TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-20-0167 Number: P-20-0167 TSCA Section 5(a)(3) Determination: The chemical substance is not likely to present an unreasonable risk (5(a)(3)(C)) Chemical Name: Generic: Phenylene, alkyl and polycarbomonocycle substituted, 1,2-dicarboxylate. Conditions of Use (intended, known, or reasonably foreseen)1: Intended conditions of use (generic): Manufacture and process for use and use as a catalyst, consistent with the manufacturing, processing, use, distribution, and disposal information described in the PMN. Known conditions of use: Applying such factors as described in footnote 1, EPA evaluated whether there are known conditions of use and found none. Reasonably foreseen conditions of use: Applying such factors as described in footnote 1, EPA evaluated whether there are reasonably foreseen conditions of use and found none. Summary: The chemical substance is not likely to present an unreasonable risk of injury to health or the environment, without consideration of costs or other nonrisk factors, including an unreasonable risk to a potentially exposed or susceptible subpopulation identified as relevant by the Administrator under the conditions of use, based on the risk assessment presented below. Although EPA estimated that the new chemical substance could be persistent, the substance has low potential for bioaccumulation, such that repeated exposures are not expected to cause food- chain effects via accumulation in exposed organisms. Based on physical/chemical properties, data submitted for the new chemical substance, and test data on analogous chemical substances, EPA estimates that the chemical substance has low environmental hazard and low human health hazard. EPA concludes that the new chemical is not likely to present unreasonable risk to human health or the environment under the conditions of use. 1 Under TSCA § 3(4), the term "conditions of use" means "the circumstances, as determined by the Administrator, under which a chemical substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used, or disposed of." In general, EPA considers the intended conditions of use of a new chemical substance to be those identified in the section 5(a) notification. Known conditions of use include activities within the United States that result from manufacture that is exempt from PMN submission requirements. Reasonably foreseen conditions of use are future circumstances, distinct from known or intended conditions of use, under which the Administrator expects the chemical substance to be manufactured, processed, distributed, used, or disposed of. The identification of "reasonably foreseen" conditions of use will necessarily be a case-by-case determination and will be highly fact-specific. Reasonably foreseen conditions of use will not be based on hypothetical or conjecture. EPA's identification of conditions of use includes the expectation of compliance with federal and state laws, such as worker protection standards or disposal restrictions, unless case-specific facts indicate otherwise. Accordingly, EPA will apply its professional judgment, experience, and discretion when considering such factors as evidence of current use of the new chemical substance outside the United States, evidence that the PMN substance is sufficiently likely to be used for the same purposes as existing chemical substances that are structurally analogous to the new chemical substance, and conditions of use identified in an initial PMN submission that the submitter omits in a revised PMN. The sources EPA uses to identify reasonably foreseen conditions of use include searches of internal confidential EPA PMN databases (containing use information on analogue chemicals), other U.S. government public sources, the National Library of Medicine's Hazardous Substances Data Bank (HSDB), the Chemical Abstract Service STN Platform, REACH Dossiers, technical encyclopedias (e.g., Kirk-Othmer and Ullmann), and Internet searches. ------- TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-20-0167 Fate: Environmental fate is the determination of which environmental compartment(s) a chemical moves to, the expected residence time in the environmental compartment(s) and removal and degradation processes. Environmental fate is an important factor in determining exposure and thus in determining whether a chemical may present an unreasonable risk. EPA estimated physical/chemical and fate properties of the new chemical substance using data submitted for the new chemical substance and EPI (Estimation Program Interface) Suite™ (http://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-program-interface). In wastewater treatment, the new chemical substance is expected to be removed with an efficiency of 90 to 95% due to sorption and biodegradation. Removal of the new chemical substance by biodegradation is moderate. Sorption of the new chemical substance to sludge, soil, and sediment is expected to be strong. Migration of the new chemical substance to groundwater is expected to be negligible due to biodegradation. Due to low estimated vapor pressure and Henry's law constant, the new