TOXICOLOGICAL PROFILE FOR 

TOTAL PETROLEUM HYDROCARBONS (TPH) 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry 

September 1999 
TOTAL PETROLEUM HYDROCARONS ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by the 

Agency for Toxic Substances and Disease Registry. 
















TOTAL PETROLEUM HYDROCARONS 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about total petroleum hydrocarbons (TPH) and the effects 

of exposure. The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the 

nation. These sites make up the National Priorities List (NPL) and are the sites targeted for long-term federal 

cleanup activities. TPH, itself, has been reported at 34 of the 1,519 current or former NPL sites. Many NPL sites are 

contaminated with components of TPH, though no estimate has been made of the number of these sites. This 

information is important because exposure to these components may harm you and because these sites may be 

sources of exposure. 

When a substance is released from a large area, such as an industrial plant, or from a container, such as a drum or 

bottle, it enters the environment. This release does not always lead to exposure. You are exposed to a substance 

only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance or by 

skin contact. 

If you are exposed to TPH, many factors determine whether you’ll be harmed. These factors 

include the dose (how much), the duration (how long), and how you come in contact with it. 

You must also consider the other chemicals you’re exposed to and your age, sex, diet, family 

traits, lifestyle, and state of health. 

1.1 WHAT ARE TOTAL PETROLEUM HYDROCARBONS? 

Total Petroleum Hydrocarbons (TPH) is a term used to describe a broad family of several 

hundred chemical compounds that originally come from crude oil. In this sense, TPH is really a 

mixture of chemicals. They are called hydrocarbons because almost all of them are made entirely 

from hydrogen and carbon. Crude oils can vary in how much of each chemical they contain, and 

so can the petroleum products that are made from crude oils. Most products that contain TPH 

will bum. Some are clear or light-colored liquids that evaporate easily, and others are thick, dark 
TOTAL PETROLEUM HYDROCARBONS 2 

1. PUBLIC HEALTH STATEMENT 

liquids or semi-solids that do not evaporate. Many of these products have characteristic gasoline, 

kerosene, or oily odors. Because modern society uses so many petroleum-based products (for 

example, gasoline, kerosene, fuel oil, mineral oil, and asphalt), contamination of the environment 

by them is potentially widespread. Contamination caused by petroleum products will contain a 

variety of these hydrocarbons. Because there are so many, it is not usually practical to measure 

each one individually. However, it is useful to measure the total amount of all hydrocarbons 

found together in a particular sample of soil, water, or air. 

The amount of TPH found in a sample is useful as a general indicator of petroleum contamination 

at that site. However, this TPH measurement or number tells us little about how the particular 

petroleum hydrocarbons in the sample may affect people, animals, and plants. By dividing TPH 

into groups of petroleum hydrocarbons that act alike in the soil or water, scientists can better 

know what happens to them. These groups are called petroleum hydrocarbon fractions. Each 

fraction contains many individual compounds. Much of the information in this profile talks about 

TPH fractions. See Chapter 2 for more information on what components make up TPH and how 

they are measured. 

1.2 WHAT HAPPENS TO TPH WHEN IT ENTERS THE ENVIRONMENT? 

TPH is released to the environment through accidents, as releases from industries, or as 

byproducts from commercial or private uses. When TPH is released directly to water through 

spills or leaks, certain TPH fractions will float in water and form thin surface films. Other heavier 

fractions will accumulate in the sediment at the bottom of the water, which may affect bottom- feeding 

fish and organisms. Some organisms found in the water (primarily bacteria and fungi) 

may break down some of the TPH fractions. TPH released to the soil may move through the soil 

to the groundwater. Individual compounds may then separate from the original mixture, 

depending on the chemical properties of the compound. Some of these compounds will evaporate 

into the air and others will dissolve into the groundwater and move away from the release area. 

Other compounds will attach to particles in the soil and may stay in the soil for a long period of 
 

TOTAL PETROLEUM HYDROCARONS 3 

1. PUBLIC HEALTH STATEMENT 

time, while others will be broken down by organisms found in the soil. See Chapter 5 for more 

information on how TPH enters and spreads through the environment. 

1.3 HOW MIGHT I BE EXPOSED TO TPH? 

Everyone is exposed to TPH from many sources, including gasoline fumes at the pump, spilled 

crankcase oil on pavement, chemicals used at home or work, or certain pesticides that contain 

TPH components as solvents. A small amount of lighter TPH components are found in the 

general air you breathe. Many occupations involve extracting and refining crude oil, 

manufacturing petroleum and other hydrocarbon products, or using these products. If you work 

with petroleum products, you may be exposed to higher levels of TPH through skin contact or by 

breathing contaminated air. If TPH has leaked from underground storage tanks and entered the 

groundwater, you may drink water from a well contaminated with TPH. You may breathe in 

some of the TPH compounds evaporating from a spill or leak if you are in the area where an 

accidental release has occurred. Children may be exposed by playing in soil contaminated with 

TPH. For more information on how you may be exposed to TPH, see Chapter 5. 

1.4 HOW CAN TPH ENTER AND LEAVE MY BODY? 

TPH can enter and leave your body when you breathe it in air; swallow it in water, food, or soil; 

or touch it. Most components of TPH will enter your bloodstream rapidly when you breathe 

them as a vapor or mist or when you swallow them. Some TPH compounds are widely 

distributed by the blood throughout your body and quickly break down into less harmful 

chemicals. Others may break down into more harmful chemicals. Other TPH compounds are 

slowly distributed by the blood to other parts of the body and do not readily break down. When 

you touch TPH compounds, they are absorbed more slowly and to a lesser extent than when you 

breathe or swallow them. Most TPH compounds leave your body through urine or when you 

exhale air containing the compounds. For more information on how TPH can enter and leave your 

body, see Chapter 6. 
TOTAL PETROLEUM HYDROCARONS 4 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN TPH AFFECT MY BODY? 

Health effects from exposure to TPH depend on many factors. These include the types of 

chemical compounds in the TPH, how long the exposure lasts, and the amount of the chemicals 

contacted. Very little is known about the toxicity of many TPH compounds. Until more 

information is available, information about health effects of TPH must be based on specific 

compounds or petroleum products that have been studied. 

The compounds in different TPH fractions affect the body in different ways. Some of the TPH 

compounds, particularly the smaller compounds such as benzene, toluene, and xylene (which are 

present in gasoline), can affect the human central nervous system. If exposures are high enough, 

death can occur. Breathing toluene at concentrations greater than 100 parts per million 

(100 ppm) for more than several hours can cause fatigue, headache, nausea, and drowsiness. 

When exposure is stopped, the symptoms will go away. However, if someone is exposed for a 

long time, permanent damage to the central nervous system can occur. One TPH compound 

(n-hexane) can affect the central nervous system in a different way, causing a nerve disorder 

called “peripheral neuropathy” characterized by numbness in the feet and legs and, in severe cases, 

paralysis. This has occurred in workers exposed to 500-2,500 ppm of n-hexane in the air. 

Swallowing some petroleum products such as gasoline and kerosene causes irritation of the throat 

and stomach, central nervous system depression, difficulty breathing, and pneumonia from 

breathing liquid into the lungs. The compounds in some TPH fractions can also affect the blood, 

immune system, liver, spleen, kidneys, developing fetus, and lungs. Certain TPH compounds can 

be irritating to the skin and eyes. Other TPH compounds, such as some mineral oils, are not very 

toxic and are used in foods. 

To protect the public from the harmful effects of toxic chemicals and to find ways to-treat people 

who have been harmed, scientists use many tests. 

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and 

released by the body; for some chemicals, animal testing may be necessary. Animal testing may 
 

 

TOTAL PETROLEUM HYDROCARBONS 5 

1. PUBLIC HEALTH STATEMENT 

also be used to identify health effects such as cancer or birth defects. Without laboratory animals, 

scientists would lose a basic method to get information needed to make wise decisions to protect 

public health. Scientists have the responsibility to treat research animals with care and 

compassion. Laws today protect the welfare of research animals, and scientists must comply with 

strict animal care guidelines. Animal studies have shown effects on the lungs, central nervous 

system, liver, kidney, developing fetus, and reproductive system from exposure to TPH 

compounds, generally after breathing or swallowing the compounds. 

One TPH compound (benzene) has been shown to cause cancer (leukemia) in people. The 

International Agency for Research on Cancer (IARC) has determined that benzene is carcinogenic 

to humans (Group 1 classification). Some other TPH compounds or petroleum products, such as 

benzo(a)pyrene and gasoline, are considered to be probably and possibly carcinogenic to humans 

(IARC Groups 2A and 2B, respectively) based on cancer studies in people and animals. Most of 

the other TPH compounds and products are considered not classifiable (Group 3) by IARC. See 

Chapter 6 for more information on how TPH can affect your body. 

1.6 IS THERE A MEDICAL TEST TO DETERMINE IF I HAVE BEEN EXPOSED TO 

TPH? 

There is no medical test that shows if you have been exposed to TPH. However, there are 

methods to determine if you have been exposed to some TPH compounds, fractions, or petroleum 

products. For example, a breakdown product of n-hexane can be measured in the urine. Benzene 

can be measured in exhaled air and a metabolite of benzene, phenol, can be measured in urine to 

show exposure to gasoline or to the TPH fraction containing benzene. Exposure to kerosene or 

gasoline can be determined by its smell on the breath or clothing. Methods also exist to determine 

if you have been exposed to other TPH compounds. For example, ethylbenzene can-be measured 

in the blood, urine, breath, and some body tissues of exposed people. However, many of these 

tests may not be available in your doctor’s office. 

If you have TPH compounds in your body, they could be from exposure to many different 

products, and tests cannot determine exactly what you were exposed to. Tests are useful if you 
 

TOTAL PETROLEUM HYDROCARONS 6 

1. PUBLIC HEALTH STATEMENT 

suspect that you were exposed to a particular product or waste that contains TPH. More 

information on testing for TPH can be found in Chapter 3. For information on tests for exposure 

to specific TPH compounds, see the ATSDR toxicological profiles for benzene, toluene, total 

xylenes, polycyclic aromatic hydrocarbons, and hexane. 

1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO

 PROTECT HUMAN HEALTH? 

The federal government develops regulations and guidelines to protect public health. Regulations 

can be enforced by law. Federal agencies that develop regulations for toxic substances include the 

EPA, the NRC (Nuclear Regulatory Commission), the Occupational Safety and Health 

Administration (OSHA), and the Food and Drug Administration (FDA). Recommendations 

provide valuable guidelines to protect public health but cannot be enforced by law. Federal 

organizations that develop recommendations for toxic substances include the Agency for Toxic 

Substances and Disease Registry (ATSDR), Centers for Disease Control and Prevention (CDC), 

and the National Institute for Occupational Safety and Health (NIOSH). 

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or 

food that are usually based on levels that affect animals. Then they are adjusted to help protect 

people. Sometimes these not-to-exceed levels differ among federal organizations because of 

different exposure times (an 8-hour workday or a 24-hour day), the use of different animal 

studies, or other factors. 

Recommendations and regulations are also periodically updated as more information becomes 

available. For the most current information, check with the federal agency or organization that 

provides it. 

Although there are no federal regulations or guidelines for TPH in general, the government has 

developed regulations and guidelines for some of the TPH fractions and compounds. These are 

designed to protect the public from the possible harmful health effects of these chemicals. To 
TOTAL PETROLEUM HYDROCARONS 7 

1. PUBLIC HEALTH STATEMENT 

protect workers, the Occupational Safety and Health Administration (OSHA) has set a legal limit 

of 500 parts of petroleum distillates per million parts of air (500 ppm) in the workplace. 

EPA regulates certain TPH fractions, products, or wastes containing TPH, as well as some 

individual TPH compounds. For example, there are regulations for TPH as oil; these regulations 

address oil pollution prevention and spill response, stormwater discharge, and underground 

injection control. EPA lists certain wastes containing TPH as hazardous. EPA also requires that 

the National Response Center be notified following a discharge or spill into the environment of 10 

pounds or more of hazardous wastes containing benzene, a component in some TPH mixtures. 

Nearly all states have cleanup standards for TPH or components of TPH (common cleanup 

standards are for gasoline, diesel fuel, and waste oil). Analytical methods are specified, many of 

which are considered to be TPH methods. 

1.8 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department or: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology
 

1600 Clifton Road NE, Mailstop E-29
 

Atlanta, GA 30333
 

* Information line and technical assistance 

Phone: l-888-42-ATSDR (l-888-422-8737)
 

Fax: (404) 639-6314 or 6324
 

ATSDR can also tell you the location of occupational and environmental health clinics. These 

clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to 

hazardous substances. 
TOTAL PETROLEUM HYDROCARONS 8 

1. PUBLIC HEALTH STATEMENT 

* To order toxicological profiles, contact: 

National Technical Information Service
 

5285 Port Royal Road
 

Springfield, VA 22 16 1
 

Phone: (800) 553-6847 or (703) 487-4650
 
TOTAL PETROLEUM HYDROCARONS 9 

2. OVERVIEW OF TOTAL PETROLEUM HYDROCARBONS
 

This document presents information in a way that is more summary in nature than the usual comprehensive 

toxicological profile. Total petroleum hydrocarbons (TPH) is such a broad family of compounds that it 

would be a large undertaking to present comprehensive environmental, chemical/physical, and health 

information on all the individual chemical components or on all petroleum products. This and subsequent 

chapters are designed to aid the reader in understanding what TPH is, what we know about it, the chance of 

significant exposure, and possible health consequences. Appendices are provided that present more 

detailed information. 

2.1 DEFINITION OF TOTAL PETROLEUM HYDROCARBONS 

TPH is defined as the measurable amount of petroleum-based hydrocarbon in an environmental media. It is, 

thus, dependent on analysis of the medium in which it is found (Gustafson 1997). Since it is a measured, 

gross quantity without identification of its constituents, the TPH “value” still represents a mixture. Thus, 

TPH itself is not a direct indicator of risk to humans or to the environment. The TPH value can be a result 

from one of several analytical methods, some of which have been used for decades and others developed in 

the past several years. Analytical methods are evolving in response to needs of the risk assessors. In 

keeping with these developments, definition of TPH by ATSDR is closely tied to analytical methods and 

their results. The ATSDR approach to assessing the public health implications of exposure to TPH is 

presented in Section 2.3. 

There are several hundred individual hydrocarbon chemicals defined as petroleum-based, with more than 

2.50 petroleum components identified in Appendix D of this profile. Further, each petroleum product has 

its own mix of constituents. One reason for this is that crude oil, itself, varies in its composition. Some of 

this variation is reflected in the finished petroleum product. The acronym PHC (petroleum hydrocarbons) is 

widely used to refer to the hydrogen- and carbon-containing compounds originating from crude oil, but 

PHC should be distinguished from TPH, because TPH is specifically associated with environmental 

sampling and analytical results. 

Petroleum crude oils can be broadly divided into paraffinic, asphaltic, and mixed crude oils (WHO 1982). 

Paraffinic crude oils are composed of aliphatic hydrocarbons (paraffins), paraffin wax (longer chain 
TOTAL PETROLEUM HYDROCARONS 10 

2. OVERVIEW OF TOTAL PETROLEUM HYDROCARBONS 

aliphatics), and high grade oils. Naphtha is the lightest of the paraffin fraction, followed by kerosene 

fractions. Asphaltic crude oils contain larger concentrations of cycloaliphatics and high viscosity 

lubricating oils. Petroleum solvents are the product of crude oil distillation and are generally classified by 

boiling point ranges. Lubricants, greases, and waxes are high boiling point fractions of crude oils. The 

heaviest, solid fractions of crude oils are the residuals or bitumen. 

Some products are highly predictable (e.g., jet fuels) with specific fractions of defined components; others, 

for example, automotive gasolines, contain broader ranges of hydrocarbon types and amounts. Table D- 1 

in Appendix D provides a comprehensive list of petroleum hydrocarbons. 

Petroleum products, themselves, are the source of the many components, but do not define what is TPH. 

They help define the potential hydrocarbons that become environmental contaminants, but any ultimate 

exposure is determined also by how the product changes with use, by the nature of the release, and by the 

hydrocarbon’s environmental fate. When petroleum products are released into the environment, changes 

occur that significantly affect their potential effects. Physical, chemical, and biological processes change 

the location and concentration of hydrocarbons at any particular site. 

Petroleum hydrocarbons are commonly found environmental contaminants, though they are not usually 

classified as hazardous wastes. Many petroleum products are used in modern society, including those that 

are fundamental to our lives (i:e., transportation fuels, heating and power-generating fuels). The volume of 

crude oil or petroleum products that is used today dwarfs all other chemicals of environmental and health 

concern. Due to the numbers of facilities, individuals, and processes and the various ways the products are 

stored and handled, environmental contamination is potentially widespread. 

Soil and groundwater petroleum hydrocarbon contamination has long been of concern and has spurred 

various analytical and site remediation developments, e.g., risk-based corrective actions (ASTM’s 

Risk-Based Corrective Action [RBCA]), EPA and state government underground storage tank (UST) 

programs, British Columbia’s Ministry of Environment’s development of remediation criteria for 

petroleum contamination (primarily environmental risks) (BC 1995), and the annual Amherst 

Massachusetts conference from which the Total Petroleum Hydrocarbon Criteria Working Group 

(TPHCWG) was formed. The TPHCWG is made up of industry, government, and academic 

scientists, working to develop a broad set of guidelines to be used by engineering and public health 
TOTAL PETROLEUM HYDROCARONS 11 

2. OVERVIEW OF TOTAL PETROLEUM HYDROCARBONS 

professionals in decisions on petroleum contaminated media. In 1997 the criteria working group 

published a technical overview of their risk management approach to TPH (TPHCWG 1997a), which 

represents the most comprehensive effort in this area to date. In 1997 the TPHCWG published two 

volumes, Selection of Representative TPH Fractions Based on Fate and Transport Considerations 

(Vol. 3) and Development of Fraction Specific Reference Doses (RfDs) and Reference Concentrations 

(RfCs) for Total Petroleum Hydrocarbons (TPH) (Vo1.4) (TPHCWG 1997b, 1997c). In 

1998 the TPHCWG published Volume 1, Analysis of Petroleum Hydrocarbons in Environmental 

Media (TPHCWG 1998a) and Volume 2, Composition of Petroleum Mixtures (TPHCWG 1998b). 

2.2 TOTAL PETROLEUM HYDROCARBONS ANALYSIS OVERVIEW 

The TPH method of analysis often used, and required by many regulatory agencies, is EPA Method 

4 18.1. This method provides a “one number” value of TPH in an environmental media; it does not 

provide information on the composition (i.e., individual constituents of the hydrocarbon mixture). 

The amount of TPH measured by this method depends on the ability of the solvent used to extract the 

hydrocarbon from the environmental media and the absorption of infrared (IR) light by the 

hydrocarbons in the solvent extract. EPA Method 418.1 is not specific to hydrocarbons and does not 

always indicate petroleum contamination (e.g., humic acid, a non-petroleum hydrocarbon, may be 

detected by this method). 

An important feature of the TPH analytical methods is the use of an Equivalent Carbon Number 

Index (EC). The EC represents equivalent boiling points for hydrocarbons and is the physical 

characteristic that is the basis for separating petroleum (and other) components in chemical analysis. 

Petroleum fractions as discussed in this profile are defined by EC. 

Another analytical method commonly used for TPH is EPA Method 8015 Modified. This method 

reports the concentration of purgeable and extractable hydrocarbons; these are sometimes referred to 

as gasoline and diesel range organics, GRO and DRO, respectively, because the boiling point ranges 

of the hydrocarbon in each roughly correspond to those of gasoline (C6 to C10-12) and diesel fuel (C8-12 

to C24-26), respectively. Purgeable hydrocarbons are measured by purge-and-trap gas chromatography 

(GC) analysis using a flame ionization detector (FID), while the extractable hydrocarbons are 

extracted and concentrated prior to analysis by GUFID. The results are most frequently reported as 
 

TOTAL PETROLEUM HYDROCARONS 12 

2. OVERVIEW OF TOTAL PETROLEUM HYDROCARBONS 

single numbers for purgeable and extractable hydrocarbons. Before the TPHCWG began publishing 

its TPH guides, the Massachusetts Department of Environmental Protection (MADEP) developed risk 

assessment and analytical methodologies for TPH (Hutcheson et al. 1996). MADEP developed a 

method based on EPA Method 801.5 Modified which gives a measure of the aromatic and aliphatic 

content of the hydrocarbon in each of several carbon number ranges (fractions). The MADEP method 

is based on standard EPA methods, which allows it to be easily implemented by laboratories, though 

there are limitations with the method (see Section 3.3). EPA has proposed a modification in its test 

procedure for analysis of “oil and grease and total petroleum hydrocarbons” that not only overcomes 

the problem of using freon as a solvent, but also provides more refined separation of aliphatic and 

aromatic fractions (EPA 1998a). 

The Risk-Based Corrective Action (RBCA) guidance of American Society for Testing and Materials 

(ASTM), published in 1995, is an important document for public and private institutions that 

remediate petroleum contaminated sites (ASTM 1995). EPA is telling agencies implementing risk- based 

decision-making that the ASTM standard may be a good starting point for risk management 

(EPA 1995c). 

2.3 TPH FRACTIONS AND THE ATSDR APPROACH TO EVALUATING THE PUBLIC 

HEALTH IMPLICATIONS OF EXPOSURE TO TPH 

The public health implications associated with TPH are common to the broader questions of chemical 

mixtures. What does one know about the makeup and adverse health effects associated with the 

whole mixture? Does one select the most toxic or carcinogenic elements or representative 

chemical(s), or does one rely on whole product toxicity results? In the case of TPH, one sample is 

likely to vary significantly in content from other samples, even with similar “single value” results. 

This profile builds on the efforts by the TPHCWG and MADEP to group chemicals into fractions 

with similar environmental transport characteristics (i.e., transport fractions). An important 

difference is ATSDR’s concern with all possible exposure periods, from acute through chronic, 

whereas other agencies or groups have focused on longer-term exposures. The common characteristic 

of all of these approaches is the attempt to gather the available information about the toxicity and the 

risks associated with transport fractions. 
TOTAL PETROLEUM HYDROCARONS 13 

2. OVERVIEW OF TOTAL PETROLEUM HYDROCARBONS 

Although chemicals grouped by transport fraction generally have similar toxicological properties, this is not 

always the case. For example, benzene is a carcinogen, but toluene, ethylbenzene, and xylenes are not. 

However, it is more appropriate to group benzene with compounds that have similar environmental 

transport properties than to group it with other carcinogens such as benzo(a)pyrene that have very 

different environmental transport properties. Section 6.1.1 provides a more detailed discussion of the 

various transport fractions. 

ATSDR’s mission of providing public health support to communities with potential exposure to hazardous 

wastes is different from that of the ASTM, for example, which developed the RBCA guide for the 

purpose of remediation of petroleum-contaminated sites. Also, ecological risk assessment is a 

fundamental feature of the ASTM and British Columbia methodologies, though not for ATSDR. 

Because a critical aspect of assessing the toxic effects of TPH is the measurement of the compounds, 

one must first appreciate the origin of the various fractions (compounds) of TPH. Transport fractions are 

determined by several chemical and physical properties (i.e. solubility, vapor pressure, and propensity to 

bind with soil and organic particles). These properties are the basis of measures of leachability and 

volatility of individual hydrocarbons and transport fractions. The TPHCWG approach defines petroleum 

hydrocarbon transport fractions by equivalent carbon number grouped into 13 fractions (see 

Section 6.1.2). The “analytical fractions” are then set to match these transport fractions, using specific 

n-alkanes to mark the analytical results for aliphatics and selected aromatics to delineate hydrocarbons 

containing benzene rings. ATSDR has used the basic TPHCWG approach and modified the fractional 

groups (see Chapter 6). Fate and transport considerations are discussed in more detail in Chapter 5. The 

TPHCWG transport fractions’ physical properties are presented in Table 2-l. 

The approach to evaluating the potential health effects for these transport fractions taken by ATSDR and 

the TPHCWG, however, uses a reduced number of fractions, namely three aliphatic fractions and three 

aromatic fractions. Health effects screening values based on representative chemicals or-mixtures for 

each of the fractions were developed using ATSDR minimal risk levels (MRLs). Table 2-2 presents the 

ATSDR TPH fractions and their representative compounds or mixtures. In general, the most toxic 

representative compound or mixture for each fraction is used to indicate the potential toxicity of the entire 

fraction. Selection of the representative compounds and mixtures is discussed in detail in Sections 6.2, 


TOTAL PETROLEUM HYDROCARONS 16 

2. OVERVIEW OF TOTAL PETROLEUM HYDROCARBONS 

6.3, and 6.6. In addition, existing cancer assessments for each fraction are presented and discussed in 

Chapter 6 and Appendix A. 

Despite the large number of hydrocarbons found in petroleum products and the widespread nature of 

petroleum use and contamination, only a relatively small number of the compounds are well characterized 

for toxicity. The health effects of some fractions can be well characterized, based on their components or 

representative compounds (e.g., light aromatic fraction-BTEX-benzene, toluene, ethylbenzene, and 

xylenes). However, heavier TPH fractions have far fewer well characterized compounds. Systemic and 

carcinogenic effects are known to be associated with petroleum hydrocarbons, but ATSDR does not 

develop health guidance values for carcinogenic end points (ATSDR 1996b). See Chapter 6 for further 

discussion of the ATSDR approaches and the approaches of other groups (MADEP, TPHCWG, and 

ASTM). 
TOTAL PETROLEUM HYDROCARONS 17 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

3.1 INTRODUCTION 

Petroleum hydrocarbons (PHCs) are common site contaminants, but they are not generally regulated 

as hazardous wastes. Methods for sampling and analysis of environmental media for the family of 

PHCs are generally thought of as TPH methods. For purposes of this profile, the term TPH refers 

not only to analytical results, but also to environmental and health properties of PHCs. In part due to 

the complexity of TPH components themselves, little is known about their potential for health or 

environmental impacts. As gross measures of petroleum contamination, TPH results simply show 

that petroleum hydrocarbons are present in the sampled media. Measured TPH values suggest the 

relative potential for human exposure and, therefore, the relative potential for human health effects. 

The assessment of health effects due to TPH exposure requires much more detailed information than 

what is provided by a single TPH value. This chapter, Chapter 5, and the accompanying Appendix E 

provide more detailed physical and chemical properties and analytical information on TPH and its 

components. 

The federal government has left much of the specific regulation and oversight of crude oil production/ 

refining to the states. Leaking underground storage tanks (LUST) are the most frequent causes of 

federal and state governmental involvement in petroleum hydrocarbon problems. Soil contamination 

has been a growing concern, because it can be a source of groundwater (drinking water) contamination; 

contaminated soils can reduce the usability of land for development; and weathered petroleum 

residuals may stay bound to soils for years. Positive TPH test results may require action on the part 

of land owners, local or state governments, and engineering firms called on to remove or reduce the 

TPH problem. 

ATSDR has the responsibility for health assessment at National Priorities List (NPL) hazardous 

waste sites, many of which have petroleum hydrocarbon contamination. Specific contaminants that 

are components of TPH, such as BTEX (benzene, toluene, ethylbenzene, and xylene), n-hexane, jet 

fuels, fuel oils, and mineral-based crankcase oil, have been studied by ATSDR and a number of 

toxicological profiles have been developed on individual constituents and petroleum products. The 
TOTAL PETROLEUM HYDROCARONS 18 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

ATSDR profiles relevant to petroleum products are listed in Table 3- 1. However, TPH itself has not 

been as extensively studied by ATSDR and no previous profile was developed. Although several 

toxicological profiles have been developed for petroleum products and for specific chemicals found in 

petroleum, TPH test results have been too nonspecific to be of real value in the assessment of its 

potential health effects. 

Several approaches are discussed in this document for interpreting TPH and related analytical results. 

The TPH approach taken by EPA and others, through the mid-1990s, followed general risk 

assessment approaches for chemical mixtures. In all approaches there is a need to reduce a 

comprehensive list of potential petroleum hydrocarbons to a manageable size. Depending on how 

conservative the approach is, methods that have been used select: (1) the most toxic among the TPH 

compounds (indicator approach); (2) one or more representative compounds (surrogate approach, but 

independent of relative mix of compounds); or (3) representative compounds for fractions of similar 

petroleum hydrocarbons. ATSDR has taken, in part, the third approach in keeping with the Total 

Petroleum Hydrocarbons Criteria Working Group (TPHCWG), but has developed its own set of TPH 

fraction representatives, many of which overlap those of the TPHCWG. In addition, this profile 

provides information on petroleum products, where such information exists. TPH risk (screening) 

values for fractions presented in this profile are based on the ATSDR MRLs previously developed for 

individual constituents and petroleum products. These MRLs are summarized in Appendix A. This 

fraction approach is the most demanding in information gathering and because of that would appear 

to be the most rigorous approach to date. Sections 6.1.2 and 6.1.3 contain a more comprehensive 

discussion of the approaches. The identity, chemical-physical, and analytical information discussed 

and listed in this chapter, in Appendices D and E, and in Chapter 5 are integral to defining TPH. 

3.2 CHEMICAL AND PHYSICAL INFORMATION 

Petroleum products are complex mixtures of hundreds of hydrocarbon compounds, ranging from light, 

volatile, short-chained organic compounds to heavy, long-chained, branched compounds. The exact 

composition of petroleum products varies depending upon (1) the source of the crude oil (crude oil is 

derived from underground reservoirs which vary greatly in their chemical composition) and (2) the 

refining practices used to produce the product. 

TOTAL PETROLEUM HYDROCARONS 20 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

During the refining process, crude oil is separated into fractions having similar boiling points. These 

fractions are then modified by cracking, condensation, polymerization, and alkylation processes, and 

are formulated into commercial products such as naphtha, gasoline, jet fuel, and fuel oils. The 

composition of any one of these products can vary based on the refinery involved, time of year, 

variation in additives or modifiers, and other factors. The chemical composition of the product can be 

further affected by weathering and/or biological modification upon release to the environment. The 

following subsections present overviews of petroleum products. Also, a master list of individual 

aliphatic and aromatic compounds found in TPH is provided in Appendix D. Further information on 

whole petroleum products, their identity, major components, and physical/chemical properties is 

found in Appendix E. 

Automotive Gasoline. Automotive gasoline is a mixture of low-boiling hydrocarbon compounds 

suitable for use in spark-ignited internal combustion engines and having an octane rating of at least 

60. Additives that have been used in gasoline include alkyl tertiary butyl ethers (e.g. MTBE), ethanol 

(ethyl alcohol), methanol (methyl alcohol), tetramethyl-lead, tetraethyl-lead, ethylene dichloride, and 

ethylene dibromide. 

Other categories of compounds that may be added to gasoline include anti-knock agents, antioxidants,
 

metal deactivators, lead scavengers, anti-rust agents, anti-icing agents, upper-cylinder
 

lubricants, detergents, and dyes (ATSDR 1995a).
 

Automotive gasoline typically contains about 150 hydrocarbon compounds, though nearly 1,000 have
 

been identified (ATSDR 1995a). The relative concentrations of the compounds vary considerably
 

depending on the source of crude oil, refinery process, and product specifications. Typical hydrocarbon
 

chain lengths range from C4 through Cl2 with a general hydrocarbon distribution consisting of
 

4-8% alkanes, 2-5% alkenes, 25-40% isoalkanes, 3-7% cycloalkanes, l-4% cycloalkenes, and
 

20-50% aromatics (IARC 1989a). However, these proportions vary greatly. Unleaded gasolines
 

may have higher proportions of aromatic hydrocarbons than leaded gasolines.
 

Table E-1.b (Appendix E) presents ranges and weight percentage means for a representative subset of
 

the hydrocarbon compounds identified in gasoline. In cases where data are not available, the range
 

and mean are left blank.
 
TOTAL PETROLEUM HYDROCARONS 21 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

Stoddard Solvent. Stoddard solvent is a petroleum distillate widely used as a dry cleaning solvent 

and as a general cleaner and degreaser. It may also be used as a paint thinner, as a solvent in some types 

of photocopier toners, in some types of printing inks, and in some adhesives. Stoddard solvent is 

considered to be a form of mineral spirits, white spirits, and naphtha; however, not all forms of mineral 

spirits, white spirits, and naphtha are considered to be Stoddard solvent (ATSDR 1995b). 

Stoddard solvent consists of 30-50% linear and branched alkanes, 30-40% cycloalkanes, and lo-20% 

aromatic hydrocarbons. Its typical hydrocarbon chain ranges from C7 through C12 in length. 

Although a complete list of the individual compounds comprising Stoddard solvent is not available (Air 

Force 1989) some of the major components are presented in Table E-2.b (Appendix E). Alcohols, 

glycols, and ketones are not included in the composition, as few, if any, of these types of compounds 

would be expected to be present in Stoddard solvent (ATSDR 1995b). Possible contaminants may 

include lead (<1 ppm) and sulfur (3.5 ppm). 

Jet Fuel. Jet fuels are light petroleum distillates that are available in several forms suitable for use in 

various types ofjet engines. The exact compositions of jet fuels are established by the U.S. Air Force, 

using specifications that yield maximum performance by the aircraft. The major jet fuels used by the 

military are JP-4, JP-5, JP-6, JP-7, and JP-8. Briefly, JP-4 is a wide-cut fuel developed for broad 

availability in times of need. JP-6 is a higher cut than JP-4 and is characterized by fewer impurities. JP-5 

is specially blended kerosene, and JP-7 is a high flash point special kerosene used in advanced supersonic 

aircraft. JP-8 is a kerosene modeled on Jet A-l fuel (used in civilian aircraft). For this profile, JP-4 will 

be used as the prototype jet fuel due to its broad availability and extensive use. 

Typical hydrocarbon chain lengths characterizing JP-4 range from C4 to C16. Aviation fuels consist 

primarily of straight and branched alkanes and cycloalkanes. Aromatic hydrocarbons are limited to 

20-25% of the total mixture because they produce smoke when burned. A maximum of5% alkenes are 

allowed in JP-4 (ATSDR 1995c). The approximate distribution by chemical class is: 32% straight 

alkanes, 31% branched alkanes, 16% cycloalkanes, and 21% aromatic hydrocarbons (ABB 

Environmental 1990). The typical hydrocarbon composition of JP-4 is presented in Table E-3.b 

(Appendix E). 
TOTAL PETROLEUM HYDROCARONS 22 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

Fuel Oil #1. Fuel oil #l is a petroleum distillate that is one of the most widely used of the fuel oil 

types. It is used in atomizing burners that spray fuel into a combustion chamber where the tiny droplets 

bum while in suspension. It is also used as a carrier for pesticides, as a weed killer, as a mold release 

agent in the ceramic and pottery industry, and in the cleaning industry. It is found in asphalt coatings, 

enamels, paints, thinners, and varnishes. 

Fuel oil #1 is a light petroleum distillate (straight-run kerosene) consisting primarily of hydrocarbons in the 

range C9-C16 (ATSDR 19958). Fuel oil #l is very similar in composition to diesel fuel oil #l; the primary 

difference is in the additives. The typical hydrocarbon composition of fuel oil #l is presented in 

Table E-4.b (Appendix E). 

Fuel Oil #2. Fuel oil #2 is a petroleum distillate that may be referred to as domestic or industrial. The 

domestic fuel oil #2 is usually lighter and straight-run refined; it is used primarily for home heating and to 

produce diesel fuel #2. Industrial distillate is the cracked type, or a blend of both. It is used in smelting 

furnaces, ceramic kilns, and packaged boilers (ABB Environmental 1990). 

Fuel oil #2 is characterized by hydrocarbon chain lengths in the C11-C20 range, whereas diesel fuels 

predominantly contain a mixture of C10-C19 hydrocarbons (ATSDR 1995g). The composition consists of 

approximately 64% aliphatic hydrocarbons (straight chain alkanes and cycloalkanes), l-2% unsaturated 

hydrocarbons (alkenes), and 35% aromatic hydrocarbons (including alkylbenzenes and 2-, 3-ring 

aromatics) (Air Force 1989). Fuel oil #2 contains less than 5% polycyclic aromatic hydrocarbons (IARC 

1989b). The typical hydrocarbon composition of fuel oil #2 is presented in Table E-4.b (Appendix E). 

Fuel Oil #6. Fuel oil #6 is also called Bunker C or residual. It is the residual from crude oil after the 

light oils, gasoline, naphtha, fuel oil #l, and fuel oil #2 have been fractioned off. Fuel oil #6 can be 

blended directly to heavy fuel oil or made into asphalt. It is limited to commercial and industrial uses 

where sufficient heat is available to fluidize the oil for pumping and combustion (ABB Environmental 

1990). 

Residual fuel oils are generally more complex in composition and impurities than distillate fuels. Limited 

data are available on the composition of fuel oil #6 (ATSDR 1995g). Clark et al. (1990) indicate that fuel 

oil #6 includes about 25% aromatics, 15% paraffins, 45% naphthenes, and 15% non-hydrocarbon 
TOTAL PETROLEUM HYDROCARONS 23 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

compounds. Polycyclic aromatic hydrocarbons (PAHs) and alkyl PAHs and metals are important 

hazardous and persistent components of fuel oil #6. Table E-4.b (Appendix E) presents the results of an 

analysis of one sample (Pancirov and Brown 1975). 

Mineral Oils, Including Mineral-based Crankcase Oil. Mineral oils are often lubricating oils, 

but they also have medicinal and food uses. A major type of hydraulic fluid is the mineral oil class of 

hydraulic fluids (ATSDR 1997b). The mineral-based oils are produced from heavy-end crude oil 

distillates. Distillate streams may be treated in several ways, such as vacuum-, solvent-, acid-, or hydro- treated, to 

produce oils with commercial properties. Hydrocarbon numbers ranging from C15 to C50 are 

found in the various types of mineral oils, with the heavier distillates having higher percentages of the 

higher carbon number compounds (IARC 1984). 

Crankcase oil or motor oil may be either mineral-based or synthetic. The mineral-based oils are more 

widely used than the synthetic oils and may be used in automotive engines, railroad and truck diesel 

engines, marine equipment, jet and other aircraft engines, and most small 2- and 4-stroke engines. 

The mineral-based oils contain hundreds to thousands of hydrocarbon compounds, including a substantial 

fraction of nitrogen- and sulfur-containing compounds. The hydrocarbons are mainly mixtures of straight 

and branched chain hydrocarbons (alkanes), cycloalkanes, and aromatic hydrocarbons. PAHs, alkyl 

PAHs, and metals are important components of motor oils and crankcase oils, with the used oils typically 

having higher concentrations than the new unused oils. Typical carbon number chain lengths range from 

Cl5 to C50 (ABB Environmental 1990). 

Because of the wide range of uses and the potential for close contact with the engine to alter oil 

composition, the exact composition of crankcase oil/motor oil has not been specifically defined. Table E5.b (Appendix E) presents analytical results for some constituents in used automotive oil (ABB 

Environmental 1990). 
TOTAL PETROLEUM HYDROCARONS 24 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

3.3 ANALYTICAL METHODS 

The purpose of this section is to describe well established analytical methods that are available for 

detecting, and/or measuring, and/or monitoring TPH and its metabolites, as well as other biomarkers 

of exposure and effect of TPH. The intent is not to provide an exhaustive list of analytical methods. 

Rather, the intention is to identify well-established methods that are used as the standard methods 

approved by federal agencies and organizations such as EPA and the National Institute for 

Occupational Safety and Health (NIOSH) or methods prescribed by state governments for water and 

soil analysis. Other methods presented are those that are approved by groups such as ASTM. 

The term “total petroleum hydrocarbons” (TPH) is generally used to describe the measurable amount 

of petroleum-based hydrocarbons in the environment; and thus the TPH information obtained depends 

on the analytical method used. One of the difficulties with TPH analysis is that the scope of the 

methods varies greatly. Some methods are nonspecific while others provide results for hydrocarbons 

in a boiling point range. Interpretation of analytical results requires an understanding of how the 

determination was made. 

Analytical methods for some petroleum products are discussed in existing ATSDR toxicological 

profiles. The very volatile gases (compounds with 4 carbons or less), crude oil, and the solid 

bituminous materials such as asphalt are not included in this discussion of analytical methods. 

ATSDR profiles relevant to petroleum products are listed in Table 3-1. The TPHCWG also 

addresses some of these issues from a different perspective which includes, in some cases, more detail 

and references than provided here (TPHCWG 1998a). 

3.3.1 Environmental Samples. 

Most of the analytical methods discussed here for TPH have been developed within the framework of 

federal and state regulatory initiatives. The initial implementation of the Federal Water Pollution 

Control Act (FWPCA) focused on controlling conventional pollutants such as oil and grease. Methods 

developed for monitoring wastewaters included EPA Method 4 13.1 (EPA 1979a) and EPA Method 

413.2 (EPA 1979d) for Total Recoverable Oil and Grease (TOG), and EPA Method 418.1 for Total 

Recoverable Petroleum Hydrocarbons (TRPH) (EPA 1979c). Freon-extractable material is reported 

as TOG. Polar components may be removed by treatment with silica gel, and the material remaining, 
TOTAL PETROLEUM HYDROCARONS 25 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

as determined by infrared (IR) spectrometry, is defined as Total Recoverable Petroleum Hydrocarbons 

(TPH, TRPH, or TPH-IR). A number of modifications of these methods exist. EPA Method 418.1 

has been one of the most widely used methods for the determination of TPH in soils. Many states use, 

or permit the use of, EPA Method 418.1 for identification of petroleum products and during 

remediation of sites (George 1992; Judge et al. 1997, 1998). This method is subject to limitations, 

such as inter-laboratory variations and inherent inaccuracies (George 1992). In addition, the EPA 

proposed to withdraw wastewater methods which use Freon- 113 extraction (EPA 1996a). These 

methods will be replaced with EPA Method 1664: n-Hexane Extractable Material (HEM) and Silica Gel 

Treated n-Hexane Extractable Material (SGT-HEM) by Extraction and Gravimetry (Oil and Grease 

and Total Petroleum Hydrocarbons) (EPA 1996a). Conventional methods of TPH analysis are 

summarized in Table 3-2. 

These conventional TPH analytical methods have been used widely to investigate sites that may be 

contaminated with petroleum hydrocarbon products. Many state and local regulatory agencies rely on 

and require EPA Method 418.1 (EPA 1979c) for determination of petroleum hydrocarbons (Murray 

1994). The important advantages of this approach are (1) the method is relatively inexpensive, and 

(2) excellent sample reproducibility can be obtained. The disadvantages are (1) petroleum 

hydrocarbon composition varies among sources and over time, so results are not always comparable; 

(2) the more volatile compounds in gasoline and light fuel oil may be lost in the solvent concentration 

step; (3) there are inherent inaccuracies in the method; and (4) the method provides virtually no 

information on the types of hydrocarbons present. Several recent reports have detailed the problems 

with this approach (George 1992; Rhodes et al. 1995/1996). Thus, these conventional TPH methods, 

although they provide adequate screening information, do not provide sufficient information on the 

extent of the contamination and product type. In addition, The Clean Air Act Amendments of 1990 

require the phaseout of the use of chlorofluorocarbons. Therefore, the EPA methods using Freon-l 13 

will be replaced with EPA Method 1664, n-Hexane Extractable Material (HEM) and Silica Gel 

Treated n-Hexane Extractable Material (SGT-HEM) by Extraction and Gravimetry (EPA 1996a). 

Proposed Method 1664 includes thorough method quality control, but results may not equivalent to 

the current methods. Examples of TPH methods for environmental media are shown in Table 3-3. 

Gas chromatography (GC) methods do provide some information about the product type. Most 

methods involve a sample preparation procedure followed by analysis using GC techniques. GC 




TOTAL PETROLEUM HYDROCARONS 30 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

determination is based on selected components or the sum of all components detected within a given 

range. Frequently the approach is to use two methods, one for the volatile range and another for the 

semivolatile range. Volatiles in water or solid samples are determined by purge-and-trap GC/FID. 

The analysis is often called the gasolines range organics (GRO) method. The semivolatile range is 

determined by analysis of an extract by GC/FID and is referred to as diesel range organics (DRO). 

Individual states have adopted methods for measuring GRO and DRO contamination in soil and 

water. The specific method details and requirements vary from state to state. Some of the GC TPH 

methods are summarized in Table 3-4. 

In the mid-1980s underground storage tank (UST) programs were a focus of federal and state 

initiatives. The criteria and methodology for determining contamination are generally state-specific. 

Although many states still use EPA Method 418.1, GC procedures have been developed to provide 

more specific information on hydrocarbon content of waters and soils (Judge et al. 1997, 1998). 

GRO and DRO are specified in some cases, and several states, such as California and Wisconsin, 

aggressively developed programs to address groundwater contamination problems. These GC 

methods, coupled with specific extraction techniques, can provide information on product type by 

comparison of the chromatogram with standards. Quantitative estimates may be made for a boiling 

range or for a range of carbon numbers by summing peaks within a specific window. Although these 

methods provide more product information than the TPH and TOG methods, they are not without 

limitations. These include high results caused by interferences, low recovery due to the standard 

selected, petroleum product changes caused by volatility, and microbial activity (Restek 1994). 

Many methods are available for analysis of petroleum hydrocarbon products, particularly in water 

and soil matrices. The current literature includes a number of studies that document the performance 

and limitations of the commonly used methods. Method modifications and new methods are being 

investigated to provide better information about the petroleum component content of environmental 

samples. However, the available analytical methodology alone may not provide adequate information 

for those who evaluate the movement of petroleum components in the environment or evaluate the 

health risks posed to humans (Heath et al. 1993a). 

In its work to develop a fraction approach to assess TPH risks the TPH Criteria Working Group 

(TPHCWG) has developed an analytical method for identifying and quantifying the presence of the 

TOTAL PETROLEUM HYDROCARONS 32 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

groups or fractions with similar mobility in soils. The technique is based on EPA Method 3611 

(Alumina Column Cleanup and Separation of Petroleum Wastes) and EPA Method 3630 (Silica Gel 

Cleanup), which are used to fractionate the hydrocarbon into aliphatic and aromatic fractions. A gas 

chromatograph equipped with a boiling point column (non-polar capillary column) is used to analyze 

whole soil samples as well as the aliphatic and aromatic fractions to resolve and quantify the 

fate-and-transport fractions selected by the TPHCWG (Gustafson 1997). The method is versatile and 

performance-based and, therefore, can be modified to accommodate data quality objectives 

(Gustafson 1997). 

