A Prioritisation Scheme for Fracturing Fluid Chemicals Based on Human and Ecological Health

Dissertation is submitted in part fulfilment of the MSc in Environmental Science and Management, University of York

By Aiden Heeley-Hill

Supervised by Professor Alistair Boxall

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Abstract

Hydraulic fracturing is a process that releases shale gas from rock fissures for energy usage. In this process, a mixture of water, proppant and chemicals are injected into geological formations. Chemicals constitute approximately 0.7% of this mixture, meaning that a meaningful amount of chemicals could potentially leach into groundwater. This study developed a simple prioritisation scheme to identify potentially hazardous substances based on ecological and human health, considering mobility, toxicity and biodegradation parameters. EPI Suite, ECOSAR and Lazar models were used to determine LogKow, LogKoc, MRDD, LC50, ChV and BIOWIN1 values. There were 12 substances identified as category four human health hazards. There were ten substances determined as category five ecological health hazards. A total of nine substances were identified as hazardous to both ecological and human health. Ecological and human health effects following exposure to these substances have been identified from the literature.

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1. Introduction

Shale gas is a natural gas resource that is found in many different rock formations, with Carboniferous sand and mudstones being the most viable sources of shale gas in the United Kingdom (Andrews, 2013 and Könitzer et al, 2016). The largest reserve identified to date is the Bowland shale reserve in Northern England, with an estimated 1300 trillion cubic feet of gas (Department of Communities and Local Government and Department of Energy and Climate Change, 2015). Hydraulic fracturing is the method by which shale gas is released, using a mix of water, proppant and chemicals. Wells are used to extract the gas, with each site being approximately 1.5-2ha in size, and containing six to eight wells (Wood et al, 2011). Wells typically have a lifetime of between 20 and 30 years (Scanlon et al, 2014). A large volume of water is typically needed to fracture seams effectively. Volumes needed range from between 10,600m3 to 21,500m3 (Yang et al, 2015). Fracturing is a multi-step process, where initially the site is prepared for the installation of the well pads. Secondly the infrastructure, including the pipelines and other facilities, is installed. Thirdly, the fracturing process takes place. Fourthly, the well is ‘completed’, where flowback fluids containing suspended particles comes to the surface. Finally, the fractured gas is transported to the main supply. Throughout all stages of this process, it is possible for the environment and human populations to be exposed to fracturing chemicals (Adgate et al, 2014; see Figure 1).

Figure 1: Source-Pathway-Receptor model for hydraulic fracturing, considering air and water

Exposure to chemicals through groundwater contamination is one of the most divisive issues of the process. Chemicals in the fracturing fluid are employed to fulfill various functions and are estimated to constitute 0.7% of the total fluid injected (see Table 1). This represents 74,200l to 150,000l of the total fluid injected, based on the above water usage estimates.

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Component %Water 90.8Sand 8.5Acids 0.15

Clay Stabilisers 0.12Scale Inhibitors 0.09

Surfactants 0.075Friction Reducers 0.07

Breakers 0.06Biocides 0.06

Gels 0.05pH Adjusting Agent 0.01

Crosslinkers 0.007Iron Control 0.006

Corrosion Inhibitors 0.002

Table 2: Fracturing fluid component and representative percentages (Ferrer and Thurman, 2015)

Studies suggest that hydraulic fracturing can impact ecological and human health in a variety of ways. A recent study found that chemicals caused reproductive and developmental toxicity (Elliott et al, 2016). Dermal exposure to certain fracturing substances increased lifetime cancer risk in workers (Durant et al, 2016). In some shale formations, namely Marcellus, increased levels of barite were observed (Renock et al, 2016). Monomer toxicity is also a risk, potentially having anti-oestrogenic effects (Thurman et al, 2016). Issues regarding insufficient regulatory frameworks, and poor well construction, have been identified as the predominant drivers in the contamination of riparian and groundwater systems (DiGiulio and Jackson, 2016; Burton et al, 2016 and Rozzel and Reaven, 2012). For instance, the dumping of wastewater into rivers caused higher salinity levels in Appalachian rivers (Rozzel and Reaven, 2012).

In the European Union, groundwater pollution is regulated in the Water Framework Directive and in the Groundwater Daughter Directive, and within the United Kingdom, it is regulated in the Environmental Permitting Regulations of 2010. The latter regulation encompasses direct and indirect discharges that impact the quality of the groundwater. Groundwater pollution is directly governed by the Environment Agency, who have the capacity to impose prohibitions on any activity which negatively effects groundwater. The Environment Agency can also require that a particular activity be done under a permit, thus regulating a polluting activity (Bell et al, 2013). Groundwater Source Protection Zones also offer an additional layer of regulation. The purpose of SPZs is to protect drinking water and other critical water sources from pollution by pathogens and other contaminants through control of major developments that pose such a risk e.g. landills (Carey et al, 2009). SPZs are critical in ensuring the prolonged feasibility of drinking water from groundwater source. They also allow the sources to be properly assessed for vulnerability, thus allowing risk to be effectively reduced (Stauffer et al, 2005).

Whilst there is gathering evidence suggesting environmental risk from fracturing fluids, there remains a considerable lack of information regarding a number of chemicals used. This was an issue highlighted by Stringfellow et al (2014), who examined 81 commonly used fracturing chemicals. Of those examined, there was no

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toxicity information evident for 30 substances. A lack of fate and ecotoxicological data is not an issue germane to fracturing fluid. A number of studies identified this as a key issue in risk assessment (Arnot et al, 2012; Smital et al, 2013; Kuzmanović et al, 2015; and Elliott et al, 2016).

From the existing literature based on U.S. studies, a certain amount of the impact from chemical constituents in fracturing fluid can be mitigated through comprehensive regulatory frameworks. Therefore, it is imperative for any weaknesses in British regulation to be identified prior to any fracturing activities. For instance, in the United States, the fracturing industry is exempt from several major environmental protection frameworks, including the Clean Water Act, Safe Drinking Water Act, Resource Conservation and Recovery Act and the Superfund law, amongst others (Meng, 2014).

Prioritisation assessments are a common approach used in scientific studies and by public health bodies to identify potentially hazardous substances, or to determine those that need further research to fully assess their implications (Harold et al, 2014; Pizzo et al, 2016 and Kuzmanović et al, 2015). Prioritisation assessments are a key notion under the European Union Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation which seeks to protect human and environmental health from persistent, bioaccumulative and toxic (PBT) compounds (European Chemicals Agency, 2014 and Pizzo et al, 2016). Key parameters ought to be measured to ensure a thorough assessment. These parameters include biodegradation, mobility and toxicity (Guillén et al, 2012).

In an attempt to bolster existing knowledge of ecotoxicological information, in silico methods are seen as a potential new paradigm in research and exposure science (Paustenbach, 2000 and Cohen Hubal, 2009). Quantitative structure-activity relationship (QSAR) models attempt to statistically predict properties of a substance by correlating structure with activity (Perkins et al, 2003). Using these methods, it has become possible to accurately predict chemical characteristics in substances where there is little or no experimental data available (Ruiz et al, 2012).

This study aims to prioritise organic substances used in hydraulic fracturing fluid for further study. The prioritisation is based upon physicochemical and toxicity properties to assess hazard to human and ecological health, namely mobility in the environment, toxicity and biodegradation. These values will be derived from in silico methods.

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2. Methodology

Prioritisation assessments are well recognised in existing literature as a key exercise in the chemical risk assessment process (Boxall et al, 2003; Arnot et al, 2012 and Kuzmanović et al, 2015). Prioritisation is vital in creating an efficient and focused research and monitoring programme (Guillén et al, 2012). The scheme used in this study is based upon the properties intrinsic to the chemical substance, considering the parameters of persistence, mobility and toxicity. Due to the paucity of information regarding the ecological impacts of hydraulic fracturing, prioritisation schemes for both ecological health and human health were included in the study, using two different sets of parameters as identified in Tables 2 and 3.

2.1. Compound Selection

A list of fracturing fluid components was extracted from the FracFocus website with 1634 chemicals identified (FracFocus, 2016a). To create a thorough and relevant dataset, only organic chemicals, with data available for all of the parameters were considered. Substances that were spelled incorrectly, those that had incorrect SMILES notations or CAS numbers were removed. Duplicates, or those which were listed as proprietary blends, were also removed. There were a total of 143 chemicals considered for the prioritisation scheme.

2.2 Fate and Effect Data Generation

To ascertain the overall hazard of a substance, several parameters were measured: Mobility (LogKow and LogKoc) persistence (BIOWIN1) and toxicity (LC50, ChV, and MRDD) values. BIOWIN1 is a measure of the probability of a substance being rapidly biodegraded in the environment, based on linear probability modelling (Arnot et al, 2005). BIOWIN1 was chosen in favour of other biodegradability models (i.e. BIOWIN2-6) due to its estimation of rapid biodegradation using a linear model, as opposed to a model that considers complete degradation only (Posthumus et al, 2005). LC50 is an acute toxicity value derived from the exposure of a contaminant to fish over 96 hours, or Daphnia over 48 hours. ChV is a measure of chronic toxicity derived from the exposure of a contaminant to either fish, Daphnia or algae. To ensure a conservative toxicity estimate, the lowest mg/l value was selected across the three taxonomic groups modelled in ECOSAR (Mayo-Bean et al, 2012).

