SUBSTANCE PROFILES

REPORT ON CARCINOGENS, ELEVENTH EDITION

Nitroarenes (Selected) 

Introduction

The nitroarenes comprise a large class of structurally related chemicals

that are normally found in particulate emissions from many

combustion sources, most notably, diesel exhausts. These compounds

were first listed in the Eighth Report on Carcinogens (1998) as reasonably

anticipated to be a human carcinogen based on carcinogenicity results

with experimental animals. Few of this large class of chemicals have

been rigorously evaluated in “state-of-the-art” rodent cancer studies.

Typically, the chemicals were administered by injection, over short

periods of time, and with less than optimal time allowed for tumors to

fully develop. Despite these factors, the experimental carcinogenesis

results are generally similar and demonstrate tumor formation at the

site of injection and at sites away from the site of injection. The

chemicals also show genotoxic activity in a variety of in vitro and in

vivo assays, and metabolic pathways for the creation of reaction

products with the ability to cause gene mutations or changes in the

structure of DNA have been described in tissues from animals as well

as humans. No adequate human studies of the relationship between

exposure to these chemicals and human cancer have been reported.

However, exposure to diesel exhaust particulates is listed in the Report

on Carcinogens as reasonably anticipated to be a human carcinogen,

based on findings of elevated lung cancer rates in occupational groups

exposed to diesel exhaust and supporting animal and mechanistic

studies. Whether the nitroarenes are responsible for, or contribute to,

the human carcinogenicity of diesel exhaust has not been determined. 

Profiles for the following nitroarenes follow this introduction. The

CAS Registry Number for each compound is listed in parentheses

after the name.

• 1,6-Dinitropyrene (42397-64-8) 

• 1,8-Dinitropyrene (42397-65-9) 

• 6-Nitrochrysene (7496-02-8)

• 1-Nitropyrene (5522-43-0) 

• 4-Nitropyrene (57835-92-4) 

Nitroarenes (Selected)

1,6-Dinitropyrene

CAS No. 42397-64-8

Reasonably anticipated to be a human carcinogen

First Listed in the Eighth Report on Carcinogens (1998)

Carcinogenicity

1,6-Dinitropyrene is reasonably anticipated to be a human carcinogen

based on sufficient evidence of malignant tumor formation in

multiple species of experimental animals, at multiple sites and by

multiple routes of exposure (IARC 1989). 

When administered by subcutaneous injections, 1,6-dinitropyrene

induced injection-site sarcomas in male mice and male and female rats,

and leukemia in female rats (Tokiwa et al. 1984, Ohgaki et al. 1985,

Imaida et al. 1995). Intraperitoneal injections of 1,6-dinitropyrene

caused an increased incidence of liver-cell tumors in male mice (Wislocki

et al. 1986) and induced sarcomas of the peritoneal cavity in female rats

(Imaida et al. 1991). In two studies, squamous cell carcinomas of the

lung were induced in male rats receiving 1,6-dinitropyrene by

intrapulmonary injection (Maeda et al. 1986, Iwagawa et al. 1989). The

incidences of myeloid leukemia and lung adenocarcinomas were

significantly increased in male and female hamsters receiving 1,6-

dinitropyrene by intratracheal instillation (Takayama et al. 1985). 1,6-

Dinitropyrene induced carcinoma of the pituitary gland in an oral study

of short-term duration in rats (Imaida et al. 1991).

No adequate data were available to evaluate the carcinogenicity of

1,6-dinitropyrene in humans.

Additional Information Relevant to Carcinogenicity

Intratracheal administration of 1,6-dinitropyrene to rats previously

inoculated to de-epithelialized trachea with an immortalized bronchial cell

line, caused tumors when the tracheas were then implanted

subcutaneously into nude mice (Iizasa et al. 1993). 1,6-Dinitropyrene is

genotoxic in a wide variety of assays in bacteria and mammalian cells

including human cells. 1,6-Dinitropyrene also demonstrates evidence of

cell transformation activity in vitro in rat tracheal epithelial cells.

