United States
                Environmental Protection
    Pollution Prevention
    and Toxics
    February 1995
wEPA     OPPT  Chemical  Fact  Sheets
               Nitrobenzene Fact Sheet: Support Document
                (CAS No. 98-95-3)
  This summary is based on information retrieved from a systematic search limited to secondary sources (see Appendix
  A). These sources include online databases, unpublished EPA information, government publications, review
  documents, and standard reference materials. The literature search was done in February of 1995. No attempt has
  been made to verify information from these databases or secondary sources.


        The chemical identity and physical/chemical properties of nitrobenzene are summarized in Table 1.

  CAS No.
  Common Synonyms
  Molecular Formula
  Chemical Structure
  Physical State
  Molecular Weight
  Boiling Point
  Water Solubility
  Specific Gravity
  Vapor Density (air =1)
  Log Kow
  Vapor Pressure
  Flash Point
  Henry's Law Constant
  Fish Bioconcentration Factor
  Odor Threshold

  Conversion Factors (in air)
nitrobenzol; oil of mirbane

5.85°C @ 760 Torr
210.9°C @ 1  atm
1.9g/L@20°C;2.1 g/L@25°C
36-650 (estimated)
0.15 mm Hg @ 20°C; 0.27 mm Hg @
88°C (closed  cup)
2.3 x  10"5 atm-m3/mole @ 25 °C
<10-15 (measured in the golden orfe)
perception, 0.0182 mg/m3 (3.6 ppb)
threshold, 1.9 ppm
1 ppm = 5.12  mg/m3; 1 mg/m3 = 0.20
     U.S. EPA 1994
     U.S. EPA 1985
     U.S. EPA1985Melting
     U.S. EPA 1985
     U.S. EPA 1985
     U.S. EPA 1985
     U.S. EPA 1985
     U.S. EPA 1985
     U.S. EPA 1987
     U.S. EPA 1987
25°CU.S. EPA 1987

     Budavari 1989
     U.S. EPA 1985
     U.S. EPA 1985
     Verschueren 1983
     U.S. EPA 1985
ppm  Verschueren 1983


        A.      Production

        There were four producers of nitrobenzene in the United States in 1991: First Chemicals Corp, Mobay,
        DuPont Chemicals, and Rubicon, Inc. In 1991, the estimated total production capacity of nitrobenzene in the
        U.S. was 1,360 million pounds (Mannsville 1991).

        Table 2 shows the producers, plant locations, and  1991 plant production capacities of

First Chemical Corp.
Mobay (now Bayer)
Rubicon, Inc.
Beaumont, TX
Pascagoula, MS
New Martinsville, WV
Geismar, LA
1991 Capacity
(Millions of Pounds)
Source:  Mannsville 1991.
        While nitrobenzene is primarily used in the production of aniline and aniline derivatives, such as methyl
        diphenyl diisocyanate (MDI), it also finds use in the manufacture of rubber chemicals, pesticides, dyes, and
        Pharmaceuticals. Nitrobenzene is also used in shoe and floor polishes, leather dressings, paint solvents, and
        other materials to mask unpleasant odors.  Substitution reactions with nitrobenzene are used to form m-
        derivatives (Mannsville 1991; Sittig 1991). Redistilled, as oil of mirbane, nitrobenzene has been used as an
        inexpensive perfume for soaps. A significant merchant market for nitrobenzene is its use in the production of
        the analgesic acetaminophen (Mannsville  1991). Table 3 presents the estimated 1991 U. S. end-use pattern
        for nitrobenzene.

(Typical Standard Industrial
Classification (SIC) Code)1
(production, SIC 2865)
Source:  Mannsville 1991.
          The Standard Industrial Classification (SIC) code is the statistical classification standard for all Federal economic statistics. The code provides a
     convenient way to reference economic data on industries of interest to the researcher. SIC codes presented here are not intended to be an exhaustive listing;
     rather, the codes listed should provide an indication of where a chemical may be likely to be found in commerce.

C.      Trends

Future demand for nitrobenzene is almost exclusively dependent on demand for aniline. Overall U.S. long-
term aniline demand, and therefore nitrobenzene demand, will probably increase at about 3 to 4 percent per
year (Mannsville 1991).

The USITC has not reported production statistics for nitrobenzene since 1986.  Nitrobenzene output is
generally in the range of 1.4 times derivative aniline output. The USITC (1994) reported the production of
aniline to be 1005 million pounds for 1992.  There is adequate capacity to meet domestic demand for nitro-
benzene for several years. Both Rubicon and First Chemical have expanded their nitrobenzene production
capacities in recent years (Mannsville 1991).


