FINAL 

9-30-2009 

Provisional Peer-Reviewed Toxicity Values for Complex 

Mixtures of Aliphatic and Aromatic Hydrocarbons 

(CASRN Various)

Superfund Health Risk Technical Support Center 

National Center for Environmental Assessment 

Office of Research and Development 

U.S. Environmental Protection Agency 

Cincinnati, OH 45268 
i 

Commonly Used Abbreviations 

BMD Benchmark Dose 

HI Hazard Index 

IRIS Integrated Risk Information System 

IUR inhalation unit risk 

LOAEL lowest-observed-adverse-effect level 

LOAELADJ LOAEL adjusted to continuous exposure duration 

LOAELHEC LOAEL adjusted for dosimetric differences across species to a human 

NOAEL no-observed-adverse-effect level 

NOAELADJ NOAEL adjusted to continuous exposure duration 

NOAELHEC NOAEL adjusted for dosimetric differences across species to a human 

NOEL no-observed-effect level 

OSF oral slope factor 

p-IUR provisional inhalation unit risk 

p-OSF provisional oral slope factor 

p-RfC provisional inhalation reference concentration 

p-RfD provisional oral reference dose 

p-sRfC provisional subchronic reference concentration 

p-sRfD provisional subchronic reference dose 

RfC inhalation reference concentration 

RfD oral reference dose 

RPF Relative Potency Factor 

UF uncertainty factor 

UFA animal to human uncertainty factor 

UFC composite uncertainty factor 

UFD incomplete to complete database uncertainty factor 

UFH interhuman uncertainty factor 

UFL LOAEL to NOAEL uncertainty factor 

UFS subchronic to chronic uncertainty factor 
FINAL 

9-30-2009 

1 

PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR COMPLEX MIXTURES 

OF ALIPHATIC AND AROMATIC HYDROCARBONS (CASRN Various) 

Executive Summary 

 This Provisional Peer-Reviewed Toxicity Value (PPRTV) document supports a 

fraction-based approach to risk assessment for complex mixtures of aliphatic and aromatic 

hydrocarbons. The approach takes into account previous efforts, most notably those of the 

Massachusetts Department of Environmental Protection (MADEP) and the Total Petroleum 

Hydrocarbon Criteria Working Group (TPHCWG). These organizations use a fraction-based 

approach that defines petroleum hydrocarbon fractions on the basis of expected transport in the 

environment and analytical methods that may be applied to identify and quantify petroleum 

hydrocarbon environmental contamination. Toxicity values are selected or derived and used as 

surrogates to represent the toxicity of these fractions; then, health risk information for the 

complex mixture is developed using chemical mixture risk assessment methods where 

dose-addition or response-addition is assumed across or within the fractions, as appropriate. For 

similar use by U.S. EPA, this PPRTV document presents toxicity values for aliphatic and 

aromatic hydrocarbon fractions—including subchronic and chronic reference doses (RfDs) and 

reference concentrations (RfCs), cancer weight-of-evidence (WOE) assessments, oral slope 

factors (OSF) and inhalation unit risks (IUR). These values have been obtained from the U.S. 

Environmental Protection Agency’s (EPA) Integrated Risk Information System (IRIS) (U.S. 

EPA, 2009o), U.S. EPA Health Effects Assessment Summary Table (HEAST) (U.S. EPA, 1997), 

and existing PPRTVs, or were derived using updated U.S. EPA methods to provide new 

provisional assessments (U.S. EPA, 2009a-i) when needed and supported by the data. 

 In the U.S. EPA’s approach, the potential health risk of each of the six aliphatic or 

aromatic hydrocarbon fractions is represented in one of three ways: 

1) Surrogate Method: the toxicity value for a surrogate (similar) aliphatic or aromatic 

hydrocarbon mixture or compound is integrated with the exposure data for the entire 

mass of the fraction; 

2) Component Method: the toxicity values for well-studied individual chemicals that make 

up a large portion of the fraction are combined with their respective exposure estimates 

using a components-based method under an assumption of dose- or response-addition; or 

3) Hybrid Method: a combination of 1) and 2) above is used for the same fraction and the 

results are combined under an assumption of dose- or response-addition. 

Table 1 summarizes the U.S. EPA approach and illustrates how these three methods are 

applied to the six hydrocarbon fractions. In the first column of Table 1, the hydrocarbon 

mixtures are first classified into Aliphatics and Aromatics; each of these two major fractions is 

further separated into low-, medium-, and high-carbon range fractions in the second column. 

The fractions are defined by the number of carbon atoms (C) in the compounds of the fraction 

and, also, by the compounds’ equivalent carbon (EC) number index, which is related to their 

transport in the environment. The surrogate chemicals or mixtures selected to represent the 

toxicity of these fractions are shown in the third column. The components method may involve 

all of the compounds in the fraction, as is done for the low-carbon-range aromatics, or may 

involve only the compounds known to have certain toxicological properties, as is done for the 

carcinogenicity of the high-carbon-range aromatics. A combination of surrogate and component 
FINAL 

9-30-2009 

2 

methods may be used for the mid-carbon-range aromatics, if naphthalene and 

2-methylnaphthalene are evaluated as target analytes, as occurs in Massachusetts (MADEP, 

2003). The remaining columns of Table 1 show the availability of noncancer and cancer toxicity 

values for use in this approach and, when available, indicates which table in this PPRTV 

document contains that information. 

Table 1. Aliphatic and Aromatic Fractionation and the Availability of Toxicity Values in 

this PPRTV Document for Surrogate Chemicals or Mixtures

Primary 

Fractions 

Secondary 

Fractions 

Surrogates and/or 

Components 

Oral 

Toxicity 

Value(s) 

Inhalation 

Toxicty 

Value(s) 

Cancer Oral 

Slope Factor 

or RPF 

Cancer 

Inhalation 

Unit Risk 

Low carbon 

range (C5–C8; 

EC5–EC8) 

Commercial hexane 

or n-hexane (surrogates) Table 7 Table 8 No Value Table 9 

Medium carbon 

range (C9–C18; 

EC > 8–EC16) 

Mid range aliphatic 

hydrocarbon streams 

(surrogate) 

Table 7 Table 8 No Value Table 9 

Aliphatics 

High carbon 

range (C19–C32; 

EC > 16–EC35) 

White mineral oil 

(surrogate) Table 7 No Value(s) No Value No Value 

Low carbon 

range (C6–C8; 

EC6–EC < 9) 

Benzene, ethylbenzene, 

xylenes, and toluene 

(components) 

Table 7 Table 8 Table 9 Table 9 

Medium carbon 

range (C9–C16; 

EC9–EC < 22) 

High-flash aromatic 

naphtha (surrogate); 

naphthalene and 

2-methylnaphthalene 

(components) 

Table 7 Table 8 No Value No Value 

Aromatics 

High carbon 

range (C17–C32; 

EC22–EC35) 

Fluoranthene (surrogate); 

benzo[a]pyrene and six 

other Group B2 PAHs 

(components) 

Table 7 No Value(s) Table 9 No Value 

To estimate total health risk or hazard for the entire hydrocarbon mixture, the estimates 

for all six of the aromatic and aliphatic fractions are summed using an appropriate additivity 

method. Figures 1 and 2 provide a graphic illustration of how cancer and noncancer risk 

assessments are carried out, respectively. The illustrated noncancer assessment (Figure 2) is 

performed at a screening level, consistent with Superfund practice and guidance (1989). Use of 

surrogate mixture data and component-based methods is consistent with the U.S. EPA’s 

supplemental mixtures guidance (U.S. EPA, 2000). The application of appropriate additivity 

methods for mixture components, also consistent with U.S. EPA (1986, 1989, 1993, 2000) 

mixtures guidance and methodology, is recommended to estimate the potential total risk within 

and across fractions. These methods include the hazard index (HI) for noncarcinogenic effects, 

the relative potency factor (RPF) method for the carcinogenic effects of the high carbon range 

aromatic fraction, and response addition for carcinogenic effects. By applying additivity 

concepts to the risk evaluation of these complex mixtures, the U.S. EPA is applying a 

straightforward approach that incorporates a number of simplifying assumptions. Because 

assumptions for complex chemical mixtures are often difficult to substantiate, this U.S. EPA 
FINAL 

9-30-2009 

3 

approach can be considered as a default approach that can be used to evaluate potential health 

risks from exposures to aliphatic and aromatic hydrocarbon mixtures when whole mixture 

toxicity data for a specific site are not available. 

Examine Uncertainties: Identify % of Hazard 

Index associated with screening values

Sum fraction specific hazard indices

assuming dose addition

Aliphatic

Fractions

HIi =

Aromatic

Fractions

HIi =

∑=

4

i 1 i

i

RfV

Hazard Index E

Arom1 Fraction

Hazard Index 

Arom3 Fraction

Hazard Index

Aliph1 Fraction

∑=

=

6

i 1

HIm HIi

Hazard Index 

Aliph2 Fraction

Hazard Index 

Aliph3 Fraction

∑=

3

i 1 i

i

RfV

E Hazard Index 

Arom2 Fraction

i = Benzene, Toluene, 

Ethylbenzene, Xylene

i = High Flash Aromatic 

Naphtha, Naphthalene, 2-

MethylNaphthalene

Fluoranthene

Arom

RfV

E 3

WhiteMineralOils

Aliph

RfV

E 3

MidRange AHS

2

RfV

EAliph

a b

n hexane

Aliph

RfV

E

,

1

−

Examine Uncertainties: Identify % of Hazard 

Index associated with screening values

Sum fraction specific hazard indices

assuming dose addition

Aliphatic

Fractions

HIi =

Aromatic

Fractions

HIi =

∑=

4

i 1 i

i

RfV

Hazard Index E

Arom1 Fraction

Hazard Index 

Arom3 Fraction

Hazard Index

Aliph1 Fraction

∑=

=

6

i 1

HIm HIi

Hazard Index 

Aliph2 Fraction

Hazard Index 

Aliph3 Fraction

∑=

3

i 1 i

i

RfV

E Hazard Index 

Arom2 Fraction

i = Benzene, Toluene, 

Ethylbenzene, Xylene

i = High Flash Aromatic 

Naphtha, Naphthalene, 2-

MethylNaphthalene

Fluoranthene

Arom

RfV

E 3

WhiteMineralOils

Aliph

RfV

E 3

MidRange AHS

2

RfV

EAliph

a b

n hexane

Aliph

RfV

E

,

1

−

Sum fraction specific hazard indices

assuming dose addition

Aliphatic

Fractions

HIi =

Aromatic

Fractions

HIi =

∑=

4

i 1 i

i

RfV

Hazard Index E

Arom1 Fraction

Hazard Index 

Arom3 Fraction

Hazard Index

Aliph1 Fraction

∑=

=

6

i 1

HIm HIi

Hazard Index 

Aliph2 Fraction

Hazard Index 

Aliph3 Fraction

∑=

3

i 1 i

i

RfV

E Hazard Index 

Arom2 Fraction

i = Benzene, Toluene, 

Ethylbenzene, Xylene

i = High Flash Aromatic 

Naphtha, Naphthalene, 2-

MethylNaphthalene

Fluoranthene

Arom

RfV

E 3

WhiteMineralOils

Aliph

RfV

E 3

MidRange AHS

2

RfV

EAliph

a b

n hexane

Aliph

RfV

E

,

1

−

Figure 2. Fraction-based Noncancer Risk Assessment for Complex Mixtures of Aliphatic 

and Aromatic Hydrocarbons 

a

For inhalation, use commercial hexane, if n-hexane present at ≤53% of fraction 

b

For inhalation, use n-hexane, if present at >53% of fraction 

Where: 

 HIm = Screening Hazard Index for the Whole Mixture 

HIi = Hazard Index Calculated for the ith Fraction 

Ei = Daily Oral or Inhalation Intake of the ith Chemical or Fraction (mg/kg-day or mg/m3, 

respectively) 

 RfV = Reference Value: Oral Reference Dose or Inhalation Reference Concentration (RfC) 

(mg/kg-day or mg/m3

, respectively) 

AHS = Aliphatic Hydrocarbon Streams 
FINAL 

9-30-2009 

4 

Finally, when evaluating risk through the application of these additivity methods, the 

U.S. EPA suggests that risk assessors carefully identify the underlying assumptions of the risk 

estimate and describe the sources of support for these. The U.S. EPA also suggests that risk 

assessors carefully identify sources of uncertainty in their estimates. For the hydrocarbon 

fractions these assumptions include: the surrogate mixture or component(s) represent the toxicity 

of the entire fraction; independence of toxic action exists when adding carcinogenic risks within 

and across fractions under response addition; there is common toxicity within and across 

fractions for dose-addition-based methods (i.e., HI, RPF); and, synergistic or potentiating 

toxicological interactions among chemicals are not likely to happen at low environmental 

contamination levels. An important source of uncertainty is the quality of the underlying toxicity 

data used to develop either a provisional or screening RfD or a provisional or screening cancer 

slope factor. To convey the difference in quality in the mixture risk assessment, the U.S. EPA 

suggests the risk assessors identify the percentage of the estimated risk or of the hazard index 

that is associated with screening toxicity estimates (i.e., screening cancer slope factors or 

screening RfDs) and the percentage based on provisional estimates (i.e., provisional cancer slope 

factors or provisional RfDs). Such examinations of mixture risk estimates are consistent with 

mixture risk assessment practices (U.S. EPA, 2000; Rice et al., 2005). 

Background

 On December 5, 2003, the U.S. Environmental Protection Agency's (U.S. EPA) Office of 

Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human 

health toxicity values for Superfund risk assessments, establishing the following three tiers as the 

new hierarchy: 

1) U.S. EPA's Integrated Risk Information System (IRIS). 

 2) Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in U.S. EPA's Superfund 

Program. 

 3) Other (peer-reviewed) toxicity values, including 

< Minimal Risk Levels produced by the Agency for Toxic Substances and Disease 

Registry (ATSDR), 

< California Environmental Protection Agency (CalEPA) values, and 

< EPA Health Effects Assessment Summary Table (HEAST) values. 

 A PPRTV is defined as a toxicity value derived for use in the Superfund Program when 

such a value is not available in U.S. EPA's IRIS. PPRTVs are developed according to a Standard 

Operating Procedure (SOP) and are derived after a review of the relevant scientific literature 

using the same methods, sources of data, and Agency guidance for value derivation generally 

used by the U.S. EPA IRIS Program. All provisional toxicity values receive internal review by 

two U.S. EPA scientists and external peer review by three independently selected scientific 

experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the multiprogram 

consensus review provided for IRIS values. This is because IRIS values are generally intended 

to be used in all U.S. EPA programs, while PPRTVs are developed specifically for the Superfund 

Program. 

 Because new information becomes available and scientific methods improve over time, 

PPRTVs are reviewed on a 5-year basis and updated into the active database. Once an IRIS 

value for a specific chemical becomes available for Agency review, the analogous PPRTV for 
FINAL 

9-30-2009 

5 

that same chemical is retired. It should also be noted that some PPRTV documents conclude that 

a PPRTV cannot be derived based on inadequate data.

Disclaimers 

 Users of this document should first check to see if any IRIS values exist for the chemical 

of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional 

Superfund and Resource Conservation and Recovery Act (RCRA) program offices are advised to 

carefully review the information provided in this document to ensure that the PPRTVs used are 

appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility 

in question. PPRTVs are periodically updated; therefore, users should ensure that the values 

contained in the PPRTV are current at the time of use. 

 It is important to remember that a provisional value alone tells very little about the 

adverse effects of a chemical or the quality of evidence on which the value is based. Therefore, 

users are strongly encouraged to read the entire PPRTV document and understand the strengths 

and limitations of the derived provisional values. PPRTVs are developed by the U.S. EPA 

Office of Research and Development’s National Center for Environmental Assessment, 

Superfund Health Risk Technical Support Center for OSRTI. Other U.S. EPA programs or 

external parties who may choose of their own initiative to use these PPRTVs are advised that 

Superfund resources will not generally be used to respond to challenges of PPRTVs used in a 

context outside of the Superfund Program. 

Questions Regarding PPRTVs

 Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on 

chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed 

to the U.S. EPA Office of Research and Development’s National Center for Environmental 

Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI. 

INTRODUCTION 

Background 

 Contamination of the environment by aliphatic and aromatic hydrocarbons is widespread. 

The initial contaminating materials range from crude oil to a wide variety of fuels and lubricating 

oils. These hydrocarbon products are complex mixtures containing hundreds to thousands of 

hydrocarbon compounds—including aliphatic compounds (straight-chain, branched-chain, and 

cyclic alkanes and alkenes) and aromatic compounds (benzene and alkyl benzenes, polycyclic 

aromatic hydrocarbons [PAHs]). In addition, some of these products contain nonhydrocarbon 

additives or contaminants. 

 Once released to the environment, the composition of a hydrocarbon product will change 

due to weathering (i.e., differential fate and transport of its components). Partitioning of the 

mixture will occur, such that the more soluble and/or volatile compounds will migrate to other 

locations and environmental media, leaving the relatively nonmobile components (the weathered 

product) at the original location. Thus, the actual aliphatic and aromatic hydrocarbon mixture to 

which a receptor population is exposed will vary with location, time, and environmental medium. 
FINAL 

9-30-2009 

6 

 The assessment of human health risks posed by hydrocarbon-contaminated sites has 

involved analysis for “total petroleum hydrocarbons” (TPH). TPH is a loosely defined aggregate 

that depends on the method of analysis as well as the contaminating material; it represents the 

total mass of hydrocarbons without identifying individual compounds. As TPH is not a 

consistent entity, the assessment of health effects and development of toxicity criteria such as 

oral reference doses (RfDs) and slope factors for the complex mixture as a whole are 

problematic. 

 Some toxicity data are available for whole, unweathered hydrocarbon products (e.g., as 

reviewed by ATSDR [1995] and IARC [2008a]). However, there are limitations to using the 

whole product data due to composition variability caused by differences in the crude oils from 

which hydrocarbon products are refined, differences in the refining processes itself, and 

differences in formulations of the final products. In addition, the identity of the released material

may not be known, or more than one product may have been released. Toxicity data for whole 

hydrocarbon products that are relatively heterogeneous are not necessarily applicable to the 

weathered materials or transport fractions to which exposure actually occurs. 

 The number of individually identified hydrocarbon components of various 

petroleum-derived fuels and crude oil has been estimated at approximately 250 by the Total 

Petroleum Hydrocarbon Criteria Working Group (TPHCWG, 1997b, 1999; Weisman, 1998). At 

the time, toxicity data were available for about 95 of the identified compounds, but only about 25 

were found by the TPHCWG (1997b) to have U.S. EPA toxicity values or sufficient data to 

develop toxicity criteria. Thus, any attempt to assess the health effects of TPH from the 

individual hydrocarbon components is impractical because many of the known components lack 

appropriate toxicity data and criteria. In addition, the cost of analyzing individually for all 

known TPH constituents would be prohibitive. 

