U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 SCREENING-LEVEL HAZARD CHARACTERIZATION SPONSORED CHEMICAL Chlorinated C3 Stream CASRN 68390-96-5 SUPPORTING CHEMICAL 1,2-Dichloropropane CASRN 78-87-5 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" 1 2 (Screening Information Data Setl ' ) 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. 2 3 The evaluation is performed according to established EPA guidance ' 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. 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 December, 2012 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. 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 December, 2012 Chemical Abstract Service Registry Number (CASRN) Sponsored Chemical 68390-96-5 Supporting Chemicals 78-87-5 Chemical Abstract Index Name CASRN 68390-96-5 CASRN 78-87-5 Sponsored chemical Hydrocarbons, C3, chloro- Supporting Chemical Propane, 1,2-dichloro- Structural Formula Sponsored chemical Not applicable Supporting Chemical CI ^CH3 CI SMILES: C(C1)C(C1)C Summary C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) is a mixture of several chlorinated 3-carbon chemicals which are produced as intermediate streams from manufacturing product lines. The composition of this substance is variable, but a commercial mixture was shown to contain 1,2-dichloropropane (CASRN 78-87-5; 85% wt maximum), 2,3-dichloropropene (CASRN 78-88-6; 5% wt maximum), 3,3-dichloropropene (CASRN 563-57-5; 5% wt maximum), and 2,2-dichloropropane (CASRN 594-20-7; 5.5% maximum). The remainder of this mixture is composed of other chlorinated propenes with no other single component present at more than 4% of the total stream. The components of C3 chlorinated hydrocarbon stream are liquids, with high vapor pressure and moderate to high water solubility. The components of C3 chlorinated hydrocarbon stream are expected to have high mobility in soil. Volatilization is expected to be high for the components of C3 chlorinated hydrocarbon stream. The rate of hydrolysis is negligible for most components; however, 2,2-dichloropropane (CASRN 594-20-7) has a moderate hydrolysis rate under environmental conditions. The rate of atmospheric photooxidation is moderate to negligible. The components of C3 chlorinated hydrocarbon stream are expected to have moderate to high persistence (P2-P3) and low bioaccumulation potential (Bl). 3 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 No human health data are available for C3 chlorinated hydrocarbon stream. Data for supporting chemical 1,2-dichloropropane are used to address all SIDS endpoints. Acute oral and dermal toxicity of 1,2-dichloropropane in rats and rabbits, respectively, is low. Acute inhalation toxicity in rats is moderate. In a 13-week repeated-dose toxicity gavage study in rats, mortality, decreased body weight and liver effects were seen at > 500 mg/kg-day. The NOAEL is 250 mg/kg-day. In a 13-week repeated-dose toxicity gavage study in mice, no significant effects were seen; the NOAEL is 500 mg/kg-day. In 103-week toxicity and carcinogenicity gavage study in rats, the NOAEL for males is 62 mg/kg-day based on effect on body weight at > 125 mg/kg-day; the NOAEL for females is 125 mg/kg-day based on mortality and effect on body weight and liver at > 250 mg/kg-day. In mice, following 103 weeks of repeated gavage administration of 1,2-dichloropropne, liver and stomach lesions were noted at >125 mg/kg-day; NOAEL is not established. Following repeated inhalation exposure to rats for 13 weeks, 1,2-dichlorproapane resulted in effect on body weight and nasal epithelial hyperplasia at >15 ppm (-0.068 mg/L-day); the NOAEC is not established. Inhalation exposure of mice to 1,2-dichlorproapane for 13 weeks resulted in no significant effects; the NOAEC is 150 ppm (0.675 mg/L-day), the highest concentration tested. In rabbits, inhalation exposure of to 1,2-dichlorproapane for 13 weeks resulted in effects on hematology parameters in males >150 ppm (0.675 mg/L-day) and in females > 500 ppm (2.25 mg/L-day); for males NOAEC is not established; while in females the NOAEC is 150 ppm (0.675 mg/L-day). In a 2-generation reproductive toxicity study in rats via drinking water with supporting chemical, 1,2-dichloropropane, parental systemic toxicity NOAEL is 0.024% (20-30 mg/kg-day) based on decreased body weights at >0.1%; the NOAEL for reproductive toxicity is 0.24% (130-250 mg/kg-day), the highest dose tested at the limit of solubility and the NOAEL for offspring toxicity is 0.1% (70-130 mg/kg-day) based on effect on body weight. In a prenatal developmental toxicity gavage study of supporting chemical, 1,2-dichlorpropane, in rats, the NOAEL for maternal and developmental toxicity is 30 mg/kg-day based on decreased body weights in dams and delayed ossification of skull bones in pups, respectively, at 125 mg/kg-day. In the prenatal developmental toxicity gavage study of supporting chemical, 1,2-dichlorpropane in rabbits, the NOAEL for maternal and developmental toxicity is 50 mg/kg-day based on decreased body weights and effect on hematology parameters in does and delayed ossification of skull bones in pups, respectively, at 150 mg/kg-day. The supporting chemical, 1,2-dichloropropane is weakly mutagenic in bacteria and mutagenic in mammalian cells in vitro. The supporting chemical, 1,2-dichloropropane induced chromosomal aberrations in vitro but did not increase micronuclei in mice in vivo. The supporting chemical, 1,2-dichloropropane induced sister chromatid exchanges in vitro but it did not induce dominant lethal mutations in vivo. The supporting chemical, 1,2-dichloropropane is irritating to rabbit skin and eyes. In the mouse local lymph-node assay, 1,2-dichloropropane was not a skin sensitizer. The supporting chemical, 1,2-dichloropropane increased tumor incidence in mice but showed equivocal evidence of an increased tumor incidence in rats. In a 13-week neurotoxicity 4 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 study in rats, the supporting chemical, 1,2-dichloropropane did not show neurotoxicity when administered up to 200 mg/kg-day. For ecotoxicity, data for all endpoints are based on the supporting chemical of 1,2-dichloropropane. The 96-h LC50 values for chlorinated C3 stream for fish range between 130 and 320 mg/L. The chronic 28-day toxicity values for chlorinated C3 stream for fish range between 6 and 11 mg/L. The 48-h LC50 values for chlorinated C3 stream for aquatic invertebrates range between 24 and 120 mg/L. The chronic 21-day NOEC values for chlorinated C3 stream for aquatic invertebrates range between 4.1 and 8.3 mg/L. The 72-h EC50 of chlorinated C3 stream for aquatic plants is 14.7 mg/L (growth) and 15.1 mg/L (biomass). No data gaps were identified under the HPV Challenge Program. The sponsor, Dow Chemical Company, submitted a Test Plan and Robust Summaries to EPA for C3 chlorinated hydrocarbon stream (CAS No. 68390-96-5; CA Index name: hydrocarbons, C3, chloro) on December 29, 2004. EPA posted the submission on the ChemRTK HPV Challenge website on January 18, 2005 (http://www.epa.gov/hpv/pubs/summaries/chlorc3s/cl5745tc.htm). EPA comments on the original submission were posted to the website on March 15, 2007. Public comments were also received and posted to the website. The sponsor submitted updated/revised documents on April 4, 2007, which were posted to the ChemRTK website on July 24, 2007. Justification for Supporting Chemicals The chlorinated C3 stream consists of "several chlorinated 3-carbon chemicals, which are produced as intermediate streams from several manufacturing product lines. The material is generated and chemically destroyed in the production of another chemical substance at the site of manufacture". The sponsored stream is described as highly variable in composition. In the 2004 test plan, the sponsor described the major components of the chlorinated C3 stream as 65% 1.2-dichloropropane (also described as PDC), 8% trichloropropene and 6.5% 2-chloropropene. The remaining 20.5% of the stream was described as consisting of "a number of chlorinated propenes with no single component present at more than 5% of the total stream." In its 2007 revised test plan, the sponsor listed the largest volume components of the 2006 chlorinated C3 stream as 1,2-dichloropropane (~ 85% maximum), 2,3-dichloropropene (~ 5% maximum), 3.3-dichloropropene (~ 5% maximum) and 2,2-dichloropropane (~ 5.5% maximum), with the remaining portion composed of "other chlorinated propenes with no other single component present at more than 4% of the total stream." Although highly variable, the propanes are the largest volume components in the 2006 chlorinated C3 stream, which is approximately 90.5%; the propenes are approximately 10% with other unidentified porpenes present as no more than 4%. 