Estimation Programme Interface (EPI Suite) was used to predict the fate properties and ecotoxicity of the study chemicals in the environment (Zarfl et al, 2012 and Strempel et al, 2012). The batch mode function was used to derive these values, following the collection of Chemical Abstract Service (CAS) registry numbers from the FracFocus registry. Ecological Structure Activity Relationships (ECOSAR) was used to predict the acute and chronic toxicity of organic chemicals on organisms inhabiting affected water bodies (Sanderson et al, 2003) using CAS numbers. Lazy Structure-Activity Relationship (Lazar) is a predictive toxicology framework tool that provides information on, amongst other parameters, human toxicity (Maunz et al, 2013). Lazar is available as both source code, and as a web interface (nano-lazar). The latter was chosen for this study, with toxicity information gained from Simplified Molecular-Input Line-Entry System (SMILES) notations entered onto the website in succession. Results were provided in mmol/kg-bw/day and mg/kg-bw/day. The latter

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was chosen so that the results were more comparable with those of the ecological toxicity data (See Appendix I and II).

2.3 Compound Prioritisation

The data collected for each parameter was ranked according to the rating system, with a score of 10, 5 or 1 attributed to a rating of high, medium or low hazard respectively. The rating bounds were based upon values found in existing literature. The substance was then attributed with an overall score (50 for ecological health and 40 for human health), with maximal scores given to the potentially most hazardous substances and minimal scores given to the potentially least hazardous substances (Tables 2 and 3). Bounds were then issued to separate categories (1-5) for both ecological and human health prioritisations (Tables 4 and 5).

Parameter Rating ScoreAcute Toxicity High (<1) 10

Medium (1≥100) 5Low (>100) 1

Chronic Toxicity High (<0.1) 10Medium (0.1≥10) 5

Low (>10) 1LogKow High (>4) 10

Medium (0≥4) 5Low (<0) 1

LogKoc High (>4) 10Medium (2≥4) 5

Low (<2) 1BIOWIN1 High (>0.5) 10

Medium (0.3≥0.5) 5Low (<0.3) 1

Total /50

Table 2: Prioritisation table for substances based on ecological health parameters

Parameter Rating ScoreMRDD High (<10) 10

Medium (10≥100) 5Low (>100) 1

LogKow High (>4) 10Medium (0≥4) 5

Low (<0) 1LogKoc High (>4) 10

Medium (2≥4) 5Low (<2) 1

BIOWIN1 High (<0.3) 10Medium (0.3≥0.5) 5

Low (>0.5) 1Total /40

Table 3: Prioritisation table for substances based on human health parameters

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Prioritisation Score Category Hazard Potential0-10 1 Very Low11-20 2 Low21-30 3 Medium31-40 4 High41-50 5 Very High

Table 4: Categorisation table based on ecological health prioritisation scores

Prioritisation Score Category Hazard Potential0-10 1 Very Low11-20 2 Low21-30 3 High31-40 4 Very High

Table 5: Categorisation table based on human health prioritisation scores

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3. Results & Discussion

Considered in the prioritisation study were 143 chemicals (see Appendix II), with 12 (representing 8.39% of organic substances) classified as category four substances, therefore potentially very hazardous to human health and in need of further study (see Table 6 and Figure 2). A further 51 chemicals (35.66%) were classified to be category three substances, and therefore potentially hazardous to human health. With regard to ecological health, ten chemicals (6.99%) were identified as category five substances, and consequently potentially very hazardous to ecological health. A further 17 chemicals (11.89%) were identified as category four substances, and consequently potentially hazardous to ecological health. A total of nine substances (6.29%) were common to both human and ecological health hazard lists. Of the total number of unique chemicals listed on the FracFocus website, category four human health substances represented 0.73% and category five ecological health substances represented 0.61% (See Table 6).

Human Health Ecological Health

CategoryOrganic Total

(%)FracFocus Total

(%)Organic Total

(%)FracFocus Total

(%)1 13.99 1.22 41.26 3.612 41.96 3.67 24.48 2.143 35.66 3.12 15.38 1.354 8.39 0.73 11.89 1.045 - - 6.99 0.61

Table 6: Percentage of compounds representing each category for organic and FracFocus substances

Figure 2: The number of compounds and their related categories with regard to human health endpoints

1 2 3 40

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Figure 3: The number of compounds and their related categories with regard to ecological health

endpoints

A similar scheme conducted by Rogers et al (2015) developed a screening process for the environmental persistence and mobility of chemicals to contaminate ground water. The study assessed 659 compounds for their transport time, ‘tenth-life’, National Primary Drinking Water Regulations, oral reference doses, inhalation reference concentrations, carcinogenic risk slope factors and their frequency of use. Under a fast transport scenario, 41 substances were identified as being present at ≥10% concentration of the initial dosage post-transport. However, only 15 of these substances were deemed to have an ‘elevated exposure potential’ due their use as stated in >50 FracFocus well reports.

3.1 Category 4 and 5 Substances

From the substances identified in the prioritisation process, several human and ecological health effects have been identified. Such effects have been recognised through occupational exposure studies, primarily in other industries beyond hydraulic fracturing, and through in vivo experimentation.

Cyclohexane, 1,1,2,2,3,3,4,5,5,6-decafluoro-4,6-bis(trifluoromethyl)- and perfluoroethylcyclohexane were identified as the most hazardous substances by the prioritisation scheme in both the human and ecological health categories. This indicated that the substances are highly mobile in the environment, posed a high level of toxicity and biodegraded slowly. Therefore, they should be a key focus for further study and monitoring efforts during fracturing activities. Cyclohexane is considered mildly toxic, however, it can cause central nervous system depression and can have narcotic effects at higher concentrations. After occupational exposure to commercial hexane, neurotoxic effects were observed. However, due to the presence of n-hexane, a known neurotoxin, it is difficult to state that cyclohexane itself is neurotoxic. Historic in vivo studies suggest that cyclohexane is lethal to mice at a single two-hour inhaled exposure of between 17460-20370ml/m3 (Scientific Committee on Occupational Exposure Limits, 2001). In a one-hour exposure period over six days per week for 113 days, in which mice were exposed to glue where the predominant ingredient was cyclohexane (36.3%), bodyweight gain was reduced, as were food and water consumption and white blood cell count, and liver weight increased. However,

1 2 3 4 50

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no organ abnormality was observed (MAK-Commission, 1999). Modern scientific literature is lacking on the effects of cyclohexane, therefore further study of cyclohexane in isolation would be beneficial.

There is a lack of evidence in academic literature surrounding the human and environmental health effects of perfluoroethylcyclohexane. Safety data sheets contain little toxicological information, though it is predicted to be insoluble in water, it is not likely to bioaccumulate and is not readily biodegradable (F2 Chemicals, 2011). De Silva et al (2011) linked perflourinated chemicals with a decline of fish stocks in the Great Lakes of North America. They also estimate that Perfluoroethylcyclohexane was resistant to biodegradation. The results and predictions are consistent with those of this study.

1-Octadecene, 1-Tetradecene, Phenol, 4-nonyl-, Naphthalenecarboxamide, Hexadecane, Propanetricarboxylic acid and 9-Octadecenoic acid were all identified as category four human health and category five ecological health hazards due to their high mobility and low toxicity thresholds. However, because these substances are readily biodegradable, they were considered less of a hazard.

1-Octadecene, 1-Tetradecene and hexadecane are categorised as long-chain hydrocarbons, and are therefore likely to partition to soil and water, and is less likely to be bioavailable than shorter chain hydrocarbons. (Organisation for Economic Co-operation and Development, 2004). Hydrocarbons in general can be highly toxic, with inhalation being the primary route of occupational exposure. Inhalation can affect multiple systems, and ingestion can cause pulmonary toxicity (TOXNET, 2002). Dermal and cardiovascular toxicity was observed during in vivo studies of hexadecane (Lindberg and Sagström, 1989). Napthalene carboxamide is used as a component in dye, there is little toxicity information beyond that it is a skin and eye irritant (Ciba Corporation, 2007). Little is known regarding the toxicity of propanetricarboxylic acid, beyond that it is a skin and eye irritant (Alfa Aesar, 2015).

Naphthalenedisulfonic acid was identified as a category four human health hazard substance, due to its low toxicity threshold and low degradation probability, but due to its high solubility to water, it is classed as less hazardous than other category four substances. It is used as a dye, and its toxicological information is sparse. There is evidence to suggest that it depresses neural progenitor cell proliferation, though this is inconclusive (Park et al, 2009). 9-Octadecenoic acid is used widely in the cosmetic industry, and is considered a mild to moderate irritant (Boelsma et al, 1996). It caused lung injury and pulmonary hypertension in adult animals (Schreiber and Soifer, 1991).

