Toxicological
Profile
for
BENZO [b] FLUOR ANTHENE
U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Agency for Toxic Substances and Disease Registry
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30772 -101
REPORT DOCUMENTATION 1 >• Report no 2.
PAGE ATSDR/TP-88/6
J- P390 -2*4 765 1
4. Title and Subtitle
Toxicological Profile for Ber.zo(b)Fluoranthene
5. Report Date
6.
'•Au,hom!
a. Performing Organisation Rapt. No.
ATSDR/TP-88/ 6
9. Performing Organization Nam* and Addreci
Agency for Toxic Substances and Disease Registry (ATSDR)
1600 Clifton Road, N.E.
Atlanta, Georgia 30333
in collaboration with
U.S. Environmental Protection Agency (EPA)
10. Proiect/Teek/Wor* Unit No.
11. ContractlQ or GraM(G) No.
~
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ATSDR/TP-88/06
TOXICOLOGICAL PROFILE FOR
BENZOMFLUORANTHENE
Date Published — March 1990
Prepared by:
ICF-Clement
under Contract No. 68-02-4235
for
U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Agency for Toxic Substances and Disease Registry (A7SDR)
in collaboration with
U.S. Environmental Protection Agency (EPA)
Technical editing/document preparation by:
Oak Ridge National Laboratory
under
DOE Interagency Agreement No. 1857-B026-A1
1
\
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DISCLAIMER
Mention of company name or product does not constitute endorsement by
the Agency for Toxic Substances and Disease Registry.
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FOREWORD
The Superfund Amendments and Reauthorization Act of 1986 (Public
Law 99-499) extended and amended the Comprehensive Environmental
Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund).
This public law (also known as SARA) directed the Agency for Toxic
Substances and Disease Registry (ATSDR) to prepare toxicological
profiles for hazardous substances which are most commonly found at
facilities on the CERCLA National Priorities List and which pose the
most significant potential threat to human health, as determined by
ATSDR and the Environmental Protection Agency (EPA). The list of the 100
most significant hazardous substances was published in the Federal
Register on April 17, 1987.
Section 110 (3) of SARA directs the Administrator of ATSDR to
prepare a toxicological profile for each substance on the list. Each
profile must include the following content:
"(A) An examination, summary, and interpretation of available
toxicological information and epidemiologic evaluations on a
hazardous substance in order to ascertain the levels of significant
human exposure for the substance and the associated acute,
subacute, and chronic health effects.
(B) A determination of whether adequate information on the health
effects of each substance is available or in the process of
development to determine levels of exposure which present a
significant risk to human health of acute, subacute, and chronic
health effects.
(C) Where appropriate, an identification of toxicological testing
needed to identify the types or levels of exposure that may present
significant risk of adverse health effects in humans."
This toxicological profile is prepared in accordance with
guidelines developed by ATSDR and EPA. The guidelines were published in
the Federal Register on April 17, 1987. Each profile will be revised and
republished as necessary, but no less often than every three years, as
required by SARA.
The ATSDR toxicological profile is intended to characterize
succinctly the toxicological and health effects information for the
hazardous substance being described. Each profile identifies and reviews
the key literature that describes a hazardous substance's toxicological
properties. Other literature is presented but described in less detail
than the key studies. The profile is not intended to be an exhaustive
document; however, more comprehensive sources of specialty information
are referenced.
iii
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Foreword
Each toxicological profile begins with a public health statement,
which describes in nontechnical language a substance's relevant
toxicological properties. Following the statement is material that
presents levels of significant human exposure and, where known,
significant health effects. The adequacy of information to determine a
substance's health effects is described in a health effects summary.
Research gaps in toxicologic and health effects information are
described in the profile. Research gaps that are of significance to
protection of public health will be identified by ATSDR, the National
Toxicology Program of the Public Health Service, and EPA. The focus of
the profiles is on health and toxicological information; therefore, we
have included this information in the front of the document.
The principal audiences for the toxicological profiles are health
professionals at the federal, state, and local levels, interested
private sector organizations and groups, and members of the public. We
plan to revise these documents in response to public comments and as
additional data become available; therefore, we encourage comment that
will make the toxicological profile series of the greatest use.
This profile reflects our assessment of all relevant toxicological
testing and information that has been peer reviewed. It has been
reviewed by scientists from ATSDR, EPA, the Centers for Disease Control,
and the National Toxicology Program. It has also been reviewed by a
panel of nongovernment peer reviewers and was made available for public
review. Final responsibility for the contents and views expressed in
this toxicological profile resides with ATSDR.
0 * h\Aj*r*-'
James 0. Mason, M.D., Dr. P.H.
Assistant Surgeon General
Administrator, ATSDR
iv
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CONTENTS
FOREWORD iii
LIST OF FIGURES ix
LIST OF TABLES xi
1. PUBLIC HEALTH STATEMENT 1
1.1 WHAT IS BENZO [b ] FLUORANTHENE? 1
1.2 HOW MIGHT I BE EXPOSED TO BENZO [b] FLUORANTHENE? 1
1.3 HOW DOES BENZO [b] FLUORANTHENE GET INTO MY BODY? 2
1.4 HOW CAN BENZO[b]FLUORANTHENE AFFECT MY HEALTH? 2
1.5 IS THERE A MEDICAL TEST TO DETERMINE IF I HAVE
BEEN EXPOSED TO BENZO[b]FLUORANTHENE? 2
1.6 WHAT LEVELS OF BENZO[b]FLUORANTHENE EXPOSURE HAVE
RESULTED IN HARMFUL HEALTH EFFECTS? 2
1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT
MADE TO PROTECT HUMAN HEALTH? 3
2. HEALTH EFFECTS SUMMARY 5
2.1 INTRODUCTION 5
2.2 LEVELS OF SIGNIFICANT EXPOSURE 6
2.2.1 Key Studies and Graphical Presentations 6
2.2.1.1 Inhalation 6
2.2.1.2 Oral 7
2.2.1.3 Dermal 7
2.2.2 Biological Monitoring 7
2.2.3 Environmental Levels as Indicators of Exposure
and Effects 10
2.2.3.1 Levels found in the environment 10
2.2.3.2 Human exposure potential 11
2.3 ADEQUACY OF DATABASE 11
2.3.1 Introduction 11
2.3.2 Health Effect End Points 12
2.3.2.1 Introduction and graphic summary 12
2.3.2.2 Description of highlights of graphs 15
2.3.2.3 Summary of relevant ongoing research .... 15
2.3.3 Other Information Needed for Human
Health Assessment 15
2.3.3.1 Toxicokinetics and mechanisms
of action 15
2.3.3.2 Adequacy of data on biological
monitoring 15
2.3.3.3 Environmental considerations 16
v
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Contents
3. CHEMICAL AND PHYSICAL INFORMATION 17
3.1 CHEMICAL IDENTITY 17
3.2 PHYSICAL AND CHEMICAL PROPERTIES 17
4. TOXICOLOGICAL DATA 21
4.1 OVERVIEW 21
4.2 TOXICOKINETICS 21
4.2.1 Overview 21
4.2.2 Absorption 21
4.2.2.1 Inhalation 21
4.2.2.2 Oral 22
4.2.2.3 Dermal 22
4.2.3 Distribution 22
4.2.4 Metabolism 22
4.2.5 Excretion 24
4.3 TOXICITY 24
4.3.1 Lethality and Decreased Longevity 24
4.3.2 Systemic/Target Organ Toxicity 24
4.3.3 Reproductive and Developmental Toxicity 24
4.3.4 Genotoxicity 24
4.3.4.1 Overview 24
4.3.4.2 General discussion 24
4.3.5 Carcinogenicity 26
4.3.5.1 Overview 26
4.3.5.2 Inhalation 26
4.3.5.3 Oral 27
4.3.5.4 Dermal 27
4.3.5.5 General discussion 27
4.4 INTERACTIONS WITH OTHER CHEMICALS 29
5. MANUFACTURE, IMPORT, USE, AND DISPOSAL 31
5.1 OVERVIEW 31
5.2 PRODUCTION 31
5.3 IMPORT 31
5.4 USE 32
5.5 DISPOSAL 32
6. ENVIRONMENTAL FATE 33
6.1 OVERVIEW 33
6.2 RELEASES TO THE ENVIRONMENT 33
6.3 ENVIRONMENTAL FATE 34
7. POTENTIAL FOR HUMAN EXPOSURE 37
7.1 OVERVIEW 37
7.2. LEVELS MONITORED IN THE ENVIRONMENT 37
7.2.1 Air 37
7.2.2 Water 37
7.2.3 Soil 38
7.2.4 Food 38
7.2.5 Cigarette Smoke 38
7.3 OCCUPATIONAL EXPOSURES 38
7.4 POPULATIONS AT HIGH RISK 39
vi
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Contents
8. ANALYTICAL METHODS 41
8.1 ENVIRONMENTAL SAMPLES 41
8.2 BIOLOGICAL SAMPLES 43
9. REGULATORY AND ADVISORY STATUS 47
9.1 INTERNATIONAL 47
9.2 NATIONAL 47
9.2.1 Regulatory Standards 47
9.2.2 Advisory Levels 49
9.2.2.1 Air advisory levels 49
9.2.2.2 Water advisory levels 49
9.2.2.3 Food advisory levels 50
9.2.2.4 Other guidance 50
9.2.3 Data Analysis 50
9.2.3.1 Carcinogenic potency 50
9.3 STATE 50
10. REFERENCES 51
11. GLOSSARY 63
APPENDIX: PEER REVIEW 67
vi j
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LIS? OF FIGURES
2.1 Effects of benzo[b]fluoranthene--dermal exposure 8
2.2 Levels of significant exposure for benzo[b]fluoranthene- -
dermal 9
2.3 Availability of information on health effects of
benzo[b]fluoranthene (human data) 13
2.4 Availability of information on health effects of
benzo[b]fluoranthene (animal data) 14
4.1 Metabolic fate of benzo[b]fluoranthene 23
i:
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LIST OF TABLES
3.1 Chemical Identity of benzo[b]fluoranthene 18
3.2 Physical and chemical properties of benzo[b]fluoranthene 19
4.1 Genetic toxicity of benzo[b]fluoranthene 25
4.2 Carcinogenic activity of benzo[b]fluoranthene
on mouse skin 28
8.1 Methods for analysis of benzo[b]fluoranthene
in environmental media 42
8.2 Methods for analysis of PAHs in biological samples 44
9.1 Regulatory standards and advisory levels 48
xi
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1
1. PUBLIC HEALTH STATEMENT
1.1 WHAT IS BSNZO[b]FLUORANTHENE?
Benzo[b]fluoranthene (B[b]F) is one of the polycyclic aromatic
hydrocarbon (PAH) compounds. Because it is formed when gasoline,
garbage, or any animal or plant material burns, it is usually found in
smoke and soot. This chemical combines with dust particles in the air
and is carried into water and soil and onto crops. Benzo[b]fluoranthene
is found in the coal tar pitch that industry uses to join electrical
parts together. It is also found in creosote, a chemical used to
preserve wood.
1.2 HOW MIGHT I BE EXPOSED TO BENZO[b]FLUORANTHENE?
People may be exposed to B[b]F from environmental sources such as
air, water, and soil and from cigarette smoke and cooked food. Workers
who handle or are involved in the manufacture of PAH-containing
materials may also be exposed to B[b]F. Typically, exposure for workers
and the general population is not to B[b]F alone but to a mixture of
similar chemicals.
The general population may be exposed to dust, soil, and other
particles that contain B[b]F. The largest sources of B[b]F in the air
are open burning and home heating with wood and coal. Factories that
produce coal tar also contribute small amounts of B[b]F into the air.
People may come in contact with B[b]F from soil on or near hazardous
waste sites, such as former gas-manufacturing sites or abandoned wood-
treatment plants that used creosote. At this time, B[b]F has been found
at 46 out of 1,177 sites on the National Priorities List (NPL) of
hazardous waste sites in the United States. As more sites are evaluated
by the Environmental Protection Agency (EPA), this number could change.
The soil near areas where coal, wood, or other products have been burned
is another source of exposure. Exposure to B[b]F and other PAHs may also
occur through skin contact with products that contain PAHs such as
creosote-treated wood, asphalt roads, or coal tar.
People may be exposed to B[b]F by drinking water from the drinking
water supplies in the U.S. that have been found to contain low levels of
the chemical. Foods grown in contaminated soil or air may contain B[b]F.
Cooking food at high temperatures, as occurs during charcoal-grilling or
charring, can increase the amount of B[b]F in the food.
Benzo[b]fluoranthene has been found in cereals, vegetables, fruits,
meats, beverages, and in cigarette smoke.
The greatest exposure to B[b]F is likely to take place in the
workplace. People who work in coal tar production plants; coking plants;
asphalt production plants; coal-gasification sites; smoke houses;
municipal trash incinerators; and facilities that burn wood, coal, or
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2 Section 1
oil may be exposed to B[b]F in the workplace air. Benzo[b]fluorantherie
may also be found in areas where high-temperature food fryers and
broilers are used.
1.3 HOW DOES BENZO[b]FLUORANTHENE GET INTO MY BODY?
The most common way B[b]F enters the body is through the lungs when
a person breathes in air or smoke containing it. It also enters the body
through the digestive system when substances containing it are
swallowed. Although B[b]F does not normally enter the body through the
skin, small amounts could enter if contact occurs with soil that
contains high levels of B[b]F (for example, near a hazardous waste site)
or if contact is made with heavy oils containing B[b]F.
1.4 HOV CAN BENZO[b]FLUORANTHENE AFFECT XY HEALTH?
Benzo[b]fluoranthene causes cancer in laboratory animals when
applied to their skin. This finding suggests that it is likely that
people exposed in the same manner could also develop cancer.
Because studies of B[b]F are not complete, we don't know if B[b]F
that is breathed in or swallowed could cause cancer or if it can cause
harmful effects other than cancer.
1.5 IS THERE A MEDICAL TEST TO DETERMINE IF I HAVE BEEN EXPOSED
TO BENZO[b]FLUORANTHENE?
Very few tests are available that can tell if exposure to B[b]F has
taken place. In the body, B[b]F is changed to related chemical
substances called metabolites. The metabolites can bind with DNA, the
genetic material of the body. The body's response after exposure can be
measured in the blood. However, this test is still being developed.
Benzo[b]fluoranthene can also be found in the urine of individuals
exposed to PAHs. It is not possible to know from these tests how much
B[b]F a person was exposed to or to predict what health effects may
happen at certain levels. Also, none of these tests have been used in
exposure situations outside the workplace.
1.6 WHAT LEVELS OF BENZO[b]FLUORANTHENE EXPOSURE HAVE RESULTED
IN HARMFUL HEALTH EFFECTS?
No information has been found about specific levels of B[b]F that
have caused harmful effects in people after breathing, swallowing, or
touching the substance.
Skin cancer has developed in mice that had B[b]F on their skin
throughout their lives. Skin cancer is the only harmful effect that can
be predicted when animals are exposed to B[b]F. It is not known if
similar levels could cause cancer in people. No information has been
found about harmful effects of B[b]F in animals that breathed in or ate
the chemical.
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Public Health Statement 3
1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO
PROTECT HUMAN HEALTH?
Based on information from another PAH chemical, the federal
government has developed standards and guidelines to protect individuals
from the potential health effects of PAHs, including B[b]F, in drinking
water. EPA has provided estimates of levels of total cancer-causing PAHs
in lakes and streams associated with various risks of developing cancer
in people. EPA has also determined that any release of PAHs of more than
1 pound should be reported to the National Response Center.
Pure B[b]F is produced in the United States only as a laboratory
chemical. However, B[b]F is a PAH, and PAHs are found in coal tar and in
the creosote oils and pitches formed from the production of coal tar.
The government's goal has been to protect workers involved with the
production of coal tar products. Although government standards are not
for B[b]F alone, they are useful in controlling exposure to total PAHs.
The National Institute for Occupational Safety and Health (NIOSH)
has determined that workplace exposure to coal products can increase the
risk of lung and skin cancer in workers and suggests a workplace
exposure limit for coal tar products of 0.1 milligram of PAHs per cubic
meter of air (0.1 mg/m-*) for a 10-hour workday, 40-hour workweek. NIOSH
has not suggested a specific workplace limit for B[b]F. The Occupational
Safety and Health Administration (OSHA) has set a legal limit of 0.2
milligram of all PAHs per cubic meter of air (0.2 mg/m^).
