# Update of Human Health Ambient Water Quality Criteria: Benzene

71

- 43 -2 Office of Water Office of Science and Technology EPA 820 -R- 15 -009 June 2015EPA 820 -R- 15

- 00 9 June 2015



# Update of Human Health Ambient Water Quality Criteria: Benzene

71

- 43 -2

Office of Science and Technology Office of Water U.S. Environmental Protection Agency Washington, DC 20460Benzene 71

- 43 -2

Table of Contents
1 Introduction: Background and Scope of Update

..................................................................... 2 2 Problem Formul ation

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

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

..................................................................................................................... 5 4.1 Body W eight

.................................................................................................................. 5 4.2 Drinking Water Intake

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

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

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

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

- specific BA Fs

.................................................................................... 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 R SC

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

.................................................................................................. 14 7.1 AWQC for Noncarcinogenic Toxicological Effects

...................................................... 14 7.2 AWQC for Carcinogenic Toxicological Effects

............................................................. 15 7.3 AWQC Summary

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

........................................................................................................ 17 9 Chemical Names and Synonyms

............................................................................................ 18 10 References

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

1Benzene 71

- 43 -2

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 th e 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 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 as sessing 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 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 nat ional 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 ref erences to national AWQC recommendations for human health. In this 2015 update, EPA has revised the human health criteria for b enzene 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 scientific 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 manner similar to a state under CWA s ection 518 for the purposes of s ection 303(c) water quality standards

.

2Benzene 71

- 43 -2

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 quali ty 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 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 a ssessments 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 en dpoint 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
nea rshore 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 (which is not included in the FCR ), non

- fish food consumption (e.g., consumption of fruits, vegetables, grains , meat s , 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 carcinogenic, 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

3Benzene 71

- 43 -2
the value obtained from the cancer analysis if it is less protective than that derived from the noncancer endpoint

. 3 Criteri a 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 human 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 orga nism

- 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 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 tr eat 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)

.

4Benzene 71

- 43 -2

The equations for deriving the criteria values are as follows (USEPA 2000a) : For consumption of water and organisms:
A WQC (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: A WQC = 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 2011) . 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.

5Benzene 71

- 43 -2

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 2011 , 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 2011, section 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 2 2.0 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 ag es 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 othe r sources (USEPA 2011, 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 2011, section 3.1 ).

6Benzene 71

- 43 -2

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 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 a n 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 pers istent and hydrophobic), the magnitude of bioaccumulation 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 biot a for those chemicals. Accordingly, the EPA guidelines 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 upd ated 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 identifyin g 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 healt h 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 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 t o four possible methods for each chemical, based on the chemical’s properties. These four methods follow:

7Benzene 71

- 43 -2

• 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 dissolved, then multiplied by the food chain multiplier wher e 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 organi c 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)

.
Fo llowing 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 pr oduce 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.

8Benzene 71

- 43 -2
In cases where the procedure 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 fo r 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 fro m 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 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 3.6 L/kg (TL2) , 4.5 L/kg (TL3) , and 5.0 L/kg (TL4) for benzene. 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 benzene. Ba sed on the characteristics of this chemical, EPA selected Procedure 3 for deriving a national BAF value. Benzene has the following characteristics:

• Nonionic organic chemical (USDHHS 2014)

• Low hydrophobicity (log K ow < 4); log K ow = 2.13 (ATSDR 2007)

• Low/unknown metabolism
EPA was not able to locate peer

- reviewed, field

- measured BAFs or lab

- measure d BCFs for TL s 2, 3, and 4. Therefore, EPA used the K ow method to derive the national BAF values for this chemical:

TL 2 = 3.6 L/kg TL 3 = 4.5 L/kg TL 4 = 5.0 L/kg

9Benzene 71

- 43 -2

5 Hazard Identification and Dose Response
5.1 Approach EPA considered all available toxicity values f or both noncarcinogenic and carcinogenic toxicological effects to develop this updated AWQC for b enzene . 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 s ection 7, Criteria Derivation: Analysis .) For noncarcinogenic toxicological effects, EPA uses a chronic

- duration oral RfD to derive human health AWQC. An RfD is an estimate (with uncertainty spa nning 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 stud y 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 deriv e 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 , ATSDR (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
ca rcinogenic effects . EPA selected IRIS toxicity value s to derive the updated AWQC if any of the following conditions were met:

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.

