P-18-0363 Page 1 of 18

P-18-0363 Chemical Name:

CASRN: None Human Health Report Status: DATE COMPLETED

HAZARD DRAFT - Pending Review 12-21-2018

HAZARD REVIEWED 02-12-2019

HAZARD FINAL

RISK DRAFT - Pending review 02-21-2019

RISK REVIEWED 02-22-2019

RISK FINAL - Uploaded 02-25-2019

UPDATE DRAFT - Pending review 06-04-2020

UPDATE REVIEWED

UPDATE FINAL - Uploaded 06-16-2020

jalwoodTypewritten TextRJA 7/1/20

jalwoodTypewritten Text

asullivanTypewritten TextVerified by AMS 07/01/2020

P-18-0363 Page 2 of 18

1 HUMAN HEALTH SUMMARY EPA estimated the human health hazard of this chemical substance based on its estimated physical/chemical properties and by comparing it to structurally analogous chemicals which there is information on human health hazard. Based on the hazard determination and available quantitative and qualitative risk information, EPA did not identify risks for the new chemical substance.

1.1 Hazard Summary EPA estimated the human health hazard of this chemical substance based on its estimated physical/chemical properties and by comparing it to structurally analogous chemicals for which there is information on human health hazard. Absorption of the new chemical substance is expected to be nil when neat and poor when in solution via all routes based on physical/chemical properties. For the new chemical substance, EPA identified hazards for irritation to the eyes, skin, and respiratory tract based on the alkalinity of the new chemical substance and information provided in the Safety Data Sheet (SDS), and corrosion to all exposed tissues based on the phenol residual of the new chemical substance. For the residual component of the new chemical substance, EPA identified hazards for acute oral, dermal, and inhalation toxicity, corrosion to all tissues, and systemic effects. EPA identified a BMDL of 93 mg/kg-bw/day based on systemic effects, which was used to derive exposure route- and population-specific points of departure for quantitative risk assessment. EPA qualitatively evaluated irritation and corrosion effects.

1.2 Exposure and Risk Summary For this assessment, EPA assessed worker exposures via the dermal route. Inhalation exposures were not expected to workers exposed to the new chemical substance. Releases to water, air, and landfill were estimated. Exposures to the general population were assessed via drinking water, fish ingestion, and groundwater ingestion impacted by landfill leaching. Exposures to the general population via inhalation were not assessed because releases to air were expected to be negligible (below modeling thresholds). Consumer exposures were not assessed because consumer uses were not identified as conditions of use. Risks to human health for the new chemical substance were evaluated using the route-specific effect level (i.e., BMDL), as described above.

1.2.1 Workers Irritation and corrosion hazards to workers were identified for all exposed tissues, including the eyes, skin, and respiratory tract based on the alkalinity of the new chemical substance, the phenol residual, and information provided 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, eye protection, and respiratory protection. EPA expects that employers will require, and that workers will use appropriate PPE consistent with the SDS prepared by the submitter, in a manner adequate to protect them.

P-18-0363 Page 3 of 18

1.2.2 General Population Risks were not identified for the general population via drinking water and fish ingestion, or groundwater ingestion impacted by landfill leaching based on quantitative hazard data for the

( (MOEAdultDW = > 100,000; MOEInfantDW = > 100,000; MOEFish = > 1,000,000; Benchmark MOE = 100). Risks were not evaluated for the general population via stack air inhalation because exposures are expected to be negligible (below modeling thresholds). Risks were not evaluated for the general population via fugitive air inhalation because releases to fugitive air are not expected. Irritation and corrosion hazards to the general population are not expected via drinking water, fish ingestion, or groundwater ingestion impacted by landfill leaching due to dilution of the chemical substance in the environmental media.

1.2.3 Consumers Risks to consumers were not evaluated because consumer uses were not identified as conditions of use.

1.3 Assumptions and Uncertainties • There are no measured data on the new chemical substance. • Absorption of the new chemical substance is based on physical/chemical properties.

1.4 Potentially Useful Information None

1.5 Hazard Language Skin Corrosion (residual only), Skin Irritation, Serious Eye Damage (residual only), and Eye Irritation

P-18-0363 Page 4 of 18

2 HUMAN HEALTH HAZARD

2.1 Chemistry Summary

P-18-0363 Page 5 of 18

2.2 Hazard Summary

2.2.1 Absorption Absorption is expected to be nil when neat and poor when in solution via all routes based on physical/chemical properties.