The Massachusetts Department of Environmental Protection (MADEP) approached its needs to 

evaluate the potential health effects of petroleum hydrocarbons similarly by defining analytical 

fractions. MADEP’s method is based on standard EPA Methods (8020/8015 Modified), which allows 

it to be easily implemented by contract laboratories (Gustafson 1997; Hutcheson et al. 1996). Lighter 

hydrocarbon fractions (C6-C12 are analyzed by purge-and-trap GC analysis using a FID to measure 

the total hydrocarbons and a photoionization detector (PID) to measure the aromatics. The aliphatic 

(e.g., hexane) component of the TPH is found by determining the difference. Aromatic and aliphatic 

fractions are divided into carbon number fractions based on the normal alkanes (e.g., n-octane) as 

markers. Heavier hydrocarbons (C12-C26) are analyzed using an extraction procedure followed by a 

column separation using silica gel (Modified EPA Method 3630) of the aromatic and aliphatic 

groupings or fractions. The two fractions are then analyzed using GC/FID. PAH markers and 

n-alkane markers are used to divide the heavier aromatic and aliphatic fractions by carbon number, 

respectively. A couple of concerns about the methodology have been expressed: (1) the PID is not 

completely selective for aromatics and can lead to an overestimate of the more mobile and toxic 

aromatic content; and (2) the results from the two analyses, purgeable and extractable hydrocarbons, 

can overlap in carbon number and cannot be simply added together to get a total TPH concentration. 

Few methods are available for monitoring petroleum products in other matrices such as plant and 

animal tissue and food. 
TOTAL PETROLEUM HYDROCARONS 33 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

3.3.1.1 Soils and Sediments 

Methods for determining TPH in soils and sediments are discussed in Section 3.3.1 above. These 

methods are used primarily for UST programs. Currently, many of the states have adopted EPA Method 

418.1 or modified EPA Method 801.5 or similar methods for analysis during remediation of contaminated 

sites. Thus, there is no standard for TPH analysis; each state has adopted its own criteria, and in some 

cases, developed its own methodologies (Murray 1994). 

There is a trend toward use of GC techniques in analysis of soils and sediments. One aspect of these 

methods is that “volatiles” and “semivolatiles” are determined separately. The volatile or GRO 

components are recovered using purge-and-trap or other stripping techniques (Chang et al. 1992; EPA 

1995d; McDonald et al. 1984). Semivolatiles are separated from the solid matrix by solvent extraction 

(EPA 1995d). Other extraction techniques have been developed to reduce the hazards and the cost of 

solvent use and to automate the process (Gere et al. 1993). Techniques include supercritical fluid 

extraction (SFE) (Fitzpatrick and Tan 1993; Gere et al. 1993; Hawthorne et al. 1993; Lopez-Avila et al. 

1993) microwave extraction (Hasty and Revesz 1995; Lopez-Avila et al. 1994) Soxhlet extraction 

(Martin 1992) sonication extraction (Martin 1992) and solid phase extraction (SPE) (Schrynemeeckers 

1993). Capillary column techniques have largely replaced the use of packed columns for analysis, as they 

provide resolution of a greater number of hydrocarbon compounds. 

3.3.1.2 Water and Waste Water 

Methods for determining TPH in aqueous samples are discussed above in Section 3.3.1. The overall 

method includes sample collection and storage, extraction, and analysis steps. Sampling strategy is an 

important step in the overall process. Care must be taken to assure that the samples collected are 

representative of the environmental medium and that they are collected without contamination. There are 

numerous modifications of the EPA, American Public Health Association (APHA), and American 

Society for Testing and Materials (ASTM) methods discussed above. Most involve alternate extraction 

methods developed to improve overall method performance for TPH or replacement of the 

chlorofluorocarbon solvents. SPE techniques have been applied to water samples (Schrynemeeckers 

1993). Solvent extraction methods with hexane (Murray and Lockhart 1981; Picer and Picer 1993) or 

methylene chloride (Mushrush et al. 1994) have been reported as well. 
TOTAL PETROLEUM HYDROCARONS 34 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

3.3.1.3 Air 

Methods for determining hydrocarbons in air matrices usually depend upon adsorption of TPH 

components onto a solid sorbent, subsequent desorption and determination by GC techniques. 

Hydrocarbons within a specific boiling range (n-pentane through n-octane) in occupational air are 

collected on a sorbent tube, desorbed with solvent, and determined using GC/FID (NIOSH 1994). 

Although method precision and accuracy are good, performance is reduced at high humidity. 

Compounds in the boiling range 80-200 oC in ambient air may be captured on a Tenax GC adsorbent 

tube which is thermally desorbed for GC/MS analysis (EPA 1988). Performance of the method had 

not been established on a compound-by-compound basis (EPA 1988). Gasoline vapor in air may be 

sampled on a tube containing Tenax adsorbent. The traps are thermally desorbed and analyzed by 

GC/FID. The minimum detectable concentration is 0.03 mg/m3

 total hydrocarbons in a 2.5 L sample. 

Excellent recovery was reported (>90%) (CONCAWE 1986). Passive adsorbent monitors (badges) 

may also be used. Compounds are solvent-desorbed from the exposed adsorbent and analyzed by GC. 

Good recovery (>80%) has been reported for target n-alkanes and for gasoline, naphtha, and Stoddard 

solvent (3M 1993). 

The Massachusetts Department of Environmental Protection (MADEP), along with ENRS, Inc., of 

Acton, Massachusetts, has developed a method for taking and analyzing air samples for the presence 

of petroleum hydrocarbons (MADEP 1999). This Air-phase Petroleum Hydrocarbon (APH) method 

uses SUMMA canisters and GC/MS for sampling and analysis of ambient air, indoor air, and soil 

gas. This method can be downloaded from the MADEP website (http://www.state.ma.us/dep). The 

complex mixture of petroleum hydrocarbons potentially present in an air sample is separated into 

aliphatic and aromatic fractions, and then these two major fractions are separated into smaller 

fractions based on carbon number. Individual compounds (e.g., benzene, toluene, ethylbenzene, 

xylenes, MTBE, naphthalene) are also identified using this method. The range of compounds that can 

be identified includes C4 (1,3-butadiene) through C 12 (n-dodecane). 

Continuous monitoring systems for total hydrocarbons in ambient air are available. These usually 

involve flame ionization detection. Detection limits are approximately 0.16 ppm (Lodge 1988). 
TOTAL PETROLEUM HYDROCARONS 35 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

3.3.2 Biological Samples 

Few analytical methods were located for determination of TPH in biological samples. However, 

analytical methods for several important hydrocarbon components of total petroleum hydrocarbons 

may be found in the ATSDR toxicological profiles listed in Table 3-1. 

Some methods developed for analysis of aquatic and terrestrial life may be adaptable to human 

biological samples. Examples are summarized in Table 3-5. Most involve solvent extraction and 

saponification of lipids, followed by separation into aliphatic and aromatic fractions on adsorption 

columns. Hydrocarbon groups or target compounds are determined by GC/FID or GC/MS. These 

methods may not be suitable for all applications, so the analyst must verify the method performance 

prior to use. 

Methods are also available for determination of specific hydrocarbon compounds in biological 

samples. Some of these methods are shown in Table 3-5. Since these methods have not been demon- strated for 

total petroleum hydrocarbons, the analyst must verify that they are suitable prior to use. 

3.3.3 Adequacy of the Database 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation 

with the Administrator of EPA and agencies and programs of the Public Health Service) to assess 

whether adequate information on the health effects of TPH is available. Where adequate information 

is not available, ATSDR, in conjunction with the NTP, is required to assure the initiation of a program 

of research to determine the health effects (and techniques for developing methods to determine 

the health effects) of TPH. Since TPH is comprised of a number of component chemicals, these 

directives and requirements can be assumed to extend to the individual compounds that may be found 

as components of TPH. 

Health assessment of the risks associated with petroleum hydrocarbons from environmental media are 

difficult because of the complex nature of petroleum products, lack of adequate knowledge about the 

movement of petroleum components in soil, and lack of knowledge about the toxicity of the components 

(Heath et al. 1993a). Health assessors often select surrogate or reference compounds (or 

combinations of compounds) to represent TPH so that toxicity and environmental fate can be 

TOTAL PETROLEUM HYDROCARONS 37 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

evaluated. One approach is based on benzene as the most appropriate substitute for TPH based on its 

toxicity, motility in the environment, and solubility in ground water (Youngren et al. 1994). Other 

researchers have investigated the use of several surrogate compounds to represent the movement of 

TPH in the environment and TPH toxicity. Potential candidates are n-hexane, benzo(a)pyrene, and 

pyrene to represent alkanes, carcinogenic PAHs, and noncarcinogenic PAHs in gasoline, respectively. 

Benzene and toluene would be included for sites where the BTEX portion of gasoline is not analyzed 

separately (Koblis et al. 1993). 

Another approach is to categorize hydrocarbon compounds into surrogate fractions characterized by 

similar chemical and physical properties (EA Engineering 1995). Compounds are assigned to a given 

fraction on the basis of similar leaching and volatilization factors. Correlation to Carbon Number 

Index was used because it closely follows GC behavior. This method has the potential to provide 

realistic evaluation of potential risks; however, a full set of parameters is not available for all the 

compounds of interest (EA Engineering 1995). 

3.3.4 Ongoing Studies 

Governmental, industrial, and environmental groups have been attempting to understand the problems 

of environmental contamination with petroleum hydrocarbons. Major agencies, such as the International 

Agency for Research on Cancer (IARC) and the EPA are involved in the discussion of potential 

health effects. Some groups have been attempting to improve the analytical consistency and 

interpretation of results in dealing with petroleum hydrocarbons, and some have looked at the health 

and environmental effects of petroleum. The ASTM publishes consensus standards, including analytical 

methods. Committee D-19 of ASTM is concerned with the study of water and is responsible for 

the standardization of methods for sampling and analysis of water, aqueous wastes, water-formed 

deposits, and sediments. Committee D-2 on Petroleum Products and Lubricants is responsible for the 

ASTM Manual on Hydrocarbon Analysis (ASTM 1992). 

The Amherst annual conference continues to address issues surrounding petroleum contamination, 

including analytical methods (Amherst 1999). Though the TPHCWG has taken on specific 

responsibilities for TPH, further analytical developments will likely grow from this conference. 
TOTAL PETROLEUM HYDROCARONS 38 

3. IDENTITY AND ANALYSIS OF TOTAL PETROLEUM HYDROCARBONS 

In another ongoing effort, EPA is looking at the problem of petroleum wastes in all media. They have 

formed an internal working group and are supporting the efforts of other groups such as the Amherst 

Conference Workgroups and Workshop on General Population Exposures to Gasoline (Lioy 1992). 

Dr. R.J. Rando, Tulane University, is investigating the use of passive samplers for measuring 

hydrocarbon components. The overall goal of the program is to characterize and improve the 

performance of passive samplers for use in ambient and indoor air monitoring. 

Petroleum companies have conducted a number of studies regarding the health effects of TPH 

constituents and products that have not appeared in the open published literature (API 1995a). 
TOTAL PETROLEUM HYDROCARONS 39 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

This chapter summarizes useful background materials dealing with petroleum production and a range 

of common products derived from petroleum contaminants that could be documented through TPH 

testing at NPL sites. The chapter concludes with a discussion of acceptable disposal practices for 

petroleum products. In conjunction with materials in Chapter 5, the section on disposal summarizes 

special features of petroleum that set it apart from a variety of more highly processed petrochemicals. 

Under normal uses as fuels, lubricants, or paving materials, petroleum products are not considered 

hazardous materials. For instance, fuels are normally consumed through combustion processes to 

drive motors or provide space heating. Some combustion by-products (e.g., carbon monoxide) may 

be regarded as hazardous, but a variety of legal exemptions apply to the initial petroleum product, at 

least under federal law. 

The special status of petroleum under normal use means that limited attention is given to monitoring 

of petroleum levels in the workplace or the environment. It is usually only in the case of accidental 

spills, pipeline breaks, or seepage from storage tanks that well defined legal requirements are in place 

that require record keeping and documentation. As a result, it is usually hard to make precise 

connections between the original petroleum products and the types of TPH materials encountered at 

NPL sites. 

Especially at older dump sites, original petroleum product mixtures become even more complex 

mixtures. Over time, biotic and abiotic weathering processes alter the types of chemical fractions still 

present on-site. This means that even the most detailed knowledge of the various original petroleum 

products does not necessarily provide clear signals on the exposure risks affecting an NPL site with 

TPH contaminants. See Chapter 5 for discussion of environmental transport and potential human 

exposure. This chapter, therefore, highlights basic information relevant to the original petroleum 

products to provide a background for the discussion on environmental fate and transport issues in the 

next chapter. 

Background on Primary Petroleum Products. Petroleum is a natural resource found in 

many types of sedimentary rock formations. Naturally occurring petroleum is a complex mixture of 

gaseous, liquid, and solid hydrocarbons. Entire industries have grown up around the activities 
TOTAL PETROLEUM HYDROCARONS 40 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

required to produce the crude oil, transport it to refineries, and convert the natural petroleum into a 

variety of end products and chemical feedstocks. Processed petroleum products provide up to 50% of 

the world’s total energy supply, major forms of transportation, electric utilities, and space heating. 

Petroleum is also used in lubricants, solvents, highway surfacing, and roofing and waterproofing 

materials, and as the source of the feedstocks used to make plastics and other modern petrochemicals. 

Early refining techniques relied primarily on the separation of different fractions from the raw 

petroleum using distillation over different temperature ranges. For straight-chain, branched, and 

aromatic hydrocarbons, there is some degree of correlation between the number of carbon atoms in a 

compound and the boiling point. Many refined products were initially given simple technical 

definitions based on the temperature range at which a certain fraction was extracted from the crude 

oil. The very lightest fractions (e.g., C4H10 or butane and other simple straight-chain compounds 

down through CH4 or methane) were traditionally vented or flared since there was little apparent 

demand for these gaseous components. The most prized fractions were liquids at normal room 

temperatures that could be used as fuels in engines or as heating oils. 

The petroleum refining industry has tried to find profitable uses for both the lighter and heavier crude 

oil fractions. Lighter gaseous fractions can now be used for space heating or fuels in the form of 

liquified petroleum gas (LPG). For the heavier fractions, a variety of technologies convert large 

hydrocarbon molecules from the distilled crude oil into lighter compounds that can be used as motor 

gasoline, aviation fuel, or fuel oil. In the process, large amounts of hydrocarbons are produced that 

can be isolated as relatively pure substances for use as solvents or petrochemical feedstocks. For 

instance, benzene was once derived from coal tars, but most supplies are now derived from oil. 

Ethane is easily converted into ethylene, a major petrochemical feedstock. Commercial techniques for 

producing xylenes, toluene, butadiene, butylenes, and propylene also involve simple adaptations of 

modern oil refinery technologies. 

Some specific refinery-generated hydrocarbons are blended into gasolines or fuel oils to enhance some 

desired property. For example, commercially pure grades of toluene and benzene are added to 

modern gasoline to boost octane ratings. Similar enhancements in basic product qualities for 

combustion or viscosity are achieved through re-distilling products from the cracking process and 

blending them with fractions obtained from primary distillation. While the resulting products are still 
TOTAL PETROLEUM HYDROCARONS 41 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

referred to as gasolines or fuel oils, the chemistry of the hydrocarbons in these mixtures often differs 

considerably from that of the hydrocarbons found in the original crude oil. 

Refining also dramatically increases the frequency of hydrocarbons in which carbon-hydrogen bonds 

have been replaced with double bonds between carbon atoms. The resultant chemicals are called 

olefins and include ethylene (C2H4), propylene (C3H6), and butylene (C4H8). While the lighter forms 

such as ethylene are relatively easy to remove for use as petrochemical feedstocks, a variety of 

heavier olefins wind up in the refinery gasoline or fuel oil products. 

In addition to aromatics with benzene ring structures, modern refinery processes tend to increase the 

number of hydrocarbons with simpler types of carbon ring structures. Typical chemicals include 

cyclopentane, where the straight-chain pentane has been wrapped into a five-carbon ring. Other 

transformations of aliphatic hydrocarbons include cylcohexane and cyclopentane. These ring 

compounds are usually called naphthenes. 

These complex alterations in the types of compounds generated from refinery operations have led to 

the development of a variety of technical nomenclatures to describe different petroleum fractions. 

Many commercial products still carry such traditional names as gasoline or heating oil. In terms of 

such basic physical and chemical properties as specific gravities and combustion performance, these 

traditional labels have held their meanings fairly well. New products, such as fuel oils derived from 

residuals, now join the original fuel oils derived from simple distillation, but the term “fuel oil” is still 

commonly used to organize data on petroleum imports, exports, and production. But the chemistry of 

these modern products is often considerably more complex than the chemistry of pre-World War II 

products with the same names. 

Petroleum Production, Import/Export, and Use in the United States. 

Petroleum Production and Use Statistics. Petroleum use and production statistics pooled from a 

variety of government and industry sources are available from the PennWell Publishing Company. A 

convenient printed compendium (also available on computer disk in a digitized form) is the Energy 

Statistics Sourcebook (PennWell 1994). 
TOTAL PETROLEUM HYDROCARONS 42 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

During 1997, total U.S. crude oil production was 2,300,000,000 barrels (API 1998a). Using 

consistent estimation methods comparable to those employed over the last decade, it is often difficult 

to match current petroleum product statistics with historical statistics developed prior to 1978. For 

1978, total U.S. crude production was 3,178,216,000 barrels. This represents a 27.6% decline in 

total production between 1978 and 1998. While total crude oil production in the United States has 

shown an overall downward trend, a comparison of statistics from 1993 and 1978 indicates that the 

total output from refineries based in the United States has remained remarkably constant. Table 4-l 

summarizes total refinery output along with output estimates for major refinery petroleum products. 

Output for specific refinery products has changed: jet fuel kerosenes and LPG have increased, and 

fuel oils recovered from heavier refinery residuals and ordinary kerosene have decreased. Crude oil 

production levels and trends for selected states are summarized in Table 4-2. 

Statistics on crude oil production or its processing into various petroleum fractions are generally 

presented using a standard barrel (42 U.S. gallons) as the basis of comparison. The barrel is still an 

international standard for crude oil statistics. While adjustments can be made for particular types of 

crude oil related to variations in their specific gravities (e.g., light oils versus heavy oils), 7.3 barrels 

of crude oil equal approximately 1 metric ton (1,000 kg or 2,204.6 pounds). Conversion factors are 

also available to make estimates of the barrel equivalents of other common petroleum products 

ranging from to liquified petroleum gas (LPG). Conversion factors for major petroleum fractions are 

given in Table 4-3. 

Although crude oil production is the source of TPH exposures to certain occupational groups and 

people living near oil production sites, the releases in workplaces or to environmental media of more 

concern for this profile begin during the stage when crude oil is refined and transformed into a variety 

of petroleum products for fuels, lubricants, and petrochemical feedstocks. 

In addition to the total production figures, percentage breakouts provide another way to summarize 

the major products stemming from U.S. based refineries. Table 4-4 presents 1993 product yields on a 

percentage basis. 




TOTAL PETROLEUM HYDROCARONS 47 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

With a long-term decline in the levels of domestic crude oil production, imports have increased to 

meet the demand for petroleum products and to sustain the fairly stable levels of U.S.-based refinery 

output. Tables 4-5, 4-6, and 4-7 summarize trends in petroleum product imports, exports, and levels 

of U.S. demand (use) for these products. 

For the most common refinery products, statistics are available showing U.S. use patterns for sectors 

such as major industrial groups or residential demand. These statistics are presented in Table 4-8. 

Disposal. An estimated 2.3 billion barrels of crude oil were produced in 1997 (API 1998a). From 

this crude oil, TPH waste may be generated in a number of ways that ultimately lead to either 

improper or acceptable disposal. Incineration is a primary method of disposal for wastes containing 

TPH. Oil spills are frequently captured and treated using various absorbents (e.g., straw, 

polyurethane foam, activated carbon, peat), gelling agents, dispersants, and mechanical systems. 

Biodegradation also has been used to treat contaminated soil (OHM/TADS 1985). 

Sources of TPH waste include 

•	 waste generated from crude oil production, 

•	 waste generated from petroleum refining, 

•	 used oil as a waste, 

•	 used petroleum refining products as wastes, and 

•	 accidental releases of crude oil, petroleum refining wastes, used oil, and petroleum refining 

products. 

Management of TPH wastes generated from the sources listed is discussed in the following sections, 

which address existing regulatory programs, quantities disposed (where data are available), waste 

management trends, recycling trends, and records of damage for each source. 

Waste Generated from Crude Oil Production. EPA’s Report to Congress, Management of Wastes 

from the Exploration, Development, and Production of Crude Oil, Natural Gas, and Geothermal 

Energy (EPA 1987a), reported that the American Petroleum Institute estimated that 361 million 

barrels of waste were generated from the drilling of 69,734 oil wells in 1985. This translates into 

about 5,183 barrels of waste per well. These wastes are not pure crude but can include petroleum 

hydrocarbons. 




TOTAL PETROLEUM HYDROCARONS 52 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Wastes include drilling fluids and produced waters which are managed in pits, discharged to surface 

waters, or injected into the producing well or an aquifer (Charbeneau et al. 1995). Records of damage 

due to both improper and acceptable management of these wastes reflects the presence of constituents of 

concern found in crude oil such as benzene, phenanthrene, lead, and barium. Numerous damage cases 

are cited in this Report to Congress, including an estimated 425 reported spills on the North Slope of 

Alaska in 1986. 

Current regulatory programs applicable to these wastes include a variety of state programs, the 

Underground Injection Control Program established under the Safe Drinking Water Act Part C (Class II 

wells are oil and gas-related), and the Bureau of Land Management regulations for the activities on 

federal and Indian lands. 

Wastes Generated from Petroleum Refining. Petroleum refining wastes are regulated by EPA in 

several ways. There are approximately 150 active petroleum refineries in the United States. RCRA 

Subtitle C currently lists four characteristics as hazardous in 40 CFR 264.21 and .24 and five waste 

categories as hazardous in 40 CFR 261.31 and .32. When most of these wastes were listed beginning in 

1980, there were 250-300 active refineries ranging in capacity from about 400,000 barrels (bbl) per day to 

only a few hundred bbl per day. 

In addition, petroleum refining wastes are subject to evaluation as characteristically hazardous waste, 

including the toxicity characteristic (40 CFR 261, Subpart C) which labels wastes “RCRA hazardous” if a 

measured constituent concentration exceeds a designated maximum (e.g., a benzene concentration of 0.5 

mg/L ) 

All Subtitle C hazardous wastes are prohibited from land disposal without prior demonstration that 

hazardous constituent concentration levels comply with regulatory limits or that prescribed methods of 

treatment are used. These two criteria are intended to reduce the toxicity of the waste or-substantially 

reduce the likelihood of migration of hazardous constituents from the waste, so that health and 

environmental threats are minimized. The primary method of treatment is waste combustion to destroy 

organic constituents. 
TOTAL PETROLEUM HYDROCARONS 53 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

RCRA-classified listed hazardous wastes are also hazardous substances under the Comprehensive 

Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), as amended. 

CERCLA hazardous substances are listed in 40 CFR 302.4 and have unique reportable quantities 

(RQs) which, when released, trigger emergency response and reporting measures. 

Oil generated and recovered during petroleum refining has also been excluded from RCRA regulation. 

In 1994, EPA limited the exclusion to recovered oil from refining, exploration, and production that is 

inserted into the petroleum refining process prior to distillation and catalytic cracking. Recovered oil 

includes materials that are primarily oil and that are recovered from any phase of petroleum 

exploration, refining production, and transportation. It is considered by EPA to be equivalent to the 

raw materials normally used in refining in composition and management. In November 1995, EPA 

proposed to expand this exclusion to encompass all oil-bearing secondary materials that are generated 

within the petroleum refining industry and that are reinserted into the refining process (including 

distillation, cracking, fractionation, or thermal cracking). 

Used Oil as a Waste. “Used oil means any oil that has been refined from crude oil, that has been 

used and as a result of such use is contaminated by physical or chemical impurities” (40 CFR 

260.10). In 1992, there were approximately 700,000 commercial, industrial, and large farm used oil 

generators in the United States. The management of used oil has a statutory, regulatory, and judicial 

history dating back to 1978. Currently, used oil exhibiting any hazardous waste characteristics must 

be managed under RCRA Subtitle C as a hazardous waste. In turn, used oils contaminated with 

CERCLA hazardous substances are subject to RQs under 40 CFR 302.4. Disposal of nonhazardous 

used oil that is not recycled is regulated under 40 CFR 257 and 258 of RCRA Subtitle D. The 

recycling of all used oils is regulated under 40 CFR 279. These regulations include programs for 

generators, collection centers, transporters and transfer facilities, processors and re-refiners, burners, 

and marketers. An estimated 750 million gallons per year of used oil enter the commercial used oil 

recycling system according to EPA. In 1992, these recycling businesses consisted of independent 

collectors (383), minor processors (70), major processors (112), re-refiners (4), fuel oil dealers 

(25-100) and burners (1,155). Products of used oil processing and re-refining include specification 

fuel, reconstituted lubricating oils and fluids, distillate fuel, lube feedstock, asphaltic bottoms, and 

other non-fuel oil-derived products. Part 279 prohibits used oil use as a dust suppressant unless a 

state successfully petitions for authority to allow its use as a suppressant. As of 1992, 41 of 50 
TOTAL PETROLEUM HYDROCARONS 54 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

states prohibited road oiling. No regulations exist for individuals who generate used oil through home 

or personal use of oil products. 

Used Petroleum Refining Products as Wastes. Government regulations presume that petroleum 

refining products are consumed and not disposed. Therefore, there are no regulatory programs 

designed for the intentional disposal of petroleum products. However, RCRA can apply to disposed 

petroleum products. These products can be declared solid wastes and, possibly, hazardous waste as 

defined under 40 CFR 261. The only exemption from the definition of solid waste for petroleum 

products is when the material is recycled. There are no exemptions from the definition of hazardous 

waste for petroleum products declared to be wastes. Used oil, in particular, has a specific RCRA 

regulatory program, as described above. 

Petroleum products such as gasoline contain certain hazardous constituents including benzene, 

toluene, and xylene. However, the presence of such constituents in gasoline does not qualify it as a 

hazardous waste under RCRA or a hazardous substance under CERCLA. The management of 

petroleum products is, however, regulated under three programs: Underground Storage Tanks (UST) 

(40 CFR Part 280) to prevent tank leakage, Hazardous Materials Transportation (HMT) (49 CFR 

Chapter 1) for petroleum distillates with combustible and flammable properties, and the Occupational 

Safety and Health standards (29 CFR Part 1910.1000) for inhalation hazard. The UST and HMT 

programs are designed to prevent and respond to accidental releases of petroleum products. Both 

programs are discussed in the next section. 

Accidental Releases of Crude Oil, Petroleum Refining Wastes, Used Oil, and Petroleum Refining 

Products 

Oil Production Wastes. Numerous damage cases are cited in the 1987 EPA Report to Congress, 

including the estimated 425 reported spills on the North Slope of Alaska in 1986. However, EPA did 

not believe the impact of these releases warranted regulating these oil production wastes as RCRA 

hazardous. Rather, they are regulated under state programs. 

Petroleum Refining Waste. The extent of mismanagement or accidental releases of petroleum 

refining wastes can be illustrated with the 1995 proposed RCRA listing determination for 16 
TOTAL PETROLEUM HYDROCARONS 55 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

additional petroleum refining waste categories (of which 3 waste categories were determined to be 

RCRA hazardous and proposed to be listed in 40 CFR 261). A search of state and federal 

enforcement records, documented CERCLA-related activities at 10 sites and RCRA-related activities 

at 29 sites. 

Accidental releases of RCRA-listed petroleum refining wastes are regulated in two ways. First, as 

part of the RCRA program, treatment storage and disposal facilities (TSDFs) that manage hazardous 

refinery wastes must obtain permits. A key component of the permit application is demonstration of 

an effective contingency plan for accidental releases, a preparedness/prevention plan, and a 

groundwater monitoring plan when wastes are managed in land-based units among other activities. 

Second, these wastes are also subject to the reportable quantity (RQ) requirements of CERCLA. 

Used Oil and Other Waste Petroleum Refining Products. Used oil and other petroleum product 

mismanagement and related risks are controlled under other regulations and statutes; these include the 

40 CFR Part 268 underground storage tank (UST) regulations, the 40 CFR Part 112 Spill Prevention, 

Control and Countermeasure (SPCC) program, the National Pollutant Discharge Elimination System 

(NPDES) storm water regulations, and the lead phase-down program. Section 311 of the Clean 

Water Act requires facilities to have an SPCC plan or contingency plan in place to ensure that oil 

spills are prevented, controlled via containment measures, and responded to when oil spills occur and 

reach navigable waterways. About 50% or more of the used oil generators, and most of the used oil 

transporters, processors/re-refiners, and off-spec used oil burners are covered by the SPCC program. 

Less than 10% of the used oil industry participants are excluded from the SPCC program because 

they are not in the vicinity of navigable waterways. The program includes non-transportation-related 

facilities located in proximity to navigable waters, USTs with capacities greater than 42,000 gallons, 

aboveground storage tanks with capacities greater than 1,320 gallons, and single tanks with capacities 

greater than 660 gallons. 

The International Convention for the Prevention of Pollution from Ships (1973) as modified by the 

1978 Protocol (MARPOL) focuses on preventing ship-generated ocean pollution. Annexes I-V of the 

MARPOL protocol address oil, noxious liquids, and other petroleum-related contaminants (MARPOL 

1978). 
TOTAL PETROLEUM HYDROCARONS 56 

4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

The Hazardous Materials Transportation Act regulates used oil and petroleum distillates if they meet 

the definitions of “flammable” or “combustible.” All used oil generators and transporters must 

comply with applicable Department of Transportation regulations for hazardous materials (49 CFR, 

Chapter I - Research and Special Programs Administration). 

The Toxic Substances Control Act (TSCA) prohibits the use of waste oil containing any detectable 

polychlorinated biphenyls (PCBs) as a sealant, coating or dust suppressant. Any spill of material 

containing >50 ppm PCBs into the sewer, drinking water, surface water, grazing land, or vegetable 

gardens must be reported (40 CFR 761). 

The UST program (40 CFR Part 280) focuses on control and prevention of petroleum leaks from 

underground petroleum storage tanks including petroleum products and waste oil tanks. The 

regulations currently exempt UST systems less than 110 gallons in capacity, machinery containing 

substances regulated under the UST program, farm or residential tanks less than 1,100 gallons in 

capacity, heating oil tanks where the heating oil is used on the premises, and flow-through process 

tanks, among others. 
TOTAL PETROLEUM HYDROCARONS 57 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.1 OVERVIEW 

Petroleum products are an integral part of our modern lives. It is nearly impossible to avoid exposure 

to hydrocarbons from petroleum products, whether it is from gasoline fumes at the pump, spilled 

crankcase oil on asphalt, solvents used at home or work, or pesticide applications that use petroleum 

products as carriers. There are concerns with both short-term (accidents) and long-term exposures to 

petroleum hydrocarbons (e.g., contaminated drinking water). Gross measures of Total Petroleum 

Hydrocarbons (TPH) in soil or water are not particularly valuable for assessing either the potential 

for exposure to TPH or the impacts of such exposure on public health. This chapter addresses 

questions related to the first point: what are the levels of contamination in the environment, what 

happens to petroleum hydrocarbons in the environment, and what is the likelihood that individuals or 

populations will be exposed to petroleum hydrocarbons at levels thought to be of concern? 

Petroleum products are released to the environment through accidents, as managed releases, or as 

unintended by-products of industrial, commercial or private actions. An understanding of the changes 

that occur over time in the composition of petroleum hydrocarbons found in soil, water, or air is 

extremely important in addressing public health issues for TPH. The TPH Criteria Working Group 

(TPHCWG 1997b) has defined its TPH fractions by the mobility of constituents in order to address 

this question of predicting risks associated with TPH contamination. 

The following sections present an overview of releases to the environment (5.2), fate and transport 

(5.3), and levels found in the environment (5.4). 

5.2 RELEASES TO THE ENVIRONMENT 

TPH has been identified in 34 of the 1,519 current or former EPA National Priorities List (NPL) 

hazardous waste sites (ATSDR 1998a). Components of TPH are common environmental contaminants 

in all media and are likely contaminants at many NPL sites. However, the number of sites 

evaluated for TPH and TPH components is not known. The frequency of the TPH reported sites 

within the United States can be seen in Figure 5- 1. 

TOTAL PETROLEUM HYDROCARONS 59 

5. POTENTIAL FOR HUMAN EXPOSURE 

Raw petroleum and refined petroleum products used as fuels or lubricants are generally excluded at 

the national level from the cradle-to-grave record-keeping associated with recognized toxics such as 

heavy metals or chlorinated solvents. With an eye to the availability of petroleum as a source of 

energy, petroleum production is tracked by the federal government as well as industry trade 

associations. Statistics are available for wellhead production as well as for production of major bulk 

fuel types from domestic refineries. These primary production statistics have been summarized in 

Chapter 4. 

Once processed into products such as motor gasoline and fuel oil, most of the petroleum is burned in 

engines or boilers to provide energy for transportation, space heating, or electricity. In these 

combustion processes, the petroleum fuel is oxidized. Because of incomplete oxidation, small 

amounts of hydrocarbon emissions result. These emissions often contain much larger percentages of 

combustion by-products such as polycyclic aromatic hydrocarbons (PAHs) than the initial petroleum 

products. Incomplete combustion and heat also alter the composition of crank case oils and 

lubricants. 

Emissions statistics are usually lacking for TPH or most TPH fractions since there is no record­

 keeping associated with smaller internal combustion engines used in cars and trucks or fuel oil boilers 

for individual buildings or homes. These individual uses account for the majority of petroleum 

product use. These releases, mostly to the atmosphere from incomplete combustion, however, are 

generally small compared to a variety of other releases connected with spills or uncontrollable losses 

during storage, transport, or fueling operations. 

The movement of raw petroleum to automobile fuel tanks or fuel oil boilers is part of a complex bulk 

product distribution and storage system, providing many opportunities for accidents, spills, leaks, and 

losses from simple volatilization. Consistent national statistics are lacking for many stages in the 

overall oil distribution and storage system. The main exceptions involve larger leaks and spills, 

especially spills in coastal areas or on larger navigable rivers. 

Data for the period from 1984 through 1993 (API 1996) show that most data reported to the U.S. 

Coast Guard occurred in inland bodies of water: rivers, lakes, and points on bays or estuaries. Spills 

from large ocean-going tankers and large spills in general (more than 1,000 gallons) are relatively 
TOTAL PETROLEUM HYDROCARONS 60 

5. POTENTIAL FOR HUMAN EXPOSURE 

infrequent, never more than 5% of the total number of reported spills in a year. The average number 

of spills during the 1984-93 period was just under 6,000 spills. The numbers in any given year can 

vary enormously, with a maximum of just under 9,600 spills reported in 1991. 

In terms of the amounts of oil estimated from spills, large spills, although rare, can dominate the 

annual totals. For instance, of about 14,000,000 total estimated gallons of oil spilled to U.S. waters 

in 1989, 10.8 million gallons resulted from the Exxon Valdez catastrophe in the coastal waters of 

Alaska. One or two large tanker spills in the course of a decade can make it very hard to draw 

conclusions on trends. The average amount of oil spilled in the 5-year period from 1984 to 1988 was 

6.3 million gallons per year, compared to 5.6 million gallons spilled from 1989 to 1993. With 

eventual implementation of double-hull requirements for large tankers required in the Oil Pollution 

Act of 1990, the releases from tankers should be greatly curtailed. 

Within the broad reporting categories of vessels (tankers and barges) and facilities (pipelines, tanks 

batteries, and other onshore facilities) in the period 1984-1993, numbers of reported spill incidents 

were roughly equivalent: 42,000 incidents from vessels and 38,000 from facilities. Over this period, 

the vessels spilled a much larger cumulative amount of oil: 45 million gallons from vessels versus 

15 million gallons for facilities. Major incidents can dominate these totals. Two vessel spills account 

for around one-third of the vessel totals. 

Most spills involve either crude oil or bulk fuels (distillates) such as fuel oils. Four tables (adapted 

from API 1996) help summarize annual figures on oil spills to coastal and inland waters of the United 

States. Table 5-l shows statistics on the number of spills broken out by size categories, where the 

prevalence of very small releases is obvious. Table 5-2 summarizes releases from vessels, and 

Table 5-3 summarizes releases from facilities. Table 5-4 summarizes spills according to the type of 

petroleum product involved. 

At the national level, virtually the only other regulatory program that provides broad-based statistics 

on petroleum product releases to the environment is EPA’s (leaking) Underground Storage Tank 

(UST) Program. In 1994, there were over a million underground storage tanks on more than 300,000 

identified UST sites; about 91% of these involve tanks at gasoline stations, truck stops, vehicle repair 

shops, or convenience stores selling gasoline or diesel fuel (EPA 1998c). There were at least 




TOTAL PETROLEUM HYDROCARONS 65 

5. POTENTIAL FOR HUMAN EXPOSURE 

119,000 confirmed instances of underground releases of gasoline or similar petroleum bulk fuels to 

soils or groundwater, with the total number of sites needing remediation likely to climb to over 

176,000 by the turn of the century (EPA 1994a). While tests to confirm contamination may involve 

TPH or tests for surrogates of specific chemicals such as benzene, the UST program does not attempt 

to make detailed estimates of releases to environmental media. 

Since many releases of petroleum to environmental media involve unintentional leakage or spillage, it 

can be helpful to present some rough estimates of release from various categories of activities or 

components within the overall petroleum production and distribution system. Results assembled from 

various sources in a study by Doyle (1994) are summarized in Table 5-5. While different estimation 

techniques could alter these leakage values, the major components of the oil production and 

distribution system include: leaking (abandoned) oil wells, large aboveground storage tanks, leaks 

from gasoline stations, tank bottoms and refinery residuals disposal, used motor oil, and evaporative 

losses. 

Doyle (1994) estimates the total amount of leakage or spillage related to petroleum product 

production, processing, and distribution to end users at around 134 million barrels per year (see 

Table 5-5); different estimation approaches could lead to slightly different total figures. For instance, 

total U.S. refinery output in 1993 was around 2,608 million gallons (PennWell 1994); total 

consumption of motor gasoline during 1992 was around 5,762 million barrels (PennWell 1994). The 

levels of spillage or leakage resulting in releases to the environment amount to about 2.3% of total 

refinery output and around 5% of total gasoline consumed; conversely, about 95% of the original 

amounts petroleum products are completely consumed, generally in combustion processes to heat 

homes or power cars, trucks, planes, boats, and trains. 

Recurrent spills or a long history of disposal at specific sites can lead to concerns. Oil dumped onto 

soils can saturate the soil matrix (see Section 5.3). This type of very concentrated contamination can 

be virtually impossible to eliminate without excavating and removing all the soil materials. 

If TPH is introduced at any depth within the soil matrix, as in the case of leaks from underground 

storage tanks, natural weather and biodegradation processes are rendered less effective and the 

chances are increased that some of the TPH fractions may contaminate groundwater. Since many 

TOTAL PETROLEUM HYDROCARONS 67 

5. POTENTIAL FOR HUMAN EXPOSURE 

TPH components have densities less than or close to that of water, these lighter nonaqueous phase 

liquids (LNAPLs) generally pose less potential for groundwater pollution than most chlorinated 

solvents (e.g., PCBs or TCE) that are denser than water (denser nonaqueous phase liquids 

[DNAPLs]). The nonaqueous phase liquid refers to liquids that are immiscible in water. Still, there 

are risks for shallow groundwater supplies, which may be used for private wells for drinking water 

purposes. 

For surface water, the relatively low density of many petroleum fractions can pose some major shortterm concerns, especially for fish and wildlife. Many petroleum fractions float in water and form thin 

surface films (Jordan and Payne 1980; Mackay 1984). Gasoline, diesel, or other common fuel oils 

when spilled to water quickly spread out into a film 0.1 millimeter or less in thickness. This means 

that a very small amount of oil can create a film over a very large area of water surface. While 

natural physical and biological weathering processes will dissipate or degrade such oil slicks in time 

frames ranging from days to a few weeks, there is considerable short-term opportunity for damage to 

water fowl, aquatic mammals, fish, and other aquatic organisms. For inland waters, large oil spills 

may force shutdowns in surface water withdrawals for public drinking water supplies until the 

surface slicks have dissipated (Clark et al. 1990). Where the spilled petroleum washes up onto 

beaches or shorelines, there may be short-term damage to fish and wildlife as well as impacts to 

recreational use of shoreline or riparian areas for human swimming or fishing. 

Some heavier petroleum fractions, including the chemicals called PAHs found in motor oils or as byproducts 

of combustion, show neutral buoyancy or may be heavier than water. Such components can 

accumulate in substrates. This can lead to stresses for benthic organisms, shellfish, or bottom feeding 

fish. PAHs or “tarballs” formed when lighter oil fractions combine with suspended sediment or algae 

can have a serious impact on a water body’s use for commercial fishing or shellfishing and its value 

for recreational swimming or sports fishing. 

In addition to releases from the various components or activities that make up the production and 

distribution system for petroleum products (the oil system), many older waste sites show TPH-related 

site contamination. Comprehensive Environmental Response, Compensation, and Liability Act 

(CERCLA) site descriptions often mention petroleum, oil and grease, or petroleum, oil, and lubricants 

(POL) as present at a former waste disposal site. An example is given below for a waste oil recycling 

site, where TPH-type chemicals were obviously a common site contaminant. The CERCLA clean-up 

actions, however, focus on a range of specific hazardous or toxic chemicals. Some of the specific 

chemicals (e.g., toluene) would show up in a TPH test, but the chlorinated solvents and metals do not. 
TOTAL PETROLEUM HYDROCARONS 68 

5. POTENTIAL FOR HUMAN EXPOSURE 

Since a site cannot be prioritized for CERCLA attention if the only problem involves TPH site 

contamination, CERCLA actions are often triggered by the presence of other site contaminants that 

can clearly be ranked as hazardous or toxic. The long-term clean-up actions may entail remediation 

steps that reduce or eliminate the TPH concerns, but these actions are secondary results of the cleanup 

activities. 

This oil exemption aspect of CERCLA introduces complications when trying to present summary data 

on the distribution of NPL sites showing TPH site contamination. The ATSDR HazDat database 

contains only 34 records dealing explicitly with TPH at current or former NPL sites (ATSDR 1998a). 

While CERCLA deals with former waste disposal sites, the RCRA program handles active waste 

disposal facilities. Many waste facilities still in use have older sites (management units) within them 

that may need corrective actions similar to those encountered at CERCLA NPL sites. At least 5,100 

RCRA hazardous waste treatment, storage, and disposal facilities (TSDFs) may need some corrective 

actions before they can be shut down (EPA 1994b). While there are no readily available statistics, 

many of these RCRA facilities needing corrective actions also contain waste oils (EPA 1994b). As 

with CERCLA, RCRA works with what amounts to a hazardous waste exclusion clause for ordinary 

petroleum products. Most clean-up efforts, therefore, focus on legally defined toxics and hazardous 

materials as the main line of attack in site remediation, with the expectation that these measures will 

also help ameliorate any TPH-related concerns. 

5.3 FATE AND TRANSPORT 

5.3.1 Overview 

Chemical analysis for all individual compounds in a petroleum bulk product released to the 

environment is generally unrealistic due to the complexity of these mixtures and the laboratory 

expense. Determining the chemical composition of a petroleum release is further complicated by 

hydrodynamic, abiotic, and biotic processes that act on the release to change the chemical character. 

The longer the release is exposed to the environment, the greater the change in chemical character and 

the harder it is to obtain accurate analytical results reflecting the identity of the release. After 

extensive weathering, detailed knowledge of the original bulk product is often less valuable than 

current site-specific information on a more focused set of hydrocarbon components, for example TPH 

fractions. 
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5. POTENTIAL FOR HUMAN EXPOSURE 

Health assessment efforts are frequently frustrated by three primary problems: (1) the inability to 

identify and quantify the individual compounds released to the environment as a consequence of a 

petroleum spill; (2) the lack of information characterizing the fate of the individual compounds in 

petroleum mixtures; and (3) the lack of specific health guidance values for the majority of chemicals 

present in petroleum products. To define the public health implications associated with exposure to 

petroleum hydrocarbons, it is necessary to have a basic understanding of petroleum properties, 

compositions, and the physical, chemical, biological, and toxicological properties of the compounds 

most often identified as the key chemicals of concern. 

5.3.2 Fate and Transport Processes 

This section describes important chemical, physical, and biological processes that affect the behavior 

of hydrocarbon compounds in the environment. This information may be used to identify the 

environmental media that are likely to be affected by a release and to predict the potential for 

subsequent human exposure. 

5.3.2.1 Bulk Oil Migration 

Petroleum products released to the environment migrate through soil via two general pathways: (1) as 

bulk oil flow infiltrating the soil under the forces of gravity and capillary action, and (2) as individual 

compounds separating from the bulk petroleum mixture and dissolving in air or water. When bulk oil 

flow occurs, it results in little or no separation of the individual compounds from the product mixture 

and the infiltration rate is usually fast relative to the dissolution rate (Eastcott et al. 1989). Many 

compounds that are insoluble and immobile in water are soluble in bulk oil and will migrate along 

with the bulk oil flow. Factors affecting the rate of bulk oil infiltration include soil moisture content, 

vegetation, terrain, climate, rate of release (e.g., catastrophic versus slow leakage), soil particle size 

(e.g., sand versus clay), and oil viscosity (e.g., gasoline versus motor oil). 

As bulk oil migrates through the soil column, a small amount of the product mass is retained by soil 

particles. The bulk product retained by the soil particles is known as “residual saturation.” 