10Benzene 71

- 43 -2

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 source other than EPA IRIS was available, but it did not introduce new science (e.g., the t oxicity 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 d erive 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 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 IRIS toxicological assessment.

5.2 Chemical

- specific Toxicity Value
5.2.1 Reference Dose
I n place of an RfD , EPA selected a chronic oral minimal risk level (MRL) of 5 × 10 –4 mg/kg

- d (0.0005 mg/kg

- d) for benzene based on a 2007 ATSDR assessment (ATSDR 2007) . A chronic oral MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse non cancer health effects for a chronic duration (365 days and longer)

. ATSDR identified the inhalation occupational exposure study by La n et al. ( 2004a; 2004b) as the critical study and decreased B cell counts in benzene

- exposed workers served as the effect for the determination of the point of departure for the derivation for the chronic

- duration ora l MRL for benzene. ATSDR cited toxicokinetic data in humans and animals exposed to low levels of benzene that demonstrate absorption of approximately 50 percent of an inhaled dose and
es sentially 100 percent of an oral dose as rationale for the use of a ro ute

- to

- route extrapolation. The lower

- bound confidence limit on the benc h mark dose ( BMDL 0.25sdADJ ) was

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

.

11Benzene 71

- 43 -2
0.014 mg/kg -d . In deriving the MRL, ATSDR applied a composite uncertainty factor of 30 to account for route

- to

- route extrapolation (3) and intraspecies v ariation (10) (ATSDR 2007)

. EPA identified two other RfD sources through the systematic searc h described in section 5 : a 200 2 EPA IRIS assessment (USEPA 2002c) and a 2001 Cal ifornia EPA assessment (CalEPA 2001)

. B ased on the selection process described in sectio n 5, the 2007 ATSDR RfD is preferred for use in AWQC development at this time. The ATSDR assessment is the most current source and relied on a newer study (Lan et al. 2004a; Lan et al. 2004b) compared to the 2002 IRIS assessment (Rothman et al. 1996)

. Additionally, ATSDR u sed a method of route

- to

- route extrapolation that is consistent with the IRIS assessment (USEPA 2002c)

. 5.2.2 Cancer Slope Factor Under the 1996 EPA Proposed Guidelines for Carcinogen Risk Assessment (USEPA 1996) , benzene is classified as G roup A , “known human carcinogen” (USEPA 2000c)

. EPA selected a CSF range of 1.5 × 10 –2 per mg/kg

- d (0.015 per mg/kg

- d) to 5.5 × 10 -2 per mg/kg

- day (0.055 per mg/kg

- day) fo r benzene b ased on a 2000 EPA IRIS assessment (USEPA 2000c)

. EPA’s IRIS program derived the CSF using a principal studies by Rinsky et al. ( 1981; 1987) , Paustenbach et al. ( 1993) , Crump ( 1994) , and USEPA ( 1998; 1999) based on the development of leukemia in humans with occupational inhalation exposure to benzene (USEPA 2000c)

. EPA identified one other CSF source through the systematic search described in section 5 : a 2001 Cal ifornia EPA assessment (CalEPA 2001)

. B ased on the selection process described in section 5, the 2000 EPA IRIS CSF is preferred for use in AWQC development at this time. The CalEPA CSF is based on studies that IRIS considered in their assessment but did not use quantitatively (Paxton et al. 1994; Hayes et al. 1997)

. 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.

12Benzene 71

- 43 -2

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 2009a; USEPA 2009b)

. • Food and Drug Administration (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 Bottled Water Association Standards of Quality (IBWA 2012)

. • National Oceanic and Atmospheric Administration ( 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 i mportant 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
. In cases where t here 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 def ensible 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)

.

