# Update of Human Health Ambient Water Quality Criteria: 1,2,4

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- 82 -1 Office of Water Office of Science and Technology EPA 820 -R-15-072 June 201 5EPA 820 -R-15- 07 2 June 201 5



# Update of Human Health Ambient Water Quality Criteria: 1,2,4

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Office of Science and Technology Office of Water U.S. Environmental Protection Agency Washington, DC 2046 01,2,4

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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

- spe cific 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

- specific RSC

................................................................................................ . 14 7 Criteria Derivation: Analysis

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

...................................................... 16 7.2 AWQC for Carcinogenic Toxicological Effects

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

......................................................................................................... 17 8 Criteria Characterization

........................................................................................................ 17 9 Chemical Name and Synonyms

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

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

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1 Introduction: Background and Scope of Update 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 304(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 cons ideration 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 w ater 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 regulati ons themselves. Thus, EPA’s recommended criteria do not impose 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 national 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 references to national AWQC recommendations for human health. In this 2015 update, EPA has revised the human health criteria for 1,2,4

- trichlorobenzene to reflect the latest scientific information , including updated exposure fa ctors (body weight [BW], drinking water intake [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 sci entific views from the public on the draft updated human health criteria for 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 prev ious recommendations.
2 Problem Formulation 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 consistent 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 derive 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 drinking 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 nonlinear 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 (whic h 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

. 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 health 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 huma n exposure to pollutants present in a particular 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 AW QC (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 cons umption) (USEPA 2000a)

. EPA recomme nds inclu ding the drinking water exposure pathway for 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 for 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 responsible for pollutant discharges and placed on downstream users that must bear the costs of upgraded or supplemental water treatment (USEPA 2000a)

.

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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: AWQC = 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 stand s 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 pre cise 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 ad ults 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 estimates ; 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 , secti on 3.2.1 ). EPA’s updated DI of 2.4 L/ d is consistent with the 2000 Methodology . In that document, EPA 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) analysis (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 pe r 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 upd ated 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 troph ic 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 numb ered 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

- spec ific 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 water 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

- specific FCRs when deriving AWQC; however, the overall FCR rate (22.0 g/d) may be used if a simplified approach is preferred.
4.4 Bio accumul ation Factor 4.4.1 Approach Several attributes of the bioaccumulation pro cess 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 bioconcentration 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 bioa ccumulation by aquatic organisms can be substantially greater 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 gu idelines presented in the 2000 Methodology emphasize using, 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 Bioaccumulation 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 a quatic 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

- rev iewed, publicly available information to classify each 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 fur ther 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 particulate organic carbon content for the national

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

. • B SAF 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 laborat ory - 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 dissolved, 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 nati onal 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 Technical 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 Document, 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 dev elop 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 ap plicable (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 procedur e called for 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 BAFs 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 four 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 no t available 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 calculating 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 2,800 L/kg (TL2) , 1,500 L/kg (TL3), and 430 L/kg (TL4) for 1,2,4

- trichlorobenzene

. 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 1,2,4

- trichlorobenzene . Based on the characteristics of this chemical, EPA selected Procedure 1 for deriving a national BAF value. 1,2,4

- Trichlorobenzene has the following characteristics:

• Nonionic organic chemica l (USDHHS 2010)

• Moderate

- high hydrophobicity (log K ow ≥ 4); log K ow = 4.02 (ATSDR 2014)

• Low/unknown metabolism EPA was able to locate peer

- reviewed, field

- measured BAFs for TL s 2, 3, and 4 (Arnot and Gobas 2006; Environment Canada 2006) . Therefore, EPA used the Field BAF method to derive the national BAF values for this chemical : TL2 = 2,800 L/kg TL3 = 1,500 L/kg TL4 = 430 L/kg

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5 Hazard I dentification and Dose Response 5.1 Approach EPA considered all available toxicity values for both noncarcinogenic and carcinogenic toxicological effects to develop this updated AWQC for 1,2,4

- trichlorobenzene . As described in the 2000 Methodology (USEPA 2000a) , where data are available EPA derives AWQC for both noncarcinogenic and carcinogenic effects and recommends the more protective value for the AWQC. (S ee section 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 derived 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 toxicological 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 systematic 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) program (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 Registry (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 de rive 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 progra m 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 r elevant toxicity value (chronic

- duration oral RfD or CSF)