Depending upon the persistence of the bulk oil, residual saturation can potentially reside in the soil 

for years (Dragun 1988). Residual saturation is important as it determines the degree of soil 

contamination and can act as a continuing source of contamination for individual compounds to 

separate from the bulk product and migrate independently in air or groundwater (Bauman 1988). If 
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5. POTENTIAL FOR HUMAN EXPOSURE 

the release is persistent in the environment, there can be impacts to extensive areas as the individual 

compounds continue to separate and migrate away from the spill area via air or groundwater. 

When the amount of product released to the environment is small relative to the volume of available 

soil, all of the product is converted to residual saturation and downward migration of the bulk product 

usually ceases prior to affecting groundwater resources. Adverse impacts to groundwater may still 

occur if rain water infiltrates through soil containing residual saturation and initiates the downward 

migration of individual compounds. 

When the amount of product released is large relative to the volume of available soil, the downward 

migration of bulk product ceases as water-saturated pore spaces are encountered. If the density of the 

bulk product is less than that of water, the product tends to “float” along the interface between the 

water saturated and unsaturated zones and spread horizontally in a pancake-like layer, usually in the 

direction of groundwater flow. Almost all motor and heating oils are less dense than water (Knox 

1993; Mackay 1988) and are referred to as LNAPLs. 

If the density of the bulk product is greater than that of water, the product will continue to migrate 

downward through the water table aquifer under the continued influence of gravity. Downward 

migration ceases when the product is converted to residual saturation or when an impermeable surface 

is encountered. Polychlorinated biphenyls and other chlorinated organic solvents are usually denser 

than water and are characterized as DNAPLs. 

In reality, bulk oil flow is affected by numerous product-specific and site-specific factors. As a 

consequence, product distribution in the subsurface can be quite complex. 

5.3.2.2 Compound Migration 

As the bulk product migrates through the soil column, individual compounds may separate from the 

mixture and migrate independently. Chemical transport properties such as volatility, solubility, and 

sorption potential are often used to evaluate and predict which compounds will likely separate from 

the mixture. 

Volatility. Volatility is defined as the propensity of a chemical to partition to air and migrate as a 

vapor. It is primarily a function of the vapor pressure of the compound. Vapor pressure is defined as 

the pressure of a chemical exerted by its vapor when in equilibrium with the solid or liquid form of 
TOTAL PETROLEUM HYDROCARONS 71 

5. POTENTIAL FOR HUMAN EXPOSURE 

that chemical. For example, if a chemical in a liquid form is placed in a closed container, molecules
 

of the chemical that possess relatively high kinetic energy will migrate to the surface of the liquid and
 

evaporate into the air space in the container.
 

Since petroleum products are complex mixtures of hundreds of compounds, the compounds
 

characterized by relatively high vapor pressures tend to volatilize and enter the vapor phase. The
 

exact composition of these vapors depends on the composition of the original product. Using gasoline
 

as an example, compounds such as butane, propane, benzene, toluene, ethylbenzene and xylene are
 

preferentially volatilized (Bauman 1988). Because volatility represents transfer of the compound
 

from the product or liquid phase to the air phase, it is expected that the concentration of that
 

compound in the product or liquid phase will decrease as the concentration in the air phase increases.
 

In general, compounds having a vapor pressure in excess of 10-2 mm Hg are more likely to be present
 

in the air phase than in the liquid phase. Compounds characterized by vapor pressures less than
 

10-7 mm Hg are more likely to be associated with the liquid phase. Compounds possessing vapor
 

pressures that are less than 10-2 mm Hg, but greater than 10-7 mm Hg, will have a tendency to exist in
 

both the air and the liquid phases (Knox 1993).
 

Although volatility is a function of vapor pressure, environmental factors affect the rate of
 

volatilization. For example, high summer temperatures enhance volatilization, particularly when soils
 

begin to dry out. The rate of volatilization is also a function of air and soil temperature, humidity,
 

wind speed, soil type, moisture content, oil composition, solar radiation, and thickness of the oil layer.
 

Volatilization of benzene, toluene, ethylbenzene, and xylene from gasoline-contaminated soils tends to
 

increase with decreasing moisture content (Frankenberger 1992). Bossert and Bartha (1986)
 

indicated that n-alkanes greater than C18 exhibit no substantial volatilization at ambient temperatures;
 

however, lighter fractions (<C18) are subject to volatilization.
 

The propensity for a compound to volatilize from an aqueous phase can be grossly estimated using
 

Henry’s law, which relates vapor pressure, solubility, and molecular weight. Henry’s law constant
 

can be estimated using these three chemical-specific parameters or it can be measured on a
 

compound-by-compound basis in the laboratory. Henry’s law constant is frequently used to assess the
 

environmental fate of organic compounds in the subsurface.
 

Solubility. Solubility is one of the key factors in determining compound behavior, and thus the
 

impact, of a chemical in the environment. Solubility is expressed in terms of the number of milli-
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5. POTENTIAL FOR HUMAN EXPOSURE 

grams of pure chemical that can be dissolved in one liter of water under standard conditions of 25 oC 

and one atmosphere of pressure. The solubility of an organic compound determines its propensity to 

dissolve into water. The greater the solubility, the greater the likelihood that the chemical will 

dissolve into infiltrating rainwater or groundwater and migrate away from the release area. 

Solubility generally decreases with increasing molecular weight of the hydrocarbon compounds. For 

compounds having similar molecular weights, the aromatic hydrocarbons are more water soluble and 

mobile in water than the aliphatic hydrocarbons (ASTM 1995) and branched aliphatics are less 

water-soluble than straight-chained aliphatics. Coleman et al. (1984) determined that the compounds 

most likely to be measured in water in contact with gasoline, kerosene, and fuel oil #2 were the 

light-fraction, aromatic hydrocarbons such as benzene, toluene, ethylbenzene, and xylenes. They 

found that although the aromatic compounds in these three fuels may comprise as much as 50% by 

weight, aromatic compounds in the C6-C13, range made up approximately 95% of the compounds 

dissolved in water. This correlates well with studies showing an enrichment of light-fraction 

hydrocarbons in the water phase and a depletion in the fuel phase. 

It is important to note that the partitioning behavior of organic compounds is affected by the presence 

of other hydrocarbons in the subsurface. The maximum dissolved concentrations achieved in the 

subsurface are always less than the concentration of any pure compound, when it is present as one of 

many constituents of a petroleum product (ASTM 1995). For example, the solubility of pure benzene 

in water is given as 1,780 mg/L, but the maximum calculated concentration in an aquifer immediately 

beneath a gasoline release has been estimated to be about 62 mg/L (Daugherty 1991). 

Organic Carbon-Water Partition Coefficient. The organic carbon-water partition coefficient 

(Koc) describes the propensity for a organic compound to partition between water and organic carbon 

in the soil. Chemical mobility can be determined based on the likelihood of a chemical to partition 

more strongly to either the organic carbon in the substrate or the water. If the chemical is strongly 

associated with the substrate (i.e., sorbed), the chemical is relatively immobile and will not be leached 

or transported great distances from the area of the release. In contrast, if the chemical is weakly 

sorbed to the substrate, the chemical has the potential to be transported greater distances and greater 

chance to contact human receptors. 

The degree of sorption not only affects the mobility of the compound, it can also affect other 

transport and transformation reactions. For example, volatilization and biodegradation rates are 

directly dependent upon the extent of partitioning (Dragun 1988). A compound that is strongly 
TOTAL PETROLEUM HYDROCARONS 73 

5. POTENTIAL FOR HUMAN EXPOSURE 

sorbed to the organic carbon in the substrate is less available and less likely to be volatilized or 

biodegraded. 

A mobility classification scheme based on the Koc indicates that compounds having Koc values 

<50 L/kg, 50-150 L/kg, and 150-500 L/kg are considered to be very mobile, mobile, and 

intermediate in mobility, respectively (Dragun 1988). Using this scheme, benzene (Koc = 60 L/kg) is 

classified as mobile; whereas toluene, ethylbenzene, and total xylenes (Koc = 182 L/kg, Koc = 363 

L/kg, and Koc ≅ 400 L/kg, respectively) are classified as having intermediate immobility. 

In summary, lighter petroleum products such as gasoline contain constituents with higher water 

solubility and volatility and lower sorption potential than heavier petroleum products such as fuel oil. 

Data compiled from gasoline spills and laboratory studies indicate that these light-fraction hydrocarbons 

tend to migrate readily through soil, potentially threatening or affecting groundwater 

supplies. In contrast, petroleum products with heavier molecular weight constituents, such as fuel oil, 

are generally more persistent in soils, due to their relatively low water solubility and volatility and 

high sorption capacity (Stelljes and Watkin 1991). 

5.3.2.3 Biodegradation 

Indigenous microbes found in many natural settings (e.g., soils, groundwater, ponds) have been shown 

to be capable of degrading organic compounds. Biodegradation occurs as microbes use organic 

compounds as a source of energy. Unlike other fate processes that disperse contaminants in the 

environment, biodegradation can eliminate the contaminants without transferring them across media. 

The final products of microbial degradation are carbon dioxide, water, and microbial biomass. 

The rate of hydrocarbon degradation depends on the chemical composition of the product released to 

the environment as well as site-specific environmental factors. Generally the straight chain 

hydrocarbons and the aromatics are degraded more readily than the highly branched aliphatic 

compounds (Havlicek 1988). The n-alkanes, n-alkyl aromatics, and the aromatics in the C10-C22 

range are the most readily biodegradable; n-alkanes, n-alkyl aromatics, and aromatics in the C5-C9 

range are biodegradable at low concentrations by some microorganisms, but are generally 

preferentially removed by volatilization and thus are unavailable in most environments; n-alkanes in 

the C1-C4 ranges are biodegradable only by a narrow range of specialized hydrocarbon degraders; and 

n-alkanes, n-alkyl aromatics, and aromatics above C22 are generally not available to degrading 

microorganisms. Hydrocarbons with condensed ring structures, such as PAHs with four or more 
TOTAL PETROLEUM HYDROCARONS 74 

5. POTENTIAL FOR HUMAN EXPOSURE 

rings, have been shown to be relatively resistant to biodegradation. PAHs with only 2 or 3 rings (e.g., 

naphthalene, anthracene) are more easily biodegraded (Park et al. 1990). 

A large proportion of the water-soluble fraction of the petroleum product may be degraded as the 

compounds go into solution. As a result, the remaining product may become enriched in the 

alicyclics, the highly branched aliphatics, and PAHs with many fused rings. 

Environmental factors such as oxygen content, pH, moisture content, temperature, nutrient 

concentrations, and the microbiota also affect the rate of biodegradation. In almost all cases, the 

presence of oxygen is essential for effective biodegradation of oil. Anaerobic decomposition of 

petroleum hydrocarbons leads to extremely low rates of degradation (Frankenberger 1992). The ideal 

pH range to promote biodegradation is close to neutral (6-8). For most species, the optimal pH is 

slightly alkaline, that is, greater than 7 (Dragun 1988). The moisture content of the contaminated soil 

will affect biodegradation of oils due to dissolution of the residual compounds, dispersive actions, and 

the need for microbial metabolism to sustain high activity. The moisture content in soil affects 

microbial locomotion, solute diffusion, substrate supply, and the removal of metabolic by-products. 

Excessive moisture will limit the gaseous supply of oxygen for enhanced decomposition of petroleum 

hydrocarbons. Most studies indicate that optimum moisture content is within 50-70% of the water 

holding capacity (Frankenberger 1992). 

All biological transformations are affected by temperature. Generally, as the temperature increases, 

biological activity tends to increase up to a temperature where enzyme denaturation occurs. The 

presence of oil should increase soil temperature, particularly at the surface. The darker color 

increases the heat capacity by adsorbing more radiation. The optimal temperature for biodegradation 

to occur ranges from 18 oC to 30 oC. Minimum rates would be expected at 5 oC or lower 

(Frankenberger 1992). 

There are at least 11 essential macronutrient and micronutrient elements that must be present in the 

soil in proper amounts, forms, and ratios to sustain microbe growth (Dragun 1988). These 

11 elements are nitrogen, phosphorus, potassium, sodium, sulfur, calcium, magnesium, iron, 

manganese, zinc, and copper. Nitrogen is usually the main limiting nutrient governing the rate of 

decomposition of petroleum hydrocarbons. However, small amounts of phosphorus fertilizers may 

also be necessary to stimulate biodegradation (Mills and Frankenberger 1994). 
TOTAL PETROLEUM HYDROCARONS 75 

5. POTENTIAL FOR HUMAN EXPOSURE 

Biodegradation rates in soils are also affected by the volume of product released to the environment. 

At concentrations of l-0.5% of oil by volume, the degradation rate in soil is fairly independent of oil 

concentrations. However, as oil concentration rises, the first order degradation rate decreases and the 

oil degradation half-life increases. Ultimately, when the oil reaches saturation conditions in the soil 

(i.e., 30-50% oil), biodegradation virtually ceases (Eastcott et al. 1989). This is substantiated by 

Borden et al. (1986) who found that biodegradation of trace quantities of hydrocarbon compounds 

occurred along contaminant plume edges in the presence of oxygenated formation water, but that little 

biodegradation occurred in the plume center where concentrations were higher. Wilson et al. (1985) 

also found biodegradation to take place selectively along plume margins controlled by the oxygen 

supply. 

The point at which biodegradation starts to become adversely affected by the amount of oil present is 

not well established. Other inhibitory effects include the generation of toxic intermediate organic 

compounds. Degradation of aromatic hydrocarbons, such as toluene, can yield phenolic and benzoic 

acid intermediates. Various microbial populations may be inhibited by compounds such as phenol 

and toluene, particularly at high concentrations. Although phenol- and toluene-degrading microorganisms 

have been isolated in soil exposed to low concentrations of these compounds, they are 

biocidal at elevated concentrations (Frankenberger 1992). 

The inhibitory effects of heavy metals can also influence biodegradation of organic materials. The 

presence of heavy metals in oil sludge, motor oil, and used crankcase oil may have deleterious effects 

on the hydrocarbon oxidizers in decomposing petroleum hydrocarbons (Frankenberger 1992). Jensen 

(1977) studied the effects of lead on biodegradation of oily waste in soil and found that the presence 

of lead caused certain changes in the population of soil microbiota. Reduction in the bacterial 

population was evident, particularly at the highest lead concentration of 5,000 ppm. Measurements 

of oxygen consumption revealed increased microbial activity after the addition of oil to soils, but the 

presence of lead markedly reduced this activity with a prolonged lag phase in the biodegradation of oil 

sludge. Other elements of concern include zinc, copper, chromium, nickel, and cadmium. With 

repeated applications of oily sludge to a landfarm operation, heavy metals may accumulate at levels 

in which biodegradation may be reduced. 
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5. POTENTIAL FOR HUMAN EXPOSURE 

5.3.3 Models 

An understanding of the factors that affect the fate and transport of contaminants in the environment, 

and the ability to develop and apply mathematical models that incorporate these factors, are important 

in risk management applications. Models are used to approximate real world processes to provide 

environmental analyses to support management decisions. If properly used, models can assist 

decision makers in effectively dealing with the complex issues related to petroleum releases in the 

environment. 

As noted earlier, petroleum products released to the environment migrate through soil by two general 

pathways: via bulk oil flow and as individual compounds dissolved in air or water. Although 

comprehensive mathematical models could be devised to treat both types of migration, the resultant 

framework would likely be excessively complex. Eastcott et al. (1989) suggests a two-stage modeling 

approach. The first stage considers transport of the bulk oil phase. After the oil is rendered 

immobile, a second stage is applied to assess the fate of the individual compounds that separate from 

the bulk phase. Models of this sort are often called solute transport models. The use of a two-stage 

approach is justified because when bulk oil flow does occur, it results in little or no component 

separation (i.e., benzene travels as fast as hexane) and the transport rate is usually fast relative to that 

of the dissolution rate (Eastcott et al. 1989). 

Modeling the bulk oil phase is complex and includes many uncertainties; consequently, it has not been 

employed extensively in decision-making processes (Bonazountas 1988). One exception is the 

Hydrocarbon Spill Screening Model (HSSM), which simulates the flow of LNAPLs through the 

unsaturated zone, LNAPL spreading in the capillary fringe, and the transport of a single chemical 

originating from the LNAPL in the water table aquifer (Charbeneau et al. 1995). HSSM may be used 

to provide an estimate of dissolved concentrations of compounds originating from a petroleum release 

of known composition, rate of release, and volume of release. It is generally assumed that modeling 

interest lies in the potential for adverse impacts to water quality, and most modeling practices have 

concentrated on the behavior of dissolved organic compounds at the edges of bulk oil plumes or 

lenses. Table 5-6 lists selected soil and groundwater models that are well documented, operational, 

and representative of types of available models. 



TOTAL PETROLEUM HYDROCARONS 80 

5. POTENTIAL FOR HUMAN EXPOSURE 

approximately one order of magnitude (TPHCWG 1997b). A set of 13 fractions were selected by the 

TPHCWG for use in evaluating TPH environmental levels (TPHCWG 1997b). 

5.3.3.3 Transport Models 

Transport models fall into four main categories: 

• unsaturated zone, 

• groundwater, 

• geochemical, and 

• ranking 

The first two categories use similar methodologies applied to different geohydrologic conditions; the 

third estimates chemical concentrations at equilibrium; and the fourth serves as a screening 

methodology to evaluate the severity of a release. As shown in Table 5-6, the majority of the models 

are geared toward assessing contaminant behavior in the unsaturated zone and groundwater. These 

types of models can appropriately be used for assessing petroleum release sites, but it is important to 

note that they have been developed for the broad spectrum of contaminants typically found at 

Superfund sites (e.g., chlorinated hydrocarbons and metals) and have not always been verified or 

validated for petroleum hydrocarbons in natural porous media (Daugherty 199 1). For example, well 

known and available models such as SESOIL, which is a one-dimensional, finite difference flow and 

transport model developed for evaluating the migration of contaminants through the unsaturated zone, 

cannot simulate the transfer of hydrocarbon compounds from the bulk oil phase to the dissolved 

aqueous phase. 

Despite their limitations, models are useful for assessing generic effects of contaminants or impacts 

over larger areas. For this purpose, however, simplified expressions derived from first principles 

appear to be as useful as more elegant computer models for the evaluation of contaminant fate and 

transport at small sites. 

For purposes of this section, the chemical-specific parameters for the petroleum hydrocarbon 

fractions are based on selecting a midpoint for the fraction, based on empirical data unified by 

equivalent carbon number (EC). The fractions labeled as C5-C7 and >C7-C8 are characterized by one 

compound only, benzene and toluene, respectively. Remaining fractions are characterized by multiple 
TOTAL PETROLEUM HYDROCARONS 81 

5. POTENTIAL FOR HUMAN EXPOSURE 

compounds, as described in TPHCWG (1997b). Representative physical parameters for TPH 

fractions are presented in Table 5-7. 

ASTM’s risk-based corrective action (RBCA) uses a tiered approach to data collection and analysis 

in supporting decisions on site assessment and response to petroleum. The RBCA procedure begins 

with the assessment of the site (see Figure 5-2 for RBCA process flow-chart). 

As part of Tier 1, a look-up table is used to determine whether site conditions satisfy the criteria for a 

quick regulatory closure or warrant a more site-specific assessment. The look-up table is a tabulation 

for potential exposure pathways, media (i.e., soil, water, and air), a range of incremental carcinogenic 

risk levels and hazard quotients equal to unity, and potential exposure scenarios for each chemical of 

concern. In Tier 2, the non-site-specific assumptions and point(s) of exposure (point at which an 

individual or population may come in contact with a chemical of concern originating from a site) used 

in Tier 1 are replaced with site-specific data and information. In Tier 2, the user applies Tier 1 riskbased screening levels (RBSL) look-up table values for the direct exposure scenario at reasonable 

point(s) of exposure (as opposed to the source areas as is done in Tier 1). The additional site-specific 

data may support alternate fate and transport analysis. Tier 2 RBCA process also involves the 

development of site-specific target levels (SSTLs) based on the measured and predicted attenuation of 

the chemical(s) of concern away from the source using relatively simplistic mathematical models. In 

Tier 3 evaluation, SSTLs for the source area(s) and the point(s) of compliance are developed on the 

basis of more sophisticated statistical and contaminant fate and transport analysis using site-specific 

input parameters for both direct and indirect exposure scenarios. Tier 3 evaluation is much more 

complex than Tiers 1 and 2 since it may include additional site assessment, probabilistic evaluations, 

and sophisticated chemical fate/transport models. 

5.4 LEVELS IN THE ENVIRONMENT 

It is extremely difficult to make general statements about typical TPH or TPH-component levels in 

environmental media. Environmental fate and transport processes of TPH mixtures are complex. 

Interactions of the chemicals within the bulk oil typically result in different environmental fate and 

transport than would be predicted for the individual components. As with the discussion of basic fate 

and transport processes (see in Section 5.3), site-specific information is nearly always needed for 


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5. POTENTIAL FOR HUMAN EXPOSURE 

correct interpretation of data for such media as surface water, soils, or groundwater. Petroleum site 

contaminants, especially the types of bulk fuel products and lubricants that are the focus of this 

profile, are usually encountered as liquids or semi-liquid sludges. The site contaminants almost 

always originate as mixtures of many different hydrocarbons typical of such initial products as motor 

gasoline, jet fuels, or fuel oils. Frequently, there are portions of a waste site where soils or sub-soil 

materials have accumulated large masses of petroleum contaminants that form nonaqueous liquid 

systems. The term nonaqueous phase liquids (NAPL) is often applied to such areas of heavy 

contamination. NAPLs propagate plumes moving away from the central mass. The NAPL complex, 

consisting of the central mass and plumes, usually reaches an equilibrium due to a combination of 

physical, chemical, and biochemical processes. TPH chemicals move into the actual soil or 

groundwater media from the edge of the NAPL plumes. 

Without some knowledge of the locations of NAPL central masses or plumes at a waste site, it can be 

very hard to interpret analyses from soil samples or test wells. Within the NAPL zone, readings for 

TPH or one or more specific petrochemicals may be very high. Such high readings are indicative of a 

soil matrix virtually engulfed by a petroleum waste and represent the bulk oil product rather than the 

environmental media. Beyond the NAPL zone, the observed levels are substantially less. Media 

sampling values taken at random from different site-specific spatial contexts should be interpreted 

within the context of the sampling location relative to the NAPL central masses and plumes. 

Since most TPH contamination involves a complex mixture of hydrocarbons, it is unlikely that 

aqueous readings beyond the NAPL zone will be near the limits of solubility (based on assumptions of 

a pure hydrocarbon type in equilibrium with water). If concentrations are near or above solubility 

limits, NAPL was probably present in the sample. TPH materials are relatively insoluble in water, 

with only the BTEX chemicals or some short-chain aliphatic hydrocarbons showing any appreciable 

potential for water solubility. When they are part of complex mixtures, the individual components 

never reach the concentrations predicted from their solubility constants as individual chemicals. For 

example, chemicals like benzene or toluene, which may constitute a small percentage within an initial 

bulk product like gasoline, jet fuel, or diesel fuel, have a much greater tendency to stay dissolved in 

the NAPL system than to become integrated into the water-based system beyond the NAPL boundary. 

Therefore, the effective solubility of these chemicals as part of a complex mixture is less than it 

would be in a release of the pure chemical. 
TOTAL PETROLEUM HYDROCARONS 85 

5. POTENTIAL FOR HUMAN EXPOSURE 

Some simple examples help illustrate this point. A study by Burris and MacIntyre (1984) compared 

the theoretical solubilities of specific chemicals in water to the solubilities of the same chemicals 

when they were part of such petroleum product mixtures as JP-4 jet fuel. The results are summarized 

in Table 5-8. Similar comparisons for all the BTEX (benzene, toluene, ethylbenzene, xylene) 

chemicals, based on materials presented by Potter (1993) are presented in Table 5-9. 

The information presented in Tables 5-8 and 5-9 shows that for common petroleum products in water, 

the solubility of the component chemicals is usually less than the potential solubility of the individual 

chemical in water by an order of magnitude or more. Table 5-9 also shows why much attention often 

focuses on site contamination involving gasoline. Gasoline mixtures have much higher percentages of 

light fraction aromatic hydrocarbons, such as the BTEX aromatics, than other bulk fuel products. 

This can lead to much higher levels of contamination in ambient water or groundwater from gasoline 

than from petroleum mixtures with less soluble components. The increased solubilities of the BTEX 

chemical components from gasoline mixtures would thus be more likely to result in groundwater 

contamination. For other bulk fuel products, BTEX levels in the mixture are generally far lower; as a 

result, their water solubility and thus, their potential for groundwater contamination, would be much 

lower. 

In light of these considerations, it becomes easier to see why it is highly desirable that available 

monitoring data from environmental media be combined with site-specific information. The basic 

needs are locational data on the spatial configuration of NAPL pockets and plumes combined with 

analyses of the types of TPH components found in the NAPL system and the surrounding, relatively 

uncontaminated media (soils, water, and groundwater). With this basic knowledge, a variety of 

modeling techniques can be applied to estimate effective solubilities of specific hydrocarbon 

compounds (Feenstra et al. 1991). Moreover, since there can be literally thousands of specific 

compounds in TPH site contaminants, it is improbable that a site analysis for a TPH-contaminated 

site would include sampling data for all TPH components. As a result, the surrogate approaches and 

screening modeling tools such as RBCA have been widely used to evaluate environmental data at 

TPH-contaminated waste sites. 


TOTAL PETROLEUM HYDROCARONS 88 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.5 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation 

with the Administrator of EPA and agencies and programs of the Public Health Service) to assess 

whether adequate information on the health effects of TPH is available. Where adequate information 

is not available, ATSDR, in conjunction with the NTP, is required to assure the initiation of a 

program of research designed to determine the health effects (and techniques for developing methods 

to determine such health effects) of TPH. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met 

would reduce the uncertainties of human health assessment. This definition should not be interpreted 

to mean that all data needs discussed in this section must be filled. In the future, the identified data 

needs will be evaluated and prioritized, and a substance-specific research agenda will be proposed. 

5.5.1 Identification of Data Needs 

Physical and Chemical Properties. The physical and chemical properties of some TPH 

compounds and petroleum products containing TPH are well defined and can be used to estimate the 

fate of TPH transport fractions following release to the environment (Air Force 1989, 1991; IARC 

1987, 1989a, 1989b, 1989c, 1989d). Data needs associated with specific TPH compounds that are 

components of petroleum products (benzene, ethylbenzene, toluene, xylenes, hexane, and PAHs) are 

presented in the ATSDR toxicological profiles for these chemicals (ATSDR 1994, 1995d, 1995f, 

1997a, 1999a, 1999b). 

Production, Import/Export, Use, Release, and Disposal. TPH compounds are the primary 

component in various petroleum products; therefore, most releases of TPH occur as a result of 

petroleum product spills either on land or water. More information on the production volumes for 

various petroleum products, environmental releases, and disposal would aid in assessing the potential 

for human exposure to TPH as a result of accidental or intentional release. Data needs for specific 

petroleum products are discussed in the ATSDR toxicological profiles for automotive gasoline 

(1995a), Stoddard solvent (1995b), jet fuels (1995c and 1998b), fuel oils (1995g), hydraulic fluids 

(1997b), and mineral-based crankcase oil (1997c). 
TOTAL PETROLEUM HYDROCARONS 89 

5. POTENTIAL FOR HUMAN EXPOSURE 

Environmental Fate. The environmental fate of TPH is based on the environmental partitioning 

of the major hydrocarbon fractions. However, the environmental fate of chemicals in mixtures and/or 

bulk oil releases may be different than that observed for releases of individual TPH chemicals (see 

Sections 5.3.2.1 and 5.3.2.2). The more soluble and volatile fractions (i.e., the low molecular weight 

aliphatic and aromatic fractions) are more likely to leach to groundwater, volatilize to the air, or 

biodegrade than the larger TPH compounds are. These higher molecular weight compounds tend to 

sorb to the soil and persist at the site of release. The movement and persistence of several TPH 

compounds and petroleum products are well studied. Data needs for specific TPH compounds and 

petroleum products have been discussed in other ATSDR toxicological profiles (ATSDR 1994, 

1995a, 1995b, 1995c, 1995d, 1995e, 1995f, 1995g, 1997a, 1997b, 1997c, 1998b, 1999a, 1999b). 

Bioavailability from Environmental Media. The extent of absorption of TPH by inhalation, 

oral, and/or dermal routes varies because of the wide range of physical/chemical properties observed 

for these chemicals. The extent of absorption by the various routes depends on the volatility, 

solubility, lipophilicity, and other properties of the specific TPH chemical or mixture. Several of the 

TPH component compounds have been discussed in individual ATSDR toxicological profiles (e.g., 

benzene, ethylbenzene, toluene, xylenes, hexane, PAHs), which should be consulted for further 

information (ATSDR 1994, 1995d, 1995f, 1997a, 1999a, 1999b). More data linking exposure levels 

of TPH mixtures with biological levels of component chemicals would be useful in determining which 

chemicals in the mixture are most likely to be absorbed and by which routes. This information would 

aid in determining daily human exposure levels and more accurately assessing the risk associated with 

exposure to TPH. 

Food Chain Bioaccumulation. Studies of the accidental and intentional release of gasoline and 

fuel oils to the aquatic environment indicate that aquatic organisms are able to bioaccumulate some 

TPH fractions, particularly PAHs (Air Force 1989; Farrington et al. 1982); however, depuration does 

occur if the source of the contamination is removed (Cox et al. 1975; Williams et al. I989). In 

general, the lower molecular weight aliphatics and aromatics do not bioaccumulate (Air Force 1989). 

Further studies are needed to determine the biomagnification potential of the TPH fractions, 

particularly PAHs, up the food chain within aquatic and terrestrial ecosystems. Specific research 

needs are presented in the individual ATSDR toxicological profiles on specific hydrocarbon 

components such as benzene, toluene, total xylenes, and PAHs (ATSDR 1994, 1995d, 1995f, 1997a). 
TOTAL PETROLEUM HYDROCARONS 90 

5. POTENTIAL FOR HUMAN EXPOSURE 

Research on the biomagnification of various petroleum products (e.g., gasoline, fuel oil) would not be 

useful because the composition of these mixtures changes rapidly in the environment. Individual 

chemicals present in the original mixture may bioaccumulate, but the mixture does not. 

Exposure Levels in Environmental Media. TPH is commonly measured where hydrocarbon 

releases have occurred (e.g., leaking gasoline, diesel, or fuel oil tanks and petroleum product spills). 

In most cases, the analytical method does not provide specific information regarding the TPH 

fractions present (see Section 3.3). More data on levels of TPH fractions and/or their components in 

the air, water, and soil around facilities where petroleum products are produced, stored, and used 

would be useful. Data on levels in contaminated surface water, groundwater, and soil are needed to 

assess the potential risk from these likely sources of exposure. 

Exposure Levels in Humans. Workers who use petroleum products in manufacturing and those 

involved in their transfer may experience increased dermal and inhalation exposures to TPH. 

Workers in the petroleum refining industry, particularly those involved with monitoring and servicing 

unit equipment, are known to have increased exposure to TPH (Runion 1988). Reliable monitoring 

data for levels of TPH in contaminated media could be used in combination with biomarkers to 

identify TPH exposure and assess the potential risk of adverse health effects in populations living 

near contaminated areas. This information is necessary for assessing the need to conduct health 

studies on these populations. 

Exposure Registries. No exposure registries for TPH or petroleum products were located. This 

substance is not currently one of the compounds for which a subregistry has been established in the 

National Exposure Registry. The substance will be considered in the future when chemical selection 

is made for subregistries to be established. The information that is amassed in the National Exposure 

Registry facilitates the epidemiological research needed to assess adverse health outcomes that may 

be related to exposure to this substance. A registry does exist for benzene, a component of TPH. 

More information on the benzene exposure registry can be found in the ATSDR toxicological profile 

for benzene (ATSDR 1997a). 
TOTAL PETROLEUM HYDROCARONS 91 

5. POTENTIAL FOR HUMAN EXPOSURE 

5.5.2 Ongoing Studies 

No summary of ongoing studies is presented in this profile. Useful summaries are provided in 

toxicological profiles for the specific petroleum hydrocarbons or petroleum products, as listed in 

Table 3-l. As of September 1999, a 90-day toxicity study of a C9 to C16 aromatic fraction in rats and 

mice was completed by Dr. D. Mattie and colleagues at Wright Patterson toxicology laboratory 

(DOD), though not published. No other petroleum fraction toxicity research can be reported. 

TOTAL PETROLEUM HYDROCARONS 93 

6. HEALTH EFFECTS 

6.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, 

and other interested individuals and groups with an overall perspective on the toxicology of total 

petroleum hydrocarbons (TPH), and an understanding of various approaches used to assess petroleum 

hydrocarbons on the basis of fractions, individual indicator compounds, and appropriate surrogates. 

This chapter also provides descriptions and evaluations of toxicological studies and epidemiological 

investigations for these TPH fractions, indicator compounds, and surrogates, and provides 

conclusions, where possible, on the relevance of toxicity and toxicokinetics data to public health. 

6.1.1 TPH Definition and Issues 

Overview. The assessment of petroleum hydrocarbon-contaminated sites has involved analysis for 

“total petroleum hydrocarbons” or TPH. TPH is a loosely defined aggregate that depends on the 

method of analysis as well as the contaminating material, and represents the total mass of 

hydrocarbons without identification of individual components (see Chapter 3). As TPH is not a 

consistent entity, the assessment of health effects and development of health guidance values, such as 

Minimal Risk Levels (MRLs) for TPH as a single entity are problematic. Earlier in the profile 

(Chapters 2 and 3), various TPH approaches were presented that divide TPH into fractions or groups 

of compounds based on analytical, fate and transport, and exposure issues. Similarly, several 

different approaches have also been evolving to assess the health effects of TPH on the basis of 

indicator compounds for separate fractions, which consist of petroleum hydrocarbons with similar 

physical and chemical properties. ATSDR’s approach to potential health effects from exposure to 

TPH uses surrogate health effects guidelines for each fraction, whether they represent an individual 

compound or a whole petroleum product. Additional discussions focusing on these various 

approaches to health effects assessment are presented in the remainder of this section (6.1). In 

particular, the ATSDR approach (Section 6.1.3) uses existing ATSDR MRLs for several individual 

TPH compounds and for specific petroleum products. The use of these MRLs to characterize the 

health effects of TPH, using an indicator compound and fraction/surrogate approach, is also 

discussed. 
TOTAL PETROLEUM HYDROCARONS 94 

6. HEALTH EFFECTS 

Scope of the Problem. Petroleum hydrocarbons are the principal components in a wide variety 

of commercial products (e.g., gasoline, fuel oils, lubricating oils, solvents, mineral spirits, mineral 

oils, and crude oil). Because of widespread use, disposal, and spills, environmental contamination is 

relatively common. It is important to understand that petroleum products are complex mixtures, 

typically containing hundreds of compounds. These include various amounts of aliphatic compounds 

(straight-chain, branched-chain, and cyclic alkanes and alkenes) and aromatic compounds (benzene 

and alkyl benzenes, naphthalenes, and PAHs). In addition, many petroleum products contain nonhydrocarbon additives such as alcohols, ethers, metals, and other chemicals that may affect the 

toxicity of the mixture. 

The number of individual identified hydrocarbon components of the various petroleum products has 

been estimated at several hundred to over a thousand. Toxicity data are available for about 95 of 

these, but only about 25 were considered to have sufficient data to develop toxicity criteria according 

to the Total Petroleum Hydrocarbon Criteria Working Group (TPHCWG 1997b). ATSDR has 

derived MRLs for 12 of these compounds (anthracene, benzene, ethylbenzene, fluoranthene, fluorene, 

n-hexane, naphthalene, toluene, m-xylene, p-xylene, xylenes, and l-methyl naphthalene). EPA has 

derived Reference Doses (RfDs) and Reference Concentrations (RfCs) for some of the remaining 

compounds. The TPHCWG (1997c) and the Massachusetts Department of Environmental Protection 

(MADEP) (Hutcheson et al. 1996) have also derived other health guidance criteria for some of these 

compounds. Two of these compounds have EPA-derived cancer slope factors and/or unit risks, and a 

relative potency approach has been developed for some of the PAHs. However, it is not yet possible 

to assess the overall health implications of TPH from the individual hydrocarbon components because 

many of the known components lack appropriate, standardized, comparable toxicity data. In addition 

the cost of analysis for all TPH constituents is usually prohibitive. 

Although health effects data are available for some petroleum products, and ATSDR-derived MRLs 

are available for fuel oil no. 2, JP-4, JP-5/JP-8, JP-7, and kerosene, there are limitations to applying 

MRLs for the whole products to TPH. A major limitation is that, when released to the environment, 

the composition of a petroleum product changes due to weathering (i.e., differential fate and transport 

of its components). Partitioning of fractions consisting of hydrocarbons with similar physical and 

chemical properties occurs, with migration of some fractions to other locations and environmental 

media, leaving the relatively nonmobile components (the weathered product) at the original location. 
TOTAL PETROLEUM HYDROCARONS 95 

6. HEALTH EFFECTS 

Thus, the actual petroleum hydrocarbon mixture to which a given population is exposed varies with 

location, time and environmental medium. Accordingly, health effects data for whole petroleum 

products that are relatively heterogeneous, such as gasoline and JP-4, are not necessarily applicable 

to the fractions to which exposure actually occurs as a result of transport and weathering. For 

example, acute inhalation exposure to a fresh spill of gasoline will be to the more volatile 

constituents, whereas intermediate or chronic oral exposure to drinking water contaminated by a 

gasoline release will be to the soluble constituents, and exposure to soil at the site of the original spill 

will be to the less volatile and less soluble constituents. Thus, none of these exposure scenarios 

would be well represented by experimental data using the whole product. 

Additional limitations to the use of health effects data for whole petroleum products include the 

variable composition of each type of petroleum product due to differences in the crude oil from which 

it was refined, in the refining processes used, and in the formulation of the final product. Also, non-hydrocarbon 

additives and contaminants, many of which have significant toxicity, are often included 

in these whole products (e.g., methyl-tert-butyl ether (MTBE) or lead in gasoline). Finally, the 

identity of the originally released material may not be known or more than one such product may have 

been released. 

Health effects data also are available for some petroleum fractions or process streams that are less 

heterogeneous. These materials are more representative of the fractions that may partition in the 

environment and are more useful for assessing health effects of intermediate and chronic exposure to 

petroleum hydrocarbons. These products are discussed further in Section 6.2. Additional discussion 

of these and also the more heterogeneous products is presented in Section 6.3. 

Mixtures Issues. Petroleum products and their environmental transport fractions are complex 

mixtures. The preferred method for assessing the health effects of complex mixtures is to use 

exposure and toxicity data for the mixture of concern, because this approach takes into account 

toxicological interactions, such as synergism or antagonism, that may occur among the constituents of 

the mixture. If data for the mixture of concern are not available, then data for a similar mixture may 

be used. In the absence of pertinent data for the same or a similar mixture, data on the individual 

components of the mixture are used, taking into account the potential for toxicological interactions. 

The default assumption, when data regarding interactions are not available or do not clearly indicate 
TOTAL PETROLEUM HYDROCARONS 96 

6. HEALTH EFFECTS 

the direction of the interaction, is that the doses or effects are additive (ATSDR 1992; De Rosa et al. 

1996; EPA 1986; Johnson and De Rosa 1995; Mumtaz et al. 1994). Other public health aspects of 

chemical mixtures and TPH have recently been reviewed (Hansen et al. 1998; Todd et al. 1999) 

The mixtures of concern for TPH are not the heterogeneous petroleum products, but rather the 

transport fractions to which populations are more likely to be exposed. Thus, use of health effects 

data for these fractions would be preferable. When health effects data for petroleum products 

(mixtures) similar in composition to these fractions are not available, data for individual constituents 

could be used as surrogates, taking into account the potential for toxicologic interactions. Given the 

complexity of the interactions data for the individual constituents (Section 6.9) however, the 

assumption that the toxicity of the constituents is additive may be the most reasonable approach. 

This implicit assumption underlies the adoption of an MRL as a surrogate value to represent the 

toxicity of an entire fraction. 

6.1.2 Existing Risk-Based Methods for TPH Health Assessment 

This section presents approaches of other organizations. The ATSDR approach is presented in 

Section 6.1.3. 

The American Society for Testing and Materials (ASTM) Approach. ASTM (1995) 

developed a Risk-Based Corrective Action (RBCA) approach for petroleum release sites. Additional 

information regarding this approach is provided in previous sections of this document and in 

Chapter 7. The present discussion is limited to health effects aspects of the approach. The RBCA 

approach is not limited to TPH, but includes any chemical that may be associated with petroleum 

product releases, including nonhydrocarbon constituents and additives. ASTM used an indicator 

compound approach that assumes 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 ASTM approach assesses the risk of exposure to each chemical of concern 

separately during the derivation of Tier 1 (general) risk-based screening levels, and Tier 2 and 3 site- specific 

target levels for contaminated media. Although the use of whole mixture toxicity data and 

the assumption of additivity for the toxicity of individual chemicals in a mixture were mentioned as 

options for Tier 2 and 3, neither approach was recommended by ASTM. The criteria to be used in 

selection of the chemicals of concern for various petroleum products are concentrations in the 
TOTAL PETROLEUM HYDROCARONS 97 

6. HEALTH EFFECTS 

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 concern are
 

PAHs. Twelve PAHs, including benzo(a)pyrene, were selected for consideration.
 

The MADEP Approach. The MADEP (Hutcheson et al. 1996; MADEP 1997, 1999)
 

recommends the use of a combination indicator compound and fraction approach for the assessment
 

of health effects from TPH in soil and water as follows:
 

Carcinogenic Effects. Specific petroleum hydrocarbon indicator compounds that have EPA cancer
 

potency factors are assessed; these are benzene and benzo(a)pyrene. EPA relative potency factors
 

can be used for benz(a)anthracene, indeno( 1,2,3-cd)pyrene, dibenz(a,h)anthracene, chrysene,
 

benzo(b)fluoranthene, and benzo(k)fluoranthene.
 

Noncarcinogenic Effects. The following petroleum hydrocarbon fractions were established based on
 

molecular structure (aromatic versus aliphatic) and then on number of carbon atoms, using toxicologically
 

similar groupings and excluding compounds with less than 5 carbons because their high
 

volatility precludes chronic exposure from spills/releases. With the exception of the aromatic C5-C8
 

fraction, the toxicity of each fraction is represented by the RfD for a representative “reference
 

compound” from the fraction. Analytical methods for these fractions have also been suggested
 

(Section 3.3). Some of these fractions include subfractions that were combined because of similarity
 

of toxicity across fractions or limitations in the toxicity data.
 

Aromatic fractions
 

C5-C8 , assessed on the basis of the individual indicator compounds-benzene (MADEP RfD
 

derived from inhalation study), toluene, ethylbenzene, and xylenes (EPA RfDi).
 

C9-C10, using an EPA RfD for pyrene (the lowest RfD for compounds in this group) as a
 

surrogate and an RfC for xylenes.
 

Cl1C12, using and EPA RfD for pyrene and an RfC for naphthalene.
 
TOTAL PETROLEUM HYDROCARONS 98 

6. HEALTH EFFECTS 

Aliphatic fractions
 

C5-C8, using an EPA RfD and RfC for n-hexane as a surrogate.
 

C9-C12, using a MADEP RfD and RfC for n-nonane as a surrogate, based on estimated
 

relative potency of n-nonane as compared with n-hexane.
 

C13-C18, using a MADEP RfD and RfC for naphthalene as a surrogate.
 

C19C35,using a MADEP RfD for white mineral oil (but listing eicosane as the reference
 

compound).
 

The MADEP (1997) has published a draft report for public comment regarding implementation of 

their approach. This report references the TPHCWG (1997a, 1997b, 1997c) approach (below), 

particularly in defining fractions with regard to transport properties, which are related to the 

equivalent (or relative) carbon number indexes for the compounds. 

The TPHCWG Approach. The TPHCWG (1997a, 1997b, 1997c) also recommends a 

combination indicator compound and fraction approach for TPH, but it differs from the MADEP 

approach in the elimination of assessment for noncarcinogenic effects if carcinogens are present 

above regulatory criteria, in the basis for selection of the fractions, and in a more extensive use of 

toxicity data for mixtures to represent the toxicity of the fraction. Some petroleum hydrocarbon 

fractions listed below include subfractions that were combined because of similarity of toxicity across 

fractions or limitations in the toxicity data. 

Carcinogenic Effects. Specific petroleum hydrocarbon indicator compounds that have EPA cancer 

potency factors are assessed (i.e., benzene and benzo(a)pyrene). 

Noncarcinogenic Effects. These effects are assessed only if the carcinogenic indicator compounds 

are not detected or are below regulatory criteria. The following petroleum hydrocarbon fractions, 

minus the carcinogenic indicator compounds, were selected as representing compounds with similar 

transport properties. Toxicity values for constituents of the fraction or for a similar mixture were 

selected to represent the toxicity of the fraction. Aromatic and aliphatic hydrocarbons are considered 

separately and further subdivided on the basis of equivalent carbon number index (EC). This index is 

equivalent to the retention time of the compounds on a boiling point GC column (non-polar capillary 

column), normalized to the n-alkanes. Physical and chemical properties of hydrocarbons that are 
TOTAL PETROLEUM HYDROCARONS 99 

6. HEALTH EFFECTS 

useful in predicting transport (vapor pressure, solubility, partition coefficient, Henry’s law constants) 

are predictably related to the EC and can be estimated using algorithms (see Chapter 5). 

Aromatic fractions
 

EC5-EC8, using EPA RfD and RfC for toluene as a surrogate.
 

EC>8-EC16, using EPA RfDs (all the same value) for two compounds (cumene
 

[isopropylbenzene] and naphthalene) as a surrogate and an RfC for C9 aromatics (hi-flash
 

aromatic naphtha).
 

EC>16EC35, using the EPA RfD for pyrene (C16) as a surrogate. Anthracene, fluorene, and
 

fluoranthene are also in this group; however, pyrene was selected because it had the lowest
 

RfD.
 