4-nonylphenol is shown to have endocrine disrupting potential in both humans and rats and mice. Bennasroune et al (2012) used the THP-1 human cell line as a proxy for macrophage cells, and exposed them to 0-10µM 4-nonylphenol. The study concluded that exposure to 10µM 4-nonylphenol in isolation, increased the TNF-α (Tumour Necrosis Factor alpha) levels by 43.2% in comparison to the control. At the same concentration, 4-nonylphenol induced a 22.7% higher secretion of IL-8 (Interleukin 8). This study suggests that exposure to 4-nonylphenol can and does affect the human endocrine and immune systems. Further, nonylphenols also had oestrogenic effects in humans, rats and mice, fish and Daphnids. Oestrogenic effects

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in fish and Daphnids occurred at 10-20µg/L. In rats and mice, the NOAEL (No Observed Adverse Effect Level) threshold was 15mg/kg/day (Bontje et al, 2004). The NOAEL for chronic effects in humans is based on renal and hepatic data in rats, and is thought to be 10mg/kg/day (Bakke, 2003).

Benzenamine was the lowest scoring category four substance, due to its low toxicity threshold, its poor degradability, but as it is moderately mobile, it is considered less hazardous. Benzenamine is considered highly toxic, if it enters the human system whether dermally, through inhalation or ingestion. Exposure can lead to the development of methemoglobinaemia and haemolysis. Occupational exposure assessments suggest that low-level concentrations (30-50ppm) over several hours leads to minor issues, whilst higher concentrations (>100ppm) over one hour elicited major health concerns (Badische Anilin und Soda Fabrik, 2012).

Cyclotetrasiloxane, octamethyl- is classified as a category five ecological health hazard, and is therefore a potential ecological health hazard. It is considered to be highly toxic, mobile, and rapidly biodegradable. It is used in the cosmetics industry and it is persistent in sediment, though it is not rapidly biodegradable in aquatic systems. It is also cited as being bioaccumulative (Brooke et al, 2009).

3.2 Additional Hazardous Substances

Whilst the most potentially hazardous substances have been prioritised, there were a number of additional substances that are well documented in the literature as having significant ecological and human health impacts.

Surfactants, such as fatty acid ethoxylates (Category three for human health), have been widely studied in the literature for their toxicity. Due to their ability to lower surface tension between different substances, they predominantly impact on the respiratory membranes of marine organisms, resulting in asphyxiation (McWilliams, 2000). There is a belief that rapid biodegradation rates of anionic surfactants mean that any toxicity is quickly nullified, though a study by Sánchez-Leal et al (1991) suggested that despite rapid degradation, some groups of anionic surfactants are more toxic than others. Ivanković and Hrenović (2010) suggest that though some classes of surfactants are toxic to organisms, their levels in the environment are such so as not to be an issue. Surfactants have been shown to act as endocrine disruptors in both wildlife and human systems, being responsible for the feminisation of male fish in UK rivers. Post-application of sewage sludge containing surfactants, physiological damage was observed in ryegrass treated with 500kg/ha of sludge (Ying, 2005).

Benzene, identified as a category three human health hazard (see Table 8), has the potential to infiltrate groundwater supplies and surface water. Benzene is a known carcinogen, and is of particular concern with regards to occupational exposure, though it is becoming increasingly prevalent as a wider public health issue. Benzene was shown to be correlated with instances of Non-Hodgkin lymphoma, with 23 of 43 reviewed studies showing a probable causal link between lymphoma occurrence and benzene exposure in industrial workers (Smith et al, 2007). In some instances, benzene concentrations have exceeded acute toxicity standards and pose a risk of cancer from chronic exposure (Sovacool, 2014). Drinking water standards for benzene are stated as 1µg/l in the United Kingdom, and 5µg/l in the United States (Drinking

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Water Inspectorate, 2010 and Agency for Toxic Substances and Disease Registry, 2007). Minimum exposures of between 32-80µg/l can lead to an increased number of leukaemia cases (Duarte-Davidson et al, 2001). In mice, increased instances of bone marrow haematopoietic hyperplasia, lymphocytopenia and leukocytopenia were observed at 5mg/kg bodyweight and above (World Health Organisation, 2003). There is a lack of ecological information regarding the impact of benzene exposure to animals and plants, due to benzene being quickly volatilised and is often not successfully bioaccumulated, and nor does it persist in soils (Irwin, 1997).

Oxirane, (butoxymethyl)-, identified as a category three human health hazard (see Table 8), has several health effects in the human population, affecting the immune and respiratory systems. It is also a known neurotoxin. Acute toxicity can induce symptoms such as wheezing and fainting, whilst chronic exposure can elicit narcosis and central nervous system depression. It is immediately dangerous to life and health at concentrations above 250ppm, based on inhalation studies. In animal toxicity studies, 5% in propylene glycol affected motor activity and caused central nervous system depression. In inhalation studies of male rats, the substance caused growth retardation and one death in ten rats at concentrations of 150ppm over seven hours for five days per week over ten weeks. When the concentration was increased to 300ppm, mortality increased to 50%, with emaciation and liver necrosis evident (Masten, 2004). The human and ecological toxicity of solvents is well recognised by the technology industry, with several incidents at chemical facilities resulting in human mortality in the 21st century (Patel et al, 2009).

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Name MRDD (mg/kg bw/day) LogKow LogKoc BIOWIN1 HHH ScoreCyclohexane, 1,1,2,2,3,3,4,5,5,6-decafluoro-4,6-bis(trifluoromethyl)- 0.97 6.02 5.813 -1.5873 40Perfluoroethylcyclohexane 6.54 5.66 5.813 -1.2508 401-Octadecene 5.01 9.04 5.247 0.7358 311-Tetradecene 5.01 7.08 4.204 0.7625 31 2,7-Naphthalenedisulfonic acid, 3-hydroxy-4-[(4-sulfo-1-naphthalenyl)azo]-, trisodium salt 2.29 -5.13 6.288 -0.3062 312-Naphthalenesulfonic acid, 6-hydroxy-5-[(4-sulfophenyl)azo]-, disodium salt 2.93 -1.18 4.4 -0.0284 31Phenol, 4-nonyl- 0.84 5.99 4.583 0.9215 312-Naphthalenecarboxamide, N-(5-chloro-2,4-dimethoxyphenyl)-4- 5- (diethylamino)sulfonyl -2-methoxyphenyl azo -3-hydro 5.70 7.65 5.378 0.7464 31Hexadecane 5.24 8.2 4.725 0.8566 311,2,3-Propanetricarboxylic acid, 2-(1-oxobutoxy)-, trihexyl ester 3.99 8.21 7.048 1.3406 319-Octadecenoic acid (Z)- 9.24 7.73 4.068 0.7942 31Benzenamine, 4,4 -methylenebis- 5.38 2.18 3.328 0.2403 30

Table 7: Category 4 substances for human health hazard potential

Name MRDD (mg/kg bw/day) LogKow LogKoc BIOWIN1 HHH Score1-Lauryl-2-pyrrolidone 3.78 5.3 3.756 0.9455 261H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, trisodium salt 6.53 -10.17 3.725 0.1278 262,3,4-Trifluorobenzoic Acid 7.17 2.13 1.861 -1.5894 262,4-Diflourobenzoate 3.22 1.93 1.638 -0.7708 261-Decanaminium, N-decyl-N,N-dimethyl-, chloride 14.50 4.66 5.686 0.792 26Oxirane, (butoxymethyl)- 2.47 1.08 1.167 0.0993 26Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (R)- 0.42 4.83 3.049 0.6827 26Decane 3.29 5.25 3.162 0.8967 26

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Dodecane 3.94 6.23 3.683 0.8833 26Nonane 2.37 4.76 2.901 0.9033 26Cyclotetrasiloxane, octamethyl- 16.50 6.79 4.159 0.6063 26Benzalkonium chloride 9.30 2.93 5.434 0.8222 26Undecane 0.81 5.74 3.422 0.89 26Benzoic acid, 2-(trifluoromethyl)- 2.36 2.49 2.064 0.3135 25m-Trifluoromethylbenzoic acid 1.17 2.84 2.056 0.3135 25Benzenamine, 4,4 -sulfonylbis- 11.20 0.77 2.411 0.1618 25Alcohols, C12-14-secondary, ethoxylated 18.10 3.32 2.142 -0.9157 251(p-NO2Ph)-2(aaatriFacetamido)ethanol 14.70 0.83 2.095 0.1585 25Quinolinium, 1-(1-naphthalenylmethyl)-, chloride 2.37 -0.34 6.21 0.602 22Pyridinium, 1-(phenylmethyl)-, Et Me derivs., chlorides 3.19 -1.27 4.529 0.867 22Isoquinolinium, 2-(phenylmethyl)-, chloride 8.62 -1.52 5.162 0.7539 22Alanine, N-(2-carboxyethyl)-N-dodecyl-, monosodium salt 1.36 -2.08 4.101 0.6392 221-Octadecanaminium, N,N,N-trimethyl-, chloride 101.00 4.17 5.385 0.6903 22Benzene, 1,2,4-trimethyl- 2.27 3.63 2.788 0.8543 212-Pentanamine, 4-methyl- 2.41 1.67 2.017 0.8532 211-Undecanol 11.70 4.28 2.365 0.9327 21Quinoline, 2-methyl- 2.29 2.69 3.394 0.734 21Thiocyanic acid, (2-benzothiazolylthio)methyl ester 1.94 3.12 3.528 0.6341 214-Nonanol, 2,6,8-trimethyl- 18.40 4.48 2.365 0.8176 219-Octadecenamide, N,N-bis(2-hydroxyethyl)-, (Z)- 13.90 5.62 3.161 1.2076 211-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acylderivs., hydroxides, inner salts 6.74 0.69 2.811 0.9753 21Pyridine, alkyl derivs. 3.13 2.39 2.547 0.6446 21Benzenesulfonic acid, C10-16-alkyl derivs., compds. with triethanolamine 11.50 4.04 3.341 0.8183 21Benzene, (1-methylethenyl)- 1.53 3.44 2.844 0.8194 21Amides, tall-oil fatty, N,N-bis(hydroxyethyl) 13.90 5.62 3.161 1.2076 21

