96 h (calculated) 50 4.2 Acute Toxicity to Daphnia magna OECD 202 EC : 8.2 mg/l/48 h (measured) 50 Aquatic Invertebrates Daphnid ECOSAR calculation EC : 9.81 mg/l/48 h (calculated) 50 *iso-butyl acrylate Daphnia magna 79/831/EEDC, static, EC (48 hours): 9.7 mg/L 50 nominal concentrations *iso-butyl acrylate Daphnia magna 79/831/EEDC, static, EC (48 hours): 19.8 mg/L 50 nominal concentrations *iso-butyl acrylate Daphnid ECOSAR calculation EC : 10.653 mg/l/48 h (calculated) 50 4.3 Toxicity to Aquatic Selenastrum OECD 201 EC : 2.6 mg/l/96 h (arithmetic mean, 50 Plants e.g. Algae capricornutum based on measured values at 0 h and 96 h) Algae ECOSAR calculation EC : 1.023 mg/l/96 h (calculated) 50 *iso-butyl acrylate Desmodesmus OECD 201, static, EC (72 hours): 3.18 mg/L (biomass) 50 subspicatus measured EC (72 hours): 5.28 mg/L (cell growth) 50 *iso-butyl acrylate Algae ECOSAR calculation EC : 1.107 mg/l/96 h (calculated) 50 4.4 Toxicity to Bacteria Activated sludge EC0 > 150 mg/l/3 days (industrial) *iso-butyl acrylate Activated OECD 209 EC50 (30 min): > 1000 mg/L sludge 4.5 Chronic Toxicity to no data Aquatic Invertebrates 4.5.1 Chronic Toxicity to no data Fish 4.6.3 Toxicity to Other Non- no data Mammalian Terrestrial Species (Including Birds) 8 UNEP PUBLICATIONS OECD SIDS N-BUTYL ACRYLATE TOXICOLOGY 5.1.1 Acute Oral Toxicity rat ca. 3143 mg/kg bw 5.1.2 Acute Inhalation rat 10.3 mg/l/4 h Toxicity 5.1.3 Acute Dermal Toxicity rabbit 2000 – 3024 mg/kg bw 5.2.1 Skin irritation rabbit irritating 5.2.2 Eye irritation rabbit highly irritating 5.3 Sensitization guinea pig skin painting test not sensitizing guinea pig maximization test sensitizing guinea pig Freund’s complete sensitizing adjuvant test mouse mouse ear swelling test not sensitizing mouse local lymph node assay sensitizing 5.4 Repeated Dose rat 90 days, inhalation NOAEL: 108 ppm (0.57 mg/l/day) Toxicity LOAEL: 211 ppm (1.12 mg/l/day) rat 90 days, drinking NOAEL: 84 mg/kg bw/day (males), water 111 mg/kg bw/day (females) 5.5 Genetic Toxicity In Vitro A. Bacterial Test S. typhimurium Ames Test negative; + / - metabolic activiation (Gene mutation) B. Non-Bacterial In Vitro CHO-cells cytogenetic assay negative; only at cytotoxic Test concentrations, an increase of aberrant (Chromosomal cells aberrations) SHE-cells in vitro micronucleus negative test SHE-cells UDS-test negative SHE-cells cell transformation negative assay 5.6 Genetic Toxicity rat cytogenetic assay, negative In Vivo inhalation hamster cytogenetic assay, negative inhalation 5.7 Carcinogenicity rat 2 years, inhalation no carcinogenic effects up to 135 ppm (0.773 mg/l/day) UNEP PUBLICATIONS 9 OECD SIDS N-BUTYL ACRYLATE 5.8 Toxicity to rat 90 d, inhalation no effect on reproductive organs Reproduction 5.9 Developmental rat inhalation, gd 6-20 NOAEL maternal toxicity: could not be Toxicity/ determined Teratogenicity NOAEL developmental toxicity: 100 ppm (1.06 mg/l/day) NOAEL teratogenicity: 300 ppm (1.6 mg/l/day) rat inhalation, gd. 6-15 NOAEL maternal toxicity: 25 ppm (0.13 mg/l/day) NOAEL developmental toxicity: 25 ppm (0.13 mg/l/day) NOAEL teratogenicity: 250 ppm (1.33 mg/l/day) , highest dose tested mouse gavage, gd. 6-15 NOAEL maternal toxicity: 100 mg/kg bw /day NOAEL develop. Toxicity: 1000 mg/kg bw/day NOAEL teratogenicity: 2000 mg/kg bw/day 5.11 Experience with skin sensitization reported; patch test Human Exposure concentration: 0.1 to 1.0 % *) Experimental data on iso-butyl acrylate have been included into the assessment, because it is expected that the two structural related chemicals (iso-butyl acrylate and n-butyl acrylate) would exhibit a very similar toxicological behaviour. The assumption is based on evidence from results of acute and in vitro experiments that showed very similar effects associated with the two substances and on the similarity of their physico-chemical properties 10 UNEP PUBLICATIONS