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5
2. HEALTH EFFECTS SUMMARY
2.1 INTRODUCTION
This section summarizes and graphs data on the health effects
concerning exposure to B[b]F. The purpose of this section is to present
levels of significant exposure for B[b]F based on key toxicological
studies, epidemiological investigations, and environmental exposure
data. The information presented in this section is critically evaluated
and discussed in Sect. 4, Toxicological Data, and Sect. 7, Potential for
Human Exposure.
This Health Effects Summary section comprises two major parts.
Levels of Significant Exposure (Sect. 2.2) presents brief narratives and
graphics for key studies in a manner that provides public health
officials, physicians, and other interested individuals and groups with
(1) an overall perspective of the toxicology of B[b]F and (2) a
summarized depiction of significant exposure levels associated with
various adverse health effects. This section also includes information
on the levels of B[b]F that have been monitored in human fluids and
tissues and information about levels of B[b]F found in environmental
media and their association with human exposures.
The significance of the exposure levels shown on the graphs may
differ depending on the user's perspective. For example, physicians
concerned with the interpretation of overt clinical findings in exposed
persons or with the identification of persons with the potential to
develop such disease may be interested in levels of exposure associated
with frank effects (Frank Effect Level, FEL). Public health officials
and project managers concerned with response actions at Superfund sites
may want information on levels of exposure associated with more subtle
effects in humans or animals (Lowest-Observed-Adverse-Effect Level,
LOAEL) or exposure levels below which no adverse effects (No-Observed-
Adverse -Effect Level, NOAEL) have been observed. Estimates of levels
posing minimal risk to humans (Minimal Risk Levels) are of interest to
health professionals and citizens alike.
Adequacy of Database (Sect. 2.3) highlights the availability of key
studies on exposure to B[b]F in the scientific literature and displays
these data in three-dimensional graphs consistent with the format in
Sect. 2.2. The purpose of this section is to suggest where there might
be insufficient information to establish levels of significant human
exposure. These areas will be considered by the Agency for Toxic
Substances and Disease Registry (ATSDR), EPA, and the National
Toxicology Program (NTP) of the U.S. Public Health Service in order to
develop a research agenda for benzo[b]fluoranthene.
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6 Section 2
2.2 LEVELS OF SIGNIFICANT EXPOSURE
2.2.1 Key Studies and Graphical Presentations
To help public health professionals address the needs of persons
living or working near hazardous waste sites, the toxicology data
summarized in this section are organized first by route of exposure--
inhalation, ingestion, and dermal--and then by toxicological end points
that are categorized into six general areas--lethality, systemic/target
organ toxicity, developmental toxicity, reproductive toxicity, genetic
toxicity, and carcinogenicity. The data are discussed in terms of three
exposure periods--acute, intermediate, and chronic.
Two kinds of graphs are used to depict the data. The first type is
a "thermometer" graph. It provides a graphical summary of the human and
animal toxicological end points and levels of exposure for each exposure
route for which data are available. The ordering of effects does not
reflect the exposure duration or species of animal tested. The second
kind of graph shows Levels of Significant Exposure (LSE) for each route
and exposure duration. The points on the graph showing NOAELs and LOAELs
reflect the actual dose (levels of exposure) used in the key studies. No
adjustments for exposure duration or intermittent exposure protocol were
made.
Adjustments reflecting the uncertainty of extrapolating animal data
to man, intraspecies variations, and differences between experimental
versus actual human exposure conditions were considered when estimates
of levels posing minimal risk to human health were made for noncancer
end points. These minimal risk levels were derived for the most
sensitive noncancer end point for each exposure duration by applying
uncertainty factors. These levels are shown on the graphs as a broken
line starting from the actual dose (level of exposure) and ending with a
concave-curved line at its terminus. Although methods have been
established to derive these minimal risk levels (Barnes et al. 1987),
shortcomings in the techniques reduce the confidence in the projected
estimates. Also shown on the graphs under the cancer end point are low-
level risks (10~^ to 10"^) reported by EPA if available. In addition,
the actual dose (level of exposure) associated with tumor incidence is
plotted.
2.2.1.1 Inhalat ion
No information was found in the available literature concerning the
effects of B[b]F following inhalation exposure.
Lethality and decreased longevity. No information is available.
Systemic toxicity. No information is available.
Developmental toxicity. No information is available.
Reproductive toxicity. No information is available.
Genotoxicity. No information is available.
Carcinogenicity. No reports directly correlating inhalation
exposure to B[b]F and cancer induction in humans are available, although
reports of cancer among individuals exposed to mixtures of PAHs
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Health Effects Summary 1
containing B[b]F lend qualitative support to its potential for
carcinogenicity in humans. No inhalation experiments in animals are
available, although B[b]F has elicited respiratory tract tumors in rats
following intratracheal instillation.
2.2.1.2 Oral
No information was found in the available literature concerning the
effects of B[b]F following oral exposure.
Lethality and decreased longevity. No information is available.
Systemic toxicity. No information is available.
Developmental toxicity. No information is available.
Reproductive toxicity. No information is available.
Genotoxicity. No information is available.
Carcinogenicity. No information is available.
2.2.1.3 Dermal
No information is available on the effects of B[b]F following
short-term dermal exposure.
B[b]F has been shown to be carcinogenic following intermediate-term
dermal exposure. This conclusion is based on observations of
experimental animals because no data are available for human exposure;
results are summarized in Figs. 2.1 and 2.2.
Lethality and decreased longevity. No information is available.
Systemic toxicity. No information is available.
Developmental toxicity. No information is available.
Reproductive toxicity. No information is available.
Genotoxicity. No information is available.
Carcinogenicity. No information directly correlating human dermal
exposure to B[b]F and cancer induction is available, although reports of
skin tumors among individuals exposed to mixtures of PAHs containing
B[b]F lend some qualitative support to its potential for human
carcinogenicity. The contribution of B[b]F to the overall
carcinogenicity of the mixtures is not known.
Studies in experimental animals have demonstrated the ability of
B[b]F to induce skin tumors following intermediate-term dermal exposure.
Mice receiving a dose of 2.9 mg/kg (equivalent to an average daily dose
of 1.2 mg/kg) and larger applied to their skin three times weekly
developed an excess of malignant skin tumors following exposure for up
to 1 year (Wynder and Hoffmann 1959). No estimate of human risk has been
calculated based on the results of this study.
2.2.2 Biological Monitoring
The available biological monitoring techniques can be useful in
predicting whether exposure to B[b]F or other PAHs has occurred, but
they may not be useful in estimating body doses. Individual variability,
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8 Section 2
ANIMALS
(mg/kg/day)
10,000
HUMANS
1,000
100
10
0.1
0.01
~ MOUSE, CANCER, INTERMEDIATE,
3 DAYS PER WEEK, INTERMITTENT
LOAEL
QUANTITATIVE DATA
WERE NOT
AVAILABLE
Fig. 2.1. Effects of benzo{b]fluoranthene—dermal exposure.
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Health Effects Summary 9
ACUTE INTERMEDIATE CHRONIC
(<14 DAYS) (15-364 DAYS) (£ 365 DAYS)
(mg/kg/day) CANCER
10,000 r- QUANTITATIVE DATA
WERE NOT
AVAILABLE
1,000 -
100 -
10 -
• m
QUANTITATIVE DATA
WERE NOT
AVAILABLE
1 -
0.1
0.01
0.001 • LOAEL
m MOUSE
fig. 2.2. Levels of significant exposure for benzo{b)fltx>r«nthe»e—dermal.
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10 Section 2
confounding effects of drugs, and the specificity of the techniques are
likely to complicate the association between B[b]F metabolites in the
body and environmental exposure. The most common tests for determining
exposure to PAHs include examination of tissues, blood, and urine for
the presence of PAHs or PAH metabolites. Currently available biological
monitoring techniques are discussed in detail in Sect. 8, Analytical
Methods.
Modica et al. (1982) and Bartosek et al. (1984) used gas-liquid
chromatography to determine the presence of PAHs in the blood, mammary
and adipose tissue, liver, and brain of rats. However, no examples of
examination of human tissue samples using this method were found in the
available literature.
In the body, B[b]F can be converted by specific cellular enzymes
(cytochrome 450 monooxygenase system and epoxide hydrolase) to a
dihydrodiol and further metabolized to epoxides or dihydrodiols that can
bind to DNA and form DNA adducts (Geddie et al. 1984). In the ^2p
postlabeling technique, a tissue sample is taken from an exposed
individual, and DNA from the exposed cells is digested and labeled with
radioactive phosphorus (^2p). Thin-layer chromatography is then used to
determine the presence of altered DNA, and scintillation counting is
used to quantify the adducts (Randerath et al. 1985; Randerath et al.
1986; Weyand et al. 1987a,b). Although the structures of the B[b]F-DNA
adducts are not known, structural analogs of potential B[b]F-DNA adducts
have been synthesized and examined using high-performance liquid
chromatography (Amin et al. 1985b). A technique using immunoassays
(Harris 1985a,b; Harris et al. 1986) has been developed that tests for
the presence of antibodies to the PAH-DNA adducts in human blood. A
patent application has been submitted for a method and kit for detecting
antibodies in human sera to diol epoxide-DNA adducts by immunoassay
(Harris 1985b). This method has been used to examine exposure to
benzo[a]pyrene and other PAHs.
PAHs have been detected in the urine of individuals occupationally
exposed to atmospheric PAHs, in smokers, and in individuals treated with
therapeutical coal tar for psoriasis (Becher and Bjorseth 1983, Becher
et al. 1984, Becher 1986, Clonfero et al. 1986).
A recently developed biological monitoring technique using an
antibody-based fiberoptics biosensor to detect PAHs has been tested.
This technique has been investigated in sample solutions containing
benzo[a]pyrene and may be useful for assessing an individual's exposure
to other PAHs provided appropriate antibodies are used (Vo-Dinh et al.
1987).
2.2.3 Environmental Levels as Indicators of Exposure and Effects
2.2.3.1 Levels found in the environment
B[b]F has been detected in the environment, but the information
available to characterize background exposures is inadequate. B[b]F air
concentrations in U.S. cities have been reported in the range of 0.09 to
1.8 ng/m^ (Gordon and Bryan 1973). B[b]F concentrations in finished
drinking waters of the United States have been reported to be <2 ng/L
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Health Effects Summary 11
(Sorrell et al. 1981). No data are available on B[b]F levels in U.S.
soil, but concentrations of total PAHs, including B[b]F, have been
reported in the range of 4 to 13 mg/kg in relatively rural areas of the
United States (summarized by Blumer et al. 1977).
B[b]F may occur in the soil and on particulate matter in the air
surrounding waste sites, such as former manufactured-gas plants and
creosote wood treatment plants. However, exposure levels at these sites
have not yet been published.
Data are not available which relate environmental levels of B[b]F
to significant health effects in humans following exposures.
2.2.3.2 Human exposure potential
Humans may be exposed to B[b]F in air, water, soil, and food. Each
of these media constitutes a normal route of background exposure in the
nonoccupational environment. Background exposures to B[b]F are expected
to be at low levels. Much higher exposure concentrations are associated
with tobacco smoke and with some occupational environments. At hazardous
waste sites, exposure concentrations may also be higher, and humans may
be exposed to B[b]F via contact with soil or inhalation of particulate
matter in air. Estimates of body doses or tissue levels associated with
B[b]F intake require (1) information on the chemical concentrations in
soil and air, (2) certain assumptions about factors controlling intake,
and (3) information on absorption of B[b]F from soil or particulate
matter.
Information on the first two of these data needs is relatively
site-specific and cannot be generalized. Quantitative toxicological
information on the absorption of B[b]F and other PAHs from soil or
particulate matter is limited, although absorption is expected to be low
(Becher et al. 1984). Consequently, estimates of dose following exposure
to B[b]F in soil or air are based on limited toxicological and
epidemiological data and on assumptions regarding dermal absorption of
B[b]F from soil and absorption of incidentally ingested B[b]F on soil or
inhaled B[b]F on particulate matter. These assumptions lend uncertainty
to any risk assessment of potential health effects following
environmental exposures.
2.3 ADEQUACY OF DATABASE
2.3.1 Introduction
Section 110 (3) of SARA directs the Administrator of ATSDR to
prepare a toxicological profile for each of the 100 most significant
hazardous substances found at facilities on the CERCLA National
Priorities List. Each profile must include the following content:
"(A) An examination, summary, and interpretation of available
toxicological information and epidemiologic evaluations on a
hazardous substance in order to ascertain the levels of
significant human exposure for the substance and the
associated acute, subacute, and chronic health effects.
-------
12 Section 2
(B) A determination of whether adequate information on the health
effects of each substance is available or in the process of
development to determine levels of exposure which present a
significant risk to human health of acute, subacute, and
chronic health effects.
(C) Where appropriate, an identification of toxicological testing
needed to identify the types or levels of exposure that may
present significant risk of adverse health effects in humans."
This section identifies gaps in current knowledge relevant to
developing levels of significant exposure for B[b]F. Such gaps are
identified for certain health effect end points (lethality,
systemic/target organ toxicity, developmental toxicity, reproductive
toxicity, and carcinogenicity) reviewed in Sect. 2.2 of this profile in
developing levels of significant exposure for B[b]F, and for other areas
such as human biological monitoring and mechanisms of toxicity. The
present section briefly summarizes the availability of existing human
and animal data, identifies data gaps, and summarizes research in
progress that may fill such gaps.
Specific research programs for obtaining data needed to develop
levels of significant exposure for B[b]F will be developed in the future
by ATSDR, NTP, and EPA.
2.3.2 Health Effect End Points
2.3.2.1 Introduction and graphic summary
The availability of data for health effects in humans and animals
is depicted on bar graphs in Figs. 2.3 and 2.4, respectively.
The bars of full height indicate that there are data to meet at
least one of the following criteria:
1. For noncancer health end points, one or more studies are available
that meet current scientific standards and are sufficient to define
a range of toxicity from no-effect levels (NOAELs) to levels that
cause effects (LOAELs or FELs). For human carcinogenicity, a
substance is classified as either a "known human carcinogen" or a
"probable human carcinogen" by both EPA and the International
Agency for Research on Cancer (IARC) (qualitative), and the data
are sufficient to derive a cancer potency factor (quantitative).
2. For animal carcinogenicity, a substance causes a statistically
significant number of tumors in at least one species, and the data
are sufficient to derive a cancer potency factor.
3. There are studies which show that the chemical does not cause this
health effect via this exposure route.
Bars of half height indicate that "some" information for the end
point exists, but does not meet any of these criteria.
The absence of a column indicates that no information exists for
that end point and route.
-------
HUMAN DATA
\
V SUFFICIENT
' INFORMATION*
SOME
INFORMATION
NO
INFORMATION
INHALATION
LETHALITY ACUTE INTERMEDIATE CHRONIC DEVELOPMENTAL REPRODUCTIVE CARCINOGENICITY
Z / TOXICITY TOXICITY
SYSTEMIC TOXICITY
'Sufficient Information exists to meet at least one of the criteria for cancer or noncancer end points.
Note: The adequacy of the database for the carcinogenicity of benzo(bWuoranthene by the inhalation and dermal route* of
exposure has bean assessed on the basis of human exposure to complex mixtures of chemicals containing this
oompound, not on the basis of the compound alone.
Fig. 2.3. Availability of information on health effects of benzolbyiaoranthene (bumaa data).
-------
ANIMAL DATA
W/j>E~Z7//II7//ZZ7/Z
V SUFFICIENT
'NFORMATION*
SOME
INFORMATION
NO
INFORMATION
LETHALITY ACUTE INTERMEDIATE CHRONIC DEVELOPMENTAL REPRODUCTIVE CARCINOGENICITY
Z / TOXICITY TOXICITY
SYSTEMIC TOXICITY
'Sufficient information exists to meet at least one of the criteria for cancer or noncancer end points.
Note: The adequacy of the database for the carcinogenicity of benzo{b]lluoranthene by the inhalation route of exposure has
been aseeeaed on the basis of Intratracheal InatMatlon experiments using rata, In the absence of Inhalation data.
Fig. 2.4. Availability of information on health effects of benzo(bJfluorandiene (animal data).
-------
Health Effects Summary 15
2.3.2.2 Description of highlights of graphs
Fig. 2.3 indicates that there are no data available to assess
significant exposure levels of B[b]F alone for humans. Reports of
adverse health effects such as carcinogenicity by the inhalation and
dermal routes of exposure do exist for mixtures of chemicals that
include B[b]F, thus providing some information to qualitatively assess
the role of B[b]F as a human carcinogen.