5 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 The sponsor proposed the use of 1,2-dichloropropane (CASRN 78-87-5) as a supporting chemical for health effects and aquatic toxicity endpoints on the basis of its "high volume percent of the stream" and "comparative toxicity with most of the lesser components of the stream." The physical chemical properties of 1,2-dichloropropane are similar to those for 2,3 dichloropropene or 1,3-dichloropropene. For example, the boiling points and vapor pressure are 94-95, 94, and 108 °C and 50, 45 and 28 mm Hg, respectively; and thus the vapor composition of the stream will be similar to that of the liquid form of the chemical. In addition, these chemicals have high water solubility and a low partition coefficient values (approximately 2.0). The limited toxicity data provided for 2,3-dichloropropene (CASRN 77-88-6), which is present in the 2006 chlorinated C3 stream sample at a maximum volume of 5% wt, indicated that 2,3-dichloropropene has greater acute oral, dermal and inhalation toxicities than 1,2-dichloropropane. However, in the stream, the toxicity will be mostly dominated by the highest volume percentage of the components. Based on the concerns that the chlorinated C3 stream has variable composition, this hazard assessment needs to be considered with caution because it is based on the submitted toxicity data for the supporting chemical, 1,2-dichloropropane. 1,2-Dichloropropane (CASRN 78-87-5) has been evaluated in the IRIS program http://www.epa.gov/iris/subst/Q601.htm 1,2-Dichloropropane (CASRN 78-87-5) has been evaluated under the OECD HPV program at SIAM 17 (http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf). Human health data for this chemical are used to read across the SIDS endpoints for CASRN 68390-96-5. IARC evaluated 1,2-dichloropropane for animal carcinogenicity. http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-90.pdf 1. Chemical Identity 1.1 Identification and Purity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) is a mixture of several chlorinated 3- carbon chemicals which are produced as intermediate streams from manufacturing product lines. The composition of this substance is variable, but a commercial mixture (2006) was shown to contain 1,2-dichloropropane (CASRN 78-87-5; 85% wt maximum), 2,3-dichloropropene (CASRN 78-88-6; 5% wt maximum), 3,3-dichloropropene (CASRN 563-57-5; 5% wt maximum), and 2,2-dichloropropane (CASRN 594-20-7; 5.5% maximum). The remainder of this mixture is composed of other chlorinated propenes with no other single component present at more than 4% of the total stream. 6 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 1.2 Physical-Chemical Properties The physical-chemical properties of the potential components of C3 chlorinated hydrocarbon stream are summarized in Table 1. The structures of the potential components of this mixture are provided in the Appendix. Table 1. Physical-Chemical Properties of Hydrocarbons, C3, chloro1 Property Propane, 1,2- dichloro- 1-Propene, 2,3- dichloro- 1-Propene, 3,3- dichloro- Propane, 2,2- dichloro- CASRN 78-87-5 78-88-6 563-57-5 594-20-7 Molecular Weight 112.99 110.97 110.97 112.99 Physical State Colorless liquid Liquid Liquid Liquid Melting Point -70°C (measured) 10°C (measured)2 -107°C (measured)3 -33.8°C (measured)2 Boiling Point 95-96°C (measured) 94°C (measured)2 84.4°C (measured)2 69.3°C (measured)2 Vapor Pressure 49.8 mm Hg at 20°C (measured) 61.2 mm Hg at 25 °C (measured)2 70.5 mmHg at 25°C (measured)2 135 mmHgat25°C (estimated)4 Dissociation Constant (pKa) Not applicable Not applicable Not applicable Not applicable Henry's Law Constant 2.82xl0"3 atm-m3/mol (measured)2 4.2 xlO"3 atm-m3/mol (estimated)4 0.12 atm-m3/mol (estimated)4 0.016 atm-m3/mol (estimated)4 Water Solubility 2,800 mg/L at 25°C (measured) 2,150 mg/L at 25°C (measured)2 1,694 mg/L at 25°C (estimated)4 390.5 mg/L at 25°C (estimated)4 Log Kow 2.0 (measured) 2.42 (estimated)4 2.11 (estimated)4 2.92 (estimated)4 'The Dow Chemical Company. 2007. Revised Test Plan and Summary for Chlorinated C3 Streams. Available online at http://www.epa.gov/chemrtk/pubs/summaries/chlorc3s/cl5745tc.htm as of April 20,2012. 2SRC. 2012. The Physical Properties Database (PHYSPROP). Syracuse, NY: Syracuse Research Corporation. Available online at http://www.svrres.com/esc/phvsprop.htm as of April 20,2012. 3WolframAlpha. 2012. 3,3-Dichloro-l-propene. Available online at http://www.wolframalpha.com/entities/chemicals/3.3- dichloro-1 -propene/ip/v4/tk/ as of April 20, 2012. 4U.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 April 20, 2012. 2. General Information on Exposure 2.1 Production Volume and Use CASRN 68390-96-5 had an aggregated production and/or import volume in the United States between 100 to 500 million pounds during calendar year 2005. Non-confidential information in the IUR indicated that the industrial processing and uses of the chemical include other basic organic chemical manufacturing as intermediates. No commercial and consumer uses were reported for the chemical. 7 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 2.2 Environmental Exposure and Fate The environmental fate properties of chlorinated hydrocarbon stream are summarized in Table 2. Table 2. Environmental Fate Properties of the Hydrocarbons, C3, chloro1 Property Propane, 1,2-dichloro- 1-Propene, 2,3- dichloro- 1-Propene, 3,3- dichloro- Propane, 2,2- dichloro- CASRN 78-87-5 78-88-6 563-57-5 594-20-7 Photodegradation Half-life 24 days (estimated)2 15 hours (estimated)2 6.3 hours (estimated)2 157 days (estimated)2 Hydrolysis Half- life 15.8 years at pH 7 and 25°C 523 days at pH 7 and 25°C3'4 No data 1.5 days at pH 7 and 25°C5'6 Biodegradation 0% after 28 days (not readily biodegradable); Half-life = 52 days in soil at 15°C and 41 days at 20°C; 0% after 14 days (not readily biodegradable)7 No data No data No data Bioaccumulation Factor BCF = 1.2-3.2 (measured in carp at 0.4 mg/L)7; BCF = 0.5-6.9 (measured in carp at 0.04 mg/L)7; BAF = 7.4(estimated)2 BAF = 26.2 (estimated)2 BAF = 13.2 (estimated)2 BAF = 71.8 (estimated)2 Log Koc 1.8 (estimated)2 1.8 (estimated)2 1.8 (estimated)2 1.6 (estimated)2 Fugacity (Level III Model)2 Air (%) Water (%) Soil (%) Sediment (%) 36.0 40.8 23.1 0.2 17.8 58.3 23.7 0.3 8.9 78.5 12.2 0.4 49.2 46.3 4.4 0.2 Persistence8 P2 (moderate) to P3 (high) P2 (moderate) to P3 (high) P2 (moderate) to P3 (high) P2 (moderate) Bioaccumulation8 B1 (low) B1 (low) B1 (low) B1 (low) 'The Dow Chemical Company. 2007. Revised Test Plan and Summary for Chlorinated C3 Streams. Available online at http://www.epa.gov/chemrtk/pubs/summaries/chlorc3s/cl5745tc.htm as of April 20,2012. 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 April 17, 2012. 3Milano JC; Guibourg A; Vernet JL. 1988. Non biological evolution in water of some three and four carbon atoms of organohalogenated compounds: hydrolysis and photolysis. Wat Res 22(12): 1553-1562. 4Data appear to suggest only the neutral (kN) rate constant is significant and the base catalyzed rate constant is essentially zero. 5Jeffers PM; Ward LM; Woytowitch LM; et al. 1989. Homogeneous hydrolysis rate constants for selected chlorinated methanes, ethanes, ethenes and propanes. Environ Sci Technol 23(8):965-969. 6The effective rate constant used to calculate the half-life was the sum of the base catalyzed rate constant and the neutral hydrolysis rate constant. There was no evidence that acid catalyzed hydrolysis occurred. 8 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 7National Institute of Technology and Evaluation. 