&EPA
united States
Environmental Protection
Agency
Office of Pesticides
and Toxic Substances
Washington, DC 20460
EPA-560/2-81-002
May 1981
Toxic Substances
Assessment of
Testing Needs:
Nitrobenzene
Support Document
Proposed Health and
Environmental Effects
Test Rule
Section 4
Toxic Substances
Control Act
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ASSESSMENT OF TESTING NEEDS:
NITROBENZENE
PROPOSED
SUPPORT DOCUMENT
HEALTH AND ENVIRONMENTAL EFFECTS
TOXIC SUBSTANCES CONTROL ACT
SECTION 4
EPA 560/2-81-002
MAY 1981
TEST RULE
ASSESSMENT DIVISION
OFFICE OF TOXIC SUBSTANCES
washington, D.C. 20460
U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF PESTICIDES AND TOXIC SUBSTANCES
Washington, D.C. 20460
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TABLE OF CONTENTS
1.
Introduction and Summary of Proposed Testing... ....... 1
2.
Production and Release................................ 5
3 .
Environmental Exposure................................ 9
4.
Section 4 (a)(1)(B)(i) Finding........................12
5 .
Sufficiency of Data and Recommended
Testing - Environmental Effects...................... .12
6.
Sufficiency of Data and Recommended
Testing - Chemical Fate.............................. .16
7.
H uma n Expo s ur e. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 7
7.1. Occupational
7.2 Consumer
7.3 General Population
8.
Sect ion 4 ( a) (1) (A) (i) Find i ng. . . . . . . . . . . . . . . . . . . . . . . . . 2 1
9.
Sufficiency of Data and Recommended
Testing - Health Effects. .............................21
9.1
9.2
9.3
9.4
9.5
9.6
9.7
9.8
9.9
Acute Effects
Subchronic Effects
Chronic Effects
Neurotoxicity/Behavioral
Reproduction
Teratogenic Effects
Mutagenicity
Oncogenic Effects
Epidemiology
Toxici ty
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26
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1 .
INTRODUCTION AND SUMMARY OF PROPOSED TESTING
Nitrobenzene (C6H5N02; CAS No 98-95-3), also named
nitrobenzol and oil of mirbane (Merck Index, 1976), is a pale
yellow. oily liquid at standard temperature and pressure with a
characteristic bitter almond odor and a sweet taste.
Approximately ninety-seven percent of the nitrobenzene produced
is used to produce aniline while the remaining three percent has
various dispersive uses such as a selective solvent and in the
production of other chemical products.
The Interagency Testing Committee (ITC). charged under
Section 4(e) of the Toxic Substances Control Act (TSCA) with
making priority testing recommendations to the Environmental
Protection Agency (EPA). r~commended that nitrobenzene be tested
for carcinogenicity, mutagenicity, and environmental effects.
EPA is proposing testing requirements for nitrobenzene under
Section 4(a)(1) (A) and ~4(a)(1) (B) of TSCA. In making the
~4(a)(1)(A) finding to require health effects testing, the Agency
has determined that the manufacture, distribution in commerce,
processing, use or disposal of nitrobenzene may present an
unreasonable risk of injury to human health. The Agency also
finds that there are insufficient data and experience upon which
the health effects can reasonably be determined or predicted, and
that testing is necessary to develop such data.
EPA also is proposing testing for environmental effects
under Section 4(a)(1) (B) of TSCA because nitrobenzene is produced
in large quantities and is believed to enter the environment in
substantial quantities. Further, the Agency believes' that there
are insufficient data upon which effects of nitrobenzene on the
environment can reasonably be determined and that testing is
necessary to develop these data.
The testing the Agency is proposing for nitrobenzene is
summarized in the following table along with EPA's conclusions as
to other effects not covered by this proposal.
The initial discussions in this document deal with the
production and exposure factors and the environmental
compartments in which releases of nitrobenzene are located. The
Section 4(a) (l)(B) finding follows these discussions. The
document then discusses human-related exposure factors and health
effects and the Section 4 (a)(l) (A) (i) finding is presented.
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Summary of Recommended Testing
HEALTH EFFECTS-Based on
4(a)(1))(A) finding
Testing Recommended
by the ITC
Disposition of
Testing
Reproductive effects
Neurotoxicity/
Behavioral Toxicity
Teratogenicity
Epidemiology
Subchronic
Carcinogenicity
Mutagenicity
Not proposede
Not proposedc
(Higher tier tests
will be proposed in
subsequent rule-
making if necessary)
Proposed
Not Proposed f
Proposed
Not proposed~
Not Proposed
ENVIRONMENTAL EFFECTS
OF CONCERN - Based on
on 4 (a)(l)(B) finding
Testing Recommended
by the ITC
Disposition of
Testing
Aquatic vertebrates
acute
freshwater coldwater
freshwater warmwater
saltwater coldwater
saltwater warmwater
chronic
freshwater coldwater
freshwater warmwater
saltwater coldwater
saltwater warmwater
Aquatic invertebrates
acute
freshwater
saltwater
chronic
freshwater
saltwater
Environmental
Effects
Proposed
Not Proposeda
Not Proposedc
Not Proposeda
Proposed
Proposed
Not Proposedc
Proposed
Not Proposeda
Not Proposeda
Proposed
Proposed
-2-
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Summary of Testing Decisions
(Continued)
Effects of
Concern
Testing Recommended
ITC
Disposition of
Testing
Aquatic plants
algae
freshwa t_er
saltwat.er
Not proposeda
Not Proposeda
vascular
freshwater
saltwat_er
Not Proposedc
Not. Proposedc
Birds
acute
t.errestrial
wat.erfowl
Propos ed
Proposed
chronic
terrestrial
waterfowl
Propos ed
Proposed
Mammals
acute
chronic
Not Proposeda
Not Proposeda
(Data needs
satisfied by
acute and chronic
human health tests)
Terrestrial invertebrat.es
Not Proposedc
Terrestrial plants
seed germination/root
elonga t.ion
early seedling growth
full life cycle
Propos ed
Proposed
Not proposedc
Bioconcentration
aquatic vertebrate
aquatic benthic invertebrate
terrestrial plant
Not Proposeda
Not Proposeda
Propos ed
-3-
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Summary of Testing Decisions
(Continued)
Effects of
Concern
Testing Recommended
ITC
Disposition of
Tes ting
Alteration of microorganism function
Ecosystem effects
Not Propos ed c
Not Proposedc
Chemical Fate
Persistence
Transport
Proposed
Not Proposedc
a Adequate information already available
bThese data will be obtained from other testing
~Agency will conduct this testing
No suitable cohort identified
eTesting will be performed by N.T.P.
fTest standards not available
results
-4-
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2 .
