TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0155, P-19- 0156 and P-19-0157 Number: P-19-0155, P-19-0156 and P-19-0157 TSCA Section 5(a)(3) Determination: The chemical substances are not likely to present an unreasonable risk (5(a)(3)(C)) Chemical Name: Specific (P-19-0155): Amides, from C8-18 and C18-unsatd. glycerides and diethylenetriamine, ethoxylated, CASRN: 2173332-72-2; Specific (P-19-0156): Amides, from diethylenetriamine and palm kernel-oil, ethoxylated, CASRN: 2173332-69-7; Specific (P-19-0157): Amides, from coconut oil and diethylenetriamine, ethoxylated, CASRN: 2173332-70-0. Conditions of Use (intended, known, or reasonably foreseen)1: Intended conditions of use (specific): Import and use as adjuvants for industrial herbicide agrochemical formulations, 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 substances are 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. EPA estimated that the new chemical substances could have limited persistence and a low 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-19-0155, P-19- 0156 and P-19-0157 potential for bioaccumulation, such that repeated exposures are not expected to cause food-chain effects via accumulation in exposed organisms. Based on test data on the new chemical substances and analogous chemical substances, EPA estimates that the chemical substances have high environmental hazard and potential for the following human health hazards: lung effects, skin corrosion, skin sensitization, and systemic effects. EPA concludes that the new chemical substances are not likely to present an unreasonable risk under the conditions of use. 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 substances using data for analogue(s) (fatty amides, diethylene triamines, polyethoxylates) and EPI (Estimation Program Interface) Suite™ (http://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-program- interface). In wastewater treatment, the new chemical substances are expected to be removed with an efficiency of 90% due to sorption and biodegradation. Removal of the new chemical substances by biodegradation is moderate to high and destruction (mineralization) of the new chemical substances by biodegradation is partial to complete. Sorption of the new chemical substances to sludge is expected to be moderate to strong and to soil and sediment is expected to be low. Migration of the new chemical substances to groundwater is expected to be slow due to rapid biodegradation. Due to low estimated vapor pressure and Henry's law constant, the new chemical substances are expected to undergo negligible volatilization to air. Overall, these estimates indicate that the new chemical substances have 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 substances using data submitted for the new chemical substances. EPA estimated that the new chemical substances' aerobic biodegradation half-lives are < 2 months and anaerobic biodegradation half-lives are 2 to 6 months. These estimates indicate that the new chemical substances may have limited persistence in aerobic environments (e.g. surface water) and may be persistent in anaerobic environments (e.g., sediment). However, based on the high water solubility and low log Kow for these substances, it is not likely that these substances will accumulate in anaerobic environments; thus, their persistence was assessed based on the estimated half-lives in aerobic environments. 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) ------- TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0155, P-19- 0156 and P-19-0157 •j 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 substances to bioaccumulate using EPI Suite™. EPA estimated that the new chemical substances have low bioaccumulation potential based on BCFBAF model result < 1000 (bioconcentration factor = 3 [estimated] and bioaccumulation factor = 1 [estimated]). EPA estimated that the new chemical substances could have limited persistence and a low potential for bioaccumulation, such that repeated exposures are not expected to cause food-chain effects via accumulation in exposed organisms. Human Health Hazard4: 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 these chemical substances based on their estimated physical/chemical properties, available data on the new chemical substances, by comparing them to structurally analogous chemical substances for which there is information on human health hazard, and other structural information. Absorption is expected to be moderate through the skin, poor through the GI tract, and good through the lungs, based on physical/chemical properties. EPA identified lung effects (surfactancy) as a hazard based on structural alerts and skin corrosion and skin sensitization as hazards based on submitted data on the new chemical substances; systemic effects were identified as hazards based on analogue data. Submitted tests of the new chemical substances reported the test substances as not acutely toxic in rats (OECD 425, OECD 402), corrosive in rabbits (OECD 404), and positive for dermal "3 sensitization in mice (OECD 429). EPA identified a BMCL of 0.6 mg/m based on lung effects (surfactant effects) and a NOAEL of 150 mg/kg/day based on systemic effects, which were used 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) 4 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. ------- TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0155, P-19- 0156 and P-19-0157 to derive exposure route- and population-specific points of departure. EPA qualitatively evaluated corrosion and sensitization effects. Environmental Hazard5: Environmental hazard is relevant to whether a new chemical substance is likely to present 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 environmental hazard of these new chemical substances using acute toxicity data submitted for the new