# Update of Human Health Ambient Water Quality Criteria: Chloroform 67

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- 02 7 June 2015EPA 820 -R- 15

- 02 7 June 2015



# Update of Human Health Ambient Water Quality Criteria: Chloroform 67

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Office of Science and Technology Office of Water U.S. Environmental Protection Agency Washington, DC 20460Chloroform 67

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Table of Contents
1 Introduction: Background and Scope of Update

..................................................................... 2 2 Problem Formulation

............................................................................................................... 3 3 Criteria Formulas: Analysis Plan

.............................................................................................. 4 4 Exposure Factors

..................................................................................................................... 5 4.1 Body Weight

.................................................................................................................. 5 4.2 Drinking W ater Intake

................................................................................................... 6 4.3 Fish Consumption Rate

................................................................................................ . 6 4.4 Bioaccumulation Factor

................................................................................................ 7 4.4.1 Approach

......................................................................................................... 7 4.4.2 Chemical

- specific BAFs

.................................................................................... 9 5 Hazard Identification and Dose Response

............................................................................. 10 5.1 Approach

..................................................................................................................... 10 5.2 Chemical

- specific Toxicity Value

................................................................................. 11 5.2.1 Reference Dose

.............................................................................................. 11 5.2.2 Cancer Slope Factor

....................................................................................... 12 6 Relative Source Contribution

................................................................................................ . 12 6.1 Approach

..................................................................................................................... 12 6.2 Chemical

- spe cific RSC

................................................................................................ . 13 7 Criteria Derivation: Analysis

.................................................................................................. 15 7.1 AWQC for Noncarcinogenic Toxicological Effects

...................................................... 15 7.2 AWQC for Carcinogenic Toxicological Effects

............................................................. 16 7.3 AWQC Summary

......................................................................................................... 16 8 Criteria Characterization

........................................................................................................ 16 9 Chemical Name and Synonyms

............................................................................................. 19 10 References

............................................................................................................................. 19

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1 Introduction: Background and Scope of Updat e EPA’s recommended ambient water quality criteria (AWQC) for human health are scientifically derived numeric values that EPA has determined will adequately protect human health from the adverse effects of pollutants in ambient water. Section 304(a)(1) of the Clean Water Act (CWA) requires EPA to develop and publish, and from time to time revise, recommended criteria for the protection of water quality that accurately reflect the latest scientific knowledge. Water quality criteria developed under section 30 4(a) are based solely on data and scientific judgments on the relationship between pollutant concentrations and environmental and human health effects. Section 304(a) criteria do not reflect consideration of economic impacts or the technological feasibility of meeting pollutant concentrations in ambient water. EPA’s recommended section 304(a) criteria provide technical information for states and authorized tribes a to consider and use in adopting water quality standards that ultimately provide the basis for assessing water body health and controlling discharges of pollutants into waters of the United States. Under the CWA and its implementing regulations, states and authorized tribes are required to adopt water quality criteria to protect the designated uses of waters (e.g., public water supply, aquatic life, recreational use, industrial use). EPA’s recommended water quality criteria do not substitute for the CWA or regulations, nor are they regulations themselves. Thus, EPA’s recommended criteria do not impos e legally binding requirements. States and authorized tribes may adopt, where appropriate, other scientifically defensible water quality criteria that differ from these recommendations. The water quality criteria that are the subject of this document are n ational AWQC recommendations for human health issued under CWA section 304(a). Unless expressly indicated otherwise, all references to “criteria,” “water quality criteria,” “ambient water quality criteria recommendations,” or similar variants thereof are r eferences to national AWQC recommendations for human health. In this 2015 update, EPA has revised the human health criteria for c hloroform to reflect the latest scientific information, including updated exposure factors (body weight [BW], drinking water in take [DI] rate, and fish consumption rate [FCR]), bioaccumulation factors (BAFs), and human health toxicity value s ( reference dose [RfD] multiplied by relative source contribution [RSC] or 10 -6 divided by cancer slope factor [CSF]). Th e criteria continue to be based on EPA’s Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health , which is referred to as the “2000 Methodology” in this document (USEPA 2000a) . EPA accepted written scientific views from the public on the draft updated human health criteria fo r this chemical (and 93 others) from May t hrough August 2014.

a Throughout this document, the term states means the 50 states, the District of Columbia, the Commonwealth of Puerto Rico, the Virgin Islands, Guam, American Samoa, and the Commonwealth of the Northern Mariana Islands. The term authorized tribe or tribe means an Indian tribe authorized for treatment in a manne r similar to a state under CWA s ection 518 for the purposes of s ection 303(c) water quality standards

.

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I t is important for s tates and authorized tribes to consider any new or updated section 304(a) recommended criteria as part of their triennial review process to ensure that state or tribal water quality standards reflect current science and protect applicable designated uses. These final 2015 updated section 304(a) human health criteria recommendations supersede EPA’s previous recommendations.
2 Problem Formulati on Problem formulation provides a strategic framework for water quality criteria development by focusing on the most relevant endpoints and increasing the transparency of the effects assessment. The structure of this criteria document is intended to be con sistent with general concepts of effects assessments as described in EPA’s Framework for Human Health Risk Assessment to Inform Decision Making (USEPA 2014a)

. In developing AWQC, EPA currently follows the assessment method outlined in its 2000 Methodology (USEPA 2000a)

. The 2000 Methodology describes different approaches for addressing water and non

- water exposure pathways to de rive human health AWQC depending on the toxicological endpoint of concern, the toxicological effect (non carcinogenic or carcinogenic ), and whether toxicity is considered a linear or threshold effect. Water sources of exposure include both consuming drinkin g water and eating fish or shellfish from inland and nearshore waters that have been exposed to pollutants in the water body

. For pollutants that exhibit a threshold of exposure before deleterious effects occur, as is the case for noncarcinogens and nonlin ear carcinogens, EPA applies an RSC to account for other potential human exposures to the pollutant (USEPA 2000a)

. Other sources of exposure m ight include, but are not limited to, exposure to a particular pollutant from ocean fish or shellfish consumption (which is not included in the FCR), non - fish food consumption (e.g., consumption of fruits, vegetables, grains , meats, or poultry ), dermal exposure, and inhalation exposure. For substances for which the toxic ity endpoint is carcinogenicity based on a linear low

