I a Database of Produced Water Constituents with Ranking Of

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A Database of Produced Water Constituents with Ranking of Human Health Risk

Sydney M. Joffre

B.S. Chemical Engineering, University of Colorado, 2018

B.S. Environmental Engineering, University of Colorado, 2019

A thesis submitted to the

Faculty of the Graduate School of the

University of Colorado in partial fulfillment

of the requirement for the degree

Master of Science

Department of Civil, Environmental, and Architectural Engineering

2020

Committee Members:

Cloelle Danforth

Karl Linden

James Rosenblum

Joseph Ryan

Abstract:

Sydney M. Joffre (Master of Science, Civil, Environmental, and Architectural Engineering)

A Database of Produced Water Constituents with Ranking of Human Health Risk

Thesis Directed by Professor Joseph N. Ryan

Produced water is the largest waste stream of upstream oil and gas production in terms of volume. This study aims to address the implications of produced water reuse applications and inadvertent releases. We created a database of compounds identified in produced water from onshore oil and gas operations in North America and developed a prioritization scheme for those chemicals based on potential risk to human health. Through a comprehensive literature review, we found 179 studies that met our inclusion criteria. In total, there were 1,337 chemicals with a Chemical Abstract Service (CAS) number and 41 general water quality parameters (e.g., total dissolved solids, alkalinity) in produced water reported by the studies. We used the database to create a list of unique chemicals that had data available through the U.S. Environmental Protection Agency’s CompTox Dashboard and were in two or more individual samples at concentrations above the method detection limit. This resulted in a working list of 581 chemicals, comprised of 458 organic chemicals, 98 inorganic chemicals, and 25 radionuclides. Our prioritization scheme focused on the 390 organic chemicals in the working list that had at least one hazard metric available. Our prioritization scheme equally integrated aspects of exposure and hazard using the Toxicological Prioritization Index (ToxPi) to generate a ranking of compounds based on risk. The seven chemicals with the highest relative risk were organochlorine insecticides that are not expected to be associated with the oil and gas industry. The eighth-ranked compound, dodecahydro-1H-phenalene, was a hydrocarbon, which are expected to be identified in produced water. As research efforts into characterizing produced water expands, this database can provide a platform for potential uses such as generating a list of chemicals from a specific location that can then be prioritized using the scheme laid out in this study.

Table of Contents LIST OF TABLES V LIST OF FIGURES VI 1 INTRODUCTION ……………………………………………………………………………………………………………………………………….. 1

1.1 PRODUCED WATER COMPOSITION AND SOURCES ………………………………………………………………………………………………….. 3 1.1.1 Produced water composition …………………………………………………………………………………………………………... 4 1.1.2 Produced water sources ………………………………………………………………………………………………………………….. 6 1.1.3 Produced water analytical challenges …………………………………………………………………………………………….. 9 1.2 POTENTIAL HEALTH AND ENVIRONMENTAL IMPACTS FROM PRODUCED WATER REUSE AND SPILLS……………………………………. 10 1.3 THE ROLE OF RISK ASSESSMENT……………………………………………………………………………………………………………………….. 14 1.4 OBJECTIVES………………………………………………………………………………………………………………………………………………… 15 2 METHODS……………………………………………………………………………………………………………………………………………….. 16

2.1 PART I: DATABASE CREATION …………………………………………………………………………………………………………………………. 16 2.1.1 Literature review …………………………………………………………………………………………………………………………… 16 2.1.2 Database development …………………………………………………………………………………………………………………. 17 2.2 PART II: RISK PRIORITIZATION STRATEGY OF CHEMICALS IN PRODUCED WATER …………………………………………………………… 20 2.2.1 Produced water chemicals working list …………………………………………………………………………………………. 20 2.2.2 Associated data sources ……………………………………………………………………………………………………………….. 23 2.2.3 Exposure pathway ………………………………………………………………………………………………………………………… 25 2.2.4 Exposure domain ………………………………………………………………………………………………………………………….. 27 2.2.5 Hazard domain ……………………………………………………………………………………………………………………………… 34 2.2.6 Data integration and prioritization using the Toxicological Prioritization Index …………………………….. 35 2.2.7 Data availability ……………………………………………………………………………………………………………………………. 39 2.2.8 Sensitivity analysis ………………………………………………………………………………………………………………………… 43 2.2.9 Reference compounds ………………………………………………………………………………………………………………….. 44 3 RESULTS AND DISCUSSION……………………………………………………………………………………………………………………… 46

3.1 PART I: DATABASE……………………………………………………………………………………………………………………………………….. 46 3.1.1 Identification of publications, samples, and chemicals in produced water through comprehensive literature review …………………………………………………………………………………………………………………………………………. 46 3.2 PART II: PRIORITIZATION OF CHEMICALS IN PRODUCED WATER ………………………………………………………………………………. 47 3.2.1 Working list for prioritization scheme ……………………………………………………………………………………………. 47 3.2.2 Collection and analysis of toxicity data for chemicals in prioritization scheme ………………………………. 50 3.2.3 Data integration and prioritization using ToxPi …………………………………………………………………………….. 53 3.2.4 Sensitivity analysis ………………………………………………………………………………………………………………………... 71 3.2.5 Inorganic compounds without toxicity data ………………………………………………………………………………….. 87 3.2.6 Radionuclides ……………………………………………………………………………………………………………………………….. 87 3.3 PART III: INTEGRATED FINDINGS …………………………………………………………………………………………………………………….. 89 3.3.1 Future use of database …………………………………………………………………………………………………………………. 89 3.3.2 Compound rank summary …………………………………………………………………………………………………………….. 90 3.3.3 Organic compounds with toxicity data ………………………………………………………………………………………….. 92 3.3.4 Prioritization scheme sensitivity ……………………………………………………………………………………………………. 93 3.3.5 Comparison to Danforth et al. (2020) …………………………………………………………………………………………… 94 4 CONCLUSION …………………………………………………………………………………………………………………………………………. 98 5 WORKS CITED ………………………………………………………………………………………………………………………………………… 99 6 APPENDIX ……………………………………………………………………………………………………………………………………………. 115

6.1 DATABASE CREATION …………………………………………………………………………………………………………………………………. 115

iii

6.1.1 Literature review search logic ……………………………………………………………………………………………………… 115 6.1.2 Abbreviations used in database ………………………………………………………………………………………………….. 116 6.2 EXPOSURE DOMAIN: IONIZED COMPOUNDS …………………………………………………………………………………………………….. 117 6.3 DATABASE RESULTS ……………………………………………………………………………………………………………………………………. 120 6.4 TOXPI RESULTS …………………………………………………………………………………………………………………………………………. 123 6.4.1 Analysis ……………………………………………………………………………………………………………………………………….. 123 6.4.2 Organic compounds without toxicity data …………………………………………………………………………………… 163 6.4.3 Inorganic compounds with toxicity data ……………………………………………………………………………………… 167 6.5 SENSITIVITY ANALYSES ………………………………………………………………………………………………………………………………… 169 6.5.1 Missing data ……………………………………………………………………………………………………………………………….. 169 6.5.2 Domain weights ………………………………………………………………………………………………………………………….. 180 6.6 INORGANIC COMPOUNDS WITHOUT TOXICITY DATA …………………………………………………………………………………………… 192 6.7 RADIONUCLIDES ……………………………………………………………………………………………………………………………………….. 194 6.8 FUTURE USE OF DATABASE …………………………………………………………………………………………………………………………… 195 6.9 COMPARISON TO DANFORTH ET AL. (2020) ……………………………………………………………………………………………………. 196

List of Tables Table 1. Isomer mixtures on the working list ...... 22 Table 2. Mobility calculation parameters ...... 32 Table 3. Search logic for identifying acids and bases ...... 33 Table 4. Scaling equations for the exposure domain metrics...... 37 Table 5. Cases used in the missing data treatment sensitivity analysis ...... 43 Table 6. Cases used to evaluate the sensitivity of the hazard and exposure domains...... 44 Table 7. Experimental values of exposure metrics for the exposure domain reference compounds ...... 45 Table 8. Experimental toxicity values for the five hazard domain reference compounds ...... 45 Table 9. Organic compounds not included on the working list ...... 48 Table 10. Availability of experimental and predicted toxicity values for the 556 organic and inorganic compounds on the working list ...... 51 Table 11. Availability of experimental and predicted toxicity values for the 458 organic compounds on the working list ...... 52 Table 12. Availability of experimental toxicity values for the 98 inorganic compounds on the working list ...... 52 Table 13. Rank and ToxPi scores for the 40 organic compounds with toxicity data that had the highest relative risk...... 56 Table 14. Exposure domain reference compounds with their overall rank, overall ToxPi score, ToxPi score of the exposure metrics, and the time it takes each compound to travel a setback distance of 94 meters ...... 63 Table 15. Hazard domain reference compounds with their overall rank and overall ToxPi score...... 64 Table 16. The seven organic compounds without toxicity data from the working list with the highest relative risk ...... 66 Table 17. ToxPi scores and ranking for the 36 inorganic compounds with data ……………………………………………….. 69 Table 18. Summary of the number of compounds that shifted rank compared to the original analysis for each case in the missing data sensitivity analysis ...... 72 Table 19. Overall and relative ranks of the exposure domain reference compounds for the original analysis and the three cases used in the missing data sensitivity analysis ...... 77 Table 20. Number of compounds that shifted rank compared to the original analysis for each of the four domain weight cases ...... 78 Table 21. Overall and relative ranks of the exposure domain reference compounds for the original analysis and the four cases used in the domain sensitivity analysis ...... 85 Table 22. Overall and relative ranks of the hazard domain reference compounds for the original analysis and the four cases used in the domain sensitivity analysis ...... 86 Table 23. Six compounds with the highest maximum reported concentration and number of samples the compound was identified in for the inorganic compounds without toxicity data...... 87 Table 24. Maximum activity concentration and number of entries in the database for each radionuclide on the working list ...... 88 Table 25. The 15 compounds with the highest rank from each of the five groups analyzed ...... 91 Table 26. Rank comparison for the top 40 organic compounds on the working list with at least one toxicity value that were also ranked in the top 40 in the prioritization by Danforth et al...... 96

List of Figures Figure 1. Number of studies published between 1975 and 2019 that present primary chemical data of flowback and produced water from onshore oil and gas wells in North America ...... 3 Figure 2. Column headers for each spreadsheet in the database ...... 18 Figure 3. Exposure pathway used for the prioritization scheme ...... 26 Figure 4. Experimental toxicity data source hierarchy ...... 35 Figure 5. ToxPi definitions and notations...... 38 Figure 6. Flow chart of the groups within the working list ...... 40 Figure 7. ToxPi profile for the analysis of the organic compounds without toxicity data ...... 41 Figure 8. ToxPi profile used in the analysis of the inorganic compounds with toxicity data ...... 42 Figure 9. Flow diagram of the requirements for a compound to be placed on the working list once identified in a sample ...... 49 Figure 10. Flow diagram of the different groups of compounds in the working list ...... 50 Figure 11. ToxPi profile for the analysis ...... 54 Figure 12. Overall ToxPi score versus rank for the 390 organic compounds with toxicity data ...... 55 Figure 13. ToxPi profile for aldrin ...... 58 Figure 14. ToxPi profile for dodecahydro-1H-phenalene ...... 59 Figure 15. ToxPi profile for 1,3-benzenedicarboxylic acid ...... 61 Figure 16. Exposure domain reference compound ToxPi profiles from the analysis ...... 63 Figure 17. Hazard domain reference compound ToxPi profiles from the analysis ...... 65 Figure 18. ToxPi profiles for the organic compounds without toxicity data that have the highest and lowest relative risk ...... 67 Figure 19. ToxPi score versus rank for the original analysis and three missing data treatment cases ...... 73 Figure 20. Heat map of the results from the three different cases evaluating the sensitivity of missing data treatment ...... 74 Figure 21. ToxPi score versus compound rank for the original analysis and the exposure domain reference compounds for each missing data treatment case ...... 75 Figure 22. ToxPi score versus compound rank for the original analysis and the hazard domain reference compounds for each missing data treatment case ...... 76 Figure 23. ToxPi score versus compound rank for the sensitivity analysis evaluating the importance of the weights of the hazard and exposure domains...... 80 Figure 24. Heat map of the results from the four different cases evaluating the sensitivity of domain weights to the original analysis ...... 81 Figure 25. ToxPi score versus compound rank for the original analysis and the exposure domain reference compounds for each domain weight case analyzed ...... 82 Figure 26. ToxPi score versus compound rank for the original analysis and the hazard domain reference compounds ...... 83 Figure 27. ToxPi profiles for the exposure domain reference compounds from the exposure-only case ...... 84 Figure 28. ToxPi profiles for hazard domain reference compounds from the hazard-only case ...... 84

1 Introduction

With oil and gas production comes the challenge of managing its waste streams. In terms of volume, produced water is the largest waste stream of upstream oil and gas production (Veil, 2020). Produced water is comprised of the water that was trapped in the formation and any additives used to develop a well, which comes back to the surface after a well begins generating oil and gas. From 2007 to 2017, there was a 94.6% growth in US oil production and a 43.6% growth in gas production, resulting in a 16.2% growth of the total volume of produced water generated (Veil, 2020). The quality of produced water is generally poor as it is usually highly saline and can contain hazardous constituents, including organic compounds, metals, and naturally-occurring radioactive materials (Hoelzer et al., 2016).

Produced water is primarily disposed of by deep well injection because, where available, it is the least expensive option for managing this waste stream (Veil, 2020). However, there has been an increasing desire to avoid deep well injection and instead use produced water as an alternative water source (GWPC, 2019b). Some potential reuse options have been considered, such as providing water for livestock and agriculture, industrial processes, and recharging groundwater (Hagström et al., 2016). Given the hazardous nature of produced water, treatment would be required before it can be used for any of these applications (Jang et al.,

2017). The level of treatment required depends on the risk to human health or the environment associated with the intended application of the produced water. The optimal treatment technology for produced water is dependent on the contaminants of concern being targeted, with some waters requiring multiple treatments to achieve the desired level of removal (Nasiri

1 et al., 2017). However, there is currently neither adequate nor comprehensive characterization of produced water compositions from either conventional or unconventional wells (Oetjen et al., 2017). Reuse outside of the oilfield may return water to the hydrologic cycle, but the complex and variable composition of produced water may make treatment expensive and difficult. Additionally, produced water from unintentional discharges entering the environment presents a risk to surface and groundwater quality. Inadvertent releases of produced water can result from spills when the produced water is being transported, or if well integrity fails, allowing for seepage of produced water from the well into surrounding soil and water (Pichtel,

2016; Gandhi et al., 2018).

A recent uptick in studies analyzing produced water has indicated a need for an easily accessible database to aggregate the available data (Figure 1). This database could then be used to aid in evaluating the risks of produced water release to the environment. Moving forward, a detailed chemical characterization aimed at identifying constituents and their potential risks will be a critical step in evaluating the suitability of produced water for reuse scenarios.

Figure 1. Number of studies published between 1975 and 2019 that present primary chemical data of flowback and produced water from onshore oil and gas wells in North America. Studies from 1975 to 1999 are in five-year groupings.

1.1 Produced water composition and sources

Oil and gas wastewater is generally described as either flowback or produced water.

Liden et al. (2017) provides succinct definitions of these two wastewater types, which are summarized in the following sentences. During development, the flowback period occurs when the fluids injected into the well for hydraulic fracturing come back to the surface before oil and gas production begins. Typically, when the water returning to the surface is more characteristic of the formation water rather than the injection fluids, the wastewater is referred to as produced water. For the purposes of this manuscript, produced water will refer to any wastewater generated during the life of a well. A total of 3.88 billion liters of produced water were generated in 2017 in the United States (Veil, 2020). Of these, 3.80 billion liters were generated from onshore oil and gas wells.

1.1.1 Produced water composition

The composition of produced water depends on multiple factors, including the formation being developed, the petroleum hydrocarbon targeted, chemicals used in production, and the length of time the well has been in production (Fakhru’l-Razi et al., 2009).

Produced water can have characteristics both from the water injected into the well and the targeted geologic formation (Engle et al., 2014; Oetjen et al., 2017). General classes of inorganic compounds found in produced water include total dissolved solids (TDS), naturally-occurring radioactive materials (NORM), and trace metals; classes of organic compounds include acids, alcohols, polycyclic aromatic hydrocarbons (PAH), and polymers (Barbot et al., 2013; Ferrer &

Thurman, 2015a).

1.1.1.1 Inorganic compounds in produced water

Total dissolved solids, trace elements, and NORM are three groups of inorganic compounds that can increase the risks associated with produced water (Neff et al., 2011). A concern of the high TDS generally found in produced water is that it renders the water unsuitable for agriculture reuse. Total dissolved solids concentrations in produced water can vary from 500 to 400,000 mg/L (Al-Ghouti et al., 2019). Elements known to be in produced water that contribute to TDS include calcium, magnesium, potassium, sodium, sulfate, and chloride (Fakhru’l-Razi et al., 2009).

Trace elements commonly found in produced water include: aluminum, antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, lead, mercury, molybdenum, nickel, rubidium, uranium, vanadium, and zinc (Jubb et al., 2020). Of these trace elements, cadmium, arsenic, beryllium, lead, and chromium are classified as carcinogens (U.S. EPA, 2014).

Mercury is known to have detrimental effects on the nervous system; molybdenum is harmful to the urinary system; and zinc negatively impacts the immune and hematologic systems (U.S.

EPA, 2014).

Two of the most common radionuclides identified in produced water are radium-226 and radium-228 (Alley et al., 2011). Other NORMs in produced water include decay products of uranium and thorium, such as lead-210, bismuth-214, and radon-222. Potassium-40 and strontium-90 have also been identified in produced water (Ferrer & Thurman, 2015a).

1.1.1.2 Organic compounds in produced water

A variety of organic compounds have been identified in produced water. Acetic acid, formic acid, and propionic acid are organic acids commonly found in produced water

(Fakhru’l-Razi et al., 2009). Of these, acetic acid and formic acid are used as additives in hydraulic fracturing fluid to control pH (Elsner & Hoelzer, 2016). Butanol, ethanol, and phenol are alcohols known to be in produced water that have also been identified as additives in hydraulic fracturing fluids. Ethanol, isopropanol, and methanol are commonly used as solvents in hydraulic fracturing fluid to maintain a homogenous solution (Elsner & Hoelzer, 2016).

Polycyclic aromatic hydrocarbons, compounds with at least two aromatic rings fused together, usually identified in produced water include naphthalene, phenanthrene, and fluoranthene

(Chowdhury et al., 2009). This compound class is toxic and persistent, and thus hazardous to human health and the environment (Neff et al., 2011). Four frequently-occurring petroleum hydrocarbons in produced water are benzene, toluene, ethylbenzene, and xylenes (BTEX)

(Guerra et al., 2011). Benzene and ethylbenzene are hazardous because they are carcinogenic, while toluene and xylene pose adverse health risks (U.S. EPA, 2014). Two important types of

5 polymers in produced water are polyethylene glycols (PEG) and polypropylene glycols (PPG).

These compounds are regularly used as surfactants and non-emulsifiers in hydraulic fracturing fluid to increase efficiency by decreasing the fluid’s friction (Elsner & Hoelzer, 2016). Despite being used in fracturing fluid, PEGs and PPGs have been found in produced water 400 days after well production began (Rogers et al., 2019).

1.1.2 Produced water sources

Both the drilling technique and desired petroleum hydrocarbon affect the volume of produced water created over the life of a well. An average vertical well creates close to 13 units of produced water for every one unit of oil, while horizontal wells generate an average of around three units of produced water per unit of oil (Scanlon et al., 2017). Up to 50% of the total produced water volume from a horizontal well comes to the surface during the first six months of production, with almost all horizontal wells having generated more than 50% of their total produced water volume by the end of the first year (Kondash et al., 2017). Kondash et al.

(2018) found that in 2015, the average gas-producing well in the Permian Basin generated 60 million liters of produced water compared to 29 million liters from the average oil-producing well in the same basin. Wells in the Eagle Ford formation also generated more produced water from gas-producing wells (20.7 million liters) than from oil-producing wells (16.9 million liters) in 2015 (Kondash et al., 2018).

1.1.2.1 Shale gas revolution

The oil and gas in formations targeted by unconventional techniques are difficult to extract because they are trapped in tight formations, typically shales (Torres et al., 2016).

Unconventional extraction is usually done by horizontal drilling and high-volume hydraulic

6 fracturing (Ratner & Tiemann, 2015). During horizontal drilling, a vertical well is drilled to a specific depth and is then extended laterally before hydraulic fracturing occurs. Hydraulic fracturing is a technique that creates fractures in these rocks by injecting fluid, which has varying compositions of approximately 90% water, 9% sand, and 1% chemical additives, into the target formation at high pressures (GWPC & ALL Consulting, 2009). Sand, a proppant, is added to the injected fluid to ensure that the fractures created in the drilling process remain

“propped open” during extraction (Barati & Liang, 2014). Operators use chemical additives to increase the efficiency of different aspects of the drilling process; including reducing friction between the pipe and injected fluid, sustaining a specific fluid viscosity, and avoiding pipe corrosion (Elsner & Hoelzer, 2016). In 2016, the average high-volume, horizontal well required approximately 30.5 million liters of injected fluid, which would include 305,000 liters of chemical additives per well (Kondash et al., 2018).

The combined technologies of horizontal drilling and hydraulic fracturing led to an uptick in production, which has been hailed as the Shale Gas Revolution in the U.S. (Wang et al.,

2014). During the Shale Gas Revolution, which spanned from approximately 2000 to 2010, U.S. shale gas production drastically increased from less than 1% to more than 20% of the total gas production in the U.S. (Stevens, 2012). This, in turn, raised concerns around the amounts and types of chemicals being used in the process. In 2011, the FracFocus database was created to document chemical additives in the fracturing fluid and to provide transparency in hydraulic fracturing during oil and gas operations; FracFocus is still in use (GWPC & IOGCC, 2011). Some states require oil and gas operators to report information on the ingredients in their fracturing fluids to FracFocus, but all operators can disclose this information on a voluntary basis

(Konschnik & Dayalu, 2016). A typical disclosure to FracFocus includes the trade name of the additive, the purpose of the additive, the chemicals that compose the additive identified by name and Chemical Abstract Service (CAS) number, the maximum chemical concentration in the additive by mass percent, and the maximum chemical concentration in the hydraulic fracturing fluid by mass percent (Nickolaus, 2013).

Since the creation of the FracFocus database, researchers have been able to evaluate the different aspects of the hydraulic fracturing process, such as the quantity and composition of fracturing fluid. Arthur et al. (2014) used the FracFocus database to query the number of disclosures to FracFocus by state, shale play, and well operators, the mixture of additives used in fracturing fluids for different formations, and the percentage of entries that were designated as proprietary. These queries demonstrated that FracFocus could be used to better understand the chemicals used in fracturing fluid and identify the extent of missing hazard and physicochemical properties. Arthur et al. (2014) concluded that FracFocus can provide a wide array of valuable information, but that the database should be combined with related information, such as permit data from state documents, to provide a more complete picture of hydraulic fracturing. Rogers et al. (2015) evaluated the risk of organic compounds in the

FracFocus database based on their mobility, persistence, and frequency of use. This analysis showed the value of having a database of chemicals used in the hydraulic fracturing process. In the study, FracFocus was used to both identify compounds and determine how frequently a compound was reported on a national level.

1.1.3 Produced water analytical challenges

The two goals of analyzing produced water are to identify constituents and determine their concentration in the wastewater. A literature review by Danforth et al. (2020) found 1,198 different compounds that have been reported as detected in produced water from studies using analytical methods classified as either “standard” or “research.” Standard methods have gone through quality assurance and quality control tests and have been validated for use in certified labs (U.S. EPA, 2015b). Research methods provide alternative analytical methods that have not been approved by the EPA for regulatory purposes. Standard methods are required for use in a regulatory context because they offer validated procedures, and thus consistent results, across different labs. Currently, approximately 75% of chemicals known to be present in produced water do not have standard analytical techniques (Danforth et al., 2020). Research methods for some compounds without standard methods have been developed and are being used to characterize produced water (Ferrer & Thurman, 2015b; Nell & Helbling, 2019; Cantlay et al., 2020). Given the dearth of standard methods and the under-characterized nature of produced water, determining adequate regulations and treatment for the reuse of this water or potential risks of a spill is difficult (Oetjen et al., 2017).

Another analytical challenge is caused by matrix interference due to the high salinity content of the produced water. Many standard methods are developed to analyze groundwater or surface water, which are less saline than produced water and have less complex matrices

(U.S. EPA, 2013). Matrix interferences can result in having to dilute the sample and thus increasing the method detection limit, measuring concentrations inaccurately and imprecisely, or amplifying the recovery loss in proportion to the compound’s concentration (Oetjen et al.,

2017). The occurrence of any of these matrix interference effects would decrease the reliability of the measurements in terms of both quantification and detection (U.S. EPA, 2018a).

1.2 Potential health and environmental impacts from produced water reuse and spills

Under the Clean Water Act (CWA), a National Pollutant Discharge Elimination System

(NPDES) permit is required for facilities that discharge pollutants to surface waters (33 U.S.C.

§1311, 1972). While the limits on types and quantities of pollutants in these permits can vary, the EPA has created effluent limitations guidelines (ELGs) that set the minimum required treatment level for produced water to be discharged into surface waters (GWPC, 2019a). In the western United States (west of the 98th meridian), produced water intended for agricultural and wildlife use can be released to surface waters if it meets the ELG of 35 mg/L for oil and grease and is “of good enough quality” for its intended purpose, and it must be shown that the water is being used for that purpose (i.e. agriculture or wildlife propagation) (40 CFR §435.53, 1995).

Permit writers can add more standards to the permit based on current technology and guidelines, but they are not required to do so (GWPC, 2019a). McLaughlin et al. (2020) analyzed produced water that was being discharged into surface waters under NPDES permits in

Wyoming. More than 50 of the organic compounds identified in the discharge did not have effluent limitations guidelines, while all inorganic compounds identified had guidelines and were found at concentrations below the permit requirements (McLaughlin et al., 2020b). The study also investigated the potential health impacts by comparing the maximum concentration of a compound to five human, aquatic, and livestock health thresholds. There were eight compounds (arsenic, benzene, cadmium, selenium, toluene, ethylbenzene, xylenes, and zinc) that had values for all five thresholds (McLaughlin et al., 2020b). It should be noted that

McLaughlin et al. (2020b) evaluated toxicity of individual constituents, not aggregate toxicity.

Analyzing the potential toxicity of the large mixture of compounds in produced water is difficult, and the inability to fully characterize this water adds complexity to the process.

However, a study by Kassotis et al. (2015) analyzed a mixture of 24 hydraulic fracturing fluid additives identified both synergistic and antagonistic effects.

A second study by McLaughlin et al. (2020b) evaluated the mutagenicity of the same produced water effluent, using a whole effluent assessment method (McLaughlin et al., 2020a).

They found that the rate of mutations was comparable to the concentration trends of the carcinogens, such as benzene and radium, in that the mutation rate decreased as distance away from the discharge site increased. The results from both studies indicate that the NPDES permits should include a more comprehensive list of compounds and have stricter ELGs to protect human, aquatic, livestock, and general environmental health (McLaughlin et al., 2020a;

McLaughlin, et al., 2020b).

Indirect discharges of produced water treated at Centralized Waste Treatment (CWT) facilities are regulated under the Code of Federal Regulations (CFR) in 40 CFR Part 437 (40 CFR

§437, 2003). An EPA report on centralized waste treatment (CWT) facilities identified 11 facilities that received oil and gas wastewaters in 2017 that were regulated with NPDES permits

(U.S. EPA, 2018b). The report found that the few facilities using a multi-step treatment process removed more pollutants than those using a single treatment technology. In general, most of the CWT facility discharges had high concentrations of TDS, metals, halides, and NORM (U.S.

EPA, 2018b).

Produced water can potentially be used for irrigation; however, the regulatory authority for this purpose is set by individual states because land applications are not covered under the

Clean Water Act (GWPC, 2019a). One of the main concerns related to produced water quality for crop irrigation is its high salinity content, which can cause soil salinization and sodification

(Echchelh et al., 2018). This processes lead to the accumulation of salts, including sodium, calcium, and chloride, in the soil; this accumulation decreases the amount of water available to crops and disturbs or destroys the soil structure (USDA Natural Resources Conservation Service,

1998). Another concern with using produced water for irrigation is the effects of organic compounds on crop growth and soil health. A study on the growth of rapeseed and switchgrass suggested that a concentration of organic matter lower than 5 mg/L and a total dissolved solids concentration of less than 3,500 mg/L are needed for a plant to adequately grow and remain healthy (Pica et al., 2017). Pica et al. (2017) concluded that organic compounds should be considered as detrimental to plant growth as salinity when using produced water for irrigation.

A similar conclusion was reached by Sedlacko et al. (2019), who evaluated the changes in physiological and morphological of spring wheat being irrigated by diluted produced water, water that was 50% sodium chloride (50% salinity), and tap water. The study found that the morphological changes in the crops watered with produced water diluted at 10% and saline water, which had five-times more TDS, followed similar trends (Sedlacko et al., 2019). These results indicate that factors other than salinity need to be considered when assessing potential agricultural reuse applications. Miller et al. (2019) investigated the effects of using produced water for irrigation on crop immune response. They identified boron and petroleum

12 hydrocarbons, along with salinity, as produced water constituents that can negatively impact crops by inhibiting their ability to combat disease.

Inadvertent releases of produced water, such as leaking from holding tanks or spills during transport, can pose risks to nearby groundwater (Gross et al., 2013). Information on spills nationwide is limited because the regulations for reporting these incidences are set by individual states (Allison & Mandler, 2018). However, a comprehensive, nine-year study of produced water spills in four states with a large number of oil and gas operations provides insight on trends associated with inadvertent releases. Between 2005 and 2014, approximately

50% of the 6,648 spills related to unconventional oil and gas wells in Colorado, New Mexico,

North Dakota, and Pennsylvania were connected to produced water storage and transferring fluids using flowlines (Patterson et al., 2017). Patterson et al. (2017) also found that 75 – 94% of spills in the four states were during the first three years of the drilling and extraction processes.

A companion paper by Maloney et al. (2017) identified a continuing upward trend in spill rates starting around the late 2000s in three of the four states, with Pennsylvania’s spill rate peaking in 2009 for unknown reasons. Armstrong et al. (2017) found that while the number of accidental spills per well increased from 2011 to 2014, the number of spills that impacted groundwater decreased from 54% to 27% in the Greater Wattenberg Area of the

Denver-Julesburg Basin in Colorado. This could be the result of an increased number of spills from individual wells, but a decrease in the number of spills per total volume of fluids in the basin. In Colorado, New Mexico, North Dakota, and Pennsylvania, only 7% of spills were closer than 30.5 meters to surface water, which is the setback regulation; 13.3% of spills were closer than 61 meters and 20.4% were within 91.4 meters (Maloney et al., 2017). A spill can be

13 upwards of 100,000 liters, so thousands of liters of produced water can be released from a single spill event. Produced water from spills can contain high concentrations of many known constituents of concern, such as BTEX, radium, TDS, and metals.

1.3 The role of risk assessment

Before contaminants of concern are discharged or released to the environment, research must be conducted on the potential effects of hazardous chemicals on human and environmental receptors (Chittick & Srebotnjak, 2017). Such research can also provide a better understanding of the potential outcomes of produced water spills. Risk assessments are performed to understand probable impacts on human health or the environment from hazardous compounds in different environmental media (ITRC, 2015). Generally, a risk assessment is done in four phases: (1) identification of the hazards, (2) determination of dose- response relationships, (3) discovery of exposure routes, and (4) combination of these aspects to illustrate the risk (NRC, 2009). Once the chemicals and associated toxicological hazards have been identified, compound-specific toxicity data derived from dose-response curves can be gathered to indicate the dose that leads to adverse effects. The exposure route is important because it determines the way a receptor would encounter different toxic compounds.

For a full risk assessment to be conducted, detailed site-specific information is required.

However, adaptations can be made to the process to allow researchers to better focus on the broader risks associated with different activities. Rogers et al. (2015) did this by designing a framework for the prioritization of exposure-based risk of chemicals found in hydraulic fracturing fluids.

1.4 Objectives

This study builds on the work done by Danforth et al. (2020), which identified and prioritized compounds in produced water based on potential toxicological hazard to human and environmental health. Our objectives here were to first create a database of produced water constituents from conventional and unconventional onshore oil and gas operations in North

America, and second, to develop a prioritization scheme for those chemicals based on potential risk to human health. This database will provide researchers with a single source of data for compounds in produced water from multiple studies. This will address the need for better information about the types of chemicals found in produced water, its potential for reuse, and impacts from spills. For the chemicals that have been identified in produced water and were used in the prioritization scheme, the database includes available physical and chemical property data.

We used the database to generate a ranking of chemicals in produced water to identify which chemicals in produced water should be prioritized when evaluating the risks associated with reuse applications or inadvertent releases. This prioritization scheme was based on a risk assessment procedure; as such, both chemical hazard and potential for exposure were considered. For this evaluation, we defined the exposure pathway to be through groundwater as this encompassed produced water released inadvertently or produced water being reused for agriculture and land applications.

2 Methods

2.1 Part I: Database creation

To create a database of produced water constituents for the purpose of aggregating available information in a single location, we identified and reviewed the available literature on produced water characterization, extracted chemical data and associated sample information from the publications, and built the database using Jupyter Notebook (Perez & Granger, 2015).

2.1.1 Literature review

We built upon previous work conducted by Danforth et al. (2020) by using the studies identified in their literature review and by duplicating their search strategy to update the initial review. The Danforth et al. (2020) review surveyed literature published on or before March 8,

2018. Data collected in their review was used to generate a method for the prioritization of compounds in produced water. Like Danforth et al. (2020), we used the Web of Science

(Clarivate Analytics, 1997) and PubMed (National Library of Medicine, 1996) databases to identify potential studies for inclusion. Almost every journal in the Web of Science and PubMed databases are peer-reviewed, but results from non-peer-reviewed sources, such as reports or conferences, can be found on Web of Science. The search logic and inclusion criteria are available in Appendix Table 1. For a paper to be included, the study needed to provide primary data on chemicals of flowback or produced water from an onshore oil and gas operation in

North America. If a paper was a review of previously published data, the original studies were identified and evaluated to determine if they should be included in the database.

Our March 9, 2018 to November 12, 2019 review used the Health Assessment

Workplace Collaborative (HAWC) program (Shapiro et al., 2013) to sort the articles highlighted 16 by Web of Science and PubMed into inclusion and exclusion categories. Danforth et al. (2020) used a program called DistillerSR (Evidence Partners, Ottawa, Canada), which is similar to

HAWC, to sort their articles. Studies that met the inclusion criteria by analyzing flowback and produced water generated from onshore oil and gas operations in North America were sorted in HAWC based on the type of well (conventional, unconventional, coalbed methane, or unidentified) to organize the studies before data extraction occurred. During the literature review, studies were excluded from the database if no specific chemicals were identified, if the well was not in North America or onshore, if the study was a review of previously published literature, or if the study did not analyze flowback and produced water.

2.1.2 Database development

Produced water data were extracted from the studies that met the inclusion criteria and sorted into three related spreadsheets. The three spreadsheets were (1) publication information, (2) sample information, and (3) chemical information. Figure 2 shows the different columns in each spreadsheet and how the publications, samples, and chemical data collected from identified studies are related to each other using their respective ID numbers.

Figure 2. Column headers for each spreadsheet in the database. The arrows show the connection between the different spreadsheets. Headers with a ‘?’ indicates that the inputs were either ‘yes’ or ‘no’. In the publication information spreadsheet, DOI is the abbreviation for ‘digital object identifier’. Both the publication information and chemical information spreadsheets reference a Chemical Abstract Services (CAS) number. ‘Dashboard’ in the chemical information spreadsheet indicates if the chemical is included in the EPA CompTox Dashboard (Williams et al., 2017).

Each publication, sample, and individual chemical reported has its own unique identification number (ID). The ID numbers were randomly assigned in ascending order. Every sample can be traced back to the publication it was reported in, and every chemical can be traced back to its sample based on the respective IDs. Column headers that end with a ‘?’ indicate that the database entry was restricted to a ‘yes’ or ‘no’.

CompTox was developed by the EPA to provide a wide array of chemical data in a single location (Williams et al., 2017). As of July 22, 2020, it contained physical and chemical data from multiple sources for over 882,000 compounds (Williams et al., 2017). Compounds can be searched by different identifiers, such as their systematic name, synonym, or CAS number.

Examples of these data include intrinsic properties, structural identifiers, properties, environmental fate and transport, hazard, and related substances. Where available, both predicted and experimental values are provided. We used CompTox over other data sources

18 because it has a feature that allowed us to do a batch download that included all physicochemical data needed for both the database and the risk-based prioritization.

In the publication information sheet, ‘Method Type’ designates whether the analytical methods used were standard or research methods, with any research methods used were listed under ‘Research Methods’. In the sample information sheet, ‘Hydrocarbon Type’ refers to the petroleum product being extracted from the well (oil, natural gas, shale oil, shale gas, or coalbed methane) and ‘Extraction Location’ identifies where the produced water sample was taken from (i.e., wellhead, oil and gas separator, impoundment tank).

Inorganic compounds were categorized as those not having a carbon-hydrogen bond using the simplified molecular-input line-entry system (SMILES) (Weininger, 1987) notation entered in the chemical information spreadsheet in the database. The SMILES for each chemical was identified using CompTox. For consistency, the preferred chemical name from CompTox for each CAS number was used. If a compound was included in a chemical characterization analysis but not detected at the method detection limit, the value “99998” was entered as the concentration with units of “BDL” (below the detection limit). For compounds detected but not quantified (NQ), the concentration was set to “99999” with units of “NQ”. Chemicals that were tested for but not found were included in the database because we wanted to be able to identify chemicals that researchers have searched for in produced water samples. General water quality parameters, including total dissolved solids (TDS) and alkalinity, provide useful information on produced water quality characteristics, but do not have CAS numbers. Instead of CAS numbers, these water quality parameters were labeled with an easily identifiable abbreviation or acronym in our database (Appendix Table 2).

2.2 Part II: Risk prioritization strategy of chemicals in produced water

The finalized database was used to identify chemicals in produced water that could be prioritized when evaluating the implications of produced water reuse or spills. Recognizing that a minimum availability of data is needed to create a prioritization scheme, a subset, or

“working” list, of the chemicals compiled in the database were selected to determine which compounds had the highest likelihood of posing risk to a human receptor via a groundwater- based exposure pathway. To prioritize the chemicals, we considered both toxicological hazard and environmental fate and transport parameters affecting exposure of receptors. We created two domains to encompass these aspects: hazard and exposure. Here, the term “domain” is used to describe the grouping of individual metrics, or parameters, used in our prioritization.

2.2.1 Produced water chemicals working list

To create a working list of chemicals that could be used to generate a risk-based ranking, we used the finalized chemical database to create a list of unique chemicals in produced water. A unique chemical defined here is a chemical with a CAS number available on

CompTox that was identified in at least two individual produced water samples in the database above the detection limit or in a non-quantitative analysis. A compound needed to be reported in at least two samples to highlight compounds that are more likely to be in produced water and to narrow the scope of the working list. General water quality parameters were not considered unique because they do not have CAS numbers and thus do not have data available on CompTox.

2.2.1.1 Homologous and undefined mixtures

In some instances, a mixture of isomers was reported as being identified in a sample.

For example, instead of individually identifying o-xylene, m-xylene, and p-xylene, the measurement or detection of the undefined isomer mixture “xylenes” or “m,p-xylene” was reported. This was problematic for two reasons when compiling the working list. First, the toxicity reported for an isomer mixture is an average of the toxicity of the isomers composing the mixture; thus, the toxicity of the mixture may be higher or lower than that of some of the individual isomers. Second, inclusion of isomer mixtures in the working list would have led to the double-counting of the isomer’s individual compounds if they were already in the working list while not accounting for the individual compounds not in the working list. When just the mixture is reported, it is impossible to determine which individual compounds were present in the sample or at what concentration. To remedy these discrepancies, we determined that mixtures on the working list would be replaced with the individual compounds that typically make up the isomer mixture. The isomer mixtures and their concentrations were not changed in the database and concentration data was not included for any compound in the working list.

The compounds that composed each isomer mixture were found using the “related compounds” option on CompTox. A list of the isomer mixtures and the compounds used to replace them can be found in Table 1.

Table 1. Isomer mixtures on the working list and the individual compounds that make them up. In the working list, the mixtures were removed and replaced with the compounds that compose them. Bolded compounds were already on the working list.

Isomer Mixture Individual Compounds o-xylene xylenes m-xylene p-xylene m-xylene m,p-xylene p-xylene 1,2,3-trimethylbenzene trimethylbenzene 1,2,4-trimethylbenzene 1,3,5-trimethylbenzene 2-methylquinoline 3-methylquinoline 4-methylquinoline methylquinoline 5-methylquinoline 6-methylquinoline 7-methylquinoline 8-methylquinoline o-cresol cresol m-cresol p-cresol m-cresol m,p-cresol o-cresol 2-methylbiphenyl methylbiphenyl 3-methylbiphenyl 4-methylbiphenyl 1-methylnaphthalene methylnaphthalene 2-methylnaphthalene 2,3-dimethylphenol 2,4-dimethylphenol 2,5-dimethylphenol dimethylphenol 2,6-dimethylphenol 3,4-dimethylphenol 3,5-dimethylphenol 1,2-dimethylnaphthalene 1,3-dimethylnaphthalene 1,4-dimethylnaphthalene 1,5-dimethylnaphthalene 1,6-dimethylnaphthalene dimethylnaphthalene 1,7-dimethylnaphthalene 1,8-dimethylnaphthalene 2,3-dimethylnaphthalene 2,6-dimethylnaphthalene 2,7-dimethylnaphthalene

2.2.1.2 Inorganic compounds

Inorganic compounds in the working list were identified and separated from the organic compounds for the risk ranking. A different approach for prioritization was employed for inorganic compounds because of the limited physicochemical properties available for them.

Many quantitative structure-activity relationship (QSAR) models, which use compound structure to predict physicochemical properties, are designed for either inorganic compounds or organic compounds, but not both (Fourches et al., 2010). This includes the OPEn structure-activity Relationship Application (OPERA) (Mansouri et al., 2018), which was the source of all predictions for the values of the metrics in the exposure domain. It is also difficult to apply general modeling to inorganic compounds because of complexation reactions, which are sensitive to media-specific factors that can vary from site to site (i.e., organic matter content of the soil, salinity content of water) (Kirchhübel & Fantke, 2019).

2.2.2 Associated data sources

To prepare for the risk prioritization, physicochemical data and toxicity values for the compounds on the working list were added to the database. OPERA was used to model the physicochemical data. Toxicity data were sourced from the ToxVal database (Martin & Judson,

2010) and the Conditional Toxicity Values (CTV) Predictor tool (Wignall et al., 2018).

2.2.2.1 Physicochemical data

All physicochemical data in the database were modeled in OPERA and were downloaded from CompTox. OPERA uses a QSAR model based on the PHYSPROP database (U.S. EPA NCCT,

2017) to predict different physical and chemical properties associated with environmental fate

23 and transport (Mansouri et al., 2018). The PHYSPROP database contains experimental and predicted data for over 40,000 chemicals (U.S. EPA NCCT, 2017), but these values cannot be downloaded using the batch search feature in CompTox. All values predicted by a QSAR model have a corresponding applicability domain, which indicates the uncertainty in the value based on the similarity of the compound structure compared to the compound structures used in the model (Roy et al., 2015). The higher the applicability domain, the less reliable the predicted value is.

2.2.2.2 Toxicity data

Toxicity values for all compounds in the working list, except radionuclides, were either downloaded from the ToxVal database on February 18, 2020 or modeled using the CTV

Predictor tool.

The ToxVal database contains an overview of data from in vivo studies that can be used for mammalian and ecotoxicological toxicity studies (Martin & Judson, 2010). There is no curation process in place, but data in ToxVal from regulatory agencies, such as the Integrated

Risk Information System (IRIS) and the Provisional Peer-Reviewed Toxicity Values (PPRTV) program, are reliable because those experiments followed standardized procedures. ToxVal is one of the databases used to build CompTox, so the data is also available there (Williams et al.,

2017).

The CTV Predictor is a tool that uses a QSAR model to estimate toxicity values (Wignall et al., 2018). When using the CTV, predicted values are presented with a 95% confidence interval on both the upper and lower end and an associated applicability domain, which indicates the uncertainty associated with the prediction (Wignall et al., 2018). If a compound

24 has an experimentally measured toxicity value from U.S. Federal and State agencies, the CTV

Predictor presents this experimental value and, when available, the agency that reported the value. An applicability domain greater than three indicates that there were not enough similar compound domains for the QSAR model to be reliable; therefore, these values were excluded.

The toxicity data from the ToxVal database were experimentally derived, so they took priority over predicted CTV. The database that the CTV Predictor used to provide experimental toxicity values was last updated in May 2018; however, the ToxVal database was updated more recently and may have contained new data not included by the predictor tool. Therefore, toxicity values were first searched for in the newer ToxVal database and the CTV Predictor used next to search for predicted values. For the compounds on the working list, there were 427 toxicity values available in ToxVal and 2,013 predicted toxicity values from the CTV.

2.2.3 Exposure pathway

A critical step in evaluating risk is determining how a receptor could be exposed to a potential contaminant. The Agency for Toxic Substances and Disease Registry (ATSDR) (2019) defines a complete exposure pathway as one that describes: (i) the source or release of the contaminant, (ii) the fate and transport mechanisms that affect the contaminant as it travels through the environment, (iii) the specific points and routes the contaminant follows to reach

(iv) a potential receptor or exposed populations. These components were incorporated into the chemical prioritization scheme, and the metrics used to define exposure were chosen based on the exposure pathway.

We focused on human oral and inhalation exposure to groundwater contaminated with produced water from reuse applications or spills (Figure 3), which is explained in detail in this section.

Figure 3. Exposure pathway used for the prioritization scheme. Produced water enters the groundwater from either a re-use application or a spill. The blue arrows indicate the path of the produced water. It is assumed that all compounds on the working list entered the groundwater. A human receptor is then exposed to the contaminated groundwater by ingestion of contaminated tap water or inhalation of contaminated shower water.

Contaminant source or release: Produced water was considered the contaminant source. A spill during transport to a disposal site can result in produced water contaminating groundwater near the site of the incident. Oil and gas wells that experience integrity failure can cause environmental releases of produced water when the water leaks into the surrounding groundwater (Gandhi et al., 2018; Pichtel, 2016). Produced water used for land applications, such as agriculture or livestock watering, can seep into the groundwater. The contaminated

26 groundwater can then flow to a well or aquifer that supplies water to homes, which is where a human receptor would encounter the contaminant.

Environmental fate, transport, and uptake: Environmental fate and transport parameters are used to evaluate how a compound moves through media and which media the compound is likely to partition to at equilibrium. Uptake accounts for the accumulation potential of a compound once it has been exposed to an organism.

Exposure point and route: An exposure point is a location where a human receptor could interact with contaminated environmental media. The exposure route describes the methods by which a human receptor interacts with the contaminated water. We considered two routes: (i) oral ingestion of tap water, (ii) inhalation of tap or shower water.

Exposed populations: The potential receptors in this pathway are humans in the general population. There are no age groups within the population that are more likely to use or come into contact with the contaminated groundwater than others. A receptor would be any person who uses the contaminated water for activities such as drinking or showering in their home.

2.2.4 Exposure domain

The exposure domain was evaluated using the following methods, which are similar to those used by the Agency for Toxic Substances and Disease Registry (ATSDR, 2019) and National

Research Council (NRC) (2014). Both agencies use an approach based on a combination of environmental fate and transport processes to measure the risk of contaminants in different exposure pathways. In this risk prioritization scheme, the Henry’s Law constant (KH), the organic carbon-water partition coefficient (Koc), the biodegradation half-life (t1/2), and the bioconcentration factor (BCF) were used to evaluate the exposure domain. We downloaded the

27 predicted values for these metrics from OPERA. Both OPERA and CompTox use the term “soil adsorption coefficient” instead of “organic carbon-water partition coefficient”, which is the term that will be used in this manuscript.

In our exposure pathway, the organic carbon-water partition coefficient, the biodegradation half-life, and the Henry’s Law constant, were used to evaluate fate and transport; and the bioconcentration factor was used to assess uptake.

