U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 SCREENING-LEVEL HAZARD CHARACTERIZATION 2-Vinylpyridine (CASRN 100-69-6) The High Production Volume (HPV) Challenge Program1 was conceived as a voluntary initiative aimed at developing and making publicly available screening-level health and environmental effects information on chemicals manufactured in or imported into the United States in quantities greater than one million pounds per year. In the Challenge Program, producers and importers of HPV chemicals voluntarily sponsored chemicals; sponsorship entailed the identification and initial assessment of the adequacy of existing toxicity data/information, conducting new testing if adequate data did not exist, and making both new and existing data and information available to the public. Each complete data submission contains data on 18 internationally agreed to "SIDS" (Screening Information Data Setl12) endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the environment. The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored chemicals by developing hazard characterizations (HCs). These HCs consist of an evaluation of the quality and completeness of the data set provided in the Challenge Program submissions. They are not intended to be definitive statements regarding the possibility of unreasonable risk of injury to health or the environment. The evaluation is performed according to established EPA guidance2 3 and is based primarily on hazard data provided by sponsors; however, in preparing the hazard characterization, EPA considered its own comments and public comments on the original submission as well as the sponsor's responses to comments and revisions made to the submission. In order to determine whether any new hazard information was developed since the time of the HPV submission, a search of the following databases was made from one year prior to the date of the HPV Challenge submission to the present: (ChemID to locate available data sources including Medline/PubMed, Toxline, HSDB, IRIS, NTP, AT SDR, IARC, EXTOXNET, EPA SRS, etc.), STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS, Merck, etc.), Science Direct and ECHA4. OPPT's focus on these specific sources is based on their being of high quality, highly relevant to hazard characterization, and publicly available. OPPT does not develop HCs for those HPV chemicals which have already been assessed internationally through the HPV program of the Organization for Economic Cooperation and Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are presented in an international forum that involves review and endorsement by governmental authorities around the world. OPPT is an active participant in these meetings and accepts these documents as reliable screening-level hazard assessments. 1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm. 2 U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm. 3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm. 4 European Chemicals Agency, http://echa.europa.eu. ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 These hazard characterizations are technical documents intended to inform subsequent decisions and actions by OPPT. Accordingly, the documents are not written with the goal of informing the general public. However, they do provide a vehicle for public access to a concise assessment of the raw technical data on HPV chemicals and provide information previously not readily available to the public. 2 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Chemical Abstract Service Registry Number (CASRN) 100-69-6 Chemical Abstract Index Name Pyridine, 2-ethenyl- CH '2 Structural Formula SMILES: n(c(cccl)C=C)cl Summary 2-Vinylpyridine is a colorless liquid with high vapor pressure and high water solubility. It is expected to have moderate mobility in soil. Volatilization of 2-vinylpyridine is moderate based on its Henry's Law constant. The rate of hydrolysis is expected to be negligible. The rate of atmospheric photooxidation is moderate. 2-Vinylpyridine is not readily biodegradable. 