Aliphatic fractions
 

EC5-EC8, using TPHCWG RfD (derived from inhalation data) as a surrogate and RfC for
 

commercial hexane, a mixture of C6 hydrocarbons containing 53% n-hexane.
 

EC>8-EC16, using TPHCWG RfD and RfC for dearomatized petroleum streams (white
 

spirit).
 

EC>14-EC35, using TPHCWG RfD for white mineral oils.
 

The MADEP (Hutcheson et al. 1996; MADEP 1997) and the TPHCWG (1997a, 1997b, 1997c) 

approaches both assume additivity of the indicator compounds and the hydrocarbon fractions in 

assessing the potential for adverse effects of TPH on health. In contrast, the ASTM approach ten 

to assess each individual TPH indicator chemical separately and without regard to the presence of 

other petroleum hydrocarbons and the potential for additivity or interactions, although it does not 

preclude a consideration of these factors. 

6.1.3 Overview of the ATSDR Approach 

In formulating an approach to health assessment of TPH, ATSDR has drawn on the experience of 

other groups that have been developing approaches to health-based assessment for TPH (i.e., ASTM 

[1995]; Hutcheson et al. [1996]; and TPHCWG [1997a, 1997b, 1997c]), but has developed an 

approach designed to address its own specific concerns and mandates. A notable difference between 

ATSDR and these other groups is that the other groups have focused on longer-term exposure 
TOTAL PETROLEUM HYDROCARONS 100 

6. HEALTH EFFECTS 

scenarios, whereas ATSDR is concerned with the entire spectrum of possible exposure periods from 

acute through chronic. In addition, the health guidance values developed by ATSDR, MRLs, are 

intended to serve as screening levels by ATSDR health assessors to identify contaminants and 

potential health effects that may be of concern at hazardous waste sites. MRLs are not intended to 

define clean-up or action levels. 

The ATSDR approach, as reflected in this profile, focuses on an assessment of the health effects of 

petroleum hydrocarbon transport fractions, as suggested by the TPHCWG (1997a, 1997b, 1997c). 

This approach is the most universally useful, given the limitations to using data for the whole 

petroleum products or individual constituents, discussed in Chapter 2 and in Section 6.2.1 above. 

Methods of analysis for these fractions are available, and modeling can be performed to predict 

exposure to the fractions. The assessment of the health effects of the fractions by ATSDR is similar 

but not identical to that of the TPHCWG. In addition, to capitalize on the best features of the 

MADEP (Hutcheson et al. 1996) and TPHCWG (1997a, 1997b, 1997c) approaches, the aromatic 

EC5-EC8 fraction has been redefined as an EC5-EC9 fraction, so that it includes all the BTEXs. The 

aromatic EC>8-EC16 fraction is then redefined as an EC>9-EC16 fraction. 

Carcinogenic Effects. Specific hydrocarbon indicator compounds that have EPA cancer risk 

estimates are assessed; these are benzene and benzo(a)pyrene. EPA relative potency factors can be 

used for benz(a)anthracene, indeno( 1,2,3-cd)pyrene, dibenz(a,h)anthracene, chrysene, 

benzo(b)fluoranthene, and benzo(k)fluoranthene. 

Noncarcinogenic Effects. The following petroleum hydrocarbon fractions, including the 

carcinogenic indicator compounds, were selected as representing compounds with similar transport 

properties, based on the recommendations of the TPHCWG (1997b, 1997c), with an adjustment of 

the lower EC aromatic fractions in order to include all the BTEXs in the first fraction, as discussed 

above. As with the MADEP and TPHCWG approaches, some of the fractions include subfractions 

that have been combined because of similarity of health effects across fractions or limitations in the 

health effects data. Provisional recommendations regarding suitable MRLs are made, using a 

surrogate approach as needed and appropriate. The MRL for the surrogate compound or for a 

petroleum product similar in composition to the fraction is used to indicate the potential toxicity of 

the entire mass of the fraction. 
TOTAL PETROLEUM HYDROCARONS 101 

6. HEALTH EFFECTS 

Aromatic Fractions
 

EC5EC9, using inhalation and oral MRLs specific to each individual indicator compound-benzene,
 

toluene, ethylbenzene, and the xylenes.
 

EC>9-EC16, using a chronic inhalation MRL and acute and intermediate oral MRLs for
 

naphthalene as surrogates.
 

EC16-EC35, using an intermediate oral MRL for fluorene and fluoranthene as a surrogate.
 

Aliphatic Fractions
 

EC5-EC8, using a chronic inhalation MRL for n-hexane as a surrogate.
 

EC>8-EC16, using a chronic inhalation MRL for JP-7.
 

EC>16-EC>35, using health effects data for mineral oils, but no MRLs are available.
 

The health effects of these fractions are discussed in Section 6.2, and details of the selection of the 

fraction-specific MRLs can be found in Section 6.6. These fraction-specific values are provisional 

values, reflecting the uncertainty inherent in this approach, as discussed in Section 6.6. Further 

information on ATSDR MRLs is given in Appendix A, while information on other toxicity criteria 

such as RfDs and RfCs, is provided in Chapter 7. 

ATSDR has already prepared toxicological profiles on a large number of individual constituents of 

TPH and on a number of whole petroleum products. In order to give an overall perspective on the 

toxicology of TPH, without duplicating the existing profiles, this toxicological profile will present 

brief summaries of the health effects of these individual petroleum hydrocarbon compounds and 

petroleum products. MRLs have been derived for a number of these compounds, which serve as 

indicator and surrogate compounds for the ATSDR approach as outlined above. Thus, consideration 

of these compounds as part of the TPH contamination profile is useful. Similarly, information 

regarding the extent and identity of petroleum product contamination may be available, and toxicity 

information and MRLs for these original products may be useful in some circumstances for assessing 

potential health effects. These brief summaries of information on the individual compounds and on 

petroleum products that are representative of particular fractions occur during the discussion of the 

health effects of the fractions in Section 6.2. Information on petroleum products, including the more 

heterogenous mixtures, also is presented in Section 6.3. The reader is encouraged to consult the 

original toxicological profiles listed in Appendix A and other cited sources for more detail. 
TOTAL PETROLEUM HYDROCARONS 102 

6. HEALTH EFFECTS 

The content of this chapter and this document is different from that of a standard toxicological 

profile, in recognition of the extensive assessments of individual petroleum hydrocarbons already 

performed by ATSDR and other agencies, and the need for an approach that focuses on the most 

important information. This chapter presents the ATSDR perspective and approach, and serves as a 

guide to sources of more detailed information. 

6.2	 DISCUSSION OF HEALTH EFFECTS BY FRACTION AND ROUTE OF 

EXPOSURE 

Because of the complexity of TPH, and the existence of extensive ATSDR and TPHCWG 

documentation for constituents of TPH and for petroleum products and mixtures corresponding to 

some of the fractions, this section of the document adopts a “handbook approach” to delineating the 

health effects of TPH. The organization and content of this section, while retaining an emphasis on 

route and duration of exposure and on type of health effect, is streamlined in order to avoid 

duplication of existing resources and to help public health professionals, and others who address the 

needs of people living or working near hazardous waste sites, to gain an understanding of the 

characteristic health effects of TPH fractions. The juxtaposition of information on fraction 

composition with information on health effects for fraction constituents facilitates evaluation of the 

suitability of the existing health effects information to represent the potential health effects of the 

entire fraction. Further discussion of the suitability and representativeness of the information is 

presented in Section 6.6. 

Thus, for each fraction, the components of the fraction are delineated first. Health effects for the 

fraction are then discussed by route of exposure. This discussion includes information on individual 

constituents of the fraction and on mixtures that correspond to the fraction. The text focuses on the 

major, sensitive, and/or characteristic end points. 

The figures give a condensed picture of exposure-effect relationships for each fraction. They show 

the lowest reliable lowest-observed-adverse-effect-level (LOAEL) in animals and humans for each 

route, exposure period, and end point, including cancer. The three exposure periods-acute (14 days 

or less), intermediate (15-365 days), and chronic (365 days or more)-are represented. Different 

symbols are used to represent different compounds or mixtures, with open symbols for animals and 
TOTAL PETROLEUM HYDROCARONS 103 

6. HEALTH EFFECTS 

closed for humans. For additional information, including no-observed-adverse-effect levels 

(NOAELs), classification of LOAELs into “less serious” or “serious” effects, and details of the 

actual studies, the reader is encouraged to consult the sources referenced in the figures. Because 

cancer effects could occur at lower exposure levels than the exposures plotted in some of the figures, 

these figures also show a range for the upper bound of estimated excess risks, ranging from an 

estimate of 1 in 10,000 to 1 in 10,000,000 (l0-4 to 10-7), as developed by EPA. 

In addition, estimates of minimal risk to humans (MRLs) are plotted. An MRL is defined as an 

estimate of daily human exposure to a substance that is likely to be without an appreciable risk of 

adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when 

reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health 

effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous 

health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, 

intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate 

methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 

199Oc), uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges 

additional uncertainties inherent in the application of the procedures to derive less than lifetime 

MRLs. As an example, acute inhalation MRLs may not be protective for health effects that are 

delayed in development or are acquired following repeated acute insults, such as hypersensitivity 

reactions, asthma, or chronic bronchitis. As these kinds of health effects data become available and 

methods to assess levels of significant human exposure improve, these MRLs will be revised. 

The figures in this section were compiled primarily from the tables and figures showing Levels of 

Significant Exposure in ATSDR toxicological profiles. To fill data gaps for some of the fractions, 

pertinent additional health effects information from EPA sources and from the TPHCWG (1997c) 

was included. MADEP also was consulted, but did not appear to provide significant additional 

information for this purpose. (RfCs and RfDs from these sources are reported in Chapter 7.) 
TOTAL PETROLEUM HYDROCARONS 104 

6. HEALTH EFFECTS 

6.2.1 Aromatic EC5-EC9 Indicator Compounds 

This fraction consists of indicator compounds: benzene, toluene, ethylbenzene, and xylene (mixture 

and individual isomers o-, m-, p-). These indicator compounds are often referred to as the BTEXs, 

and are commonly assessed using MRLs (or EPA toxicity values) specific to each compound. 

Styrene also would fall in this fraction, but does not appear to be a significant constituent of the 

petroleum products whose composition was reported by TPHCWG (1997c). The BTEXs are the 

subject of separate ATSDR toxicological profiles (ATSDR 1994, 1995b, 1997a, 1999a); these 

profiles should be consulted for detailed information on these compounds. The information in 

Sections 6.2.1.1 through 6.2.1.3 is taken from these profiles; for the sake of readability, references to 

these ATSDR profiles will not be repeated in these sections. 

6.2.1.1 Inhalation Exposure 

All the BTEXs cause neurological effects. Neurological effects are the basis for MRLs for both 

acute and chronic exposures to toluene and mixed xylenes, and for intermediate exposures to benzene; 

neurological effects are not as sensitive for ethylbenzene. The neurological effects consist primarily 

of central nervous system depression. Toluene’s neurotoxicity also includes ototoxicity. Evidence of 

hearing loss has been seen in both occupationally exposed humans and in animals. There is limited 

evidence that chronic inhalation exposure to benzene may affect the peripheral nervous system; this 

evidence is from a single study of occupationally exposed humans who also had aplastic anemia. 

Benzene is the only BTEX that has well characterized hematological, immunological, and 

lymphoreticular effects in humans and animals at low levels of inhalation exposure. Immunological 

and lymphoreticular effects are the basis for the derivation of the acute inhalation MRL for benzene. 

Benzene affects hematopoiesis, decreasing the production of all major types of blood cells, and can 

also cause hyperplasia. 

Developmental effects are the basis for intermediate MRLs for ethylbenzene and mixed xylene, 

indicating that the embryo/fetus may be particularly sensitive to these two BTEXs. 

Benzene is considered to be carcinogenic to humans by the inhalation route of exposure (EPA weight-ofevidence Group A, human carcinogen). Occupational exposure to benzene was associated with 
TOTAL PETROLEUM HYDROCARONS 105 

6. HEALTH EFFECTS 

increased incidences of nonlymphocytic leukemia. Studies in animals also found increased incidences 

of neoplasia in animals treated by inhalation or gavage with benzene. 

Although ethylbenzene was classified in EPA weight-of-evidence Group D (not classifiable as to 

human carcinogenicity), subsequent publication of a chronic inhalation study of ethylbenzene 

provides evidence of carcinogenicity in rats and mice, and indicates a need for reassessment. Toluene 

and mixed xylene are classified in Group D. 

The lowest reliable LOAEL values for the BTEXs are summarized in Figure is 6-l through 6-4, as 

are MRLs and cancer risk levels. The data for each compound are presented in a separate figure 

because of the voluminous data available for each and because these compounds are commonly 

assessed using the exposure data and MRLs (or EPA toxicity values) specific for each. The data for 

mixed xylene are extensive, and MRLs are available for all three durations, whereas little data and no 

MRLs are available for the individual isomers (o-, m-, and p-). The inhalation toxicity data for the 

individual isomers are reasonably similar to those for the mixture. Accordingly, only the data for 

mixed xylene are included in the figure. More detailed information is available in the ATSDR 

toxicological profiles on the individual compounds (ATSDR 1994, 1995d, 1997a, 1999a), from which the 

information in this section is drawn. 

6.2.1.2 Oral Exposure 

Data for the oral route of exposure are less extensive. The BTEXs cause neurological effects, 

generally central nervous system depression, by the oral route. This is a sensitive effect for toluene 

and p-xylene, for which it is the basis of acute and/or intermediate MRLs. Renal and hepatic effects 

are also seen with oral exposure to these compounds. Renal effects are the basis for the intermediate 

MRL for mixed xylenes and hepatic effects are the basis for the intermediate MRL for m-xylene. The 

hepatic effects tend to be mild, including increased liver weight and cytochromes P-450 and b5 

contents. Benzene causes hematological effects by the oral route that are similar to those seen from 

inhalation exposure. 




TOTAL PETROLEUM HYDROCARONS 110 

6. HEALTH EFFECTS 

Benzene is considered to be carcinogenic (EPA weight-of-evidence Group A) to humans by either 

inhalation or oral exposure, based on occupational studies that showed increased incidences of 

nonlymphocytic leukemia in humans exposed by inhalation, with supporting data from oral and 

inhalation studies in animals. Results of a recently published study of ethylbenzene in animals 

indicate carcinogenicity by the inhalation route, but there is no evidence of carcinogenicity by the oral 

route. Toluene and mixed xylene are classified in EPA weight of evidence Group D (not classifiable 

as to human carcinogenicity). 

The lowest reliable LOAEL values for the BTEXs are summarized in Figures 6-5 through 6-7, as are 

MRLs and cancer risk levels. With the exception of ethylbenzene, the data for each of the BTEXs are 

presented in a separate figure because of the voluminous data available for each and because these 

compounds are commonly assessed using the exposure data and MRLs (or EPA toxicity values) 

specific for each. There are only two pertinent LOAELs and no MRLs for ethylbenzene, so the 

LOAELs for ethylbenzene are plotted with those for toluene, and indicated by a different symbol. 

More detailed information is available in the ATSDR toxicological profiles on the individual 

compounds (ATSDR 1994, 1995d, 1997a, 1999a), from which the information in this section is 

drawn. 

6.2.1.3 Dermal Exposure 

Information on the health effects of dermal exposure to the BTEXs is limited. Skin and eye irritation 

are well documented, but effects from systemic absorption are not. ATSDR (1997a) concluded that it 

is reasonable to expect that adverse hematological and immunological effects might occur following 

dermal exposure to benzene, because benzene is absorbed through the skin and absorption through 

any route would increase the risk of these effects. For more detailed information, see the ATSDR 

toxicological profiles on the individual compounds (ATSDR 1994, 1995d, 1997a, 1999a), from which 

the information in this section is drawn. 

6.2.2 Aromatic EC>9-EC16 Combined Fractions 

EC>9-EC10 fraction: includes cumene (isopropylbenzene), n-propylbenzene, the methyl-ethylbenzenes, some 

trimethylbenzene isomers, and the branched-chain butylbenzenes. None of these 

compounds is the subject of an ATSDR toxicological profile. 



TOTAL PETROLEUM HYDROCARONS 114 

6. HEALTH EFFECTS 

EC>10-EC12 fraction: includes n-butyl and n-pentylbenzene, a trimethylbenzene isomer and
 

various other multi-substituted alkylbenzenes, as well as indan, methylindans and naphthalene. The
 

only compound in this fraction for which an ATSDR toxicological profile is available is naphthalene
 

(ATSDR 1995e).
 

EC>12- EC16 fraction: includes a few longer-chain and multi-substituted alkyl benzenes,
 

biphenyls, the mono- and dimethylnaphthalenes, and PAHs, including acenaphthene and acenaphthylene.
 

The monomethylnaphthalenes (l- and 2-methyl naphthalene) are discussed in the ATSDR
 

toxicological profile on naphthalene (ATSDR 1995e) and acenaphthene and acenaphthylene are
 

included in the ATSDR toxicological profile on PAHs (ATSDR 1995f).
 

6.2.2.1 Inhalation Exposure 

No toxicological profiles are available for petroleum hydrocarbons in the EC>9-EC10 fraction. 

Inhalation exposure to isopropylbenzene (cumene) and to the trimethylbenzene is known to have 

neurological and respiratory irritant effects (EPA 1997a, 1998b; TPHCWG 1997c), but these may 

not be the most sensitive effects of inhalation exposure to the compounds in this fraction. EPA 

(1998b) concluded that the critical effect of inhalation exposure to isopropylbenzene was increased 

renal weights in female rats and increased adrenal weights in both sexes of rats in a 13-week 

inhalation study (Cushman et al. 1995). An RfC was based on these data. Toxicity data for a 

mixture of C9 aromatics, consisting primarily of trimethylbenzene and methylethylbenzene isomers, 

have been assessed (as the basis for an RfC) by the TPHCWG (1997c). The critical effects were 

hepatic and renal. 

Hemolytic anemia is a frequent consequence of acute inhalation exposure to naphthalene in humans, 

particularly infants and those with a G6PD genetic defect. Exposure-effect relationships for 

hemolytic anemia are not well characterized. Ocular effects, including cataracts, have been reported 

in humans exposed to naphthalene vapors, but exposure levels were not known. In mice, respiratory 

effects are a sensitive effect of inhalation exposure to naphthalene. A chronic MRL has been derived 

for naphthalene based on respiratory effects in mice-chronic inflammation and regeneration of the 

nasal epithelium and inflammation of the lung epithelium. In addition, the same study in mice 

reported an increased incidence of lung adenomas in female but not in male mice (ATSDR 1995e). 
TOTAL PETROLEUM HYDROCARONS 115 

6. HEALTH EFFECTS 

The EPA classified naphthalene in Group D (not classifiable as to human carcinogenicity) prior to 

publication of this study, but notes that naphthalene may be more appropriately classified in Group C 

(possible human carcinogen) (EPA 1998b). 

No MRLs have been developed for compounds in the EC>9 –EC16 fraction. Only acenaphthylene has 

been assessed by the EPA for carcinogenicity; the data were considered inadequate (Group D) 

(ATSDR 1995e, 1995f). 

The lowest reliable LOAEL values for the combined aromatic EC>9-EC16 fraction are summarized in 

Figure 6-8, as are MRLs. Because so few of the compounds in this fraction have been assessed by 

ATSDR, additional information from EPA sources and the TPHCWG (1997c) have been added. 

More detailed information is available in the ATSDR toxicological profiles on the individual 

compounds and in the other sources noted above. 

6.2.2.2 Oral Exposure 

There are no toxicological profiles or MRLs for compounds in the EC>9-EC10 fraction. Toxicity data, 

primarily from subchronic oral studies in rats, have been assessed by EPA during the derivation of 

RfDs for two of the compounds-isopropylbenzene (cumene) (EPA 1997a) and 1,3,5-trimethylbenzene 

(EPA 1996). The critical effect for isopropylbenzene was renal; for 1,3,5trimethylbenzene, 

the critical effect was a combination of renal, hepatic, and other systemic effects. Oral data for these 

compounds were limited. Isopropylbenzene has been classified in Group D (not classifiable as to 

human carcinogenicity) (EPA 1998b). 1,3,5-Trimethylbenzene has not been classified and does not 

appear to have been studied for carcinogenicity. 

Naphthalene, a constituent of the EC>10-EC12 fraction, produces hemolytic anemia in humans when 

ingested. As mentioned previously, individuals with a genetic G6PD deficiency have an increased 

susceptibility to this effect. Little dose-effect information is available for this effect in humans or in 

animals; dogs appear to be more susceptible than other animal species. Ocular effects occur with 

high-dose oral administration of naphthalene in animals. The most common effect is cataract 

formation, but retinal damage has also been noted (ATSDR 1995e). More sensitive effects in animals 

are neurological effects (central nervous system depression in pregnant animals) and mild hepatic 

TOTAL PETROLEUM HYDROCARONS 117 

6. HEALTH EFFECTS 

effects (altered microsomal enzyme activities and blood chemistry findings). The EPA classified 

naphthalene in Group D (not classifiable as to human carcinogenicity) prior to publication of an 

inhalation study that reported an increased incidence of pulmonary adenomas in female mice, but 

notes that naphthalene may be more appropriately classified in Group C (possible human carcinogen) 

(EPA 1998b). No studies documenting carcinogenic effects by the oral route were found (ATSDR 

1995e). 

Some of the constituents of the EC>12-EC16 fraction have been evaluated in ATSDR toxicological 

profiles. Although the database for l-methyl naphthalene is very limited, it includes a chronic study 

in mice, which serves as the basis for a MRL (ATSDR 1995e). The only effects seen were 

respiratory (nodular alveolar proteinosis) and hematological (slight increases in hemoglobin 

parameters and elevated monocyte counts). The limited database for acenaphthene indicates that 

hepatic effects may be a sensitive consequence of intermediate exposure in mice; the intermediate 

MRL was based on this finding (ATSDR 1995f). Biphenyl, not included in an ATSDR toxicological 

profile, has been evaluated by EPA (1998b), which derived an RfD based on renal effects in a chronic 

study in rats. Hematological effects (reduced hemoglobin), decreased food intake, and decreased 

longevity also occurred, but renal effects appeared more sensitive. Although the database for this 

compound is limited, it indicates that reproductive and developmental end points are not as sensitive 

as renal. 

Biphenyl (EPA 1998b) and acenaphthylene (ATSDR 199X) have been classified in Group D (not 

classifiable as to human carcinogenicity). 

The lowest reliable LOAEL values and the available MRLs for the combined aromatic EC>9-EC16 

fraction are summarized in Figure 6-9. Because only a few of the compounds in this fraction have 

been assessed by ATSDR, additional information from EPA sources and the TPHCWG (1997c) has 

been added. More detailed information is available in the ATSDR toxicological profiles on the 

individual compounds and in the other sources noted above. 

TOTAL PETROLEUM HYDROCARONS 119 

6. HEALTH EFFECTS 

6.2.2.3 Dermal Exposure 

The compounds in the combined EC>9-EC16 fraction are known to be irritating to the skin, but little 

information is available to suggest systemic toxicity from dermal exposure alone. Naphthalene, 

however, has caused hematological effects in human infants exposed to diapers that had been treated 

with naphthalene moth balls (ATSDR 1995e). 

6.2.3 Aromatic EC>16- EC35 Combined Fractions 

This fraction consists entirely of PAHs. The more environmentally and toxicologically significant
 

PAHs are the subjects of the ATSDR toxicological profile on PAHs (ATSDR 1995f); two of these
 

PAHs, acenaphthene and acenaphthylene, are constituents of the EC>12-EC16 fraction, discussed
 

previously, and the remaining 15 are constituents of the EC>16- EC35 combined fraction, described
 

below.
 

EC>16- EC21 fraction: includes anthracene, fluorene, phenanthrene and pyrene, which are
 

discussed in ATSDR (1995f), and other, less well known PAHs such as substituted fluorenes,
 

anthracenes, and phenanthrenes.
 

EC>21- EC35 fraction: includes benz(a)anthracene; benzo(b)-, benzo(j)-, and benzo(k)fluoranthene;
 

benzo(g,h,i)perylene; benzo(a)- and benzo(e)pyrene; chrysene; dibenz(a,h)anthracene;
 

fluoranthene; and indeno( 1,2,3-c,d)pyrene, which are discussed in ATSDR (1995f), as well as other,
 

less well known PAHs, that include substituted pyrenes, fluorenes, and fluoranthenes.
 

6.2.3.1 Inhalation Exposure 

Little information regarding the inhalation toxicity of PAHs in the EC>16-EC35 combined fraction is 

available, and no inhalation MRLs have been derived. A 4-week study of nose-only inhalation 

exposure of rats to an aerosol of benzo(a)pyrene identified no treatment-related lesions in the 

respiratory tract or the kidneys at the single exposure level tested. Respiratory effects, including 

reduced lung function and abnormal chest X-ray, have been seen in humans exposed occupationally to 

benzo(a)pyrene and particulate matter. Hamsters exposed by inhalation of benzo(a)pyrene particles 

developed respiratory tract tumors (nasal, pharyngeal, laryngeal, and tracheal) (ATSDR 1995f). 
TOTAL PETROLEUM HYDROCARONS 120 

6. HEALTH EFFECTS 

Assessments of carcinogenicity by EPA have placed some of these compounds in EPA Weight-ofEvidence Group B2 (probable human carcinogen) and others in D (not classifiable as to human 

carcinogenicity). These classifications were based on evidence from dermal and parenteral studies, 

and for a few PAHs, oral and inhalation studies, all in animals. See Section 6.2.3.2 and Section 6-6 

for specific information regarding EPA cancer assessments. The compounds in this EC range are not 

volatile (TPHCWG 1997c), so inhalation exposure to any of these PAHs as a result of contamination 

at hazardous waste sites is expected to be minimal under most circumstances. However, people may 

be exposed by inhaling dust or particles containing PAHs, or by inhaling PAHs released to the air, as 

vapors or aerosols, from shower water as a result of contamination of groundwater at hazardous 

waste sites. 

The few available inhalation LOAEL values for the combined aromatic E16-EC35 fraction are 

summarized in Figure 6-10. More detailed information is available in the ATSDR (199%) 

toxicological profile. 

6.2.3.2 Oral Exposure 

Data for oral exposure, while more extensive than for inhalation exposure, are nonetheless limited. 

Hepatic effects appear to be a common sensitive end point of oral exposure to the PAHs in this 

combined fraction. Renal effects have been seen with some (ATSDR 1995f; EPA 1998b). Aplastic 

anemia and immunological/lymphoreticular effects have been seen at higher exposure levels. 

Intermediate oral MRLs are available for two of the compounds in the EC>16 –EC21 fraction, fluorene 

and anthracene, based on subchronic studies in mice. The MRL for fluorene was based on hepatic 

effects (increased liver weight); the MRL for anthracene was based on the absence of any effects, 

including hepatic, in a similar study (ATSDR 1995f). An EPA-sponsored subchronic oral study of 

pyrene in mice was used by that agency as the basis for developing subchronic and chronic RfDs 

(EPA 1997a, 1998b). The critical effect was renal (nephropathy). Hepatic effects were not seen in 

this study, which is the only subchronic or chronic oral toxicity study of pyrene encountered. All four 

of the PAHs in this fraction that have been assessed for carcinogenicity by EPA have been classified 

in EPA Weight-of-Evidence Group D (not classifiable as to human carcinogenicity) (ATSDR 199%). 

TOTAL PETROLEUM HYDROCARONS 122 

6. HEALTH EFFECTS 

The only oral MRL available for compounds in the EC>21- EC35 fraction is an intermediate MRL for 

fluoranthene, based on hepatic effects in mice. The sensitive noncancer effect of oral exposure to 

benzo(a)pyrene is developmental, also determined in animals. 

Studies of the compounds in this fraction have focused primarily on potential carcinogenicity. Of the 

nine compounds in this EC range that have been assessed for carcinogenicity by EPA, seven have 

been classified in Group B2 (probable human carcinogen), and the remaining two, fluoranthene and 

benzo(g,h,i)perylene, in group D (ATSDR 1995f; EPA 1997a, 1998b). The evidence has come in 

large part from parenteral and dermal studies. Oral studies of carcinogenicity have been conducted 

for six of the PAHs in this EC fraction, with positive results for benzo(a)pyrene, benz(a)anthracene, 

and dibenz(a,h)anthracene, and with negative results for anthracene, fluoranthene, and fluorene 

(ATSDR 1995f). 

The lowest reliable LOAEL values and the available MRLs for the combined aromatic EC>16-EC35 

combined fraction are summarized in Figure 6- 11, as are cancer risk levels. Information on pyrene is 

discussed above in this section. Additional information from EPA sources has been added for pyrene. 

More detailed information on the constituents of this fraction is available in the ATSDR (1995f) 

toxicological profile. 

6.2.3.3 Dermal Exposure 

The PAHs tend to be irritating to the skin. In addition, benzo(a)pyrene has been shown to cause 

immunological/lymphoreticular effects evidence as contact hypersensitivity or suppression of this 

response to other sensitizers. The PAHs classified as B2 carcinogens induce skin tumors following 

intermediate dermal application to animals (ATSDR 1995f). 

6.2.4 Aliphatic EC5-EC8 Combined Fractions 

EC5-EC6 Fraction: includes n-pentane, n-hexane, the dimethylbutanes and methylpentanes, 

cyclopentane, and some alkenes. n-Hexane is the only compound in this group that is the subject of 

an ATSDR toxicological profile; some information on commercial hexane (n-hexane plus branched 

and cyclic C6 alkanes) is included in the same toxicological profile (ATSDR 1999b). 

TOTAL PETROLEUM HYDROCARONS 124 

6. HEALTH EFFECTS 

EC>6-EC8 Fraction: includes n-heptane, n-octane, some branched chain C6-C9 alkanes including 

the trimethylpentanes (note that other branched chain C9 alkanes fall in the EC>8 category) and 

cycloalkanes, including cyclohexane, methylcyclopentane, and methylcyclohexane, as well as some 

alkenes. None of these is the subject of an ATSDR toxicological profile. 

6.2.4.1 Inhalation Exposure 

Inhalation exposure for acute, intermediate or chronic durations to n-hexane causes peripheral 

neuropathy in humans and animals (ATSDR 1999b). The chronic MRL for n-hexane is based on this 

effect in humans. Respiratory and renal effects have been seen in animals exposed to n-hexane by 

inhalation at higher exposure levels than associated with peripheral neuropathy in the same studies. 

Calculation of human equivalent concentrations (HECs) using EPA dosimetric methodology, however, 

indicates that respiratory effects were seen in mice exposed subchronically to n-hexane at a HEC 

similar to that for neurological effects in the human study used as the basis for the chronic MRL 

(EPA 1998b). Thus, respiratory effects also may be sensitive, although confirmation of this in human 

studies is not available. The other compounds in the EC5-EC6 fraction do not appear to cause 

peripheral neuropathy (ATSDR 1999b; TPHCWG 1997c). Depression of the central nervous system 

has been seen at relatively high levels of exposure to n-hexane. n-Hexane has been classified as in 

weight-of-evidence Group D (not classifiable as to human carcinogenicity) (EPA 1989a). 

Commercial hexane, which consists of a mixture of C6 aliphatic compounds including 20-80% 

n-hexane and other straight, branched, and cyclic alkanes in the range of EC5.68-EC6.59,has been the 

subject of extensive recent testing as part of a EPA Test Rule under TSCA Section 4. Commercial 

hexane mixtures have the potential to represent the toxicity of the EC5-EC8 combined fraction better 

than any single compound. The non n-hexane components of commercial hexane, when tested 

separately as a mixture, do not cause peripheral neuropathy, whereas the commercial mixture 

containing n-hexane has been demonstrated to cause peripheral neuropathy in one study in rats 

(ATSDR 1999b; IRDC 1981). The commercial hexane mixtures tested under the Test Rule contained 

53% n-hexane, 16% 3-methylpentane, 14% methylcyclopentane, 12% 2-methylpentane, 3% 

cyclohexane, 1% 2,3-dimethylbutane, and <1% other constituents. According to the TPHCWG 

(1997c), which developed an RfC for commercial hexane based on preliminary reports of these 

unpublished studies, the critical effects were respiratory (mucosal irritation in nasal turbinates and 
TOTAL PETROLEUM HYDROCARONS 125 

6. HEALTH EFFECTS 

larynx in rats) and reproductive (decreased severity and incidence of cystic uterine endometrial 

hyperplasia in mice) in chronic studies. In addition, liver tumors developed in the female mice, 

indicating carcinogenic potential. 

Cyclohexane also has undergone testing under EPA TSCA Section 4. The TPHCWG (1997c) 

summarized the preliminary report of the developmental toxicity study in rats, which indicates 

neurological effects (reduced response to a sound stimulus) in the dams exposed to cyclohexane by 

inhalation. Hepatic and renal effects were seen in published subchronic studies in animals. No 

histopathological changes in the peripheral nervous system were seen in a chronic study in animals 

(TPHCWG 1997c). 

Two additional chemicals in the E>6-EC8 fraction that have been the subject of limited toxicity 

testing are n-heptane and methylcyclohexane. Both appear to cause depression of the central nervous 

system following relatively high inhalation exposures (EPA 1989b, 1989c). n-Heptane was suspected 

to have the potential to cause peripheral neuropathy because of its structural similarity to n-hexane 

and because it is metabolized, although to a much lesser extent, to the same type of metabolite (a 

γ-diketone) as is thought to mediate the neurotoxicity of n-hexane. The available human occupational 

and animal experimental studies, however, give no clear evidence that n-heptane causes peripheral 

neuropathy (EPA 1989b). Methylcyclohexane caused renal effects (medullary mineralization and 

papillary hyperplasia) in male but not in female rats or in other species exposed for 1 year by 

inhalation followed by an observation period; this study is the basis for an RfC derived by EPA 

(1997a). The renal effect appears to be associated with α2μ-globulin nephropathy and, therefore, may 

be of questionable significance to human health. Both these compounds have been classified in Group 

D (not classified as to human carcinogenicity) (EPA 1989c, 1998b). 

The lowest reliable LOAEL values for n-hexane are summarized in Figure 6-12, along with the 

available MRL. Because so few of the compounds in this fraction have been assessed by ATSDR, 

limited additional information from EPA sources and the TPHCWG (1997c) regarding commercial 

hexane, cyclohexane, and methylcyclohexane has been added. More detailed information is available 

in ATSDR (1997c) and the EPA and TPHCWG sources noted above. 

TOTAL PETROLEUM HYDROCARONS 127 

6. HEALTH EFFECTS 

6.2.4.2 Oral Exposure 

Oral health effects information for the EC5-EC6 fraction is limited and is available mainly for 

n-hexane. n-Hexane caused peripheral neuropathy in rats given the compound subchronically and in 

chickens given the compound acutely and subchronically. The chicken is considered to be a valuable 

model for human neurotoxicity of this type. 2-Methylpentane and methylcyclopentane affected nerve 

conduction velocity in a subchronic study in rats, but were not as effective as n-hexane in that same 

study. Reproductive (testicular) and developmental effects have been seen in animals at higher doses 

of n-hexane than associated with neurological effects. No oral MRLs were derived for n-hexane 

because of the incompleteness of the database (ATSDR 1999b). n-Hexane has been classified as a 

Group D agent (not classifiable as to human carcinogenicity) (EPA 1989a). 

An oral 90-120-day study in rats of a commercial hexane containing 40% n-hexane, 24% each of 

3-methylpentane and dimethylbutane, 9% cyclopentane, 2.5% cyclohexane, and 12% 2-methylpentane 

was conducted in comparison with n-hexane. This mixture includes compounds in both the EC5-EC6 

and EC>5-EC8 range. Peripheral neuropathy was not seen when commercial hexane was tested at the 

same dose as was effective for pure n-hexane (ATSDR 1999b), but the dose of n-hexane resulting 

from this dose of commercial mixture was only 40% the effective dose of the pure n-hexane. Some 

evidence of carcinogenic potential has been reported in chronic inhalation studies in mice, as 

discussed in the previous section. 

The lowest reliable LOAELs for n-hexane are plotted in Figure 6- 13. More detailed information, 

including some information on oral toxicity of related isomers and commercial hexane, is available in 

ATSDR (1997c). 

6.2.4.3 Dermal Exposure 

Some of the compounds in the combined EC>9-EC16 fraction are known to be irritating to the skin and 

eyes, but little information is available to suggest systemic toxicity from dermal exposure. 

TOTAL PETROLEUM HYDROCARONS 129 

6. HEALTH EFFECTS 

6.2.5 Aliphatic EC>8- EC16 Combined Fractions 

EC>8-EC10 fraction: includes n-nonane, n-decane, branched-chain C9 -C10, compounds, a few 

substituted cycloalkanes, and a few alkenes 

EC>10- EC12 fraction: includes n-undecane, n-dodecane, and pentylcyclopentane 

EC>12- EC16fraction: n-tri-, tetra-, penta-, and hexadecane (Note that EC values for a number of 

branched and cyclic alkanes that potentially belong in these fractions were not listed by the TPHCWG 

[1997c1; see Appendix D: Table D-l for listing). 

None of the individual compounds in the combined aliphatic EC>8-EC16 fraction is the subject of an 

ATSDR toxicological profile. Some petroleum products, however, are mixtures primarily of aliphatic 

hydrocarbons in the range covered by this fraction. The TPHCWG (1997c) identifies JP-8 jet fuel as 

a mixture containing aliphatic petroleum hydrocarbons ranging from C9-C16 and ATSDR has 

developed a toxicological profile on JP-8 (ATSDR 1998b). JP-8 contains up to 20% aromatics 

(C10-C11, EC10.5-EC12.99) (ATSDR 1998b; TPHCWG 1997b). Other petroleum products that are 

composed primarily of C9 -C16, aliphatics are JP-5, JP-7, and kerosene (fuel oil #l). These fuels also 

are the subjects of ATSDR toxicological profiles, and have at least one MRL (ATSDR 1995c, 1995g, 

1998b). They contain approximately 16%, a maximum of 5%, and approximately 24% aromatic 

hydrocarbons, respectively. The jet fuels contain a number of additives such as antioxidants, metal 

deactivators, fuel system icing inhibitors, corrosion inhibitors, and static dissipaters. Stoddard 

solvent contains primarily C9-C16, aliphatics, with approximately 14% aromatics, and is also the 

subject of an ATSDR toxicological profile, but has no MRLs (ATSDR 1995b). 

TPHCWG (1997c) also identifies a number of published and unpublished studies on dearomatized 

petroleum streams that correspond to portions of this range, and that contain at most 1.5% aromatics 

and more typically less than 0.1% aromatics. These studies on dearomatized petroleumstreams 

would appear to be a better basis for the assessment of health effects of this fraction, because they 

contain much smaller amounts of aromatics than do the petroleum products discussed in the previous 

paragraph and no additives. Their exact compositions and EC ranges were not reported, but EC 

numbers for the aliphatics tend to be close to the actual carbon numbers. 
TOTAL PETROLEUM HYDROCARONS 130 

6. HEALTH EFFECTS 

6.2.5.1 Inhalation Exposure 

Hepatic effects are the most sensitive end points for inhalation exposure to JP-5, JP-7, JP-8, and 

kerosene (ATSDR 1995c, 199.58, 1998b). The available intermediate and chronic MRLs for these 

fuels are based on hepatic effects in animals. Neurological effects, particularly central nervous 

depression, have been seen in humans exposed acutely to JP-5 vapors, but exposure-effect 

relationships have not been established. Male rat α2μ-globulin nephropathy occurred with exposure to 

JP-5 and JP-7, but this effect is not considered relevant to humans. A l-year exposure to JP-7 

produced a small increase in the incidence of C-cell adenomas and kidney adenomas in male rats 

exposed to the vapor; the kidney adenomas may have been related to male rat α2μ-globulin 

nephropathy, an effect with questionable relevance to human health. 

The inhalation studies of dearomatized petroleum streams included a C10-C11 isoparaffinic solvent 

(branched chain alkanes), and C7-C11 dearomatized white spirit (branched, straight and cyclic 

alkanes). Subchronic toxicity studies of these streams reported male rat nephropathy of the type that 

is of questionable relevance to humans health, according to the TPHCWG (1997c). In addition, 

increased liver weights were observed in male rats, but were said to be not significant. 

Developmental toxicity studies of these streams in rats revealed no developmental or maternal toxicity 

at the same exposure levels. These unpublished studies have been used as the basis for RfCs by the 

TPHCWG (1997c). 

The lowest reliable LOAEL values for the jet fuels and kerosene discussed in this section are 

summarized in Figure 6-14, along with the available MRLs. Because these products have a 

significant aromatic component, limited additional information from the TPHCWG (1997c) regarding 

dearomatized petroleum streams has been added. More detailed information is available in the 

ATSDR toxicological profiles and the TPHCWG source noted above. 

6.2.5.2 Oral Exposure 

Oral data regarding JP-5, JP-7, JP-8, and kerosene were limited and judged inadequate for MRL 

development (ATSDR 19958, 1995c, 1998b). Hepatic effects and neurological effects have been seen 

from acute-duration oral exposure, but dose-effect relationships are either not well defined, or effects 

occurred at doses that also were fatal. Male rat nephropathy and decreased body weight were seen in 

TOTAL PETROLEUM HYDROCARONS 132 

6. HEALTH EFFECTS 

a 90-day oral study of JP-8 in male rats (Mattie et al. 1995) that was used by the TPHCWG (1997c) 

as the basis for an RfD, but ATSDR declined to derive an intermediate oral MRL because of the 

general lack of data and limitations of this study. 

Subchronic studies of the dearomatized petroleum streams in rats were conducted on C9-C12, and 

C10-C13 dearomatized aliphatic mixtures containing branched, straight, and cyclic alkanes, and a 

C11-C17 isoparaffinic solvent containing branched and cyclic alkanes. Two of these studies reported 

male rat nephropathy. All three studies reported hepatic effects including hepatocellular hypertrophy 

and increased liver weight. Developmental toxicity was not seen at the same doses in a study of a 

similar mixture in rats. These unpublished subchronic studies were used as the basis for RfDs by the 

TPHCWG (1997c). 

The lowest reliable LOAEL values for the jet fuels and kerosene discussed in this section are 

summarized in Figure 6-15. Because these products have a significant aromatic component, limited 

additional information from the TPHCWG (1997c) regarding dearomatized petroleum streams has 

been added. More detailed information is available in the ATSDR toxicological profiles, the 

TPHCWG source noted above, and Section 6.3. 

6.2.5.3 Dermal Exposure 

Information on the health effects of dermal exposure to JP-5, JP-7, and JP-8, and kerosene is limited. 

Skin and eye irritation are well documented, but effects from systemic absorption are not (ATSDR 

1995c, 19958, 1998b). 

6.2.6 Aliphatic EC>16-EC35 Combined Fractions 

EC>16-EC21 fraction: includes n-hepta-, n-octa-, and n-nonadecane; and n-eicosadecane 

EC>21-EC35 fraction: includes n-heneicosane, n-docosane, n-tetracosane, and n-hexacosane. 

(Note that aliphatic compounds other than the above straight-chain alkanes were not listed by the 

TPHCWG [ 1997b] as constituents of petroleum and petroleum-based fuels that are the focus of the 

fraction-selection approach. See Appendix D, Table D-l.) Petroleum products such as mineral-based 

crankcase oil and mineral-based hydraulic fluids, however, contain branched and cyclic 

TOTAL PETROLEUM HYDROCARONS 134 

6. HEALTH EFFECTS 

aliphatics within these equivalent carbon ranges, as do food-grade and medicinal-grade mineral oils. 

Although ATSDR toxicological profiles are available for mineral-based used crankcase oil and 

mineral-based hydraulic fluids (ATSDR 1997b, 1997c), these products contain additives and 

contaminants, including substantial levels of aromatics and metals (used crankcase oil) and 

organophosphate esters (hydraulic fluids). Little information is available regarding health effects of 

these products. No MRLs have been derived. The TPHCWG (1997c) has reviewed data regarding 

food and medicinal grade mineral oils, which are relatively pure and therefore a better choice to 

represent this fraction. 

6.2.6.1 Inhalation Exposure 

No information was located on the potential health effects of inhalation exposure to compounds or 

mixtures of petroleum hydrocarbons that fall within this fraction. 

6.2.6.2 Oral Exposure 

Purified mineral oils have been used medicinally and in foods. Subchronic toxicity studies of selected 

mixtures of mineral oil hydrocarbons (composed primarily of branched chain alkanes or cyclic 

alkanes) in F344 rats have identified the liver and the mesenteric lymph nodes as potential targets of 

toxicity for these mineral oils. The TPHCWG (1997c) derived chronic RfDs for low and high 

molecular weight mineral oils based on the hepatic effects (lipid granulomas) seen in these studies. 

The effect on the mesenteric lymph nodes (histiocytosis), which occurred at lower exposure levels 

than did the hepatic effects, was judged a nonadverse, adaptive response to the ingestion of foreign 

material (TPHCWG 1997c). Subchronic oral toxicity testing has also been conducted with low- and 

intermediate-molecular weight paraffin waxes, which contain a high proportion of straight chain 

alkanes and also branched alkanes and small amounts of cyclic alkanes, with C ranges primarily 

within this fraction range (Smith et al. 1996). Results indicate that these mixtures have toxicity 

similar to that of the oils for which the RfDs were derived. Strains of rats other than F344 appeared 

to be less sensitive to these mixtures. 

Hepatic lipid granulomas have also been seen in humans exposed to mineral oils through the diet and 

by ingestion of medicinal mineral oils, but doses associated with the effect in humans are not known. 

According to TPHCWG (1997c), the granulomas in humans were circumscribed lesions with no 
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6. HEALTH EFFECTS 

inflammation, fibrosis, or significant liver dysfunction, whereas the granulomas in F344 rats were 

reactive with associated inflammation and occasional parenchymal cell necrosis. 

The LOAELs identified for the “low” molecular weight mineral oils (C16-C35) are plotted in 

Figure 6-16. Additional information on health effects is provided in the review by TPHCWG 

(1997c). 

6.2.6.3 Dermal Exposure 

Information regarding health effects of dermal exposure to this fraction was not encountered in the 

cited source (TPHCWG 1997c). 