PRODUCTION AND RELEASE
2 .1.
Production Volumes
Total domestic production of nitrobenzene was reported by
the U.S. International Trade Commission (USITC) to be 575.5
million pounds*(261 million kilograms) in 1978. This estimate,
based on production of nitrobenzene, differs from estimates based
on nitrobenzene requirements in aniline production. These data
have nitrobenzene production at 848 million pounds (385.5 million
kg) for a comparable time period (Moleski et al., 1980). The
USITC reported 1979 production to be 952.4 million pounds (433
million kilograms) (US lTC, 1980).
Table 2-1 lists Stanford Research Institute International's
estimates of producers' annual capacities (SRI, 1980) and 1977
production volumes as reported to EPA's Chemicals in Commerce
Information System (CICIS) (USEPA, 1980b).
According to the non-confidential CICIS file, Ungerer and
Company, BASF Wyandotte Corp., American Cyanamid Company and
Cresent Chemical Company are all importers of nitrobenzene but
only Ungerer and Company reported importation activity (1,000-
10,000 Ibs.; 455-4,545 kilograms) for 1977. The other companies
showed no importation or manufacturing activity for 1977 (USEPA,
1980b).
Nitrobenzene production and demand is tied 1:0 the
requirements for aniline and other compounds derived from
nitrobenzene including isocyanates, rubber, dyes, hydroquinone,
pes1:icides, and drugs. The Chemical Marketing Reporter (1977)
estimated U.S. demand in 1980 at 1,150 million pounds (based on
aniline production requirements) and estimated the growth rate at
8.5 percent per year.
*
Based on reported aniline demand since 1970, MOleski et al.,
suggested that this figure underestimated annual
production. Assuming that 1.4 pounds of nitrobenzene are
consumed per pound of aniline produced, Moleski estima1:ed
that 848 million pounds of nitrobenzene were produced in the
U.S. during 1978.
-5-
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TABLE 2-1 - PRODUCTION CAPACITIES AND REPORTED PRODUCTION VOLUMES
(millions of pounds: millions of kilograms noted in parentheses)
Allied, Moundsville, WV
American Cyanamid
Bound Brook, NJ
Willow Island, WV
DuPont
Beaumont, TX
Gibbstown, NJ
Fi rs t Chemical,
Pascagoula, MS
Mobay, New Martinsville WV
Monsanto, Sauget, IL
Rubicon, Geismar, LA
Ungerer, Totowa, NJ
TOTAL
EKtimafeda
nnua
Capacity
1975
55 (25)
85 (39)
60 (27)
310 (141)
200 (91)
135 (61)
135 (61)
10 (4.5)
75 (34)
1065 (483.5)
Estimatedb
Annual
Capaci ty
1980
105
75
(48)
(34)
ReportedC
Production
Volumes,
1977
Conf idential
100-500 (45-227)
100-500 (45-227)
100-500 (45-227)
10-50 (4.5-22.7)
Conf idential
.001-.01 (.0005-.005)
1550 (703.7)
a.
(EPA, 1976) source - Stanford Research Institute, Directory
of Chemical Producers, United States of America, Millions of
pounds as of January 1, 1975.
350 (159)
240 (109)
335 (152)
190
(86)
b.
Stanford ResearCh Institute, Directory of Chemical Producers,
United States of America, 1980.
375
(170 )
c.
These volumes reported to EPA' s Chemicals in Commerce
Information System (CICIS), 1977.
-6-
1670 (758)
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2.2.
Production Releases
Nitrobenzene is manufactured by the direct nitration of
benzene, using either a batch or continuous process. Figure 2-2
describes the general production process for any production
method employed.
While each manufacturing process has its own unique
procedure in terms of starting materials, reaction times, etc.,
all processes whether batch, continuous flow, or Biazzi have the
same point sources for emission of nitrobenzene and other
contaminants into the environment. These sources are described
by Lowenbach et al., (1979) (Figure 2-2) and described below.
The major process waste streams produced include the
nitrobenzene wash wa~er from the washer, (figure 2-1, point 3),
and the nitrobenzene distillation column overhead (point 5)
(Lowenbach, et al., 1979). The primary pollutants from the
process include nitrobenzene, nitrophenols, carboxylic acids,
nitrates and nitrites (see point source summary, figure 2-1,
Lowenbach et al., 1979). Small additional amounts of
nitrobenzene may be released from other points but these are not
significant additions to the total release.
2.3.
Post-Production Release
Aniline production via direc~ conversion from nitrobenzene
accounts for 97% (1,115.5 million pounds, [507 million
kiiograms*J) of the nitrobenzene produced (Chemical Marketing
Reporter, 1977). While there is no direct release of
nitrobenzene to the environment from this process, fugitive
emissions can be expected (Lowenbach, 1979).
*
Based on the Chemical Marketing Reporter's 1977 estimate of a
1980 demand of 1,150 million pounds.
-7-
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Figure 2-2
Nitrobenzene Process (USEPA, 1976; Lowenbach et a1., 1979)
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-8-
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The remaining 3%, totaling 34.5 million pounds (15 million
kilograms), is used in production of cellulose ethers, in
alkylation reactions, and in the production of dye intermediates,
metal polishes, shoe blacking, soap perfume, and propellants
(Austin 1974). Additionally, nitrobenzene is used as a solvent
for petroleum refining, and for depolymerization of rubber, and
chlorination reactions (Lee, 1979). While no quantitative
estimates for each minor use can be made, the total amount
included in this range of uses is significant, and much of the
material is likely to be deposited into the environment.
2.4.
Release fram Disposal
Current Federal regulations allow small quantities of
nitrobenzene to be burned in areas where combustion products will
not reach people, and slurries of less than one percent can be
routed to sewers with permission of local sewer authorities.
Nitrobenzene can also be buried in toxic landfills but this will
allow leaching into ground water or evaporation into the
atmosphere in an unproperly maintained area (USEPA, 1980a).
The regulations implementing Subtitle C of the Resource
conservation and Recovery Act of 1976, (RCRA), among other
things, identify and list hazardous wastes, and establish
standards for generators and transporters of hazardous wastes.
As indicated in ~261.33 of the regulations implementing RCRA, (45
FR 78532, November 25, 1980) commercial products containing
nitrobenzene are considered to be hazardous wastes when
discarded.
3.
ENVIRONMENTAL EXPOSURE
3.1.
Release to Air
Nitrobenzene released to the atmosphere during 1978
production and use in aniline manufacture was estimated (Anderson
et al., 1980) to be 275,000 pounds (125,000 kg).