2-Vinylpyridine is expected to have moderate persistence (P2) and low bioaccumulation potential (B1). Acute oral toxicity of 2-vinylpyridine to rats and acute dermal toxicity to rabbits is moderate. In a 90-day oral repeated-dose toxicity study in rats, changes in the relative kidney to body weight ratio were observed in males in all tested doses and histopathological effects in the non-glandular portion of the stomach were observed in males and females at 180 mg/kg-day (highest dose tested). The NOAEL for systemic toxicity in male rats was not established and for female rats is 60 mg/kg-day. In a 28-day oral repeated-dose toxicity study in rats, histopathological effects in the non-glandular portion of the stomach were observed in male and female rats at 50 mg/kg-day; the NOAEL for systemic toxicity is 12.5 mg/kg-day. No specific reproductive toxicity study is available for 2-vinylpyridine. However, in the 90-day oral repeated-dose toxicity study, increases in testes to body weight ratios, incidences of chronic inflammation of epididymides and prostate in male rats and increased ovary to body and ovary to brain weight ratios in female rats were observed. No data are available for the developmental toxicity endpoint. 2-Vinylpyridine induced gene mutations in Escherichia coli, but not in Salmonella typhimurium in vitro. 2-Vinylpyridine induced chromosomal aberrations in vitro, but was not genotoxic in a DNA repair test. 2-Vinylpyridine is irritating to guinea pig skin, corrosive to rabbit skin, irritating to rabbit eyes and sensitizing to guinea pig skin. For 2-vinylpyridine, the 96-h LCso value for fish is 6.48 mg/L, the 48-h ECso value for aquatic invertebrates is 9.48 mg/L and the 72-h ECso values for aquatic plants are 50.8 mg/L and 64.4 mg/L, for biomass and growth rate, respectively. The 21-d LCso values for aquatic invertebrates are 0.933 mg/L and 1.06 mg/L for mortality and reproduction, respectively. Data gaps for the reproductive and developmental toxicity endpoints were identified under the HPV Challenge Program. 3 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 The sponsor, Reilly Industries, Inc., submitted a Test Plan and Robust Summaries to EPA for 2-vinylpyridine (CASRN 100-69-6; CA Index name: pyridine, 2-ethynl-) on December 30, 2003 EPA posted the submission on the ChemRTK HPV Challenge website on March 3, 2004 (http://www.epa.gov/chemrtk/pubs/summaries/2vinvlpv/cl5018tc.htm). EPA comments on the original submission were posted to the website on March 30, 2005. Public comments were also received and posted to the website. 1. Chemical Identity 1.1 Identification and Purity The 2-vinylpyridine solutions evaluated in the submitted studies have a purity ranging from 97.34 to > 99%, unless otherwise indicated. 1.2 Physical-Chemical Properties 2-Vinylpyridine is a colorless liquid with high vapor pressure and high water solubility. The physical-chemical properties of 2-vinylpyridine are summarized in Table 1. Table 1. Physical-Chemical Properties of 2-Vinylpyridine 1 Property Value CASRN 100-69-6 Molecular Weight 105.14 Physical State Colorless liquid Melting Point -50°C (measured)2 Boiling Point 159.5°C (measured) Vapor Pressure 2.45 mm Hg at 25°C (extrapolated from boiling points); 2.57 mm Hg at 25°C (estimated); 2.78 mm Hg at 25°C (measured); and 2.93 mm Hg at 25°C (estimated)3 Dissociation Constant (pKa) pKb = 9.02 (measured)4 Henry's Law Constant 1.4xl0"5 atm-m3/mole (estimated)5 Water Solubility 2.75xl04mg/L at 20°C (measured) Log Kow 1.54 (measured) 'Reilly Industries, Inc. 2003. Test Plan and Robust Summary for 2-Vinylpyridine. Available online at http://www.epa. gov/chemrtk/pubs/summaries/2 vinvlpy/c 15018tc.htm as of May 22, 2012. 2Sigma-Aldrich Co. LLC. 2012. Material Safety Data Sheet for 2-Vinylpyridine. Available online at http://www.sigmaaldrich.eom/catalog/product/aldrich/l 32292?lang=en®ion=US as of May 22,2012. 3N0M05. 1987. Programs to Enhance PC-Gems Estimates of Physical Properties for Organic Compounds. The Mitre Corp. 4SRC. 2012. Hie Physical Properties Database (PHYSPROP). Syracuse, NY: Syracuse Research Corporation. Available online at http://www.svrres.com/esc/phvsprop.htm as of May 22,2012. 5U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Environmental Protection Agency, Washington, DC, USA. Available online at http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of May 22, 2012. ' 4 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 2. General Information on Exposure 2.1 Production Volume and Use Pattern 2-Vinylpyridine had an aggregated production and/or import volume in the United States between 1 and 10 million pounds during calendar year 2005. Non-confidential information in the IUR indicated that the industrial processing and uses of the chemical include resin and synthetic rubber manufacturing as process regulators, used in vulcanization or polymerization processes. No commercial and consumer uses were reported for the chemical. 