6.3 DISCUSSION OF HEALTH EFFECTS FOR WHOLE PETROLEUM PRODUCTS 

Whole petroleum products are generally complex mixtures of hydrocarbons of varying carbon number 

and additives (usually representing a smaller weight percentage of the whole mixture) of varying 

chemical identities that are added to impart special qualities or enhance particular functional 

properties of the whole petroleum product. Additional impurities may be generated during use of the 

product. Non-hydrocarbon additives and impurities are not included in the definition of TPH. 

Toxicological information on important petroleum products that are the subjects of other ATSDR 

toxicological profiles, and on other petroleum products that are the subject of assessment by other 

agencies, is briefly reviewed in this section. Such information may be useful in characterizing acute 

exposure to fresh spills of petroleum products, but its usefulness is limited because of the limited 

availability of MRLs, the variability in the composition of petroleum products, and the change in 

composition due to environmental fate and transport processes. The whole petroleum products that 

have compositions similar to the transport fractions have been discussed in Section 6.2. 

6.3.1 Jet Fuels 

Jet fuels are middle distillates of petroleum crude oils that are composed of hydrocarbons generally 

coming off distillation columns at temperatures between 150 and 300 oC (ATSDR 1998b; IARC 

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6. HEALTH EFFECTS 

1989c). Kerosene-type jet fuels such as JP-5, JP-7, and JP-8 have the same basic composition as 

kerosene (consisting predominately of hydrocarbons with carbon numbers in the range of C9-C16), 

whereas “wide-cut” jet fuels such as JP-4 are blends of kerosene and lower-boiling naphtha streams 

(C4-C16). Jet fuels are refined under more stringent conditions than kerosene and contain various 

additives (anti-oxidants, dispersants and/or corrosion inhibitors) not found in kerosene. The exact 

chemical composition varies depending on the source of crude oil and additives included in the 

formulated product. Generally, aliphatic hydrocarbons represent the major part and aromatic 

hydrocarbons represent about 10-20% of kerosene and jet fuels. The benzene content of kerosenetype 

jet fuels is generally <0.02%, whereas “wide-cut” jet fuels typically contain more benzene 

(normally <0.5%). PAHs, with boiling points above 300 oC, are generally excluded from jet fuels 

and kerosene. 

Health effects of concern from exposure to jet fuels include eye and skin irritation from acute direct 

contact; respiratory, neurotoxic and gastrointestinal effects from acute accidental ingestion; and 

possible hepatic damage from inhalation exposure of intermediate duration as indicated by results 

from animal studies (ATSDR 1998b). 

ATSDR (1998b) derived an intermediate-duration inhalation MRL of 3 mg/m3

 for jet fuels JP-5 and 

JP-8, based on a LOAEL for hepatocellular fatty changes and vacuolization in mice exposed 

continuously for 90 days to vapors of JP-5 at a concentration of 150 mg/m3

 (Gaworski et al. 1984). 

The exposure concentration was converted to a human equivalent exposure concentration (853 mg/m3

) 

by multiplying by the ratio of the alveolar ventilation rate divided by the body weight of mice to the 

same parameters for humans. The human equivalent concentration was divided by an uncertainty 

factor of 300 (10 for interspecies variability, 3 for intraspecies variability, and 10 for the use of a 

LOAEL) to derive the MRL. 

ATSDR (1998b) derived no other MRLs for JP-5 or JP-8 (e.g., for acute or chronic inhalation 

exposures, or for oral exposures of any duration), due to the lack of data suitable for MRL 

derivation. 

ATSDR (1995c) derived an intermediate-duration inhalation MRL of 9 mg/m3

 for JP-4 based on a 

LOAEL of 500 mg/m3

 for hepatic fatty degeneration in mice exposed continuously to the vapor for 
TOTAL PETROLEUM HYDROCARONS 138 

6. HEALTH EFFECTS 

90 days. The MRL was derived from this LOAEL by dosimetrically adjusting to a human equivalent 

concentration and applying an uncertainty factor of 300 (10 for the use of a LOAEL, 3 for interspecies 

extrapolation, and 10 for human variability). ATSDR (199%) derived a chronic-duration 

inhalation MRL of 0.3 mg/m3

 for JP-7, based on a LOAEL of 150 mg/m3 for hepatic inflammation in 

rats exposed to the vapor (6 hours/day, 5 days/week) for 1 year and observed for an additional year. 

The MRL was calculated from this LOAEL by dosimetrically adjusting to a human equivalent 

continuous exposure concentration and applying an uncertainty factor of 300 (10 for the use of a 

LOAEL, 3 for interspecies extrapolation, and 10 for human variability). 

ATSDR (199%) derived no other MRLs for jet fuels JP-4 and JP-7, due to the lack of additional 

suitable inhalation data and the absence of data for oral exposure to these jet fuels. 

ATSDR (1995c) found no studies regarding cancer in humans exposed to the jet fuels JP-4 and JP-7. 

Inhalation animal studies provided no evidence that JP-7 was carcinogenic (Air Force 1991). A 

l-year study of rats and mice exposed by inhalation to vapors of JP-4 was identified in which 

increased tumors were found in the respiratory tract of female rats and mice, increased renal tumors 

(associated with the α2μ-globulin nephropathy syndrome) were found only in male rats, and increased 

liver tumors were found in female, but not male mice (Bruner et al. 1993). ATSDR (1995c) 

concluded that the animal data provided equivocal evidence for the carcinogenicity of JP-4 and that 

there was insufficient evidence to draw conclusions regarding the carcinogenic potential of JP-4 or 

JP-7 in humans. 

ATSDR (1998b) concluded from a review of several studies of mice dermally exposed to jet fuels 

(including JP-5 and Jet A) that chronic dermal application of jet fuels can act as a skin carcinogen, 

but noted that further investigation is needed to more fully elucidate “the impact of dermal exposure 

of jet fuels on humans.” 

IARC (1989d) concluded that there was inadequate evidence for the carcinogenicity of jet fuel in 

humans and animals, but noted that there is limited evidence for the carcinogenicity in experimental 

animals of straight-run kerosene and hydrotreated kerosene. IARC’s review included: a cohort 

mortality study that found no increased cancer risk in men exposed to jet fuel, aviation kerosene, and 

other fuels in the Swedish Air Force; elevated risk for kidney cancer in men exposed to jet fuel in a 
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6. HEALTH EFFECTS 

Canadian case-control study; and both positive and negative findings for skin cancer in studies of 

mice dermally exposed to jet fuels. 

6.3.2 Fuel Oils 

Fuel oils refined from crude petroleum can be classified either as distillate fuels consisting 

predominately of distilled process streams or as residual fuels consisting of residues remaining after 

distillation or blends of residues and distillates (ATSDR 19958; IARC 1989b). Both types of fuel 

oils are complex mixtures of aliphatic hydrocarbons (representing approximately 80-90% of these 

oils) and aromatic hydrocarbons (representing 10-20%). Light distillate fuels (e.g., fuel oil #l, 

straight-run kerosene) consist primarily of hydrocarbons in the C9-C16, whereas hydrocarbons in 

middle distillate fuels (e.g., fuel oil #2) may range from approximately C11-C20. Diesel fuels are 

similar to fuel oils with the exception that the diesel fuels contain additives. Light and middle 

distillate fuels generally contain less than 5% polycyclic aromatic hydrocarbons. Heavier fuel oils 

(e.g., fuel oil #4 and marine diesel fuel) may contain up to 15% distillation residues and more than 

5% polycyclic aromatic hydrocarbons. Residual fuel oils are more complex in composition than 

distillate fuels, and can contain significant portions of compounds with sulfur and nitrogen. 

Reports of cases of accidental ingestion of kerosene identify respiratory effects (e.g., pulmonary 

edema and difficulty in breathing from aspiring the liquid into the lungs), nervous system depression, 

and gastrointestinal irritation as effects of concern from acute exposure to fuel oils (ATSDR 1995g). 

These effects (and others including skin and eye irritation, and increased blood pressure) have been 

observed in humans in a few cases after inhalation and/or dermal acute exposures. Animal studies 

provide supporting data for neurological impairment from acute inhalation exposure to fuel oil #2 and 

hepatic effects (including decreased blood glucose levels and hepatocellular fatty changes and 

vacuolization) from intermediate-duration exposure to fuel oil #l and jet fuel JP-5. 

ATSDR (19958) derived an acute-duration inhalation MRL of 0.02 mg/m3

 for diesel fuel (fuel oil #2) 

based on observations of mild transient ataxia and disturbed gait in mice exposed for 8 hours/day for 

5 days to vapors of diesel fuel #2 at concentrations as low as 65 mg/m3

 (Kainz and White 1984). The 

LOAEL was adjusted to a continuous exposure basis and divided by an uncertainty factor of 1,000 

(10 for intraspecies variability, 10 for interspecies variability, and 10 for the use of a LOAEL). 

ATSDR (1995g) did not discuss the potential applicability of this MRL to other fuel oils. 
TOTAL PETROLEUM HYDROCARONS 140 

6. HEALTH EFFECTS 

ATSDR (19958) derived an intermediate-duration MRL of 0.01 mg/m3 for kerosene (also called fuel 

oil #l) based on a LOAEL for decreased blood glucose levels (thought to be indicative of hepatic 

effects) in rats exposed 6 hours/day, 6 days/week for 14 weeks to fuel oil #l at concentrations of 

58 mg/m3

 (Starek and Vojtisek 1986). The LOAEL was adjusted to a continuous exposure basis and 

divided by an uncertainty factor of 1,000 (10 for intraspecies variability, 10 for interspecies 

variability, and 10 for the use of a LOAEL). ATSDR (19958) did not discuss the potential 

applicability of this MRL to other fuel oils, but cited, as supporting data for the MRL, findings of 

hepatocellular changes and vacuolization in mice exposed continuously to 150 mg/m3

 IP-5 for 

90 days, and findings of no systemic or neurological effects in rats or dogs exposed to a deodorized 

kerosene concentration of 100 mg/m3

, 6 hours/day, 5 days/week for 13 weeks. 

ATSDR (1995g) did not derive chronic inhalation MRLs or any oral MRLs (for any duration of 

exposure) because suitable data were not available. 

From a review of available human and animal studies, ATSDR (1995g) concluded that epidemiological 

studies have provided “only equivocal evidence of an association between cancer and 

exposures to fuel oils” and that animal studies suggest that dermal exposure to fuel oils can produce 

skin or liver cancer. ATSDR (1995g) noted that the animal studies are restricted to one species 

(mice) and not all studies found carcinogenic responses. The conclusion was drawn that “further 

investigation utilizing other species is required to more fully elucidate the mechanism of dermal 

carcinogenesis and the impact of dermal exposure of fuel oils on humans.” 

Based on their review, IARC (1989b) concluded that there was inadequate evidence for the carcinogenicity 

in humans of fuel oils; sufficient evidence for the carcinogenicity in experimental animals of 

residual (heavy) fuel oils; limited evidence for the carcinogenicity in experimental animals of fuel oil 

#2; sufficient evidence for the carcinogenicity in experimental animals of light and heavy catalytically 

cracked distillates, of light and heavy vacuum distillates and of cracked residues, all derived from the 

refining of crude oil; and limited evidence for the carcinogenicity in experimental animals of straight-run 

kerosene. Overall evaluations were made that residual (heavy) fuel oils are possibly carcinogenic 

to humans (Group 2B), and that distillate (light) fuel oils are not classifiable as to their carcinogenicity 

to humans (Group 3). 
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6. HEALTH EFFECTS 

6.3.3 Automotive Gasoline 

Gasoline is a complex mixture of volatile petroleum-derived hydrocarbons, additives, and blending 

agents (ATSDR 1995a; IARC 1989a). The composition of gasoline varies widely depending on the 

composition of the crude oil from which it is refined, the refining processes used, the type and relative 

amount of different petroleum refining streams blended in the finished product, and the types and 

amounts of nonhydrocarbon compounds added to enhance or impart specific functional properties of 

the gasoline. Specific market conditions, partly in response to regulations, mandate the refining and 

manufacturing of certain gasolines. Gasoline contains predominately hydrocarbons in the C4-C12 

range, with the following typical distributions: alkanes (4-8 wt%); alkenes (2-5 wt%); isoalkanes 

(25-40 wt%); cycloalkanes (3-7 wt%); cycloalkenes (l-4 wt%); and total aromatics (20-50 wt%). 

The benzene content of gasoline is 0.12-3.5% (see Table E-l .b for additional detail regarding 

individual hydrocarbon constituents). Additives found in gasoline include anti-knock agents (e.g., 

tetraethyllead), lead scavengers (e.g., 1,2-dibromoethane), detergents, anti-rust agents (e.g., 

sulfonates), antioxidants (e.g., p-phenylenediamine), and anti-icing agents (e.g., alcohols). Leaded 

gasoline is no longer allowed to be used by on-road vehicles, though it still is used in farm machinery 

boats, competetive vehicles, and in piston engine airplanes. (EPA 1998d). A variety of products are 

added to gasoline to boost octane, including ethanol and MTBE. 

Acute-duration inhalation, oral, or dermal exposures to gasoline have been associated with irritation 

at portals of entry in humans, and high-level inhalation or oral acute exposure produces symptoms of 

transient neurological impairment such as headache, nausea, dizziness, euphoria, and drowsiness 

(ATSDR 1995a). Acute ingestion of large amounts of gasoline also produces respiratory effects such 

as pneumonitis and pulmonary edema due to the aspiration of gasoline. Chronic exposure to gasoline 

vapors by intentional inhalation also has been associated with symptoms providing evidence for more 

permanent neurological damage in humans such as postural tremor, abnormal gait, and affected 

speech. The relative degrees to which hydrocarbons and additives such as lead contribute to gasoline-induced 

neurological impairment are unknown. Studies with rats and mice with chronic inhalation 

exposure to gasoline vapors have found hepatocellular tumors in female mice, and α2μ-globulin 

nephropathy and related renal tumors in male rats. The renal tumors are believed to be unique to 

male rats and of questionable relevance to humans. 

ATSDR (1995a) derived no inhalation or oral MRLs for gasoline, “because of the variability in the 

composition of gasoline;” the toxicity would depend on the specific composition. ATSDR (1995a) 
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6. HEALTH EFFECTS 

also commented, regarding oral exposure, that there is no “quantitative information on adverse effects 

other than α2μ-globulin nephropathy in male rats,” an end point that is considered “not relevant to 

human risk assessment.” 

Numerous epidemiology studies have examined possible relationships between exposure to gasoline 

and development of various types of cancer in humans, but none of the studies were adequate to 

conclusively demonstrate that exposure to gasoline causes cancer in humans (ATSDR 1995a). The 

most common problems with these studies were the failure to adequately characterize exposure and 

the failure to control for confounding exposures to other fuels and exhaust emissions. In a chronic 

inhalation study, exposure to whole vapors of unleaded gasoline produced an increased incidence of 

renal tumors in male rats and liver tumors in female mice (MacFarland et al. 1984b). The renal 

tumors in male rats were considered to arise as a result of a process involving α2μ-globulin 

accumulation, a process not expected to occur in humans. ATSDR (1995a) further questioned the 

relevance of the MacFarland findings, because the animals were exposed to whole vapors of gasoline 

and “gasoline emissions found in the environment contain lower concentrations of hydrocarbons with 

very low vapor pressures” than those found in whole vapors of gasoline. 

EPA (1987c) classified gasoline as a Group B2 compound, a probable human carcinogen, based on 

inadequate evidence of carcinogenicity in humans and sufficient evidence in animals. This evaluation 

was made before EPA adopted a policy excluding α2μ-globulin-related renal tumors in male rats from 

cancer weight-of-evidence classifications. EPA derived an inhalation unit risk of 2.1x10-3 ppm for 

gasoline based on an analysis of tumor incidence data for hepatocellular adenomas and carcinomas in 

female mice exposed to unleaded gasoline vapors for 2 years (MacFarland et al. 1984b). EPA has 

not published a more recent classification for gasoline. 

IARC (1989a) concluded that there was inadequate evidence for carcinogenicity of gasoline in 

humans and limited evidence for carcinogenicity of unleaded automotive gasoline in experimental 

animals (the evidence in MacFarland et al. [1984a]). IARC (1989a) classified gasoline-as “possibly 

carcinogenic to humans (Group 2B),” based on the preceding conclusions and supporting data 

showing that gasoline induces unscheduled DNA synthesis in mice in vivo and in mouse, rat and 

human hepatocytes in vitro; that light, straight-run naphtha and light catalytically cracked naphtha 

petroleum refinery streams used to blend gasoline produce skin tumors in dermally exposed mice; ant 

that gasoline components such as benzene and 1,3-butadiene are known or suspected carcinogens. 
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6. HEALTH EFFECTS 

6.3.4 Various Petroleum Refinery Streams 

A number of health effects studies in animals of petroleum streams that correspond with the transport 

fractions have been reviewed by the TPHCWG (1997c); however, most of these are unpublished 

industry studies. 

6.3.5 Stoddard Solvent 

Stoddard solvent is a petroleum distillate mixture of C7-Cl2 hydrocarbons, approximately 80-90% 

aliphatics (30-50% linear and branched alkanes, and 30-40% cyclic alkanes) and l0-20% aromatics 

(not PAHs). It is similar to white spirits, which is also included in the toxicological profile on 

Stoddard solvent (ATSDR 1995b). For additional detail, see Section 3.2 and Table E-2.b. Data 

regarding the health effects of Stoddard solvent in either humans or animals are limited and were 

judged inadequate for MRL development. Upper respiratory irritant effects were seen in animals 

exposed by inhalation for acute and intermediate durations; these appear to be the most sensitive 

effects by the inhalation route. Male rat nephropathy has been reported in intermediate inhalation 

studies, but is not considered relevant to human health. No oral studies were located. Information on 

the potential carcinogenicity of Stoddard solvent is inadequate. 

6.3.6 Mineral-Based Crankcase Oil 

Mineral-based crankcase oil is a petroleum product that is a complex mixture of low and high 

molecular weight (C15-C50) aliphatic and aromatic hydrocarbons, metals, and additives. The chemical 

composition of mineral-based crankcase oil varies widely, depending on the original crude oil, the 

processes used in refining, the types of additives included in the oil, the efficiency and type of engine 

in which it is used, the type of fuel used in the engine, and the length of time the oil was used in an 

engine. The hydrocarbon constituents are mainly straight and branched chain alkanes, cycloalkanes, 

and aromatics (see Table E-5.b for additional detail). Additives (which can account for-up to 20% of 

the weight of oil formulations) include detergents, metallic salts (e.g., molybdenum and zinc salts), 

and organometallic compounds. Metals (e.g., cadmium, lead and zinc) and PAHs have been 

demonstrated to increase in oil with continued use in an engine. 
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6. HEALTH EFFECTS 

Studies examining petroleum-stream stocks used to formulate mineral-based crankcase oil indicate that 

these stocks are nontoxic relative to used crankcase oils; therefore, the toxicity of used oils has been 

attributed to additives present in the oil or to decomposition products or contaminants that accumulate in 

the oil with use (ATSDR 1997c). Studies of mechanics and auto-workers exposed to used mineral-based 

crankcase oil found elevated incidence of skin rashes, anemia, headaches and tremors, but these studies do 

not establish a causal relationship with exposure to used crankcase oil, due to several limitations of the 

studies including the likelihood that the workers were exposed to other chemicals which may have caused 

the effects. There are only a few toxicological studies of animals exposed to mineral-based crankcase oil. 

Acute exposures to mists of used mineral-based crankcase oil were irritating to the eyes and upper 

respiratory tract of some volunteer human subjects. Studies of rats ingesting large single doses 

(9,000-22,500 mg/kg) of used mineral-based crankcase oil found no adverse health effects other than 

diarrhea. Cattle that ingested an unknown amount of used mineral-based crankcase oil while grazing in 

contaminated pastures exhibited several health effects including death, anemia, and neurological 

dysfunction; it was postulated that the observed effects were caused by metals (molybdenum and lead) in 

the oil. Long-term dermal application of used mineral-based crankcase oil to the skin of mice produced an 

increased incidence of dermal papillomas and carcinomas and increased levels of DNA adducts associated 

with reactive metabolites of PAHs. The carcinogenicity of used mineral-based crankcase oil has been 

correlated with the PAH content of oils. ATSDR (1997e) judged that no meaningful MRL values could 

be derived for used mineral-based crankcase oil, due to the limitations of the toxicological data on used 

mineral-based crankcase oils and the wide compositional variance among used mineral-based crankcase 

oils. 

EPA (1998b) and IARC (1996) have not classified used mineral-based crankcase oil as to its carcinogenicity 

in humans. IARC (1984, 1987) noted that exposure to mineral oils used in a variety of 

occupations (including mulespinning, metal machining, and jute processing) has been strongly and 

consistently associated with increased occurrence of squamous-cell cancers of the skin, especially of the 

scrotum, but that production processes have changed over time so that more modern, highly refined oils 

contain smaller amounts of “contaminants, such as polycyclic aromatic hydrocarbons.” IARC (1987) 

judged that there was sufficient evidence for the carcinogenicity of untreated and mildly-treated mineral 

oils in humans and animals, whereas there was inadequate evidence for the carcinogenicity of highly-refined 

mineral oils in humans or animals. 
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6. HEALTH EFFECTS 

6.3.7 Mineral Oil Hydraulic Fluids 

Most mineral oil hydraulic fluids are made from processed petroleum crude oils that are blended with 

various types of nonhydrocarbon additives to impart specific, use-related properties to the fluid (ATSDR 

1997b). The carbon number range of hydrocarbons in hydraulic fluids varies depending on the intended 

application of the fluid, but mostly is in the range of C15-C50. Toxicity data for mineral oil hydraulic 

fluids are restricted to acute lethality studies of rats exposed by gavage or by inhalation to several types of 

mineral oil hydraulic fluids, and single-dose gavage neurotoxicity tests that found no effects in chickens. 

ATSDR (1997b) did not derive inhalation or oral MRLs for mineral oil hydraulic fluids for any duration 

of exposure, because of the lack of suitable data. 

IARC (1984) reviewed the evidence that certain types of mineral oils are carcinogenic in animals, whereas 

other types are not. IARC (1984) concluded that mineral oil is not classifiable as to its carcinogenicity, 

because of the apparent dependence of mineral oil’s carcinogenic activity in animals on the chemical 

makeup of the crude oil starting material, the presence of additives and the conditions of use. 

6.3.8 Asphalt 

Asphalts are complex mixtures containing relatively high molecular weight hydrocarbons, predominantly 

cyclic alkanes and aromatic compounds (IARC 1985). They also contain some sulfur-, nitrogen- and 

oxygen-containing compounds and heavy metals. They are viscous liquids or solids. Inhalation studies of 

these mixtures in animals have involved heating the materials to produce fumes, which is relevant to 

human occupational exposure (e.g., roofing, road surfacing), but not particularly relevant to exposure 

resulting from contamination at hazardous waste sites. Respiratory effects were seen in these studies. 

Respiratory effects were reported in workers who were exposed to fumes of asphalts. No oral studies 

were reported. IARC concluded that there is sufficient evidence that extracts of asphalts (applied to the 

skin of experimental animals in solvents such as benzene or toluene or injected subcutaneously) are 

carcinogenic to animals. Evidence for undiluted asphalts ranged from limited to inadequate, depending on 

type of asphalt. IARC (1985) concluded that there is inadequate evidence that asphalts alone are 

carcinogenic to humans 
 

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6. HEALTH EFFECTS 

6.3.9 Crude Oil 

ATSDR has not prepared a toxicological profile on crude oil. IARC (1989c) prepared a monograph on 

crude oils, from which the following information is summarized. Crude oils are exceedingly complex 

mixtures that vary greatly depending on their source. The bulk of chemicals in crude oils are 

hydrocarbons: straight, branched and cyclic alkanes; and aromatics including benzene, alkylbenzenes, 

naphthalenes and PAHs. Non-hydrocarbon constituents of crude oil include sulfur-, nitrogen-, oxygen-and 

metal-containing compounds. 

No studies of potential health effects from inhalation exposure were located. Acute oral administration of 

crude oil to animals has resulted in hepatic effects and development effects. Aspiration of crude oil by a 

laborer resulted in pneumonia and hepatic and renal effects. Petroleum field workers who had direct 

dermal contact with crude oil developed adverse dermal effects, including dryness and hyperkeratosis. 

A number of studies of the carcinogenicity of dermal application of crude oil to animals have been 

reviewed by IARC (1989c), which concluded that there is limited evidence for the carcinogenicity of crude 

oil to experimental animals. A cohort study of U.S. petroleum-producing and pipeline workers, and case 

control studies that included exposure during crude oil exploration and production, were evaluated by 

IARC (1989c), which concluded that there is inadequate evidence for the carcinogenicity of crude oil in 

humans. 

An additional monograph on occupational exposures in petroleum refining (IARC 1989e) concluded that 

there is limited evidence that working in petroleum refineries entails a risk of skin cancer and leukemia. 

Exposures during refining, however, are not particularly relevant to exposures resulting from 

contamination of hazardous waste sites with crude oil. 

6.4 TOXICOKINETICS 

Overview. Because TPH is a broadly defined entity consisting of complex mixtures of hydrocarbons of 

varying chemical composition (due to differences in original petroleum products and differential, time-dependent, 

fate and transport of components within any particular TPH mixture), this section discusses 

available information for absorption, distribution, metabolism and excretion of components and petroleum 

products corresponding to the transport fractions of TPH. Limited additional information regarding the 
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more heterogenous whole petroleum products can be found in the ATSDR toxicological profiles and other
 

assessments of these products referenced in Section 6.3. In general, however, there is little information
 

regarding toxicokinetics of these heterogeneous products and the discussions often deal with the individual
 

constituents, including additives and impurities that are not petroleum hydrocarbons, and hydrocarbon
 

mixtures that are similar to portions of the product.
 

Hydrocarbons in the aromatic EC>9 –EC16, fraction may be readily absorbed following inhalation or oral
 

exposure, based on studies with humans and animals exposed to the BTEXs. BTEXs are absorbed by the
 

skin to a lesser extent, especially with exposure to vapors. BTEXs and their metabolites are widely
 

distributed throughout tissues and organs following absorption. BTEXs are metabolized (via oxidative
 

metabolic pathways involving cytochrome P-450 oxidases and conjugation reactions with glucuronides,
 

sulfates, glutathione, or amino acids) to more water-soluble metabolites that are excreted predominately in
 

urine. Metabolism represents a toxification pathway for some effects of certain BTEXs (e.g., cancer and
 

hematopoietic effects appear to be caused by reactive metabolic intermediates of benzene) and a
 

detoxification pathway for other effects (e.g., neurological effects from acute exposure to toluene). In
 

addition to urinary excretion of metabolites, BTEXs are eliminated by exhalation of unchanged parent
 

compound and fecal excretion (ATSDR 1994, 1995d, 1997a, 1999a).
 

Hydrocarbons in the aromatic EC>9 –EC16 fraction may be absorbed following inhalation, oral, or dermal
 

exposure, based on studies of humans and animals exposed to cumene, naphthalene or monomethyl-naphthalenes,
 

but data concerning the rate and extent of absorption are limited. Animal studies indicate
 

that these indicator compounds and their metabolites are widely distributed following absorption and that
 

urinary excretion of metabolites is the primary route of elimination. Metabolism of cumene, naphthalene,
 

and methyl naphthalenes involves aromatic ring oxidation (especially for naphthalene)-forming epoxide,
 

alcohol, dihydrodiol, and quinone derivatives that can be conjugated to glutathione, glucuronic acid, or
 

sulfate-and oxidation of the alkyl side groups (i.e., in cumene or methyl naphthalenes)-forming alcohol
 

and carboxylic acid derivatives that can be conjugated to glucuronic acid or amino acids (ATSDR 1995e;
 

EPA 1987a, 1997b).
 

Hydrocarbons in the aromatic EC>16 –EC35 fraction may be absorbed to varying extents following
 

inhalation, oral, or dermal exposure, depending on the lipophilicity and molecular size of the compound
 

and the vehicle of administration, as indicated by studies of humans exposed to workplace-air complex
 
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mixtures containing PAHs (i.e., hydrocarbons with more than two 5- or 6-carbon aromatic rings) and 

studies of animals exposed to individual PAHs by inhalation, oral administration, or dermal application. 

Increasing lipophilicity of vehicles or of the PAH compound tends to increase absorption, whereas 

adsorption to particles of increasing size (especially for inhalation exposure) or increasing molecular 

weight of the PAH compound tends to decrease absorption. Following absorption, PAHs are widely 

distributed to tissues and organs and eliminated by urinary and biliary excretion of metabolites. 

Metabolism of PAHs involves the production of arene oxides, phenols, quinones, dihydrodiols (i.e., diols), 

phenol-diols, and diol-epoxides, and the conjugation of these oxidized intermediates to glutathione, 

glucuronic acid or sulfate. Reactive metabolic intermediates, including stereospecific isomers of arene 

oxides and diol-epoxides, are thought to cause the genotoxic and carcinogenic effects produced by 

carcinogenic PAHs (ATSDR 1995f). 

Hydrocarbons in the aliphatic EC5 –EC8 fraction may be readily absorbed in the lungs, as indicated by 

studies of humans and animals exposed to n-hexane, but absorption by the oral and dermal route is not 

well characterized. Aspiration to the lungs can occur following ingestion of hydrocarbons in this fraction. 

Absorbed n-hexane, based on determined partition coefficients in human and animal tissues, is expected to 

be widely distributed to tissues and organs with preferential partitioning into fatty tissues and well 

perfused tissues. Studies with humans and animals indicate that n-hexane is oxidatively metabolized to 

alcohol, ketone, carboxylic acid, dihydrodiol, and diketone derivatives, predominately in the liver. Urinary 

excretion of metabolites and, to a lesser extent, exhalation of unchanged n-hexane are the predominant 

means of elimination with low-level exposure, whereas exhalation of unchanged compound becomes a 

more important elimination pathway with high exposures (ATSDR 1999b). 

Hydrocarbons in the aliphatic EC>8 –EC16 fraction may be readily absorbed in the lungs, widely 

distributed to tissues with preferential distribution and accumulation occurring in fatty tissues, and slowly 

eliminated from fatty tissue, as indicated by studies of humans exposed by inhalation to a mixture of 

C10-C12 alkanes (“white spirit”) and studies of rats exposed by inhalation to single alkanes or cycloalkanes 

in the C6-C10 range. Results from these studies suggest that metabolism of hydrocarbons in this fraction, 

especially following distribution to fatty tissue, may be slow relative to aromatic hydrocarbons. 

Aspiration to the lungs may occur following ingestion of hydrocarbons in this fraction, especially those at 

the lower end of the ranges of molecular weight and viscosity for the fraction. Studies with rats indicate 
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that percentage absorption of ingested aliphatic hydrocarbons decreases with increasing carbon number 

from about 60% for Cl4 compounds to 5% or less for hydrocarbons with 228 carbons. 

Hydrocarbons in the aliphatic EC>16 –EC35 fraction may be poorly absorbed, regardless of the route of 

exposure, preferentially distributed to the liver and fatty tissues, slowly metabolized to fatty acids or 

triglycerides, and slowly excreted in the feces via the bile and as urinary metabolites, as indicated by 

studies with animals exposed to food-grade mineral oil or motor oil (ATSDR 1997b). The common 

presence of lipogranulomata in human autopsies (benign structures in human liver and spleen tissue which 

are composed of lipoid droplets surrounded by lymphocytes and macrophages and caused by dietary 

exposure to mineral oils) is consistent with the concept that aliphatic hydrocarbons in this fraction are 

slowly metabolized. 

6.4.1 Absorption 

6.4.1.I Inhalation Exposure 

Aromatic EC5 –EC9Fraction. Studies with humans and animals are available for each of the 

BTEXs; these studies indicate that BTEX compounds are rapidly and efficiently absorbed following 

inhalation exposure. Published retention percentages for inspired BTEXs in human studies range from 

approximately 30% to 70-80% (see ATSDR 1994, 1995d, 1997a, 1999a). 

Aromatic EC>9 –EC16 Fraction. Studies measuring the rate and extent of absorption in humans or 

animals following inhalation exposure to naphthalene or the monomethyl naphthalenes were not available, 

but observations of systemic health effects in humans and animals provide qualitative evidence of 

absorption of these indicator compounds (ATSDR 1995e). Studies of humans following inhalation 

exposure to isopropylbenzene (cumene) indicated a retention percentage of about 50% (EPA 1987a, 

1997b). 

Aromatic EC>16 –EC35 Fraction. Studies directly measuring the rate and extent of absorption in 

humans or animals following inhalation exposure to PAHs were not available, but measurement of the 

appearance of radioactivity in blood, tissues, and excreta within hours of exposure of animals to airborne, 

radioactively labeled benzo(a)pyrene indicate that rapid absorption can occur. Particle size and vehicle are 

expected to influence the absorption of inhaled PAHs, as indicated by measurements of lung clearance 
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following inhalation exposure of rats to benzo(a)pyrene adsorbed onto particles of differing sizes and 

measurements of excretion rates in rats following intratracheal instillation of benzo(a)pyrene in various 

vehicles (ATSDR 1995f) 

Aliphatic EC5 –EC8 Fraction. Studies with humans exposed to vapors of n-hexane indicate that 

20-25% of inhaled compound is absorbed and retained (ATSDR 1999b). In studies with rats exposed by 

inhalation, 12 hours/day for 3 days, to 100 ppm single hydrocarbons in the C6-C10 alkane series (n-hexane 

through n-decane) and a C6-C10, naphthene series (cyclohexane, methylcyclohexane, dimethylcyclohexane, 

trimethylcyclohexane and t-butylcyclohexane), absorption was demonstrated by the measurement of 

concentrations of hydrocarbons in blood, brain, liver, kidneys, and fat (Zahlsen et al. 1992). Within each 

series, tissue concentrations (μmol/kg) generally increased with increasing carbon number. 

Aliphatic EC>8 –EC16 Fraction. Hydrocarbons in this fraction may be readily absorbed following 

inhalation, as indicated by studies of humans exposed to airborne mixtures of mostly C10-C12 

hydrocarbons and by the studies of rats exposed to single hydrocarbons conducted by Zahlsen et al. 

(1992). 

For human volunteers exposed by inhalation to 100 ppm white spirit for 3 hours, a mean pulmonary 

uptake of 392 mg white spirit was measured, based on concentrations of white spirit in inspiratory and 

expiratory air (Pedersen et al. 1987). Following exposure to the same concentration, 6 hours/day for 

5 consecutive days, the mean pulmonary uptake was 3,464 mg white spirit. The test material was a 

mixture of aliphatic hydrocarbons containing 99% linear and branched alkanes (0.99% C8-C9, 15% C10, 

39% C11, and 44% C12 ), and 1% C9-C10 cycloalkanes. 

Absorption of inhaled hydrocarbons in the lower range of this fraction was demonstrated by detection of 

hydrocarbons in blood, brain, liver, kidneys, and fat in rats following exposure to single hydrocarbons 

(C6 -C10, n-alkanes [n-hexane through n-decane] and C6-C10, naphthenes [cyclohexane, methylcyclohexane, 

dimethylcyclohexane, trimethylcyclohexane, and t-butylcyclohexane]) at 100 ppm, 12 hours/day, for 

3 days (Zahlsen et al. 1992). 

Aliphatic EC>16 –EC35 Fraction. Studies measuring the rate and extent of absorption of aliphatic 

hydrocarbons in this fraction were not located, but animal studies with mineral oil aerosols suggest that 
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absorption is not rapid and lung clearance may be mediated by macrophages. Mice, rats, and rabbits 

exposed to aerosols of diesel-engine lubricating oil for up to 343 days showed oil in alveolar macrophages, 

mediastinal lymph nodes, lymphatic channels of the lungs, and the pleura; in mice, concentrations (w/w) of 

oil were 0.13% in lungs and 0.03% in livers (ATSDR 1999b). 

6.4.1.2 Oral Exposure 

Aromatic EC5 –EC9 Fraction. Animal studies are available for each of the BTEXs, indicating that 

these compounds are rapidly and efficiently absorbed following oral exposure. Published absorption 

percentages for oral doses of BTEXs in animal studies range from about 80% to 97% (see ATSDR 1994, 

1995d, 1997a, 1999a). 

Aromatic EC>9 –EC16 Fraction. No data regarding the extent or rate of absorption of ingested 

naphthalene or monomethyl naphthalenes were available, except for a report that 80% of an oral dose of 

2-methyl naphthalene was recovered as metabolites in the urine of rats within 24 hours (ATSDR 1995e). 

Studies with animals indicate that orally administered isopropylbenzene (cumene) rapidly appeared in the 

blood and that 90% of the administered dose was accounted for in urinary metabolites (EPA 1987a, 

1997b). 

Aromatic EC>16 –EC35 Fraction. Studies with animals following oral exposure to benzo(a)pyrene and 

other PAHs indicate that the extent of oral exposure to PAHs can vary depending on lipophilicity of the 

PAH compound and lipophilicity of the vehicle in which it is administered (ATSDR 1995f). 

Aliphatic EC5 –EC8, EC>8 –EC16, and EC>16 –EC35 Fractions. No studies were located regarding 

absorption of hydrocarbons in these fractions after oral exposure in humans. Studies in rats show that 

absorption of ingested aliphatic hydrocarbons (n-alkanes, isoparaffins, and naphthenes) is inversely related 

to molecular weight, ranging from complete absorption at the lower end of the molecular weight range to 

about 60% for C14 hydrocarbons, 5% for C28 hydrocarbons, and essentially no absorption for aliphatic 

hydrocarbons with >32 carbons (Albro and Fishbein 1970; Miller et al. 1996) 
 

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6.4.1.3 Dermal Exposure 

Aromatic EC5 –EC9 Fraction. Studies with animals indicate that BTEXs are dermally absorbed, but 

to a lesser extent than absorption via inhalation or oral exposure, especially when exposure is to vapors of 

these compounds (as opposed to the liquids or liquid solutions) (see ATSDR 1994, 1995d, 1997a, 1999a). 

Aromatic EC>9 –EC16 Fraction. Data regarding the rate and extent of dermally administered 

isopropylbenzene (cumene), naphthalene, or monomethyl naphthalenes were restricted to observations of 

systemic effects in humans and animals following dermal exposure to these compounds (ATSDR 1995e; 

EPA 1987a, 1997b). 

Aromatic EC>16 –EC35 Fraction. Studies that monitored radioactivity in rat tissues, organs, and 

excreta following the dermal application of individual radiolabeled PAHs in an organic solvent measured 

absorption percentages in the approximate range of 50-80% (% of applied dose that was absorbed), but 

found that absorption percentages declined to less than 20% when soil particles were included in the 

applied material (ATSDR 1995f). 

Aliphatic EC5 –EC8 Fraction. In vitro studies with human skin indicate that the permeability of 

n-hexane through skin was about l00-fold lower than the permeability of benzene, suggesting that 

hydrocarbons in this fraction may have a low potential for skin absorption (ATSDR 1999b). 

Aliphatic EC>8 –EC16 Fraction. No studies were located regarding absorption of hydrocarbons in this 

fraction after dermal exposure in humans or animals. 

Aliphatic EC>16 –EC35 Fraction. No studies were located that measured the rate or extent of dermal 

absorption of hydrocarbons in mineral oil or similar materials in animals or humans. Dermal absorption 

of hydrocarbons in this fraction, however, may be expected to be slow, based on studies with monkeys 

administered subcutaneous doses of radiolabeled mineral oil in an aqueous emulsion. Radioactivity 

remaining at the sites of injection accounted for 85-99% and 25-33% of the administered radioactivity, at 

1 week and 10 months following injection, respectively (ATSDR 1997b). 
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6.4.2 Distribution 

Aromatic EC5 –EC9 Fraction. Studies with humans and animals exposed predominately to vapors of 

individual BTEXs (there are fewer data for oral and dermal exposure) indicate that, following absorption, 

compounds in this fraction are widely distributed, especially to lipid-rich and highly perfused tissues (see 

ATSDR 1994, 1995d, 1997a, 1999a). Studies of rats exposed by inhalation to single hydrocarbons at 

100 ppm, 12 hours/day, for 3 days found that C6-C10 aromatics (benzene, toluene, xylene, trimethylbenzene, 

and t-butylbenzene), compared with C6-C10, n-alkanes (n-hexane through n-decane) and C6-C10, 

naphthenes (cyclohexane, methylcyclohexane, dimethylcyclohexane, trimethylcyclohexane, and 

t-butylcyclohexane), showed high concentrations (μmol/kg) in blood, low concentrations in organs, and a 

lower potential for accumulation in fat and other organs presumably due to faster metabolic disposition 

(Zahlsen et al. 1992). 

Aromatic EC>9 –EC16 Fraction. Studies of swine after oral exposure to naphthalene, rats after 

dermal exposure to naphthalene, and guinea pigs after oral exposure to 2-methyl naphthalene indicate that 

these compounds, and their metabolites, are distributed throughout tissues and organs following absorption 

(ATSDR 1995e). Studies with rats exposed to isopropylbenzene (cumene) by inhalation, oral 

administration, or intravenous injection indicated that absorbed isopropylbenzene (cumene) is distributed 

to many tissues and organs with some preferential distribution in fatty tissues (EPA 1987a, 1997b). 

Aromatic EC>16 –EC35 Fraction. Studies with animals exposed to individual radiolabeled PAHs by 

inhalation, oral administration, or dermal administration indicate that, following absorption, PAHs are 

widely distributed to tissues and organs (ATSDR 1995f). Studies with pregnant animals found that, 

following oral exposure to radiolabeled benzo(a)pyrene, placental levels of radioactivity were higher than 

levels in embryonic tissue, suggesting that benzo(a)pyrene does not readily cross the placental barrier 

(ATSDR 199%). 

Aliphatic EC5 –EC8 Fraction. Determination of partition coefficients (blood:air and tissue:air) for 

n-hexane in human and rat tissues indicates that hydrocarbons in this fraction, once absorbed, will be 

widely distributed to tissues and organs with preferential distribution to fatty tissues and well perfused 

tissues (ATSDR 1999b). Asphyxia and chemical pneumonitis can be a health concern from ingestion of 

hydrocarbons in this fraction, due to aspiration to the lungs. The aspiration potential of ingested 
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6. HEALTH EFFECTS 

hydrocarbons increases with decreasing viscosity; within the alkane series, C6-C10, viscosity decreases 

with decreasing molecular weight (Cavender 1994). 

Studies of rats exposed by inhalation to single hydrocarbons at 100 ppm, 12 hours/day, for 3 days found 

that C6-C10 n-alkanes (n-hexane through n-decane) and C6-C10 naphthenes (cyclohexane, methylcyclohexane, 

dimethylcyclohexane, trimethylcyclohexane, and t-butylcyclohexane), compared with C6-C10 

aromatics (benzene, toluene, xylene, trimethylbenzene, and t-butylbenzene), generally showed low 

concentrations (μmol/kg) in blood, high concentrations in brain and other organs, and a high potential for 

accumulation in fat (Zahlsen et al. 1992). Within any of these three categories of hydrocarbons, 

hydrocarbon concentrations in tissues (blood, brain, kidney, liver and fat) generally increased with 

increasing carbon number (Zahlsen et al. 1992). Twelve hours after cessation of exposure, concentrations 

of alkanes and naphthenes in fat and brain were 2- to 3-fold higher than concentrations of aromatics, 

suggesting faster metabolic disposition for the aromatics. 

Aliphatic EC>8 –EC16 Fraction. Studies of rats exposed by inhalation to individual C6-C10, n-alkanes 

and cycloalkanes indicate that hydrocarbons in this fraction are distributed widely to tissues and organs 

after absorption and can accumulate in fat (Zahlsen et al. 1992). Aspiration to the lungs can occur 

following ingestion of hydrocarbons in this fraction (Cavender 1994). Following absorption from the 

gastrointestinal tract, smaller molecular weight aliphatic hydrocarbons and/or their metabolites are 

transported in the body via the blood and the lymph system, whereas larger molecular weight aliphatic 

hydrocarbons may be distributed predominately via the lymph system (see for review Albro and Fishbein 

1970; Miller et al. 1996). 

Aliphatic EC>16 –EC35 Fraction. Lung accumulation of hydrocarbons from this fraction is of concern 

with prolonged or high-level exposure to aerosols or ingestion, as indicated by numerous case reports of 

lipoid pneumonia in humans exposed to mineral oil through intranasal application of liquid petrolatum in 

medicinal nose drops and by a case of lipoid pneumonia in a child who ingested a 5-10 mL dose of 

mineral oil automobile transmission fluid (ATSDR 1997b). Following absorption, hydrocarbons in this 

fraction may be expected to accumulate to some degree in liver and fatty tissues, as indicated by the 

observation that, 24 hours after administration of an oral dose of tritiated mineral oil to rats, concentrations 

of tritiated mineral oil were about 7-fold greater in fatty tissues and liver than in kidney and brain 

(ATSDR 1997b). Lipogranulomata (clusters of lipoid droplets surrounded by lymphocytes and 
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6. HEALTH EFFECTS 

macrophages) are commonly found in human autopsies, particularly in liver, spleen, and abdominal lymph 

nodes (Miller et al. 1996; Wanless and Geddie 1985). These structures are associated with dietary 

exposure to mineral oils and waxes, and are considered a benign response without adverse consequences 

(Miller et al. 1996; Wanless and Geddie 1985). 

6.4.3 Metabolism 

Aromatic EC5 –EC9 Fraction. As indicated by studies with humans and animals exposed to 

individual BTEXs, compounds in this fraction may be expected to be metabolized via cytochrome P-450 

oxidases, either at carbons in the aromatic ring or in alkyl side groups, to metabolic intermediates that can 

be conjugated with glucuronides, sulfates, glutathione, or ammo acids (e.g., cysteine or glycine). The 

resultant oxidated metabolites or conjugated metabolites are more water-soluble than parent compounds 

and are subject to urinary or, in some cases, biliary excretion. Metabolism of the BTEXs can represent 

both a detoxification process (e.g., enhancement of the formation and excretion of hippuric acid can 

counteract the acute neurotoxicity of toluene in animals) and a toxification process (e.g., cancer and 

hematopoietic effects from chronic exposure to benzene appear to be caused by reactive metabolic 

intermediates) (see ATSDR 1994, 1995d, 1997a, 1999a). 