- dose extrapolation, only the exposures from drinking water and fish ingestion are reflected in human health AWQC; that is , non - water sources are not explicitly included and no RSC is applied (USEPA 2000a) . In these situations, AWQC are deri ved with respect to the incremental lifetime
cancer risk posed by the presence of a substance in water, rather than an individual’s total risk from all sources of exposure. The resulting criterion represent s the water concentration that is expected to incr ease an individual’s lifetime risk of ca ncer from exposure to the particular pollutant by no more than one chance in one million for the general population. EPA calculates AWQC at a 10 -6 (one in one million) cancer risk level for the general population (USEPA 2000a)

. The 2000 Methodology re commends that states set human health criteria cancer risk levels for the target general population at either 10 -5 or 10 - 6 and also notes that states and authorized t ribes can choose a more stringent risk level, such as 10 -7

. For substances that are carcin ogenic, EPA takes an integrated approach and considers both cancer and n oncancer effects when deriving AWQC (USEPA 2000a; USEPA 2000b)

. Where sufficient data are available, EPA derives AWQC using both c arcinogenic and noncarcinogenic toxicity endpoints and recommends the lower value fo r the AWQC. The AWQC might not utilize

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the value obtained from the cancer analysis if it is less protective than that derived from the noncancer endpoint

. Chloroform is a trihalomethane (THM) that was regulated in EPA’s Stage 1 and Stage 2 Disinfection Byproduct (DBP) Rule (USEPA 1998a; USEPA 2006) . DBPs are formed by the reaction of disinfectants with constituents in the water, especially natural organic matter (NOM), but also inorganic constituents such as bromide and iodide. The concentration of DBPs within a public water system can vary depending on source water quality, treatment (e.g., type of disinfectant), and distribution system conditions. For example, THM concentrations might be lower when chloramine is used as the disinfectant compared to when chlorine is used

. 3 Criteria Formulas : Analysis Plan Human health AWQC for toxic pollutants are necessary to protect any designated uses related to ingestion of water and ingestion of aquatic organisms. These uses can include, but are not limited to, recreation in and on the water, consumption of fish or shellfish (including consumption associated with fishing or shellfish harvesting), and protection of drinking water supplies.
The derivation of human he alth AWQC requires information about both the toxicological endpoints of concern for water pollutants and the pathways of human exposure to those pollutants. EPA considers the following two primary pathways of human exposure to pollutants present in a part icular water body when deriving human health 304(a) AWQC: (1) d irect ingestion of drinking water obtained from the water body and (2) c onsumption of fish or shellfish obtained from the water body. The equations for deriving human health AWQC for non carcinogenic effects and carcinogenic effects are presented as Eq s . 1 and 2. EPA d erives recommended human health AWQC based on the consumption of both water and aquatic organisms (Eq

. 1) and based on the consumption of aquatic organisms alone (Eq

. 2). The use of one criterion over the other depends on the designated use of a particular water body or water bodies (i.e., drinking water source and/or fishable waters). EPA recommends applying organism

- only AWQC (Eq. 2) to a water bod y where the designated use includes supporting fishable uses under section 101(a) of the CWA but the water body is not a drinking water supply source (e.g., non

- potable estuarine waters that support fish or shellfish for human consumption) (USEPA 2000a)

. EPA recommends inclu ding the drinking water exposure pathway fo r ambient surface waters where drinking water is a designated use for the following reasons: (1) drinking water is a designated use for surface waters under the CWA , and therefore criteria are needed to en sure that this designated use can be protected and maintained; (2) although they are rare, some public water supplies provide drinking water from surface water sources without treatment; (3) even among the majority of water supplies that do treat surface waters, existing treatments
m ight not be effective f or reducing levels of particular contaminants; and (4) in consideration of the Agency’s goals of pollution prevention, ambient waters should not be contaminated to a level where the burden of achieving health objectives is shifted away from those responsib le

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for pollutant discharges and placed on downstream users that must bear the costs of upgraded or supplemental water treatment (USEPA 2000a)

. The equations for deriving the criteria values are as follows (USEPA 2000a) : For consumption of water and organisms: AWQC (μg/L) = toxicity value (mg/kg

- d) × BW (kg) × 1 , 000 ( μg/mg ) b (Eq. 1) DI (L/d) + ∑ (FCR i (kg/d) × BAF i (L/kg)) 4 i=2 For consumption of organisms only: AWQC (μg/L) = toxicity value (mg/kg

- d) × BW (kg) × 1 , 000 ( μg/mg ) c (Eq. 2) ∑ (FCR i (kg/d) × BAF i (L/kg))

4 i=2 Where: AW QC = ambient water quality criteria toxicity value = RfD x RSC ( mg/kg

- d) for non carcinogenic effects
or 10 -6 /CSF ( kg

- d/mg) for carcinogenic effects d RSC = relative source contribution (applicable to only noncarcinogenic and nonlinear low

- dose extrapolation for carcinogenic effects) BW = body weight DI = drinking water intake ∑ 4

i=2 = summation of values for aquatic trophic levels (TLs), where the letter i stands for the TLs to be considered, starting with TL2 and proceeding to TL4 FCR i = fish consumption rate for aquatic TLs 2, 3, and 4 BAF i = bioaccumulation factor for aquatic TLs 2, 3, and 4 EPA rounds AWQC to the number of significant figures in the least precise parameter as described in the 2000 Methodology (USEPA 2000a , s ection 2.7.3).

4 Exposure Factors
4.1 Body Weight EPA updated the default BW assumption to 80 .0 kg based on National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2006 as reported in Table 8.1 of EPA’s Exposure Factors Handbook (USEPA 2011a) . The updated BW represents the mean weight for adults ages 21 and older. EPA’s previously recommended BW assumption for adults was 70 kg, which was based on the mean BW of adults from the NHANES III database (1988

– 1994) and a 1989 study conducted by the National Cancer Institute (USEPA 2000a)

.

b 1,000 μg/mg is used to convert the units of mass from milligrams to micrograms.

c 1,000 μg/mg is used to convert the units of mass from milligrams to micrograms. d 10 -6 or 1 in 1,000,000 risk level for the general population.