2.2 Environmental Exposure and Fate 2-Vinylpyridine is expected to have moderate mobility in soil. 2-Vinylpyridine achieved 0% of its theoretical biochemical oxygen demand (BOD) over the course of a 28-day incubation period using an activated sludge inoculum during the modified MITI (OECD 301C) test and is considered not readily biodegradable. This substance is a reactive monomer that is produced with an inhibitor to prevent spontaneous polymerization; therefore, it is not likely to be highly persistent in the environment. Volatilization of 2-vinylpyridine is moderate based on the Henry's Law constant. The rate of hydrolysis is expected to be negligible. The rate of atmospheric photooxidation is moderate. 2-Vinylpyridine is expected to have moderate persistence (P2) and low bioaccumulation potential (Bl). The environmental fate properties of 2-vinylpyridine are summarized in Table 2. 5 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Table 2. Environmental Fate Properties of 2-Vinylpyridine1 Property Value CASRN 100-69-6 Photodegradation Half-life 4.8 hours (estimated reaction with hydroxyl radicals)2; 13.0 hours (estimated reaction with ozone) Hydrolysis Half-life Stable Biodegradation 0% after 28 days (not readily biodegradable) Bioaccumulation Factor BAF = 3.9 (estimated)3 Log Koc 2.3 (estimated)3 Fugacity (Level III Model)2 Air (%) 0.4 Water (%) 25.8 Soil (%) 73.6 Sediment (%) 0.3 Persistence3 P2 (moderate) Bi oaccumul ati on3 Bl (low) 'Reilly Industries, Inc. 2003. Test Plan and Robust Summary for 2-Vinylpyridine. Available online at http://www.epa. gov/chemrtk/pubs/summaries/2 vinvlpv/c 15018tc.htm as of May 22, 2012. 2U.S. EPA. 2012. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.10. U.S. Environmental Protection Agency, Washington, DC, USA. Available online at http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm as of May 22, 2012. ' 'Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64, Number 213 (November 4, 1999) pp. 60194-60204. Conclusion: 2-Vinylpyridine is a colorless liquid with high vapor pressure and high water solubility. It is expected to have moderate mobility in soil. Volatilization of 2-vinylpyridine is moderate based on its Henry's Law constant. The rate of hydrolysis is expected to be negligible. The rate of atmospheric photooxidation is moderate. 2-Vinylpyridine is not readily biodegradable. 2-Vinylpyridine is expected to have moderate persistence (P2) and low bioaccumulation potential (Bl). 3. Human Health Hazard A summary of the health effects data submitted for SIDS endpoints is provided in Table 3. Acute Oral Toxicity (1) Male and female rats (number and strain not specified) were administered undiluted 2- vinylpyridine (98.95% purity) via an unspecified oral route at unspecified doses. No details regarding the length of the observation period or dose-specific timing of mortalities were noted. The LD50 confidence interval is 240-472 mg/kg. Additional details were obtained from TSCATS OTS0546362. LD50 = 336 mg/kg (2) Fasted male and female rats (number and strain not specified) were administered 2- vinylpyridine (20% solution, 98.95% purity) in corn oil via gavage at unspecified doses. The 6 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 LD50 confidence interval for fasted male and female rats is 677-1336 mg/kg and 479-945 mg/kg, respectively and for fed male and female rats is 677-1336 mg/kg. Additional details were obtained from OTS0546362. LD5o= 951 mg/kg (for fed male and female rats and fasted male rats) LD50 = 673 mg/kg (for fasted female rats) Acute Dermal Toxicity (1) New Zealand White rabbits (5/sex/dose) were (98.7% purity) via the dermal route at 400, 650 or conditions for 24 hours and observed for 14 days, hours and 900 (10/10) mg/kg within one hour. LD50 = 640 mg/kg (2) Male New Zealand White rabbits (1/dose) were administered undiluted 2-vinylpyridine (97.689% purity) via the dermal route at 60, 90, 200, 300, 450 or 670 mg/kg to the back under occluded conditions for 24 hours and observed for 14 days. Mortality occurred at various time intervals at the three highest dose levels of 300 (died within 2 hours), 450 (died within 2.5 hours) and 670 (died within 1 day) mg/kg doses, respectively. Additional details were obtained from OTS0571402. LD50 > 200 and < 300mg/kg Repeated-Dose Toxicity (1) Sprague-Dawley rats (30/sex/dose) were administered 2-vinylpyridine (97.93% purity) in corn oil via gavage at 0, 20, 60 or 180 mg/kg-day for 90 days. An unspecified decrease in body weight gain and feed consumption were observed in male rats at the 180 mg/kg-day. At the high dose, a statistically significant (slight but unspecified) increase in the number of platelets in male and female rats and a statistically significant (slight but unspecified) decrease in aspartate aminotransferase in male rats were observed. In male rats, the absolute weights of the brain and heart were affected at the high dose and absolute adrenal weights were affected at the low and high doses. In males, relative brain and testes weights were affected in the high-dose group, relative liver weights at the mid- and high-dose levels, relative adrenal weights at the low- and high-dose groups and relative kidney weights at all dose levels. In female rats, absolute liver weight changes were observed along with effects on relative organ weights of the kidneys and ovaries at the high dose. At the mid-dose, relative liver to body and liver to brain weights were affected for female rats. The only microscopic effects observed were related to the irritation of the non-glandular stomach epithelium characterized by degeneration, hyperkeratosis and acanthosis in both sexes in the high-dose group. LOAELmaies = 20 mg/kg -day (based on effects on relative kidney to body weight ratios observed at all dose levels in male rats; lowest dose tested) NOAELmaies = Not Established LOAELfemaies = 180 mg/kg-day (based on microscopic effects related to the irritation of the non-glandular stomach epithelium characterized by degeneration, hyperkeratosis and acanthosis) NOAELfemaies = 60 mg/kg-day administered undiluted 2-vinylpyridine 900 mg/kg to intact skin under occluded Mortality occurred at 650 (8/10) within 3 7 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 (2) Crj: CD (SD) rats (5/sex/dose) were administered 2-vinylpyridine (98.3% purity) in corn oil via gavage at 0, 12.5, 50 or 200 mg/kg-day for 28 days. Additional groups of control and 200 mg/kg-day rats were allowed a 14-day recovery after the exposure period. Statistically significant decreases in body weight gain and food consumption were observed in male rats at 200 mg/kg-day. Salivation was observed in both male and female rats at 50 and 200 mg/kg-day. Urinalysis of female rats exhibited statistically significant decreases in specific gravity at 50 and 200 mg/kg-day and increases in urine volume at 200 mg/kg-day. The urinalysis changes were not observed in the recovery animals. Relative testes weights were statistically significant increased (% or not specified) in male rats at 200 mg/kg-day. Female rats exposed to 200 mg/kg-day exhibited statistically significant decreases (% or not specified) in absolute and relative spleen weights and increased relative liver weights. Changes in organ weights or ratios were not observed in the recovery animals. Squamous hyperplasia and submucosal edema in the forestomach were observed in male and female rats exposed to 50 and 200 mg/kg-day with thickening of the mucosa at 200 mg/kg-day in both sexes. Erosions and cellular infiltration in the forestomach in male rats exposed to 200 mg/kg-day and submucosal edema and erosion in the glandular stomach in the female rats exposed to 50 and 200 mg/kg-day was observed. LOAEL = 50 mg/kg-day (based on histopathological effects to the non-glandular portion of the stomach in male and female rats and decreased specific gravity in urine of female rats) NOAEL = 12.5 mg/kg-day Reproductive Toxicity No specific reproductive toxicity data are available for this endpoint. In the 90-day oral repeated-dose toxicity study in rats described previously, reproductive organs were weighed and examined for gross lesions; any observed gross lesion was examined microscopically. The reproductive organs of the control and high-dose groups and interim kill groups animals were also examined microscopically. Chronic inflammation of the epididymides was observed in 7/20 high-dose males (180 mg/kg-day), compared with 4/20 control males. Chronic inflammation of the prostate was observed in 9/20 high-dose males, compared with 6/20 control males. In male rats, there was a statistically significant (20.3%) increase in the relative testes to body weight in the high-dose group (compared with the controls). Statistical significance was also reached in relative testes weight to body weights at 20 and 180 mg/kg-day in rats killed mid-way through the experiment (at day 43), with 9.7 and 14.6% increases, respectively. Statistically significant increases in relative ovary weight to body weight and ovary to brain weight (24.1 and 18.2%, respectively) were observed at 180 mg/kg-day. There were no gross pathology and histopathology findings corresponding to the statistically significant changes in the relative testes and ovary weights. One rat in the high-dose group of 30 female rats exhibited ovarian congestion. Developmental Toxicity No data were available for this endpoint. 