2002. Biodegradation and Bioaccumulation of the Existing Chemical Substances under the Chemical Substances Control Law. Available online at http://www.safe.nite.go.ip/english/kizon/KIZON start hazkizon.html as of April 18,2012. sFederal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64, Number 213 (November 4, 1999) pp. 60194-60204. Conclusion: C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) is a mixture of several chlorinated 3-carbon chemicals which are produced as intermediate streams from manufacturing product lines. The composition of this substance is variable, but a commercial mixture was shown to contain 1,2-dichloropropane (CASRN 78-87-5; 85% wt maximum), 2,3- dichloropropene (CASRN 78-88-6; 5% wt maximum), 3,3-dichloropropene (CASRN 563-57-5; 5% wt maximum), and 2,2-dichloropropane (CASRN 594-20-7; 5.5% maximum). The remainder of this mixture is composed of other chlorinated propenes with no other single component present at more than 4% of the total stream. The components of C3 chlorinated hydrocarbon stream are liquids, with high vapor pressure and moderate to high water solubility. The components of C3 chlorinated hydrocarbon stream are expected to have high mobility in soil. Volatilization is expected to be high for the components of C3 chlorinated hydrocarbon stream. The rate of hydrolysis is negligible for most components; however, 2,2-dichloropropane (CASRN 594-20-7) has a moderate hydrolysis rate under environmental conditions. The rate of atmospheric photooxidation is moderate to negligible. The components of C3 chlorinated hydrocarbon stream are expected to have moderate to high persistence (P2-P3) and low bioaccumulation potential (Bl). 3. Human Health Hazard A summary of health effects data for SIDS and other endpoints is provided in Table 3. The table also indicates where data for the supporting chemical are read-across (RA) to the sponsored substance. Acute Oral Toxicity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) Carforth-Wistar rats (non fasted, 5 males and females total) were administered undiluted 1,2-dichloropropane (purity >99%) at doses that were arranged in a logarithmic series and differed by a factor of two. Animals were observed for 14 days post-treatment. The LD50 value is 1.9 mL/kg (equivalent to 2200 mg/kg based on a density of 1.155 g/mL). LD50 = 2200 mg/kg http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-2fb649ce-3024-4f6b-887a-6d 184694be9c PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-2fb649ce-3024-4f6b-887a-6dl84694be9c 9 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 Acute Inhalation Toxicity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) (1) Six Sherman rats (males and females) were exposed to 1,2-dichloropropane (>99% purity) vapor at a nominal concentration up to 2000 ppm (approximately 9.4 mg/L) for 4 or 8 hours and observed for 14 days post-exposure. After 4 hour exposure, mortality was 33-76%. Following 8 hour exposure, there were 3/6 deaths. LC5o = 9.4 mg/L http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-33aab966-934d-4989-8f9f-44f7fl78e9e4 DISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-33aab966-934d-4989-8f9f-44f7fl78e9e4 (2) Sprague-Dawley rats (33, sex not reported) and Guinea pigs (33, sex not reported) were exposed to 1,2-dichloropropane (purity not stated) vapor at a nominal concentration of up to 2000 ppm (approximately 9.4 mg/L) for 7 hours and observed for 14 and 21 days, respectively. Two rats died; and no deaths occurred in guinea pigs. LC50 > 9.4 mg/L http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf Acute Dermal Toxicity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) Albino rabbits (4 males per treatment) were administered l,2-dichloropropane(purity and doses not specified) to clipped skin under occlusive conditions and observed for 14 days. The LD50 value is 8.75 mL/kg (equivalent to 10,100 mg/kg based on a density of 1.155 g/mL) LD 50 = 10,100 mg/kg http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-1134b0a8-9df7-4ce0-9541 -b29P 52b0606 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-1134b0a8-9df7-4ce0-9541 -b29P 52b0606 10 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 Repeated-Dose Toxicity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) Oral (1) In an NTP, 13-week study, Fischer 344 rats (10/sex/dose) were administered 1,2-dichloropropane (99.4% purity) via gavage in corn oil, 5 days/week, at 0, 60, 125, 250, 500 or 1000 mg/kg-day. The animals were observed for mortality and clinical signs; body weights were recorded; necropsies were performed and microscopic examinations were conducted on animals from control and 500 and 1000 mg/kg-day groups. All animals at 1000 mg/kg-day and 5/10 males at 500 mg/kg-day died. At 500 mg/kg-day, final mean body weights were decreased by 16% in males and 8% in females. Centrilobular congestion was seen in the liver of 5/10 males and 2/10 females (deceased) given 1000 mg/kg-day. In addition, hepatic fatty change and centrilobular necrosis were observed in 1/10 females (deceased) at 1000 mg/kg-day. LOAEL = 500 mg/kg-day (based on mortality and effects on body weights and liver) NOAEL = 250 mg/kg-day http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-6ed3b472-ffad-42c7-9cf5-8315c2aafe6a DISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-6ed3b472-ffad-42c7-9cf5-8315c2aafe6a (2) In another NTP 13-week, B6C3F1 mice (10/sex/dose) were administered 1,2-dichloropropane (>99% purity) via gavage in corn oil, 5 days/week at 0, 30, 60, 125, 250 or at 500 mg/kg-day. The animals were observed for mortality and clinical signs; body weights were recorded; necropsies were performed and microscopic examinations were conducted on animals from control and 500 mg/kg-day groups. One male given 60 mg/kg-day died during the first week of the study and one female given 500 mg/kg-day died during week 12. In males body weights were decreased (approximately 4-5%) at 30 and 500 mg/kg-day; in females body weights were decreased (3-4%) at 250 and 500 mg/kg-day compared to controls. No treatment- related histopathological effects were seen. NOAEL = 500 mg/kg-day (highest dose tested) http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 (3) In an NTP chronic toxicity/oncogenicity study, Fischer 344 rats (50/sex/dose) were administered 1,2-dichloropropane (>99% purity) via gavage, in corn oil, at 0, 62, or 125 mg/kg-day (males) and 0, 125 or 250 mg/kg-day (females), 5 days/week for 103 weeks. The animals were observed for mortality and clinical signs; body weights were measured; necropsies and microscopic examinations were conducted on all animals. A dose-related reduction in body weight was seen. Final body weights were approx. 5% lower than control at 60 or 62 mg/kg-day, 11 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 and 14% and 24% lower than control at 125 and 250 mg/kg-day in males and females, respectively. The survival of females at 250 mg/kg-day was significantly (P<0.001) less than that at 125 mg/kg-day and controls. Mortality and morbidity was significant at wk 94 of the study. Survival in males was comparable at all doses. Non-neoplastic changes were seen only in females at 250 mg/kg-day and include the incidence of hepatic foci of clear change (22% versus 6% in controls) and liver necrosis (focal and centrilobular combined; 18% versus 2% in controls). LOAELmaies = 125 mg/kg-day (based on effect on body weight) NOAELmaies = 62 mg/kg-day LOAELfemaies = 250 mg/kg-day (based on mortality, effects on body weights and liver) NOAELfemaies = 125 mg/kg-day (4) In an NTP chronic toxicity/oncogenicity study, B6C3F1 mice (50/sex/dose) were administered 1,2-dichloropropane (>99% purity) via gavage, in corn oil, at 0, 125 or 250 mg/kg-day, 5 days/week for 103 weeks. The animals were observed for mortality and clinical signs; body weights were measured; necropsies and microscopic examinations were conducted on all animals. Mean body weights of treated and vehicle control animals were comparable. No treatment-related clinical signs were noted. The survival of females at 250 mg/kg-day was significantly (P<0.035) lower than at 125 mg/kg-day and controls with 70%, 58%) and 52% of animals surviving to study termination at control, 125 mg/kg-day and 250 mg/kg-day, respectively. Survival in males was comparable for all groups with 70%, 66% and 70% alive at wk 103 for the control, 125 and 250 mg/kg-day groups, respectively. The report notes that the lower survival in female mice was related to an increased incidence of reproductive tract infections in animals that died before the end of the study (45%, 64% and 64% at control, 125 and 250 mg/kg-day, respectively). In male mice, hepatocytomegaly (6%, 10% and 30% at control, 125 and 250 mg/kg-day, respectively) and hepatic focal necrosis (4%, 10% and 