Metabolic pathways leading to mutagenic and clastogenic metabolites and

DNA adducts of 1,6-dinitropyrene have been described (IARC 1989). 

No data were available that would suggest that the mechanisms

thought to account for tumor induction by 1,6-dinitropyrene in

experimental animals would not also operate in humans.

Properties

1,6-Dinitropyrene occurs as light-brown needles or as a yellow

crystalline solid. The water solubility was not reported, but it is

moderately soluble in toluene. The melting point is greater than

300°C (IARC 1989). 

Use

There is no evidence that 1,6-dinitropyrene has been used for any

commercial applications. 1,6-Dinitropyrene is available for research

purposes at ≥98% purity. It is also available in 14C- or 3H-labeled

form at ≥98% radiochemical purity (IARC 1989).

Production

One foreign company synthesized >99.9% pure 1,6-dinitropyrene

(IARC 1989). One U.S. company produced 1,6-dinitropyrene (SRI

1992), and there are at least four U.S. suppliers (Chem Sources 2001).

No data on imports or exports were available.

Exposure

The primary route of potential human exposure to 1,6-dinitropyrene is

inhalation. Detectable levels have been found in ambient atmospheric

samples. Higher amounts have been reported in heavy industrialized

areas when compared to nonindustrialized urban and suburban sites.

1,6-Dinitropyrene has been found in various concentrations in extracts

of particles from the exhaust of heavy-duty and light-duty diesel

engines. It has also been found in small amounts in particulate

emissions from kerosene heaters and gas burners used for home heating

and cooking. Prior to 1980, some carbon black samples, known to be

used in photocopy machines, were found to contain considerable

quantities of 1,6-dinitropyrene (IARC 1989). 1,6-Dinitropyrene is not

listed in the National Occupational Exposure Survey or the National

Occupational Hazard Survey conducted by NIOSH.

Regulations

No specific regulations or guidelines relevant to reduction of exposure to 1,6-

dinitropyrene were identified.

REFERENCES

ChemSources. 2001. Chemical Sources International, Inc. http://www.chemsources.com.

IARC. 1989. Diesel and Gasoline Engine Exhausts and Some Nitroarenes. IARC Monographs on the

Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 46. Lyon, France: International Agency

for Research on Cancer. 458 pp.

Iizasa, T., S. Momiki, B. Bauer, J. Caamano, R. Metcalf, J. Lechner, C. C. Harris and A. J. Klein-Szanto.

NO2

O2N
SUBSTANCE PROFILES

1993. Invasive tumors derived from xenotransplanted, immortalized human cells after in vivo exposure to chemical carcinogens. Carcinogenesis 14(9): 1789-94.

Imaida, K., M. S. Lee, S. J. Land, C. Y. Wang and C. M. King. 1995. Carcinogenicity of nitropyrenes in the

newborn female rat. Carcinogenesis 16(12): 3027-30.

Imaida, K., M. S. Lee, C. Y. Wang and C. M. King. 1991. Carcinogenicity of dinitropyrenes in the weanling

female CD rat. Carcinogenesis 12(7): 1187-91.

Iwagawa, M., T. Maeda, K. Izumi, H. Otsuka, K. Nishifuji, Y. Ohnishi and S. Aoki. 1989. Comparative doseresponse study on the pulmonary carcinogenicity of 1,6-dinitropyrene and benzo[a]pyrene in F344

rats. Carcinogenesis 10(7): 1285-90.

Maeda, T., K. Izumi, H. Otsuka, Y. Manabe, T. Kinouchi and Y. Ohnishi. 1986. Induction of squamous cell

carcinoma in the rat lung by 1,6-dinitropyrene. J Natl Cancer Inst 76(4): 693-701.

Ohgaki, H., H. Hasegawa, T. Kato, C. Negishi, S. Sato and T. Sugimura. 1985. Absence of carcinogenicity

of 1-nitropyrene, correction of previous results, and new demonstration of carcinogenicity of 1,6-dinitropyrene in rats. Cancer Lett 25(3): 239-45.