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4.2 Drinking Water Intake
EPA updated the default DI to 2.4 L/d, rounded from 2.414 L/ d, based on NHANES data from 2003 to 2006 as reported in EPA’s Exposure Factors Handbook (USEPA 2011a , Table 3

- 23)

. This rate represents the per capita estimate of combined direct and indirect community water e ingestion at the 90 th percentile for adults ages 21 and older

. EPA selected the per capita rate for the updated DI because it represents the average daily dose es timates ; that is , it includes both people who drank water during the survey period and those who did not , which is appropriate for a national

- scale assessment such as CWA section 304(a) national human health criteria development (USEPA 2011a, section 3.2.1 ).
EPA’s updated DI of 2.4 L/ d is consistent with the 2000 Methodology . In that document, E PA recommended a default DI of 2 L/d , which represented the per capita community water ingestion rate at the 86 th percentile for adults surveyed in the U .S. Department of Agriculture’s 1994

– 1996 Continuing Survey of Food Intake by Individuals (CSFII) analy sis (USEPA 2000a , section 4.3.2.1 ).
4.3 Fish Consumption Rate The updated FCR for the general adult population is 22.0 g/d, or 0.0220 kg/d (USEPA 2014b , Table 9a ). This FCR represents the 90 th percentile per capita consumption rate of fish from inland and nearshore waters for U.S. adults ages 21 years and older based on NHANES data from 2003

– 2010. The 95 percent confidence interval (CI) of the 90 th percentile per capita FCR is 19.1 g/d and 25.4 g/d. This updated FCR replaces EPA’s previously recommended default FCR of 17.5 g/d, which represented an estimate of the 90 th percentile per capita consumption rate of fish from inland and nearshore waters for U.S. adults ages 21 years and older. That default FCR was based on USDA’s CSFII 1994

– 1996 data (USEPA 2002a)

. As recommended in the 2000 Methodology, EPA updated the AWQC to reflect trophic level - (TL -) specific FCRs to better represent human dietary consumption of fish. An organism ’s trophic position in the aquatic food web can have an important effect on the magnitude of bioaccumulation of certain chemicals. The TL

- specific FCRs are numbered 2, 3, and 4, and they account for different categories of fish and shellfish species based on their position in the aquatic food web: TL2 accounts for benthic filter feeders; TL3 accounts for forage fish; and TL4 accounts for predatory fish (USEPA 2000a)

. EPA used the following TL

- specific FCRs to derive the updated AWQC: TL2 = 7.6 g/d (0.0076 kg/d ) (95 percent CI [6.4, 9.1] g/d ) ; TL3 = 8.6 g/d (0.0086 kg/d) (95 percent CI [7.2, 10.2] g/d ) ; and TL4 = 5 .1 g/d (0.005 1 kg/d) (95 percent CI [4.0, 6.4] g/d )

. Each TL

- specific FCR represent s the 90 th percentile per capita consumption rate of fish and shellfish from inland and nearshore waters from that particular TL for U.S. adult s ages 21 years and older (USEPA 2014b ,

e Community water includes direct and indirect use of tap water for household uses and excludes bottled water and other sources (USEPA 2011a, section 3.3.1.2 ). Direct ingestion is defined as direct consumption of water as a beverage, while indirect ingestion includes wa ter added during food preparation (e.g., cooking, rehydration of beverages) but not water intrinsic to purchased foods (USEPA 2011a, section 3.1 ).

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Tables 16a, 17a, and 18a ) . The sum of these three TL

- specific FCRs is 21.3 g/d, which is within the 95 percent CI of the overall FCR of 22.0 g/d. EPA recommends using the TL

- spec ific FCRs when deriving AWQC; however, the overall FCR rate (22.0 g/d) may be used if a simplified approach is preferred.
4.4 Bioaccumulation Factor
4.4.1 Approach Several attributes of the bioaccumulation process are important to understand when deriving national BAFs for use in developing national recommended section 304(a) AWQC. First, the term bioaccumulation refers to the uptake and retention of a chemical by an aquatic organism from all surrounding media, such as water, food, and sediment. The term bioconcentra tion refers to the uptake and retention of a chemical by an aquatic organism from water only. For some chemicals (particularly those that are highly persistent and hydrophobic), the magnitude of bioaccumulation by aquatic organisms can be substantially gre ater than the magnitude of bioconcentration. Thus, an assessment of bioconcentration alone might underestimate the extent of accumulation in aquatic biota for those chemicals. Accordingly, the EPA guidelines presented in the 2000 Methodology emphasize usin g, when possible, measured or estimated BAFs, which account for chemical accumulation in aquatic organisms from all potential exposure routes (USEPA 2000a)

. EPA estimated BAFs for this updated AWQC using EPA’s 2000 Methodology (USEPA 2000a) and its Technical Support Document, Volume 2: Development of National Bioaccumula tion Factors (Technical Support Document, Volume 2) (USEPA 2003a) . Specifically, these documents provide a framework for identifying alternative procedures to derive national TL

- specific BAFs for a chemical based on the chemical’s properties (e.g., ionization and hydrophobicity), metabolism, and biomagnification potential (USEPA 2000a; USEPA 2003a)

. EPA’s approach for developing national BAFs represents the long

- term average bioaccumulation potential of a pollutant in aquatic organisms that are commonly consumed by humans across the United States. National BAFs are not intended to reflect fluctuations in bioaccumulation over short periods (e.g., a few days) because human health AWQC are generally designed to protect humans from long

- term (lifetime) exposures to waterborne chemicals (USEPA 2003a)

. EPA followed the approach described in Figure 3

- 1 of the Technical Support Document, Volume 2 (USEPA 2003a) . EPA used peer

- reviewed, publicly available information to classify ea ch chemical using this framework to derive the most appropriate BAFs according to EPA’s 2000 Methodology (USEPA 2000a) . The framework provides six alternatives, or procedures, resulting in up to four possible methods for each chemical, based on the chemical’s properties. These four methods follow:

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• BAF Method. This method uses measured BAFs derived from data obtained from field studies. Field

- measured BAFs were normalized by adjusting for the water

- dissolved portions of the chemical and the lipid fraction of fish tissue for each species, as well as the fraction of the total concentration of chemical in water that is freely dissolved. EPA averaged multiple field BAFs using a geometric mean of the normalized BAFs by species and TL ; then EPA further averaged the BAFs across species to compute TL baseline BAFs. The national

- level BAF adjusts the TL baseline BAFs by national default values for lipid content, dissolved and particulate organic carbon content, and the n

- octanol

- water partition coefficient (K ow ). EPA chose the recommended 50 th percentile dissolved and par ticulate organic carbon content for the national

- level default values, as described in section 6.3 of the Technical Support Document, Volume 2 (USEPA 2003a)

. • BSAF Method. This method uses biota

- sediment accumulation factors (BSAFs) to estimate BAFs. EPA did not use measured BSAFs to calculate national BAFs because the two major compilations of these data

— EPA’s Biota

- Sediment Accumulation Factor Data Set, Version 1.0 (USEPA 2015a) , and the U.S. Army Corps of Engineers’ BSAF database (USACE 2015)

— have not been peer

- reviewed.