20%) at control, 125 and 250 mg/kg-day, respectively) were seen. Acanthosis of the surface epithelium of the forestomach occurred at increased incidence in high dose males (0%, 0%, 4%) and both groups of females (0%, 10%, 8%). Suppurative inflammation (affecting ovary, uterus or multiple organs, and a presumed consequence of reproductive tract infection) was found in 5/11 control, 9/14 low dose and 14/22 high dose females that died before the end of the study. LOAEL = 125 mg/kg-day (based on liver lesions in male mice and acanthosis of the stomach in females) NOAEL = not established http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 Inhalation (1) In a 13-week study, Fischer 344 rats (10/sex/concentration) were exposed (whole body) to 1,2-dichloropropane (99.4% purity) vapor at 0, 15, 50 or 150 ppm (approximately 0, 0.068, 0.225, and 0.675 mg/L-day, respectively) 6 hr/day, 5 d/week. The following parameters were evaluated: clinical signs, hematology, clinical chemistry, urinalyses, organ weights, necropsy observations and histopathology examination. Body weights at 150 ppm were significantly (7% females and 10% males, significance not provided) decreased; smaller decreases (4-8%) were 12 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 seen at 50 ppm. Several slight but statistically significant effects on organ weights were noted in rats exposed to 50 and 150 ppm: increased relative brain weight (8%), and relative heart weight (6%) were seen in males and decreased absolute brain weight in females at 50 ppm. These changes were considered secondary to lower body weights. Histopathological effects were limited to the upper respiratory tract. Very slight to slight degeneration of olfactory mucosa in the anterior portion of the nasal cavity and very slight to slight hyperplasia of the respiratory mucosa were seen for all rats exposed to 50 and 150 ppm with slight nasal epithelial hyperplasia in the animals at 15 ppm. The hyperplasia, which is focally restricted to the anterior portion of the nasal tissue, was considered by the study pathologist to be an adaptive, protective response. LOAEC = 15 ppm (0. 068 mg/L-day) (based on effects on body weight and nasal epithelial hyperplasia) NOAEC = not established http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/PISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 (2) In another 13-week study, B6C3F1 mice (10/sex/concentration) were exposed (whole body) to 1,2-dichloropropane (>99% purity) at 0, 15, 50 and 150 ppm (approximately 0, 0.068, 0.225, or 0.675 mg/L-day, respectively) 6 hr/day, 5 days/weeks. The following parameters were evaluated: clinical signs, hematology, clinical chemistry, urinalyses, organ weights, necropsy observations and histopathology examination. Evaluation of hematology parameters showed slightly but significantly decreased red blood cell (RBC) count and hemoglobin (HGB) concentration in male mice at 15 and 150 ppm. Females were not affected. Packed cell volume (PCV) was statistically significantly increased at 15 ppm only. Since there was no clear dose response and in absence of corresponding histopathology, these effects were considered to be of questionable significance. No abnormalities during necropsy and histopathological examinations were seen. NOAEC = 150 ppm (0.675 mg/L-day) (highest concentration tested) http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 (3) In a 13-week study, New Zealand white rabbits (7/sex/concentration) were exposed (whole body) to 1,2-dichloropropane (>99% purity) vapor at 0, 150, 500 or 1000 ppm (approximately 0, 0.675, 2.25 or 4.5 mg/L-day, respectively) 6 hr/day, 5 days/week. The following parameters were evaluated: clinical signs, hematology, clinical chemistry, organ weights, necropsy observations and histopathology examination. There were no clinical signs or effects on body weight. Effects on hematology parameters include decreased RBC counts at in rabbits exposed to 150 ppm (10%), males only), 500 ppm (approx. 15-20%), both sexes) and 1000 ppm (approx. 20-25%o, both sexes). HGB was decreased at 500 ppm (10-13%>, both sexes) and 1000 ppm (14-16%o, both sexes). PCV (packed cell volume) was decreased (11-15%, both sexes) at 500 ppm and (17%, both sexes) at 1000 ppm. Increased MCV (mean corpuscular volume) and MCH 13 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 (mean corpuscular hemoglobin) values were noted in both sexes, in a non-significant but dose- related manner. In addition, the number of nucleated erythrocytes was non-significantly increased in males exposed to 1000 ppm, while the percentage of reticulocytes (regenerative response) was increased significantly at 500 (approx. 2-fold) and 1000 ppm (3-4 fold) in both sexes. Overall, these findings were consistent with regenerative macrocytic normochromic anemia. Absolute liver weights for males exposed to 500 and 1000 ppm were significantly increased by approx. 25-30%; and relative liver weights were significantly increased by approx. 20%. However, these values were within the historical control rage and were not considered treatment related. No other organ weight changes or gross lesions were present. Bone marrow hyperplasia (regenerative response) was present in some rabbits exposed to 500 and 1000 ppm, with a qualitative increase in hemosiderin-laden macrophages present in bone marrow in animals exposed to 1000 ppm. Minimal degeneration of olfactory epithelium occurred in nasal tissue in males from all groups, including the controls, however the prevalence in males exposed to 1000 ppm (5/7 affected, versus 2/7 controls) was considered suggestive of a treatment-related effect. No other treatment related histopathological changes were observed. LOAECmaies = 150 ppm (0.675 mg/L-day) (based on effects on hematology parameters, effect on nasal tissue) NOAECmaies = not established LOAECfemales = 500 ppm (2.25 mg/L-day) (based on effects on hematology parameters) http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 Reproductive Toxicity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) In a two-generation study, Sprague-Dawley rats (30/sex/dose) were administered 1,2- dichloroprapane via the drinking water at 0, 0.024, 0.1, or 0.24% (equivalent to approximately 0, 20-30, 70-130, and 130-250 mg/kg-day for males and 0, 30-40, 110-140, 190-270 mg/kg-day for females, respectively). After approx. 10 wks treatment, animals were mated (F0) to produce the F1 litters. Thirty males and 30 females from the F1 litters were randomly selected to be the parents of the next generation and following approximately 12 week-treatment, the F1 adults were mated to produce the F2 litters. F1 and F2 litters were reduced to 8 pups (4 males and 4 females) per litter. Litters with 8 or fewer pups were not culled. Parental observations included body weight, food and water consumption necropsy observations, organ weights, hematology parameters and histopathological examination of reproductive organs. Litter observations included litter size, weight and sex of each pup, number of live ad dead pups on 14 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 PND 0-21, and physical abnormalities at birth or during lactation period. From F0 and F1 generations, 10 pups/sex/dose were randomly selected for necropsy at weaning; liver and kidney were weighed and hematology parameters were evaluated. The food consumption was decreased sporadically. There was a dose-related decrease in water consumption from both F0 and F1 generations, presumably because of reduced palatability at the mid and high dose. Overall water consumption of the high-dose males and pregnant females was 50-60% of control and 70% of control in lactating females. Water intake in the mid-dose males and pregnant females was 70-80% of control and in lactating females it was 75-86% of control. Body weights of high-dose females of F0 and F1 generations were 5 and 11% lower than control during premating, 10-12%) lower during gestation and approximately 15% during lactation. Gestation body weight gains were decreased by approximately 20% in F0 and F1 females given 0.24% test substance and by 7-13% in females given 0.1% test substance. There were no significant treatment-related differences in male and female reproductive performance. Increased kidney weights were noted in males and females dosed at 0.24%. Treatment-related histological changes were limited