United States
Environmental Protection
Agency
Air Risk Information Support Center EPA 450/3-90-026
Research Triangle Park, NC 27711 September 1990
Air
Health Hazard
Assessment Summary:
Steel Mill Emissions
AIR RISK INFORMATION SUPPORT CENTER
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DCN No. 89-239-009-07-02
EPA Contract No. 68-D9-0011
HEALTH HAZARD
ASSESSMENT SUMMARY:
STEEL MILL EMISSIONS
Work Assignment 07
Prepared for:
U. S. Environmental Protection Agency
Emission Standards Division
Pollutant Assessment Branch
Research Triangle Park, North Carolina 27711
Prepared by:
Radian Corporation
3200 E. Chapel Hill Road
Research Triangle Park, North Carolina 27709
September 29, 1989
B.g. EnvTronmentaT Fro'J-ot' i • I-ency
Fr-f;Ion 5, Library (£?!•.!
';-.0 S. Dearborn Street, UL-J^I 1670
Chicago, IL 60604
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DISCLAIMER
This report has been reviewed by the Office of Air Quality Planning and
Standards and the Environmental Criteria and Assessment Office of the Office
of Health and Environmental Assessment, United States Environmental Protection
Agency, and approved for publication. Approval does not signify that the
contents necessarily reflect the views and policy of the United States
Environmental Protection Agency, nor does the mention of trade or commercial
products constitute endorsement or recommendations for use.
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PREFACE
This report has been prepared for the Air Risk Information Support
Center (Air RISC) which is a cooperative endeavor between the Office of Air
Quality Planning and Standards (OAQPS) and the Office of Health and
Environmental Assessment (OHEA), U.S. Environmental Protection Agency (EPA).
The purpose of the Air RISC is to provide technical support to EPA Regional
Offices and State and local air pollution control agencies on matters
pertaining to health, exposure and risk assessment. This report contains
information residing in EPA's Integrated Risk Information System (IRIS) and is
current as of September 1989. The IRIS is a computer-based compilation of
pollutant health effect information and is subject to frequent updates. The
reader should note that information such as reference doses or concentrations,
lowest adverse effect levels and no effect levels may have been changed since
publication of this report. For more information on how to access IRIS,
contact IRIS User Support, Environmental Criteria and Assessment Office, U. S.
EPA, 26 W. Martin Luther King Drive, Cincinnati, OH 45268, telephone
513-569-7254.
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TABLE OF CONTENTS
Section Page
1.0 INTRODUCTION 1
2.0 HEALTH EFFECTS OF METALS EMITTED FROM STEEL MILLS 4
2.1 Chromium 4
2.1.1 Noncancer Heal th Effects 4
2.1.2 Carcinogenicity of Chromium 5
2.1.2 Interaction with Other Compounds 7
2.2 Manganese 7
2.2.1 Noncancer Heal th Effects 7
2.2.2 Carcinogenicity of Manganese 10
2.2.3 Interaction with Other Compounds 11
2.3 Zinc 11
2.3.1 Noncancer Health Effects 11
2.3.2 Carcinogenicity of Zinc 12
2.3.3 Interaction with Other Compounds 12
2.4 Copper 13
2.4.1 Noncancer Health Effects 13
2.4.2 Carcinogenicity of Copper 14
2.5 Nickel 15
2.5.1 Noncancer Health Effects 15
2.5.2 Carcinogenicity of Nickel 16
2.5.3 Interaction with Other Compounds 17
2.5.4 Populations at Risk 17
2.6 Cadmium 17
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Table of Contents Continued
Section Page
2.6.1 Noncancer Health Effects 18
2.6.2 Carcinogenicity of Cadmium 19
2.6.3 Interaction with Other Compounds 20
2.6.4 Populations at Risk 20
2.7 Vanadium 20
2.7.1 Noncancer Health Effects 21
2.7.2 Carcinogenicity of Vanadium 22
2.7.3 Interaction with Other Compounds 22
3.0 HEALTH EFFECTS OF OTHER COMPOUNDS EMITTED FROM STEEL MILLS 23
3.1 Ammonia and Ammonium sulfate 23
3.1.1 Noncancer Health Effects 23
3.1.2 Carcinogenicity of Ammonia and Ammonium Sul fate 25
.3.1.3 Interaction with Other Compounds 25
3.2 Hydrogen chloride 25
3.2.1 Noncancer Health Effects 26
3.2.2 Carcinogenicity of Hydrogen chloride 26
3.3 Toluene 26
3.3.1 Noncancer Health Effects 27
3.3.2 Carcinogenicity of Toluene 28
3.4 Benzene 28
3.4.1 Noncancer Health Effects 28
3.4.2 Carcinogenicity of Benzene 29
IV
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Table of Contents Continued
Section Page
3.4.3 Interaction with Other Compounds 29
3.5 Naphtha! ene 30
3.5.1 floncancer Health Effects 30
3.5.2 Carcinogenicity of Naphthalene 31
4.0 HEALTH EFFECTS OF COMPLEX MIXTURES 32
4.1 Polycycl ic Organic Matter 32
4.1.1 Noncancer Health Effects 32
4.1.2 Carcinogenicity of Polycycl ic Organic Matter 34
4.2 Coke Oven Emissions 34
4.2.1 Noncancer Health Effects 35
4.2.2 Carcinogenicity of Coke Oven Emissions 36
5.0 REFERENCES 38
LIST OF TABLES
Table Page
1. Substances of Concern Potentially Emitted from Steel Mills 2
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1.0 INTRODUCTION
The U. S. Environmental Protection Agency's (EPA) Air Risk Information
Support Center (Air RISC) was developed and is maintained by the Pollutant
Assessment Branch of the Office of Air Quality Planning and Standards
(PAB/OAQPS) and the Environmental Criteria and Assessment Office of the Office
of Health and Environmental Assessment (ECAO/OHEA) to assist State and local
air pollution control agencies and EPA regional offices on technical matters
pertaining to toxic air pollutants. In response to an Air RISC request on the
public health hazards associated with steel mill emissions, this document was
prepared to assist State and local air pollution control officials in the
identification of possible health hazards, and can be used with its companion
document, "Emission Factors For Iron and Steel Sources/Criteria and Toxic
Pollutants" (Barnard, 1989) to quantify steel mill emissions and assess the
health impacts on affected populations.
The majority of the information presented in this assessment is derived
from summary documents prepared by the EPA for the specific compounds shown in
Table 1. These compounds have been identified in steel mill emissions by
Barnard (1989). When information was available for a mixture of compounds
known to be emitted during steel production, the discussion considers the
mixture as a whole rather than the individual chemicals. This is the case for
polycyclic organic matter and coke oven emissions (see Section 4).
One of the objectives of this document is to present the Lowest Observed
Effect Levels (LOEL) (or Lowest Observed Adverse Effect Levels) and the No
Observed Effect Levels (NOEL) (or the No Observed Adverse Effect Levels) for
the noncancer health effects associated with exposure to steel mill emissions.
The LOEL and the NOEL presented here are derived from the EPA's reviews of
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animal toxicity and human epidemiology studies, and it is possible that
further research may find an alternate NOEL or LOEL.
For some pollutants, the "critical" study or effect for a NOEL or a LOEL
has been identified by the EPA and used to calculate a Reference Dose (RfD).
An RfD is defined as an estimate (within uncertainty spanning perhaps an order
of magnitude) of the daily exposure to the human population (including
sensitive sub-populations) that is likely to be without deleterious effects
during a lifetime. When the RfD is reported in units of milligrams of
substance per cubic meter of air breathed it is designated an Inhalation
Reference Dose (RfD^x. If an RfD^ has been verified from the substance it can
be found in the EPA's Integrated Risk Information System (IRIS), a computer-
Table 1. Substances of Concern Potentially Emitted from Steel Mills
Chromium
Manganese
Zinc
Copper
Nickel
Cadmium
Vanadium
Ammonia/Ammonium sulfate
Hydrogen chloride
Toluene
Benzene
Naphthalene
Polycyclic organic matter
Coke oven emissions
based compilation of pollutant health effects information. For additional
information on IRIS, contact IRIS User Support, Environmental Criteria and
Assessment Office, U. S. EPA, 26 W. Martin Luther King Drive, Cincinnati, OH
45268, telephone 513-569-7254.