A.      Environmental Release

        Depending on its purity, nitrobenzene is a pale yellow to yellow-brown, oily liquid at room
        temperature.  It has a characteristic odor that has been associated with bitter almonds and shoe polish
        (vapor pressure, 0.27 mm Hg @ 25°C) (U.S. EPA 1985; Budavari 1989). It is released into the
        environment primarily from industrial uses but can also be formed in the atmosphere by the nitration
        of benzene, a common air pollutant (ATSDR 1990). The largest sources of nitrobenzene  release  are
        from its manufacture and primary use as a chemical intermediate in the synthesis of aniline (U.S.
        EPA 1985).  The amounts of nitrobenzene released to surface water and to land by industry have  been
        greatly reduced  since  1988 (TRI92  1994). Smaller amounts are also released from consumer
        products in which nitrobenzene is used as a solvent. The most familiar of these are metal and shoe
        polishes (ATSDR 1990).

        Nitrobenzene levels in air have been measured in urban, rural, and waste disposal areas in New
        Jersey. Most air samples taken in 1982 were negative for nitrobenzene, and the positive samples
        taken from residential areas were about 0.3 parts per billion (ppb) or less. Samples from industrial
        areas were 0.9 ppb or more with the highest samples being 3.5 to 5.7 ppb. The atmospheric
        nitrobenzene concentration was higher in the summer than winter and lower during periods of heavy
        rain or snow.  Air samples taken over landfills in 1985, contained a maximum of 14.48 ppb nitroben-
        zene.  Nitrobenzene has been detected in samples taken during rain or snow (ATSDR 1990). In
        surface water, nitrobenzene was detected in only 0.4% of 836 ambient surface water stations, and in
        1.8% of 1245 reporting stations on  industrial waste waters (ATSDR 1990).  Soil samples  taken along
        the banks of the Buffalo River in New York contained 8 ppm nitrobenzene in 1980, but the chemical
        was not found in sediment samples (ATSDR 1990).

        In 1992, releases of nitrobenzene to environmental media, as reported to the Toxic Chemical Release
        Inventory by certain types of U.S. industries, totaled about 917 thousand pounds. Of this amount, 52
        thousand pounds (5.6%) were released to the atmosphere; 442 pounds (0.05%) were released to
        surface water; and 865 thousand pounds (94.32%) were released in underground injection sites; no
        nitrobenzene was reported to have  been released to land (TRI92 1994).

B.      Transport

        Nitrobenzene will volatilize slowly from soil and surface water (vapor pressure,  0.27 mm Hg @
        25°C) and is subject to biodegradation (U.S. EPA 1985).  Adsorption to sediment and
        bioconcentration are not thought to be significant fate processes in water. Nitrobenzene may leach
        through the soil and is considered to have intermediate mobility (ATSDR 1990).
C.      Transformation/Persistence

        1.       Air — Nitrobenzene apparently undergoes direct photolysis in the atmosphere.
                Photoproducts formed from nitrobenzene in the atmosphere include ortho- andpara-
                nitrophenols, and nitrosobenzene.  Phenol was found as a photodegradation product of
                nitrobenzene in the absence of oxygen (U.S. EPA 1985; ATSDR 1990).  In laboratory tests,

                        38% of nitrobenzene in air was photochemically degraded in 5 hours by irradiation from a
                        xenon lamp (U.S. EPA 1985; Howard 1989). The chemical reacts slowly with hydroxyl
                        radicals and ozone.  The half-lives calculated for reactions of nitrobenzene with hydroxyl
                        radicals and ozone in moderately polluted air are 90 days and 2 years, respectively (ATSDR
                        1990).  Removal of nitrobenzene from the atmosphere by wet deposition is not believed to
                        be significant (U.S. EPA 1985).

                2.       Soil — Nitrobenzene is subject to biodegradation in the soil, but the rates of decomposition
                        based on screening tests are conflicting. Results range from 98% removal in 5 days with
                        activated sludge inoculum, to no degradation in 10 days with activated sludge inoculum.
                        Higher concentrations of nitrobenzene have been shown to be toxic to microorganisms, but
                        this explanation alone cannot account for the varying results (Howard 1989; ATSDR 1990).

                3.       Water — Nitrobenzene in solution is subject to biodegradation and photodegradation; small
                        amounts also adsorb  to sediment or volatilize from the surface.  The half-life of nitrobenzene
                        in model waste stabilization ponds was measured at 3.8 days; 89.5%  of the added chemical
                        was degraded, 4.9% volatilized, 2.3% adsorbed to sediment, 2.3% was lost in effluent, and
                        1% remained (Howard 1989). The half-life of nitrobenzene in aquatic environments has
                        been estimated at 0.3 days by the U.S. EPA (1987).

                4.       Biota — The bioconcentration factors in two species of fish, L.  idus (golden orfe) and P.
                        promelas  (fathead minnow), have been estimated at 15 and less than 10, respectively (U.S.
                        EPA 1987). A bioconcentration factor of 3 has also been calculated for P. reticulata
                        (guppy) (Howard 1989).  Nitrobenzene is not expected to accumulate significantly in aquatic
                        organisms, however, it has been shown to be taken up and may bioconcentrate in terrestrial
                        plants (ATSDR 1990).