Ninety-five percent of manufacturing release consists of
fugitive emissions (plant equipment leaks). The largest quantity
comes from DuPont plants located in Texas and New Jersey, and
from First Chemical in Mississippi (Anderson et al., 1980).
Anderson reported that the total quantity of nitrobenzene
used in solvent applications, 12.75 million pounds (5.8 million
kilograms). is eventually released to the atmosphere. He assumed
50 percent are lost through solvent uses in petroleum refinery
operations while the remaining 50 percent are lost through
solvent uses in cellulose ether manufacture. The plants emitting
the largest quantities are in Virginia, Georgia, West Virginia,
and Louisana While lesser amounts are released in Mississippi,
New Jersey, Indiana, Illinois, and Tennessee (Anderson et al.,
1980) .
-9-
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Anderson estimated that air emissions from industries which
use nitrobenzene as a chemical intermediate to produce
dichloroanilines and dinitrobenzenes amounted to 6,375 pounds.
These industries are located in New York, New Jersey, and
Louisiana (Anderson et al., 1980).
Estimates of levels of nitrobenzene released from individual
sites involved in aniline production activities ranged from
16,800 Ibs to 78,800 Ibs. However, release volumns from plants
associated with cellulose ether manufacture were estimated to be
much higher, with individual site estimates ranging from 44,625
Ibs to 2,263,125 Ibs.
Collectively, the estimated emission levels from production
and subsequent use to produce aniline, nitrobenzene use in
solvent applications, and its use as a chemical intermediate
amounted to 13.03 million pounds.
3.2
Release to Water
The release of nitrobenzene to the environment has been
estimated to be about 20 million pounds annually, including
losses in production and formulation (USEPA, 1977). Of the 8.3
million pounds of nitrobenzene that is estimated to be lost
during production each year (Brown, 1975), most will be in the
acid wash effluent discharge produced during acid regeneration
and the raffinate* water layer used to extract the acid from
crude nitrobenzene prior to distillation (Dorigan, 1976).
There are several points in the manufacturing process where
nitrobenzene could be released to effluent wastewater. Data on
the levels of nitrobenzene found in streams monitored at some
distance from manufacturing plants show that the chemical is
present in the aquatic environment.
In the Rhine River, concentrations averaged by quarter year
in 1974 were found to be in the range.O.l to 5.4 ug/L, with a
maximum of 13.8 ug/L. Lower values were found for both
substances in the Maas river (Meijers and Van der Leer, 1976).
The nearest chemical manufacturing plants identified as potential
sources lie in the upper Rhine drainage basin many miles upstream
from the sites where samples were taken.
At a South Carolina dye-manufacturing plant, effluent
samples were taken near the plant and also upstream and
downstream along the Cooper River (Games and Hites, 1977).
composite samples collected weekly over a 2.5 month period,
nitrobenzene was observed at 15 to 240 ppb levels in 4 out of 17
samples.
In
*The liquid product resulting from the extraction of a liquid
with a solvent.
-10-
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Nitrobenzene was monitored in drinking water in several
geographic locations, in a compilation of all organic compounds
that have been found in water collected throughout sites in the
United States. Nitrobenzene was present in raw wa~er and
finished drinking water samples from the Mississippi River in
Louisiana in 1970 (USEPA, 1972), in Cincinnati finished drinking
water in 1976 (Shackelford, 1976), and in an unspecified river
water sample in 1975 (Junk and Stanley, 1975). No data were
provided concerning the levels.
Neptune (USEPA, 1980c) reports nitrobenzene as
pollutant number 56 in a list of 129 substances.
it was found 56 times in amounts greater than 10
data received up to October 1979.
priority
In 3268 samples
ppb, based on
Whether it arrives directly by transport from aqueous plant
emissions or by transfer from the atmosphere, nitrobenzene is
present in the aqueous environment.
3.2.1.
Rain-Out.
Nitrobenzene volatilizes into the air but it iS3soluble enough
[partitioning ratio C (H20) Ic (air) = 1.4 x 10- (USEPA, 1980d)
that it could be carried back into the aqueous environments or to
soil by rain-out. Nitrobenzene in the atmosphere may move into
the water from the air, and this would add to the concent_ra'tions
of nitrobenzene in water that result from direct release.
3.2.2.
Solubility (Freshwater and Marine Environments)
Industrial plants located near marine wat.ers may discharge
nitrobenzene into effluent wast.ewa~er wi~hout sufficient
treatment. This discharge could contribute to environmental
exposure that differs from the exposure in freshwater areas
because the solubility of nitrobenzene in marine water is
unknown. Verschueren (1977) hypothesized that a ten-fold
increase in solubility could result from the introduction of
nitrobenzene into marine environments. There are no measured
data for this event, therefore, effects on marine organisms
cannot be predicted.
3.3.
Release to Soil
The adsorption of nitrobenzene on several types of soils has
been determined experimentally. Yariv et ale (1966) showed that
nitrobenzene may be held more tightly on montmorillonite (a clay
mineral with an expanding lattice) than on other types of soil.
Monitoring studies of wastewater samples have not reported soil
or sediment concentrations of nitrobenzene.
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An investigation by Alexander and Lustigman (1966) found
very little degradation of nitrobenzene by microflora in Niagara
silt loam after 64 days. The study indicates the physical and
chemical stability and persistence of nitrobenzene in association
with the test soil, however, results from one soil type are not
representative of the many soils possibly associated with
nitrobenzene.
These studies do not provide sufficient data to predict
nitrobenzene's mobility in soils once deposited there by rain-
out. Therefore, testing of nitrobenzene for mobility in a
variety of soils and sediments is recommended as a part of
chemical fate data needed for prediction of exposure (Refer to
Section 6).
SECTION 4 (a)(l)(B)(i) FINDING
4.
From the information presented in the preceeding sections,
it is evident that nitrobenzene is produced in substantial
quantities (from 575.5 million pounds to 848 million pounds
[261.6-385.5 million kilograms]), and released to the environment
in substantial quantities (approximately 20 million pounds [9.09
million kilograms] annually) (USEPA 1977).
Further, the Agency believes that this widespread release to
the environment can result in ubiquitous exposure to freshwater,
marine and terrestrial species because of the deposition of
nitrobenzene into the various environmental compartments.
5.
SUFFICIENCY OF DATA AND RECOMMENDED TESTING-ENVIRONMENTAL
EFFECTS
5.1.
Aquatic Vertebrates
~.l.l.