 In recognition of the impact of weathering, the inapplicability of whole product toxicity 

data to many contamination scenarios, the impracticality of chemically analyzing each 

constituent separately, and the need for risk-based assessment of hydrocarbons, an approach has 

been developed to assess aliphatic and aromatic hydrocarbons on the basis of fractions with 

similar physical and chemical properties. The advantages of this approach are that these 

fractions can be defined analytically and that constituents of a fraction have similar 

environmental transport properties. This type of approach appears to have been initiated by the 

Massachusetts Department of Environmental Protection (MADEP) to assess TPH, and it has 

served as the starting point for the TPHCWG. These two groups continued to evolve their 

approaches somewhat independently. Key publications and technical reports describing the 

MADEP approach include Hutcheson et al. (1996) and MADEP (1994, 1996, 1997, 2001, 2002, 

2003, 2008). Key publications describing the TPHCWG approach are TPHCWG (1997a, b, 

1998a, b, 1999), Twerdok (1999) and Weisman (1998). The following sections describe the 

U.S. EPA Approach. Appendix A contains related discussions on the existing approaches 

established or adopted by MADEP, TPHCWG, the American Society for Testing and Materials 

(ASTM), and the Agency for Toxic Substances and Disease Registry (ATSDR). 

U.S. EPA Approach: An Overview

 At the outset, it is important to emphasize that the present U.S. EPA approach represents 

expert judgment for the purpose of establishing toxicity values, including PPRTVs, and a risk 
FINAL 

9-30-2009 

7 

assessment method for evaluating complex mixtures of aliphatic and aromatic hydrocarbons. As 

further scientific advancements are made on the toxicology and chemical mixture risk 

assessment methodologies, it is anticipated that these toxicity values and this U.S. EPA approach 

will be revisited periodically and appropriate adjustments will be made. 

 A fractional approach, similar to those advanced by the MADEP and TPHCWG (see 

separate discussions in Appendix A), is adopted by the U.S. EPA in this PPRTV document. In 

doing so, some modifications have been incorporated. The present PPRTV document is the 

principal document outlining the approach, the methodology, and the definition of fractions, 

selection of surrogates or components, and derivation/selection of toxicity values. In addition, 

there are nine accompanying PPRTV documents for n-hexane, benzene, toluene, ethylbenzene, 

xylenes, commercial or practical grade hexane, midrange aliphatic hydrocarbon streams, white 

mineral oil, and high-flash aromatic naphtha (U.S. EPA, 2009a-i). These are surrogate chemicals 

or mixtures selected for the six fractions (see Table 1 and discussion in following paragraphs), 

and for which complete toxicity and carcinogenicity assessments were not available from IRIS 

(U.S. EPA, 2009o) or existing PPRTVs. 

 Thus, collectively, this PPRTV document plus the nine additional PPRTV documents 

constitute the entire PPRTV effort undertaken by the U.S. EPA specifically for complex 

mixtures of aliphatic and aromatic hydrocarbons. As shown in Table 1, prior to defining 

“fractions,” the components are first classified into Aliphatics and Aromatics; each of these two 

major fractions is further separated into low-, medium-, and high-carbon range fractions. 

Surrogate chemicals or mixtures are then selected (see section below on method for surrogate 

compound or mixture selection) from the available toxicity data for each of these fractions. In 

the U.S. EPA’s approach, the potential health risk of each of the six aliphatic or aromatic 

hydrocarbon fractions is represented in one of three ways: 

1) Surrogate Method: the toxicity value for a surrogate (similar) aliphatic or aromatic 

hydrocarbon mixture or compound is integrated with the exposure data for the entire 

mass of the fraction; 

2) Component Method: the toxicity values for well-studied individual chemicals that make 

up a large portion of the fraction are combined with their respective exposure estimates 

using a components-based method under an assumption of dose- or response-addition; or 

3) Hybrid Method: a combination of 1) and 2) above is used for the same fraction and the 

results are combined under an assumption of dose- or response-addition. 

The fractionation scheme described above is consistent with the analytical chemistry performed 

on the field samples in the laboratory (Hutcheson et al., 1996). Thus, in field offices of the 

U.S. EPA, it is anticipated that analytical information in conjunction with the “fraction 

approach” described herein are to be used for risk assessment of complex mixtures of aliphatic 

and aromatic hydrocarbons on a specific site. In those fractions where components were 

isolated, these components may be evaluated individually according to a component method 

(U.S. EPA, 2000). The components either represent that whole fraction (e.g., aromatic low 

carbon range) or are indicators for the carcinogenicity of that fraction (e.g., aromatic high carbon 

range). 

 The rationale for U.S. EPA’s adoption of the fractional approach developed by the 

MADEP and TPHCWG is based on several factors. First, the development of the “fraction 

approach” by MADEP and TPHCWG represents the collective wisdom and scientific consensus 
FINAL 

9-30-2009 

8 

of numerous scientists involved from governmental agencies, professional organizations, 

academia, and industry. Second, risk assessment of a chemical mixture, particularly one that is 

changing due to weathering, is a very difficult and complex issue. The “fraction approach” 

coupled with analytical information on complex mixtures of aliphatic and aromatic hydrocarbons 

from a given hazardous waste site, represents a reasonable, flexible, and best available 

methodology for risk assessment. Third, U.S. EPA scientists have employed computational 

chemistry and statistical methods to assess the fractionation scheme and found supporting 

evidence for selecting the fractions in this report. 

Risk assessment for complex mixtures of aliphatic and aromatic hydrocarbons, using the 

fraction approach, is consistent with U.S. EPA mixtures guidelines and supplemental guidance 

(U.S. EPA, 1986, 2000) and with specific guidance for Superfund (e.g., U.S. EPA, 1989). The 

basic approach treats fractions as components of the complex mixture and uses additivity 

methods within and across fractions to conduct the risk assessment. Thus, the risk of exposure to 

a fraction, or several fractions at any given time is the sum of the risks within and across 

fractions. 

The U.S. EPA (2000) recommends use of dose-addition methods (HI or RPFs) for 

characterization of potential risk from exposure to a mixture of chemicals that are toxicologically 

similar1

. Response addition is recommended for mixture components that act on different 

systems or produce effects that do not influence each other, and, thus, can be assumed to act 

independently. Summaries of these methods are provided below. For further guidance, details, 

and discussion, see U.S. EPA (2000) and the other references cited below. 

Hazard Index (HI) (U.S. EPA, 2000)

• Assumes a common mode of action and similarly shaped dose-response curves across the 

components. The common mode of action assumption can be based on the same target 

organ or similar effect. 

• Component exposures (oral intakes or inhalation concentrations) are scaled by a measure 

of relative potency—typically the RfD for oral doses and the RfC for inhalation exposure. 

• The scaled intakes or concentrations are then summed to provide an indicator of risk from 

exposure to the mixture. 

• Exposures should be relatively low so that interaction effects are not expected. 

• Used extensively as an indicator of potential noncancer health risk. Method is commonly 

used in Superfund site assessments (U.S. EPA, 1989), for which a screening approach is 

generally used to estimate the HI for all chemicals with pertinent exposure data and 

toxicity values, regardless of mode of action or target organ. If the resulting HI is greater 

than unity, additional procedures, including estimating HIs on a subset of components 

that have a similar mode of action or target organ may be used to further assess the 

potential hazard (U.S. EPA, 1989, 2000). 

 

1U.S. EPA (2000) defines “similar components” as single chemicals that cause the same biologic activity or are 

expected to cause a type of biologic activity based on chemical structure. Evidence of similarity may include 

similarly shaped dose-response curves, or parallel log dose-probit response curves for quantal data on the number of 

animals (people) responding, and the same mechanism of action or toxic endpoint. These components may also be 

expected to have comparable characteristics for fate, transport, physiologic processes, and toxicity. 
FINAL 

9-30-2009 

9 

Relative Potency Factors (RPFs) (U.S. EPA, 2000)

• Assumes a common mode of action or similar toxicity and similarly shaped 

dose-response curves across the components at least in exposure levels of interest to the 

risk assessment. The common mode of action assumption can be met by toxicological 

similarity but for specific conditions (endpoint, route, duration). 

• Used when toxicity data are incomplete for some components. 

• Component exposures (oral intakes or inhalation concentrations) are scaled relative to the 

potency of an index chemical (typically the best-studied component). 

• Scaled intakes or concentrations are then summed, and the dose-response curve of the 

index chemical is used to generate a response (risk) estimate for the mixture. 

• Used for carcinogenic PAHs (U.S. EPA, 1993). 

Response Addition (U.S. EPA, 2000) 

• Assumes toxicological independence of action and is calculated using the law of 

statistical independence. 

• Risk of an effect is estimated for each component using its dose-response curve (in 

percent responding) at the component’s exposure (oral intake or inhalation 

concentration). 

• Risks are summed (simple sum for small number of chemicals or using the independence 

formula for large number of chemicals) to yield a risk estimate for the mixture. 

• Exposures should be relatively low so that interaction effects are not expected. 

• Used extensively for cancer risk characterization. Used in Superfund site assessments 

(U.S. EPA, 1989). 

The overall risk of exposure to complex mixtures of aliphatic and aromatic hydrocarbons 

is the sum of the risks or HI’s from all fractions to which a population is exposed, as shown in 

Figures 1 and 2, respectively, and discussed in the following paragraphs. The quantitative 

exposure information for these individual chemicals or fractions/subfractions is based on 

analytical data from the hazardous waste sites. For the sake of completeness, Figures 1 and 2 

show a summation across all six fractions, but, depending on the source of the mixture and 

weathering and transport, exposure may be limited to only one or a few fractions. Each of the 

six fractions is represented by (1) an individual surrogate chemical; (2) a surrogate mixture; 

and/or (3) actual components (e.g., aromatic low carbon range, see Table 1). In the case of (1) 

and (2), the surrogate chemical or mixture is the entity that meets criteria for similarity with the 

fraction or its components (as discussed later in this PPRTV), and for which there is sufficient 

information for derivation of toxicity values. In one instance (i.e., mid carbon range aromatic 

fraction, see Table 1), a surrogate mixture is selected to represent the remainder of the fraction 

after the components with different and more potent toxicities (i.e., naphthalene and 2-

methylnaphthalene) are assessed individually. Figures 1 and 2 provide a graphic illustration of 

how cancer and noncancer risk assessments are carried out, respectively. The illustrated 

noncancer assessment (Figure 2) is performed at a screening level, consistent with Superfund 

practice and guidance (1989). 

 

By applying additivity concepts to the risk evaluation of these complex mixtures, the 

U.S. EPA is applying a straightforward approach that incorporates a number of simplifying 

assumptions. Because assumptions for complex chemical mixtures are often difficult to 

substantiate, this U.S. EPA approach can be considered as a default approach that can be used to 
FINAL 

9-30-2009 

10 

evaluate potential health risks from exposures to aliphatic and aromatic hydrocarbon mixtures 

when whole mixture toxicity data for a specific site are not available. These assumptions 

include: the surrogate mixture or component(s) represent the toxicity of the entire fraction; 

independence of toxic action exists when adding carcinogenic risks within and across fractions 

under response addition; there is common toxicity within and across fractions for 

dose-addition-based methods (i.e., HI, RPF); and, synergistic or potentiating toxicological 

interactions among chemicals are not likely to happen at low environmental contamination 

levels. Discussions are presented in the next section of this document regarding how well each 

of the surrogate mixtures or component(s) represents the toxicity of its associated fraction; 

information from these discussions can be used in a risk characterization. Because the 

composition of hydrocarbon mixtures is complex and varies with time-dependent weathering and 

transport changes, it will be difficult to provide evidence that the other three assumptions 

mentioned here are being met for every exposure scenario. For cancer risk estimation, response 

addition (for most chemicals) and RPFs (for PAHS) are well-established chemical mixture 

methods. Response addition has been identified as a default method for evaluating carcinogenic 

risk for mixtures, assuming independence of toxic action, whose result is interpreted as the risk 

of any cancer regardless of tumor site (U.S. EPA, 1989, 2000). The RPF method, based on an 

assumption of dose-addition, has long been used by U.S. EPA to evaluate seven PAHs for 

carcinogenicity (U.S. EPA, 1993); B[a]P has been used as the surrogate to represent the 

carcinogenicity of the other PAHs. These methods, shown in Figure 1, are recommended in this 

document and may be used as defaults within the fraction approach to evaluate potential cancer 

risks. Application of the HI to the fractions, as shown in Figure 1 may be performed at a 

screening level, consistent with Superfund practice and guidance (U.S. EPA, 1989). Although 

exposures to the surrogate mixtures and components that represent the fractions may produce 

different toxic effects, it may be argued that a screening level HI is appropriate because it is 

unknown whether the effects caused by other compounds in the fractions may indeed cause 

similar toxicity across fractions. Finally, when two or more chemicals at a site are identified as 

having high exposure concentrations, the toxicology literature should be consulted for evidence 

of toxicological interactions among these chemicals. If synergism is found for these chemicals, 

then this should be called out in the risk characterization along with the quantitative risk or 

hazard estimates. In general, these four assumptions should be evaluated and verified whenever 

possible and the results articulated as part of the final risk characterization. 
FINAL 

9-30-2009 

11 

Cancer Risk

Arom1 Fraction

Data not supportive

of toxicity-value

derivation

Cancer Risk

Arom3 Fraction

i = benzene, toluene, 

ethylbenzene, xylene

BaP i

7

i 1

∑Dosei ×RPF ×CSF

=

i = B[a]P and 6 other Group 

B2 PAHs with RPFs

∑=

=

6

i 1

Rm R i

Sum fraction specific risk estimates assuming 

response addition

Aliphatic

Fractions

Ri =

Aromatic

Fractions

Ri = 

Cancer Risk

CSFcom-hexane × DoseAliph1 Aliph1 Fraction

Cancer Risk

Aliph2 Fraction

CSFMidRangeAHS × DoseAliph2

Cancer Risk

Aliph3 Fraction

Data not supportive

of toxicity-value

derivation

Cancer Risk

Arom2 Fraction

i

4

i 1

∑ Dose i × CSF

=

Examine Uncertainties: Identify % of risk 

estimate associated with screening values

Cancer Risk

Arom1 Fraction

Data not supportive

of toxicity-value

derivation

Cancer Risk

Arom3 Fraction

i = benzene, toluene, 

ethylbenzene, xylene

BaP i

7

i 1

∑Dosei ×RPF ×CSF

=

i = B[a]P and 6 other Group 

B2 PAHs with RPFs

∑=

=

6

i 1

Rm R i

Sum fraction specific risk estimates assuming 

response addition

Aliphatic

Fractions

Ri =

Aromatic

Fractions

Ri = 

Cancer Risk

CSFcom-hexane × DoseAliph1 Aliph1 Fraction

Cancer Risk

Aliph2 Fraction

CSFMidRangeAHS × DoseAliph2

Cancer Risk

Aliph3 Fraction

Data not supportive

of toxicity-value

derivation

Cancer Risk

Arom2 Fraction

i

4

i 1

∑ Dose i × CSF

=

Examine Uncertainties: Identify % of risk 

estimate associated with screening values

∑=

=

6

i 1

Rm R i

Sum fraction specific risk estimates assuming 

response addition

Aliphatic

Fractions

Ri =

Aromatic

Fractions

Ri = 

Cancer Risk

CSFcom-hexane × DoseAliph1 Aliph1 Fraction

Cancer Risk

Aliph2 Fraction

CSFMidRangeAHS × DoseAliph2

Cancer Risk

Aliph3 Fraction

Data not supportive

of toxicity-value

derivation

Cancer Risk

Arom2 Fraction

i

4

i 1

∑ Dose i × CSF

=

Examine Uncertainties: Identify % of risk 

estimate associated with screening values

Figure 1. Fraction-based Cancer Risk Assessment for Complex Mixtures of Aliphatic and 

Aromatic Hydrocarbons 

Where: 

 Rm = Risk posed by the mixture 

 Ri = Risk function associated with the ith fraction 

Dosei

 = Oral Exposure Dose or Inhalation Exposure Concentration for the ith fraction (mg/kg-day 

or mg/m3, respectively) 

CSFi = Cancer Slope Factor (OSF) or Inhalation Unit Risk (IUR) of surrogate chemical or 

components in (mg/kg-day)-1 or (μg/m3

)

-1, respectively 

Com-hexane = commercial hexane 

AHS = Aliphatic Hydrocarbon Streams 

RPFi

 = Relative Potency Factor for the ith PAH 

BaP = Benzo(a)pyrene 
FINAL 

9-30-2009 

12 

 In addition to describing the underlying assumptions when evaluating risks posed by 

hydrocarbon mixtures, risk assessors also will consider sources of uncertainty in the assessment. 

One source of uncertainty pertains to the quality of the data underlying toxicity values. 

Differences or perceived differences in the quality of the underlying data led the U.S. EPA to 

categorize some hydrocarbon RfDs and cancer slope factors as provisional values, while others 

with less information or lower quality information were categorized as screening values, which 

appear in appendices of the PPRTVs. For example, in some cases, U.S. EPA could not 

determine whether the relevant toxicity data had undergone independent, external, scientific peer 

review; in these cases, a screening RfD or screening cancer slope factor was developed (see 

Table 1). To convey this difference in the quality of the data used in the mixture risk assessment, 

the U.S. EPA suggests that risk assessors identify the percentage of the estimated risk or of the 

hazard index that is associated with screening toxicity estimates (i.e., screening cancer slope 

factors or screening RfDs) and the percentage based on provisional estimates (i.e., provisional 

cancer slope factors or provisional RfDs). It is likely that there will be less confidence in 

estimates utilizing a higher percentage of screening RfDs or screening cancer slope factors when 

compared to those estimates comprised of a lower percentage of screening RfDs or screening 

cancer slope factors. Such examinations of mixture risk estimates are consistent with mixture 

risk assessment practices (U.S. EPA, 2000; Rice et al., 2005). 

DEFINITION OF FRACTIONS AND DERIVATION/ 

SELECTION OF TOXICITY VALUES 

Rationale and Recommendations for U.S. EPA Approach 

 The U.S. EPA approach to evaluating complex mixtures of aliphatic and aromatic 

hydrocarbons is fundamentally a fraction-based approach, building on the contributions of the 

MADEP and the TPHCWG. Some modifications are recommended in (1) fraction definition, (2) 

selection of a surrogate compound or mixture, or of a components-based method for the fraction, 

and (3) selection or derivation of toxicity values based on up-to-date methods and data. 