Aromatic EC>9 –EC16 Fraction. Studies with animals following oral, intraperitoneal, or subcutaneous 

administration of naphthalene or 2-methyl naphthalene indicate that ring oxidation occurs via an initial 

epoxide intermediate that subsequently is converted to alcohol, dihydrodiol and quinone derivatives, some 

of which are conjugated to glutathione, glucuronic acid, or glycine, and that the presence of alkyl side 

groups presents another site for oxidation and conjugation (ATSDR 1995e). Naphthol and 

naphthoquinone derivatives have been detected in the urine of humans following exposure to naphthalene 

(ATSDR 1995e). Studies with animals exposed to isopropylbenzene (cumene), and with in vitro animal 

preparations, indicate that cumene is predominately oxidized at the l- or 2-carbon of the propyl side group 

to form alcohol or carboxylic acid derivatives that are conjugated predominately to glucuronic acid (EPA 

1987a, 1997b). A study that analyzed urinary metabolites in humans following acute inhalation exposure 

to cumene provided supporting data (EPA 1987a). 

Aromatic EC>16 –EC35 Fraction. In vitro studies with human tissues and in vitro and in vivo animal 

studies with benzo(a)pyrene and other PAHs indicate that compounds in this TPH fraction will undergo 

oxidative metabolism involving the production of arene oxides, phenols, quinones, dihydrodiols (i.e., diols), 
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6. HEALTH EFFECTS 

phenol-diols, and diol-epoxides (catalyzed by enzyme systems including cytochrome P-450 oxidases and 

epoxide hydrolase), and the conjugation of these intermediates to glutathione, glucuronic acid, or sulfate 

(ATSDR 1995f). Metabolism of PAHs facilitates both the elimination of more water soluble metabolites 

and the production of reactive intermediates (e.g., stereospecific isomers of arene oxides and diol-epoxides) 

thought to be responsible for the mutagenic and carcinogenic activity of carcinogenic PAHs (ATSDR 

1995f). 

Aliphatic EC5 –EC8 Fraction. Examination of urinary metabolites in humans and rats after exposure 

to n-hexane indicates that hydrocarbons in this fraction may be oxidatively metabolized via cytochrome 

P-450 oxidases to several alcohol, ketone, and carboxylic acid derivatives. Based on studies of urinary 

metabolites after exposure to n-hexane, proposed metabolites include l-, 2-, and 3-hexanol, 2-hexanone, 

5-hydroxy-2-hexanone, 2,5-hexanedione, and hexanoic acid (ATSDR 1999b). 

Aliphatic EC>8 –EC16 Fraction. Hydrocarbons in this fraction are oxidatively metabolized to fatty 

acids and alcohols, apparently mediated by cytochrome P-450 isozymes (see Miller et al. 1996 for review). 

Studies regarding the metabolism of hydrocarbons in this fraction in humans or animals provide suggestive 

evidence that metabolism may be slow. In a study of humans exposed to 100 ppm white spirit 

6 hours/day for 5 days (white spirit is a mixture comprised predominately of C10-C12, linear and branched 

alkanes), only minor differences were observed in the GC-MS spectrum of hydrocarbons in biopsied fatty 

tissue, than in the spectrum of hydrocarbons in the test material (Pedersen et al. 1984). In rats exposed by 

inhalation to single C6-C10, alkanes, cycloalkanes, or aromatic hydrocarbons at 100 ppm, 12 hours/day for 

3 days, concentrations of alkanes and cycloalkanes were 2- to 3-fold higher than concentrations of 

aromatics 12 hours after cessation of exposure, suggesting that aliphatic hydrocarbons in this fraction may 

be metabolized more slowly than aromatic hydrocarbons of equivalent molecular weight (Zahlsen et al. 

1992). 

Aliphatic EC>16 –EC35 Fraction. Aliphatic hydrocarbons in this fraction are not expected to undergo 

extensive metabolism in animals or humans. In monkeys, 2 days after intramuscular injection of a mineral 

oil emulsion with a radiolabeled C16 hydrocarbon (n-hexanedecane), substantial portions (30-90s) of 

radioactivity in various tissues existed as unmetabolized n-hexanedecane. The remainder of the 

radioactivity was found as phospholipids, free fatty acids, triglycerides, and sterol esters. No radioactivity 

was found in water-soluble fractions (ATSDR 1997b). The common presence of lipogranulomata in 
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human autopsies and the widespread dietary exposure to mineral oils and waxes (Wanless and Geddie 

1985) are consistent with the concept that aliphatic hydrocarbons in this fraction are slowly metabolized. 

6.4.4 Elimination and Excretion 

Aromatic EC5 –EC9 Fraction. Studies with humans and animals exposed by various routes to 

BTEXs, indicate that compounds in this fraction may be expected to be eliminated predominately by 

urinary excretion of metabolites and to lesser degrees by exhalation of unchanged parent compound or 

biliary excretion of metabolites (see ATSDR 1994, 1995d, 1997a, 1999a). 

Aromatic EC>9–EC16 Fraction. Data from studies with animals exposed by several routes to 

naphthalene, monomethyl naphthalenes and isopropylbenzene (cumene) indicate that urinary excretion of 

metabolites represents the predominant pathway of elimination for these compounds. Detection of urinary 

metabolites in humans exposed to naphthalene or cumene provide supporting evidence (ATSDR 1995e; 

EPA 1987a, 1997b). 

Aromatic EC>16 –EC8 Fraction. Studies with animals exposed by inhalation, and by oral, dermal, or 

parenteral administration, indicate that PAHs are eliminated by urinary and biliary excretion of 

metabolites (ATSDR 1995f). 

Aliphatic EC5 –EC8 Fraction. Studies with humans and animals exposed to n-hexane suggest that 

hydrocarbons in this fraction, under low-exposure conditions, may be eliminated predominately as urinary 

metabolites and to a lesser extent in exhaled air as unchanged compound. Studies with rats indicate that 

the importance of exhalation of unchanged hexane as an elimination pathway increased from about 12% to 

62% of body burden after inhalation exposure to 500 ppm and 10,000 ppm, respectively (ATSDR 1999b). 

Aliphatic EC>8 –EC16 Fraction. Results from studies with humans exposed by inhalation to white 

spirit (a mixture of C10-C12 aliphatic hydrocarbons) suggest that hydrocarbons in this fraction are slowly 

eliminated following distribution to fatty tissues (Pedersen et al. 1984). Immediately after 5 consecutive 

days of 6-hour daily exposure to 100 ppm white spirit, the mean concentration of white spirit in fatty 

tissue was 41.1 mg/kg fat; approximately 60 exposure-free hours later, mean fatty tissue concentrations 

had declined by only 23% to 3 1.7 mg/kg fat. No studies were located regarding the routes of excretion for 

hydrocarbons in this fraction in humans or animals. 
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6. HEALTH EFFECTS 

Aliphatic EC>16 –EC35 Fraction. Hydrocarbons in this fraction may be expected to be eliminated 

predominately in the feces, based on experiments with rats given oral or intraperitoneal doses of tritiated 

mineral oil. With oral exposure, 90% of administered radioactivity appeared rapidly (within 2 days) in the 

feces, predominately as unchanged mineral oil; less than 10% of administered radioactivity appeared in the 

urine within 2 days of administration. With intraperitoneal exposure, radioactivity appeared more slowly 

in the feces (11% of administered radioactivity appeared in the feces within 8 days of dosing); urinary 

excretion of metabolites, within 8 days of dosing, represented about 8% of administered radioactivity 

(ATSDR 1997b). 

6.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

No studies were located regarding the development of PBPK/PD models for complex mixtures of TPH in 

general. 

Verhaar et al. (1997), however, recently reported on progress in developing PBPK/PD models for use in 

assessing human health risks from exposure to JP-5, a Navy Jet petroleum fuel containing a complex 

mixture of hydrocarbons in the C9C18, range. Verhaar et al. (1997) noted that their in-progress 

development of a PBPK/PD model for JP-5 is focused on the prediction of kinetics of JP-5 components in 

relevant tissues after acute inhalation exposure and the resultant toxicity (neurological effects linked to the 

dissolution of xenobiotic chemicals in the membrane of nerve cells). Verhaar et al. (1997) discussed how 

the development of PBPK/PD model(s) for complex mixtures involves: 

(1) determining a lumping scheme to be used (in which similar mixture components are grouped 

[i.e., lumped] into a pseudocomponent for which necessary chemical parameters such as tissue 

partition coefficients are estimated), based on knowledge of the mixture’s chemical composition, 

the route and duration of exposure that is of interest, and the mixture’s toxicological effect(s) and 

mechanism of action (a lumping scheme based on the octanol-water partition coefficients of 

components was chosen for JP-5); 

(2) formulating PBPK/PD model(s) with physiological compartments, reaction kinetic equations, 

and mass transfer equations that are appropriate to the toxicological effect(s) of concern (a brain 

compartment, including a pharmacodynamic subroutine, was proposed to be included in the 

PBPK/PD model for JP-5); 
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6. HEALTH EFFECTS 

(3) determining whether there is enough information to include interactive effects between 

pseudocomponents in the model(s); and 

(4) using quantitative structure-activity relationships (QSAR) to estimate necessary model 

parameters for pseudocomponents such as tissue-blood and air-blood partition coefficients, and 

metabolic rate constants. 

The approach discussed by Verhaar et al. (1997) suggests that development of PBPK/PD models to use in 

assessing health risks from TPH will require similar focusing on relevant lumping schemes, exposure 

pathways and durations, and toxicological effects and mechanisms of action. Thus, it is likely that a 

PBPK/PD model developed to aid in the assessment of potential cancer risk from chronic exposure to TPH 

may substantially differ from a PBPK/PD model for assessing risk for potential neurological effects from 

acute exposure to TPH. 

6.5 MECHANISM OF ACTION 

Because TPH is a broadly defined entity consisting of complex mixtures of hydrocarbons of varying 

chemical composition (due to differences in original petroleum products and differential, time-dependent, 

fate and transport of components within any particular TPH mixture), this section discusses available 

information for components and petroleum products corresponding to the transport fractions of TPH. 

Limited additional information regarding the more heterogenous whole petroleum products can be found in 

the ATSDR toxicological profiles and other assessments of these products referenced in Section 6.3. In 

general, however, there is little information regarding mechanisms for these heterogenous products. The 

discussions of mechanisms in these documents often deal with the individual constituents, including 

additives and impurities that are not petroleum hydrocarbons, and with hydrocarbon mixtures that are 

similar to portions of the product. 

6.5.1 Pharmacokinetics Mechanisms 

Absorption. Available data suggest that hydrocarbons in the aliphatic EC5-EC5 and aromatic 

EC5-EC9 fractions may be more readily absorbed by the lungs, gastrointestinal tract, and skin than 

hydrocarbons in the aliphatic or aromatic hydrocarbons in larger molecular weight fractions. This 
TOTAL PETROLEUM HYDROCARONS 160 

6. HEALTH EFFECTS 

difference is due to their smaller molecular size and the presumed dependence of absorption of
 

hydrocarbons on diffusion or facilitated diffusion.
 

Distribution, Storage and Excretion. Hydrocarbons in each of the aliphatic and aromatic fractions
 

are expected to be distributed throughout tissues and organs following absorption. Preferential
 

distribution to fatty tissues occurs especially with aliphatic hydrocarbons. Ingested or inhaled volatile
 

aliphatic and aromatic hydrocarbons in the EC5-EC8 and EC5-EC9 fractions can be eliminated in exhaled
 

breath as unchanged parent compound. Metabolic elimination of aromatic hydrocarbons in each EC
 

fraction predominately occurs via oxidative metabolic pathways involving initial oxidation by cytochrome
 

P-450 isozymes and conjugation to more water-soluble compounds such as glutathione and glucuronic
 

acid. Some studies in animals suggests that aliphatic hydrocarbons (especially in the EC>8-EC16 and
 

EC>16-EC35 fractions) may be metabolized more slowly than aromatic hydrocarbons. Metabolites of both
 

aliphatic and aromatic hydrocarbons are excreted in urine and in feces via biliary excretion.
 

Route-dependent Toxicity. Ingested aliphatic hydrocarbons in the EC5-EC8 and EC>8-EC16
 

fractions are aspirated to the lungs and can lead to pulmonary irritation, edema, and pneumonia.
 

Materials with low viscosity (in the range of 30-35 centipoise) present an extreme aspiration risk, whereas
 

those with high viscosity (150-250 centipoise) present very low aspiration risk (Snodgrass 1997).
 

6.5.2 Mechanisms of Toxicity 

Central nervous system (CNS) depression caused by acute inhalation exposure to volatile aliphatic and 

aromatic petroleum hydrocarbons is generally thought to occur when the lipophilic parent hydrocarbon 

dissolves in nerve cell membranes and disrupts the function of membrane proteins by disrupting their lipid 

environment or by directly altering protein conformation. Oxidative metabolism of CNS-depressing 

hydrocarbons reduces their lipophilicity and represents a process that counteracts CNS-depression 

toxicity. More detailed information on this mechanism of toxicity can be found in ATSDR profiles on 

toluene (ATSDR 1994), ethylbenzene (ATSDR 1999a), and xylene (ATSDR 1995d). 

Pulmonary irritation and pneumonia from inhalation and oral exposure to complex mixtures of petroleum 

hydrocarbons such as gasoline and kerosene are thought to involve direct parent hydrocarbon interaction 

with nerve cell membranes resulting in bronchoconstriction and dissolution into membranes of lung 
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6. HEALTH EFFECTS 

parenchyma resulting in a hemorrhagic exudation of proteins, cells, and fibrin into alveoli (ATSDR 

1998b; Klaassen 1996). 

In contrast, metabolic bioactivation, mediated by pathways involving cytochrome P-450 isozymes, is 

thought to be responsible for hemolytic anemia and leukemia from exposure to benzene (ATSDR 1997a) 

genotoxic effects and cancer from exposure to carcinogenic PAHs (ATSDR 19950; hemolytic anemia, 

ocular effects, and lung effects from naphthalene and methyl naphthalenes (ATSDR 1995e); peripheral 

neuropathy from n-hexane (ATSDR 1999b); lung effects from ethylbenzene (ATSDR 1999a); and 

α2μ-globulin nephropathy (which is unique to male rats) from hydrocarbons in gasoline (ATSDR 1995a). 

6.5.3 Animal-to-Human Extrapolations 

Rats and mice are much less sensitive than humans to the hemolytic effects of naphthalene. The dog 

appears to be a better model for humans for this effect (ATSDR 1995e). 

Inhalation or oral exposure to a number of the individual constituents of the TPH fractions (particularly 

branched-chain alkanes) and also the petroleum products whose composition is similar to these fractions 

(e.g., JP-5, JP-7, and the dearomatized streams) induces a hydrocarbon-related nephropathy unique to 

male rats (ATSDR 1995c, 1995g, 1998b; TPHCWG 1997c). This lesion involves the formation of 

hyaline droplets in the cytoplasm of the proximal tubule cells of the cortex. The hyaline droplets contain 

high concentrations of the protein α2μ-globulin, a protein found in male rats but not in humans. A likely 

mechanism for this accumulation is the slowing of the degradation of α2μ-globulin as a result of binding 

with specific substances, such as petroleum hydrocarbons or their metabolites. Single cell necrosis and 

exfoliation of the proximal tubular epithelium occurs, and the tubules near the cortico-medullary junction 

become dilated and are eventually filled with coarsely granular casts and necrotic debris. Regenerative 

tubule cell proliferation and mineralization of the renal papillar tubules occurs with continued exposure. 

The nephropathy induced by accumulation of this protein has not been noted in female rats, in male rats 

that lack the ability to synthesize α2μ-globulin, or in other species. Thus, it does not appear that the 

nephrotoxicity attributable to the α2μ-globulin syndrome observed in male rats is relevant to humans. 

Food grade and medicinal mineral oils which correspond to the aliphatic EC>16-EC35 fraction of TPH 

produce liver granulomas in F344 rats. These granulomas are reactive, with associated inflammation and 

occasional parenchymal cell necrosis. The inflammatory effects are not seen in dogs, mice, or Long-Evans 
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6. HEALTH EFFECTS 

or Sprague-Dawley rats fed comparable doses of similar mineral oils, according to TPHCWG (1997c). In 

addition, humans, who are exposed to mineral oils in the diet and by intentional ingestion of medicinal 

mineral oils, develop granulomas, but without evidence of inflammation or significant liver dysfunction. 

Whether the exposure levels for humans are comparable to those tested in experimental animals is not 

known. Nevertheless, the issue has been raised that F344 rats may be uniquely predisposed to the 

development of inflammatory granulomatous lesions, and that this difference in sensitivity may justify use 

of a smaller uncertainty factor in extrapolating from the F344 rat to humans (TPHCWG 1997c). 

6.6 SELECTION OF FRACTION-SPECIFIC HEALTH EFFECTS CRITERIA 

6.6.1 Overview 

The focus of this section is the selection, when possible, of appropriate MRLs for the assessment of health 

effects of the aromatic and aliphatic fractions of TPH. Approaches to cancer assessment are also 

discussed. The TPH fractions are environmental transport fractions, as suggested by the TPHCWG 

(1997c), with a slight modification to include all the BTEXs in a redefined aromatic EC5-EC9 fraction. 

Other agencies have addressed the problem of selection of health effects criteria for fractions or 

representative constituents of TPH (ASTM 1995; Hutcheson et al. 1996; TPHCWG 1997c), and their 

approaches were carefully evaluated during the preparation of this profile, as discussed in Sections 6.1 

and 6.2. Nevertheless, ATSDR’s concerns and mandate encompass a broader range of exposure periods 

than those of the other agencies, and ATSDR health criteria are developed somewhat differently and for a 

slightly different purpose. These issues were discussed in Section 6.1 and 6.2. 

Tables 6-l and 6-2 summarize the suggested fraction-specific MRLs for inhalation and oral exposure. 

These fraction-specific MRLs are provisional values, reflecting the uncertainty inherent in this approach 

(see Section 6.6.2 for a more complete discussion). As with any ATSDR MRL, the MRLs in Tables 6-l 

and 6-2 are intended to serve as health guidance values and are not to be used to define clean-up or action 

levels. Information listed in brackets in Table 6-2 is from sources other than ATSDR toxicological 

profiles. This information indicates potentially sensitive end points but does not have the same level of 

confidence as information from the ATSDR toxicological profiles. Additional details and tables listing all 

the candidate MRLs and relevant cancer assessments are presented in Section 6.6.2. Chapter 7 also 


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6. HEALTH EFFECTS 

presents MRLs for constituents and whole petroleum products and health effects criteria developed by 

other agencies (EPA and TPHCWG RfDs and RfCs). 

6.6.2 Minimal Risk Levels, Critical Effects, and Cancer Assessments for Fractions of 

TPH 

The information in the following text is taken from the references cited in the tables that accompany the 

text. For the sake of readability, the references will not be cited in the text. Additional health effects 

information is available in the pertinent toxicological profiles (ATSDR 1994, 1995c, 1995d, 1995e, 

1995f, 1995g, 1997a, 1998b, 1999a, 1999b), TPHCWG (1997c), EPA references cited in the tables 

including EPA (1998b), and in Section 6.2. In order to fill data gaps, some compounds, representative 

mixtures, or studies that have not been assessed in ATSDR toxicological profiles are listed, with the 

critical or sensitive effects as evaluated by other agencies (EPA and TPHCWG) shown in brackets. This 

was done to give a more complete picture of the potential health effects of fraction constituents, to aid in 

judging whether the available MRLs may be useful in assessing health effects of the entire fraction. 

Aromatic EC5-9 Fraction: Indicator Compounds. This fraction consists of benzene, toluene, 

ethylbenzene and the xylenes (the BTEXs). 

Inhalation Exposure. The available inhalation MRLs for each of the BTEXs, and the EPA cancer risk 

for benzene, can be used to assess the potential for health effects for each of these indicator compounds 

individually. This is consistent with current practice. These MRLs and their associated effects, as well as 

the EPA cancer assessments, are summarized in Table 6-3. Health effects that are common to the BTEXs 

are neurological effects. Developmental effects appear to be a sensitive effect of inhalation exposure to 

ethylbenzene and xylene. Benzene has hematological and immunological/lymphoreticular effects and is 

classified in EPA Group A (human carcinogen). 

Oral Exposure. The oral MRLs for each of the BTEXs, and the EPA cancer risk for benzene, can be 

used to assess the potential for health effects for each of these compounds individually. No oral MRLs 

exist for ethylbenzene, but the limited oral data for this compound are reasonably similar to those for 

toluene. These MRLs and their associated effects, and the available EPA cancer assessments, are 

summarized in Table 6-4. Effects of oral exposure to these compounds are similar to those of inhalation 

exposure. In addition, renal and hepatic effects appear to be sensitive effects of xylene exposure. 


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6. HEALTH EFFECTS 

Aromatic EC>9-EC16 Combined Fraction. The combined fraction consists of the following three 

fractions: 

EC>9-EC10 : a variety of alkylbenzenes (propyl-, methylethyl, trimethyl, and branched-chain butyl) 

EC>10-EC12: a few alkylbenzenes (n-butyl-, n-pentyl-, a trimethyl-, and other multisubstituted), indans, 

and naphthalene 

EC>12-EC16: a few longer chain and multi-substituted alkylbenzenes; biphenyls, methyl naphthalenes, 

and some smaller PAHs. 

Inhalation Exposure. A chronic inhalation MRL is available for naphthalene; this MRL is listed in 

Table 6-5. There are no other inhalation MRLs for this fraction. All of the compounds in this fraction 

that have EPA carcinogenicity assessments have been classified in group D (not classifiable as to human 

carcinogenicity). Given the few health effects benchmarks available for the constituents of this fraction, 

and the general paucity of inhalation data for this fraction (see Section 6.2.2.1), selection of surrogate 

values for the combined fraction is problematic. Health effects that appear to be common to the 

compounds in this fraction are respiratory irritant effects, neurological effects, and renal effects, but it is 

not clear that they are common to all, or even that adequate investigation of respiratory or neurological 

effects was conducted for all compounds in the table. Based on some commonality of effect, the chronic 

MRL of 0.002 ppm for naphthalene could be adopted as a surrogate value for the combined fraction as a 

provisional measure. Great uncertainties are attendant on this selection, but the alternative is to disregard 

the potential for health effects of much of the mass of this fraction. 

Oral Exposure. The only MRLs available for this fraction are acute and subchronic MRLs for 

naphthalene, an intermediate MRL for acenaphthene, and a chronic MRL for l-methyl naphthalene; these 

MRLs are listed in Table 6-6. Although more health effects data are available for oral exposure than for 

inhalation exposure to the constituents of this fraction, selection of surrogate values to use for oral 

exposure to this fraction is problematic. The acute and intermediate MRLs for naphthalene, 0.05 and 

0.02 mg/kg/day, are equivalent to or lower than any other MRLs for this fraction, including the chronic 

MRL for l-methyl naphthalene. The compounds in this fraction tend to cause hepatic and renal effects. 

Naphthalene and l-methyl naphthalene have respiratory effects following oral exposure; it is expected that 


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6. HEALTH EFFECTS 

2-methyl naphthalene will as well. Neurological effects have been seen from acute exposure to 

naphthalene, and would also be expected with the alkyl benzenes, based on the inhalation data. Thus, 

there is some commonality in the health effects. Naphthalene appears to be one of the more toxic 

constituents of this fraction, so adoption of the MRLs for naphthalene as surrogate values for the entire 

mass of this fraction should be relatively protective. There is no chronic MRL for naphthalene, however, 

and the chronic MRL for l-methyl naphthalene (0.07 mg/kg/day) is similar to, but slightly higher than the 

intermediate MRL for naphthalene. 

Aromatic EC>16- EC35 Combined Fraction. The combined fraction consists of the following two 

fractions: 

EC>16- EC21: anthracene, fluorene, phenanthrene, pyrene and other less well-known PAHs 

EC>21- EC35: benz(a)anthracene; benzo(b)-, benzoCj)- and benzo(k)fluoranthene; benzo(g,h,i)perylene; 

benzo(a)- and benzo(e)pyrene; chrysene; dibenz(a,h)anthracene; fluoranthene; and indeno( 1,2,3­

c,d)pyrene, and other less well-known PAHs. 

Inhalation Exposure. Very few health effects data for inhalation exposure and no inhalation MRLs are 

available for this fraction. Given the nonvolatile nature of these compounds, inhalation exposure as a 

result of contamination at hazardous waste sites would be anticipated to occur only through exposure to 

dust or particles containing PAHs. 

Oral Exposure. The limited oral data for these PAHs indicate that hepatic effects are a common sensitive 

effect; renal effects have been seen with some. Intermediate MRLs of 0.4 mg/kg/day have been derived 

for fluorene and fluoranthene and of 10 mg/kg/day for anthracene; these are listed in Table 6-7. All of the 

commonly studied PAHs in the EC>16-EC21 portion of the combined fraction have been classified in Group 

D (not classifiable as to human carcinogenicity). Many of the commonly studied PAHs in the EC>21-EC35 

portion of the combined fraction have been classified in Group B2 (probable human carcinogen). An 

intermediate MRL of 0.4 mg/kg/day was selected as a surrogate value for the combined fraction and 

should be applied to the non-carcinogenic PAHs in this fraction. A method for assessing the potential 

carcinogenic effects of these PAHs would be to use the EPA cancer risk levels for benzo(a)pyrene and the 

relative potency factors for the individual PAHs (Table 6-7). 

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6. HEALTH EFFECTS 

Aliphatic EC5-EC8 Combined Fraction. The combined fraction consists of the following two 

fractions: 

EC5- EC6: n-pentane, n-hexane, dimethylbutanes, and methylpentanes, cyclopentane, some alkenes 

EC>6- EC8: n-heptane, n-octane, some branched chain C6-C9 alkanes including trimethylpentanes, 

cyclohexane, methylcyclohexane, other cycloalkanes, some alkenes. 

Inhalation Exposure. Only one inhalation MRL, a chronic MRL for n-hexane, is available for this 

combined fraction; this is listed in Table 6-8. n-Hexane produces a characteristic peripheral nephropathy 

in humans and animals; the chronic MRL is based on this effect in humans. Commercial hexane, which 

contains n-hexane plus other C6 branched chain and cyclic alkanes (see Table 6-8), also has been shown to 

cause this effect in animals, due to its content of n-hexane (IRDC 1981) (see Section 6.2.4.1). The non 

n-hexane portion of the mixture does not. In addition, the non n-hexane constituents of this combined 

fraction do not appear to cause peripheral neuropathy when tested singly although, like n-hexane, they do 

cause neurological effects (depression of the central nervous system). n-Hexane and commercial hexane 

are respiratory irritants. Commercial hexane has undergone extensive recent testing as part of an EPA 

Test Rule under TSCA Section 4. However, until the database for commercial hexane can be more fully 

evaluated, the chronic MRL for n-hexane has been determined to be the most appropriate surrogate for a 

health guidance value for this fraction. 

Oral Exposure. Health effects data regarding oral exposure to this fraction are limited and available 

mainly for n-hexane. n-Hexane caused peripheral neuropathy in two species of animals, indicating that 

effects by the oral route may be similar to those by the inhalation route. ATSDR concluded that the 

incompleteness of the oral database precluded derivation of oral MRLs for this compound. 

Aliphatic EC>8-EC16 Combined Fraction. The combined fraction consists of the following three 

fractions: 

EC>8- EC10: n-nonane, n-decane, branched chain C9C10 alkanes, substituted cycloalkanes, a few alkenes 

TOTAL PETROLEUM HYDROCARONS 175 

6. HEALTH EFFECTS 

EC>10- EC12 and EC>12- EC16: longer chain n-alkanes; probably larger branched and cyclic alkanes, but 

EC values not provided (TPHCWG 1997a). 

Inhalation Exposure. Health effects data are available for inhalation exposure to some petroleum 

products corresponding to this combined fraction. Intermediate MRLs of 3 mg/m3

 for JP-5 and JP-8 and 

0.01 mg/m3

 for kerosene, and a chronic MRL of 0.3 mg/m3 for JP-7 have been derived; these are listed in 

Table 6-9. These four fuels are similar in composition, consisting primarily of aliphatics in the C9-C16 

range. All contain some significant aromatic components. In addition, health effects data from studies of 

two dearomatized petroleum streams have been evaluated by the TPHCWG (1997c). The sensitive effect 

for exposure to all these products is hepatic. The effect for kerosene, however, was a decrease in blood 

glucose levels, attributed to hepatic effects. The MRL for kerosene, based on this effect, appears to 

involve greater uncertainty as to the toxicological significance of the effect. As a result, the intermediate 

MRL of 3 mg/m3

 and chronic MRL of 0.3 mg/m3 for the jet fuels have been determined to be the most 

appropriate surrogate values for the assessment of health effects due to exposure to this fraction. 

Oral Exposure. Limited data are available for health effects of oral exposure to this combined fraction. 

Three studies of dearomatized petroleum streams have been evaluated by the TPHCWG (1997c) for use in 

RfD derivations, but these studies are unpublished and unreferenced. In addition, a study of JP-8 (Mattie 

et al. 1995) was used for RfD derivation by the TPHCWG (1997c). The critical effects are listed in Table 

6-10. There are no MRLs relevant to this fraction. The sensitive effect of the dearomatized streams was 

hepatic. Some slight indications of hepatic effects were also seen in the study of JP-8, but no 

histopathological effects or changes in absolute organ weight. 

Aliphatic EC>16- EC35 Combined Fraction. The combined fraction consists of the following 

fractions: 

EC>16- EC21: n-hepta-, n-octa-, and n-nonadecane, n-eicosadecane, and probably branched and cyclic 

alkanes 

EC>21- EC35: longer chain n-alkanes and probably branched and cyclic alkane 


 

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6. HEALTH EFFECTS 

Inhalation Exposure. No information was located on the health effects of inhalation exposure to 

compounds or mixtures of petroleum hydrocarbons that fall within this fraction. 

Oral Exposure. No pertinent assessments by ATSDR exist, but studies of mixtures of mineral oil 

hydrocarbons have been evaluated by the TPHCWG (for use in deriving RfDs for this fraction). 

Table 6-l 1 summarizes the pertinent information. The critical effect of these mineral oils was judged to 

be hepatic. 

6.7 RELEVANCE TO PUBLIC HEALTH 

This profile covers total petroleum hydrocarbons (TPH), which is defined as the measurable amount of 

petroleum-based hydrocarbon in an environmental medium (Chapter 2). TPH is measured as the total 

quantity of hydrocarbons without identification of individual constituents. Sources of TPH contamination 

in the environment range from crude oil, to fuels such as gasoline and kerosene, to solvents, to mineral- based 

crankcase oil and mineral-based hydraulic fluids. These products contain not only a large number 

and variety of petroleum hydrocarbons, but also other chemicals that, strictly speaking, are not the subject 

of this profile, such as non-hydrocarbon additives and contaminants. The TPH issue is further 

complicated by the number of petroleum-derived hydrocarbons that have been identified-more than 

250-and the variability in composition of crude oils and petroleum products (see Section 3.2 and 

Appendices D and E for details). 

Following a spill, leak, or other release of a petroleum product into the environment, changes occur in the 

location and composition of the released hydrocarbons, as described in Section 5.3. The smaller molecular 

weight hydrocarbons, which tend to have relatively high vapor pressures and/or water solubilities, tend to 

volatilize into the air, dissolve into infiltrating rainwater or groundwater and migrate away from the 

release area, and biodegrade. The larger molecular weight constituents tend to sorb to soil or sediment and 

remain relatively immobile. 

Because TPH is a complex and highly variable mixture, assessment of health impacts depends on several 

factors, assumptions, and circumstances. Of prime importance is the specific exposure scenario. For 

example, immediately following a large release of a “lighter” petroleum product (e.g., automotive 

gasoline), central nervous system depression could occur in people in the immediate vicinity of the spill if 

TOTAL PETROLEUM HYDROCARONS 180 

6. HEALTH EFFECTS 

they inhaled the volatilized components. In a confined or poorly ventilated area, asphyxiation would even 

be a concern. Contamination of groundwater and surface water with the soluble components (e.g., the 

BTEXs) could impact drinking water sources. Exposure to a contaminated water supply may take place 

over a period of weeks or years, and raises concerns for more subtle nervous system effects, 

developmental effects, and cancer. The less volatile or soluble constituents (such as benzo(a)pyrene) may 

tend to remain in the area of the release for extended periods. Even during the early stages of this release 

scenario, exposures will tend to be to fractions of the product (the more volatile or more soluble 

compounds) rather than to the whole product. Therefore, public health assessments for TPH require 

knowledge of the specific fractions and/or chemicals at the point of exposure (e.g., drinking water well, 

soil, air). These data are summarized in this toxicological profile (particularly Sections 3.2 and 6.3) and 

provided in more detail in the toxicological profiles on the individual components and whole products. 

A central tool in ATSDR assessment of public health impacts is the minimal risk level (MRL) health 

guidance value. MRLs have been developed by ATSDR for many hazardous waste constituents, though 

no new MRLs have been developed for TPH. A limited number of existing MRLs can be applied to TPH 

assessment. Most are MRLs for individual TPH components (e.g., benzene); however, a few MRLs are 

available for whole petroleum products. MRLs for substances that represent the fractions defined by the 

ATSDR approach to assessing TPH health impacts are provided and discussed in this profile. In recognition 

of the likelihood that even acute exposures to fresh releases will be to fractions of a product, the 

information on pertinent fractions of TPH should also be consulted (particularly Sections 2.3, 6.1, 6.2 

and 6.6). 

In the case of weathered releases, the fraction approach is likely to be the most useful. Analytical methods 

that support the fraction approach should be chosen to characterize exposures (Section 3.3, TPHCWG 

approach). The identity of the original contaminating product(s) need not be known. Health effects data 

for these fractions are discussed in Section 6.2 and recommendations for fraction-specific MRLs and for 

cancer assessment are presented in Section 6.6. 

The issue of exposure to complex mixtures was introduced and briefly discussed in Section 6.1.1. In 

Sections 6.1.2 and 6.1.3 other related TPH approaches are discussed. The ATSDR fraction approach 

preferentially adopts MRLs for petroleum products that are similar in composition to the transport 

fraction. When no such data are available, a surrogate MRL from a representative constituent of the 
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6. HEALTH EFFECTS 

fraction is adopted for the entire mass of the fraction, a practice which implicitly assumes that the toxicity 

of the constituents of a fraction is additive. This approach is consistent with existing ATSDR and EPA 

guidance (ATSDR 1992; De Rosa et al. 1996; EPA 1986; Johnson and De Rosa 1995; Mumtaz et al. 

1994). 

Additional refinements to the fraction approach for assessing health effects include estimation of an index 

of concern (IOC) for the indicator compounds (the BTEXs) of the aromatic EC5-EC9 fraction, or to 

account for exposure to more than one fraction. This approach is also based on the assumption of 

additivity, and is reasonable for compounds or fractions that affect the same system or target organ. The 

IOC is the sum of the ratios of the monitored level of exposure to the accepted level of exposure for each 

of the constituents of a mixture: 

IOC = E1,/AL1 + E2AL2... + Ei/ALi 

where: 

EI = the actual exposure level to the ith component 

AL, = the acceptable exposure level for the ith component 

The accepted levels of exposure for ATSDR assessments would be inhalation MRLs, or soil or water 

concentrations calculated from oral MRLs. For example, the IOC method could be applied to acute oral 

exposures to the aromatic EC5-EC9 fraction (toluene, p-xylene) and the aromatic EC>9-EC16 fraction, for 

which the critical effects are neurological (Table 6-2). 

Other refinements could be provided by implementing the target-organ toxicity dose approach, which 

attempts to estimate the plausible critical effect and IOC that would have been calculated had the 

particular mixture been tested (Mumtaz et al. 1994, 1997). This approach is complicated, and would be 

suggested only when additional assessment is needed, perhaps to resolve differences between expected and 

actual health effects outcomes, or where critical effects are different across constituents or fractions that 

make up the “mixture.” 

Another complicated mixtures assessment method under investigation by ATSDR is the weight-of- evidence 

method for interactions (De Rosa et al. 1996; Johnson and De Rosa 1995; Mumtaz et al. 1994; 
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6. HEALTH EFFECTS 

Mumtaz and Durkin 1992). This method provides adjustments to the IOC to take into account 

interactions between the constituents of the mixture. Application to the BTEXs, particularly benzene and 

toluene, for which interactions have been reasonably well characterized, may be fruitful if needed to 

resolve issues in a health assessment. 

Regardless of the circumstances and methods, TPH health assessments are limited by data gaps in the 

toxicology for many of the compounds, transport fractions, and mixtures of petroleum products and 

wastes. The limitations of the analytical method(s) used to generate the TPH data must be understood 

(e.g., whether the analytical method identified transport fractions or specific compounds) (see Section 3.3). 

As long as the uncertainties and data limitations are recognized, the method described in Section 6.1.3 and 

the health effects information in Sections 6.2 and 6.3 provide general guidance for health assessments for 

TPH. 

6.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s), or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in 

readily obtainable body fluid(s) or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 
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6. HEALTH EFFECTS 

copper, zinc, and selenium). Biomarkers of exposure to total petroleum hydrocarbons are discussed in 

Section 6.8.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health impairment 

or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of tissue 

dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial cells), 

as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung capacity. 

Note that these markers are not often substance specific. They also may not be directly adverse, but can 

indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused by total petroleum 

hydrocarbons are discussed in Section 6.8.2. 

A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism’s ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. Biomarkers of susceptibility are discussed in 

Section 6.10, Populations That Are Unusually Susceptible. 

More information on biomarkers of exposure and effect to specific petroleum hydrocarbons can be found 

in ATSDR toxicological profiles on benzene (ATSDR 1997a), toluene (ATSDR 1994), ethylbenzene 

(ATSDR 1999a), xylenes (ATSDR 1995d), hexane (ATSDR 1999b), naphthalene (ATSDR 1995e) and 

polycyclic aromatic hydrocarbons (ATSDR 1995f); information for specific petroleum products can be 

found in ATSDR profiles on automotive gasoline (ATSDR 1995a), fuel oils (ATSDR 1995g), jet fuels 

(ATSDR 1995c 1998b), mineral-based crankcase oils (ATSDR 1997c), hydraulic fluids (ATSDR 

1997b), and Stoddard solvent (ATSDR 1995b). 

6.8.1. Biomarkers Used to Identify or Quantify Exposure to TPH 

Because of the compositional complexity of TPH, detection of specific hydrocarbons or their metabolites 

in biological fluids or tissues cannot be expected to provide a reliable biomarker of exposure to petroleum-derived 

hydrocarbons in general. However, detection of specific hydrocarbons (or their metabolites) from 

several aromatic and/or aliphatic fractions in biological fluids or tissues can provide reliable evidence of 

exposure. Examples of proposed biomarkers of exposure to petroleum products include: benzene in 
TOTAL PETROLEUM HYDROCARONS 184 

6. HEALTH EFFECTS 

exhaled air and phenol in urine to indicate exposure to gasoline (IARC 1989a), the odor of kerosene on the 

breath or clothing to indicate oral or dermal exposure to kerosene, and radiological findings of lung 

infiltrations to indicate oral or inhalation exposure to kerosene or other petroleum products (ATSDR 

199.58; Snodgrass 1997). Lipid granulomatas found in autopsied livers and spleens (i.e., lipoid droplets 

surrounded by lymphocytes and macrophages) are thought to be caused by dietary exposure to mineral oils 

and waxes (Wanless and Geddie 1985; Miller et al. 1996); their detection in autopsied tissues may be 

useful as an index of exposure to petroleum hydrocarbons, especially hydrocarbons in the aliphatic 

EC>16-EC35 fractions. 

6.8.2 Biomarkers Used to Characterize Effects Caused by TPH 

Symptoms of neurological dysfunction, such as ataxia, poor coordination and gait irregularities, are 

potential biomarkers of effect from acute or repeated high-level exposure to petroleum-derived 

hydrocarbons in the aliphatic EC5-EC8 and aromatic EC5-EC9 fractions (see ATSDR 1994, 1995a, 

1995c, 1995d, 1995f, 1997a, 1998b, 1999a, 1999b). Such symptoms, while shared by many 

hydrocarbons in these fractions, are not specific to petroleum hydrocarbons and could indicate exposure to 

other substances such as halogenated hydrocarbons or neurotoxic metals. Such symptoms, however, are 

not expected from the low-level exposure to hydrocarbons in these fractions that is likely to be experienced 

by people residing in the vicinity of disposal sites contaminated with petroleum hydrocarbons. 

Measurements of motor and sensory nerve conduction velocities and action potential amplitudes have been 

proposed as sensitive preclinical biomarkers of peripheral neuropathy in workers repeatedly exposed to 

n-hexane (ATSDR 1999b), but this effect is specific to n-hexane (and perhaps a few other aliphatic 

hydrocarbons in the EC5-EC8 fraction) among petroleum hydrocarbons. 

Many, but not all, PAHs (aromatic EC>16-EC35 hydrocarbons) are genotoxic in various test systems and 

carcinogenic in animal test systems. The measurement of benzo(a)pyrene-DNA adducts in human body 

tissues or fluids has been proposed as a biomarker of effect from exposure to combustion or pyrolytic 

products containing genotoxic and carcinogenic PAHs, of which benzo(a)pyrene is the most extensively 

studied (see ATSDR 1995f). These measurements, however, are specific to benzo(a)pyrene and do not 

identify the source of the benzo(a)pyrene (PAHs are ubiquitous in the environment because they are 

produced by the pyrolysis or combustion of any material containing hydrocarbons). 
TOTAL PETROLEUM HYDROCARONS 185 

6. HEALTH EFFECTS 

Hematological effects from exposure to hydrocarbons in the aromatic EC5-EC9 and EC>9-EC16 fractions 

include hemolytic anemia from naphthalene exposure and decreased hematopoiesis and leukemia from 

benzene exposure. Because these effects are not specific to these hydrocarbons, frequent monitoring of 

blood cell counts in benzene-exposed workers has been used as a biomarker of hematotoxic effects (see 

ATSDR 1997a). 

6.9 INTERACTIONS WITH OTHER SUBSTANCES 

Individuals exposed to TPH in the environment are exposed to complex mixtures that are not generally 

restricted to hydrocarbons alone. It is reasonable to expect that components of such complex mixtures 

may interact to produce additive effects that do not influence the toxicity of individual components, and 

synergistic or antagonistic effects that do. Studies with the BTEXs (see ATSDR 1994, 1995d, 1997a, 

1999a), with naphthalene and methylnaphthalenes (see ATSDR 1995e), with PAHs (ATSDR 1995f), and 

with hexane (ATSDR 1999b) indicate that competitive or non-competitive inhibitory interactions with 

active sites of cytochrome P-450 isozymes, epoxide hydrolases, or other enzymes can influence 

metabolism of individual hydrocarbons. This can lead to antagonism of toxic effects mediated by 

metabolic intermediates (e.g., hematopoietic and cancer effects from benzene, cancer, or genotoxic effects 

from carcinogenic PAHs such as benzo(a)pyrene or dibenz(a,h)anthracene; peripheral neuropathy from 

hexane) or synergism or potentiation of toxic effects mediated by the parent hydrocarbon (e.g., acute CNS 

depression from the BTEXs). In addition, inductive or enhancing effects on enzyme activities can increase 

metabolic rate or capacity leading to potential non-additive interactive effects on hydrocarbon toxicities: 

potential synergism or potentiation toxic effects with induction of enzymes catalyzing the production of 

toxic intermediates, and potential antagonism of toxic effects with induction of detoxifying enzymes. 

Given the compositional complexity of TPH mixtures that may be found in the environment, it is difficult, 

if not impossible, to make reliable statements predicting the magnitude and direction of specific 

interactions that may occur. In the face of such large uncertainty, assuming that chemicals in complex 

mixtures interact in an additive manner at a particular target organ may be the most reasonable approach 

because it is the most simple. 
TOTAL PETROLEUM HYDROCARONS 186 

6. HEALTH EFFECTS 

6.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to petroleum hydrocarbons than will 

most people exposed to the same level of petroleum hydrocarbons in the environment. Reasons may 

include genetic makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., 

cigarette smoke). These parameters may result in reduced detoxification or excretion of petroleum 

hydrocarbons, or compromised function or organs affected by petroleum hydrocarbons. 

Factors that inhibit or alter the activity of the mixed function oxidase enzymes may increase the risk from 

exposure to the indicator compounds in the aromatic EC5-EC9 fraction (the BTEXs), the aromatic 

EC>16-EC35 fraction (the carcinogenic PAHs in this fraction) and a constituent of the aliphatic EC5-EC8 

fraction (n-hexane). For example, concurrent alcohol consumption may increase the risk of central 

nervous system depression from the BTEXs, ototoxicity from toluene, and hematotoxicity from benzene. 

Acetone exposure may increase the risk of peripheral neuropathy of n-hexane. People who take 

haloperidol, acetaminophen, or aspirin, or who have a nutritionally inadequate diet, may also be more 

susceptible to the toxicity of these agents. ATSDR (1995f) noted that a substantial percentage of children 

consume less than the recommended dietary allowances of certain nutrients. 

Other populations are unusually susceptible to the aromatic EC5-EC9 fraction. People with l3-thalassemia 

may be at risk for benzene exposure because some forms of β-thalassemia may exacerbate the adverse 

effects of benzene on the hematopoietic system. Children and fetuses may be at increased risk to benzene 

toxicity because their hematopoietic cell populations are expanding and dividing cells are at a greater risk 

than quiescent cells. Developmental effects in animals are the basis for intermediate inhalation MRLs for 

ethylbenzene and mixed xylene, indicating that the embryo/fetus may be particularly sensitive to these two 

BTEXs. People with subclinical and clinical epilepsy are considered at increased risk of seizures from 

xylene because of its central nervous system effects. 