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Information is also presented here on the carcinogenic potential of
steel mill emissions. This information was also, derived from EPA documents
and IRIS. The EPA's Human Health Assessment Group has calculated unit risk
estimates for several of the compounds discussed in this document. The
incremental unit risk estimate for an air pollutant is defined as the
additional lifetime cancer risk for a given population exposed continuously
for their lifetimes (70 years) to a concentration of 1 ug/nr of an airborne
pollutant (U. S. EPA, 1986a). These unit risk estimates are then used to
compare the carcinogenic potency between air pollutants and to help give an
estimate of the population risk that might be associated with exposures to air
or water that contains the carcinogenic substance. The data used to calculate
these unit risk numbers come either from lifetime animal studies or human
epidemiological studies. The EPA also assigns a weight-of-evidence judgment
of the likelihood that an agent is a human carcinogen (U.S. EPA, 1989).
The Integrated Risk Information System also includes an estimation of the air
concentrations expected to result in 1 in 10,000; 1 in 100,000; and 1 in
1,000,000 risk.
Finally, it should be noted that, for some of the compounds discussed in
this document, little or no information is available concerning their effects
from chronic inhalation exposure. For these compounds, acute inhalation
studies are summarized to provide some indication of their potential toxicity.
Oral exposures may also be discussed, but it must be kept in mind that route-
to-route extrapolation for some effects may be inappropriate.
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2.0 HEALTH EFFECTS OF METALS EMITTED FROM STEEL MILLS
2.1 CHROMIUM
Chromium is a naturally occurring essential element that can also be
carcinogenic (U. S. EPA, 1984a). Chromium can be present in the atmosphere in
several valence states, but this discussion will center on the two valence
states that humans are most likely to encounter. Trivalent chromium [Cr
(III)] and hexavalent chromium [Cr (VI)] are the two most stable forms of
chromium (U. S. EPA, 1984a). Chromium (III) is emitted naturally from the
earth's crust. Chromium (VI) is readily reduced to Cr (III) in the presence
of organic matter, but is emitted from anthropogenic sources such as steel
mills (U. S. EPA, 1984a). Steel mills are one source category thought to emit
both Cr (III) and Cr (VI) but the relative proportions are unknown (U. S. EPA,
1984a).
Because the mineral chromite occurs naturally, chromium can be taken
into the body through air, food, and water exposures. All of these exposure
routes must be taken into consideration in making an estimate of total
chromium uptake.
2.1.1 Noncancer Health Effects
Epidemiologic studies by Bloomfield and Blum (1928), Langard and Norseth
(1979), Seeber et al. (1976), Lindberg and Hedenstierna (1983), and others
reviewed by the World Health Organization (WHO, 1988) and the Agency for Toxic
Substances and Disease Registry (ATSDR, 1989) indicate that perforation of the
nasal septum is the critical noncancer health effect associated with chronic,
low-level exposure to chromium (VI). Lindberg and Hedenstierna (1983) studied
workers in the chrome plating industry who were exposed to "low".chromic acid
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concentrations (8-hour mean below 2 ug/m3) and "high" chromic acid
concentrations (above 2 ug/m3) for an average exposure time of 2.5 years.
Lindberg and Hedenstierna (1983) also studied lung function in chrome plating
workers, and reported that an 8-hour mean exposure level of more than 2 ug/m3
might cause a transient decrease in lung function (WHO, 1988).
On the basis of this study, the World Health Organization (1988)
concluded that long term exposure to doses greater than 1 ug chromium (VI) can
cause nasal irritation, atrophy of the nasal mucosa, and ulceration or
perforation of the nasal septum. This concentration can be considered to be
the unadjusted NOEL for exposure to chromic acid, and 2 ug/m3 can be
considered the LOEL.
The effects of chromium have been studied in animal experiments, with
the chronic studies primarily evaluating chromium's carcinogenic potential.
These experiments are discussed below, and support the finding of
carcinogenicity seen in human occupational studies.
2.1.2 Carcinogenicitv of Chromium
Animal studies have not shown lung cancer resulting from chromium
inhalation exposures, but epidemiologic studies of several chromate production
facilities have shown an association between chromium exposure among workers
and lung cancer. Epidemiology studies conducted in the chrome pigment
industry and the chromium plating industry also have shown an association
between lung cancer and exposure to chromium (Mancuso, 1975; Langard et al.,
1980; Axelsson et al., 1980; and Pokrovskaya and Shabynina, 1973) as cited in
U.S. EPA (1989). These exposures have been to both Cr (III) and Cr (VI), but
animal studies suggest that Cr (VI) rather than Cr (III) causes cancer
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following exposure via other routes (U.S. EPA, 1989), thus implicating Cr (VI)
as the carcinogenic form of chromium. Research is currently underway to
elucidate the issue. Because of the excess cancers seen in chromate
production facilities, chromium (VI) is considered by the EPA's Human Health
Assessment Group (HHAG) to have sufficient evidence for designation as a human
carcinogen. Epidemiologic evidence has been derived from studies in the
United States, Great Britain, Japan, and West Germany.
The HHAG estimated a unit risk number based on the epidemiologic studies
of Mancuso (1975), Langard et al. (1980), Axelsson et al. (1980), and
Pokrovskaya and Shabynina (1973). The Human Health Assessment Group thus
2 3
calculated a unit risk number of 1.2 x 10 /ug/m . This means that if a
person continuously breathes 1 ug/m3 of Cr (VI) for 70 years, the probability
of getting lung cancer would not exceed 1.2 chances in 100. The Integrated
Risk Information System presents the carcinogenic risk levels for chromium
(VI), showing a conservative estimate of lung cancer risk of 1 in 10,000 for a
population exposed continuously to 0.008 ug/m3 Cr(VI) for 70 years.
As mentioned previously, lung cancer has not been observed in animal
assays with Cr (VI). The HHAG's review of the supporting data for
carcinogenicity comes from animal assays in which intramuscular injection site
tumors were seen (Furst et al, 1976; Maltoni, 1974, 1976; Payne, 1960; Hueper
and Payne, 1959), as cited in U.S. EPA (1989). In addition, intrapleural
implant site tumors, intrabronchial implantation site tumors, and subcutaneous
injection site sarcomas have been seen in rats in several studies.
On the basis of the human and animal studies, chromium (VI) is
considered by the EPA to be a Group A carcinogen, with sufficient evidence as
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a human carcinogen and sufficient evidence as an animal carcinogen (U.S. EPA,
1989).
2.1.3 Interaction with Other Compounds
Chromium's carcinogenicity has been tested in laboratory animals
preexposed with virus infections, ionizing radiation, and 20-methyl-
cholanthrene, another known carcinogen (Nettesheim et al., 1970, 1971; Steffee
and Baetjer, 1965; Shimkin and Leiter, 1940). No synergism was detected in
any of the experiments (WHO, 1988).
2.2 MANGANESE
Manganese, like chromium, is present in the earth's crust and is
released to the atmosphere through entrainment of road dusts, wind erosion,
soil disturbances through farming and construction activities, combustion, and
the manufacture of ferroalloys, iron and steel, batteries, and chemical
products (U. S. EPA, 1984b). Exposure can occur from contact with food,
water, and air that contains either naturally occurring or anthropogenically
released manganese. Manganese-containing particles released during the steel
manufacturing process are submicron in size, ranging from 0.5 to 5.0 urn mass
median diameter (U. S. EPA, 1971). Manganese is emitted in the form of the
metal, as trimanganese tetraoxide (Mn304), and as manganese oxide (MnO) during
steel manufacture (U. S. EPA, 1971).