 Given the complexity of the problem and the number of individual compounds that are 

constituents of complex mixtures of aliphatic and aromatic hydrocarbons, a fraction approach is 

a practical method for assessing the health risks from exposure to these mixtures that accounts 

for variation in mixture composition across sites. MADEP (2003) establishes hydrocarbon 

fractions based first on molecular structure (aromatic versus aliphatic), and then, secondly, on 

number of carbon atoms (C), using toxicologically similar groupings and excluding compounds 

with less than five carbons because their high volatility precludes chronic exposure from 

spills/releases. The TPHCWG (1997a) also establishes hydrocarbon fractions based on 

molecular structure, but, as the second delineator, it uses equivalent carbon (EC) number index. 

This index is equivalent to the retention time of the compounds on a boiling-point gas 

chromatography (GC) column (nonpolar capillary column), normalized to the n-alkanes. For 

example, benzene, a C6 aromatic compound has an EC of 6.5 because its boiling point and GC 

retention time are approximately halfway between those of n-hexane (C6, EC6) and n-heptane 

(C7, EC7). The assessment of transport fractions, as defined by the TPHCWG (1997a) for TPH, 

appears particularly useful because these fractions relate to transport in the environment (at least 

under certain conditions). Their transport can be modeled, and they are consistent with the 
FINAL 

9-30-2009 

13 

analytical methods used to quantify and identify hydrocarbons. These fractions are defined by 

the ranges of their EC number indices, which are related to their transport in the environment. 

 The following sections of this PPRTV document present the aliphatic and aromatic 

fractions and discuss the available toxicity assessments for individual compounds and similar 

mixtures (if any) for each fraction. Both the C and EC ranges of the fractions are noted. In 

addition, recommendations are presented for a fraction-based assessment of complex mixtures of 

aliphatic and aromatic hydrocarbons. The recommendations include selection of appropriate 

surrogates or a components method for each fraction and selection of appropriate toxicity values 

for those surrogates/components. 

 The aliphatic hydrocarbon fractions are discussed first. These compounds pose a 

particular problem because little or no toxicity data are available for most of the individual 

constituents, and, although data for mixtures corresponding to these fractions have been 

generated, many of the studies originally were unpublished industry studies. Some of the studies 

are now available as Toxic Substances Control Act Test Submissions (TSCATS) microfiche, or 

were provided by MADEP, and a few have been published. 

 The aromatic hydrocarbon fractions, discussed subsequently, pose less of a problem 

because of the availability not only of toxicity data, but also, in many cases, of U.S. EPA RfDs 

and cancer assessments. The definition of the fractions, however, is not as clear. 

 As a preliminary step in identifying potential surrogate compounds to represent the 

toxicity of the fractions or identifying compounds useful in a components method, a list of 

individual hydrocarbons was compiled and additional background searching was performed. 

The list included all individual hydrocarbons considered previously by the U.S. EPA NCEA’s 

Superfund Technical Support Center in the evaluation of hydrocarbons, as well as all those with 

toxicity data reviewed by MADEP (2003) or the TPHCWG (1997b). Similarly, a list of 

mixtures, primarily hydrocarbon streams, was compiled from these sources. Background 

searching focused on the IRIS database (U.S. EPA, 2009o), the HEAST (U.S. EPA, 1997), 

ATSDR Toxicological Profiles (ATSDR, 2008), the Chemical Assessments and Related 

Activities (CARA) list (U.S. EPA, 1991, 1994), and the Drinking Water Standards and Health 

Advisories list (U.S. EPA, 2006). Additionally, CalEPA (2008), the National Toxicology 

Program (NTP, 2008), the World Health Organization (WHO, 2008), and the International 

Agency for Research on Cancer (IARC, 2008a, b) were consulted for information. The 

U.S. EPA’s (2007a) High Production Volume (HPV) Challenge Program, and particularly the 

Petroleum HPV Testing Group (2007) publications, as well as the Organisation for Economic 

Co-operation and Development (OECD) HPV Programme Screening Information Data Set 

(SIDS) documents (OECD/SIDS, 2007) were searched for pertinent information. Additional 

pertinent individual compounds and mixtures encountered during this background search were 

added to the list for further consideration. On the basis of the information found during 

background searches, some compounds and mixtures that appeared to be possible candidates for 

use as surrogates were subjected to preliminary searching in MEDLINE (PUBMED) and 

TSCATS. If chosen for PPRTV development on the basis of the results of the background 

searching or the preliminary searching, compounds and mixtures were then subjected to the full 

suite of searching (through 2009). The search details are described in the front matter of the 

PPRTV documents (U.S. EPA, 2009a-i). Final lists of candidate toxicity values for 
FINAL 

9-30-2009 

14 

consideration as surrogates for the aromatic and aliphatic fractions are compiled in Tables 2–6 of 

this document; the sources are identified in the left column as IRIS, PPRTV, HEAST, MADEP, 

TPHCWG, or ATSDR. 

Method for Surrogate Compound or Mixture Selection 

 The criteria used for selecting chemicals or mixtures for potential use as surrogates, or for 

choosing a components method, are as follows: 

• The surrogate mixture or compound had to be a relevant aliphatic or aromatic 

hydrocarbon or composed exclusively of aliphatic or aromatic hydrocarbons. 

• The surrogate mixture or compound had to have either U.S. EPA toxicity values or 

adequate data for the derivation of toxicity values—particularly subchronic and chronic 

RfDs and/or RfCs. The ability to support the development of a carcinogenicity 

assessment was desirable but not required. 

• First preference was given to mixtures that are similar2 to the fraction in composition, and 

that have toxicity values or adequate toxicity data to support the derivation of toxicity 

values. 

o Criteria for similarity of composition included similar C and EC number range, 

similar aliphatic or aromatic hydrocarbon components, and purity (e.g., lack of 

contamination of aliphatic mixtures with aromatics and vice versa, and lack of 

contamination with nonaliphatic or aromatic hydrocarbon compounds). 

o Toxicity considerations include similarity of effect of the surrogate mixture with 

known toxicities of the individual components of the fraction. 

• If suitable mixture data were lacking, the next step was to select from the fraction a 

representative compound that was known or could be assumed to be similar 

toxicologically (defined previously), in terms of types of effects in vivo and potency, to 

the other compounds in the fraction, and that had either suitable toxicity values or 

adequate toxicity data to support the derivation of toxicity values. 

• If the components of the fraction varied highly in type or potency of toxic action, the 

more toxic component (e.g., n-hexane, low carbon range aliphatic fraction) was used as 

the surrogate when it exceeded the percentage found in the surrogate mixture (e.g., 

commercial hexane, inhalation assessment) or when other suitable values were not 

available for the exposure route (oral). Alternatively, the components with different and 

more potent toxicities (naphthalene and 2-methylnaphthalene) were recommended to be 

assessed separately, and the remaining mass of the fraction (medium carbon range 

aromatics) assessed using values for a surrogate mixture (high-flash aromatic naphtha). 

• If the toxicities of all the individual compounds were well characterized, toxicity values 

were available or could be derived for the individual compounds, and these compounds 

were monitored at sites of aliphatic or aromatic hydrocarbon contamination, then toxicity 

values were provided for the individual compounds to support a components method 

 

2

Similar mixtures are mixtures that differ slightly, but they are expected to have comparable characteristics for fate, 

transport, physiologic processes, and toxicity. These mixtures may have the same components but in slightly 

different proportions, or they have most components in nearly the same proportions with only a few different (more 

or fewer) components. Similar mixtures cause the same biologic activity or are expected to cause the same type of 

biologic activity due to chemical composition. Similar mixtures act by the same mechanism of action or affect the 

same toxic endpoint (U.S. EPA, 2000). 
FINAL 

9-30-2009 

15 

wherein the potential risk from exposure to each component is assessed individually (e.g., 

the low carbon range aromatic fraction), followed by application of appropriate additivity 

methods. 

• For the high carbon range aromatic fraction, a components method was recommended for 

the carcinogenic (Group B2) PAHs, using an existing method, the RPF method, to assess 

carcinogenicity. 

• Uncertainties regarding the suitability of the surrogate compound or mixture to represent 

the toxicity of the fraction were discussed. 

Toxicity Values for Aliphatic Fractions

 The aliphatic fractions as defined by MADEP in terms of C range are similar to the 

fractions as defined by the TPHCWG (1997a, b) in terms of EC range. This provisional 

assessment adopts these fractions and lists both C and EC ranges. 

Low Carbon Range Aliphatic Fraction: C5–C8, EC5–EC8

 This fraction includes n-pentane, n-hexane, cyclohexane, the dimethylbutanes and 

methylpentanes, cyclopentane, n-heptane, n-octane, some branched chain alkanes including the 

trimethylpentanes, cyclohexane, methylcyclopentane, and methylcyclohexane. According to the 

TPHCWG, this fraction also includes some alkenes, such as 1-hexene. MADEP, however, 

includes alkenes with aromatics and says they are not present in high concentrations in petroleum 

products. Previous efforts by MADEP (2003) and TPHCWG (1997b) to identify toxicity data 

for hydrocarbons in this fraction reported toxicity data for n-pentane, 2- and 3-methypentane, 

n-hexane, methylcyclopentane, cyclohexane, n-heptane, methylcyclohexane, 

2,2,4-trimethylpentane, and 1-hexene, as well as for two mixtures: commercial hexane and 

technical-grade heptane (MADEP, 2003; TPHCWG, 1997b).

 Commercial hexane generally contains approximately 50–53% n-hexane 

(TPHCWG, 1997b; U.S. EPA, 2005b). The remaining constituents of commercial hexane are 

the following branched and cyclic C6 aliphatic compounds: 3-methylpentane, 

methylcyclopentane, 2-methylpentane, cyclohexane, 2,3-dimethylbutane, and <1% of several 

minor constituents. Technical-grade heptane, in the only toxicity study located for this mixture 

(Truhaut et al., 1973), contained approximately 52% n-heptane, with the remainder of the 

mixture consisting of the following C6-C8 aliphatic compounds: 2- and 3-methylhexane, 

2,3-dimethylpentane, cyclohexane, methylcyclohexane, 2,4-dimethylhexane, and approximately 

3% aromatic compounds (benzene and toluene). It did not contain n-hexane. 

 For this low carbon range aliphatic fraction, derivations of toxicity values have been 

considered by the U.S. EPA, ATSDR, MADEP, and TPHCWG and are summarized in Table 2. 

RfCs are available for n-hexane and cyclohexane, but no RfDs are available on IRIS 

(U.S. EPA, 2009o). A subchronic provisional RfD (p-RfD) and a subchronic p-RfC have been 

developed for n-hexane (U.S. EPA, 2009c). The only aliphatic hydrocarbon mixture in this 

fraction range that has sufficient toxicity data for derivation of oral or inhalation toxicity values 
 16

Table 2. Toxicity Values for the Low-Carbon Range Aliphatic Fraction: C5–C8, EC5–EC8a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE OSF (per mg/kg-day) IUR (p

IRIS and PPRTV Values

6 6 n-Hexane RfD: Inadequate data RfC: 7 ×10-1, peripheral neuropathy, 

Huang et al., 1989 

Inadequate data NA NA 

6 6.59 Cyclohexane RfD: Inadequate data RfC: 6 × 100, reduced pup weight, 

DuPont HLR, 1997a 

Inadequate data NA NA 

7 7 n-Heptane Not assessed Not assessed Group D (not 

classifiable) 

NA NA 

IRIS (U.S. EPA, 

2009o)

8 6.98 2,2,4-Trimethylpentane RfD: Inadequate data RfC: Inadequate data Inadequate data NA NA 5 5 n-Pentane 6 6 n-Hexane sRfD: 3 × 10-1, reduced 

nerve conduction velocity (Ono et al., 1981) RfD: Not assessed 

sRfC: 2 × 100, decreased motor nerve 

conduction velocity, Huang et al., 1989 RfC: Not assessed 

Not assessed Not assessed Not asse

7 7 n-Heptane sRfD: Inadequate data 

RfD: Inadequate data 

sRfC: Inadequate data RfC: Inadequate data 

Inadequate data Inadequate data Inadequ

PPRTV (U.S. EPA, date in 

last column)

7 7.22 Methylcyclohexane sRfD: Inadequate data 

RfD: Inadequate data 

sRfC: Inadequate data RfC: Inadequate data 

Cannot be determinedsuggestive 

NA NA 

PPRTV (U.S. 

EPA, date in last 

6 – Commercial hexane sRfD: Inadequate data 

RfD: Inadequate data 

sRfC: 27 × 100, clinical and 

histopathological signs of neuropathy, IRDC, 1992a,b RfC: 6 × 10-1, nasal epithelial cell 

hyperplasia, Biodynamics, 1993a/Daughtrey et al.,1999 

Suggestive evidence 

Inadequate data 1.9 × 10

pituitary or carcinBiodyna1993b; Det al., 19(*ScreenValue) 
 17

Table 2. Toxicity Values for the Low-Carbon Range Aliphatic Fraction: C5–C8, EC5–EC8a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE OSF (per mg/kg-day) IUR (p

Other Peer-Reviewed or Relevant Toxicity Values

6 6 n-Hexane sRfD: 6 × 10-1neuropathy 

and testicular atrophy, Krasavage et al., 1980 RfD: 6 × 10-2neuropathy 

and testicular atrophy, Krasavage et al., 1980 

sRfC: 2 × 10-1 adopted RfC on IRIS at 

the time as sRfC 

Not assessed Not assessed Not asse

HEAST (U.S. EPA, 1997) 7 7.22 Methylcyclohexane Not assessed sRfC: 3 × 100, possible male rat hyaline droplet nephropathy, Kinkead et al., 1985 RfC: 3 × 100, possible male rat hyaline droplet nephropathy, Kinkead 

et al., 1985 

Not assessed Not assessed Not asse

MADEP 

(2003)

6 6 n-Hexane RfD: 4 × 10-2, reduced 

body weight (peripheral neuropathy at high dose), Krasavage et al., 1980 

RfC: 2 × 10-1, neurotoxicity, 1993 

IRIS value 

Not assessed Not assessed Not asse

TPHCW

G (1997b)6 – Commercial hexane RfD: 5 × 100, extrapolated from TPHCWG RfC 1.84 × 101, neurotoxicity and other systemic and portal of entry effects (several industry studies, mostly referenced to abstracts) Not assessed Not assessed Not asse

ATSDR (date 

in last column)6 6 n-Hexane Intermediate MRL: Inadequate data Chronic MRL: Inadequate data Intermediate MRL: Inadequate data Chronic MRL: 6 × 10-1 ppm, reduced motor nerve conduction velocity, Sanagi et al., 1980 Not assessed Not assessed Not asse
 18

Table 2. Toxicity Values for the Low-Carbon Range Aliphatic Fraction: C5–C8, EC5–EC8a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE OSF (per mg/kg-day) IUR (p

aComplete citations for the principal studies can be found in the source documents (e.g., IRIS [U.S. EPA, 2009o]) bDate of IRIS assessment (last revision) or of PPRTV or ATSDR toxicological profile; dates for HEAST, MADEP and TPHCWG are provided in far left c

ATSDR = Agency for Toxic Substances and Disease Registry, C = carbon number, EC = equivalent carbon number index, HEAST = Health Effects AssessINPROC = in process, IRIS = Integrated Risk Information System, IUR = inhalation unit risk, MADEP = Massachusetts Department of Environmental ProMinimal Risk Level, NA = Not applicable, OSF = oral slope factor, p- = provisional, PPRTV = Provisional Peer-Reviewed Toxicity Value, PTV = Provisio

(draft), RfC = inhalation reference concentration, sRfC = subchronic RfC, RfD = oral reference dose, sRfD = subchronic RfD, TPHCWG = Total Petroleum 

Working Group, WOE = weight of evidence 
FINAL 

9-30-2009 

 19

is commercial hexane. Although the oral data do not support derivation of RfDs, a subchronic 

p-RfC, a p-RfC, and a cancer assessment, including a screening3

 inhalation unit risk, have been 

developed for commercial hexane (U.S. EPA, 2009f). Updated literature searches were 

performed for cyclohexane in 2009, but no newer data that would support derivation of oral 

toxicity values or impact the inhalation RfC were found. n-Heptane and methylcyclohexane 

were the subjects of PPRTV development; the data did not support development of subchronic or 

chronic RfDs or RfCs for these compounds (U.S. EPA, 2004d, 2005a). Development of a 

PPRTV for n-pentane is in process; information from that PPRTV will be considered for use in 

evaluating hydrocarbon mixtures when this mixtures PPRTV document is revised. 

 ATSDR has considered n-hexane, but it has not developed oral MRLs for this compound 

(ATSDR, 1999b). The HEAST (U.S. EPA, 1997) lists subchronic and chronic RfDs for 

n-hexane and subchronic and chronic RfCs for methylcyclohexane, but these values are 

superseded by the more recent PPRTV documents for these chemicals. MADEP (2003) has 

developed an RfD for n-hexane and has adopted the previous IRIS RfC for this compound (the 

current RfC became available in 2005). The TPHCWG (1997b) has derived an inhalation RfC 

for commercial hexane using methods inconsistent with current U.S. EPA practice, and they 

performed a route-to-route extrapolation of this value to derive an RfD. 

 

 As per MADEP’s (2003) update of its toxicity values and the 2004 PPRTV on n-heptane 

(which also covered technical-grade heptanes; U.S. EPA, 2004d), pertinent data for 

technical-grade heptane are limited to a single study (i.e., Truhaut et al., 1973) that suggested 

peripheral neuropathy in rats exposed by inhalation. Information in the study, however, does not 

support development of toxicity values, and the mixture contained both toluene and benzene, as 

previously described. Literature searches conducted in 2009 revealed no newer data or any data 

on an aromatic-free heptane mixture that could be used to develop toxicity values. 

 Data on the individual aliphatic hydrocarbons of this fraction suggest nervous system 

effects. While some of the compounds have central nervous system effects, as well as liver and 

kidney effects, peripheral neuropathy is the critical effect of n-hexane, mediated through its 

metabolite, 2,5-hexandione (a gamma-diketone; U.S. EPA, 2009o). Concern has focused on the 

potential for some of the other compounds in this fraction to be metabolized to gamma-diketones 

and, therefore, also cause peripheral neuropathy. As reviewed by MADEP (2003), studies with 

the putative gamma-diketone metabolites (e.g., 2,5-heptanedione, 3,6-octanedione) of some of 

the compounds in this fraction have suggested that they may cause peripheral neuropathy, but 

data showing that exposure to the parent compound may cause peripheral neuropathy are 

inadequate. For example, neither oral nor inhalation exposure to n-heptane caused peripheral 

neuropathy in rats in studies that specifically investigated this potential outcome 

(U.S. EPA, 2004d). In a study of the potential peripheral neurotoxicity of n-hexane isomers, 

2-methylpentane, 3-methylpentane, and methylcyclopentane were administered by gavage to rats 

in increasing amounts over the course of 8 weeks (Ono et al., 1981). Although n-hexane, 

administered in the same manner, significantly decreased peripheral nerve conduction velocity 

(motor nerve, mixed nerve-distal portion, and mixed nerve-proximal portion of the tail), the other 

compounds were less effective or ineffective. The data, however, were reported graphically, no 

 

3

 Screening values are developed in the Appendix of a PPRTV. For example, in cases where a high degree of 

uncertainty exists. Screening values are intended for use in limited circumstances when no Tier 1, 2, or 3 values are 

available. 
FINAL 

9-30-2009 

 20

clinical signs of neuropathy were seen for any of the compounds, and histopathological 

examinations of the peripheral nerves were not conducted. Thus, the effects of these hexane 

isomers are not readily quantifiable and the clinical significance of the isomer results is unclear. 