• BCF Method. This method uses BAFs estimated from laboratory

- measured bioconcentration factors (BCFs) with or without adjustment by a food chain multiplier. Similar to field BAFs, laboratory

- measured BCFs are normalized with the lipid fraction and the fraction of the total concentration of chemical in water that is freely d issolved, then multiplied by the food chain multiplier where applicable. Multiple values are averaged using a geometric mean across species and then across TL to compute baseline BAFs. The national

- level BAF adjusts the TL baseline BAFs by national default values for lipid content, dissolved and particulate organic carbon content, and the K ow . EPA chose the recommended 50 th percentile dissolved and particulate organic carbon content for the national

- level default values, as described in section 6.3 of the T echnical Support Document, Volume 2 (USEPA 2003a)

. • K ow Method. This method predicts BAFs based on a chemical’s K ow , with or without adjustment using a food chain multiplier, as described in section 5.4 of the Technical Support Doc ument, Volume 2 (USEPA 2003a)

. Following the decision framework presented in Figure 3

- 1 of the Technical Support Document, Volume 2 (USEPA 2003a) , EPA selected one of the six procedures to develop a national

- level BAF for this chemical. For a given procedure, EPA selected the method that provided BAF estimates for all three TL s (TL2

– TL4) in the following priority:
1. BAF estimates using the BAF method (i.e., based on field

- measured BAFs) if possible. 2. BAF estimates using the BCF method if (a) the BAF method did not produce estimates for all three TL s and (b) the BCF method produced national

- level BAF estimates for all three TL s. 3. BAF estimates using the K ow method if (a) Procedure 1 or 3 was applicable ( see Figure 3- 1 of the Technical Support Document, Volume 2 [ USEPA 2003a ] ) and (b) the BAF and BCF methods did not produce BAF estimates for all three TL s.

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In cases where the procedure called f or the BAF method but there were fewer than three TL estimates and the K ow method did not apply (i.e., Procedures 2, 4, 5, and 6), EPA used the BAF method estimate for the reported TL s by averaging the estimates using a geometric mean when there were two B AFs and us ing the single estimate when only one was available. EPA did not mix values from the BAF and BCF methods. If the BAF method did not have sufficient reliable data for any TL s, EPA used the BCF method estimates in the same manner. If none of the fo ur methods provided sufficient data, or if none were appropriate for the procedure, EPA used the BCF from the previously recommended 2002/2003 criteria (USEPA 2002b; USEPA 2003b)

. EPA primarily used field

- measured BAFs and laboratory

- measured BCFs available from peer

reviewed, publicly available databases (Arnot and Gobas 2006; Environment Canada 2006) to develop national BAFs. If field

- measured BAFs and laboratory

- measured BCFs were not availabl e from those sources, EPA selected K ow values from peer

- reviewed sources (i.e., Agency for Toxic Substances and Disease Registry [ATSDR] preferentially, followed by U.S. Department of Health and Human Services ’ Hazardous Substances Data Bank ) for use in ca lculating national BAFs using the K ow method described in EPA’s Technical Support Document, Volume 2 (USEPA 2003a) . For those chemicals for which the K ow method was not applicable based on the Technical Support Document, Volume 2 (USEPA 2003a) , EPA performed open literature searches of peer

- reviewed journal articles to find field

- measured BAFs or laboratory

- measured BCFs.
4.4.2 Chemical

- specific BAFs EPA selected national BAF values of 2.8 L/kg (TL2), 3.4 L/kg (TL3), and 3.8 L/kg (TL4) for
c hloroform

. EPA followed the framework for selection of methods for deriving national BAFs in Figure 3

- 1 of the Technical Support Document, Volume 2 (USEPA 2003a) to select a procedure for estimating national BAFs for chloroform. Based on the characteristics of this chemical, EPA selected Procedure 3 for deriving a national BAF value. Chloroform has the following characteristics:

• Nonionic organic chemical (USDHHS 2014)

• Low hydrophobicity (log K ow < 4); log K ow = 1.97 (ATSDR 1997)

• Low/unknown metabolism

EPA was not able to locat e pee r- reviewed, field

- measured BAFs or lab

- measured BCFs for TL s 2, 3, and 4. Therefore, EPA used the K ow method to derive the national BAF values for this chemical:
TL2 = 2.8 L/kg TL 3 = 3.4 L/kg T L4 = 3.8 L/kg

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5 Hazard Identification and Dose Response
5.1 Appr oach EPA considered all available toxicity values for both noncarcinogenic and carcinogenic toxicological effects to develop this updated AWQC for c hloroform . As described in the 2000 Methodology (USEPA 2000a) , where data are available EPA derives AWQC for both noncarcinogenic and carcinoge nic effects and recommends the more protective value for the AWQC. (S ee s ection 7, Criteria Derivation: Analysis .) For noncarcinogenic toxicological effects, EPA uses a chronic

- duration oral RfD to derive human health AWQC. A n RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure of the human population to a substance that is likely to be without an appreciable risk of deleterious effects during a lifetime. An RfD is typically de rived from a laboratory animal dosing study in which a no

- observed

- adverse

- effect level (NOAEL), lowest

observed

- adverse

- effect level (LOAEL), or benchmark dose can be obtained. Uncertainty factors are applied to reflect the limitations of the data (USEPA 2000a)

. For carcinogenic toxicologi cal effects, EPA uses an oral CSF to derive human health AWQC . The oral CSF is an upper bound, approximating a 95 percent confidence limit, on the increased cancer risk from a lifetime oral exposure to a stressor. For this update, EPA conducted a systemati c search of eight peer - reviewed, publicly available sources to obtain the toxicity value (RfD or CSF) for use in developing AWQC

. EPA’s primary source of toxicity values for developing human health AWQC is its Integrated Risk Information System (IRIS) prog ram (USEPA 2015b)

. EPA also systematically searched for toxicological assessments from the following EPA program offices, other national and international programs, and state programs:

• EPA , Office of Pesticide Programs (USEPA 2015c)

• EPA, Office of Pollution Prevention and Toxics (USEPA 2015d)

• EPA, Office of Water (USEPA 2015e)

• EPA, Office of Solid Waste and Emergency Response (USEPA 2015f)

• U.S. Department of Health and Human Services , Agency for Toxic Substances and Disease Registr y (ATSDR 2015)

• Health Canada (HC 2015)