SRI. 1992. Directory of Chemical Producers, United States, 1992. Stanford Research Institute, Menlo Park,

CA: SRI International. 

Takayama, S., T. Ishikawa, H. Nakajima and S. Sato. 1985. Lung carcinoma induction in Syrian golden

hamsters by intratracheal instillation of 1,6-dinitropyrene. Jpn J Cancer Res 76(6): 457-61.

Tokiwa, H., T. Otofuji, K. Horikawa, S. Kitamori, H. Otsuka, Y. Manabe, T. Kinouchi and Y. Ohnishi. 1984.

1,6-Dinitropyrene: mutagenicity in Salmonella and carcinogenicity in BALB/c mice. J Natl Cancer Inst

73(6): 1359-63.

Wislocki, P. G., E. S. Bagan, A. Y. Lu, K. L. Dooley, P. P. Fu, H. Han-Hsu, F. A. Beland and F. F. Kadlubar.

1986. Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and

benzo[a]pyrene in the newborn mouse assay. Carcinogenesis 7(8): 1317-22.

Nitroarenes (Selected) 

1,8-Dinitropyrene

CAS No. 42397-65-9

Reasonably anticipated to be a human carcinogen

First Listed in the Eighth Report on Carcinogens (1998)

Carcinogenicity

1,8-Dinitropyrene is reasonably anticipated to be a human carcinogen

based on sufficient evidence of malignant tumor formation in multiple

species of experimental animals, at multiple sites, and by multiple routes

of exposure (IARC 1989). When administered by subcutaneous

injections, 1,8-dinitropyrene induced injection-site sarcomas in male

mice and male and female rats, and leukemia in female rats (Imaida et

al. 1995, Ohgaki et al. 1984, 1985, Otofuji et al. 1987). Intraperitoneal

injections of 1,8-dinitropyrene induced sarcomas of the peritoneal

cavity, leukemia, and mammary adenocarcinoma in female rats (Imaida

et al. 1991, 1995). The incidences of mammary tumors, including

adenocarcinomas, were increased in female rats receiving 1,8-

dinitropyrene by gavage (Imaida et al. 1991, IARC 1989).

No adequate data were available to evaluate the carcinogenicity of

1,8-dinitropyrene in humans.

Additional Information Relevant to Carcinogenicity

1,8-Dinitropyrene is genotoxic in a wide variety of assays in bacteria

and mammalian cells demonstrating evidence of cell transformation

activity in vitro, and metabolic pathways leading to mutagenic and

clastogenic metabolites and DNA adducts have been described (IARC

1989).

No data were available that would suggest that the mechanisms

thought to account for tumor induction of 1,8-dinitropyrene in

experimental animals would not also operate in humans.

Properties

1,8-Dinitropyrene occurs as light-brown needles or as a yellow, fluffy,

crystalline solid. It has a melting point of ≥300°C (IARC 1989).

When heated to decomposition, 1,8-dinitropyrene emits toxic fumes

of nitrogen oxides. No information on the solubility of 1,8-

dinitropyrene was found in the published literature. 

Use

1,8-Dinitropyrene has been reported to be a photosensitizer; however,

there is no evidence that 1,8-dinitropyrene has ever been used

commercially for this or other applications. 1,8-Dinitropyrene is

available for research purposes at ≥98% purity. It is also available in

14C- or 3H-labeled form at ≥98% radiochemical purity (IARC 1989).

Production

One U.S. company produced 1,8-dinitropyrene (SRI 1992), and two

U.S. suppliers were identified (Chem Sources 2001). No data on

imports or exports of 1,8-dinitropyrene were available.

Exposure

The primary route of potential human exposure to 1,8-dinitropyrene is

inhalation. Detectable levels have been found in respirable particulates

from ambient atmospheric samples. Higher amounts have been

reported in heavy industrialized areas when compared to

nonindustrialized urban and suburban sites. 1,8-Dinitropyrene has been

found in various concentrations in extracts of particles from the exhaust

of heavy-duty and light-duty diesel engines. It has also been found in

small amounts in particulate emissions from kerosene heaters and gas

burners used for home heating and cooking. Prior to 1980, some

carbon black samples, known to be used in photocopy machines, were

found to contain considerable quantities of 1,8-dinitropyrene (IARC

1989). 1,8-Dinitropyrene is not listed in the National Occupational

Exposure Survey or the National Occupational Hazard Survey

conducted by NIOSH.