. 6. A more current toxicological assessment from a source 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 the 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 w ere 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 s ource of a toxicity value. 3. A more current toxicological assessment from a source other than EPA IRIS introduced 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 IR IS toxicological assessment.
5.2 Chemical
- specific Toxicity Value 5.2.1 Reference Dose EPA sele cted an RfD of 1 × 10 –2 mg/kg

- d (0.01 mg/kg

- d) for 1,2,4 -t richlorobenzene based on a 1991 EPA IRIS assessment (USEPA 1991) . EPA’s IRIS program identified a study by Robinson et al. ( 1981) as the critical study and increased adrenal weights and vacuolization of the zona fasciculata in the cortex of the adrenal gland as the critical effects in rats o rally exposed to 1,2,4

- trichlorobenzene. The study had a NOAEL of 14.8 mg/kg

- d. In deriving the RfD, EPA’s IRIS program applied a composite uncertainty factor of 1000 to account for interspecies extrapolation (10), intraspecies variation (10 ), and subchron ic

- to

- chronic study variation (10 ) (USEPA 1991)

.

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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In 2001, EPA’s IRIS program conducted a screening

- level review of the more recent toxicology literature pertinent to the RfD for 1,2,4 -t richlorobenzene and did not identify any critical new studies.
EPA identified three other potential RfD source s through the systematic search described in section 5: a 2009 EPA Office of Solid Waste and Emergency Response (OSWER) Provisional Peer Reviewed Toxicity Value (PPRTV) (USEPA 2009a) , a 2014 ATSDR assessment (ATSDR 2014) , and a 1999 California EPA assessment (CalEPA 1999) . B ased on the s election process described in section 5, the 1991 EPA IRIS RfD is preferred for use in AWQC development at this time

. Neither the 2009 OSWER PPRTV nor the 2014 ATSDR assessment include the relevant (chronic oral) toxicity factor. CalEPA relied on the same principal study as EPA IRIS (Robinson et al. 1981) , but used a composite uncertainty factor of 10,000 which is inconsistent with current EPA policy (USEPA 2000a)

. 5.2.2 Cancer Slope Factor Under the 1986 EPA Guidelines for Carcinogen Risk Assessment (USEPA 1986) , 1,2,4 -t richlorobenzene is c lassified as Group D, “ not classifiable as to human carcinogenicity ” (USEPA 19 88)

. Under the 2005 Guidelines for Carcinogen Risk Assessment (USEPA 2005) , 1,2,4

- trichlorobenzene is considered “likely to be carcinogenic to human s” b y the oral route of exposure based on a finding of increased tumor incidence in more than one sex of mouse (USEPA 2009a ). EPA selected a CSF of 2.9 × 10 –2 per mg/kg

- d (0.029 per mg/kg

- d) for 1,2,4 -t richlorobenzene based on a 2009 EPA OSWER PPRTV (USEPA 2009a). EPA OSWER derived the provisional CSF using a principal study by Chemical Manufacturers Association (CMA ) (Moore 1994) based on an increase in hepatocellular carcinoma in male mice orally exposed to 1,2,4

- trichlorobenzene. EPA OSWE R obtain ed a point of departure (POD) for a quantitative assessment of cancer risk using d ose - response modeling of the data. The lower

- bound confidence limit on the benchmark dose ( BMDL 10[HED] ) for liver tumors in male mice (3.50 mg/kg

- day) was selected as the POD. The provisional CSF was calculated by dividing 0.1 (10 percent ) by the BMDL 1 0[HED] of 3.50 mg/kg

- day (USEPA 2009a)

. EPA identified one other CSF source through the systematic search described in section 5 : a 1999 California EPA assessment (CalEPA 1999)

. B ased on the selection process described in section 5, the 2009 EPA OSWER CSF is preferred for use in AWQC development at this time

. The OSWER PPRTV is the m ost current available CSF source.
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

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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 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 2009b; USEPA 2009c)

. • FDA Total Diet Study (USFDA 2015)

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

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

. • EPA Toxic Release Inventory (USEPA 2015g)

. • International Bottled 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 relevant 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 water and fish/seafood from those waters)

. • W hether information o n each source is available to make a characterization of exposure
.