to increased hepatocellular granularity (adaptive change) in males and females of both generations at all dose levels. The incidence in high dose females (17% and 10% for F0 and Fl, respectively) and high dose F1 males (13%) appears greater than control (0 - 2% for all sex/generation groups). All other tissues, including reproductive organs from both sexes, were unremarkable. There were no significant treatment-related external observations or difference in sex ratio in either generation. The number of pups born alive was similar in the control and test groups from both phases of the study, however postnatal survival in high dose Fl litters was significantly lower than control while that of the high dose F2 litters was 10% lower than controls on PND 14 and 21. Bodyweights for high dose F0 neonates were significantly decreased compared to controls. Bodyweights of Fl litters were less severely affected (4 - 7% reduction), and attained significance only on lactation day 21. An increased hemoglobin concentration in high dose Fl males and an increased mean relative kidney weight in high dose Fl females appeared related to a lowered water intake and body weight, respectively. All other hematological and gross necropsy observations were comparable to control in both the Fl and the F2 generations. LOAEL (systemic toxicity) = 0.1% (based on decreased body weight) NOAEL (systemic toxicity) = 0.024% LOAEL (neonatal toxicity) = 0.24% (based on decreased body weight) NOAEL (neonatal toxicity) = 0.1% NOAEL (reproductive toxicity) = 0.24% (highest dose tested at the limit of solubility) http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 15 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 Developmental Toxicity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) (1) In a prenatal developmental toxicity study, pregnant Sprague-Dawley rats (30/dose) were administered 1,2-dichloropropane (>99% purity) in corn oil via gavage at 0, 10, 30, or 125 mg/kg-day during gestation days 6-15. Maternal observations included clinical signs, food and water intake, body weight measurements and liver, kidney, spleen and gravid uterine weights. Fetal observations included the number of corpora lutea, the number and position of implantations, and the number of live and dead fetuses, sex and body weight of each fetus, gross external alterations, visceral alterations and skeletal abnormalities. Clinical signs (decreased movement and muscle tone, increased lacrimation, decreased extensor reflex and increased salivation) were present at 125 mg/kg-day group animals on GD 6 and to a lesser extent on GD 7. Despite the transitory nature of these changes, they appeared indicative of an adverse effect in dams at the high dose. Body weights were slightly (3-5%) but significantly lower (significance not provided) in 125 mg/kg-day dams throughout the study. Body weight gain was significantly lower (significance not provided) in 125 mg/kg-day dams on GD 6-9. The overall weight gain in the 125 mg/kg-day group was approx. 30% lower than controls during GD 6-16. Food consumption was reduced approximately 25% on GD 6-9, and water consumption increased by the same amount on GD 9-12 and 12-15. There were no significant effects on absolute or relative organ weights, or on uterine weights or pregnancy parameters (including number of litters, corpora lutea per dam, implantations per dam, live fetuses per litter, resorptions, fetal body weight). The only treatment-related effect was a significant increase in the incidence of delayed ossification of the bones of the skull among fetuses at 125 mg/kg-day. All other parameters were comparable to the controls. LOAEL (maternal toxicity) = 125 mg/kg-day (based on effect on body weight) NOAEL = (maternal toxicity) = 30 mg/kg-day LOAEL = (developmental toxicity) = 125 mg/kg-day (based on delayed ossification of skull bones) NOAEL = (developmental toxicity) = 30 mg/kg-day http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 (2) In a prenatal developmental toxicity study, pregnant New Zealand white rabbits (18/dose) were administered 1,2-dichloropropane (>99% purity) in corn oil via gavage at 0, 15, 50, or 150 mg/kg-day during gestation days 7-19. Maternal observations included clinical signs, food and water intake, body weight measurements and liver, kidney, spleen and gravid uterine weights. Fetal observations included the number of corpora lutea, the number and position of implantations, and the number of live and dead fetuses, sex and body weight of each fetus, gross external alterations, visceral alterations and skeletal abnormalities. 16 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 One rabbit from the high dose group died on GD 22; no cause of death could be identified at necropsy. The remainder of the high dose does exhibited intermittent anorexia. There were no other significant changes in behavior or demeanor among rabbits during the course of the study. Body weight gain among the high dose does was significantly (significance not provided) lower than that of the controls (165 g compared to a net gain of 49 g in the controls during GD 7-20), although there was no effect on absolute body weights. At 150 mg/kg-day decreases in red cell counts, hemoglobin concentration and hematocrit; all decreased by 18-20% while platelet and white cell counts were increased 20-25%. The percentage of reticulocytes was approximately doubled at 150 mg/kg-day animals when compared to the controls. There were no significant effects on absolute or relative organ weights, or on uterine weights or pregnancy parameters (including number of litters, corpora lutea per dam, implantations per dam, live fetuses per litter, resorptions, fetal body weight). There was no increase in the incidence of malformations in any of the treated groups when compared with the controls. Fetal variations were present in both control and treated groups. The only treatment-related effect was a significant increase in the incidence of delayed ossification of the bones of the skull among fetuses at 150 mg/kg-day. All other parameters were comparable to the controls. LOAEL (maternal toxicity) = 150 mg/kg-day (based on effects on body weight and hematology parameters) NOAEL (maternal toxicity) = 50 mg/kg-day LOAEL (Developmental toxicity) = 150 mg/kg-day (based on delayed ossification of skull bones) NOAEL (developmental toxicity) = 50 mg/kg-day http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 Genetic Toxicity - Gene Mutation C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) In vitro (1) In bacterial reverse mutation (preincubation) assay, Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were exposed to 1,2-dichloroprapane (>99% purity) at 0 (DMSO), 33, 100, 333, 1000 and 2000 |ig/plate with and without metabolic activation using triplicate plates. The assay was run in duplicate. There is no information on the controls used or their responses. The cytotoxic concentration was >2000 |ig/plate. There was no increase in number of revertants in any tester strains either with or without metabolic activation. 1,2-Dichloropropane is not mutagenic in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf 17 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 (2) In Ames test (plate incorporation method), Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were exposed to 1,2-dichloroprapane (purity not specified) at 0 (DMSO), 31.5, 100, 315, 1000 and 3150 |ig/plate with and without metabolic activation using duplicate plates. The assay was run in duplicate. Positive and solvent controls showed appropriate response. The cytotoxic concentration was >3150 |ig/plate. There was no mutagenic response either with or without metabolic activation. 1,2-Dichloropropane is not mutagenic in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf (3) In Ames test, Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were exposed to 1,2-dichloroprapane (purity not specified) vapor with and without metabolic activation under closed system (0.3 - 10 mL test substance placed in a desiccator). Positive control showed appropriate response. There was no mutagenic response for 1,2-Dichloropropane either with or without metabolic activation. 