As displayed in Fig. 2.4, some data are available in animals to
assess only the dermal and inhalation carcinogenicity of B[b]F; however,
in the absence of inhalation data, the latter are based on intratracheal
instillation experiments. No information could be found on the effects
of B[b]F following oral or inhalation exposure.
2.3.2.3 Summary of relevant ongoing research
Research is ongoing in the areas of the molecular dosimetry of
B[b]F, as well as into its biological mechanisms of action such as those
of DNA binding and repair. B[b]F has been listed in both the National
Toxicology Program (NTP) Fiscal Year 1986 Annual Plan and the NTP Review
of Current DHHS, DOE, and EPA Research Related to Toxicology. (DHHS is
the acronym for the Department of Health and Human Services; DOE is the
acronym for the Department of Energy.) This chemical is being tested in
Salmonella (status C: test started in February 1986) for
mutagenesis/genetic toxicity by the National Institute of Environmental
Health Sciences. A comparative potency method to quantitatively assess
the carcinogenic effects for PAHs is under development by the Carcinogen
Assessment Group, the Office of Solid Waste, the Office of Drinking
Water, and the Office of Air Quality Planning and Standards of the EPA
(EPA Contract Number 68-02-4403) and is being applied to the data
available for B[b]F.
2.3.3 Other Information Needed for Human Health Assessment
2.3.3.1 Toxicokinetics and mechanisms of action
There is no specific information available on the absorption,
tissue distribution, and excretion of B[b]F in animals and humans.
There is limited information on the metabolism of B[b]F. Metabolic
data on B[b]F have been derived from mouse skin and in vitro hepatic
preparations. A clear mechanistic picture of the steps involved in the
metabolic activation of B[b]F is lacking. The literature on B[b]F
suggests that this hydrocarbon is the subject of active research in the
area of metabolism.
2.3.3.2 Adequacy of data on biological monitoring
Many of the biological monitoring techniques have not been used to
examine exposure to B[b]F specifically. Additional research should be
focused on using these tests to examine exposure to other PAHs.
The biological monitoring techniques by which DNA adducts are
quantified are limited because inborn factors, environmental chemistry,
and drugs can alter the activity of the enzymes responsible for
converting PAHs to the dihydrodiols or epoxides that bind to DNA. There
-------
16 Section 2
is limited information concerning the use of these techniques in
occupationally or environmentally exposed individuals. Additional
research should include further investigation of the formation of
adducts following these exposure situations.
The technique that uses immunoassays to determine the presence of
antibodies to adducts in blood has been tested in occupationally exposed
humans and smokers (Harris 1985b, Harris et al. 1986). This technique
has shown an association between sera positive for antibodies and
occupational exposure or smoking. The reliability of this method needs
to be further examined in other, nonoccupational, exposure situations.
The presence of PAHs or PAH metabolites in urine is an indication
that exposure has occurred. However, in occupational studies, the amount
of PAH concentrated in the urine did not adequately reflect
environmental PAH concentrations (Becher and Bjorseth 1983, Becher et
al. 1984, Becher 1986). The lack of a direct quantitative relationship
may be the result of the nonbioavailability of particle-bound PAHs;
therefore, this method should be further examined for its applicability
in other exposure situations (Becher et al. 1984).
In addition, some occupationally related activities and cigarette
smoking result in human exposure to PAHs; therefore, the determination
of biological levels of PAHs in smokers and in the general population
must be examined more fully to properly assess environmental exposure.
2.3.3.3 Environmental considerations
The accuracy and precision of the analytical methods used to
measure ambient B[b]F are somewhat limited; but the current methods, if
properly conducted, are sufficient to record ambient levels of B[b]F.
However, some methods have limited sensitivity.
Inadequate data are available to characterize background levels of
B[b]F and other PAHs, or levels typically found at hazardous waste
sites. Comprehensive monitoring studies are being conducted by EPA at
and around many hazardous waste sites, but the data are not yet
available in a single database.
No quantitative data are available on the bioavailability of B[b]F
in soil or sorbed onto particulate matter in air. This lack of
information limits our understanding of potential health risks in humans
following exposure to these media.
Information on the fate of B[b]F sorbed onto particulate matter in
air is presently unclear. The role of photochemical oxidation in the
removal of B[b]F from air needs to be elucidated. Also, additional
information on biodegradation processes and rates in aquatic and
terrestrial systems is needed.
Inadequate information is available on the interactions of B[b]F
with other chemicals typically found in the environment and at hazardous
waste sites. Consequently, risks associated with exposure to B[b]F in
the environment are not completely understood.
-------
17
3. CHEMICAL AND PHYSICAL INFORMATION
3.1 CHEMICAL IDENTITY
The chemical formula, structure, synonyms, and identification
numbers for B[b]F are listed in Table 3.1.
3.2 PHYSICAL AND CHEMICAL PROPERTIES
Important physical and chemical properties of B[b]F are given in
Table 3.2.
-------
18 Section 3
Table 3.1. Chemical identity of benzo(b]fluoranthene
Chemical name: Benzo[b]fluoranthene
Synonyms: 3,4-benzofluoranthene; benz[e]acephenanthrylene;
2,3-benzfluoranthrene; 2,3-benzofluoranthene;
2,3-benzofluoranthrene; 3,4-benzfluoranthene;
benzo[e]fluoranthene; B[b]F (IARC 1983)°
Trade name: Not applicable
Chemical formula: C20H12 (IARC 1983)
Wiswesser line notation: L C65 K666 1A TJ (HSDB 1987)
Chemical structure:
Identification numbers:
CAS Registry No.: 205-99-2
NIOSH RTECS No.: CU1400000
EPA Hazardous Waste No.: Not available
OHM-TADS No.: Not available
DOT/UN/NA/IMCO Shipping No.: Not available
STCC No.: Not available
Hazardous Substances Data Bank No.: 403S
National Cancer Institute No.: Not available
"Confusion exists in the literature concerning the
naming of this compound, mainly because two different
systems (Richter and IUPAC) of numbering ring structures
have been used; the IARC reference, unfortunately, does
not acknowledge that this confusion exists and that the
nomenclature of some of the synonyms listed is incorrect.
-------
Chemical and Physical Information 19
Table 3.2. Physical and chemical properties of benzofljjfluorantheie
Property
Value
Reference
Molecular weight
252.32 g/mol
IARC 1983
Color
Colorless
IARC 1983
Physical state
Needles (recrystallized
from benzene)
CRC 1987
Odor
Unknown
Melting point
167-168°C
CRC 1987
Boiling point
Unknown
Autoignition temperature
Unknown
Solubility
Water
14 iig/L
EPA 1982
Organic solvents
Slightly soluble in benzene
and acetone
IARC 1983
Biological fluids
Unknown
Density
Unknown
Partition coefficients
Octanol-water (Kow)
1.15 X 106
EPA 1982
log
6.06
Soil-organic carbon-water
(*oc)
5.5 X 105
EPA 1982
Vapor pressure (20°C)
5 X 1(T7 mm Hg
EPA 1982
Henry's law constant
1.22 X 10"5
EPA 1982
Flash point
Unknown
Flammability limits
Unknown
Conversion factor (in air)"
1 ppm = 10.32 mg/m3
Verschueren
1983
"Calculated using the ideal gas law, PV = nRT at 25°C.
-------
Intentionally Blank Page
-------
21
4. TOXICOLOGICAL DATA
4.1 OVERVIEW
No data on the absorption, distribution, or excretion of B[b]F were
identified. Evidence of dermal absorption in animals is found in skin
carcinogenicity studies conducted with B[b]F. B[b]F is metabolized under
in vitro incubation conditions to phenol and dihydrodiol metabolites.
B[b]F is thought to be metabolized to reactive derivatives other
than diol epoxides that may be responsible for its mutagenic activity in
experimental systems, although it is a weak mutagen. B[b]F is a weak
experimental dermal carcinogen (compared to benzo[a]pyrene). Its
carcinogenicity has not been studied by the inhalation or oral routes of
exposure, although it is active following intratracheal instillation.
Mutation is thought to be a necessary (albeit insufficient) step for the
carcinogenic activity of B[b]F.
There is no information on other toxic effects of B[b]F in humans
and experimental animals following inhalation, oral, or dermal
exposures. Carcinogenic PAHs as a group, however, cause skin disorders
and have an immunosupressive effect.
4.2 TOXICOKINETICS
4.2.1 Overview
No data on the absorption, distribution, or excretion of B[b]F were
identified. Evidence of dermal absorption in animals is found in skin
carcinogenicity studies conducted with B[b]F. B[b]F is metabolized under
in vitro incubation conditions to phenol and dihydrodiol metabolites. No
evidence for formation of bay-region diol epoxide metabolites or their
corresponding dihydrodiol precursor intermediates was obtained under in
vitro conditions. Under in vivo conditions, dihydrodiol metabolites have
been identified, but only one has shown tumor-initiating activity
comparable to that of B[b]F. The metabolic activation of B[b]F to a
reactive intermediate is therefore thought to occur primarily via
metabolites other than diol epoxides in a departure from the pathways
established for benzo[a]pyrene and other carcinogenic PAHs with bay-
region systems.
4.2.2 Absorption
4.2.2.1 Inhalation
Human. No information on the absorption of B[b]F via the
respiratory tract was found. Absorption of B[b]F via this route may be
-------
22 Section 4
Inferred from the identification of metabolites in individuals exposed
to PAHs in an industrial environment (Becher and Bjorseth 1983).
Animal. No information was found on the absorption of B[b]F via
the respiratory tract. By analogy to benzo[a]pyrene, pulmonary
absorption of B[b]F is expected to be efficient and to be subject to
similar controlling factors; specifically, the role of metabolism in
absorption mechanisms (Kao et al. 1985), particle size matrix effects,
and mucociliary clearance is anticipated to influence the rate of
absorption via the respiratory tract (Creasia et al. 1976, Tornquist et
al. 1985, Medinsky and Kampcik 1985).
4.2.2.2 Oral
Human. No data on the absorption of B[b]F via the gastrointestinal
tract in humans were identified.
Animal. No data on the absorption of B[b]F via the
gastrointestinal tract in animals were identified.
4.2.2.3 Dermal
Human. No data on the dermal absorption of B[b]F in humans were
identified. The rate of dermal penetration of B[b]F may be expected to
be reasonably close to that of benzo[a]pyrene. For the latter, under in
vitro conditions, 3% of an applied dose of [^C]benzo[a]pyrene (10
fig/cm2) permeated human skin in 24 h (Kao et al. 1985).
Animal. No quantitative data on the dermal absorption of B[b]F in
animals were identified. Evidence of dermal absorption in animals is
found in skin carcinogenicity studies conducted with B[b]F (Amin et al.
1985a, IARC 1973).
4.2.3 Distribution
No data on the distribution of absorbed B[b]F were identified.
4.2.4 Metabolism
The metabolism of B[b]F has been investigated in vitro using
hepatic S9 preparations (Amin et al. 1982). The general
biotransformation pathways established for benzo[a]pyrene are also
active on B[b]F (Cooper et al. 1983, Levin et al. 1982, Grover 1986)
(see Fig. 4.1).
The metabolites isolated under the above conditions consisted of
phenols and dihydrodiols. The major phenolic metabolites were identified
as the 5-, 6-, and 4- or 7-hydroxy B[b]F. The predominant diol formed
was the trans-ll,12-dihydrodiol B[b]F, accompanied by smaller amounts of
trans-1,2,-dihydrodiol B[b]F (Amin et al. 1982). No evidence was
obtained to indicate the formation of trans-9,10-dihydrodiol B[b]F. The
latter would be a precursor to a bay-region diol epoxide, a metabolite
class implicated in the carcinogenic activity of other PAHs (Sims 1982,
Thakker et al. 1985). Although the evidence is not conclusive at this
point, it is possible that the reactive metabolites associated with the
tumorigenic effects of B[b]F are not diol epoxides (Amin et al. 1982,
Amin et al. 1985a).
-------
5-. 6-. 4-,
and 7-hydroxy
B[blF (Phenols)
11,12-oxid©
1.2-oxlde
Berizolblfluoranthene
OH
OH
11,12-Dihydrodiol 1,2-DihydrodioI
12
11
9,10-oxide
OH
9,10-DihydrodioI
OH
9,10-Diol epoxide
NOT OBSERVED
Fig. 4.1. Metabolic fate of benzo{b}fluoraiitfaene.
-------
24 Section 4
4.2.5 Excretion
The steps involved in the excretion of B[b]F are likely to be those
established for other PAHs. Metabolism, hepatobiliary excretion, and
elimination through feces are the dominant features in this process
(Schlede et al. 1970). As for other PAHs, the material excreted is
expected to consist predominantly of dihydrodiol and phenol conjugates
(e.g., glucuronide and sulfate esters) and glutathione conjugates
(Grover 1986).
4.3 TOXICITY
4.3.1 Lethality and Decreased Longevity
Pertinent data regarding lethality and decreased longevity in
humans or experimental animals following inhalation, oral, and dermal
exposure to B[b]F could not be found in the available literature.
4.3.2 Systemic/Target Organ Toxicity
No information is available on the systemic effects of B[b]F in
humans or experimental animals following inhalation, oral, and dermal
exposures. The carcinogenic PAHs as a group cause skin disorders and
have an immunosuppressive effect; however, specific effects of B[b]F
have not been reported.
4.3.3 Reproductive and Developmental Toxicity
Pertinent data regarding the reproductive and developmental
toxicity of B[b]F in humans or experimental animals following
inhalation, oral, and dermal exposure could not be found in the
available literature.
4.3.4 Genotoxicity
4.3.4.1 Overview
The genetic toxicity of B[b]F has been evaluated experimentally in
a limited number of short-term bioassays utilizing two bacterial cell
strains and a mammalian cell system as target organisms. The test
systems used to evaluate the genotoxicity of B[b]F and the results
obtained are summarized in Table 4.1.
4.3.4.2 General discussion
The genotoxicity of B[b]F has been demonstrated equivocally in
three in vitro studies. B[b]F showed mutagenic activity in Salmonella,
typhimurium in the presence of an exogenous rat-liver preparation
(LaVoie et al. 1979b). Some mutagenic activity was also reported by
Hermann (1981) in a similar study, but negative results were reported by
Mossanda et al. (1979). The data in these studies are inadequate to
support a positive or negative determination for B[b]F mutagenicity.
These studies cannot be used as primary evidence for B[b]F mutagenic
activity. In the one available in vivo study, B[b]F exposure resulted in
-------
Table 4.1. Genetic toxicity of benzo(blfluoraiitheiie
End points
Species (test systems)
Result0
References
Gene mutation
(in vitro)
Salmonella typhimurium
TA100 (his+/his—)
Positive-activation
LaVoie et al. 1979b
Salmonella typhimurium
TA98 (his+/his-)
Equivocal-activation
Hermann 1981
Salmonella typhimurium
TA98, TA100 (his+/his-)
Negative-activation
Mossanda et al. 1979
Sister chromatid exchange
(in vivo)
Chinese hamster bone
marrow cells
Positive
Roszinsky-Kocher et al. 1979
Chromosomal aberration
(in vivo)
Chinese hamster bone
marrow cells
Negative
Roszinsky-Kocher et al. 1979
"The results presented in Table 4.1 are based on activity profiles prepared by Waters et al. (1987), Gene-Tox
data files supplied by John S. Wassom, and/or personal review of the original citation.
-------
26 Section 4
a weak induction of sister chromatid exchange (SCE) but no significant
induction of chromosomal aberrations in Chinese hamster bone marrow
cells (Roszinsky-Kocher et al. 1979). The SCE results are, at best,
weakly or marginally positive, but the data are insufficient to assess
the negative determination for chromosomal aberrations because no
indices of toxicity are given (Roszinsky-Kocher et al. 1979).
There is inadequate evidence that B[b]F is active in short-term
genetic assays. Further studies are needed in order to evaluate the
genotoxic potential of B[b]F.
4.3.5 Carcinogenicity
4.3.5.1 Overview
The carcinogenicity of B[b]F has not been adequately studied. There
are no reports directly correlating human B[b]F exposure and tumor
development, although humans are likely to be exposed by all routes.
There are a number of reports, however, associating human cancer with
exposure to mixtures of PAHs that include B[b]F. There is experimental
evidence that B[b]F is a skin carcinogen in animals following dermal
application and a lung carcinogen following intratracheal instillation.