However, Krasavage et al. (1980) also directly showed that none of these compounds produced 

toxicity to the extent that 2,5-hexandione did. This study showed a correlation between 

neurotoxicity index and the peak serum concentrations of 2,5-hexandione from several peripheral 

neurotoxicants including n-hexane. 

 To represent the toxicity of this fraction, the inhalation PPRTVs for commercial hexane 

(U.S. EPA, 2009f) are recommended, unless n-hexane accounts for >53% of the analyzed 

fraction, in which case the n-hexane toxicity values should be used (see Table 2). Use of the 

mixture data better represents the toxicity of the fraction, although there are uncertainties with 

this method because it is predominantly a C6 mixture. Exposure to airborne commercial 

mixtures has been associated in a few studies with neurological effects in workers (e.g., 

Passero et al., 1983), and a subchronic continuous inhalation exposure study of commercial 

hexane in experimental animals (IRDC, 1992a, b) reported peripheral neuropathy as the critical 

effect. In contrast, the critical effect for chronic inhalation exposure to this mixture was nasal 

lesions. While histopathological evaluation of the respiratory tract was performed in the 

subchronic study, no adverse findings were observed. Therefore, a chronic p-RfC based on nasal 

and laryngeal lesions is protective for the peripheral neuropathy seen in the subchronic 

continuous exposure study (IRDC, 1992a, b). Because no oral toxicity values could be derived 

for commercial hexane, the oral toxicity of the fraction can be assessed using the subchronic 

p-RfD for n-hexane (U.S. EPA, 2009c). The data for commercial hexane are considered 

adequate to develop a quantitative estimate of cancer risk from inhalation exposure for this 

fraction. However, because the WOE indicates “Suggestive Evidence for the Carcinogenic 

Potential,” there is some uncertainty associated with the quantification. For these reasons, 

Appendix A of the commercial hexane PPRTV document contains a screening p-IUR that may 

be useful in certain instances (i.e., when n-hexane accounts for ≤ 53% of this fraction). Please 

see the that Appendix for details (U.S. EPA, 2009f). Table 2 lists these values and assessments. 

Medium Carbon Range Aliphatic Fraction: C9–C18, EC > 8–EC16 

 This fraction includes n-nonane, n-decane, and longer chain n-alkanes; a few n-alkenes 

(e.g., tridecene); branched chain alkanes and alkenes; and alkyl-substituted cycloalkanes (see 

comment about alkenes at the beginning of the previous section). Derivations of toxicity values 

for these compounds are not available from the U.S. EPA’s IRIS or HEAST, or from ATSDR, 

MADEP, or TPHCWG. PPRTVs for n-nonane and n-decane are completed; information from 

those PPRTVs will be considered for use in evaluating hydrocarbon mixtures when this mixtures 

PPRTV document is revised. Limited toxicity data are available for n-undecane (VCCEP, 2004). 

ATSDR toxicological profiles and inhalation MRLs are available for various jet fuels and 

kerosene, but these mixtures have a substantial aromatic content and are therefore not suitable to 

represent the toxicity of this fraction. The toxicity of this fraction may be better represented by 

dearomatized hydrocarbon streams and solvents that fall within this carbon range and have 

minimal (<1.0%) aromatic content. Subchronic oral toxicity studies were performed with the 

mixtures listed in the following bullets (note that the term n-paraffins refers to n-alkanes, the 

term isoparaffins refers to branched chain alkanes, and the terms naphthenes and cycloparaffins 

refer to cyclic alkanes): 
FINAL 

9-30-2009 

 21

• C11–C17 isoparaffin mixture, typical aromatic content <0.05% (Anonymous, 1990); 

• C9–C12 isoparaffin/n-alkane/naphthene mixture with an aromatic content <0.5% 

(Anonymous, 1991b); 

• C10–C13 isoparaffin/naphthene/n-alkane mixture with an aromatic content of 0.1% 

(Anonymous, 1991a). 

 Subchronic and 6-month inhalation toxicity studies have been performed with the 

following mixtures: 

• C10–C11 isoparaffin mixture with no aromatic content (Phillips and Egan, 1984); 

• C11–C12 dearomatized white spirit (paraffin/naphthene mixture) with an aromatic 

content <0.5% (Phillips and Egan, 1984); 

• C range not reported, dearomatized white spirit (content not reported; Lund et al., 1996). 

 Subchronic toxicity and 2-year toxicity/carcinogenicity studies have been performed with 

the following mixture: 

• C10–C13 Stoddard Solvent IIC (n-paraffins, isoparaffins, cycloparaffins) with an 

aromatic content <1.0% (NTP, 2004). 

 Complete citations for these studies are provided in U.S. EPA (2009h). Some additional 

supporting toxicity studies on similar mixtures are available as well. 

 

Table 3 lists the available toxicity information for this fraction. The MADEP (2003) and 

TPHCWG (1997b) have based their toxicity values for this fraction on some of the studies of 

aliphatic hydrocarbon streams. Other suitable data have not been located. The mixture data are 

considered preferable to single component data, as previously discussed. Accordingly, PPRTVs 

were derived based on the mixture data as part of the effort to provide suitable toxicity values for 

this fraction (U.S. EPA, 2009h) using current U.S. EPA methods. These PPRTVs, listed in 

Table 3, are the recommended values for this fraction and include subchronic and chronic 

p-RfCs and a provisional cancer WOE of “Suggestive Evidence of Carcinogenic Potential.” In 

addition, Table 3 contains several screening values that may be useful in evaluating this fraction, 

developed in Appendix A of U.S. EPA (2009h). Because the toxicity data based on the three 

unpublished studies (Anonymous, 1990, 1991a,b) are not peer-reviewed, only screening chronic 

or subchronic RfDs are available in Table 3. The data are considered adequate to develop a 

quantitative estimate of cancer risk from inhalation exposure. However, because the WOE 

indicates “Suggestive Evidence for the Carcinogenic Potential,” there is some uncertainty 

associated with the quantification. Appendix A of the PPRTV document on the Midrange 

Aliphatic Hydrocarbon Streams contains a screening p-IUR and screening chronic or subchronic 

RfDs that may be useful in certain instances (U.S. EPA, 2009h). Please see that Appendix for 

details. The screening IUR is listed in Table 3 (U.S. EPA, 2009h). 
 22

Table 3. Toxicity Values for the Medium Carbon Range Aliphatic Fraction: C9–C18, EC > 8–EC

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE OSF (per mg/kg-day) 

PPRTV Values

9 9 n-Nonane 10 10 n-Decane 

PPRTV (U.S. EPA, date in 

last column) 9–18 8–16 Aliphatic hydrocarbon streams/solvents within the C9–C18 range and containing <0.5% to <1% aromatics sRfD: 1 × 10-1, liver, kidney and hematologic effects, Anonymous, 1990, 1991a,b (*Screening Value) RfD: 1 × 10-2, based on same study as the sRfD 

(*Screening Value) 

sRfC: 1 × 10-1, nasal goblet cell 

hypertrophy, NTP, 2004RfC: 1 × 10-1, nasal goblet cell 

hypertrophy and adrenal hyperplasia, NTP, 2004 

Suggestive evidence 

Inadequate data 

Other Peer-Reviewed or Relevant Toxicity Values

MADEP 

(2003)

9–18 8–16 Aliphatic hydrocarbon 

streams within the C9–C18 range and containing <0.5% aromatics 

RfD: 1 × 10-1, liver effects, Anonymous, 1990, 1991a,b 

RfC: 2 × 10-1, neurological 

effects, Lund et al., 1995 

Not assessed 

Not assessed 

TPHCW

G (1997b)9–18 8–16 Aliphatic hydrocarbon streams within the C9–C18 range and containing <0.5% aromatics RfD: 1 × 10-1, liver effects, unpublished studies not further referenced RfC: 1 × 100, NOAELs, multiple studies Not assessed Not assessed 

aComplete citations for the principal studies can be found in the source documents (e.g., MADEP, 2003).bDate of PPRTV; dates for MADEP and TPHCWG are provided in far left column of table. 

*Screening values are developed in the Appendix of a PPRTV. For example, in cases where a high degree of uncertainty exists. Screening Values are inten

circumstances when no Tier 1, 2, or 3 values are available. C = carbon number, EC = equivalent carbon number index, INPROC = in process, IUR = inhalation unit risk, MADEP = Massachusetts Department of Env

NOAEL = no-observed-adverse-effect level, OSF = oral slope factor, p- = provisional, PPRTV = Provisional Peer-Reviewed Toxicity Value, RfC = inhalatconcentration, sRfC = subchronic RfC, RfD = oral reference dose, sRfD = subchronic RfD, TPHCWG = Total Petroleum Hydrocarbon Criteria Working G

evidence
FINAL 

9-30-2009 

 23

High Carbon Range Aliphatic Fraction: C19–C32, EC > 16–EC35 

 This fraction includes longer n-alkanes, such as eicosane, and branched and cyclic 

alkanes. Toxicity values are not available for the individual compounds. A search for toxicity 

information on eicosane in particular was desirable because MADEP (1994) had suggested it as a 

reference compound for this fraction, but data supportive of derivation of toxicity values were 

not located. Food-grade and medicinal-grade mineral oils are pure (aromatic-free) mixtures of 

aliphatic hydrocarbons that correspond to this carbon range fraction and have data suitable for 

toxicity-value derivation. Both MADEP (2003) and TPHCWG (1997b) have based RfDs on 

these data. To support this update of the PPRTV on aliphatic and aromatic hydrocarbons, 

literature searches on mineral oils were performed and the medical literature on mineral oils was 

consulted. Oral PPRTVs and a cancer assessment, including a WOE of “Inadequate Information 

to Assess the Carcinogenic Potential” of white mineral oil, were derived (U.S. EPA, 2009i) 

using current U.S. EPA methods. Table 4 summarizes the resulting values and the previous 

MADEP and TPHCWG values. The PPRTVs are recommended for assessment of this fraction. 

Toxicity Values for Aromatic Fractions

Low Carbon Range Aromatic Fraction: C6–C8, EC6–EC < 9 

 This fraction contains aromatic hydrocarbons in the C6-C8 range: benzene, toluene. 

ethylbenzene, and o-, m-, and p-xylenes (commonly referred to as BTEX). The TPHCWG 

(1997b) defined this fraction variously as EC > 7–EC8 and EC5–EC8. Benzene was not 

included in the noncancer assessment because it was a carcinogenic indicator compound. 

Toluene, ethylbenzene, styrene, and xylene were included, but, with the exception of toluene, the 

EC values for these C8 compounds are all >8 (and <9), so it appears that the TPHCWG (1997b) 

was using actual C number rather than EC number. The MADEP recommended that the 

low-carbon-range aromatics (BTEX [MADEP 1994, 2003] and styrene [MADEP, 2003]) be 

assessed individually. It is unclear, however, whether styrene is a constituent of petroleum 

products. For example, styrene is not reported as a constituent of any of the petroleum mixtures 

including gasoline, kerosene, jet fuels, diesel fuel, fuel oils, lubricating and motor oils, and crude

oil in the TPHCWG (1998b) Volume 2. The TPHCWG (1997a) Volume 3 lists styrene as a 

constituent for only one mixture, diesel, at a very low weight percentage of <0.002%, which may 

mean that it was detected but was below the quantitation limit. The reference provided for that 

information is a personal communication prepared for British Petroleum; thus, the information 

cannot readily be confirmed. 

 Because U.S. EPA toxicity values and cancer assessments are available for the individual 

compounds in this fraction, and because the BTEX routinely are monitored at sites of aromatic 

hydrocarbon contamination, the recommendation for this fraction is to assess the BTEX 

individually. Consistent with this recommendation, the low carbon range aromatic fraction is 

defined as a C6–C8 and EC6–EC < 9 fraction so that it includes all of the BTEX. RfDs, RfCs, 

and cancer assessments are available on IRIS (U.S. EPA, 2009o) for these compounds, and 

provisional toxicity values were derived for subchronic oral and inhalation exposure 

(U.S. EPA, 2009a-d) as part of this effort. The HEAST (U.S. EPA, 1997) lists some values or 

assessments for the compounds, but they are superseded by the newer IRIS and PPRTV 

assessments. ATSDR has derived MRLs for the BTEX as well, but their methods sometimes 

differ from U.S. EPA methods and some of their assessments of these compounds are older. 

Table 5 summarizes these values and the bases for their derivations.
 24

Table 4. Toxicity Values for the High Carbon Range Aliphatic Fraction: C19–C32, EC > 16–

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE OSF (

mg/kg-

PPRTV Values

PPRTV (U.S. EPA, 

date in last column)19–32 >16–35 White mineral oils generally in the C and EC range of interest sRfD: 3 × 101 lower end of human therapeutic dose range for laxative effects, NASPGHN, 2006 RfD: 3 × 100, based on same data as the sRfD sRfC: NA RfC: NA Inadequate information to assess Inadequ

data 

Other Peer-Reviewed or Relevant Toxicity Values

MADEP 

(2003)

19–32 >16–35 White mineral oils 

generally in the C and EC range of interest 

RfD: 2 × 100, liver granuloma Smith et 

al., 1996 

RfC: Inadequate data, not volatile Not assessed Not asse

TPHCWG 

(1997b)

19–32 >16–35 White mineral oils 

generally in the C and EC range of interest 

RfD: 2 × 100, liver granuloma, Smith et 

al., 1996 

RfC: Not assessed Not assessed Not asse

aComplete citations for the principal studies can be found in the source documents (e.g., MADEP, 2003).bDate of PPRTV; dates for MADEP and TPHCWG are provided in far left column of table. 

C = carbon number, EC = equivalent carbon number index, IUR = inhalation unit risk, MADEP = Massachusetts Department of Environmental Protec

OSF = oral slope factor, p- = provisional, PPRTV = Provisional Peer-Reviewed Toxicity Value, PTV = Provisional Toxicity Value (draft); RfC = inha

concentration, sRfC = subchronic RfC, RfD = oral reference dose, sRfD = subchronic RfD, TPHCWG = Total Petroleum Hydrocarbon Criteria Workievidence 
 25

Table 5. Toxicity Values for the Low Carbon Range Aromatic Fraction: C6–C8, EC6–EC < 9

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE OSF (per mg/kg-day) 

IRIS and PPRTV Values

6 6.5 Benzene RfD: 4 × 10-3, decreased lymphocyte 

count, Rothman et al., 1996, extrapolated from inhalation 

RfC: 3 × 10-2, decreased 

lymphocyte count, Rothman et al., 1996 

Group A (human carcinogen), known/likely human carcinogen 

1.5 × 10-2 to 

5.5 × 10-2, leukemia, several studieextrapolated from inhalatio

7 7.58 Toluene RfD: 8 × 10-2, increased kidney weight, 

NTP, 1990 

RfC: 5 × 100, neurological 

effects, multiple studies 

Inadequate data 

NA 

8 8.5 Ethylbenzene RfD: 1 × 10-1, liver and kidney lesions, 

Wolf et al., 1956 

RfC: 1 × 100, developmental 

effects, Andrew et al., 1981; Hardin et al., 1981 

Group D (not classifiable) 

NA 

IRIS (U.S. EPA, 2009o)

8 8.6–

8.81 

Xylenes RfD: 2 × 10-1, decreased body weight, 

increased mortality, NTP, 1986 

RfC: 1 × 10-1, impaired motor 

coordination, Korsak et al., 1994 

Inadequate data 

NA 

6 6.5 Benzene sRfD: 1 × 10-2, decreased lymphocyte 

count, Rothman et al., 1996, extrapolated from inhalation (U.S. EPA, 2009o) RfD: Not assessed 

sRfC: 8 × 10-2, decreased 

lymphocyte count, Rothman et al., 1996 RfC: Not assessed 

Not assessed Not assessed 

7 7.58 Toluene sRfD: 8 × 10-1, increased kidney weight, 

NTP, 1990 RfD: Not assessed 

sRfC: 5 × 100, neurological 

effects, multiple studies, U.S. EPA, 2009o RfC: Not assessed 

Not assessed Not assessed 

8 8.5 Ethylbenzene sRfD: 5 × 10-2, centrilobular hepatocyte 

hypertrophy, Mellert et al., 2007 RfD: Not assessed 

sRfC: 9 × 100, ototoxicity, 

Gagnaire et al., 2007 RfC: Not assessed

Not assessed Not assessed 

PPRTV (U.S. EPA, date in last column) 8 8.6– 8.81 Xylenes sRfD: 4 × 10-1, reduced body weight, Wolfe et al., 1988a RfD: Not assessed sRfC: 4 × 10-1,neurological effects, Korsak et al., 1994 RfC: Not assessed Not assessed Not assessed 
 26

Table 5. Toxicity Values for the Low Carbon Range Aromatic Fraction: C6–C8, EC6–EC < 9

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE OSF (per mg/kg-day) 

Other Peer-Reviewed or Relevant Toxicity Values

6 6.5 Benzene Not assessed sRfC: [Comment: Contact 

Superfund Health Risk Technical Support Center]RfC: Not assessed 

Not assessed Not assessed 

7 7.58 Toluene sRfD: 2 × 100, altered liver and kidney 

weight, NTP, 1989 RfD: Not assessed 

sRfC: [Comment: Contact the Superfund Health Risk Technical Support Center] RfC: Not assessed 

Not assessed Not assessed 

8 8.5 Ethylbenzene sRfD: [Comment: Contact Superfund 

Health Risk Technical Support Center] RfD: Not assessed 

sRfC: [Comment: Contact Superfund Health Risk Technical Support Center] RfC: Not assessed

Not assessed Not assessed 

HEAST (U.S. EPA, 1997) 

8 8.6–

8.81 

Xylenes sRfD: [Comment: Contact Superfund 

Health Risk Technical Support Center] RfD: Not assessed 

sRfC: Not assessed RfC: Not assessed 

Not assessed Not assessed 

6 6.5 Benzene Intermediate MRL: Inadequate data 

Chronic MRL: 5 × 10-4, extrapolated 

from inhalation 

Intermediate MRL: 6 × 10-3

ppm, delayed splenic lymphocyte reaction to antigens (Rosenthal and Snyder, 1987) RfC: 3 × 10-3 ppm, decreased 

B-lymphocyte counts, Lan et al., 

2004a,b 

Not assessed Not assessed 

7 7.58 Toluene Intermediate MRL: 2 × 10-2, regional 

increases in brain monoamine neurotransmitters, Hsieh et al., 1990b Chronic MRL: Inadequate data

Intermediate MRL: Inadequate 

data; use chronic MRL Chronic MRL: 8 × 10-2 ppm 

(3 × 10-1 mg/m3), color vision 

impairment, Zavalic et al., 1998a 

Not assessed Not assessed 

ATSDR (date in last column) 8 8.5 Ethylbenzene Intermediate MRL: Inadequate data 

Chronic MRL: Inadequate data

Intermediate MRL: 1 × 100 

ppm, developmental effects, Andrew et al., 1981 Chronic MRL: Inadequate data

Not assessed Not assessed 
 27

Table 5. Toxicity Values for the Low Carbon Range Aromatic Fraction: C6–C8, EC6–EC < 9

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE OSF (per mg/kg-day) 

ATSDR (date in last column) 

8 8.6–

8.81 

Xylenes Intermediate MRL: 4 × 10-1, 

neurotoxic effects (NTP, 1986) Chronic MRL: 2 × 10-1, decreased body 

weight gain and survival (NTP, 1986) 

sRfC: 6 × 10-1 ppm, neurotoxic 

effects, Korsak et al., 1994 RfC: 5 × 10-2 ppm, respiratory 

and neurological effects, Uchida et al., 1993 

Not assessed Not assessed 

aComplete citations for the principal studies can be found in the source documents (e.g., IRIS [U.S. EPA, 2009o]). bDate of IRIS assessment (last revision) or of PPRTV; date for the HEAST is provided in far left column of table. 