Person with inherited erythrocyte G6PD deficiency have an enhanced susceptibility to the hemolytic effects 

of naphthalene, a constituent of the aromatic EC>9-EC16 fraction. Infants appear to be more sensitive than 

adults to this effect, and infants are more prone to permanent neurological damage as a consequence of the 

jaundice that results from the hemolysis. Naphthalene has been shown to cross the human placenta to 
TOTAL PETROLEUM HYDROCARONS 187 

6. HEALTH EFFECTS 

cause hemolysis and hemolytic anemia in the newborn infants of mothers who consumed naphthalene 

during pregnancy (ATSDR 1995e). 

People with aryl hydrocarbon hydroxylase (AHH) that is particularly susceptible to induction may be 

more susceptible to the carcinogenic PAHs found in the aromatic EC>16-EC35 fraction. Individuals 

undergoing rapid weight loss that includes loss of body fat are anticipated to be at risk because of the 

systemic release and activation of PAHs that had been stored in fat. People with genetic diseases that are 

associated with DNA-repair deficiencies (e.g., xeroderma pigmentosum, ataxia telangiectasia, familial 

retinoblastoma, Down’s syndrome) may be more susceptible to PAH-related malignancy. Individuals who 

have significant exposure to ultraviolet radiation, as from sunlight, may be at increased risk of developing 

skin cancer from PAH exposure. The human fetus may also be particularly susceptible to PAH toxicity 

because of increased permeability of the embryonic/fetal blood-brain barrier and a decreased liver-enzyme 

conjugating function. Based on studies of benzo(a)pyrene in animals, women may be at increased risk of 

reproductive dysfunction following exposure to high levels of PAHs. 

Individuals with impaired pulmonary function may be more susceptible to the respiratory irritant effects of 

the volatile petroleum hydrocarbons (primarily the aromatic EC5-EC9 and aliphatic EC5-EC9 fractions). 

Additional information regarding populations unusually susceptible to the aliphatic EC5-EC8, EC>8-EC16, 

and EC>16-EC35, fractions is limited. Factors that alter the function of mixed function oxidase enzymes 

may increase the risk of peripheral neuropathy from exposure to n-hexane, a constituent of the EC5-EC8 

fraction. A single animal study indicates that susceptibility to the neuropathic effects of n-hexane was 

more severe in young adults than in weanlings. A single study of kerosene (EC>8-EC16) in rats showed 

that younger animals, and particularly preweanlings, were more susceptible than older rats to the lethality 

of kerosene, but whether these findings for n-hexane and kerosene can be extrapolated to humans is 

uncertain. Case reports of accidental poisoning through ingestion indicate that children 5 years old or 

younger often mistakenly drank kerosene because it was accessible. The applicability of this scenario to 

hazardous waste sites is questionable. 

More detailed information regarding populations that are unusually susceptible to petroleum hydrocarbons 

can be obtained from the ATSDR toxicological profiles (ATSDR 1994, 1995d, 1995e, 1995f, 1997a, 
TOTAL PETROLEUM HYDROCARONS 188 

6. HEALTH EFFECTS 

1998b, 1999a, 1999b) on which this section was based. Other pertinent toxicological profiles (ATSDR 

1995b, 1995c, 1995g) noted a lack of information on susceptible populations. 

6.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to petroleum hydrocarbons. However, because some of the treatments discussed may be 

experimental and unproven, this section should not be used as a guide for treatment of exposures to 

petroleum hydrocarbons. When specific exposures have occurred, poison control centers and medical 

toxicologists should be consulted for medical advice. The following texts provide specific information 

about treatment following exposures to petroleum hydrocarbons: 

Snodgrass, W.R. 1997. Clinical Toxicology. In: Cassarett and Doull’s Toxicology. The Basic 

Science of Poisons. Fifth Edition. pp. 969-986. C.D. Klaassen, M.O. Amdur, and J. Doull, eds 

McGraw-Hill, New York. 

Friedman, P.A. 1987. Poisoning and Its Management. In: Harrison’s Principles of Internal 

Medicine. Eleventh Edition. pp. 838-850. J.D. Jeffers, E.J. Scott and M. Ramos-Englis, eds. 

McGraw-Hill. New York. 

Klaasen, C.D. 1996. Nonmetallic Environmental Toxicants. Air Pollutants, Solvents and Vapors, 

and Pesticides. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Ninth 

Edition. J.G. Hardman and L.E. Limbird, eds. McGraw-Hill, New York. 

Information on methods that may be effective in reducing absorption, reducing body burdens, or 

interfering with mechanisms of toxic action of specific petroleum hydrocarbons can be found in ATSDR 

profiles on the BTEXs (ATSDR 1994, 1995d, 1997a, 1999a), hexane (ATSDR 1999b), naphthalene 

(ATSDR 1995f), and PAHs (1995f). Additional information for petroleum products can be found in 

ATSDR profiles on automotive gasoline (ATSDR 1995a), fuel oils (ATSDR 19958) jet fuels (ATSDR 

199512, 1998b), mineral-based crankcase oils (ATSDR 1997c) hydraulic fluids (1997b), and Stoddard 

solvent (ATSDR 1995b). 
TOTAL PETROLEUM HYDROCARONS 189 

6. HEALTH EFFECTS 

6.11.1 Reducing Peak Absorption Following Exposure 

It is commonly recognized that, in the treatment of poisoning from ingestion of low viscosity, aliphatic or 

aromatic hydrocarbons found in petroleum products such as gasoline and kerosene, care must be taken to 

prevent aspiration into the respiratory tract (Friedman 1987; Klaassen 1996; Snodgrass 1997). Emesis, 

gastric lavage, and treatment with activated charcoal are often avoided unless large amounts have been 

ingested (>l00 mL) or there is a known risk of absorption of non-hydrocarbon additives (e.g., metals, 

pesticides) that may produce systemic effects. If gastric lavage is applied, an endotracheal tube with 

inflatable cuff is often used to prevent aspiration. Viscous, large molecular weight aliphatic hydrocarbons 

such as those in mineral oil, heavy lubricants, and Vaseline are not aspirated to the lung and have cathartic 

properties; removal treatments are not usually used. Absorption of petroleum hydrocarbons by the skin 

following dermal exposure can be reduced by washing with a mild soap or detergent and water, taking 

care not to abrade the skin. 

6.11.2 Reducing Body Burden 

Petroleum-derived hydrocarbons and their metabolites (e.g., fatty acids), especially those in the aliphatic 

and aromatic EC>16-EC35 fractions, tend to accumulate in the liver, spleen, and adipose tissues. There are 

no known clinical methods to facilitate or accelerate removal of petroleum hydrocarbons or their 

metabolites from these tissues. 

6.11.3 Interfering with the Mechanism of Action for Toxic Effects 

Acute inhalation or aspiration of ingested aliphatic or aromatic petroleum hydrocarbons of low viscosity 

can lead to pulmonary irritation and hydrocarbon pneumonia, an acute hemorrhagic necrotizing disease. 

To counteract secondary bacterial infections and pulmonary edema, antibiotics and oxygen therapy are 

often applied when indicated by symptoms in particular patients (Klaassen 1996; Snodgrass 1997). 

Specific aliphatic and aromatic hydrocarbons found in petroleum products are known to be-metabolized 

via cytochrome P-450 pathways to reactive metabolic intermediates that are thought to cause non-cancer 

and cancer effects from chronic exposure (e.g., peripheral neuropathy from 2,5-hexadione, a metabolite of 

hexane, and cancer effects from various intermediary metabolites of benzene and carcinogenic PAHs). 

There are no known clinical methods to interfere with these mechanisms of action. However, current 

research programs are studying the basis of how the consumption of cruciferous vegetables may protect 
TOTAL PETROLEUM HYDROCARONS 190 

6. HEALTH EFFECTS 

against chemical carcinogenesis, and examining the protective role that may be played by dietary 

antioxidants and the induction of Phase II enzymes (enzymes involved in the detoxification of products of 

cytochrome P-450 enzymes) (see Prochaska and Talalay 1992; Zhang et al. 1992; Talalay 1992; Fahey et 

al. 1997). Results from this type of research may lead to clinical methods counteracting the toxic effects 

of chronic exposure to bioactivated hydrocarbons. 

6.12 ADEQUACY OF THE DATABASE 

The adequacy of the database for many of the constituents of TPH and for petroleum products has been 

fully discussed in the corresponding toxicological profiles. This section will briefly discuss adequacy of 

the database to support a fraction-based assessment of TPH. 

The database for the aromatic EC5-EC9 fraction is that for the individual BTEXs; the recommendation in 

this profile is to assess each of these compounds individually as indicator compounds. The database for 

inhalation exposure is more adequate than for oral exposure. Details are provided in the respective 

ATSDR profiles (ATSDR 1994, 1995d, 1997a, 1999a). 

The database for the aromatic EC>9-EC16 fraction lacks information on a mixture or mixtures that could 

represent the entire combined fraction. Limited inhalation data are available on a mixture of C9 aromatics 

(high flash aromatic naphtha, primarily EC9.47-EC9.84). Health effects data from these mixtures and from 

potential representative chemicals, including naphthalene, suggest some commonality of effect among 

constituents of this fraction. MRLs are available for chronic inhalation exposure and all three periods of 

oral exposure. Surrogate MRL values are suggested for chronic inhalation exposure and acute and 

intermediate oral exposure to this fraction. Nevertheless, the data do not strongly support a surrogate 

approach. Additional information on the database for naphthalene, 1- and 2-methyl naphthalene, 

acenaphthylene and acenaphthene is discussed in ATSDR (1995e, 1995f). 

The adequacy of the database for the aromatic EC>16-EC35 fraction, which consists of PAHs, is discussed 

in ATSDR (1995f). Data for suitable mixtures were not identified. Inhalation data for the individual 

constituents were particularly limited; no MRLs were available. The oral data support the selection of a 

surrogate MRL for intermediate exposure to the noncarcinogenic constituents of this fraction, but it is 

uncertain whether this value is appropriate to represent the noncancer effects of the carcinogenic PAHs. 
TOTAL PETROLEUM HYDROCARONS 191 

6. HEALTH EFFECTS 

The database for inhalation exposure to the aliphatic EC5-EC8 fraction includes data for a representative 

mixture, commercial hexane, but many of the studies were performed under a TSCA test rule and have 

been published only as abstracts (TPHCWG 1997c). ATSDR (1999b) briefly discussed commercial 

hexane in the toxicological profile on n-hexane, but did not consider MRL derivation for commercial 

hexane, as it was not the subject of the profile. The only compound or petroleum product corresponding 

to this fraction that has been the focus of MRL derivation by ATSDR is n-hexane, for which a chronic 

inhalation MRL is available. The data were considered inadequate for the derivation of oral MRLs for 

this compound (ATSDR 1999b). Details of the adequacy of the database for n-hexane are provided by 

ATSDR (1999b). 

For the aliphatic EC>8-EC16 fraction, the database includes a number of studies of petroleum products 

whose major constituents fall within the EC range of this fraction. These included dearomatized petroleum 

streams and fuels (JP-5, JP-7, JP-8, kerosene). Studies of the dearomatized petroleum streams are largely 

unpublished, include oral studies in animals, and have been reviewed by the TPHCWG (1997c). The 

critical effects were judged to be hepatic. MRLs were available for intermediate and chronic inhalation 

exposure to JP-7 and JP-5 and JP-8; these are based on hepatic effects. The MRLs for these jet fuels 

appeared suitable to represent the health effects of the fraction. Detailed analyses of the adequacy of the 

database for the fuels are provided by ATSDR (1995c, 1995g), 1998). 

Mineral oils, which are petroleum products similar in composition to the aliphatic EC>16-EC35 fraction, 

have been tested by the oral route, as reviewed by the TPHCWG (1997c); the TPHCWG based its 

derivation of health effects criteria on these studies. Issues regarding the TPHCWG’s derivation include 

the classification of histiocytosis as a nonadverse effect and the suitability of the F344 rat to serve as a 

model for humans for this class of compounds (Section 6.2.6.2). ATSDR has not considered the health 

effects of these products in a toxicological profile, and there are no other petroleum products or 

constituents corresponding to this fraction that have MRLs. 

Ongoing studies of interest are the studies performed under a Section 4 TSCA test rule of commercial 

hexane and of cyclohexane mentioned by the TPHCWG (1997c). In addition, the Verhaar et al. (1997) 

describe a proposed approach and ongoing research to develop PBPK/PD models for use in assessing 

human health risks from exposure to JP-5. 

TOTAL PETROLEUM HYDROCARONS 193 

7. REGULATIONS AND ADVISORIES 

The international, national, and state regulations and guidelines regarding total petroleum hydrocarbons 

(TPH) in air, water, and other media are summarized in Table 7-1. No health or environmental 

benchmarks have been developed for TPH as a general category, though many exist for individual 

petroleum chemicals or products, such as gasoline. 

Benzene is on the list of chemicals in “The Emergency Planning and Community Right-to-Know Act of 

1986” (EPA 1988c, 1989c, 1989d). Section 313 of Title III of the Superfund Amendments and 

Reauthorization Act (SARA) requires owners and operators of certain facilities that manufacture, import, 

process, or otherwise use the chemicals on this list to report annually any release of those chemicals to any 

environmental media over a specified threshold level. 

OSHA requires employers of workers who are occupationally exposed to petroleum distillates to institute 

engineering controls and work practices to reduce and maintain employee exposure at or below permissible 

exposure limits (PEL). The PEL for petroleum distillates is 500 ppm (OSHA 1974). 

TPH as oil is regulated by the Clean Water Act as stated in Title 40, Sections 109-l 14 and Section 112 

of the Code of Federal Regulations. Sections 109-l14 address oil pollution prevention and spill response. 

Section 112 pertains to stormwater discharge permitting under the National Pollutant Discharge 

Elimination System. Underground injection control is regulated according to 40 CFR Sections 144 

and 146. 

Under Subtitle C of the Resource Conservation and Recovery Act (RCRA), certain wastes containing 

designated TPH compounds and petroleum-related industrial wastes are listed as hazardous. However, 

RCRA excludes some TPH-related wastes from regulations (e.g., certain exploration, well development, 

and productions wastes). The RCRA-listed wastes are also controlled under the Comprehensive 

Environmental, Response, Compensation, and Liability Act (CERCLA) for accidental releases to the 

environment. 

The American Society for Testing and Materials (ASTM) developed a guide for the community of 

engineering firms, environmental and risk assessment scientists, and governmental agencies to deal with 
TOTAL PETROLEUM HYDROCARONS 194 

7. REGULATIONS AND ADVISORIES 

petroleum contaminated sites. In 1995 ASTM published its Standard Guide for Risk-Based Corrective 

Action Applied at Petroleum Release Sites partly in response to Subtitle I of the Resource Conservation 

and Recovery Act (RCRA) (ASTM 1995). RCRA directed the U.S. Environmental Protection Agency 

(EPA) establish programs to prevent, detect, and clean up releases from underground storage tank systems 

(UST). ASTM’s risk-based corrective action (RBCA) is a widely used, decision-making process for the 

assessment and response to chemical releases, with particular emphasis on petroleum release, based on the 

protection of human health and the environment. RBCA integrates site assessment, remedial action 

selection, and monitoring with risk and exposure assessment practices suggested by the EPA. The RBCA 

process is implemented in a tiered approach that involves increasingly sophisticated levels of data 

collection and analysis. Site assessment is followed by site classification whereby sites are classified by 

the urgency of initial response action based on information collected during the site assessment. Section 

5.3.3.3, Transport Models, in Chapter 5 presents a brief overview of the tiered RBCA approach and also 

provides the basic flow chart of the RBCA approach, Figure 5-2. 






TOTAL PETROLEUM HYDROCARONS 201 

8. REFERENCES 

3M. 1993. Organic vapor monitor analysis guide for organic vapor monitors 3500/3510 and organic 

vapor monitors 3520/3530. 3M Company, Occupational Health and Sefety Division, St. Paul. 70-0702­

1914-5(113.5)R. 

ABB-Environmental. 1990. Compilation of data on the composition, physical characteristics and water 

solubility of fuel products. Prepared for Massachusetts Department of Environmental Protection. 

Wakefield, Massachusetts. 

ACGIH. 1994. American conference of governmental industrial hygienists 1993-1994. Threshold Limit 

Values for Chemical Substances and Physical Agents and Biological Exposure Indices, 22. 

ACGIH. 1997. Threshold limit values for chemical substances and physical agents and biological 

exposure indices. ACGIH, Cincinnati, OH., 44-46. 

Air Force. 1989. Gasoline. In: The installation restoration program toxicology guide. Volume 4. 

Contract no. DE-AC05840R21400. Wright-Patterson Air Force Base, OH. Document no. 65-l-65-46. 

Air Force. 1991. Tumorigenic evaluation of jet fuels JP-TS and JP-7. Report No, AAMRL-TR-91­

0020. Wright-Patterson Air Force Base, OH. Aerospace Medical Research Laboratory, Aerospace 

Medical Division, U.S. Air Force Systems Command. 

Akamaguna AI, Odita JC. 1983. Radiology of kerosene poisoning in young children. Ann Trop Paediatr 

3(2):85-88. 

Albro, PW, Fishbein RO. 1970. Absorption of aliphatic hydrocarbons by rats. Biochem Biophys Acta 

219:437-446. 

Aldy D, Siregar R, Siregar H. 1978. Accidental poisoning in children with special reference to kerosene 

poisoning. Paediatr Indones 18( l-2):45-50. 

Amherst. 1999. Annual conferences. American Association for the Environmental Health of Soils. 

Http://www.aehs.com. Amherst, Massachusettes. 

Andrew FD, Buschborn RL, Cannon WC, et al. 1981. Teratologic assessment of ethylbenzene and 

2-ethoxyethanol. Richland, WA: Battelle Pacific Northwest Laboratory. PB83-208074, 108. 

Annobil SH. 1983. Chest radiographic patterns following kerosene poisoning in Ghanaian children. Clin 

Radio 134(6):643-646. 

Annobil SH, Ogunbiyi OA. 1991. Pulmonary radiology changes in kerosene poisoning in the Asir region 

of Saudia Arabia. Ann Trop Paediatr 11(4):391-395. 

Anziulewicz, JA, Dick HJ, Chiarulli EE. 1959. Transplacental naphthalene poisoning. Am J Obstet 

Gynecol78:519-521. 
TOTAL PETROLEUM HYDROCARONS 202 

8. REFERENCES 

APHA. 1992. Standard methods for the examination of water and wastewater. Prepared and published 

jointly by American Public Health Association, American Water Works Association, and Water 

Environment Federation. Washington, DC. 

API. 1993. Petroleum product surveys. American Petroleum Institute, Washington, DC. 

API. 1995a. Index and abstracts of API health-related Research. 13th Edition. 1959-1994. Health and 

Environmental Sciences Department, American Petroleum Institute. Washington, DC. 

API. 1995b. Protecting our planet: Strategies for today’s environmental partnership. Washington, DC: 

American Petroleum Institute (available at http://www.api.org/step/). 

API. 1996. Petroleum facts at a glance. January-December 1995. American Petroleum Institute. 

http:llwww.api.orglnews/faqsl 

API. 1998a. Monthly petroleum facts at a glance. January-December 1997. American Petroleum 

Institute. http://www.api.org/faqs/ 

API. 1998b. Petroleum industry environmental performance, 6’h annual report. American Petroleum 

Institute, Washington, DC. 

Ashley DL, Bonin MA, Cardinali FL, et al. 1992. Determining volatile organic compounds in human 

blood from a large sample population by using purge and trap gas chromatography/mass spectrometry. 

Anal Chem 64(9):1021-1029. 

ASTM. 1992. Manual on hydrocarbon analysis, 5th. American Society for Testing and Materials. West 

Conshohocken, PA. 

ASTM. 1994. Annual book of ASTM standards; section 11, water and environmental technology. 

Standard test methods for analysis of selected elements in waterborne oils. American Society for Testing 

and Materials. Philadelphia, PA. 

ASTM. 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. American 

Society for Testing and Materials. West Conshohocken, PA. 

Atlas RM, Cerniglia CE. 1995. Bioremediation of petroleum pollutants. Bioscience 45(5):332-338. 

ATSDR. 1992. Public health assessment guidance manual. Agency for Toxic Substances and Disease 

Registry, Atlanta, GA. 

ATSDR. 1994. Toxicological profile for toluene (update). Agency for Toxic Substances and Disease 

Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

TP-93/14. 

ATSDR. 1995a. Toxicological profile for automotive gasoline. Agency for Toxic Substances and 

Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

NTIS PB95-264206. 
TOTAL PETROLEUM HYDROCARONS 203 

8. REFERENCES 

ATSDR. 1995b. Toxicological profile for Stoddard solvent. Agency for Toxic Substances and Disease 

Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. NTIS 

PB95-264263. 

ATSDR. 1995c. Toxicological profile for jet fuels (JP-4 and JP-7). Agency for Toxic Substances and 

Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

NTIS PB95-264230. 

ATSDR. 1995d. Toxicological profile for xylenes (update). Agency for Toxic Substances and Disease 

Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

ATSDR. 1995e. Toxicological profile for naphthalene (update). Agency for Toxic Substances and 

Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

ATSDR. 1995f. Toxicological profile for polycyclic aromatic hydrocarbons (PAHs) (update). Agency 

for Toxic Substances and Disease Registry, Public Health Service, U.S. Department of Health and Human 

Services, Atlanta, GA. 

ATSDR. 1995g. Toxicological profile for fuel oils. Agency for Toxic Substances and Disease Registry, 

Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. NTIS PB95­

264222. 

ATSDR. 1996a. Toxicological profile for methyl-tert-butyl ether. Agency for Toxic Substances and 

Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

ATSDR. 1996b. Minimal risk levels for priority substances and guidance for derivation, republication. 

Federal Register. 61 FR 125:335 1 l-33520. 

ATSDR. 1997a. Toxicological profile for benzene (update). Agency for Toxic Substances and Disease 

Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

ATSDR. 1997b. Toxicological profile for hydraulic fluids. Agency for Toxic Substances and Disease 

Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

ATSDR. 1997c. Toxicological profile for mineral-based crankcase oil. Agency for Toxic Substances 

and Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, 

GA. 

ATSDR. 1998a. Hazardous Substance Release/Health Effects Database. Internet. Agency for Toxic 

Substances and Disease Registry. http://www.atsdr.cdc.gov/hazdat.html. 

ATSDR. 1998b. Toxicological profile for jet fuels (JP-5 and JP-8). Agency for Toxic Substances and 

Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

ATSDR. 1998c. Toxicological profile for mineral-based crankcase oil. Agency for Toxic Substances 

and Disease Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, 

GA. 
TOTAL PETROLEUM HYDROCARONS 204 

8. REFERENCES 

ATSDR. 1999a. Toxicological profile for ethylbenzene. Agency for Toxic Substances and Disease 

Registry, Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

ATSDR. 1999b. Toxicological profile for hexane. Agency for Toxic Substances and Disease Registry, 

Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 

Baelum J, Andersen I, Lundqvist GR, et al. 1985. Response of solvent-exposed printers and unexposed 

controls to six-hour toluene exposure. Stand J Work Environ Health 11:27 l-280. 

Barnes D, Dourson M. 1988. Reference dose (RfD): Description and use in health risk assessments. 

Regul Toxicol Pharmacol 8:471-486. 

Bauman BJ. 1988. Soils contaminated by motor fuels: Research activities and perspectives of the 

American Petroleum Institute. In: Petroleum contaminated soils, vol. 1. Chelsea, MI: Lewis Publishers, 

3-19. 

BC. 1995. Recommendations to British Columbia environment for development of remediation criteria or 

petroleum hydrocarbons in soil and groundwater, Vol 1. Industrial Wastes and Hazardous Contaminants 

Branch, Ministry of Environment, Lands and Parks. Victoria, B.C. 

Belisle AA, Gay ML, Coon NC. 1981. Comparison of 2 extraction methods for the analysis of petroleum 

hydrocarbon residues in mallard duck eggs by gas chromatography and gas chromatography-mass 

spectrometry. Chemosphere 10( 11-12): 1197-1204. 

BLM. 1982. Requirements for operating rights owners and operators. Bureau of Land Management, 

Interior. Code of Federal Regulations. 43 CFR 3 162. 

BNA. 1999. State environment and safety regulatory monitoring report, CD Rom. Bureau of National 

Affairs, Washington, DC. 

Bonazountas M. 1988. Mathematical pollutant fate modeling of petroleum products in soil systems. In: 

Calabrese EJ, Kostecki, eds. Soils contaminated by petroleum: Environmental and public health effects. 

New York, NY: John Wiley and Sons, 31-97. 

Bonazountas M. 1991. Fate of hydrocarbons in soils: review of modeling practices. In: Kostecki PT, 

Calabrese EJ, Bell CE, eds. Hydrocarbon contaminated soils and groundwater; Vol. I: Analysis, fate, 

environmental and public health effect remediation. Chelsea, MI: Lewis Publishers, 167-185. 

Borden RC, Bedient PB, Lee MD, et al. 1986. Transport of dissolved hydrocarbons influenced by 

oxygen-limited biodegradation: 2. Field application. Water Resources Research Vol 22(13):1983-1990. 

Bossert ID, Bartha R. 1986. Structure-biodegradability relationships of polycyclic aromatic 

hydrocarbons in soil. Bull Environ Contam Toxicol, 37(4):490-495. 

BP. 1996. Summary tables of laboratory analysis for diesel and fuel oil #2, personal communication 

from B. Albertson, Friedman and Bruya, Inc., Seattle, WA, developed for British Petroleum. 
TOTAL PETROLEUM HYDROCARONS 205 

8. REFERENCES 

Bruner RH, Kinkead ER, O’Neill TP, et al. 1993. The toxicologic and oncogenic potential of JP-4 jet fuel 

vapors in rats and mice: 12-month intermittent inhalation exposures. Fund Appl Toxicol 20:97-l 10. 

Burris DR, MacIntyre WG. 1984. Water solubility behavior of hydrocarbon mixtures -- Implications for 

petroleum dissolution. In: Vandermeulen JH, Hiudey SE, eds. Oil in freshwater: Chemistry, biology, 

countermeasure technology. New York,NY: Pergamon Press, 85-94. 

Bus JS, White EL, Tyl RW, et al. 1979. Perinatal toxicity and metabolism of n-hexane in Fischer-344 

rats after inhalation exposure during gestation. Toxicol Appl Pharmacol 51(2):295-302. 

Bushy Run. 1989a. Developmental toxicity study of commercial hexane vapor in CD (Sprague-Dawley) 

Rats. Unpublished study by Bushy Run Research Center, Export PA. Prepared for the American 

Petroleum Institute Washington DC. EPA TSCA Section 4 submission OTS0524323. 

Bushy Run. 1989b. Developmental toxicity study of commercial hexane vapor in CD-l mice. 

Unpublished study by Bushy Run Research Center, Export PA. Prepared for the American Petroleum 

Institute, Washington DC. EPA TSCA Section 4 submission OTS0524323. 

Calabrese E. 1978. Pollutants and high risk groups: The biological basis of increased human 

susceptibility to environmental and occupational pollutants. New York, NY: John Wiley and Sons. 

Castilla-Serna L, Rodriguez-Perez, Osorio-Cruces F, et al. 1991. Effects of chronic toluene inhalation on 

avoidance conditioned behavior in rats. Arch Invest Med 22:295-301. 

Cavender F. 1994. Aliphatic hydrocarbons. In: Clayton GD, Clayton FE, eds. Patty’s industrial hygiene 

and toxicology. Fourth Edition, Vol. II, Part B. New York: John Wiley & Sons, 1221-1266. 

Chang DY, Lopez I, Yocklovich, SG. 1992. Determination of kerosene and #2 diesel in soil by purge and 

trap vs. extraction procedure. Journal of Soil Contamination 1(3):239-25 1. 

Charbeneau RJ, Weaver JW. 1992. Modeling contaminant transport through subsurface systems. 4’h 

Annual Symposium “Groundwater: the problem and some solutions” proceedings, April 2-3, 1992. pp 

179-198. 

Charbeneau R, Weaver JW, Lien BK. 1995. Hydrocarbon spill screening model (HSSM). Vol. 2. 

Theoretical background and source codes. U.S. Environmental Protection Agency. Robert Kerr 

Environmental Research Lab, Ada, OK. 

Clark DB, Butterworth ST, Martin JG, et al. 1989. Inhalation toxicity of high flash aromatic naphtha. 

Toxic Ind Health 5(3):415-428. 

Clark RM, Vicory AH, Goodrich JA. 1990. The Ohio River oil spill: A case study. Journal of the 

American Water Works Association (March 1990):39-44. 

Coate WB, Hoberman AM, Durloo RS. 1984. Inhalation teratology study of benzene in rats. Adv Mod 

Environ Toxicol 6:187-198. 
TOTAL PETROLEUM HYDROCARONS 206 

8. REFERENCES 

Coleman E, Munch JW, Streicher RP, et al. 1984. The identification and measurement of components in 

gasoline, kerosene, and No. 2 fuel oil that partitions into the aqueous phase after mixing. Arch Env Cont 

Tox 13:171-178. 

CONCAWE. 1986. Method for monitoring exposure to gasoline vapour in air. The Hague, 

Netherlands. PB90-2697 13. 

Condie LW, Hill JR, Borzelleca JF. 1988. Oral toxicology studies with xylene isomers and mixed 

xylenes. Drug Chem Toxicol 11:329-354. 

Cox BA, Anderson JW, Parker JC. 1975. An experimental oil spill: The distribution of aromatic 

hydrocarbons in the water, sediment, and animal tissues within a shrimp pond. In: Proceedings of the 

Conference on the Prevention and Control of Oil Pollution, 607-612. 

Cushman JR, Norris JC, Dodd DE, et al. 1995. Subchronic inhalation toxicity and neurotoxicity 

assessment of cumene in Fischer 344 rats. J Am Co11 Toxicol 14(2): 129-147. 

Daugherty SJ. 1991. Regulatory approaches to hydrocarbon contamination and underground storage 

tanks. In: Hydrocarbon contaminated soils and groundwater: analysis, fate, environmental and public 

health effects, and remediation. Vol. 1. Chelsea MI: Lewis Publishers, Inc., 23-53. 

Daugherty SJ. 1993. Hydrocarbon contamination in the subsurface: Realities, issues, and prospects. In: 

Kostecki P, Calabrese E, eds. Hydrocarbon contaminated soils and groundwater, vol 3. Chelsea MI: 

Lewis Publishers, Inc., 3-18. 

Daughtrey WC, Duffy JS, Haddock LS, et al. 1994. Chronic inhalation study of commercial hexane in 

mice. Toxicologist 14:317 (Abstract #1234). 

Deerhake, ME, et al. n.d. Human and ecological risk assessment for the petroleum refining waste listing 

determinations background document. Prepared for the Office of Solid Waste, U.S. Environmental 

Protection Agency, by Research Triangle Institute under Contract No. 68-W-4-0042. 

Deichmann WB, Kitzmiller KV, Witherup BS, et al. 1944. Kerosene intoxication. Ann Intern Med 

21:803-823. 

De Rosa CT, Johnson BL, Fay M, Hansen H, Mumtaz MM. 1996. Public health implications of 

hazardous waste sites: Findings, assessment and research. Food Chem Toxicol 34: 1131-l 138. 

De Rosa CT, Stevens Y-W, Johnson BL. 1993. Cancer policy framework for: Public health assessment 

of carcinogens in the environment. Toxicol Ind Health 9:559-575. 

DOD. 1995. Defense environmental restoration program: Annual report to congress for fiscal year 1994, 

March 31, 1995. Washington, DC. U.S. Department of Defense (available at 

http://www.dtic.dla.mil/envirodod/derpreport/toc.htmI). 
TOTAL PETROLEUM HYDROCARONS 207 

8. REFERENCES 

DOT 1990. Hazardous materials table, special provisions, hazardous materials communications, 

emergency response information, and training requirements. Subpart B: Tables of Hazardous Materials 

and Special Provisions. Purpose and Use of Hazardous Materials Table. U.S. Department of 

Transportation. Code of Federal Regulations. 49 CFR 172.101. 

Dowty BJ, Laseter JL, Storer J. 1976. The transplacental migration and accumulation in blood of 

volatile organic constituents. Pediatr Res 10:696-701. 

Doyle, Jack. 1994. Crude awakening: The oil mess in America. Washington, DC: Friends of the Earth. 

Dragun J. 1988. Microbial degradation of petroleum products in soil. In: Calabrese E, Kostecki P, eds. 

Soils contaminated by petroleum: Environmental and public health effects. New York, NY: John Wiley 

and Sons, 289-298. 

Dudek B, Gralewicz K, Jakubowski M, et al. 1990. Neurobehavioral effects of experimental exposure to 

toluene, xylene and their mixture. Pol J Occup Med 3:109-116. 

Dyer RS, Bercegeay MS, Mayo LM. 1988. Acute exposures to p-xylene and toluene alter visual 

information processing. Neurotoxicol Teratol 10:147-153. 

EA Engineering. 1995. Selection of surrogate fractions based on fate and transport considerations. Total 

Petroleum Hydrocarbon Criteria Working Group Project #3. Prepared for U.S. Air Force, Armstrong 

Laboratory 

Eastcott L, Shiu WY, Mackay D. 1989. Modeling petroleum products in soils. In: Petroleum 

contaminated soils, Vol. 1. Chelsea, MI: Lewis Publishers, Inc., 63-80. 

Elovaara E, Engstrom K, Hayri L, et al. 1989. Metabolism of antipyrine and m-xylene in rats after 

prolonged pretreatment with xylene alone or xylene with ethanol, phenobarbital, or 3-methylcholanthrene. 

Xenobiotica 19:945-960. 

EPA. 1971. Criteria for state, local, and regional oil removal contingency plans. U.S. Environmental 

Protection Agency. Code of Federal Regulations. 40 CFR 109. 

EPA. 1973a. Oil pollution prevention. U.S. Environmental Protection Agency. Code of Federal 

Regulations. 40 CFR 112. 

EPA. 1973b. Liability limits for small onshore storage facilities. U.S. Environmental Protection Agency. 

Code of Federal Regulations. 40 CFR 113. 

EPA. 1974. Civil penalties for violation of oil pollution prevention regulations. U.S. Environmental 

Protection Agency. Code of Federal Regulations. 40 CFR 114. 

EPA. 1979a. Criteria for classification of solid waste disposal facilities and practices. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 257. 
TOTAL PETROLEUM HYDROCARONS 208 

8. REFERENCES 

EPA. 1979b. Polychlorinated biphenyls (PCBs) manufacturing, processing, distribution in commerce, 

and use prohibitions. Subpart D: Storage and disposal. Disposal Requirements. U.S. Environmental 

Protection Agency. Code of Federal Regulations. 40 CFR 761.60. 

EPA. 1979c. Methods for chemical analysis of water and wastes: Method 418.1 (spectrophotometric, 

infrared); petroleum hydrocarbons, total recoverable. U.S. Environmental Protection Agency, EPA-600­

79-020. 

EPA. 1979d. Methods for chemical analysis of water and wastes: Method 413.2 (spectrophotometric, 

infrared); oil and grease, total recoverable. U.S. Environmental Protection Agency, EPA-600-79-020. 

EPA. 1979e. Methods for chemical analysis of water and wastes: Method 413.1 (gravimetric, separatory 

funnel extraction); oil and grease, total recoverable. U.S. Environmental Protection Agency, EPA-600-79­

020. 

EPA. 1980a. Underground injection control program: criteria and standards. Subpart C: Criteria and 

standards applicable to class ii wells. U.S. Environmental Protection Agency. Code of Federal 

Regulations. 46 CFR 146. 

EPA. 1980b. Hazardous waste management system: General. Subpart B: Definitions. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 260.10. 

EPA. 1980c. Identification and listing of hazardous waste. Exclusions: Solid wastes which are not 

hazardous wastes. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 261.4. 

NTIS No. PB81-190019. 

EPA. 1981a. Hazardous wastes from non-specific sources: Petroleum refinery primary and secondary 

oil/water/solids separation sludges (F037, F038). U.S. Environmental Protection Agency. Code of 

Federal Regulations. 40 CFR 261.3 1. 

EPA. 1981b. Identification and listing of hazardous waste. Subpart D: Lists of hazardous wastes; 

hazardous wastes from specific sources: Petroleum refining wastes (K048 - K0.52). U.S. Environmental 

Protection Agency. Code of Federal Regulations. 40 CFR 261.32. 

EPA. 1983a. Underground injection control program. U.S. Environmental Protection Agency. Code of 

Federal Regulations. 40 CFR 144. 

EPA. 1983b. EPA administered permit programs: The national pollutant discharge elimination system. 

Subpart B: Permit application and special NPDES program requirements. General Permits. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 122.28. 

EPA. 1984. State underground injection control programs. U.S. Environmental Protection Agency. 

Code of Federal Regulations. 40 CFR 147. 

EPA. 1985a. Identification and listing of hazardous waste. Definition of solid waste. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 261.2. 
TOTAL PETROLEUM HYDROCARONS 209 

8. REFERENCES 

EPA. 1985b. Identification and listing of hazardous waste. Requirements for recyclable materials. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 261.6. 

EPA. 1985c. Designation, reportable quantities, and notification. Designation of hazardous substances. 

U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 302.4. 

EPA. 1986. Guidelines for the health risk assessment of chemical mixtures. Fed Reg 51:34014-34025. 

EPA. 1987a. Report to Congress: Management of wastes from the exploration, development, and 

production of crude oil, natural gas, and geothermal energy. U.S. Environmental Protection Agency 

Office of Solid Waste and Emergency Response, Washington, DC. EPA/530-SW-88-003. December 

1987. 

EPA. 1987b. Discharge of oil. U.S. Environmental Protection Agency. Code of Federal Regulations. 

40 CFR 110. 

EPA. 1987c. Evaluation of the carcinogenicity of unleaded gasoline. U.S. Environmental Protection 

Agency. Washington, DC. EPA/600/6-87/001. 

EPA. 1987d. Criteria for the classification of solid waste disposal facilities and practices. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 257. 

EPA. 1987e. Underground storage tanks; proposed rule. U.S. Environmental Protection Agency. Code 

of Federal Regulations, 40CFR280-28 1. 

EPA. 1988a. Compendium of Methods for the determination of toxic organic compounds in ambient air. 

U.S. Environmental Protection Agency. EPA 600/4-89/017, June 1988. 

EPA. 1988b. Technical standards and corrective action requirements for owners and operators of 

underground storage tanks (UST). U.S. Environmental Protection Agency. Code of Federal Regulations. 

40 CFR 280. 

EPA. 1988c. Treatment standards. U.S. Environmental Protection Agency. Code of Federal 

Regulations, 40CFR268, Subpart D. Washington, DC. 

EPA. 1989a. Health and environmental effects document for n-hexane. U.S. Environmental Protection 

Agency, Office of Solid Waste and Emergency Response, Washington, DC. 

EPA. 1989b. Health and environmental effects document for n-heptane. U.S. Environmental Protection 

Agency, Office of Solid Waste and Emergency Response, Washington, DC. 

EPA. 1989c. Health and environmental effects document for methylcyclohexane. U.S. Environmental 

Protection Agency, Office of Solid Waste and Emergency Response, Washington, DC. 

EPA. 1989d. Risk assessment guidance for superfund. Volume I. Human health evaluation manual 

(Part A). Office of Emergency and Remedial Response, Washington, DC. EPA/540/i-89/001. 
TOTAL PETROLEUM HYDROCARONS 210 

8. REFERENCES 

EPA. 1990a. Identification and listing of hazardous waste. Subpart C: Characteristic of hazardous 

waste; toxicity characteristic. U.S. Environmental Protection Agency. Code of Federal Regulations. 

40 CFR 261.24. 

EPA. 1990b. EPA administered permit programs: The national pollutant discharge elimination system. 

Subpart B: Permit application and special NPDES program requirements. Storm Water Discharges. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 122.26. 

EPA. 1990c. Interim methods for development of inhalation reference doses. U.S. Environmental 

Protection Agency, Office of Research and Development. Washington, DC. EPA 600/8-90-066A. 

EPA. 1991a. Standards for the management of specific hazardous wastes and specific types of hazardous 

waste management facilities. Subpart H: Hazardous waste burned in boilers and industrial furnaces. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 266, Subpart HH. 

EPA. 1991b. Criteria for municipal solid waste landfills. U.S. Environmental Protection Agency. Code 

of Federal Regulations. 40 CFR 258. 

EPA. 1992a. Hazardous waste management system: Identification and Listing of hazardous waste; 

recycled used oil management standards. Part IX: Relationship to other programs--International 

Convention for Prevention of Pollution from Ships (MARPOL 73/78). U.S. Environmental Protection 

Agency. Final Rule. Federal Register. 57 FR 41605. September 10, 1992. 

EPA. 1992b. Recycled used oil management standards. U.S. Environmental Protection Agency. Federal 

Register. 57 FR 41566. 

EPA. 1992c. Identification and listing of hazardous waste. Definition of hazardous waste. U.S. 

Environmental Protection Agency. Code of Federal Regulations. 40 CFR 261.3. 

EPA. 1992d. Standards for the management of used oil. U.S. Environmental Protection Agency. Code 

of Federal Regulations. 40 CFR 279. 

EPA. 1993a. Report to congress on hydrogen sulfide air emissions Associated with the extraction of oil 

and natural gas. U.S. Environmental Protection Agency, Office of Air Quality Planning and Standards, 

Research Triangle Park, NC. EPA-453/R-93-045. 

EPA. 1993b. Fact sheet for the multi-sector stormwater general permit. Part VIII: Specific requirements 

for discharges associated with specific industrial activities. U.S. Environmental Protection Agency. 

Notice. Federal Register. 60 FR 61146. November 19, 1993. 

EPA. 1993c. Provisional guidance for quantitative risk assessment of polycyclic aromatic-hydrocarbons. 

U.S. Environmental Protection Agency, Office of Health and Environmental Assessment, Cincinnati, OH. 

EPA/600/02 1. 

EPA. 1994a. Cleaning up the nation’s waste sites: Markets and technology trends. EPA 542-R-92-012 

(PB93-140762). Rockville, MD: Government Institutes Inc. for EPA Office of Solid Waste and 

Emergency Response. 
TOTAL PETROLEUM HYDROCARONS 211 

8. REFERENCES 

EPA. 1994b. Recovered oil exclusion. U.S. Environmental Protection Agency. Federal Register. 59 FR 

38542. 

EPA. 1995a. Identification and listing of hazardous wastes: Petroleum refining. U.S. Environmental 

Protection Agency. Federal Register. 60 FR 57752 

EPA. 1995b. Hazardous waste management system; identification and listing of hazardous waste: 

Petroleum refining process wastes; land disposal restrictions for newly identified wastes; and CERCLA 

hazardous substance designation and reportable quantities. U.S. Environmental Protection Agency. 

Notice of Proposed Rule Making. Federal Register. 60 FR 57747. November 20, 1995. 

EPA. 1995c. RBCA Leaflet. U.S. Environmental Protection Agency, Office of Underground Storage 

Tanks. EPA 5 10-F-95-001. 

EPA. 1995d. Test methods for evaluating solid waste; physical/chemical methods. U.S. Environmental 

Protection Agency, Office of Solid Waste and Emergency Response. SW-846. 

EPA. 1996a. Guidelines establishing test procedures for the analysis of oil and grease and total 

petroleum hydrocarbons. Environmental Protection Agency. Proposed Rule. Federal Register. 61 FR 

1730. January 23, 1996 

EPA. 1996b. Risk assessment issue paper for: Derivation of a provisional oral RfD for 

1,3,5-trimethylbenzene. Superfund Health Risk Technical Support Center, National Center for 

Environmental Assessment, Cincinnati, OH. (96-012/03-08-96) 

EPA. 1997a. Health effects assessment summary tables FY 1997 update. Office of Research and 

Development, Office of Emergency and Remedial Response, Washington, DC. NTIS PB97-921199. 

EPA. 1997b. Toxicological review of cumene (CAS No. 98-82-8). In Support of Summary Information 

on the Integrated Risk Information System. June 1997. U.S. Environmental Protection Agency, 

Washington, DC. 

EPA. 1998a. Fact sheet: Proposed test procedure for the analysis of oil and grease and total petroleum 

hydrocarbons. http://www.epa.gov/ostwater/oilgreas.html 

EPA. 1998b. Integrated risk information system (IRIS). Online. National Center for Environmental 

Assessment, Cincinnati, OH. http://www.epa.gov/iris/subst/index.html 

EPA. 1998c. Identification and listing of hazardous waste, definition of hazardous waste. U. S. 

Environmental Protection Agency, Washington, DC. Code of Federal Regulations. 40 CFR 261.3. 

EPA. 1998d. Binational toxics strategy: stockholders forum November 16,1998. U.S. Environmental 

Protection Agency, Great Lakes National Program Office, Chicago. 
TOTAL PETROLEUM HYDROCARONS 212 

8. REFERENCES 

Etkina EI, IA Etkina. 1995. Chemical mixtures exposure and children’s health. Chemosphere 

31( 1):2463-2474. 

Fahey, JW, Zhang Y, Talalay P. 1997. Broccoli sprouts: An exceptionally rich source of inducers of 

enzymes that protect against chemical carcinogenesis. U.S. Proc Nat1 Acad Sci. 94:10367-10372. 

Farrington JW, Teal JM, Quinn JG, et al. 1973. Intercalibration of analyses of recently biosynthesized 

hydrocarbons and petroleum hydrocarbons in marine lipids. Bull Environ Contam Toxicol, vol 

10 (3): 129-36. 

Farrington JW, Tripp BW, Teal JM, et al. 1982. Biogeochemistry of aromatic hydrocarbons in the 

benthos of microcosms. Toxicol Environ Chem 5 (3-4):33 l-346. 

Feenstra S, Makay DM, Cherry JA. 1991. A method for assessing residual NAPL based on organic 

chemical concentrations in soil samples. Ground Water Monitoring Review 11: 128-136. 

Firriolo JM, Morris CF, Trimmer GW, et al. 1995. Comparative 90-day feeding study with low viscosity 

white mineral oils in Fischer 344 and Sprague-Dawley-derived CRL: CD rats. Toxicol Pathol 23:26-33. 