It is likely that B[b]F would cause cancer in humans as well.
4.3.5.2 Inhalation
Human. No studies on the carcinogenicity of B[b]F in humans
following inhalation exposure were found in the available literature.
However, epidemiologic studies have shown an increased incidence of lung
cancer in humans exposed to coke-oven emissions (Lloyd 1971, Redmond et
al. 1972, Mazumdar et al. 1975), roofing tar emissions (Hammond et al.
1976), and cigarette smoke (Wynder and Hoffmann 1967, Maclure and
KacMahon 1980, Schottenfeld and Fraumeni 1982). Each of these mixtures
contains B[b]F as well as other carcinogenic PAHs and other potentially
carcinogenic chemicals such as nitrosamines. It is thus impossible to
evaluate the contribution of B[b]F to the total human carcinogenicity of
these mixtures because of their complexity and the presence of other
carcinogens. Reports of this nature nonetheless provide a qualitative
suggestion of the potential for B[b]F-induced carcinogenicity.
Animal. No studies on the carcinogenicity of B[b]F in animals
following inhalation exposure were found in the available literature.
However, B[b]F has been shown to cause respiratory tract tumors in rats
following intratracheal instillation (Deutsch-Wenzel et al. 1983). In
this experiment, B{b]F was prepared in solution with trioctanoin and
molten beeswax and injected into the left lobe of the lungs of female
Osborne-Mendel rats. The mixture congealed into a pellet from which the
test compound diffused over time into the surrounding tissue. Doses of
0, 0.1, 0.3, or 1.0 mg B[b]F were administered, eliciting 0/35, 1/35,
3/35, or 13/35 lung-tumor-bearing animals per group, respectively.
Tumors were epidermoid carcinomas or pleomorphic sarcomas. This
experiment indicates that B[b]F is a moderately active respiratory tract
carcinogen.
-------
ToxLcological Data 27
4.3.5.3 Oral
Human. No studies on the carcinogenicity of B[b]F in humans
following oral exposure were found in the available literature.
Animal. No studies on the carcinogenicity of B[b]F in animals
following oral exposure were found in the available literature.
4.3.5.4 Dermal
Human. No studies on the carcinogenicity of B[b]F in humans
following dermal exposure were found in the available literature. As
with inhalation exposure, however, there are reports of skin cancer
among individuals exposed derraally to mixtures of PAHs containing B[b]F.
The earliest of these is the report of Pott (1775) of scrotal cancer
among chimney sweeps. More recently, skin cancer among those exposed
dermally to shale oils has been reported (Purde and Etlin 1980). These
reports provide only qualitative suggestions pertaining to the human
carcinogenic potential of B[b]F, however, because of the presence of
other putative carcinogens in the mixtures.
Animal. B[b]F has been shown to cause skin tumors in mice
following dermal application. The results of a key study by Wynder and
Hoffmann (1959) are shown in Table 4.2. As part of a study of the
carcinogenicity of tobacco and its constituents, these authors tested
the benzofluoranthenes as carcinogens on mouse skin. Groups of 20 female
Swiss mice had concentrations of 0.01, 0.1, or 0.5% B[b]F dissolved in
acetone applied three times a week to their backs with a brush
throughout their lifetimes. No solvent control group was reported;
however, since no papillomas or carcinomas were obtained for several of
the benzofluoranthenes tested, a solvent control group would most likely
have been negative as well. A dose-response relationship for the dermal
carcinogenicity of B[b]F was demonstrated over an order-of-magnitude
dose range. Survival was also dose related. Although this study was
designed as a long-term (chronic) bioassay, malignant tumors appeared as
early as 4 months in the high-dose group and 5 months in the
intermediate-dose group. As a result, this study is considered to
provide evidence that B[b]F is carcinogenic following intermediate-term
exposure. The lowest dose at which B[b]F elicited malignant tumors was
0.1%, which is approximately equal to a dose of 2.9 mg/kg received three
times weekly, or an average daily dose of 1.2 mg/kg. This study had a
number of weaknesses, including no reporting of compound purity and no
statistical treatment.
The skin-tumor-initiating ability of B[b]F has also been
demonstrated in mice using a standard initiation/promotion protocol with
either croton oil or phorbol myristate acetate as a tumor promoter (Amin
et al. 1985a; LaVoie et al. 1979a, 1982).
4.3.5.5 General discussion
The only end point of toxicity that has been established for B[b]F
using routes of exposure that can be extrapolated to human environmental
exposures is dermal carcinogenicity. There is evidence that
intratracheal instillation in rats (Deutsch-Wenzel et al. 1983),
intraperitoneal injection in newborn mice (LaVoie et al. 1987), and
-------
Section 4
Table 4.2. Carcinogenic activity of benzo{b]fliiorantheiie
on mouse skin
Number with tumors/
effective number (%)
Dose" Dose
{% concentration) (mg/kg/day) Papillomas Carcinomas
0.01
0.12
1/20 (5)
0/20 (0)
0.1
1.2
13/19 (68)
17/19 (89)
0.5
6.0
20/20 (100)
18/20 (90)
"Solutions of B[b]F in 100 ftL acetone were applied three
times weekly to the backs of female Swiss mice throughout their
lifetimes.
Source: Wynder and Hoffmann 1959.
-------
Toxicological Data 29
subcutaneous injection in mice (Lacassagne et al. 1963) can lead to
tumor formation as well. The mechanism of B[b]F-induced carcinogenicity
appears to be somewhat different from that of other PAHs, involving
metabolic activation to reactive metabolites other than bay-region diol
epoxides that may form adducts with DNA that lead to mutation and tumor
initiation under certain circumstances (IARC 1983).
4.4 INTERACTIONS WITH OTHER CHEMICALS
Host human exposures to B[b]F are not to the pure compound but to
particle-bound B[b]F; the presence of particles is likely to affect its
pharmacokinetics and carcinogenicity. Sun et al. (1982) showed that when
the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene was
particle-bound, it was cleared from hamster lungs much more slowly than
a pure B[a]P aerosol, thus increasing the length of time the lungs were
exposed and increasing the dose to the gastrointestinal tract as a
result of mucociliary clearance. Respirable PAH-containing particulates
such as diesel exhaust, when coated with the phospholipid component of a
pulmonary surfactant, are genotoxic (Wallace et al. 1987). Dusts can
increase the rates of pulmonary cell proliferation (Harris et al. 1971,
Stenback et al. 1976, Stenback and Rowland 1979), which in turn
increases the susceptibility of those cells to an initiation event in
the presence of a carcinogen. Coadministration of B[a]P and particles
greatly increases respiratory tract tumor yields in experimental animals
(Stenback et al. 1976, Stenback and Rowland 1979). The effects of
particles on potential B[b]F carcinogenesis is likely to be similar.
Human exposure to B[b]F in the environment seldom, if ever, occurs
to B[b]F alone, but rather to B[b]F as a component of complex mixtures
of PAHs and other chemicals. Interactions between B[b]F and other
mixture components are likely to occur. In particular, interactions may
play a large part in carcinogenesis resulting from experimental exposure
to PAHs. For example, Mahlum et al. (1984) have shown that different
temperature range distillates of coal liquids have different skin-
tumor- initiating activities in mice despite the fact that they contain
similar levels of known carcinogenic PAHs. This difference is believed
to be due to the modifying effects of the spectrum of noncarcinogenic
PAHs obtained at different temperatures. Host of the PAH components of
coal liquid fractions obtained at different temperatures will vary both
qualitatively and quantitatively; consequently, their abilities to
modify carcinogenesis will vary accordingly. The relative roles of the
PAH components of each of such mixtures is unknown, however, so that
quantitative evaluation is not possible. Because human exposure occurs
to mixtures of PAHs and not individual components, the quantitative
evaluation of the toxicity of individual PAHs is probably insufficient.
Human exposure to complex mixtures of PAHs has been extensive, and
some adverse effects are well-documented, particularly carcinogenic
effects following long-term exposure. The extent of human exposures to
well-defined PAH mixtures that are responsible for producing excess
disease is generally not known in quantitative terms. Coke-oven
emissions and related substances such as coal tar have probably been the
most widely studied. Coal tar derivatives were most likely responsible
for the first observation of occupational cancer, that of scrotal cancer
among London chimney sweeps, made by Percival Pott in 1775. More recent
-------
30 Section 4
mortality studies have demonstrated strong associations between human
exposure to coke-oven emissions and excess disease; specifically,
significant increases in lung and genitourinary cancer mortality have
been observed (XARC 1983). The earliest of these reports was made in
1936 by investigators in Japan and England (Kennaway and Kennaway 1936)
who were studying lung cancer mortality among persons employed in coal
carbonization and gasification processes. Subsequent studies conducted
in the United States clearly demonstrated substantial increases in lung
and genitourinary system cancer mortality among coke-oven workers (Lloyd
1971, Redmond et al. 1972, IARC 1984). Human tumorigenicity has also
been reported to result from exposure to creosote. Creosote is a generic
term that refers to wood preservatives derived from coal tar, creosote,
or coal tar neutral oil, and includes extremely complex mixtures of
liquid and solid aromatic hydrocarbons. Workers who engaged in
activities such as dipping timbers in creosote were reported to have
developed malignant and pre-malignant skin lesions of the face, arms,
and scrotum (O'Donovan 1920, Cookson 1924, Henry 1947, Lenson 1956).
Many of the individual PAH components of creosote, such as B[b]F, have
been shown to be both mutagenic and carcinogenic in laboratory
bioassays, supporting the evidence of its human carcinogenicity (IARC
1983).
Exposures to many other complex chemical mixtures that include PAHs
have been associated with human disease incidence, such as the use of
tobacco products and exposure to roofing tar emissions and shale oils.
Although this discussion falls short of providing a thorough review of
the extensive literature available on the experimental and
epidemiological observations of the toxicity of PAH mixtures, its
purpose has been to provide examples wherein such toxicity has been
documented in order to emphasize that human exposure to multiple PAHs
does occur.
Predicting the toxicity of a complex mixture on the basis of one or
several of its components may be misleading because of the possibility
of interactions among the components that may modify toxicity. For
example, both carcinogenic and noncarcinogenie PAHs may compete for the
same metabolic activating enzymes and thereby reduce the toxicity of
carcinogenic PAHs. Exposure to other PAHs may induce enzyme levels
leading to more rapid detoxification of B[b]F, thus reducing its
carcinogenicity (Slaga and diGiovanni 1984, Weibel 1980). Naturally
occurring compounds have been found to induce the enzymes that
metabolize PAHs, leading to either increased or decreased toxicity. For
example, plant flavonoids can induce microsomal monooxygenases and
reduce the carcinogenicity of B[b]F (Weibel 1980). Environmental
contaminants such as tetrachlorodibenzo-p-dioxin can also increase
microsomal enzyme activity and consequently affect PAH toxicity (Kouri
et al. 1978). Interactions can thus play important modulating roles in
PAH toxicity that may not be adequately reflected in the identification
of significant human exposure levels based on the toxicity of single
PAHs, because human exposure to mixtures of PAHs does occur.
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31
5. MANUFACTURE, IMPORT, USE, AND DISPOSAL
5.1 OVERVIEW
B[b]F occurs in fossil fuels and as a result of the incomplete
combustion of fuel and wood and other organic matter. B[b]F is available
as a research chemical from some specialty chemical firms. B[b]F is a
PAH and may be found in coal tar and in the creosote oils and pitches
formed from the distillation of coal tars. Coal tar pitch is primarily
used as a binder for electrodes. Creosote is primarily used as a wood
preservative. Coal tar is also used as a therapeutical treatment for
skin diseases such as psoriasis. PAHs are also found in limited amounts
in bitumens and asphalt.
5.2 PRODUCTION
The primary source of B[b]F in air is the incomplete combustion of
fuel or wood for heating (EPA 1985).
Crude coal tar is produced as a by-product in the formation of coke
from coal. Hot gases and vapors released from the conversion of coal to
coke are collected in a scrubber that condenses these gases into
ammonia, water, crude tar, and other by-products. A typical coke oven
produces 80% coke, 12% coke-oven gas, 3% coal tar, and 1% crude benzene.
The coal tar is then distilled to yield a number of chemical oils,
creosote, and coal tar pitch. The coal tar pitch residue is 40.5% of the
crude tar; creosote is -11.5%. Heavy and light creosote also make up a
small percentage of distillate (NIOSH 1977). Coal tar contains -0.3%
B[b]F (IARC 1985).
As of 1981, the world output of crude coal tar was 18 x 10^ metric
tons; 14 x 10*> metric tons was of coke-oven origin. In 1980, the U.S.
production of crude tar was 2.4 x 10*> metric tons. Creosote oil
production in the United States in 1981 was estimated to be 0.5 x 10~*>
metric tons. The coal tar pitch production in the United States in 1974
was estimated to be 1 X 10° metric tons (McNeil 1983).
Bitumens and asphalt (a mixture of bitumen with mineral materials)
are derived from crude oil. Bitumen samples have been reported to
contain a number of PAHs (IARC 1985).
5.3 IMPORT
In 1985, the United States imported a total of almost 12 X 10^ gal
of creosote oil from the Netherlands, France, West Germany, and other
countries and almost 185 X 10*> lb of coal tar pitch, blast furnace tar,
and oil-gas tar from Canada, Mexico, West Germany, Asian countries,
Australia, and other countries (USD0C 1986).
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32 Section 5
5.4 USE
B[b]F has some use as a research chemical. It is available from
some specialty chemical firms in low quantities (25-100 mg) (Aldrich
Chemical Co. 1986).
Coal tar pitch is primarily used as a binder for electrodes in the
aluminum reduction process; it is used to bind the carbon electrodes
used in the reduction pots (NIOSH 1977). In North America, coal tar
pitch is also used as the adhesive in membrane roofs (McNeil 1983).
Almost 99% of the creosote produced is sold to wood preservation
plants; 0.1 to 0.2% is sold to individual customers (NIOSH 1977).
Creosote is used in the preservation of railroad ties, marine pilings,
and telephone and telegraph poles. Some creosote is also consumed as
fuel by steel producers (NIOSH 1977).
Coal tar is also used in the clinical treatment of skin disorders
such as eczema, dermatitis, and psoriasis. The use of dermatological
coal tar preparations is extensive (NIOSH 1977) .
Bitumens and asphalt are primarily used for paving roads, in
waterproofing and roofing, for electrical and sound insulation, and for
pipe coating (IARC 1985).
5.5 DISPOSAL
In 1978, following the release of small amounts of B[b]F present in
coal tar creosote, a 0.39-mg/L concentration of B[b]F was found in
aqueous raw discharges from timber product industries (EPA 1985).
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33
6. ENVIRONMENTAL FATE
6.1 OVERVIEW
B[b]F in the environment is derived from both natural (e.g.,
wildfires, volcanoes) and man-made sources, but B[b]F originating from
man-made sources is quantitatively the most significant. B[bjF, like all
PAHs, is formed during high-temperature pyrolytic processes.
Consequently, combustion is the major source of environmental B[b]F.
Virtually all direct releases of B[b]F into the environment are to the
air. Small amounts are released to water and land. B[b]F is removed from
the atmosphere by photochemical oxidation and dry or wet deposition to
land or water. B[b]F that reaches the surface will likely remain and be
partitioned primarily to soil/sediment, where it is very persistent. The
dominant degradation process for B[b]F in soil/sediment is most likely
biodegradation. Biodegradation is a slow process, with a half-life of
610 days estimated for B[b]F in soil.
6.2 RELEASES TO THE ENVIRONMENT
Incomplete combustion of carbonaceous material is the major source
of B[b]F in the environment. Residential heating and open burning (man-
induced and natural) are the largest combustion sources. The large
quantity of B[b]F released by these sources is a consequence of
inefficient combustion processes and uncontrolled emissions. Of all home
heating sources, wood heating is the greatest contributor to B[b]F
emissions. In a recent assessment of B[b]F sources and release volumes
across the United States, EPA (1985) estimated that home wood combustion
contributed 92 metric tons, or 43% of all released volumes. Open-burning
sources overall are responsible for 100 metric tons, or 47% of the total
B[b]F releases; prescribed burning is responsible for 50 metric tons of
that total, wildfire for 30 metric tons, and agricultural burning for 20
metric tons. Small amounts of B[b]F are likely formed and released into
the environment during coal tar production and use and during gasoline
and diesel fuel combustion. Also, PAH-containing products such as
creosote-treated wood and asphalt roads may release small amounts of
B[b]F and other PAHs into the environment. These other sources
individually are estimated to contribute 1% or less to total B[b]F
releases.