Acute Effects
Adequate data are available to assess the acute toxicity of
nitrobenzene to warmwater freshwater fish, and warmwater
saltwater fish but not to coldwater freshwater fish or coldwater
saltwater fish. Nitrobenzene is moderately toxic to warmwater
freshwater fish and there is concern that rainbow trout may be
more sensitive. EPA is proposing to require acute toxicity
testing in coldwater freshwater fish (trout) to provide data on
this effect. The Agency itself will sponsor testing on a
coldwater saltwater fish because TSCA Section 4 standards are not
available at this time.
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Studies by USEPA (1978) have reported a 96-hr. LCSO* of 42.6
mg/l for the bluegill. Juhnke and Luedemann (1978) reported LCSO
values of 69 and 89 mg/l for the golden orfe7 and Verschueren
(1977) reported 6 hr. TLM's of 20-24 mg/L and 90-100 mg/L in
distilled and hard water, respectively, for the Varian, another
freshwater fish. The 96-hr LCSO for the sheepshead minnow, a
warmwater saltwater variety, is reported as S8.6 mg/ (USEPA,
1978).
S.1.2
Chronic Effects
There are no data available concerning the chronic toxicity of
nitrobenzene to aquatic vertebrates and testing is needed to
produce these data. Therefore, the Agency is proposing to
require early life stage tests in a freshwater coldwater species,
a freshwater warmwater species7 and a saltwater warmwater
species. Because there are no standards in place for the chronic
testing of saltwater coldwater species, the Agency will conduct
this testing.
S.2.
Aquatic Invertebrates
S.2.1.
Acute Toxicity
Sufficient data are available to perform an adequate assessment
of the acute effects of nitrobenzene on freshwater and saltwater
invertebrates. Studies have reported a 48 hr. LC50 of 27 mg/L
for Daphnia and a 96 hr. LCSO of 6.7 mg/L for mysld shrimp
(USEPA, 1978).
S.2.2.
Chronic Toxicity
There are no data to assess the chronic toxicity of
nitrobenzene to aquatic invertebrates. Therefore, the Agency is
proposing to require complete life cycle testing on both a
freshwater and saltwater species.
*Several terms are used to describe toxicity. An LCSO is the
concentration at which half of the test organisms have been
killed. Similarly, LDSO is the dose which kills half of the
test population. Toxiclty values reported as LCLO or LDLO are
the concentration at which the test population is first
affe~ted. Because ~he LCSO or LD50 valu~s in these cases would
be hlgher, an LCLO lS a conservatlve estlffiate ~f the actual
toxicity. Conversely, values of LCIOO or LC hlgh are the level
at which the whole test population is affected and
underestimates toxicity to sensitive members of the
population. Median threshold limit (TLM, a term used in the
19S0's are equivalent to LCSO values. An ECSO is the
concentration of a chemical that has a designated effect on
half of the test population.
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5.3.
Aquatic Plant Life
There are adequate data to assess the toxicity of
nitrobenzene to freshwater and saltwater species of algae. The
USEPA (1978) reported 96 hr. EC50 values (for cell reproduction
as measured by cell numbers) of 42.8 mg/L for Selenastrum
capricornutum and 9.65 mg/L for Skeletonema costatum. Verschuen
(1977) reported a threshold toxicity value of 1.9 mg/L for
inhibition of cell multiplication in an assay with Microcystis
aeruginosa.
No data are available on aquatic vascular plant toxicity.
The Agency itself will sponsor testing on an .aquatic vascular
plant because TSCA Section 4 standards are not available at this
time.
5.4
Birds
5.4.1.
Acute Effects
There are no good data concerning the acute toxicity of
nitrobenzene to avian species. An inhalation study by Chandler
(1919) on chickens was identified but because of differences in
the physiology and behavior of the chicken compared to wild type
species, the Agency has determined this information is inadequate
for assessment of nitrobenzene's effects on wild avian species.
Therefore, EPA is proposing to require acute toxicity
testing in two species of birds.
5.4.2.
Chronic Effects
There are no data on the chronic effects of nitrobenzene
exposure to avian species. Therefore, EPA is proposing to
require reproductive toxicity testing in two species of birds.
5.5.
Terrestrial Plants
5.5.1.
Seed Germination and Root Elongation
Testing of the toxicity of nitrobenzene to plants has been
conducted on several crop species. Eckart (1962) reported EC50
values for inhibition of seed germination of 1600 mg/L for the
cucumber and 1800 mg/L for the mung bean. Although the above
testing has been done, the Agency approach for a 4 a(l)(B)
finding requires commerically important plant species to be
tested to adequately address concerns of differences in species
sensitivity from one plant type to another. Therefore, the
Agency is proposing to require seed germination/root elongation
testing.
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5.5.2.
Early Seedling Growth
Hikino and Fugii (1979) reported that doses greater than
1,000 mg/L inhibited early seedling growth of turnips, rice and
soybeans. However, the data are inadequate in that the
continuous exposure period was short, the soil selected would not
maximize sensitivity and only three species were tested, limiting
the sensitivity of the test. The Agency feels a broader range of
species, more typical of commerically important plants in the
U.S., needs to be tested to adequately address concerns of
differences in species sensitivity from one plant type to
another. Therefore, the Agency is proposing to require early
seedling growth testing.
5.5.3
Full Life Cycle
No data are available to assess full life cycle effects.
However, no TSCA Section 4 standards are available and therefore
EPA will sponsor testing.
5.6 Bioconcentration
Although there are no data concerning the bioconcentration
of nitrobenzene in aquatic benthic organisms, the Agency is not
proposing "Lo require such testing for several reasons: 1) the
log P (octanol/water) is low (1.85 + 0.1. at 250C); 2) the
bioconcentration factor, as determined by a freshwater fish test
(Lu and Metcalf, 1975) is low (15x)i 3) there is no significant
difference in acute toxicity testing results among freshwater and
saltwater fish speciesi and 4) based on a modeling exercise by
EPA's Athens Lab (USEPA, 1981), low concentrations of
nitrobenzene are expected in sediments. partitioningdata
indicated that in an aquatic ecosystem, only .01-5% of
nitrobenzene was associated with the sediments (95-99.9% was
associated with the water column) which suggests that exposure to
organisms associated ~.ith the sediments is not likely to be
high. . From this evidence, the Agency concludes the data
available are adequate to perform a risk assessment on
bioconcentration potential in aquatic benthic invertebrates.
There are no data concerning plant uptake/translocation.
Agency is proposing to require that plant uptake/translocation
testing be performed according to Agency test standards.
The
5.7.
Other Effects of Concern
EPA is not proposing testing for other effects of concern
(i.e., toxicity to terrestrial invertebrates, microorganisms,
ecosystems, reptiles/amphibians) because no TSCA Section 4
standards are available. Test for such effects will be
undertaken by EPA~
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6.