2.2.2 Structural Alerts None

2.2.3 Human Health Category (From US EPA 2010 document) Chemical Category: N/A for human health Chemical Category Health Concerns: N/A Category Testing Strategy: N/A

2.2.4 OECD QSAR Toolbox The new chemical substance was not analyzed using the OECD QSAR Toolbox because it is outside the domain of applicability of the software. The residual of the new chemical substance were analyzed using the OECD QSAR Toolbox.

P-18-0363 Page 6 of 18

2.2.4.1

US EPA New Chemical Category Not classified

Respiratory sensitization alert No alert found Protein binding alerts for skin sensitization according to GHS

No alert found

Oncologic Primary Classification Phenol Type Compounds

2.2.4.2

US EPA New Chemical Category Not classified

Respiratory sensitization alert No alert found Protein binding alerts for skin sensitization according to GHS

No alert found

Oncologic Primary Classification Phenol Type Compounds

2.2.5 Hazard Meeting Summary There are concerns for irritation to the eyes, skin, and respiratory tract based on the alkalinity of the new chemical substance (pH , and the submitted SDS on the new chemical substance ethanol and

There are concerns for carcinogenicity based on the QSAR Toolbox alert for compounds, but this concern is reduced because the

are completely reacted and the PMN polymer is stable indicating those components will not result in hazards. In addition, phenol is not considered to be carcinogenic in animals. There are no data revealing an association of exposure to increased tumor rates in humans. No firm conclusion on risk levels could be drawn from a case-control study on respiratory cancer of workers exposed to . IARC has concluded that is not classifiable as a carcinogen. Therefore, EPA concluded that the new chemical substance is unlikely to be carcinogenic. For the hazards were identified for acute dermal, oral and inhalation toxicity, corrosion to all exposed tissues and systemic effects.

2.3 Toxicity Data

2.3.1 New Chemical Substance Data None

2.3.2 Analogue/Metabolite Data

P-18-0363 Page 7 of 18

2.3.2.1

analogue • OECD 425 acute oral toxicity-up-and-down procedure in rats: dose level of 2000 mg/kg-

bw; 15 days study. Substance was given to a single animal and upon observation of no severe effects, four additional animals were sequentially dosed at approximately 2- to 6-day intervals. The animals were then observed for systemic toxicity during the study period. No animals exposed to the test substance died or exhibited signs/symptoms of toxicity during test duration. All animals exhibited positive weight change and were observed as normal. Gross pathology showed nothing remarkable. Based on these results, the acute oral LD50 was > 2000 mg/kg-bw in female rats (low acute toxicity).

2.3.2.2

• European Union Risk Assessment Report (2006)

Signs and symptoms of acute toxicity of in humans and experimental animals are similar regardless of the route of administration. Acute doses of can produce symptoms of toxicity within minutes of administration thus a rapid absorption occurs. Oral toxicity of in humans leading to death is reported for doses as low as 140-290 mg/kg bw. Absorption from spilling solutions on the skin of humans seems to be very rapid, and death resulted from collapse within 30 minutes to several hours. Death has resulted from absorption of through a skin area of 64 inch², too. For animals, oral LD50 values of 340 mg/kg bw are reported (rats), of approximately 300 mg/kg bw (mice), and of less than 620 mg/kg bw (rabbits). A dermal LD50 value of 660-707 mg/kg bw was determined for female rats. LC50 values are not available; however, rats are reported to tolerate concentrations as high as 236 ppm (900 mg/m³) for 8 hours, resulting in ocular and nasal irritation, loss of co-ordination, tremors, and prostration. Based on the frequent reports on human experience with occupational exposure to in earlier times phenol is classified as “toxic” and labelled with “R 23/24/25 (Toxic by inhalation, in contact with skin and if swallowed)”. Initial skin contact with produces a white wrinkled discoloration with no experience of pain due to the local anaesthetic properties of causes severe chemical burns; occasionally skin necrosis is seen with solutions as dilute as 1%. Eye irritation in rabbits caused

P-18-0363 Page 8 of 18

by a 5% aqueous solution was irreversible after an observation period of 7 days. Thus, local irritation caused by solutions cannot be assessed properly. Based on the corrosive properties is labelled with the R-phrase “R 34, causes burns”.