8 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Genetic Toxicity - Gene Mutations In vitro (1) Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli strain WV2wvrA were exposed to 2-vinylpyridine (98.3% purity) in DMSO at concentrations of 39.1 - 2500 [j,g/plate in the absence of metabolic activation or 156 - 5000 [j,g/plate in the presence of metabolic activation. Positive and negative controls were tested concurrently, but control responses were not provided. Cytotoxicity was observed at high doses. Precipitation was not observed during the test. A positive mutagenic response was observed with E. coli in the presence of metabolic activation. 2-Vinylpyridine was mutagenic in this assay. (2) Salmonella typhimurium strains TA98, TA100 and TA1535 were exposed to 2-vinylpyridine (> 98% purity) at concentrations of 0, 0.1 or 0.5 mL/9 L desiccators in the presence or absence of metabolic activation. Exposure was conducted in sealed desiccators for 7 hours, followed by incubation for 40 - 50 hours. Severe cytotoxicity was observed at the high concentration. Positive and negative controls were tested concurrently, but no details regarding control responses were provided. No evidence of mutagenicity was observed in any of the strains. 2-Vinylpyridine was not mutagenic in this assay. (3) Salmonella typhimurium strains TA98, TA100, TA1535 and TA1538 were exposed to 2- vinylpyridine (>99% purity) at concentrations of 5, 10, 25 or 50 |imol/plate in the presence of absence of metabolic activation. Cytotoxicity (with survival rates ranging from 30-65%) was observed at 25 and 50 |imol/plate. No data regarding the use or response of positive and negative controls were provided. No further experimental details were provided. No evidence of mutagenicity was observed in any of the strains. 2-Vinylpyridine was not mutagenic in this assay. Genetic Toxicity — Chromosomal Aberrations In vitro Chinese hamster adenofibroblast cells were exposed to 2-vinylpyridine (98.3% purity) for 6, 24 or 48 hours in the presence and absence of metabolic activation. Tested concentrations ranged from 37.5 - 300 |ag/mL for the 6-hour exposures with metabolic activation, 15 - 120 |ag/mL for 6-hour exposures without metabolic activation, 3.75 - 30 |ag/mL for 24-hour exposures and 1.88 -15.0 |ig/mL for 48-hour exposures. Negative and positive controls were tested concurrently, but control responses were not provided. Cytotoxic responses with > 50% inhibition of cell proliferation occurred at the highest or two highest concentrations. Precipitation was not observed at the tested doses. Dose-dependent induction of chromosomal aberrations was observed with all exposure duration protocols. No polyploidy was observed. 2-Vinylpyridine induced chromosomal aberrations in this assay. 9 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Genetic Toxicity - Other In vitro In a DNA repair test, rat hepatocytes were exposed to 2-vinylpyridine (>99% purity) at concentrations of 2.5, 5.0, 7.5 or 10 mmol. 2-Vinylpyridine was toxic to rat hepatocytes at 5, 7.5 and 10 mmol. Positive controls were tested concurrently, but control responses were not provided. No genotoxicity was observed at the non-toxic concentration of 2.5 mmol. 2-Vinylpyridine did not induce DNA repair in this assay. Additional Information Skin Irritation (1) Guinea pigs (10/dose, sex/strain not specified) were administered undiluted 2-vinylpryridine (98.95% purity) at 0.05, 0.1, 0.2, 0.35, 0.5, 1, 2 or 5 mL/kg under occluded conditions for an unspecified duration. No further experimental details were provided. All animals exposed to doses > 0.35 mL/kg died, 6/10 at 0.2 mg/kg, and 1/10 at each of the two lowest dose groups. Skin irritation was observed in this standardized 24-hour test. Additional details were obtained from OTS0546362 2-Vinylpyridine was severely irritating to guinea pig skin in this assay. (2) Five guinea pigs (sex/strain