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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 exposure 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 1,2,4

- Trichlorobenzene is used as a solvent and chemical intermediate in the production of certain chemicals and is also used to produce dy es and textiles (ATSDR 2014)

. 1,2,4

- Trichlorobenzene was once registered as a pesticide, but is not currently registered (USEPA 2015c)

. Trichlorobenzenes are volatile substances; consequently, they partition to the atmosphere and are frequently detected in ambient air samples. In addition , trichlorobenzenes have been identified in water, soil, sediment, plants, fish, animals, and food samples (ATSDR 2014)

. 1,2,4 -T richlorobenzene has been detected in air (ATSDR 20 14) . The vapor pressure (0.46 mm Hg at 25 °C) of 1,2,4

- trichlorbenzene indicates that volatilization is an important fate process for this chemical (ATSDR 2014) . Recent data from EPA’s Toxic Release Inventory (USEPA 2015g) indicate that 7,618 pounds of 1,2,4

- trichlorobenzene were released to the a ir in 2013. 1,2,4

- trichlorobenzene is listed as a hazardous air pollutant (USEPA 2013)

. Thus, based on its physical properties and prevalence, air is a potentially significant source of exposure to 1,2,4

- trichlorobenzene. 1,2,4

- Trichlorobenzene has been detected in various food sources in the past, including potatoes, cabbage, cauliflower, lettuce, peas, fruits, meat, milk, and eggs (ATSDR 2014)

. Additional, more recent information regarding concentrations of 1,2,4

- trichlorobenzene in food could not be identified. Thus, based on its detection in food, ingestion of food i s a potentially significant source of exposure to 1,2,4

- trichlorobenzene. The log K ow is 4.02 (ATSDR 2 014) . The national

- level BAF estimates for 1,2,4

- trichlorobenzene range from 430 L/kg (TL4) to 2,800 L/kg (TL2), which indicates 1,2,4

- trichlorobenzene has a moderate

- to

- high potential for bioaccumulation (USEPA 2011b) . 1,2,4

- Trichlorobenzene was detected at elevated concentrations in catfish as well as in tro ut from the Great Lake s and the Niagara River; however, these findings are from the 1980s (ATSDR 2014)

. 1,2,4

- Trichlorobe nzene was not detected in EPA ’ s National Lake Fish Tissue Study (USEPA 2009d) ; however, in other studies, this chemical was detected in Atlantic croakers, blue crabs, and spotted sea trout (ATSDR 201 4) . 1,2,4

- Trichlorobenzene was not a target analyte in NOAA’s Mussel Watch Survey (NOAA 2014) . Thus, based on its potential to bioaccumulate and detection in fish and shellfish, ingestion of fish and shellfish is a potentially significant source of exposure to 1,2,4

- trichlorobenzene

.

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1,2,4

- Trichlorobenzene is regulated under the Safe Drinking Water Act and EPA’s drinking water standard (maximum contaminant level) is 70 μg/L (USEPA 2014c). 1,2,4

- Trichlorobenzene has a relatively high solubility in water and is expected to degrade slow ly as it has a half

- life of 3.4 years in water (ATSDR 2014) . EPA ’ s Six

- Year Reviews detected 1,2,4

- trichlorobenzene in some sur face water and groundwater sources of drinking water (USEPA 2009b; USEPA 2009c)

. A Standard of Quality for bottled water of 9 μg/L for 1,2,4

- trichlorobenzene has been established (IBWA 2012) . Therefore, based on its physical properties and half

- life, ingestion of drinking water is a potentially significant source of exposure to 1,2,4

- trichlorobenzene. In summary, based on the chemical properties and available exposure information for 1,2,4

- trichlorobenzene, air, non - fish food, fish and shellfish from inland and nearshore waters and ocean fish and shellfish, and drinking water are potentially significant sources. Following the Exposure Decision Tree in EPA’s 2000 Methodo logy (USEPA 2000a) , significant pot ential 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 these different sources (Box 8B in the Decision Tree). Therefore, EPA recommends an RSC of 20 percent (0.20) for 1,2,4

- trichlorobenzene.
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 1,2,4

- trichlorobenzene from consuming drinking water and 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 assumptio ns described above . ( See section 4, Exposure Factors ; 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 1,2,4 -T richlorobenzene Input Parameter Value RfD 0. 0 1 mg/kg

- d CSF 0.0 29 per mg/kg

- d RSC 0.20 BW 80 .0 kg DI 2.4 L/d

FCR TL2 0.00 76 kg/d TL3 0.00 86 kg/d TL4 0.00 51 kg/d

BAF TL2 2,800 L/kg TL3 1,500 L/kg TL4 430 L/kg

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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 × 2,800 L/kg) + (0.00 86 kg/d × 1,500 L/kg) + (0.00 51 kg/d × 430 L/kg))