We used Koc to measure the potential transport of a compound, or its mobility, in the groundwater. The Koc evaluates a compound’s equilibrium partitioning between the organic carbon in soil and water. A higher Koc indicates that a compound has a higher affinity for soil than water, which decreases the transport potential in the groundwater. We also considered using the octanol-water partition coefficient (Kow) to evaluate mobility. The Kow is the ratio of a compound’s concentration in octanol, an organic fatty acid, to its concentration in water at equilibrium conditions. There is a positive correlation between the Koc and Kow, with some Koc estimates being a function of the Kow (Briggs, 1981). A relationship also exists between the Kow and the bioconcentration factor, which measures the concentration of a compound in an organism’s tissue to the compound’s concentration in the adjacent environmental media. We used the BCF to evaluate uptake because it determines whether a compound will bioaccumulate in a human receptor or be excreted by the human receptor. Like the Koc, the BCF can be calculated using the Kow (National Research Council, 2014). Compounds with larger BCF values are more lipophilic and compounds with larger Kow values are more hydrophobic, which is representative of the positive correlation between the two values. Because a higher BCF indicates a higher exposure potential, including Kow as a metric would merely amplify the

28 effects of the BCF. Thus, we determined that including the Kow as a measure of transport in our analysis was redundant.

A compound’s degradation half-life in different media is commonly used to evaluate its environmental fate. We used the biodegradation half-life instead of a media-specific half-life, such as the water or air degradation half-life, in our analysis because it accounts for multiple environmental media in a single value. The biodegradation half-life is defined as the length of time required for microorganisms to degrade a compound in water, soil, or sediment to half of its initial concentration (Aronson et al., 2006). Higher half-lives, which correspond to slower degradation rates, indicate that a compound is more likely to remain in the water long enough to reach a receptor.

The Henry’s Law constant measures the equilibrium partitioning of a compound between water and air. Compounds with higher KH values are more volatile so are more likely to be in air than water. Therefore, KH may be used to describe two, potentially contradicting scenarios in our exposure pathway: volatilization potential in groundwater and inhalation exposure from shower or tap water. In the first scenario, a compound with a higher KH is more likely to volatilize before reaching a receptor, which means there would be a lower risk of exposure to a receptor. In the second scenario, higher KH values would increase the exposure risk for inhalation of the compound because volatilization would occur at the receptor’s point of contact. Both scenarios are possible, but the inhalation exposure from shower or tap water is more likely to occur (Lee et al., 2002; Franco et al., 2007). This scenario is not only possible, but also represents a worst-case scenario and is thus the better option for the risk-based prioritization in this study.

2.2.4.1 Mobility

To determine the appropriateness of using the organic carbon-water partition coefficient (Koc) to describe the transport category of the exposure domain, we estimated the mobility of five well-studied reference compounds (Table 2). We also compared their respective

Koc and octanol-water partition coefficients (Kow) to verify that, given the interrelationship of Koc and Kow (Briggs, 1981), the Kow is redundant. We selected these five chemicals because they have experimental data from the PHYSPROP database (U.S. EPA NCCT, 2017) for all four metrics in the exposure domain and for the Kow.

We used Equation 1 to estimate mobility by calculating the time for these compounds to travel a setback distance of 94 meters (t94), which is the average distance required between a well and buildings or water sources in the U.S. (Richardson et al., 2013). Physical properties of the subsurface were estimated based on a porous aquifer with sandy soil. We assumed that the groundwater could be characterized as having a “fast” flow of 1 m/day and a soil porosity of

0.4, which is approximately the average of sandy soil. Equation 1 uses the setback distance (d), retardation coefficient (R), and the average linear groundwater velocity (vw) to calculate the transport time.

푑푅 Equation 1 푡 = 푣

Equation 2 uses the density of the aquifer sediment (ρs), the distribution coefficient (Kd), and the soil porosity (n) to calculate the retardation coefficient as follows:

푅 = 1 + 휌 퐾 − 1 Equation 2

Following Rogers et al. (2015), the density of the aquifer sediment was assumed to be that of sand (2.65 kg/L). In calculating the distribution coefficient, we accounted for sorption of the neutral form of the compound to organic matter (Equation 3). To identify Koc, Rogers et al.

(2015) used EPISuite (U.S. EPA, 2015c), which uses the program KOCWIN to calculate Koc for the compounds. KOCWIN can estimate the soil adsorption coefficient using different methods, including the use of a relationship with the Kow (U.S. EPA, 2015c). This supports the earlier assumption that including the octanol-water partition coefficient as an exposure metric might be redundant if the organic carbon-water partition coefficient were also being considered.

퐾 = 훼퐾푓 Equation 3

1 Equation 4 훼 = 1 + 10()

1 Equation 5 훼 = 1 − 1 + 10()

In the above equations, αn is the neutral fraction of the organic compound, which is calculated for acids using Equation 4 and for bases using Equation 5. Here, we assumed that the pH of the water is seven. The fraction of organic carbon of the sediment (foc) was assumed to be

0.001 kgoc/kgsed.

The Koc for the five compounds were taken from the PHYSPROP dataset, meaning that the values were found experimentally and are more accurate than the modeled values used by

Rogers et al. (2015). Each compound had a neutral fraction of one. Table 2 summarizes the inputs for Equation 1 through Equation 3 and the mobility assessment results.

Table 2. Mobility calculation parameters for the exposure domain reference compounds. The organic carbon-water partition coefficient (Koc), neutral fraction (αn), distribution coefficient (Kd), retardation coefficient (R), and the transport time for the fluoranthene, 2-methylnaphthalene, biphenyl, toluene, and benzene. The compounds are listed from highest transport time to lowest transport time.

Kd Compound (CAS) Koc (L/kgoc) αn R t94 (day) (L/kgsediment) Fluoranthene 63,100 1 63.1 252 23,671 (206-44-0) 2-Methylnaphthalene 3,980 1 3.98 17 1,581 (91-57-6) Biphenyl 1,860 1 1.86 8.4 789 (92-52-4) Toluene 117 1 0.117 1.5 138 (108-88-3) Benzene 56.2 1 0.056 1.2 115 (71-43-2)

The results (Table 2) show that as the value of Koc decreases, so does the value of the calculated transport time. Fluoranthene has the highest Koc of the five compounds, which means it has the lowest relative exposure potential because it has more affinity for organic matter than for water at equilibrium conditions. This is reflected in its calculated transport time

(23,671 days), which is 15-times slower than the next fastest time.

2.2.4.2 Ionized compounds

For both acids and bases, the Koc, BCF, and KH are applicable to only the neutral fraction

(αn) of the compound. The ionized fraction of a compound will remain in the water and will not sorb, bioconcentrate, or volatilize. We incorporated this into our prioritization scheme because we did not want to over- or under-estimate the exposure potential of ionized compounds. The

32 neutral fraction of an acid is the protonated fraction of the compound and the neutral fraction of base is the deprotonated fraction. Acids and bases on the working list were identified by searching chemical names and SMILES notation for functional groups (Table 3). The acidic functional groups searched for were alcohols, carboxyls, phenols, and thiols. The basic functional groups were amines and pyridines.

Table 3. Search logic for identifying acids and bases on the working list. Alcohols, carboxyls, and phenols were the acid functional groups searched for. The base functional groups searched for were amines and thiols. An ‘R’ indicates that an alkyl is attached to the functional group and an ‘Ar’ indicates that an aromatic ring is attached to the functional group. The simplified molecular input line entry system (SMILES) (Weininger, 1987) notation were searched for all functional groups except alcohols because there are no hydrogen atoms in SMILES notation. Chemical names were also searched for the common way compounds with each functional group are named.

Chemical Name Functional Group Acid or Base SMILES Search Logic Search Logic Alcohols (ROH) Acid - “nol”; “ol” Amines (RNH and ArNH) Base CCN and N “amine”; “pyrid” Carboxyls (RCOOH and Acid C(=O)O “carbox”; “oic” ArCOOH) Phenols (ArOH) Acid OC1=CC=CC=C1 “nol”; “ol” Thiols (RSH and ArSH) Acid S -

The αn of acids was calculated with Equation 4 and the αn of bases was calculated with

Equation 5 using a groundwater pH of seven. Neutral fractions for pentanoate, formate, and

-6 2-hydroxypropanoate were set to 1 × 10 because they are very acidic and have pKa values that would result in a neutral fraction of almost zero. The Koc, BCF, and KH were multiplied by the αn and these modified values were used in the prioritization. A complete list of the pKa values and calculated neutral fractions for the identified acids and bases can be found in Appendix Table 3 and Appendix Table 4.

2.2.5 Hazard domain

The hazard domain contains both cancer and non-cancer toxicity values. We used commonly identified human health toxicity values for hazard domain metrics (Wignall et al.,

2018). These metrics were the: reference dose (RfD), no observed adverse effect level (NOAEL), benchmark dose (BMD), benchmark dose lower limit (BMDL), reference concentration (RfC), oral slop factor (OSF), cancer potency value (CPV), and inhalation unit risk (IUR). The RfC and

IUR account for the inhalation exposure route and the remaining metrics account for the ingestion exposure route.

Toxicity values are available from multiple sources. We used the hierarchy of sources described by Wignall et al. (2018), which is based on the EPA Office of Solid Waste and

Emergency Response (OSWER) Directive 9285.7-53 (U.S. EPA, 2003). The EPA directive describes tiers of peer-reviewed toxicity data sources that should be used when conducting a risk assessment and is presented in Figure 4.

Figure 4. Experimental toxicity data source hierarchy, adapted from Wignall et al. (2018), used in the hazard domain for (A) the reference dose, no observed adverse effect level, benchmark dose, and benchmark dose lower limit; and (B) the reference concentration, oral slope factor, and inhalation unit risk. Cancer Potency values are not included in this hierarchy because they only reported by the California EPA. If experimental toxicity values from a source on the hierarchy, available predicted values from the Conditional Toxicity Value tool were used.

2.2.6 Data integration and prioritization using the Toxicological Prioritization Index

The prioritization scheme in this study was based on the two aspects of a risk assessment: exposure and hazard. Exposure is used to measure the likelihood that a receptor will contact a compound following a specific exposure pathway and hazard represents the potential toxicological threats posed to a receptor that interacts with the contaminated media.

If a compound is toxic but has a low exposure potential, the compound would pose a lower risk because the human receptor would be less likely to be in contact with the contaminant. Thus, both exposure and hazard were used to prioritize the risk of the compounds on the working list.

We used a program called the Toxicological Prioritization Index (ToxPi) to integrate complex, non-homologous metrics from our hazard and exposure domains (Marvel et al.,

2018). ToxPi uses a combination of normalization and weighted averages to generate a dimensionless score between zero and one. Higher ToxPi scores indicate that a compound poses a higher risk relative to the other compounds in the analysis. Missing data in ToxPi are automatically assigned a score of zero. In ToxPi, each metric is represented by a “pie” slice, the

35 weight of which can be changed based on the relative importance of the metric to the overall goal. The radius of a slice represents the metric’s score, with a longer radius being a score closer to one, and the width or angle of the slice indicates the metric’s weight relative to the other metrics. Before using ToxPi, we scaled the data so that the values within each metric were on the same order of magnitude and thus more comparable to each other after the data was normalized. ToxPi replaces any missing data with a value of zero, which indicates minimum activity. A study by To et al. (2018) evaluated the impacts of missing data treatment on both

ToxPi score and ranking for a chemical prioritization. They found that while using the average value to replace missing values resulted in statistically significant ToxPi score disparities compared to those from using the default ToxPi method for missing data, the chemicals ranked similarly. Thus, they concluded that this was a more ideal option for replacing missing data when ToxPi is being used for a chemical prioritization scheme (To et al., 2018).

The design of our prioritization strategy was to integrate the metrics from both the hazard and exposure domains. We chose the following four metrics to define the exposure domain: (1) Henry’s Law constant (KH); (2) organic carbon-water partition coefficient (Koc); (3) biodegradation half-life (t1/2); and (4) bioconcentration factor (BCF). Scaling equations were applied to all metrics (Table 4). The Koc values were inverted because a higher Koc means a compound is more likely to sorb to organic matter than remain in the groundwater long enough to reach a human receptor.

Table 4. Scaling equations for the exposure domain metrics in ToxPi. The “Roundup” function in Excel rounds any decimal up when applied and was used so that all non-missing values were above zero. A value of ten was added to the BCF to shift all values above zero.

Metric Domain Scaling Equation Henry’s Law Exposure log[퐾] − 푅푂푈푁퐷푈푃(log( min [퐾]) , 0) constant (KH) Organic carbon- water partition Exposure − log[퐾표푐] + 푅푂푈푁퐷푈푃(log(max[퐾표푐]), 0) coefficient (Koc) Biodegradation half- Exposure log[퐵푖표푑푒푔퐻푎푙푓퐿푖푓푒] life (t1/2) Bioconcentration Exposure log [퐵퐶퐹] + 10 factor (BCF)

We used the following eight metrics to define the hazard domain: (1) reference dose

(RfD); (2) no observed adverse effect level (NOAEL); (3) benchmark dose (BMD); (4) benchmark dose lower limit (BMDL); (5) reference concentration (RfC); (6) oral slope factor (OSF); (7) cancer potency value (CPV); and (8) inhalation unit risk (IUR). Toxicity values within each metric were of the same order of magnitude and linear because a logarithm of base ten was already applied, so no scaling equations were needed. One compound (dichloromethane) had a negative IUR value, which would have been assigned a score of zero in ToxPi, so the maximum

IUR was added to each entry to shift all data above zero.

Our analysis focused on the organic compounds with data and weighted the hazard and exposure domains equally. In the analysis, each of the eight toxicity metrics were given a weight a 6.25% and each of the four exposure metrics were weighted at 12.5%. The ToxPi profile, which shows how the domains and metrics were broken up, and notation used for the analysis is in Figure 5.

Figure 5. ToxPi definitions and notations for the analysis where the hazard and exposure domains are equally weighted. The categories within each domain are represented by slices of the same color scheme: toxicity data (blue), and fate and transport data (orange). Each slice corresponds to a different metric within each category. The radius of each slice represents the score of the individual metric and the width of each slice indicates its weight relative to the other metrics. Reference dose (RfD), RfD No observed adverse effect level (NOAEL), RfD Benchmark dose (BMD), RfD Benchmark dose lower limit (BMDL), Reference concentration (RfC), Oral slope factor (OSF), Cancer potency value (CPV), Inhalation unit risk (IUR), Bioconcentration factor (BCF), Henry’s Law constant (KH), Organic carbon-water partition coefficient (Koc), and Biodegradation half-life (t1/2).

Here, missing cancer toxicity values were left blank and missing non-cancer toxicity values were replaced with the average of the available data in each metric. The missing cancer values were left blank because we wanted to place an emphasis on the known carcinogens in the working list. The average of the available toxicity values for each respective non-cancer metric were used to fill in missing values; this will centrally shift the ToxPi scores (To et al.,

2018). The results of the To et al. (2018) analysis indicated that when using ToxPi to generate a ranking of chemicals based on risk, shifting the data centrally (i.e. using the average to replace missing values) is the ideal missing data treatment. To et al. (2018) found that using the maximum to replace missing values shifted the ToxPi scores but did not significantly change compound rank; and using the minimum value would decrease the scores in a way that may not be strict enough for risk assessments evaluating a worst-case scenario.

2.2.7 Data availability

We further split the organic and inorganic compounds in the working list based on data availability. We made this distinction because we could not adequately evaluate hazard for compounds with no experimental or predicted toxicity data available. A lack of toxicity data does not indicate that a compound is not hazardous, just that we cannot confidently compare it to compounds known to be hazardous.

The organic compounds on the working list were split into two groups based on the available data points in the hazard domain. After the radionuclides were separated from the other inorganic compounds on the working list, the inorganic compounds were also split into groups based on hazard domain data availability. The different groups and the way we analyzed them are summarized in Figure 6.

Figure 6. Flow chart of the groups within the working list and the way they were analyzed.

2.2.7.1 Organic compounds

The organic compounds were split into two groups for the prioritization based on data availability. All the organic compounds had full data availability for the exposure domain, so the two groups were distinguished based on the availability of toxicity data. Compounds with at least one toxicity value available were categorized as having toxicity data and compounds with no toxicity values available were categorized as being without toxicity data.

The organic compounds without toxicity data were prioritized using ToxPi with exposure metrics and no hazard metrics (Figure 7). There were no missing values in the exposure metrics because they were all able to be modeled with OPERA.

Figure 7. ToxPi profile for the analysis of the organic compounds without toxicity data. All four of the exposure metrics are weighted equally at 25%, with each metric being represented by a slice.

2.2.7.2 Inorganic compounds

The inorganic compounds were split into three categories:

 Compounds with at least one toxicity value (with toxicity data),  Compounds with no toxicity data (without toxicity data), and  Radionuclides

The inorganic compounds on the working list did not have any physicochemical properties available because OPERA, the source of physicochemical properties for our study, does not predict physicochemical properties for inorganic compounds. Experimental physicochemical properties may be available for some compounds, but it cannot be downloaded using a batch search on CompTox. For the compounds with at least one toxicity value available, a ToxPi analysis was conducted to generate a ranking based on hazard

(Figure 8). In this analysis, missing non-cancer toxicity values were replaced with the average of

41 the known values for the respective metric. Missing cancer toxicity values were left blank, which placed an emphasis on the known carcinogens.

Figure 8. ToxPi profile used in the analysis of the inorganic compounds with toxicity data. Each slice represents one of the toxicity metrics, which are equally weighted at 12.5% each. The non-cancer toxicity metrics are the Reference concentration (RfC), Benchmark dose lower limit (BMDL), Benchmark dose (BMD), No observed adverse effect level (NOAEL), and Reference dose (RfD). The cancer toxicity metrics are the Inhalation unit risk (IUR), Cancer potency value (CPV), and Oral slope factor (OSF).

The inorganic compounds with no toxicity values were simply presented using the total number of times they were reported in the database and their maximum reported concentration in the database. The radionuclides were presented separately based on their maximum concentrations because they are not measured with the same toxicity values as the other inorganic compounds.

2.2.8 Sensitivity analysis

Two sensitivity analyses were completed to assess the effect of decisions made regarding missing data and the weights of each domain on relative compound rank.

Replacing missing non-cancer values with the maximum and minimum of the available values for that metric were the first two scenarios examined using the same weighting scheme as the original analysis. In the third case, which also had the same weighting scheme as the original analysis, all missing values were replaced with the average of the available values for each respective metric. By replacing the missing cancer metric values with the average of the known values for the respective metric, every compound in the analysis was assumed to be carcinogenic. This removed the emphasis that was place on the known carcinogens in the original analysis and the first two cases of this sensitivity analysis. A summary of the different cases used for the sensitivity analysis can be found in Table 5.

Table 5. Cases used in the missing data treatment sensitivity analysis. Blank cells mean that the missing data or weights used were the same as those in the original analysis.

Case Treatment of Missing Toxicity Data Missing cancer values left blank; missing non-cancer values Original Analysis set to the average Case 1 Missing non-cancer values set to the maximum Case 2 Missing non-cancer values set to the minimum Case 3 All missing values set as the average

The effects on the chemical rankings resulting from an equal weight of the hazard and exposure domains was unclear, so the following range of domain weights were analyzed: exposure domain only, hazard domain only, hazard domain 75%/exposure domain 25%, and hazard domain 25%/exposure domain 75%. Table 6 describes the four different scenarios used

43 to evaluate the sensitivity of the weight given to the two domains. In all cases, the metrics within each domain were equally weighted and missing toxicity data was treated the same way as the original analysis.

Table 6. Cases used to evaluate the sensitivity of the hazard and exposure domains.

Case Description Original Analysis Hazard weighted 50%; exposure weighted 50% Case A Hazard weighted 0%; exposure weighted 100% Case B Hazard weighted 100%; exposure weighted 0% Case C Hazard weighted 75%; exposure weighted 25% Case D Hazard weighted 25%; exposure weighted 75%

2.2.9 Reference compounds

A total of ten reference compounds were tracked across the different analyses to evaluate the results. For each analysis, we compared their actual relative ranks to the relative ranks that we expected. We also analyzed their rankings within in each sensitivity analysis and compared them to the original analysis. Five of these compounds were used to evaluate the exposure domain and five were used to evaluate the hazard domain. In both cases, the reference compounds had full data availability within their respective domain. For the exposure domain, the compounds needed to have experimental values from the PHYSPROP database for all four exposure metrics. The reference compounds in the hazard domain were required to have values from either the ToxVal database or the CTV Predictor for all eight hazard metrics.

The following five compounds were chosen as the reference compounds for the exposure domain: benzene, 2-methylnaphthalene, biphenyl, fluoranthene, and toluene (Table 7).

Reference compounds for the hazard domain were methanol, tetrachloroethylene, decane, decahydro-2,6-dimethylnaphthalene, and chloromethane hexanoate (Table 8).

Table 7. Experimental values of exposure metrics for the exposure domain reference compounds.

2-methylnaphthalene Benzene Biphenyl Fluoranthene Toluene Exposure Metric (91-57-6) (71-43-2) (92-52-4) (206-44-0) (108-88-3) Henry’s Law Constant 5.18×10-4 5.55×10-3 3.08×10-4 8.86×10-6 6.64×10-3 (atm-m3/mol) Biodegradation Half-Life 14 6 31 147 2 (days) Organic Carbon- Water Partition 3,980 56.2 1,860 63,100 117 Coefficient Bioconcentration 74.1 4.27 437 3,630 8.32 Factor

Table 8. Experimental toxicity values for the five hazard domain reference compounds. The metrics are the cancer potency value (CPV), oral slope factor (OSF), inhalation unit risk (IUR), reference dose (RfD), no observed adverse effect level (NOAEL), benchmark dose (BMD), benchmark dose lower limit (BMDL), and reference concentration (RfC).

2,6-Dimethyl- Chloromethyl Hazard Metric Decane Methanol decahydro- Tetrachloroethylene hexanoate [Units] (124-18-5) (67-56-1) naphthalene (127-18-4) (66542-51-6) (1618-22-0) CPV 5.08 4.79 4.09 5.78 3.91 [log10(kg*day)/mol] OSF 4.70 4.86 4.06 5.48 2.54 [log10(kg*day)/mol] IUR 3 4.63 4.44 3.01 4.72 1.63 [log10m /mol] RfD 6.97 7.50 4.20 7.62 7.44 [-log10mol/(kg*day)] NOAEL 4.00 3.73 1.81 4.61 4.84 [-log10mol/(kg*day)] BMD 3.59 2.61 1.13 3.16 4.10 [-log10mol/(kg*day)] BMDL 3.90 3.04 2.37 3.42 4.58 [-log10mol/(kg*day)] RfC 3 7.54 6.58 3.20 8.12 6.62 [-log10mol/m ]

3 Results and Discussion

3.1 Part I: Database

The first part of the results focuses on the creation of database, which laid the groundwork for the chemical prioritization. The database contains information on publications, samples, and chemicals from the studies that analyzed produced water generated from onshore oil and gas operations in North America.

3.1.1 Identification of publications, samples, and chemicals in produced water through comprehensive literature review

After the comprehensive literature review was completed, 179 studies met the criteria for inclusion in the database. Studies met the inclusion criterion if they provided primary chemical data of flowback or produced water from an onshore oil and gas operation in North

America. Of these studies, 129 were examined during the literature review by Danforth et al.

(2020) and the remaining 50 studies were examined during this literature review. The number of studies included in the database that were published over the last 45 years (the earliest publication identified) is shown in Figure 1. Almost all journals in the Web of Science and

PubMed databases are peer-reviewed, so the database is largely inclusive in terms of peer-reviewed studies but is less inclusive of non-peer-reviewed studies.

The 179 studies included in the database analyzed a total of 2,395 samples of produced water. Within these samples, 56,179 chemicals and bulk water quality parameters were identified. There were 1,337 different Chemical Abstract Service (CAS) numbers and 41 individual bulk water quality parameters identified. Approximately 49% (591) of these CAS numbers were identified in two or more samples. Of the 1,337 CAS numbers reported, 119 are

46 not on CompTox (Appendix Table 5). This left 1,218 distinct CAS numbers that were measured in at least one sample above the detection limit and were available on CompTox.

3.2 Part II: Prioritization of chemicals in produced water

The prioritization scheme was based on a groundwater exposure pathway, with the assumption that all chemicals on the working list made it into the groundwater. A key limitation in our exposure pathway is that we chose not to use site-specific physical and chemical properties of the subsurface, which affect a compound’s fate and transport. Seasonal variations, such as precipitation and infiltration, can also affect subsurface conditions, so there is uncertainty in assuming that compounds will have the same properties year-round. Increases in precipitation during the spring lead to higher infiltration rates, which could result in a spill reaching the groundwater faster.

3.2.1 Working list for prioritization scheme

Of the 591 CAS numbers that were identified in two or more samples, 12 were not on

CompTox and were thus removed from the list. There were ten isomer mixtures that needed to be replaced with their individual compounds. In total, there were 37 individual compounds within the mixtures, and 16 of them were already on the list (Table 1). There were nine organic compounds, including polyethylene glycol and polypropylene glycol, on the list that did not have any quality control data available and were thus removed from the list (Table 9).

Table 9. Organic compounds not included on the working list because they did not have sufficient quality control data available on CompTox. CAS Name 4013-34-7 (1-Methoxyethyl)benzene 67254-71-1 Alcohols, C10-C12, ethoxylated 67774-74-7 Benzene, C10-C13-alkyl derivatives 26603-23-6 Bis(octylphenyl)amine 27554-26-3 Diisooctyl phthalate 68987-90-6 Ethoxylated octylphenol 68140-01-2 N-[3-(Dimethylamino)propyl] coco amides 25322-68-3 Polyethylene glycol 25322-69-4 Polypropylene glycol

This left 581 unique compounds on the working list. A unique chemical defined here is a chemical with a CAS number available on CompTox that was identified in at least two individual produced water samples in the database above the detection limit or in a non-quantitative analysis. The process is shown in Figure 9.

Figure 9. Flow diagram of the requirements for a compound to be placed on the working list once identified in a sample. Compounds were considered distinctive if they had a Chemical Abstract Services (CAS) number and appeared in at least one produced water sample. The compounds on the working list are considered unique compounds because they were identified in two or more samples, their CAS numbers are in CompTox, and they have sufficient toxicity and physicochemical data available in CompTox.

The working list was then split into three main categories for the analysis process: organic compounds (458), inorganic compounds (98), and radionuclides (Figure 10). For the organic compounds, 390 compounds had at least one hazard metric (compounds with toxicity data) and 68 compounds had physicochemical data but no hazard metrics (compounds without

49 toxicity data). There were 98 inorganic compounds on the working list. Thirty-six inorganic chemicals had at least one toxicity value available (compounds with toxicity data) and 62 compounds had no hazard data (compounds without toxicity data). Radionuclides accounted for 25 of the working list compounds.

Figure 10. Flow diagram of the different groups of compounds in the working list. Compounds with at least one toxicity value available were classified as being with toxicity data and compounds with no available toxicity values were classified as being without toxicity data. Radionuclides were considered their own group because their hazard and exposure are not modeled using the same metrics as organic and inorganic compounds.

3.2.2 Collection and analysis of toxicity data for chemicals in prioritization scheme

Toxicity values for the metrics in the analysis were found in either the ToxVal database or modeled the Conditional Toxicity Value (CTV) Predictor tool (Wignall et al., 2018). Table 10 contains the number of organic and inorganic compounds on the working list with experimental, predicted, or no value for each toxicity metric in the hazard domain. The cancer

50 toxicity metric with the highest fraction of compounds with experimental data compared to predicted or no value was the inhalation unit risk (IUR), with 41 out of 556 compounds, followed by the oral slope factor (OSF) and the cancer potency value (CPV). Of the non-cancer toxicity metrics, the reference dose (RfD) had the most experimental data available with 123 out of 556 compounds (22%) and the benchmark dose lower limit (BMDL) had the lowest number of compounds with experimental data at 13 (2%). Over half of the compounds on the working list did not have a value for the CPV (55%) or the IUR (57%).

Table 10. Availability of experimental and predicted toxicity values for the 556 organic and inorganic compounds on the working list. The percentages are relative to each metric and represent the percent of total compounds with an experimental, predicted, or no value per toxicity metric. Experimental values were taken from the following sources: IRIS, Office of Pesticide Programs (OPP), Superfund Regional Screening Levels (ATSDR, PPRTV, HEAST), and California EPA Office of Environmental Health Hazard, all sourced through the ToxVal database.

Hazard Metric Experimental Predicted No Value Cancer potency value (CPV) 27 (5%) 222 (40%) 307 (55%) Oral slope factor (OSF) 39 (7%) 242 (44%) 275 (49%) Inhalation unit risk (IUR) 41 (7%) 196 (35%) 319 (57%) Reference dose (RfD) 123 (22%) 247 (44%) 186 (33%) RfD no observed adverse effect 87 (16%) 296 (53%) 173 (31%) level (NOAEL) RfD benchmark dose (BMD) 33 (6%) 287 (52%) 236 (42%) RfD benchmark dose lower limit 13 (2%) 302 (54%) 241 (43%) (BMDL) Reference concentration (RfC) 64 (12%) 221 (40%) 271 (49%)

The data in Table 10 were then separated based on the organic and inorganic compounds on the working list, results of which are in Table 11 and Table 12, respectively.

Table 12 does not have a column for predicted values because the CTV Predictor tool can only be used to model organic compounds. For each toxicity metric, the inorganic compounds had a higher percent of unavailable toxicity data than the organic compounds. More than half of the 51 inorganic compounds had no value for each toxicity metric, while over half the organic compounds had either experimental or predicted values for each metric.

Table 11. Availability of experimental and predicted toxicity values for the 458 organic compounds on the working list. The percentages are relative to each metric and represent the percent of total compounds with an experimental, predicted, or no value per toxicity metric. Experimental values were taken from the following sources: IRIS, Office of Pesticide Programs (OPP), Superfund Regional Screening Levels (ATSDR, PPRTV, HEAST), and California EPA Office of Environmental Health Hazard, all sourced through the ToxVal database.

Toxicity Value Experimental Predicted No Value Cancer potency value (CPV) 27 (6%) 222 (48%) 209 (46%) Oral slope factor (OSF) 38 (8%) 242 (53%) 178 (39%) Inhalation unit risk (IUR) 35 (8%) 196 (43%) 227 (50%) Reference dose (RfD) 92 (20%) 247 (54%) 119 (26%) RfD no observed adverse effect 67 (15%) 296 (64%) 95 (21%) level (NOAEL) RfD benchmark dose (BMD) 33 (7%) 287 (63%) 138 (30%) RfD benchmark dose lower limit 13 (3%) 302 (66%) 143 (31%) (BMDL) Reference concentration (RfC) 54 (12%) 221 (48%) 183 (40%)

Table 12. Availability of experimental toxicity values for the 98 inorganic compounds on the working list. The percentages are relative to each metric and represent the percent of total compounds with an experimental or no value per toxicity metric. Experimental values were taken from the following sources: IRIS, Office of Pesticide Programs (OPP), Superfund Regional Screening Levels (ATSDR, PPRTV, HEAST), and California EPA Office of Environmental Health Hazard, all sourced through the ToxVal database.

Toxicity Value Experimental No Value Cancer potency value (CPV) 0 (0%) 98 (100%) Oral slope factor (OSF) 1 (1%) 97 (99%) Inhalation unit risk (IUR) 6 (6%) 92 (94%) Reference dose (RfD) 31 (32%) 67 (68%) RfD no observed adverse effect level (NOAEL) 20 (20%) 78 (80%) RfD benchmark dose (BMD) 0 (0%) 98 (100%) RfD benchmark dose lower limit (BMDL) 0 (0%) 98 (100%) Reference concentration (RfC) 10 (10%) 88 (90%)

3.2.3 Data integration and prioritization using ToxPi

The Toxicological Prioritization Index (ToxPi) program (Marvel et al., 2018) was used to create a chemical prioritization for each of the three groups of compounds on the working list that had at least one toxicity metric available (Figure 10).

3.2.3.1 Organic compounds with toxicity data

This study analyzed the 390 organic compounds on the working list with hazard data.

The hazard and exposure domains were weighted equally. Thus, each of the eight hazard metrics were weighted at 6.25% and each of the four exposure metrics were weighted at

12.5%. Missing non-cancer toxicity values were replaced with the average of the available values for the respective metric. Missing cancer toxicity values were left blank and were automatically assigned a score of zero by ToxPi. The ToxPi profile used for the analysis is found in Figure 11.

Figure 11. ToxPi profile for the analysis. The slices represent the following metrics: biodegradation half-life (t1/2), organic carbon-water partition coefficient (Koc), Henry’s Law constant (KH), bioconcentration factor (BCF), inhalation unit risk (IUR), cancer potency value (CPV), oral slope factor (OSF), reference concentration (RfC), benchmark dose lower limit (BMDL), benchmark dose (BMD), no observed adverse effect level (NOAEL), and reference dose (RfD).

The results of the analysis and the ToxPi profiles for the hazard domain and exposure domain reference compounds are found in Figure 12. The 40 compounds, which is approximately the top 10%, that pose the highest risk and their overall ToxPi scores are shown in Table 13. A complete list of compounds, overall scores, and scores for individual metrics can be found in Appendix Table 6 through Appendix Table 9. Overall ToxPi scores ranged from 0.80 to 0.32, with the median 80% of compounds having scores between approximately 0.56 and

0.38. The compound that poses the highest risk is aldrin and 1,3-benzenedicarboxylic acid poses the lowest risk.

Figure 12. Overall ToxPi score versus rank for the 390 organic compounds with toxicity data on the working list. Each compound is represented by a data point. The reference compounds for the hazard domain (top) are represented by blue triangles and the reference compounds for the exposure domain (bottom) are represented by orange diamonds. In the ToxPi profiles, slices that represent hazard metrics are blue and slices for the exposure domain metrics are orange. The ToxPi profiles for the hazard domain reference compounds are outlined in blue and the profiles for the exposure domain reference compounds are outlined in orange. The distance of each slice from the center of circle to the black outline corresponds to the metric’s ToxPi score, with slices farther out from the center having scores closer to one. The width of each slice indicates the metric’s weight relative to the other metrics. Starting from the left-most orange slice and going clockwise, the metrics are as follows: biodegradation half-life (t1/2), organic carbon-water partition coefficient (Koc), Henry’s Law constant (KH), bioconcentration factor (BCF), inhalation unit risk (IUR), cancer potency value (CPV), oral slope factor (OSF), reference concentration (RfC), benchmark dose lower limit (BMDL), benchmark dose (BMD), no observed adverse effect level (NOAEL), and reference dose (RfD).

Table 13. Rank and ToxPi scores for the 40 organic compounds with toxicity data that had the highest relative risk.

Rank CAS Name ToxPi Score 1 309-00-2 Aldrin 0.802 2 1024-57-3 Heptachlor epoxide B 0.786 3 72-20-8 Endrin 0.786 4 76-44-8 Heptachlor 0.748 5 319-86-8 delta-Hexachlorocyclohexane 0.662 6 58-89-9 Lindane 0.661 7 319-85-7 beta-Hexachlorocyclohexane 0.660 8 2935-07-1 Dodecahydro-1H-phenalene 0.659 9 118-74-1 Hexachlorobenzene 0.655 10 50-32-8 Benzo(a)pyrene 0.626 11 281-23-2 Adamantane 0.625 12 54823-98-2 4,4'-Dimethyl-1,1'-bi(cyclohexane) 0.621 13 1660-04-4 Methyl tricyclo(3.3.1.13,7)dec-1-yl ketone 0.611 14 1750-51-2 1,6-Dimethyldecahydronaphthalene 0.599 15 56-55-3 Benz(a)anthracene 0.599 16 3178-23-2 Dicyclohexylmethane 0.598 17 6305-52-8 2-n-Butyldecahydronaphthalene 0.597 18 66552-62-3 1,5-Dimethyldecahydronaphthalene 0.597 19 5743-97-5 Tetradecahydrophenanthrene 0.597 20 1618-22-0 2,6-Dimethyldecahydronaphthalene 0.595 21 1008-80-6 2,3-Dimethyldecahydronaphthalene 0.595 22 294-62-2 Cyclododecane 0.595 23 92-51-3 1,1'-Bicyclohexyl 0.594 24 53-70-3 Dibenz(a,h)anthracene 0.591 25 66660-42-2 2-Ethyldecahydronaphthalene 0.583 26 1687-34-9 1-Ethyl-3-methyladamantane 0.581 27 4431-89-4 (Cyclopentylmethyl)cyclohexane 0.581 28 205-99-2 Benzo(b)fluoranthene 0.580 29 702-79-4 1,3-Dimethyladamantane 0.572 30 629-62-9 Pentadecane 0.570 31 629-59-4 Tetradecane 0.568 32 1606-08-2 Cyclopentylcyclohexane 0.567 33 218-01-9 Chrysene 0.567 34 2958-76-1 Decahydro-2-methylnaphthalene 0.567 35 16538-89-9 (Butan-2-yl)cyclooctane 0.561 36 23609-46-3 1,2-Diethylcyclooctane 0.560 37 2883-02-5 Nonylcyclohexane 0.556 38 1795-15-9 Octylcyclohexane 0.556 39 629-50-5 Tridecane 0.555 40 111-84-2 Nonane 0.554

Aldrin is an organochlorine insecticide that has been banned in the United States because of the risks it posed to both human and environmental health (U.S. EPA, 2002). This compound could have been in the makeup water used for the injected fluids. In our analysis, aldrin had the highest risk relative to the other compounds for the benchmark dose (BMD) and benchmark dose lower limit (BMDL). The reference concentration (RfC) was aldrin’s lowest scoring toxicity value with a ToxPi score of 0.72. All other ToxPi scores for the toxicity metrics were greater than 0.92. As expected of a persistent organic pollutant, aldrin has a high ToxPi score for the bioconcentration factor (BCF) and biodegradation half-life (t1/2). It also has a relatively high score for Henry’s Law constant (KH), meaning that it has a relatively high potential of volatilizing from shower or tap water. Aldrin’s lowest individual metric score (0.12) is for the organic carbon-water partition coefficient (Koc), which indicates that it is more likely to sorb to the organic matter in the soil than be transported in the groundwater. While this decreases the risk to human health for our exposure route, it increases risk to environmental health because it is a toxic compound that will remain in the soil and biodegrade slowly. The

ToxPi profile and individual metric scores for aldrin are shown in Figure 13.

Figure 13. ToxPi profile for aldrin, the organic compound with data on the working list with the highest relative risk. The black outline of the circle corresponds to a ToxPi score of one. Slices representing exposure domain metrics are orange and slices representing hazard domain metrics are blue. The metrics are biodegradation half-life (t1/2), organic carbon-water partition coefficient (Koc), Henry’s Law constant (KH), bioconcentration factor (BCF), inhalation unit risk (IUR), cancer potency value (CPV), oral slope factor (OSF), reference concentration (RfC), benchmark dose lower limit (BMDL), benchmark dose (BMD), no observed adverse effect level (NOAEL), and reference dose (RfD).

Dodecahydro-1H-phenalene, ranked eighth, is the highest-ranking compound that is not an organochlorine insecticide. It is a hydrocarbon, which is a class of organic compounds commonly identified in produced water. The ToxPi profile for dodecahydro-1H-phenalene can be seen in Figure 14. Its highest exposure potential is from its volatilization, with the ToxPi score for the KH being 0.89. This is closely followed by its tendency to bioconcentrate, which is indicated by the ToxPi score for the BCF (0.88). Dodecahydro-1H-phenalene is not readily

58 biodegradable, which increases the compound’s exposure potential. However, it has a relatively high potential to sorb to soil organic matter instead of being transported in the groundwater, which can be seen in the small Koc contribution to the overall ToxPi score. This was the lowest scoring metric (0.17) for the compound. The ToxPi scores for the three cancer metrics (OSF,

CPV, and IUR) and the RfC are all higher than 0.70, with the IUR having the highest score (0.77) of all eight hazard metrics.

Figure 14. ToxPi profile for dodecahydro-1H-phenalene, the highest-ranking, organic compound with data that is not an organochlorine insecticide. The black outline of the circle corresponds to a ToxPi score of one. Slices representing exposure domain metrics are orange and slices representing hazard domain metrics are blue. The metrics are biodegradation half-life (t1/2), organic carbon-water partition coefficient (Koc), Henry’s Law constant (KH), bioconcentration factor (BCF), inhalation unit risk (IUR), cancer potency value (CPV), oral slope factor (OSF), reference concentration (RfC), benchmark dose lower limit (BMDL), benchmark dose (BMD), no observed adverse effect level (NOAEL), and reference dose (RfD).

The compound that poses the least risk relative to the other organic compounds in the analysis is 1,3-benzenedicarboxylic acid. This acid has a pKa of 3.54 and its neutral fraction in groundwater at pH 7 is 0.00035. The neutral fraction is relatively small, which means the compound is mostly deprotonated and the modified KH, Koc, and BCF are almost 3,000-times smaller than the unmodified values. The biodegradation half-life of 1,3-benzenedicarboxylic acid has the lowest ToxPi score (0.14) of the four exposure domain metrics. The Koc (0.64) has the highest ToxPi score for the exposure domain, followed by the BCF (0.41) and KH (0.23). This means that the neutral fraction of the compound is more likely to be transported through the groundwater than sorb to the organic matter in soil, but that it is not likely to bioaccumulate or volatilize if it does reach a human receptor. The compound 1,3-benzenedicarboxylic acid does not have values for any of the three cancer toxicity metrics and has relatively low non-cancer toxicity. The ToxPi profile for 1,3-benzenedicarboxylic acid is shown in Figure 15.

Figure 15. ToxPi profile for 1,3-benzenedicarboxylic acid, the organic compound with data that has the least relative risk. The black outline of the circle corresponds to a ToxPi score of one. Slices representing exposure domain metrics are orange and slices representing hazard domain metrics are blue. The metrics are as follows: biodegradation half-life (t1/2), organic carbon- water partition coefficient (Koc), Henry’s Law constant (KH), bioconcentration factor (BCF), inhalation unit risk (IUR), cancer potency value (CPV), oral slope factor (OSF), reference concentration (RfC), benchmark dose lower limit (BMDL), benchmark dose (BMD), no observed adverse effect level (NOAEL), and reference dose (RfD).

3.2.3.1.1 Reference compounds

The five reference compounds for the exposure domain with their overall rank, overall score, and scores for the individual metrics in the exposure domain are found in Table 14 and their ToxPi profiles are in Figure 16. The relative ranks of the compounds based on the overall

ToxPi score are different than the relative ranks when the exposure domain metrics are

61 considered without the hazard domain metrics. However, the compounds rank as expected within the KH, t1/2, Koc, and BCF, respectively. Toluene has the highest volatilization potential at the exposure point, which is reflected in the fact that it has the highest ToxPi score for KH.

Benzene has the highest score for Koc and is thus the compound most likely to remain in the groundwater instead of sorbing to soil. Fluoranthene, a polycyclic aromatic hydrocarbon (PAH), will degrade the slowest and has the highest bioaccumulation potential, as seen in its high ToxPi scores for t1/2 and BCF. The relative ranks within the Koc and BCF metrics are almost completely inverted, meaning the compound with the highest exposure potential in terms of mobility has the lowest exposure potential in terms of bioaccumulation. The results indicate that the Koc is a good representation of compound mobility because the compounds have the same relative rank within that metric as they do with the time it takes them to travel a setback distance of 94 meters (t94). For comparison, the t94 values of the compounds are included in Table 14. The overall relative ranks of the five compounds makes sense when the toxicity metrics are examined. Benzene has both a high exposure potential and a high hazard potential, thus increasing its risk. This can be compared to fluoranthene, which has a relatively high exposure potential, but a relatively low hazard potential.

Table 14. Exposure domain reference compounds with their overall rank, overall ToxPi score, ToxPi score of the exposure metrics, and the time it takes each compound to travel a setback distance of 94 meters (t94). Compounds are listed from most relative risk to least relative risk. The metrics in the table are the Henry’s Law constant (KH), biodegradation half-life (t1/2), bioconcentration factor (BCF), and organic carbon-water partition coefficient (Koc). Name ToxPi KH t1/2 BCF Koc t94 Rank (CAS) Score Score Score Score Score (days) Benzene 103 0.510 0.866 0.177 0.695 0.347 115 (71-43-2) 2-methylnaphthalene 237 0.439 0.808 0.313 0.797 0.204 1,581 (91-57-6) Biphenyl 243 0.437 0.795 0.440 0.861 0.229 789 (92-52-4) Fluoranthene 259 0.428 0.707 0.692 0.936 0.110 23,671 (206-44-0) Toluene 378 0.354 0.871 0.001 0.719 0.322 138 (108-88-3)

Figure 16. Exposure domain reference compound ToxPi profiles from the analysis. The black outline of the circle indicates a score of one and the width of each slice represents its weight. Slices representing exposure domain metrics are orange and slices representing hazard domain metrics are blue. Starting from the arrow and moving clockwise, the metrics are as follows: biodegradation half-life (t1/2), organic carbon-water partition coefficient (Koc), Henry’s Law constant (KH), bioconcentration factor (BCF), inhalation unit risk (IUR), cancer potency value (CPV), oral slope factor (OSF), reference concentration (RfC), benchmark dose lower limit (BMDL), benchmark dose (BMD), no observed adverse effect level (NOAEL), and reference dose (RfD).

Table 15 summarizes the rank, overall ToxPi score, and individual toxicity metric scores for the five hazard domain reference compounds and their ToxPi profiles are shown in

Figure 17. The overall ranking of these compounds relative to each other is almost the same as

63 the order they follow when only the hazard domain is considered. When only the hazard domain is analyzed, the relative rank of chloromethyl hexanoate is two and that of decane is three. Decane is ranked higher in the original analysis because it takes longer to biodegrade than chloromethyl hexanoate and is less likely to sorb to organic matter. If only analyzing toxicity, 2,6-dimethyldecahydronaphthalene poses the highest relative risk, especially because it has the highest ToxPi scores for all three cancer metrics. The risk of this compound is further increased because it is relatively volatile and is likely to bioconcentrate, which generates higher

ToxPi scores for KH and BCF, respectively.

Table 15. Hazard domain reference compounds with their overall rank and overall ToxPi score listed from highest rank to lowest rank. ToxPi scores for the eight hazard domain metrics are also included: reference dose (RfD), no observed adverse effect level (NOAEL), benchmark dose (BMD), benchmark dose lower limit (BMDL), reference concentration (RfC), oral slope factor (OSF), cancer potency value (CPV), and inhalation unit risk (IUR). Name ToxPi Rank RfD NOAEL BMD BMDL RfC OSF CPV IUR (CAS) Score 2,6- Dimethyldecahydro- 20 0.595 0.58 0.51 0.42 0.26 0.62 0.69 0.70 0.75 naphthalene (1618-22-0) Decane 80 0.522 0.57 0.38 0.31 0.17 0.43 0.57 0.49 0.71 (124-18-5) Chloromethyl hexanoate 98 0.511 0.49 0.43 0.52 0.38 0.55 0.53 0.55 0.74 (66542-51-6) Tetrachloroethylene 105 0.507 0.56 0.59 0.63 0.55 0.43 0.07 0.30 0.27 (127-18-4) Methanol 387 0.335 0.09 0.03 0.00 0.00 0.00 0.39 0.34 0.48 (67-56-1)

Figure 17. Hazard domain reference compound ToxPi profiles from the analysis. The black outline of the circle corresponds to a ToxPi score of one and the width of each slice represents its weight. Slices representing exposure domain metrics are orange and slices representing hazard domain metrics are blue. Starting from arrow and moving clockwise, the metrics are as follows: biodegradation half-life (t1/2), organic carbon-water partition coefficient (Koc), Henry’s Law constant (KH), bioconcentration factor (BCF), inhalation unit risk (IUR), cancer potency value (CPV), oral slope factor (OSF), reference concentration (RfC), benchmark dose lower limit (BMDL), benchmark dose (BMD), no observed adverse effect level (NOAEL), and reference dose (RfD).

3.2.3.2 Organic compounds without toxicity data

There were 68 organic compounds on the working list that did not have any available toxicity data. Thus, these compounds were prioritized using only the metrics in the exposure domain. The results of this analysis will indicate which of these organic compounds human receptors are most likely to be exposed to. Researchers could then use this list to identify and prioritize compounds that need to be evaluated for toxicity. Each of the four metrics was assigned a weight of 25% (Figure 7). There were no missing values in this analysis because all of the data in the exposure domain were modeled with OPERA.

The ToxPi scores of the seven organic compounds without toxicity data, approximately the top 10% compounds, on the working list are summarized in Table 16. A complete list of the organic compounds without toxicity data, their overall ToxPi score, and their ToxPi scores for the individual metrics can be found in Appendix Table 10 and Appendix Table 11. Overall ToxPi

65 scores ranged from 0.69 to 0.29, with the median 80% of compounds have ToxPi scores between approximately 0.61 and 0.37.