ATSDR = Agency for Toxic Substances and Disease Registry, C = carbon number, EC = equivalent carbon number index, HEAST = Health Effects AssessIRIS = Integrated Risk Information System, IUR = inhalation unit risk, MRL = Minimal Risk Level, NA = Not applicable, OSF = oral slope factor, PPRTV 

Reviewed Toxicity Value, PTV = Provisional Toxicity Value (draft), RfC = inhalation reference concentration, sRfC = subchronic RfC, RfD = oral referen

subchronic RfD, RPF = Relative potency factor, WOE = weight of evidence 
FINAL 

9-30-2009 

 28

 The IRIS RfDs, RfCs, and cancer assessments and the PPRTVs (subchronic p-RfDs and 

subchronic p-RfCs) provided in Table 5 are the recommended values for assessment of the 

components of this fraction. 

Medium Carbon Range Aromatic Fraction: C9–C16, EC9–EC < 22 

 The MADEP (2003) grouped the entire range of aromatics from C9–C32 into a single 

fraction for the assessment of oral noncancer toxicity and divided the fraction into C9–C18 and 

C19–C32 fractions for the assessment of inhalation noncancer toxicity. The TPHCWG 

(1997a, b) defined their transport fractions by EC number rather than C number, but in selecting 

and deriving toxicity values, they actually used the C number range of C>8–C16 rather than the 

EC number range (TPHCWG, 1997b). For the aromatic hydrocarbons, the difference between C 

and EC can be large (e.g., the C16 compound fluoranthene has an EC of 21.85). An EC range of 

EC9–EC < 22 is recommended in this document, which corresponds to a C range of about 

C9–C16, for this medium carbon range aromatic fraction based on environmental transport and 

toxicological considerations—including volatility and carcinogenicity. This fraction is virtually 

the same as the fraction defined by the TPHCWG (1997b). 

 This medium carbon range aromatic fraction includes longer chain and multi-substituted 

benzenes (e.g., cumene [isopropylbenzene], n-propylbenzene, methylethylbenzenes, and 

trimethylbenzenes), indan, methylindans, naphthalenes, and some lower molecular weight PAHs 

(e.g., acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, and pyrene). As listed 

in Table 6, toxicity values and cancer assessments are available for some of these individual 

compounds. IRIS values include RfDs for cumene, napththalene, 2-methylnaphthalene, 

1,1-biphenyl, acenaphthene, fluorene, anthracene, and pyrene, RfCs for cumene and naphthalene 

and only qualitative cancer assessments for many of these compounds with the exception of an 

oral slope factor (OSF) for benzo(a)pyrene. Also listed in Table 6 are a mix of provisional 

toxicity values including values for p-RfDs, subchronic p-RfDs, p-RfCs, subchronic p-RfCs, pOSFs, screening RPFs, cancer assessments, and screening p-RfDs, subchronic p-RfDs, p-RfCs 

and subchronic p-RfCs (see entries for n-propylbenzene, 1,3,5-trimethylbenzene, 

1,2,4-trimethylbenzene, high-flash aromatic naphtha, 2-methylnaphthalene, 

1-methylnaphthalene, anthracene, pyrene, and benz(a)anthracene). A PPRTV for 1,2,3-

trimethylbenzene is completed (U.S. EPA, 2009k); information from that PPRTV will be 

considered for use in evaluating hydrocarbon mixtures when this mixtures PPRTV document is 

revised. Table 6 includes both the medium and high carbon range fractions to facilitate 

evaluation of the selected C and EC ranges for these two fractions, and because of the overlap 

between ranges in the MADEP approach and the TPHCWG’s classification by C rather than the 

EC number range. 
 29

Table 6. Toxicity Values for the Medium and High Carbon Range Aromatic Fractions

C9–C16, EC9–EC < 22 and C17–C32, EC22–EC35a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE, RPF OSF (p

mg/k

day

IRIS and PPRTV Values

9 9.13 Cumene 

(isopropylbenzene) 

RfD: 1 × 10-1, increased kidney 

weight, Wolf et al., 1956 

RfC: 4 × 10-1, increased 

kidney and adrenal weights, Cushman et al., 1995 

Group D (not classifiable) 

NA 

10 11.69 Naphthalene RfD: 2 × 10-2, decreased body 

weight, BCL, 1980 

RfC: 3 × 10-3, nasal lesions, 

NTP, 1992 

Group C (possible human carcinogen) 

Inadequdata 

11 12.84 2-Methylnaphthalene RfD: 4 × 10-3, alveolar proteinosis, 

Murata et al., 1997 

Inadequate data Inadequate 

data 

NA 

12 14.26 1,1-Biphenyl RfD: 5 × 10-2, kidney damage, 

Ambrose et al., 1960 

Inadequate Data Group D (not 

classifiable) 

NA 

12 15.06 Acenaphthylene Not assessed Not Assessed Group D (not 

classifiable) 

Inadequdata 

12 15.5 Acenaphthene RfD: 6 × 10-2, hepatotoxicity, 

U.S. EPA, 1989 

Not Assessed Not assessed Not 

assessed 

13 16.55 Fluorene RfD: 4 × 10-2, decreased red blood 

cells, packed cell volume and Hgb, U.S. EPA, 1989 

Not assessed Group D (not 

classifiable) 

NA 

14 19.36 Phenanthrene Not assessed Not assessed Group D (not 

classifiable) 

NA 

IRIS (U.S. EPA, 2009o), RPF from U.S. EPA (1993)

14 19.43 Anthracene RfD: 3 × 10-1, freestanding NOEL, 

U.S. EPA, 1989 

Not Assessed Group D (not 

classifiable) 

NA 
 30

Table 6. Toxicity Values for the Medium and High Carbon Range Aromatic Fractions

C9–C16, EC9–EC < 22 and C17–C32, EC22–EC35a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE, RPF OSF (p

mg/k

day

16 20.8 Pyrene RfD: 3 × 10-2, kidney effects, 

U.S. EPA, 1989 

Not assessed Group D (not 

classifiable)

NA 

16 21.85 Fluoranthene RfD: 4 × 10-2, kidney, liver, 

hematologic and clinical effects, U.S. EPA, 1988 

Not assessed Group D (not 

classifiable) 

NA 

18 26.37 Benz(a)anthracene Not assessed Not assessed Group B2 

(probable human carcinogen), RPF=0.1 

Not assessed 

IRIS (U.S. EPA, 2009o), RPF from 

U.S. EPA (1993)

18 27.41 Chrysene Not assessed Not assessed Group B2 

(probable human carcinogen), RPF=0.001 

Inadequdata 

20 30.14 Benzo(b)fluoranthene Not assessed Not assessed Group B2 

(probable human carcinogen), RPF=0.1 

Inadequdata 

IRIS (U.S. EPA, 2009o), 

RPF from U.S. EPA 20 30.14 Benzo(k)fluoranthene Not assessed Not assessed Group B2 (probable human carcinogen), 

RPF=0.01 

Inadequdata 
 31

Table 6. Toxicity Values for the Medium and High Carbon Range Aromatic Fractions

C9–C16, EC9–EC < 22 and C17–C32, EC22–EC35

a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m

3) 

Cancer 

WOE, RPF

OSF (p

mg/k

day

20 31.34 Benzo(a)pyrene Not assessed Not assessed Group B2 

(probable human carcinogen), RPF=1 

7.3× 10

0

forestomach (larynx, 

esophag4 data s

22 33.92 Dibenz(a,h)anthracene Not assessed Not assessed Group B2 

(probable human carcinogen), RPF=1 

Inadequdata 

22 34.14 Benzo(g,h,i)perylene Not assessed Not assessed Group D (not 

classifiable) 

NA 

IRIS (U.S. EPA, 2009o), RPF from U.S. EPA 22 35.01 Indeno(1,2,3-c,d)pyrene Not assessed Not assessed Group B2 (probable human carcinogen), 

RPF=0.1 

Inadequdata 

PPRTV (U.S. EPA, date in 

last column)

9 9.47 n-Propylbenzene sRfD: 1 × 10-1, liver and kidney 

toxicity, based on IRIS RfD for ethylbenzene, Wolf et al., 1956, using a surrogate analysis RfD: 1 × 10-1, liver and kidney 

toxicity, based on IRIS RfD for ethylbenzene, Wolf et al., 1956, using a surrogate analysis (*Screening Values)

sRfC: 1 × 10

0, developmental 

toxicity, based on IRIS RfC for ethylbenzene, Andrews et al., 1981; Hardin et al., 1981, using a surrogate analysis RfC: 1 × 10

0, developmental 

toxicity, based on IRIS RfC for ethylbenzene, Andrews et al., 1981; Hardin et al., 1981, using a surrogate analysis (*Screening Values)

Inadequate data 

NA 
 32

Table 6. Toxicity Values for the Medium and High Carbon Range Aromatic Fractions

C9–C16, EC9–EC < 22 and C17–C32, EC22–EC35

a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m

3) 

Cancer 

WOE, RPF

OSF (p

mg/k

day

9 9.62 1,3,5-Trimethylbenzene sRfD: 1 × 10-1, increased liver 

weight, Koch Industries, 1995 RfD: 1 × 10-2, increased liver 

weight, Koch Industries, 1995 (*Screening Values)

sRfC: 1 × 10-2, Wiaderna et 

al., 2002

RfC: Inadequate data

Inadequate data 

NA 

9 9.84 1,2,4-Trimethylbenzene sRfD: Inadequate data 

RfD: Inadequate data

sRfC: 7 × 10-2, decreased 

clotting time, Korsak et al., 2000 RfC: 7 × 10-3, based on sRfC 

study

Inadequate data 

Inadequdata 

9 10.06 1,2,3-Trimethylbenzene 10 9.84 tert-Butylbenzene sRfD: Inadequate data 

RfD: Inadequate data 

sRFC: Inadequate data RfC: Inadequate data 

Inadequate data 

Inadequdata 

10 9.98 sec-Butylbenzene sRfD: Inadequate data 

RfD: Inadequate data 

sRfC: Inadequate data RfC: Inadequate data 

Inadequate data 

Inadequdata 

10 10.5 n-Butylbenzene sRfD: Inadequate data 

RfD: Inadequate data 

sRfC: Inadequate data RfC: Inadequate data 

Inadequate data 

Inadequdata 

PPRTV (U.S. EPA, date in last column) 9-10 High-flash aromatic 

naphtha 

sRfD: 3 × 10-1, anemia, 

Bio/Dynamics, 1990b RfD: 3 × 10-2, from sRfD study 

(*Screening Values) 

sRfC: 1 × 10

0 maternal body 

weight depression, McKee et al.,1990 RfC: 1 × 10-1, from sRfC 

study 

Inadequate information to assess 

Inadequdata 

11 12.84 2-Methylnaphthalene sRfD: 4 × 10-3, alveolar proteinosis, 

Murata et al., 1997 RfD: Not assessed 

sRfC: Inadequate data RfC: Inadequate data 

Inadequate data 

NA 

PPRTV (U.S. EPA, 

date in last column) 11 12.99 1-Methylnaphthalene RfD: 7 × 10-3 (*Screening value) sRfC: Inadequate data RfC: Inadequate data Suggestive evidence 2.9 × 10
 33

Table 6. Toxicity Values for the Medium and High Carbon Range Aromatic Fractions

C9–C16, EC9–EC < 22 and C17–C32, EC22–EC35a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE, RPF OSF (p

mg/k

day

12 15.06 Acenaphthylene sRfD: Inadequate data 

RfD: Inadequate data

sRfC: Inadequate data RfC: Inadequate data

Inadequate data 

NA 

14 19.36 Phenanthrene sRfD: Inadequate data 

RfD: Inadequate data

sRfC: Inadequate data RfC: Inadequate data

Group D (not classifiable) 

NA 

14 19.43 Anthracene sRfD: 1 × 100 free standing NOEL, 

Wolfe, 1989 (RfD on IRIS) 

sRfC: Inadequate data RfC: Inadequate data

Inadequate data 

NA 

16 20.8 Pyrene sRfD: 3 × 10-1, kidney damage, 

U.S. EPA, 1989 RfD: Not assessed 

sRfC: Inadequate data RfC: Inadequate data 

Not likely to be a human carcinogen 

Inadequdata 

18 26.37 Benz(a)anthracene sRfD: Not assessed 

RfD: Inadequate data

sRfC: Not assessed RfC: Inadequate data

Not assessed, RPF=0.1 (*Screening Value) 

Inadequdata 

PPRTV (U.S. EPA, date in last column) 20 31.34 Perylene sRfD: Inadequate data 

RfD: Inadequate data 

sRfC: Inadequate data RfC: Inadequate data 

Inadequate data 

Inadequdata 

Other Peer-Reviewed or Relevant Toxicity Values

9 9.13 Cumene 

(isopropylbenzene) 

sRfD: 4 × 10-1, increased kidney 

weight, Wolf et al., 1956 

sRfC: 9 × 10-2 CNS effect, 

nasal irritation, Monsanto Co., 1986 RfC: 9 × 10-3, CNS effect, nasal irritation, Monsanto Co., 1986 

Not assessed Not 

assessed 

12 14.26 1,1-Biphenyl sRfD: 5 × 10-2 kidney damage, 

Ambrose et al., 1960 (RfD on IRIS)

RfC: considered not verifiable by RfD/RfC Work Group 

Not assessed Not 

assessed 

HEAST (U.S. EPA, 1997) 12 15.5 Acenaphthene sRfD: 6 × 10-1, liver effects, U.S. EPA, 1989 Not assessed Not assessed Not assessed 
 34

Table 6. Toxicity Values for the Medium and High Carbon Range Aromatic Fractions

C9–C16, EC9–EC < 22 and C17–C32, EC22–EC35a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE, RPF OSF (p

mg/k

day

13 16.55 Fluorene sRfD: 4 × 10-1, decreased red blood 

cells, U.S. EPA, 1989 

Not assessed Not assessed Not 

assessed 

14 19.43 Anthracene sRfD: 3 × 100, freestanding NOEL, 

U.S. EPA, 1989 

RfC: considered not verifiable 

by RfD/RfC Work Group 

Not assessed Not 

assessed 

16 20.8 Pyrene sRfD: 3 × 10-1, kidney damage, 

U.S. EPA, 1989 

RfC: considered not verifiable 

by RfD/RfC Work Group 

Not assessed Not 

assessed 

HEAST (U.S. EPA, 

1997)

16 21.85 Fluoranthene sRfD: 4 × 10-1, kidney, liver and 

hematologic effects, U.S. EPA, 1988 

RfC: considered not verifiable 

by RfD/RfC Work Group 

Not assessed Not 

assessed 

MADEP 

(2003)

9-10 High flash aromatic 

naphtha 

Not assessed RfC: 5 × 10-2, increased liver 

weight and possible CNS effects, Clark et al., 1989

Not assessed Not 

assessed 

TPHCWG 

(1997b)

9 9.47 High-flash aromatic 

naphtha (called C9 Aromatics by TPHCWG) 

Not assessed RfC: 2 × 10-1, increased liver 

and kidney weight, Clark et al., 1989

Not assessed Not 

assessed 

10 11.69 Naphthalene Intermediate MRL: 6 × 10-1, 

transient CNS signs rat dams, NTP, 1991 Chronic MRL: Inadequate data 

Intermediate MRL: Inadequate dataChronic MRL: 7 × 10-4 ppm 

(3 × 10-3 mg/m3), nasal 

lesions, NTP, 2000 

Not assessed Not 

assessed 

ATSDR (date in last 

column) 11 12.84 2-Methylnaphthalene Intermediate MRL: Inadequate 

dataChronic MRL: 4 × 10-2, alveolar 

proteinosis, Murata et al., 1993 

Intermediate and chronic MRL: Inadequate data 

Not assessed Not 

assessed 
 35

Table 6. Toxicity Values for the Medium and High Carbon Range Aromatic Fractions

C9–C16, EC9–EC < 22 and C17–C32, EC22–EC35a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE, RPF OSF (p

mg/k

day

ATSDR (date 

in last column)11 12.99 1-Methylnaphthalene Intermediate MRL: Inadequate data Chronic MRL: 7 × 10-2, alveolar proteinosis, Murata et al., 1997 Intermediate and chronic MRL: Inadequate data Not assessed Not assessed 

12 15.5 Acenaphthene Intermediate MRL: 6 × 10-1,liver 

effects, U.S. EPA, 1989c Chronic MRL: Inadequate data 

Intermediate and chronic MRL: Inadequate data 

Not assessed Not 

assessed 

13 16.55 Fluorene Intermediate MRL: 4 × 10-1, liver 

effects, U.S. EPA, 1989e Chronic MRL: Inadequate data 

Intermediate and chronic MRL: Inadequate data 

Not assessed Not 

assessed 

14 19.43 Anthracene Intermediate MRL: 1 × 101, free 

standing NOAEL (concern for liver effects), U.S. EPA, 1989d Chronic MRL: Inadequate data 

Intermediate and chronic MRL: Inadequate data 

Not assessed Not 

assessed 

ATSDR (date in last column) 16 21.85 Fluoranthene Intermediate MRL: 4 × 10-1, liver effects, U.S. EPA, 1989e 

Chronic MRL: Inadequate data 

Intermediate and chronic MRL: Inadequate data 

Not assessed Not 

assessed 
 36

Table 6. Toxicity Values for the Medium and High Carbon Range Aromatic Fractions

C9–C16, EC9–EC < 22 and C17–C32, EC22–EC35a

Derived Value 

Source C EC Name Oral (mg/kg-day) Inhalation (mg/m3) Cancer WOE, RPF OSF (p

mg/k

day

aComplete citations for the principal studies can be found in the source documents (e.g., IRIS [U.S. EPA, 2009o]). bDate of IRIS assessment (last revision), PPRTV, or ATSDR toxicological profile; dates for HEAST, MADEP, and TPHCWG are prov

table. *Screening values are developed in the Appendix of a PPRTV. For example, in cases where a high degree of uncertainty exists . Scree

for use in limited circumstances when no Tier 1, 2, or 3 values are available. RPF = Relative potency factor (U.S. EPA, 1993) listed with IRIS Cancer WOE for convenience of the reader. 