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Phosphonic acid, nitrilotris(methylene) tris- 5.18 -5.45 2.005 0.3999 211-Decanamine, N,N-dimethyl-, N-oxide 3.20 3.69 3.382 0.7601 21Fatty acids, coco, ethoxylated 13.60 3.21 1.957 -0.4008 21Phenol, [(dimethylamino)methyl]- 1.52 1.27 2.566 0.5861 21Butanedioic acid, sulfo-, 1,4-bis(2-ethylhexyl) ester, sodium salt 3.80 3.95 2.881 1.22 21Dodecene-1-sulfonic acid, sodium salt 1.64 0.87 2.541 0.8451 212-chloromethylquinazoline 0.99 1.92 3.078 0.5511 21Glycerides, C14-18 mono- and di- 29.00 5.63 2.507 1.1903 21Heptane 2.32 3.78 2.38 0.8083 21Isoquinoline 3.96 2.14 3.189 0.6861 21Dodecyl sulfate, sodium salt 2.66 1.69 3.504 0.7292 21Naphthalene 7.43 3.17 3.189 1.0057 212-Pyrrolidinone, 1-ethenyl-, homopolymer 35.00 0.29 4.889 1.3755 21Sulfonic acids, C14-16-alkane hydroxy and C14-16-alkene, sodium salts 0.96 2.35 3.323 0.8251 21Sulfuric acid, monodecyl ester, sodium salt 3.29 0.71 2.983 0.7425 21Tridecane 24.30 6.73 3.944 0.8766 21

Table 8: Category 3 substances for human health hazard potential

Name Acute (LC50 mg/l) Chronic (ChV mg/l) LogKow LogKoc BIOWIN1 EH ScoreCyclohexane, 1,1,2,2,3,3,4,5,5,6-decafluoro-4,6-bis(trifluoromethyl)- 0.067 0.0120 6.02 5.813 -1.5873 50Perfluoroethylcyclohexane 0.135 0.0250 5.66 5.813 -1.2508 50

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1-Octadecene 0.0001 0.000 9.04 5.247 0.7358 411-Tetradecene 0.0040 0.001 7.08 4.204 0.7625 41Phenol, 4-nonyl- 0.039 0.0070 5.99 4.583 0.9215 412-Naphthalenecarboxamide, N-(5-chloro-2,4-dimethoxyphenyl)-4- 5- (diethylamino)sulfonyl -2-methoxyphenyl azo -3-hydro 0.004 0.0008 7.65 5.378 0.7464 41Hexadecane 0.001 0.0001 8.2 4.725 0.8566 411,2,3-Propanetricarboxylic acid, 2-(1-oxobutoxy)-, trihexyl ester 0.001 0.0002 8.21 7.048 1.3406 41Cyclotetrasiloxane, octamethyl- 0.011 0.0020 6.79 4.159 0.6063 419-Octadecenoic acid (Z)- 0.016 0.0030 7.73 4.068 0.7942 41

Table 9: Category 5 substances for ecological hazard potential

Name Acute (LC50 mg/l) Chronic (ChV mg/l) LogKow LogKoc BIOWIN1 EH Score1-Lauryl-2-pyrrolidone 0.176 0.032 5.3 3.756 0.9455 369-Octadecenamide, N,N-bis(2-hydroxyethyl)-, (Z)- 0.136 0.0250 5.62 3.161 1.2076 361-Decanaminium, N-decyl-N,N-dimethyl-, chloride 0.885 0.1590 4.66 5.686 0.792 36Amides, tall-oil fatty, N,N-bis(hydroxyethyl) 0.136 0.0250 5.62 3.161 1.2076 36Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (R)- 0.238 0.0430 4.83 3.049 0.6827 36Decane 0.107 0.0200 5.25 3.162 0.8967 36Dodecane 0.018 0.0030 6.23 3.683 0.8833 36Glycerides, C14-18 mono- and di- 0.117 0.0210 5.63 2.507 1.1903 36Nonane 0.256 0.0460 4.76 2.901 0.9033 36Tridecane 0.008 0.0020 6.73 3.944 0.8766 36Undecane 0.045 0.0080 5.74 3.422 0.89 361-Undecanol 0.8910 0.156 4.28 2.365 0.9327 314-Nonanol, 2,6,8-trimethyl- 0.653 0.1170 4.48 2.365 0.8176 31Butanedioic acid, sulfo-, 1,4-bis(2-ethylhexyl) ester, sodium salt 0.060 0.0110 3.95 2.881 1.22 311-Octadecanaminium, N,N,N-trimethyl-, chloride 2.245 0.3820 4.17 5.385 0.6903 31

17

Alcohols, C12-14-secondary, ethoxylated 13.859 1.8990 3.32 2.142 -0.9157 30Benzenamine, 4,4 -methylenebis- 64.614 6.6020 2.18 3.328 0.2403 30

Table 10: Category 4 substances for ecological hazard potentia

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3.3 Limitations of Study

This prioritisation scheme only considered modelled outcomes, as predicted by the appropriate software. This allowed for consistency across all data, as opposed to a composite data set comprising experimental and modelled data. However, experimental data can be imperfect and models can potentially be misleading due to incomplete data and the complex nature of the environment and its interactions. Models are also constrained by their paramaters, either being too conservative or speculative. Because of this, models sometimes to do not accurately represent, for example, ecological systems (Jaqaman and Danuser, 2006 and Chatzinikolaou, 2012). It is suggested by the United States Environmental Protection Agency (2015) that experimental data should be used in favour of modelled data when using EPI Suite. Toxicity, biodegradation and mobility parameters were all identically weighted, however, in a more comprehensive scheme, these should be given a different weighting to indicate how the substance is hazardous and in what way. Nonetheless, weighting can be arbitrary and less important than uncertainty in data (Faludi et al, 2016).

It is important to recongise that this study assesses the relative risk and hazard of organic substances across the entire catalogue of fracturing chemicals. This does not mean to say that every substance will be used in every well, but rather some of these substances will be selected. There is also the assumption that one substance will be used per category as outlined in Table 1. This is unlikely to be the case in practice, where multiple substances could be used, therefore making contamination more, or less, hazardous.

Ideally, inorganic compounds would have been included in this study, but due to the inability of EPI Suite to predict certain characteristics, they were omitted. Inorganic compounds contribute a large proportion to the fracturing fluid and are well noted more generally in the literature for their toxicity (Ruby et al, 1995; Galal, 2016 and Rodriguez-Hernandez et al, 2016). Degradation products were not included, nor was the hazard of chemical mixtures considered. Toxicity of chemical mixtures, whilst understood at least from a theoretical standpoint, is difficult to estimate due to the myriad mechanisms and systems in which it takes place, along with other variable factors. Whilst not considered in this study, it is something that should be addressed once the field is understood more comprehensively (McCarthy and Borgert, 2006).

In the United States, there is no law at the federal level requiring hydraulic fracturing companies to disclose information regarding chemicals used and their amounts. However, some states do require this disclosure. Currently, 28 states require full disclosure of the chemicals used, with the majority of states (82%) electing to use FracFocus (Konschnik and Dayalu, 2016). There are presently 109,955 wells registered on the database (FracFocus, 2016b). In addition, the constituents of proprietary mixtures do not need to be divulged (Maule et al, 2013). FracFocus does provide information on chemicals usage per well, but this is stated as a percentage of the total fluid, as opposed to mass. This makes it difficult to properly assess risk from contaminants, as data on the exact amounts used are not published. Whist the information provided about each well registered with FracFocus is relatively comprehensive, the number of wells would make a thorough assessment time consuming and complex. Further, it was hoped that the prioritised substances could be

19

categorised into the usage groups as outlined by Ferrer and Thurman (2015). However, there was little in the way of scientific evidence to suggest the usages of the priortised substances, so this was omitted. Complete transparency in the industry is something that may improve public perception, and would aid in the characterization of risk (McFeeley, 2012 and Boudet et al, 2014).