Fitzpatrick MG, Tan SS. 1993. Recent advances in the determination of total petroleum hydrocarbons in 

soil. Chemistry in New Zealand, 22. 

Fowler SW, Readman JW, Oregioni B, et al. 1993. Petroleum hydrocarbons and trace metals in 

nearshore Gulf sediments and biota before and after the 1991 war: An assessment of temporal and spatial 

trends. Marine Pollution Bulletin 27: 17 1-182. 

Frankenberger WT. 1992. The need for laboratory feasibility study in bioremediation of petroleum 

hydrocarbons. In: Calabrese E, Kostecki P, eds. Hydrocarbon contaminated soils and groundwater, vol 2. 

Chelsea, MI: Lewis Publishers, 237-293. 

Friedman PA. 1987. Poisoning and its management. In: Jeffers JD, Scott EJ, Ramos-Englis M, eds. 

Harrison’s principles of internal medicine. Eleventh Edition. New York: McGraw-Hill, 838-850. 

FSTRAC. 1990. Federal-state toxicology and regulatory alliance committee. Summary of state and 

federal drinking water standards and guidelines. U.S. Environmental Protection Agency. p. 16. February, 

1990. 

Gaworski, CL, MacEwen JD, Vernot EH, et al. 1984. Comparison of the subchronic inhalation toxicity 

of petroleum and oil shale JP-5 jet fuels. In: MacFarland HN, Holdsworth, CE, MacGregor JA, et al. eds. 

Advances in modern environmental toxicology. Volume VI: Applied toxicology of petroleum 

hydrocarbons. Princeton, NJ: Princeton Scientific Publishers, 33-47. 

Gay ML, Belisle AA, Patton JF. 1980. Quantification of petroleum-type hydrocarbons in avian 

tissue. J Chromatogr 187(l): 153-160. 

George S. 1992. Positive and negative bias associated with the use of EPA Method 418.1 for the 

determination of total petroleum hydrocarbons in soil. Environmental Science and Engineering, Inc. 
TOTAL PETROLEUM HYDROCARONS 213 

8. REFERENCES 

Gere DR, Knip, CR Castelli, Hendrick J et al. 1993. Bridging the automation gap between sample 

preparation and analysis: An overview of SFE, GC-MS and HPLC applied to environmental samples. J 

Chromatogr Sci, 3 1(7):246-258. 

Gidron E, Leurer J. 1956. Naphthalene poisoning. Lancet (February 4): 228-230. 

Goodwin TM. 1988. Toluene abuse and renal tubular acidosis in pregnancy. Obstet Gynecol 

71:715-718. 

Green JD, Leong BKJ, Laskin S. 1978. Inhaled benzene fetotoxicity in rats. Toxicol Appl Pharmacol 

46:9-18. 

Guiney PD, Sykora JL, Kelett G. 1987. Qualitative and quantitative analyses of petroleum hydrocarbon 

concentrations in a trout stream contaminated by an aviation kerosene spill. Env Tox Chem 6: 105-l 14. 

Gustafson J. 1995. Personal communication with Mary Siedlecki, Research Triangle Institute. 

Gustafson J. 1997. Using TPH in risk-based corrective action. Shell Development Corporation. 

Published on Internet by U.S. Environmental Protection Agency, Office of Underground Storage Tanks. 

http://www.epa.gov/swerust l/rbdm/tphrbca.htm 

Haggerty RJ. 1956. Toxic hazards: Naphthalene poisoning. The New England Journal of Medicine 255: 

9 19-920. 

Hansch C, Leo A. 1979. Substituent constants for correlation analysis in chemistry and biology. New 

York, NY: John Wiley and Sons. 

Hansen H, De Rosa CT, Pohl H, Fay M, Mumtaz MM. 1998. Public health challenges posed by 

chemical mixtures. Environ Health Persp 106:1271-1280. 

Hass U, Jakobsen BM. 1993. Prenatal toxicity of xylene inhalation in the rat: A teratogenicity and 

postnatal study. Pharmacology and Toxicity 73:20-23. 

Hasty E, Revesz F. 1995. Total petroleum hydrocarbon determination by microwave solvent extraction. 

American Laboratory 27(4):66. 

Havlicek SC. 1988. Characterization of fuels an fuel spills. Central coast analytical services, San Louis 

Obispo, California. 

Hawthorne ST, Miller DJ, Hegvik, KM. 1993. Field evaluation of the SFE-infrared method for total 

petroleum hydrocarbon (TPH) determinations. Journal of Chromatographic Science 31:26-30. 

HazDat. 1999. Database. Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA. 

Heath JS, Koblis K, Sager SH. 1993a. Risk assessment for total petroleum hydrocarbons. Chapter 16. 

In: Kostecki P, Calabrese E. eds. Hydrocarbon contaminated soils. Chelsea, MI: Lewis Publishers, 

267-301. 
TOTAL PETROLEUM HYDROCARONS 214 

8. REFERENCES 

Heath JS, Koblis K, Sager SH. 1993b. Review of chemical, physical, and toxicological properties of 

components of TPH. J Soil Contam, 2( 1): l-25. 

Hersh JH. 1989. Toluene embryopathy: Two new cases. J Med Genet 26:333-337. 

Hersh JH, Podruch PE, Rogers G, et al. 1985. Toluene embryopathy. J Pediatr 106:922-927. 

Howd RA, Rebert CS, Dickinson J, et al. 1983. A comparison of the rates of development of functional 

hexane neuropathy in weanling and young adult rats. Neurobehav Toxicol Teratol5:63-68. 

Hseih GC, Sharma RP, Parker RD. 1989. Immunological evaluation of toluene exposure via drinking 

water in mice. Environ Res 49:93-103. 

Hunter AGW, Thompson D, Evans JA. 1979. Is there a fetal gasoline syndrome? Teratology 20:75-79. 

Hutcheson MS, Pedersen D, Anastas ND, Fitzgerald J, Silverman D. 1996. Beyond TPH: Health-based 

evaluation of petroleum hydrocarbon exposures. Reg Toxicol Pharmacol24:85-101. 

IARC. 1984. Mineral oils. IARC monographs on the evaluation of the carcinogenic risk of chemicals to 

humans. International Agency for Research on Cancer. 33:87-168. 

IARC. 1985. Polynuclear aromatic compounds. Part 4, Bitumens, coal-tars and derived products, shaleoils 

and soots. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. 

International Agency for Research on Cancer. 35:39-8 1. 

IARC. 1987. Mineral oils: Untreated and mildly-treated oils (Group l), highly-refined oils (Group 3). 

IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. International 

Agency for Research on Cancer. Supplement 7: 252-259. 

IARC. 1989a. Gasoline. IARC monographs on the evaluation of the carcinogenic risk of chemicals to 

humans. International Agency for Research on Cancer. 45: 159-201. 

IARC. 1989b. Fuel oils (heating oils). IARC monographs on the evaluation of carcinogenic risks to 

humans. International Agency for Research on Cancer. 45:239-270. 

IARC. 1989c. Crude oil. IARC monographs on the evaluation of the carcinogenic risks of chemicals to 

humans. International Agency for Research on Cancer. 45:119-158. 

IARC. 1989d. Jet fuels. IARC monographs on the evaluation of carcinogenic risks to humans. 

International Agency for Research on Cancer. 45:203-237. 

IARC. 1989e. IARC monographs on the evaluation of the carcinogenic risks of chemicals to humans. 

International Agency for Research on Cancer. 45:39-l 17. 

IARC. 1989f. IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 47: Some 

organic solvents, resin monomers and related compounds, pigments and occupational exposures in paint 

manufacturing and painting. Lyon, France: World Health Organization, International Agency for 

Research on Cancer. 
TOTAL PETROLEUM HYDROCARONS 215 

8. REFERENCES 

IARC. 19898. IARC monographs on the evaluation of the carcinogenic risks of chemicals to humans. 

International Agency for Research on Cancer. 35:39-8 1. 

IARC. 1996. Cumulative cross index to IARC Monograph on the evaluation of carcinogenic risks to 

humans. International Agency for Research on Cancer. 66:487-5 14. 

IRDC. 198 1. Six-month continuous inhalation exposure of rats to hexane mixtures-Phase II. 

Unpublished study by International Research and Development Corporation, Mattawa MI. Prepared for 

the American Petroleum Institute, Washington DC. EPA FYI-AX-0282-0166 Addendum. 

Jensen K. 1977. Sources and routes of removal of petroleum hydrocarbons in a Danish marine inlet. Oil 

and Petroleum Production, 1(3):207-216. 

Johnson B, De Rosa CT. 1995. Chemical mixtures released from hazardous waste sites: Implications for 

health risk assessment. Toxicol 105: 145-56. 

Johnson Barry, Andrews JS Jr., Xintaras C, Mehh-nan MA, eds. 1998. Advances in modem 

environmental toxicology. Vol. XXV. Hazardous waste: Toxicology and health effects. Princeton, NJ: 

Princeton Scientific Publishing, Inc. 

Jordan RE, Payne JR. 1980. Fate and weathering of petroleum spills in the marine environment: A 

literature review and synopsis. Ann Arbor, MI: Ann Arbor Science Publisher, Inc. 

Judge C, Kostecki P, Calabrese E. 1997. State summaries of soil cleanup standards. Soil and 

Groundwater Cleanup. November, pp. 10-34. 

Judge C, Kostecki P, Calabrese E. 1998. State by state groundwater standards. Soil and Groundwater 

Cleanup. May, pp. 11-31. 

Kainz RJ, White LE. 1984. Depressant effects associated with the inhalation of uncombusted diesel 

vapor. In: MacFarland, HN, Holdsworth CE, MacGregor JA, et al. eds. Advances in modern 

environmental toxicology. Volume VI: Applied toxicology of petroleum hydrocarbons. Princeton, NJ: 

Princeton Scientific Publishers, Inc. 

Kelly DW, Duffy JS, Haddock LX, et al. 1994. Chronic inhalation study of commercial hexane in rats. 

Toxicologist 14:317 (Abstract #1233). 

Kimura K, Nagata T, Kudo K, et al. 1991. Determination of kerosene and light oil components in blood. 

Biol Mass Spectra, 20:493-497. 

Kinkead ER, Haun CC, Schneider MG, et al. 1985. Chronic inhalation exposure of experimental animals 

to methylcyclohexane. Govt Reports Announcements and Index, Issue 21. 

Klaasen, CD. 1996. Nonmetallic environmental toxicants. Air pollutants, solvents and vapors, and 

pesticides. In: Hardman JG, Limbird, LE, eds. Goodman and Gilman’s The pharmacological basis of 

therapeutics. 9th Edition. New York,NY: McGraw-Hill. 
TOTAL PETROLEUM HYDROCARONS 216 

8. REFERENCES 

Knox RC. 1993. Spatial moment analysis for mass balance calculations and tracing movement of a 

subsurface hydrocarbon mound. Ground Water Monitoring & Remediation, 13(3):139-147. 

Koblis K, Day C, Heath J. 1993. Impact of surrogate selection on risk assessment for total petroleum 

hydrocarbons. Journal of Soil Contamination, 2(2):125-136. 

Legaverend C, Guenther TM, Nebert DW. 1984. Importance of the route of administration for genetic 

differences in benzo(a)pyrene-induced in utero toxicity and teratogenicity. Teratology 29:35-47. 

Li L, Sun W, Gong Z, et al. 1992. Effect of low benzene exposure on neurobehavioral function, AChE in 

blood and brain and bone marrow picture in mice. Biomed Environ Sci 5(4):349-354. 

Lindemann R. 1991. Congenital renal tubular dysfunction associated with maternal sniffing of organic 

solvents. Acta Pediatr Stand 80:882-884. 

Lioy PJ. 1992. General summary and recommendations of the workshop on general population exposures 

to gasoline. J Expo Anal Environ Epidemiol2( 1):5-8. 

Litton Bionetics. 1978. Teratology study in rats: Unleaded gasoline. Final report submitted to American 

Petroleum Institute, Washington, DC. Kensington, MD: Litton Bionetics, Inc. 

Lodge JP, Jr, ed. 1988. Methods of air sampling and analysis. Lewis Publishers, Inc., 262-264. 

Lopez-Avila V, Young R, Kin R, et al. 1993. Interlaboratory evaluation of an off-line supercritical fluid 

extraction/infrared spectrometric method for determination of petroleum hydrocarbons in solid matrixes. 

JAOAC Int 76(3):555-562. 

Lopez-Avila V, Young R, Beckert WF. 1994. Microwave-assisted extraction of organic compounds from 

standard reference soils and sediments. Analytical Chemistry, 66(7):1097-l 106. 

LUFT. 1988. Leaking underground fuel tank manual: Guidelines for site assessment, Cleanup, and 

underground storage tank closure. State of California Leaking Underground Fuel Tank Force, May 1988. 

Sacramento California. 

Lyman WJ, Noonan DC, Reidy PJ. 1990. Cleanup of petroleum contaminated soils at underground 

storage tanks. Noyes Data Corporation, Park Ridge, New Jersey. 

MacFarland I-IN Holdsworth CE, MacGregor JA, et al. eds. 1984a. Applied toxicology of petroleum 

hydrocarbons. Advances in modem environmental toxicology. Vol. VI. Princeton, NJ: Princeton 

Scientific Publishing, Inc. 

MacFarland I-IN, Ulrich, CE, Holdsworth, CE, et al. 1984b. A chronic inhalation study with unleaded 

gasoline vapor. J Amer Col1 Toxicol 3:231-248. 

Mackay D. 1984. Chemical and physical behavior of hydrocarbons in freshwater. In: Vandermeulen, 

Hrudey SE, eds., Oil in freshwater: Chemistry, biology, countermeasure technology. New York: 

Pergamon Press, 85-94. 
TOTAL PETROLEUM HYDROCARONS 217 

8. REFERENCES 

Mackay D. 1988. The chemistry and modeling of soil contamination with petroleum. In: Calabrese E, 

Kostecki P, eds. Soils contaminated by petroleum. New York, NY: John Wiley and Sons, 5-18. 

MADEP. 1994. Interim final petroleum report: development of health-based alternative to the total 

petroleum hydrocarbon (TPH) parameter. Massachusetts Department of Environmental Protection, 

Bureau of Waste Site Cleanup. August 1994. 

MADEP. 1996. Issues paper: Implementation of the VPH/EPH approach. Public comment draft. 

Massachusetts Department of Environmental Protection, Bureau of Waste Site Cleanup, Boston, MA. 

May 1996. 

MADEP. 1997. Characterizing risks posed by petroleum contaminated sites: implementation of MADEP 

VPH/EPH Approach, public comment draft. Massachusetts Department of Environmental Protection, 

Bureau of Waste Site Cleanup, Boston, MA. October 31, 1997. 

MADEP. 1999. Massachusetts Department of Environmental Protection. http://www.state.ma.us/dep. 

Mahdi AH. 1988. Kerosene poisoning in children in Riyadh. J Trop Pediatr 34(6):316-318. 

Marks TA, Ledoux TA, Moore JA. 1982. Teratogenicity of a commercial xylene mixture in the mouse. 

J Toxicol Environ Health 9:97-105. 

MARPOL. 1978. International convention for prevention of pollution from ships (MARPOL). 1978 

Protocol: Annexes I-V - Oil, Noxious Liquids, etc. 

Martin MJ. 1992. Sonication vs. Soxhlet extraction for soil analysis. Environ Lab, June/July, 34-35. 

Mattie, DR, Marit GB, Flemming CD, Cooper JR. 1995. The effects of JP-8 jet fuel on male SpragueDawley rats after a 90-day exposure by oral gavage. Toxicol Ind Health 11:423-435. 

McDonald TJ, Brooks JM, and Kennicut MC. 1984. Release of volatile liquid hydrocarbons from spilled 

petroleum. Bull Contam Toxicol 32(5):621-628. 

McMurray WC. 1977. Essentials of human metabolism. 2”d ed. Philadelphia, PA: Harper & Row, 

252-254. 

Mehhnan MA, ed. 1983. Carcinogenicity and toxicity of benzene. In: Advances in modern 

environmental toxicology. Vol. IV. Princeton, NJ: Princeton Scientific Publishing, Inc. 

Mehlman MA, ed. 1989. Benzene: Occupational and environmental hazards - scientific update. In: 

Advances in modem environmental toxicology. Vol. XVI. Princeton, NJ: Princeton Scientific Publishing, 

Inc. 

Mehlman MA, ed. 199 1. Health hazards and risks from exposure to complex mixtures and air toxic 

chemicals. In: Advances in modem environmental toxicology. Vol. XIX. Princeton, NJ: Princeton 

Scientific Publishing, Inc. 
TOTAL PETROLEUM HYDROCARONS 218 

8. REFERENCES 

Mehlman MA, ed. 1992. Dangerous and cancer-causing properties of products and chemicals in the oil 

refining and petrochemical industry: VII. Health effects of motor fuels: carcinogenicity of gasoline -­

scientific update. Environmental Research 59:238-240. 

Mehlman MA. 1996. Dangerous and cancer-causing properties of products and chemicals in the oil 

refining and petrochemical industry: XI. Carcinogenicity and environmental hazards of crude oil, 

gasoline, and its components. J Clean Technol, Environ Toxicol, and Occup Med 5(2)115-130. 

Mehlman MA, Henstreet CP III, Thorpe JJ, Weaver NK, eds. 1984. Renal effects of petroleum 

hydrocarbons. In: Advances in modern environmental toxicology. Vol. VII. Princeton, NJ: Princeton 

Scientific Publishing, Inc. 

Mehhnan MA, Upton A, eds. Identification and control of environmental and occupational diseases: 

Hazards and risks of chemical sin the oil refining industry. Vol. XXIII. Princeton, NJ: Princeton 

Scientific Publishing, Inc. 

Miller MJ, Lonardo EC, Greer RD, et al. 1996. Variable responses of species and strains to white 

mineral oils and paraffin waxes. Reg Toxicol Pharmacol 23:55-68 

Mills SA, Frankenberger WT Jr. 1994. Evaluation of phosphorus sources promoting bioremediation of 

diesel fuel in soil. Bull Environ Contam Toxicol 53(2):280-4. 

Mumtaz MM, De Rosa C, Durkin PR. 1994. Approaches and challenges in risk assessments of chemical 

mixtures. In: Toxicology of chemical mixtures. New York, NY: Academic Press, 565-597. 

Mumtaz MM, Durkin PR. 1992. A weight of evidence scheme for assessing interactions in chemical 

mixtures. Toxicol Indust Health 8:377-406. 

Mumtaz MM, Poirier KA, Colman JT. 1997. Risk assessment for chemical mixtures: Fine-tuning the 

hazard index approach. J Clean Technol, Environ Toxicol & Occup Med 6(2): 189-204. 

Murray DA, Lockhart WL. 1981. Microextraction and gas chromatographic analysis of selected 

petroleum hydrocarbons in water and fish tissue. J Chromatogr 212(3):305- 11. 

Murray KS. 1994. The TRPH controversy. American Laboratory, October, 1994. p. 8. 

Murray FJ, John JA, Rampy LW, et al. 1979. Embryotoxicity of inhaled benzene in mice and rabbits. 

Am Ind Hyg Assoc J 40:993-998. 

Mushrush GW, Mose DG, and Sullivan KT. 1994. Soil vapor and groundwater analysis from a recent 

oils spill. Bull Environ Contam Toxicol 52:3 l-38. 

NAS/NRC. 1989. Biologic markers in reproductive toxicology. National Academy of Sciences/National 

Research Council. Washington, DC: National Academy Press, 15-35. 

NATICH 1992. National air toxics information clearinghouse. NATICH data base report on state, local 

and EPA air toxics activities. Final. U.S. Environmental Protection Agency. EPA 453/R-92-008. Pp. 

4-87, 4-120, 4-121, 4-171, and 4-189. September 1, 1992. 
TOTAL PETROLEUM HYDROCARONS 219 

8. REFERENCES 

NIOSH. 1992. NIOSH recommendations for occupational safety and health. Compendium of policy 

documents and statements. U.S. Department of Health and Human Services. Cincinnati, Ohio. Page 85. 

January, 1992. 

NIOSH. 1994. NIOSH manual of analytical methods. 4th ed. U.S. Department of Health and Human 

Services. 

NTP. 1991. Developmental toxicity of naphthalene (CAS No. 91-20-3) administered by gavage to 

Sprague-Dawley (CD) rats on gestational days 6 through 15. Research Triangle Park, NC: National 

Toxicology Program, National Institute of Environmental Health Sciences, U.S. Department of Health and 

Human Services, Public Health Service, National Institutes of Health. TER-91006. 

NTP. 1992. National Toxicology Program. Technical report series No. 410. Toxicology and 

carcinogenesis studies of naphthalene (CAS No. 91-20-3) in B6C3F, mice (inhalation studies). Research 

Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service, National 

Institutes of Health. NIH Publication No. 92-3 14 1. 

NTP. 1996. Toxicology and carcinogenesis studies of ethylbenzene in F344/N rats and B6C3Fl mice. 

(Inhalation Studies). National Toxicology Program. TR-466. Draft. 

OHM/TADS. 1985. Oil and Hazardous Materials/Technical Assistance Data System. Baltimore, MD: 

Chemical Information Systems, Inc. December 1985. 

Orbaek P, Nise G. 1989. Neurasthenic complaints and psychometric function of toluene-exposed 

rotogravure printers. Am J Ind Med 16:67-77. 

OSHA. 1974. Limits for air contaminants: Petroleum distillates. Occupational Safety and Health 

Administration. Code of Federal Regulations. 29 CFR 1910.1000. 

Pancirov, R. J. and R. A. Brown. 1975. Analytic methods for polynuclear aromatic hydrocarbons in crude 

oils, heating oils, and marine tissues. In: Proceedings of the 1975 Conference on Prevention and Control of 

Oil Pollution, March 25-27, 1975. San Francisco, CA. American Petroleum Institute: Washington, DC., 

103-l 14. 

Park KS, Sims RC, DuPont RR, et al. 1990. The fate of PAH compounds in two soil types: Influence of 

volatilization of abiotic loss and biological activity. Environ Toxicol Chem 9(2): 187-196. 

Pedersen, LM, Larsen, K, Cohr, K. 1984. Kinetics of white spirit in human fat and blood during short-term 

experimental exposure. Acta Pharmacol. Toxicol 55: 308-316. 

Pedersen LM, Rasmussen S, Cohr C. 1987. Further evaluation of the kinetics of white spirit in human 

volunteers. Pharmacol Toxicol 60:135-137. 

Pellizzari ED, Hartwell TD, Harris BS, et al. 1982. Purgeable organic compounds in mothers milk. Bull 

Environ Contam Toxicol, 28(3):322-328. 

Pellizzari ED, Wallace LA, Gordon SM. 1992. Elimination kinetics of volatile organics in humans using 

breath measurements. J Expo Anal Environ Epidemiol, 2(3):34l-55. 
TOTAL PETROLEUM HYDROCARONS 220 

8. REFERENCES 

PennWell. 1994. Energy statistics sourcebook, 9th Edition. Tulsa, OK: Oil & Gas Journal Energy
 

Database Publications, PennWell Publishing Company.
 

PennWell. 1998. Energy statistics sourcebook, 13th Edition. Tulsa, OK: Oil & Gas Journal Energy
 

Database Publications, PennWell Publishing Company.
 

Phillips RD, Eagan GF. 1984. Subchronic inhalation exposure of dearomatized white spirit and Cl0-Cl1
 

isoparaffinic hydrocarbon in Sprague-Dawley rats. Fund Appl Toxic 4:808-818.
 

Picer M, Picer N. 1993. Evaluation of modification o the simple spectrofluorimetry method for
 

estimating petroleum hydrocarbon levels in sea water. Bull Environ Contam Toxicol 50(6):802-810.
 

Potter TL. 1993. Analysis of petroleum contaminated soil and water: An overview. In: Calabrese EJ,
 

Kostecki PT, eds. Principles and practices for petroleum contaminated soils, 1-14. Ann Arbor, MI:
 

Lewis Publishers.
 

Prochaska, HJ, Talalay P. 1992. Phenolic antioxidants as inducers of anticarcinogenic enzymes. In:
 

Huang, M-T, Ho C-T, Lee CY, eds. Phenolic compounds in food and their effects on health. Vol. II.
 

150-159. American Chemical Society Symposium Series No. 507.
 

Pykko K. 1983. Time-course of effects of toluene on microsomal enzymes in rat liver, kidney and lung
 

during and after inhalation exposure. Chem Biol Interact 44:299-3 10.
 

Restek Corporation. 1994. Guide for the analysis of petroleum hydrocarbons in soil and water. Restek
 

Corporation, Bellafonte, Pennsylvania.
 

Rhodes IA, Hinojosa EM, Barker DA, et al. 1995/1996. Determination of total petroleum hydrocarbons
 

by capillary gas chromatography. Shell Development Company, Environmental Analysis Department,
 

Houston.
 

Rozen MG, Snyder CA, Albert RE. 1984. Depression in B- and T-lymphocyte mitogen-induced
 

blastogenesis in mice exposed to low concentrations of benzene. Toxicol Lett 20:343-349.
 

Runion HE. 1988. Occupational exposures to potentially hazardous agents in the petroleum industry.
 

Occupational Medicine: State of the Art Reviews 3(3):431-444.
 

Santhanakrishnan BR, Chithra S. 1978. Accidental kerosene poisoning in infants and children. Indian J
 

Pediatr 45(367):265-273.
 

Schafer WB. 1951. Acute hemolytic anemia related to naphthalene: Report of a case in a newborn infant.
 

Pediatrics &; 172-174.
 

Schlien HH. 1992. Physical and chemical characteristics of mineral oils. CONCAWE/DGMK Scientific
 

Seminar; Remediation of oil spills, May 18-21, 1992.
 

Schrynemeeckers R. 1993. Immunoassay in the environmental industry. Environ Testing & Analysis
 

2( 1)56-60.
 
TOTAL PETROLEUM HYDROCARONS 221 

8. REFERENCES 

Shendrikova IA, Aleksandrov VA. 1974. Comparative penetration of polycyclic hydrocarbons through 

the rat placenta into the fetus. Bull Exp Biol Med 77: 169-171. 

Shopp GM, White KL Jr, Holsapple MP, et al. 1984. Naphthalene toxicity in CD-l mice: General 

toxicology and immunotoxicology. Fundam Appl Toxicol4:406-419. 

Smith, JH, Mallett AK, Priston RAJ, et al. 1996. Ninety-day feeding study in Fischer-344 rats of highly 

refined petroleum-derived food-grade white oils and waxes. Toxicol. Pathol. 24:214-130. 

Snodgrass, WR. 1997. Clinical Toxicology. In: Klaassen CD, Amdur MO, Doull J, eds. Cassarett and 

Doull’s toxicology. The basic science of poisons. Fifth Edition. New York, NY: McGraw-Hill, 

969-986. 

Speight JG. 1991. The chemistry and technology of petroleum 2nd edition. New York,NY: Mercel 

Dekker. Inc. 

St. John MA. 1982. Kerosene poisoning in children in Barbados. Ann Trop Paediatr 2( 1):37-40. 

Starek A, Vojtisek M. 1986. Effects of kerosene hydrocarbons on tissue metabolism in rats. Pol J 

Pharmacol Pharm 38(5-6):461-469 

Steimle FW, Boehm PD, Zdanowicz VS, et al. 1986. Organic and trace metal levels in ocean quahog 

Arctica islandica from the northwestern Atlantic. U.S. Nat Mar Fish Serv Fish Bull, 84( 1):133-140. 

Stelljes ME, Watkin GE. 1991. Comparison of environmental impacts posed by different hydrocarbon 

mixtures: a need for site-specific composition analyses. Hydrocarbon Contam Soils Groundwater, 

3:549-69 

Stelljes ME, Watkin GE. 1993. Comparison of environmental impacts posed by different hydrocarbon 

mixtures: a need for site-specific composition analysis. In: Kostecki P, Calabrese E, eds. Hydrocarbon 

contaminated soils and groundwater, Vol 3. Chelsea, MI: Lewis Publishers, 549-570. 

Stevens P, ed. 1988. Oil and gas dictionary. New York, NY: Nichols Publishing. 

Talalay, P. 1992. The role of enzyme induction in protection against carcinogenesis. In: Wattenberg L, 

Lipkin M, Boone CW, Kelloff GJ, eds. Cancer chemoprevention. Boca Raton, FL: CRC Press, 469-478. 

Tan YA, Kuntum A. 1994. Hydrocarbons in crude palm kernel oil. JAOAC Int 77( 1):67-73. 

Tatrai E, Rodrics K, Ungvary G. 1980a. Embryotoxic effects of simultaneously applied exposure of 

benzene and toluene. Folia Morph01 (Praha) 28:286-289. 

Tatrai E, Ungvary GY, Hudak A, et al. 1980b. Concentration dependence of the embryotoxic effects of 

benzene inhalation in CFY rats. J Hyg Epidemiol Microbial Immunol 24:363-371. 

Thomas KW, Pellizzari ED, Cooper SD. 1991. A canister-method for collection and GC/MS analysis of 

volatile organic compounds in human breath. J Anal Toxicol, 15(2):54-59. 
TOTAL PETROLEUM HYDROCARONS 222 

8. REFERENCES 

Todd GD, Hansen HJ, Mehlman MA, De Rosa CT. 1999. The public health challenges of total petroleum 

hydrocarbons (TPH). Environ Epi Toxicol. In press. 

TPHCWG. 1997a. A risk-based approach for the management of total petroleum hydrocarbons in soil. 

Total petroleum hydrocarbon criteria working group. March 1997. http://www.aehs.com. 

TPHCWG. 1997b. Total petroleum hydrocarbon criteria working group series, volume 3. Selection of 

representative TPH factions based on fate and transport considerations. Gustafson J, Tell JG, Orem D, 

eds. Amherst, MA: Amherst Scientific Publishers. 

TPHCWG. 1997c. Total petroleum hydrocarbon criteria working group series, volume 4. Development 

of fraction specific reference doses (RfDs) and reference concentrations (RfCs) for total petroleum 

hydrocarbons (TPH). Edwards DA, Amoroso MD, Tummey AC, et al. eds. Amherst, MA: Amherst 

Scientific Publishers. 

TPHCWG. 1998a. Total petroleum hydrocarbon criteria working group series, volume 1. Analysis of 

petroleum hydrocarbons in environmental media. Weisman W, ed. Amherst, MA: Amherst Scientific 

Publishers. 

TPHCWG. 1998b. Total petroleum hydrocarbon criteria working group series, volume 2. Composition 

of petroleum mixtures. Potter TL, Simmons K, eds. Amherst, MA: Amherst Scientific Publishers. 

Uchida Y, Nakatsuka H, Ukai H, et al. 1993. Symptoms and signs in workers exposed predominantly to 

xylenes. Int Arch Occup Environ Health 64597-605. 

Ungvary G. 1985. The possible contribution of industrial chemicals (organic solvents) to the incidence of 

congenital defects caused by teratogenic drugs and consumer goods: An experimental study. In: Marois 

M, ed. Prevention of physical and mental congenital defects. Part B: Epidemiology, early detection and 

therapy, and environmental factors. New York: Alan R. Liss, Inc., 295-300. 

Ungvary G, Tatrai E. 1985. On the embryotoxic effects of benzene and its alkyl derivatives in mice, rats, 

and rabbits. Arch Toxicol [Supplement to] 8:425-430. 

Ungvary G, Tatrai E, Hudak A, et al. 1980b. Studies on the embryotoxic effects of ortho-, meta, and 

para-xylene. Toxicology 18:61-74. 

Ungvary G, Varga B, Horvath E, et al. 1981. Study on the role of maternal sex steroid production and 

metabolism in the embryotoxicity of para-xylene. Toxicology 19:263-268. 

Urso P, Gengozian N. 1980. Depressed humoral immunity and increased tumor incidence in mice 

following in utero exposure to benzo(a)pyrene. J Toxicol Environ Health 6:569-576. -

Urso P, Johnson RA. 1987. Early changes in T lymphocytes and subsets of mouse progeny defective as 

adults in controlling growth of a syngeneic tumor after in utero insult with benzo(a)pyrene. 

Immunopharmacology 14: l-10. 

Valaes T, Doxiadis SA, Fessas P. 1963. Acute hemolysis due to naphthalene inhalation. J Pediatr 

63:904-915. 
TOTAL PETROLEUM HYDROCARONS 223 

8. REFERENCES 

Verhaar HJM, Morroni JR, Reardon KF, et al. 1997. A proposed approach to study the toxicology of 

complex mixtures of petroleum products: The integrated use of QSAR, lumping analysis and PBPWPD 

modeling. Environ Health Perspect 105:179-195. 

Wanless IR, Geddie, WR. 1985. Mineral oil lipogranulomata in liver and spleen. Arch Pathol Lab Med 

109: 283-286. 

WHO. 1982. Selected petroleum products, environmental health criteria 20. IPCS International 

Programme on Chemical Safety. World Health Organization, Geneva. 

Wilkins-Haug L, Gabow PA. 1991. Toluene abuse during pregnancy: Obstetric complications and 

perinatal outcomes. Obstet Gynecol 77:504-509. 

Wilson BH, Armstong JM, Wilson JT, et al. 1991. Biotransformation of monoaromatic chlorinated 

hydrocarbons at an aviation gasoline spill site. Geomicrobiology Journal 8:225-240. 

Wilson JT, McNabb JF, Cochran JW, et al. 1985. Influence of microbial adaptation on the fate of 

organic pollutants in groundwater. Environmental Toxicology and Chemistry 4(6):721-726. 

Williams UP, Kiceniuk JW, Fancey LL, et al. 1989. Tainting and depuration of taint by lobsters 

(Homarus americanus) exposed to water contaminated with a no. 2 fuel oil: Relationship with aromatic 

hydrocarbon content in tissue. J Food Sci 54(2):240-243. 

Xiang Y, Morgan SL, Watt BE. 1995. TPH and BTEX quantitation in gasoline and diesel contaminated 

soils by capillary gas chromatography-mass spectrometry. J Chromatographic Science 33:98-108. 

Youngren SH, McKenna EA, Piccin TB, et al. 1994. Evaluation of the total petroleum hydrocarbon 

standard at jet fuel contaminated Air Force sites. Final Report, Brooks Air Force Base, Texas. 

Zahlsen K, Eide I, Nilsen AM, et al. 1992. Inhalation kinetics of C6 to C10 aliphatic, aromatic and 

naphthenic hydrocarbons in rat after repeated exposures. Pharmacol Toxicol 7 1: 144- 149. 

Zhang Y, Talalay P, Cho C-G, et al. 1992. A major inducer of anticarcinogenic protective enzymes from 

broccoli: Isolation and elucidation of structure. US Proc Nat1 Acad Sci 89:2399-2403. 

Zinkham WH, Childs B. 1957. Effect of vitamin K and naphthalene metabolites on glutathione 

metabolism of erythrocytes from normal newborns and patients with naphthalene hemolytic anemia. Am J 

Dis Child 94: 420-423. 

Zinkham WH, Childs B. 1958. A defect of glutathione metabolism of erythrocytes from patients with 

naphthalene-induced hemolytic anemia. Pediatrics 22: 46 l-47 1. 

TOTAL PETROLEUM HYDROCARONS 225 

9. GLOSSARY 

Absorption-The taking up of liquids by solids, or of gases by solids or liquids. 

Acute (Exposure)- Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption-The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)-The ratio of the amount of a chemical adsorbed per unit weight of organic 

carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)-The amount of a chemical adsorbed by a sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)-is usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the dose 

at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 10%. 

The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model-is a statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)-The quotient of the concentration of a chemical in aquatic organisms at 

a specific time or during a discrete time period of exposure divided by the concentration in the surrounding 

water at the same time or during the same period. 

Biomarkers-are broadly defined as indicators signaling events in biologic systems or samples. They 

have been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)-The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen-A chemical capable of inducing cancer. 

Case-Control Study-A type of epidemiological study which examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report-describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research but are not actual research studies. 
TOTAL PETROLEUM HYDROCARONS 226 

9. GLOSSARY 

Case Series-describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research but are not actual research studies. 

Ceiling Value-A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure-Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study-A type of epidemiological study of a specific group or groups of people who have had a 

corm-non insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study-A type of epidemiological study of a group or groups which examines the 

relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs-substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity-The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship-the quantitative relationship between the amount of exposure to a toxicant 

and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity-Any toxic effect on the conceptus as a result of prenatal exposure to a 

chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and 

in utero death. 

Environmental Protection Agency (EPA) Health Advisory-An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology-refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Equivalent Carbon Number Index-an index based on the boiling point of a chemical normalized to the 

boiling point of n-alkanes or its retention time in a boiling point gas chromatographic column (GC). 

Genotoxicity-a specific adverse effect on the genome of living cells that, upon the duplication of affected 

cells, can be expressed as a mutagenic, clastogenic or carcinogenic event because of specific alteration of 

the molecular structure of the genome. 

Half-life-a measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 
TOTAL PETROLEUM HYDROCARONS 227 

9. GLOSSARY 

Human Equivalent Concentration--the test concentration from an animal study adjusted for continuous 

exposure and dosimetric differences in humans and the test animal. 

Immediately Dangerous to Life or Health (IDLH)-The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 

Incidence-The ratio of individuals in a population who develop a specified condition to the total number 

of individuals in that population who could have developed that condition in a specified time period. 

Index of Concern-the ratio of exposure to the minimal risk level (MRL). A value greater than one 

indicates that there may be some concern for potential noncancer effects. 

Intermediate Exposure-Exposure to a chemical for a duration of 15-364 days, as specified in the 

Toxicological Profiles. 

Immunological Effects-are functional changes in the immune response. 

Immunologic Toxicity-The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

In Vitro-Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo-Occurring within the living organism. 

Lethal Concentration(LO) ( LCLO)-The lowest concentration of a chemical in air which has been reported 

to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)-A calculated concentration of a chemical in air to which exposure for a 

specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(LO) ( LDLO)-The lowest dose of a chemical introduced by a route other than inhalation that 

has been reported to have caused death in humans or animals. 

Lethal Dose(50)( LD50)-The dose of a chemical which has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)-A calculated period of time within which a specific concentration of a chemical is 

expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)-The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects-represent morphological effects involving lymphatic tissues such as the lymph 

nodes, spleen, and thymus. 
TOTAL PETROLEUM HYDROCARONS 228 

9. GLOSSARY 

Malformations-Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL) -An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)-A value (greater than zero) that is applied to the derivation of a minimal risk 

level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 

Morbidity-State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 

Mortality-Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 

Mutagen-A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy-The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity-The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)-The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (KOW)-The equilibrium ratio of the concentrations of a chemical in 

n-octanol and water, in dilute solution. 

Odds Ratio-a means of measuring the association between an exposure (such as toxic substances and a 

disease or condition) which represents the best estimate of relative risk (risk as a ratio of the incidence 

among subjects exposed to a particular risk factor divided by the incidence among subjects who were not 

exposed to the risk factor). An odds ratio of greater than 1 is considered to indicate greater risk of disease 

in the exposed group compared to the unexposed. 

Organophosphate or Orgauophosphorus Compound-a phosphorus containing organic compound and 

especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)-An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40 hour workweek. 

Pesticide-general classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 
 

TOTAL PETROLEUM HYDROCARONS 229 

9. GLOSSARY 

Pharmacokinetics-is the science of quantitatively predicting the fate (disposition) of an exogenous 

substance in an organism. Utilizing computational techniques, it provides the means of studying the 

absorption, distribution, metabolism and excretion of chemicals by the body. 

Pharmacokinetic Model-is a set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments 

which, in general, do not represent real, identifiable anatomic regions of the body whereby the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model-is a type of physiologically-based dose- response 

model which quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly describe 

the biological effect (response) produced by the system following exposure to an exogenous substance. 

Physiologically Based Pharmacokinetic (PBPK) Model-is comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates and, possibly membrane permeabilities. The models also use biochemical information 

such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called 

biologically based tissue dosimetry models. 

Prevalence-The number of cases of a disease or condition in a population at one point in time. 

Prospective Study--a type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*-The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L. for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)-A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentrations for up to a l0-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)-An estimate (with uncertainty spanning perhaps an order of magnitude) 

of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely 

to be without an appreciable risk of deleterious noncancer health effects during a lifetime. The inhalation 

reference concentration is for continuous inhalation exposures and is appropriately expressed in units of 

mg/m3

 or ppm. 
TOTAL PETROLEUM HYDROCARONS 230 

9. GLOSSARY 

Reference Dose (RFD)-An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the No-Observed-Adverse-Effect Level 

(NOAEL- from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to nonthreshold 

effects such as cancer. 

Reportable Quantity (RQ)-The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 

24-hour period. 

Reproductive Toxicity-The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of this 

system. 

Retrospective Study-A type of cohort study based on a group of people known to have been exposed at 

some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to casual factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 

Risk-the possibility or chance that some adverse effect will result from a given exposure to a chemical. 

Risk Factor-An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic, that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio-The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed. 

Short-Term Exposure Limit (STEL)-The American Conference of Governmental Industrial Hygienists 

(ACGIH) maximum concentration to which workers can be exposed for up to 1.5 min continually. No 

more than four excursions are allowed per day, and there must be at least 60 min between exposure 

periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA) may not be exceeded. 

Target Organ Toxicity-This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen-A chemical that causes structural defects that affect the development of an organism. 
TOTAL PETROLEUM HYDROCARONS 231 

9. GLOSSARY 

Threshold Limit Value (TLV)-An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. The 

TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit (STEL), or 

as a ceiling limit (CL). 

Time-Weighted Average (TWA)-An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)-A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic-The study of the absorption, distribution and elimination of toxic compounds in the living 

organism. 

Uncertainty Factor (UF)-A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using LowestObserved-Adverse-Effect Level (LOAEL) data rather than No-Observed-Adverse-Effect Level (NOAEL) 

data. A default for each individual UF is 10; if complete certainty in data exists, a value of one can be 

used; however, a reduced UF of three may be used on a case-by-case basis, three being the approximate 

logarithmic average of 10 and 1. 

Xenobiotic-any chemical that is foreign to the biological system. 
TOTAL PETROLEUM HYDROCARONS A-1 

APPENDIX A
 

MRLS AND CANCER CLASSIFICATION FOR TPH COMPONENTS AND
 

WHOLE PRODUCTS
 

MRLs listed in Table A-l are found in Appendix A of the individual Toxicological Profile referenced. 

Appendix A of each profile describes the basis for ATSDR MRL’s derivation and use and includes 

worksheets showing calculations used to derive each MRL. 


TOTAL PETROLEUM HYDROCARONS B-l 

APPENDIX B 

USER’S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public especially people living in the vicinity of a hazardous waste site or chemical 

release. If the Public Health Statement were removed from the rest of the document, it would still 

communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 6 

Tables and Figures for Fraction-Specific Critical Effects 

Tables (6-l through 6-l 1) and Figures (6-l through 6-16) summarize health effects and illustrate 

graphically levels of exposure associated with those effects. These levels cover health effects observed at 

increasing dose concentrations and durations, differences in response by species, minimal risk levels 

(MRLs) to humans for noncancer end points, and EPA’s estimated range associated with an upper- bound 

individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use these tables and figures for a quick 

review of the health effects and to locate data for a specific exposure scenario. The Critical Effects tables 

and Exposure Assessment figures in Chapter 6 should always be used in conjunction with the text. All 

entries in these tables and figures represent studies that provide reliable, quantitative estimates of NoObserved-Adverse-Effect Levels (NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or 

Cancer Effect Levels (CELs). 

Chapter 6 (Section 6.7) 

Relevance to Public Health 

The Relevance to Public Health section provides a health effects summary based on evaluations of existing 

toxicologic, epidemiologic, and toxicokinetic information. This summary is designed to present 

interpretive, weight-of-evidence discussions for human health end points by addressing the following 

questions. 

1 . What effects are known to occur in humans? 

2 . What effects observed in animals are likely to be of concern to humans? 

3 . What exposure conditions are likely to be of concern to humans, especially around hazardous

 waste sites? 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency 
TOTAL PETROLEUM HYDROCARONS B-2 

APPENDIX B 

or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if derived) and 

the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, minimal risk levels (MRLs) for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic) are provided. Though no 

new MRLs are derived for TPH, all available MRLs for TPH components and petroleum products are 

reviewed in Chapter 6 and presented in Appendix A. These MRLs are not meant to support regulatory 

action; but to acquaint health professionals with exposure levels at which adverse health effects are not 

expected to occur in humans. They should help physicians and public health officials determine the safety 

of a community living near a chemical emission, given the concentration of a contaminant in air or the 

estimated daily dose in water. MRLs are based largely on toxicological studies in animals and on reports 

of human occupational exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. In 

particular, the user should review the profile of the specific substance of concern (see Appendix A). 

Section 6.7, “Relevance to Public Health,” contains basic information known about the substance. Other 

sections such as 6.9, “Interactions with Other Substances,” and 6.10, “Populations that are Unusually 

Susceptible” provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a modified 

version of the risk assessment methodology the Environmental Protection Agency (EPA) provides (Barnes 

and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR cannot 

make this judgement or derive an MRL unless information (quantitative or qualitative) is available for all 

potential systemic, neurological, and developmental effects. If this information and reliable quantitative 

data on the chosen end point are available, ATSDR derives an MRL using the most sensitive species 

(when information from multiple species is available) with the highest NOAEL that does not exceed any 

adverse effect levels. When a NOAEL is not available, a lowest-observed-adverse-effect level (LOAEL) 

can be used to derive an MRL, and an uncertainty factor (UP) of 10 must be employed. Additional 

uncertainty factors of 10 must be used both for human variability to protect sensitive subpopulations 

(people who are most susceptible to the health effects caused by the substance) and for interspecies 

variability (extrapolation from animals to humans). In deriving an MRL, these individual uncertainty 

factors are multiplied together. The product is then divided into the inhalation concentration or oral 

dosage selected from the study. Uncertainty factors used in developing a substance-specific MRL are 

provided in the footnotes of the LSE Tables in the profiles listed in Appendix A. 

The section covers end points in the same order they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data are 

presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro 

data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered 

in this section. If data are located in the scientific literature, a table of genotoxicity information is 

included.