ATSDR = Agency for Toxic Substances and Disease Registry, C = carbon number, CNS = central nervous system, EC = equivalent ca

HEAST = Health Effects Assessment summary Table, INPROC = in process, IRIS = Integrated Risk Information System, IUR = inhal

Massachusetts Department of Environmental Protection, MRL = Minimal Risk Level, NA = Not applicable, NOEL = no-observed-effe

factor, p- = provisional, PPRTV = Provisional Peer-Reviewed Toxicity Value, PTV = Provisional Toxicity Value (draft), RfC = inhalaconcentration, sRfC = subchronic RfC, RfD = oral reference dose, sRfD = subchronic RfD, RPF = Relative potency factor, TPHCWG 

Hydrocarbon Criteria Working Group, WOE = weight of evidence 
FINAL 

9-30-2009 

 37

 A mixture of predominantly C9–C10 alkylbenzenes, high-flash aromatic naphtha, has

been studied toxicologically. Basing a value for at least the alkyl benzenes on a mixture, rather 

than a single chemical, is preferable since the data support development of toxicity values. 

Although MADEP (2003) and TPHCWG (1997b) derived inhalation RfCs for this mixture, some 

additional studies were located, including oral studies, and it was considered advisable to 

perform an updated assessment using current U.S. EPA methods. Therefore, a PPRTV 

document was developed for high-flash aromatic naphtha (U.S. EPA, 2009g). The PPRTVs for 

high-flash aromatic naphtha, listed in Table 6, include subchronic and chronic p-RfCs. In 

addition, Table 6 contains several screening values for high-flash aromatic naphtha that may be 

useful in evaluating this fraction, developed in Appendix A of U.S. EPA (2009g). Because the 

toxicity data based on the three unpublished studies (Bio/Dynamics Inc., 1990a,;b; Mobil Oil 

Corporation, 1994) are not peer-reviewed, only screening chronic or subchronic RfDs are 

available in Table 6. Subchronic and chronic RfD values for individual alkylbenzenes in Table 6 

(n-propylbenzene, 1,3,5-trimethylbenzene) are also limited to screening values due to database 

weaknesses. 

 The effects of compounds in this fraction are commonly kidney, liver, and body weight 

effects. Hematological effects are seen with some of these compounds. The subchronic and 

chronic p-RfCs and subchronic and chronic screening RfDs derived for high-flash aromatic 

naphtha are the same order of magnitude as those for the single compounds in this fraction, 

including biphenyl and the low molecular weight PAHs. Exceptions on IRIS are the 

2-methylnaphthalene RfD, which is an order of magnitude lower and is based on alveolar 

proteinosis, and the naphthalene RfC, which is two orders of magnitude lower and based on 

nasal lesions. Other exceptions are the p-RfD for 1-methylnaphthalene, which is, however, only 

a screening value, and subchronic p-RfC and p-RfC values for 1,3,5-trimethylbenzene and 

1,2,4-trimethylbenzene. 

 According to MADEP (2003), both naphthalene and 2-methylnaphthalene are target 

analytes assessed separately under the Massachusetts Contingency Plan. The recommendation in 

this PPRTV is to assess exposure to these compounds separately if possible, using their specific 

toxicity values (oral RfD and subchronic p-RfD for 2-methylnaphthalene, oral RfD and 

inhalation RfC for naphthalene). Their mass should be subtracted from the total fraction mass 

before use of the high-flash aromatic naphtha toxicity values listed in Table 6 for the remaining 

fraction. Specific monitoring data are unlikely to be available for 1-methylnaphthalene or the 

trimethylbenzene isomers, but if such data are available, then these chemicals could be treated 

similarly to naphthalene and 2-methylnaphthalene. 

 Because high-flash aromatic naphtha is a mixture of predominantly C9–C10 

alkylbenzenes, the provisional values for this mixture are most relevant to the alkylbenzene 

portion of this fraction. Although there may be greater uncertainty involved in using these 

values when the fraction includes less closely structurally-related compounds, the available 

toxicity values for these other compounds (1,1-biphenyl, and the lower molecular weight PAHs, 

listed in Table 6) are similar to those for high-flash aromatic naphtha, which supports the use of 

that mixture as a surrogate for the fraction. Carcinogenicity data are generally inadequate for 

compounds in this fraction and also for high-flash aromatic naphtha. 
FINAL 

9-30-2009 

 38

High Carbon Range Aromatic Fraction: C17–C32, EC22–EC35

 To help readers understand clearly the U.S. EPA approach for this fraction, a brief 

explanation is provided here, followed by more extensive discussions below. For noncancer oral 

toxicity values, fluoranthene, an IRIS and HEAST listed chemical, was selected as a surrogate. 

Since this fraction is basically nonvolatile, no inhalation toxicity values were attempted. For 

cancer toxicity values, seven PAH are to be evaluated together as indicator components for this 

fraction, using the RPF method. As shown in Table 6, these seven are IRIS-listed B2 

carcinogenic PAHs with RPFs from U.S. EPA, 1993 (i.e., benzo[a]pyrene, benz[a]anthracene, 

chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, dibenz[a,h]anthracene, 

indeno[1,2,3-c,d]pyrene). 

 As explained previously, MADEP grouped the entire range of aromatics from C9–C32 

into a single fraction for the assessment of oral noncancer toxicity and divided the fraction into 

C9–C18 and C19–C32 fractions for the assessment of inhalation noncancer toxicity. The 

TPHCWG (1997a) defined their transport fractions by EC number rather than C number, but in 

selecting and deriving toxicity values, they actually used the C number ranges. Because the EC 

value for aromatic hydrocarbons is higher than the C value, the low end of their fraction range 

actually was EC22, rather than the stated EC > 16 (TPHCWG, 1997b). The use of the EC 

number range of EC22–EC35 is recommended in this document, which corresponds to a C 

number range of about C17–C32, for the high carbon range aromatic fraction based on 

environmental transport and toxicological considerations, including volatility and 

carcinogenicity. This fraction is virtually the same as the fraction defined by the TPHCWG 

(1997b). 

 This fraction includes the medium and high molecular weight PAHs, which generally are 

not volatile when released to soil or water (ATSDR, 1995)4

. Although PAHs can bind to soil 

particulates, methods and data to estimate toxicity values or assess risk from inhaled 

soil-particulate-bound PAHs are not available. 

 

Data on noncancer toxicity are limited for the PAHs of this fraction, and RfDs, RfCs, and 

MRLs have not been derived for them. The noncancer oral toxicity of this fraction can be 

assessed through the use of the oral toxicity values for fluoranthene. Although fluoranthene is a 

C16 compound, it has an EC of 21.85, which is very close to the lower end (22) of the EC range 

for this fraction. The RfD for fluoranthene is available on IRIS and the subchronic RfD, based 

on the same study, is listed in the HEAST. Table 6 reports these values. The uncertainty 

involved in the use of fluoranthene as a surrogate for the noncancer oral toxicity of this fraction 

is high due to the lack of relevant data on the noncancer toxicity of the compounds in this 

fraction. 

 

A cancer slope factor is available only for the Group B2 (probable human carcinogen) 

PAH benzo(a)pyrene. The other six Group B2 PAHs can be assessed using the RPFs estimated 

and recommended by U.S. EPA (1993). This is an indicator component method that assumes the 

carcinogenicity of the fraction is approximated by the components with known carcinogenicity 

 

4When released to air through combustion processes, these PAHs exist primarily in the particulate phase—except for 

chrysene and benzo(a)anthracene, which can exist partially in the vapor phase (ATSDR, 1995). PAHs created and 

released to air by combustion, however, are not within the scope of this document on aliphatic and aromatic 

hydrocarbons. 
FINAL 

9-30-2009 

 39

and quantitative estimates (slope factor or RPF). When U.S. EPA develops new RPFs for 

additional PAHs or recommends changes in the current set of seven RPF values for evaluation of 

the PAHs, these can be incorporated into the risk assessment. 

CONCLUSIONS AND RECOMMENDATIONS 

 Building upon the contributions of MADEP and TPHCWG to the fractional approach for 

evaluation of hazard/risk of exposure to petroleum hydrocarbons (see Appendix A), this PPRTV 

document updates and expands the selection and derivation of toxicity values to include both 

subchronic and chronic RfDs and RfCs, as well as cancer WOE assessments, OSFs, and IURs. 

Newer data and updated U.S. EPA methods are used to provide new provisional assessments 

(U.S. EPA, 2009a-i) as needed and supported by the available data. The approach is generally 

consistent with the MADEP and the TPHCWG approaches, using toxicity values for a surrogate 

compound or similar mixture to represent the toxicity of the fraction. Where the components of 

the fraction vary in type or potency of toxic action, it is recommended that the more toxic 

component (e.g., n-hexane of the low range aliphatic fraction) be used as the surrogate when it 

exceeds the percentage in the surrogate mixture (e.g., commercial hexane, inhalation 

assessment), or when other suitable values are not available for the exposure route (oral). In 

some cases, a components method is recommended: i.e., for the BTEX (low carbon range 

aromatic fraction); and for seven PAHs of the high carbon range aromatic fraction, which are 

IRIS-listed Group B2 (probable human carcinogen) carcinogenic PAHs with RPFs from U.S. 

EPA (1993). A combination components and surrogate mixture approach is recommended for 

the medium carbon range aromatic fraction, with the target analytes naphthalene and 

2-methylnaphthalene assessed separately using their specific toxicity values (oral for both 

compounds and inhalation for naphthalene). The mass of the target analyte(s) is subtracted from 

the fraction mass, which is then assessed using toxicity values for the surrogate mixture (highflash aromatic naphtha). 

 The recommended toxicity values and cancer assessments and methods are summarized 

in Table 7 (noncancer oral), Table 8 (noncancer inhalation), and Table 9 (cancer oral and 

inhalation). The rationales for these recommendations have been presented in previous sections 

of this document. The use of additivity methods (U.S. EPA, 1986, 1989, 1993, 2000) is 

recommended when applicable to assess potential risk within and across fractions. These 

methods include the HI for noncancer effects of oral and inhalation exposure, RPFs for the 

Group B2 (probable human carcinogen) PAHs, and response addition for assessing cancer risk 

across fractions. These methods are essentially component-based methods wherein the fractions 

(or in the cases described previously, individual chemicals in the fraction) are considered 

components of aliphatic and aromatic hydrocarbons. 
FINAL 

9-30-2009 

 40

Table 7. Recommended Oral Noncancer Toxicity Values for Aliphatic and Aromatic 

Hydrocarbon Fractionsa

Aliphatics 

Fraction: 

Surrogate or 

Components sRfD (mg/kg-day) Source RfD (mg/kg-day) Source 

Low carbon range C5–C8, EC5–EC8: 

n-hexane 3 × 10-1, reduced nerve 

conduction velocity, 

Ono et al., 1981 

PPRTV 

(U.S. EPA, 2009c) 

Not assessed under 

IRIS program 

IRIS (U.S. EPA, 

2009j) 

Medium carbon range C9–C18, EC > 8–EC16:

Hydrocarbon 

streams or solvents 

within the range 

and containing <1% 

aromatics

1 × 10-1, liver, kidney 

and hematologic 

effects, Anonymous, 

1990, 1991a,b 

(*Screening value) 

PPRTV 

(U.S. EPA, 2009h) 

1 × 10-2, liver, kidney 

and hematologic 

effects, Anonymous, 

1990, 1991a,b 

(*Screening value) 

PPRTV 

(U.S. EPA, 2009h) 

High carbon range C19–C32, EC > 16–EC35:

White mineral oils 

generally within the

range 

3 × 101, lower end of 

human therapeutic 

dose range for laxative 

effects, NASPGHN, 

2006 

PPRTV 

(U.S. EPA, 2009i) 

3 × 100, lower end of 

human therapeutic 

dose range for laxative 

effects, NASPGHN, 

2006 

PPRTV 

(U.S. EPA, 2009i) 

Aromatics 

Fraction: 

Surrogate or 

Components sRfD (mg/kg-day) Source RfD (mg/kg-day) Source 

Low carbon range C6–C8, EC6–EC < 9:

Benzene 1 × 10-2, decreased 

lymphocyte count, 

Rothman et al., 1996, 

extrapolated from 

inhalation, U.S. EPA, 

2009j 

PPRTV 

(U.S. EPA, 2009a) 

4 × 10-3, decreased 

lymphocyte count, 

Rothman et al., 1996, 

extrapolated from 

inhalation 

IRIS 

(U.S. EPA, 2009j) 

Toluene 8 × 10-1, increased 

kidney weight, NTP, 

1990 

PPRTV 

(U.S. EPA, 2009d) 

8 × 10-2, increased 

kidney weight, NTP, 

1990 

IRIS 

(U.S. EPA, 2009j) 

Ethylbenzeneb 5 × 10-2, centrilobular 

hepatic hypertrophy, 

Mellert et al., 2007 

PPRTV 

(U.S. EPA, 2009b) 

1 × 10-1, liver and 

kidney lesions, Wolf et 

al., 1956 

IRIS 

(U.S. EPA, 2009j) 

Xylenes 4 × 10-1, reduced body 

weight, Wolfe et al., 

1988a 

PPRTV 

(U.S. EPA, 2009e) 

2 × 10-1, decreased 

body weight, increased 

mortality, NTP, 1986 

IRIS 

(U.S. EPA, 2009j) 
FINAL 

9-30-2009 

 41

Table 7. Recommended Oral Noncancer Toxicity Values for Aliphatic and Aromatic 

Hydrocarbon Fractionsa

Aromatics (cont’d) 

Fraction: 

Surrogate or 

Components sRfD (mg/kg-day) Source RfD (mg/kg-day) Source 

Medium carbon range C9–C16, EC9–EC < 22: 

High flash aromatic 

naphtha (except 

naphthalene and 

2-naphthalene) 

3 × 10-1, anemia, 

Bio/Dynamics, 1990b 

(*Screening Value) 

PPRTV 

(US. EPA, 2009g) 

3 × 10-2, anemia, 

Bio/Dynamics, 1990b 

(*Screening Value) 

PPRTV 

(US. EPA, 2009g) 

Naphthalene Not available – 2 × 10-2, decreased 

body weight, BCL, 

1980 

IRIS 

(U.S. EPA, 2009j) 

2-Methylnaphthalene 4 × 10-3, alveolar 

proteinosis, Murata et 

al., 1997 

PPRTV 

(U.S. EPA, 2007c) 

4 × 10-3, alveolar 

proteinosis, Murata et 

al., 1997 

IRIS 

(U.S. EPA, 2009j) 

High carbon range C17–C32, EC22–EC35: 

Fluoranthene 4 × 10-1, kidney, liver 

and hematologic 

effects, U.S. EPA, 

1988 

HEAST 

(U.S. EPA, 1997) 

4 × 10-2, kidney, liver, 

hematologic and 

clinical effects, U.S. 

EPA, 1988 

IRIS 

(U.S. EPA, 2009j) 

aComplete citations for the principal studies can be found in the source documents (e.g., IRIS [U.S. EPA, 2009j]). 

bThe lower sRfD relative to the RfD for ethylbenzene reflects the more recent derivation of the sRfD (new critical 

study, BMD modeling). 

*Screening values are developed in the Appendix of a PPRTV. For example, in cases where a high degree of 

uncertainty exists. Screening Values are intended for use in limited circumstances when no Tier 1, 2, or 3 values are 

available. 

C = carbon number, EC = equivalent carbon number index, HEAST = Health Effects Assessment summary Table, 

IRIS = Integrated Risk Information System, PPRTV = Provisional Peer-Reviewed Toxicity Value, RfD = oral 

reference dose, sRfD = subchronic RfD 
FINAL 

9-30-2009 

 42

Table 8. Recommended Inhalation Noncancer Toxicity

Values for Aliphatic and Aromatic Hydrocarbon Fractionsa

Aliphatics 

Fraction: 

Surrogate or 

Components sRfC mg/m3

) Source RfC (mg/m3) Source 

Low carbon range C5–C8, EC5–EC8: 

n-hexane, if present 

at >53% of fraction 

2 × 100, Decreased 

motor nerve 

conduction velocity, 

Huang et al., 1989 

PPRTV 

(U.S. EPA, 2009c) 

7 × 10-1, peripheral 

neuropathy, Huang et 

al., 1989 

IRIS 

(U.S. EPA, 2009j) 

Commercial 

hexane, if n-hexane 

present at ≤53% of 

fraction 

27 × 100, clinical and 

histopathological signs 

of neuropathy, IRDC, 

1992a,b 

PPRTV 

(U.S. EPA, 2009f) 

6 × 10-1, nasal 

epithelial cell 

hyperplasia, 

Biodynamics, 1993a; 

Daughtrey et al.,1999 

PPRTV 

(U.S. EPA, 2009f) 

Medium carbon range C9–C18, EC > 8–EC16:

Hydrocarbon 

streams or solvents 

within the range 

and containing <1% 

aromatics 

1 × 10-1, nasal goblet 

cell hypertrophy, NTP, 

2004 

PPRTV 

(U.S. EPA, 2009h) 

1 × 10-1, nasal goblet 

cell hypertrophy and 

adrenal hyperplasia, 

NTP, 2004 

PPRTV 

(U.S. EPA, 2009h) 

High carbon range C19–C32, EC > 16–EC35:

White mineral oils 

generally within the

range 

NA, not volatile PPRTV 

(U.S. EPA, 2009i) 

NA, not volatile PPRTV 

(U.S. EPA, 2009i) 

Aromatics 

Fraction: 

Surrogate or 

Components sRfC( mg/m3

) Source RfC (mg/m3) Source 

Low carbon range: C6–C8, EC6–EC < 9:

Benzene 8 × 10-2, decreased 

lymphocyte count, 

Rothman et al., 1996 

PPRTV 

(U.S. EPA, 2009a) 

3 × 10-2, decreased 

lymphocyte count, 

Rothman et al., 1996 

IRIS 

(U.S. EPA, 2009j) 

Toluene 5 × 100, neurological 

effects, multiple 

studies, U.S. EPA, 

2009j 

PPRTV 

(U.S. EPA, 2009d) 

5 × 100, neurological 

effects, multiple 

studies 

IRIS 

(U.S. EPA, 2009j) 

Ethylbenzene 9 × 100, ototoxic 

effects, Gagnaire et al., 

2007 

PPRTV 

(U.S. EPA, 2009b) 

1 × 100

, developmental 

effects, Andrew et al., 

1981; Hardin et al., 

1981 

IRIS 

(U.S. EPA, 2009j) 

Xylenes 4 × 10-1, neurological 

effects, Korsak et al., 

1994 

PPRTV 

(U.S. EPA, 2009e) 

1 × 10-1, impaired 

motor coordination, 

Korsak et al., 1994 

IRIS 

(U.S. EPA, 2009j) 
FINAL 

9-30-2009 

 43

Table 8. Recommended Inhalation Noncancer Toxicity

Values for Aliphatic and Aromatic Hydrocarbon Fractionsa

Aromatics (cont’d) 

Fraction: 

Surrogate or 

Components sRfC( mg/m3

) Source RfC (mg/m3) Source 

Medium carbon range C9–C16, EC9–EC < 22: 

High flash aromatic 

naphtha (except 

naphthalene) 

1 × 100, maternal body 

weight depression, 

McKee et al.,1990 

PPRTV 

(U.S. EPA, 2009g) 

1 × 10-1, maternal 

body weight 

depression, McKee et 

al.,1990 

PPRTV 

(U.S. EPA, 2009g) 

Naphthalene Not available – 3 × 10-3, nasal lesions, 

NTP 1992 

IRIS 

(U.S. EPA, 2009j) 

High carbon range C17–C32, EC22–EC35:

NA, not volatile – NA, not volatile – 

aComplete citations for the principal studies can be found in the source documents (e.g., IRIS [U.S. EPA, 2009j]). 