Regulations and Guidelines

No specific regulations or guidelines relevant to reduction of exposure to 1,8-

dinitropyrene were identified.

REFERENCES

ChemSources. 2001. Chemical Sources International, Inc. http://www.chemsources.com.

IARC. 1989. Diesel and Gasoline Engine Exhausts and Some Nitroarenes. IARC Monographs on the

Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 46. Lyon, France: International Agency

for Research on Cancer. 458 pp.

Imaida, K., M. S. Lee, S. J. Land, C. Y. Wang and C. M. King. 1995. Carcinogenicity of nitropyrenes in the

newborn female rat. Carcinogenesis 16(12): 3027-30.

Imaida, K., M. S. Lee, C. Y. Wang and C. M. King. 1991. Carcinogenicity of dinitropyrenes in the weanling

female CD rat. Carcinogenesis 12(7): 1187-91.

Ohgaki, H., H. Hasegawa, T. Kato, C. Negishi, S. Sato and T. Sugimura. 1985. Absence of carcinogenicity

of 1-nitropyrene, correction of previous results, and new demonstration of carcinogenicity of 1,6-dinitropyrene in rats. Cancer Lett 25(3): 239-45.

Ohgaki, H., C. Negishi, K. Wakabayashi, K. Kusama, S. Sato and T. Sugimura. 1984. Induction of sarcomas

in rats by subcutaneous injection of dinitropyrenes. Carcinogenesis 5(5): 583-5.

Otofuji, T., K. Horikawa, T. Maeda, N. Sano, K. Izumi, H. Otsuka and H. Tokiwa. 1987. Tumorigenicity test

of 1,3- and 1,8-dinitropyrene in BALB/c mice. J Natl Cancer Inst 79(1): 185-8.

SRI. 1992. Directory of Chemical Producers, United States, 1992. Stanford Research Institute, Menlo Park,

CA: SRI International. 

O2N NO2

REPORT ON CARCINOGENS, ELEVENTH EDITION
SUBSTANCE PROFILES

REPORT ON CARCINOGENS, ELEVENTH EDITION

Nitroarenes (Selected) 

6-Nitrochrysene 

CAS No. 7496-02-8

Reasonably anticipated to be a human carcinogen

First Listed in the Eighth Report on Carcinogens (1998)

Carcinogenicity

6-Nitrochrysene is reasonably anticipated to be a human carcinogen

based on sufficient evidence of carcinogenicity at multiple sites in

multiple species of experimental animals (IARC 1989). In seven

studies, when administered by intraperitoneal injection, 6-

nitrochrysene caused lung tumors in male and female mice and also

induced liver tumors in female and/or male mice in three of these

studies and malignant lymphoma in one study (Busby et al. 1985,

1989, El-Bayoumy et al. 1992, Li et al. 1994, Fu et al. 1994, Imaida et

al. 1992, Wislocki et al. 1986). Dysplastic and/or adenomatous lesions

of the colon were increased in male and female rats, and colon

adenocarcinomas were increased in male rats receiving 6-nitrochrysene

by intraperitoneal injection (Imaida et al. 1992). Mammary

fibroadenoma, adenocarcinoma, and spindle cell sarcomas were

increased in female rats receiving 6-nitrochrysene by injection into the

mammary gland (El-Bayoumy et al. 1993).

No data were available to evaluate the carcinogenicity of 6-

nitrochrysene in humans.