chemical substance is expected to undergo negligible volatilization to air. Overall, these estimates indicate that the new chemical substance has low potential to volatilize to air or migrate to groundwater. Persistence : Persistence is relevant to whether a new chemical substance is likely to present an unreasonable risk because chemicals that are not degraded in the environment at rates that prevent substantial buildup in the environment, and thus increase potential for exposure, may present a risk if the substance presents a hazard to human health or the environment. EPA estimated degradation half-lives of the new chemical substance using data submitted for the new chemical substance and EPI Suite™. EPA estimated that the new chemical substance's aerobic and anaerobic biodegradation half-lives are 2 to 6 months. These estimates indicate that the new chemical substance may be persistent in aerobic environments (e.g., surface water) and anaerobic environments (e.g., sediment). -2 Bioaccumulation : Bioaccumulation is relevant to whether a new chemical substance is likely to present an unreasonable risk because substances that bioaccumulate in aquatic and/or terrestrial species pose the potential for elevated exposures to humans and other organisms via food chains. EPA estimated the potential for the new chemical substance to bioaccumulate using EPI Suite™. EPA estimated that the new chemical substance has low bioaccumulation potential based on the BCFBAF model result, mitigated by expected metabolism (bioconcentration factor = 1,995 [estimated by linear regression from log Kow] and bioaccumulation factor =1.8 2 Persistence: A chemical substance is considered to have limited persistence if it has a half-life in water, soil or sediment of less than 2 months or there are equivalent or analogous data. A chemical substance is considered to be persistent if it has a half-life in water, soil or sediments of greater than 2 months but less than or equal to 6 months or if there are equivalent or analogous data. A chemical substance is considered to be very persistent if it has a half- life in water, soil or sediments of greater than 6 months or there are equivalent or analogous data. (64 FR 60194; November 4, 1999) 3 Bioaccumulation: A chemical substance is considered to have a low potential for bioaccumulation if there are bioconcentration factors (BCF) or bioaccumulation factors (BAF) of less than 1,000 or there are equivalent or analogous data. A chemical substance is considered to be bioaccumulative if there are BCFs or BAFs of 1,000 or greater and less than or equal to 5,000 or there are equivalent or analogous data. A chemical substance is considered to be very bioaccumulative if there are BCFs or BAFs of 5,000 or greater or there are equivalent or analogous data. (64 FR 60194; November 4 1999) ------- TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-20-0167 [estimated by the Arnot-Gobas method (2003)]).4 The bioaccumulation factor was selected because this model accounts for metabolism of the new chemical substance. Although EPA estimated that the new chemical substance could be persistent, the substance has low potential for bioaccumulation, such that repeated exposures are not expected to cause food-chain effects via accumulation in exposed organisms. Human Health Hazard5: Human health hazard is relevant to whether a new chemical substance is likely to present an unreasonable risk because the significance of the risk is dependent upon both the hazard (or toxicity) of the chemical substance and the extent of exposure to the substance. EPA estimated the human health hazard of this chemical substance based on its estimated physical/chemical properties, available data on the new chemical substance and potential metabolites, and by comparing it to structurally analogous chemical substances for which there is information on human health hazard. Absorption of the new chemical substance is expected to be poor to moderate through the skin, and nil through the gastro intestinal (GI) tract and lungs, based on physical/chemical properties. Submitted tests of the new chemical substance reported the test substance as having no effects in an acute oral toxicity study (OECD 423), not irritating to skin or eyes in vitro (OECD 439 and 492), not genotoxic in vitro (OECD 471, 476, and 487), and negative for estrogenic or androgenic agonistic and antagonistic activity in vitro (OECD 455). For the new chemical substance, EPA identified no hazards based on new chemical substance data, analogue data, or structure. Environmental Hazard6: Environmental hazard is relevant to whether a new chemical substance is likely to present unreasonable risk because the significance of the risk is dependent 4 Arnot JA, Gobas FAPC. 2003. A generic QSAR for assessing the bioaccumulation potential of organic chemicals in aquatic food webs. QSAR and Combinatorial Science 22: 337-345. 