2.2.1 Noncancer Health Effects
Following exposure to manganese particles, deposition is dependent upon
the mass median diameter of the inhaled particles. According to the
Environmental Protection Agency (1984b), 25 to 65% of the particles between 2
and 4 urn are deposited in the alveoli of the lungs, with the remainder
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deposited in the tracheobronchial region. Nearly all of the particles smaller
than 2 urn are deposited in the alveoli. Particles less than 1 urn are likely
to be adsorbed directly into the blood (Task Group on Metal Accumulation,
1973), and the GI tract is the portal of entry for the larger particles (Mena
et al., 1969).
Although manganese has been shown to be necessary for normal growth and
reproduction in laboratory animals, there is no minimum daily requirement for
humans, and no human studies have demonstrated a manganese deficiency.
Chronic occupational exposures to manganese concentrations above
300 ug/m often result in manganism, which predominantly affects the central
nervous system. The symptoms of manganism range from anorexia, insomnia, and
abnormal behavior to severe rigidity, tremors, and autonomic dysfunction
(U. S. EPA, 1984b).
The U.S. Environmental Protection Agency (1984b) examined over ten
epidemiologic studies of workers exposed to several chemical forms of
manganese and particle sizes to determine a NOEL for manganism (Flinn et al.,
1941; Ansola et al., 1944a,b; Rodier, 1955; Schuler et al., 1957; Tanaka and
Lieben, 1969; Emara et al., 1971; Smyth et al., 1973; Suzuki et al., 1973a,b;
Saric et al., 1977; Chandra et al., 1981). The occupations examined were ore
crushing, mining, general industrial, dry-cell battery production,
ferromanganese production, and welding. From review of these studies, the EPA
concluded that the dose-response information was insufficient to establish the
NOEL, but that enough information was available to estimate a LOEL.
Ansola et al. (1944b) and Rodier (1955) concluded that manganism can
develop after a few months of occupational exposure, but most cases are seen
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following several years of exposure. The EPA found that the data identifying
a LOEL below 0.3 mg/m3 (300 ug/m3) were equivocal or inadequate, but the
duration of exposure to this level was not stated, and the chemical form and
the particle sizes of the manganese were not reported in the original studies.
However, the study by Saric et al. (1977) of ferromanganese plant dust and
fumes estimated the duration of exposure to be less than 4 years for 27% of
the study population. A NOEL could not be established because of an inability
to evaluate the early stages of the disease (U. S. EPA, 1984b).
Bronchitis and pneumonitis are the primary pulmonary effects of
manganese, but these effects are thought to be due to particulate matter in
general, rather than manganese specifically (U. S. EPA, 1984b). Pulmonary
effects below 1 mg/m3 are generally reversible. Several reports suggested a
relationship between manganese levels and the rate of pneumonia and other
respiratory ailments in populations living near sources of manganese. The
lowest exposure level where pulmonary effects occurred was reported in a study
of junior high school students exposed to emissions from a ferromanganese
plant in Japan. Nogawa et. al. (1973) studied school children who lived from
50 to 1500 meters from the plant and attended a school that was 100 meters
from the plant. They found a relationship between the distance of the
children's homes and the plant, with those closest to the plant showing a
higher number of cases of "throat swelling and soreness in summer" and a "past
history of pneumonia" (Nogawa et al., 1973). They estimated that more than
1500 meters from the plant, manganese concentrations were negligible, and 300
meters from the plant suspended dust and manganese concentrations were 160
3 3
ug/m and 6.7 ug/m , respectively (Nogawa et al., 1973). Other measurements
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100 meters from the plant indicated dust levels of 299 ug/m and manganese
levels of 4 ug/m3. The U. S. Environmental Protection Agency (1984b)
concluded on the basis of this study that the LOAEL for pulmonary effects for
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exposure to manganese-containing particulate matter is 3-11 ug/m .
Based on the high incidence of pneumonia or other acute respiratory
diseases in many occupational studies (Heine, 1943; Rodier, 1955; Cauvin,
1943; Lloyd-Davies, 1946), the EPA (1984b) concluded that manganese-containing
particulate matter may disturb normal lung clearance mechanisms, thus
increasing susceptibility. Animal studies have been undertaken to investigate
this possibility. Several investigators found that manganese had an effect on
the number and phagocytic activity of alveolar macrophages. Ulrich et al.
(1979a,b,c) found no pulmonary effects, however, in rats and monkeys exposed
to 0.113 mg/m3 (113 ug/m3) Mn304 for 24 hours/day for 9 months, and the EPA
concluded that this level was the highest available animal NOEL. Suzuki et
al. (1978) found positive radiologic findings in monkeys exposed for 10 months
(22 hours/day) to 0.7 mg/m3 Mn02, and the EPA considers this to be the animal
LOAEL.
2.2.2 Carcinogenicitv of Manganese
The U. S. EPA's review of manganese carcinogenicity studies is presented
in IRIS (1989). No evidence exists in the epidemiology studies to support a
claim that manganese is carcinogenic, and the animal data are considered to be
inadequate by the EPA's HHAG. The weight-of-evidence classification for
manganese is that it is a group D compound, not classifiable as to human
carcinogenicity.
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2.2.3 Interaction with Other Compounds
Populations at risk for manganese exposure are those with iron
deficiencies, as an iron deficiency may exacerbate manganese toxicity (Thomson
et al., 1971). Manganese has also been shown to inhibit local sarcoma
induction by benzo(a)pyrene (U. S. EPA, 1984b).
2.3 ZINC
Zinc is found in nature in its salt or oxide form and does not occur
naturally in its elemental form (U. S. EPA, 1987a). Elemental zinc is,
however, used extensively in the galvanizing of iron and steel. Exposure to
zinc may occur via inhalation and ingestion of food and water.
2.3.1 Noncancer Health Effects
The form in which zinc is emitted from steel mills is not known,
therefore the health effects presented here pertain to elemental zinc and zinc
oxide. The primary health effect observed in the occupational settings is
"metal fume fever." It has been reported that this condition exists at zinc
oxide concentrations greater than 15 mg/m3 (Batchelor et al., 1926; Kemper and
Troutman, 1972; Hammond, 1944). Symptoms associated with metal fume fever are
headache, fever, hyperpnea, nausea, sweating, and muscle pain. Metal fume
fever symptoms tend to recur at the beginning of the work week (U. S. EPA,
1987a).
One epidemiologic study has shown that exposure to zinc oxide (0.2 to
5.1 mg/m3) over a 5 year period resulted in increased respiratory effects
(Bobrishchev-Pushkin et al., 1977). These effects included chronic bronchitis
and diffuse pneumosclerosis. In another epidemiologic study, Batchelor et
al., (1926) found slight leukocytosis in 14 of 24 workers at a zinc smelter in
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New Jersey. The smelter workers were exposed to elemental zinc in
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concentrations ranging from 35 to 130 mg/m .
The effects of zinc have been studied in animals to determine its
subchronic toxicity. Pistorius (1976) investigated the effects of inhalation
of zinc oxide particles (less than 1 micron in size) on rat lungs. The only
differences noted in lung function between the controls and exposed animals
were a decrease in specific conductance and difference volume in the exposed
group given 15 mg/m zinc oxide for 1, 4, or 8 hours/day for 84 days. In
another study Pistorius et al. (1976) examined the effect of zinc oxide dust
administered to rats for 4 hours/day, 5 days/week for 1, 14, 28, and 56 days.
Histological examination showed leukocytic inflammatory changes and fluid in
the alveolar region. These inflammatory changes decreased by days 28 and 56.
On the basis of the above epidemiologic and animal studies, the
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unadjusted LOEL for zinc oxide is 0.2 mg/m for humans and 15 mg/nr in
laboratory animals. No data were found from which a NOEL could be determined.