• California Environmental Protection Agency, Office of Environmental Health Hazard Assessment (CalEPA 2014)
After identifying and documenting all available toxicity values, EPA followed a systematic process to select the toxicity value s used to derive the AWQC for noncarcinogenic and carcinogenic effects. EPA selected IRIS toxicity value s to derive the updated AWQC if any of the following conditions were met:

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1. EPA’s IRIS toxicological assessment was the only available source of a toxicity value. 2. EPA’s IRIS toxicological assessment was the most current source of a toxicity value. 3. EPA’s IRIS program was reassessing the chemical in question and had published the draft Toxicological Review for public review and comment, discussion at a public meeting, and subsequent expert peer review

. f 4. The toxicity value from a more current toxicological assessment from a source other than EPA IRIS was based on the same principal study and was numerically the same as
an older EPA IRIS toxicity value

. 5. A more current toxicological assessment from a source other than EPA IRIS was available, but it did not include the relevant toxicity value (chronic

- duration oral RfD or CSF)

. 6. A more current toxicological assessment from a s ource other than EPA IRIS was available, but it did not introduce new science (e.g., the toxicity value was not based on a newer principal study) or use a more current modeling approach compared to an older EPA IRIS toxicological assessment.

EPA selected t he toxicity value from a peer - reviewed, publicly available source other than EPA IRIS to derive the upd a ted AWQC if any of the following conditions were met:
1. The chemical is currently used as a pesticide , and EPA Office of Pesticide Programs had a toxicity value that was used in pesticide registration decision

- making

. 2. A toxicological assessment from a source other than EPA IRIS was the only available source of a toxicity value. 3. A more current toxicological assessment from a source other than EPA IRIS introd uced new science (e.g., the toxicity value was based on a newer principal study) or used a more current modeling approach compared to an older EPA IRIS toxicological assessment.

5.2 Chemical

- specific Toxicity Value
5.2.1 Reference Dose EPA selected an RfD of 1 × 10 – 2 mg/kg -d (0.01 mg/kg -d ) for chloroform based on a 2001 EPA IRIS assessment (USEPA 2001a) . EPA ’s IRIS program calculated the RfD using a principal study by Heywood et al. ( 1979) based on moderate to marked fatty cyst formation in the liver and elevated serum glutamate

- pyruvate transaminase as the critical effects in dogs orally exposed to chloroform. The study ha s a lower

- bound confidence l imit on the benchmark dose of 1 mg/kg

- d as the point of departure (POD)

. In deriving the RfD, EPA ’s IRIS program applied a composite uncertainty factor of 100 to a ccount for interspecies extrapolation (10) and intraspecies variation (10) (USEPA 2001a)

.

f Equivalent to Step 4 in the July 2013 EPA Process for Developing IRIS Health Assessments. Available online at http://www.epa.gov/iris/process.htm

.

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EPA identified two other RfD sources based on the systematic search described in section 5: a 2006 EPA Offi ce of Water (OW) assessment and a 1997 ATSDR assessment (ATSDR 1997)

. Based on the selection process described in section 5 , the 2001 EPA IRIS assessment is preferred for use in AWQC development at this time. The EPA OW assessment i s based on the same princip al study and is numerically the same as the IRIS assessment

. The 20 01 IRIS assessment is more current than the 1997 ATSDR assessment

. 5.2.2 Cancer Slope Factor Under the 1986 EPA Guidelines for Carcinogen Risk Assessment (USEPA 1986) , chloroform has been classified as Group B2, “ probable human carcinogen” (USEPA 2001b)

. Under the 1999 EPA Review Draft Guidelines for Carcinogen Risk Assessment (USEPA 1999) , chloroform is characterized as “likely to be carcinogenic to humans by all routes of exposure under high

exposure conditions that lead to cytotoxicity and regenerative hyperplasia in susceptible tissues” and “not likely to be carcinogenic to humans by any route of exposure under exposure conditions that do not cause cytotoxicity and cell regeneration” (USEPA 1998b; USEPA 2001b)

. EPA’s IRIS program used a nonlinear dose

- response approach for characterizing the cancer risk from chloroform. A vailable evidence indicates that chloroform

- induced c arcinogenicity is secondary to cytotoxicity and regenerative hyperplasia; hence, the Agency relies on a nonlinear approach and the use of a margin

- of

- expo sure analysis for cancer risk. EPA’s IRIS chose not to rely on a mathematical model to estimate a POD for a cancer risk estimate because the mode of action indicates that cytotoxicity is the critical effect and the RfD value is considered protective for this effect. Thus, the RfD for noncancer effects is also considered adequately protective of public heal th for cancer effects by the oral route (USEPA 2001b)

. 6 Relative Source Contribution
6.1 Approach Th e RSC component of the AWQC calculation allows a percentage of the RfD’s exposure to be attributed to the consumption of ambient water and fish and shellfish from inland and nearshore waters when there are other potential exposure sources. The RSC describes the portion of the RfD available for AWQC

- related sources (USEPA 2000a) ; the remainder of the RfD is allocated to other sources of the pollutant. The rationale for this approach is that for pollutants exhibiting threshold effects, the objective of the AWQC is to ensure that an individual’s total exposure from all sources does not exceed that threshold level. Exposures outside the RSC include, but are not limited to, exposure to a particular pollutant from ocean fish and shellfish consumption (which is not included in the FCR ), non

- fish food consumption (e.g., fruits, vegetables, grains, meats, poultry), dermal exposure, and respiratory exposure.
EPA derived a n RSC for each chemica l included in this 2015 update by using the Exposure Decision Tree approach described in the 2000 Methodology (USEPA 2000a)

. To u s e th at approach, EPA compiled information for each chemical on its uses, chemical and physical properties, occurrences in other potential sources (e.g., air, foo d), and releases to the environment, as well as regulatory restrictions on other sources that are specific to the

12Chloroform 67

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chemical (e.g., air quality standards, food tolerance levels) . The ATSDR “Toxicological Profiles” (ATSDR 2015) were the primary sources for this information. EPA used t he Hazardous Substance Data Bank (HSDB) (USDHHS 2015) from the National Library of Medicine’s Toxicology Data Network (TOXNET) as the primary source for chemicals without ATSDR Toxicological Profiles. Both sources are peer

- reviewed compilations of chemical information.
EPA used a dditional references , including the following, to obtain specific types of information and to supplement the information from ATSDR and the HSDB :

• EPA ’s Six

- Year Review s (drinking water data) (USEPA 2009a; USEPA 2009b)

. • FDA Total Diet Study (USFDA 2015)

. • FDA Everything Added to Food in the United States (USFDA 2013)

. • EPA National Lake Fish Tissue Study (USEPA 2009c)

. • EPA Toxic Release Inventory (USEPA 2015g)

. • International Bot tled Water Association Standards of Quality (IBWA 2012)

. • NOAA Mussel Watch (NOAA 2014)

. • A dditional sources as needed.