Ninety-seven percent of all estimated environmental releases of
B[b]F are to air. Of the remaining 3%, approximately equal amounts of
B[b]F are released to water and land.
Although they are the source of small amounts of B[b]F and other
PAHs on a national scale, hazardous waste sites can be concentrated
sources of PAHs on a local scale. For example, abandoned wood treatment
plants are sources of high concentrations of creosote, and former
-------
34 Section 6
manufactured-gas plants (town gas sites) are sources of high
concentrations of coal tar. Both creosote and coal tar are composed of a
variety of PAHs, including B[b]F. PAHs at these sites are likely to
occur on the soil and on suspended particulate matter in the air.
6.3 ENVIRONMENTAL FATE
Few data are available which describe the environmental fate of
B[b]F specifically, and much of the understanding of the fate of B[b]F
is based upon analogy to benz[a]anthracene (B[a]A), benzo[a]pyrene
(B[a]P), and PAHs in general. The discussion below is based primarily on
these generalizations. Fate information specific to B[b]F is identified
when available.
The environmental fate of B[b]F is determined to a large degree by
the chemical'9 low water solubility and high propensity for binding to
particulate or organic matter. As a result, B[b]F in the atmosphere is
expected to be associated primarily with particulate matter, especially
soot, whereas most of the B[b]F in aquatic systems is expected to be
strongly bound to suspended particles or bed sediments. Likewise, B[b]F
will be strongly sorbed to surface soils. The dispersion of particle-
bound B[b]F is the primary transport process within air, water, and
land.
Based upon an analogy to benzo[a]pyrene, the dry deposition of
particle-bound B[b]F is probably the most significant transport process
between air and land or water (EPA 1979), although wet deposition is
known to occur (Den Hollander et al. 1986). Because of a very low vapor
pressure, B[b]F that reaches the surface will likely remain and be
partitioned primarily to soils/sediments. Sediment/particle adsorption
or biotic uptake are the primary transport processes for the removal of
waterbome B[b]F. Desorption into water from soil is very unlikely, and
erosion of contaminated soils by surface runoff is the most probable
process for transport of soil-bound B[b]F to aquatic systems.
Information on the fate of particulate PAHs, including B[b]F,
released to the atmosphere is presently unclear. It is generally
assumed, however, that photochemical oxidation processes play an
important role. Atmospheric half-lives on the order of days have been
suggested (NAS 1972). PAHs strongly absorb solar radiation at
wavelengths above 300 nm, and there is sufficient evidence to indicate
that PAHs undergo photooxidation in solution, as pure solids, and when
adsorbed onto certain solid substrates such as alumina (NAS 1972).
Singlet oxygen has been implicated as the primary oxidant; endoperoxides
and, ultimately, quinones have been implicated as the reaction products
(NAS 1972).
It has been inferred that similar processes take place when the
compounds are adsorbed on airborne particles. Kamens et al. (1986)
reported that B[b]F and other PAHs adsorbed on soot particles rapidly
decayed In the presence of sunlight. However, photooxidation of PAHs
adsorbed on carbon black particles was extremely slow (Barofsky and Baum
1976). Similarly, Korfmacher et al. (1980a,b) found that benzo[a]pyrene
and other PAHs adsorbed on fly ash are highly resistant to
photodegradation. More research is needed to elucidate the rate and
substrate dependency of atmospheric B[b]F degradation.
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Environmental Fate 35
Data collected by Smith et al. (1978) indicate that within aquatic
systems, most PAHs accumulate in the sediment and are transported with
suspended sediment. PAHs in the water column also accumulate in aquatic
organisms. However, many organisms metabolize and excrete PAHs rapidly;
therefore, bioaccumulation is a short-term process. For example, in
bluegill sunfish, an 89% loss of B[a]P was recorded 4 h after exposure
(Leversee et al. 1981). Lee et al. (1972) reported rapid elimination of
B[a]P in three species of California marine teleosts. Depuration rates
in invertebrate species vary more widely. Some species, such as hard-
shell clams, show little or no depuration, whereas others, such as many
oysters, eliminate virtually all PAHs following exposure (Eisler 1987).
Aquatic organisms can also assimilate PAHs from food. For example,
crustaceans and fish have been reported to readily assimilate PAHs from
contaminated food (Eisler 1987). However, in many cases where
assimilation of PAHs has been demonstrated, metabolism and excretion of
PAHs were rapid (Eisler 1987). In laboratory aquatic ecosystem studies
in which radiolabeled B[a]P was used, Lu et al. (1977) found that high
levels of B[a]P can be accumulated through the food in the mosquito
fish. After 3 days of exposure, the intact parent compound comprised
over 50% of the extractable radiolabeled carbon in fish. However, after
33 days of exposure, the intact parent compound comprised only 7% of the
total extractable radiolabeled carbon, indicating metabolism of B[a]P.
The tendency of fish to metabolize PAHs may explain why PAHs are
frequently undetected, or only detected in low concentrations in the
livers of fish from environments heavily contaminated with PAHs.
A minimal amount of PAHs is dissolved in the water column and
degraded rapidly by direct photolysis. Smith et al. (1978) calculated a
half-life of 1.2 h for midday direct photolysis of dissolved B[a]P.
Chemical oxidation may be a significant fate process for B[b]F in water
when chlorine or ozone (both oxidants) exist in sufficient
concentrations (EPA 1979).
The major fate of sediment-bound PAHs, including B[b]F, is most
likely biodegradation (EPA 1979). In general, biodegradation processes
are quite slow; a half-life of 7,000 h has been reported for
benz[a]anthracene (EPA 1979), and it is possible that the degradation
rate for B[b]F is similar. Biodegradation half-lives in contaminated
streams can be 10 to 400 times longer. These long half-lives indicate
that PAHs are relatively persistent in sediments and aquatic systems.
Within terrestrial systems, biodegradation is also the probable
fate process. Since this process is very slow, B[b]F is very persistent
in soils. Coover and Sims (1987) estimated a half-life of B[b]F in soil
of 610 days.
At hazardous waste sites, half-lives may be longer, because other
contaminants present at the site may be toxic to the degrading
microorganism. Bossert and Bartha (1986) reported reduced biodegradation
of PAHs in soil containing a chemical toxic to microorganisms.
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Intentionally Blank Page
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37
7. POTENTIAL FOR HUMAN EXPOSURE
7.1 OVERVIEW
As the previous discussions indicate, the greatest portion of B[b]F
releases to the environment is directly into the atmosphere.
Consequently, inhalation is one of the primary routes of background
human exposure to B[b]F in the environment. Part of the B[b]F in the
atmosphere returns to the surface via dry and wet deposition. This input
leads to B[b]F in soil and water to which humans may be exposed. Humans
may also be exposed to B[b]F in food, tobacco smoke, and certain
occupational settings, and through contact with PAH-containing products
such as coal tar, asphalt, and creosote-treated wood. At hazardous waste
sites, humans most likely will be exposed to B[b]F in the soil and on
particulate matter in the air. At this time, B[b]F has been found at 46
of the 1,177 hazardous waste sites on the National Priorities List (NPL)
in the United States (View 1989).
7.2 LEVELS MONITORED IN THE ENVIRONMENT
7.2.1 Air
Very few data are available to characterize B[b]F levels in air,
and estimates of ambient concentrations are limited to two relatively
outdated monitoring studies in Los Angeles and a report of average
concentrations in U.S. cities in 1958. Consequently, definitive
statements about average background exposure levels cannot be made. In
the most recent monitoring study, Gordon (1976) reported ambient B[b]F
concentrations in Los Angeles County to range between 0.24 and 1.30
ng/m^. Gordon and Bryan (1973) reported levels in the range of 0.09 to
1.8 ng/m^ in Los Angeles County during the years 1971-1972. Hoffmann and
Wynder (1976) summarized data on B[b]F levels across U.S. cities in 1958
and reported concentrations in the range of 2.3 to 7.4 ng/w?.
7.2.2 Water
B[b]F has been detected in raw and finished drinking waters in the
United States, but minimal data limit the degree to which background
levels can be adequately characterized. Sorrell et al. (1981) reported
B[b]F concentrations between 4 and 16 ng/L in raw water and less than 2
ng/L in finished drinking water. These data were based on a very small
sample (10 cities) and may not be representative of drinking water
concentrations in the United States.
Because of a high propensity to bind to organic matter, it is
unlikely that B[b]F will occur to any appreciable extent in surface
water or groundwater at hazardous waste sites or other sites.
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38 Section 7
7.2.3 Soil
No data are available on B[b]F levels in U.S. soils. However,
Blumer et al. (1977) summarized information that indicated
concentrations of total PAHs to be between 4 and 13 mg/kg in the soil
from relatively rural areas of the eastern United States. Soil levels in
more populated and industrialized areas may be higher. Butler et al.
(1984) examined soil PAH levels in Switzerland and demonstrated that
much higher soil PAH concentrations are found near complex road
interchanges than in areas more distant. Also, the soils at waste sites,
such as former manufactured-gas sites and creosote wood treatment
plants, may contain high levels of PAHs, including B[b]F.
7.2.4 Food
Data on B[b]F levels in food are limited, primarily because the
substance is not one of the PAHs commonly analyzed in food. However,
B[b]F has been detected in vegetables and fruits grown in PAH-
contaminated soil near areas of high vehicular traffic (Wang and Meresz
1982). Thus, the possible consumption of food grown in contaminated soil
near hazardous waste sites, industrial areas, or highways may contribute
to human exposure.
Humans may also be exposed to B[b]F and other PAHs in aquatic
organisms that are typical components of the diet. Specifically, PAHs
have been detected in bivalve mollusks (i.e., clams, oysters, mussels),
crabs, and lobsters (Eisler 1987). PAHs have also been detected in fish;
however, levels in fish are usually low, because this group rapidly
metabolizes PAHs.
7.2.5 Cigarette Smoke
B[b]F has been reported to occur in cigarette mainstream smoke at
between 4 and 22 ng per cigarette (IARC 1983). Concentrations in
sidestream smoke may potentially be higher, because levels 2 to 4 times
higher than those in mainstream smoke have been reported for other PAHs
(DHHS 1986).
Today there is an increasing concern regarding indoor air pollution
by environmental tobacco smoke. A report by the U.S. Surgeon General
(DHHS 1986) concluded that environmental tobacco smoke can be a
substantial contributor to the concentration of respirable particles of
indoor air pollution. These higher concentrations of sidestream smoke
constitutents, such as B[b]F, in conjunction with the fact that many
people spend many hours in indoor polluted atmospheres, may lead to
increased health risks to individuals passively exposed to cigarette
smoke.
7.3 OCCUPATIONAL EXPOSURES
PAHs, such as B[b]F, have been isolated in numerous occupational
situations, including coal-tar production and coking plants, coal
gasification sites, smokehouses, aluminum production plants, bitumen and
asphalt production plants, coal-tarring activities, and around municipal
incinerators. Within these environments, B[b]F and other PAHs occur as a
complex mixture; thus, exposure to B[b]F alone does not occur.
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Potential for Human Exposure 39
Historically, the highest level of human exposure to PAHs has occurred
in industrial situations. B[b]F and other PAHs have been detected in the
occupational environments of coke production plants, aluminum reduction
plants, and coal gasification plants in the United States (IARC 1984).
B[b]F and other benzofluoranthenes have been detected at a level of 140
/ig/g at the top of a fixed-bed gasifier of a U.S. coal gasification
plant (IARC 1984). Concentrations of benzo[a]pyrene (often used as an
indicator of total PAH concentration) have been reported to range from
0.8 to 23.1 fig/m^ in the workroom air of coke-oven operations in the
United Kingdom (Davies et al. 1986). Similarly, high values have been
reported by Lindstedt and Solenberg (1982) in Swedish industries.
7.4 POPULATIONS AT HIGH RISK
At highest risk for cancer induced by PAHs are those people who are
exposed to high levels of PAHs. Examples of high-risk populations
include workers in certain occupations that have elevated PAH
concentrations in the ambient work environment; smokers and involuntary
(passive) smokers who receive elevated PAH intake via tobacco smoke; and
populations living near industries, such as creosote and coal tar
manufacturers, that generate PAHs as a by-product of production.
Individuals in these high-exposure groups may have varying
susceptibility to PAH toxicity. Some of the available data on PAH
carcinogenicity suggest a relationship between aryl hydrocarbon
hydroxylase (AHH) activity and cancer risk. Genetic variation in AHH
inducibility has been implicated as a determining factor for
susceptibility to lung and laryngeal cancer (EPA 1980). Attempts have
been made to demonstrate that persons with lung cancer have higher
inducibility of AHH in cultured lymphocytes. A review by Calabrese
(1984) indicates that several studies support this hypothesis, and some
genetic data indicate that the human population can be segregated based
on this trait (EPA 1980). Thus, individuals that are AHH-inducible may
constitute a high-risk population. However, the data regarding genetic
susceptibility are not yet conclusive.
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41
8. ANALYTICAL METHODS
8.1 ENVIRONMENTAL SAMPLES
The procedures used to sample and extract B[b]F in different media
are very similar. In air and tobacco smoke, PAHs, including B[b]F, are
adsorbed predominantly on particulate matter, which is collected on a
filter. In water and soil, PAHs are extracted directly without
filtration.
The extraction of PAHs from the filter can be accomplished by a
variety of techniques with or without solvents. The following extraction
techniques are most commonly used: soxhlet, sublimation at elevated
temperatures, ultrasonic, and polytron extractions (Sawicki 1976).
A cleanup step is necessary to separate B[b]F and PAHs from other
pollutants. Typically, this step involves liquid-liquid extraction of
the dry organic particulate extract, followed by adsorption
chromatography using silica gel or alumina columns (Sawicki 1976, Riggin
and Strup 1984). These adsorbents selectively remove interfering
compounds. Thin-layer chromatography (TLC) can also be used as a cleanup
method (Sawicki 1976).
The most commonly used analytical methods for determining B[b]F in
environmental samples are column gas chromatography (GC) and high-
performance liquid chromatography (HPLC). Table 8.1 summarizes common
analytical methods, detection limits, and accuracy (percent recovery)
for the determination of B[b]F in air, water, soil, and food.
GC is an analytical technique in which components of a sample are
separated by differential distribution between a gaseous mobile phase
and a solid or liquid stationary phase (EPA 1983). Following separation
in the GC column, sample components are identified and quantified by a
detection system such as flame ionization detection (FID) or mass
spectrometry (MS). These techniques are described in detail in NIOSH
(1984) and EPA (1983, 1984a).
HPLC is an analytical method in which components are separated
based on their polarity (EPA 1983). Reverse-phase HPLC, which is used
more widely for the analysis of PAHs, uses a nonpolar stationary phase
and a polar mobile phase; hydrophilic components are eluted earlier than
hydrophobic components. The detection systems most appropriate for HPLC
analysis of PAHs are UV absorption spectroscopy and fluorescence
spectroscopy (FS). FS is useful for extremely dilute solutions;
therefore, pretreatment by concentration and cleanup of the sample
before HPLC is not necessary (Das and Thomas 1978).
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42
Section 8
Table 8.1. Methods for ualyiis of beszoibifluoranUiefle in eariromaeatal media
Media
Sample preparation
Analytical
method0
Detection limit
Accuracy*
References
Air
Ultrasonic extraction with
cyclohexane
HPLC
3 ng/mJ
(1500-m3 sample)
95%
NIOSH 1984
(Method 5506)
Ultrasonic extraction with
benzene, pentane, or dichloro-
methane
HPLC/FS
10 pg
NA
Andersson et al. 1983
Soxhlet extraction
with benzene-methanol
GC/MS
0.05 ng/m3
NA
Matsumoto and
Kashimoto 1985
Extraction with solvent
GC/MS
NA
NA
NIOSH 1984
(Method 5515)
Water
Extraction with methylene
chloride
HPLC/FS
0.018 Mg/L
Approx. 78%c
EPA 1984a
(Method 610)
UV
4«5/L
76-135%
Riggin and Strap 1984
Extraction with methylene
chloride at pH < 2 and pH > 11
GC/MS
4.8 ns/L
Approx. 93%c
EPA 1984a
(Method 625)
Extraction with methylene
chloride at pH 12-13 and
and pH < 2
GC/MS
GC/MS
10Mg/L
NA
NA
NA
EPA 1984a
(Method 1625)
EPA 1986a
Extraction with dichloro-
methanc
HPLC/UV
73 pg
NA
Ogan et al. 1979
Extraction with cyclohexane
TLC/FS
0.5-1 ng/L
NA
Borne ff and Kunte
1979
SoU
Extraction with n-pentane
TLC/UV
NA
NA
Butler et al. 1984
Extraction with methylene
chloride
GC/MS
NA
NA
EPA 1986a
Food
Extraction with isooctane
TLC/UV
0.2 Mg/kg
NA
Howard 1979
"Abbreviations: HPLC, high-performance liquid chromatography; TLC, thin-layer chromatography; FS, fluorescence
spectroscopy, QLL, quasi-linear luminescence; GC, gas chromatography; MS, mass spectrometry; UV, ultraviolet
absorption spectroscopy.