2.3.2 Carcinogenicitv of Zinc
No evidence was found in the literature reviewed to indicate that
inhalation, ingestion, or parenteral administration of zinc induces the
formation of tumors. Based on the EPA carcinogenic classification system,
zinc has a group D weight-of evidence, not classifiable as to human
carcinogenicity. Wai 1 enius et al. (1979) found that 4-nitro-quinoline-n-
oxide-induced cancer of the oral cavity in female rats appeared earlier in
animals ingesting a diet containing 200 mg/kg zinc than animals fed 15 or 50
mg/kg zinc. Another researcher discovered that a zinc-deficient diet (7
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mg/kg) promoted the formation of methylbenzylnitrosamine-induced esophageal
tumors (Fong et al., 1978).
2.3.3 Interaction with Other Compounds
Zinc oxide fumes have been reported to cause hypocalcemia in workers
exposed at a zinc oxide factory (Klucik and Koprda, 1979). The range of
employee exposure was 0.5 to 7.15 mg/m3. Mulhern and co-workers (1986)
reported that excess dietary zinc (2000 ppm zinc/day) produced copper
deficiency in the offspring of C57 BL/GJ mice. The development of alopecia
was also noted in the offspring by five weeks of age.
2.4 COPPER
Copper (Cu) is an essential element that occurs naturally in the +1 and
+2 valence states. The biological availability and toxicity of copper are
thought to be related to free Cu+2 ion activity (U. S. EPA, 1987b). Emissions
of copper occur from natural (windblown dust, volcanoes, vegetation, forest
fires, and sea spray) and anthropogenic sources (Nriagu, 1979). The valence
state of copper emissions from iron and steel production is not known.
2.4.1 Noncancer Health Effects
The primary manifestations of exposure to copper fumes, dusts, or mists
are dermatologic and respiratory symptoms (U. S. EPA, 1987b). "Metal fume
fever" has been reported to occur following exposure to fine copper dusts
(Gleason, 1968), copper fumes (Armstrong et al., 1983), and copper oxide and
copper acetate dusts (Stokinger, 1981; Cohen, 1974). Copper concentrations as
low as 0.1 mg/m are reported to cause this disease (Gleason, 1968).
Human studies have been conducted to determine the chronic effects of
copper exposure. Chronic effects observed for occupational exposure to copper
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include contact dermatitis (Stokinger, 1981; Cohen, 1974; Williams, 1982) and
leukocytosis (Armstrong et al., 1983). Mild anemia was reported by Finelli et
al. (1984) in workers exposed to 0.6 to 1.0 mg/m copper. Enterline and co-
workers (1986) examined the overall mortality of 14,562 workers from the
copper and zinc smelting industries and found no increased mortality.
Plamenac et al. (1985) found that copper sulfate affected the respiratory
epithelium and the pulmonary parenchyma.
In an animal study conducted by Johansson et al. (1984), 0.6 mg/m3
copper chloride administered to rabbits 6 hours/day, 5 days/week for 4 to 6
weeks showed no significant changes in phospholipid content or histological
lesions in the lungs of exposed rabbits. The only significant change observed
was an increase in the number of alveolar type II cells. Another study,
conducted by Lundberg and Camner (1984) and using the same concentrations and
exposure times listed above, resulted in no observed changes in the number of
alveolar macrophages or theJysozyme concentration in lavage fluid.
These data indicate that the unadjusted LOEL for humans exposed to
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copper and laboratory animals exposed to copper chloride is 0.6 mg/m . The
investigations presented do not allow the estimation of a NOEL in either
humans or laboratory animals.
2.4.2 Carcinogenicitv of Copper
There is no available evidence to indicate that copper exposure can
cause cancer (U. S. EPA, 1987b). Studies concerning the carcinogenicity,
mutagenicity, and teratogenicity of inhaled copper or copper compounds could
not be located in the available literature. As a result, the U. S.
14
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Environmental Protection Agency has assigned copper to Group D, not
classifiable as to human carcinogenicity.
2.5 NICKEL
Nickel emitted from steel mills is thought to be in the form of complex
oxides of nickel and other metals (Page, 1983; Koponen et al., 1981). The
following discussion includes any specific information found in the literature
on chronic inhalation studies with nickel oxide. Where these data are
lacking, the general effects of the nickel ion and other nickel compounds are
presented.
2.5.1 Noncancer Health Effects
The direct respiratory effects of nickel compounds include asthma, nasal
septa! perforations, chronic rhinitis, and sinusitis (U. S. EPA, 1986a).
Human exposure information for nickel is derived from occupational studies,
and the literature reviewed contained no specific human data on the
respiratory effects of nickel oxide. Asthma has been seen following working
exposure to nickel carbonyl (Sunderman and Sunderman, 1961), and nickel
sulfate exposure has resulted in septal perforation, chronic rhinitis, and
sinusitis (Kucharin, 1970).
Respiratory effects studies of animals indicate that the nickel ion
affects the viability and phagocytic activity of alveolar macrophages, and
thus may affect resistance to respiratory infection (Graham et al., 1975a,b).
o
Rabbits exposed to 1 mg/m of metallic nickel dust for 3 and 6 months showed
changes in the number and volume of alveolar epithelial cells, and the 6-month
exposure group showed pneumonia (Johansson et al., 1981). Adult Wistar rats
•»
exposed to 25 ug Ni/m for 4 months showed a significant increase in the size
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and number of polynucleated macrophages and a 130% increase in phagocytic
activity (Spiegelberg et al., 1984).
Studies of nickel effects on other systems are not well documented.
Animal studies indicate that the nickel ion may affect carbohydrate metabolism
(U. S. EPA, 1986a). Nickel has been shown to have low neurotoxic potential
(NIOSH, 1977).
On the basis of the studies reviewed by the U. S. EPA (1986a), the
increase in the size and number of polynucleated macrophages and increase in
3
phagocytic activity in rats following 4 months of exposure to 25 ug/m is
estimated to represent the LOEL for exposure to nickel.
2.5.2 Carcinogenicitv of Nickel
None of the three carcinogenic nickel compounds are known to be emitted
from steel mills. These compounds are nickel refinery dust (Group A), nickel
subsulfide (also Group A because it is the major species in refinery dust),
and nickel carbonyl (Group B2, probable human carcinogen). The incremental
unit risk due to lifetime exposure to 1 ug/m3 is 2.4 x 10"4 for nickel
refinery dust and twice that for nickel subsulfide (U. S. EPA, 1986a). The
human evidence for nickel carbonyl's carcinogenicity is equivocal, but the
presence of distal site tumors in animal studies implicate it as a Group B2
carcinogen (U. S. EPA, 1986a). No incremental unit risk has been calculated
for nickel carbonyl.
Some studies indicate that the nickel ion may be the carcinogenic form,
thus implicating all forms of nickel as potential carcinogens. Inhalation
studies of nickel metal do not show the development of respiratory tract
tumors, but one investigation found adenomatoid lung lesions in rats,
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bronchial adenomatoid lesions in guinea pigs, an alveolar anaplastic carcinoma
in one guinea pig lung, and a "metastatic lesion" in another animal (Hueper,
1958). This information (aside from the lack of controls in the guinea pig
study), together with a strong tumor response from intramuscular injection (at
the injection site), lends credence to the possibility that metallic nickel
has limited evidence of carcinogenicity in animals (U. S. EPA, 1986a). Human
epidemiologic studies of workers exposed to nickel metal are confounded by the
presence of other possible carcinogens (U. S. EPA, 1986a).
2.5.3 Interaction with Other Compounds
Waalkes and co-workers (1985) reported that the injection of zinc offset
renal damage and hyperglycemia seen in animals exposed to nickel.
Pretreatment with nickel was shown to offset the effects of cadmium exposure
in rats (Tandon et al., 1984).
2.5.4 Populations at Risk
Populations at special risk to adverse effects from nickel exposure are
those with nickel hypersensitivity, generally from dermal exposures. While
there is no information that nickel exposure of pregnant women leads to
adverse effects, it has been shown that nickel can cross the placental barrier
in animals (Stack et al., 1976).
2.6 CADMIUM
The toxicologic effects of cadmium exposure are important because the
metal tends to accumulate and be retained in soft body tissues (especially in
the kidneys); exposure occurs from ambient air, food, water, and from
cigarette smoking; and the adverse health effects which occur following
17
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exposure are generally irreversible (U. S. EPA, 1981). In addition, cadmium
has been classified as a probable human carcinogen.