C = carbon number, EC = equivalent carbon number index, IRIS = Integrated Risk Information System, NA = Not 

applicable, PPRTV = Provisional Peer-Reviewed Toxicity Value, RfC = inhalation reference concentration, 

sRfC = subchronic RfC 
FINAL 

9-30-2009 

 44

Table 9. Recommended Cancer Assessments for 

Aliphatic and Aromatic Hydrocarbon Fractionsa

Aliphatics 

Fraction: 

Surrogate or 

Components Cancer WOE, RPF OSF (per mg/kg-day) IUR (per μg/m3

) Source 

Low carbon range C5–C8, EC5–EC8: 

Commercial 

hexane, if n-hexane 

present at ≤53% of 

the fraction 

Suggestive evidence Inadequate data 1.9 × 10-7, 

pituitary adenoma or 

carcinoma, 

Biodynamics, 1993b; 

Daughtrey et al., 1999 

(*Screening value) 

PPRTV 

(U.S. EPA, 2009f) 

Medium carbon range C9–C18, EC > 8–EC16: 

Petroleum streams 

or solvents within 

the range and 

containing <1% 

aromatics 

Suggestive evidence NA 4.5 × 10-6, benign or 

malignant adrenal 

pheochromocytoma, 

NTP, 2004 

(*Screening Value) 

PPRTV 

(U.S. EPA, 2009h) 

High carbon range C19–C32, EC > 16–EC35: 

White mineral oils 

generally within the 

range 

Inadequate 

information to assess 

Inadequate data NA, not volatile PPRTV 

(U.S. EPA, 2009i) 

Aromatics 

Fraction: 

Surrogate or 

Components Cancer WOE, RPF OSF (per mg/kg-day IUR (per μg/m3

) Source 

Low carbon range C6–C8, EC6–EC < 9:

Benzene Group A (human 

carcinogen); 

known/likely human 

carcinogen 

1.5 × 10-2 to 5.5 × 10-2, 

leukemia, several 

studies, extrapolated 

from inhalation 

2.2 × 10-2 to 7.8 × 10-6, 

leukemia, several 

studies 

IRIS 

(U.S. EPA, 2009j) 

Toluene Inadequate data NA NA IRIS 

(U.S. EPA, 2009j) 

Ethylbenzene Group D (not 

classifiable) 

NA NA IRIS 

(U.S. EPA, 2009j) 

Xylenes Inadequate data NA NA IRIS 

(U.S. EPA, 2009j) 

Medium carbon range C9–C16, EC9–EC < 22: 

High flash aromatic 

naphtha (except 

naphthalene) 

Inadequate 

information to assess 

Inadequate data Inadequate data PPRTV (US. EPA, 

2009g) 

Naphthalene Group C (possible 

human carcinogen) 

Inadequate data Inadequate data IRIS (U.S. EPA, 

2009j) 
FINAL 

9-30-2009 

 45

Table 9. Recommended Cancer Assessments for 

Aliphatic and Aromatic Hydrocarbon Fractionsa

Aromatics (cont’d) 

Fraction: 

Surrogate or 

Components Cancer WOE, RPF OSF (per mg/kg-day IUR (per μg/m3

) Source 

High carbon range C17–C32, EC22–EC35:

Benzo(a)pyrene Group B2 (probable 

human carcinogen), 

RPF=1 

7.3 × 100, forestomach 

(larynx, esophagus) 

4 data sets 

NA, not volatile IRIS (U.S. EPA, 

2009j); U.S. EPA, 

1993 

Benz(a)anthracene Group B2 (probable 

human carcinogen), 

RPF=0.1 

Inadequate data, use 

RPF 

NA, not volatile IRIS (U.S. EPA, 

2009j); U.S. EPA, 

1993 

Chrysene Group B2 (probable 

human carcinogen), 

RPF=0.001 

Inadequate data, use 

RPF 

NA, not volatile IRIS (U.S. EPA, 

2009j); U.S. EPA, 

1993 

Benzo(b)fluoranthene Group B2 (probable 

human carcinogen), 

RPF=0.1 

Inadequate data, use 

RPF 

NA, not volatile IRIS (U.S. EPA, 

2009j); U.S. EPA, 

1993 

Benzo(k)fluoranthene Group B2 (probable 

human carcinogen), 

RPF=0.01 

Inadequate data, use 

RPF 

NA, not volatile IRIS (U.S. EPA, 

2009j); U.S. EPA, 

1993 

Dibenz(a,h)anthracene Group B2 (probable 

human carcinogen), 

RPF=1 

Inadequate data, use 

RPF 

NA, not volatile IRIS (U.S. EPA, 

2009j); U.S. EPA, 

1993 

Indenol(1,2,3-c,d) 

pyrene 

Group B2 (probable 

human carcinogen), 

RPF=0.1 

Inadequate data, use 

RPF 

NA, not volatile IRIS (U.S. EPA, 

2009j); U.S. EPA, 

1993 

aComplete citations for the principal studies can be found in the source documents (e.g., IRIS [U.S. EPA, 2009j]). 

*Screening values are developed in the Appendix of a PPRTV. For example, in cases where a high degree of 

uncertainty exists. Screening Values are intended for use in limited circumstances when no Tier 1, 2, or 3 values are 

available. 

C = carbon number, EC = equivalent carbon number index, IRIS = Integrated Risk Information System, IUR = 

inhalation unit risk, NA = Not applicable, OSF = oral slope factor, PPRTV = Provisional Peer-Reviewed Toxicity 

Value, RPF = Relative potency factor (U.S. EPA, 1993), WOE = weight of evidence 
FINAL 

9-30-2009 

 46

REFERENCES

ASTM (American Society for Testing and Materials). 1995. E 1739-95: Standard Guide for 

Risk-based Corrective Action Applied at Petroleum Release Sites. Published November 1995. 

Editorial changes made throughout in December 1996. ASTM, West Conshohocken, PA. 

ASTM (American Society for Testing and Materials). 2002. E 1739-95 (reapproved 2002): 

Standard Guide for Risk-based Corrective Action Applied at Petroleum Release Sites. ASTM, 

West Conshohocken, PA. 

ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological Profile for 

Polycyclic Aromatic Hydrocarbons (Update). Agency for Toxic Substances and Disease 

Registry, U.S. Public Health Service, Atlanta, GA. Online. http://www.atsdr.cdc.gov/

toxpro2.html. 

ATSDR (Agency for Toxic Substances and Disease Registry). 1999a. Toxicological Profile for 

Total Petroleum Hydrocarbons (TPH). Agency for Toxic Substances and Disease Registry, U.S. 

Public Health Service, Atlanta, GA. Online. http://www.atsdr.cdc.gov/toxpro2.html. 

ATSDR (Agency for Toxic Substances and Disease Registry). 1999b. Toxicological Profile for 

n-Hexane (Update). Agency for Toxic Substances and Disease Registry, U.S. Public Health 

Service, Atlanta, GA. Online. http://www.atsdr.cdc.gov/toxpro2.html. 

ATSDR (Agency for Toxic Substances and Disease Registry). 1999c. Toxicological Profile for 

Ethylbenzene. Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, 

Atlanta, GA. Online. http://www.atsdr.cdc.gov/toxpro2.html. 

ATSDR (Agency for Toxic Substances and Disease Registry). 2005. Toxicological Profile for 

Naphthalene (Update). Agency for Toxic Substances and Disease Registry, U.S. Public Health 

Service, Atlanta, GA. Online. http://www.atsdr.cdc.gov/toxpro2.html. 

ATSDR (Agency for Toxic Substances and Disease Registry). 2007a. Toxicological Profile for 

Benzene. Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, 

Atlanta, GA. Online. http://www.atsdr.cdc.gov/toxpro2.html. 

ATSDR (Agency for Toxic Substances and Disease Registry). 2007b. Toxicological Profile for 

Xylenes. Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, 

Atlanta, GA. Online. http://www.atsdr.cdc.gov/toxpro2.html. 

ATSDR (Agency for Toxic Substances and Disease Registry). 2008. Toxicological Profile 

Information Sheet. Agency for Toxic Substances and Disease Registry, U.S. Public Health 

Service, Atlanta, GA. Online. http://www.atsdr.cdc.gov/toxpro2.html. 

CalEPA (California Environmental Protection Agency). 2008. Consolidated Table of 

OEHHA/ARB Approved Risk Assessment Health Values. Online. http://www.arb.ca.gov/toxics/

healthval/contable.pdf. 
FINAL 

9-30-2009 

 47

Hutcheson, M.S., D. Pedersen, N.D. Anastas, et al. 1996. Beyond TPH: health-based evaluation 

of petroleum hydrocarbon exposures. Reg. Toxicol. Pharmacol. 24:85–101. 

IARC (International Agency for Research on Cancer). 2008a. IARC Summaries and 

Evaluations. Online. http://www.inchem.org/pages/iarc.html. 

 

IARC (International Agency for Research on Cancer). 2008b. IARC Search Page. Online. 

http://www.iarc.fr/index.html. 

MADEP (Massachusetts Department of Environmental Protection). 1994. Interim Final 

Petroleum Report: Development of Health-Based Alternative to the Total Petroleum 

Hydrocarbon (TPH) Parameter. Bureau of Waste Site Cleanup, Boston, MA. Online. 

http://www.state.ma.us/dep/bwsc/vph_eph.htm. 

MADEP (Massachusetts Department of Environmental Protection). 1996. Issues Paper: 

Implementation of the VPH/EPH Approach. Public Comment Draft. Bureau of Waste Site 

Cleanup, Boston, MA. Online. http://www.state.ma.us/dep/bwsc/vph_eph.htm. 

MADEP (Massachusetts Department of Environmental Protection). 1997. Characterizing Risks 

Posed by Petroleum Contaminated Sites: Implementation of the MADEP VPH/EPH Approach. 

Public Comment Draft. Bureau of Waste Site Cleanup, Boston, MA. Online. http://www.state.

ma.us/dep/bwsc/vph_eph.htm. 

MADEP (Massachusetts Department of Environmental Protection). 2001. Characterizing Risks 

Posed by Petroleum Contaminated Sites: Implementation of the MADEP VPH/EPH Approach. 

Final Draft. June 2001. Bureau of Waste Site Cleanup, Boston, MA. Online. 

http://www.state.ma.us/dep/bwsc/vph_eph.htm. 

MADEP (Massachusetts Department of Environmental Protection). 2002. Characterizing Risks 

Posed by Petroleum Contaminated Sites: Implementation of the MADEP VPH/EPH Approach. 

Final Policy. October 31, 2002. Bureau of Waste Site Cleanup, Boston, MA. Online. 

http://www.state.ma.us/dep/bwsc/vph_eph.htm. 

MADEP (Massachusetts Department of Environmental Protection). 2003. Updated Petroleum 

Hydrocarbon Fraction Toxicity Values for the VPH/EPH/APH Methodology. Office of 

Research and Standards, Massachusetts Department of Environmental Protection, Boston, MA. 

Online. http://www.state.ma.us/dep/bwsc/vph_eph.htm

MADEP (Massachusetts Department of Environmental Protection). 2008. Polycyclic Aromatic 

Hydrocarbons (PAHs). Online. http://www.mass.gov/dep/toxics/pahs.htm. 

NTP (National Toxicology Program). 2008. Management Status Report. Available online at 

http://ntp-server.niehs.nih.gov/cgi/iH_Indexes/ALL_SRCH/iH_ALL_SRCH_Frames.html. 
FINAL 

9-30-2009 

 48

OECD/SIDS (Organisation for Economic Co-operation and Development/Screening Information 

Data Set). 2007. Chemical Screening Information Data Set (SIDS) for High Volume Chemicals. 

Online. http://www.inchem.org/pages/sids.html. 

Ono, Y., Y. Takeuchi, N. Hisanga. 1981. A comparative study on the toxicity of n-hexane 

and its isomers on the peripheral nerve. Int. Arch. Occup. Environ. Health. 48:289–294. 

Petroleum High Production Volume (HPV) Testing Group. 2007. The Petroleum High 

Production Volume Testing Group [Home Page]. Online. http://www.petroleumhpv.org/. 

Rice, G., L.K. Teuschler, J.E. Simmons and R.C. Hertzberg. 2005. Mixtures, toxicology and 

risk assessment. In: Encyclopedia of Toxicology, 2nd, ed., P. Wexler, Ed. Elsevier Press, New 

York. p. 120–123. 

TPHCWG (Total Petroleum Hydrocarbon Criteria Working Group). 1997a. Volume 3. 

Selection of Representative TPH Fractions Based on Fate and Transport Considerations. 

Amherst Scientific Publishers, Amherst, MA. Available at http://www.aehs.com/publications/

catalog/contents/tph.htm. 

TPHCWG (Total Petroleum Hydrocarbon Criteria Working Group). 1997b. Volume 4. 

Development of Fraction Specific Reference Doses (RfDs) and Reference Concentrations (RfCs) 

for Total Petroleum Hydrocarbons (TPH). Amherst Scientific Publishers, Amherst, MA. 

Online. http://www.aehs.com/publications/catalog/contents/tph.htm. 

TPHCWG (Total Petroleum Hydrocarbon Criteria Working Group). 1998a. Volume 1. 

Analysis of Petroleum Hydrocarbons in Environmental Media. Amherst Scientific Publishers, 

Amherst, MA. Online. http://www.aehs.com/publications/catalog/contents/tph.htm. 

TPHCWG (Total Petroleum Hydrocarbon Criteria Working Group). 1998b. Volume 2. 

Composition of Petroleum Mixtures. Amherst Scientific Publishers, Amherst, MA. Online. 

http://www.aehs.com/publications/catalog/contents/tph.htm. 

TPHCWG (Total Petroleum Hydrocarbon Criteria Working Group). 1999. Volume 5. Human 

Health Risk-Based Evaluation of Petroleum Release Sites: Implementing the Working Group 

Approach. Amherst Scientific Publishers, Amherst, MA. Online. http://www.aehs.com/

publications/catalog/contents/tph.htm. 

Truhaut R., P. Laget, G. Piat et al. 1973. [Preliminary electrophysiological results following 

experimental poisoning with technical hexane and heptane in white rats.] Arch. Mal. Prof. Med. 

Trav. Secur. Soc. 34:417–426. [French] 

Twerdok, L.E. 1999. Development of toxicity criteria for petroleum hydrocarbon fractions in 

the Petroleum Hydrocarbon Criteria Working Group approach for risk-based management of 

total petroleum hydrocarbons in soil. Drug Chem. Toxicol. 22:275–291. 
FINAL 

9-30-2009 

 49

U.S. EPA (U.S. Environmental Protection Agency). 1986. Guidelines for the Health Risk 

Assessment of Chemical Mixtures. Fed. Reg. 51(185):34014–34025. Online. 

http://www.epa.gov/iris/backgr-d.htm. 

U.S. EPA (U.S. Environmental Protection Agency). 1989. Risk Assessment Guidance for 

Superfund Volume I. Human Health Evaluation Manual (Part A). U.S. Environmental 

Protection Agency, Washington, DC. EPA540189002. Online. http://www.epa.gov/oswer/

riskassessment/ragsa/pdf/rags-vol1-pta_complete.pdf. 

U.S. EPA (U.S. Environmental Protection Agency). 1991. Chemical Assessments and Related 

Activities (CARA). U.S. Environmental Protection Agency, Office of Health and Environmental 

Assessment, Washington, DC. April. 

U.S. EPA (U.S. Environmental Protection Agency). 1993. Provisional Guidance for 

Quantitative Risk Assessment of Polycyclic Aromatic Hydrocarbons. U.S. Environmental 

Protection Agency, Environmental Criteria and Assessment Office, Cincinnati, OH. NTIS 

PB94-116571. 

U.S. EPA (U.S. Environmental Protection Agency). 1994. Chemical Assessments and Related 

Activities (CARA). U.S. Environmental Protection Agency, Office of Health and Environmental 

Assessment, Washington, DC. December. 

U.S. EPA (U.S. Environmental Protection Agency). 1997. Health Effects Assessment Summary 

Tables. Annual Update. FY-1997. U.S. Environmental Protection Agency, Office of Research 

and Development, Office of Emergency and Remedial Response, Washington, DC. July 1997. 

EPA/540/R-97/036. NTIS PB97-921199. 

U.S. EPA (U.S. Environmental Protection Agency). 2000. Supplementary Guidance for 

Conducting Health Risk Assessment of Chemical Mixtures. U.S. Environmental Protection 

Agency, Risk Assessment Forum, Washington, DC. EPA/630/R-00/002. Online. 

http://www.epa.gov/iris/backgr-d.htm. 

U.S. EPA (U.S. Environmental Protection Agency). 2004a. Provisional Peer Reviewed Toxicity 

Values for n-Butylbenzene(CASRN 104-51-8), sec-Butylbenzene(CASRN 135-98-8), and tertButylbenzene (CASRN 98-06-6) Derivation of a Carcinogenicity Assessment. U.S. 