        A.      Pharmacokinetics
                1.       Absorption — Studies in humans and animals have demonstrated that nitrobenzene is
                        absorbed through the skin, the lungs, and the gastrointestinal tract. The maximum dermal
                        absorption of liquid nitrobenzene was 0.2 - 3.0 mg/cmVhour (U.S. EPA 1985). When
                        volunteers were exposed to 1 or 5.5 ppm nitrobenzene in air, it was estimated that about half
                        of the absorbed dose of nitrobenzene was absorbed through the skin (ATSDR 1990).
                        Volunteers breathing 6 ppm nitrobenzene had an average absorption rate of 80% (ATSDR
                        1990; U.S. EPA 1985).  Animal experiments have shown that  nitrobenzene is metabolized
                        and excreted following oral administration.  Absorption from the gastrointestinal tract can
                        also be inferred from animal and human studies that demonstrate toxic effects following the
                        ingestion of nitrobenzene (U.S. EPA 1985).

                2.       Distribution — Two days after oral administration of 14[C]-nitrobenzene to rabbits, about
                        56%  of the radioactivity was bound by the tissues, localized primarily in fat and the
                        intestinal tract.  After 8 days, about 8% of the original dose remained in the fat tissues.
                        Analysis of the tissue indicated that the radioactivity represented metabolites of nitrobenzene
                        rather than unaltered nitrobenzene (U.S. EPA 1985).  The day  after the oral administration of
                        radiolabeled nitrobenzene to rats the amount of radioactivity bound to various tissues
                        included 229 mmol/mol  bound to hemoglobin in the blood, 129 mmol/kg bound in liver, 204
                        mmol/kg bound in kidney, and 62 mmol/kg bound in lung (ATSDR 1990).

                3.       Metabolism — The primary metabolite of nitrobenzene in rabbits was reported to be p-
                        aminophenol (U.S. EPA 1985).  This urinary metabolite accounted for 31-56% of the
                        administered oral dose within 2-5 days. Other metabolites  representing 3-9% of the oral
                        dose  included Tw-aminophenol, o-aminophenol,/>-nitrophenol,  and Tw-nitrophenol. Minor
                        metabolites accounting for less than 1 % of the administered dose were identified as aniline,
                        o-nitrophenol, 4-nitrocatechol, nitroquinol, and/>-nitrophenylmercapturic acid (U.S.  EPA
                        1985). />-Aminophenol was a major urinary metabolite in mice,  but did not appear in the
                        urine of either CD or Fischer 344 rats following oral exposure to nitrobenzene. U.S. EPA
                        (1995) has suggested this species difference in nitrobenzene metabolism be considered when
                        discussing possible metabolism of nitrobenzene in humans.  Other urinary metabolites

                   identified in rat and mouse studies include />-hydroxy acetanilide,/>-aminophenol,/>-
                   nitrophenol, and w-nitrophenol.  These metabolites have been found in the free state and
                   conjugated with glucuronide and sulfate with varying frequencies in rats and different strains
                   of mice (U.S. EPA 1985).  The reduction of nitrobenzene by microflora of the intestinal tract
                   appears to occur following oral exposure. Sterilization of the intestinal tract altered the
                   proportion of urinary metabolites excreted by rats, decreasing the excretion ofp-
                   hydroxyacetanilide and an unidentified metabolite by 94 and 86%, respectively (U.S. EPA

           4.       Excretion — Nitrobenzene metabolites are excreted in the urine predominantly with smaller
                   amounts excreted in feces and in expired air. />-Nitrophenol and
                   />-aminophenol and their glucuronate and/or sulfate conjugates have been identified in the
                   urine of humans and mice; />-aminophenol was apparently not excreted by the rat strains
                   tested.  Rats eliminated a total of 75-79% of the initial dose in 72 hours following oral
                   administration of 14[C]nitrobenzene; 60.8-65.8% of the dose was found in the urine. Mice
                   were able to eliminate  54.3% of the administered dose in 72 hours with 34.7% found in the
                   urine.  The rest of the radioactivity recovered was found in the feces (11.8-21.4%) and in
                   expired air (0.8-2.5%)  from the rats and mice tested (U.S. EPA 1985). The major urinary
                   metabolites in humans are/>-nitrophenol and/>-aminophenol; however, the metabolites are
                   excreted more slowly than in rats, mice, or rabbits. Urinary />-nitrophenol, which can be
                   utilized to estimate the nitrobenzene exposure level, reached peak levels  about 4 days after
                   exposure (U.S. EPA 1985).
   B.      Acute Toxicity
           The primary toxic effect resulting from acute exposure to nitrobenzene by inhalation, oral or dermal
           routes is methemoglobinemia and accompanying anoxia and erythrocyte damage. Nervous system
           effects may also be experienced, but may be partially due to the anoxia from the methemoglobinemia
           (see section IV.G.).