Table 16. The seven organic compounds without toxicity data from the working list with the highest relative risk. The table includes compound rank, Chemical Abstract Services (CAS) number, approved name, and overall ToxPi score. Compounds with rankings closer to one are associated with higher ToxPi scores and thus pose more risk relative to the other compounds.

Rank CAS Name ToxPi Score 1 54832-83-6 2,2,4,4,7,7-Hexamethyloctahydro-1H-indene 0.686 2 204781-73-7 28-Nor-17alpha(H)-hopane 0.662 3 1079-71-6 1,2,3,4,5,6,7,8-Octahydroanthracene 0.646 4 191-24-2 Benzo(g,h,i)perylene 0.620 5 644-08-6 4-methylbiphenyl 0.614 6 1718-52-1 Pyrene-d_10_ 0.612 7 32038-83-8 3-Fluoroprop-2-ynenitrile 0.607

The compound with the most exposure potential is 2,2,4,4,7,7-hexamethyloctahydro-

1H-indene and the compound with the least exposure potential is 3,4-dihydro-1,9(2H,10H)- acridinedione. ToxPi profiles for these two compounds can be found in Figure 18. The highest risk of 2,2,4,4,7,7-hexamethyloctahydro-1H-indene is related to bioaccumulation potential and volatilization at the exposure point, which are reflected in the high ToxPi scores for the BCF

(0.954) and KH (0.947), respectively. The compound also biodegrades slowly, which increases the possibility that it will reach a human receptor. However, the ToxPi score for the Koc is relatively low (0.192), so the compound is more likely to sorb to organic matter than to be transported in the groundwater. A key factor that contributes to 3,4-dihydro-1,9(2H,10H)- acridinedione having such a low ranking is that it is a base with a pKa of 11.12. This results in a neutral fraction of 7.6E-5 at pH 7. The modified Koc is thus relatively small, which means the compound will likely remain in the groundwater and reach a receptor. However, the modified

BCF and KH are relatively small and decrease the exposure potential of the compound. The t1/2 of the compound is also small, so there is a high probability that the compound would degrade before reaching a human receptor.

Figure 18. ToxPi profiles for the organic compounds without toxicity data that have the highest and lowest relative risk. The compound 2,2,4,4,7,7-hexamethyloctahydro-1H-indene (left) has the highest risk and 3,4-dihydro-1,9(2H,10H)-acridinedione (right) has the lowest risk. The slices are the organic carbon-water partition coefficient (Koc), the Henry’s Law constant (KH), the bioconcentration factor (BCF), and biodegradation half-life (t1/2). The ToxPi score for the Koc of 2,2,4,4,7,7- hexamethyloctahydro-1H-indene is 0.192, its score for KH is 0.947, its BCF score is 0.954, and the t1/2 score is 0.650. For 3,4-dihydro-1,9(2H,10H)- acridinedione, the Koc score is one, the KH score is 0.063, the BCF has a score of zero, and the t1/2 has a score of 0.078.

3.2.3.3 Inorganic compounds with toxicity data

The inorganic compounds with toxicity data were defined here as those that had at least one toxicity metric available. There were no physicochemical properties available for inorganic compounds, so this group was analyzed using ToxPi for only the hazard domain (Figure 8). This means that the results will be a prioritization of compounds based only on toxicity and does not account for the mechanisms by which a human receptor would be exposed to the compound. 67

Overall ToxPi scores ranged from 0.58 to 0.13 and the median 80% of compounds had

ToxPi scores from approximately 0.38 to 0.16 (Table 17). The ToxPi scores for the individual metrics can be found in Appendix Table 12 and Appendix Table 13. None of the 36 inorganic compounds with toxicity data have a value for the CPV or the BMD, so every compound had a score of zero for these two metrics. Arsenic poses the highest risk relative to the other compounds on the list. A key factor that made arsenic the compound with the most risk is that it has the highest scores for both NOAEL and OSF, while also having the second highest score for IUR. The limited cancer toxicity values available for the inorganic compounds also affected the overall scores. Of the 36 compounds on the list, 30 compounds did not have any cancer toxicity values, with another five compounds only having one cancer value available. Chromium

(III), which had no cancer toxicity values and had a ToxPi score of zero for the NOAEL, was the compound with the lowest risk.

Table 17. ToxPi scores and ranking for the 36 inorganic compounds with data. A rank of one corresponds to the compound with the highest risk.

Rank CAS Name ToxPi Score 1 7440-38-2 Arsenic 0.579 2 7440-43-9 Cadmium 0.436 3 18540-29-9 Chromium (VI) ion 0.408 4 7439-91-0 Lanthanum 0.376 5 7440-28-0 Thallium 0.352 6 7440-41-7 Beryllium 0.338 7 7440-02-0 Nickel 0.320 8 7723-14-0 Phosphorus 0.320 9 7439-92-1 Lead 0.311 10 7440-62-2 Vanadium 0.295 11 7553-56-2 Iodine 0.292 12 7440-67-7 Zirconium 0.287 13 7782-49-2 Selenium 0.286 14 7440-36-0 Antimony 0.275 15 7440-33-7 Tungsten 0.272 16 7440-48-4 Cobalt 0.271 17 7439-97-6 Mercury 0.268 18 7439-96-5 Manganese 0.260 19 7440-22-4 Silver 0.250 20 7439-98-7 Molybdenum 0.249 21 7439-93-2 Lithium 0.234 22 14797-65-0 Nitrite 0.227 23 57-12-5 Cyanide 0.225 24 7783-06-4 Hydrogen sulfide 0.212 25 7440-66-6 Zinc 0.210 26 7440-31-5 Tin 0.207 27 7664-41-7 Ammonia 0.202 28 7439-89-6 Iron 0.199 29 7782-50-5 Chlorine 0.198 30 14797-55-8 Nitrate 0.189 31 7440-39-3 Barium 0.188 32 7440-24-6 Strontium 0.163 33 7440-50-8 Copper 0.158 34 7429-90-5 Aluminum 0.140 35 7440-42-8 Boron 0.131 36 16065-83-1 Chromium (III) 0.129

An interesting result is that phosphorus has a higher ranking than lead. This ranking is likely the result of limited data availability for both compounds. Lead only has a toxicity value for the IUR, so all non-cancer metrics were replaced with the average. References doses represent the lowest dose of a compound that is safe, and any higher dose is considered not safe. It is possible that lead does not have a reference dose because any consumption of lead is considered hazardous, or not safe. Phosphorus has toxicity values for the RfD and NOAEL, both of which are higher than the respective metric’s average of the available data and thus resulted in phosphorus having a higher overall ToxPi score. It should be noted that phosphorus cannot be found as a free element on earth, so a researcher using the database should trace the sample back to its publication to determine which phosphorus species was measured. We did not do this because it was outside the scope of our study, which is meant to provide a method for prioritization. The most common phosphorus species in water is phosphate, which is an important nutrient in aquatic ecosystems and is not toxic to humans (Spivakov et al., 1999).

The relative ranking of phosphorus compared to lead and the extent of missing toxicity data are indications that the results of this analysis, or any similar analysis, should be carefully examined. Overall, using ToxPi with our toxicity metrics to prioritize inorganic compounds based on hazard is not sufficient for evaluating relative risk and should be done with caution.

Instead, a researcher might identify the compounds on their list that are regulated under different water quality standards and use the available values to rank the compounds. The toxicity metrics used could also be narrowed down based on the data available, or the researcher could use a wider range of sources for the toxicity values.

3.2.4 Sensitivity analysis

We conducted two sensitivity analyses to determine if our analysis on the organic compounds with toxicity data was appropriate for the prioritization of chemicals in produced water. The first sensitivity analysis evaluated the effect of missing data on the prioritization scheme ranking and the second analysis examined its sensitivity to the weights of the hazard and exposure domains relative to each other. The five reference compounds from each of the two domains were tracked across the analyses for changes in relative ranking.

3.2.4.1 Missing data treatment

To determine the impact of missing data treatment on the ToxPi results, we ran the following three analyses:

(1) Case 1 (maximum): missing non-cancer toxicity values were replaced with the maximum value of the metric’s available data and missing cancer toxicity values were left blank (2) Case 2 (minimum): missing non-cancer toxicity values were replaced with the minimum value of the metric’s available data and missing cancer toxicity values were left blank (3) Case 3 (average): all missing toxicity values were replaced with the average of the available values of the respective metric

The general trends in the scores of each case compared to the original analysis followed the conclusions of To et al. (2018), who found that replacing missing values with the maximum or minimum of available data will shift the ToxPi scores higher or lower, respectively. In Case 1, where missing non-cancer values were replaced with the maximum of the respective metric, the ToxPi scores are generally higher than those in the original analysis. The opposite trend occurs in Case 2 because missing values were replaced with the minimum instead of the maximum. Case 3 ToxPi scores were generally higher than both the original analysis and Case 1 because all missing toxicity values were replaced with the average of their respective metric.

Case 3 is the only evaluation where the missing cancer toxicity values were replaced instead of being assigned a score of zero. A score of zero for the cancer metrics in ToxPi means that the compound is not carcinogenic. Over 90% of compounds had a rank shift of ten or more places in Case 1 and Case 3, and approximately 70% of compounds in Case 2 shifted rank by ten or more compared to their original ranking. The summary of the number of chemicals that shifted rank compared to the original analysis can be found in Table 18.

Table 18. Summary of the number of compounds that shifted rank compared to the original analysis for each case in the missing data sensitivity analysis. In Case 1, missing non-cancer toxicity data were replaced with the maximum of the available values of the respective metric. In Case 2, missing non-cancer toxicity data were replaced with the minimum of the available values for the respective metric. In Case 3, all missing toxicity data were replaced with the average of the available values for the respective metric.

Rank Shift Original vs. Case 1 Original vs. Case 2 Original vs. Case 3 No Rank Shift 0 14 9 5 or less 14 47 25 10 or more 351 279 359

The results of these sensitivity analyses can be seen in Figure 19 and

Figure 20. Variations in the overall ToxPi score compared to the original analysis are more evident for compounds with lower-risk ranks, as these compounds generally had fewer available toxicity values. There were 26 compounds that were ranked in the top 40 in all four cases (Appendix Table 14), but 1,3-benzenedicarboxylic acid was the singular compound in the bottom 40 for all cases. The ToxPi scores of the compounds with full data availability for hazard domain metrics did not change across the different scenarios. This is because ToxPi scores are calculated by normalizing the data and the maximum value in each metric was not changed in any of the scenarios. These results indicate that the prioritization scheme is sensitive to missing data treatment and becomes less reliable as the number of missing data points increases.

Figure 19. ToxPi score versus rank for the original analysis and three missing data treatment cases. The ranks from the original analysis were held constant to better depict how the overall ToxPi score changed. The original analysis is represented by grey circles, Case 1 (maximum) where missing non-cancer values were replaced with the maximum of the respective metric is represented by red triangles, Case 2 (minimum) where missing non-cancer values were replaced with the minimum of the respective metric is represented with green squares, and Case 3 (average) where all missing toxicity values were replaced with the average of the respective metric is represented by purple diamonds.

Figure 20. Heat map of the results from the three different cases evaluating the sensitivity of missing data treatment compared to the original analysis. The rank-change from the original analysis was held constant to better depict how the overall ToxPi score shifted. Case 1, where missing non- cancer values were replaced with the maximum of the respective metric, is labeled “Maximum.” Case 2, where missing non-cancer values were replaced with the minimum of the respective metric, is labeled “Minimum.” Case 3, where all missing toxicity values were replaced with the average of the respective metric, is labeled “Average.”

The effect of missing data treatment on the reference compounds from exposure domain and hazard domain compared to the original analysis are presented in Figure 21 and

Figure 22, respectively. The hazard domain reference compounds had the same score across all four cases, and thus the same ranks relative to each other. This was expected because these

74 compounds have values for each of the eight toxicity metrics, so there were no missing values to replace. The ranks of the exposure domain reference compounds relative to each other changed across the different cases, which is a result of missing toxicity values. A summary of the results from all cases for the reference compounds in each domain can be found in

Appendix Table 15.

Figure 21. ToxPi score versus compound rank for the original analysis and the exposure domain reference compounds for each missing data treatment case. The reference compounds for the original analysis are orange circles. Case 1 (maximum), where missing non-cancer values were replaced with the maximum of the respective metric, reference compounds are represented by red triangles; Case 2 (minimum), where missing non-cancer values were replaced with the minimum of the respective metric, reference compounds are represented with green squares; and Case 3 (average), where all missing toxicity values were replaced with the average of the respective metric, reference compounds are represented by purple diamonds.

Figure 22. ToxPi score versus compound rank for the original analysis and the hazard domain reference compounds for each missing data treatment case. The reference compounds for the original analysis are blue circles. Case 1 (maximum), where missing non- cancer values were replaced with the maximum of the respective metric, reference compounds are represented by red triangles; Case 2 (minimum), where missing non-cancer values were replaced with the minimum of the respective metric, reference compounds are represented with green squares; and Case 3 (average), where all missing toxicity values were replaced with the average of the respective metric, reference compounds are represented by purple diamonds.

The overall ranks and relative ranks of the five exposure domain reference compounds are found in Table 19. Of these compounds, benzene has the highest toxicity data availability and is only missing a value for the BMD. Toluene, which has the second most toxicity values available, does not have a value for the OSF or IUR. The compounds 2-methylnaphthalene does not have any cancer metric values and does not have a value for the RfC. Fluoranthene only has values for the RfD, NOAEL, and BMD. The only toxicity values available for biphenyl are the RfD,

RfC, and OSF. Toluene was the only exposure domain reference compound that maintained the same rank for all cases with a relative rank of five. The compound 2-methylnaphthene, which has no cancer toxicity values, had the highest rank compared to the other exposure domain reference compounds in Case 3. Fluoranthene also does not have any values for the cancer toxicity metrics but ranks higher than both benzene and toluene in Case 3. These results provide indication that our prioritization is highly sensitive both to how missing data is treated and the number of missing data points.

Table 19. Overall and relative ranks of the exposure domain reference compounds for the original analysis and the three cases used in the missing data sensitivity analysis. The hazard and exposure domains were equally weighted in all cases. In the original analysis, missing non-cancer toxicity values were replaced with the average of the available values for the respective metric and missing cancer toxicity values were left blank. Case 1 had all missing non-cancer toxicity values replaced with the maximum value in the metric and Case 2 replaced missing non-cancer toxicity values with the minimum available value in the metric; both Case 1 and Case 2 kept missing cancer toxicity values blank. In Case 3, all missing toxicity values were replaced with the average of the respective metric.

Case 1 Rank Case 2 Rank Case 3 Rank Compound Main Rank (Relative (Relative (Relative (CAS) (Relative Rank) Rank) Rank) Rank) Benzene 103 64 143 184 (71-43-2) (1) (2) (1) (4) 2-Methylnaphthalene 237 251 262 74 (91-57-6) (2) (4) (2) (1) Biphenyl 243 57 307 180 (92-52-4) (3) (1) (4) (3) Fluoranthene 259 162 295 96 (206-44-0) (4) (3) (3) (2) Toluene 378 389 315 350 (108-88-3) (5) (5) (5) (5)

3.2.4.2 Domain weights

The second sensitivity analysis evaluated the importance of the hazard and exposure domains relative to each other. We chose the following four weighting schemes in this analysis:

(1) Exposure domain only (2) Hazard domain only (3) Exposure domain weighted 25%; hazard domain weighted 75% (4) Exposure domain weighted 75%; hazard domain weighted 25%

Based on the results, the scores of compounds that pose lower risk are more sensitive to the weights of the domains than the scores of compounds with higher risk. When only the exposure domain was analyzed, every compound shifted at least one rank and less than 10% of compounds shifted less than five ranks. For the hazard domain analysis, approximately 15% of compounds remained within five spots of their original rank. Table 20 provides a summary of the number of compounds that shifted rank compared to the original analysis.

Table 20. Number of compounds that shifted rank compared to the original analysis for each of the four domain weight cases evaluated. The exposure only case is labeled ‘E100/H0’, the hazard only case is labeled ‘E0/H100’, the case where exposure was weighted 25% and hazard was weighted 75% is labeled ‘E25/H75’, and the case where exposure was weighted 75% and hazard was weighted 25% is labeled ‘E75/H25’.

Original vs. Original vs. Original vs. Original vs. Rank Shift E100/H0 E0/H100 E25/H75 E75/H25 No Rank Shift 0 15 12 8 5 or less 36 57 92 73 10 or more 336 306 260 284

There is still variation in compound rankings for both high risk and low risk compounds across the five cases. Seventeen compounds are ranked in the top 40 for all cases (Appendix

Table 16), but benzyl butyl phthalate is the only compound ranked in the bottom 40 for each case. The ToxPi scores for the two cases that emphasize the exposure domain (exposure only

78 and exposure 75%/hazard 25%) are generally higher than the scores from the original analysis, while the scores for the cases that emphasize the hazard domain (hazard only and exposure

25%/hazard 75%) are typically lower than the original analysis scores. The most extreme deviations in score occur when only the exposure domain is considered and when only the hazard domain is considered. In all cases, the ToxPi scores follow a linear trend similar to the original analysis. The large deviations in ToxPi scores compared to the original analysis indicate that our prioritization scheme is sensitive to the weights of the hazard and exposure domains, especially for compounds with lower risk. The results of this sensitivity analysis are shown in

Figure 23 and Figure 24. A summary of the ToxPi scores from the different domain weighting cases analyzed here are in Appendix Table 17.

Figure 23. ToxPi score versus compound rank for the sensitivity analysis evaluating the importance of the weights of the hazard and exposure domains relative to each other. The ranks for the original analysis were held constant to better depict how the overall ToxPi score changed. The original analysis is represented by black circles, the case with only the exposure domain is represented by red squares, the hazard domain only case is represented by purple triangles, the case where exposure is weighted 25% and hazard is weighed 75% (E25%/H75%) is represented by green diamonds, and the case where exposure is 75% and hazard is 25% (E75%/H25%) is represented by yellow octagons.

Figure 24. Heat map of the results from the four different cases evaluating the sensitivity of domain weights to the original analysis. The rank from the original analysis was held constant to better depict how the overall ToxPi score shifted. ‘E25%/H75%’ is the case where the exposure domain is weighted at 25% and the hazard domain is weighted at 75%. The label ‘E75%/H25%’ is for the case where the weight of the exposure domain is 75% and the weight of the hazard domain is 25%.

The five reference compounds for each domain were tracked across the different cases to understand the effects of changing the relative importance of the hazard and exposure domains. The ToxPi score versus compound rank for the exposure domain and hazard domain reference compounds is shown in Figure 25 and Figure 26, respectively.

Figure 25. ToxPi score versus compound rank for the original analysis and the exposure domain reference compounds for each domain weight case analyzed. Reference compounds for the original analysis are orange circles. The reference compounds for the case with only the exposure domain are represented by red squares, the reference compounds for the hazard domain only case are represented by purple triangles, the reference compounds for the case where exposure is weighted 25% and hazard is weighed 75% (E25%/H75%) are represented by green diamonds, and the reference compounds for the case where exposure is 75% and hazard is 25% (E75%/H25%) are represented by yellow octagons.

Figure 26. ToxPi score versus compound rank for the original analysis and the hazard domain reference compounds for each domain weight case analyzed. Reference compounds for the original analysis are blue circles. The reference compounds for the case with only the exposure domain are represented by red squares, the reference compounds for the hazard domain only case are represented by purple triangles, the reference compounds for the case where exposure is weighted 25% and hazard is weighed 75% (E25%/H75%) are represented by green diamonds, and the reference compounds for the case where exposure is 75% and hazard is 25% (E75%/H25%) are represented by yellow octagons.

ToxPi profiles for the exposure domain reference compounds of the case where only exposure potential was analyzed can be seen in Figure 27 and the ToxPi profiles for the hazard domain reference compounds from the case where only hazard potential was analyzed can be seen in Figure 28.

Figure 27. ToxPi profiles for the exposure domain reference compounds from the exposure- only case. The black circle represents a ToxPi score of one. Going clockwise from the black arrow in the first ToxPi profile, the metrics are the organic carbon-water partition coefficient (Koc), Henry’s Law constant (KH), bioconcentration factor (BCF), and biodegradation half-life (t1/2).

Figure 28. ToxPi profiles for hazard domain reference compounds from the hazard-only case. The black circle represents a ToxPi score of one. Going clockwise from the black arrow in the first ToxPi profile, the metrics are the benchmark dose (BMD), no observed adverse effect level (NOAEL), reference dose (RfD), inhalation unit risk (IUR), cancer potency value (CPV), oral slope factor (OSF), reference concentration (RfC), and benchmark dose lower limit (BMDL).

The overall ranks and relative ranks of the reference compounds for the exposure domain are in Table 21 Relative ranks for these reference compounds matched those from the original analysis when only the hazard domain was evaluated and when the hazard domain was weighted at 75%. The compounds did not rank relative to each as expected based on the mobility calculations for the exposure only analysis. Benzene has the highest mobility potential of the five reference compounds and fluoranthene has the least mobility potential. However, fluoranthene has the largest biodegradation half-life and benzene has the second-smallest

84 biodegradation half-life. Fluoranthene also has the most bioaccumulation potential and benzene has the least bioaccumulation potential of the exposure domain reference compounds. When comparisons are considered, the relative rankings for the exposure-only case make sense.

Table 21. Overall and relative ranks of the exposure domain reference compounds for the original analysis and the four cases used in the domain sensitivity analysis. In all cases, missing non-cancer toxicity values were replaced with the average of the metric’s available values and missing cancer toxicity values were left blank.

Exposure Exposure Original Exposure Hazard 25%/Hazard 75%/Hazard Rank Only Rank Only Rank Compound 75% Rank 25% Rank (Relative (Relative (Relative (Relative (Relative Rank) Rank) Rank) Rank) Rank) 103 222 87 86 160 Benzene (1) (4) (1) (1) (2) 237 202 268 257 212 2-Methylnaphthalene (2) (3) (2) (2) (4) 243 65 318 294 169 Biphenyl (3) (2) (3) (3) (3) 259 31 373 332 133 Fluoranthene (4) (1) (4) (4) (1) 378 291 380 383 351 Toluene (5) (5) (5) (5) (5)

Overall and relative ranks for the hazard domain reference compounds can be seen in

Table 22. These reference compounds did not have the same relative ranks in any of the four cases compared to the original analysis. However, the reference compounds from the hazard domain ranked as expected relative to each other for the case where the exposure domain was weighted 25% and the hazard domain was weighted 75%. The relative rankings were also more stable than those for the exposure domain reference compounds. Compared to the original analysis, the relative ranks of each hazard domain compound shifted by only one spot. The exposure domain reference compounds had almost completely opposite relative ranks

85 between the original analysis and the exposure-only case. This could be a because of the limited toxicity data available for the exposure domain reference compounds, which resulted in each compound being assigned an average non-cancer toxicity. This increased the hazard potential of the compounds without toxicity data and would account for the stark relative rank change of the analysis only evaluating exposure potential.

Table 22. Overall and relative ranks of the hazard domain reference compounds for the original analysis and the four cases used in the domain sensitivity analysis. In all cases, missing non-cancer toxicity values were replaced with the average of the metric’s available values and missing cancer toxicity values were left blank.

Hazard Exposure Exposure Exposure Original Rank Only 25%/Hazard 75%/Hazard Only Rank Compound (Relative Rank 75% Rank 25% Rank (Relative Rank) (Relative (Relative (Relative Rank) Rank) Rank) Rank) 2,6-Dimethyldecahydro- 20 17 25 21 16 naphthalene (1) (1) (1) (1) (1) 80 54 125 105 50 Decane (2) (2) (3) (3) (2) Chloromethyl 98 259 49 74 182 hexanoate (3) (5) (2) (2) (4) 105 55 171 142 67 Tetrachloroethylene (4) (3) (4) (4) (3) 387 252 390 390 347 Methanol (5) (4) (5) (5) (5)

The results show that the compounds with both high hazard potential and exposure potential are less sensitive to changes in the weights of the domains. The larger score variations for compounds with lower ranks indicate that these compounds may have high hazard potential or high exposure potential, but not both. Thus, the analysis with the two domains weighted equally is appropriate for our prioritization scheme.

3.2.5 Inorganic compounds without toxicity data

There were 62 non-radioactive inorganic compounds that did not have any toxicity data available. The six compounds (approximately 10%) with the highest maximum concentration reported in the database and the number of times they were reported in the database are listed in Table 23. This data for all 62 compounds can be found in Appendix Table 18.

Table 23. Six compounds with the highest maximum reported concentration and number of samples the compound was identified in for the inorganic compounds without toxicity data.

Maximum Number of CAS Name Concentration (mg/L) Times Reported 7440-70-2 Calcium 828,000 1,470 16887-00-6 Chloride 389,000 1,456 7440-23-5 Sodium 228,904 1,452 471-34-1 Calcium carbonate 103,026 18 7727-37-9 Nitrogen 96,026 178 7439-95-4 Magnesium 27,570 1,325 7440-09-7 Potassium 18,200 1,033 71-52-3 Bicarbonate 17,000 466 24959-67-9 Bromide 13,600 1,102 14808-79-8 Sulfate 5,590 807

3.2.6 Radionuclides

There were 25 radionuclides on the working list measured at activity concentrations above the detection limit. The activity of a radionuclide, units of becquerel (Bq), is a measure of the quantity of ionizing radiation released as the compound decays. In water, the amount of a radionuclide is measured using the activity concentration (Bq/L). Radionuclides are usually hazardous and exposure to them has been linked to cancer, kidney disease, anemia, compromised immune systems, and other health problems (Lesikar et al., 2019). A full list of the radionuclides on the working list with the maximum concentration and the number of samples they were reported in is in Table 24. There were 22 radionuclides out of the 25 total 87 that had their maximum concentration measured in Pennsylvania. One maximum concentration was in New York, one in West Virginia, and the third was an aggregate sample with produced water from New Mexico and Colorado. The complete summary of the information presented in this section can be found in Appendix Table 19.

Table 24. Maximum activity concentration and number of entries in the database for each radionuclide on the working list.

Maximum Activity Number of Times CAS Name Concentration (Bq/L) Reported 14331-85-2 Protactinium-231 8.88 2 15100-28-4 Protactinium-234 51.8 2 14331-83-0 Actinium-228 76 4 14952-40-0 Actinium-227 0.074 2 12587-46-1 Alpha particle 4,551 153 12587-47-2 Beta particle 22,111 153 14913-49-6 Bismuth-212 5.55 2 14733-03-0 Bismuth-214 271 7 10045-97-3 Caesium-137 0.333 7 14255-04-0 Lead-210 11.5 8 15092-94-1 Lead-212 2.4 6 15067-28-4 Lead-214 294 11 13966-00-2 Potassium-40 181 43 7440-14-4 Radium 668 144 15623-45-7 Radium-223 0.074 2 13233-32-4 Radium-224 21 22 13982-63-3 Radium-226 984 327 15262-20-1 Radium-228 1,348 289 10098-97-2 Strontium-90 2.62 9 15623-47-9 Thorium-227 0.111 5 14274-82-9 Thorium-228 312 12 14269-63-7 Thorium-230 0.347 8 15065-10-8 Thorium-234 6.29 5 13966-29-5 Uranium-234 0.818 8 15117-96-1 Uranium-235 1.48 14

3.3 Part III: Integrated findings

Our database contains information on publications, samples, and chemicals from studies that analyzed produced water in North America. We identified 179 studies that met our inclusion criterion by providing primary data on chemicals in flowback or produced water for onshore oil and gas operations in North America. Most studies targeted either organic or inorganic chemicals and used a single analytical method for compound identification. There are

1,337 different chemicals with CAS numbers that were measured at concentrations above the method detection limited in the database, but 119 (8.9%) of those CAS numbers are not available on CompTox (Appendix Table 5). We did not include chemicals without CAS numbers in our database, so there are chemicals known to be in produced water (i.e. polyethylene glycols and polypropylene glycols) that are not accounted for in either our database or prioritization scheme. Chemicals not on CompTox and chemicals without CAS numbers could be constituents of concern, but we could not use them in our prioritization scheme because they do not have exposure or hazard data available from the sources we used.

3.3.1 Future use of database

Once made publicly available, the database we created could be used to generate more region-specific information of general produced water quality. Our prioritization included chemicals from multiple oil and gas formations, but the database is designed to easily identify samples from specific formations depending on a researcher’s focus. The database could also be used to find all available concentration data for an individual chemical. This information could be narrowed down based on well type (conventional or unconventional), the petroleum product being extracted from a well, or the formation where the well is located.

A list of chemicals from the database could be used to assist a regulator evaluating whether or not CFR Part 136 is sufficient for produced water. The chemicals on their list could then be compared to the compounds regulated under CFR Part 136. If the regulator used the

390 organic compounds with toxicity data from our working list, they would find that 86% of them are not regulated (40 CFR §136, 2017). This is a significant fraction of the compounds, which would indicate that CFR Part 136 is currently not appropriate for adequately regulating produced water. Appendix Table 20 contains the organic compounds with toxicity data that are regulated under CFR Part 136.

3.3.2 Compound rank summary

The 15 compounds with the highest rank from each of the five groups analyzed in this study are listed in Table 25.

Table 25. The 15 compounds with the highest rank from each of the five groups analyzed: organic compounds with toxicity data, organic compounds without toxicity data, inorganic compounds with toxicity data, inorganic compounds without toxicity data, and radionuclides. The inorganic compounds without toxicity data and the radionuclides are ranked based on maximum concentration.

Inorganic Inorganic Compounds Organic Compounds Organic Compounds Compounds w/out Radionuclides w/ Toxicity Data w/out Toxicity Data w/ Toxicity Toxicity Data Data 2,2,4,4,7,7- 1 Aldrin Hexamethyloctahydro Arsenic Calcium Beta particle -1H-indene 28-Nor-17alpha(H)- 2 Heptachlor epoxide B Cadmium Chloride Alpha particle hopane 1,2,3,4,5,6,7,8- Chromium 3 Endrin Sodium Radium-228 Octahydroanthracene (VI) ion Calcium 4 Heptachlor Benzo(g,h,i)perylene Lanthanum Radium-226 carbonate delta- 5 4-methylbiphenyl Thallium Nitrogen Radium Hexachlorocyclohexane 3-Fluoroprop-2- 6 Lindane Beryllium Magnesium Lead-214 ynenitrile beta- 1,4,5,8-Tetramethyl- 7 Nickel Potassium Bismuth-214 Hexachlorocyclohexane naphthalene Dodecahydro-1H- 8 Diphenylmethane Phosphorus Bicarbonate Potassium-40 phenalene 2,3,6- 9 Hexachlorobenzene Lead Bromide Actinium-228 Trimethylnaphthalene Protactinium- 10 Benzo(a)pyrene 1-Methylfluorene Vanadium Sulfate 234 2,6- 11 Adamantane Iodine Silicon Radium-224 Dimethylnaphthalene 4,4'-Dimethyl-1,1'- 12 Phenanthrene Zirconium Carbon Lead-210 bi(cyclohexane) Methyl 2,7- 13 tricyclo(3.3.1.13,7)dec- Selenium Phosphate Protactinium Dimethylnaphthalene 1-yl ketone 1,6- 14 Decahydrodimethyl- m-Xylene Antimony Ammonium Thorium-234 naphthalene 15 Benz(a)anthracene 3-Methylbiphenyl Tungsten Carbonate Bismuth-212

3.3.3 Organic compounds with toxicity data

In the original analysis, the seven compounds with the highest risk (aldrin, heptachlor epoxide B, endrin, heptachlor, delta-hexachlorocyclohexane, lindane, and beta-hexachlorocyclohexane) are all organochlorine insecticides or by-products of insecticides and persistent organic pollutants that are not used for oil and gas operations. Aldrin was banned by the U.S. Department of Agriculture (USDA) in 1970 and banned by the EPA in 1987

(U.S. EPA, 2002). The production of endrin in the U.S. stopped in 1986 (U.S. EPA, 1996).

Heptachlor epoxide B is a biodegradation product of the heptachlor, which has not been used as a common insecticide since 1988 (U.S. EPA, 2007). Delta-hexachlorocyclohexane, lindane

(gamma-hexachlorocyclohexane), and beta-hexachlorocyclohexane are isomers of hexachlorocyclohexane (HCH), production of which stopped in the U.S. in 1976 (U.S. EPA, 2005).

The fact that these seven compounds are still being identified in produced water is reflective of how persistent they are. Not only are these compounds persistent, but they are also hazardous.

In the analysis, aldrin has the highest ToxPi score for the BMD and BMDL, endrin has the highest score for the NOAEL and all three cancer metrics (OSF, CPV, and IUR), and heptachlor epoxide B has the highest score for the RfD. It is unknown how persistent organic pollutants (POP), like organochlorine insecticides, become constituents of produced water. Although, it has been suggested that they could be from the makeup water used for hydraulic fracturing fluids (Yost et al., 2016).

In general, there are four sources of constituents in produced water: (1) the injection fluid makeup water, (2) chemical additives used in fracturing fluid, (3) the oil- and gas-bearing formation, and (4) transformation reactions. A study by Hoelzer et al. (2016) analyzed produced

92 water for potential transformation products and a study by Elsner & Hoelzer (2016) evaluated chemical additives from FracFocus disclosures for potential transformation products. Hoelzer et al. (2016) discussed the possibility that some fracturing fluid additives are meant to transform once injected, but that these reactions can also create unknown byproducts. Elsner & Hoelzer

(2016) found similar results. Both studies concluded that more comprehensive disclosures of chemical additives are needed to better characterize potential transformation reactions.

3.3.4 Prioritization scheme sensitivity

In our prioritization scheme, we made two key decisions on data availability and domain importance by considering any compound on the working list with at least one available toxicity value as having data and assigning equal weights to the hazard and exposure domains.

We tracked five reference compounds selected for each domain across the sensitivity analyses because we knew the way they should rank relative to each other for each metric within their domain. The hazard domain reference compounds were chosen because they had data available for each hazard metric. The reference compounds for the exposure domain were chosen because they had experimental data for each exposure metric. When doing a batch search in CompTox, all modeled OPERA values are downloaded without their corresponding applicability domain. To check if data were inside the applicability domain, we would have had to individually search for each compound, However, there were too many compounds on our to list to do this, so we used the OPERA values provided in the CompTox download. To apply the prioritization scheme described in this study to a risk assessment, a researcher would need to examine the available data for each compound individually and assess the validity of each value. It is likely that our prioritization was impacted by including data outside the applicability

93 domain, which is why we picked reference compounds with experimental data to check the rankings.

The results of the sensitivity analyses indicated that our prioritization is sensitive to both the way missing data is handled and the way the domains are weighted, but it is more sensitive to missing data. None of the exposure domain reference compounds had values for all eight of the toxicity metrics, and their relative ranks changed throughout the missing data sensitivity analysis. The prioritization scheme became less reliable as the amount of missing data increased. Different domain weighting had a larger effect on compounds that have either high exposure potential or high hazard potential than compounds that had relatively higher potential for both exposure and hazard.

Overall, the prioritization scheme developed in this report provides a ranking of compounds in produced water based on relative risk. It also underscored the extent of missing information for these compounds, which increases the uncertainty of the risk ranking. The scheme can be easily modified and applied to site-specific analyses by using the database to identify compounds from specific states or formations. Domain weights can also be changed if the researcher is more concerned with hazard or exposure.

3.3.5 Comparison to Danforth et al. (2020)

Danforth et al. (2020) used a comprehensive literature review to generate a list of compounds in produced water that were then prioritized. Their working list contained 122 compounds. Out of the 122 compounds, 101 were on our list of organic compounds with data list and 16 were on list of organic compounds without data (Appendix Table 21). Two compounds included in Danforth et al. (2020), cresol and xylenes, were identified as isomer

94 mixtures in our framework and were thus replaced with the individual compounds that make up the mixture for our working list.

The prioritization scheme created by Danforth et al. (2020) used ToxPi to integrate metrics from three toxicological domains: in vivo ecotoxicology, in vitro high throughput screening assays, and known or conditional human health toxicity values. The in vivo ecotoxicology domain contained the in vivo assays metric. Percent active assays and in vitro assays were the two metrics in the in vitro high throughput screening assays domain. Known or conditional human health toxicity values included reference dose (RfD), no observed adverse effect level (NOAEL), benchmark dose (BMD), benchmark dose lower limit (BMDL), cancer potency value (CPV), and oral slope factor (OSF). Danforth et al. (2020) used two weighting schemes, one with all metrics equally weighted and the other with the three domains equally weighted, to evaluate the effects of missing data. In both analyses, missing values were replaced with the minimum value of the respective metric, thus assuming that every compound had at the least a minimal activity (Danforth et al., 2020).

The top 40 compounds (top third) from both domain weighting schemes in Danforth et al. (2020) were compared against the top 40 compounds top tenth) from the analysis for organic compounds with data. There were five compounds with data in the top 40 of all three cases, and two compounds in the top 40 for the domain unweighted and our analysis of compounds with data (Table 26). One organic compound without data, benzo(g,h,i)perylene, in the top 40 compounds from our analysis was present in the top 40 compounds from the domain weighted analysis in Danforth et al. (2020). This could be because the organic

95 compounds without toxicity data in our analysis were still evaluated for exposure potential, while Danforth et al. (2020) only evaluated all compounds for toxicological hazard potential.

Table 26. Rank comparison for the top 40 organic compounds on the working list with at least one toxicity value that were also ranked in the top 40 in the prioritization by Danforth et al. (2020). Two cases from Danforth et al. (2020) were compared: one where the three domains were equally weighted and the other where the domains were unweighted.

Analysis Weighted Unweighted CAS Name Rank domains rank rank 319-86-8 Delta-Hexachlorocyclohexane 5 26 1 50-32-8 Benzo(a)pyrene 10 1 8 56-55-3 Benzo(a)anthracene 15 6 20 53-70-3 Dibenz(a,h)anthracene 24 4 31 205-99-2 Benzo(b)fluoranthene 28 8 32 629-59-4 Tetradecane 31 - 24 629-50-5 Tridecane 39 - 35

A notable compound that is not in the top 40 for our analysis is endosulfan, which is ranked 155. However, the in the prioritization framework in Danforth et al. (2020), endosulfan is ranked second. The key differences between the two studies are the metrics used to analyze risk and the treatment of missing toxicity data for ToxPi. We used metrics for both hazard and exposure domains, but Danforth et al. (2020) only used hazard metrics, which were different than the ones we used. The hazard metrics in our study accounted for oral and inhalation exposure routes with the reference concentration and inhalation unit risk (IUR), which were not used in the Danforth et al. (2020) framework. However, the main exposure route for endosulfan is ingestion, not inhalation, so the inclusion of inhalation hazard metrics in our analysis likely does not fully account for the different rankings (U.S. EPA, 2015a). Danforth et al.

(2020) considered ecological toxicity and cellular activity in their analysis, but we did not include either of these metrics in our analysis. By including the IUR, we had three cancer hazard

96 metrics compared to their two. Endosulfan does not have a value for any of the cancer toxicity metrics, and these values had a score of zero in ToxPi because we wanted to emphasize the known carcinogens in our analysis. Danforth et al. (2020) replaced all missing toxicity values with the minimum value of the respective metric, which elevated the risk of endosulfan. The differences in risk for endosulfan, which is a banned persistent organic pollutant, between our study and Danforth et al. (2020) indicate that the metrics used in ToxPi have a significant effect on the resulting rankings.

4 Conclusion

The first aim of this project was to create a database of compounds that have been identified in produced water from onshore oil and gas operations in North America. After the database was built, it was used to generate a prioritized list of potential constituents of concern. The risk-based prioritization scheme incorporated hazard and exposure by characterizing a groundwater exposure route using toxicity, transport, and bioaccumulation metrics.

The framework laid out in this study can be used to address different aspects of produced water composition. It can create a prioritization of the compounds known to be in produced water based on their relative risk. The framework can also be tailored to only look at hazard or exposure, depending on the researcher’s goal. Data collected for the prioritization scheme are also useful as they can be used to highlight the extent of missing information.

Again, this can be narrowed down to just hazard or just exposure. The resulting rankings of the compounds are useful because there are so many compounds in produced water that it is hard to determine which ones should be focused on the most. The focus could be based on either resulting rank or number of missing data, again depending on the focus of the study.

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6 Appendix 6.1 Database creation 6.1.1 Literature review search logic Appendix Table 1. Literature review search logic used in both PubMed and Web of Science.

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6.1.2 Abbreviations used in database Appendix Table 2. Abbreviations used in the database and their meaning.

Abbreviation Meaning Abbreviation Meaning ACID Acidity O&G Oil & Gas ACIDOC AcidOC pH pH ALK Alkalinity S.U. Standard Units Alpha Total Alpha SALIN Salinity BDL Below detection limit SS Suspended Solids Beta Total Beta TDN Total Dissolved Nitrogen BOD Biochemical Oxygen TDOC Total Dissolved Organic Demand Carbon C-HARD Calcium Hardness TDS Total Dissolved Solids COD Chemical Oxygen Demand TFS Total Fixed Solids COND Conductivity TKN Total Kjeldahl Nitrogen DC Dissolved Carbon TN Total Nitrogen DIC Dissolved Inorganic Carbon TOC Total Organic Carbon DO Dissolved Oxygen TPH Total Petroleum Hydrocarbons DOC Dissolved Organic Carbon TRS Total Residue Solids Gam Gamma TS Total Solids G-TDS Gravimetric Total TSS Total Suspended Solids Dissolved Solids HARD Hardness TURB Turbidity I-TDS Ionic Total Dissolved Solids TVS Total Volatile Solids mS/cm Millisiemens per VDS Volatile Dissolved Solids centimeter NA No information VolAc Volatile Acids NQ Not quantified VSS Volatile Suspended Solids NVDOC Nonvolatile Dissolved Organic Carbon

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6.2 Exposure domain: Ionized compounds Appendix Table 3. Acids on the working list with their pKa at 25°C and their calculated neutral fraction (αn).*

CAS Name pKa αn 64275-73-6 (Z)-5-Octen-1-ol 16.92 0.9999999999 121-91-5 1,3-Benzenedicarboxylic acid 3.54 0.000346617 1',4-Dihydroxy-7'-methoxy-2,3'-dimethyl-,(-)-[1,2'- 119736-96-8 9.34 0.995449916 binaphthalene]-5,5',8,8'-tetrone 71-36-3 1-Butanol 15.6 0.999999997 112-30-1 1-Decanol 15.21 0.999999994 6750-34-1 1-dodecanol, 3,7,11-trimethyl- 15.13 0.999999993 86-55-5 1-Naphthalenecarboxylic acid 3.7 0.000500936 90-15-3 1-Naphthol 9.44 0.996382354 2885-00-9 1-Octadecanethiol 10.49 0.999676511 111-87-5 1-Octanol 15.27 0.999999995 71-23-8 1-Propanol 16 0.999999999 112-70-9 1-Tridecanol 15.2 0.999999994 112-34-5 2-(2-Butoxyethoxy)ethanol 14.37 0.999999957 2136-72-3 2-(Octadecyloxy)ethanol 14.42 0.999999962 144-19-4 2,2,4-Trimethyl-1,3-pentanediol 14.81 0.999999985 5842-53-5 2,2,4-Trimethylpent-3-en-1-ol 15 0.99999999 526-75-0 2,3-Dimethylphenol 10.5 0.999683872 26746-38-3 2,3-di-tert-butylphenol 10.9 0.999874123 105-67-9 2,4-Dimethylphenol 10.6 0.999748874 96-76-4 2,4-Di-tert-butylphenol 10.87 0.999865122 95-87-4 2,5-Dimethylphenol 10.4 0.999602051 576-26-1 2,6-Dimethylphenol 10.6 0.999748874 3055-93-4 2-[2-(Dodecyloxy)ethoxy]ethanol 14.37 0.999999957 111-76-2 2-Butoxyethanol 14.2 0.999999937 104-76-7 2-Ethyl-1-hexanol 15.05 0.999999991 149-57-5 2-Ethylhexanoic acid 4.76 0.005721476 118-90-1 2-Methylbenzoic acid 3.92 0.000831073 116-53-0 2-Methylbutanoic acid 4.8 0.006270012 2490-48-4 2-Methylhexadecan-1-ol 15.04 0.999999991 79-31-2 2-Methylpropanoic acid 4.76 0.005721476 93-09-4 2-Naphthalenecarboxylic acid 4.2 0.001582385 135-19-3 2-Naphthalenol 9.6 0.997494407 122-99-6 2-Phenoxyethanol 15.1 0.999999992 95-65-8 3,4-Dimethylphenol 10.3 0.999499064 108-68-9 3,5-Dimethylphenol 10.1 0.999206302 99-06-9 3-Hydroxybenzoic acid 3.84 0.000691353 584-02-1 3-Pentanol 15.31 0.999999995 140-66-9 4-(1,1,3,3-Tetramethylbutyl)phenol 10.15 0.999292555 121-33-5 4-Hydroxy-3-methoxybenzaldehyde 7.38 0.70578136 98-54-4 4-tert-Butylphenol 10.3 0.999499064

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CAS Name pKa αn 99328-46-8 5-Methylhept-1-en-4-ol 15 0.99999999 65-85-0 Benzoic acid 4.18 0.001511274 80-05-7 Bisphenol A 10.29 0.999487402 107-92-6 Butanoic acid 4.8 0.006270012 105-60-2 Caprolactam 16.61 0.9999999998 334-48-5 Decanoic acid 4.89 0.007702679 143-07-7 Dodecanoic acid 4.89 0.007702679 64-17-5 Ethanol 15.5 0.999999997 141-78-6 Ethyl acetate 17 0.9999999999 107-21-1 Ethylene glycol 15.1 0.999999992 111-14-8 Heptanoic acid 4.86 0.007192256 57-10-3 Hexadecanoic acid 4.78 0.005989506 25447-95-4 Hexadecenoic acid 4.69 0.004873917 142-62-1 Hexanoic acid 4.85 0.007029691 67-63-0 Isopropanol 16.1 0.999999999 503-74-2 Isovaleric acid 4.79 0.006128164 108-39-4 m-Cresol 10.05 0.999109543 74-93-1 Methanethiol 10.33 0.999532484 67-56-1 Methanol 15.5 0.999999997 95-48-7 o-Cresol 10.28 0.999475468 57-11-4 Octadecanoic acid 5.01 0.010129278 26764-26-1 Octadecenoic acid 4.69 0.004873917 124-07-2 Octanoic acid 4.89 0.007702679 106-44-5 p-Cresol 10.25 0.999437975 109-52-4 Pentanoic acid 4.82 0.006563569 646-07-1 Pentanoic acid, 4-methyl- 4.84 0.006870776 108-95-2 Phenol 9.97 0.998929628 107-19-7 Propargyl alcohol 13.3 0.999999499 79-09-4 Propionic acid 4.83 0.006715428 544-63-8 Tetradecanoic acid 4.9 0.007880684 2315-61-9 Triton X-100.2 14.36 0.999999956 *Pentanoate (10023-74-2), formate (71-47-6), and 2-hydroxypropanoate (113-21-3), which were assigned neutral fraction values of 1×10-6, are not included in the table

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Appendix Table 4. Bases on the working list with their pKa at 25°C and their calculated neutral fraction (αn).

CAS Name pKa αn 1-Hydroxy-3-(2-methylpropyl)-6,7,8,8a- 2873-36-1 11.12 7.59E-05 tetrahydropyrrolo[1,2-a]pyrazin-4(3H)-one 1205-39-6 2-Methyl-N-phenylaniline 0.65 0.9999996 109-06-8 2-Methylpyridine 5.98 0.912826 80061-31-0 3,4-Dihydro-1,9(2H,10H)-acridinedione 11.12 7.59E-05 612-58-8 3-Methylquinoline 5.15 0.986071 100-01-6 4-Nitroaniline 1.03 0.999999 104-90-5 5-Ethyl-2-methylpyridine 6.51 0.755519 7661-55-4 5-Methylquinoline 5 0.990099 91-62-3 6-Methylquinoline 5.1 0.987567 612-60-2 7-Methylquinoline 5.25 0.982528 611-32-5 8-Methylquinoline 4.87 0.992641 79-06-1 Acrylamide 15.35 4.47E-09 62-53-3 Aniline 4.6 0.996035 95-16-9 Benzothiazole 2.28 0.999981 934-34-9 Benzothiazolone 10.41 0.000389 122-39-4 Diphenylamine 0.76 0.999999 119-65-3 Isoquinoline 5.36 0.977604 112-18-5 N,N-Dimethyldodecan-1-amine 9.78 0.001657 5618-62-2 O-Isobutylhydroxylamine 4.71 0.994898 110-86-1 Pyridine 5.26 0.982128 91-22-5 Quinoline 4.89 0.992297 122-20-3 Triisopropanolamine 14.37 4.27E-08

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6.3 Database results Appendix Table 5. The 139 chemicals in the database that are not available on CompTox.