NA — not available.
cIn large samples.
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Analytical Methods 43
TLC has also been used to analyze for PAHs. With quasi-linear
luminescence methods (QLL), quasi-linear spectra can be obtained for
PAHs at liquid nitrogen temperatures (Sawicki 1976).
GC and HPLC are the chromatographic methods routinely used for
determining 10 to 20 of the major PAHs in air and water samples.
Detailed analysis of major and minor PAHs in a complex PAH mixture
requires a combination of chromatographic techniques (Wise et al. 1986).
GC/MS has a detection limit of greater than 10 pg; HPLG/FS has an
approximate detection limit for PAHs of 25 to 50 pg (Santodonato et al.
1981).
HPLC (5506) or GC/MS (5515) are the methods recommended by NI0SH
(1984) for analyzing PAHs in workplace air. These methods incorporate a
sampling train consisting of a filter and a solid sorbent (NIOSH 1984).
The use of a high-volume sampler to sample a large quantity of air
allows for the detection of small amounts of PAH. The analytical methods
required by EPA (1984a) for the analysis of B[b]F in water are
procedures 610 (HPLC/FS), 625 (GC/MS), and 1625 (GC/MS). These are
required test procedures under the Clean Water Act for municipal and
industrial wastewater-discharging sites. GC/MS is also the method
required by the EPA Contract Laboratory Program for analysis of B(b]F
and other PAHs in water and soil. The contract required quantitation
limit (CRQL) for B[b]F in water is 10 /ig/L; in soil/sediment, the limit
is 330 /ig/kg (EPA 1986a) .
8.2 BIOLOGICAL SAMPLES
The available biological monitoring techniques are useful for
detecting whether occupational or environmental exposure to PAHs has
occurred; however, because there have been no population-based studies
to determine normal body levels of PAHs, it is not yet possible to
predict environmental exposure from body PAH levels or to predict what
health effects are likely to be associated with these levels. In
general, techniques that measure PAH or PAH metabolite concentration in
the urine are most appropriate for use in determining occupational
exposure, since a high level of PAH exposure is necessary to result in
the presence of these compounds in the urine. Methods that detect diol
epoxide-DNA adducts are more sensitive to low exposure levels and are
most appropriate for use in determining environmental exposure. The
techniques presently available for determining exposure to PAHs are
summarized in Table 8.2 and discussed in detail below.
Modica et al. (1982) and Bartosek et al. (1984) examined PAHs
(specifically chrysene and benz[a]anthracene) present in blood, mammary,
adipose, liver, and brain tissue from rats orally exposed to PAHs using
gas-liquid chromatography with a flame-ionization detector. PAHs were
determined in all tissues examined. No information concerning the use of
this technique in determining PAH concentrations in human tissue samples
was found in the available literature.
In mammalian systems, B(b]F is converted by specific cellular
enzymes to dihydrodiols or diol epoxides that are capable of binding to
DNA (Geddie et al. 1984). The structure of these adducts is not known.
However, Amin et al. (1985b) used HPLC/FS to examine structural analogs
of potential B[b]F-DNA adducts.
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44 Section 8
Table 8.2. Methods for analysis of PAHs in biological samples
Medium
Technique
Measured
parameter
Reference
Tissue
Gas chromatography
PAH concentration
Modica et al. 1982,
Bartosek et al. 1984
Postlabeling of DNA
PAH diol epoxide-
DNA adducts
Randerath et al. 1985,
1986; Weyand et al.
1987a,b
Blood
Immunoassay
Antibodies to diol
epoxide-DNA adducts
Harris 1985a,b,
Harris et al. 1986
Urine
Gas chromatography
PAH concentration
Clonfero et al. 1986
High-performance
liquid chromatography
PAH concentration
Becher and Bjorseth
1983, Becher et al.
1984
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Analytical Methods 45
The degree of DNA adduct formation can be used as a measure of dose
in target tissues or organs using the -^p postlabeling technique. In
this technique, radioactivity ("p) is incorporated into the DNA removed
from the exposed cells, and the digested DNA is separated using TLG or
HPLC. Quantitation of the adducts is achieved by scintillation counting.
Small amounts of DNA are needed for analysis. These techniques have not
been examined in humans or in actual biological samples to determine
whether abnormal levels can be detected. Randerath et al. (1985, 1986)
examined PAH-DNA adducts in skin tissue from mice dermally treated with
cigarette smoke condensate. Tissues from the placenta, bronchus, and
larynx of smokers were also examined. Weyand et al. (1987a,b) evaluated
the ability of B[b]F to bind to mouse skin following single dermal
application.
Procedures are currently available to examine for the presence of
antibodies to PAH-DNA adducts in the blood using enzymatic immunoassays
(Harris 1985a, Harris et al. 1986). Harris (1985b) developed a technique
for determining human exposure to PAHs by detecting antibodies, in sera,
to diol epoxide-DNA adducts using an immunoassay. The technique was
tested on coke-oven workers exposed to substantial amounts of
benzo[a]pyrene and other PAHs in the work atmosphere and in smokers and
nonsmokers. Antibodies to benzo[a]pyrene diol epoxide-DNA adducts were
quantified by enzyme-linked immunosorbent assay (ELISA). Higher
proportions of sera positive for antibodies were found in a group of
smokers and in the occupationally exposed group. This technique may be
applicable for determining exposure to B[b]F, but further investigation
of the formation of B[b]F-DNA adducts is necessary.
The urine of exposed humans was examined for the presence of PAHs.
PAHs and their metabolites can be extracted from urine and analyzed
using HPLC/FS or GC/MS. PAHs were found in the urine of workers in an
aluminum plant. However, the level of environmental exposure could not
be determined from the chrysene content in urine, because high
environmental concentrations of PAHs in the workplace were not found to
be reflected to the same extent in the excretion of PAHs in urine
(Becher and Bjorseth 1983, Becher et al. 1984, Becher 1986). This
problem was suggested to result from the nonbioavailability of
particle-bound PAHs, and this method may still be applicable in other
exposure situations. Clonfero et al. (1986) detected PAHs using GC/MS in
the urine of individuals treated therapeutically with crude coal tar.
However, this is not necessarily a useful test for occupational
exposure, because high levels of PAHs in the coal tar were necessary to
concentrate PAHs in the urine.
Vo-Dinh et al. (1987) developed an antibody-based fiber-optic
biosensor that can be used to detect benzo[a]pyrene or other PAHs in
sample solutions. In this technique, antibodies to benzo[a]pyrene are
covalently bound to the tip of the sensing probe. A helium-cadmium laser
excites the molecules of benzo[a]pyrene bound to the antibodies, and the
resulting fluorescence of these molecules is recorded by a
photomultiplier; the intensity of the fluorescence signal is
proportional to the amount of antigen bound to the sensor tip. The
-------
46 Section 8
fiber-optic device can detect 1 femtomole (fmol; one-quadrillionth of a
mole) benzo[a]pyrene in a 5-^L sample drop. This technique can be useful
in the assessment of an individual's exposure to benzo[a]pyrene and
other PAHs, provided appropriate antibodies are used.
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47
9. REGULATORY AND ADVISORY STATUS
Regulatory standards have been developed for the carcinogenic PAHs
in the benzene- or cyclohexane-soluble fraction of coal tar pitch
volatiles. B[b]F is not extracted in the benzene- or cyclohexane-soluble
fraction. However, the regulatory standards were developed to regulate
exposures to all PAHs in coal tar pitch volatiles and are appropriate
for B[b]F. These standards and advisory guides are presented in
Table 9.1.
B[b]F has been shown to be carcinogenic in experimental animals;
similar to other PAHs, it likely undergoes metabolism to reactive
electrophiles capable of binding covalently to DNA and inducing
bacterial mutation and DNA damage. EPA has not classified B[b]F based on
carcinogenicity data. IARG (1973) has classified B[b]F in Group 2B
because of sufficient evidence of carcinogenicity in experimental
animals. IARG (1985) has also concluded that there is sufficient
evidence of the carcinogenicity of coal tars, creosote, and coal tar
pitches in experimental animals. In addition, IARC (1985) concluded that
there is sufficient evidence that occupational exposure to coal tar and
coal tar pitch is associated with skin cancer, and limited evidence of
the carcinogenicity of creosote in occupationally exposed individuals.
9.1 INTERNATIONAL
The World Health Organization European standards for drinking water
recommend a concentration of PAHs not to exceed 0.2 ng/~L. This is based
on the composite of six PAHs in drinking water: fluoranthene,
benzo[a]pyrene, benzo[g,h,i]perylene, B[b]F, benzo[k]fluoranthene, and
indeno[1,2,3-cd]pyrene (WHO 1971). This limit was not chosen on the
basis of potential health effects.
9.2 NATIONAL
9.2.1 Regulatory Standards
Coal tar, coal tar pitch, and creosote are considered by NIOSH and
EPA to be human carcinogens (NIOSH 1977; EPA 1978, 1981, 1984c, 1986b).
NIOSH reviewed epidemiologic and experimental toxicological evidence and
concluded that inhalation exposure to these coal products, which contain
a number of PAHs, increases the risk of lung and skin cancer in workers
(NIOSH 1977). The Secretary of Labor has taken the position that no safe
occupational exposure can be established for a carcinogen.
The current workroom air standard determined by the Occupational
Safety and Health Administration (OSHA) is an 8-h time-weighted average
permissible exposure limit (PEL) of 0.2 mg/m^ for the benzene-soluble
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Section 9
Table 9.1. Regulatory standards and advisory levels
Regulatory standard
or advisory level Basis Concentration References
Air
Regulatory standard
8-h Time- Benzene-soluble frac- 0.2 mg/m3 OSHA 1985
weighted average tion of coal tar
permissible pitch volatiles
exposure limit
(PEL)
Advisory levels
8-h Time-
weighted average
threshold limit
value
10-h Time-
weighted average
threshold limit
value
Benzene-soluble frac-
tion of coal tar
pitch volatiles
Cyclohexane-soluble
fraction of coal
tar pitch volatiles
0.2 mg/m3
0.1 mg/m3
ACGIH 1986
NIOSH 1977
Advisory levels
Ambient water
quality criterion
Water
Benzo[a]pyrene
0 (28, 2.8, and EPA 1980
0.28 ng/L)fl
The EPA recommended concentration for ambient water is zero. However,
because attainment of this level may not be possible to achieve, the EPA
recommended concentrations of total carcinogenic PAHs for ambient water
corresponding to a 10~3, 10~6, and 10~7 upper-bound lifetime excess risk
estimate, respectively, are presented.
-------
Regulatory and Advisory Status 49
fraction of coal tar pitch volatiles (OSHA 1985). The PEL was
established to minimize exposure to those PAHs believed to
be carcinogens.
9.2.2 Advisory Levels
9.2.2.1 Air advisory levels
ACG1H Time-Weighted Average Threshold Limit Value. The American
Conference of Governmental Industrial Hygienists (ACGIH 1986)
recommended a time-weighted average threshold limit value (TLV) for
occupational exposure to coal tar pitch volatiles based on an 8-h
workday and a 40-h week. The ACGIH time-weighted average TLV of 0.2
mg/m^ is based on the benzene-soluble fraction of coal tar pitch
volatiles (including benzo[a]pyrene, anthracene, phenanthrene, acridine,
chrysene, and pyrene). The TLV is based on the ACGIH conclusion that at
concentrations below 0.2 mg/m^, any increase in the incidence of lung
and other tumors caused by occupational exposure to coal tar pitch
volatiles should be minimal.
NIOSH Time-Weighted Average Threshold Limit Value. The National
Institute for Occupational Safety and Health (NIOSH) examined the
epidemiologic and experimental toxicological evidence on coal tar, coal
tar pitch, and creosote; conclusions were that these compounds are
carcinogenic to experimental animals and potentially carcinogenic to
humans (NIOSH 1977). PAHs have been identified in coal tar products.
Because of the carcinogenic potential of these compounds, NIOSH
recommended that the permissible exposure limit be set at the lowest
concentration detected by the NIOSH-recommended method of environmental
monitoring, that is, 0.1 mg/m^ (NIOSH 1977). NIOSH proposed this time-
weighted average threshold limit value to reduce the risk of cancer
associated with exposure to coal tar products in the workplace.
9.2.2.2 Water advisory levels
Ambient Water Quality Criterion. EPA (1980) developed an ambient
water quality criterion (AWQC) to protect human health from the
potential carcinogenic effects caused by exposure to PAHs through
ingestion of contaminated water and contaminated aquatic organisms.
B[b]F is an animal carcinogen. Because there is no recognized safe
concentration for a human carcinogen, EPA (1980) recommended that the
concentration of total carcinogenic PAHs in ambient water be zero.
However, EPA (1980) recognized that a zero concentration level may not
be possible to attain. The present criteria for total carcinogenic PAHs
were based on the carcinogenicity assay reported by Neal and Rigdon
(1967), in which a statistically higher incidence of stomach tumors
developed in CFtf-Swiss mice exposed to doses of 1 to 250 ppm
benzo[a)pyrene in the diet than in controls. Assuming that an individual
consumes 2 L of water and 6.5 g fish and shellfish each day, the sum of
the concentrations of total carcinogenic PAHs corresponding to upper-
bound lifetime excess cancer risks of 10"^, 10"^, and 10are 28, 2.8,
and 0.28 ng/L, respectively. These risk estimates may be revised by EPA
depending on the ongoing reevaluation of the studies and methods of
risk estimation.
-------
50 Section 9
9.2.2.3 Food advisory levels
No food advisory levels for B[b]F were located in the available
literature.
9.2.2.4 Other guidance
Sections 103(a) and 103(b) of the Comprehensive Environmental
Response, Compensation, and Liability Act of 1980 (CERCLA) require that
persons in charge of vessels or facilities from which a hazardous
substance has been released in quantities that are equal to or greater
than its reportable quantity (RQ) immediately notify the National
Response Team of the release. Potential carcinogens are grouped into
high-, medium-, or low-hazard categories on the basis of the biological
information available. The RQ for B[b]F is 1 lb (EPA 1987).
9.2.3 Data Analysis
9.2.3.1 Carcinogenic potency
Although EPA previously published inhalation and oral risk
estimates for carcinogenic benzo[a]pyrene (EPA 1984b) based on the
studies of Thyssen et al. (1981) and Neal and Rigdon (1967), these
numbers are currently under review and have not been included here
pending recalculation.
9.3 STATE
The State of New York has recommended a guidance level of 0.2 /*g/L
for the sum of benz[a]anthracene, benzofluoranthene, benzo[a]pyrene,
fluoranthene, indeno[1,2,3-cd]pyrene, methylbenz[a]anthracene, and
pyrene in ambient water (NYSDEC 1984). Regulations and advisory guidance
from the states were still being compiled at the time of printing.
-------
51
10. REFERENCES
Aldrich Chemical Company. 1986. Catalog of Fine Chemicals. Aldrich
Chemical Co., Milwaukee, Wis.
ACGIH (American Conference of Governmental Industrial Hygienists). 1986.
Threshold Limit Values and Biological Exposure Indices. 5th ed. ACGIH,
Cincinnati, Ohio.
* Amin S, LaVoie EJ, Hecht SS. 1982. Identification of metabolites of
benzo[b]fluoranthene. Carcinogenesis. 3:171-174.
* Amin S, Huie K, Hecht SS. 1985a. Mutagenicity and tumor initiating
activity of methylated benzo[b]fluoranthenes. Carcinogenesis
6:1023-1025.
* Amin S, Balanikas G, Huie K, Hussaur N, Geddie JE, Hecht SS. 1985b.