= 4.13 μg/L

= 4 μg/L (rounded) 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 × 2,800 L/kg) + (0.00 86 kg/d × 1,500 L/kg) + (0.00 51 kg/d × 430 L/kg)

= 4.40 μg/L

= 4 μg/L (rounded)
7.2 AWQC for C arcinogenic Toxicological E ffects For consumption of water and organisms: AWQC (μg /L) = toxicity value ( 10 -6 / CSF ) [mg/kg

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

= (1 0 -6 / 0.029 ) mg/ kg

- d × 80.0 kg × 1 , 000 μg/mg

2.4 L/d + ((0.0076 kg/d × 2,800 L/kg) + (0.0086 kg/d × 1,500 L/kg) + (0.0051 kg/d × 430 L/kg))

= 0.07115 μg/L

= 0.071 μg/L (rounded) For consumption of organisms only: AWQC (μg/L) = toxicity value (1 0 -6 / CSF ) [mg/kg

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

4 i=2

= (1 0 -6 / 0.029 ) mg/ kg

- d × 80.0 kg × 1 , 000 μg/mg

(0.0076 kg/d × 2,800 L/kg) + (0.00 86 kg/d × 1,500 L/kg) + (0.005 1 kg/d × 430 L/kg)

= 0.07584 μg/L

= 0.076 μg/L (rounded)

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7.3 AWQC Summary EPA derived the AWQC for 1,2,4

- trichlorobenzene using both noncarcinogenic and carcinogenic toxicity endpoints. The updated human health AWQC for noncarcinogenic effects for 1,2,4

- trichlorobenzene are 4 μg/L for consumption of water and organisms and 4 μg/L for consumption of organisms only. The update d human health AWQC for carcinogenic effects (at a 10 -6 cancer risk level) for 1,2,4

- trichlorobenzene are 0.071 μg/L for consumption of water and organisms and 0.076 μg/L for consumption of organisms only. EPA recommends the lower AWQC, based on the carcin ogenic effects of 1,2,4

- trichlorobenzene , as the updated human health AWQC (Table 2). These updated criteria replace EPA’s previously published values (USEPA 2003b)

. Table 2. Summary of EPA’s Previously Recommended (2003 ) and U pdated ( 2015 ) Human H ealth AWQC for 1,2,4 -T richlorobenzene 200 3 Human Health AWQC 201 5 Human Health AWQC Water and Organism 35 μg/L 0.071 μg/L Organism Only 70 μg/L 0.076 μg/L

Thes e AWQC are intended to be protective of the general adult population from an increased cancer risk due to exposure to 1,2,4

- trichlorobenzene at a 10 -6 , o r one in one million, risk level. The 10 -6 risk level associated with the AWQC represents the concentration that would be exp e cted to increase an individual’s lifetime cancer risk from exposure to the particular pollutant by no more than one chance in one million, regardless of the additional lifetime cancer risk due to exposure, if any, to that particular substance from other sources.
8 Criteria Characterization The updated 2015 human health AWQC for 1,2,4

- trichlorobenzene 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. Body Weight EPA’s updated AWQC assume a higher B W 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 prev ious 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 contaminant in water at or below which negativ e health effects are not anticipated from a lifetime of exposure also increases.

171,2,4

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Drinking Water Intake The updated DI assumption is 2.4 L/d , which is higher than the previously 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 below which negative health effects are not anticipated fr om 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 2,800, 1,500, and 430 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 replac e EPA’s previously recommended BCF of 114 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 processes f or 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 biotran sformation rate constant as input parameters to predict BAF values. The EPI Suite model estimates are as follows : TL 2 = 642.8 L/kg TL 3 = 714.7 L/kg TL 4 = 1,010 L/kg Assuming all other input parameters remain constant, higher BAFs or BCFs result in lower AWQC. That is, as bioaccumulation or bioconcentration of a contaminant in fish and shellfish increases, the level of a contaminant in water at or below which negative health effects are not anticipated from a lifetime of exposure decreases

.
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The utilization 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 surrounding 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 retained an RfD of 0.01 mg/kg -d for 1,2,4

- trichlorobenzene based on a 1991 EPA IRIS assessment (USEPA 1991; USEPA 2003b)

. EPA used this RfD to derive AWQC for non carcinogenic effects. Assuming all other input parameters remain constant, no change in the values used for the RfD in the AWQC calculations (Eqs

. 1 and 2) results in no change in AWQC. Cancer Slope Factor EPA selected a CSF of 0.029 per mg/kg