1,2-Dichloropropane is not mutagenic in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf (4) In two Ames tests Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 were exposed to 1,2-dichloroprapane (>99% purity) with and without metabolic activation at 10-10,000 |ig/plate and 100-1500 |ig/plate. Positive controls showed appropriate response. There was an increase in the number of revertants although the magnitude of the increase was not two-fold. The results were ambiguous. 1,2-Dichloropropane was a weakly mutagenic in this assay. (5) I ARC summarized the results obtained for 13 studies in Salmonella typhimurium strains with and without metabolic activation. Overall, 4 out of 13 results were positive in the absence of metabolic activation and 4 out 13 were positive in the presence of metabolic activation. 1,2-Dichloropropane was a weakly mutagenic in these assays. (6) In the mouse lymphoma assay, L5178Y cells were exposed to 1,2-dichloroprapane (purity not stated) in the presence of metabolic activation at 3.13-100 |ig/mL and one trial and 10-80 |ig/mL in the second. In the first trial, 50 |ig/mL induced a 2-3 fold increase in mutation frequency. A dose of 100 |ig/mL was lethal. In the second trial, dose-related increase in mutation frequency was seen over the 10-80 |ig/mL range with 80 |ig/mL being highly toxic. 1,2-Dichloropropane was mutagenic in the presence of metabolic activation in this assay. Genetic Toxicity — Chromosomal Aberrations C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) In vitro In an NTP chromosomal aberration test, Chinese Hamster Ovary (CHO) cells were exposed to 18 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 1,2-dichloroprapane (>99% purity) in the absence of metabolic activation at 0 (DMSO), 1180, 1370 and 1580 |ig/mL and in the presence of metabolic activation at 0 (DMSO), 460, 660 and 950 |ig/mL, Cells were harvested at appropriate time intervals and 100 cells per dose were scored for chromosomal aberrations. There was an increase in the aberrant cells after incubation with 1370 and 1580 |ig/mL in absence and with 660 and 950 |ig/mL in the presence of metabolic activation. Positive controls responded appropriately. 1,2-Dichloropropane induced chromosomal aberration in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf In vivo In a mouse micronucleus assay, CD-I mice (6 males/dose) were administered 1,2-dichloroprapane (>99% purity) via gavage (in corn oil) at 0, 150, 300, and 600 mg/kg-day on two consecutive days. After sacrifice 24 hours following the second dose, bone marrow cells were evaluated for the incidence of micronuclei in polychromatic erythrocytes (200 PCEs/animal). There was no statistically significant increase in the frequencies of micronucleated-PCEs compared to negative control. The positive control responded appropriately. 1,2-Dichloropropane did not induce micronuclei in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf Genetic Toxicity — Other C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) (1) In an NTP sister chromatid exchange assay, CHO cells were incubated with 1,2-dichloroprapane (>99% purity) at 112.7, 376 and 1127 |ig/mL in the absence and presence of metabolic activation. The solvent control was DMSO. There was an increase in the number of SCE/cell in the absence and presence of metabolic activation at 376 and 1127 |ig/mL. Positive controls responded appropriately. 1,2-Dichloropropane induced sister chromatid exchanges in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf (2) In a dominant lethal assay, Sprague-Dawley rats (30/dose) were administered 1,2-dichloroprapane (>99% purity) via drinking water at 0.024, 0.1, or 0.24% (equivalent to 0, 28, 91 or 162 mg/kg-day) for at least 13 weeks. The high dose was a saturated solution of 1,2-dichloroprapane in water. The rats were then mated with untreated females for two successive one-week periods. A positive control group was included in the study. The results showed mating and fertility indices were comparable between the control and treated groups, but decreased significantly in the positive controls. Slight variations in number of corpora lutea, number of implantations, pre-implantation losses and resorption rates were noted in the first or second week of mating at 28 and 162 mg/kg-day groups (91 mg/kg-day group was comparable to the control group), but the magnitude of the change was within the normal control ranges. The 19 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 positive control group showed a 2-fold increase in pre-implantation loss and a 10-fold increase in resorption rate. 1,2-Dichloropropane did not induce dominant lethal mutation in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf Additional Information Skin Irritation C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) White Vienna rabbits (2 males, 1 female) were administered undiluted, 0.5 mL 1,2-dichloropropane (>99% purity) on to the skin for 4 hrs under semi-occlusive conditions. After removal of the patch, the application site was cleaned with lutrol/water (1:1) and skin reactions were recorded at 24, 48, 72 hrs and 8 d post-treatment. Redness and edema was observed in all animals at 24 hr; redness persisted in all animals up to 72 hr and in one animal at 8 d observation. Flaking skin at application site was seen in all animals. 1,2-Dichloropropane was slightly irritating to rabbit skin in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf Eye Irritation C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) A single rabbit (strain not provided) was instilled undiluted, 0.05 mL 1,2-dichloropropane (>99% purity) into the conjunctival sac. The reactions were recorded at 1 and 24 hr. Slight redness and edema with slight opacity were present 1 hr post-treatment, with marked redness and edema and slight opacity at 24 hr. These effects were fully reversed after 8 days (no interim results are available). 1,2-Dichloropropane was irritating to rabbit eyes in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf 20 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 Sensitization C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) In a mouse local lymph node assay, six female BALB/c mice/dose received topical applications (25 |iL/ear, total 50 |iL/mouse), of 5, 20, 80% 1,2-dichloropropane (>99% purity) in aceton:olive oil, on three consecutive days. On day 6, all mice received a 250 |iL intravenous injection of 3H-thymidine and were sacrificed 5 hours later. Cell suspensions were prepared and counted for radioactivity. 1,2-dichloropropane did not stimulate proliferation of lymphocytes in the lymph nodes. The positive controls responded appropriately. 1,2-dichloropropane is not sensitizer in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-b4d6965a-a60a-42a3-8592-6bla2d50a665 DISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-b4d6965a-a60a-42a3-8592-6bla2d50a665 Carcinogenicity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) (1) In an NTP toxicity and carcinogenicity study, Fischer rats (50/sex/dose) were administered 1,2-dichloropropane (>99% purity) via gavage, in corn oil, at 0, 62 and 125 mg/kg-day (males) and 0, 125, 250 mg/kg-day (females) for 103 weeks. No significant or treatment-related increase in tumor incidence was observed in male rats given 0, 62 or 125 mg/kg-day fori 03 wk. Female rats given 125 or 250 mg/kg-day showed a positive trend for mammary adenocarcinoma incidence (adjusted rates: 3%, 5%, 27%), which was increased significantly in the high dose group. These were neither metastatic, anaplastic, nor highly invasive, and were diagnosed by some NTP pathologists as highly cellular fibroadenomas. Affected high dose females showed a marked decrease in survival (32% alive at study end versus 74%-86% in the control and low-dose groups) and a significant reduction (>20%) in body weight, suggesting that 250 mg/kg bw/day was in excess of the Maximum Tolerated Dose for the test substance. There was no increase in liver tumors despite the occurrence of chronic histopathological changes, including foci of clear change and necrosis. Based on these findings, NTP concluded that "under the conditions of this study, there was no evidence that 1,2-dichloropropane was a carcinogen in male rats receiving 62 or 125 mg/kg-day. For female rats, there was equivocal evidence of carcinogenicity in that 250 mg/kg-day 21 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 1,2-dichloropropane caused a marginally increased incidence of adenocarcinoma in the mammary gland; these borderline malignant lesions occurred concurrently with decreased survival and reduced body weight gain." 1,2-Dichloropropane showed equivocal evidence of an increase in tumor incidence. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 (2) In an NTP toxicity and carcinogenicity study, B6C3F1 mice (50/sex/dose) were administered 1,2-dichloropropane (>99% purity) via gavage, in corn oil, at 0, 125, 250 mg/kg-day for 103 weeks. Dose-related increases were observed for adenomas of the liver in both male (control, 7/50; low-dose, 10/50; high-dose, 17/50) and female (1/50, 5/50, 5/50) mice. The increase in the frequency of liver carcinomas supported the evidence that there was a neoplastic response in the mouse liver for both sexes (males, 11/50, 17/50, 16/50; females: 1/50, 3/50, 4/50). Hepatcytomegaly and hepatic necrosis were increased in male mice, but not in female mice. NTP concluded that "there was some evidence of carcinogenicity for male and female B6C3F1 mice exposed to 1,2-dichloropropane, as indicated by increased incidence of hepatocellular neoplasms, primarily adenomas." 1,2-Dichloropropane showed increased tumor incidence in this assay. http://www.chem.unep.ch/irptc/sids/OECDSIDS/78875.pdf http://apps.echa.europa.eu/registered/data/dossiers/PISS-9d8b8392-060b-2142-e044- 00144f67d249/AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 PISS-9d8b8392-060b-2142- e044-00144f67d249.html#AGGR-0a227e5d-81 c0-4c31 -bb20-d08ff8be6167 IARC concluded that there is limited evidence in experimental animals for the carcinogenicity of 1,2-dichloropropane. IARC's overall classification is "1,2-Pichloropropane is not classifiable as to its carcinogenicity to humans (Group 3 http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-90.pdf Neurotoxicity C3 chlorinated hydrocarbon stream (CASRN 68390-96-5) No data. 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) In a 13-week neurotoxicity study, Fischer 344 rats (15/sex/dose) were administered 1,2-dichloropropane (>99% purity) via gavage, in corn oil, at 0, 20, 65 and 200 mg/kg-day. After 13-wk treatment, 4 rats/sex/dose were selected for terminal examinations. The remaining rats were allowed a 9-wk recovery period, and 5 rats/sex/dose were taken for necropsy. All rats survived the 13-wk treatment period. Clinical signs included lacrimation and blinking in a dose- dependent manner on the first day, with decreased spontaneous motor activity (for up to 4 hr post-treatment in the high dose group). No effect on motor activity was noticeable in the low- and mid dose groups by day 3, or in the high dose animals by day 4. No other treatment-related 22 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 clinical signs were present. At 200 mg/kg-day, males had a significant decrease in body weight during the first week which persisted throughout the 13-wk dosing period (6-10% reduction overall). At 65 mg/kg-day, the decrease in body weights of males was seen which was not always significant. In females, body weights were also slightly decreased (equivocal, non-significant effect). During functional observation battery evaluation, no differences were seen between control and treated animals at any intervals. No significant differences between control and treated animals were noted in motor activity parameters. There was a slight but significant decrease in body temperature at 200 mg/kg-day at the end of the main phase of the study (0.6 °C reduction in females, 0.3 °C reduction in males). No treatment-related changes were seen at necropsy. Absolute brain weight was decreased by approx. 10% at 200 mg/kg-day animals, probably reflecting the lower body weight. Relative brain weight was marginally increased. No treatment-related changes were seen during the histopathological examination. Recovery animals showed continued decreases in body weights at 200 mg/kg-day throughout the 9-wk recovery phase (significant 8% decrease in high dose males at wk 22). Males at 65 mg/kg-day and females at 200 mg/kg-day showed a non-significant 3-4% reduction in body weights over the same period. Body temperature differences at 200 mg/kg-day generally remained during the recovery period (significantly decreased by 0.6 - 1.0 degree C in females throughout recovery phase, 0.3-0.5 degree C reduction in males during wk 1-4 only). No gross lesions were identified at necropsy. LOAEL for systemic effects,™^ = 65 mg/kg-day (based on effect on body weight) NOAEL for systemic effectSmaies = 20 mg/kg-day LOAEL for systemic effectSfemaies = 200 mg/kg-day (based on effect on body weight) NOAEL for systemic effectSfemaies = 65 mg/kg-day NOAEL for neurotoxicitymaies/femaies = 200 mg/kg-day (highest dose tested) Conclusion: No human health data are available for C3 chlorinated hydrocarbon stream. Data for supporting chemical 1,2-dichloropropane are used to address all SIDS endpoints. Acute oral and dermal toxicity of the supporting chemical 1,2-dichloropropane in rats and rabbits, respectively, is low. Acute inhalation toxicity in rats is moderate. In a 13-week repeated-dose toxicity gavage study in rats, mortality, decreased body weight and liver effects (centrilobular congestion, hepatic fatty change and centrilobular necrosis) were seen at > 500 mg/kg-day. The NOAEL is 250 mg/kg-day. In a 13-week repeated-dose toxicity gavage study in mice, no significant effects were seen; the NOAEL is 500 mg/kg-day. In 103-week toxicity and carcinogenicity gavage study in rats, the NOAEL for males is 62 mg/kg-day based on effect on body weight at > 125 mg/kg-day; the NOAEL for females is 125 mg/kg-day based on mortality and effect on body weight and liver at > 250 mg/kg-day. In mice, following 103 weeks of repeated gavage administration of 1,2-dichloropropne, liver and stomach lesions were noted at >125 mg/kg-day; NOAEL is not established. Following repeated inhalation exposure to rats for 13 weeks, 1,2-dichlorproapane resulted in effect on body weight and nasal epithelial hyperplasia at >15 ppm (-0.068 mg/L-day); the NOAEC is not established. Inhalation exposure of mice to 1,2-dichlorproapane for 13 weeks 23 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 resulted in no significant effects; the NOAEC is 150 ppm (0.675 mg/L-day), the highest concentration tested. In rabbits, inhalation exposure of to 1,2-dichlorproapane for 13 weeks resulted in effects on hematology parameters in males >150 ppm (0.675 mg/L-day) and in females > 500 ppm (2.25 mg/L-day); for males NOAEC is not established; while in females the NOAEC is 150 ppm (0.675 mg/L-day). In a 2-generation reproductive toxicity study in rats via drinking water with supporting chemical, 1,2-dichloropropane, parental systemic toxicity NOAEL is 0.024% (20-30 mg/kg-day) based on decreased body weights at >0.1%; the NOAEL for reproductive toxicity is 0.24% (130-250 mg/kg-day), the highest dose tested at the limit of solubility and the NOAEL for offspring toxicity is 0.1% (70-130 mg/kg-day) based on effect on body weight. In a prenatal developmental toxicity gavage study of supporting chemical, 1,2-dichlorpropane, in rats, the NOAEL for maternal and developmental toxicity is 30 mg/kg-day based on decreased body weights in dams and delayed ossification of skull bones in pups, respectively, at 125 mg/kg-day. In the prenatal developmental toxicity gavage study of supporting chemical, 1,2-dichlorpropane in rabbits, the NOAEL for maternal and developmental toxicity is 50 mg/kg-day based on decreased body weights and effect on hematology parameters in does and delayed ossification of skull bones in pups, respectively, at 150 mg/kg-day. The supporting chemical, 1,2-dichloropropane is weakly mutagenic in bacteria and mutagenic in mammalian cells in vitro. The supporting chemical, 1,2-dichloropropane induced chromosomal aberrations in vitro but did not increase micronuclei in mice in vivo. The supporting chemical, 1,2-dichloropropane induced sister chromatid exchanges in vitro but it did not induce dominant lethal mutations in vivo. The supporting chemical, 1,2-dichloropropane is irritating to rabbit skin and eyes. In the mouse local lymph-node assay, 1,2-dichloropropane was not a skin sensitizer. The supporting chemical, 1,2-dichloropropane increased tumor incidence in mice but showed equivocal evidence of an increased tumor incidence in rats. In a 13-week neurotoxicity study in rats, the supporting chemical, 1,2-dichloropropane did not show neurotoxicity when administered