5 A chemical substance is considered to have low human health hazard if effects are observed in animal studies with a No Observed Adverse Effect Level (NOAEL) equal to or greater than 1,000 mg/kg/day or if there are equivalent data on analogous chemical substances; a chemical substance is considered to have moderate human health hazard if effects are observed in animal studies with a NOAEL less than 1,000 mg/kg/day or if there are equivalent data on analogous chemical substances; a chemical substance is considered to have high human health hazard if there is evidence of adverse effects in humans or conclusive evidence of severe effects in animal studies with a NOAEL of less than or equal to 10 mg/kg/day or if there are equivalent data on analogous chemical substances. EPA may also use Benchmark Dose Levels (BMDL) derived from benchmark dose (BMD) modeling as points of departure for toxic effects. See https://www.epa.gov/bmds/what-benchmark-dose-software-bmds. Using this approach, a BMDL is associated with a benchmark response, for example a 5 or 10 % incidence of effect. The aforementioned characterizations of hazard (low, medium, high) would also apply to BMDLs. In the absence of animal data on a chemical or analogous chemical substance, EPA may use other data or information such as from in vitro assays, chemical categories (e.g., Organization for Economic Co-operation and Development, 2014 Guidance on Grouping of Chemicals, Second Edition. ENV/JM/MONO(2014)4. Series on Testing & Assessment No. 194. Environment Directorate, Organization for Economic Co-operation and Development, Paris, France. (http://www.oecd.org/officialdocuments/publicdisplavdocumentpdf/?cote=env/im/mono(2014)4&doclanguage=en)). structure-activity relationships, and/or structural alerts to support characterizing human health hazards. 6 A chemical substance is considered to have low ecotoxicity hazard if the Fish, Daphnid and Algae LC50 values are greater than 100 mg/L, or if the Fish and Daphnid chronic values (ChVs) are greater than 10.0 mg/L, or there are not effects at saturation (occurs when water solubility of a chemical substance is lower than an effect concentration), or the log Kow value exceeds QSAR cut-offs. A chemical substance is considered to have moderate ecotoxicity hazard if the lowest of the Fish, Daphnid or Algae LC50s is greater than 1 mg/L and less than 100 mg/L, or where the Fish or Daphnid ChVs are greater than 0.1 mg/L and less than 10.0 mg/L. A chemical substance is considered to have ------- TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-20-0167 upon both the hazard (or toxicity) of the chemical substance and the extent of exposure to the substance. EPA estimated environmental hazard of this new chemical substance using hazard data for an analogous chemical, acute toxicity data submitted for the new chemical substance, and predictions based on the negligible water solubility of the new chemical substance. This n substance falls within the TSCA New Chemicals Category of Esters. Acute and chronic aqueous-only toxicity values estimated for fish, aquatic invertebrates, and algae are all no effects at saturation. Acute (on the new chemical substance) and chronic (analogue test data) sediment toxicity values measured for aquatic invertebrates are all > 400 mg/kg. These toxicity values indicate that the new chemical substance is expected to have low environmental hazard. Because aqueous-only hazards are not expected up to the water solubility limit, acute and chronic concentrations of concern are not identified. Exposure and Risk Characterization: The exposure to a new chemical substance is potentially relevant to whether a new chemical substance is likely to present unreasonable risks because the significance of the risk is dependent upon both the hazard (or toxicity) of the chemical substance and the extent of exposure to the substance. EPA considers workers to be a potentially exposed or susceptible subpopulation (PESS) on the basis of greater exposure potential compared to the general population. EPA also considers PESS in conducting general population drinking water exposures by evaluating risks associated with water intake rates for multiple age groups, ranging from infants to adults. EPA considers consumers of specific products to be a potentially exposed or susceptible subpopulation on the basis of greater exposure potential compared to the general population who do not use specific products. Due to low hazard, EPA believes that this chemical substance would be not likely to present an unreasonable risk even if potential exposures were high. Therefore, EPA concludes that the new chemical substance is not likely to present unreasonable risk under the conditions of use. 03/26/21 IsL Date: Madison H. Le, Director New Chemicals Division Office of Pollution Prevention and Toxics high ecotoxicity hazard, or if either the Fish, Daphnid or Algae LC50s are less than 1 mg/L, or any Fish or Daphnid ChVs is less than 0.1 mg/L (Sustainable Futures https://www.epa.gov/sustainable-futures/sustainable-futures-p2- framework-manual). 7 TSCA New Chemicals Program (NCP) Chemical Categories, https://www.epa.gov/reviewing-new-chemicals- under-toxic-substances-control-act-tsca/chemical-categories-used-review-new. ------- TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-20-0167 U.S. Environmental Protection Agency ------- |