CAS Chemical Name 100463-01-2 2,4-Dimethyl-1,5-diazabicyclo[3.1.0]hexane (cis) 105882-89-1 Ethanamine, 2,2'-azobis[N,N,1,1,2,2-hexafluoro- 1123-09-7 2-Cyclohexen-1-one, 3,5-dimethyl- 1124-25-0 Cyclohexane, 1-methyl-4-(1-methylethenyl)-, trans- 1137-00-4 2-Amino-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoic acid 114774-79-7 p-Nitrophenyl 1-azetidinecarboxylate 117177-34-1 Valeric acid, tridecyl ester 135241-50-8 Propanamide, 2-(4-isobutylphenyl)-N-(3,5-dinitrophenyl)- 13943-77-6 Naphthalene, 1,2,3,4,4a,5,6,7-octahydro-4a-methyl- 13966-28-4 Lead-208 142132-75-0 Propane, 1-(di-t-butylphosphino)-3-(2,4,6-tri-t-butylphenyl)phosphino- 14280-49-0 Thallium-205 14398-67-5 Decalin, syn-1-methyl-, cis- 14398-71-1 cis-Decalin, 2-syn-methyl- 14449-42-4 1-sec-Butyladamantane 14451-88-8 2-n-Propyladamantane 14913-50-9 Thallium-208 14914-65-9 Tin-118 15229-37-5 Bismuth-211 15496-01-2 Ditrifluoromethyl(chlorocarbonyloxy)amine 1595-10-4 1-Methyl-2-n-hexylbenzene 1618-23-1 Naphthalene, 2-ethyldecahydro- 166773-56-4 2,3-Dimethyl-5-(2,6,10-trimethylundecyl) furan 1671-77-8 1-Pentanone, 1-(4-methylphenyl)- 1687-35-0 1,3-Dimethyl-5-ethyladamantane 17312-59-3 Undecane, 4-ethyl- 17312-60-6 Undecane, 6-ethyl- 17453-94-0 Undecane, 5-ethyl- 18294-04-7 Ethanedioic acid, bis(trimethylsilyl) ester 18420-41-2 2-(Chloromethyl)tetrahydropyran 188645-81-0 3,4-Dichlorophenol, tert-butyldimethylsilyl ether 19126-15-9 9-Methoxyﬂuorene 19385-87-6 1,3-Dimethyl-5-n-propyl-adamantane 219783-06-9 1-Isopropyl-1,4,5-trimethylcyclohexane 227327-87-9 N-Adamantan-1-ylmethyl-2-chloro-5-nitro-benzamide 25117-35-5 Octadecane, 5-methyl- 26321-98-2 Cyclohexane, (1-ethylpropyl)- 2658-24-4 2,2-Dimethylaziridine 268543-19-7 1-Ethanone, 1-(1-adamantyl)-2-phenyl-

120

CAS Chemical Name 26967-64-6 Sec-Butylcyclohexane Dithiocarbaminic acid, N-cyano-, S-[3-(4-ethylphenyl)-3-oxo-1-propenyl]-S'-methyl 274691-67-7 diester 28980-74-7 3,5-Dodecadiene, 2-methyl- 29799-19-7 Cyclohexane, 1-(1,5-dimethylhexyl)-4-methyl- 30159-17-2 Tricyclo[7.3.0.0(2,6)]dodecane, trans-anti-trans- 31032-94-7 2-Ethyl-3-methylnaphthalene 31061-61-7 Tricyclo[4.3.1.1(3,8)]undecane-3-carboxylic acid, methyl ester Pyrazolo[3,4-b]pyran-5-carbonitrile, 1,4-dihydro-6-amino-4-(3,4-dichlorophenyl)- 315244-85-0 3-methyl- 32367-54-7 Naphthalene, 2-ethyl-1,2,3,4-tetrahydro- 331835-05-3 1-(2,4-Dihydroxybenzoyl)-3-ethyl-5-trifluoromethyl-5-hydroxy-2-pyrazoline 337503-48-7 4-Pentenoic acid, 2,2-diethyl-3-oxo-5-phenyl-, ethyl ester 33933-74-3 3-Heptene, 4-ethyl- 343270-50-8 2-(Butyliden-2-one)tetrahydrofuran 34694-70-7 1,3,5,6-Tetramethyladamantane 3877-19-8 Naphthalene, 1,2,3,4-tetrahydro-2-methyl- 39546-79-7 Pentylidenecyclohexane 41446-60-0 7-Tetradecene, (Z)- 41446-65-5 4-Tetradecene, (Z)- 41446-68-8 3-Tetradecene, (E)- 4175-54-6 Naphthalene, 1,2,3,4-tetrahydro-1,4-dimethyl- 4551-51-3 1H-Indene, octahydro-, cis- 4701-36-4 Benzene, (1-ethyl-1-propenyl)- 47145-46-0 3,4-Dihydroisoquinolin-7-ol, 1-[4-hydroxybenzyl]-6-methoxy- 480-72-8 Acenaphthylene, 1,2,2a,3,4,5-hexahydro- 497-32-5 Bicyclo[2.2.1]heptane, 2,2-dimethyl-5-methylene- 50617-19-1 2,5,8-Triphenyl benzotristriazole 50991-09-8 1,1'-Bicyclohexyl, 2-methyl-, trans- 50991-13-4 1,1'-Bicyclohexyl, 2-ethyl-, trans- 52745-93-4 (R)-(-)-4-Methylhexanoic acid 52856-01-6 2-Ethoxy-4,4,5,5-tetramethyloxazoline 52873-50-4 1,3-Dimethyl-5-n-hexyladamantane 52896-90-9 3-Ethyl-5-methylheptane 53485-49-7 Tricyclo[6.4.0.0(2,7)]dodecane 53907-60-1 Cyclopentane, 1,1,3,4-tetramethyl-, cis- 54163-69-8 Isopilocarpine 54411-17-5 Cyclohexane, 1,4-dimethyl-2-(2-methylpropyl)-, (1à,2á,4à)- 54699-35-3 1,2,4-Benzenetricarboxylic acid, 1,2-dimethyl ester 54965-05-8 Cyclohexane, 1,1,3-trimethyl-2-(3-methylpentyl)- 55170-90-6 Bicyclo[2.2.1]heptane, 2-(1-buten-3-yl)- 56292-69-4 Tetradecane, 2,5-dimethyl-

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CAS Chemical Name 56325-56-5 Cyclodecene, 3-bromo- 5661-80-3 Bicyclo[5.3.0]decane 56936-67-5 Henicosane 5744-03-6 Perhydrofluorene 58422-90-5 1,3-Dioxolane-2-heptanenitrile, à-methyl-ë-oxo-2-phenyl- 58462-32-1 trans,trans-3-Ethylbicyclo[4.4.0]decane 61141-80-8 Cyclohexane, 1,2-diethyl-3-methyl- 61142-32-3 Cyclopentene, 1,3-dimethyl-2-(1-methylethyl)- 61142-38-9 Cyclohexane, (3-methylpentyl)- 61177-16-0 Bicyclo[2.2.1]heptane, 2-butyl- 61208-94-4 Cyclohexane, (1-methylbutyl)- 62185-55-1 Nonane, 4-methyl-5-propyl- 62238-15-7 Decane, 2,3,4-trimethyl- 623-55-2 3-Hexanol, 5-methyl- 624-29-3 Cyclohexane, 1,4-dimethyl-, cis- 62960-77-4 4-Octene, 2,6-dimethyl-, [S-(Z)]- 63088-19-7 (4R*,5R*,9S*)-5,9-Dimethylspiro[3.5]nonan-1-one 63263-09-2 1,3-Dimethyladamantan-5-carboxylic acid, ethyl ester 63798-30-1 2-Butynamide, N-methyl- 66660-37-5 Trans, trans-2-ethylbicyclo[4.4.0]decane 66660-38-6 cis,cis,cis-1-Isobutyl-2,5-dimethylcyclohexane 6982-25-8 DL-2,3-Butanediol 700000-97-1 2,3,3-Trimethyl-1-hexene 71940-29-9 3,4-Dimethyl-2-(3-methyl-butyryl)-benzoic acid, methyl ester 74421-27-5 (2,4-Dimethylcyclopentyl)benzene 74630-16-3 Phosphonous dichloride, (1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)- 74630-54-9 3-Undecene, 9-methyl-, (E)- 74663-66-4 Cyclohexane, 1,5-diethyl-2,3-dimethyl- 7667-60-9 1,2,4-Trimethylcyclohexane 80655-44-3 Decahydro-1,1,4a,5,6-pentamethylnaphthalene 823-17-6 Cyclohexene, 3,5-dimethyl- 826-18-6 Benzene, 1-pentenyl- 82736-95-6 1,2,4-Triazine-3,5(2H,4H)-dione, 6-fluoro- 83173-76-6 Benzenemethanol, 4-methyl-à-(1-methyl-2-propenyl)-, (R*,R*)- 90832-26-1 4,5-Dihydro-á,á,4,4-tetramethyl-1H-pyrazole-1-propanol 90921-72-5 N-Allyl-p-hydroxybenzamide 91242-57-8 Cyclopentane, 1,2-dipropyl- 932-40-1 trans-1,2-Diethyl cyclopentane 94492-10-1 2-Dimethylamino-4-methyl-pent-4-enenitrile 99133-89-8 4-Imidazolacetic acid, butyl ester

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6.4 ToxPi results 6.4.1 Analysis Appendix Table 6. Compound rank and ToxPi score for the 390 organic compounds with toxicity data on the working list.

ToxPi Rank CAS Name Score 1 0.802 309-00-2 Aldrin 2 0.786 1024-57-3 Heptachlor epoxide B 3 0.786 72-20-8 Endrin 4 0.748 76-44-8 Heptachlor 5 0.662 319-86-8 delta-Hexachlorocyclohexane 6 0.661 58-89-9 Lindane 7 0.660 319-85-7 beta-Hexachlorocyclohexane 8 0.659 2935-07-1 1H-Phenalene, dodecahydro- 9 0.655 118-74-1 Hexachlorobenzene 10 0.626 50-32-8 Benzo(a)pyrene 11 0.625 281-23-2 Adamantane 12 0.621 54823-98-2 Cyclohexane, 1-(cyclohexylmethyl)-4-methyl-, trans- 13 0.611 1660-04-4 Methyl tricyclo(3.3.1.13,7)dec-1-yl ketone 14 0.599 1750-51-2 Naphthalene, decahydro-1,6-dimethyl- 15 0.599 56-55-3 Benz(a)anthracene 16 0.598 3178-23-2 Dicyclohexylmethane 17 0.597 6305-52-8 2-n-Butyldecahydronaphthalene 18 0.597 66552-62-3 Naphthalene, decahydro-1,5-dimethyl- 19 0.597 5743-97-5 phenanthrene, tetradecahydro- 20 0.595 1618-22-0 * naphthalene, decahydro-2,6-dimethyl- 21 0.595 1008-80-6 2,3-Dimethyldecahydronaphthalene 22 0.595 294-62-2 Cyclododecane 23 0.594 92-51-3 1,1'-Bicyclohexyl 24 0.591 53-70-3 Dibenz(a,h)anthracene 25 0.583 66660-42-2 cis, cis-3-ethylbicyclo[4.4.0]decane 26 0.581 1687-34-9 1-Ethyl-3-methyladamantane 27 0.581 4431-89-4 (Cyclopentylmethyl)cyclohexane 28 0.580 205-99-2 Benzo(b)fluoranthene 29 0.572 702-79-4 1,3-Dimethyladamantane 30 0.570 629-62-9 Pentadecane 31 0.568 629-59-4 Tetradecane 32 0.567 1606-08-2 Cyclopentylcyclohexane 33 0.567 218-01-9 Chrysene 34 0.567 2958-76-1 Decahydro-2-methylnaphthalene 35 0.561 16538-89-9 cyclooctane, (1-methylpropyl)- 36 0.560 23609-46-3 cyclooctane, 1,2-diethyl-

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ToxPi Rank CAS Name Score 37 0.556 2883-02-5 Cyclohexane, nonyl- 38 0.556 1795-15-9 Cyclohexane, octyl- 39 0.555 629-50-5 Tridecane 40 0.554 111-84-2 Nonane 41 0.554 1795-16-0 Decylcyclohexane 42 0.551 62199-52-4 1,2-Dibutylcyclopentane 43 0.546 1560-93-6 2-Methylpentadecane 44 0.546 74-83-9 Methyl bromide 45 0.545 6165-40-8 7-Methylpentadecane 46 0.543 295-17-0 Cyclotetradecane 47 0.542 3891-98-3 2,6,10-Trimethyldodecane 48 0.539 79-34-5 1,1,2,2-Tetrachloroethane 49 0.539 61142-68-5 1-Hexyl-3-methylcyclopentane 50 0.539 112-40-3 Dodecane 51 0.538 207-08-9 Benzo(k)fluoranthene 52 0.536 17312-57-1 3-Methyldodecane 53 0.536 13287-21-3 6-Methyltridecane 54 0.536 26730-14-3 7-Methyltridecane 55 0.535 707-35-7 1,3,5-Trimethyladamantane 56 0.534 17312-80-0 2,4-Dimethylundecane 57 0.533 1560-97-0 2-Methyldodecane 58 0.533 645-10-3 1,7-dimethyl-4-(1-methylethyl)cyclodecane 59 0.533 4292-75-5 Hexylcyclohexane 60 0.533 6117-97-1 4-Methyldodecane 61 0.533 67-66-3 Chloroform 62 0.532 1120-21-4 Undecane 63 0.532 17301-23-4 2,6-Dimethylundecane 64 0.531 6418-41-3 tridecane, 3-methyl- 65 0.531 1560-95-8 2-Methyltetradecane 66 0.530 56292-65-0 2,5-Dimethyldodecane 67 0.530 112-70-9 1-Tridecanol 68 0.529 25117-31-1 5-Methyltridecane 69 0.529 54411-00-6 cyclohexane, 1-methyl-4-(1-methylbutyl)- 70 0.529 41446-57-5 3-Tridecene, (3E)- 71 0.529 26730-12-1 4-Methyltridecane 72 0.528 25117-32-2 5-Methyltetradecane 73 0.528 13150-81-7 2,6-Dimethyldecane 74 0.528 1560-96-9 2-Methyltridecane 75 0.527 15232-86-7 1-Heptylcyclohexene 76 0.527 442662-72-8 2-Ethyl-1,1,3-trimethylcyclohexane 77 0.526 4457-00-5 Cyclopentane, hexyl-

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ToxPi Rank CAS Name Score 78 0.523 4292-92-6 Pentylcyclohexane 79 0.523 544-76-3 Hexadecane 80 0.522 124-18-5 * Decane 81 0.521 71312-54-4 1,4-Dimethyl-2,3-diazabicyclo[2.2.1]hept-2-ene 82 0.520 61142-66-3 cyclopentene, 5-hexyl-3,3-dimethyl- 83 0.519 2207-01-4 (Z)-1,2-Dimethylcyclohexane 84 0.519 6750-34-1 1-dodecanol, 3,7,11-trimethyl- 85 0.518 193-39-5 Indeno(1,2,3-cd)pyrene 86 0.518 7045-71-8 2-Methylundecane 87 0.516 1786-12-5 1,7,11-Trimethyl-4-(1-methylethyl)cyclotetradecane 88 0.515 61142-70-9 2,4-Diethyl-1-methylcyclohexane 89 0.514 2847-72-5 4-Methyldecane 90 0.514 115-96-8 Tris(2-chloroethyl) phosphate 91 0.514 110-82-7 Cyclohexane 92 0.513 17302-32-8 3,7-Dimethylnonane 93 0.513 17302-28-2 2,6-Dimethylnonane 94 0.513 13151-34-3 3-Methyldecane 95 0.513 16580-24-8 1-Methyl-3-(propan-2-yl)cyclohexane 96 0.513 74-93-1 Methanethiol 97 0.512 13151-35-4 5-Methyldecane 98 0.511 66542-51-6 * Chloromethyl hexanoate 99 0.511 591-21-9 1,3-Dimethylcyclohexane 100 0.511 62016-37-9 2,4,6-Trimethyloctane 101 0.511 2234-75-5 1,2,4-Trimethylcyclohexane 102 0.510 6975-98-0 2-Methyldecane 103 0.510 71-43-2 * Benzene 104 0.508 5402-53-9 Chloromethyl propanoate 105 0.507 127-18-4 * Tetrachloroethylene 106 0.506 3728-56-1 1-Ethyl-4-methylcyclohexane 107 0.506 14113-60-1 rel-(1R,2S)-1,2-Diethylcyclohexadecane 108 0.505 77877-94-2 Chloromethyl pentanoate 109 0.505 1678-93-9 Butylcyclohexane 110 0.505 112-18-5 N,N-Dimethyldodecan-1-amine 111 0.505 73105-67-6 1-Iodo-2-methylundecane 112 0.504 142-82-5 Heptane 113 0.504 1072-05-5 2,6-Dimethylheptane 114 0.504 62199-51-3 1-Pentyl-2-propylcyclopentane 115 0.504 26730-20-1 7-Methylhexadecane 116 0.504 111-65-9 Octane 117 0.502 111-44-4 Bis(2-chloroethyl) ether 118 0.502 3728-55-0 1-Ethyl-3-methylcyclohexane

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ToxPi Rank CAS Name Score 119 0.502 1560-92-5 2-Methylhexadecane 120 0.501 1678-92-8 Propylcyclohexane 121 0.501 2040-96-2 Propylcyclopentane 122 0.500 4291-79-6 1-Methyl-2-propyl-cyclohexane 123 0.500 75-25-2 Bromoform 124 0.500 5911-04-6 3-Methylnonane 125 0.500 54676-39-0 2-BUTYL-1,1,3-TRIMETHYL-CYCLOHEXANE 126 0.499 107-13-1 Acrylonitrile 127 0.499 16580-26-0 cyclohexane, 1-isopropyl-1-methyl- 128 0.499 3073-66-3 1,1,3-Trimethylcyclohexane 129 0.498 31295-56-4 2,6,11-Trimethyldodecane 130 0.498 17301-94-9 4-Methylnonane 131 0.497 871-83-0 2-Methylnonane 132 0.496 15869-86-0 4-Ethyloctane 133 0.496 79-06-1 Acrylamide 134 0.495 16747-30-1 2,4,4-Trimethylhexane 135 0.495 107-06-2 1,2-Dichloroethane 136 0.493 2883-05-8 2-Cyclohexyloctane 137 0.491 100-44-7 Benzyl chloride 138 0.491 54411-01-7 1-Methyl-2-pentylcyclohexane 139 0.490 15869-93-9 3,5-Dimethyloctane 140 0.490 2051-30-1 2,6-Dimethyloctane 141 0.489 74054-92-5 1,1,6,6-tetramethylspiro[4.4]nonane 142 0.489 2406-25-9 Di-tert-butyl nitroxide 143 0.489 98-95-3 Nitrobenzene 144 0.489 959028-24-1 4-Ethyl-2,3-dimethylhex-2-ene 145 0.487 2815-58-9 1,2,4-Trimethylcyclopentane 146 0.487 123-25-1 Diethyl butanedioate 147 0.487 75-15-0 Carbon disulfide 148 0.487 706-14-9 gamma-Decanolactone 149 0.486 143-07-7 Dodecanoic acid 150 0.485 109-74-0 Butanenitrile 151 0.484 1921-70-6 Norphytane 152 0.483 4810-09-7 3-Methyl-1-heptene 153 0.483 108-87-2 Methylcyclohexane 154 0.481 959-98-8 Endosulfan I 155 0.481 33213-65-9 Endosulfan II 156 0.481 1678-91-7 Ethylcyclohexane 157 0.481 2980-69-0 4-Methylundecane 158 0.481 3386-33-2 Octadecyl chloride 159 0.480 55282-11-6 11-Pentan-3-ylhenicosane

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ToxPi Rank CAS Name Score 160 0.480 112-30-1 1-Decanol 161 0.480 2453-00-1 1,3-Dimethylcyclopentane 162 0.479 74-84-0 Ethane 163 0.479 629-97-0 Docosane 164 0.479 1632-70-8 5-methylundecane 165 0.479 1002-43-3 3-Methylundecane 166 0.478 591-48-0 3-Methylcyclohexene 167 0.477 1192-18-3 (Z)-1,2-Dimethylcyclopentane 168 0.477 629-78-7 Heptadecane 169 0.474 592-27-8 2-Methylheptane 170 0.473 74-87-3 Chloromethane 171 0.473 7320-37-8 1,2-Epoxyhexadecane 172 0.472 593-45-3 Octadecane 173 0.471 110-75-8 2-Chloroethyl vinyl ether 174 0.471 562-28-7 (-)-Kaur-16-ene 175 0.470 111-30-8 Glutaraldehyde 176 0.469 821-55-6 2-Nonanone 177 0.468 638-36-8 2,6,10,14-Tetramethylhexadecane 178 0.468 50991-08-7 2-Methyl-1,1'-bi(cyclohexane) 179 0.468 106-65-0 Dimethyl succinate 180 0.467 109-66-0 Pentane 181 0.464 126-73-8 Tributyl phosphate 182 0.463 75-83-2 2,2-Dimethylbutane 183 0.463 110-54-3 n-Hexane 184 0.462 59887-80-8 1,3,5-Trimethyl-1,3,5-triazinane-2-thione 185 0.462 6418-44-6 heptadecane, 3-methyl- 186 0.461 111-87-5 1-Octanol 187 0.460 74-98-6 Propane 188 0.460 513-35-9 2-Methyl-2-butene 189 0.457 112-95-8 Eicosane 190 0.456 107-83-5 2-Methylpentane 191 0.456 91-20-3 Naphthalene 192 0.455 72-03-7 Propanoate 193 0.454 3892-00-0 2,6,10-Trimethylpentadecane 194 0.454 334-48-5 Decanoic acid 195 0.454 41446-78-0 4-Tetradecene, (4E)- 196 0.453 120-82-1 1,2,4-Trichlorobenzene 197 0.453 111-76-2 2-Butoxyethanol 198 0.453 629-92-5 Nonadecane 199 0.452 629-94-7 Heneicosane 200 0.452 68-12-2 N,N-Dimethylformamide

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ToxPi Rank CAS Name Score 201 0.452 106-46-7 1,4-Dichlorobenzene 202 0.451 112-88-9 1-Octadecene 203 0.451 297-35-8 Cyclotriacontane 204 0.451 104-76-7 2-Ethyl-1-hexanol 205 0.450 10374-74-0 7-Tetradecene 206 0.449 112-34-5 2-(2-Butoxyethoxy)ethanol 207 0.449 123-20-6 Butanoic acid, ethenyl ester 208 0.449 64275-73-6 (Z)-5-Octen-1-ol 209 0.448 18435-22-8 3-methyl-tetradecane 210 0.448 1768-36-1 Propyl cyanate 211 0.447 18435-45-5 1-Nonadecene 212 0.447 123-86-4 Butyl acetate 213 0.447 544-85-4 Dotriacontane 214 0.447 55000-52-7 2,6,10-Trimethylhexadecane 215 0.447 99328-46-8 5-Methylhept-1-en-4-ol 216 0.447 591-78-6 2-Hexanone 217 0.447 4360-57-0 2-Pentadecyl-1,3-dioxolane 218 0.446 638-67-5 Tricosane 219 0.446 87-61-6 1,2,3-Trichlorobenzene 220 0.445 1630-94-0 1,1-Dimethylcyclopropane 221 0.445 55030-62-1 4,8-Dimethyltridecane 222 0.444 18344-37-1 heptadecane, 2,6,10,14-tetramethyl- 223 0.444 144-19-4 2,2,4-Trimethyl-1,3-pentanediol 224 0.443 461-55-2 Butyrate 225 0.443 71-23-8 1-Propanol 226 0.443 646-31-1 Tetracosane 227 0.443 629-99-2 Pentacosane 228 0.442 5989-27-5 D-Limonene 229 0.442 54833-48-6 Heptadecane, 2,6,10,15-tetramethyl 230 0.442 57-60-3 Pyruvate 231 0.442 593-49-7 Heptacosane 232 0.441 79-09-4 Propionic acid 233 0.441 630-01-3 Hexacosane 234 0.440 54105-67-8 2,6-Dimethylheptadecane 235 0.440 110-94-1 Glutaric acid 236 0.440 544-63-8 Tetradecanoic acid 237 0.439 91-57-6 * 2-Methylnaphthalene 238 0.439 2885-00-9 1-Octadecanethiol 239 0.439 25117-24-2 4-Methyltetradecane 240 0.439 630-02-4 Octacosane 241 0.438 638-68-6 Triacontane

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ToxPi Rank CAS Name Score 242 0.437 71-36-3 1-Butanol 243 0.437 92-52-4 * Biphenyl 244 0.437 598-89-0 Diiodoacetic acid 245 0.436 13287-24-6 9-Methylnonadecane 246 0.436 96-04-8 2,3-Heptanedione 247 0.435 129-00-0 Pyrene 248 0.433 132-65-0 Dibenzothiophene 249 0.432 563-46-2 2-Methylbut-1-ene 250 0.432 2490-48-4 2-Methylhexadecan-1-ol 251 0.432 938-06-7 (4aS,8aR)-4a-Methyloctahydronaphthalen-2(1H)-one 252 0.431 695-06-7 gamma-Caprolactone 253 0.431 80-62-6 Methyl methacrylate 254 0.431 149-57-5 2-Ethylhexanoic acid 255 0.431 124-07-2 Octanoic acid 256 0.431 5618-62-2 O-Isobutylhydroxylamine 257 0.430 100-01-6 4-Nitroaniline 258 0.429 95-50-1 1,2-Dichlorobenzene 259 0.428 206-44-0 * Fluoranthene 260 0.427 57-11-4 Octadecanoic acid 261 0.427 630-03-5 Nonacosane 262 0.425 5842-53-5 2,2,4-Trimethylpent-3-en-1-ol 263 0.425 91-22-5 Quinoline 264 0.424 108-29-2 4-Pentanolide 265 0.424 111-14-8 Heptanoic acid 266 0.422 107-92-6 Butanoic acid 267 0.422 141-78-6 Ethyl acetate 268 0.422 142-62-1 Hexanoic acid 269 0.422 542-28-9 Tetrahydro-2H-pyran-2-one 270 0.422 98-82-8 Cumene 271 0.422 64-19-7 Acetic acid 272 0.422 544-77-4 1-Iodohexadecane 273 0.421 60212-33-1 4-Tetradecyne 274 0.421 71-50-1 Acetate 275 0.420 117-81-7 Di(2-ethylhexyl) phthalate 276 0.419 75-09-2 Dichloromethane 277 0.418 3055-93-4 2-[2-(Dodecyloxy)ethoxy]ethanol 278 0.418 123-91-1 1,4-Dioxane 279 0.418 4860-03-1 1-Chlorohexadecane 280 0.418 544-25-2 1,3,5-Cycloheptatriene 281 0.417 83-32-9 Acenaphthene 282 0.417 35216-11-6 7-Tetradecyne

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ToxPi Rank CAS Name Score 283 0.417 100-41-4 Ethylbenzene 284 0.417 132-64-9 Dibenzofuran 285 0.417 108-90-7 Chlorobenzene 286 0.416 766-76-7 Benzoate 287 0.415 109-52-4 Pentanoic acid 288 0.415 61886-62-2 3-Hexadecyne 289 0.415 584-02-1 3-Pentanol 290 0.414 120-12-7 Anthracene 291 0.413 57-55-6 1,2-Propylene glycol 292 0.413 79-31-2 2-Methylpropanoic acid 293 0.413 74-82-8 Methane 294 0.412 64-17-5 Ethanol 295 0.411 67-63-0 Isopropanol 296 0.411 575-41-7 1,3-Dimethylnaphthalene 297 0.411 57-10-3 Hexadecanoic acid 298 0.411 75-34-3 1,1-Dichloroethane 299 0.410 110-86-1 Pyridine 300 0.410 646-07-1 Pentanoic acid, 4-methyl- 301 0.410 86-30-6 N-Nitrosodiphenylamine 302 0.409 90-12-0 1-Methylnaphthalene 303 0.409 86-73-7 Fluorene 304 0.409 576-26-1 2,6-Dimethylphenol 305 0.409 573-98-8 1,2-Dimethylnaphthalene 306 0.407 116-53-0 2-Methylbutanoic acid 307 0.407 569-41-5 1,8-Dimethylnaphthalene 308 0.407 571-58-4 1,4-Dimethylnaphthalene 309 0.406 575-37-1 1,7-Dimethylnaphthalene 310 0.405 2049-95-8 tert-Pentylbenzene 311 0.405 1599-67-3 1-Docosene 312 0.404 62-53-3 Aniline 313 0.403 50-00-0 Formaldehyde 314 0.403 503-74-2 Isovaleric acid 315 0.402 533-18-6 Acetic acid, 2-methylphenyl ester 316 0.401 122-20-3 Triisopropanolamine 317 0.401 3055-94-5 Triethylene glycol monododecyl ether 318 0.399 113-21-3 Lactate ion(1-) 319 0.399 941228-34-8 7-(Bromomethyl)pentadec-7-ene 320 0.398 10023-74-2 Pentanoic acid, ion(1-) 321 0.398 75-07-0 Acetaldehyde 322 0.398 95-65-8 3,4-Dimethylphenol 323 0.397 35365-59-4 9-Octadecyne

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ToxPi Rank CAS Name Score 324 0.395 90-15-3 1-Naphthol 325 0.394 541-73-1 1,3-Dichlorobenzene 326 0.394 122-99-6 2-Phenoxyethanol 327 0.393 95-87-4 2,5-Dimethylphenol 328 0.392 106-44-5 p-Cresol 329 0.391 107-21-1 Ethylene glycol 1-Hydroxy-3-(2-methylpropyl)-6,7,8,8a-tetrahydropyrrolo[1,2- 330 0.390 2873-36-1 a]pyrazin-4(3H)-one 331 0.390 2136-72-3 2-(Octadecyloxy)ethanol 332 0.390 526-73-8 1,2,3-Trimethylbenzene 333 0.388 575-43-9 1,6-Dimethylnaphthalene 334 0.388 98-86-2 Acetophenone 335 0.388 611-14-3 1-Ethyl-2-methylbenzene 336 0.387 95-63-6 1,2,4-Trimethylbenzene 337 0.387 1074-43-7 1-Methyl-3-propylbenzene 338 0.386 135-19-3 2-Naphthalenol 339 0.386 104-90-5 5-Ethyl-2-methylpyridine 340 0.386 98-06-6 tert-Butylbenzene 341 0.384 3333-52-6 Tetramethylsuccinonitrile 342 0.384 78-93-3 Methyl ethyl ketone 343 0.383 107-19-7 Propargyl alcohol 344 0.382 620-14-4 3-Ethyltoluene 345 0.382 108-68-9 3,5-Dimethylphenol 346 0.381 526-75-0 2,3-Dimethylphenol 347 0.380 99-06-9 3-Hydroxybenzoic acid 348 0.379 108-10-1 4-Methyl-2-pentanone 349 0.379 105-60-2 Caprolactam 350 0.378 118-90-1 2-Methylbenzoic acid 351 0.378 122-39-4 Diphenylamine 352 0.378 95-47-6 o-Xylene 353 0.377 95-48-7 o-Cresol 354 0.377 106-42-3 p-Xylene 355 0.376 80-05-7 Bisphenol A 356 0.374 65-85-0 Benzoic acid 357 0.373 108-67-8 1,3,5-Trimethylbenzene 358 0.372 135-98-8 sec-Butylbenzene 359 0.372 71-47-6 Formic acid, ion(1-) 360 0.371 78-51-3 Tris(2-butoxyethyl) phosphate 361 0.369 104-51-8 Butylbenzene 362 0.369 108-39-4 m-Cresol 363 0.366 109-06-8 2-Methylpyridine 364 0.365 100-52-7 Benzaldehyde

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ToxPi Rank CAS Name Score 365 0.364 611-32-5 8-Methylquinoline 366 0.364 67-64-1 Acetone 367 0.363 103-65-1 Propylbenzene 368 0.363 7661-55-4 5-Methylquinoline 369 0.361 105-67-9 2,4-Dimethylphenol 370 0.361 91-62-3 6-Methylquinoline 371 0.361 108-95-2 Phenol 372 0.361 612-60-2 7-Methylquinoline 373 0.361 612-58-8 3-Methylquinoline 374 0.360 491-35-0 Lepidine 375 0.360 117-84-0 Di-n-octyl phthalate 376 0.360 498-02-2 Acetovanillone 377 0.355 100-51-6 Benzyl alcohol 378 0.354 108-88-3 * Toluene 379 0.354 131-11-3 Dimethyl phthalate 380 0.351 26764-26-1 Octadecenoic acid 381 0.350 84-74-2 Dibutyl phthalate 382 0.349 28631-86-9 2,2-Dihydroxy-1-phenylethanone 383 0.349 100-42-5 Styrene 384 0.341 4376-20-9 MEHP 385 0.338 25447-95-4 Hexadecenoic acid 386 0.336 86-55-5 1-Naphthalenecarboxylic acid 387 0.335 67-56-1 * Methanol 388 0.326 85-68-7 Benzyl butyl phthalate 389 0.326 84-66-2 Diethyl phthalate 390 0.319 121-91-5 1,3-Benzenedicarboxylic acid

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6.4.1.1 Exposure domain metric ToxPi scores Appendix Table 7. ToxPi scores for each exposure domain metric from the 376 organic compounds with toxicity data on the working list: Henry’s Law constant (KH), organic carbon- water partition coefficient (Koc), biodegradation half-life (t1/2), and bioconcentration factor (BCF).

CAS Name KH Koc t1/2 BCF 309-00-2 Aldrin 0.75 0.12 0.82 0.95 1024-57-3 Heptachlor epoxide B 0.73 0.17 0.76 0.95 72-20-8 Endrin 0.71 0.17 0.82 0.97 76-44-8 Heptachlor 0.79 0.14 0.69 0.97 319-86-8 delta-Hexachlorocyclohexane 0.68 0.24 0.36 0.89 58-89-9 Lindane 0.68 0.24 0.36 0.89 319-85-7 beta-Hexachlorocyclohexane 0.68 0.24 0.36 0.89 2935-07-1 1H-Phenalene, dodecahydro- 0.89 0.17 0.84 0.88 118-74-1 Hexachlorobenzene 0.84 0.19 0.35 1.00 50-32-8 Benzo(a)pyrene 0.63 0.02 0.76 0.89 281-23-2 Adamantane 0.87 0.20 1.00 0.86 Cyclohexane, 1-(cyclohexylmethyl)-4- 54823-98-2 0.88 0.24 0.54 0.88 methyl-, trans- Methyl tricyclo(3.3.1.13,7)dec-1-yl 1660-04-4 0.78 0.18 0.74 0.79 ketone Naphthalene, decahydro-1,6- 1750-51-2 0.91 0.21 0.50 0.86 dimethyl- 56-55-3 Benz(a)anthracene 0.71 0.07 0.80 0.84 3178-23-2 Dicyclohexylmethane 0.87 0.22 0.49 0.87 6305-52-8 2-n-Butyldecahydronaphthalene 0.87 0.21 0.44 0.87 Naphthalene, decahydro-1,5- 66552-62-3 0.92 0.21 0.48 0.88 dimethyl- 5743-97-5 phenanthrene, tetradecahydro- 0.87 0.17 0.82 0.87 * naphthalene, decahydro-2,6- 1618-22-0 0.91 0.22 0.50 0.87 dimethyl- 1008-80-6 2,3-Dimethyldecahydronaphthalene 0.91 0.21 0.51 0.88 294-62-2 Cyclododecane 0.93 0.22 0.35 0.97 92-51-3 1,1'-Bicyclohexyl 0.91 0.22 0.48 0.87 53-70-3 Dibenz(a,h)anthracene 0.65 0.00 0.86 0.90 66660-42-2 cis, cis-3-ethylbicyclo[4.4.0]decane 0.91 0.21 0.39 0.88 1687-34-9 1-Ethyl-3-methyladamantane 0.89 0.17 0.96 0.89 4431-89-4 (Cyclopentylmethyl)cyclohexane 0.91 0.22 0.42 0.88 205-99-2 Benzo(b)fluoranthene 0.72 0.05 0.72 0.88 702-79-4 1,3-Dimethyladamantane 0.89 0.19 0.96 0.90 629-62-9 Pentadecane 0.85 0.21 0.41 0.92 629-59-4 Tetradecane 0.90 0.21 0.39 0.91 1606-08-2 Cyclopentylcyclohexane 0.91 0.20 0.41 0.89

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CAS Name KH Koc t1/2 BCF 218-01-9 Chrysene 0.69 0.07 0.84 0.86 2958-76-1 Decahydro-2-methylnaphthalene 0.91 0.20 0.45 0.86 16538-89-9 cyclooctane, (1-methylpropyl)- 0.93 0.22 0.26 0.87 23609-46-3 cyclooctane, 1,2-diethyl- 0.93 0.20 0.25 0.88 2883-02-5 Cyclohexane, nonyl- 0.85 0.19 0.29 0.88 1795-15-9 Cyclohexane, octyl- 0.88 0.22 0.27 0.88 629-50-5 Tridecane 0.95 0.23 0.29 0.89 111-84-2 Nonane 0.95 0.29 0.24 0.89 1795-16-0 Decylcyclohexane 0.83 0.18 0.28 0.88 62199-52-4 1,2-Dibutylcyclopentane 0.93 0.22 0.26 0.87 1560-93-6 2-Methylpentadecane 0.88 0.20 0.26 0.90 74-83-9 Methyl bromide 0.87 0.38 0.38 0.72 6165-40-8 7-Methylpentadecane 0.88 0.20 0.23 0.90 295-17-0 Cyclotetradecane 0.89 0.18 0.35 0.88 3891-98-3 2,6,10-Trimethyldodecane 0.90 0.20 0.24 0.90 79-34-5 1,1,2,2-Tetrachloroethane 0.80 0.34 0.35 0.73 61142-68-5 1-Hexyl-3-methylcyclopentane 0.93 0.24 0.22 0.88 112-40-3 Dodecane 0.95 0.24 0.26 0.84 207-08-9 Benzo(k)fluoranthene 0.64 0.15 0.83 0.90 17312-57-1 3-Methyldodecane 0.95 0.23 0.17 0.89 13287-21-3 6-Methyltridecane 0.95 0.23 0.17 0.87 26730-14-3 7-Methyltridecane 0.95 0.23 0.17 0.87 707-35-7 1,3,5-Trimethyladamantane 0.89 0.17 0.96 0.91 17312-80-0 2,4-Dimethylundecane 0.95 0.24 0.20 0.88 1560-97-0 2-Methyldodecane 0.95 0.23 0.17 0.89 1,7-dimethyl-4-(1- 645-10-3 0.89 0.17 0.33 0.88 methylethyl)cyclodecane 4292-75-5 Hexylcyclohexane 0.93 0.24 0.13 0.87 6117-97-1 4-Methyldodecane 0.95 0.23 0.17 0.87 67-66-3 Chloroform 0.86 0.36 0.42 0.73 1120-21-4 Undecane 0.95 0.26 0.20 0.89 17301-23-4 2,6-Dimethylundecane 0.95 0.24 0.16 0.89 6418-41-3 tridecane, 3-methyl- 0.90 0.23 0.18 0.88 1560-95-8 2-Methyltetradecane 0.85 0.20 0.23 0.89 56292-65-0 2,5-Dimethyldodecane 0.95 0.23 0.17 0.88 112-70-9 1-Tridecanol 0.73 0.23 0.22 0.91 25117-31-1 5-Methyltridecane 0.90 0.23 0.17 0.87 cyclohexane, 1-methyl-4-(1- 54411-00-6 0.93 0.23 0.14 0.89 methylbutyl)- 41446-57-5 3-Tridecene, (3E)- 0.89 0.23 0.16 0.88 26730-12-1 4-Methyltridecane 0.90 0.23 0.17 0.87 25117-32-2 5-Methyltetradecane 0.85 0.20 0.17 0.89

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CAS Name KH Koc t1/2 BCF 13150-81-7 2,6-Dimethyldecane 0.95 0.26 0.19 0.87 1560-96-9 2-Methyltridecane 0.90 0.23 0.18 0.88 15232-86-7 1-Heptylcyclohexene 0.88 0.23 0.12 0.86 442662-72-8 2-Ethyl-1,1,3-trimethylcyclohexane 0.93 0.20 0.26 0.88 4457-00-5 Cyclopentane, hexyl- 0.93 0.27 0.16 0.87 4292-92-6 Pentylcyclohexane 0.93 0.27 0.12 0.87 544-76-3 Hexadecane 0.83 0.21 0.34 0.95 124-18-5 * Decane 0.95 0.28 0.24 0.90 1,4-Dimethyl-2,3- 71312-54-4 0.80 0.34 0.22 0.72 diazabicyclo[2.2.1]hept-2-ene 61142-66-3 cyclopentene, 5-hexyl-3,3-dimethyl- 0.88 0.23 0.11 0.87 2207-01-4 (Z)-1,2-Dimethylcyclohexane 0.95 0.29 0.35 0.87 6750-34-1 1-dodecanol, 3,7,11-trimethyl- 0.73 0.24 0.16 0.87 193-39-5 Indeno(1,2,3-cd)pyrene 0.63 0.00 0.82 0.90 7045-71-8 2-Methylundecane 0.95 0.24 0.14 0.87 1,7,11-Trimethyl-4-(1- 1786-12-5 0.83 0.21 0.46 0.95 methylethyl)cyclotetradecane 61142-70-9 2,4-Diethyl-1-methylcyclohexane 0.93 0.20 0.14 0.88 2847-72-5 4-Methyldecane 0.95 0.26 0.14 0.88 115-96-8 Tris(2-chloroethyl) phosphate 0.60 0.39 0.10 0.65 110-82-7 Cyclohexane 0.95 0.33 0.52 0.80 17302-32-8 3,7-Dimethylnonane 0.95 0.27 0.13 0.88 17302-28-2 2,6-Dimethylnonane 0.95 0.27 0.15 0.87 13151-34-3 3-Methyldecane 0.95 0.26 0.14 0.87 16580-24-8 1-Methyl-3-(propan-2-yl)cyclohexane 0.93 0.23 0.27 0.85 74-93-1 Methanethiol 0.86 0.45 0.24 0.71 13151-35-4 5-Methyldecane 0.95 0.26 0.11 0.88 66542-51-6 * Chloromethyl hexanoate 0.80 0.33 0.13 0.72 591-21-9 1,3-Dimethylcyclohexane 0.95 0.29 0.26 0.87 62016-37-9 2,4,6-Trimethyloctane 0.95 0.25 0.13 0.87 2234-75-5 1,2,4-Trimethylcyclohexane 0.93 0.26 0.25 0.86 6975-98-0 2-Methyldecane 0.95 0.26 0.14 0.88 71-43-2 * Benzene 0.87 0.35 0.18 0.69 5402-53-9 Chloromethyl propanoate 0.78 0.36 0.12 0.73 127-18-4 * Tetrachloroethylene 0.89 0.30 0.38 0.78 3728-56-1 1-Ethyl-4-methylcyclohexane 0.93 0.22 0.20 0.87 rel-(1R,2S)-1,2- 14113-60-1 0.79 0.19 0.62 0.86 Diethylcyclohexadecane 77877-94-2 Chloromethyl pentanoate 0.80 0.35 0.13 0.73 1678-93-9 Butylcyclohexane 0.93 0.21 0.12 0.88 112-18-5 N,N-Dimethyldodecan-1-amine 0.66 0.43 0.14 0.67 73105-67-6 1-Iodo-2-methylundecane 0.87 0.22 0.16 0.86 142-82-5 Heptane 0.97 0.29 0.20 0.84 135

CAS Name KH Koc t1/2 BCF 1072-05-5 2,6-Dimethylheptane 0.96 0.28 0.32 0.82 62199-51-3 1-Pentyl-2-propylcyclopentane 0.93 0.22 0.24 0.87 26730-20-1 7-Methylhexadecane 0.83 0.21 0.30 0.89 111-65-9 Octane 0.97 0.31 0.24 0.85 111-44-4 Bis(2-chloroethyl) ether 0.70 0.34 0.09 0.73 3728-55-0 1-Ethyl-3-methylcyclohexane 0.93 0.26 0.15 0.86 1560-92-5 2-Methylhexadecane 0.79 0.21 0.34 0.89 1678-92-8 Propylcyclohexane 0.93 0.22 0.11 0.88 2040-96-2 Propylcyclopentane 0.94 0.29 0.17 0.86 4291-79-6 1-Methyl-2-propyl-cyclohexane 0.93 0.21 0.15 0.87 75-25-2 Bromoform 0.81 0.32 0.35 0.74 5911-04-6 3-Methylnonane 0.95 0.28 0.14 0.89 2-BUTYL-1,1,3-TRIMETHYL- 54676-39-0 0.93 0.20 0.12 0.89 CYCLOHEXANE 107-13-1 Acrylonitrile 0.77 0.44 0.10 0.70 16580-26-0 cyclohexane, 1-isopropyl-1-methyl- 0.93 0.21 0.23 0.86 3073-66-3 1,1,3-Trimethylcyclohexane 0.93 0.27 0.27 0.81 31295-56-4 2,6,11-Trimethyldodecane 0.90 0.20 0.24 0.89 17301-94-9 4-Methylnonane 0.95 0.28 0.11 0.89 871-83-0 2-Methylnonane 0.95 0.29 0.14 0.89 15869-86-0 4-Ethyloctane 0.95 0.24 0.11 0.89 79-06-1 Acrylamide 0.09 1.00 0.15 0.00 16747-30-1 2,4,4-Trimethylhexane 0.97 0.26 0.29 0.85 107-06-2 1,2-Dichloroethane 0.83 0.37 0.26 0.71 2883-05-8 2-Cyclohexyloctane 0.89 0.23 0.16 0.88 100-44-7 Benzyl chloride 0.85 0.34 0.14 0.79 54411-01-7 1-Methyl-2-pentylcyclohexane 0.93 0.24 0.17 0.88 15869-93-9 3,5-Dimethyloctane 0.95 0.27 0.12 0.87 2051-30-1 2,6-Dimethyloctane 0.95 0.28 0.13 0.85 74054-92-5 1,1,6,6-tetramethylspiro[4.4]nonane 0.92 0.17 0.46 0.89 2406-25-9 Di-tert-butyl nitroxide 0.67 0.34 0.32 0.74 98-95-3 Nitrobenzene 0.73 0.33 0.15 0.70 959028-24-1 4-Ethyl-2,3-dimethylhex-2-ene 0.92 0.25 0.15 0.85 2815-58-9 1,2,4-Trimethylcyclopentane 0.95 0.29 0.15 0.86 123-25-1 Diethyl butanedioate 0.69 0.38 0.12 0.68 75-15-0 Carbon disulfide 0.89 0.30 0.35 0.75 706-14-9 gamma-Decanolactone 0.63 0.30 0.15 0.76 143-07-7 Dodecanoic acid 0.49 0.41 0.17 0.67 109-74-0 Butanenitrile 0.75 0.40 0.10 0.70 1921-70-6 Norphytane 0.75 0.21 0.49 0.93 4810-09-7 3-Methyl-1-heptene 0.95 0.28 0.16 0.87 108-87-2 Methylcyclohexane 0.97 0.29 0.11 0.83