3.4 Scope

It is hoped that this study will add to the existing knowledge surrounding the hydraulic fracturing process, so as to recognise potentially hazardous substances for human and ecological health. Further study is needed to complete experimental data sets to accurately convey the hazard imposed by substances used in fracturing fluid, as in silico methods are not always accurate. Chemicals that are used in the United States fracturing industry may not necessarily be used in the United Kingdom, therefore these should be identified and assessed for their hazard potential. Cuadrilla Resources, who initiated the first fracturing operations at Preese Hall in Lancashire, state that thus far, they have only used water, polyacrylamide and salt to fracture shale gas. They also have the approval of the Environment Agency to use hydrochloric acid and glutaradehyde (Cuadrilla Resources, 2016). A comprehensive regulatory framework needs to be implemented to ensure that fracturing fluid does not contain hazardous materials that impact human and ecological health, as identified by this prioritisation study.

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4. Conclusion

Shale gas reserves present the United Kingdom with a significant energy source. However, the abundance of possibly hazardous substances, and the hydraulic fracturing process itself, means that it is potentially dangerous to human and ecological health. This prioritisation study has identified several substances that could be deleterious to these endpoints. The study utilised established prediction software, as well as newer models to estimate physicochemical and toxicity values, in order to create a valuable dataset for future use. Whilst the risk from hydraulic fracturing is yet to be fully researched, it is clear that current regulatory frameworks are insufficient in safeguarding human and ecological health. It is important to recognise that this study is an initial step toward characterising the full risk posed by fracturing fluid substances.

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Acknowledgements

I would like to thank my project supervisor, Alistair Boxall, for his continued support and guidance throughout my project. I would also like to thank friends and family for their support and interest in this project.

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Appendix I – SMILES Notation, CAS Numbers and Chemical Name

SMILES CAS NameO(CCCC)CCO 111762 Ethanol, 2-butoxy-C(n3(Cl)cccc4ccccc34)c1cccc2ccccc12 65322658 Quinolinium, 1-(1-naphthalenylmethyl)-, chlorideOCCCCCCCC 111875 1-Octanol

ClC=CC[N+](CN(C1)C2)(CN1C3)CN32.[Cl-] 40803133,5,7-Triaza-1-azoniatricyclo[3.3.1.13,7]decane, 1-(3-chloro-2-propenyl)-, chloride

O=C(N)C(C#N)(Br)Br 10222012 Acetamide, 2,2-dibromo-2-cyano-OCC(O)CO 56815 1,2,3-Propanetriolc(ccc(c1C)C)(c1)C 95636 Benzene, 1,2,4-trimethyl-NC(CC(C)C)C 108098 2-Pentanamine, 4-methyl-O=C(O)C(O)(CC(=O)O)CC(=O)O 77929 1,2,3-Propanetricarboxylic acid, 2-hydroxy-O=C(NSc1cccc2)c12 2634335 1,2-Benzisothiazol-3(2H)-oneOCCO 107211 1,2-EthanediolC(=CCl)CCl 542756 1-Propene, 1,3-dichloro-

CN(C)(C)(Cl)CC(O)CN(Cl)(C)(C)C 556360941,3-Propanediaminium, 2-hydroxy-N,N,N,N ,N ,N -hexamethyl-,dichloride

O=C(c1ccc(cc1)C(=O)O)O 9016880 1,4-Benzenedicarboxylic acidO=C(O)C(N)CCC(=O)N 56859 L-GlutamineO(CC(O)C)CCCC 5131668 2-Propanol, 1-butoxy-OCCCCCCCCCCCCS(=O)(=O)[O-].[Na+] 128824306 1-Dodecanesulfonic acid, hydroxy-, sodium saltO=C1CCCN1CCCCCCCCCCCC 2687969 1-Lauryl-2-pyrrolidone[O-]c2c(N=Nc1ccc(cc1)S([O-])(=O)=O)c(nn2c3ccc(cc3)S([O-])(=O)=O)C([O-])=O.[Na+].[Na+].[Na+].[Na+] 1934210

1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, trisodium salt

OCCCCCCCCCC 112301 1-DecanolC[N+](C)(C)C.[Cl-] 75570 Methanaminium, N,N,N-trimethyl-, chlorideC(=C)CCCCCCCCCCCCCCCC 112889 1-Octadecene

23

OS(=O)(=O)CC(CN(CC(O)COCCCC)(C)C)O 1087978481-Propanaminium, 3-butoxy-2-hydroxy-N-(2-hydroxy-3-sulfopropyl)-N,N-dimethyl-, hydroxide, inner salt

C(=C)CCCCCCCCCCCC 1120361 1-TetradeceneOCCCCCCCCCCC 112425 1-UndecanolOCC(CCCC)CC 104767 1-Hexanol, 2-ethyl-OCCS 60242 Ethanol, 2-mercapto-n(c(c(ccc1)cc2)c1)c2C 91634 Quinoline, 2-methyl-O=C(O)C(P(=O)(O)O)(CC(=O)O)CCC(=O)O 37971361 1,2,4-Butanetricarboxylic acid, 2-phosphono-O=C(O)C=C 79107 2-Propenoic acidc1ccc2N=C(SCSC(#N))Sc2c1 21564170 Thiocyanic acid, (2-benzothiazolylthio)methyl esterOC(=O)c1ccccc1C(F)(F)F 433976 Benzoic acid, 2-(trifluoromethyl)-N(CCN)CCN 111400 1,2-Ethanediamine, N-(2-aminoethyl)-O=C(N)C(Br)(Br)C(=O)N 73003802 Propanediamide, 2,2-dibromo-OC(=O)c1c(c(c(cc1)F)F)F 61079729 2,3,4-Trifluorobenzoic AcidOC(=O)c1c(F)cc(F)cc1 1583580 2,4-DiflourobenzoateOC(CC(O)(C)C)C 107415 2,4-Pentanediol, 2-methyl-OC(CC(CC(C)C)C)CC(C)C 123171 4-Nonanol, 2,6,8-trimethyl-OCC=C(CCC=C(C)C)C 106241 2,6-Octadien-1-ol, 3,7-dimethyl-, (E)-[O-]c4c(N=Nc1ccc(c2ccccc12)S([O-])(=O)=O)c3ccc(cc3cc4S([O-])(=O)=O)S([O-])(=O)=O.[Na+].[Na+].[Na+].[Na+] 915673

2,7-Naphthalenedisulfonic acid, 3-hydroxy-4-[(4-sulfo-1-naphthalenyl)azo]-, trisodium salt

Oc2ccc1cc(ccc1c2N=Nc3ccc(cc3)S([O-])(=O)=O)S([O-])(=O)=O.[Na+].[Na+] 27839402-Naphthalenesulfonic acid, 6-hydroxy-5-[(4-sulfophenyl)azo]-, disodium salt

OC(=O)CC(C(=O)O)(P(=O)(O)O)CCC(=O)[O-].[K+] 938587871,2,4-Butanetricarboxylic acid, 2-phosphono-, potassium salt

OCC#C 107197 2-Propyn-1-olOC(=O)c1cccc(c1)C(F)(F)F 454922 m-Trifluoromethylbenzoic acid[Si](O)(O)(O)CCCN 58160999 Silanetriol, (3-aminopropyl)-O=S(=O)(c(ccc(N)c1)c1)c(ccc(N)c2)c2 80080 Benzenamine, 4,4 -sulfonylbis-

24

Oc(ccc(c1)CCCCCCCCC)c1 104405 Phenol, 4-nonyl-O=C(NC(C1=O)(C)C)N1 77714 2,4-Imidazolidinedione, 5,5-dimethyl-O=C(N(CCO)CCO)CCCCCCCC=CCCCCCCCC 93834 9-Octadecenamide, N,N-bis(2-hydroxyethyl)-, (Z)-O=C(O)C 64197 Acetic acidO=C(C)C 67641 2-PropanoneO=C(c(cccc1)c1)C 98862 Ethanone, 1-phenyl-

O=C(OC(C(=O)OCC)(CC(=O)OCC)CC(=O)OCC)C 778941,2,3-Propanetricarboxylic acid, 2-(acetyloxy)-, triethyl ester

O=C(O)CCCCC(=O)O 124049 Hexanedioic acid

CCCCCCCCCCCC(=O)NCCCN(C)(C)CC(=O)O 617894001-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acylderivs., hydroxides, inner salts

CCCCCCCCCC(CC)OCCOCCOCCOCCOCCO 84133506 Alcohols, C12-14-secondary, ethoxylated

CCC1=C(C)C=N(CC2=CC=CC=C2)(Cl)C=C1 68909182Pyridinium, 1-(phenylmethyl)-, Et Me derivs., chlorides

n1ccc(C)cc1CC 68391117 Pyridine, alkyl derivs.N(Cl)(C)(C)(CCCCCCCCCC)CCCCCCCCCC 7173515 1-Decanaminium, N-decyl-N,N-dimethyl-, chloride