SUFFICIENCY OF DATA AND RECOMMENDED TESTING-CHEMICAL FATE
The Agency is proposing additional chemical fate testing
because existing information is insufficient to characterize the
persistence, location, concentration and transport of
nitrobenzene in the environment. Certain additional
physicochemical testing will be performed by the Agency, however,
the Agency is proposing that other testing be performed by
i ndu st:ry.
6.1. melting point 5.700c (The Condensed Chemical Dictionary, 1977)
6.2. boiling point 210.850C II II II II
6.3. density 1. 2037 (20/40c) (Handbook of Chemistry
and Physics, 1980-81)
6.4. U.V.-visible Adequately characterized
absorption spectra
6.5. Solubility in
freshwater
6.6. Solubility in
sal twat.er
6.7. Partition
coefficients
6.8. Adsorption
desorption
6.9. Soil thin-layer
chromotography
1.9 g/L at 20°C
Stephen and Stephen (1963)
Nitrobenzene's solubility in
marine water has not been reported.
The Agency will perform this testing.
log P (octanol/water) = 1.~5+ 0.01 at 25°C
C(H20)/C (air) = 1.4 x 10- TUSEPA, 1980d)
where C(H20) is the concentration of
nitrobenzene in water; C(air)
concentration of nitrobenzene in air.
Da t.a concerning the adsorption and
desorption of nitrobenzene in soils
are not adequate. The Agency intends
to perform this testing.
Because of the lack of data concerning
persistence and mobility the Agency is
. proposing to require the development of
soil adsorption data. Soil adsorption data
will be developed through the use of soil
thin-layer chromotography techniques. This
screening test is used to measure
relatively mobile compounds in soils.
Testing should proceed according to the
Agency test standard (Proposed
Environmental Test Standards, ~772.l22-5 FR
Vol. 45, November 21, 1980).
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7.
HUMAN EXPOSURE
7.1.
Occupational Exposure
The National Occupational Hazard Survey (NOHS Survey), a two
year study initiated in 1972 by NIOSH (National Institute for
occupational Safety and Health). was designed to determine the
extent of worker exposure to chemical and physical agents.
Although the data reported in this study have certain
limitations, the results indicate that an estimated 13,547 people
in the U.S. are potentially exposed to nitrobenzene in the
workplace. The figures indicate that chemical and allied
products industries, various business services, medical. and other
health services, fabricated metal product industries and apparel
and accessory stores show the greatest potential for exposure of
their employees to nitrobenzene. Of the occupations within these
industries, janitors and other cleaning personnel, machine
operators, chemists, chemical technicians, mechanics and
repairmen, and metal platers are most likely to be exposed.
The American Conference of Governmental Industrial
Hygenists' recommendations (1978) (threohold limit values, TLV's)
for levels of worker exposure to airborne concentrations of
nitrobe~zene without adverse effects are a TWA* of 1 ppm
(5 mg/m ) and a STEL** of 2 ppm (10 mg/m3). Current OSHA 3
regulations limit ambient nitrobenzene exposure to this 5 mg/m
level (time weighted average over an eight-hour period day).
pacseri and Magos (1958) studied the environmental factors
(air contamination and the possibility of percutaneous
absorption) in several types of plants, including a nitrobenzene-
*(a) Threshold Limit Value-Time Weighted Average (TLV-TWA)-- the
time-weighted average concentration for a normal 8-hour work day
or 40-hour work week, to which nearly all workers may be
repeatedly exposed, day after day. without adverse effect.
**(b) Threshold limit Value-Short Term Exposure Limit (TLV-
STEL)--the maximal concentration to which workers can be exposed
1) irritation, 2) chronic or irreversible tissue change, or
3) narcosis of sufficient degree to increase accident proneness,
impare self-rescue, or materially reduce work efficiency,
provided that no more than four excurisons per day are permitted,
with at least 60 minutes between exposure periods, and provided
that the daily TLV-TWA also is not exceeded. The STEL should be
considered a maximal allowable concentration, or ceiling, not to
be exceeded at any time during the IS-minute excursion period.
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producing facility. In all eight of the plant typesl studied,
the toxic chemicals could be inhaled and also absorbed through
the skin. Air sampling of nitrobenzene in the work area produced
an average value of 29.0 mg/cu. meter. Evaluation of blood
changes (involving blood pigment derivatives, i.e.,
methemoglobinaemia and sulfhemoglobin) showed the plant
employees' methemolobin levels and sulfhemoglobin levels ~xceeded
the normal upper limit values (pacseri, 1958). The elevated
levels of methemoglobin and sulfhemoglobin and the occurrence of
Heinz bodies in erythocytes are similar to those effects noted in
animal studies with nitrobenzene.
In an investigation of the absorption of nitrobenzene vapors
through the skin through repeated exposures, Piotowski (1964),
summarized that the absorption rate appears to be proportional to
the concentration, and that work clothing reduces the absorption
by only 20 to 30 percent. Air temperature has no evident effect
on absorption rate. Increases in humidity increase the
absorption. Piotroski, in summarizing his findings and earlier
findings, (Salmowa et al., 1963) concluded that a person exposed
to nitrobenzene vapors (6-hour work day) only at a concentration
equal to the MAC* (5 ug/l) may retain about 25 mg. of
nitrobenzene daily.
Nitrobenzene vapor is rapidly absorped through the lungs
with 80 prcent retention. Lung absorption rates are twice the
cutaneous values (Piotrowski, 1967). A man exposed to the
current OSHA (Occupational Safety and Health Administration)
standard for nitrobenzene of 1 ppm (eight-hour time weighted
average) (Ha~ -.n, 1967) (OSHA, 1972) would be expected to absorb
approximately 24 mg. by inhalation and 9 mg percutaneously in an
eight-hour period (Salmowa, et al., 1963). Dosages exceeding 35
mg/day have been reported for factory workers (Salmowa, et al.,
1963) and clinical records indicate the poisoning of factory
workers by exposure to nitrobenzene (Chandler, 1919: Ikeda,
1964).
Percutaneous absorption is a hazard in industry, and
probably is the most significant route of exposure for the
general population. This route appears to cause the most common
marked acute toxic effects. Nitrobenzene penetrates readily
throug~ the gastr?intestinal mu~osa, lungs, a~d even intact skin,
for whlch absorptlon rates as hlgh as 2 mg/cm /hours have been
reported (Piotrowski, 1967).
Iplant types included production of acetanilide, ethyl-aniline,
ethyl-aniline distillation, anisidine, phenacetine, aromatic
nitro compounts, p chloraniline and textile dyeing.