           1.       Humans — Inhalation exposure to nitrobenzene concentrations equal to or greater than 6
                   ppm in air (30.72 mg/m3; 4.4 mg/kg/day)2 was reported to result in nervous system effects
                   (see section IV.G.) and methemoglobin production (U.S. EPA 1985). Sulfhemoglobinemia
                   has also been observed following nitrobenzene poisoning (U.S. EPA 1985).  Atmospheric
                   concentrations of nitrobenzene resulting in these effects are well above the odor threshold of
                   1.9 ppm, which may help limit human exposures (U.S. EPA 1985). Oral exposures to
                   nitrobenzene have been reported, although rare and poorly documented.
                   Methemoglobinemia is the primary acute effect following nitrobenzene ingestion.  The dose
                   resulting in methemoglobinemia was estimated in one case study at 4.3  to 11 g based on
                   urinary p-nitrophenol levels. A latency period of 30 minutes to  12 hours, varying inversely
                   with the dose, followed ingestion (ATSDR 1990).  Nitrobenzene is rapidly absorbed through
                   the skin and is a contact irritant (Keith and Walters 1985).

           2.       Animals — Increased methemoglobin production has been reported in mice, rats, rabbits,
                   and dogs following acute exposure to nitrobenzene. Mice appear to be the most resistant to
                   methemoglobinemia probably because of a higher  level of methemoglobin reductase activity.
                   However, germ-free or antibiotic-treated rats do not develop methemoglobinemia, which
                   demonstrates a likely role of intestinal bacteria in methemoglobin production in the rat (U.S.
                   EPA 1985).  Hepatic lesions were recorded following a single oral dose of nitrobenzene in
                   rats (amount not given in the secondary source) (U.S. EPA 1985).

                   LD50 values for various routes of administration have been calculated for rats including 640
                   mg/kg for oral administration and 2100 mg/kg for dermal administration (U.S. EPA 1985).
                   An inhalation LC50 value of 556 ppm was calculated for Crl:CD rats exposed for 4 hours.
    2For dose comparison purposes, this has been calculated by multiplying by 0.143 (the adult
occupational breathing rate, 10 rrrVday, divided by the assumed adult body weight, 70 kg) to obtain the
dose in mg/kg/day assuming 100% absorption (U.S. EPA 1988).

                   Clinical observations reported during exposure included cyanosis, weakness,
                   chromodacryorrhea, slight reddish-brown nasal discharge, slight corneal clouding, and
                   lacrimation.  Following exposure, survivors exhibited tremors, tachypnea, weight loss,
                   diarrhea, and prostration. Some animals were hyperactive and exhibited aggressive behavior
                   (TSCATS 1994).

   C.      Subchronic/Chronic Effects

           Limited evidence suggests that the liver may be a target organ in humans following extended
           inhalation exposure to nitrobenzene.  Adverse effects on the liver and kidneys have been reported in
           animal studies.   A lowest-observed-adverse-effect level of 25 mg/m3 was identified in rats and mice
           based on hematologic, adrenal, renal, and hepatic lesions. This value was converted to an equivalent
           continuous oral dose for mice and utilized by the U.S. EPA (1994) to derive an oral reference dose
           (RfD)3 of 0.0005 mg/kg/day for nitrobenzene exposure.
           1.       Humans— An enlarged liver, jaundice, and a decreased liver function test
                   (bromosulfophthalein retention) were reported in a case history of a woman occupationally
                   exposed to unspecified concentrations of nitrobenzene for 17 months.  The exposure
                   concentration for 2 of the  17 months has been qualitativiely described as "high" (U.S. EPA
                   1985).  The consumption of alcohol has been reported to result in an acute crisis including
                   coma in individuals previously exposed chronically or subchronically to nitrobenzene.  In
                   one case history, an acute crisis was precipitated by the consumption of one beer 6 weeks
                   after recovering from a subchronic nitrobenzene poisoning episode; however, no numerical
                   data on nitrobenzene exposure were given (U.S. EPA 1987).

           2.       Animals — Groups of 10  male and 10 female Fischer 344 rats, Sprague-Dawley CD  rats,
                   and B6C3F[ mice were exposed by inhalation to nitrobenzene concentrations of 0, 5,  16, or
                   50 ppm (0, 25, 81, or 252  mg/m3), 6 hours/day, 5 days/week for 90 days. Increased
                   methemoglobin levels were seen in Fischer rats  at 25 mg/m3, in Sprague-Dawley rats at 81
                   mg/m3, and in mice at 252 mg/m3.  Hemosiderosis was seen in the spleens of both rats and
                   mice, but was mild in mice and also occurred in the control group.  Increased hematopoiesis
                   and hemolytic anemia including reticulocytosis was observed at 81 mg/m3 in Fischer rats
                   and at 252 mg/m3 in Sprague-Dawley rats. Very slight to minimum nephrosis was recorded
                   for both rat strains at 25 mg/m3.  Increased kidney weights were seen at 252 mg/m3. No
                   kidney effects were recorded in mice.  Nitrobenzene treatment resulted in liver lesions in
                   both rats and mice. Hepatocellular hypertrophy  and Kupffer cell pigmentation were
                   observed in Sprague-Dawley rats at 25 mg/m3. At 81 mg/m3, increased periportal basophilia
                   and enlarged nucleoli were seen in rats, and centrilobular hepatocellular hyperplasia was
                   recorded for mice.  Increased severity  and incidence of vacuolization of the adrenal zona
                   reticularis in female mice  were also observed at 25 mg/m3 (U.S. EPA 1985).  The 25  mg/m3
                   concentration defined a lowest-observed-adverse level  (LOAEL) for rats and mice based on
                   hematologic,  adrenal, renal, and hepatic lesions  (U.S. EPA 1994).  This value  in mice was
                   converted to an equivalent continuous oral dose  of 4.6 mg/kg/day and was utilized by the
                   U.S. EPA (1994) to calculate a chronic oral RfD of 0.0005 mg/kg/day for nitrobenzene.