did not cause any signs of skin sensitization in tests with guinea pigs (modified Buehler Test) and mice (Mouse Ear Swelling Assay), and there is no evidence of allergic contact dermatitis in humans. Long-term exposure to has shown effects on the nervous system and liver (in humans and animals), and on hematopoietic and immune system, kidneys, and skin (animals). Limited data are available on chronic effects of in humans from oral, dermal or inhalation exposure indicating reduced spontaneous activity, muscle weakness, pain and disordered cognitive capacities. In animals dysfunctions of the nervous system including tremor, convulsions, loss of co-ordination, paralysis, reduced motor and spontaneous activity, and reduced body temperature have been reported. In -exposed workers elevated activities for serum transaminases (especially ALAT) and increased clotting time were observed at a concentration of 0.021 mg/l indicating hepatotoxicity after chronic inhalation. Repeated dose studies in animals have reported unscheduled deaths after inhalation (0.1-0.2 mg/l, hamster), dermal (783 mg/kg bw/day, rabbit) or gavage (120 mg/kg bw/day, rat) exposure to but no treatment-related mortalities have been seen after long-term exposure of within the drinking water at dosages up to 450 mg/kg-bw/day in rats and 375 mg/kg-bw/day in mice. In some studies, mortalities were associated with growth retardation or respiratory distress. The following overall N(L)OAELs/NOAECs are recommended for risk assessment purposes. Oral administration: LOAEL of 1.8 mg/kg/day from the mouse study on subacute toxicity (Hsieh et al., 1992). Inhalative administration: NOAEC of 0.0963 mg/l for local effects from the 14-day rat study (CMA, 1998a), whereas a LOAEC of 0.021 mg/l for systemic effects was derived from a time weighted average exposure of workers (Shamy et al., 1994).

is positive with respect to various genetic effects in mammalian cell cultures. In general, relatively weak effects are induced. In vivo, is a weak inducer of micronuclei in mouse bone marrow cells; the effect is bound to high doses which are equivalent to or near to the maximum tolerable dose. The induction of micronuclei at high doses may be based on an indirect mode-of-action (hypothermia). is classified by the EU C&L working group as a mutagen category 3 and labelled with R 68 “Possible risks of irreversible effects”. Oral long term studies in rats and mice revealed no effect of on tumour induction. A medium-term study in a transgenic mouse model did not give any indication on treatment-related proliferative responses. was shown to act as a promoter in skin cancer bioassays in mice. A weak carcinogenic effect was observed after long-term skin application of a 10% solution of in benzene (without initiation), but was considered less relevant. The test solution was strongly irritative, and it contained the carcinogen benzene. However, there is some concern on the basis of positive in vivo mutagenicity data and from the metabolite hydroquinone classified as a suspected carcinogen (Category 3). This concern is considered to be of minor significance, as long term studies revealed no relevant indication for carcinogenicity. However, in conclusion,

l is considered not to be carcinogenic in animals. There are no data revealing an association of exposure to increased tumor rates in humans. No firm conclusion on risk

asullivanTypewritten Text

P-18-0363 Page 9 of 18

levels could be drawn from a case-control study on respiratory cancer of workers exposed to

• EPA IRIS (2002)