*MAC-Maximum Allowable Concentration
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Other than the few published cases, the Agency does not have
specific data on the extent of human exposure to nitrobenzene
during its manufacture, processing, distribution in commerce, use
and/or disposal. Nevertheless, it appears that nitrobenzene is
absorbed but. there are insufficient dat.a available to adequately
quantitate the extent of exposure.
7.2.
Consumer Exposure
The Consumer Product Safety Commission (CPSC) issued a
General Order (CPSC, 1978b) which required manufacturers of
consumer product.s containing nitrobenzene to supply the
Commission with information regarding these products. From the
five responses received, the Commission could not det.ermine
whether the manufactueres were representat_ives of producers using
nitrobenzene in consumer products or whether t.he products
identified constituted all the classes of products in the market
place containing the chemical. It was suggested that the very
small number of responses indicated that use of t.he chemical in
consumer products was not widespread. Four of t.he five responses
indicated that nitrobenzene is added in small concentrations for
various uses, e.g., as a solvent in a gun cleaner, a fragrance in
shoe polish, a fuel additive, and a stabilizer (CPSC, 1978a). An
importer of inks report.ed that the chemical was present. in its
product, probably as a contaminant. One respondent, producing
shoe polishes and waxes, reported t.hat nitrobenzene in the amount
of 0.67 percent (6700 ppm of the product by weight) is added as a
fragrance. The CPSC reports that these shoe care products may be
found in most households.
The CPSC noted that three of the report.ing firms
intentionally add nitrobenzne to products that are sold to
limited population groups. One firm adds nitrobenzene to its
fuel additive mixtures, 0.10 percent (1,000 ppm) and 0.75 percent
(7,500 ppm) by volume in two products and 0.25 percent (2500) by
weight in another product. Another firm produces an antiseize
compound containing 0.19 percent (1900 ppm) for use on contacting
metal surfaces. The third firm manufacturers gun-cleaning
solvents with nitrobenzene levels ranging from 0.2 percent (2,000
ppm) to 1.0 percent (10,000 ppm by weight or volume, not
specified (CPSC, 1978a).
The University of Rochester Medical Center's product data
file (University of Rochester, Inquire System, 1980) lists
certain wax shoe polish, black shoe dye, black indelible writing
ink, toilet bowl cleaner, veterinary liniment and paint products
as containing nitrobenzene. The NIOSH Tradename Ingredient Data
Base (NIOSH, 1977b) identifies specific shoe polish, printing
press cleaner and metal polish products as containing
nitrobenzene.
-19-
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As stated earlier, it has been reported that the dispersive
uses of nitrobenzene account for three percent of total
production, (1,150 million pounds, Chemical Marketing Reporter,
1977) or about 34.5 million pounds per year. Of this, the bulk
is used as a solvent for t.he production of cellulose ethers and
in Friedel-Crafts alkylations, while the remaining 1.0 percent is
used in the manufacture of dye intermediates, metal polishes,
shoe blacking, soap perfume and propellants (Austin, 1974).
Based on Brown's (1975) estimate that two percent of the
nitrobenzene produced is lost through dispersive uses, 23 million
pounds would be expected to be released yearly to the environment
through these uses.
There are two major exposure routes for nitrobenzene uptake
in the general population: vapor inhalation and cutaneous
absorption (liquid or vapor). Ingestion (liquid) is not expected
to be a major route but nitrobenzene's toxicity has been
demonstrated as the result of its use as an abortifacient (in the
late 19th Century) and in suicide attempts (Von Oettinger, 1941~
Chandler, 1919~ Dollinger, 1949).
7.3.
General Population
The quantities of nitroaromatic compounds released to the
environment can only be estimated because monitoring data are
inadequate and there is only limited information on treatJnent and
disposal procedures. In the case of nitrobenzene, it is believed
that the major potential source of environmental contamination is
from chemical manufacturing plants and not through the use of
final product s.
Water that is used in the production process can be a major
source of contamination if left uncontrolled and untreated.
Nitrobenzene has been detected in the wastewater effluents of
chemical plants and in drinking water (Howard, 1976).
Although nitroaromatic compounds have not been detected in
air samples, large volume nitroaromatic compounds such as
nitrobenzene have relatively high vapor pressures which could
result in sizeable vapor releases. Therefore, some vapors are
probably released to the atJnosphere during production, transport,
storage and disposal (Dorigan, 1976).
Ambient levels of nitrobenzene have been estimated for
locations near a plant releasing nitrobenzene through ventilation
and exhaust of internal air (Dorigan, 1976). Atmospheric
dispersion from this plant would distribute the gaseous emissions
downwind, as affected by the turbulent diffusion of the air
(Dorigan, 1976). In a modeling study, a downwind distance of 500
meters from the emission source was chosed as the hypothetical
measurement ~oint and ground level concentrations were estimated
at 1.56 mg/m. An individual positioned at this spot would have
to remain for about 25 hours to inh~le an amount equivalent to
the exposure of a worker to 40 mg/m during an eight-hour work
day (Dorigan, 1976).
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Control effort_s to mitigate the effects ()f dispel.-sion of
nitrobenzene (calculated from the production loss of the entire
industry) we re not taken into accouni~ in tltls cal cu 12 t.lon. Has t,
if not all, plants have employed some form of 3 L emissions
cont_rol technology to reduce t~he resulting ~-,ii::.rc>l'<-C'i.!z,ene plant~
emissions to a permissible level (Dorigan, 1976).
The report- noted t~hat individual indusl.ries refused 1.0
disclose emissions data, and the need for effect--ive monitoring
and control of air emissions of nitrobenzene was ~~phcisized.
The Section 4(a) (1)(A)(i) FINDING
B.
On the basis of t.he info:ollaion presented above, i.t is clear
to EPA that persons may be exposed t~o niU:.-obenzene as a result of
release of the chemical during product. ion, t.ranspo:cl.., sLc'rage and
disposal.
In addition, as stated below, EPA possesses
suggest that exposure to nitrobenzene may result
or teratogenic effects.
evidence t~o
in ):-eproduct. i ve
Finally, EPA's assessment indicates that the cost of
t~eratogen ic and reproductive testing would no-I- have a s igni f icant
impact. on the availability of benefits from Uie chemical.
Therefore, EPA has found that nit.robenzene may present~ an
unreasonable risk of t~erat:ogenic and reproductive effect.s. EPA' s
analysis with respect t:o t:he potential haza:cds posed by
nitrobenzene, the sufficiency of inforr~a t:ion, ancli.he neces s i t:y
of testing for these effects, is detailed below.
9.
POTENTIAL UNREASONABLE RISK, SUFFICIENCY OF DATA AND
--~--~~-~
RECOMMENDED TESTING - HEAL'rH EFFECTS
9.1.