13Benzene 71

- 43 -2

6.2 Chemical

- specific R SC EPA derived recommended AWQC for this chemical using both noncarcinogenic and carcinogenic toxicity endpoints (RfD and CSF). For comparative purposes only , a default RSC of 20 percent was applied for AWQC derivation for no ncarcinogenic effects (USEPA 2000a)

. 7 Criteria D erivation : Analysis Table 1 summarizes the model inputs used to derive the 2015 updated human health AWQC that are protective of exposure to b enzene 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 assumptions described above . ( See s ection 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 B enzene Input Parameter Value RfD 0.0005 mg/kg

- d CSF 0.015 per mg/ kg

- d to 0.055 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 3.6 L/kg TL3 4.5 L/kg TL4 5.0 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) × BW (kg) × 1 , 000 (μg/mg) DI (L/d) + ∑ (FCR i (kg/d) × BAF i (L/kg)) 4 i=2

= 0.0005 mg/kg

- d × 0.20 × 80.0 kg × 1 , 000 μg/mg

2.4 L/d + ((0.00 76 kg/d × 3.6 L/kg) + (0.00 86 kg/d × 4.5 L/kg) + (0.00 51 kg/d × 5.0 L/kg))

= 3.21 μg/L

= 3 μg/L (rounded)

14Benzene 71

- 43 -2
For consumption of organisms only: AWQC (μg/L) = toxicity value (RfD [mg/kg

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

4 i=2

= 0.0005 mg/kg

- d × 0.20 × 80.0 kg × 1 , 000 μg/mg

(0.0076 kg/d × 3.6 L/kg) + (0.00 86 kg/d × 4.5 L/kg) + (0.00 51 kg/d × 5.0 L/kg)

= 87.4 μg/L

= 90 μg/L (rounded)
7.2 AWQC for C arcinogenic Toxicological E ffects For consumption of water and organisms: AWQC (μg /L) = toxicity value (1 0 -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

• Lower CSF

= (1 0 -6 / 0.015) mg/ kg

- d × 80.0 kg × 1 , 000 μg/mg

2.4 L/d + ((0.00 76 kg/d × 3.6 L/kg) + (0.00 86 kg/d × 4.5 L/kg) + ( 0.00 51 kg/d × 5.0 L/kg))

= 2.141 μg /L

= 2.1 μg/L (rounded)

• Upper CSF

= (1 0 -6 / 0.055) mg/ kg

- d × 80.0 kg × 1 , 000 μg/mg

2.4 L/d + ((0.0076 kg/d × 3.6 L/kg) + (0.0086 kg/d × 4.5 L/kg) + (0.00 51 kg/d × 5.0 L/kg))

= 0.5838 μg/L

= 0.58 μg/L (rounded)

15Benzene 71

- 43 -2
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

• Lower CSF

= (1 0 -6 / 0.015) mg/ kg

- d × 80.0 kg × 1 , 000 μg/mg

(0.0076 kg/d × 3.6 L/kg) + (0.00 86 kg/d × 4.5 L/kg) + (0.00 51 kg/d × 5.0 L/kg)

= 58.25 μg/L

= 58 μg/L (rounded)

• Upper CSF

= (1 0 -6 / 0.055) mg/ kg

- d × 80.0 kg × 1 , 000 μg/mg

(0.0076 kg/d × 3.6 L/kg) + (0.00 86 kg/d × 4 .5 L/kg) + (0.00 51 kg/d × 5.0 L/kg)

= 15.89 μg /L

= 16 μg/L (rounded)
7.3 AWQC Summary
EPA derived the AWQC for b enzene using both noncarcinogenic and carcinogenic toxicity endpoints. The updated human health AWQC for noncarcinogenic effects for b enzene are 3 μg/L for consumption of water and organisms and 9 0 μg/L for consumption of organisms only. The updated human health AWQC for carcinogenic effects (at a 10 -6 cancer risk level) for benzene are 0.58
– 2.1 μg/L for consumption of water and organisms and 16
– 58 μg/L for consumption of organisms only. EPA recommends the lower AWQC, based on the carcinogenic effects of b enzene , as the updated human health AWQC (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 ) H uman H ealth AWQC for B enzene 2002 Human Health AWQC 201 5 Human Health AWQC

Water and Organism 0.61

- 2.2 μg/L 0. 58
- 2.1 μg/L Organism Only 14

- 51 μg/L 16
- 58 μg/L

Th ese AWQC are intended to be protective of the general adult population from an increased cancer risk due to exposure to b enzene a t a 10 -6 , o r one in one million, risk level. The 10 -6 risk level associated with the AWQC represents the concent ration 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 particula r substance from other sources.