T o determine the RSC to be used in the AWQC calculation , EPA then used the information compiled for each chemical to address the questions posed in the Exposure Decision Tree

. Some of the important items evaluated in the Exposure Decision Tree follow:

• T he adequacy of the data available for each rel evant exposure source and pathway

. • T he availability of sufficient information to characterize the likelihood of exposure to relevant sources

. • W hether there are significant known or potential uses/sources other than the source of concern (i.e., ambient wate r and fish/seafood from those waters)

. • W hether information o n each source is available to make a characterization of exposure
. In cases where there is a lack of environmental or exposure data, or both, the Exposure Decision Tree approach results in a recommended RSC of 20 percent. This 20 percent value for the RSC may be replaced where sufficient data are available to develop a scientifically defensible alternative value. When appropriate, if scientific data demonstrating that sources and routes of ex posure other than water and fish from inland and nearshore waters are not anticipated for the pollutant in question, the RSC may be raised to 80 percent based on the available data (USEPA 2000a)

. 6.2 Chemical

- specific RSC Chloroform is most often used in the manufacture of other chemicals, and environmental sources are typically from industrial sources (ATSDR 1997)

. Chloroform is not currently registered for use as a pesticide (USEPA 2015c)

. The general population is exposed to chloroform primarily from non

- fish food, drinking water, and indoor air (USDHHS 2014)

.

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Chloroform is found in beverages (e.g., soft drinks ) and various foods (ATSDR 1997) . For example, a 5 year study (1996

– 2000) revealed that chloroform is present in various food items in supermarkets in the United States (USDHHS 2014) . It has been repo rted in different foods in the Everything Added to Food in the United States database (USFDA 2013) . Thus, based on its detection in beverages and food, ingestion of food is a potentially significant source of exposure to chloroform. Water that contains organic material and is chlorinated can generate chloroform (A TSDR 1997)

. It is commonly detected in tap water throughout much of the United States because of the chlorination of drinking water for disinfection (USDHHS 2014) . Chloroform is regulated under the Safe Drinking Water Act and EPA’s dri nking water standard (maximum contaminant level) of 70 μg/L (USEPA 2014c) . Chloroform was not a chemical of concern in EPA’s Six

- Year Reviews (USEPA 2009a; USEPA 2009b) . There is a Standard of Quality of 10 μg/L for total trihalomethanes in bottled water (IBWA 2012) . Thus, based on its chemical properties and detection in drinking waters, ingestion of drinking water is a potentially significant so urce of exposure to chloroform. Air is a poten tial source of chloroform because the chemical is volatile and also released in to the air through fugitive and point source emissions (ATSDR 1997) . The vapor pressure of chloroform (160 mm Hg at 20 °C) indicates that volatilization from soil and water is an important fate process (ATSDR 1997) . Recent data from EPA’s Toxic Release Inventory reports
over that 360,000 pounds of chloroform were released to the air in 2013 (USEPA 2015g)

. Chloroform is listed as a hazardous air pollutant (USEPA 2013) . Thus, based on its physical properties and prevalence, air is a potentially significant so urce of exposure to chloroform. The log K ow for chloroform is 1.97 (ATSDR 1997) . The national

- level BAF estimates for chloroform range from 2.8 L/kg (T2) to 3.8 L/kg (TL4), which indicates that chloroform has a low potential for bioaccumulation (USEPA 2011b) . Recent expos ure information regarding concentrations of chloroform in fish and shellfish from inland and nearshore waters and ocean fish and shellfish could not be identified. Chl oroform was not included in EPA’s National Lake Fish Tissue Study (USEPA 2009c) or in NOAA’s Mussel Watch Survey (NOAA 2014) . Thus, the potential exposure to chloroform from ingestion of fish and shellfish is unknown

. In summary, based on the physical properties and available exposure information for chloroform, air , drinking water, and non

- fish food are potentially significant sources. Following the Exposure Decision Tree in EPA’s 2000 Methodology (USEPA 2000a) , significant potential sources other than fish and shellfish from inland and nearshore waters and water ingestion exist (Box 8A in the Decision Tree); however, information is not available to quantitatively characterize exposure from th o se different sources (Box 8B in the Decision Tree). Therefo re, EPA recommends an RSC of 20 percent (0.20) for chloroform.

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7 Criteria Derivation : Analysis Table 1 summarizes the model inputs used to derive the 2015 updated human health AWQC that are protective of exposure to c hloroform from consuming drinking water a nd eating fish and shellfish (organisms) from inland and nearshore waters

. The c riteria calculations are presented below. These updated criteria recommendations are based on the 2000 Methodology (USEPA 2000a) and the updated exposure assumptions described above . ( See s ection 4, Exposure Fac tors ; section 5, Hazard Identification and Dose Response; and section 6, Relative Source Contribution.)

Table 1. Summary of I nput P arameters for 2015 H uman H ealth AWQC for C hloroform Input Parameter Value RfD 0.01 mg/kg

- d CSF No data RSC 0.20 BW 80 .0 kg DI 2.4 L/d

FCR TL2 0.0076 kg/d TL3 0.0086 kg/d TL4 0.0051 kg/d

BAF TL2 2.8 L/kg TL3 3.4 L/kg TL4 3.8 L/kg

7.1 AWQC for N oncarcinogenic Toxicological E ffects For consumption of water and organisms: AWQC (μg/L) = toxicity value (RfD [mg/kg

- d] × RSC) × B W (kg) × 1 , 000 ( μg/mg) DI (L/d) + ∑ (FCR i (kg/d) × BAF i (L/kg)) 4 i=2

= 0.01 mg/kg

- d × 0.20 × 80.0 kg × 1 , 000 μg/mg

2.4 L/d + ((0.00 76 kg/d × 2.8 L/kg) + (0.00 86 kg/d × 3.4 L/kg) + (0.00 51 kg/d × 3.8 L/kg))

= 64.8 μg/L

= 60 μg/L (rounded)

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- 66 -3
For consumption of organisms only: AWQC (μg/L) = toxicity value (RfD [mg/kg