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CAS Name KH Koc t1/2 BCF 959-98-8 Endosulfan I 0.73 0.16 0.33 0.69 33213-65-9 Endosulfan II 0.73 0.16 0.33 0.69 1678-91-7 Ethylcyclohexane 0.94 0.29 0.00 0.86 2980-69-0 4-Methylundecane 0.95 0.24 0.16 0.88 3386-33-2 Octadecyl chloride 0.72 0.21 0.37 0.87 55282-11-6 11-Pentan-3-ylhenicosane 0.65 0.17 0.66 0.82 112-30-1 1-Decanol 0.74 0.28 0.17 0.76 2453-00-1 1,3-Dimethylcyclopentane 0.96 0.29 0.11 0.82 74-84-0 Ethane 0.97 0.44 0.26 0.72 629-97-0 Docosane 0.65 0.16 0.66 0.84 1632-70-8 5-methylundecane 0.95 0.26 0.12 0.88 1002-43-3 3-Methylundecane 0.95 0.24 0.14 0.87 591-48-0 3-Methylcyclohexene 0.92 0.30 0.10 0.81 1192-18-3 (Z)-1,2-Dimethylcyclopentane 0.96 0.28 0.11 0.84 629-78-7 Heptadecane 0.75 0.21 0.37 0.91 592-27-8 2-Methylheptane 0.97 0.30 0.07 0.86 74-87-3 Chloromethane 0.88 0.40 0.31 0.72 7320-37-8 1,2-Epoxyhexadecane 0.73 0.22 0.31 0.90 593-45-3 Octadecane 0.74 0.20 0.38 0.88 110-75-8 2-Chloroethyl vinyl ether 0.76 0.38 0.12 0.73 562-28-7 (-)-Kaur-16-ene 0.78 0.05 0.78 0.91 111-30-8 Glutaraldehyde 0.61 0.38 0.10 0.67 821-55-6 2-Nonanone 0.80 0.31 0.15 0.79 638-36-8 2,6,10,14-Tetramethylhexadecane 0.74 0.23 0.38 0.92 50991-08-7 2-Methyl-1,1'-bi(cyclohexane) 0.91 0.21 0.56 0.87 106-65-0 Dimethyl succinate 0.71 0.37 0.12 0.68 109-66-0 Pentane 1.00 0.36 0.15 0.77 126-73-8 Tributyl phosphate 0.66 0.29 0.10 0.76 75-83-2 2,2-Dimethylbutane 0.98 0.33 0.36 0.81 110-54-3 n-Hexane 0.98 0.31 0.24 0.82 1,3,5-Trimethyl-1,3,5-triazinane-2- 59887-80-8 0.52 0.33 0.23 0.69 thione 6418-44-6 heptadecane, 3-methyl- 0.74 0.21 0.36 0.89 111-87-5 1-Octanol 0.73 0.36 0.14 0.78 74-98-6 Propane 0.97 0.41 0.21 0.72 513-35-9 2-Methyl-2-butene 0.96 0.36 0.26 0.73 112-95-8 Eicosane 0.69 0.20 0.41 0.85 107-83-5 2-Methylpentane 0.98 0.30 0.18 0.81 91-20-3 Naphthalene 0.80 0.25 0.07 0.80 72-03-7 Propanoate 0.63 0.41 0.13 0.69 3892-00-0 2,6,10-Trimethylpentadecane 0.79 0.21 0.28 0.88 334-48-5 Decanoic acid 0.49 0.44 0.15 0.54

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CAS Name KH Koc t1/2 BCF 41446-78-0 4-Tetradecene, (4E)- 0.88 0.23 0.19 0.87 120-82-1 1,2,4-Trichlorobenzene 0.83 0.24 0.11 0.92 111-76-2 2-Butoxyethanol 0.66 0.34 0.13 0.69 629-92-5 Nonadecane 0.70 0.21 0.35 0.87 629-94-7 Heneicosane 0.67 0.19 0.41 0.84 68-12-2 N,N-Dimethylformamide 0.59 0.39 0.21 0.63 106-46-7 1,4-Dichlorobenzene 0.85 0.28 0.14 0.86 112-88-9 1-Octadecene 0.74 0.20 0.26 0.90 297-35-8 Cyclotriacontane 0.65 0.17 0.80 0.82 104-76-7 2-Ethyl-1-hexanol 0.74 0.34 0.12 0.73 10374-74-0 7-Tetradecene 0.88 0.23 0.17 0.87 112-34-5 2-(2-Butoxyethoxy)ethanol 0.53 0.36 0.10 0.68 123-20-6 Butanoic acid, ethenyl ester 0.79 0.37 0.13 0.69 64275-73-6 (Z)-5-Octen-1-ol 0.73 0.35 0.09 0.73 18435-22-8 3-methyl-tetradecane 0.85 0.20 0.23 0.91 1768-36-1 Propyl cyanate 0.61 0.39 0.12 0.66 18435-45-5 1-Nonadecene 0.70 0.21 0.35 0.89 123-86-4 Butyl acetate 0.79 0.36 0.13 0.69 544-85-4 Dotriacontane 0.65 0.15 0.80 0.81 55000-52-7 2,6,10-Trimethylhexadecane 0.75 0.24 0.28 0.88 99328-46-8 5-Methylhept-1-en-4-ol 0.73 0.37 0.08 0.72 591-78-6 2-Hexanone 0.75 0.37 0.13 0.70 4360-57-0 2-Pentadecyl-1,3-dioxolane 0.64 0.22 0.30 0.87 638-67-5 Tricosane 0.65 0.17 0.69 0.84 87-61-6 1,2,3-Trichlorobenzene 0.83 0.22 0.12 0.88 1630-94-0 1,1-Dimethylcyclopropane 0.96 0.35 0.17 0.72 55030-62-1 4,8-Dimethyltridecane 0.90 0.20 0.18 0.90 18344-37-1 heptadecane, 2,6,10,14-tetramethyl- 0.70 0.15 0.36 0.88 144-19-4 2,2,4-Trimethyl-1,3-pentanediol 0.60 0.36 0.16 0.64 461-55-2 Butyrate 0.64 0.39 0.12 0.69 71-23-8 1-Propanol 0.70 0.45 0.13 0.69 646-31-1 Tetracosane 0.65 0.17 0.65 0.84 629-99-2 Pentacosane 0.65 0.17 0.66 0.83 5989-27-5 D-Limonene 0.90 0.22 0.06 0.84 54833-48-6 Heptadecane, 2,6,10,15-tetramethyl 0.70 0.15 0.37 0.85 57-60-3 Pyruvate 0.51 0.40 0.13 0.70 593-49-7 Heptacosane 0.65 0.17 0.68 0.82 79-09-4 Propionic acid 0.51 0.57 0.13 0.51 630-01-3 Hexacosane 0.65 0.17 0.63 0.83 54105-67-8 2,6-Dimethylheptadecane 0.74 0.20 0.31 0.87 110-94-1 Glutaric acid 0.43 0.37 0.21 0.68 544-63-8 Tetradecanoic acid 0.50 0.37 0.17 0.61

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CAS Name KH Koc t1/2 BCF 91-57-6 * 2-Methylnaphthalene 0.81 0.20 0.31 0.80 2885-00-9 1-Octadecanethiol 0.69 0.21 0.37 0.89 25117-24-2 4-Methyltetradecane 0.85 0.20 0.17 0.89 630-02-4 Octacosane 0.65 0.17 0.67 0.82 638-68-6 Triacontane 0.65 0.17 0.72 0.82 71-36-3 1-Butanol 0.71 0.44 0.13 0.70 92-52-4 * Biphenyl 0.79 0.23 0.44 0.86 598-89-0 Diiodoacetic acid 0.53 0.32 0.20 0.69 13287-24-6 9-Methylnonadecane 0.70 0.17 0.37 0.85 96-04-8 2,3-Heptanedione 0.64 0.35 0.14 0.69 129-00-0 Pyrene 0.71 0.10 0.77 0.91 132-65-0 Dibenzothiophene 0.76 0.17 0.46 0.89 563-46-2 2-Methylbut-1-ene 0.96 0.36 0.11 0.73 2490-48-4 2-Methylhexadecan-1-ol 0.70 0.23 0.17 0.89 (4aS,8aR)-4a- 938-06-7 Methyloctahydronaphthalen-2(1H)- 0.78 0.24 0.18 0.80 one 695-06-7 gamma-Caprolactone 0.56 0.37 0.13 0.69 80-62-6 Methyl methacrylate 0.77 0.39 0.12 0.69 149-57-5 2-Ethylhexanoic acid 0.52 0.52 0.14 0.50 124-07-2 Octanoic acid 0.53 0.49 0.15 0.52 5618-62-2 O-Isobutylhydroxylamine 0.66 0.40 0.10 0.70 100-01-6 4-Nitroaniline 0.49 0.34 0.19 0.69 95-50-1 1,2-Dichlorobenzene 0.84 0.28 0.15 0.84 206-44-0 * Fluoranthene 0.71 0.11 0.69 0.94 57-11-4 Octadecanoic acid 0.47 0.36 0.36 0.70 630-03-5 Nonacosane 0.65 0.17 0.63 0.82 5842-53-5 2,2,4-Trimethylpent-3-en-1-ol 0.68 0.37 0.11 0.71 91-22-5 Quinoline 0.71 0.24 0.31 0.69 108-29-2 4-Pentanolide 0.57 0.38 0.13 0.69 111-14-8 Heptanoic acid 0.53 0.52 0.14 0.51 107-92-6 Butanoic acid 0.51 0.56 0.12 0.51 141-78-6 Ethyl acetate 0.77 0.39 0.12 0.68 142-62-1 Hexanoic acid 0.52 0.54 0.14 0.51 542-28-9 Tetrahydro-2H-pyran-2-one 0.57 0.38 0.13 0.66 98-82-8 Cumene 0.88 0.27 0.32 0.77 64-19-7 Acetic acid 0.60 0.48 0.13 0.70 544-77-4 1-Iodohexadecane 0.74 0.22 0.37 0.89 60212-33-1 4-Tetradecyne 0.88 0.23 0.20 0.87 71-50-1 Acetate 0.60 0.48 0.13 0.70 117-81-7 Di(2-ethylhexyl) phthalate 0.62 0.10 0.14 0.87 75-09-2 Dichloromethane 0.85 0.37 0.33 0.75

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CAS Name KH Koc t1/2 BCF 3055-93-4 2-[2-(Dodecyloxy)ethoxy]ethanol 0.53 0.22 0.15 0.86 123-91-1 1,4-Dioxane 0.69 0.39 0.25 0.62 4860-03-1 1-Chlorohexadecane 0.73 0.21 0.38 0.87 544-25-2 1,3,5-Cycloheptatriene 0.87 0.33 0.22 0.76 83-32-9 Acenaphthene 0.78 0.20 0.48 0.88 35216-11-6 7-Tetradecyne 0.88 0.23 0.18 0.87 100-41-4 Ethylbenzene 0.87 0.31 0.22 0.75 132-64-9 Dibenzofuran 0.77 0.18 0.30 0.90 108-90-7 Chlorobenzene 0.85 0.32 0.15 0.75 766-76-7 Benzoate 0.62 0.37 0.19 0.69 109-52-4 Pentanoic acid 0.51 0.55 0.12 0.51 61886-62-2 3-Hexadecyne 0.83 0.21 0.19 0.88 584-02-1 3-Pentanol 0.72 0.39 0.12 0.69 120-12-7 Anthracene 0.75 0.15 0.66 0.91 57-55-6 1,2-Propylene glycol 0.58 0.45 0.12 0.69 79-31-2 2-Methylpropanoic acid 0.52 0.57 0.10 0.51 74-82-8 Methane 0.93 0.44 0.36 0.00 64-17-5 Ethanol 0.69 0.47 0.13 0.66 67-63-0 Isopropanol 0.70 0.44 0.21 0.70 575-41-7 1,3-Dimethylnaphthalene 0.81 0.21 0.34 0.86 57-10-3 Hexadecanoic acid 0.39 0.40 0.23 0.64 75-34-3 1,1-Dichloroethane 0.87 0.37 0.17 0.71 110-86-1 Pyridine 0.71 0.36 0.14 0.69 646-07-1 Pentanoic acid, 4-methyl- 0.52 0.54 0.12 0.51 86-30-6 N-Nitrosodiphenylamine 0.65 0.24 0.17 0.75 90-12-0 1-Methylnaphthalene 0.81 0.22 0.24 0.79 86-73-7 Fluorene 0.77 0.20 0.50 0.87 576-26-1 2,6-Dimethylphenol 0.70 0.28 0.16 0.72 573-98-8 1,2-Dimethylnaphthalene 0.81 0.21 0.32 0.86 116-53-0 2-Methylbutanoic acid 0.53 0.54 0.12 0.51 569-41-5 1,8-Dimethylnaphthalene 0.81 0.21 0.30 0.86 571-58-4 1,4-Dimethylnaphthalene 0.83 0.20 0.32 0.84 575-37-1 1,7-Dimethylnaphthalene 0.81 0.21 0.30 0.86 2049-95-8 tert-Pentylbenzene 0.87 0.21 0.21 0.86 1599-67-3 1-Docosene 0.65 0.16 0.38 0.84 62-53-3 Aniline 0.67 0.36 0.17 0.66 50-00-0 Formaldehyde 0.63 0.45 0.23 0.66 503-74-2 Isovaleric acid 0.52 0.56 0.13 0.51 533-18-6 Acetic acid, 2-methylphenyl ester 0.58 0.36 0.13 0.71 122-20-3 Triisopropanolamine 0.00 0.94 0.17 0.01 3055-94-5 Triethylene glycol monododecyl ether 0.56 0.18 0.14 0.79 113-21-3 Lactate ion(1-) 0.20 0.87 0.16 0.20

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CAS Name KH Koc t1/2 BCF 941228-34-8 7-(Bromomethyl)pentadec-7-ene 0.75 0.19 0.15 0.89 10023-74-2 Pentanoic acid, ion(1-) 0.29 0.85 0.12 0.19 75-07-0 Acetaldehyde 0.76 0.45 0.21 0.67 95-65-8 3,4-Dimethylphenol 0.63 0.32 0.16 0.72 35365-59-4 9-Octadecyne 0.74 0.23 0.18 0.89 90-15-3 1-Naphthol 0.58 0.27 0.39 0.81 541-73-1 1,3-Dichlorobenzene 0.85 0.28 0.10 0.84 122-99-6 2-Phenoxyethanol 0.62 0.34 0.16 0.70 95-87-4 2,5-Dimethylphenol 0.65 0.32 0.16 0.72 106-44-5 p-Cresol 0.65 0.27 0.16 0.74 107-21-1 Ethylene glycol 0.58 0.43 0.21 0.68 1-Hydroxy-3-(2-methylpropyl)- 2873-36-1 6,7,8,8a-tetrahydropyrrolo[1,2- 0.24 0.63 0.08 0.34 a]pyrazin-4(3H)-one 2136-72-3 2-(Octadecyloxy)ethanol 0.58 0.16 0.36 0.86 526-73-8 1,2,3-Trimethylbenzene 0.86 0.27 0.11 0.83 575-43-9 1,6-Dimethylnaphthalene 0.84 0.21 0.16 0.84 98-86-2 Acetophenone 0.71 0.34 0.16 0.72 611-14-3 1-Ethyl-2-methylbenzene 0.87 0.27 0.11 0.82 95-63-6 1,2,4-Trimethylbenzene 0.87 0.26 0.11 0.82 1074-43-7 1-Methyl-3-propylbenzene 0.88 0.23 0.08 0.87 135-19-3 2-Naphthalenol 0.56 0.24 0.37 0.81 104-90-5 5-Ethyl-2-methylpyridine 0.70 0.36 0.08 0.70 98-06-6 tert-Butylbenzene 0.87 0.26 0.16 0.85 3333-52-6 Tetramethylsuccinonitrile 0.64 0.36 0.21 0.74 78-93-3 Methyl ethyl ketone 0.75 0.39 0.10 0.69 107-19-7 Propargyl alcohol 0.70 0.42 0.14 0.69 620-14-4 3-Ethyltoluene 0.88 0.27 0.07 0.82 108-68-9 3,5-Dimethylphenol 0.64 0.26 0.16 0.72 526-75-0 2,3-Dimethylphenol 0.65 0.28 0.11 0.72 99-06-9 3-Hydroxybenzoic acid 0.36 0.61 0.09 0.44 108-10-1 4-Methyl-2-pentanone 0.75 0.36 0.12 0.71 105-60-2 Caprolactam 0.65 0.37 0.13 0.67 118-90-1 2-Methylbenzoic acid 0.47 0.59 0.09 0.44 122-39-4 Diphenylamine 0.59 0.27 0.19 0.82 95-47-6 o-Xylene 0.86 0.31 0.18 0.74 95-48-7 o-Cresol 0.66 0.32 0.16 0.73 106-42-3 p-Xylene 0.87 0.30 0.24 0.74 80-05-7 Bisphenol A 0.60 0.24 0.33 0.78 65-85-0 Benzoic acid 0.46 0.59 0.19 0.46 108-67-8 1,3,5-Trimethylbenzene 0.88 0.26 0.07 0.83 135-98-8 sec-Butylbenzene 0.88 0.22 0.11 0.83

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CAS Name KH Koc t1/2 BCF 71-47-6 Formic acid, ion(1-) 0.27 0.89 0.18 0.20 78-51-3 Tris(2-butoxyethyl) phosphate 0.70 0.17 0.10 0.71 104-51-8 Butylbenzene 0.88 0.22 0.11 0.87 108-39-4 m-Cresol 0.65 0.32 0.09 0.74 109-06-8 2-Methylpyridine 0.71 0.35 0.11 0.74 100-52-7 Benzaldehyde 0.73 0.37 0.17 0.73 611-32-5 8-Methylquinoline 0.75 0.24 0.14 0.74 67-64-1 Acetone 0.74 0.44 0.21 0.67 103-65-1 Propylbenzene 0.88 0.26 0.11 0.82 7661-55-4 5-Methylquinoline 0.75 0.27 0.10 0.74 105-67-9 2,4-Dimethylphenol 0.65 0.32 0.16 0.72 91-62-3 6-Methylquinoline 0.75 0.25 0.11 0.74 108-95-2 Phenol 0.63 0.37 0.13 0.74 612-60-2 7-Methylquinoline 0.75 0.25 0.11 0.74 612-58-8 3-Methylquinoline 0.75 0.25 0.11 0.73 491-35-0 Lepidine 0.75 0.24 0.10 0.74 117-84-0 Di-n-octyl phthalate 0.62 0.14 0.17 0.82 498-02-2 Acetovanillone 0.50 0.32 0.09 0.71 100-51-6 Benzyl alcohol 0.63 0.40 0.19 0.71 108-88-3 * Toluene 0.87 0.32 0.00 0.72 131-11-3 Dimethyl phthalate 0.59 0.36 0.10 0.69 26764-26-1 Octadecenoic acid 0.45 0.40 0.17 0.65 84-74-2 Dibutyl phthalate 0.67 0.24 0.12 0.83 28631-86-9 2,2-Dihydroxy-1-phenylethanone 0.54 0.35 0.09 0.69 100-42-5 Styrene 0.85 0.25 0.19 0.74 4376-20-9 MEHP 0.49 0.25 0.09 0.81 25447-95-4 Hexadecenoic acid 0.39 0.41 0.16 0.62 86-55-5 1-Naphthalenecarboxylic acid 0.36 0.58 0.14 0.41 67-56-1 * Methanol 0.69 0.45 0.21 0.66 85-68-7 Benzyl butyl phthalate 0.57 0.19 0.08 0.74 84-66-2 Diethyl phthalate 0.56 0.34 0.15 0.72 121-91-5 1,3-Benzenedicarboxylic acid 0.23 0.64 0.14 0.42

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6.4.1.2 Hazard domain cancer metric ToxPi scores Appendix Table 8. ToxPi scores for each cancer metric in the hazard domain from the 376 organic compounds with toxicity data on the working list: oral slope factor (OSF), cancer potency value (CPV), and inhalation unit risk (IUR). CAS Name OSF CPV IUR 309-00-2 Aldrin 0.98 0.92 0.99 1024-57-3 Heptachlor epoxide B 0.93 0.87 0.95 72-20-8 Endrin 1.00 1.00 1.00 76-44-8 Heptachlor 0.86 0.77 0.90 319-86-8 delta-Hexachlorocyclohexane 0.74 0.67 0.86 58-89-9 Lindane 0.74 0.67 0.79 319-85-7 beta-Hexachlorocyclohexane 0.74 0.67 0.82 2935-07-1 1H-Phenalene, dodecahydro- 0.72 0.74 0.77 118-74-1 Hexachlorobenzene 0.74 0.68 0.81 50-32-8 Benzo(a)pyrene 0.87 0.85 0.82 281-23-2 Adamantane 0.66 0.69 0.70 54823-98-2 Cyclohexane, 1-(cyclohexylmethyl)-4- methyl-, trans- 0.72 0.79 0.80 1660-04-4 Methyl tricyclo(3.3.1.13,7)dec-1-yl ketone 0.62 0.70 0.68 1750-51-2 Naphthalene, decahydro-1,6- dimethyl- 0.70 0.70 0.75 56-55-3 Benz(a)anthracene 0.96 0.90 0.70 3178-23-2 Dicyclohexylmethane 0.66 0.72 0.76 6305-52-8 2-n-Butyldecahydronaphthalene 0.70 0.77 0.79 66552-62-3 Naphthalene, decahydro-1,5- dimethyl- 0.69 0.69 0.74 5743-97-5 phenanthrene, tetradecahydro- 0.73 0.80 0.00 1618-22-0 * naphthalene, decahydro-2,6- dimethyl- 0.69 0.70 0.75 1008-80-6 2,3-Dimethyldecahydronaphthalene 0.68 0.69 0.74 294-62-2 Cyclododecane 0.64 0.69 0.74 92-51-3 1,1'-Bicyclohexyl 0.66 0.72 0.75 53-70-3 Dibenz(a,h)anthracene 0.83 0.76 0.88 66660-42-2 cis, cis-3-ethylbicyclo[4.4.0]decane 0.69 0.70 0.75 1687-34-9 1-Ethyl-3-methyladamantane 0.75 0.00 0.00 4431-89-4 (Cyclopentylmethyl)cyclohexane 0.63 0.69 0.73 205-99-2 Benzo(b)fluoranthene 0.87 0.81 0.71 702-79-4 1,3-Dimethyladamantane 0.69 0.00 0.00 629-62-9 Pentadecane 0.57 0.59 0.73 629-59-4 Tetradecane 0.57 0.58 0.73 1606-08-2 Cyclopentylcyclohexane 0.62 0.67 0.72 218-01-9 Chrysene 0.74 0.68 0.54 2958-76-1 Decahydro-2-methylnaphthalene 0.60 0.65 0.72

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CAS Name OSF CPV IUR 16538-89-9 cyclooctane, (1-methylpropyl)- 0.62 0.68 0.73 23609-46-3 cyclooctane, 1,2-diethyl- 0.64 0.70 0.74 2883-02-5 Cyclohexane, nonyl- 0.60 0.61 0.72 1795-15-9 Cyclohexane, octyl- 0.60 0.59 0.72 629-50-5 Tridecane 0.58 0.58 0.73 111-84-2 Nonane 0.57 0.49 0.71 1795-16-0 Decylcyclohexane 0.61 0.63 0.73 62199-52-4 1,2-Dibutylcyclopentane 0.60 0.56 0.71 1560-93-6 2-Methylpentadecane 0.53 0.62 0.72 74-83-9 Methyl bromide 0.30 0.23 0.42 6165-40-8 7-Methylpentadecane 0.54 0.63 0.72 295-17-0 Cyclotetradecane 0.67 0.77 0.00 3891-98-3 2,6,10-Trimethyldodecane 0.52 0.57 0.70 79-34-5 1,1,2,2-Tetrachloroethane 0.49 0.46 0.64 61142-68-5 1-Hexyl-3-methylcyclopentane 0.57 0.52 0.70 112-40-3 Dodecane 0.57 0.54 0.73 207-08-9 Benzo(k)fluoranthene 0.70 0.00 0.71 17312-57-1 3-Methyldodecane 0.52 0.57 0.71 13287-21-3 6-Methyltridecane 0.51 0.58 0.71 26730-14-3 7-Methyltridecane 0.52 0.58 0.71 707-35-7 1,3,5-Trimethyladamantane 0.00 0.00 0.00 17312-80-0 2,4-Dimethylundecane 0.48 0.54 0.69 1560-97-0 2-Methyldodecane 0.50 0.56 0.70 645-10-3 1,7-dimethyl-4-(1- methylethyl)cyclodecane 0.63 0.77 0.00 4292-75-5 Hexylcyclohexane 0.59 0.54 0.71 6117-97-1 4-Methyldodecane 0.52 0.56 0.71 67-66-3 Chloroform 0.30 0.24 0.55 1120-21-4 Undecane 0.59 0.53 0.72 17301-23-4 2,6-Dimethylundecane 0.48 0.54 0.69 6418-41-3 tridecane, 3-methyl- 0.52 0.58 0.72 1560-95-8 2-Methyltetradecane 0.51 0.59 0.71 56292-65-0 2,5-Dimethyldodecane 0.49 0.54 0.70 112-70-9 1-Tridecanol 0.51 0.58 0.70 25117-31-1 5-Methyltridecane 0.52 0.58 0.71 54411-00-6 cyclohexane, 1-methyl-4-(1- methylbutyl)- 0.52 0.52 0.69 41446-57-5 3-Tridecene, (3E)- 0.55 0.56 0.71 26730-12-1 4-Methyltridecane 0.51 0.58 0.71 25117-32-2 5-Methyltetradecane 0.53 0.61 0.72 13150-81-7 2,6-Dimethyldecane 0.46 0.49 0.69 1560-96-9 2-Methyltridecane 0.50 0.57 0.70

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CAS Name OSF CPV IUR 15232-86-7 1-Heptylcyclohexene 0.58 0.55 0.73 442662-72-8 2-Ethyl-1,1,3-trimethylcyclohexane 0.43 0.51 0.66 4457-00-5 Cyclopentane, hexyl- 0.59 0.54 0.70 4292-92-6 Pentylcyclohexane 0.59 0.55 0.70 544-76-3 Hexadecane 0.59 0.61 0.00 124-18-5 * Decane 0.57 0.49 0.71 1,4-Dimethyl-2,3- 71312-54-4 diazabicyclo[2.2.1]hept-2-ene 0.62 0.71 0.74 61142-66-3 cyclopentene, 5-hexyl-3,3-dimethyl- 0.47 0.49 0.68 2207-01-4 (Z)-1,2-Dimethylcyclohexane 0.56 0.61 0.66 6750-34-1 1-dodecanol, 3,7,11-trimethyl- 0.50 0.62 0.71 193-39-5 Indeno(1,2,3-cd)pyrene 0.71 0.00 0.71 7045-71-8 2-Methylundecane 0.50 0.51 0.70 1,7,11-Trimethyl-4-(1- 1786-12-5 methylethyl)cyclotetradecane 0.72 0.00 0.00 61142-70-9 2,4-Diethyl-1-methylcyclohexane 0.53 0.55 0.69 2847-72-5 4-Methyldecane 0.52 0.50 0.70 115-96-8 Tris(2-chloroethyl) phosphate 0.39 0.59 0.75 110-82-7 Cyclohexane 0.61 0.58 0.64 17302-32-8 3,7-Dimethylnonane 0.46 0.50 0.69 17302-28-2 2,6-Dimethylnonane 0.46 0.50 0.69 13151-34-3 3-Methyldecane 0.52 0.51 0.70 16580-24-8 1-Methyl-3-(propan-2-yl)cyclohexane 0.46 0.49 0.66 74-93-1 Methanethiol 0.52 0.44 0.55 13151-35-4 5-Methyldecane 0.52 0.50 0.70 66542-51-6 * Chloromethyl hexanoate 0.53 0.55 0.74 591-21-9 1,3-Dimethylcyclohexane 0.58 0.60 0.67 62016-37-9 2,4,6-Trimethyloctane 0.46 0.49 0.68 2234-75-5 1,2,4-Trimethylcyclohexane 0.47 0.60 0.66 6975-98-0 2-Methyldecane 0.50 0.49 0.69 71-43-2 * Benzene 0.30 0.30 0.45 5402-53-9 Chloromethyl propanoate 0.63 0.61 0.76 127-18-4 * Tetrachloroethylene 0.07 0.30 0.27 3728-56-1 1-Ethyl-4-methylcyclohexane 0.57 0.62 0.69 rel-(1R,2S)-1,2- 14113-60-1 Diethylcyclohexadecane 0.69 0.00 0.00 77877-94-2 Chloromethyl pentanoate 0.54 0.54 0.73 1678-93-9 Butylcyclohexane 0.58 0.50 0.68 112-18-5 N,N-Dimethyldodecan-1-amine 0.51 0.60 0.74 73105-67-6 1-Iodo-2-methylundecane 0.58 0.00 0.00 142-82-5 Heptane 0.59 0.48 0.70 1072-05-5 2,6-Dimethylheptane 0.43 0.46 0.65 62199-51-3 1-Pentyl-2-propylcyclopentane 0.59 0.56 0.00 145

CAS Name OSF CPV IUR 26730-20-1 7-Methylhexadecane 0.54 0.62 0.00 111-65-9 Octane 0.57 0.48 0.70 111-44-4 Bis(2-chloroethyl) ether 0.64 0.65 0.74 3728-55-0 1-Ethyl-3-methylcyclohexane 0.57 0.61 0.68 1560-92-5 2-Methylhexadecane 0.53 0.62 0.00 1678-92-8 Propylcyclohexane 0.61 0.65 0.69 2040-96-2 Propylcyclopentane 0.62 0.61 0.68 4291-79-6 1-Methyl-2-propyl-cyclohexane 0.54 0.50 0.66 75-25-2 Bromoform 0.23 0.20 0.39 5911-04-6 3-Methylnonane 0.51 0.48 0.68 54676-39-0 2-BUTYL-1,1,3-TRIMETHYL- CYCLOHEXANE 0.51 0.54 0.00 107-13-1 Acrylonitrile 0.48 0.47 0.57 16580-26-0 cyclohexane, 1-isopropyl-1-methyl- 0.35 0.46 0.64 3073-66-3 1,1,3-Trimethylcyclohexane 0.36 0.58 0.65 31295-56-4 2,6,11-Trimethyldodecane 0.51 0.57 0.00 17301-94-9 4-Methylnonane 0.51 0.49 0.68 871-83-0 2-Methylnonane 0.48 0.48 0.68 15869-86-0 4-Ethyloctane 0.51 0.49 0.69 79-06-1 Acrylamide 0.50 0.62 0.61 16747-30-1 2,4,4-Trimethylhexane 0.34 0.43 0.63 107-06-2 1,2-Dichloroethane 0.37 0.30 0.54 2883-05-8 2-Cyclohexyloctane 0.60 0.59 0.00 100-44-7 Benzyl chloride 0.45 0.00 0.60 54411-01-7 1-Methyl-2-pentylcyclohexane 0.57 0.53 0.00 15869-93-9 3,5-Dimethyloctane 0.45 0.47 0.67 2051-30-1 2,6-Dimethyloctane 0.44 0.46 0.67 74054-92-5 1,1,6,6-tetramethylspiro[4.4]nonane 0.00 0.00 0.00 2406-25-9 Di-tert-butyl nitroxide 0.37 0.49 0.66 98-95-3 Nitrobenzene 0.00 0.62 0.59 959028-24-1 4-Ethyl-2,3-dimethylhex-2-ene 0.43 0.47 0.65 2815-58-9 1,2,4-Trimethylcyclopentane 0.49 0.58 0.63 123-25-1 Diethyl butanedioate 0.44 0.51 0.68 75-15-0 Carbon disulfide 0.36 0.32 0.41 706-14-9 gamma-Decanolactone 0.43 0.50 0.66 143-07-7 Dodecanoic acid 0.45 0.60 0.68 109-74-0 Butanenitrile 0.59 0.55 0.66 1921-70-6 Norphytane 0.56 0.00 0.00 4810-09-7 3-Methyl-1-heptene 0.49 0.45 0.63 108-87-2 Methylcyclohexane 0.60 0.59 0.67 959-98-8 Endosulfan I 0.00 0.00 0.00 33213-65-9 Endosulfan II 0.00 0.00 0.00

146

CAS Name OSF CPV IUR 1678-91-7 Ethylcyclohexane 0.62 0.62 0.69 2980-69-0 4-Methylundecane 0.52 0.51 0.00 3386-33-2 Octadecyl chloride 0.56 0.00 0.00 55282-11-6 11-Pentan-3-ylhenicosane 0.55 0.00 0.00 112-30-1 1-Decanol 0.46 0.48 0.66 2453-00-1 1,3-Dimethylcyclopentane 0.59 0.58 0.63 74-84-0 Ethane 0.42 0.34 0.54 629-97-0 Docosane 0.60 0.00 0.00 1632-70-8 5-methylundecane 0.52 0.51 0.00 1002-43-3 3-Methylundecane 0.52 0.53 0.00 591-48-0 3-Methylcyclohexene 0.59 0.59 0.67 1192-18-3 (Z)-1,2-Dimethylcyclopentane 0.57 0.58 0.60 629-78-7 Heptadecane 0.59 0.00 0.00 592-27-8 2-Methylheptane 0.46 0.46 0.67 74-87-3 Chloromethane 0.25 0.24 0.41 7320-37-8 1,2-Epoxyhexadecane 0.56 0.00 0.00 593-45-3 Octadecane 0.60 0.00 0.00 110-75-8 2-Chloroethyl vinyl ether 0.44 0.40 0.62 562-28-7 (-)-Kaur-16-ene 0.00 0.00 0.00 111-30-8 Glutaraldehyde 0.53 0.51 0.65 821-55-6 2-Nonanone 0.41 0.44 0.61 638-36-8 2,6,10,14-Tetramethylhexadecane 0.56 0.00 0.00 50991-08-7 2-Methyl-1,1'-bi(cyclohexane) 0.00 0.00 0.00 106-65-0 Dimethyl succinate 0.46 0.48 0.70 109-66-0 Pentane 0.60 0.47 0.67 126-73-8 Tributyl phosphate 0.25 0.66 0.00 75-83-2 2,2-Dimethylbutane 0.26 0.27 0.51 110-54-3 n-Hexane 0.58 0.45 0.70 1,3,5-Trimethyl-1,3,5-triazinane-2- 59887-80-8 thione 0.53 0.62 0.00 6418-44-6 heptadecane, 3-methyl- 0.54 0.00 0.00 111-87-5 1-Octanol 0.46 0.46 0.67 74-98-6 Propane 0.47 0.36 0.56 513-35-9 2-Methyl-2-butene 0.41 0.36 0.58 112-95-8 Eicosane 0.60 0.00 0.00 107-83-5 2-Methylpentane 0.44 0.41 0.64 91-20-3 Naphthalene 0.42 0.36 0.58 72-03-7 Propanoate 0.50 0.48 0.65 3892-00-0 2,6,10-Trimethylpentadecane 0.54 0.00 0.00 334-48-5 Decanoic acid 0.41 0.51 0.65 41446-78-0 4-Tetradecene, (4E)- 0.57 0.00 0.00 120-82-1 1,2,4-Trichlorobenzene 0.32 0.00 0.00

147

CAS Name OSF CPV IUR 111-76-2 2-Butoxyethanol 0.51 0.49 0.65 629-92-5 Nonadecane 0.60 0.00 0.00 629-94-7 Heneicosane 0.60 0.00 0.00 68-12-2 N,N-Dimethylformamide 0.61 0.57 0.73 106-46-7 1,4-Dichlorobenzene 0.32 0.26 0.51 112-88-9 1-Octadecene 0.57 0.00 0.00 297-35-8 Cyclotriacontane 0.00 0.00 0.00 104-76-7 2-Ethyl-1-hexanol 0.46 0.46 0.64 10374-74-0 7-Tetradecene 0.57 0.00 0.00 112-34-5 2-(2-Butoxyethoxy)ethanol 0.47 0.49 0.64 123-20-6 Butanoic acid, ethenyl ester 0.45 0.48 0.65 64275-73-6 (Z)-5-Octen-1-ol 0.48 0.45 0.67 18435-22-8 3-methyl-tetradecane 0.52 0.00 0.00 1768-36-1 Propyl cyanate 0.52 0.56 0.74 18435-45-5 1-Nonadecene 0.57 0.00 0.00 123-86-4 Butyl acetate 0.44 0.45 0.66 544-85-4 Dotriacontane 0.00 0.00 0.00 55000-52-7 2,6,10-Trimethylhexadecane 0.55 0.00 0.00 99328-46-8 5-Methylhept-1-en-4-ol 0.45 0.48 0.61 591-78-6 2-Hexanone 0.44 0.40 0.61 4360-57-0 2-Pentadecyl-1,3-dioxolane 0.54 0.00 0.00 638-67-5 Tricosane 0.00 0.00 0.00 87-61-6 1,2,3-Trichlorobenzene 0.00 0.61 0.00 1630-94-0 1,1-Dimethylcyclopropane 0.42 0.34 0.50 55030-62-1 4,8-Dimethyltridecane 0.51 0.00 0.00 18344-37-1 heptadecane, 2,6,10,14-tetramethyl- 0.53 0.00 0.00 144-19-4 2,2,4-Trimethyl-1,3-pentanediol 0.31 0.55 0.66 461-55-2 Butyrate 0.54 0.53 0.67 71-23-8 1-Propanol 0.57 0.50 0.65 646-31-1 Tetracosane 0.00 0.00 0.00 629-99-2 Pentacosane 0.00 0.00 0.00 5989-27-5 D-Limonene 0.52 0.52 0.00 54833-48-6 Heptadecane, 2,6,10,15-tetramethyl 0.53 0.00 0.00 57-60-3 Pyruvate 0.48 0.46 0.61 593-49-7 Heptacosane 0.00 0.00 0.00 79-09-4 Propionic acid 0.49 0.49 0.63 630-01-3 Hexacosane 0.00 0.00 0.00 54105-67-8 2,6-Dimethylheptadecane 0.54 0.00 0.00 110-94-1 Glutaric acid 0.52 0.48 0.67 544-63-8 Tetradecanoic acid 0.48 0.61 0.00 91-57-6 * 2-Methylnaphthalene 0.00 0.00 0.00 2885-00-9 1-Octadecanethiol 0.00 0.00 0.00

148

CAS Name OSF CPV IUR 25117-24-2 4-Methyltetradecane 0.53 0.00 0.00 630-02-4 Octacosane 0.00 0.00 0.00 638-68-6 Triacontane 0.00 0.00 0.00 71-36-3 1-Butanol 0.59 0.52 0.66 92-52-4 * Biphenyl 0.19 0.00 0.00 598-89-0 Diiodoacetic acid 0.00 0.45 0.00 13287-24-6 9-Methylnonadecane 0.55 0.00 0.00 96-04-8 2,3-Heptanedione 0.47 0.51 0.62 129-00-0 Pyrene 0.00 0.00 0.00 132-65-0 Dibenzothiophene 0.00 0.00 0.00 563-46-2 2-Methylbut-1-ene 0.39 0.34 0.54 2490-48-4 2-Methylhexadecan-1-ol 0.55 0.00 0.00 (4aS,8aR)-4a- Methyloctahydronaphthalen-2(1H)- 938-06-7 one 0.49 0.00 0.00 695-06-7 gamma-Caprolactone 0.52 0.62 0.67 80-62-6 Methyl methacrylate 0.50 0.58 0.68 149-57-5 2-Ethylhexanoic acid 0.43 0.53 0.65 124-07-2 Octanoic acid 0.43 0.50 0.67 5618-62-2 O-Isobutylhydroxylamine 0.50 0.47 0.63 100-01-6 4-Nitroaniline 0.26 0.00 0.00 95-50-1 1,2-Dichlorobenzene 0.00 0.57 0.00 206-44-0 * Fluoranthene 0.00 0.00 0.00 57-11-4 Octadecanoic acid 0.52 0.00 0.00 630-03-5 Nonacosane 0.00 0.00 0.00 5842-53-5 2,2,4-Trimethylpent-3-en-1-ol 0.23 0.37 0.59 91-22-5 Quinoline 0.72 0.00 0.00 108-29-2 4-Pentanolide 0.57 0.62 0.64 111-14-8 Heptanoic acid 0.45 0.48 0.68 107-92-6 Butanoic acid 0.53 0.52 0.67 141-78-6 Ethyl acetate 0.52 0.53 0.65 142-62-1 Hexanoic acid 0.46 0.47 0.67 542-28-9 Tetrahydro-2H-pyran-2-one 0.55 0.64 0.68 98-82-8 Cumene 0.00 0.58 0.00 64-19-7 Acetic acid 0.36 0.31 0.51 544-77-4 1-Iodohexadecane 0.00 0.00 0.00 60212-33-1 4-Tetradecyne 0.00 0.00 0.00 71-50-1 Acetate 0.37 0.31 0.51 117-81-7 Di(2-ethylhexyl) phthalate 0.32 0.09 0.48 75-09-2 Dichloromethane 0.00 0.12 0.00 3055-93-4 2-[2-(Dodecyloxy)ethoxy]ethanol 0.52 0.00 0.00 123-91-1 1,4-Dioxane 0.37 0.17 0.42

149

CAS Name OSF CPV IUR 4860-03-1 1-Chlorohexadecane 0.00 0.00 0.00 544-25-2 1,3,5-Cycloheptatriene 0.00 0.00 0.63 83-32-9 Acenaphthene 0.00 0.00 0.00 35216-11-6 7-Tetradecyne 0.00 0.00 0.00 100-41-4 Ethylbenzene 0.22 0.16 0.39 132-64-9 Dibenzofuran 0.00 0.00 0.00 108-90-7 Chlorobenzene 0.00 0.54 0.00 766-76-7 Benzoate 0.00 0.00 0.66 109-52-4 Pentanoic acid 0.44 0.44 0.66 61886-62-2 3-Hexadecyne 0.00 0.00 0.00 584-02-1 3-Pentanol 0.50 0.47 0.62 120-12-7 Anthracene 0.00 0.00 0.00 57-55-6 1,2-Propylene glycol 0.51 0.47 0.61 79-31-2 2-Methylpropanoic acid 0.49 0.53 0.58 74-82-8 Methane 0.45 0.36 0.49 64-17-5 Ethanol 0.36 0.31 0.52 67-63-0 Isopropanol 0.52 0.45 0.55 575-41-7 1,3-Dimethylnaphthalene 0.00 0.00 0.00 57-10-3 Hexadecanoic acid 0.52 0.00 0.00 75-34-3 1,1-Dichloroethane 0.11 0.05 0.36 110-86-1 Pyridine 0.00 0.00 0.00 646-07-1 Pentanoic acid, 4-methyl- 0.42 0.44 0.63 86-30-6 N-Nitrosodiphenylamine 0.16 0.15 0.44 90-12-0 1-Methylnaphthalene 0.30 0.00 0.00 86-73-7 Fluorene 0.00 0.00 0.00 576-26-1 2,6-Dimethylphenol 0.00 0.00 0.64 573-98-8 1,2-Dimethylnaphthalene 0.00 0.00 0.00 116-53-0 2-Methylbutanoic acid 0.42 0.52 0.64 569-41-5 1,8-Dimethylnaphthalene 0.00 0.00 0.00 571-58-4 1,4-Dimethylnaphthalene 0.00 0.00 0.00 575-37-1 1,7-Dimethylnaphthalene 0.00 0.00 0.00 2049-95-8 tert-Pentylbenzene 0.00 0.00 0.00 1599-67-3 1-Docosene 0.00 0.00 0.00 62-53-3 Aniline 0.11 0.06 0.35 50-00-0 Formaldehyde 0.30 0.27 0.42 503-74-2 Isovaleric acid 0.41 0.43 0.63 533-18-6 Acetic acid, 2-methylphenyl ester 0.00 0.00 0.65 122-20-3 Triisopropanolamine 0.48 0.50 0.64 3055-94-5 Triethylene glycol monododecyl ether 0.51 0.00 0.00 113-21-3 Lactate ion(1-) 0.49 0.48 0.61 941228-34-8 7-(Bromomethyl)pentadec-7-ene 0.00 0.00 0.00 10023-74-2 Pentanoic acid, ion(1-) 0.52 0.52 0.67

150

CAS Name OSF CPV IUR 75-07-0 Acetaldehyde 0.06 0.00 0.32 95-65-8 3,4-Dimethylphenol 0.00 0.00 0.63 35365-59-4 9-Octadecyne 0.00 0.00 0.00 90-15-3 1-Naphthol 0.00 0.00 0.00 541-73-1 1,3-Dichlorobenzene 0.00 0.00 0.00 122-99-6 2-Phenoxyethanol 0.00 0.51 0.00 95-87-4 2,5-Dimethylphenol 0.00 0.00 0.62 106-44-5 p-Cresol 0.00 0.56 0.00 107-21-1 Ethylene glycol 0.49 0.41 0.68 1-Hydroxy-3-(2-methylpropyl)- 6,7,8,8a-tetrahydropyrrolo[1,2- 2873-36-1 a]pyrazin-4(3H)-one 0.64 0.63 0.00 2136-72-3 2-(Octadecyloxy)ethanol 0.00 0.00 0.00 526-73-8 1,2,3-Trimethylbenzene 0.00 0.00 0.00 575-43-9 1,6-Dimethylnaphthalene 0.00 0.00 0.00 98-86-2 Acetophenone 0.00 0.58 0.00 611-14-3 1-Ethyl-2-methylbenzene 0.00 0.00 0.00 95-63-6 1,2,4-Trimethylbenzene 0.00 0.00 0.00 1074-43-7 1-Methyl-3-propylbenzene 0.00 0.00 0.00 135-19-3 2-Naphthalenol 0.00 0.00 0.00 104-90-5 5-Ethyl-2-methylpyridine 0.00 0.00 0.64 98-06-6 tert-Butylbenzene 0.00 0.00 0.00 3333-52-6 Tetramethylsuccinonitrile 0.00 0.00 0.00 78-93-3 Methyl ethyl ketone 0.50 0.45 0.56 107-19-7 Propargyl alcohol 0.00 0.00 0.00 620-14-4 3-Ethyltoluene 0.00 0.00 0.00 108-68-9 3,5-Dimethylphenol 0.00 0.00 0.63 526-75-0 2,3-Dimethylphenol 0.00 0.00 0.63 99-06-9 3-Hydroxybenzoic acid 0.00 0.00 0.65 108-10-1 4-Methyl-2-pentanone 0.30 0.36 0.55 105-60-2 Caprolactam 0.00 0.67 0.71 118-90-1 2-Methylbenzoic acid 0.00 0.00 0.64 122-39-4 Diphenylamine 0.00 0.00 0.00 95-47-6 o-Xylene 0.00 0.00 0.00 95-48-7 o-Cresol 0.00 0.58 0.00 106-42-3 p-Xylene 0.00 0.00 0.00 80-05-7 Bisphenol A 0.00 0.00 0.00 65-85-0 Benzoic acid 0.00 0.61 0.00 108-67-8 1,3,5-Trimethylbenzene 0.00 0.00 0.00 135-98-8 sec-Butylbenzene 0.00 0.00 0.00 71-47-6 Formic acid, ion(1-) 0.30 0.28 0.43 78-51-3 Tris(2-butoxyethyl) phosphate 0.00 0.00 0.00

151

CAS Name OSF CPV IUR 104-51-8 Butylbenzene 0.00 0.00 0.00 108-39-4 m-Cresol 0.00 0.57 0.00 109-06-8 2-Methylpyridine 0.00 0.00 0.00 100-52-7 Benzaldehyde 0.00 0.00 0.00 611-32-5 8-Methylquinoline 0.00 0.00 0.00 67-64-1 Acetone 0.44 0.39 0.49 103-65-1 Propylbenzene 0.00 0.00 0.00 7661-55-4 5-Methylquinoline 0.00 0.00 0.00 105-67-9 2,4-Dimethylphenol 0.00 0.00 0.00 91-62-3 6-Methylquinoline 0.00 0.00 0.00 108-95-2 Phenol 0.00 0.54 0.00 612-60-2 7-Methylquinoline 0.00 0.00 0.00 612-58-8 3-Methylquinoline 0.00 0.00 0.00 491-35-0 Lepidine 0.00 0.00 0.00 117-84-0 Di-n-octyl phthalate 0.00 0.00 0.00 498-02-2 Acetovanillone 0.00 0.00 0.00 100-51-6 Benzyl alcohol 0.00 0.00 0.00 108-88-3 * Toluene 0.00 0.56 0.00 131-11-3 Dimethyl phthalate 0.00 0.00 0.00 26764-26-1 Octadecenoic acid 0.00 0.00 0.00 84-74-2 Dibutyl phthalate 0.00 0.00 0.00 28631-86-9 2,2-Dihydroxy-1-phenylethanone 0.00 0.00 0.00 100-42-5 Styrene 0.00 0.00 0.00 4376-20-9 MEHP 0.00 0.00 0.00 25447-95-4 Hexadecenoic acid 0.00 0.00 0.00 86-55-5 1-Naphthalenecarboxylic acid 0.00 0.00 0.00 67-56-1 * Methanol 0.39 0.34 0.48 85-68-7 Benzyl butyl phthalate 0.12 0.00 0.00 84-66-2 Diethyl phthalate 0.00 0.00 0.00 121-91-5 1,3-Benzenedicarboxylic acid 0.00 0.00 0.00

152

6.4.1.3 Hazard domain non-cancer metric ToxPi scores Appendix Table 9. ToxPi scores for each non-cancer metric in the hazard domain from the 376 organic compounds with toxicity data on the working list: reference dose (RfD), no observed adverse effect level (NOAEL), benchmark dose (BMD), benchmark dose lower limit (BMDL), and reference concentration (RfC).