Additional Information Relevant to Carcinogenicity

6-Nitrochrysene induced skin tumors, mainly papillomas, in a dermal

initiation-promotion study in which 6-nitrochrysene was used as the

initiator, followed by promotion with a phorbol ester (El-Bayoumy et

al. 1982). It also caused lung and forestomach tumors when given by

intraperitoneal injection to transgenic mice carrying a human hybrid cHa-ras gene (Ogawa et al. 1996). 6-Nitrochrysene is genotoxic in

several assays in bacteria and mammalian cells and induces cell

transformation in finite lifespan cells in vitro. Metabolic pathways

leading to mutagenic and clastogenic metabolites and DNA adducts

have been described (IARC 1989). The presence of 6-nitrochryseneDNA adducts in tumor target tissue supports the possibility that

tumors induced by this chemical are at least in part a result of

chemical-induced DNA damage.

No data were available that would suggest that the mechanisms

thought to account for tumor induction by 6-nitrochrysene in

experimental animals would not also operate in humans.

Properties

6-Nitrochrysene occurs as chrome-red, thick prismatic crystals;

orange-yellow needles; and light-yellow needles. It can be transferred

from a solid state to a vapor state without decomposition, and has a

melting point of 209°C. 6-Nitrochrysene is slightly soluble in cold

ethanol, diethyl ether, and carbon disulfide; slightly more soluble in

benzene and acetic acid; and soluble in hot nitrobenzene. Heating 6-

nitrochrysene with tin and concentrated hydrochloric acid in acetic

acid at 100°C forms 6-aminochrysene. 6-Nitrochrysene also reacts

with bromine to form 12-bromo-6-nitrochrysene, and it reacts with

fuming nitric acid to form 6,12-dinitrochrysene (IARC 1989). 

Use

6-Nitrochrysene is used as an internal standard in the chemical

analysis of nitroarenes. It is available for research purposes at ≥98%

purity and is also available at a certified purity of 98.9% as a reference

material. No evidence has been found that 6-nitrochrysene has been

used commercially (IARC 1989).

Production

6-Nitrochrysene was first synthesized in 1890 (IARC 1989). One U.S.

company produced 6-nitrochrysene (SRI 1992), and Chem Sources

(2001) identified five U.S. suppliers. No data on imports or exports of

6-nitrochrysene were available.

Exposure

The primary route of potential human exposure to 6-nitrochrysene is

inhalation. Low concentrations of 6-nitrochrysene have been found in

ambient airborne particulates. Prior to 1980, some carbon black samples,

known to be used in photocopy machines, were found to contain

considerable quantities of nitropyrenes (IARC 1989). 6-Nitrochrysene is

not listed in the National Occupational Exposure Survey or the National

Occupational Hazard Survey conducted by NIOSH.

Regulations and Guidelines

No specific regulations or guidelines relevant to reduction of exposure to 6-

nitrochrysene were identified.

REFERENCES

Busby, W. F., Jr., R. C. Garner, F. L. Chow, C. N. Martin, E. K. Stevens, P. M. Newberne and G. N. Wogan.

1985. 6-Nitrochrysene is a potent tumorigen in newborn mice. Carcinogenesis 6(5): 801-3.

Busby, W. F., Jr., E. K. Stevens, C. N. Martin, F. L. Chow and R. C. Garner. 1989. Comparative lung tumorigenicity of parent and mononitro-polynuclear aromatic hydrocarbons in the BLU:Ha newborn mouse

assay. Toxicol Appl Pharmacol 99(3): 555-63.

ChemSources. 2001. Chemical Sources International, Inc. http://www.chemsources.com.

El-Bayoumy, K., D. Desai, P. Upadhyaya, S. Amin and S. S. Hecht. 1992. Comparative tumorigenicity of

nitrochrysene isomers in newborn mice. Carcinogenesis 13(12): 2271-5.

El-Bayoumy, K., S. S. Hecht and D. Hoffmann. 1982. Comparative tumor initiating activity on mouse skin of

6-nitrobenzo[a]pyrene, 6-nitrochrysene, 3-nitroperylene, 1-nitropyrene and their parent hydrocarbons.

Cancer Lett 16(3): 333-7.

El-Bayoumy, K., A. Rivenson, P. Upadhyaya, Y. H. Chae and S. S. Hecht. 1993. Induction of mammary

cancer by 6-nitrochrysene in female CD rats. Cancer Res 53(16): 3719-22.