chemical substances and the Ecological Structure Activity Relationships (ECOSAR) Predictive Model (https://www.epa.gov/tsca-screening- tools/ecological-structure-activity-relationships-ecosar-predictive-model); specifically the QSAR for Amphoteric Surfactants. Acute toxicity values estimated for fish, aquatic invertebrates, and algae are 2.2 mg/L (ECOSAR), 5.1 mg/L (new chemical test data), and 0.11 mg/L (new chemical test data), respectively. Chronic toxicity values estimated for fish, aquatic invertebrates, and algae are 0.22 mg/L (ECOSAR), 0.51 mg/L (new chemical test data), and <0.02 mg/L (new chemical test data), respectively. These toxicity values indicate that the new chemical substances are expected to have high environmental hazard. Application of assessment factors of 4 and 10 to acute and chronic toxicity values, respectively, results in acute and chronic concentrations of concern of 0.028 mg/L (28 ppb) and 0.002 mg/L (2 ppb), respectively. Exposure: 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 estimates occupational exposure and environmental release of the new chemical substances under the intended conditions of use described in the PMNs using ChemSTEER (Chemical Screening Tool for Exposures and Environmental Releases; https://www.epa.gov/tsca-screening- tools/chemsteer-chemical-screening-tool-exposures-and-environmental-releases). EPA uses EFAST (the Exposure and Fate Assessment Screening Tool; https://www.epa.gov/tsca- screening-tools/e-fast-exposure-and-fate-assessment-screening-tool-version-2014) to estimate general population, consumer, and environmental exposures. 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 5 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 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). ------- TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0155, P-19- 0156 and P-19-0157 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. For this assessment, EPA assessed worker exposure via dermal exposure and inhalation exposures to workers are not expected. Releases to air were estimated, and no releases to water or landfill are expected. Exposure to the general population via inhalation is expected to be negligible (below modeling thresholds). Consumer exposures were not assessed because consumer uses were not identified as conditions of use. Risk Characterization: EPA applies a margin of exposure approach to calculate potential human health risks of new chemicals. A benchmark (acceptable) margin of exposure is derived by applying uncertainty factors for the following types of extrapolations: intra-species extrapolation (UFH = 10 to account for variation in sensitivity among the human population), inter-species extrapolation (UFa = 10 to account for extrapolating from experimental animals to humans) and LOAEL-to-NOAEL extrapolation (UFL = 10 to account for using a LOAEL when a NOAEL is not available). Hence, in the New Chemicals Program, a benchmark MOE is typically 100 and 1,000 when NOAELs and LOAELs, respectively, are used to identify hazard. When allometric scaling or pharmacokinetic modeling is used to derive an effect level, the UFh may be reduced to 3, for a benchmark MOE of 30. The benchmark MOE is used to compare to the MOE calculated by comparing the toxicity NOAEL or LOAEL to the estimated exposure concentrations. When the calculated MOE is equal to or exceeds the benchmark MOE, the new chemical substance is not likely to present an unreasonable risk. EPA assesses risks to workers considering engineering controls described in the PMN but in the absence of personal protective equipment (PPE) such as gloves and respirators. If risks are preliminarily identified, EPA then considers whether the risks would be mitigated by the use of PPE (e.g., impervious gloves, respirator). Risks to human health for the new chemical substances were evaluated using the route-specific effect levels (i.e., NOAEL and BMCL). Risks were identified for workers for systemic effects via dermal exposure based on quantitative data for an analogue (MOE =13; Benchmark MOE = 100). Corrosion and sensitization hazards to workers via dermal contact were identified based on the surfactant-like properties of the new chemical substances, pH, submitted and analogue data, and information in the SDS. Risks for these endpoints were not quantified due to a lack of dose- response for these hazards. However, exposures can be mitigated by the use of appropriate personal protective equipment (PPE), including impervious gloves and eye protection. EPA expects that employers will require and that workers will use appropriate PPE consistent with the Safety Data Sheet prepared by the new chemical submitter, in a manner adequate to protect them. Risks were not evaluated for workers for lung effects via dermal exposure because the hazards are not relevant to the exposure route. Risks were not evaluated for workers via inhalation exposures because inhalation exposures are expected to be negligible. Risks to the general population were not evaluated because general population exposures are not expected. Risks to consumers were not evaluated because consumer uses were not identified as conditions of use. ------- TSCA Section 5(a)(3) Determination for Premanufacture Notice (PMN) P-19-0155, P-19- 0156 and P-19-0157 Risks to the environmental were not identified due to no releases to water. Because worker exposures can be controlled by PPE, no unreasonable risks to the general population or environment were identified, and there are no expected exposures to consumers, EPA has determined that the new chemical substance is not likely to present unreasonable risk to human health or the environment under the conditions of use. Date: 12/18/2019 /s/ Tala R. Henry, Ph.D. Deputy Director for Programs Office of Pollution Prevention and Toxics ------- |