In an unpublished developmental toxicity study conducted according to GLP guidelines (Argus Research Laboratories, 1997), pregnant Crl:CDRBR VAF/Plus Sprague-Dawley rats (25/group) received by oral gavage on gestation days (GDs) 6 through 15. Dosing was three times daily with 0, 20, 40, or 120 mg /kg/dosage, using a dosing volume of 10 mL/kg. The corresponding daily doses were 0, 60, 120, and 360 mg/kg-day. The exposed dams were observed twice a day for viability and daily for clinical signs, abortions, and premature deliveries. In addition, the maternal body weights were recorded every day, and food consumption was also recorded periodically. The rats were sacrificed on GD 20 and gross necropsy was performed and the number of corpora lutea in each ovary was recorded. The uterus of each rat was excised and examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Each fetus was weighed, sexed, and examined for gross external alterations. One half of the fetuses were examined for soft tissue alterations and the rest were examined for skeletal alterations. One high-dose dam died on GD 11. The study authors attributed this death to treatment, because it occurred only at the high dose, although there were no adverse clinical observations and no abnormal necropsy findings in this animal. Other high-dose animals exhibited excess salivation and tachypnea (rapid breathing). There were no other treatment- related clinical observations and no treatment-related necropsy findings. Dose-dependent decreases in body weight of the exposed animals as compared with the controls were observed. Statistically significant decreases in both maternal body weight (8%) and body weight gain (38% for GDs 6-16) were observed at the high dose; although a statistically significant decrease in body weight gain (11%) was observed at the mid dose, the decrease at the mid dose (relative to controls) in absolute maternal weight at the end of dosing (3%) was not statistically significant. Dose-dependent decreases in food consumption were also observed during the dosing period. Fetal body weights in the high-dose group were significantly lower than those of controls-by 5-7%. The high-dose group had a statistically significant decrease in ossification sites on the hindlimb metatarsals, but it is unlikely that this small change is biologically significant. The incidence of litters with incompletely ossified or unossified sternal centra was 0/23, 0/25, 3/23, and 3/24; this increase was not statistically significant. There were small, dose-related increases in the number of litters with fetuses with "any alteration" and with "any variation" at 120 mg/kg-bw/day and higher. However, neither of these changes was statistically significant, and the response was not clearly dose-related. In addition, an increase in total variations is of questionable significance in the absence of any increase in individual variations. No other treatment-related effects were observed in uterine contents, malformations, or variations.

P-18-0363 Page 10 of 18

The maternal NOAEL was 60 mg/kg-day, based on small decreases in maternal body weight gain at 120 mg/kg-day, and the developmental NOAEL was 120 mg/kg-day, based on decreased fetal body weight and delayed ossification at 360 mg/kg-day. Benchmark dose (BMD) modeling was also conducted for the decreased maternal weight. Defining the benchmark response as a one-standard-deviation decrease in maternal body weight gain, the 95% lower confidence limit on the BMD (i.e., the BMDL) was 93 mg/kg-day. This BMDL was calculated using the polynomial model, which gave slightly better fit than the power and Hill models, using BMDS Version 1.3.

2.3.3 SDS Data The SDS is relevant to the new chemical substance based on matching CASRNs and trade names and is for an aqueous formulation of the PMN substance, described as a clear reddish-brown liquid with a pH of at 25°C

P-18-0363 Page 11 of 18

P-18-0363 Page 12 of 18

P-18-0363 Page 13 of 18

P-18-0363 Page 14 of 18

P-18-0363 Page 15 of 18

2.3.4 Other Information None

2.4 Exposure Routes of Interest

Route of Interest

X Inhalation:

X Dermal:

X Ingestion:

2.5 Point of Departure (POD) Selected and Basis

2.5.1 POD for Oral Exposures Type: BMDL Value: 93 mg/kg-bw/day Chemical: Route: Oral (gavage) Study type: Developmental toxicity study (Test Guideline Not Specified) Hazard Endpoint: systemic effects (maternal body weight gain) Selection rationale: is a present as a residual up to 8% the new chemical substance and repeated dose oral toxicity data were available for this substance. In an oral developmental

P-18-0363 Page 16 of 18

study in rats, the systemic NOAEL of 60 mg/kg-day was identified based on small decreases in maternal body weight gain, and the developmental NOAEL was 120 mg/kg-bw/day based on decreased fetal body weight and delayed ossification. Benchmark dose (BMD) modeling was also conducted for the decreased maternal weight and the resulting BMDL of 93 mg/kg-bw/day was selected as POD. The selected POD is expected to be protective for all health effects via oral exposures. Benchmark MOE: 100 (10x for interspecies, 10x for intraspecies) Reference: EPA IRIS (2002)

2.5.2 POD for Dermal Exposures No dermal POD was selected to evaluate the systemic effects for workers due to the anticipated corrosive effects of the residual present in the new chemical substance up to thereby reducing the potential for repeated exposures. No POD was identified to evaluate local dermal effects.

2.5.3 POD for Inhalation Exposures No inhalation POD was identified for local respiratory effects. The residual present in the new chemical substance up to is expected to be corrosive to all tissues.