- d for 1,2,4

- trichlorobenzene ba sed on a 2009 EPA OSWER PPRTV (USEPA 2009a) . EPA used the CSF of 0.029 per mg/kg

- d to derive AWQC for carcinogenic effects. EPA did not derive AWQC for carcinogenic effects of 1,2,4

- trichlorobenze ne in its previous criteria update (USEPA 2003b)

. Relativ e Source Contribution An RSC of 20 percent is included in the AWQC calculation. This is the same RSC used in the previous AWQC (USEPA 2003b)

. 9 Chemical Name and Synonyms

• 1,2,4

- trichlorobenzene (CAS Number 120

- 82 -1)

• Benzene, 1,2,4

- trichloro - • Trichlorobenzene, 1,2,4 - • Trojchlorobenzen

• UN 2321
• unsym - trichlorobenzene
10 Refer e nces Arnot, J.A., and A.P.C. Gobas. 2003. A Generic QSAR 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 for organic chemicals in aquatic organisms. Environmental Reviews 14(4):257

– 297.

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ATSDR. 2014. Toxicological Profile for Trichlorobenzenes . 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/tp199.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

. CalEPA. 1999. Public Health Goal for 1,2,4

- Trichlorobenzene in Drinking Water . California Environmental Protection Agency, Office of Environmental Health Hazard Assessment. Accessed March 2015. http://www.oehha.ca.gov/water/phg/pdf/124tcb_f.pdf

. CalEPA. 2014. All Public Health Goals . California Environmental Protection Agency, Office of Environmental Health Hazard Assessment. Accessed February 2015. http://www.oehha.ca.gov/water/phg/allphgs.html

. Environment Canada. 2006. Bioaccumulation Canada. In The OECD QSAR Toolbox, Version 3.3.2. An online database. Retrieved January 5, 2015. Organisation for Economic Co

- operatio n and Development, Paris, France. http://www.oecd.org/chemicalsafety/risk

- assessment/theoecdqsartoolbox.htm

. HC. 2015. Health Canada . Home page. Health Canada, Ottawa, Ontario. Accessed February 2015. http://www.hc

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- eng.php

. IBWA. 2012. International Bottled Water Association Bottled Water Code of Practice (Revised Dece mber, 2012) . International Bottled Water Association, Alexandria, VA. Accessed January 2015. Moore, M.. 1994. Final report, 104

- week dietary carcinogenicity study with 1,2,4

- trichlorobenzene in mice, with cover letter dated 6/15/94 . Letter from L. Spurlock , Vice President of CHEMSTAR. Submitted to the U.S. Environmental Protection Agency. June 15, 1994. EPA Document No. OPPTS

- 44612. OTS0558831.
NOAA. 2014. National Centers for Ocean and Coastal Science, National Status and Trends Data Portal (NCCOS NS&T Dat a Portal) . U.S. Department of Commerce, National Oceanic and Atmospheric Administration, National Centers for Ocean and Coastal Science, Silver Spring, MD. Accessed March 2015. http://egisws02.nos.noaa.gov/nsandt/index.html#

. Robinson, K.S., R.J. Kavlock, N. Chernoff, and E. Gray. 1981. Multi

- generation study of 1,2,4

- trichlorobenzene in rats. Journal of Toxicology and Environmental Health 8:489

– 500.
USACE. 2015. Biota

- 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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USDHHS. 2010. 1,2,4

- Tr ichlorobenzene (CASRN: 120

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- 1) . Hazardous Substances Data Bank, a TOXNET database. Retrieved February 23, 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

. USEPA. 1986. Guidelin es for Carcinogen Risk Assessment. Risk Assessment Forum . EPA

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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=439779

. USEPA. 1988. 1,2,4

- Trichlorobenzene (CASRN 120

- 82

- 1) . Integrated Risk Information System. Carcinogenicity assessment verification date October 19, 1988. U.S. Environmental Pro tection Agency, Office of Research and Development, Washington, DC. Accessed February 2015. http://www.epa.gov/iris/subst/0119.htm

. USEPA. 1991. 1,2,4

- Trichlorobenzene (CASRN 120

- 82

- 1) . Integrated Risk Information System. Oral RfD assessment verification date December 12, 1991. U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed February 2015. http://www.epa.gov/iris/subst/0119.htm

. 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_hu m anhealth_method_complete.pdf

. USEPA. 2000b. Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health (2000), Technical Support Document. Vol. 1, Risk Assessment . EPA

- 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

. USEPA. 2002a. Estimated Per Capita Fish Consumption in the United States . EPA

- 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_r eport.pdf

.