Fu, P. P., D. Herreno-Saenz, L. S. Von Tungeln, J. O. Lay, Y. S. Wu, J. S. Lai and F. E. Evans. 1994. DNA

adducts and carcinogenicity of nitro-polycyclic aromatic hydrocarbons. Environ Health Perspect 102

Suppl 6: 177-83.

IARC. 1989. Diesel and Gasoline Engine Exhausts and Some Nitroarenes. IARC Monographs on the

Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 46. Lyon, France: International Agency

for Research on Cancer. 458 pp.

Imaida, K., C. Uneyama, H. Ogasawara, S. Hayashi, K. Fukuhara, N. Miyata and M. Takahashi. 1992.

Induction of colon adenocarcinomas in CD rats and lung adenomas in ICR mice by 6-nitrochrysene:

comparison of carcinogenicity and aryl hydrocarbon hydroxylase induction in the target organs of

each species. Cancer Res 52(6): 1542-5.

Li, E. E., R. H. Heflich, T. J. Bucci, M. G. Manjanatha, B. S. Blaydes and K. B. Delclos. 1994. Relationships

of DNA adduct formation, K-ras activating mutations and tumorigenic activities of 6-nitrochrysene

and its metabolites in the lungs of CD-1 mice. Carcinogenesis 15(7): 1377-85.

Ogawa, K., K. Imaida, T. Masui, M. Kawabe, R. Hasegawa, K. Kato, N. Ito and T. Shirai. 1996. Chemically

induced lung and forestomach neoplasias in transgenic mice carry mutant forms of the human c-Haras transgene. Carcinogenesis 17(2): 341-5.

SRI. 1992. Directory of Chemical Producers, United States, 1992. Stanford Research Institute, Menlo Park,

CA: SRI International. 

Wislocki, P. G., E. S. Bagan, A. Y. Lu, K. L. Dooley, P. P. Fu, H. Han-Hsu, F. A. Beland and F. F. Kadlubar.

1986. Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and

benzo[a]pyrene in the newborn mouse assay. Carcinogenesis 7(8): 1317-22.

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SUBSTANCE PROFILES

Nitroarenes (Selected)

1-Nitropyrene 

CAS No. 5522-43-0

Reasonably anticipated to be a human carcinogen

First Listed in the Eighth Report on Carcinogens (1998)

Carcinogenicity

1-Nitropyrene is reasonably anticipated to be a human carcinogen based

on sufficient evidence of malignant tumor formation in multiple

species of experimental animals, at multiple sites and by multiple

routes of exposure (IARC 1989). 

Intraperitoneal (i.p.) injections of 1-nitropyrene in the strain A

mouse increased lung tumors in males and females, and the numbers

of adenomas per mouse lung also increased (El-Bayoumy and Hecht

1983, El Bayoumy et al. 1984). When administered by subcutaneous

injections, 1-nitropyrene induced injection-site sarcomas in male and

female rats and mammary tumors (including adenocarcinomas) in

female rats (Hirose et al. 1984, Imaida et al. 1995). Intraperitoneal

injections of 1-nitropyrene in mice caused liver-cell tumors in males

(Wislocki et al. 1986). A study in female rats injected i.p. with 1-

nitropyrene showed increased mammary tumors; a second i.p. study

demonstrated a nonstatistically significant increase in mammary

tumors (IARC 1989, Imaida et al. 1991). Mammary gland tumors

were also increased following oral administration of 1-nitropyrene to

female rats (El-Bayoumy et al. 1988, 1995). Intratracheal

administration of 1-nitropyrene, adsorbed onto carbon black particles,

to hamsters demonstrated a weak, but significant, increase in lung

tumors over particle only controls (Moon et. al. 1990). 

No data were available to evaluate the carcinogenicity of 1-

nitropyrene in humans.