- d] × RSC) × B W (kg) × 1 , 000 ( μg/mg) ∑ (FCR i (kg/d) × BAF i (L/kg))

4 i=2

= 0.01 mg/kg

- d × 0.20 × 80.0 kg × 1 , 000 μg/mg

(0.0076 kg/d × 2.8 L/kg) + (0.00 86 kg/d × 3.4 L/kg) + (0.00 51 kg/d × 3.8 L/kg)

= 2,289 μg/L

= 2,000 μg/L (rounded)
7.2 AWQC for C arcinogenic Toxicological E ffects
EPA identif ied no CSF sources through the systematic search described above. (See s ection 5, Hazard Identification and Dose Response .) The RfD for noncancer ef fects is considered adequately protective of public health for cancer effects by the oral route (USEPA 2001a)

. Therefore, the AWQC derived using the RfD are protective of carcinogenic effects.
7.3 AWQC Summary EPA derive d the AWQC for c hloroform using a toxicity endpoint that is protective of noncarcinogenic and carcinogenic effects . The updated human health AWQC for chloroform are 60 μg/L for consumption of water and organisms and 2, 000 μg/L for consumption of organisms only (Table 2). These updated criteria replace EPA’s previously published values (USEPA 2002b)

.
Table 2. Summary of EPA’s Previously Recommended (2002 ) and U pdated ( 2015 ) Human H ealth AWQC for C hloroform 2002 Human Health AWQC 201 5 Human Health AWQC

Water and Organism 5.7 μg/L 6 0 μg/L Organism Only 470 μg/L 2 ,000 μg/L

The se AWQC are intended to be protective of the general adult population from noncarcinogenic and carcinogenic effects due to chronic (up to a lifetime) e xposure to c hloroform from ingesting water and/or consuming fish and shellfish from inland and nearshore waters.
8 Criteria Characterization The updated 2015 human health AWQC for ch loroform take into account current data on health effects and exposure input parameters, consistent with the 2000 Methodology (USEPA 2000a)

. The following paragraphs describe the individual influence of each of the revised inputs and exposure assumptions on the overall change in value.

16Chloroform 67

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Body Weight EPA’s updated AWQC assume a higher BW compared to the previously recommended 2002 criteria, reflecting a recent rise in average adult BW among the U.S. population. The updated BW assumption of 80.0 kg, based on recent survey data from the 1999−2006 NHANES data, is 10 kg greater than the previous assumption of 70 kg. Assuming all other input parameters remain constant, a higher average BW in the AWQC calculations (Eq s . 1 and 2 above) results in higher AWQC. That is, as BW increases, the level of a co ntaminant in water at or below which negative health effects are not anticipated from a lifetime of exposure also increases. Drinking Water Intake The updated DI assumption is 2.4 L/d , which is higher than the previo usly recommended rate of 2 L/d . Assuming all other input parameters remain constant, a higher DI assumption in the AWQC calculations (Eq s . 1 and 2 above) results in lower AWQC. That is, as DI increases, and thus overall exposure increases, the level of a contaminant in water at or belo w which negative health effects are not anticipated from a lifetime of exposure decreases. Fish Consumption Rate The updated FCR for fish and shellfish from inland and nearshore waters is 22.0 g/d; the TL

- specific FCRs are 7.6 g/d, 8.6 g/d, and 5.1 g/d for TLs 2, 3, and 4, respectively. The previously recommended FCR was 17.5 g/d. Assuming all other input parameters remain constant, a higher FCR assumption in the AWQC calculations (Eqs. 1 and 2 above) results in lower AWQC. That is, as fish consumption increases, and thus overall exposure increases, the level of a contaminant in water at or below which negative health effects are not anticipated from a lifetime of exposure decreases.
Bioaccumulation Factor The national lower (TL2), mid (TL3), and upper (TL4) TL BAFs used in the updated AWQC (Eqs. 1 and 2 above) are 2.8, 3.4, and 3.8 L/kg wet

- weight, respectively. These BAFs were derived using EPA’s 2000 Methodology (USEPA 2000a) and its Technical Support Document, Volume 2 (USEPA 2003a) . These national TL BAFs replace EPA’s previously recommended BCF of 3.75 L/kg. As an additional line of evidence, EPA used model

- estimated BAFs from the Estimation Progr am Interface (EPI) Suite (USEPA 2012) to support field

- measured or predicted BAFs developed using the four methods described above. The BCFBAF program wit hin EPI Suite estimates fish BAF s by using K ow and biotransformation data from a model designed by Arnot and Gobas ( 2003) . The model includes mechanistic process es for bioaccumulation , such as chemical uptake from the water at the gill surface and from the diet, chemical elimination at the gill surface, fecal egestion, growth dilution , and metabolic biotransformation. Other processes included in the calculations are bioavailability in the water column (only the freely dissolved fraction can bioconcentrate) and absorption efficiencies at the gill and in the gastrointestinal tract. The model requires the K ow of the chemical and the normalized whole

- body metabolic

17Chloroform 67

- 66 -3

bio transformation rate constant as input parameters to predict BAF values. The EPI Suite model estimates are as follows :
TL 2 = 6.003 L/kg TL 3 = 6.591 L/kg TL 4 = 8.706 L/kg
Assuming all other input parameters remain constant, lower BAFs or BCF s result in highe r AWQC. That is, as bioaccumulation or bioconcentration of a contaminant in fish and shellfish decreases, the level of a contaminant in water at or below which negative health effects are not anticipated from a lifetime of exposure increases.
The utilizati on of a national

- level BAF rather than a BCF better represents the amount of a contaminant accumulating in an organism because it accounts not only for the organism’s exposure to the pollutant in the water column, but also from the food chain and surroundi ng environment as well as biotransformation of the pollutant in the organism due to metabolic processes. The utilization of the three TL s of fish and shellfish consumed, as opposed to representing all TL s of fish and shellfish consumed by a single value, allows for better exposure representation.
Reference Dose EPA selected an RfD of 0.01 mg/kg

- d for chloroform based on a 2001 EPA IRIS assessment (USEPA 2001a)

. This RfD, which was used to derive AWQC for noncancer effects, is also considered adequately protective of public health for cancer effects by the oral route (USEPA 2001a)

. EPA did not derive AWQC for noncarcinogenic effects of chloroform in its previous criteria update (USEPA 2002c)

. Cancer Slope Factor EPA did not select a CSF for chloroform because EPA’s IRIS program used a nonlinear dose

response approach for characterizing the cancer risk from chloroform in its most recent toxicological assessment (USEPA 2001a)

. EPA’s AWQC derived using the RfD described above (0.01 mg/k g- d) are protective of both non carcinogenic and carcinogenic effects. E PA used a CSF (0.0061 per mg/kg

- d) to derive AWQC for carcinogenic effects of chloroform in its previous criteria update (USEPA 2002c)

. Relative Source Contribution An RSC of 20 percent is included in the AWQC calculation. Previously, the AWQC did not include an RSC (or, in other words, the RSC was 100 percent) (USEPA 2002c) . Assuming all other input parameters remain constant, a lower RSC in the AWQC calculations (Eqs. 1 and 2) results in lower AWQC.