                   Inhalation exposure to 35  ppm for 2 weeks resulted in hepatocyte necrosis in male Sprague-
                   Dawley rats (ATSDR 1990).

   D.      Carcinogenicity

           Nitrobenzene causes in rats and mice in lifetime inhalation studies. This has been used as  a basis for
           a recommendation to classify nitrobenzene as a B2, probable human carcinogen.

           1.       Humans - No information was found in the secondary sources search on the carcinogenicity
   3The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of the exposure level
for the human population, including sensitive subpopulations, that is likely to be without an appreciable risk of
deleterious effects during the time period of concern.

                of nitrobenzene in humans.

        2.       Animals - A recent assessment of the carcinogenicity of nitrobenzene has been completed by
                U.S. EPA (1995).  The assessment is based on a single 1983 Chemical Industry Institute of
                Toxicology inhalation study of both sexes of B6C3F, F344/N rats, and Sprague-Dawely (CD
                strain) rats.4 Mice were exposed to 0, 5, 25, and 50 ppm; rats, to 0, 1, 5, and 25 ppm.
                Exposures were for 6 hours per day, 5 days per week, for 104 weeks.  Nitrobenzene induced
                tumors in several sites over different species, sexes, and doses. Significant increases in
                tumors were observed in the alveolus and bronchus, the thyroid, and the mammary gland of
                mice.  F344/N rats showed significant increases in tumors of the liver, the thyroid, the
                kidney, and the endometrium.  Sprague-Dawley (CD) rats showed significant increases in
                tumors of the liver.

E.      Genotoxicity

        Results of short term mutagenicity testing show nitrobenzene is not genotoxic. Nitrobenzene was
        negative in the Ames assay with Salmonella typhimurium  strains TA92, TA94, TA98, TA100,
        TA1537, and TA1538 with, or without metabolic activation (U.S. EPA 1987).  Intragastric treatment
        of mice with nitrobenzene did not result in micronuclei or chromosome aberrations in bone marrow
        cells or dominant lethal mutations.  No increase in unscheduled DNA synthesis in rat hepatocytes
        was seen 12 hours following gavage treatment with 200 or 500 mg/kg nitrobenzene (U.S. EPA  1987).

F.      Developmental/Reproductive Toxicity

        Animal studies have shown that inhalation exposure to nitrobenzene can cause adverse testicular
        effects resulting in decreased fertility index.

        1.       Humans — No information was found in the secondary sources searched on the
                developmental/reproductive toxicity of nitrobenzene to humans.

        2.       Animals — A decrease in fertility indices was recorded following inhalation exposure to 40
                ppm nitrobenzene, 6 hours/day, 7 days/week for 12 weeks prior to and including the mating
                period in a two-generation study  in rats. Exposure was continued with the females through
                day 19 of gestation.  Microscopic examination revealed atrophy of the seminiferous tubules,
                spermatocyte degeneration, absence of mature sperm in the epididymis, and decreased
                testicular and epididymal weights in both F0 and Fj generations. The fertility index
                increased five-fold during 9 weeks of recovery following exposure to nitrobenzene. There
                was no observed maternal toxicity,  and no effects on survival or lactation indices at any dose
                tested ( 0, 1, 10, or 40 ppm) (U.S. EPA 1987). Inhalation exposure of B6C3Fl mice, and
                Fischer 344 and Sprague-Dawley rats to nitrobenzene concentrations of 0, 5, 16, or 50 ppm,
                6  hours/day, 5 days/week for 90 days resulted in severe degeneration of the spermatogenic
                epithelium with decreased testicular weight, and an absence of mature sperm in the
                epididymis of both rat strains.  Only slight effects were observed at the lower doses, and no
                testicular changes were seen in the mice (U.S. EPA 1987).

                Inhalation  studies have shown no fetotoxic, embryotoxic, or teratogenic effects at
                concentrations up to 40 ppm in rats and 100 ppm in rabbits. Maternal toxicity did occur at
                these levels, demonstrated by increased methemoglobin levels and increased spleen and liver
                weights (ATSDR 1990; U.S. EPA 1987).