Environmental Protection Agency, Superfund Technical Support Center, National Center for 

Environmental Assessment, Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2004b. Provisional Peer Reviewed Toxicity 

Values for n-Butylbenzene(CASRN 104-51-8), sec-Butylbenzene(CASRN 135-98-8), and 

tert-Butylbenzene (CASRN 98-06-6) Derivation of Subchronic and Chronic RfCs. 

U.S. Environmental Protection Agency, Superfund Technical Support Center, National Center 

for Environmental Assessment, Cincinnati, OH. 
FINAL 

9-30-2009 

 50

U.S. EPA (U.S. Environmental Protection Agency). 2004c. Provisional Peer Reviewed Toxicity 

Values for n-Butylbenzene(CASRN 104-51-8), sec-Butylbenzene(CASRN 135-98-8), and tertButylbenzene (CASRN 98-06-6) Derivation of Subchronic and Chronic RfDs. 

U.S. Environmental Protection Agency, Superfund Technical Support Center, National Center 

for Environmental Assessment, Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2004d. Provisional Peer Reviewed Toxicity 

Values for n-Heptane (CASRN 142-82-5). U.S. Environmental Protection Agency, Superfund 

Technical Support Center, National Center for Environmental Assessment, Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2005a. Provisional Peer Reviewed Toxicity 

Values for Methylcyclohexane (CASRN 142-82-5). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2005b. Toxicological Review of n-Hexane 

(CAS No. 110-54-3) in Support of Summary Information on the Integrated Risk Information 

System (IRIS). Integrated Risk Information Systems, U.S. Environmental Protection Agency, 

Washington, DC. EPA/635/R-03/012. Online. http://www.epa.gov/iris/toxreviews/. 

U.S. EPA (U.S. Environmental Protection Agency). 2006. 2006 Edition of the Drinking Water 

Standards and Health Advisories. U.S. Environmental Protection Agency, Office of Water, 

Washington, DC. EPA/822/R-02/038. Online. http://www.epa.gov/waterscience/drinking/

standards/dwstandards.pdf. 

U.S. EPA (U.S. Environmental Protection Agency). 2007a. High Production Volume (HPV) 

Challenge Program. U.S. Environmental Protection Agency. Online. http://www.epa.gov/

chemrtk/index.htm and http://cfpub.epa.gov/hpv%2Ds/. 

U.S. EPA (U.S. Environmental Protection Agency). 2007b. Provisional Peer Reviewed Toxicity 

Values for Benz[a]anthracene (CASRN 56-55-3). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2007c. Provisional Peer Reviewed Toxicity 

Values for 2-Methylnaphthalene (CASRN 91-57-6). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2007d. Provisional Peer Reviewed Toxicity 

Values for Perylene (CASRN 198-55-0). U.S. Environmental Protection Agency, Superfund 

Technical Support Center, National Center for Environmental Assessment, Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2007e. Provisional Peer Reviewed Toxicity 

Values for Pyrene (CASRN 129-00-0). U.S. Environmental Protection Agency, Superfund 

Technical Support Center, National Center for Environmental Assessment, Cincinnati, OH. 
FINAL 

9-30-2009 

 51

U.S. EPA (U.S. Environmental Protection Agency). 2007f. Provisional Peer Reviewed Toxicity 

Values for 1,2,4-Trimethylbenzene (CASRN 95-63-6). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2008. Provisional Peer Reviewed Toxicity 

Values for 1-Methylnaphthalene (CASRN 90-12-0). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009a. Provisional Peer Reviewed 

Subchronic Toxicity Values for Benzene (CASRN 71-43-2). U.S. Environmental Protection 

Agency, Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009b. Provisional Peer Reviewed 

Subchronic Toxicity Values for Ethylbenzene (CASRN 100-41-4). U.S. Environmental 

Protection Agency, Superfund Technical Support Center, National Center for Environmental 

Assessment, Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009c. Provisional Peer Reviewed 

Subchronic Toxicity Values for n-Hexane (CASRN 110-54-3). U.S. Environmental Protection 

Agency, Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009d. Provisional Peer Reviewed 

Subchronic RfDs and RfC Toxicity Values for Toluene (CASRN 108-88-3). Superfund 

Technical Support Center, National Center for Environmental Assessment, Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009e. Provisional Peer Reviewed 

Subchronic Toxicity Values for Xylenes (CASRN 1330-20-7). U.S. Environmental Protection 

Agency, Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009f. Provisional Peer Reviewed Toxicity 

Values for Commercial or Practical Grade Hexane. U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009g. Provisional Peer Reviewed Toxicity 

Values for High-Flash Aromatic Naphtha (CASRNs 64724-95-6 and 8845-25-4). U.S. 

Environmental Protection Agency, Superfund Technical Support Center, National Center for 

Environmental Assessment, Cincinnati, OH. 
FINAL 

9-30-2009 

 52

U.S. EPA (U.S. Environmental Protection Agency). 2009h. Provisional Peer Reviewed Toxicity 

Values for Midrange Aliphatic Hydrocarbon Streams. U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009i. Provisional Peer Reviewed Toxicity 

Values for White Mineral Oil (CASRNs 8012-95-1 and 8020-83-5). U.S. Environmental 

Protection Agency, Superfund Technical Support Center, National Center for Environmental 

Assessment, Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009j. Provisional Peer Reviewed Toxicity 

Values for n-Propylbenzene (CASRN 103-65-1). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009k. Provisional Peer Reviewed Toxicity 

Values for 1,3,5-Trimethylbenzene (CASRN 108-67-8). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009l. Provisional Peer Reviewed Toxicity 

Values for Acenaphthylene (CASRN 208-96-8). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009m. Provisional Peer Reviewed 

Toxicity Values for Phenanthrene (CASRN 85-01-8). U.S. Environmental Protection Agency, 

Superfund Technical Support Center, National Center for Environmental Assessment, 

Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009n. Provisional Peer Reviewed Toxicity 

Values for Anthracene (CASRN 120-12-7). U.S. Environmental Protection Agency, Superfund 

Technical Support Center, National Center for Environmental Assessment, Cincinnati, OH. 

U.S. EPA (U.S. Environmental Protection Agency). 2009o. Integrated Risk Information System 

(IRIS). Online. U.S. Environmental Protection Agency, Office of Research and Development, 

National Center for Environmental Assessment, Washington, DC. Online. 

http://www.epa.gov/iris/. Accessed August, 2009. 

VCCEP (Voluntary Children’s Chemical Evaluation Program). 2004. Voluntary Children’s 

Chemical Evaluation Program (VCCEP) Tier 1 Pilot Submission. n-Alkane Category: Decane, 

Undecane, Dodecane (CAS Nos. 124-18-5, 1120-21-4, 112-40-3). Docket Number 

OPPTS–00274D. American Chemistry Council n-Alkane VCCEP Consortium. Sponsors: 

Chevron Phillips Chemical Company LP, Sasol North America Inc., Shell Chemical LP. June 

17, 2004. 
FINAL 

9-30-2009 

 53

Wang, C. Y., Yang, R. S. H., Rice, G., Colman, J., Teuschler, L. In preparation. A 

Computational Approach to Assessing Total Petroleum Hydrocarbons Mixture. Part I. Support 

and validation of fraction-based approach for TPH mixture risk assessment. Manuscript under 

internal review. 

Weisman, W.H. 1998. Total petroleum hydrocarbon criteria working group: A risk-based 

approach for the management of total petroleum hydrocarbons in soil. J. Soil Contam. 7:1–15. 

WHO (World Health Organization). 2008. Environmental Health Criteria Monographs (EHCs). 

Online. http://www.inchem.org/pages/ehc.html. 
FINAL 

9-30-2009 

 54

APPENDIX A. EXISTING APPROACHES FOR EVALUATING COMPLEX 

MIXTURES OF ALIPHATIC AND AROMATIC HYDROCARBONS 

Massachusetts Department of Environmental Protection (MADEP) Approach 

 The MADEP recommended the use of a combination indicator compound and fraction 

approach for the assessment of health effects from petroleum hydrocarbons in soil and water, 

with a focus on oral exposure (Hutcheson et al., 1996; MADEP, 1994). Subsequently, 

MADEP (1996, 1997, 2001) published public comment and final drafts regarding 

implementation of their approach. These drafts and the final version of the implementation 

document (MADEP, 2002) contained some modifications to take into account the strengths of 

the TPHCWG approach (discussed in the next section of this document)—particularly the 

TPHCWG-determined transport properties of hydrocarbon fractions, which are related to the 

equivalent (or relative) carbon number indices for the compounds (TPHCWG, 1997a). In 

addition, these documents incorporated inhalation assessment and inhalation reference 

concentrations (RfCs). In 2003, MADEP updated the MADEP (1994) report, providing new and 

revised petroleum hydrocarbon fraction toxicity values, and a review of the literature to support 

the derivations of these values (MADEP, 2003). The MADEP approach is as follows: 

Carcinogenic Effects

• Specific hydrocarbon indicator compounds that have U.S. EPA cancer potency factors 

are assessed; these are benzene and benzo(a)pyrene.

• MADEP is reviewing the U.S. EPA (1993) relative potency factors (RPFs) for PAHs, and 

in the meantime recommends the use of those values and the slope factor for 

benzo(a)pyrene for cancer assessment of the high-carbon-range aromatics (MADEP, 

2008). 

Noncarcinogenic Effects 

• Hydrocarbon fractions are established based on molecular structure (aromatic versus 

aliphatic), and then on number of carbon atoms (C), using toxicologically similar 

groupings and excluding compounds with less than five carbons because their high 

volatility precludes chronic exposure from spills/releases. Analytical methods for these 

fractions are suggested. 

• With the exception of the aromatic C5-C8 fraction, the toxicity of each fraction initially 

was represented by the RfD for a representative “reference compound” from the fraction, 

usually chosen because of the availability of an RfD on IRIS or adequate data to support 

derivation of an RfD. The toxicities of other compounds in the subclass were assumed to 

equal that of the reference compound. Some of these fractions include subfractions that 

were combined because of similarity of toxicity across fractions or limitations in the 

toxicity data. The approach is now broadened to include the selection of similar mixtures 

to represent the toxicity of a fraction and the inclusion of inhalation toxicity values. 

 The MADEP (1994, 2001, 2003; Hutcheson et al., 1996) approach assumes additivity of 

the hydrocarbon fractions and the indicator compounds in assessing the potential for adverse 

effects of petroleum hydrocarbons on human health (dose-addition using the hazard index [HI] 

approach for noncarcinogenic effects and RPF approach for carcinogenic PAHs; response 

addition for carcinogenic effects across fractions). 
FINAL 

9-30-2009 

 55

Total Petroleum Hydrocarbon Criteria Working Group (TPHCWG) Approach

 The TPHCWG (1997a, b; Weisman, 1998) also recommended a combination indicator 

compound and fraction approach for TPH, which differed from the MADEP approach: (1) in its 

application only to soil contamination (to develop risk-based screening levels [RBSLs]); (2) in 

the elimination of assessment for noncarcinogenic effects if carcinogens are present above 

regulatory criteria; (3) in the basis for selection of the fractions; and (4) initially, in a more 

extensive use of toxicity data for mixtures to represent the toxicity of the fraction. Subsequently, 

the TPHCWG (1999) appeared to broaden its focus to include RBSLs for groundwater as well as 

for soil. Some of the TPHCWG hydrocarbon fractions include subfractions that were combined 

for toxicological assessment because of similarity of toxicity across fractions or limitations in the 

toxicity data. The TPHCWG approach is as follows: 

Carcinogenic Effects 

• Specific carcinogenic indicator compounds (i.e., benzene, benzo[a]pyrene) are assessed. 

• The use of (relative) potency factors and the benzo(a)pyrene slope factor is mentioned for 

benzo(a)anthracene, indeno(1,2,3-cd)pyrene, dibenzo(a,h)anthracene, chrysene, 

benzo(b)fluoranthene and benzo(k)fluoranthene, but they are not further described or 

referenced. 

Noncarcinogenic Effects 

These effects are assessed only if the carcinogenic indicator compounds are not detected 

or are below regulatory criteria. 

• Hydrocarbon fractions are established based on molecular structure (aromatic versus 

aliphatic) and then on the basis of equivalent carbon (EC) number index. This index is 

equivalent to the retention time of the compounds on a boiling point gas chromatography 

(GC) column (nonpolar capillary column), normalized to the n-alkanes. For example, 

benzene, a C6 aromatic compound, has an EC of 6.5 because its boiling point and GC 

retention time are approximately halfway between those of n-hexane (C6, EC6) and 

n-heptane (C7, EC7). Physical and chemical properties of hydrocarbons that are useful in 

predicting fate and transport (vapor pressure, solubility, partition coefficient, Henry’s 

Law constants) are predictably related to the EC and can be estimated using algorithms. 

The mass of the carcinogenic indicator compounds is subtracted from the mass of the 

fraction. 

• Following subtraction of the mass of the carcinogenic hydrocarbons, the noncancer 

effects of the remaining mass of each fraction are assessed by comparison with a 

surrogate compound or mixture. 

 The TPHCWG (1997a, b; 1999) approach assumes additivity of the hydrocarbon 

fractions and the indicator compounds in assessing the potential for adverse effects of petroleum 

hydrocarbons on human health, as in deriving risk-based screening levels for soil (dose-addition 

using HI approach for noncarcinogenic effects and RPFs for carcinogenic PAHs). 

 One caveat to this fate and transport fraction approach is that simplified models, such as 

the ones used by the TPHCWG (1997a) to perform the fraction groupings, neglect cosolvency 

effects and saturation of active sorption sites in soils (for nonionic hydrophobic chemicals, the 

organic carbon content of soil is the primary soil property controlling sorption). The actual 
FINAL 

9-30-2009 

 56

transport properties at a waste site may be significantly influenced by the quantity of material 

spilled or leaked into the soil (e.g., 500 gallons of gasoline will behave differently than 500 mL). 

For example, although PAHs may have a strong predicted adsorption to soil, when present in a 

large spill, they may initially have no or very low sorption due to cosolvent and saturation 

effects. As the spill migrates and becomes diluted, however, the influence of cosolvent and 

saturation effects will diminish. Another observation with regard to the approach to selection of 

fractions is that it appears to focus on petroleum hydrocarbons identified in petroleum fuels 

(JP-4, JP-5, JP-8, kerosene, diesel, and fuel oil #2) and crude oil. Although lubricating oils such 

as motor oil and mineral-based hydraulic fluids are included in the volumes on analytical 

methods and composition of petroleum mixtures (TPHCWG, 1998a, b), they are not included in 

the volume on selection of fractions (TPHCWG, 1997a). The lubricating oils contain high 

molecular weight branched alkanes and cyclic alkanes with >1 ring that are not well represented 

in the petroleum products of focus. Nevertheless, the toxicity assessments did consider these 

constituents in deriving toxicity values for the fractions that include them. The term “fate and 

transport fraction” is something of a misnomer as the fractions are based on properties that will 

affect transport, and do not take into account fate processes. The TPHCWG (1999) accordingly 

changed its nomenclature to “transport fraction” and that term is used in this PPRTV document. 

American Society for Testing and Materials (ASTM) Approach 

 ASTM (1995) developed a Standard Guide for Risk-Based Corrective Action Applied at 

Petroleum Release Sites (RBCA, pronounced “Rebecca”). RBCA, reapproved in 2002 

(ASTM, 2002) is a tiered decision-making framework for the integration of site assessment, 

remedial action selection and monitoring with U.S. EPA-recommended risk and exposure 

assessment. It includes any chemical that may be associated with petroleum product releases, 

including nonhydrocarbon constituents and additives, such as lead, methyl tert-butyl ether, and 

ethylene dibromide. The RBCA approach focuses on indicator compounds, assuming that a 

significant portion of the total potential impact on human health from all chemicals in a 

petroleum product spill is due to the indicator compounds, termed chemicals of concern. The 

risk or hazard of exposure to each chemical of concern is assessed separately during the 

derivation of Tier 1 (general) RBSLs, and Tier 2 and Tier 3 site-specific target levels (SSTLs) 

for contaminated media. The RBSLs and SSTLs are based on carcinogenicity for chemicals that 

have been classified as carcinogens and on RfDs or RfCs for chemicals that have not been 

classified as carcinogens. Each pathway of exposure is assessed separately. Thus, the RBSLs 

for toluene are based on hazard quotients of 1 for each potential pathway and the RBSLs for 

benzene are based on cancer risks of 1× 10-6 and 1 × 10-4 for each potential pathway. The 

rationale presented for this approach is that the risk-based screening levels “are typically for a 

limited number of chemical(s) of concern considered at most sites.” RBCA mentions—but does 

not recommend or explain—the use of additivity approaches for mixtures of chemicals for Tier 2 

and Tier 3 assessments. 

 Selection of the chemicals of concern for various petroleum products in the 

ASTM (1995, 2002) RBCA approach is based on concentrations in the product, solubility and 

mobility, toxicological properties, aesthetic characteristics (e.g., odor), and availability of 

sufficient information to conduct risk assessments. For gasoline, kerosene, and jet fuels, 

commonly selected hydrocarbon chemicals of concern are benzene, toluene, ethylbenzene, and 

xylene (BTEX). Additional chemicals of concern for kerosene and jet fuels are PAHs. For 

diesel fuel, light fuel oils, and heavy fuel oils, the commonly selected hydrocarbon chemicals of 
FINAL 

9-30-2009 

 57

concern are PAHs. ASTM (1995, 2002) developed example Tier 1 RBSLs for benzene, 

ethylbenzene, toluene, mixed xylenes, naphthalene, and benzo(a)pyrene for various media and 

exposure pathways, using U.S. EPA cancer and noncancer toxicity values and U.S. EPA 

exposure assessment methods. 

 The TPHCWG (1999) discussed how the TPHCWG fractions and toxicity criteria may be 

used with any risk-based decision framework, including the ASTM (1995) RBCA, and provided 

example calculations of RBSLs. MADEP (2001, 2002), under the Massachusetts Contingency 

Plan, uses a tiered risk assessment approach similar to the ASTM (1995, 2002) RBCA. 

Agency for Toxic Substances and Disease Registry (ATSDR) Approach 

 ATSDR (1999a) developed a toxicological profile on TPH that recommended an 

indicator compound/fraction approach, based on an evaluation and synthesis of the MADEP and 

TPHCWG approaches, and a consideration of the ASTM approach. ATSDR (1999a) used 

ATSDR MRLs and U.S. EPA cancer assessments to evaluate the toxicity and carcinogenicity of 

the compounds and fractions. The recommendations with regard to selection of the fractions are 

similar to those in this report. ATSDR (1999a) noted that an assumption of additivity underlies 

use of a surrogate toxicity value from a representative compound to assess the health effects of 

the entire mass of the fraction. ATSDR discussed the use of an HI method (called index of 

concern by ATSDR) for the constituents (BTEX) of the low-carbon-range aromatics.