2.6.1 Noncancer Health Effects
Deposition following inhalation of cadmium is higher for smaller
particles, and the absorbed cadmium is incorporated into metallothionein and
deposited in the kidney (Task Group on Lung Dynamics, 1966). Chronic cadmium
exposures thus typically result in renal dysfunction, which is the "critical"
noncancer effect following cadmium exposure (Nordberg, 1976). Animal studies
indicate a dose-related progression of kidney damage from early degenerative
proximal tubule changes to interstitial edema and basement membrane fibrosis
(U. S. EPA, 1981). Proteinuria is the biochemical index of renal dysfunction
(U. S. EPA, 1981), and Kjellstrom (1976) estimated that workplace cadmium
o
levels of 50 ug/m increased the incidence of proteinuria in workers exposed
for 10 to 20 years. The EPA (1981) estimated that .industrial exposure for 10
years to cadmium levels of 23 to 25 ug/m would result in renal cadmium levels
sufficient to induce proteinuria.
The chief chronic pulmonary effect of cadmium exposure is centrilobular
emphysema and bronchitis (U. S. EPA, 1981). These effects have been found
following occupational exposure to cadmium-oxide fumes, cadmium-oxide dust,
and cadmium-pigment dust (Friberg et al., 1974). Lung impairment has been
seen in workers exposed to cadmium oxide levels below 100 ug/m , depending on
exposure length (Lauwerys et al., 1974).
Several investigators have found that cadmium exerts immunosuppressive
effects in animal studies (Koller et al. 1975, Cook et al., 1975a,b; Exon et
al., 1975), but these effects have not been demonstrated in humans.
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In order to estimate a NOEL and a LOEL for cadmium inhalation exposure,
exposure from other routes must also be considered because of cadmium's
accumulation and retention within the body. The U. S. EPA (1981) specified a
critical cadmium renal cortex concentration for renal dysfunction, and
assessed the impact of ambient air cadmium exposures taking into account
differing dietary intake levels and smoking status. In general, the EPA
(1981) concluded that ambient levels below 10 ng/m3 do not significantly
increase kidney cortex concentrations of cadmium, but above 100 ng/m3 renal
accumulation begins to occur and 1,000 ng/m3 approaches the critical level for
renal dysfunction. Thus, 10 ng/m3 can be considered the NOEL for cadmium
•3
inhalation exposure, and 100 ng/m the LOEL.
2.6.2 Carcinogenicitv of Cadmium
Cadmium is listed by the EPA's HHAG as a Bl carcinogen (probable human
carcinogen by inhalation). The basis for this classification is limited
evidence from epidemiologic studies and sufficient evidence of carcinogenicity
in two animal species (U.S. EPA, 1989).
Thun and co-workers (1985) studied the incidence of lung cancer among
cadmium smelter workers, and reported a 2-fold excess risk of lung cancer.
Like the other epidemiologic studies of cadmium-exposed workers (Varner, 1983;
Sorahan and Waterhouse, 1983; Armstrong and Kazantzis, 1983), however, the
presence of other carcinogens may have confounded the results. The U. S. EPA
thus considers cadmium to have only limited evidence of human carcinogenicity
(U.S. EPA, 1989).
Evidence of cadmium's carcinogenic potential in animal studies is based
on increased lung tumors in rats exposed to cadmium and cadmium oxide via
19
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inhalation (Takenaka et al., 1983), and injection site tumors in rats and mice
following intramuscular and subcutaneous injection (U.S. EPA, 1989).
On the basis of these results, the EPA calculated a unit risk number of
1.8 x 10~3/ug/m3 for cadmium exposure. Thus, a person exposed continuously to
1 ug/m3 of cadmium-for life has a probability of getting lung cancer of not
more than 1.8 chances in 1000. A conservative estimate is that a lung cancer
risk of 1 in 10,000 would occur at a concentration of 0.06 ug/m3 annual
average cadmium (U.S. EPA, 1989).
2.6.3 Interaction with Other Compounds
Cadmium is affected by or can affect levels of other metals in the body.
A deficiency of zinc increases the toxicity of cadmium, and increased zinc
levels offset cadmium's toxic effects (Choudhury et al., 1977; Pond and
Walker, 1975). Individuals with low iron levels may have a four-fold increase
in cadmium absorption.
2.6.4 Populations at Risk
Populations especially at risk to cadmium exposure are the elderly (due
to its long retention in the body), cigarette smokers, and those whose diets
add high amounts of the metal. The reader should refer to the U. S. EPA
(1981) document for detailed information on the estimated relative
contribution of cadmium through diet, smoking, and ambient air exposures.
2.7 VANADIUM
Vanadium is a naturally occurring metal that is widely distributed in
small amounts in the earth's crust. It is also found in trace amounts in
fossil fuels (U. S. EPA, 1987c). Vanadium in the air is believed to be solely
a result of industrial processes. The oxidation states of vanadium are +2,
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+3, -1-4 and +5 (NLM, 1986). It could not be determined which species of
vanadium are emitted from steel mills. The following discussion is focused
primarily on the effects of vanadium pentoxide exposure because the literature
contains little to no other information concerning inhalation exposures to
vanadium or its salts.
2.7.1 Noncancer Health Effects
The chronic effects of various vanadium compounds have been studied in
man with most reporting only minor irritations of the respiratory tract.
Sjoberg (1950) evaluated 36 workers exposed to vanadium pentoxide (0.05-5.58
mg/rrr) at a vanadium processing plant in Sweden. Severe respiratory
irritation was the most common manifestation found in the workers, whom the
study followed for a two year period. In a study by Lewis (1959), 24 men
exposed to vanadium pentoxide concentrations ranging from 0.018 to 0.38 mg/m
had an increased incidence of respiratory distress (cough, bronchospasm,
pulmonary congestion). The average duration of worker exposure was 2.5 years
and the author concluded that there were no permanent effects from chronic
vanadium exposure. Other chronic manifestations reported in the literature
include conjunctivitis, tracheobronchitis, and contact dermatitis (Tebrock and
Machle, 1968; Symanski, 1939).
Subchronic effects resulting from relatively high concentrations of
vanadium have also been reported. A number of studies have documented the
development of respiratory symptoms (wheezing, coughing,, dyspnea) after
exposure to high concentrations of vanadium over short time periods (Musk and
Tees, 1982; Zenz et al., 1962; McTurk et al., 1956). Zenz and Berg (1967)
exposed 2 volunteers to 1 mg/m vanadium pentoxide for 8 hours and reported
21
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the presence of persistent cough in both. These investigators also exposed 5
other volunteers to 0.2 mg/m3 of vanadium pentoxide for 8 hours and reported
the development of a cough that lasted from 7 to 10 days. The unadjusted LOEL
•a
based upon the above human studies would be 0.018 mg/nr for vanadium
pentoxide. A NOEL could not be determined from the data.
2.7.2 Carcinogenicitv of Vanadium
The available literature on vanadium is not sufficient to evaluate its
carcinogenicity in laboratory animals or man. As a result, EPA has classified
vanadium a Group D carcinogen, not classifiable as to carcinogenic potential.
2.7.3 Interaction with Other Compounds
Vanadyl sulfate (25 ppm) has been found to inhibit the carcinogenic
effects of 1-methyl-1-nitrosourea in rats (Dimond et al., 1963). In terms of
antidotes, ascorbic acid and ethylenediaminetetraacetate were effective in
sequestering vanadium poisoning in mice, rats and dogs (Mitchell and Floyd,
1954).. .
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3.0 HEALTH EFFECTS OF OTHER COMPOUNDS EMITTED FROM STEEL MILLS
3.1 AMMONIA AND AMMONIUM SULFATE
This section discusses the health effects associated with exposure to
ammonia and ammonium sulfate. Both of these compounds are known to be emitted
from steel mill operations (Barnard, 1989).