                Treatment of Fischer 344 and Sprague-Dawley rats with a single oral dose of 300 mg/kg
                nitrobenzene resulted in necrotic primary and secondary spermatocytes, multinucleated giant
                cells, and decreased numbers of spermatocytes in  the epididymis within 1-4 days after
                treatment.  These effects were not seen at 50-200 mg/kg (U.S. EPA 1985).
  The study was finalized in 1993.

        G.      Neurotoxicity

                Adverse central nervous system effects can occur in humans and animals following nitrobenzene
                exposure. Many of these effects may be secondary to the anoxia resulting from methemoglobinemia.

                1.       Humans — Exposure to nitrobenzene for up to 17 months was reported to cause headache,
                        nausea, vertigo, confusion, hyperalgesia, and paresthesia (U.S. EPA 1985;  ATSDR 1990).
                        Acute nervous system effects include nausea, nystagmus, convulsions, and coma.  Exposure
                        to concentrations greater than 40 ppm has resulted in intoxication.  Methemoglobinemia has
                        also been shown to occur, and the resulting anoxia may partially account for the nervous
                        system effects (U.S. EPA 1985).

                2.       Animals — Bilateral cerebellar perivascular hemorrhage and cell breakdown in the
                        hindbrain (cerebellar peduncle) were seen in B6C3F[ mice and Sprague-Dawley rats exposed
                        to 125 ppm nitrobenzene for two weeks.  Fischer rats given nitrobenzene at the same
                        exposure level and duration did not develop any brain lesions (ATSDR 1990).


        Available information indicates that nitrobenzene is moderately toxic to aquatic life. Several reported 96-
        hour LC50 values are in the range of >1 mg/L to 100 mg/L.

        A.      Toxicity to Aquatic Organisms

                Ninety-six-Hour LC50 values for fish are: 42.6 mg/L for Lepomis macrohirus (bluegill sunfish), 117
                mg/L for Pimephales promelas (fathead minnow), 112.5 mg/L for Brachydanio rerio (zebrafish),
                and 58.6 for Cyprinodon variegatus (sheepshead minnow). Forty-eight-Hour LC50  values for fish
                are: 105 mg/L for Lepomis macrohirus (bluegill sunfish), 156 mg/L for Pimephales promelas
                (fathead minnow), 60-89 mg/L for Leuciscus idus melanotus (golden orfe), 20 mg/L for Oryzias
                latipes (medaka), and >120 mg/L for Cyprinodon variegatus (sheepshead minnow) (U.S. EPA

        B.      Toxicity to Terrestrial Organisms

                Nitrobenzene is unlikely to exist in U.S. terrestrial environments in sufficient concentrations to cause
                serious acute or chronic effects to terrestrial organisms. Toxicity  information reported for rats, mice,
                and rabbits (see sections IV.B.2., IV.C.2. and IV.G.) suggest that no acute effects would be seen at
                normally expected U.S. environmental concentrations.

        C.      Abiotic Effects

                Nitrobenzene reacts with hydroxyl radicals and ozone in the atmosphere. In moderately polluted
                conditions the half-life of nitrobenzene in the atmosphere may be reduced by a factor of 10.  The rate
                constant calculated for the reaction with ozone (5xl023 cmVmolecule-sec) indicates  that the reaction
                has no environmental  significance (U.S. EPA 1985).

        The Clean Air Act Amendments of 1990 list nitrobenzene as a hazardous air pollutant.  Occupational
        exposure to nitrobenzene is regulated by the Occupational Safety and Health Administration (OSHA). The
        OSHA permissible exposure limit (PEL) is 1 part per million parts of air (ppm) as an 8-hour time-weighted
        average (TWA) (29 CFR 1910.1000).  In addition to OSHA, other federal agencies and groups may develop
        recommendations to assist in controlling workplace exposure. These agencies and groups (listed in Tables 4
        and 5) should be contacted regarding workplace exposures, and for additional information on nitrobenzene.
EPA Office
Contact Number
Pollution Prevention & Toxics

Solid Waste &
 Emergency Response
                                  TSCA (§8A, §8D, §4)b

                                  Clean Air Act (§111, §112B)C

                                  RCRA (Action levels:
                                   2.0 |jg/m3, air
                                   0.02 mg/L, water
                                   40 mg/kg, soil)d
                                  CERCLA (RQ, 1000 pounds)6
                                  SARA (§110, §302A, §313)

                                  Clean Water Act (§304b,
                                  §307a, §311, CWA  Priority)
                                  WQC (l7ug/L[ao/do];
(800) 535-0202


(800) 535-0202

(800) 535-0202

(202) 260-7588
 "EPCRA: Emergency Planning and Community Right to Know Act of 1986

bTSCA: Toxic Substances Control Act

°Listed as hazardous air pollutant under § 112 of Clean Air Act [42 U.S.C. 7401 etseq.]

dRCRA: Resource Conservation and Recovery Act (40 CFR 264.94). Action Level : Health and environmental-based levels used by the
EPA as indicators for the protection of human health and the environment and as triggers for a Corrective Measure Study.