up to 200 mg/kg-day. 24 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 Table 3. Summary of the Screening Information Data Set under the U.S. HPV Challenge Program - Human Health Data Endpoint SPONSORED CHEMICAL Chlorinated C3 Stream (68390-96-5) SUPPORTING CHEMICAL 1,2-Dichloropropane (78-87-5) Acute Toxicity Oral LD50 (mg/kg) No data 2200 (RA) 2200 Acute Toxicity Inhalation LC50 (mg/L) No data 9.4 (RA) 9.4 Acute Toxicity Dermal LD50 (mg/kg) No data 10,100 (RA) 10,100 Repeated-Dose Toxicity NOAEL/LOAEL Oral No data (13 wk, rat) NOAEL = 250 LOAEL = 500 (13 wk, rat) NOAEL = 250 LOAEL = 500 (13 wk, mice) NOAEL = 500 Highest dose tested (13 wk, mice) NOAEL = 500 Highest dose tested (103 wk, rat) NOAEL = 62/125 (m/f) LOAEL = 125/250 (m/f) (103 wk, rat) NOAEL = 62/125 (m/f) LOAEL = 125/250 (m/f) 103 wk, mice) NOAEL = not established LOAEL = 125 (RA) 103 wk, mice) NOAEL = not established LOAEL = 125 25 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 Table 3. Summary of the Screening Information Data Set under the U.S. H PV Challenge Program - Human Health Data Endpoint SPONSORED CHEMICAL Chlorinated C3 Stream (68390-96-5) SUPPORTING CHEMICAL 1,2-Dichloropropane (78-87-5) Repeated-Dose Toxicity NOAEC/LOAEC Inhalation (mg/L-day) No data (13 wk, rat) NOAEC = not established LOAEC = 0.068 (13wk, mice) NOAEC = 0.675 Highest conc. Tested (13 wk, rabbit) NOAEC = not established (m) LOAEC = 0.675 NOAEC = 0.675(f) LOAEC = 2.25 (RA) (13 wk, rat) NOAEC = not established LOAEC = 0.068 (13wk, mice) NOAEC = 0.675 Highest conc. Tested (13 wk, rabbit) NOAEC = not established (m) LOAEC = 0.675 NOAEC = 0.675(f) LOAEC = 2.25 Reproductive Toxicity NOAEL/LOAEL (mg/kg-day) Systemic Toxicity Offspring Toxicity Reproductive Toxicity No data (2-gen, drinking water) NOAEL = 20-30 LOAEL = 70-130 NOAEL = 70-130 LOAEL= 130-250 NOAEL = 130-250 Highest dose tested (RA) (2-gen, drinking water) NOAEL = 20-30 LOAEL = 70-130 NOAEL LOAEL = =70-130 130-250 NOAEL = 130-250 Highest dose tested 26 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 Table 3. Summary of the Screening Information Data Set under the U.S. H PV Challenge Program - Human Health Data Endpoint SPONSORED CHEMICAL SUPPORTING CHEMICAL Chlorinated C3 Stream 1,2-Dichloropropane (68390-96-5) (78-87-5) Developmental Toxicity No data NOAEC/LOAEC (rat) (rat) Inhalation (ppm) NOAEL = 30 NOAEL = 30 Maternal Toxicity LOAEL = 125 LOAEL = 125 NOAEL = 30 NOAEL = 30 Developmental Toxicity LOAEL = 125 LOAEL = 125 (rabbit) (rabbit) NOAEL = 50 NOAEL = 50 Maternal Toxicity LOAEL = 150 LOAEL = 150 Developmental Toxicity NOAEL = 50 NOAEL = 50 LOAEL = 150 LOAEL = 150 (RA) Genetic Toxicity - Gene No data Mutation (Bacteria) Negative Negative In vitro (RA) Genetic Toxicity - Gene No data Mutation (Mamm.Cells) Positive Positive In vitro (RA) Genetic Toxicity - No data Chromosomal Aberrations Positive Positive In vitro (RA) Genetic Toxicity - No data Chromosomal Aberrations Negative Negative In vivo (RA) Genetic Toxicity - Chromosomal Aberrations Other No data Sister Chromatic Exchange Positive Positive Dominant Lethal Negative Negative (RA) 27 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 Table 3. Summary of the Screening Information Data Set under the U.S. H PV Challenge Program - Human Health Data Endpoint SPONSORED CHEMICAL Chlorinated C3 Stream (68390-96-5) SUPPORTING CHEMICAL 1,2-Dichloropropane (78-87-5) Additional Information Skin Irritation Eye Irritation Sensitization Neurotoxicity Carcinogenicity - Irritating Irritating Negative Negative Equivocal (rat) Increased tumor incidence (mice) Measured data in bold; RA = read-across; - indicates endpoint not addressed for this chemical; m=male; f = female 4. Hazard to the Environment A summary of aquatic toxicity data submitted for SIDs endpoints is provided in Table 4. Acute Toxicity to Fish 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) (1) Fathead minnows (Pimephalespromelas) were exposed to unspecified measured concentrations of 1,2-dichlorpropane under flow-through conditions for 96 hours. A 96-hour LC50 of 140 mg/L was reported. 96-hour LC50 =140 mg/L (2) Fathead minnows (Pimephalespromelas) were exposed to unspecified measured concentrations of 1,2-dichlorpropane under flow-through conditions for 96 hours. A 96-hour LC50 of 139 mg/L was reported. 96-hour LC50 =139 mg/L (3) Bluegills (Lepomis macrochirus) were exposed to unspecified concentrations of 1,2-dichlorpropane under static conditions for 96 hours. A 96-hour LC50 of 280 mg/L was reported. 96-hour LC50 =280 mg/L (4) Bluegills (Lepomis macrochirus) were exposed to unspecified concentrations of 1,2-dichlorpropane under static conditions for 96 hours. A 96-hour LC50 of 320 mg/L was reported. 96-hour LC50 =320 mg/L (5) Silversides (Menidia beryllina) were exposed to unspecified concentrations of 28 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 1,2-dichlorpropane under static conditions for 96 hours. A 96-hour LC50 of 240 mg/L was reported. 96-hour LC50 =240 mg/L Chronic Toxicity to Fish 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) (1) Fathead minnows (Pimephalespromelas) were exposed to unspecified measured concentrations of 1,2-dichlorpropane under flow-through conditions for 28 days. A 28-day NOEC of 6 mg/L was reported. 28-day NOEC = 6 mg/L (2) Fathead minnows (Pimephalespromelas) were exposed to unspecified measured concentrations of 1,2-dichlorpropane under flow-through conditions for 28 days. A 28-day NOEC of 11 mg/L was reported. 28-day NOEC = 11 mg/L Acute Toxicity to Aquatic Invertebrates 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) (1) Water fleas (Ceriodaphnia dubia) were exposed to unspecified concentrations of 1,2-dichlorpropane under static conditions for 48 hours. A 48-hour LC40 of 120 mg/L was reported. 48-hour LC50 =120 mg/L (2) Water fleas (Daphnia magna) were exposed to unspecified concentrations of 1,2-dichlorpropane under flow-through conditions for 48 hours. A 48-hour LC40 of 55 mg/L was reported. 48-hour LC50 = 55mg/L (3) Opossum shrimp (Americamysis bahia) were exposed to unspecified measured concentrations of of 1,2-dichlorpropane under flow-through conditions for 96 hours. A 96-hour LC40 of 24 mg/L was reported. 48-hour LC50 = 24 mg/L Chronic Toxicity to Aquatic Invertebrates Supporting Chemical 1,2-Dichloropropane (CASRN 78-87-5) (1) Water fleas (Daphnia magna) were exposed to unspecified concentrations of 1,2-dichlorpropane under flow-through conditions for 21days. A 21-day NOEC of 8.3 mg/L was reported. 21-day NOEC = 8.3 mg/L 29 ------- U.S. Environmental Protection Agency Hazard Characterization Document December, 2012 (2) Mysid shrimp (Mysidopsis bahia) were exposed to unspecified concentrations of 1,2-dichloropropane under flow-through conditions for 28 days. A 28-day NOEC of 4.1 mg/L was reported. 28-day NOEC = 4.1 mg/L Toxicity Aquatic Plants 1,2-Dichloropropane (CASRN 78-87-5, supporting chemical) Diatoms (Skeletonema costatum) were exposed to unspecified measured concentrations of 1,2-dichlorpropane under static conditions for 120 hours. A 72-hour EC50 of 14.7 mg/L (growth) and a 72-hour EC50 (biomass) of 15.1 were reported. 72-hour EC50 =14.7 mg/L (growth) 72-hour EC50 =15.1 mg/L (biomass) Conclusion: For ecotoxicity, data for all endpoints are based on the supporting chemical of 1,2-dichloropropane. The 96-h LC50 values for chlorinated C3 stream for fish range between 130 and 320 mg/L. The chronic 28-day toxicity values for chlorinated C3 stream for fish range between 6 and 11 mg/L. The 48-h LC50 values for chlorinated C3 stream for aquatic invertebrates range between 24 and 120 mg/L. The chronic 21-day NOEC values for chlorinated C3 stream for aquatic invertebrates range between 4.1 and 8.3 mg/L. The 72-h EC50 of chlorinated C3 stream for aquatic plants is 14.7 mg/L (growth) and 15.1 mg/L (biomass). Table 4. Screening Information Data Set as submitted under the U.S. HPV Challenge Program Aquatic Toxicity Data Endpoints Chlorinated C3 stream Propane, 1,2-dichloro- (68390-96-5) (78-87-5) Fish RA 139 - 320 96-h LC50 (mg/L) 139-320 Aquatic Invertebrates RA 24 - 120 48-h EC50 (mg/L) 24 - 120 Aquatic Plants 72-h EC50 (mg/L) RA (growth rate) 14.7 14.7 (biomass) 15.1 15.1 Fish RA 6-11 Chv (NOEC) 6-11 Aquatic Invertebrates RA Chv. (NOEC) 4.1 - 8.3 4.1 - 8.3 measured data are in bold text; (m) = measured data (i.e., derived from testing); (RA) = Read-Across; 30 ------- |