18Chloroform 67

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9 Chemical Name and Synonyms

• Chloroform (CA S Number 67

- 66

- 3)

• Formyl Trichloride

• Freon 20

• Methane Trichloride

• Methane, Trichloro -
• Methenyl Chloride

• Methenyl Trichloride

• Methyl Trichloride

• NCI

- CO2686

• R- 20

• TCM

• Trichloroform

• Trichloromethane

10 References Arnot, J.A., and A.P.C. Gobas. 2003. A Generic QSA R for Assessing the Bioaccumulation Potential of Organic Chemicals in Aquatic Food Webs. QSAR & Combinatorial Science 22:337

– 345. Arnot, J.A., and A.P.C. Gobas. 2006. A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments fo r organic chemicals in aquatic organisms. Environmental Reviews 14(4):257

– 297.
ATSDR. 1997. Toxicological Profile for Chloroform . U.S. Department of Health and Human Services, U.S. Public Health Service, Agency for Toxic Substances and Disease Registry, At lanta, GA. Accessed February 2015. http://www.atsdr.cdc.gov/toxprofiles/tp6.pdf

. ATSDR. 2015. Toxic Substances Portal . U.S. Department of Health and Human Services, U.S. Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA. Accessed February 2015. http://www.atsdr.cdc.gov/toxprofiles/index.asp

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. HC. 2015. Health Canada . Home page. Health Canada, Ottawa, Ontario. Accessed February 2015. http://www.hc -s c.gc.ca/index

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Heywood, R., R.J. Sortwell, P.R.B. Noel, A.E. Street, D.E. Prentice, F.J. Roe, P.F. Wadsworth, A.N. Worden, and N.J. Van Abbé. 1979. Safety evaluation of toothpaste containing chloroform: III. Long

- term study in beagle dogs. Journal of Environmental Pathology Toxicology 2(3):835

– 851.
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- Sediment Accumulation Factor Database . U.S. Army Corps of Engineers, Engineer Research and Development Center, Vicksburg, MS. Accessed March 2015. http://el.erdc.usace.army.mil/bsafnew/BSAF.html

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- 3) . Hazardous Substances Data Bank, a TOXNET database. Retrieved February 17, 2015. U.S. Department of Health and Human Services, National Institutes of Health, U.S. National Library of Medicine, Bethesda, MD. http://toxnet.nlm.nih.gov/cgi

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. USDHHS. 2015. TOXNET . Home page. Hazardous Substances Data Bank, a TOXNET database. U.S. Department of Health and Human Services, National Institutes of Health, U.S. National Library of Medicine, Bethesda, MD. Accessed January 2015. http://toxnet.nlm.nih.gov/newtoxnet/hsdb.htm

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- 004. U .S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed February 2015. http://ofmpub.epa.gov/eims/eimscomm.getfile?p_download_id=4397 79

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– 15692.
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. Review Draft. NCEA -F- 0644. U.S. Environmental Protection Agency, Washington, DC. Accessed February 2015. http://ofmpub.epa.gov/eims/eimscomm.getfile?p_download_id=437005

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USEPA. 2000a. Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health (2000) . EPA

- 822 -B- 00

- 004. U.S. Environmental Protection Agency, Office of Water, Office of Science and Technology, Washington, DC. Accessed February 2015. http://water.epa.gov/scitech/swguidance/standards/upload/2005_05_06_criteria_hum anhealth_method_complete.pdf

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- 822 -B00

- 005. U.S. Environmental Protection Agency, Office of Water, Office of Science and Technology, Washington, DC. Accessed February 2015. http://water.epa.gov/scitech/swguidance/standards/criteria/health/methodology/uplo ad/2005_05_06_criteria_humanhealth_method_supportdoc.pdf

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- 3) . Inte grated Risk Information System. Oral RfD assessment Agency consensus date July 27, 2001. U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed April 2015. h ttp://www.epa.gov/iris/subst/0025.htm

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- 3) . Integrated Risk Information System. Carcinogenicity Agency consensus date July 27, 2001. U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed March 2015. http://www.epa.gov/iris/subst/0025.htm

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- 821 -C- 02

- 003. U.S. Environmental Protection Agency, Office of Water, Washington, DC. Accessed February 2015. http://water.epa.gov/scitech/swguidance/standards/criteria/health/upload/consumpti on_report.pdf

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- 2002.pdf

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.

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- 030. U.S. E nvironmental Protection Agency, Office of Water, Office of Science and Technology, Washington, DC. Accessed March 2015. http://www.epa.gov/scipoly/sap/meetings/2008/octobe r/methodology.pdf

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– 75515. Accessed February 2015. http://www.gpo.gov/fdsys/pkg/FR

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– 493. Accessed March 2015. https ://www.federalregister.gov/articles/2006/01/04/06

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- complete.pdf

.

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- 01/documents/aa_criteria_v 2.pdf

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. EPA

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- 001. U.S. Environmental Protection Agency, Office of the Science Advisor, Washington, DC. Accessed February 2015. http://www2.epa.gov/sites/production/files/2014

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- 2010) . EPA

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.

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USEPA. 2015d. Existing Chemicals . U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics, Washington, DC. Accessed February 2015. http://www.epa.gov/oppt/existingchemicals/

. USEPA. 2015e. Water Home . U.S. Environmental Protection Agency, Office of Water, Washington, DC. Accessed February 2015. http://water.epa.gov/

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. U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response, Washington, DC. Accessed February 2015. http://hhpprtv.ornl.gov/quickview/pprtv.php

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. USFDA. 2015. Total Diet Study: Introduction . Home page. U.S. Depar tment of Health and Human Services, U.S. Food and Drug Administration, Silver Spring, MD. Accessed March 2015. http://www.fda.gov/Food/FoodScienceResearch/TotalDietStudy/default.htm

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