16Benzene 71

- 43 -2

8 Criteria Characterization The updated 2015 human health AWQC for benzene take into account current data on health effects and exposure input parameters, consistent with the 2000 Methodology (USEPA 2000a)

. The following paragraphs describe the ind ividual influence of each of the revised inputs and exposure assumptions on the overall change in value. Body W eight EPA’s updated AWQC assume a higher BW compared to the previously recommended 2002 criteria, reflecting a recent rise in average adult BW am ong 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 contaminant 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 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, a s DI 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

. 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 3.6, 4.5, and 5.0 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 5.2 L/kg. As an additional line of evidence, EPA used model

- estimated BAFs from the Estimation Progr am Inte rface (EPI) Suite (USEPA 2012) to su pport field

- measured or predicted BAFs developed using the four methods described above. The BCFBAF program within EPI Suite estimates fish BAFs by using K ow and biotransformation data from a model designed by Arnot and Gobas ( 2003) . The model includes mechanistic processes for bioaccumulation , such as chemical uptake from the

17Benzene 71

- 43 -2
water at the gill surface and from the diet, chemical elimination at the gill surface, feca l 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 ga strointestinal tract. The model requires the K ow of the chemical and the normalized whole

- body metabolic biotransformation rate constant as input parameters to predict BAF values. The EPI Suite model estimates are as follows :
TL 2 = 8.9 L/kg TL 3 = 10.01 L/kg TL 4 = 14.79 L/kg
Assuming all other input parameters remain constant, lower BAFs or BCFs result in higher 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 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 an d 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 In place of an RfD, EPA selected a chronic oral MRL of 0.0005 mg/kg

- d for benzene based on a 2007 ATSDR assessment (ATSDR 2007)

. EPA used the MRL of 0.0005 mg/kg

- d to derive AWQC for noncarcinogenic e ffects. EPA did not derive AWQC for noncarcinogenic effects of benzene in its previous criteria update (USEPA 2002d)

. Cancer Slope F actor EPA retained a CSF range of 0.015 per mg/kg

- d to 0.055 per mg/kg

- day for benzene based on a 2000 EPA IRIS assessment (USEPA 2000c; USEPA 2002d) . EPA used th is CSF range to derive AWQC for carcinogenic effects. Assuming all other input parameters remain constant, no change in the values used for the CSF in the AWQC calculations (Eqs

. 1 and 2) results in no change in AWQC.
Relative Source Contribution
An RSC of 20 percent was used for comparative purposes to calculate AWQC for noncarcinogenic effects. P reviously , the recommended AWQC were derived for carcinogenic effects only, and ther efore, an RSC was not included

.

18Benzene 71

- 43 -2

9 Chemical Names and Synonyms

• Benzene (CAS Number 71

- 43

- 2)

• Benzol

• Coal naphtha

• Cyclohexatriene

• Phene

• Phenyl hydride

• Polystream

• Pyrobenzol

10 References 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.
ATSDR. 2007. Toxicological Profile for Benzene . 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/ tp3.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. 2001. Public Health Goals for Benzene in Drinking Water . California Environmental Protection Agency, Office of Environmental Health Hazard Assessment. Accessed April 2015. http://oehha.ca.gov/water/phg/pdf/BenzeneFinPHG.pdf

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

. Crump, K.S. 1994. Risk of benzene

- induced leukemia: A sensitivity analysis of the pliofilm cohort with additional follow

- up and new expo sure estimates. Journal of Toxicology and Environmental Health 42(2):219

– 242.
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

- operation a nd Development, Paris, France. http://www.oecd.org/chemicalsafety/risk

- assessment/theoecdqsartoolbox.htm

.

19Benzene 71

- 43 -2
Hayes, R.B., M. Dosemeci, S. Wacholder, L.B. Travis, N. Rothman, R.N. Hoover, M.S. Linet, S. Yin, G. Li, and C. Li. 1997. Benzene and the dose

- related incidence of hematologic neoplasms in China. Journal of the National Cancer Institute 89(14):1065

– 1071.
HC. 2015. Health Canada . Home page. Health Canada, Ottawa, O ntario. Accessed February 2015. http://www.hc