Synthesis and fluorescence spectra of structural analogues of potential
benzo[b]fluoranthene-DNA adducts. J Org Chem 50:4642-4646.
Andersson K, Levin J-0, Nilsson C-A. 1983. Sampling and analysis of
particulate and gaseous polycyclic aromatic hydrocarbons from coal tar
sources in the working environment. Chemosphere 12:197-207.
Barnes D et al. 1987. Reference dose (RfD): Description and use in
health risk assessments. Appendix A in the Integrated Risk Information
System Supportive Documentation. Vol. 1. Office of Health and
Environmental Assessment, Environmental Protection Agency, Washington,
DC, EPA/600/8-86/032a.
Barofsky DF, Baum EJ. 1976. Exploratory field desorption mass analysis
of the photoconversion of adsorbed polycyclic aromatic hydrocarbons. J
Am Chem Soc 98:25-26.
Bartosek I, Guaitani A, Modica R, Fiume M, Urso R. 1984. Comparative
kinetics of oral benz[a]anthracene, chrysene, and triphenylene in rats:
study with hydrocarbon mixtures. Toxicol Lett 23:333-339.
*Key studies.
-------
52 Section 10
* Becher G, Bjorseth A. 1983. Determination of exposure to polycyclic
aromatic hydrocarbons by analysis of human urine. Cancer Lett
17:301-311.
Becher G, Haugen A, Bjorseth A. 1984. Multinethod determination of
occupational exposure to polycyclic aromatic hydrocarbons in an aluminum
plant. Carcinogenesis 5:647-651.
Becher G. 1986. Determination of exposure to PAH by analysis of urine
samples. In: Hoffmann D, Harris CC, eds. Mechanisms in Tobacco
Carcinogenesis. Banbury Report 23. Cold Spring Harbor Laboratory.
Blumer M, Blumer W, Reich T. 1977. Polycyclic aromatic hydrocarbons in
soils of a mountain valley: correlation with highway traffic and cancer
incidence. Environ Sci Technol 11:1082-1084.
Borneff J, Kunte H. 1979. Analysis of polycyclic aromatic hydrocarbons
in water using thin layer chromatography and spectrofluorometry. In:
Egan H, ed. Environmental Carcinogens: Selected Methods of Analysis.
Vol. 3. Analysis of Polyaromatic Hydrocarbons in Environmental Samples.
International Agency for Research on Cancer (IARC), Lyon, France,
pp. 129-139.
Bossert ID, Bartha R. 1986. Structure-biodegradability relationship of
polycyclic aromatic hydrocarbons in soil. Bull Environ Contam Toxicol
37:490-495.
Butler JD, Butterworth V, Kellow C, Robinson HG. 1984. Some observations
on the polycyclic aromatic hydrocarbon (PAH) content of surface soils in
urban areas. Sci Total Environ 38:75-85.
Calabrese EJ. 1984. Ecogenetics: Genetic Variation in Susceptibility to
Environmental Agents. John Wiley and Sons, New York.
CRC (Chemical Rubber Company). 1987. CRC Handbook of Chemistry and
Physics. 6th ed. CRC Press, Boca Raton, Fla.
* Clonfero E, Zordan M, Cottica D, et al. 1986. Mutagenic activity and
polycyclic aromatic hydrocarbon levels in urine of humans exposed to
therapeutical coal tar. Carcinogenesis 7:819-823.
Cookson HA. 1924. Epithelioma of the skin after prolonged exposure to
creosote. Br Med J 68(1):368.
Cooper CS, Grover PL, Sims P. 1983. The metabolism and activation of
benzo[a]pyrene. In: Bridges JW, Chase LF, eds. Progress in Drug
Metabolism, Vol. 7. John Wiley and Sons, New York, pp. 295-395.
* Coover MP, Sims RC. 1987. The effect of temperature on polycyclic
aromatic hydrocarbon persistence in an unacclimated agricultural soil.
Haz Waste Haz Mat 4:69-82.
-------
References 53
Creasia DA, Poggenburg JK Jr., Nettesheim P. 1976. Elution of
benzo[a]pyrene from carbon particles in the respiratory tract of mice. J
Toxicol Environ Health 1:967-975.
Das BS, Thomas GH. 1978. Fluorescence detection in high performance
liquid chromatographic determination of polycyclic aromatic
hydrocarbons. Anal Chem 50:967-973.
* Davies GH, Hodkinson A, DiVetta P. 1986. Measurement and analysis of
occupational exposures to coke oven emissions. Ann Occup Hyg 30:51-62.
DHHS (Department of Health and Human Services). 1986. The Health
Consequences of Involuntary Smoking, a Report of the Surgeon General.
Office on Smoking and Health, Rockville, Md. (CDC).
Den Hollander H, Van DeMeet D, VanNoort P, Wondergem E. 1986. Wet
deposition of polycyclic aromatic hydrocarbons in the Netherlands. Sci
Total Environ 52:211-219.
* Deutsch-Wenzel RP, Brune H, Grimmer 0, Dettbarn G, Misfeld J. 1983.
Experimental studies in rat lungs on the carcinogenicity and dose-
response relationships of eight frequently occurring environmental
polycyclic aromatic hydrocarbons. J Natl Cancer Inst 71:539-544.
Eisler R. 1987. Polycyclic Aromatic Hydrocarbon Hazards to Fish,
Wildlife, and Invertebrates. A Synoptic Review. Biological Report 85.
Contam Haz Rev Rep 11. U.S. Fish and Wildlife Service, U.S. Department
of the Interior, Washington, D.C.
EPA (Environmental Protection Agency). 1978. Notices of Rebuttable
Presumption Against Registration and Continued Registration (RPAR) of
Pesticide Products Containing Coal Tar Creosote and Coal Tar Neutral
Oils. Position Document (PD) 1. Office of Pesticide Programs,
Washington, D.C.
* EPA (Environmental Protection Agency). 1979. Water-Related
Environmental Fate of 129 Priority Pollutants. Washington, D.C., EPA
440/4-79-029.
EPA (Environmental Protection Agency). 1980. Ambient Water Quality
Criteria for Polynuclear Aromatic Hydrocarbons. Office of Water
Regulations and Standards, Washington, D.C., EPA 440/5-80-069, NTIS
PB81-117806.
EPA (Environmental Protection Agency). 1981. Wood Preservative
Pesticides. Creosote, Pentachlorophenol, and the Inorganic Arsenicals
(Wood Uses). Position Document (PD) 2/3, Office of Pesticide Programs,
Washington, D.C.
EPA (Environmental Protection Agency). 1982. Aquatic Fate Process Data
for Organic Priority Pollutants. Office of Water Regulations and
Standards, Washington, D.C., EPA 440/4-81-014.
-------
54 Section 10
EPA (Environmental Protection Agency). 1983. Technical Assistance
Document for Sampling and Analysis of Toxic Organic Compounds in Ambient
Air. Environmental Monitoring Systems Laboratory, Research Triangle
Park, NC, EPA 600/4-83-027.
EPA (Environmental Protection Agency). 1984a. Guidelines establishing
test procedures for the analysis of pollutants under the Clean Water
Act; final rule and interim final rule and proposed rule. Fed Regist
49:1-210 (Oct. 26, 1984).
EPA (Environmental Protection Agency). 1984b. Health Effects Assessment
for Polycyclic Aromatic Hydrocarbons (PAH). Environmental Criteria and
Assessment Office, Cincinnati, Ohio, EPA 540/1-86-013.
EPA (Environmental Protection Agency). 1984c. Wood Preservative
Pesticides: Creosote, Pentachlorophenol, and Inorganic Arsenicals.
Position Document (PD4). Office of Pesticide Programs, Washington, D.C.,
NTIS TB-84-241538.
* EPA (Environmental Protection Agency). 1985. An Exposure and Risk
Assessment for Benzo[ajpyrene and Other Polycyclic Aromatic
Hydrocarbons. Vol. IV. Office of Water, Washington, D.C., EPA
440/4-85-020-V4.
EPA (Environmental Protection Agency). 1986a. Statement of Work for
Organics Analysis. EPA Contract Laboratory Program, October 1986.
EPA (Environmental Protection Agency). 1986b. Creosote,
pentachlorophenol, and inorganic arsenicals: Amendment of notice of
intent to cancel registrations. Fed Regist 51:1334 (Jan. 10, 1986).
EPA (Environmental Protection Agency). 1987. 40 CFR Parts 117 and 302.
Reportable quantity adjustments. Fed Regist 52:8140-8153 (Mar. 16,
1987).
Geddie JE, Amin S, Hussain N, Hecht SS. 1984. Metabolism, DNA adduct
formation, and tumorigenicity of benzo[b]fluoranthene and its
metabolites in mouse skin. Proc Am Assoc Cancer Res 25:122.
* Gordon RJ, Bryan RJ. 1973. Patterns in airborne polynuclear
hydrocarbon concentrations at four Los Angeles sites. Environ Sci
Technol 7:1050-1053.
* Gordon RJ. 1976. Distribution of airborne polycyclic aromatic
hydrocarbons throughout Los Angeles. Environ Sci Technol 10:370-373.
* Grover PL. 1986. Pathways involved in the metabolism and activation of
polycyclic hydrocarbons. Xenobiotica 16:915-931.
Hammond ED, Selikoff IJ, Lawther PO, Seidman H. 1976. Inhalation of
B[a]P and cancer in man. Ann NY Acad Sci 271:116-124.
-------
References 55
* Harris CC. 1985a. Future directions in the use of DNA adducts as
internal dosimeters for monitoring human exposure to environmental
mutagens and carcinogens. Environ Health Perspect 62:185-191.
* Harris CC. 1985b. Method and Kit for Detecting Human Exposure to
Genotoxic Agents. U.S. Department of Health and Human Services,
Washington, DC, PAT-APPL-6-778 669, PB86-131620.
Harris CC, Newman MJ, Weston A, Mann DL. 1986. Identification of human
antibodies to polycyclic aromatic hydrocarbon-DNA adducts. Clin Res
34:690A
Harris CC, Sporn MB, Kaufman DG, Smith JM, Baker MS, Saffiotti V. 1971.
Acute ultrastructural effects of benzo(a)pyrene and ferric oxide on the
hamster tracheobronchial epithelium. Cancer Res 31:1977.
Hazardous Substances Data Bank (HSDB). 1987. Benzo[b]fluoranthene.
National Library of Medicine, Toxicology Information Program,
Bethesda, Md.
Henry SA. 1947. Occupational cutaneous cancer attributable to certain
chemicals in industry. Br Med Bull 4:398-401.
Hermann M. 1981. Synergistic effects of Individual polycyclic aromatic
hydrocarbons on the mutagenicity of their mixtures. Mutat Res
90:399-409.
Hoffmann D, Wynder E. 1976. Environmental respiratory carcinogenesis.
In: Searle CE, ed. Chemical Carcinogens. American Chemical Society
Monograph 173. American Chemical Society, Washington, D.C.
Howard J. 1979. Analysis of B[a]P and other polycyclic aromatic
hydrocarbons in food. In: Egan, H, ed. Environmental Carcinogens:
Selected Methods of Analysis. Vol. 3. Analysis of Polyaromatic
Hydrocarbons in Environmental Samples. International Agency for Research
on Cancer (IARC), Lyon, France, pp. 175-191.
IARC (International Agency for Research on Cancer). 1973. IARC
Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Man. Vol. 3. Certain Polycyclic Aromatic Hydrocarbons and Heterocyclic
Compounds. IARC, Lyon, France, pp. 46-68.
IARC (International Agency for Research on Cancer). 1983. IARC
Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans. Vol. 32. Polynuclear Aromatic Compunds, Part 1. Chemical,
Environmental, and Experimental Data. IARC, Lyon, France.
IARC (International Agency for Research on Cancer). 1984. IARC
Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans. Vol. 34. Polynuclear Aromatic Compounds, Part 3, Industrial
Exposures in Aluminum Production, Coal Gasification, Coke Production,
and Iron and Steel Founding. IARC, Lyon, France.
-------
56 Section 10
IARC (International Agency for Research on Cancer). 1985. IARC
Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to
Humans. Vol. 34. Polynuclear Aromatic Compounds, Part 4. Bitumens,
Coal-tars and Derived Products, Shale Oils, and Soots. IARC, Lyon,
France.
* Kamens RM, Fulcher JN, Zhishi G. 1986. Effects of temperature on wood
soot PAH decay in atmospheres with sunlight and low NOx. Atmos Environ
20:1579-1587.
Kao JK, Patterson FK, Hall LJ. 1985. Skin penetration and metabolism of
topically applied chemicals in six mammalian species, including man: an
in vitro study with benzo[a]pyrene and testosterone. Toxicol Appl
Pharmacol 81:502-516.
Kennaway NM, Kennaway EL. 1936. Study of the incidence of cancer of the
lung and larynx. J Hyg 36:236-267.
Korfmacher WA, Natusch DFS, Taylor DR, Mamantov G, Wehry EL. 1980a.
Oxidative transformation of polycyclic aromatic hydrocarbons adsorbed on
coal fly ash. Science 207:763-765.
Korfmacher WA, Wehry EL, Mamantov G, Natusch DFS. 1980b. Resistance to
photochemical decomposition of polycyclic aromatic hydrocarbons vapor-
adsorbed on coal fly ash. Environ Sci Technol 14:1094-1099.
Kouri RE, Rude TH, Joglekar R, et al. 1978. 2,3,7,8-Tetrachloro-
dibenzo-p-dioxin as cocarcinogens causing 3-methylcholanthrene initiated
subcutaneous tumors in mice genetically 'nonresponsive' at Ah locus.
Cancer Res 38:2777-2783.
Lacassagne A, Buu-Hoi NP, Zajdela F, Lavit-Laray D, Chalvet 0. 1963.
Activite carcinogene d'hydrocarbons aromatiques polycycliques a noyau
fluoranthene. Un Int Cancer Acta 19:490-496.
LaVoie E, Bedenko V, Hirota N, Hecht SS, Hoffmann D. 1979a. A
comparison of the mutagenicity, tumor initiating activity, and complete
carcinogenicity of polynuclear aromatic hydrocarbons. In: Jones PW,
Leber P, eds. Polynuclear Aromatic Hydrocarbons. Ann Arbor Science, Ann
Arbor, Mich.
LaVoie EJ, Hecht SS, Bedenko V, Amin S, Mazzarese R, Hoffmann, D. 1979b.
On the metabolic activation of the environmental carcinogens
benzo[j]fluoranthene and benzofb]fluoranthene. Proc Am Assoc Ca 20:81
(abstract).
LaVoie EJ, Amin S, Hecht SS, Furuya K, Hoffmann D. 1982. Tumour
initiating activity of dihydrodiols of benzo[b]fluoranthene,
benzo[j]fluoranthene, and benzofk]fluoranthene. Carcinogenesis 3:49-52.
LaVoie EJ, Braley J, Rice JE, Rivenson A. 1987. Turaorigenic activity of
non-alternant polynuclear aromatic hydrocarbons in newborn mice. Cancer
Lett 34:15-20.
-------
References 57
Lee RF, Sauerheber R, Dobbs GD. 1972. Uptake, metabolism, and discharge
of polycyclic aromatic hydrocarbons by marine fish. Mar Biol 17:201-208
(as cited in Eisler 1987).
Lenson N. 1956. Multiple cutaneous carcinoma after creosote exposure. N
Eng J Med 254:520-523.
Leversee GJ, Geisy JP, Landrum PF, et al. 1981. Disposition of
benzo[a]pyrene in aquatic systems components: periphyton, chironomids,
daphnia, fish. In: Cooke H, Dennis AJ, eds. Chemical Analysis and
Biological Fate: Polynuclear Aromatic Hydrocarbons. Fifth International
Symposium. Battelle Press, Columbus, Ohio, pp. 357-366 (as cited in
Eisler 1987).
Levin W, Wood A, Chang RL, et al. 1982. Oxidative metabolism of
polycyclic aromatic hydrocarbons to ultimate carcinogens. Drug Metab Rev
13:555-580.
* Lindstedt G, Sollenberg J. 1982. Polycyclic aromatic hydrocarbons in
the occupational environment. Scan J Work Environ Health 8:1-19.
Lloyd JW. 1971. Long-term mortality study of steelworkers. V.
Respiratory cancer in coke plant workers. J Occup Med 13:53-68.