"CERCLA: Comprehensive Environmental Response, Compensation, and Liability Act of 1980, as amended.  RQ:  level of hazardous
substance, which, if equaled or exceeded in a spill or release, necessitates the immediate reporting of that release to the National Response
Center (40 CFR Part 302).

VVQC: Federal ambient water quality criteria for the protection of human health (56 FR 58420). Ambient Water Quality Criteria standards  :
established pursuant to the Clean Water Act, 57 FR 60848,  December 22, 1992. ao/dw: protection for consuming aquatic organisms and
drinking water; ao: protection for consuming aquatic organisms.


Other Agency/Department/Group                                          Contact Number

Agency of Toxic Substances & Disease Registry                              (404) 639-6000
American Conference of Governmental Industrial Hygienists                  (513) 742-2020
 [TLV-TWA, 1  ppm (5 mg/m3),*]3
Consumer Product Safety Commission                                      (301) 504-0994
Food & Drug Administration                                                 (301) 443-3170
National Institute for Occupational Safety & Health                            (800) 356-4674
 [TWA, 1 ppm (5 mg/m3); IDLH, 200 ppm; *]b
Occupational Safety & Health Administration                                  (202) 639-7960
 [TWA, 1 ppm (5 mg/m3]c

"TLV-TWA: Time-weighted-average concentration for a normal 8-hour workday and a 40-hour workweek to which nearly all workers
may be repeatedly exposed without adverse effects; *: Skin designation, air sampling alone is insufficient to accurately quantitate
exposure. Measures to prevent significant cutaneous absorption may be required (ACGIH 1994-1995).

bTWA: Time-weighted-average concentrations for up to a 10-hour workday during a 40-hour workweek; IDLH: immediately dangerous
to life or health concentration, the maximum concentration from which, in the event of respirator failure, one could escape within 30
minutes without a  respirator and without experiencing any escape-impairing or irreversible health effects;  *: Skin designation, air
sampling alone is  insufficient to accurately quantitate exposure. Measures to prevent significant cutaneous absorption may be required
(NIOSH 1990; 1992).

CTWA: Time-weighted-average that must not be exceeded during any 8-hour work shift of a 40-hour workweek.
Standard promulgated pursuant to the Occupational Safety and Health Act, 29 CFR 1910 (OSHA 1993).


ACGIH.  1994-1995.  American Conference of Governmental Industrial Hygienists.  Threshold Limit Values for
Chemical Substances and Physical Agents and Biological Exposure Indices. ACGIH, Cincinnati, OH.

ATSDR.  1990. Agency for Toxic Substances and Disease Registry. Toxicological Profile for Nitrobenzene.
U.S. Department of Health and Human Services, Public Health Service. Atlanta, GA.

Budavari S, O'Neil MJ, Smith A, Heckelman PE  (Eds.). 1989. The Merck Index, 11th ed. Merck & Co., Inc.,
Rahway, N.J., p. 1042.

Howard  PH.  1989. Handbook of Environmental Fate and Exposure Data for Organic Chemicals, Vol. I, Large
Production and Priority Pollutants. Lewis Publishers, Inc., Chelsea, Michigan, pp. 421-430.

Keith LH and Walters DB. 1985. Nitrobenzene, in Compendium of Safety Data Sheets for Research and
Industrial Chemicals,  Part III. VCH Publishers, Inc., pp. 1218-1219.

Mannsville.  1991.  Mannsville Chemical Products Corporation. Nitrobenzene.  Chemical Products Synopsis.
Asbury Park. February 1991.

Newsome L. 1995. Memorandum from Larry Newsome (HERD/EEB) to R Wormell (CSRAD/AIMB).  Subject:
Comments on OPPT  Fact Sheets. July 13, 1995.

NIOSH.  1990.  National Institute for Occupational Safety and Health. NIOSH Pocket Guide to Chemical
Hazards. Cincinnati, OH.

NIOSH.  1992.  National Institute for Occupational Safety and Health. 1992. NIOSH Recommendations for
Occupational Safety and Health.  Compendium of Policy Documents and Statements. NIOSH, Cincinnati,

OSHA.  1993. Occupational Safety and Health Administration. Air Contaminants. Final Rule. 29 CFR part
1910.  Fed Reg 58:35338-35351.

Sittig,  M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, Third edition.  New Jersey:  Noyes
Publications, 1991.

TRI92. 1994. 1992 Toxics Release Inventory, Public Data Release. Office of Pollution Prevention and
Toxics, U.S. EPA, Washington, D.C., p. 244.

TSCATS. 1994. MEDLARS Online Information Retrieval system, National Library of Medicine. Retrieved
12/94. Doc. #878220423.

U.S. EPA. 1985.  U.S. Environmental Protection Agency. Health and Environmental Effects Profile for
Nitrobenzene. Office of Solid Waste and Emergency Response, Washington, D.C. ECAO-CIN-P145.

U.S. EPA. 1987.  U.S. Environmental Protection Agency. Health Effects Assessment for Nitrobenzene. Office
of Research and Development, Cincinnati, OH. EPA/600/8-88/049. ECAO-C-H073.