- sc.gc.ca/index

- eng.php

. IBWA. 2012. International Bottled Water Association Bottled Water Code of Practice (Revised December, 2012) . International Bottled Wa ter Association, Alexandria, VA. Accessed January 2015. Lan, Q., L. Zhang, G. Li, R. Vermeulen, R.S. Weinberg, M. Dosemeci, S.M. Rappaport, M. Shen, B.P. Alter, Y. Wu, W. Kopp, S. Waidyanatha, C. Rabkin, W. Guo, S. Chanock, R.B. Hayes, M. Linet, S. Kim, S. Yin, N. Rothman, and M.T. Smith. 2004a. Hematotoxicity in workers exposed to low levels of benzene. Science 306:1774

– 1776. Lan, Q., L. Zhang, G. Li, R. Vermeulen, R.S. Weinberg, M. Dosemeci, S.M. Rappaport, M. Shen, B.P. Alter, Y. Wu, W. Kopp, S. Waidyanatha, C. Rabkin, W. Guo, S. Chanock, R.B. Hayes, M. Linet, S. Kim, S. Yin, N. Rothman, and M.T. Smith. 2004b. Hematotoxicity in workers exposed to low levels of benzene: Supporting online material. Science 306(5702):1774

– 1776. http://www.sciencemag.org/cgi/data/306/5702/1774/DC1/1

. NOAA. 2014. National Centers for Ocean and Coastal Science, National Status and Trends Data Portal (NCCOS NS&T Data Portal) . U.S. D epartment 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#

. Paustenbach, D.J., R.D. Bass, and P. Price. 1993. Benzene toxicity and risk assessment, 1972

– 1992: Implications for future regulation. Environmental Health Perspectives Supplements 101(6):177

– 200. Paxton, M.B., V.M. Chinchilli, S.M. Brett, and J.V. Rodricks. 1994. Leukemia risk associated with benzene exposure in the Pliofilm cohort. II. Risk estimate. Risk Analysis 14(2):155

– 161. Rinsky, R.A., A.B. Smith, R. Horning, T.G. Filloon, R.J. Young, A.H. Okun, and P.J. Landrigan. 1987. Benzene and leukemia: An epidemiologic risk assessment. The New England Journal of Medicine 316:1044

– 1050. Rinsky, R.A., R.J. Young, and A.B. Smith. 1981. Leukemia in benzene workers. American Journal of Industrial Medicine 2(3):217

– 245. Rothman, N., G.L. Li, M. Dose meci, W.E. Bechtold, G.E. Marti, Y.Z. Wang, M. Linet, L.Q. Xi, W. Lu, M.T. Smith, N. Titenko

- Holland, L.P. Zhang, W. Blot, S.N. Yin, and R.B. Hayes. 1996. Hematotoxicity among Chinese workers heavily exposed to benzene. American Journal of Industrial Medic ine 29:236

– 246.

20Benzene 71

- 43 -2

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

. USDHHS. 2014. Benzene (CASRN: 71

- 43

- 2) . Hazardous Substances Data Bank, a TOXNET database. Retrieved February 16, 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

- bin/sis/search2/r?dbs+hsdb:@term+@DOCNO+35

. 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. 1996. Proposed Guidelines for Carcinogen Risk Assessment . EPA

- 600 -P- 92

- 003C. U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed February 2015. http://nepis.epa.gov/Exe/ZyPDF.cgi/3000261D.PDF?Dockey=3000261D.PDF

. USEPA. 1998. Carcinogenic Effects of Benzene: An Update . EPA

- 600 -P- 97

- 001F. U.S. Environmental Protection Agency, Office of Research and Deve lopment, Washington, DC. Accessed February 2015. ofmpub.epa.gov/eims/eimscomm.getfile?p_download_id=428659

. USEPA. 1999. Extrapolation of the Benzene Inhalation Unit Risk Estimate to the Oral Route of Exposure . NCEA -W- 0517. U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed February 2015. http://www.epa.gov/iris/supdocs/benzsup.pdf

. 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 Februa ry 2015. http://water.epa.gov/scitech/swguidance/standards/upload/2005_05_06_criteria_hum 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 Technol ogy, Washington, DC. Accessed February 2015. http://water.epa.gov/scitech/swguidance/standards/criter ia/health/methodology/uplo ad/2005_05_06_criteria_humanhealth_method_supportdoc.pdf

.