211,2,4

- Trichlorobenzene 120

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USEPA. 2002b. National Recommended Water Quality Criteria: 2002 . EPA

- 822 -R- 02

- 047. 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/2008_04_29_criteria_wqct able_nrwqc

- 2002.pdf

. USEPA. 2003a. Methodology for Deriving Ambient Water Quality Criteria for the Protection of Human Health (2000), Technical Support Document. Vol. 2, Development of National Bioaccumulation Factors . EPA

- 822 -R- 03

- 030. U.S. Environmental Protection Agency, Office of Water, Office of Science and Technology, Washington, DC. Acces sed March 2015. http://www.epa.gov/scipoly/sap/meetings/2008/october/methodology.pdf

. USEPA. 2003b. National Recommended Water Quality Criteria for the Protection of Human Health. U.S. Environmental Protection Agency. Federal Register, December 31, 2003, 68:75507

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

- 2003

- 12

- 31/html/03

- 322 11.htm

. USEPA. 2005. Guidelines for Carcinogen Risk Assessment . EPA

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- 001F. U.S. Environmental Protection Agency, Washington, DC. Accessed February 2015. http://www2.epa.gov/sites/production/files/2013

- 09/documents/cancer_guidelines_final_3

- 25

- 05.pdf

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- Reviewed Toxicity Values for 1,2,4

- Trichlorobenzene (CASRN 120

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- 1) . U.S. Environmental Protection Agency, O ffice of Research and Development, Cincinnati, OH. Accessed May 2015. http://hhpprtv.ornl.gov/issue_papers/Trichlorobenzene124.pdf

. USEPA. 2009b. Contaminant Occurrence Support Document for Category 1 Contaminants for the Second Six

- Year Review of National Primary Drinking Water Regulations . EPA 815 -B- 09

- 010. U.S. Environmental Protection Agency, Office of Water, Office of Ground Water and Drinking Water, Washington, DC. Accessed March 2015. http://water.epa.gov/lawsregs/rulesregs/regulatingcontaminants/sixyearreview/second _review/upload/6YearC ategory1Report.pdf

. USEPA. 2009c. Contaminant Occurrence Support Document for Category 2 Contaminants for the Second Six

- Year Review of National Primary Drinking Water Regulations . EPA

- 815 -B- 09

- 011. U.S. Environmental Protection Agency, Office of Water, Office of Ground Water and Drinking Water, Washington, DC. Accessed March 2015. http://water.epa.gov/lawsregs/rulesregs/regulatingcontaminants/sixyearreview/second _review/upload/6YearCategory2Report_final.pdf

.

221,2,4

- Trichlorobenzene 120

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USEPA. 2009d. The National Study of Chemical Residues in Lake Fish Tissue . EPA

- 823 -R- 09

- 006. U.S. Environmental Protection Agency, Office of Water, Office of Science and Technology, Washington, DC. Accessed March 2015. http://water.epa.gov/scitech/swguidance/fishstudies/upload/2009_9_28_fish_study_ data_finalreport.pdf

. USEPA. 2011a. Exposure Factors Handbook: 2011 Edition . EPA

- 600 -R- 09

- 052F. U.S. Environmental Protection Agency, Office of Research and Development, Washingt on, DC. Accessed February 2015. http://www.epa.gov/ncea/efh/pdfs/efh

- complete.pdf

. USEPA. 2011b. Design for the Environment Program Alternatives Assessment Criteria for Hazard Evaluation. V ersion 2.0 . U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics, Washington, DC. Accessed March 2015. http://www2.epa.gov/sites/prod uction/files/2014

- 01/documents/aa_criteria_v2.pdf

. USEPA. 2012. Estimation Programs Interface (EPI) Suite TM for Microsoft® Windows, v 4.10

. U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics, Washington, DC. Accessed February 2 015. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

. USEPA. 2013. The Clean Air Act Amendments of 1990 List of Hazardous Air Pollutants . Air toxics web site. U.S. Environmental Protection Agency, Office of Air and Radiation, Office of Air Quality Planning and Standards, Washington, DC. Accessed January 2015. http://www.epa.gov/airt oxics/orig189.html

. USEPA. 2014a. Framework for Human Health Risk Assessment to Inform Decision Making

. EPA

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