CAS Name RfD NOAEL BMD BMDL RfC 309-00-2 Aldrin 0.94 1.00 1.00 1.00 0.72 1024-57-3 Heptachlor epoxide B 1.00 0.93 1.00 0.99 0.71 72-20-8 Endrin 0.80 1.00 0.99 0.98 0.49 76-44-8 Heptachlor 0.77 0.87 0.97 0.94 0.68 319-86-8 delta-Hexachlorocyclohexane 0.74 0.79 0.92 0.84 0.70 58-89-9 Lindane 0.78 0.79 0.92 0.84 0.70 319-85-7 beta-Hexachlorocyclohexane 0.74 0.79 0.92 0.84 0.70 2935-07-1 1H-Phenalene, dodecahydro- 0.65 0.56 0.48 0.34 0.70 118-74-1 Hexachlorobenzene 0.72 0.90 0.84 0.31 0.72 50-32-8 Benzo(a)pyrene 0.66 0.44 0.45 0.31 1.00 281-23-2 Adamantane 0.57 0.39 0.37 0.21 0.55 Cyclohexane, 1-(cyclohexylmethyl)-4- 54823-98-2 0.57 0.56 0.48 0.32 0.63 methyl-, trans- Methyl tricyclo(3.3.1.13,7)dec-1-yl 1660-04-4 0.57 0.59 0.54 0.41 0.67 ketone Naphthalene, decahydro-1,6- 1750-51-2 0.59 0.54 0.43 0.26 0.62 dimethyl- 56-55-3 Benz(a)anthracene 0.48 0.44 0.45 0.31 0.49 3178-23-2 Dicyclohexylmethane 0.60 0.53 0.46 0.31 0.65 6305-52-8 2-n-Butyldecahydronaphthalene 0.57 0.55 0.45 0.31 0.65 Naphthalene, decahydro-1,5- 66552-62-3 0.60 0.55 0.43 0.26 0.62 dimethyl- 5743-97-5 phenanthrene, tetradecahydro- 0.66 0.60 0.48 0.34 0.49 * naphthalene, decahydro-2,6- 1618-22-0 0.58 0.51 0.42 0.26 0.62 dimethyl- 1008-80-6 2,3-Dimethyldecahydronaphthalene 0.59 0.53 0.41 0.24 0.62 294-62-2 Cyclododecane 0.60 0.53 0.44 0.27 0.67 92-51-3 1,1'-Bicyclohexyl 0.59 0.51 0.42 0.24 0.64 53-70-3 Dibenz(a,h)anthracene 0.48 0.44 0.45 0.31 0.49 66660-42-2 cis, cis-3-ethylbicyclo[4.4.0]decane 0.57 0.51 0.41 0.25 0.64 1687-34-9 1-Ethyl-3-methyladamantane 0.67 0.65 0.52 0.40 0.49 4431-89-4 (Cyclopentylmethyl)cyclohexane 0.58 0.51 0.41 0.24 0.64 205-99-2 Benzo(b)fluoranthene 0.48 0.44 0.45 0.31 0.49 702-79-4 1,3-Dimethyladamantane 0.63 0.59 0.44 0.28 0.64 629-62-9 Pentadecane 0.52 0.51 0.46 0.32 0.63 629-59-4 Tetradecane 0.52 0.51 0.43 0.29 0.63 1606-08-2 Cyclopentylcyclohexane 0.57 0.44 0.39 0.22 0.61

153

CAS Name RfD NOAEL BMD BMDL RfC 218-01-9 Chrysene 0.48 0.44 0.45 0.31 0.49 2958-76-1 Decahydro-2-methylnaphthalene 0.55 0.43 0.39 0.25 0.60 16538-89-9 cyclooctane, (1-methylpropyl)- 0.55 0.52 0.43 0.27 0.63 23609-46-3 cyclooctane, 1,2-diethyl- 0.56 0.52 0.42 0.26 0.63 2883-02-5 Cyclohexane, nonyl- 0.53 0.55 0.47 0.35 0.64 1795-15-9 Cyclohexane, octyl- 0.53 0.54 0.46 0.31 0.64 629-50-5 Tridecane 0.52 0.51 0.41 0.27 0.59 111-84-2 Nonane 0.73 0.30 0.30 0.56 0.46 1795-16-0 Decylcyclohexane 0.52 0.54 0.48 0.35 0.65 62199-52-4 1,2-Dibutylcyclopentane 0.53 0.56 0.43 0.28 0.59 1560-93-6 2-Methylpentadecane 0.50 0.50 0.46 0.32 0.61 74-83-9 Methyl bromide 0.62 0.59 0.81 0.56 0.52 6165-40-8 7-Methylpentadecane 0.50 0.50 0.46 0.33 0.63 295-17-0 Cyclotetradecane 0.62 0.57 0.47 0.32 0.68 3891-98-3 2,6,10-Trimethyldodecane 0.51 0.54 0.45 0.33 0.57 79-34-5 1,1,2,2-Tetrachloroethane 0.48 0.47 0.64 0.51 0.50 61142-68-5 1-Hexyl-3-methylcyclopentane 0.53 0.52 0.41 0.26 0.59 112-40-3 Dodecane 0.53 0.49 0.39 0.23 0.59 207-08-9 Benzo(k)fluoranthene 0.48 0.44 0.45 0.31 0.49 17312-57-1 3-Methyldodecane 0.51 0.51 0.43 0.28 0.58 13287-21-3 6-Methyltridecane 0.50 0.51 0.43 0.29 0.58 26730-14-3 7-Methyltridecane 0.51 0.51 0.43 0.29 0.58 707-35-7 1,3,5-Trimethyladamantane 0.68 0.65 0.51 0.37 0.49 17312-80-0 2,4-Dimethylundecane 0.52 0.53 0.41 0.27 0.57 1560-97-0 2-Methyldodecane 0.51 0.51 0.42 0.27 0.57 1,7-dimethyl-4-(1- 645-10-3 0.58 0.57 0.48 0.34 0.63 methylethyl)cyclodecane 4292-75-5 Hexylcyclohexane 0.53 0.52 0.43 0.27 0.60 6117-97-1 4-Methyldodecane 0.51 0.52 0.42 0.27 0.58 67-66-3 Chloroform 0.51 0.45 0.77 0.61 0.36 1120-21-4 Undecane 0.56 0.44 0.33 0.20 0.54 17301-23-4 2,6-Dimethylundecane 0.52 0.54 0.42 0.28 0.57 6418-41-3 tridecane, 3-methyl- 0.51 0.51 0.44 0.29 0.57 1560-95-8 2-Methyltetradecane 0.50 0.50 0.45 0.31 0.57 56292-65-0 2,5-Dimethyldodecane 0.50 0.52 0.42 0.28 0.57 112-70-9 1-Tridecanol 0.50 0.53 0.48 0.36 0.64 25117-31-1 5-Methyltridecane 0.50 0.51 0.43 0.28 0.59 cyclohexane, 1-methyl-4-(1- 54411-00-6 0.53 0.53 0.44 0.30 0.57 methylbutyl)- 41446-57-5 3-Tridecene, (3E)- 0.53 0.52 0.41 0.27 0.60 26730-12-1 4-Methyltridecane 0.50 0.51 0.43 0.29 0.58 25117-32-2 5-Methyltetradecane 0.50 0.51 0.45 0.32 0.59

154

CAS Name RfD NOAEL BMD BMDL RfC 13150-81-7 2,6-Dimethyldecane 0.52 0.51 0.41 0.26 0.57 1560-96-9 2-Methyltridecane 0.51 0.51 0.43 0.28 0.57 15232-86-7 1-Heptylcyclohexene 0.54 0.53 0.45 0.30 0.60 442662-72-8 2-Ethyl-1,1,3-trimethylcyclohexane 0.55 0.56 0.40 0.24 0.53 4457-00-5 Cyclopentane, hexyl- 0.53 0.45 0.37 0.21 0.57 4292-92-6 Pentylcyclohexane 0.53 0.45 0.37 0.22 0.58 544-76-3 Hexadecane 0.53 0.53 0.46 0.33 0.64 124-18-5 * Decane 0.57 0.38 0.31 0.17 0.43 1,4-Dimethyl-2,3- 71312-54-4 0.52 0.43 0.42 0.26 0.49 diazabicyclo[2.2.1]hept-2-ene 61142-66-3 cyclopentene, 5-hexyl-3,3-dimethyl- 0.54 0.61 0.46 0.31 0.56 2207-01-4 (Z)-1,2-Dimethylcyclohexane 0.44 0.33 0.32 0.15 0.33 6750-34-1 1-dodecanol, 3,7,11-trimethyl- 0.48 0.52 0.48 0.37 0.63 193-39-5 Indeno(1,2,3-cd)pyrene 0.48 0.44 0.45 0.31 0.49 7045-71-8 2-Methylundecane 0.53 0.49 0.38 0.22 0.56 1,7,11-Trimethyl-4-(1- 1786-12-5 0.61 0.61 0.53 0.39 0.49 methylethyl)cyclotetradecane 61142-70-9 2,4-Diethyl-1-methylcyclohexane 0.52 0.45 0.38 0.23 0.56 2847-72-5 4-Methyldecane 0.53 0.45 0.34 0.19 0.54 115-96-8 Tris(2-chloroethyl) phosphate 0.58 0.46 0.71 0.56 0.69 110-82-7 Cyclohexane 0.39 0.31 0.27 0.10 0.12 17302-32-8 3,7-Dimethylnonane 0.52 0.47 0.35 0.23 0.54 17302-28-2 2,6-Dimethylnonane 0.52 0.47 0.36 0.21 0.55 13151-34-3 3-Methyldecane 0.53 0.44 0.34 0.19 0.53 16580-24-8 1-Methyl-3-(propan-2-yl)cyclohexane 0.52 0.41 0.37 0.20 0.52 74-93-1 Methanethiol 0.52 0.44 0.48 0.37 0.37 13151-35-4 5-Methyldecane 0.53 0.45 0.34 0.18 0.54 66542-51-6 * Chloromethyl hexanoate 0.49 0.43 0.52 0.38 0.55 591-21-9 1,3-Dimethylcyclohexane 0.44 0.32 0.34 0.16 0.32 62016-37-9 2,4,6-Trimethyloctane 0.52 0.47 0.38 0.22 0.56 2234-75-5 1,2,4-Trimethylcyclohexane 0.51 0.35 0.36 0.20 0.41 6975-98-0 2-Methyldecane 0.52 0.44 0.34 0.19 0.52 71-43-2 * Benzene 0.54 0.93 0.45 0.61 0.41 5402-53-9 Chloromethyl propanoate 0.44 0.37 0.50 0.38 0.45 127-18-4 * Tetrachloroethylene 0.56 0.59 0.63 0.55 0.43 3728-56-1 1-Ethyl-4-methylcyclohexane 0.51 0.34 0.35 0.18 0.39 rel-(1R,2S)-1,2- 14113-60-1 0.56 0.57 0.50 0.37 0.49 Diethylcyclohexadecane 77877-94-2 Chloromethyl pentanoate 0.50 0.38 0.49 0.38 0.50 1678-93-9 Butylcyclohexane 0.53 0.41 0.34 0.19 0.55 112-18-5 N,N-Dimethyldodecan-1-amine 0.49 0.51 0.48 0.34 0.60 73105-67-6 1-Iodo-2-methylundecane 0.48 0.61 0.80 0.70 0.69 142-82-5 Heptane 0.72 0.29 0.28 0.14 0.28 155

CAS Name RfD NOAEL BMD BMDL RfC 1072-05-5 2,6-Dimethylheptane 0.51 0.36 0.34 0.17 0.37 62199-51-3 1-Pentyl-2-propylcyclopentane 0.53 0.55 0.43 0.29 0.59 26730-20-1 7-Methylhexadecane 0.50 0.50 0.46 0.33 0.64 111-65-9 Octane 0.49 0.31 0.30 0.15 0.33 111-44-4 Bis(2-chloroethyl) ether 0.49 0.38 0.53 0.41 0.49 3728-55-0 1-Ethyl-3-methylcyclohexane 0.51 0.35 0.33 0.17 0.41 1560-92-5 2-Methylhexadecane 0.51 0.50 0.47 0.33 0.62 1678-92-8 Propylcyclohexane 0.53 0.34 0.33 0.18 0.41 2040-96-2 Propylcyclopentane 0.44 0.32 0.33 0.15 0.33 4291-79-6 1-Methyl-2-propyl-cyclohexane 0.52 0.41 0.35 0.20 0.54 75-25-2 Bromoform 0.51 0.36 0.77 0.65 0.45 5911-04-6 3-Methylnonane 0.54 0.38 0.32 0.16 0.42 2-BUTYL-1,1,3-TRIMETHYL- 54676-39-0 0.57 0.70 0.50 0.37 0.55 CYCLOHEXANE 107-13-1 Acrylonitrile 0.60 0.46 0.48 0.39 0.53 16580-26-0 cyclohexane, 1-isopropyl-1-methyl- 0.53 0.44 0.39 0.23 0.50 3073-66-3 1,1,3-Trimethylcyclohexane 0.50 0.36 0.37 0.20 0.41 31295-56-4 2,6,11-Trimethyldodecane 0.52 0.54 0.46 0.34 0.57 17301-94-9 4-Methylnonane 0.53 0.39 0.32 0.15 0.43 871-83-0 2-Methylnonane 0.53 0.38 0.32 0.16 0.42 15869-86-0 4-Ethyloctane 0.53 0.40 0.33 0.17 0.45 79-06-1 Acrylamide 0.58 0.87 0.85 0.94 0.49 16747-30-1 2,4,4-Trimethylhexane 0.50 0.38 0.36 0.17 0.38 107-06-2 1,2-Dichloroethane 0.53 0.36 0.55 0.43 0.50 2883-05-8 2-Cyclohexyloctane 0.52 0.54 0.44 0.29 0.59 100-44-7 Benzyl chloride 0.61 0.38 0.53 0.41 0.62 54411-01-7 1-Methyl-2-pentylcyclohexane 0.53 0.52 0.41 0.26 0.58 15869-93-9 3,5-Dimethyloctane 0.51 0.40 0.33 0.17 0.44 2051-30-1 2,6-Dimethyloctane 0.51 0.40 0.34 0.18 0.43 74054-92-5 1,1,6,6-tetramethylspiro[4.4]nonane 0.67 0.67 0.61 0.50 0.49 2406-25-9 Di-tert-butyl nitroxide 0.50 0.49 0.43 0.25 0.48 98-95-3 Nitrobenzene 0.61 0.45 0.75 0.47 0.50 959028-24-1 4-Ethyl-2,3-dimethylhex-2-ene 0.50 0.41 0.37 0.20 0.45 2815-58-9 1,2,4-Trimethylcyclopentane 0.43 0.33 0.35 0.17 0.32 123-25-1 Diethyl butanedioate 0.46 0.48 0.47 0.34 0.66 75-15-0 Carbon disulfide 0.33 0.40 0.61 0.53 0.23 706-14-9 gamma-Decanolactone 0.51 0.54 0.50 0.35 0.62 143-07-7 Dodecanoic acid 0.49 0.52 0.51 0.39 0.66 109-74-0 Butanenitrile 0.50 0.36 0.46 0.33 0.40 1921-70-6 Norphytane 0.51 0.56 0.50 0.35 0.49 4810-09-7 3-Methyl-1-heptene 0.45 0.31 0.34 0.17 0.36 108-87-2 Methylcyclohexane 0.39 0.31 0.32 0.14 0.29

156

CAS Name RfD NOAEL BMD BMDL RfC 959-98-8 Endosulfan I 0.70 0.82 0.95 0.90 0.49 33213-65-9 Endosulfan II 0.70 0.82 0.95 0.90 0.49 1678-91-7 Ethylcyclohexane 0.44 0.33 0.33 0.16 0.33 2980-69-0 4-Methylundecane 0.53 0.50 0.38 0.23 0.58 3386-33-2 Octadecyl chloride 0.53 0.57 0.66 0.56 0.49 55282-11-6 11-Pentan-3-ylhenicosane 0.52 0.57 0.53 0.42 0.49 112-30-1 1-Decanol 0.49 0.44 0.40 0.26 0.61 2453-00-1 1,3-Dimethylcyclopentane 0.42 0.31 0.34 0.15 0.28 74-84-0 Ethane 0.45 0.38 0.36 0.21 0.21 629-97-0 Docosane 0.55 0.54 0.50 0.36 0.49 1632-70-8 5-methylundecane 0.53 0.50 0.38 0.23 0.59 1002-43-3 3-Methylundecane 0.53 0.50 0.39 0.23 0.57 591-48-0 3-Methylcyclohexene 0.40 0.31 0.35 0.16 0.30 1192-18-3 (Z)-1,2-Dimethylcyclopentane 0.41 0.32 0.34 0.15 0.28 629-78-7 Heptadecane 0.53 0.55 0.48 0.35 0.64 592-27-8 2-Methylheptane 0.47 0.31 0.31 0.17 0.34 74-87-3 Chloromethane 0.49 0.43 0.48 0.34 0.32 7320-37-8 1,2-Epoxyhexadecane 0.51 0.54 0.53 0.41 0.71 593-45-3 Octadecane 0.53 0.55 0.48 0.35 0.64 110-75-8 2-Chloroethyl vinyl ether 0.44 0.36 0.49 0.36 0.45 562-28-7 (-)-Kaur-16-ene 0.48 0.76 0.45 0.31 0.49 111-30-8 Glutaraldehyde 0.37 0.53 0.41 0.26 0.75 821-55-6 2-Nonanone 0.48 0.34 0.39 0.25 0.48 638-36-8 2,6,10,14-Tetramethylhexadecane 0.50 0.55 0.49 0.36 0.49 50991-08-7 2-Methyl-1,1'-bi(cyclohexane) 0.59 0.53 0.45 0.31 0.49 106-65-0 Dimethyl succinate 0.40 0.37 0.44 0.32 0.55 109-66-0 Pentane 0.39 0.25 0.25 0.07 0.21 126-73-8 Tributyl phosphate 0.56 0.53 0.63 0.54 0.64 75-83-2 2,2-Dimethylbutane 0.41 0.32 0.33 0.14 0.22 110-54-3 n-Hexane 0.37 0.28 0.07 0.03 0.24 1,3,5-Trimethyl-1,3,5-triazinane-2- 59887-80-8 0.51 0.46 0.58 0.49 0.67 thione 6418-44-6 heptadecane, 3-methyl- 0.50 0.50 0.47 0.34 0.63 111-87-5 1-Octanol 0.48 0.32 0.36 0.22 0.39 74-98-6 Propane 0.44 0.28 0.32 0.13 0.17 513-35-9 2-Methyl-2-butene 0.39 0.29 0.32 0.14 0.24 112-95-8 Eicosane 0.52 0.54 0.50 0.36 0.49 107-83-5 2-Methylpentane 0.40 0.26 0.28 0.08 0.24 91-20-3 Naphthalene 0.47 0.30 0.45 0.31 0.56 72-03-7 Propanoate 0.33 0.35 0.45 0.30 0.50 3892-00-0 2,6,10-Trimethylpentadecane 0.50 0.52 0.46 0.34 0.59 334-48-5 Decanoic acid 0.47 0.48 0.49 0.35 0.67

157

CAS Name RfD NOAEL BMD BMDL RfC 41446-78-0 4-Tetradecene, (4E)- 0.52 0.52 0.42 0.28 0.60 120-82-1 1,2,4-Trichlorobenzene 0.53 0.45 0.45 0.71 0.60 111-76-2 2-Butoxyethanol 0.36 0.28 0.44 0.64 0.21 629-92-5 Nonadecane 0.52 0.54 0.49 0.36 0.49 629-94-7 Heneicosane 0.53 0.54 0.50 0.36 0.49 68-12-2 N,N-Dimethylformamide 0.33 0.23 0.46 0.24 0.40 106-46-7 1,4-Dichlorobenzene 0.40 0.49 0.45 0.31 0.26 112-88-9 1-Octadecene 0.49 0.49 0.47 0.35 0.65 297-35-8 Cyclotriacontane 0.48 0.62 0.45 0.31 0.49 104-76-7 2-Ethyl-1-hexanol 0.46 0.35 0.35 0.20 0.41 10374-74-0 7-Tetradecene 0.52 0.52 0.42 0.28 0.60 112-34-5 2-(2-Butoxyethoxy)ethanol 0.46 0.43 0.37 0.23 0.76 123-20-6 Butanoic acid, ethenyl ester 0.39 0.33 0.34 0.17 0.39 64275-73-6 (Z)-5-Octen-1-ol 0.48 0.33 0.34 0.19 0.42 18435-22-8 3-methyl-tetradecane 0.50 0.51 0.45 0.32 0.49 1768-36-1 Propyl cyanate 0.37 0.29 0.40 0.25 0.47 18435-45-5 1-Nonadecene 0.49 0.48 0.49 0.37 0.49 123-86-4 Butyl acetate 0.40 0.28 0.37 0.20 0.40 544-85-4 Dotriacontane 0.48 0.61 0.45 0.31 0.49 55000-52-7 2,6,10-Trimethylhexadecane 0.49 0.51 0.47 0.34 0.49 99328-46-8 5-Methylhept-1-en-4-ol 0.46 0.38 0.36 0.20 0.41 591-78-6 2-Hexanone 0.54 0.22 0.40 0.22 0.42 4360-57-0 2-Pentadecyl-1,3-dioxolane 0.51 0.54 0.56 0.44 0.49 638-67-5 Tricosane 0.55 0.54 0.50 0.37 0.49 87-61-6 1,2,3-Trichlorobenzene 0.69 0.50 0.45 0.31 0.49 1630-94-0 1,1-Dimethylcyclopropane 0.41 0.32 0.33 0.16 0.23 55030-62-1 4,8-Dimethyltridecane 0.50 0.50 0.44 0.33 0.49 18344-37-1 heptadecane, 2,6,10,14-tetramethyl- 0.50 0.55 0.50 0.35 0.49 144-19-4 2,2,4-Trimethyl-1,3-pentanediol 0.48 0.45 0.41 0.23 0.50 461-55-2 Butyrate 0.31 0.27 0.39 0.22 0.47 71-23-8 1-Propanol 0.39 0.26 0.32 0.14 0.33 646-31-1 Tetracosane 0.56 0.55 0.51 0.37 0.49 629-99-2 Pentacosane 0.56 0.55 0.50 0.37 0.49 5989-27-5 D-Limonene 0.49 0.40 0.38 0.21 0.50 54833-48-6 Heptadecane, 2,6,10,15-tetramethyl 0.50 0.55 0.48 0.36 0.49 57-60-3 Pyruvate 0.36 0.40 0.47 0.35 0.47 593-49-7 Heptacosane 0.48 0.57 0.51 0.38 0.49 79-09-4 Propionic acid 0.37 0.32 0.48 0.32 0.51 630-01-3 Hexacosane 0.57 0.56 0.51 0.37 0.49 54105-67-8 2,6-Dimethylheptadecane 0.49 0.50 0.46 0.33 0.49 110-94-1 Glutaric acid 0.34 0.29 0.47 0.34 0.56 544-63-8 Tetradecanoic acid 0.49 0.51 0.53 0.41 0.70

158

CAS Name RfD NOAEL BMD BMDL RfC 91-57-6 * 2-Methylnaphthalene 0.58 0.53 0.63 0.56 0.49 2885-00-9 1-Octadecanethiol 0.54 0.56 0.61 0.53 0.49 25117-24-2 4-Methyltetradecane 0.50 0.51 0.45 0.32 0.49 630-02-4 Octacosane 0.48 0.57 0.51 0.37 0.49 638-68-6 Triacontane 0.48 0.58 0.45 0.31 0.49 71-36-3 1-Butanol 0.33 0.21 0.32 0.14 0.28 92-52-4 * Biphenyl 0.28 0.44 0.45 0.31 0.68 598-89-0 Diiodoacetic acid 0.48 0.52 0.80 0.71 0.56 13287-24-6 9-Methylnonadecane 0.50 0.50 0.45 0.31 0.49 96-04-8 2,3-Heptanedione 0.40 0.33 0.37 0.19 0.46 129-00-0 Pyrene 0.47 0.33 0.39 0.31 0.49 132-65-0 Dibenzothiophene 0.53 0.57 0.45 0.31 0.49 563-46-2 2-Methylbut-1-ene 0.37 0.28 0.32 0.14 0.22 2490-48-4 2-Methylhexadecan-1-ol 0.48 0.51 0.51 0.40 0.49 (4aS,8aR)-4a- 938-06-7 Methyloctahydronaphthalen-2(1H)- 0.53 0.54 0.46 0.29 0.60 one 695-06-7 gamma-Caprolactone 0.35 0.33 0.36 0.18 0.37 80-62-6 Methyl methacrylate 0.18 0.23 0.38 0.18 0.25 149-57-5 2-Ethylhexanoic acid 0.43 0.38 0.39 0.23 0.51 124-07-2 Octanoic acid 0.44 0.34 0.39 0.24 0.51 5618-62-2 O-Isobutylhydroxylamine 0.38 0.22 0.34 0.21 0.41 100-01-6 4-Nitroaniline 0.57 0.44 0.87 0.80 0.53 95-50-1 1,2-Dichlorobenzene 0.38 0.29 0.45 0.61 0.34 206-44-0 * Fluoranthene 0.45 0.29 0.42 0.31 0.49 57-11-4 Octadecanoic acid 0.50 0.54 0.56 0.43 0.49 630-03-5 Nonacosane 0.48 0.57 0.45 0.31 0.49 5842-53-5 2,2,4-Trimethylpent-3-en-1-ol 0.46 0.39 0.41 0.22 0.39 91-22-5 Quinoline 0.48 0.44 0.45 0.31 0.49 108-29-2 4-Pentanolide 0.32 0.31 0.33 0.13 0.36 111-14-8 Heptanoic acid 0.40 0.30 0.37 0.21 0.51 107-92-6 Butanoic acid 0.31 0.26 0.37 0.20 0.48 141-78-6 Ethyl acetate 0.20 0.07 0.33 0.15 0.37 142-62-1 Hexanoic acid 0.38 0.28 0.37 0.21 0.48 542-28-9 Tetrahydro-2H-pyran-2-one 0.31 0.30 0.31 0.12 0.38 98-82-8 Cumene 0.36 0.26 0.45 0.31 0.29 64-19-7 Acetic acid 0.32 0.39 0.39 0.22 0.44 544-77-4 1-Iodohexadecane 0.48 0.59 0.45 0.31 0.49 60212-33-1 4-Tetradecyne 0.53 0.53 0.42 0.28 0.59 71-50-1 Acetate 0.30 0.35 0.39 0.23 0.45 117-81-7 Di(2-ethylhexyl) phthalate 0.54 0.58 0.45 0.31 0.49 75-09-2 Dichloromethane 0.52 0.46 0.41 0.34 0.25

159

CAS Name RfD NOAEL BMD BMDL RfC 3055-93-4 2-[2-(Dodecyloxy)ethoxy]ethanol 0.50 0.52 0.54 0.42 0.68 123-91-1 1,4-Dioxane 0.42 0.43 0.36 0.21 0.41 4860-03-1 1-Chlorohexadecane 0.53 0.55 0.45 0.31 0.49 544-25-2 1,3,5-Cycloheptatriene 0.43 0.34 0.38 0.22 0.31 83-32-9 Acenaphthene 0.41 0.44 0.34 0.31 0.49 35216-11-6 7-Tetradecyne 0.54 0.53 0.42 0.28 0.59 100-41-4 Ethylbenzene 0.35 0.26 0.45 0.31 0.23 132-64-9 Dibenzofuran 0.67 0.44 0.45 0.31 0.49 108-90-7 Chlorobenzene 0.46 0.39 0.45 0.31 0.40 766-76-7 Benzoate 0.48 0.38 0.48 0.37 0.53 109-52-4 Pentanoic acid 0.34 0.26 0.39 0.24 0.50 61886-62-2 3-Hexadecyne 0.52 0.51 0.45 0.31 0.64 584-02-1 3-Pentanol 0.32 0.24 0.29 0.11 0.26 120-12-7 Anthracene 0.32 0.11 0.45 0.31 0.49 57-55-6 1,2-Propylene glycol 0.00 0.22 0.46 0.28 0.37 79-31-2 2-Methylpropanoic acid 0.30 0.28 0.40 0.23 0.42 74-82-8 Methane 0.48 0.39 0.38 0.27 0.31 64-17-5 Ethanol 0.41 0.33 0.33 0.13 0.28 67-63-0 Isopropanol 0.13 0.19 0.27 0.07 0.29 575-41-7 1,3-Dimethylnaphthalene 0.48 0.44 0.44 0.27 0.49 57-10-3 Hexadecanoic acid 0.51 0.52 0.55 0.43 0.70 75-34-3 1,1-Dichloroethane 0.31 0.09 0.60 0.53 0.31 110-86-1 Pyridine 0.63 0.60 0.74 0.31 0.49 646-07-1 Pentanoic acid, 4-methyl- 0.37 0.31 0.37 0.20 0.42 86-30-6 N-Nitrosodiphenylamine 0.48 0.44 0.45 0.31 0.49 90-12-0 1-Methylnaphthalene 0.54 0.31 0.53 0.27 0.49 86-73-7 Fluorene 0.44 0.27 0.39 0.31 0.49 576-26-1 2,6-Dimethylphenol 0.69 0.44 0.42 0.25 0.39 573-98-8 1,2-Dimethylnaphthalene 0.48 0.44 0.45 0.27 0.49 116-53-0 2-Methylbutanoic acid 0.31 0.30 0.35 0.16 0.42 569-41-5 1,8-Dimethylnaphthalene 0.48 0.44 0.44 0.27 0.49 571-58-4 1,4-Dimethylnaphthalene 0.48 0.44 0.44 0.27 0.49 575-37-1 1,7-Dimethylnaphthalene 0.48 0.44 0.44 0.27 0.49 2049-95-8 tert-Pentylbenzene 0.48 0.45 0.45 0.31 0.49 1599-67-3 1-Docosene 0.50 0.51 0.51 0.39 0.49 62-53-3 Aniline 0.51 0.37 0.45 0.31 0.60 50-00-0 Formaldehyde 0.23 0.31 0.40 0.18 0.42 503-74-2 Isovaleric acid 0.32 0.25 0.38 0.18 0.42 533-18-6 Acetic acid, 2-methylphenyl ester 0.48 0.42 0.48 0.30 0.55 122-20-3 Triisopropanolamine 0.47 0.57 0.50 0.37 0.63 3055-94-5 Triethylene glycol monododecyl ether 0.50 0.53 0.56 0.45 0.49 113-21-3 Lactate ion(1-) 0.34 0.34 0.48 0.33 0.46

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CAS Name RfD NOAEL BMD BMDL RfC 941228-34-8 7-(Bromomethyl)pentadec-7-ene 0.60 0.57 0.45 0.31 0.49 10023-74-2 Pentanoic acid, ion(1-) 0.34 0.27 0.41 0.26 0.47 75-07-0 Acetaldehyde 0.38 0.41 0.37 0.19 0.44 95-65-8 3,4-Dimethylphenol 0.65 0.41 0.41 0.23 0.36 35365-59-4 9-Octadecyne 0.52 0.51 0.45 0.31 0.49 90-15-3 1-Naphthol 0.48 0.42 0.50 0.33 0.49 541-73-1 1,3-Dichlorobenzene 0.48 0.44 0.45 0.31 0.49 122-99-6 2-Phenoxyethanol 0.48 0.40 0.45 0.31 0.49 95-87-4 2,5-Dimethylphenol 0.48 0.42 0.42 0.25 0.39 106-44-5 p-Cresol 0.48 0.34 0.45 0.31 0.49 107-21-1 Ethylene glycol 0.13 0.16 0.21 0.12 0.25 1-Hydroxy-3-(2-methylpropyl)- 2873-36-1 6,7,8,8a-tetrahydropyrrolo[1,2- 0.47 0.51 0.52 0.39 0.49 a]pyrazin-4(3H)-one 2136-72-3 2-(Octadecyloxy)ethanol 0.51 0.54 0.45 0.31 0.49 526-73-8 1,2,3-Trimethylbenzene 0.51 0.44 0.45 0.31 0.39 575-43-9 1,6-Dimethylnaphthalene 0.48 0.44 0.44 0.27 0.49 98-86-2 Acetophenone 0.36 0.15 0.45 0.31 0.49 611-14-3 1-Ethyl-2-methylbenzene 0.48 0.32 0.45 0.31 0.49 95-63-6 1,2,4-Trimethylbenzene 0.51 0.44 0.45 0.31 0.38 1074-43-7 1-Methyl-3-propylbenzene 0.48 0.36 0.45 0.31 0.49 135-19-3 2-Naphthalenol 0.48 0.41 0.50 0.33 0.49 104-90-5 5-Ethyl-2-methylpyridine 0.48 0.36 0.39 0.22 0.39 98-06-6 tert-Butylbenzene 0.37 0.27 0.45 0.31 0.49 3333-52-6 Tetramethylsuccinonitrile 0.50 0.47 0.46 0.31 0.50 78-93-3 Methyl ethyl ketone 0.22 0.00 0.30 0.12 0.12 107-19-7 Propargyl alcohol 0.56 0.44 0.45 0.31 0.49 620-14-4 3-Ethyltoluene 0.48 0.32 0.45 0.31 0.49 108-68-9 3,5-Dimethylphenol 0.48 0.44 0.40 0.22 0.36 526-75-0 2,3-Dimethylphenol 0.48 0.44 0.41 0.23 0.38 99-06-9 3-Hydroxybenzoic acid 0.48 0.44 0.51 0.36 0.62 108-10-1 4-Methyl-2-pentanone 0.22 0.18 0.30 0.12 0.17 105-60-2 Caprolactam 0.26 0.32 0.06 0.00 0.40 118-90-1 2-Methylbenzoic acid 0.48 0.41 0.47 0.30 0.56 122-39-4 Diphenylamine 0.47 0.59 0.45 0.31 0.49 95-47-6 o-Xylene 0.31 0.44 0.45 0.31 0.36 95-48-7 o-Cresol 0.40 0.31 0.45 0.31 0.26 106-42-3 p-Xylene 0.31 0.31 0.45 0.31 0.36 80-05-7 Bisphenol A 0.45 0.44 0.45 0.31 0.49 65-85-0 Benzoic acid 0.13 0.51 0.45 0.31 0.58 108-67-8 1,3,5-Trimethylbenzene 0.51 0.24 0.45 0.31 0.39 135-98-8 sec-Butylbenzene 0.37 0.27 0.45 0.31 0.49

161

CAS Name RfD NOAEL BMD BMDL RfC 71-47-6 Formic acid, ion(1-) 0.28 0.35 0.41 0.27 0.54 78-51-3 Tris(2-butoxyethyl) phosphate 0.57 0.79 0.45 0.31 0.49 104-51-8 Butylbenzene 0.41 0.36 0.34 0.15 0.49 108-39-4 m-Cresol 0.40 0.31 0.45 0.31 0.26 109-06-8 2-Methylpyridine 0.48 0.31 0.45 0.31 0.49 100-52-7 Benzaldehyde 0.35 0.23 0.45 0.31 0.49 611-32-5 8-Methylquinoline 0.48 0.39 0.45 0.28 0.49 67-64-1 Acetone 0.18 0.03 0.12 0.04 0.01 103-65-1 Propylbenzene 0.36 0.31 0.45 0.31 0.24 7661-55-4 5-Methylquinoline 0.48 0.39 0.46 0.28 0.49 105-67-9 2,4-Dimethylphenol 0.51 0.32 0.45 0.31 0.49 91-62-3 6-Methylquinoline 0.48 0.38 0.46 0.29 0.49 108-95-2 Phenol 0.28 0.39 0.35 0.16 0.31 612-60-2 7-Methylquinoline 0.48 0.39 0.46 0.28 0.49 612-58-8 3-Methylquinoline 0.48 0.38 0.46 0.29 0.49 491-35-0 Lepidine 0.48 0.38 0.46 0.29 0.49 117-84-0 Di-n-octyl phthalate 0.58 0.44 0.45 0.31 0.49 498-02-2 Acetovanillone 0.48 0.50 0.51 0.37 0.65 100-51-6 Benzyl alcohol 0.36 0.23 0.45 0.31 0.49 108-88-3 * Toluene 0.36 0.31 0.42 0.05 0.13 131-11-3 Dimethyl phthalate 0.39 0.54 0.45 0.31 0.49 26764-26-1 Octadecenoic acid 0.50 0.52 0.45 0.31 0.49 84-74-2 Dibutyl phthalate 0.42 0.31 0.36 0.31 0.49 28631-86-9 2,2-Dihydroxy-1-phenylethanone 0.48 0.44 0.48 0.34 0.49 100-42-5 Styrene 0.31 0.20 0.48 0.31 0.23 4376-20-9 MEHP 0.48 0.46 0.45 0.31 0.49 25447-95-4 Hexadecenoic acid 0.50 0.51 0.45 0.31 0.49 86-55-5 1-Naphthalenecarboxylic acid 0.48 0.47 0.56 0.41 0.49 67-56-1 * Methanol 0.09 0.03 0.00 0.00 0.00 85-68-7 Benzyl butyl phthalate 0.38 0.30 0.45 0.31 0.49 84-66-2 Diethyl phthalate 0.27 0.15 0.45 0.31 0.49 121-91-5 1,3-Benzenedicarboxylic acid 0.48 0.44 0.49 0.34 0.49

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6.4.2 Organic compounds without toxicity data Appendix Table 10. Organic compounds without toxicity data rank and ToxPi score.

ToxPi Rank CAS Name Score 1 0.686 54832-83-6 2,2,4,4,7,7-Hexamethyloctahydro-1H-indene 2 0.662 204781-73-7 28-Nor-17alpha(H)-hopane 3 0.646 1079-71-6 1,2,3,4,5,6,7,8-Octahydroanthracene 4 0.620 191-24-2 Benzo(g,h,i)perylene 5 0.614 644-08-6 4-methylbiphenyl 6 0.607 32038-83-8 3-Fluoroprop-2-ynenitrile 7 0.600 2717-39-7 1,4,5,8-Tetramethylnaphthalene 8 0.586 101-81-5 Diphenylmethane 9 0.586 829-26-5 2,3,6-Trimethylnaphthalene 10 0.585 1730-37-6 1-Methylfluorene 11 0.575 581-42-0 2,6-Dimethylnaphthalene 12 0.574 85-01-8 Phenanthrene 13 0.574 582-16-1 2,7-Dimethylnaphthalene 14 0.571 108-38-3 m-Xylene 15 0.570 643-93-6 3-Methylbiphenyl 16 0.570 208-96-8 Acenaphthylene 17 0.568 581-40-8 2,3-Dimethylnaphthalene 18 0.568 2131-41-1 1,4,5-Trimethylnaphthalene 19 0.566 630-07-9 Pentatriacontane 20 0.564 630-06-8 Hexatriacontane 21 0.564 2245-38-7 1,6,7-Trimethylnaphthalene 22 0.563 879-12-9 1,2,3-Trimethylnaphthalene 23 0.563 2381-21-7 1-Methylpyrene 24 0.562 643-58-3 2-Methylbiphenyl 25 0.561 99-87-6 p-Cymene 26 0.560 571-61-9 1,5-Dimethylnaphthalene 27 0.557 119-64-2 Tetralin 28 0.555 7098-22-8 Tetratetracontane 29 0.552 700-12-9 Benzene, pentamethyl- 30 0.552 2809-64-5 Naphthalene, 1,2,3,4-tetrahydro-5-methyl- 31 0.549 95-93-2 1,2,4,5-Tetramethylbenzene 32 0.547 6971-40-0 17-pentatriacontene 33 0.545 1576-67-6 3,6-Dimethylphenanthrene 34 0.545 1559-81-5 1-Methyltetraline 35 0.542 852228-22-9 1,54-Dibromotetrapentacontane 36 0.532 4466-77-7 1,2,3,4-Tetramethylphenanthrene 37 0.530 874-41-9 1,3-Dimethyl-4-ethylbenzene 38 0.529 1595-16-0 1-(Butan-2-yl)-4-methylbenzene

163

ToxPi Rank CAS Name Score 39 0.522 832-69-9 1-Methyl phenanthrene 40 0.507 26746-38-3 2,3-di-tert-butylphenol 41 0.490 483-65-8 Retene 42 0.489 25414-22-6 2-Methoxyfuran 43 0.486 96-76-4 2,4-Di-tert-butylphenol 44 0.479 321-60-8 2-Fluorobiphenyl 45 0.472 496-11-7 Indan 46 0.470 119-65-3 Isoquinoline 47 0.456 56221-91-1 13-Tetradecen-1-yl acetate 48 0.454 95-16-9 Benzothiazole 49 0.448 89-74-7 1-(2,4-Dimethylphenyl)ethanone 50 0.447 140-66-9 4-(1,1,3,3-Tetramethylbutyl)phenol 51 0.445 1205-39-6 2-Methyl-N-phenylaniline 52 0.436 91-63-4 Quinaldine 53 0.436 123731-75-9 1-Allyl-3-methylindole-2-carbaldehyde 54 0.421 78-67-1 Azobisisobutyronitrile 55 0.417 98-54-4 4-tert-Butylphenol 56 0.402 115-86-6 Triphenyl phosphate 57 0.396 19261-13-3 1-(2-Furanyl)-3-butene-1,2-diol 58 0.390 2315-61-9 Triton X-100.2 59 0.384 84-69-5 Diisobutyl phthalate 60 0.383 17851-53-5 Butyl isobutyl phthalate 61 0.375 84-77-5 Didecyl phthalate 62 0.371 2682-20-4 2-Methyl-3(2H)-isothiazolone 1',4-Dihydroxy-7'-methoxy-2,3'-dimethyl-,(-)-[1,2'- 63 0.366 119736-96-8 binaphthalene]-5,5',8,8'-tetrone 64 0.357 89-16-7 Bis(8-methylnonyl) phthalate 65 0.342 93-09-4 2-Naphthalenecarboxylic acid 66 0.333 121-33-5 4-Hydroxy-3-methoxybenzaldehyde 67 0.304 934-34-9 Benzothiazolone 68 0.285 80061-31-0 3,4-Dihydro-1,9(2H,10H)-acridinedione

164

6.4.2.1 Individual metric scores Appendix Table 11. Organic compounds without data ToxPi scores for the individual exposure domain metrics: Henry’s Law constant (KH), organic carbon-water partition coefficient (Koc), biodegradation half-life (t1/2), and bioconcentration factor (BCF).

CAS Name KH Koc t1/2 BCF 2,2,4,4,7,7-Hexamethyloctahydro-1H- 54832-83-6 0.947 0.192 0.650 0.954 indene 204781-73-7 28-Nor-17alpha(H)-hopane 0.700 0.035 0.946 0.969 1079-71-6 1,2,3,4,5,6,7,8-Octahydroanthracene 0.799 0.205 0.743 0.835 191-24-2 Benzo(g,h,i)perylene 0.448 0.080 1.000 0.953 644-08-6 4-methylbiphenyl 0.794 0.295 0.474 0.895 32038-83-8 3-Fluoroprop-2-ynenitrile 1.000 0.642 0.160 0.625 2717-39-7 1,4,5,8-Tetramethylnaphthalene 0.799 0.266 0.406 0.927 101-81-5 Diphenylmethane 0.794 0.341 0.279 0.932 829-26-5 2,3,6-Trimethylnaphthalene 0.800 0.282 0.337 0.927 1730-37-6 1-Methylfluorene 0.795 0.205 0.458 0.882 581-42-0 2,6-Dimethylnaphthalene 0.802 0.276 0.331 0.892 85-01-8 Phenanthrene 0.677 0.125 0.496 1.000 582-16-1 2,7-Dimethylnaphthalene 0.802 0.268 0.333 0.892 108-38-3 m-Xylene 0.917 0.482 0.214 0.669 643-93-6 3-Methylbiphenyl 0.794 0.261 0.332 0.895 208-96-8 Acenaphthylene 0.723 0.227 0.474 0.857 581-40-8 2,3-Dimethylnaphthalene 0.820 0.267 0.293 0.892 2131-41-1 1,4,5-Trimethylnaphthalene 0.799 0.246 0.298 0.927 630-07-9 Pentatriacontane 0.490 0.132 0.890 0.752 630-06-8 Hexatriacontane 0.490 0.132 0.884 0.751 2245-38-7 1,6,7-Trimethylnaphthalene 0.800 0.258 0.274 0.927 879-12-9 1,2,3-Trimethylnaphthalene 0.800 0.258 0.269 0.927 2381-21-7 1-Methylpyrene 0.614 0.013 0.647 0.975 643-58-3 2-Methylbiphenyl 0.794 0.261 0.298 0.895 99-87-6 p-Cymene 0.923 0.305 0.113 0.901 571-61-9 1,5-Dimethylnaphthalene 0.776 0.276 0.295 0.892 119-64-2 Tetralin 0.871 0.316 0.172 0.871 7098-22-8 Tetratetracontane 0.466 0.131 0.874 0.751 700-12-9 Benzene, pentamethyl- 0.922 0.344 0.103 0.839 Naphthalene, 1,2,3,4-tetrahydro-5- 2809-64-5 0.928 0.247 0.163 0.868 methyl- 95-93-2 1,2,4,5-Tetramethylbenzene 0.921 0.334 0.144 0.797 6971-40-0 17-pentatriacontene 0.489 0.132 0.816 0.751 1576-67-6 3,6-Dimethylphenanthrene 0.664 0.116 0.458 0.942 1559-81-5 1-Methyltetraline 0.922 0.274 0.089 0.895 852228-22-9 1,54-Dibromotetrapentacontane 0.468 0.131 0.817 0.751

165

CAS Name KH Koc t1/2 BCF 4466-77-7 1,2,3,4-Tetramethylphenanthrene 0.633 0.000 0.553 0.944 874-41-9 1,3-Dimethyl-4-ethylbenzene 0.923 0.309 0.035 0.851 1595-16-0 1-(Butan-2-yl)-4-methylbenzene 0.922 0.262 0.028 0.903 832-69-9 1-Methyl phenanthrene 0.683 0.110 0.377 0.918 26746-38-3 2,3-di-tert-butylphenol 0.563 0.270 0.324 0.873 483-65-8 Retene 0.601 0.007 0.412 0.942 25414-22-6 2-Methoxyfuran 0.673 0.610 0.049 0.625 96-76-4 2,4-Di-tert-butylphenol 0.605 0.270 0.218 0.852 321-60-8 2-Fluorobiphenyl 0.737 0.280 0.054 0.845 496-11-7 Indan 0.750 0.362 0.115 0.660 119-65-3 Isoquinoline 0.601 0.389 0.274 0.617 56221-91-1 13-Tetradecen-1-yl acetate 0.487 0.311 0.098 0.929 95-16-9 Benzothiazole 0.607 0.401 0.182 0.627 89-74-7 1-(2,4-Dimethylphenyl)ethanone 0.670 0.436 0.089 0.597 140-66-9 4-(1,1,3,3-Tetramethylbutyl)phenol 0.597 0.288 0.040 0.861 1205-39-6 2-Methyl-N-phenylaniline 0.377 0.331 0.295 0.777 91-63-4 Quinaldine 0.679 0.350 0.061 0.655 123731-75-9 1-Allyl-3-methylindole-2-carbaldehyde 0.713 0.344 0.011 0.675 78-67-1 Azobisisobutyronitrile 0.405 0.553 0.158 0.569 98-54-4 4-tert-Butylphenol 0.508 0.301 0.093 0.768 115-86-6 Triphenyl phosphate 0.529 0.127 0.118 0.834 19261-13-3 1-(2-Furanyl)-3-butene-1,2-diol 0.406 0.578 0.000 0.600 2315-61-9 Triton X-100.2 0.260 0.339 0.106 0.854 84-69-5 Diisobutyl phthalate 0.446 0.331 0.050 0.708 17851-53-5 Butyl isobutyl phthalate 0.472 0.320 0.051 0.691 84-77-5 Didecyl phthalate 0.381 0.183 0.187 0.748 2682-20-4 2-Methyl-3(2H)-isothiazolone 0.323 0.569 0.049 0.542 1',4-Dihydroxy-7'-methoxy-2,3'- 119736-96-8 dimethyl-,(-)-[1,2'-binaphthalene]- 0.006 0.123 0.636 0.698 5,5',8,8'-tetrone 89-16-7 Bis(8-methylnonyl) phthalate 0.384 0.183 0.191 0.668 93-09-4 2-Naphthalenecarboxylic acid 0.000 0.981 0.225 0.165 121-33-5 4-Hydroxy-3-methoxybenzaldehyde 0.187 0.559 0.012 0.575 934-34-9 Benzothiazolone 0.035 0.996 0.099 0.086 80061-31-0 3,4-Dihydro-1,9(2H,10H)-acridinedione 0.063 1.000 0.078 0.000

166

6.4.3 Inorganic compounds with toxicity data Appendix Table 12. Overall rank and individual scores for each cancer metric in the hazard domain: oral slope factor (OSF), cancer potency value (CPV), and inhalation unit risk (IUR).