not specified) were administered undiluted 2-vinylpryridine (98.95%) purity) at 0.1 mL/kg in repeated doses to uncovered skin. All animals died after 4-7 applications. Evidence of "strong exacerbation" and percutaneous absorption were noted. No further details were provided. Additional details were obtained from OTS0546362 2-Vinylpyridine was irritating to guinea pig skin in this assay. Skin Sensitization Ten guinea pigs (sex not specified) were administered undiluted 2-vinylpyridine (98.95%) purity) to the skin. Sensitization responses were 2/10 showed no response, 3/10 showed a weak response, 4/10 showed a moderated response, and 1/10 showed a potent response. 2- vinylpyridine elicited reactions indicating an estimated moderate risk to human sensitization. 2-Vinylpyridine is a dermal sensitizer to guinea pig skin in this assay. Skin Corrosion (1) New Zealand White rabbits (5 males and 1 female) were administered 0.5 mL undiluted 2- vinylpyridine (purity not stated) to the intact, shaved skin for 1 hour under occluded conditions. Skin necrosis was observed at all test sites 48 hours after dosing. 2-Vinylpyridine was corrosive to rabbit skin in this assay. 10 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 (2) In the acute dermal toxicity study described above that resulted in a LD50 of 640 mg/kg, the site of application of the New Zealand White rabbits was not abraded intentionally or accidentally during preparation. The test substance was introduced under gauze patches 2 single layers thick and applied directly to the skin. Necrosis of the skin was observed at all dosing sites. 2-Vinylpyridine was corrosive to rabbit skin in this assay. Eye Irritation Undiluted 2-vinylpyridine (98.95% purity) was instilled into the eyes of three rabbits. One eye of each rabbit was unwashed after dosing, and one eye of each rabbit was washed after dosing. Irritation was strong in all unwashed eyes and moderate in all eyes washed following application of 2-vinylpyridine. Corneal and adnexal staining was observed in both washed and unwashed eyes of all rabbits. 2-Vinylpyridine was irritating to rabbit eyes in this assay. Conclusion: Acute oral toxicity of 2-vinylpyridine to rats and acute dermal toxicity to rabbits is moderate. In a 90-day oral repeated-dose toxicity study in rats, changes in the relative kidney to body weight ratio were observed in males in all tested doses and histopathological effects in the non-glandular portion of the stomach were observed in males and females at 180 mg/kg-day (highest dose tested). The NOAEL for systemic toxicity in male rats was not established and for female rats is 60 mg/kg-day. In a 28-day oral repeated-dose toxicity study in rats, histopathological effects in the non-glandular portion of the stomach were observed in male and female rats at 50 mg/kg-day; the NOAEL for systemic toxicity is 12.5 mg/kg-day. No specific reproductive toxicity study is available for 2-vinylpyridine. However, in the 90-day oral repeated-dose toxicity study, increases in testes to body weight ratios, incidences of chronic inflammation of epididymides and prostate in male rats and increased ovary to body and ovary to brain weight ratios in female rats were observed. No data are available for the developmental toxicity endpoint. 2-Vinylpyridine induced gene mutations in Escherichia coli, but not in Salmonella typhimurium in vitro. 2-Vinylpyridine induced chromosomal aberrations in vitro, but was not genotoxic in a DNA repair test. 2-Vinylpyridine is irritating to guinea pig skin, corrosive to rabbit skin, irritating to rabbit eyes and sensitizing to guinea pig skin. 11 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Table 3. Summary Table of the Screening Information Data Set under the U.S. HPV Challenge Program - Human Health Data Endpoint SPONSORED CHEMICAL 2-Vinylpyridine (100-69-6) Acute Oral Toxicity LDso (mg/kg) 336 Acute Dermal Toxicity LD50 (mg/kg) ~ 200 - 300 Repeated-Dose Toxicity NOAEL/LOAEL (oral, mg/kg-day) (rat; 90-d) NOAELmaies = Not Established LOAELmales = 20 NO AELfemales = 180 LOAELfemales = 60 (rat; 28-d) NOAEL = 12.5 LOAEL = 50 Reproductive Toxicity NOAEL/LOAEL (mg/kg-day) No specific reproductive toxicity data available. However, increased relative weights of testes and ovaries were observed in the 90-day oral repeated dose toxicity study in rats. Developmental Toxicity NOAEL/LOAEL (oral, mg/kg-day) No Data Genetic Toxicity - Gene Mutation In vitro Positive Genetic Toxicity - Chromosomal Aberrations In vitro Positive Genetic Toxicity - Other In vitro DNA Repair Assay Negative Additional Information Skin Irritation Eye Irritation Skin Sensitization Skin Corrosion Irritating Irritating Not sensitizing Corrosive Measured data in bold 4. Hazard to the Environment A summary of aquatic toxicity data submitted for SIDs endpoints is provided in Table 4. 