21Benzene 71

- 43 -2

USEPA. 2000c. Benzene (CASRN 71

- 43

- 2) . Integrated Risk Information System. Carcinogenicity assessment Agency consensus date January 3, 2000. U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed March 2015. http://www.epa.gov/iris/subst/0276.htm

. 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_report.pdf

. USEPA. 2002b. National Recommended Water Quality Criteria: 200 2 . 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. 2002c. Benzene (CASRN 71

- 43

- 2) . Integrated Risk Information System. Oral RfD assessment Agency consensus date January 23, 2002. U.S. Env ironmental Protection Agency, Office of Research and Development, Washington, DC. Accessed March 2015. http://www.epa.gov/iris/subst/0276.htm

. USEPA. 2002d. National Recommended Water Quality Criteria: 2002 Human Health Criteria Calculation Matrix . EPA

- 822 -R- 02

- 012. U.S. Environmental Protection Agency, Office of Water, Washington, DC. Accessed February 2015. http://water.epa.gov/scitech/swguidance/standards/upload/2002_12_30_criteria_wqct able_hh_calc_matrix.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. Accessed 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

- 32211.htm

. USEPA. 2009a. 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/6YearCa tegory1Report.pdf

.

22Benzene 71

- 43 -2

USEPA. 2009b. 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

. USEPA. 2009c. 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 Sc ience and Technology, Washington, DC. Accessed March 2015. http://water.epa.gov/scitech/swguidance/fishstudies/upload/2009_9_28_fish_study_ data_finalreport.pdf

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

- 600 -R- 09

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

- complete.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 2015. http://www.epa.gov/oppt/exposure/pubs/episuite.htm

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

. EPA

- 100 -R- 14

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

- 12/documents/hhra

- framework

final

- 2014.pdf

. USEPA. 2014b. Estimated Fish Consumption Rates for the U.S. Population and Selected Subpopulations (NHANES 2003

- 2010) . EPA

- 820 -R- 14

- 002. U.S. Environmental Protection Agency, Office of Water, Washington, DC. Accessed February 2015. http://water.epa.gov/scitech/swguidance/fishshellfish/fishadvisories/upload/Estimated

- Fish

- Consumption

- Rates

- for

- the -U-S- Population

- and

- Selected

- Subpopulations

NHANES

- 2003

- 2010.pdf

. USEPA. 2015a. Biota

- Sedi ment Accumulation Factor Data Set, Version 1.0 . U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed March 2015. http://www.epa.gov/med/Prods_Pubs/bsaf .htm

. USEPA. 2015b. Integrated Risk Information System . Home page. U.S. Environmental Protection Agency, Office of Research and Development, Washington, DC. Accessed February 2015. http://www.epa.gov/iris/

.

23Benzene 71

- 43 -2

USEPA. 2 015c. Pesticide Chemical Search . U.S. Environmental Protection Agency, Office of Pesticide Programs, Washington, DC. Accessed February 2015. http://iaspub.epa.gov/apex/pesticides/f? p=chemicalsearch:1

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

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

. USEPA. 2015f. Provisional Peer Reviewed Toxicity Values for Superfund (PPRTV)

. U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response, Washington, DC. Accessed February 2015. http://hhpprtv.ornl.gov/quickview/pprtv.ph p
. USEPA. 2015g. TRI Explorer . (2013 Dataset [released March 2015]) (Internet database) Retrieved from http://www.epa.gov/triexplorer , March 13, 2015. http://iaspub.epa.gov/triexplorer/release_chem?p_view=USCH&trilib=TRIQ1&sort=_VIE W_&sort _fmt=1&state=All+states&county=All+counties&chemical=All+chemicals&indus try=ALL&year=2013&tab_rpt=1&fld=RELLBY&fld=TSFDSP

. USFDA. 2013. Everything Added to Food in the United States (EAFUS) . Home page. Priority

based Assessment of Food Additives database. U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Silver Spring, MD. Accessed January 2015. http://www.access data.fda.gov/scripts/fcn/fcnNavigation.cfm?filter=msg&sortColumn= &rpt=eafusListing

. USFDA. 2015. Total Diet Study: Introduction . Home page. U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Silver Spring, MD. Accessed March 2 015. http://www.fda.gov/Food/FoodScienceResearch/TotalDietStudy/default.htm

.

24