Acute Effect_s
The Agency is not: propos ing addi -I:ional acu'.e -toxici t::.y
testing because the exist::.ing data a:ce adequat.e -1.0 charac-Le:cize
the risks of acute injury to the health of exposed worke:cs and
consumers.
Methemoglobinemia is the majo:c acute t::.oxic effect::. of
nitrobenzene exposure ":0 mammals. This effect. :cesults in
decreased oxygen transpor1. and severe cyanosis followed by t.issue
anoxia, dypsnea, fainting, coma, and eventually, in some cases,
death (Chandler, 1919; Von Oe":tengen, 1941), Du:cing the course
of intoxication, hemoglobin, erythrocyte, and platelet levels in
the ci rcula tion drop rapid ly, and t:hen return i~o nOJ::T~al,
Reticulocyte, Heinz body, and "basophilic ery-I::.h):ocyt,e" levels
increase rapidly. Hemolytic and secondaDJ anemia, some of which
may be due to the t.:.reatment used to :ceduce 1:he me'l::.herooglobin
levels, may also be observed.
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9.2.
Subchronic Effects
Animal studies have demonstrated that nitrobenzene results
in methemoglobinemia and sulfhemoglobinemia (Andreeshcheva,
1970). The acute and subchronic reports show that repeated
exposure to nitrobenzene causes significant toxic effects.
However, none of the subchronic animal studies are adequate to
show a no-effect level, a dose-response relationship, or the
cause-effect correlation between continued levels of
methemoglobin in the blood and organ damage, blood dyscrasias or
other toxic end points. Although the Agency is not cognizant of
any current subchronic testing, the National Toxicology Program
(NTP) proposes the oncogenic testing of nitrobenzene in mice and
rats of both sexes, using administration by gavage. Subchronic
range-finding studies are to be included in the program.
Therefore, EPA is not proposing to require subchronic testing.
9.3.
Chronic Effects
The Agency is not proposing to require chronic effects
testing. While no studies of chronic effects have been
identified, the nature of the acute and subchronic effects
suggests that no significant additional information would be
obtained from chronic studies. Additionally, the proposed
oncogenicity testing by NTP will provide information on chronic
effects. Therefore, the Agency is not proposing chronic testing
at this time.
9.4.
Neurotoxicity/Behavioral Toxicity
The Agency has reviewed data concerning the neuro-behavioral
toxic effe~ts of nitrobenzene, however, because the Agency does
not have standards for neuro-behavioral testing, no testing is
being proposed at this time.
9.5.
Reproduction
Data concerning the reproductive effects of nitrobenzene are
inadequate to perform a hazard assessment but indicate that a
risk may be present, and therefore the Agency is proposing to
require testing to produce these data. Information on the
effects of nitrobenzene on the reproductive system in
experimental animals, including histopathology of the
reproductive organs, are not available.
A metabolite of nitrobenzene has been observed to reduce the
activities of enzymes associated with the reproductive systems of
rats. Nitrobenzene is metabolized to 4-nitrophenol and 4-
aminophenol. Although these two metabolites have not been tested
for reproductive effects, aniline (an intermediate metabolite in
the metabolic pathway of nitrobenzene to 4-aminophenol in humans
and experimental animals) has been reported to reduce the
activities of an enzyme associated with the reproductive systems
of treated rats (Hatakeyama et al., 1971).
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Although these data are suggestive of a potential metabolic
effect of nitrobenzene on the reproductive system, the data are
inadequate to provide a hazard assessment and testing is needed
to provide additional data. The Agency is unaware of any ongoing
testing and is proposing to require, under Section 4(a) (l)(A), 2-
generation reproductive effects testing of nitrobenzene in one
rodent species.
9.6.
Teratogenic Effects
The available data concerning teratogenic effects indicate
that exposure to nitrobenzene may present a human teratogenic
hazard. However, the data are not adequate to evaluate the
extent of the hazard and therefore, the Agency is proposing to
require additional testing to produce these data.
No human studies concerning the teratogenic effects of
nitrobenzene have been identified. Reports on a study by
Kazanina (1967, 1968a, 1968b) indicate that nitrobenzene produces
significant histochemical changes within the placenta and may
have some teratogenic activity. Enzymatic changes within the
placenta may be responsible for the fetal effects observed as a
result of treatment during organogenesis. Altered placental
enzymatic patterns may have a more pronounced effect 'In human
development than observed by Kazania in the rat because of
developmental differences. Accordingly, because of the
possibility of teratogenic effects during organogene~~s and
because of the general poor quality of this study, the need for
further testing is indicated.
Indirect evidence of possible affects also exists. Exposure
to nitrobenzene reportedly results in methemoglobinemia which
ultimately causes anoxia, a reduction of oxygen in body tissue.
Indirect supportive studies indicate that maternal anoxia does
produce fetal and neonatal effects (Astrup et al., 1972; Warkany,
1971; Schwetz et al., 1979; Hoffman and Campbell, 1978)
It has also been reported that prenatal exposure to CO
produces altered CNS function postnatally (Dyer et al., 1979).
The majority of the isolated cases of CO poisoning in humans also
reported alterations in CNS function and in some instances
associated changes in neuroanatomy were observed (cited in
Warkany, 1971).
Further testing is needed to identify teratogenic potential
and the Agency is unaware of any ongoing testing that would
provide the necessary data. Therefore, under ~4(a) (1) (A) EPA is
proposing that teratogenicity testing be undertaken on
nitrobenzene in both rats and mice. Standards for development of
data on teratogenic health effects have been proposed (EPA,
1979).
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9.7.
Mutagenici ty:
Three inves"tigai,;.ions (Garner and Nu1:man, 1977; Chiu et al.,
1978; Anderson and Styles, 1978) of the ability of nitrobenzene
to induce gene mutations in Salmonella typhimurium have been
published and negative results were reported in each study.
However, the Agency does not recognize negative Ames assay
results as evidence that a compound is non-mutagenic because the
Ames test, by itselt, is inconclusive.
Mutagenici-ty screening tests involving nitrobenzene and its
major metabolite, p~nitrophenol, have been completed by the
National Toxicology Program (NTP) and negative results
(Salmonella ~himurium bacterial assay) have" been reported
(National Toxicology Program NTP Technical Bulletin, December
1980) .
The available evidence on the ability of metabolities of
nitrobenzene to induce gene mutations suggests that the agent may
represent- a health hazard due to induct:ion of gene mutations.
Two nitrobenzene metabolites, 4-aminophenol and
phenylhydroxylamine, appear able to induce gene mutations. In a
study by Mitra and Manna (1971) 4-aminophenol was shown to induce
a dose dependent increase in chromosomal aberrations in vivo in
the bone marrow of mice. However, no control data were
presented, and due to the small size of this experiment, it was
not possible to evaluate thoroughly the relevance of the result.