12 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 Acute Toxicity to Fish Medaka (Oryzias latipes; 5 organisms per replicate, 2 replicates per test concentration) were exposed to 2-Vinylpyridine (purity 99.2 %) for 96 hours under semi-static conditions. Nominal concentrations were 0 (control), 0.938, 1.88, 3.75, 7.50, 15.0, and 30.0 mg/L and mean measured concentrations were 0 (control), 0.908, 1.77, 3.57, 7.15, 14.3, and 28.8 mg/L which were 96.3 - 99.1 % of nominal at test preparation and 91.7 - 94.5 % (before the renewal). Temperature = 23.5 - 24 °C, DO = 6.8 - 8.4 mg/L, and pH = 7.2 - 7.8. Mortality was 10 %, 60 %, 100%, and 100 % in the 3.75, 7.50, 15.0 and 30.0 nominal test concentrations, respectively. Sub-lethal responses were also observed in all test concentrations except the 0.938 mg/L. http ://echa. europa. eu 96-h LCso = 6.48 mg/L (95% C.I. = 4.90 - 8.55 mg/L) Acute Toxicity to Aquatic Invertebrates Daphnia (Daphnia magna; 5 organisms per replicate / 4 replicates per test concentration) were exposed to 2-Vinylpyridine (purity 99.2 %) for 48 hours under semi-static conditions. Nominal concentrations were 25.0, 15.6, 9.77, 6.10, 3.81 mg/L, and 0 (control). Measured concentrations were 19.4, 12.5, 7.93, 5.18, 3.23, and 0 (control) mg/L and were % 101 - 103 % of nominal at the start of the exposure and 58.1 - 70.7 % at the end of the exposure. Temperature = 20.2 - 20.7°C, pH = 7.2 - 7.8, and DO = 8.7 - 8.8 mg/L. Mortality was 5, 10, 100 and 100 % in the 5.18, 7.93, 12.5, and 19.4 mg/L test concentrations, respectively at 48 hours. Sub-lethal responses were also observed in all test concentrations except the 3.23 mg/L test concentrations. http ://echa. europa. eu 48-h ECso = 9.48 mg/L (95% C.I. = 7.93 - 12.5 mg/L) Toxicity to Aquatic Plants Green algae (Pseudokirchneriella subcapitata) were exposed to 2-Vinylpyridine (99.2 % purity) for 72 hours under static conditions. Nominal concentrations were 0 (control), 9.53, 17.1, 30.9, 55.6, and 100 mg/L and corresponding measured concentrations were 0 (control), 8.25, 15.0, 27.2, 48.1, and 87.4 mg/L which were 98.2 -102 % of nominal at 0 h and 72.7 -78.1 % of nominal at 72 h. Temperature 22.9 - 23.0 °C, pH = 7.7 - 7.9. http://echa.europa.eu 72-h ECso = 50.8 mg/L (biomass) 72-h ECso = 64.4 mg/L (growth rate) NOEC = 30.9 mg/L (biomass) Chronic Toxicity to Aquatic Invertebrates Daphnia (Daphnia magna; 1 organism per replicate, 10 replicates per test concentration) were exposed to 2-Vinylpyridine (purity 99.2 %) under semi-static conditions for 21 days. Nominal concentrations were 4.00, 2.00, 1.00, 0.500, 0.250, and 0 (control) mg/L. Measured concentrations: 3.71, 1.80, 0.901, 0.452, 0.223, and 0 (control) mg/L (% of the nominal: 94.2 - 13 ------- U.S. Environmental Protection Agency Hazard Characterization Document September, 2014 102 % (at freshly prepared test solution) and 78.5 - 87.7 % (before renewal of the test solution). Hardness = 36.0 - 41.6 mg/L (as CaCCb), Temperature = 20.2 - 20.7 °C, pH = 7.8 - 8.0, DO = 8.3 - 8.7 mg/L. http://echa.europa.eu 21-d LCso = 0.933 mg/L (mortality) (95% C.I. = 0.648-1.35 mg/L) 21-d LCso = 1.06 mg/L (reproduction) (95% C.I. = 0.939-1.19 mg/L) LOEC = 1.8 mg/L (reproduction) NOEC = 0.901 mg/L (reproduction) Conclusion: For 2-vinylpyridine, the 96-h LC50 value for fish is 6.48 mg/L, the 48-h EC50 value for aquatic invertebrates is 9.48 mg/L and the 72-h EC50 values for aquatic plants are 50.8 mg/L and 64.4 mg/L, for biomass and growth rate, respectively. The 21-d LC50 values for aquatic invertebrates are 0.933 mg/L and 1.06 mg/L for mortality and reproduction, respectively. Table 4. Summary of the Screening Information Data Set as Submitted under the U.S. HPV Challenge Program - Aquatic Toxicity Data Endpoints SPONSORED CHEMICAL 2-Vinylpyridine (100-69-6) Fish 96-h LCso (mg/L) 6.48 Aquatic Invertebrates 48-h ECso (mg/L) 9.48 Aquatic Plants 72-h ECso (mg/L) biomass growth rate 50.8 64.4 Chronic Toxicity to Aquatic Invertebrates 21-d LCso (mg/L) 0.993 (mortality) 1.06 (reproduction) Bold = measured data (i.e., derived from testing) 14 ------- |