Rank CAS Name OSF CPV IUR 1 7440-38-2 Arsenic 1 0 0.948 2 7440-43-9 Cadmium 0 0 0.911 3 18540-29-9 Chromium (VI) ion 0 0 1 4 7439-91-0 Lanthanum 0 0 0 5 7440-28-0 Thallium 0 0 0 6 7440-41-7 Beryllium 0 0 0.734 7 7440-02-0 Nickel 0 0 0.706 8 7723-14-0 Phosphorus 0 0 0 9 7439-92-1 Lead 0 0 0.562 10 7440-62-2 Vanadium 0 0 0 11 7553-56-2 Iodine 0 0 0 12 7440-67-7 Zirconium 0 0 0 13 7782-49-2 Selenium 0 0 0 14 7440-36-0 Antimony 0 0 0 15 7440-33-7 Tungsten 0 0 0 16 7440-48-4 Cobalt 0 0 0 17 7439-97-6 Mercury 0 0 0 18 7439-96-5 Manganese 0 0 0 19 7440-22-4 Silver 0 0 0 20 7439-98-7 Molybdenum 0 0 0 21 7439-93-2 Lithium 0 0 0 22 14797-65-0 Nitrite 0 0 0 23 57-12-5 Cyanide 0 0 0 24 7783-06-4 Hydrogen sulfide 0 0 0 25 7440-66-6 Zinc 0 0 0 26 7440-31-5 Tin 0 0 0 27 7664-41-7 Ammonia 0 0 0 28 7439-89-6 Iron 0 0 0 29 7782-50-5 Chlorine 0 0 0 30 14797-55-8 Nitrate 0 0 0 31 7440-39-3 Barium 0 0 0 32 7440-24-6 Strontium 0 0 0 33 7440-50-8 Copper 0 0 0 34 7429-90-5 Aluminum 0 0 0 35 7440-42-8 Boron 0 0 0 36 16065-83-1 Chromium (III) 0 0 0

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Appendix Table 13. Individual scores for each non-cancer metric in the hazard domain: reference dose (RfD), no observed adverse effect level (NOAEL), benchmark dose (BMD), benchmark dose lower limit (BMDL), and reference concentration (RfC).

Rank CAS Name RfD NOAEL BMD BMDL RfC 1 7440-38-2 Arsenic 0.675 1 0 0.351 0.658 2 7440-43-9 Cadmium 0.667 0.904 0 0.351 0.658 3 18540-29-9 Chromium (VI) ion 0.478 0.431 0 0.351 1 4 7439-91-0 Lanthanum 0.853 0.500 0 1 0.658 5 7440-28-0 Thallium 1 0.803 0 0.351 0.658 6 7440-41-7 Beryllium 0.378 0.409 0 0.324 0.857 7 7440-02-0 Nickel 0.346 0.500 0 0.351 0.658 8 7723-14-0 Phosphorus 0.809 0.742 0 0.351 0.658 9 7439-92-1 Lead 0.415 0.500 0 0.351 0.658 10 7440-62-2 Vanadium 0.754 0.594 0 0.351 0.658 11 7553-56-2 Iodine 0.415 0.912 0 0.351 0.658 12 7440-67-7 Zirconium 0.787 0.500 0 0.351 0.658 13 7782-49-2 Selenium 0.471 0.805 0 0.351 0.658 14 7440-36-0 Antimony 0.689 0.500 0 0.351 0.658 15 7440-33-7 Tungsten 0.668 0.500 0 0.351 0.658 16 7440-48-4 Cobalt 0.657 0.500 0 0.351 0.658 17 7439-97-6 Mercury 0.415 0.500 0 0.351 0.878 18 7439-96-5 Manganese 0.198 0.630 0 0.351 0.905 19 7440-22-4 Silver 0.494 0.500 0 0.351 0.658 20 7439-98-7 Molybdenum 0.485 0.500 0 0.351 0.658 21 7439-93-2 Lithium 0.359 0.500 0 0.351 0.658 22 14797-65-0 Nitrite 0.210 0.594 0 0.351 0.658 23 57-12-5 Cyanide 0.542 0.285 0 0.351 0.619 24 7783-06-4 Hydrogen sulfide 0.276 0.388 0 0.351 0.682 25 7440-66-6 Zinc 0.154 0.516 0 0.351 0.658 26 7440-31-5 Tin 0.147 0.500 0 0.351 0.658 27 7664-41-7 Ammonia 0.415 0.500 0 0.351 0.350 28 7439-89-6 Iron 0.080 0.500 0 0.351 0.658 29 7782-50-5 Chlorine 0.241 0.334 0 0.351 0.658 30 14797-55-8 Nitrate 0.027 0.473 0 0.351 0.658 31 7440-39-3 Barium 0.239 0.356 0 0.081 0.831 32 7440-24-6 Strontium 0.125 0.174 0 0.351 0.658 33 7440-50-8 Copper 0.415 0.500 0 0.351 0.000 34 7429-90-5 Aluminum 0 0.144 0 0.351 0.621 35 7440-42-8 Boron 0.051 0.500 0 0 0.498 36 16065-83-1 Chromium (III) 0.019 0 0 0.351 0.658

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6.5 Sensitivity analyses 6.5.1 Missing data Appendix Table 14. The 26 compounds that were in the top 40 in all three missing data analyses and the original analysis. Also included are the ranks of each compound in each respectively analysis. In Case 1, missing non-cancer values were replaced with the maximum of the respective metric. In Case 2, missing non-cancer values were replaced with the minimum of the respective metric. In Case 3, all missing values were replaced with the average of the known values for the respective metric.

Original Case 1 Case 2 Case 3 CAS Compound Rank Rank Rank Rank 309-00-2 Aldrin 1 2 1 1 1024-57-3 Heptachlor epoxide B 2 3 2 2 72-20-8 Endrin 3 1 3 3 76-44-8 Heptachlor 4 7 4 4 319-86-8 delta-Hexachlorocyclohexane 5 13 5 5 58-89-9 Lindane 6 14 6 6 319-85-7 beta-Hexachlorocyclohexane 7 15 7 7 2935-07-1 1H-Phenalene, dodecahydro- 8 16 8 8 118-74-1 Hexachlorobenzene 9 11 9 9 50-32-8 Benzo(a)pyrene 10 9 38 14 281-23-2 Adamantane 11 18 10 15 Cyclohexane, 1-(cyclohexylmethyl)- 54823-98-2 12 19 11 16 4-methyl-, trans- Methyl tricyclo(3.3.1.13,7)dec-1-yl 1660-04-4 13 22 12 17 ketone Naphthalene, decahydro-1,6- 1750-51-2 14 24 13 18 dimethyl- 3178-23-2 Dicyclohexylmethane 16 25 14 20 6305-52-8 2-n-Butyldecahydronaphthalene 17 26 15 21 Naphthalene, decahydro-1,5- 66552-62-3 18 27 16 22 dimethyl- 5743-97-5 phenanthrene, tetradecahydro- 19 17 28 13 * naphthalene, decahydro-2,6- 1618-22-0 20 28 17 23 dimethyl- 2,3- 1008-80-6 21 29 18 25 Dimethyldecahydronaphthalene 294-62-2 Cyclododecane 22 30 19 26 92-51-3 1,1'-Bicyclohexyl 23 31 20 27 66660-42-2 cis, cis-3-ethylbicyclo[4.4.0]decane 25 35 21 33 1687-34-9 1-Ethyl-3-methyladamantane 26 20 37 10 4431-89-4 (Cyclopentylmethyl)cyclohexane 27 36 22 34 702-79-4 1,3-Dimethyladamantane 29 38 23 11

169

6.5.1.1 Overall ToxPi scores each case Appendix Table 15. Overall ToxPi score for the three missing data analyses and the original analysis. The original analysis rank was held constant. In Case 1, missing non-cancer values were replaced with the maximum of the respective metric. In Case 2, missing non-cancer values were replaced with the minimum of the respective metric. In Case 3, all missing values were replaced with the average of the known values for the respective metric.

Rank CAS Name Original Case 1 Case 2 Case 3 1 309-00-2 Aldrin 0.802 0.802 0.802 0.802 2 1024-57-3 Heptachlor epoxide B 0.786 0.786 0.786 0.786 3 72-20-8 Endrin 0.786 0.818 0.756 0.786 4 76-44-8 Heptachlor 0.748 0.748 0.748 0.748 5 319-86-8 delta-Hexachlorocyclohexane 0.662 0.662 0.662 0.662 6 58-89-9 Lindane 0.661 0.661 0.661 0.661 7 319-85-7 beta-Hexachlorocyclohexane 0.660 0.660 0.660 0.660 8 2935-07-1 1H-Phenalene, dodecahydro- 0.659 0.659 0.659 0.659 9 118-74-1 Hexachlorobenzene 0.655 0.699 0.636 0.655 10 50-32-8 Benzo(a)pyrene 0.626 0.738 0.551 0.626 11 281-23-2 Adamantane 0.625 0.625 0.625 0.625 Cyclohexane, 1-(cyclohexylmethyl)-4- 12 54823-98-2 0.621 0.621 0.621 0.621 methyl-, trans- Methyl tricyclo(3.3.1.13,7)dec-1-yl 13 1660-04-4 0.611 0.611 0.611 0.611 ketone 14 1750-51-2 Naphthalene, decahydro-1,6-dimethyl- 0.599 0.599 0.599 0.599 15 56-55-3 Benz(a)anthracene 0.599 0.776 0.463 0.599 16 3178-23-2 Dicyclohexylmethane 0.598 0.598 0.598 0.598 17 6305-52-8 2-n-Butyldecahydronaphthalene 0.597 0.597 0.597 0.597 18 66552-62-3 Naphthalene, decahydro-1,5-dimethyl- 0.597 0.597 0.597 0.597 19 5743-97-5 phenanthrene, tetradecahydro- 0.597 0.629 0.566 0.638 * naphthalene, decahydro-2,6- 20 1618-22-0 0.595 0.595 0.595 0.595 dimethyl- 21 1008-80-6 2,3-Dimethyldecahydronaphthalene 0.595 0.595 0.595 0.595 22 294-62-2 Cyclododecane 0.595 0.595 0.595 0.595 23 92-51-3 1,1'-Bicyclohexyl 0.594 0.594 0.594 0.594 24 53-70-3 Dibenz(a,h)anthracene 0.591 0.768 0.456 0.591 25 66660-42-2 cis, cis-3-ethylbicyclo[4.4.0]decane 0.583 0.583 0.583 0.583 26 1687-34-9 1-Ethyl-3-methyladamantane 0.581 0.613 0.551 0.655 27 4431-89-4 (Cyclopentylmethyl)cyclohexane 0.581 0.581 0.581 0.581 28 205-99-2 Benzo(b)fluoranthene 0.580 0.757 0.445 0.580 29 702-79-4 1,3-Dimethyladamantane 0.572 0.572 0.572 0.646 30 629-62-9 Pentadecane 0.570 0.570 0.570 0.570 31 629-59-4 Tetradecane 0.568 0.568 0.568 0.568 32 1606-08-2 Cyclopentylcyclohexane 0.567 0.567 0.567 0.567 33 218-01-9 Chrysene 0.567 0.743 0.431 0.567

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Rank CAS Name Original Case 1 Case 2 Case 3 34 2958-76-1 Decahydro-2-methylnaphthalene 0.567 0.566 0.567 0.567 35 16538-89-9 cyclooctane, (1-methylpropyl)- 0.561 0.561 0.561 0.561 36 23609-46-3 cyclooctane, 1,2-diethyl- 0.560 0.560 0.560 0.560 37 2883-02-5 Cyclohexane, nonyl- 0.556 0.556 0.556 0.556 38 1795-15-9 Cyclohexane, octyl- 0.556 0.556 0.556 0.556 39 629-50-5 Tridecane 0.555 0.555 0.555 0.555 40 111-84-2 Nonane 0.554 0.554 0.554 0.554 41 1795-16-0 Decylcyclohexane 0.554 0.554 0.554 0.554 42 62199-52-4 1,2-Dibutylcyclopentane 0.551 0.551 0.551 0.551 43 1560-93-6 2-Methylpentadecane 0.546 0.546 0.546 0.546 44 74-83-9 Methyl bromide 0.546 0.545 0.546 0.546 45 6165-40-8 7-Methylpentadecane 0.545 0.545 0.545 0.545 46 295-17-0 Cyclotetradecane 0.543 0.543 0.543 0.584 47 3891-98-3 2,6,10-Trimethyldodecane 0.542 0.542 0.542 0.542 48 79-34-5 1,1,2,2-Tetrachloroethane 0.539 0.539 0.539 0.539 49 61142-68-5 1-Hexyl-3-methylcyclopentane 0.539 0.539 0.539 0.539 50 112-40-3 Dodecane 0.539 0.539 0.539 0.539 51 207-08-9 Benzo(k)fluoranthene 0.538 0.715 0.402 0.571 52 17312-57-1 3-Methyldodecane 0.536 0.536 0.536 0.536 53 13287-21-3 6-Methyltridecane 0.536 0.536 0.536 0.536 54 26730-14-3 7-Methyltridecane 0.536 0.536 0.536 0.536 55 707-35-7 1,3,5-Trimethyladamantane 0.535 0.567 0.505 0.641 56 17312-80-0 2,4-Dimethylundecane 0.534 0.534 0.534 0.534 57 1560-97-0 2-Methyldodecane 0.533 0.533 0.533 0.533 1,7-dimethyl-4-(1- 58 645-10-3 0.533 0.533 0.533 0.574 methylethyl)cyclodecane 59 4292-75-5 Hexylcyclohexane 0.533 0.533 0.533 0.533 60 6117-97-1 4-Methyldodecane 0.533 0.533 0.533 0.533 61 67-66-3 Chloroform 0.533 0.533 0.533 0.533 62 1120-21-4 Undecane 0.532 0.532 0.532 0.532 63 17301-23-4 2,6-Dimethylundecane 0.532 0.532 0.532 0.532 64 6418-41-3 tridecane, 3-methyl- 0.531 0.531 0.531 0.531 65 1560-95-8 2-Methyltetradecane 0.531 0.531 0.531 0.531 66 56292-65-0 2,5-Dimethyldodecane 0.530 0.530 0.530 0.530 67 112-70-9 1-Tridecanol 0.530 0.530 0.530 0.530 68 25117-31-1 5-Methyltridecane 0.529 0.529 0.529 0.529 cyclohexane, 1-methyl-4-(1- 69 54411-00-6 0.529 0.529 0.529 0.529 methylbutyl)- 70 41446-57-5 3-Tridecene, (3E)- 0.529 0.529 0.529 0.529 71 26730-12-1 4-Methyltridecane 0.529 0.529 0.529 0.529 72 25117-32-2 5-Methyltetradecane 0.528 0.528 0.528 0.528 73 13150-81-7 2,6-Dimethyldecane 0.528 0.528 0.528 0.528

171

Rank CAS Name Original Case 1 Case 2 Case 3 74 1560-96-9 2-Methyltridecane 0.528 0.528 0.528 0.528 75 15232-86-7 1-Heptylcyclohexene 0.527 0.527 0.527 0.527 76 442662-72-8 2-Ethyl-1,1,3-trimethylcyclohexane 0.527 0.527 0.527 0.527 77 4457-00-5 Cyclopentane, hexyl- 0.526 0.526 0.526 0.526 78 4292-92-6 Pentylcyclohexane 0.523 0.523 0.523 0.523 79 544-76-3 Hexadecane 0.523 0.523 0.523 0.564 80 124-18-5 * Decane 0.522 0.522 0.522 0.522 1,4-Dimethyl-2,3- 81 71312-54-4 0.521 0.553 0.490 0.521 diazabicyclo[2.2.1]hept-2-ene 82 61142-66-3 cyclopentene, 5-hexyl-3,3-dimethyl- 0.520 0.520 0.520 0.520 83 2207-01-4 (Z)-1,2-Dimethylcyclohexane 0.519 0.519 0.519 0.519 84 6750-34-1 1-dodecanol, 3,7,11-trimethyl- 0.519 0.519 0.519 0.519 85 193-39-5 Indeno(1,2,3-cd)pyrene 0.518 0.695 0.382 0.551 86 7045-71-8 2-Methylundecane 0.518 0.517 0.518 0.518 1,7,11-Trimethyl-4-(1- 87 1786-12-5 0.516 0.548 0.485 0.590 methylethyl)cyclotetradecane 88 61142-70-9 2,4-Diethyl-1-methylcyclohexane 0.515 0.515 0.515 0.515 89 2847-72-5 4-Methyldecane 0.514 0.514 0.514 0.514 90 115-96-8 Tris(2-chloroethyl) phosphate 0.514 0.514 0.514 0.514 91 110-82-7 Cyclohexane 0.514 0.514 0.514 0.514 92 17302-32-8 3,7-Dimethylnonane 0.513 0.513 0.513 0.513 93 17302-28-2 2,6-Dimethylnonane 0.513 0.513 0.513 0.513 94 13151-34-3 3-Methyldecane 0.513 0.513 0.513 0.513 95 16580-24-8 1-Methyl-3-(propan-2-yl)cyclohexane 0.513 0.513 0.513 0.513 96 74-93-1 Methanethiol 0.513 0.513 0.513 0.513 97 13151-35-4 5-Methyldecane 0.512 0.512 0.512 0.512 98 66542-51-6 * Chloromethyl hexanoate 0.511 0.511 0.511 0.511 99 591-21-9 1,3-Dimethylcyclohexane 0.511 0.511 0.511 0.511 100 62016-37-9 2,4,6-Trimethyloctane 0.511 0.511 0.511 0.511 101 2234-75-5 1,2,4-Trimethylcyclohexane 0.511 0.511 0.511 0.511 102 6975-98-0 2-Methyldecane 0.510 0.510 0.510 0.510 103 71-43-2 * Benzene 0.510 0.544 0.482 0.510 104 5402-53-9 Chloromethyl propanoate 0.508 0.508 0.508 0.508 105 127-18-4 * Tetrachloroethylene 0.507 0.506 0.507 0.507 106 3728-56-1 1-Ethyl-4-methylcyclohexane 0.506 0.506 0.506 0.506 rel-(1R,2S)-1,2- 107 14113-60-1 0.506 0.538 0.476 0.580 Diethylcyclohexadecane 108 77877-94-2 Chloromethyl pentanoate 0.505 0.505 0.505 0.505 109 1678-93-9 Butylcyclohexane 0.505 0.505 0.505 0.505 110 112-18-5 N,N-Dimethyldodecan-1-amine 0.505 0.505 0.505 0.505 111 73105-67-6 1-Iodo-2-methylundecane 0.505 0.537 0.475 0.579 112 142-82-5 Heptane 0.504 0.504 0.504 0.504 113 1072-05-5 2,6-Dimethylheptane 0.504 0.504 0.504 0.504 172

Rank CAS Name Original Case 1 Case 2 Case 3 114 62199-51-3 1-Pentyl-2-propylcyclopentane 0.504 0.504 0.504 0.545 115 26730-20-1 7-Methylhexadecane 0.504 0.504 0.504 0.545 116 111-65-9 Octane 0.504 0.504 0.504 0.504 117 111-44-4 Bis(2-chloroethyl) ether 0.502 0.502 0.502 0.502 118 3728-55-0 1-Ethyl-3-methylcyclohexane 0.502 0.502 0.502 0.502 119 1560-92-5 2-Methylhexadecane 0.502 0.502 0.502 0.543 120 1678-92-8 Propylcyclohexane 0.501 0.501 0.501 0.501 121 2040-96-2 Propylcyclopentane 0.501 0.501 0.501 0.501 122 4291-79-6 1-Methyl-2-propyl-cyclohexane 0.500 0.500 0.500 0.500 123 75-25-2 Bromoform 0.500 0.500 0.500 0.500 124 5911-04-6 3-Methylnonane 0.500 0.500 0.500 0.500 2-BUTYL-1,1,3-TRIMETHYL- 125 54676-39-0 0.500 0.500 0.500 0.541 CYCLOHEXANE 126 107-13-1 Acrylonitrile 0.499 0.499 0.499 0.499 127 16580-26-0 cyclohexane, 1-isopropyl-1-methyl- 0.499 0.499 0.499 0.499 128 3073-66-3 1,1,3-Trimethylcyclohexane 0.499 0.499 0.499 0.499 129 31295-56-4 2,6,11-Trimethyldodecane 0.498 0.498 0.498 0.539 130 17301-94-9 4-Methylnonane 0.498 0.498 0.498 0.498 131 871-83-0 2-Methylnonane 0.497 0.497 0.497 0.497 132 15869-86-0 4-Ethyloctane 0.496 0.496 0.496 0.496 133 79-06-1 Acrylamide 0.496 0.496 0.496 0.496 134 16747-30-1 2,4,4-Trimethylhexane 0.495 0.495 0.495 0.495 135 107-06-2 1,2-Dichloroethane 0.495 0.495 0.495 0.495 136 2883-05-8 2-Cyclohexyloctane 0.493 0.493 0.493 0.534 137 100-44-7 Benzyl chloride 0.491 0.491 0.491 0.524 138 54411-01-7 1-Methyl-2-pentylcyclohexane 0.491 0.491 0.491 0.532 139 15869-93-9 3,5-Dimethyloctane 0.490 0.490 0.490 0.490 140 2051-30-1 2,6-Dimethyloctane 0.490 0.490 0.490 0.490 141 74054-92-5 1,1,6,6-tetramethylspiro[4.4]nonane 0.489 0.521 0.459 0.595 142 2406-25-9 Di-tert-butyl nitroxide 0.489 0.489 0.489 0.489 143 98-95-3 Nitrobenzene 0.489 0.489 0.489 0.521 144 959028-24-1 4-Ethyl-2,3-dimethylhex-2-ene 0.489 0.489 0.489 0.489 145 2815-58-9 1,2,4-Trimethylcyclopentane 0.487 0.487 0.487 0.487 146 123-25-1 Diethyl butanedioate 0.487 0.487 0.487 0.487 147 75-15-0 Carbon disulfide 0.487 0.487 0.487 0.487 148 706-14-9 gamma-Decanolactone 0.487 0.487 0.487 0.487 149 143-07-7 Dodecanoic acid 0.486 0.486 0.486 0.486 150 109-74-0 Butanenitrile 0.485 0.485 0.485 0.485 151 1921-70-6 Norphytane 0.484 0.516 0.453 0.557 152 4810-09-7 3-Methyl-1-heptene 0.483 0.483 0.483 0.483 153 108-87-2 Methylcyclohexane 0.483 0.483 0.483 0.483 154 959-98-8 Endosulfan I 0.481 0.513 0.451 0.587

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Rank CAS Name Original Case 1 Case 2 Case 3 155 33213-65-9 Endosulfan II 0.481 0.513 0.451 0.587 156 1678-91-7 Ethylcyclohexane 0.481 0.481 0.481 0.481 157 2980-69-0 4-Methylundecane 0.481 0.481 0.481 0.522 158 3386-33-2 Octadecyl chloride 0.481 0.513 0.450 0.554 159 55282-11-6 11-Pentan-3-ylhenicosane 0.480 0.512 0.450 0.554 160 112-30-1 1-Decanol 0.480 0.480 0.480 0.480 161 2453-00-1 1,3-Dimethylcyclopentane 0.480 0.480 0.480 0.480 162 74-84-0 Ethane 0.479 0.479 0.479 0.479 163 629-97-0 Docosane 0.479 0.511 0.449 0.553 164 1632-70-8 5-methylundecane 0.479 0.479 0.479 0.520 165 1002-43-3 3-Methylundecane 0.479 0.479 0.479 0.520 166 591-48-0 3-Methylcyclohexene 0.478 0.478 0.478 0.478 167 1192-18-3 (Z)-1,2-Dimethylcyclopentane 0.477 0.477 0.477 0.477 168 629-78-7 Heptadecane 0.477 0.477 0.477 0.551 169 592-27-8 2-Methylheptane 0.474 0.474 0.474 0.474 170 74-87-3 Chloromethane 0.473 0.473 0.473 0.473 171 7320-37-8 1,2-Epoxyhexadecane 0.473 0.473 0.473 0.547 172 593-45-3 Octadecane 0.472 0.472 0.472 0.546 173 110-75-8 2-Chloroethyl vinyl ether 0.471 0.471 0.471 0.471 174 562-28-7 (-)-Kaur-16-ene 0.471 0.613 0.363 0.577 175 111-30-8 Glutaraldehyde 0.470 0.470 0.470 0.470 176 821-55-6 2-Nonanone 0.469 0.469 0.469 0.469 177 638-36-8 2,6,10,14-Tetramethylhexadecane 0.468 0.500 0.438 0.542 178 50991-08-7 2-Methyl-1,1'-bi(cyclohexane) 0.468 0.500 0.437 0.574 179 106-65-0 Dimethyl succinate 0.468 0.468 0.468 0.468 180 109-66-0 Pentane 0.467 0.467 0.467 0.467 181 126-73-8 Tributyl phosphate 0.464 0.464 0.464 0.505 182 75-83-2 2,2-Dimethylbutane 0.463 0.463 0.463 0.463 183 110-54-3 n-Hexane 0.463 0.463 0.463 0.463 1,3,5-Trimethyl-1,3,5-triazinane-2- 184 59887-80-8 0.462 0.462 0.462 0.503 thione 185 6418-44-6 heptadecane, 3-methyl- 0.462 0.462 0.462 0.536 186 111-87-5 1-Octanol 0.461 0.461 0.461 0.461 187 74-98-6 Propane 0.460 0.460 0.460 0.460 188 513-35-9 2-Methyl-2-butene 0.460 0.460 0.460 0.460 189 112-95-8 Eicosane 0.457 0.489 0.426 0.531 190 107-83-5 2-Methylpentane 0.456 0.456 0.456 0.456 191 91-20-3 Naphthalene 0.456 0.534 0.409 0.456 192 72-03-7 Propanoate 0.455 0.455 0.455 0.455 193 3892-00-0 2,6,10-Trimethylpentadecane 0.454 0.454 0.454 0.528 194 334-48-5 Decanoic acid 0.454 0.454 0.454 0.454 195 41446-78-0 4-Tetradecene, (4E)- 0.454 0.454 0.454 0.528

174

Rank CAS Name Original Case 1 Case 2 Case 3 196 120-82-1 1,2,4-Trichlorobenzene 0.453 0.488 0.425 0.527 197 111-76-2 2-Butoxyethanol 0.453 0.453 0.453 0.453 198 629-92-5 Nonadecane 0.453 0.485 0.423 0.527 199 629-94-7 Heneicosane 0.452 0.484 0.422 0.526 200 68-12-2 N,N-Dimethylformamide 0.452 0.452 0.452 0.452 201 106-46-7 1,4-Dichlorobenzene 0.452 0.530 0.405 0.452 202 112-88-9 1-Octadecene 0.451 0.451 0.451 0.525 203 297-35-8 Cyclotriacontane 0.451 0.593 0.343 0.557 204 104-76-7 2-Ethyl-1-hexanol 0.451 0.451 0.451 0.451 205 10374-74-0 7-Tetradecene 0.450 0.450 0.450 0.524 206 112-34-5 2-(2-Butoxyethoxy)ethanol 0.449 0.449 0.449 0.449 207 123-20-6 Butanoic acid, ethenyl ester 0.449 0.449 0.449 0.449 208 64275-73-6 (Z)-5-Octen-1-ol 0.449 0.449 0.449 0.449 209 18435-22-8 3-methyl-tetradecane 0.448 0.480 0.418 0.522 210 1768-36-1 Propyl cyanate 0.448 0.448 0.448 0.448 211 18435-45-5 1-Nonadecene 0.447 0.479 0.417 0.521 212 123-86-4 Butyl acetate 0.447 0.447 0.447 0.447 213 544-85-4 Dotriacontane 0.447 0.589 0.339 0.553 214 55000-52-7 2,6,10-Trimethylhexadecane 0.447 0.479 0.417 0.521 215 99328-46-8 5-Methylhept-1-en-4-ol 0.447 0.447 0.447 0.447 216 591-78-6 2-Hexanone 0.447 0.447 0.447 0.447 217 4360-57-0 2-Pentadecyl-1,3-dioxolane 0.447 0.478 0.416 0.520 218 638-67-5 Tricosane 0.446 0.478 0.416 0.553 219 87-61-6 1,2,3-Trichlorobenzene 0.446 0.556 0.368 0.519 220 1630-94-0 1,1-Dimethylcyclopropane 0.445 0.445 0.445 0.445 221 55030-62-1 4,8-Dimethyltridecane 0.445 0.477 0.414 0.518 222 18344-37-1 heptadecane, 2,6,10,14-tetramethyl- 0.444 0.476 0.413 0.518 223 144-19-4 2,2,4-Trimethyl-1,3-pentanediol 0.444 0.444 0.444 0.444 224 461-55-2 Butyrate 0.443 0.443 0.443 0.443 225 71-23-8 1-Propanol 0.443 0.443 0.443 0.443 226 646-31-1 Tetracosane 0.443 0.475 0.413 0.549 227 629-99-2 Pentacosane 0.443 0.475 0.413 0.549 228 5989-27-5 D-Limonene 0.442 0.442 0.442 0.483 229 54833-48-6 Heptadecane, 2,6,10,15-tetramethyl 0.442 0.474 0.411 0.515 230 57-60-3 Pyruvate 0.442 0.442 0.442 0.442 231 593-49-7 Heptacosane 0.442 0.506 0.381 0.548 232 79-09-4 Propionic acid 0.441 0.441 0.441 0.441 233 630-01-3 Hexacosane 0.441 0.473 0.410 0.547 234 54105-67-8 2,6-Dimethylheptadecane 0.440 0.472 0.410 0.514 235 110-94-1 Glutaric acid 0.440 0.440 0.440 0.440 236 544-63-8 Tetradecanoic acid 0.440 0.440 0.440 0.481 237 91-57-6 * 2-Methylnaphthalene 0.439 0.471 0.409 0.545

175

Rank CAS Name Original Case 1 Case 2 Case 3 238 2885-00-9 1-Octadecanethiol 0.439 0.471 0.408 0.545 239 25117-24-2 4-Methyltetradecane 0.439 0.471 0.408 0.513 240 630-02-4 Octacosane 0.439 0.503 0.378 0.545 241 638-68-6 Triacontane 0.438 0.580 0.330 0.544 242 71-36-3 1-Butanol 0.437 0.437 0.437 0.437 243 92-52-4 * Biphenyl 0.437 0.550 0.362 0.511 244 598-89-0 Diiodoacetic acid 0.437 0.469 0.407 0.510 245 13287-24-6 9-Methylnonadecane 0.436 0.546 0.359 0.510 246 96-04-8 2,3-Heptanedione 0.436 0.436 0.436 0.436 247 129-00-0 Pyrene 0.435 0.511 0.386 0.541 248 132-65-0 Dibenzothiophene 0.433 0.543 0.356 0.540 249 563-46-2 2-Methylbut-1-ene 0.432 0.432 0.432 0.432 250 2490-48-4 2-Methylhexadecan-1-ol 0.432 0.464 0.402 0.506 (4aS,8aR)-4a- 251 938-06-7 Methyloctahydronaphthalen-2(1H)- 0.432 0.432 0.432 0.505 one 252 695-06-7 gamma-Caprolactone 0.431 0.431 0.431 0.431 253 80-62-6 Methyl methacrylate 0.431 0.431 0.431 0.431 254 149-57-5 2-Ethylhexanoic acid 0.431 0.431 0.431 0.431 255 124-07-2 Octanoic acid 0.431 0.431 0.431 0.431 256 5618-62-2 O-Isobutylhydroxylamine 0.431 0.431 0.431 0.431 257 100-01-6 4-Nitroaniline 0.430 0.465 0.403 0.504 258 95-50-1 1,2-Dichlorobenzene 0.429 0.464 0.401 0.503 259 206-44-0 * Fluoranthene 0.428 0.503 0.378 0.534 260 57-11-4 Octadecanoic acid 0.427 0.459 0.397 0.501 261 630-03-5 Nonacosane 0.427 0.569 0.319 0.533 262 5842-53-5 2,2,4-Trimethylpent-3-en-1-ol 0.425 0.425 0.425 0.425 263 91-22-5 Quinoline 0.425 0.601 0.289 0.498 264 108-29-2 4-Pentanolide 0.424 0.424 0.424 0.424 265 111-14-8 Heptanoic acid 0.424 0.424 0.424 0.424 266 107-92-6 Butanoic acid 0.422 0.422 0.422 0.422 267 141-78-6 Ethyl acetate 0.422 0.422 0.422 0.422 268 142-62-1 Hexanoic acid 0.422 0.422 0.422 0.422 269 542-28-9 Tetrahydro-2H-pyran-2-one 0.422 0.422 0.422 0.422 270 98-82-8 Cumene 0.422 0.499 0.374 0.495 271 64-19-7 Acetic acid 0.422 0.422 0.422 0.422 272 544-77-4 1-Iodohexadecane 0.422 0.563 0.313 0.528 273 60212-33-1 4-Tetradecyne 0.421 0.421 0.421 0.527 274 71-50-1 Acetate 0.421 0.421 0.421 0.421 275 117-81-7 Di(2-ethylhexyl) phthalate 0.420 0.530 0.342 0.420 276 75-09-2 Dichloromethane 0.419 0.419 0.419 0.419 277 3055-93-4 2-[2-(Dodecyloxy)ethoxy]ethanol 0.418 0.418 0.418 0.492

176

Rank CAS Name Original Case 1 Case 2 Case 3 278 123-91-1 1,4-Dioxane 0.418 0.418 0.418 0.418 279 4860-03-1 1-Chlorohexadecane 0.418 0.528 0.340 0.524 280 544-25-2 1,3,5-Cycloheptatriene 0.418 0.418 0.418 0.483 281 83-32-9 Acenaphthene 0.417 0.528 0.340 0.524 282 35216-11-6 7-Tetradecyne 0.417 0.417 0.417 0.524 283 100-41-4 Ethylbenzene 0.417 0.495 0.370 0.417 284 132-64-9 Dibenzofuran 0.417 0.562 0.312 0.523 285 108-90-7 Chlorobenzene 0.417 0.495 0.370 0.490 286 766-76-7 Benzoate 0.416 0.448 0.385 0.481 287 109-52-4 Pentanoic acid 0.415 0.415 0.415 0.415 288 61886-62-2 3-Hexadecyne 0.415 0.492 0.367 0.521 289 584-02-1 3-Pentanol 0.415 0.415 0.415 0.415 290 120-12-7 Anthracene 0.414 0.524 0.336 0.520 291 57-55-6 1,2-Propylene glycol 0.413 0.413 0.413 0.413 292 79-31-2 2-Methylpropanoic acid 0.413 0.413 0.413 0.413 293 74-82-8 Methane 0.413 0.413 0.413 0.413 294 64-17-5 Ethanol 0.412 0.412 0.412 0.412 295 67-63-0 Isopropanol 0.411 0.411 0.411 0.411 296 575-41-7 1,3-Dimethylnaphthalene 0.411 0.510 0.323 0.517 297 57-10-3 Hexadecanoic acid 0.411 0.411 0.411 0.485 298 75-34-3 1,1-Dichloroethane 0.411 0.411 0.411 0.411 299 110-86-1 Pyridine 0.410 0.486 0.361 0.516 300 646-07-1 Pentanoic acid, 4-methyl- 0.410 0.410 0.410 0.410 301 86-30-6 N-Nitrosodiphenylamine 0.410 0.587 0.274 0.410 302 90-12-0 1-Methylnaphthalene 0.409 0.441 0.379 0.483 303 86-73-7 Fluorene 0.409 0.484 0.359 0.515 304 576-26-1 2,6-Dimethylphenol 0.409 0.444 0.381 0.474 305 573-98-8 1,2-Dimethylnaphthalene 0.409 0.508 0.321 0.515 306 116-53-0 2-Methylbutanoic acid 0.407 0.407 0.407 0.407 307 569-41-5 1,8-Dimethylnaphthalene 0.407 0.506 0.318 0.513 308 571-58-4 1,4-Dimethylnaphthalene 0.407 0.506 0.318 0.513 309 575-37-1 1,7-Dimethylnaphthalene 0.406 0.505 0.318 0.512 310 2049-95-8 tert-Pentylbenzene 0.405 0.547 0.297 0.511 311 1599-67-3 1-Docosene 0.405 0.437 0.374 0.511 312 62-53-3 Aniline 0.404 0.482 0.357 0.404 313 50-00-0 Formaldehyde 0.403 0.403 0.403 0.403 314 503-74-2 Isovaleric acid 0.403 0.403 0.403 0.403 315 533-18-6 Acetic acid, 2-methylphenyl ester 0.402 0.402 0.402 0.467 316 122-20-3 Triisopropanolamine 0.401 0.401 0.401 0.401 317 3055-94-5 Triethylene glycol monododecyl ether 0.401 0.433 0.370 0.474 318 113-21-3 Lactate ion(1-) 0.399 0.399 0.399 0.399 319 941228-34-8 7-(Bromomethyl)pentadec-7-ene 0.399 0.508 0.321 0.505

177

Rank CAS Name Original Case 1 Case 2 Case 3 320 10023-74-2 Pentanoic acid, ion(1-) 0.398 0.398 0.398 0.398 321 75-07-0 Acetaldehyde 0.398 0.398 0.398 0.398 322 95-65-8 3,4-Dimethylphenol 0.398 0.398 0.398 0.463 323 35365-59-4 9-Octadecyne 0.397 0.506 0.319 0.503 324 90-15-3 1-Naphthol 0.395 0.460 0.335 0.501 325 541-73-1 1,3-Dichlorobenzene 0.394 0.536 0.286 0.500 326 122-99-6 2-Phenoxyethanol 0.394 0.536 0.286 0.467 327 95-87-4 2,5-Dimethylphenol 0.393 0.426 0.363 0.459 328 106-44-5 p-Cresol 0.392 0.534 0.284 0.466 329 107-21-1 Ethylene glycol 0.391 0.391 0.391 0.391 1-Hydroxy-3-(2-methylpropyl)- 330 2873-36-1 6,7,8,8a-tetrahydropyrrolo[1,2- 0.390 0.422 0.360 0.431 a]pyrazin-4(3H)-one 331 2136-72-3 2-(Octadecyloxy)ethanol 0.390 0.500 0.312 0.496 332 526-73-8 1,2,3-Trimethylbenzene 0.390 0.502 0.315 0.496 333 575-43-9 1,6-Dimethylnaphthalene 0.388 0.487 0.300 0.494 334 98-86-2 Acetophenone 0.388 0.498 0.311 0.461 335 611-14-3 1-Ethyl-2-methylbenzene 0.388 0.530 0.280 0.494 336 95-63-6 1,2,4-Trimethylbenzene 0.387 0.499 0.312 0.493 337 1074-43-7 1-Methyl-3-propylbenzene 0.387 0.529 0.279 0.493 338 135-19-3 2-Naphthalenol 0.386 0.450 0.325 0.492 339 104-90-5 5-Ethyl-2-methylpyridine 0.386 0.386 0.386 0.451 340 98-06-6 tert-Butylbenzene 0.386 0.496 0.308 0.492 341 3333-52-6 Tetramethylsuccinonitrile 0.384 0.384 0.384 0.490 342 78-93-3 Methyl ethyl ketone 0.384 0.384 0.384 0.384 343 107-19-7 Propargyl alcohol 0.383 0.493 0.305 0.489 344 620-14-4 3-Ethyltoluene 0.382 0.524 0.274 0.488 345 108-68-9 3,5-Dimethylphenol 0.382 0.449 0.324 0.447 346 526-75-0 2,3-Dimethylphenol 0.381 0.448 0.323 0.446 347 99-06-9 3-Hydroxybenzoic acid 0.380 0.412 0.349 0.445 348 108-10-1 4-Methyl-2-pentanone 0.379 0.379 0.379 0.379 349 105-60-2 Caprolactam 0.379 0.379 0.379 0.411 350 118-90-1 2-Methylbenzoic acid 0.378 0.410 0.348 0.443 351 122-39-4 Diphenylamine 0.378 0.487 0.300 0.484 352 95-47-6 o-Xylene 0.378 0.490 0.303 0.484 353 95-48-7 o-Cresol 0.377 0.455 0.330 0.450 354 106-42-3 p-Xylene 0.377 0.455 0.330 0.483 355 80-05-7 Bisphenol A 0.376 0.521 0.271 0.482 356 65-85-0 Benzoic acid 0.374 0.451 0.326 0.447 357 108-67-8 1,3,5-Trimethylbenzene 0.373 0.451 0.326 0.479 358 135-98-8 sec-Butylbenzene 0.372 0.482 0.295 0.479 359 71-47-6 Formic acid, ion(1-) 0.372 0.372 0.372 0.372

178

Rank CAS Name Original Case 1 Case 2 Case 3 360 78-51-3 Tris(2-butoxyethyl) phosphate 0.371 0.481 0.294 0.477 361 104-51-8 Butylbenzene 0.369 0.401 0.339 0.475 362 108-39-4 m-Cresol 0.369 0.447 0.322 0.442 363 109-06-8 2-Methylpyridine 0.366 0.508 0.258 0.472 364 100-52-7 Benzaldehyde 0.365 0.475 0.287 0.471 365 611-32-5 8-Methylquinoline 0.364 0.428 0.303 0.470 366 67-64-1 Acetone 0.364 0.364 0.364 0.364 367 103-65-1 Propylbenzene 0.363 0.441 0.316 0.469 368 7661-55-4 5-Methylquinoline 0.363 0.427 0.302 0.469 369 105-67-9 2,4-Dimethylphenol 0.361 0.471 0.283 0.467 370 91-62-3 6-Methylquinoline 0.361 0.425 0.300 0.467 371 108-95-2 Phenol 0.361 0.361 0.361 0.434 372 612-60-2 7-Methylquinoline 0.361 0.425 0.300 0.467 373 612-58-8 3-Methylquinoline 0.361 0.425 0.300 0.467 374 491-35-0 Lepidine 0.360 0.424 0.299 0.466 375 117-84-0 Di-n-octyl phthalate 0.360 0.470 0.282 0.466 376 498-02-2 Acetovanillone 0.360 0.392 0.330 0.466 377 100-51-6 Benzyl alcohol 0.355 0.465 0.277 0.461 378 108-88-3 * Toluene 0.354 0.354 0.354 0.427 379 131-11-3 Dimethyl phthalate 0.354 0.464 0.276 0.460 380 26764-26-1 Octadecenoic acid 0.351 0.460 0.273 0.457 381 84-74-2 Dibutyl phthalate 0.350 0.425 0.300 0.456 382 28631-86-9 2,2-Dihydroxy-1-phenylethanone 0.349 0.413 0.288 0.455 383 100-42-5 Styrene 0.349 0.392 0.329 0.455 384 4376-20-9 MEHP 0.341 0.483 0.233 0.447 385 25447-95-4 Hexadecenoic acid 0.338 0.448 0.261 0.444 386 86-55-5 1-Naphthalenecarboxylic acid 0.336 0.401 0.276 0.442 387 67-56-1 * Methanol 0.335 0.335 0.335 0.335 388 85-68-7 Benzyl butyl phthalate 0.326 0.436 0.248 0.400 389 84-66-2 Diethyl phthalate 0.326 0.435 0.248 0.432 390 121-91-5 1,3-Benzenedicarboxylic acid 0.319 0.383 0.258 0.425

179

6.5.2 Domain weights Appendix Table 16. Compounds in top 40 in all domain weight cases. The case where only exposure was evaluated is labeled ‘E100’, and the case where only hazard was evaluated is labeled ‘H100’. The case when exposure was weighted 25% and hazard was weighted 75% is labeled ‘E25/H75’, and the case when exposure was weighted 75% and hazard was weighted 25% is labeled ‘E75/H25’.

Original E100 H100 E25/H75 E75/H25 CAS Compound Rank Rank Rank Rank Rank 309-00-2 Aldrin 1 8 1 1 1 1024-57-3 Heptachlor epoxide B 2 9 2 2 3 72-20-8 Endrin 3 7 3 3 2 76-44-8 Heptachlor 4 10 4 4 4 1H-Phenalene, 2935-07-1 8 5 11 10 6 dodecahydro- Cyclohexane, 1- 54823-98-2 (cyclohexylmethyl)-4- 12 13 12 11 11 methyl-, trans- Methyl 1660-04-4 tricyclo(3.3.1.13,7)dec-1-yl 13 21 13 12 13 ketone Naphthalene, decahydro- 1750-51-2 14 18 19 16 15 1,6-dimethyl- 56-55-3 Benz(a)anthracene 15 36 16 14 21 3178-23-2 Dicyclohexylmethane 16 30 17 15 20 Naphthalene, decahydro- 66552-62-3 18 20 21 19 17 1,5-dimethyl- * naphthalene, decahydro- 1618-22-0 20 17 25 21 16 2,6-dimethyl- 2,3- 1008-80-6 Dimethyldecahydronaphthal 21 16 27 23 14 ene 294-62-2 Cyclododecane 22 26 20 20 19 92-51-3 1,1'-Bicyclohexyl 23 22 23 22 18 53-70-3 Dibenz(a,h)anthracene 24 39 18 18 26 (Cyclopentylmethyl)cyclohex 4431-89-4 27 34 30 27 28 ane

180

Appendix Table 17. Overall ToxPi scores for every case in domain weight sensitivity with the rank from the original analysis held constant. The case where only exposure was evaluated is labeled ‘E100’, and the case where only hazard was evaluated is labeled ‘H100’. The case when exposure was weighted 25% and hazard was weighted 75% is labeled ‘E25/H75’, and the case when exposure was weighted 75% and hazard was weighted 25% is labeled ‘E75/H25’.