CCCCCCCCCCc1ccc(cc1)S(=O)(=O)OCCN(CCO)CCO 68584258Benzenesulfonic acid, C10-16-alkyl derivs., compds. with triethanolamine

c(C(=C)C)(cccc1)c1 98839 Benzene, (1-methylethenyl)-CCCCCCCCC=CCCCCCCCC(=O)N(CCO)CCO 68155204 Amides, tall-oil fatty, N,N-bis(hydroxyethyl)CCCCCCCCCCCC(=O)N(CCO)CCO 68603429 Amides, coco, N,N-bis(hydroxyethyl)OCCN 141435 Ethanol, 2-amino-O=P(O)(O)CN(CP(=O)(O)O)CP(=O)(O)O 6419198 Phosphonic acid, nitrilotris(methylene) tris-N(CCNC1)(C1)CCN 140318 1-PiperazineethanamineC[N+](C)(C)CCO.[Cl-] 67481 Choline chloride

CC3(C)SC2C(NC(=O)C(N)c1ccccc1)C(=O)N2C3C(=O)(O) 69534

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(aminophenylacetyl)amino]-3,3-dimethyl-7-oxo, [2s-[2‡,5‡,6 (s*)

O=Cc(cccc1)c1 100527 Benzaldehyde

25

Nc(ccc(c1)Cc(ccc(N)c2)c2)c1 101779 Benzenamine, 4,4 -methylenebis-c1(C[N+](C)(C)C)ccccc1.[Cl-] 56939 Benzenemethanaminium, N,N,N-trimethyl-, chlorideOCCCC 71363 1-Butanol

CC(C)CC(C)OC(=O)C(S(=O)(=O)[O-])CC(=O)OC(C)CC(C)C.[Na+] 2373388Butanedioic acid, sulfo-, 1,4-bis(1,3-dimethylbutyl) ester, sodium salt

O(C1COCCCC)C1 2426086 Oxirane, (butoxymethyl)-

O=C(Nc(c(OC)cc(OC)c1Cl)c1)c(c(O)c(N=Nc(c(OC)ccc2S(=O)(=O)N(CC)CC)c2)c(c3ccc4)c4)c3 6410419

2-Naphthalenecarboxamide, N-(5-chloro-2,4-dimethoxyphenyl)-4- 5- (diethylamino)sulfonyl -2-methoxyphenyl azo -3-hydro

O=N(CCCCCCCCCC)(C)C 2605790 1-Decanamine, N,N-dimethyl-, N-oxideO=CC=Cc(cccc1)c1 104552 2-Propenal, 3-phenyl-CCCCCCCCCCCC(=O)OCCOCCOCCOCCOCCO 61791295 Fatty acids, coco, ethoxylatedC(=CCC(C(=C)C)C1)(C1)C 5989275 Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (R)-C(CCCCCCCC)C 124185 Decane

OCC(O)C1OC(=O)C(=C1O)[O-].[Na+] 6381777D-erythro-Hex-2-enonic acid, ‚-lactone, monosodiumsalt

OCC(O)C(O)C(O)C(O)CO 50704 D-GlucitolO=CN(C)C 68122 Foramide, N,N-dimethyl-O=C(OC)CCCC(=O)OC 1119400 Pentanedioic acid, dimethyl esterOc1ccc(cc1)CN(C)C 25338550 Phenol, [(dimethylamino)methyl]-

CCCCC(CC)COC(=O)CC(C(=O)OCC(CC)CCCC)S(=O)(=O)[O-].[Na+] 577117Butanedioic acid, sulfo-, 1,4-bis(2-ethylhexyl) ester, sodium salt

O(CCOC1)C1 123.911 1,4-DioxaneC(CCCCCCCCCC)C 112403 DodecaneO=S(=O)([O-])CCCCCCCCCCCC.[Na+] 30965856 Dodecene-1-sulfonic acid, sodium saltNCCN 107153 1,2-EthanediamineOCC(O)C1C(O)=C(O)C(=O)O1 89656 D-erythro-Hex-2-enonic acid, .gamma.-lactoneCCCCC(CC)COS([O-])(=O)=O.[Na+] 126921 Sodium 2-ethylhexyl sulfateSCC 75081 Ethanethiol

26

O=C(O)CN(CCN(CC(=O)O)CC(=O)O)CC(=O)O 60004 Glycine, N,N -1,2-ethanediylbis[N-(carboxymethyl)-ClCc(nc(ccc1)c2c1)nc2 5000 2-chloromethylquinazolineO=C(O)C=CC(=O)O 110178 2-Butenedioic acid (E)-C1=C(CO)OC=C1 98000 2-FuranmethanolOCC(O)COC(CCCCCCCCCCCCCCC)=O 67701331 Glycerides, C14-18 mono- and di-C(CCCCC)C 142825 HeptaneC(CCCCCCCCCCCCCC)C 544763 HexadecaneCC(=O)NC(=O)C 57136 UreaO=C(N)N 75285 Propane, 2-methyl-CCCCCCCCCCOCCOCCOCCOCCOCCO 35674567 Isoquinolinium, 2-(phenylmethyl)-, chloridec(ccc1cn2(Cl)Cc(ccc3)cc3)cc1cc2 119653 IsoquinolineCCCCCCCCCCCC 63423 D-Glucose, 4-O-.beta.-D-galactopyranosyl-

O=CC(O)C(O)C(OC(OC(C(O)C1O)CO)C1O)C(O)CO 131977671-Dodecanaminium, N-(2-hydroxy-3-sulfopropyl)-N,N-dimethyl-, hydroxide, inner salt-

CCCCCCCCCCCCOCC 151213 Dodecyl sulfate, sodium saltO=C(CCCCCCCC=CCC=CCC=CCC)OCC(OC(CCCCCCCC=CCC=CCCCCC)=O)COC(CCCCCCCC=CCC=CCC=CCC)=O 108316 2,5-FurandioneO=C(O)C(C#N)C 591 1(p-NO2Ph)-2(aaatriFacetamido)ethanol

OC(c1ccc(N(=O)(=O))cc1)CNC(=O)C(F)(F)F 335273Cyclohexane, 1,1,2,2,3,3,4,5,5,6-decafluoro-4,6-bis(trifluoromethyl)-

O=C(CC(C)C)C 108112 2-Pentanol, 4-methyl-OC(CC(C)C)C 121437 Trimethyl borateO(C1C)C1 110918 MorpholineO(CCNC1)C1 91203 Naphthalenec(c(ccc1)ccc2)(c1)c2 1760243 1,2-Ethanediamine, N-[3-(trimethoxysilyl)propyl]-NCCNCCC[Si](OC)(OC)OC 106978 Butane

C(CC)C 824697921,2,3-Propanetricarboxylic acid, 2-(1-oxobutoxy)-, trihexyl ester

27

[O-]C(=O)CN(CC([O-])=O)CC([O-])=O.[Na+].[Na+].[Na+] 18662538 Trisodium nitrilotriacetate monohydrateO=C1CCCN1C 111842 NonaneC(C)CC(C)CC(C)Cc1ccc(OCCOCCOCCOCCOCCO)cc1 109660 PentaneOCCC 556672 Cyclotetrasiloxane, octamethyl-O(CC1O)C(C1O)C(O)COC(=O)CCCCCCCC=CCCCCCCCC 112801 9-Octadecenoic acid (Z)-c1cc(CCCCCCCCC)ccc1OCCOCCOCCOCCOCCO 4067167 3,6,9,12-Tetraazatetradecane-1,14-diamineCCCCCCCCCCCCCCCCCCCC 335217 (pentafluoroethyl)undecafluorocyclohexaneCCCCCCCCC=CCCCCCCCCOCCOCCOCCOCCOCCO 9002895 Ethenol, homopolymerOCC(C)OC(C)COCC(C)OC(C)COCC(C)O 9003398 2-Pyrrolidinone, 1-ethenyl-, homopolymerCC(N2CCCC2=O)CC(N3C(CCC3)=O)CC(N4C(CCC4)=O)CCN1CCCC1=O 128030 Carbamodithioic acid, dimethyl-, potassium saltS=C([S-])N(CC)CC.[K+] 8001545 Benzalkonium chloride

CCCCCCCCC=CCCCCCCCC(=O)OC 51659791-Propanesulfonic acid, 2-methyl-2-[(1-oxo-2-propenyl)amino]-, monosodium salt

S(=O)(=O)([O-])CC(C)(C)NC(=O)C=C.[Na+] 68439576Sulfonic acids, C14-16-alkane hydroxy and C14-16-alkene, sodium salts

CCCCCCCCCCCCCCCS(=O)(=O)[O-].[Na+] 144558 Sodium bicarbonateOC([O-])=O.[Na+] 35249695 2,2'-Oxybisacetic acid, disodium salt[O-]C([O-])=O.[Na+].[Na+] 870724 Methanesulfonic acid, hydroxy-, monosodium salt

S(=O)(=O)([O-])CO.[Na+] 14960066Alanine, N-(2-carboxyethyl)-N-dodecyl-, monosodium salt

[O-]C(=O)C(O)C.[Na+] 540727 Sodium thiocyanateOCC(C(C(C(COC(=O)CCCCCCCC=CCCCCCCCC)OC(=O)CCCCCCCC=CCCCCCCCC)OC(=O)CCCCCCCC=CCCCCCCCC)OC(=O)CCCCCCCC=CCCCCCCCC)OC(=O)CCCCCCCC=CCCCCCCCC 57501 .alpha.-D-Glucopyranoside, .beta.-D-fructofuranosylCCCCCCCCCC 142870 Sulfuric acid, monodecyl ester, sodium salt