* Lu P-Y, Metcalf RL, Plummer N, Mandel D. 1977. The environmental fate
of three carcinogens: benzo[a]pyrene, benzidine, and vinyl chloride
evaluated in laboratory model ecosystems. Arch Environ Contam Toxicol
6:129-142.
Maclure KM, MacMahon B. 1980. An epidemiologic perspective of
environmental carcinogenesis. Epidemiol Rev 2:19-48.
Mahlum DD, Wright CW, Chess EK, Wilson BW. 1984. Fractionation of skin
tumor-initiating activity in coal liquids. Cancer Res 44:5176-5181.
Matsumoto H, Kashimoto T. 1985. Average daily respiratory intake of
polycyclic aromatic hydrocarbons in ambient air determined by capillary
gas chromatography. Bull Environ Contam Toxicol 34:17-23.
Mazumdar S, Redmond CK, Sollecito W, Sussman N. 1975. An epidemiological
study of exposure to coal tar pitch volatiles among coke oven workers. J
Air Pollut Control Assoc 25:382-389.
McNeil D. 1983. Tar and pitch. In: Kirk-Othmer Encyclopedia of Chemical
Technology. Vol. 22. 3rd ed. John Wiley and Sons, New York, pp. 564-600.
Medinsky MA, Kampcik SJ. 1985. Pulmonary retention of [^C]
benzo[a]pyrene in rats as influenced by the amount instilled. Toxicol
35:327-336.
Modica R, Fiume M, Bartosek I. 1982. Gas-liquid chromatographic assay of
polycyclic aromatic hydrocarbon mixtures: specifically modified method
for rat tissues. J Chromatogr 24:352-355.
-------
58 Section 10
Mossanda K, Poncelet F, Fouassin A, Mercier M. 1979. Detection of
mutagenic polycyclic aromatic hydrocarbons in African smoked fish. Food
Cosraet Toxicol 17:141-143.
* NAS (National Academy of Sciences). 1972. Particulate Polycyclic
Organic Matter. National Academy of Sciences, Washington, D.C.
NIOSH (National Institute for Occupational Safety and Health). 1977.
Criteria for a Recommended Standard ... Occupational Exposure to Coal
Tar Products. DHEW (NIOSH) Publication 78-107.
NIOSH (National Institute for Occupational Safety and Health). 1984.
NIOSH Manual of Analytical Methods. 3rd ed. NIOSH, Cincinnati, Ohio.
Neal J, Rigdon RH. 1967. Gastric tumors in mice fed benzo[a]pyrene: a
quantitative study. Tex Rep Biol Med 25:553-557.
NYSDEC (New York State Department of Environmental Conservation). 1984.
Ambient Water Quality Criteria. Memo to Regional Water Engineers, Bureau
Directors, and Section Chiefs, May 10, 1984.
OSHA (Occupational Safety and Health Administration). 1985. Permissible
Exposure Limits. Code of Federal Regulations 29:1910.1002.
0'Donovan WJ. 1920. Epitheliomatous ulceration among tar workers. Br J
Dermatol Syph 32:215-252.
Ogan K, Katz E, Slavin W. 1979. Determination of polycyclic aromatic
hydrocarbons in aqueous samples by reversed-phase liquid chromatography.
Anal Chem 51:1315-1320.
Pott P. 1775. Surgical observations relative to the cancer of the
scrotum. London. Reprinted In National Cancer Institute Monograph
10:7-13 (1973).
Purde M, Etlin S. 1980. Cancer cases among workers in the Estonia oil
shale processing industry. In: Rom WN, Archer VE, eds. Health
Implications of New Energy Technologies. Ann Arbor Science, Ann Arbor,
Mich., pp. 527-528.
* Randerath K, Randerath E, Agrawal HP, Gupta RC, Schurdak ME, Reddy MV.
1985. Postlabeling methods for carcinogen-DNA adduct analysis. Environ
Health Perspect 62:57-65.
Randerath E, Avitts TA, Reddy MV, Miller RH, Everson RB, Randerath K.
1986. Comparative -^P-analysis of cigarette smoke-induced DNA damage in
human tissues and mouse skin. Cancer Res 46:5869-5877.
Redmond CK, Ciocco A, Lloyd JW, Rush HW. 1972. Long-term mortality study
of steelworkers. VI. Mortality from malignant neoplasms among coke oven
workers. J Occup Med 14:621-629.
-------
References 59
Riggin R, Strup PE. 1984. Screening Methods for PAH Priority Pollutants
in Wastewater. Prepared for the Environmental Monitoring Support
Laboratory, Environmental Protection Agency, Cincinnati, Ohio, EPA
600/S4-84-007.
Roszinsky-Kocher G, Basler A, Rohrborn G. 1979. Mutagenicity of
polycyclic hydrocarbons. V. Induction of sister chromatid exchanges in
vivo. Mutat Res 66:65-67.
Santodonato J, Howard P, Basu D. 1981. Health and ecological assessment
of polynuclear aromatic hydrocarbons. J Environ Pathol Toxicol 5:51-75.
Sawicki E. 1976. Analysis of Atmospheric Carcinogens and Their
Cofactors. INSERM Symposia Series, Vol. 52, pp. 297-354.
Schlede E, Kuntzman R, Haber S, Conney AH. 1970. Effect of enzyme
induction on the metabolism and tissue distribution of benzo[a]pyrene.
Cancer Res 30:2898-2904.
Schottenfeld D, Fraumeni YP, Jr., eds. 1982. Cancer Epidemiology and
Prevention. W.B. Sanders Co., Philadelphia, Pa.
Sellakumar A, Stenb&ck F, Rowland J. 1976. Effects of different dusts on
respiratory carcinogenesis in hamsters induced by benzo(a)pyrene and
diethylnitrosamine. Europ J Cancer 12:313-319.
Sims P. 1982. The metabolic activation of some polycyclic hydrocarbons:
the role of dihydrodiols and diol epoxides. Adv Exp Med Biol
136:487-500.
Slaga TJ, diGiovanni J. 1984. Inhibition of chemical carcinogenesis. In:
Searle CE, ed. Chemical Carcinogenesis. 2nd ed. Vol. 2. ACS Monograph
182. Washington, D.C.
Smith JH, Mabey WR, Bohomos N, et al. 1978. Environmental Pathways of
Selected Chemicals in Freshwater Systems; Part II: Laboratory Studies.
Environmental Protection Agency, Athens, GA, EPA-600/7-78-074 (as cited
in EPA 1979).
Sorrell RK, Brass HJ, Reding R. 1981. A Review of Occurrences and
Treatment of Polynuclear Aromatic Hydrocarbons. Environmental Protection
Agency, Washington, D.C., EPA-600/0-81-066.
Stenback F, Rowland J. 1979. Experimental respiratory carcinogenesis in
hamsters: environmental, physicochemical, and biological aspects. Oncol
36:63-71.
Stenback F, Rowland J, Sellakumar A. 1976. Carcinogenicity of
benzo(a)pyrene and dusts in the hamster lung (instilled intratracheally
with titanium oxide, aluminum oxide, carbon, and ferric oxide). Oncol
33:29-34.
-------
60 Section 10
Thakker DR, Yagi H, Levin W, Wood AH, Conney AH, Jerina DM. 1985.
Polycyclic aromatic hydrocarbons: metabolic activation of ultimate
carcinogens. In: Anders MW, ed. Bloactivation of Foreign Compounds.
Academic Press, New York, pp. 178-242.
Thyssen J, Althoff J, Kiramerle G, Mohr U. 1981. Inhalation studies with
benzo[a]pyrene in Syrian golden hamsters. J Natl Cancer Inst 66:575-577.
Tornquist A, Wlklund L, Toftgard R. 1985. Investigation of absorption,
metabolism kinetics, and DNA-binding of intratracheally administered
benzo[a]pyrene in the isolated, perfused rat lung: a comparative study
between microcrystalline and particulate absorbed benzo[a]pyrene. Chem
Biol Interact 54:185-198.
USDOC (U.S. Department of Commerce). 1986. U.S. Imports for Consumption
and General Imports. FT 246/Annual 1985.
Verschueren K. 1983. Handbook of Environmental Data on Organic
Chemicals. 2nd ed. Van Nostrand Reinhold, New York.
View Database. 1989. Agency for Toxic Substances and Disease Registry
(ATSDR), Division of Health Studies, Atlanta, Ga., Nov. 8, 1989.
* Vo-Dinh T, Tromberg BJ, Griffin GD, Ambrose KR, Sepaniak MJ,
Gardenhire EM. 1987. Antibody-based fiberoptics biosensor for the
carcinogen benzo[a]pyrene. Appl Spectrosc 41:735-738.
Wallace WE, Keane MJ, Hill CA, Xu J, Ong T. 1987. Mutagenicity of diesel
exhaust particles and oil shale particles dispersed in lecithin
surfactant. J Toxicol Environ Health 21:163-171.
* Wang DT, Meresz 0. 1982. Occurrence and potential uptake of
polynuclear aromatic hydrocarbons of highway traffic origin by
proximally grown food crops. In: Cooke M, Dennis AS, Fisher GL, eds.
Polynuclear Aromatic Hydrocarbons: Physical and Biological Chemistry:
Sixth International Symposium. Battelle Press, Columbus, Ohio, pp. 885-
896.
Waters MD, Stack HF, Brady AL, Lohman PH, Haroun L, Vainio H. 1987. Use
of computerized data listings and activity profiles of genetic and
related effects in the review of 195 compounds. Genetic Toxicology
Division. Health Effects Research Laboratory, Environmental Protection
Agency, Research Triangle Park, N.C.
Weibel FJ. 1980. Activation and inactivation of carcinogens by
microsomal monooxygenases: modification by benzoflavones and polycyclic
aromatic hydrocarbons. In: Slaga TJ, ed. Carcinogenesis. Vol. 5.
Modifers of Chemical Carcinogenesis. Raven Press, New York.
Weyand EH, Rice JE, Hussain N, LaVoie EJ. 1987a. Detection of DNA
Adducts of Turaorigenic Nonalternant Polycyclic Aromatic Hydrocarbons by
Postlabeling. Proceedings of the 78th Annual Meeting of the American
Association for Cancer Research, March 1987, Atlanta, Ga., 28:102.
-------
References 61
Weyand EH, Rice JE, LaVoie EJ. 1987b. ^2p.postlabeling analysis of DNA
adducts from nonalternant PAH using thin-layer and high-performance
liquid chromatography. Cancer Lett (in press).
Wise SA, Benner BA, Chesler SN, Hilpert LR, Vogt CR, May WE. 1986.
Characterization of the polycyclic aromatic hydrocarbons from two
standard reference material air particulate samples. Anal Chem
58:3067-3077.
WHO (World Health Organization). 1971. International Standards for
Drinking Water. 3rd ed. World Health Organization, Geneva, Switzerland.
* Wynder EL, Hoffmann D. 1959. The carcinogenicity of
benzofluoranthenes. Cancer 12:1194-1199.
Wynder EL, Hoffmann D. 1967. Tobacco and Tobacco Smoke. Academic Press,
New York.
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63
11. GLOSSARY
Acute Exposure--Exposure to a chemical for a duration of 14 days or
less, as specified in the Toxicological Profiles.
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 time period.
Carcinogen--A chemical capable of inducing cancer.
Ceiling value (CL)--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.
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.
Embryotoxicity and Fetotoxicity--Any toxic effect on the conceptus as a
result of prenatal exposure to a chemical; the distinguishing feature
between the two terras is the stage of development during which the
insult occurred. The terms, as used here, include malformations and
variations, altered growth, and in utero death.
Frank Effect Level (FEL)--That level of exposure which produces a
statistically or biologically significant increase in frequency or
severity of unmistakable adverse effects, such as irreversible
functional impairment or mortality, in an exposed population when
compared with its appropriate control.
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.
Immediately Dangerous to Life or Health (IDLH)--The maximum
environmental concentration of a contaminant from which one could escape
within 30 min without any escape-impairing symptoms or irreversible
health effects.
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64 Section 11
Intermediate Exposure--Exposure to a chemical for a duration of 15-364
days, as specified in the Toxicological Profiles.
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.
Key Study--An animal or human toxicological study that best illustrates
the nature of the adverse effects produced and the doses associated with
those effects.
Lethal Concentratlon(LO) (LCLO)--The lowest concentration of a chemical
in air which has been reported to have caused death in humans or
animals.
Lethal Concentratlon(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 Is expected to have caused death in
humans or animals.
Lethal Dose(50) (LDso)--The dose of a chemical which has been calculated
to cause death in 50% of a defined experimental animal population.
Lowest-Observed-Adverse-Effect Level (LOAEL)--The lowest dose of
chemical in a study or group of studies which produces statistically or
biologically significant increases in frequency or severity of adverse
effects between the exposed population and its appropriate control.
Lowest-Observed-Effect Level (LOEL)--The lowest dose of chemical in a
study or group of studies which produces statistically or biologically
significant increases in frequency or severity of effects between the
exposed population and its appropriate control.
Malformations--Permanent structural changes that may adversely affect
survival, development, or function.
Minimal Risk Level--An estimate of daily human exposure to a chemical
that is likely to be without an appreciable risk of deleterious effects
(noncancerous) over a specified duration of exposure.
Mutagen--A substance that causes mutations. A mutation is a change in
the genetic material in a body cell. Mutations can lead to birth
defects, miscarriages, or cancer.
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Glossary 65
Neurotoxicity--The occurrence of adverse effects on the nervous system
following exposure to a chemical.
No-Observed-Adverse-Effect Level (NOAEL)--That dose of chemical at which
there are 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.
No-Observed-Effect Level (NOEL)--That dose of chemical at which there
are no statistically or biologically significant increases in frequency
or severity of effects seen between the exposed population and its
appropriate control.
Permissible Exposure Limit (PEL)--An allowable exposure level in
workplace air averaged over an 8-h shift.
q^ --The upper-bound estimate of the low-dose slope of the dose-response
curve as determined by the multistage procedure. The q^* can be used to
calculate an estimate of carcinogenic potency, the incremental excess
cancer risk per unit of exposure (usually pg/L for water, mg/kg/day for
food, and ng/n? for air).
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
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 CERCLA. Reportable quantities are: (1) 1 lb
or greater or (2) for selected substances, an amount established by
regulation either under CERCLA or under Sect. 311 of the Clean Water
Act. Quantities are measured over a 24-h 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.
Short-Term Exposure Limit (STEL)--The maximum concentration to which
workers can be exposed for up to 15 rain continually. No more than four
excursions are allowed per day, and there must be at least 60 min
between exposure periods. The daily TLV-TWA may not be exceeded.
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66 Section 11
Target Organ Toxicity--This terra 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.
Threshold Limit Value (TLV)--A concentration of a substance to which
most workers can be exposed without adverse effect. The TLV may be
expressed as a TWA, as a STEL, or as a CL.
Time-weighted Average (TWA)--An allowable exposure concentration
averaged over a normal 8-h workday or 40-h workweek.
Uncertainty Factor (UF)--A factor used in operationally deriving the RfD
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 humans,
(3) the uncertainty in extrapolating from data obtained in a study that
is of less than lifetime exposure, and (4) the uncertainty in using
LOAEL data rather than NOAEL data. Usually each of these factors is set
equal to 10.
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67
APPENDIX: PEER REVIEW
A peer review panel was assembled for benzo[b]fluoranthene. The
panel consisted of the following members: Dr. Dietrich Hoffmann, Naylor
Dana Institute for Disease Prevention; Dr. Roger 0. McClellan, Lovelace
Inhalation Toxicology Research Institute; and Dr. Alexander Wood, Roche
Institute of Molecular Biology. These experts collectively have
knowledge of benzofb]fluoranthene's physical and chemical properties,
toxicokinetics, key health end points, mechanisms of action, human and
animal exposure, and quantification of risk to humans. All reviewers
were selected in conformity with the conditions for peer review
specified in the Superfund Amendments and Reauthorization Act of 1986,
Section 110.
A joint panel of scientists from ATSDR and EPA has reviewed the
peer reviewers' comments and determined which comments will be included
in the profile. A listing of the peer reviewers' comments not
incorporated in the profile, with a brief explanation of the rationale
for their exclusion, exists as part of the administrative record for
this compound. A list of databases reviewed and a list of unpublished
documents cited are also included in the administrative record.
The citation of the peer review panel should not be understood to
imply their approval of the profile's final content. The responsibility
for the content of this profile lies with the Agency for Toxic
Substances and Disease Registry.
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