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 1 309-00-2 Aldrin 0.80 0.66 0.94 0.87 0.73 2 1024-57-3 Heptachlor epoxide B 0.79 0.65 0.92 0.85 0.72 3 72-20-8 Endrin 0.79 0.66 0.91 0.85 0.72 4 76-44-8 Heptachlor 0.75 0.65 0.85 0.80 0.70 5 319-86-8 delta-Hexachlorocyclohexane 0.66 0.54 0.78 0.72 0.60 6 58-89-9 Lindane 0.66 0.54 0.78 0.72 0.60 7 319-85-7 beta-Hexachlorocyclohexane 0.66 0.54 0.78 0.72 0.60 8 2935-07-1 1H-Phenalene, dodecahydro- 0.66 0.70 0.62 0.64 0.68 9 118-74-1 Hexachlorobenzene 0.66 0.60 0.72 0.68 0.62 10 50-32-8 Benzo(a)pyrene 0.63 0.58 0.67 0.65 0.60 11 281-23-2 Adamantane 0.62 0.73 0.52 0.57 0.68 Cyclohexane, 1- 12 54823-98-2 (cyclohexylmethyl)-4-methyl-, 0.62 0.64 0.61 0.61 0.63 trans- Methyl tricyclo(3.3.1.13,7)dec- 13 1660-04-4 0.61 0.62 0.60 0.61 0.62 1-yl ketone Naphthalene, decahydro-1,6- 14 1750-51-2 0.60 0.62 0.57 0.59 0.61 dimethyl- 15 56-55-3 Benz(a)anthracene 0.60 0.61 0.59 0.59 0.60 16 3178-23-2 Dicyclohexylmethane 0.60 0.61 0.58 0.59 0.61 2-n- 17 6305-52-8 0.60 0.60 0.60 0.60 0.60 Butyldecahydronaphthalene Naphthalene, decahydro-1,5- 18 66552-62-3 0.60 0.62 0.57 0.58 0.61 dimethylphenanthrene, 19 5743-97-5 0.60 0.68 0.51 0.56 0.64 tetradecahydro- * naphthalene, decahydro-2,6- 20 1618-22-0 0.60 0.63 0.57 0.58 0.61 dimethyl- 2,3- 21 1008-80-6 Dimethyldecahydronaphthalen 0.60 0.63 0.56 0.58 0.61 e 22 294-62-2 Cyclododecane 0.59 0.62 0.57 0.58 0.61 23 92-51-3 1,1'-Bicyclohexyl 0.59 0.62 0.57 0.58 0.61 24 53-70-3 Dibenz(a,h)anthracene 0.59 0.60 0.58 0.59 0.60 cis, cis-3- 25 66660-42-2 0.58 0.60 0.57 0.57 0.59 ethylbicyclo[4.4.0]decane

181

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 26 1687-34-9 1-Ethyl-3-methyladamantane 0.58 0.73 0.43 0.51 0.66 (Cyclopentylmethyl)cyclohexan 27 4431-89-4 0.58 0.61 0.55 0.57 0.60 e 28 205-99-2 Benzo(b)fluoranthene 0.58 0.59 0.57 0.57 0.59 29 702-79-4 1,3-Dimethyladamantane 0.57 0.74 0.41 0.49 0.66 30 629-62-9 Pentadecane 0.57 0.60 0.54 0.56 0.59 31 629-59-4 Tetradecane 0.57 0.60 0.53 0.55 0.59 32 1606-08-2 Cyclopentylcyclohexane 0.57 0.61 0.53 0.55 0.59 33 218-01-9 Chrysene 0.57 0.62 0.52 0.54 0.59 Decahydro-2- 34 2958-76-1 0.57 0.61 0.53 0.55 0.59 methylnaphthalene 35 16538-89-9 cyclooctane, (1-methylpropyl)- 0.56 0.57 0.55 0.56 0.57 36 23609-46-3 cyclooctane, 1,2-diethyl- 0.56 0.56 0.56 0.56 0.56 37 2883-02-5 Cyclohexane, nonyl- 0.56 0.55 0.56 0.56 0.55 38 1795-15-9 Cyclohexane, octyl- 0.56 0.56 0.55 0.55 0.56 39 629-50-5 Tridecane 0.56 0.59 0.52 0.54 0.57 40 111-84-2 Nonane 0.55 0.59 0.52 0.54 0.57 41 1795-16-0 Decylcyclohexane 0.55 0.54 0.56 0.56 0.55 42 62199-52-4 1,2-Dibutylcyclopentane 0.55 0.57 0.53 0.54 0.56 43 1560-93-6 2-Methylpentadecane 0.55 0.56 0.53 0.54 0.55 44 74-83-9 Methyl bromide 0.55 0.59 0.50 0.53 0.57 45 6165-40-8 7-Methylpentadecane 0.55 0.55 0.54 0.54 0.55 46 295-17-0 Cyclotetradecane 0.54 0.58 0.51 0.53 0.56 47 3891-98-3 2,6,10-Trimethyldodecane 0.54 0.56 0.53 0.53 0.55 48 79-34-5 1,1,2,2-Tetrachloroethane 0.54 0.56 0.52 0.53 0.55 49 61142-68-5 1-Hexyl-3-methylcyclopentane 0.54 0.57 0.51 0.53 0.55 50 112-40-3 Dodecane 0.54 0.57 0.51 0.52 0.56 51 207-08-9 Benzo(k)fluoranthene 0.54 0.63 0.45 0.49 0.59 52 17312-57-1 3-Methyldodecane 0.54 0.56 0.51 0.52 0.55 53 13287-21-3 6-Methyltridecane 0.54 0.56 0.52 0.53 0.55 54 26730-14-3 7-Methyltridecane 0.54 0.56 0.52 0.53 0.55 55 707-35-7 1,3,5-Trimethyladamantane 0.54 0.73 0.34 0.44 0.64 56 17312-80-0 2,4-Dimethylundecane 0.53 0.57 0.50 0.52 0.55 57 1560-97-0 2-Methyldodecane 0.53 0.56 0.51 0.52 0.55 1,7-dimethyl-4-(1- 58 645-10-3 0.53 0.57 0.50 0.52 0.55 methylethyl)cyclodecane 59 4292-75-5 Hexylcyclohexane 0.53 0.54 0.52 0.53 0.54 60 6117-97-1 4-Methyldodecane 0.53 0.55 0.51 0.52 0.54 61 67-66-3 Chloroform 0.53 0.59 0.47 0.50 0.56 62 1120-21-4 Undecane 0.53 0.58 0.49 0.51 0.55 63 17301-23-4 2,6-Dimethylundecane 0.53 0.56 0.51 0.52 0.55 64 6418-41-3 tridecane, 3-methyl- 0.53 0.55 0.52 0.52 0.54

182

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 65 1560-95-8 2-Methyltetradecane 0.53 0.54 0.52 0.52 0.54 66 56292-65-0 2,5-Dimethyldodecane 0.53 0.56 0.50 0.52 0.54 67 112-70-9 1-Tridecanol 0.53 0.52 0.54 0.53 0.53 68 25117-31-1 5-Methyltridecane 0.53 0.54 0.52 0.52 0.54 cyclohexane, 1-methyl-4-(1- 69 54411-00-6 0.53 0.55 0.51 0.52 0.54 methylbutyl)- 70 41446-57-5 3-Tridecene, (3E)- 0.53 0.54 0.52 0.52 0.53 71 26730-12-1 4-Methyltridecane 0.53 0.54 0.51 0.52 0.54 72 25117-32-2 5-Methyltetradecane 0.53 0.53 0.53 0.53 0.53 73 13150-81-7 2,6-Dimethyldecane 0.53 0.57 0.49 0.51 0.55 74 1560-96-9 2-Methyltridecane 0.53 0.55 0.51 0.52 0.54 75 15232-86-7 1-Heptylcyclohexene 0.53 0.52 0.53 0.53 0.52 2-Ethyl-1,1,3- 76 442662-72-8 0.53 0.57 0.49 0.51 0.55 trimethylcyclohexane 77 4457-00-5 Cyclopentane, hexyl- 0.53 0.56 0.50 0.51 0.54 78 4292-92-6 Pentylcyclohexane 0.52 0.55 0.50 0.51 0.54 79 544-76-3 Hexadecane 0.52 0.58 0.46 0.49 0.55 80 124-18-5 * Decane 0.52 0.59 0.45 0.49 0.56 1,4-Dimethyl-2,3- 81 71312-54-4 0.52 0.52 0.52 0.52 0.52 diazabicyclo[2.2.1]hept-2-ene cyclopentene, 5-hexyl-3,3- 82 61142-66-3 0.52 0.52 0.52 0.52 0.52 dimethyl- 83 2207-01-4 (Z)-1,2-Dimethylcyclohexane 0.52 0.61 0.42 0.47 0.57 84 6750-34-1 1-dodecanol, 3,7,11-trimethyl- 0.52 0.50 0.54 0.53 0.51 85 193-39-5 Indeno(1,2,3-cd)pyrene 0.52 0.59 0.45 0.48 0.55 86 7045-71-8 2-Methylundecane 0.52 0.55 0.49 0.50 0.53 1,7,11-Trimethyl-4-(1- 87 1786-12-5 0.52 0.61 0.42 0.47 0.57 methylethyl)cyclotetradecane 2,4-Diethyl-1- 88 61142-70-9 0.51 0.54 0.49 0.50 0.53 methylcyclohexane 89 2847-72-5 4-Methyldecane 0.51 0.56 0.47 0.49 0.54 90 115-96-8 Tris(2-chloroethyl) phosphate 0.51 0.44 0.59 0.55 0.47 91 110-82-7 Cyclohexane 0.51 0.65 0.38 0.45 0.58 92 17302-32-8 3,7-Dimethylnonane 0.51 0.56 0.47 0.49 0.54 93 17302-28-2 2,6-Dimethylnonane 0.51 0.56 0.47 0.49 0.54 94 13151-34-3 3-Methyldecane 0.51 0.56 0.47 0.49 0.54 1-Methyl-3-(propan-2- 95 16580-24-8 0.51 0.57 0.45 0.48 0.54 yl)cyclohexane 96 74-93-1 Methanethiol 0.51 0.56 0.46 0.49 0.54 97 13151-35-4 5-Methyldecane 0.51 0.55 0.47 0.49 0.53 98 66542-51-6 * Chloromethyl hexanoate 0.51 0.50 0.52 0.52 0.50 99 591-21-9 1,3-Dimethylcyclohexane 0.51 0.59 0.43 0.47 0.55

183

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 100 62016-37-9 2,4,6-Trimethyloctane 0.51 0.55 0.47 0.49 0.53 101 2234-75-5 1,2,4-Trimethylcyclohexane 0.51 0.58 0.45 0.48 0.55 102 6975-98-0 2-Methyldecane 0.51 0.56 0.46 0.49 0.54 103 71-43-2 * Benzene 0.51 0.52 0.50 0.50 0.52 104 5402-53-9 Chloromethyl propanoate 0.51 0.50 0.52 0.51 0.50 105 127-18-4 * Tetrachloroethylene 0.51 0.59 0.42 0.47 0.55 106 3728-56-1 1-Ethyl-4-methylcyclohexane 0.51 0.56 0.46 0.48 0.53 rel-(1R,2S)-1,2- 107 14113-60-1 0.51 0.62 0.40 0.45 0.56 Diethylcyclohexadecane 108 77877-94-2 Chloromethyl pentanoate 0.51 0.50 0.51 0.51 0.50 109 1678-93-9 Butylcyclohexane 0.51 0.54 0.47 0.49 0.52 110 112-18-5 N,N-Dimethyldodecan-1-amine 0.50 0.48 0.53 0.52 0.49 111 73105-67-6 1-Iodo-2-methylundecane 0.50 0.53 0.48 0.49 0.52 112 142-82-5 Heptane 0.50 0.58 0.43 0.47 0.54 113 1072-05-5 2,6-Dimethylheptane 0.50 0.60 0.41 0.46 0.55 114 62199-51-3 1-Pentyl-2-propylcyclopentane 0.50 0.56 0.44 0.47 0.54 115 26730-20-1 7-Methylhexadecane 0.50 0.56 0.45 0.48 0.53 116 111-65-9 Octane 0.50 0.59 0.42 0.46 0.55 117 111-44-4 Bis(2-chloroethyl) ether 0.50 0.46 0.54 0.52 0.48 118 3728-55-0 1-Ethyl-3-methylcyclohexane 0.50 0.55 0.46 0.48 0.53 119 1560-92-5 2-Methylhexadecane 0.50 0.56 0.45 0.47 0.53 120 1678-92-8 Propylcyclohexane 0.50 0.54 0.47 0.48 0.52 121 2040-96-2 Propylcyclopentane 0.50 0.57 0.44 0.47 0.53 1-Methyl-2-propyl- 122 4291-79-6 0.50 0.54 0.46 0.48 0.52 cyclohexane 123 75-25-2 Bromoform 0.50 0.55 0.45 0.47 0.53 124 5911-04-6 3-Methylnonane 0.50 0.56 0.44 0.47 0.53 2-BUTYL-1,1,3-TRIMETHYL- 125 54676-39-0 0.50 0.53 0.47 0.48 0.52 CYCLOHEXANE 126 107-13-1 Acrylonitrile 0.50 0.50 0.50 0.50 0.50 cyclohexane, 1-isopropyl-1- 127 16580-26-0 0.50 0.56 0.44 0.47 0.53 methyl- 128 3073-66-3 1,1,3-Trimethylcyclohexane 0.50 0.57 0.43 0.46 0.54 129 31295-56-4 2,6,11-Trimethyldodecane 0.50 0.56 0.44 0.47 0.53 130 17301-94-9 4-Methylnonane 0.50 0.56 0.44 0.47 0.53 131 871-83-0 2-Methylnonane 0.50 0.56 0.43 0.46 0.53 132 15869-86-0 4-Ethyloctane 0.50 0.55 0.44 0.47 0.52 133 79-06-1 Acrylamide 0.50 0.31 0.68 0.59 0.40 134 16747-30-1 2,4,4-Trimethylhexane 0.50 0.59 0.40 0.45 0.55 135 107-06-2 1,2-Dichloroethane 0.49 0.54 0.45 0.47 0.52 136 2883-05-8 2-Cyclohexyloctane 0.49 0.54 0.45 0.47 0.52 137 100-44-7 Benzyl chloride 0.49 0.53 0.45 0.47 0.51

184

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 138 54411-01-7 1-Methyl-2-pentylcyclohexane 0.49 0.55 0.43 0.46 0.52 139 15869-93-9 3,5-Dimethyloctane 0.49 0.55 0.43 0.46 0.52 140 2051-30-1 2,6-Dimethyloctane 0.49 0.55 0.43 0.46 0.52 1,1,6,6- 141 74054-92-5 0.49 0.61 0.37 0.43 0.55 tetramethylspiro[4.4]nonane 142 2406-25-9 Di-tert-butyl nitroxide 0.49 0.52 0.46 0.47 0.50 143 98-95-3 Nitrobenzene 0.49 0.48 0.50 0.49 0.48 144 959028-24-1 4-Ethyl-2,3-dimethylhex-2-ene 0.49 0.54 0.44 0.46 0.52 145 2815-58-9 1,2,4-Trimethylcyclopentane 0.49 0.56 0.41 0.45 0.53 146 123-25-1 Diethyl butanedioate 0.49 0.47 0.51 0.50 0.48 147 75-15-0 Carbon disulfide 0.49 0.57 0.40 0.44 0.53 148 706-14-9 gamma-Decanolactone 0.49 0.46 0.51 0.50 0.47 149 143-07-7 Dodecanoic acid 0.49 0.44 0.54 0.51 0.46 150 109-74-0 Butanenitrile 0.49 0.49 0.48 0.48 0.49 151 1921-70-6 Norphytane 0.48 0.60 0.37 0.43 0.54 152 4810-09-7 3-Methyl-1-heptene 0.48 0.57 0.40 0.44 0.53 153 108-87-2 Methylcyclohexane 0.48 0.55 0.41 0.45 0.52 154 959-98-8 Endosulfan I 0.48 0.48 0.48 0.48 0.48 155 33213-65-9 Endosulfan II 0.48 0.48 0.48 0.48 0.48 156 1678-91-7 Ethylcyclohexane 0.48 0.52 0.44 0.46 0.50 157 2980-69-0 4-Methylundecane 0.48 0.56 0.41 0.44 0.52 158 3386-33-2 Octadecyl chloride 0.48 0.54 0.42 0.45 0.51 159 55282-11-6 11-Pentan-3-ylhenicosane 0.48 0.58 0.38 0.43 0.53 160 112-30-1 1-Decanol 0.48 0.49 0.47 0.48 0.48 161 2453-00-1 1,3-Dimethylcyclopentane 0.48 0.55 0.41 0.45 0.51 162 74-84-0 Ethane 0.48 0.60 0.36 0.42 0.54 163 629-97-0 Docosane 0.48 0.58 0.38 0.43 0.53 164 1632-70-8 5-methylundecane 0.48 0.55 0.41 0.44 0.52 165 1002-43-3 3-Methylundecane 0.48 0.55 0.41 0.44 0.52 166 591-48-0 3-Methylcyclohexene 0.48 0.53 0.42 0.45 0.51 167 1192-18-3 (Z)-1,2-Dimethylcyclopentane 0.48 0.55 0.41 0.44 0.51 168 629-78-7 Heptadecane 0.48 0.56 0.39 0.44 0.52 169 592-27-8 2-Methylheptane 0.47 0.55 0.40 0.44 0.51 170 74-87-3 Chloromethane 0.47 0.58 0.37 0.42 0.53 171 7320-37-8 1,2-Epoxyhexadecane 0.47 0.54 0.41 0.44 0.51 172 593-45-3 Octadecane 0.47 0.55 0.39 0.43 0.51 173 110-75-8 2-Chloroethyl vinyl ether 0.47 0.50 0.45 0.46 0.48 174 562-28-7 (-)-Kaur-16-ene 0.47 0.63 0.31 0.39 0.55 175 111-30-8 Glutaraldehyde 0.47 0.44 0.50 0.49 0.45 176 821-55-6 2-Nonanone 0.47 0.51 0.42 0.45 0.49 2,6,10,14- 177 638-36-8 0.47 0.57 0.37 0.42 0.52 Tetramethylhexadecane 185

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 178 50991-08-7 2-Methyl-1,1'-bi(cyclohexane) 0.47 0.64 0.30 0.38 0.56 179 106-65-0 Dimethyl succinate 0.47 0.47 0.46 0.47 0.47 180 109-66-0 Pentane 0.47 0.57 0.36 0.42 0.52 181 126-73-8 Tributyl phosphate 0.46 0.45 0.48 0.47 0.46 182 75-83-2 2,2-Dimethylbutane 0.46 0.62 0.31 0.39 0.55 183 110-54-3 n-Hexane 0.46 0.59 0.34 0.40 0.53 1,3,5-Trimethyl-1,3,5- 184 59887-80-8 0.46 0.44 0.48 0.47 0.45 triazinane-2-thione 185 6418-44-6 heptadecane, 3-methyl- 0.46 0.55 0.37 0.42 0.51 186 111-87-5 1-Octanol 0.46 0.50 0.42 0.44 0.48 187 74-98-6 Propane 0.46 0.58 0.34 0.40 0.52 188 513-35-9 2-Methyl-2-butene 0.46 0.58 0.34 0.40 0.52 189 112-95-8 Eicosane 0.46 0.54 0.38 0.42 0.50 190 107-83-5 2-Methylpentane 0.46 0.57 0.34 0.40 0.51 191 91-20-3 Naphthalene 0.46 0.48 0.43 0.44 0.47 192 72-03-7 Propanoate 0.46 0.47 0.44 0.45 0.46 193 3892-00-0 2,6,10-Trimethylpentadecane 0.45 0.54 0.37 0.41 0.50 194 334-48-5 Decanoic acid 0.45 0.40 0.50 0.48 0.43 195 41446-78-0 4-Tetradecene, (4E)- 0.45 0.54 0.36 0.41 0.50 196 120-82-1 1,2,4-Trichlorobenzene 0.45 0.52 0.38 0.42 0.49 197 111-76-2 2-Butoxyethanol 0.45 0.46 0.45 0.45 0.46 198 629-92-5 Nonadecane 0.45 0.53 0.38 0.42 0.49 199 629-94-7 Heneicosane 0.45 0.53 0.38 0.42 0.49 200 68-12-2 N,N-Dimethylformamide 0.45 0.46 0.45 0.45 0.45 201 106-46-7 1,4-Dichlorobenzene 0.45 0.53 0.37 0.41 0.49 202 112-88-9 1-Octadecene 0.45 0.52 0.38 0.42 0.49 203 297-35-8 Cyclotriacontane 0.45 0.61 0.29 0.37 0.53 204 104-76-7 2-Ethyl-1-hexanol 0.45 0.48 0.42 0.43 0.47 205 10374-74-0 7-Tetradecene 0.45 0.54 0.36 0.41 0.50 206 112-34-5 2-(2-Butoxyethoxy)ethanol 0.45 0.42 0.48 0.46 0.43 207 123-20-6 Butanoic acid, ethenyl ester 0.45 0.50 0.40 0.42 0.47 208 64275-73-6 (Z)-5-Octen-1-ol 0.45 0.48 0.42 0.43 0.46 209 18435-22-8 3-methyl-tetradecane 0.45 0.55 0.35 0.40 0.50 210 1768-36-1 Propyl cyanate 0.45 0.45 0.45 0.45 0.45 211 18435-45-5 1-Nonadecene 0.45 0.53 0.36 0.40 0.49 212 123-86-4 Butyl acetate 0.45 0.49 0.40 0.42 0.47 213 544-85-4 Dotriacontane 0.45 0.60 0.29 0.37 0.53 214 55000-52-7 2,6,10-Trimethylhexadecane 0.45 0.54 0.36 0.40 0.49 215 99328-46-8 5-Methylhept-1-en-4-ol 0.45 0.48 0.42 0.43 0.46 216 591-78-6 2-Hexanone 0.45 0.49 0.41 0.43 0.47 217 4360-57-0 2-Pentadecyl-1,3-dioxolane 0.45 0.51 0.38 0.42 0.48

186

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 218 638-67-5 Tricosane 0.45 0.59 0.31 0.38 0.52 219 87-61-6 1,2,3-Trichlorobenzene 0.45 0.51 0.38 0.41 0.48 220 1630-94-0 1,1-Dimethylcyclopropane 0.45 0.55 0.34 0.39 0.50 221 55030-62-1 4,8-Dimethyltridecane 0.44 0.54 0.35 0.40 0.50 heptadecane, 2,6,10,14- 222 18344-37-1 0.44 0.52 0.37 0.41 0.49 tetramethyl- 2,2,4-Trimethyl-1,3- 223 144-19-4 0.44 0.44 0.45 0.45 0.44 pentanediol 224 461-55-2 Butyrate 0.44 0.46 0.43 0.44 0.45 225 71-23-8 1-Propanol 0.44 0.49 0.40 0.42 0.47 226 646-31-1 Tetracosane 0.44 0.58 0.31 0.38 0.51 227 629-99-2 Pentacosane 0.44 0.58 0.31 0.38 0.51 228 5989-27-5 D-Limonene 0.44 0.51 0.38 0.41 0.48 Heptadecane, 2,6,10,15- 229 54833-48-6 0.44 0.52 0.36 0.40 0.48 tetramethyl 230 57-60-3 Pyruvate 0.44 0.43 0.45 0.45 0.44 231 593-49-7 Heptacosane 0.44 0.58 0.30 0.37 0.51 232 79-09-4 Propionic acid 0.44 0.43 0.45 0.45 0.44 233 630-01-3 Hexacosane 0.44 0.57 0.31 0.38 0.51 234 54105-67-8 2,6-Dimethylheptadecane 0.44 0.53 0.35 0.40 0.49 235 110-94-1 Glutaric acid 0.44 0.42 0.46 0.45 0.43 236 544-63-8 Tetradecanoic acid 0.44 0.41 0.47 0.45 0.43 237 91-57-6 * 2-Methylnaphthalene 0.44 0.53 0.35 0.39 0.49 238 2885-00-9 1-Octadecanethiol 0.44 0.54 0.34 0.39 0.49 239 25117-24-2 4-Methyltetradecane 0.44 0.53 0.35 0.40 0.49 240 630-02-4 Octacosane 0.44 0.57 0.30 0.37 0.51 241 638-68-6 Triacontane 0.44 0.59 0.29 0.36 0.52 242 71-36-3 1-Butanol 0.44 0.49 0.38 0.41 0.47 243 92-52-4 * Biphenyl 0.44 0.58 0.29 0.37 0.51 244 598-89-0 Diiodoacetic acid 0.44 0.43 0.44 0.44 0.43 245 13287-24-6 9-Methylnonadecane 0.44 0.52 0.35 0.39 0.48 246 96-04-8 2,3-Heptanedione 0.44 0.45 0.42 0.43 0.44 247 129-00-0 Pyrene 0.44 0.62 0.25 0.34 0.53 248 132-65-0 Dibenzothiophene 0.43 0.57 0.29 0.37 0.51 249 563-46-2 2-Methylbut-1-ene 0.43 0.54 0.33 0.38 0.49 250 2490-48-4 2-Methylhexadecan-1-ol 0.43 0.50 0.37 0.40 0.47 (4aS,8aR)-4a- 251 938-06-7 Methyloctahydronaphthalen- 0.43 0.50 0.36 0.40 0.47 2(1H)-one 252 695-06-7 gamma-Caprolactone 0.43 0.44 0.43 0.43 0.43 253 80-62-6 Methyl methacrylate 0.43 0.49 0.37 0.40 0.46 254 149-57-5 2-Ethylhexanoic acid 0.43 0.42 0.44 0.44 0.43

187

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 255 124-07-2 Octanoic acid 0.43 0.42 0.44 0.44 0.43 256 5618-62-2 O-Isobutylhydroxylamine 0.43 0.47 0.39 0.41 0.45 257 100-01-6 4-Nitroaniline 0.43 0.43 0.43 0.43 0.43 258 95-50-1 1,2-Dichlorobenzene 0.43 0.53 0.33 0.38 0.48 259 206-44-0 * Fluoranthene 0.43 0.61 0.24 0.34 0.52 260 57-11-4 Octadecanoic acid 0.43 0.47 0.38 0.40 0.45 261 630-03-5 Nonacosane 0.43 0.57 0.29 0.36 0.50 262 5842-53-5 2,2,4-Trimethylpent-3-en-1-ol 0.43 0.47 0.38 0.40 0.45 263 91-22-5 Quinoline 0.42 0.49 0.36 0.39 0.46 264 108-29-2 4-Pentanolide 0.42 0.44 0.41 0.42 0.43 265 111-14-8 Heptanoic acid 0.42 0.42 0.42 0.42 0.42 266 107-92-6 Butanoic acid 0.42 0.43 0.42 0.42 0.42 267 141-78-6 Ethyl acetate 0.42 0.49 0.35 0.39 0.46 268 142-62-1 Hexanoic acid 0.42 0.43 0.42 0.42 0.42 269 542-28-9 Tetrahydro-2H-pyran-2-one 0.42 0.43 0.41 0.42 0.43 270 98-82-8 Cumene 0.42 0.56 0.28 0.35 0.50 271 64-19-7 Acetic acid 0.42 0.48 0.37 0.39 0.45 272 544-77-4 1-Iodohexadecane 0.42 0.55 0.29 0.36 0.49 273 60212-33-1 4-Tetradecyne 0.42 0.55 0.30 0.36 0.49 274 71-50-1 Acetate 0.42 0.48 0.36 0.39 0.45 275 117-81-7 Di(2-ethylhexyl) phthalate 0.42 0.43 0.41 0.41 0.43 276 75-09-2 Dichloromethane 0.42 0.58 0.26 0.34 0.50 2-[2- 277 3055-93-4 0.42 0.44 0.40 0.41 0.43 (Dodecyloxy)ethoxy]ethanol 278 123-91-1 1,4-Dioxane 0.42 0.49 0.35 0.38 0.45 279 4860-03-1 1-Chlorohexadecane 0.42 0.55 0.29 0.36 0.48 280 544-25-2 1,3,5-Cycloheptatriene 0.42 0.55 0.29 0.36 0.48 281 83-32-9 Acenaphthene 0.42 0.59 0.25 0.34 0.51 282 35216-11-6 7-Tetradecyne 0.42 0.54 0.30 0.36 0.48 283 100-41-4 Ethylbenzene 0.42 0.54 0.30 0.36 0.48 284 132-64-9 Dibenzofuran 0.42 0.54 0.30 0.36 0.48 285 108-90-7 Chlorobenzene 0.42 0.52 0.32 0.37 0.47 286 766-76-7 Benzoate 0.42 0.47 0.36 0.39 0.44 287 109-52-4 Pentanoic acid 0.42 0.42 0.41 0.41 0.42 288 61886-62-2 3-Hexadecyne 0.41 0.53 0.30 0.36 0.47 289 584-02-1 3-Pentanol 0.41 0.48 0.35 0.38 0.45 290 120-12-7 Anthracene 0.41 0.62 0.21 0.31 0.52 291 57-55-6 1,2-Propylene glycol 0.41 0.46 0.37 0.39 0.44 292 79-31-2 2-Methylpropanoic acid 0.41 0.42 0.40 0.41 0.42 293 74-82-8 Methane 0.41 0.43 0.39 0.40 0.42 294 64-17-5 Ethanol 0.41 0.49 0.33 0.37 0.45

188

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 295 67-63-0 Isopropanol 0.41 0.51 0.31 0.36 0.47 296 575-41-7 1,3-Dimethylnaphthalene 0.41 0.56 0.27 0.34 0.49 297 57-10-3 Hexadecanoic acid 0.41 0.42 0.40 0.41 0.41 298 75-34-3 1,1-Dichloroethane 0.41 0.53 0.29 0.35 0.47 299 110-86-1 Pyridine 0.41 0.48 0.34 0.38 0.44 300 646-07-1 Pentanoic acid, 4-methyl- 0.41 0.42 0.40 0.40 0.42 301 86-30-6 N-Nitrosodiphenylamine 0.41 0.45 0.37 0.39 0.43 302 90-12-0 1-Methylnaphthalene 0.41 0.51 0.30 0.36 0.46 303 86-73-7 Fluorene 0.41 0.58 0.24 0.33 0.50 304 576-26-1 2,6-Dimethylphenol 0.41 0.46 0.35 0.38 0.44 305 573-98-8 1,2-Dimethylnaphthalene 0.41 0.55 0.27 0.34 0.48 306 116-53-0 2-Methylbutanoic acid 0.41 0.42 0.39 0.40 0.42 307 569-41-5 1,8-Dimethylnaphthalene 0.41 0.55 0.27 0.34 0.48 308 571-58-4 1,4-Dimethylnaphthalene 0.41 0.55 0.27 0.34 0.48 309 575-37-1 1,7-Dimethylnaphthalene 0.41 0.55 0.27 0.34 0.48 310 2049-95-8 tert-Pentylbenzene 0.41 0.54 0.27 0.34 0.47 311 1599-67-3 1-Docosene 0.40 0.51 0.30 0.35 0.46 312 62-53-3 Aniline 0.40 0.46 0.35 0.38 0.44 313 50-00-0 Formaldehyde 0.40 0.49 0.31 0.36 0.45 314 503-74-2 Isovaleric acid 0.40 0.43 0.38 0.39 0.42 Acetic acid, 2-methylphenyl 315 533-18-6 0.40 0.44 0.36 0.38 0.42 ester 316 122-20-3 Triisopropanolamine 0.40 0.28 0.52 0.46 0.34 Triethylene glycol 317 3055-94-5 0.40 0.42 0.38 0.39 0.41 monododecyl ether 318 113-21-3 Lactate ion(1-) 0.40 0.36 0.44 0.42 0.38 7-(Bromomethyl)pentadec-7- 319 941228-34-8 0.40 0.50 0.30 0.35 0.45 ene 320 10023-74-2 Pentanoic acid, ion(1-) 0.40 0.36 0.43 0.41 0.38 321 75-07-0 Acetaldehyde 0.40 0.52 0.27 0.34 0.46 322 95-65-8 3,4-Dimethylphenol 0.40 0.46 0.34 0.37 0.43 323 35365-59-4 9-Octadecyne 0.40 0.51 0.28 0.34 0.46 324 90-15-3 1-Naphthol 0.40 0.51 0.28 0.34 0.46 325 541-73-1 1,3-Dichlorobenzene 0.39 0.52 0.27 0.33 0.46 326 122-99-6 2-Phenoxyethanol 0.39 0.46 0.33 0.36 0.43 327 95-87-4 2,5-Dimethylphenol 0.39 0.46 0.32 0.36 0.43 328 106-44-5 p-Cresol 0.39 0.46 0.33 0.36 0.43 329 107-21-1 Ethylene glycol 0.39 0.48 0.31 0.35 0.44 1-Hydroxy-3-(2-methylpropyl)- 6,7,8,8a- 330 2873-36-1 0.39 0.32 0.46 0.42 0.35 tetrahydropyrrolo[1,2- a]pyrazin-4(3H)-one

189

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 331 2136-72-3 2-(Octadecyloxy)ethanol 0.39 0.49 0.29 0.34 0.44 332 526-73-8 1,2,3-Trimethylbenzene 0.39 0.52 0.26 0.33 0.46 333 575-43-9 1,6-Dimethylnaphthalene 0.39 0.51 0.27 0.33 0.45 334 98-86-2 Acetophenone 0.39 0.48 0.29 0.34 0.44 335 611-14-3 1-Ethyl-2-methylbenzene 0.39 0.52 0.26 0.32 0.46 336 95-63-6 1,2,4-Trimethylbenzene 0.39 0.51 0.26 0.32 0.45 337 1074-43-7 1-Methyl-3-propylbenzene 0.39 0.51 0.26 0.33 0.45 338 135-19-3 2-Naphthalenol 0.39 0.50 0.28 0.33 0.44 339 104-90-5 5-Ethyl-2-methylpyridine 0.39 0.46 0.31 0.35 0.43 340 98-06-6 tert-Butylbenzene 0.39 0.54 0.24 0.31 0.46 341 3333-52-6 Tetramethylsuccinonitrile 0.38 0.49 0.28 0.33 0.44 342 78-93-3 Methyl ethyl ketone 0.38 0.48 0.28 0.33 0.44 343 107-19-7 Propargyl alcohol 0.38 0.49 0.28 0.33 0.44 344 620-14-4 3-Ethyltoluene 0.38 0.51 0.26 0.32 0.45 345 108-68-9 3,5-Dimethylphenol 0.38 0.45 0.32 0.35 0.42 346 526-75-0 2,3-Dimethylphenol 0.38 0.44 0.32 0.35 0.41 347 99-06-9 3-Hydroxybenzoic acid 0.38 0.38 0.38 0.38 0.38 348 108-10-1 4-Methyl-2-pentanone 0.38 0.48 0.27 0.33 0.43 349 105-60-2 Caprolactam 0.38 0.46 0.30 0.34 0.42 350 118-90-1 2-Methylbenzoic acid 0.38 0.40 0.36 0.37 0.39 351 122-39-4 Diphenylamine 0.38 0.47 0.29 0.33 0.42 352 95-47-6 o-Xylene 0.38 0.52 0.23 0.31 0.45 353 95-48-7 o-Cresol 0.38 0.47 0.29 0.33 0.42 354 106-42-3 p-Xylene 0.38 0.54 0.22 0.30 0.46 355 80-05-7 Bisphenol A 0.38 0.49 0.27 0.32 0.43 356 65-85-0 Benzoic acid 0.37 0.42 0.32 0.35 0.40 357 108-67-8 1,3,5-Trimethylbenzene 0.37 0.51 0.24 0.31 0.44 358 135-98-8 sec-Butylbenzene 0.37 0.51 0.24 0.31 0.44 359 71-47-6 Formic acid, ion(1-) 0.37 0.38 0.36 0.37 0.38 360 78-51-3 Tris(2-butoxyethyl) phosphate 0.37 0.42 0.33 0.35 0.40 361 104-51-8 Butylbenzene 0.37 0.52 0.22 0.30 0.45 362 108-39-4 m-Cresol 0.37 0.45 0.29 0.33 0.41 363 109-06-8 2-Methylpyridine 0.37 0.48 0.26 0.31 0.42 364 100-52-7 Benzaldehyde 0.37 0.50 0.23 0.30 0.44 365 611-32-5 8-Methylquinoline 0.36 0.47 0.26 0.31 0.42 366 67-64-1 Acetone 0.36 0.52 0.21 0.29 0.44 367 103-65-1 Propylbenzene 0.36 0.52 0.21 0.29 0.44 368 7661-55-4 5-Methylquinoline 0.36 0.46 0.26 0.31 0.42 369 105-67-9 2,4-Dimethylphenol 0.36 0.46 0.26 0.31 0.41 370 91-62-3 6-Methylquinoline 0.36 0.46 0.26 0.31 0.41 371 108-95-2 Phenol 0.36 0.47 0.25 0.31 0.42

190

E25/ E75/ Rank CAS Name Original E100 H100 H75 H25 372 612-60-2 7-Methylquinoline 0.36 0.46 0.26 0.31 0.41 373 612-58-8 3-Methylquinoline 0.36 0.46 0.26 0.31 0.41 374 491-35-0 Lepidine 0.36 0.46 0.26 0.31 0.41 375 117-84-0 Di-n-octyl phthalate 0.36 0.44 0.28 0.32 0.40 376 498-02-2 Acetovanillone 0.36 0.41 0.31 0.34 0.38 377 100-51-6 Benzyl alcohol 0.35 0.48 0.23 0.29 0.42 378 108-88-3 * Toluene 0.35 0.48 0.23 0.29 0.42 379 131-11-3 Dimethyl phthalate 0.35 0.44 0.27 0.31 0.40 380 26764-26-1 Octadecenoic acid 0.35 0.42 0.28 0.32 0.39 381 84-74-2 Dibutyl phthalate 0.35 0.46 0.24 0.29 0.41 2,2-Dihydroxy-1- 382 28631-86-9 0.35 0.42 0.28 0.31 0.39 phenylethanone 383 100-42-5 Styrene 0.35 0.51 0.19 0.27 0.43 384 4376-20-9 MEHP 0.34 0.41 0.27 0.31 0.38 385 25447-95-4 Hexadecenoic acid 0.34 0.39 0.28 0.31 0.37 386 86-55-5 1-Naphthalenecarboxylic acid 0.34 0.37 0.30 0.32 0.35 387 67-56-1 * Methanol 0.33 0.50 0.17 0.25 0.42 388 85-68-7 Benzyl butyl phthalate 0.33 0.40 0.26 0.29 0.36 389 84-66-2 Diethyl phthalate 0.33 0.44 0.21 0.27 0.39 390 121-91-5 1,3-Benzenedicarboxylic acid 0.32 0.36 0.28 0.30 0.34

191

6.6 Inorganic compounds without toxicity data Appendix Table 18. Inorganic compounds without toxicity data, the maximum concentration they were reported at in the database, and the number of times they were reported in the database.

Maximum Number of Times CAS Name Concentration Reported (mg/L) 14798-03-9 Ammonium 2,520 153 71-52-3 Bicarbonate 17,000 466 7440-69-9 Bismuth 161 25 24959-67-9 Bromide 13,600 1,102 7440-70-2 Calcium 828,000 1,470 471-34-1 Calcium carbonate 103,026 18 7440-44-0 Carbon 3,660 12 124-38-9 Carbon dioxide 701 5 3812-32-6 Carbonate 1,178 76 7440-45-1 Cerium 0.010 4 7440-46-2 Cesium 537 144 16887-00-6 Chloride 389,000 1,456 7440-47-3 Chromium 13.6 242 1308-38-9 Chromium(III) oxide 0.209 29 7429-91-6 Dysprosium 0.002 4 7440-52-0 Erbium 0.001 4 7440-53-1 Europium 0.013 5 15438-31-0 Fe +2 ion 53 25 16984-48-8 Fluoride 780 252 7440-54-2 Gadolinium 0.003 4 7440-55-3 Gallium 130 23 7440-56-4 Germanium 0.440 15 7440-57-5 Gold 0.018 10 7440-58-6 Hafnium 0.002 3 7440-60-0 Holmium 0.001 4 15035-72-0 Hydrosulfide 103 2 7440-74-6 Indium 12 6 20461-54-5 iodide ion 54.2 62 7439-94-3 Lutetium 0.001 4 7439-95-4 Magnesium 27,570 1,325 7440-00-8 Neodymium 0.004 4 7440-03-1 Niobium 0.010 2 7727-37-9 Nitrogen 96,026 178 10102-44-0 Nitrogen dioxide 24 3 10544-50-0 Octasulfur 0.001 66

192

Maximum Number of Times CAS Name Concentration Reported (mg/L) 7440-04-2 Osmium 0.975 9 7440-05-3 Palladium 0.020 2 14265-44-2 Phosphate 3,570 18 7440-06-4 Platinum 0.020 2 7440-09-7 Potassium 18,200 1,033 7440-10-0 Praseodymium 0.114 5 7440-15-5 Rhenium 0.001 2 7440-16-6 Rhodium 0.533 8 7440-17-7 Rubidium 47 223 7440-19-9 Samarium 0.005 5 7440-20-2 Scandium 1 46 7631-86-9 Silica 225 59 7440-21-3 Silicon 4,417 380 7440-23-5 Sodium 228,904 1,452 14808-79-8 Sulfate 5,590 807 18496-25-8 Sulfide 33.9 70 14265-45-3 Sulfite 73.6 55 7704-34-9 Sulfur 441 77 7440-25-7 Tantalum 0.010 2 13494-80-9 Tellurium 0.429 13 7440-27-9 Terbium 0.001 4 7440-29-1 Thorium 35.9 57 7440-30-4 Thulium 0.001 4 7440-32-6 Titanium 16.2 130 7440-61-1 Uranium 18.4 63 7440-64-4 Ytterbium 0.003 4 7440-65-5 Yttrium 0.011 5

193

6.7 Radionuclides Appendix Table 19. Activity concentration range for the 25 radionuclides on the working list, the state where the maximum concentration was reported, and the number of times the compound was identified in a sample.

Minimum Maximum Number State of Max CAS Name Concentration Concentration of Times Concentration (Bq/L) (Bq/L) Reported 14331-85-2 Protactinium -0.74 8.88 Pennsylvania 2 14952-40-0 Actinium-227 -1.11 0.074 Pennsylvania 2 14331-83-0 Actinium-228 4.48 76 Pennsylvania 4 12587-46-1 Alpha particle -1.15 4,551 New York 2 12587-47-2 Beta particle -2.61 22,111 Pennsylvania 153 14913-49-6 Bismuth-212 2.89 5.55 Pennsylvania 153 14733-03-0 Bismuth-214 0.009 271 Pennsylvania 2 10045-97-3 Caesium-137 -0.481 0.333 Pennsylvania 7 14255-04-0 Lead-210 -0.74 11.5 Pennsylvania 7 15092-94-1 Lead-212 -0.37 2.4 Pennsylvania 8 15067-28-4 Lead-214 0.222 272 Pennsylvania 6 13966-00-2 Potassium-40 0.133 146 Pennsylvania 11 15100-28-4 Protactinium-234 -22.2 51.8 Pennsylvania 43 7440-14-4 Radium 0.0071 668 Pennsylvania 144 15623-45-7 Radium-223 -1.11 0.074 Pennsylvania 2 13233-32-4 Radium-224 0.019 21 Pennsylvania 22 13982-63-3 Radium-226 0.006 984 Pennsylvania 327 15262-20-1 Radium-228 -0.004 1,348 Pennsylvania 289 New Mexico; 10098-97-2 Strontium-90 0.0002 2.62 9 Colorado 15623-47-9 Thorium-227 -1.81 0.111 Pennsylvania 5 14274-82-9 Thorium-228 0.049 1.7 Pennsylvania 12 14269-63-7 Thorium-230 0.007 0.347 West Virginia 8 15065-10-8 Thorium-234 -4.81 6.29 Pennsylvania 5 13966-29-5 Uranium-234 0.003 0.818 Pennsylvania 8 15117-96-1 Uranium-235 -1.48 1.48 Pennsylvania 14

194

6.8 Future use of database Appendix Table 20. Organic compound without toxicity regulated under 40 CFR Part 136. Bolded CAS numbers are pesticides.

CAS Name CAS Name 1,1,2,2- 79-34-5 319-86-8 delta-Hexachlorocyclohexane Tetrachloroethane 75-34-3 1,1-Dichloroethane 117-81-7 Di(2-ethylhexyl) phthalate 120-82-1 1,2,4-Trichlorobenzene 53-70-3 Dibenz(a,h)anthracene 95-50-1 1,2-Dichlorobenzene 84-74-2 Dibutyl phthalate 107-06-2 1,2-Dichloroethane 75-09-2 Dichloromethane 541-73-1 1,3-Dichlorobenzene 84-66-2 Diethyl phthalate 106-46-7 1,4-Dichlorobenzene 131-11-3 Dimethyl phthalate 105-67-9 2,4-Dimethylphenol 117-84-0 Di-n-octyl phthalate 110-75-8 2-Chloroethyl vinyl ether 959-98-8 Endosulfan I 83-32-9 Acenaphthene 33213-65-9 Endosulfan II 107-13-1 Acrylonitrile 72-20-8 Endrin 309-00-2 Aldrin 100-41-4 Ethylbenzene 120-12-7 Anthracene 206-44-0 Fluoranthene 56-55-3 Benz(a)anthracene 86-73-7 Fluorene 71-43-2 Benzene 76-44-8 Heptachlor 50-32-8 Benzo(a)pyrene 1024-57-3 Heptachlor epoxide B 205-99-2 Benzo(b)fluoranthene 118-74-1 Hexachlorobenzene 207-08-9 Benzo(k)fluoranthene 193-39-5 Indeno(1,2,3-cd)pyrene 85-68-7 Benzyl butyl phthalate 58-89-9 Lindane 100-44-7 Benzyl chloride 74-83-9 Methyl bromide beta- 319-85-7 91-20-3 Naphthalene Hexachlorocyclohexane 111-44-4 Bis(2-chloroethyl) ether 98-95-3 Nitrobenzene 80-05-7 Bisphenol A 86-30-6 N-Nitrosodiphenylamine 75-25-2 Bromoform 108-95-2 Phenol 108-90-7 Chlorobenzene 129-00-0 Pyrene 67-66-3 Chloroform 127-18-4 Tetrachloroethylene 74-87-3 Chloromethane 108-88-3 Toluene 218-01-9 Chrysene

195

6.9 Comparison to Danforth et al. (2020) Appendix Table 21. Compounds that were on the Danforth et al. (2020) ‘working’ list and on our ‘working’ list. Compounds that are bolded were organic compounds without data in our analysis while the rest were organic compounds with data.

CAS Name CAS Name 79-34-5 1,1,2,2-Tetrachloroethane 112-40-3 Dodecane 75-34-3 1,1-Dichloroethane 143-07-7 Dodecanoic acid 87-61-6 1,2,3-Trichlorobenzene 959-98-8 Endosulfan I 120-82-1 1,2,4-Trichlorobenzene 100-41-4 Ethylbenzene 95-63-6 1,2,4-Trimethylbenzene 107-21-1 Ethylene glycol 95-50-1 1,2-Dichlorobenzene 206-44-0 Fluoranthene 57-55-6 1,2-Propylene glycol 86-73-7 Fluorene 108-67-8 1,3,5-Trimethylbenzene 111-14-8 Heptanoic acid 1,3-Benzenedicarboxylic 121-91-5 544-76-3 Hexadecane acid 106-46-7 1,4-Dichlorobenzene 57-10-3 Hexadecanoic acid 123-91-1 1,4-Dioxane 142-62-1 Hexanoic acid 112-30-1 1-Decanol 193-39-5 Indeno(1,2,3-cd)pyrene 118-90-1 2-Methylbenzoic acid 67-63-0 Isopropanol 99-06-9 3-Hydroxybenzoic acid 503-74-2 Isovaleric acid 123-25-1 Diethyl butanedioate 67-56-1 Methanol 110-94-1 Glutaric acid 78-93-3 Methyl ethyl ketone 611-14-3 1-Ethyl-2-methylbenzene 80-62-6 Methyl methacrylate 90-12-0 1-Methylnaphthalene 91-20-3 Naphthalene 112-88-9 1-Octadecene 98-95-3 Nitrobenzene 112-34-5 2-(2-Butoxyethoxy)ethanol 86-30-6 N-Nitrosodiphenylamine 105-67-9 2,4-Dimethylphenol 95-48-7 o-Cresol 111-76-2 2-Butoxyethanol 57-11-4 Octadecanoic acid 110-75-8 2-Chloroethyl vinyl ether 3386-33-2 Octadecyl chloride 104-76-7 2-Ethyl-1-hexanol 124-07-2 Octanoic acid 91-57-6 2-Methylnaphthalene 95-47-6 o-Xylene 79-31-2 2-Methylpropanoic acid 106-44-5 p-Cresol 108-10-1 4-Methyl-2-pentanone 108-95-2 Phenol 83-32-9 Acenaphthene 79-09-4 Propionic acid 64-19-7 Acetic acid 103-65-1 Propylbenzene 67-64-1 Acetone 106-42-3 p-Xylene 98-86-2 Acetophenone 129-00-0 Pyrene 120-12-7 Anthracene 110-86-1 Pyridine 56-55-3 Benz(a)anthracene 135-98-8 sec-Butylbenzene 71-43-2 Benzene 100-42-5 Styrene 50-32-8 Benzo(a)pyrene 98-06-6 tert-Butylbenzene 205-99-2 Benzo(b)fluoranthene 127-18-4 Tetrachloroethylene

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CAS Name CAS Name 207-08-9 Benzo(k)fluoranthene 629-59-4 Tetradecane 65-85-0 Benzoic acid 544-63-8 Tetradecanoic acid 100-51-6 Benzyl alcohol 108-88-3 Toluene 85-68-7 Benzyl butyl phthalate 126-73-8 Tributyl phosphate 92-52-4 Biphenyl 629-50-5 Tridecane 80-05-7 Bisphenol A 1120-21-4 Undecane 107-92-6 Butanoic acid 208-96-8 Acenaphthylene 104-51-8 Butylbenzene 191-24-2 Benzo(g,h,i)perylene 105-60-2 Caprolactam 95-16-9 Benzothiazole 218-01-9 Chrysene 84-77-5 Didecyl phthalate 98-82-8 Cumene 101-81-5 Diphenylmethane 124-18-5 Decane 496-11-7 Indan delta- 319-86-8 108-38-3 m-Xylene Hexachlorocyclohexane 117-81-7 Di(2-ethylhexyl) phthalate 99-87-6 p-Cymene 53-70-3 Dibenz(a,h)anthracene 832-69-9 1-Methyl phenanthrene 132-65-0 Dibenzothiophene 85-01-8 Phenanthrene 84-74-2 Dibutyl phthalate 119-64-2 Tetralin 75-09-2 Dichloromethane 115-86-6 Triphenyl phosphate 84-66-2 Diethyl phthalate 2381-21-7 1-Methylpyrene 131-11-3 Dimethyl phthalate 96-76-4 2,4-Di-tert-butylphenol 4-(1,1,3,3- 106-65-0 Dimethyl succinate 140-66-9 Tetramethylbutyl)phenol 117-84-0 Di-n-octyl phthalate 98-54-4 4-tert-Butylphenol 122-39-4 Diphenylamine

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