O=C(N(C(=O)C)CCN(C(=O)C)C(=O)C)C 67038

Thiazolium, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methyl- chloride, monohydrochloride

N(CCNCCNCCN)CCN 62566 Thiourea

28

NC(=S)N 4719044 1,3,5-Triazine-1,3,5(2H,4H,6H)-triethanolO=P(OCC)(OCC)OCC 629505 TridecaneOC(C)CN(CC(O)C)CC(O)C 112038 1-Octadecanaminium, N,N,N-trimethyl-, chlorideCCCCCCCCCCCCCCCCCC[N+](C)(C)C.[Cl-] 1120214 Undecane

29

Appendix II – Chemical Name and Hazard Information

Name

Maximum Recommended Daily Dose (mg/kg bw/day) Acute (LC50)

Chronic (ChV)

LogKow

LogKoc

BIOWIN1

Ethanol, 2-butoxy- 4.31 935.818 63.143 0.570.45

1 0.6111Quinolinium, 1-(1-naphthalenylmethyl)-, chloride 2.37 14629.571 720.325 -0.34 6.21 0.602

1-Octanol 1.69 12.373 1.484 2.811.58

3 0.95273,5,7-Triaza-1-azoniatricyclo[3.3.1.13,7]decane, 1-(3-chloro-2-propenyl)-, chloride 29.00 732000000.000

1360000.000 -5.92

1.532 -0.0992

Acetamide, 2,2-dibromo-2-cyano- 21.30 803.166 60.678 1.010.73

1 0.8733

1,2,3-Propanetriol 19.10 58451.7541334.35

2 -1.76 0 1.1799

Benzene, 1,2,4-trimethyl- 2.27 2.218 0.329 3.632.78

8 0.8543

2-Pentanamine, 4-methyl- 2.41 90.592 8.116 1.672.01

7 0.8532

1,2,3-Propanetricarboxylic acid, 2-hydroxy- 15.70 1270000.00028660.2

52 -1.67 1 0.6902

1,2-Benzisothiazol-3(2H)-one 1.84 1042.151 71.597 0.641.53

8 0.67561,2-Ethanediol 32.50 16103.915 479.638 -1.2 0 1.0355

1-Propene, 1,3-dichloro- 12.80 29.199 3.068 2.291.85

8 0.47191,3-Propanediaminium, 2-hydroxy-N,N,N,N ,N ,N -hexamethyl-,dichloride 2680.00

1400000000000.000

274000000.000 -9.75 1 0.7886

1,4-Benzenedicarboxylic acid 16.40 1255.403 114.982 1.761.89

9 1.022L-Glutamine 22.30 25400000.000 109000. -4.49 1 1.1146

30

000

2-Propanol, 1-butoxy- 2.33 458.778 34.462 0.980.63

6 0.6044

1-Dodecanesulfonic acid, hydroxy-, sodium salt 1.67 2989.699 260.095 -0.591.48

4 0.8878

1-Lauryl-2-pyrrolidone 3.78 0.176 0.032 5.33.75

6 0.9455

1H-Pyrazole-3-carboxylic acid, 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-4-[(4-sulfophenyl)azo]-, trisodium salt 6.53 11668.466 678.277

-10.1

73.72

5 0.1278

1-Decanol 10.80 2.160 0.333 3.792.10

4 0.9393

Methanaminium, N,N,N-trimethyl-, chloride 0.35 10300000.00053181.1

99 -4.180.91

5 0.6954

1-Octadecene 5.01 0.0001 0.000 9.045.24

7 0.73581-Propanaminium, 3-butoxy-2-hydroxy-N-(2-hydroxy-3-sulfopropyl)-N,N-dimethyl-, hydroxide, inner salt 10.90

14300000000.0000

23300000.000 -6.14 1 0.7848

1-Tetradecene 5.01 0.0040 0.001 7.084.20

4 0.7625

1-Undecanol 11.70 0.8910 0.156 4.282.36

5 0.9327

1-Hexanol, 2-ethyl- 7.85 14.307 1.6840 2.731.54

7 0.9527

Ethanol, 2-mercapto- 50.60 2799.436150.206

0 -0.2 0.28 0.8691

Quinoline, 2-methyl- 2.29 17.091 1.9900 2.693.39

4 0.734

1,2,4-Butanetricarboxylic acid, 2-phosphono- 8.41 1740000.00039499.4

060 -1.661.40

4 0.6531

2-Propenoic acid 0.37 7306.543477.401

0 0.440.15

8 0.7859

31

Thiocyanic acid, (2-benzothiazolylthio)methyl ester 1.94 12.211 1.5870 3.123.52

8 0.6341

Benzoic acid, 2-(trifluoromethyl)- 2.36 333.588 36.9440 2.492.06

4 0.3135

1,2-Ethanediamine, N-(2-aminoethyl)- 40.20 169000.0002910.52

40 -2.131.52

9 1.1599

Propanediamide, 2,2-dibromo- 17.50 3020.389193.875

0 0.370.57

1 0.7679

2,3,4-Trifluorobenzoic Acid 7.17 631.464 63.7240 2.131.86

1 -1.5894

2,4-Diflourobenzoate 3.22 842.345 80.7380 1.931.63

8 -0.77082,4-Pentanediol, 2-methyl- 20.20 911.009 61.6840 0.58 0 0.6661

4-Nonanol, 2,6,8-trimethyl- 18.40 0.653 0.1170 4.482.36

5 0.8176

2,6-Octadien-1-ol, 3,7-dimethyl-, (E)- 2.70 3.943 0.5610 3.471.97

4 0.8328 2,7-Naphthalenedisulfonic acid, 3-hydroxy-4-[(4-sulfo-1-naphthalenyl)azo]-, trisodium salt 2.29 521.648 46.2590 -5.13

6.288 -0.3062

2-Naphthalenesulfonic acid, 6-hydroxy-5-[(4-sulfophenyl)azo]-, disodium salt 2.93 621.444 51.9650 -1.18 4.4 -0.0284

1,2,4-Butanetricarboxylic acid, 2-phosphono-, potassium salt 13.10 1740000.00039499.4

060 -5.471.40

4 0.6531

2-Propyn-1-ol 9.54 3128.298147.141

0 -0.42 0.28 0.8796

m-Trifluoromethylbenzoic acid 1.17 169.568 20.5070 2.842.05

6 0.3135

Silanetriol, (3-aminopropyl)- 29.00 931000.00010509.9

780 -2.852.24

3 0.8361

Benzenamine, 4,4 -sulfonylbis- 11.20 1307.812 93.0490 0.772.41

1 0.1618Phenol, 4-nonyl- 0.84 0.039 0.0070 5.99 4.58 0.9215

32

3

2,4-Imidazolidinedione, 5,5-dimethyl- 6.04 5320.082289.369

0 -0.270.45

2 0.5026

9-Octadecenamide, N,N-bis(2-hydroxyethyl)-, (Z)- 13.90 0.136 0.0250 5.623.16

1 1.2076

Acetic acid 16.20 12270.444731.892

0 0.09 0 0.7916

2-Propanone 0.34 2241.103117.629

0 -0.240.37

4 0.7267

Ethanone, 1-phenyl- 1.60 106.803 9.5780 1.671.71

5 0.8253

1,2,3-Propanetricarboxylic acid, 2-(acetyloxy)-, triethyl ester 10.40 547.714 45.0730 1.343.37

9 1.1088

Hexanedioic acid 6.71 22596.6111397.58

10 0.231.38

6 0.82341-Propanaminium, 3-amino-N-(carboxymethyl)-N,N-dimethyl-, N-coco acylderivs., hydroxides, inner salts 6.74 17977.443 7.0030 0.69

2.811 0.9753

Alcohols, C12-14-secondary, ethoxylated 18.10 13.859 1.8990 3.322.14

2 -0.9157

Pyridinium, 1-(phenylmethyl)-, Et Me derivs., chlorides 3.19 74198.7502117.67

10 -1.274.52

9 0.867

Pyridine, alkyl derivs. 3.13 26.149 2.8190 2.392.54

7 0.6446

1-Decanaminium, N-decyl-N,N-dimethyl-, chloride 14.50 0.885 0.1590 4.665.68

6 0.792Benzenesulfonic acid, C10-16-alkyl derivs., compds. with triethanolamine 11.50 3.546 0.5840 4.04

3.341 0.8183

Benzene, (1-methylethenyl)- 1.53 3.190 0.4510 3.442.84

4 0.8194

Amides, tall-oil fatty, N,N-bis(hydroxyethyl) 13.90 0.136 0.0250 5.623.16

1 1.2076Amides, coco, N,N-bis(hydroxyethyl) 4.89 23.336 2.8570 2.89 1.59 1.2467

33

7

Ethanol, 2-amino- 16.80 35809.410836.999

0 -1.610.06

7 1.031

Phosphonic acid, nitrilotris(methylene) tris- 5.18 345000000.000846000.

0000 -5.452.00

5 0.3999

1-Piperazineethanamine 28.20 69369.9771664.37

60 -1.571.63

4 0.7884

Choline chloride 2.11 89800000.000262000.