3 HUMAN HEALTH RISK

3.1 USES and EXPOSURES

3.1.1 Uses Intended use:

3.1.2 Worker Exposure Per Engineering Report dated 05-27-2020

3.1.2.1 Inhalation MFG: Batch Negligible (VP < 0.001 torr); mist or vapor generation are not expected USE: Negligible (VP < 0.001 torr); mist or vapor generation are not expected

3.1.2.2 Dermal MFG: Batch Loading Liquid Product into Tank Trucks Exposure to Liquid at concentration High End PDR: mg/day over days/yr High End LADD: 2.7E-1 mg/kg-bw/day over days/yr

P-18-0363 Page 17 of 18

Sampling Liquid Product Exposure to Liquid at concentration High End PDR: mg/day over days/yr High End LADD: 1.3E-1 mg/kg-bw/day over days/yr USE: Unloading Liquid Raw Material from Tank Trucks Exposure to Liquid at concentration High End PDR: mg/day over days/yr LADD: 4.4E+0 mg/kg-bw/day over days/yr

3.1.3 General Population Exposure Per Exposure Report dated 05-28-2020

3.1.3.1 Drinking Water ADR as high as 2.39E-6 mg/kg/day and LADD as high as 1.11E-9 mg/kg/day

3.1.3.2 Fish Ingestion ADR as high as 9.43E-7 mg/kg/day and LADD as high as 8.82E-11 mg/kg/day

3.1.3.3 Landfill (multiply LADD*2.36) ADD as high as 6.49E-4 mg/kg/day and LADD as high as 2.75E-4 mg/kg/day

3.1.3.4 Air/Inhalation Stack air: Exposures are expected to be negligible (below modeling thresholds) Fugitive air: Not released

3.1.4 Consumer Exposure No identified consumer exposures

P-18-0363 Page 18 of 18

3.2 RISK CALCULATIONS

3.2.1 Worker Calculations Irritation and corrosion hazards to workers were identified for all exposed tissues, including the eyes, skin, and respiratory tract based on the alkalinity (pH ) of the new chemical substance, the phenol residual, and information provided 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 PPE, including impervious gloves, eye protection, and respiratory protection. EPA expects that employers will require, and that workers will use appropriate PPE consistent with the SDS prepared by the submitter, in a manner adequate to protect them.

3.2.2 General Population Calculations

Benchmark MOE

Endpoint Type

ExposureRoute

PODmg/kg-day

PODExposureFrequencyDays/Wk

PODRoute %Absorp

Exposure mg/kg-day Acute Dose Rate (ADR)

ExposureFrequencyDays/Wk

ExposureRoute %Absorp

Multiplier for Susceptible Subpopulations

StructuralAlert as %of PMN

Margin ofExposureMOE

100 BMDL

Drinking Water (adult) 93.00 5 100% 7 100% 1.0 100% 27,794,381Drinking Water (infant) 93.00 5 100% 7 100% 4.2 100% 6,617,710Fish Ingestion 93.00 5 100% 7 100% 1.0 100% 70,443,872 Landfil l 93.00 5 100% 7 100% 1.0 100% 102,355

Population Margin of Exposure (MOE) Calculations using Animal Oral POD and Exposure Report ADR

Animal or Human Human

Risks were not identified for the general population via drinking water and fish ingestion, or groundwater ingestion impacted by landfill leaching based on quantitative hazard data for the

(MOEAdultDW = > 100,000; MOEInfantDW = > 100,000; MOEFish = > 1,000,000; Benchmark MOE = 100). Risks were not evaluated for the general population via stack air inhalation because exposures are expected to be negligible (below modeling thresholds). Risks were not evaluated for the general population via fugitive air inhalation because releases to fugitive air are not expected. Irritation and corrosion hazards to the general population are not expected via drinking water, fish ingestion, or groundwater ingestion impacted by landfill leaching due to dilution of the chemical substance in the environmental media.

3.2.3 Consumer Calculations Risks to consumers were not evaluated because consumer uses were not identified as conditions of use.

P-18-03631 HUMAN HEALTH SUMMARY1.1 Hazard Summary1.2 Exposure and Risk Summary1.2.1 Workers1.2.2 General Population1.2.3 Consumers

1.3 Assumptions and Uncertainties1.4 Potentially Useful Information1.5 Hazard Language

2 HUMAN HEALTH HAZARD2.1 Chemistry Summary2.2 Hazard Summary2.2.1 Absorption2.2.2 Structural Alerts2.2.3 Human Health Category (From US EPA 2010 document)2.2.4 OECD QSAR Toolbox2.2.4.1 5-Methyl-1,3-benzenediol, CASRN 504-15-4, (residual at