3.1.1 Noncancer Health Effects
Exposure to ammonia will cause rapid increases in blood ammonia concen-
trations, as it is readily absorbed through the lungs (U. S. EPA, 1988). The
U. S. Environmental Protection Agency (1986b) reported that no adequate animal
studies with chronic exposures were found in the literature. Similarly, the
available human chronic exposure information is limited. The available
subchronic animal information and the human exposure information as presented
by the EPA (1988) are summarized below.
The National Research Council (1977) reported the average odor threshold
for ammonia to be 5 ppm (3.5 mg/m ). Continuous exposure to ammonia may cause
an increase in the occurrence or severity of respiratory tract infections
(National Research Council, 1977). Retention of ammonia in the respiratory
tract is about 80 percent for humans (not dose-related) (Silverman et al.,
1949).
No clinically significant effects were seen in one study of rats, guinea
pigs, rabbits, dogs, or monkeys exposed continuously to 57 ppm (40 mg/m3)
ammonia for 114 days (Coon et al., 1970). Mice and guinea pigs exposed to 20
2
ppm (14 mg/m ) for 28 days also showed no effect (Anderson et al., 1964), but
no exposure time was given. However, when exposure duration was increased to
42 days or concentration was increased to 50 ppm (35 mg/m3), pulmonary edema,
23
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congestion, and hemorrhage occurred (Anderson et al., 1964). These studies
considered the lowest observed effect levels (14 mg/m3 for 42 days and 35
mg/m for 28 days) and the no observed effect level (14 mg/m3 for 28 days) as
presented by the U. S. EPA (1986b). The limited data available and the fact
that these studies are based on subchronic rather than chronic exposures make
it difficult to conclude that these are the true NOELs and LOELs.
Chronic exposure to humans at 30 mg/m3 ammonia caused headaches, nausea,
and reduced appetite (National Research Council, 1977), but again no averaging
time was reported. Repeated exposure to 17, 35, or 69 mg/m3 for 6 hours per
day per week, for 6 weeks showed no changes in respiratory rate, blood
pressure, pulse, or forced vital capacity, but mild eye irritation occurred in
the early sessions (Ferguson et al., 1977).
In its review of the health effects of acid aerosol exposure, EPA found
that most of the studies of acid aerosols involve sulfuric acid, but some
effects of ammonium sulfate [(NH4)2S04] can be inferred from these studies
(U.S. EPA, 1988). Most of the studies of acid aerosol exposure to humans do
not involve ammonium sulfate, and the only studies described by the
Environmental Protection Agency (1988) involved short exposure durations. One
study showed no effects in asthmatic and normal human subjects exposed to up
•j
to 1.0 mg/nr (0.5-1.0 mass median aerodynamic diameter, MMAD) for 16 minutes
(Utell et al., 1982).
The LOAEL based on animal studies reviewed by the Environmental
Protection Agency (1988) was determined from a study by Godleski et al. (1984)
in which emphysemic lesions were seen in hamsters exposed to 187 ug/m3 (0.187
mg/m3) (NH4)2S04 (0.3 MMAD) for 6 hours per day, 5 days per week, for
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15 weeks. Busch et al. (1984) found interstitial thickening in rats and
guinea pigs exposed to 1.03 mg/m3 (NH4)2S04 (0.42 MMAD) for 6 hours/day, 5
days/week, for 20 days. Other studies of ammonium sulfate exposure were based
*j
on short term exposures (usually 1 hour) to 0.4 to 9.54 mg/m (Amdur et al.,
1978; Loscutoff et al., 1985; Schlesinger et al, 1978).
3.1.2 Carcinogenicitv of Ammonia and Ammonium sulfate
No inhalation information is available to assess the carcinogenicity of
ammonia, but it has been shown to be noncarcinogenic in mice following oral
administration (Toth, 1972; Uzvolgi and Bojan, 1980). The EPA's HHAG
considers ammonia a group D compound, with insufficient evidence to judge its
carcinogenic potential in humans. No discussion of ammonium sulfate's
carcinogenic potential is provided by the Environmental Protection Agency
(1988), and this pollutant is not currently included in the IRIS data base.
3.1.3 Interaction with Other Compounds
The effect of ammonium sulfate exposure in conjunction with exposure to
other pollutants has been examined. Exposure to 2.6 mg/m3 S02 and 528 ug/m3
(NH4)2S04 in human subjects for 4 hours showed upper airway irritation in 9 of
20 subjects, as compared to 4 of 20 subjects receiving S02 exposure only
(Kulle et al., 1984). Acid aerosols of ammonia have also been shown to
provide short-term protection (up to 6 months) against benzo(a)pyrene-induced
tumors (Godleski et al., 1984).
3.2 HYDROGEN CHLORIDE
Hydrogen chloride (hydrochloric acid) is an acutely toxic gas because it
is highly soluble in water, and the resulting hydronium ion is reactive with
organic molecules and causes cellular injury and necrosis (U. S. EPA, 1987d).
25
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The World Health Organization (WHO, 1982) reports a threshold for odor
perception of 0.2 ppm (0.3 mg/nr), but other reports range from 0.1 to 459
mg/m3 (U. S. EPA, 1987d).
3.2.1 Noncancer Health Effects
There are little chronic or subchronic inhalation data available for
hydrogen chloride in the literature. One subchronic study of guinea pigs
exposed to 0.15 mg/m hydrogen chloride for 2 hours/day for 28 days showed no
effect (Kirch and Drabke, 1982). Guinea pigs exposed to 15 mg/m3 for 2
hours/day, 5 days/week for 49 days showed no differences in lung function
compared to controls (Oddoy et al., 1982).
The only chronic study of hydrogen chloride exposure evaluated the
effects of inhalation of 15 mg/m on Sprague-Dawley rats exposed for 6
hours/day, 5 days/week for life (Albert et al., 1982). Nasal mucosa lesions
found at autopsy included rhinitis, epithelial or squamous hyperplasia, and
squamous metaplasia. Because of the limited data available, 15 mg/m hydrogen
chloride can be considered the LOAEL, and a NOAEL of 0.15 mg/m3 can be
estimated from the subchronic hamster study of Kirche and Drabke (1982).
3.2.2 Carcinogenicitv of Hydrogen chloride
There are no adequate epidemiologic or animal carcinogenicity studies of
hydrogen chloride, thus it is classified as a Group D carcinogen.
3.3 TOLUENE
Toluene, another compound that may be emitted during the steel -
manufacturing process, has its primary effects on the central nervous system,
with occupational studies reporting symptoms of headache, dizziness, fatigue
and feelings of intoxication among those exposed. Gusev (1965) estimated the
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minimum toluene odor threshold to be 0.40 to 0.85 ppm (1.5 to 3.2 mg/m3). May
(1966), however, found the minimum odor threshold to be 37 ppm (140 mg/m3).
3.3.1 Noncancer Health Effects
Several investigators (Anderson et al., 1983; Baelum et al., 1985; Ogato
et al., 1970; von Oettingen et al., 1942) evaluated the effects of toluene in
workers exposed for 1 day to concentrations of 0, 10, 40, 100, and 200 parts
per million (ppm). At 100 ppm (377 mg/m3), nasal and eye irritation,
headache, dizziness, and intoxication were reported among those exposed for 6
hours (Andersen et al., 1983). Groups exposed for 6 hours to 10 and 40 ppm
(38 and 151 mg/m3) reported no effects. Baelum and co-workers (1985) also
found neurotoxic effects in workers (with a history of toluene exposure)
exposed to 100 ppm for 6.5 hours.
Ogata and co-workers (1970) examined subjects exposed to 200 ppm (754
mg/m3) for 7 hours and found prolongation of reaction time and decreased pulse
rate. Dr. von Oettingen et al. (1942) reported that muscular weakness,
confusion, and impaired coordination occurred following exposure to 200 ppm
for 8 hours, and at 100 ppm moderate fatigue and headache occurred. Wilson
(1943) reported headaches and lassitude among humans exposed for 1 to 3 weeks
to 50 and
100 ppm toluene.