U.S. EPA. 1988.  U.S. Environmental Protection Agency. Methodology for Evaluating Potential
Carcinogenicity in Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102. Carcinogen
Assessment Group, Office of Health and Environmental Assessment, U.S. EPA, Washington, D.C., pp. 21,22.
U.S. EPA. 1994.  Integrated Risk Information System (IRIS) Online. Coversheet for Nitrobenzene. Office of
Health and Environmental Assessment, U.S. EPA, Cincinnati,  OH. Retrieved 10/94.

U.S. EPA. 1995.  U.S. Environmental Protection Agency Hazardous Air Pollutant (HAP) Nitrobenzene
Carcinogenicity.  Office of Research and Development, National Center for Environmental Assessment, U.S.
EPA, Washington, D.C.

USITC.  1994. United States International Trade Commission. Synthetic Organic Chemicals: United  States
Production and Sales, 1992. 76th edition.  USITC Publication 2720, February 1994.

Verschueren, K. 1983. Nitrobenzene, in: Handbook of Environmental Data on Organic Chemicals, Second
Edition. Van Nostrand Reinhold Co., New York, pp. 910-912.


ACGIH.  Most recent. American Conference for Governmental Industrial Hygienists, Inc. TLVs®. Documentation of the Threshold Limit
Values and  Biological Exposure Indices, ... ed. ACGIH, Cincinnati, OH.

AQUIRE. 1994. Aquatic Information Retrieval online data base. Chemical Information Systems, Inc., a subsidiary of Fein-Marquart

ATSDR. 1989-1994. Agency for Toxic Substances and Disease Registry.  Toxicological Profiles. Chamblee, GA: ATSDR.

Budavari S, O'Neil MJ, Smith A, Heckelman PE (Eds.). 1989. The Merck Index, 11th ed. Rahway, N.J.:  Merck & Co., Inc.

Clayton GD, Clayton FE. 1981-1982. Patty's Industrial Hygiene and Toxicology, 3rd ed., Vol. 2C. New York: John Wiley & Sons.
(Soon to be updated)

Clean Air Act. 1990. As amended. 42 U.S.C. 7412.

GENETOX. 1994. U.S. EPA GENETOX Program, computerized database.

Howard, P.H., Ed. 1989. Handbook of Environmental Fate and Exposure Data. Lewis Publishers, Chelsea, Ml.

HSDB. 1994. Hazardous Substances Data Bank. MEDLARS Online Information Retrieval System, National Library of Medicine.

IARC. 1979-1994. International Agency for Research on Cancer.  IARC Monographs on the Evaluation of Carcinogenic Risk of
Chemicals to Man. Lyon: IARC.

IPCS. 19....  International Programme on Chemical Safety.  Environmental  Health Criteria. World Health Organization, Geneva,

NIOSH (National Institute for Occupational Safety and Health). 1992. NIOSH Recommendations for Occupational Safety and Health.
Compendium of Policy Documents and Statements. Cincinnati, OH: NIOSH.

NTP.  199...  National Toxicology Program.  Toxicology and  Carcinogenesis Studies. Tech Rep Ser.

NTP.  199...  National Toxicology Program.  Management Status Report. Produced from NTP Chemtrack system. Aprils, 1994.
National Toxicology  Program, Research Triangle Park, NC.

OSHA. 1993. Occupational Safety and Health Administration. Table Z-2.  Limits for Air Contaminants.

TRI92. 1994. 1992  Toxics Release Inventory. Public Data  Release. Office of Pollution Prevention  and Toxics  (7408), U.S.
Environmental Protection Agency, Washington, D.C.

TSCATS. 199... MEDLARS Online Information Retrieval System, National Library of Medicine.

U.S. Air Force.  1989. The Installation Restoration Toxicology Guide, Vols.  1-5.  Wright-Patterson Air Force Base, OH.

U.S. EPA .  1991. U.S. Environmental Protection Agency. Table 302.4 List of Hazardous Substances and Reportable Quantities 40
CFR, part 302.4:3-271.

U.S. EPA.  U.S. Environmental Protection Agency. Appendix A. Examples of Concentrations Meeting Criteria for Action Levels.  40
CFR Part 264.521 (a)(2)(i-iv). Fed. Reg. 55:30865-30867.

U.S. EPA.  Most current. Drinking Water Regulations and Health Advisories. Office of Drinking Water, U.S. Environmental Protection
Agency, Washington, D.C.

U.S. EPA.  Most Current. Health Effects Assessment Summary Tables. Cincinnati, OH: Environmental Criteria and Assessment
Office, U.S.EPA.

U.S. EPA reviews such as Health and Environmental Effects Documents, Health and Environmental Effect Profiles, and Health and
Environmental Assessments, HERD Analogue Profiles, ITC  Documents.

U.S. EPA.  1994.  Integrated Risk Information System (IRIS) Online. Cincinnati, OH:  Office of Health and Environmental Assessment.