No studies were identified where nitrobenzene's ability to
induce chromosome aberrations or other chromosomal changes were
investiga t_ed.
Given the potential of nitrobenzene exposure to humans and
the environment and given the known mutagenic potential of two
metabolites of nitrobenzene, additional data are needed regarding
nitrobenzene's ability to induce both gene and chromosomal
mutations. Testing is needed to provide these data. The Agency
believes tnat the mutagenic risk from exposure to nitrobenzene
can most reasonably be determined by additional test sequences
for both gene mutations and chromosomal aberrations. In such
tired sequences, the performance of certain tests is triggered by
pisitive or negative results from previous tests. While the
tests for such a scheme are currently available, the Agency is
unable to propose triggers for the process, i.e., criteria for
determining whether a given result is positive or negative. The
Agency is in the process of defining these triggers and in the
meantime will perform and evaluate the lower and middle tier
chromosomal ~t'2si:s invol ving nitrobenzene. However, the Agency
may require higher organism sequenced testing if the initial
testing results dictate this need.
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9.8.
Oncogenic Effects
The ITC recommended that nitrobenzene be tested for
carcinogenicity. No studies on oncogenic effects in humans or
animals have been identified.
Additional information is needed to characterize the
oncogenic potential as elicited directly by nitrobenzene or via
intermediates in its metabolic reduction. However, the Agency is
not proposing to require testing for oncoginicity because the
National Toxicology Program is scheduled to begin (August, 1982)
a carcinogenesis bioassay evaluation of nitrobenzene. The
results of these investiga1:ions, involving rats and mice of both
sexes, will identify the need for any furt.her testing.
9.9.
Epidemiology
At this time, the Agency will not require an epidemiologic
study on nitrobenzene because a suitable population has not been
identified. The Agency is proposing a rule under Section
8(a)(2)(F) of TSCA for nitrobenzene as well as other ITC
chemicals. Section (8) (a) authorizes EPA to obtain readily
accessible information on specified chemicals from the files of
manu facturers, processors, and import.:.ers concerning use,
production, and worker exposure. This information may playa key
role in the identification of a population for epidemiologic
study and if an appropriate population can be identified, the
Agency may, in the future, propose to require performance of an
epidemiologic study.
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morphology and histochemistry of hemochorial placentas of albino
rats (trans. fro Russian). Bull. Exp. BioI. Med. 65(5):679-681.
kazanina S. 1968b. The effect of nitrobenzene on the
development of the fetus and placenta in the rat. Nauchni Tr.
Novosibirskgos., Med. Inst. 48:42-44.
Kirk R, Othmer D. 1967. Nitrobenzene and nitrobenzenes
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Organic solvent use study.
Lowenbach W, et ale 1979.. Toxic pollutant identification:
Nitrobenzene/Aniline Manufacturing. Mitre Corporation.
Environmental Protection Agency, Washington, D.C. Grant No.
805620. Industrial Manufacturing Process Quality Control
Evaluation Series, 01/79-04.
Lu PV, Metcalf RL. 1975. Environmental fate and
biodegradability of benzene derivatives as studies in a model
aquatic ecosystem. Environ. Health Perspect. 10:269-284.
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-28-
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13.
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REPORT DOCUMENTATION 1.1._RUO,", NO. I~ 3- R8CiIlienC'. -- No.
PAGE I SPA 560/2-!H-fi}02
4. r.tle .nd Subtitle NITROBENZENE SUPPORT DOCUMENT 5. Re",,~ Dete
ASSESSMENT OF TESTING NEEDS: M~" 1 QQl
PROPOSED HEALTH AND ENVIRONMENTAL EFFECTS TEST RULE ..
7. AutIIor(sl 41. -ne 0""'_011 R8IIL No.
t. Perform;,. O...nlution He- end _rea 10. ,,",;ectITe.klW- Unit No.
Assessment Divisionl0ffice of Pesticides and Toxic Substances
401 M Street, S.W. 11. Contr8ct(C) III-ry Hot..
-. --_. _. ~ --
.141. - (Umlt: 200 _I
Current est.Uta.tes of the yearly nitrobm~ene production raI13e fran 1,150 to 1,670
million pounds. Approxi.ITa.tely ninety-seven percent of the nitrobenzene is used to
produce aniline While the rana~ three percent has variOlS dispersive uses such
as a selective 9:11 vent and in the production of other dlemical products.
The AgenCf believes that nitro1:::enzene nay present an unreasonable risk of injury to
hurran health. This is based on existing toxicological data and experience and the
belief that persons are E!XfOsed in r..he wotkplace, as consurrers am. as a result of
general environmmtal release. Nitrobenzene is produced in large quantitites, and
the AgenCf also believes that there may be substantial release to the envirorment..
Because there are insufficient data upon Whidl the effects of nitrobenzene on hurrans
am the emironnent can reasonably be detemned, the AgenCf has prcposed further
testing of ni tro1:::enzene. Proposed hurran health effects testing includes testiD:J for
texatogenic am reproductive effects. Prcposed emironnental effects test:i.rg
includes cquatic vertebrates (acute toxicity, chronic toxicity), aquatic
imertebrates (cnronic t.oxici 1:y), birds (acute toxici 1:y, cnronic toxici 1:y) ,
. terrestrial plants (seed getmination/root elongation), early seedliing growth), and
bioconc;ntration (plant uptcke/translocation). C1anical fate testin;; (persistence)
is also 'Proposed.
Biblograpl„ included.
17. ~ An81ysi8 ..~
... Identl_/ODeft.Encl8cI T......
Nitrobenzene
Nitrobenzene Support Document
Co COSA n Fleld/Gl'OUo
lL A....lebility Stat- 1'. Security Cle.. (TIll. R8I>CIItI n. Ho. of P-
Release Unlimited 1I~~1~~";.f;",,,(
2IL Security CIa.. (TIlls Pep, 2Z. Plica.
Unclilsc:ifi<>rI
5027'2'J 01
(See ANSI-QI.111
Seel__....R-
OrnONAL. FORM 27'2 (4-77)
(Formerty HTI5-35)
Oeo8ttmem "" c:om-
'U S GOVERNI'IENT PRINTING OFFICE: 19BI 720-016/5994
-------
United States
Environmental Protection
Agency
Washington DC 20460
Postage and
Fees paid
Environmental
Protection
Agency
EPA 335
~.
-
U.S.MA'L
-.'
Official Business
Penalty for Private Use $300
Third-Class
EPA 560/2-81-002
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