On the basis of these 1-day occupational studies, it can be concluded
that the LOAEL for toluene exposure is 100 ppm (377 mg/m3) and the NOAEL is 40
ppm (151 mg/m ). This information has strong support even though the studies
are based on one-day exposure periods. This support includes longer-term
animal studies such as those of the American Petroleum Institute (1980),
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Gibson and Hardisty (1983), Kyrklund et al. (1987), and Okeda et al. (1986).
The American Petroleum Institute (1980) conducted a chronic rat study for 26
weeks with exposure levels of 0, 100, and 1500 ppm for 6 hr/day, 5 days/week.
The LOAEL for this study was 100 ppm. Gibson and Hardisty (1983) exposed "rats
to 0, 30, 100 and 300 ppm for 6 hr/day, 5 days/week for up to 24 months, and
reported a LOEL of 100 ppm.
3.3.2 Carcinogenicitv of Toluene
Toluene's carcinogenic potential has been evaluated by the National
Toxicology Program (U. S. DHHS, 1989). Toxicology and carcinogenesis studies
in rats and mice exposed to toluene by inhalation for 15 or 24 months (0, 600,
and 1200 ppm) indicated no evidence of carcinogenicity (U. S. DHHS, 1989).
The Chemical Industry Institute of Toxicology (1980) also concluded that
exposure to toluene levels of 30, 100 and 300 ppm for 24 months did not
implicate toluene as a carcinogen. As a result, the U. S. Environmental
Protection Agency has assigned toluene to Group D, not classifiable as to
human carcinogenicity.
3.4 BENZENE
Benzene is an aromatic hydrogen that is slightly soluble in water. Once
a widely used solvent, benzene can produce narcotic effects similar to those
of toluene. Of most concern, however, are the hematotoxic effects of benzene.
3.4.1 Noncancer Health Effects
Deichmann and co-workers (1963) studied the effects of subchronic
benzene inhalation exposure in rats at concentrations ranging from 15 to 83
ppm (48 to 2600 mg/m3). Groups exposed to 47 and 44 ppm (150 and 140 mg/m3)
for 7 hours/day, 5 days/week for 8 weeks or more showed siight or moderate
28
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leukopenia. Groups exposed to < 31 ppm (99 mg/m3) showed no effects, and this
level is reported by the EPA (1984c) to be the NOEL for leukopenia in rats.
Chronic mouse inhalation studies conducted by Snyder et al. (1980)
revealed marked lymphocytopenia, slight anemia, and bone marrow hypoplasia in
mice exposed to 100 ppm (320 mg/m ) benzene for 6 hours/day, 5 days/week for
life. Chronic human exposure to benzene may cause pancytopenia (a reduction
in blood erythrocytes, leucocytes, and thrombocytes)(U. S. EPA, 1984c). Mild
cases of anemia, leukopenia, and thrombocytopenia are generally reversible if
exposure is ceased. Studies by NIOSH (1974) indicate that the lowest limit of
hematologic effects in humans is less than 100 ppm (Hardy and Elkins, 1948;
Pagnotto et al., 1961). Elkins (1976) and Pagnotto et al. (1977) conclude
that a benzene level of 25 ppm (80 mg/m3) is safe for most workers.
3.4.2 Carcinogenicitv of Benzene
There is substantial evidence from epidemiologic studies that benzene
causes leukemia (U. S. EPA, 1985). Benzene is thus a Group A known human
carcinogen. Animal studies have not demonstrated this effect, however.
Epidemiologic studies by Pinsky et al. (1981), Ott et al. (1978), and Wong et
al. (1983) were reviewed by the U. S. EPA (1985) in order to prepare an
inhalation unit risk estimate of 8.3 x 10~6/iig/ni3 for benzene. This can be
translated to indicate that a person's risk of getting lung cancer, following
continuous lifetime (70 years) exposure to 1 ug/m3 of benzene will not exceed
8.3 chances in one million.
3.4.3 Interaction with Other Compounds
The metabolism and toxicity of benzene can be affected by the presence
of other solvents that are oxidized by the same hepatic enzymes (Ikeda et al.,
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1972). These solvents include xylene and toluene. The inability of benzene
alone to induce leukemia in experimental animals has lead some researchers to
hypothesize that the hematotoxic effects seen in humans are actually the
result of exposure to benzene along with other solvents. (Andrews et al.,
1977; U. S. EPA, 1980).
3.5 NAPHTHALENE
Naphthalene is an aromatic hydrocarbon that can be released to the
ambient environment either in a gaseous or particulate form. While airborne,
naphthalene will undergo photochemical degradation and has a half-life of
eight hours during sunlight hours. At night, it has been estimated that
naphthalene has a half-life of 15 hours as a result of reaction with nitrate
radicals (U. S. EPA, 1987e).
3.5.1 Noncancer Health Effects
The health effects associated with inhalation exposure to naphthalene
have not been well documented in either humans or laboratory animals (U. S.
EPA, 1987e). Cataracts have been found to develop in individuals exposed to
naphthalene by the oral, dermal, and inhalation routes (U. S. EPA, 1980).
Naphthalene exposure in the occupational setting also has resulted in cataract
development (Ghetti and Mariani, 1956; Hollowich et al., 1975). Acute effects
of naphthalene exposure have been reported in humans, the most common
manifestation being acute hemolytic anemia. Investigators have described
incidences where acute hemolytic anemia has developed after combined dermal
absorption and inhalation of naphthalene vapors by neonates (Grigor et al.,
1966) and adults (Younis et al., 1957), and inhalation of naphthalene vapors
alone by neonates (Hanssler, 1964) and adults (Linick, 1983). The
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concentration of the naphthalene in the above cases was not reported in the
literature due to the poorly defined nature of the exposure.
Few studies have been conducted on laboratory animals to determine the
effect of naphthalene exposure. An 8-hour Median Lethal Concentration (LCc0)
o
value of 180 ppm (940 mg/m ) for naphthalene in laboratory animals was
reported by Union Carbide (1968). However, Buckpitt (1985) suggests that this
value may be too low based on the oral and intraperitoneal Median Lethal Dose
(LD50) values. Male and female Wistar rats exposed to 78 ppm (408 mg/m3)
naphthalene for 4 hours resulted in no mortalities, nor any lung, liver,
kidney or nasal passage abnormalities (Fait and Nachreiner, 1985). This
value, 78 ppm naphthalene, could be considered the unadjusted NOEL in
laboratory animals. In an unpublished inhalation study by Buckpitt (1985),
male Swiss-Webster mice were exposed to 90 ppm (470 mg/m3) naphthalene for 4
hours without any resulting mortalities. The researcher did note the
development of prominent lesions in the lungs of the exposed mice, however.
This value reported by Buckpitt, 90 ppm naphthalene, is the unadjusted LOEL in
laboratory animals.
3.5.2 Carcinogenicitv of Naphthalene
Because of the lack of definitive data, naphthalene is classified as a
Group D carcinogen. The available evidence is inadequate to evaluate the
carcinogenic potential of naphthalene in man.
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4.0 HEALTH EFFECTS OF COMPLEX MIXTURES
Sections 2.0 and 3.0 of this report presented health effects information
for individual pollutants that comprise steel mill emissions. This section
discusses the effects of mixtures known to be emitted during steel
manufacture. Polycyclic organic matter is one such mixture, and denotes many
chemical groups, including polycyclic aromatic hydrocarbons, aza-, imino-, and
carbonyl-arenes, and polychloro compounds, among others.
The coke oven emission mixture includes not only polycyclic organic
matter, but also includes many of the individual pollutants discussed in
Sections 2.0 and 3.0. These pollutants include cadmium, chromium, nickel,
ammonia, toluene, and benzene.
4.1 POLYCYCLIC ORGANIC MATTER
Polycyclic organic matter (POM) is a mixture of many groups of compounds
commonly formed in combustion or high temperature processes involving carbon
and hydrogen (Santodonato et al., 1979). The two POM groups most commonly
detected in ambient air are polycyclic aromatic hydrocarbons (PAH) and PAH
nitrogen analogs (aza- and imino- arenes). Polycyclic organic matter is
generally present in the atmosphere as particulate matter or attached to
particulate matter.