0000 -5.160.15

8 0.83984-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(aminophenylacetyl)amino]-3,3-dimethyl-7-oxo, [2s-[2‡,5‡,6 (s*) 19.70 479.481 40.6360 1.45

1.926 1.1722

Benzaldehyde 0.90 87.754 7.9440 1.711.04

5 1.1097

Benzenamine, 4,4 -methylenebis- 5.38 64.614 6.6020 2.183.32

8 0.2403

Benzenemethanaminium, N,N,N-trimethyl-, chloride 1.67 597000.0008416.34

10 -2.472.52

7 0.78721-Butanol 4.57 341.334 24.7140 0.84 0.54 0.9794

Butanedioic acid, sulfo-, 1,4-bis(1,3-dimethylbutyl) ester, sodium salt 4.42 57.144 1.6860 1.841.64

8 1.0298

Oxirane, (butoxymethyl)- 2.47 373.880 28.7850 1.081.16

7 0.09932-Naphthalenecarboxamide, N-(5-chloro-2,4-dimethoxyphenyl)-4- 5- (diethylamino)sulfonyl -2-methoxyphenyl azo -3-hydro 5.70 0.004 0.0008 7.65

5.378 0.7464

1-Decanamine, N,N-dimethyl-, N-oxide 3.20 3.327 0.5010 3.693.38

2 0.7601

2-Propenal, 3-phenyl- 1.53 88.322 8.2200 1.021.56

6 1.0973

Fatty acids, coco, ethoxylated 13.60 17.868 2.3800 3.211.95

7 -0.4008

Cyclohexene, 1-methyl-4-(1-methylethenyl)-, (R)- 0.42 0.238 0.0430 4.833.04

9 0.6827

34

Decane 3.29 0.107 0.0200 5.253.16

2 0.8967

D-erythro-Hex-2-enonic acid, ‚-lactone, monosodiumsalt 109.00 13677.381175000.

0000 -7.05 1 1.4728

D-Glucitol 51.40 1690000.00017398.0

310 -3.01 1 1.6132

Foramide, N,N-dimethyl- 0.49 11215.138390.497

0 -0.93 0 0.9229Pentanedioic acid, dimethyl ester 0.54 661.763 48.5940 0.9 1 1.0197

Phenol, [(dimethylamino)methyl]- 1.52 300.594 24.2770 1.272.56

6 0.5861

Butanedioic acid, sulfo-, 1,4-bis(2-ethylhexyl) ester, sodium salt 3.80 0.060 0.0110 3.952.88

1 1.22

1,4-Dioxane 17.50 4019.757200.733

0 -0.320.42

1 0.0109

Dodecane 3.94 0.018 0.0030 6.233.68

3 0.8833

Dodecene-1-sulfonic acid, sodium salt 1.64 155.572 19.7200 0.872.54

1 0.8451

1,2-Ethanediamine 6.81 35666.352830.625

0 -1.621.17

2 1.0266

D-erythro-Hex-2-enonic acid, .gamma.-lactone 86.70 175000.0003499.59

40 -1.88 1 1.4728

Sodium 2-ethylhexyl sulfate 5.49 2389.094153.807

0 -0.352.42

6 0.7559

Ethanethiol 13.70 123.242 9.9560 1.271.33

7 0.718

Glycine, N,N -1,2-ethanediylbis[N-(carboxymethyl)- 41.00 14500000.00090389.3

440 -3.862.49

5 0.4887

2-chloromethylquinazoline 0.99 98.066 9.3630 1.923.07

8 0.55112-Butenedioic acid (E)- 0.23 25294.803 1496.16 0.05 0.86 0.8377

35

70 5

2-Furanmethanol 2.97 987.410 64.5780 0.451.07

1 0.8596

Glycerides, C14-18 mono- and di- 29.00 0.117 0.0210 5.632.50

7 1.1903Heptane 2.32 1.391 0.2140 3.78 2.38 0.8083

Hexadecane 5.24 0.001 0.0001 8.24.72

5 0.8566

Urea 3.73 31463.209760.407

0 -1.560.49

9 0.719

Propane, 2-methyl- 6.66 17.133 1.7740 2.331.50

3 0.7199

Isoquinolinium, 2-(phenylmethyl)-, chloride 8.62 125000.0003082.49

10 -1.525.16

2 0.7539

Isoquinoline 3.96 45.455 4.5980 2.143.18

9 0.6861

D-Glucose, 4-O-.beta.-D-galactopyranosyl- 3.94 170000000.000536000.

0000 -5.03 1 1.44431-Dodecanaminium, N-(2-hydroxy-3-sulfopropyl)-N,N-dimethyl-, hydroxide, inner salt- 41.80 1120000.000

31318.3870 -1.3

1.989 0.9552

Dodecyl sulfate, sodium salt 2.66 54.004 5.8960 1.693.50

4 0.72922,5-Furandione 12.50 97.150 8.5900 1.62 0 0.7009

1(p-NO2Ph)-2(aaatriFacetamido)ethanol 14.70 1298.108 93.8250 0.832.09

5 0.1585

Cyclohexane, 1,1,2,2,3,3,4,5,5,6-decafluoro-4,6-bis(trifluoromethyl)- 0.97 0.067 0.0120 6.025.81

3 -1.5873

2-Pentanol, 4-methyl- 0.29 90.360 8.1090 1.680.91

1 0.8576

Trimethyl borate 5.50 107000.0002119.93

70 -1.92.34

4 0.6981Morpholine 0.06 6381.099 276.817 -0.56 0.87 0.5125

36

0 6

Naphthalene 7.43 5.937 0.7820 3.173.18

9 1.0057

1,2-Ethanediamine, N-[3-(trimethoxysilyl)propyl]- 2.76 147000.0003321.66

70 -1.673.47

7 0.9493

Butane 60.00 14.818 1.5630 2.311.59

8 0.8283

1,2,3-Propanetricarboxylic acid, 2-(1-oxobutoxy)-, trihexyl ester 3.99 0.001 0.0002 8.217.04

8 1.3406

Trisodium nitrilotriacetate monohydrate 55.10 8590000.0001340000

.0000

-10.0

81.41

9 0.6694

Nonane 2.37 0.256 0.0460 4.762.90

1 0.9033

Pentane 10.00 6.971 0.8340 2.81.85

8 0.8216

Cyclotetrasiloxane, octamethyl- 16.50 0.011 0.0020 6.794.15

9 0.6063

9-Octadecenoic acid (Z)- 9.24 0.016 0.0030 7.734.06

8 0.7942

3,6,9,12-Tetraazatetradecane-1,14-diamine 3.35 8010000.00055755.2

420 -3.672.59

8 1.5599

(pentafluoroethyl)undecafluorocyclohexane 6.54 0.135 0.0250 5.665.81

3 -1.2508

Ethenol, homopolymer 14.30 413000000.0001110000

.0000 -5.35.94

8 2.2619

2-Pyrrolidinone, 1-ethenyl-, homopolymer 35.00 6053.863380.889

0 0.294.88

9 1.3755

Carbamodithioic acid, dimethyl-, potassium salt 14.00 132.738 11.9030 -1.432.31

1 0.6765

Benzalkonium chloride 9.30 25.344 3.1370 2.935.43

4 0.8222

37

1-Propanesulfonic acid, 2-methyl-2-[(1-oxo-2-propenyl)amino]-, monosodium salt 3.54 383000.00

6364.2520 -4.34 1 0.7835

Sulfonic acids, C14-16-alkane hydroxy and C14-16-alkene, sodium salts 0.96 9.892 1.7750 2.35

3.323 0.8251

Sodium bicarbonate 3.76 3736.610171.793

0 -4.01 0 0.718

2,2'-Oxybisacetic acid, disodium salt 17.20 1710000.00031957.0

100 -7.270.25

4 0.4817

Methanesulfonic acid, hydroxy-, monosodium salt 21.70 54300000.000342000.

0000 -5.99 0 0.9613

Alanine, N-(2-carboxyethyl)-N-dodecyl-, monosodium salt 1.36 832.194 65.1490 -2.084.10

1 0.6392

Sodium thiocyanate 115.00 453.059 30.6980 -2.520.66

9 0.7194

.alpha.-D-Glucopyranoside, .beta.-D-fructofuranosyl 49.10 38300000.000188000.

0000 -4.27 1 0.6284

Sulfuric acid, monodecyl ester, sodium salt 3.29 336.379 28.4050 0.712.98

3 0.7425Thiazolium, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methyl- chloride, monohydrochloride 13.20 43000000.000

193000.0000 -4.42

2.587 0.7

Thiourea 73.70 24556.568685.706

0 -1.310.93

3 0.9215

1,3,5-Triazine-1,3,5(2H,4H,6H)-triethanol 0.19 53800000.000209000.

0000 -4.67 1 0.5036

Tridecane 24.30 0.008 0.0020 6.733.94

4 0.8766

1-Octadecanaminium, N,N,N-trimethyl-, chloride 101.00 2.245 0.3820 4.175.38

5 0.6903

Undecane 0.81 0.045 0.0080 5.743.42

2 0.89

38

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