4.1.1 Noncancer Health Effects
Benzo(a)pyrene (BaP) is the best known and most studied PAH, and much of
the POM health effects knowledge is derived from BaP studies. The major
health-related effects of POM inhalation involve local lesions of the
respiratory tract (Santodonato et al., 1979). Particle size of the POM or POM
carrier is very important in determining deposition, cellular reactions, and
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clearance of inhaled POM. Mucociliary clearance plays an important role in
the reactivity and clearance of POM. Scala (1975) has shown that irritants
that inhibit ciliary activity can increase the length of time POM is present
in the tracheobronchial tract, thus increasing the potential to form reactive
electrophiles. These reactive electrophiles are capable of interacting with
cellular constituents such as RNA, DNA, and proteins, which can lead to the
formation of tumors (Lehr et al., 1978). This process will be covered in more
detail in Section 4.1.2. Tumor formation is also possible due to particles
that are cleared via mucociliary activity, swallowed, and absorbed through the
gastrointestinal tract (Santodonato et al., 1979)
There is little information in the literature on the noncancer health
effects of POM. Several POM are known to be noncarcinogens (i.e.,
benzo(e)pyrene, anthracene). Several POM have been shown to be
immunosuppressives (Malmgren et al., 1952), but immunosuppression is thought
to be correlated with carcinogenic potency (Baldwin, 1973). Benzo(e)pyrene
and anthracene show no immunosuppression.
Other noncancer effects occur associated with exposure to carcinogenic
POM. Gross and co-workers (1965) administered 100 ug of 7-12
dimethylbenz(a)anthracene (DMBA) or BaP via intratracheal application to
hamsters for 4 to 16 months that resulted in acute pneumonia and chronic
pneumonitis.
Because of the complexity of the POM mixture and the lack of noncancer
data in the literature, it is not possible to delineate NOEL or LOEL values.
It is thought, however, that the noncarcinogenic effects of POM will occur at
the same dose levels that induce tumor formation.
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4.1.2 Carcinoaenicitv of Polvcvclic Organic Matter
There is little quantitative cancer data available for POM. Most of the
information available concerns PAH compounds. Benzo(a)pyrene,
benz(a)anthracene, dibenzo(a,h)pyrene, dibenz(a,h)anthracene, and
dibenzo(a,i)pyrene are considered animal carcinogens. Benzo(a)pyrene and
dibenz(a,h)anthracene are complete carcinogens (capable of initiation and
promotion), and have similar carcinogenic potency (Santodonato et al., 1979).
Benz(a)anthracene, dibenzo(a,i)pyrene, and dibenzo(a,h)pyrene are weaker
carcinogens (Santodonato et al., 1979).
Benzo(a)pyrene is the only POM included in IRIS with quantitative
carcinogenic information, and it is classified as a Bl probable human
carcinogen (U.S. EPA, 1989). The human data are inadequate to judge BaP's
ability to induce cancer because BaP cannot be delineated as the cancer
causing agent in studies of cigarette smoke, roofing tar, and coke oven
emission exposures.
Benzo(a)pyrene has sufficient evidence as an animal carcinogen, with
subcutaneous, intramuscular, intratracheal, and oral administration resulting
in tumors in mice, rats, rabbits, and hamsters (U.S. EPA, 1989). Inhalation
of BaP at concentrations of 2.2, 9.5, and 45 mg/m3 for up to 24 months in
hamsters resulted in respiratory tract tumors in the groups exposed to 9.5 and
45 mg/m3 (Thyssen et al., 1981). Based on this study, the unit risk number
for BaP is calculated to be 1.7 x 10"3/ug/m3.
4.2 COKE OVEN EMISSIONS
Coke is used primarily in the steel industry's blast furnaces to
generate iron which is subsequently refined into steel (U. S. EPA, 1984d).
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During the production of coke, chemically-complex emissions are released which
consist of gases and respirable particulate matter. An extensive list of
these emissions can be found in the EPA document "Carcinogen Assessment of
Coke Oven Emissions" (U. S. EPA, 1984d).
4.2.1 Noncancer Health Effects
The available literature on the effects of coke oven emissions focuses
on coal tar, which results from the condensation of coke oven emissions.
Kinkead (1973) exposed Sprague-Dawley yearling rats, Sprague-Dawley weanling
rats, ICR mice, and CAF-1 mice to an aerosol of coal tar continuously for 90
days at concentrations of 0.2, 2.0, and 10 mg/m3. The result was a high
degree of mortality among the exposed animals attributable to general
debilitation resulting in greater chance of infection. A high incidence of
chronic murine pneumonia was observed in all species studied (Kinkead, 1973).
In another study, MacEwen and co-workers (1976) investigated the effect
of a coal tar mixture collected from multiple coke ovens in the greater
Pittsburgh area. ICR-CF-1 mice, CAF-1-JAX mice, weanling Sprague-Dawley rats,
New Zealand white rabbits, and Macaca mullata monkeys were exposed to a coal
tar aerosol at 10 mg/m3, 6 hour/day, 5 days/week, for 18 months.
The investigators reported a significant inhibition of body growth rate in the
rabbits after 1 month and in the rats after 4 months. None of the monkeys
showed significant inhibition of growth (MacEwen et al., 1976).
On the basis of these animal studies, an unadjusted LOAEL of 0.2 mg/m3
can be estimated for exposure to coke oven emissions (coal tar).
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4.2.2 Carcinogenicitv of Coke Oven Emissions
A large body of literature exists concerning the carcinogenic activity
of coke oven emissions in humans. In a review of the available epidemiologic
literature by the U. S. EPA (1984d), it was concluded that exposure to coke
oven emissions increases the risk of lung, tracheal, bronchial, kidney, and
prostrate cancer, as well as cancer at all sites combined. Redmond et al.
(1972, 1976, 1979) conducted a number of epidemiologic studies to determine if
coke oven emissions result in increased cancer risk. In the 1979 study this
group found a significant excess of lung, trachea, and bronchus cancer
mortality in coke oven workers. The investigation also showed an increase in
prostate and kidney cancer (Redmond et al., 1979). Lloyd (1971) found an
increase in death from respiratory neoplasms and an increase in mortality from
all causes in steelworkers employed in 1953 in the coke plants of two
Allegheny County, Pennylvania steel mills.
Animal models have also been used to assess the carcinogenic potential
of coal tar. C3H mice were exposed to 0.30 mg/1iter coal tar aerosol for 2-
hour periods, 3 times a week for up to 36 weeks (Morton et al., 1963). Six of
the 33 mice tested developed squamous cell tumors in the periphery of the
lung. Tye and Stemmer (1967) studied the carcinogenic effects of different
fractions of coal tar in male C3H/HeJ mice. The mice were exposed to 0.20
mg/1iter for 2 hours every 3 weeks during the first 8 weeks, but, because so
many mice died during this time period, the concentration was reduced to 0.12
mg/1iter for the remainder of the experiment (55 weeks). Upon histological
examination, adenomas and adenocarcinomas of the lung were observed in 60 to
36
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100% of the mice inhaling aerosols of coal tars while control mice developed
no observable tumors.
The available epidemiologic and animal data overwhelmingly prove that
coke oven emissions are carcinogenic in man and experimental animals. Three
separate organizations have classified the coke oven emission mixture as a
known human carcinogen. The U. S. EPA lists coke oven emissions as a Group A
carcinogen; the International Agency for Cancer Research groups coke oven
emissions into category 1; and the National Toxicology Program also classifies
coke oven emissions as a known human carcinogen. The EPA's unit risk number
for coke oven emissions, based on lifetime continuous exposure to 1 ug/m3
Benzene Soluble Organics (BSO), is 6.2 x 10"4/ug/m3, based on epidemiologic
studies of steelworkers exposed to coke oven emissions for up to 15 years.
37
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