Additional Information Relevant to Carcinogenicity

1-Nitropyrene is genotoxic in a wide variety of assays in bacteria and

mammalian cells including human cells and cells from likely target

organs (i.e. lung). Further, 1-nitropyrene demonstrates consistent

evidence of cell transformation activity in vitro in both finite life-span

and immortal cell lines including human cells, and has demonstrated

the ability to form DNA adducts in vitro and in vivo. Importantly,

adducts have been detected in the lung following intratracheal

instillation of 1-nitropyrene thus supporting potential genotoxic

activity in a likely target organ in humans (IARC 1989, Chan 1996).

No data were available that would suggest that the mechanisms

thought to account for tumor induction of 1-nitropyrene in

experimental animals would not also operate in humans.

Properties

1-Nitropyrene occurs as yellow needles or prisms from ethanol, and it

has a melting point of 155°C. It is partially insoluble in water (0.02

mg/L @ 25°C); very soluble in diethyl ether, and soluble in acetone,

ethanol, benzene, toluene, and tetrahydrofluorenone. 1-Nitropyrene

reacts with ethanolic potassium hydroxide and with zinc powder in

ethanol (in the presence of catalytic amounts of ammonium chloride or

ammonia) to form 1,1 ́-azoxypyrene. 1-Nitropyrene degrades to 2-

propanol following exposure to ultraviolet/visible light. When heated to

decomposition, 1-nitropyrene emits toxic fumes of nitrogen oxides

(IARC 1989, HSDB 2003).

Use

1-Nitropyrene has been reported to be a chemical photosensitizer.

One foreign company used 1-nitropyrene as an intermediate in the

production of 1-azidopyrene, which is used in photosensitive printing.

It is available for research purposes at 97% or ≥99.5% purity with

≤0.1% total dinitropyrenes and pyrene. It is available at a purity of

99.68% as a reference material (IARC 1989).

Production

Since 1972, one foreign company has produced 1-nitropyrene by the

reaction of pyrene with nitric acid (IARC 1989). One U.S. producer

(SRI 1992) and 11 U.S. suppliers were identified (Chem Sources

2001). No data on imports or exports of 1-nitropyrene were

available.

Exposure

The primary route of potential human exposure to 1-nitropyrene is

inhalation. It is one of the most abundant mononitroarenes detected

in ambient air. Concentrations in ambient air are generally less than

0.1 ng/m3 and less than 0.5 mg/kg in airborne particulates. 1-

Nitropyrene has also been detected in stack gases from coal-fired

power plants and aluminum smelters, in particulate emissions from

many stationary combustion sources and diesel engines, in used oil

from diesel and gasoline engines, in fly-ash extracts from commercial

power plants, and particles emitted from fireplaces and coal-fired

boilers. Prior to 1980, some carbon black samples, known to be used

in photocopy machines, were found to contain considerable quantities

of nitropyrenes. 1-Nitropyrene has also been detected in the

wastewater from gasoline service stations and in river sediment (IARC

1989). 1-Nitropyrene is not listed in the National Occupational

Exposure Survey or the National Occupational Hazard Survey

conducted by NIOSH.

Regulations

EPA

Emergency Planning and Community Right-To-Know Act

Toxics Release Inventory: Listed substance subject to reporting requirements

REFERENCES

Chan, P. 1996. NTP technical report on the toxicity studies of 1-Nitropyrene (CAS No. 5522-43-0)

Administered by Inhalation to F344/N Rats. Toxic Rep Ser 34: 1-D2.

ChemSources. 2001. Chemical Sources International, Inc. http://www.chemsources.com.

El-Bayoumy, K., Y. H. Chae, P. Upadhyaya, A. Rivenson, C. Kurtzke, B. Reddy and S. S. Hecht. 1995.

Comparative tumorigenicity of benzo[a]pyrene, 1-nitropyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine administered by gavage to female CD rats. Carcinogenesis 16(2): 431-4.

El-Bayoumy, K. and S. S. Hecht. 1983. Identification and mutagenicity of metabolites of 1-nitropyrene

formed by rat liver. Cancer Res 43(7): 3132-7.

El-Bayoumy, K., S. S. Hecht, T. Sackl and G. D. Stoner. 1984. Tumorigenicity and metabolism of 1-nitropyrene in A/J mice. Carcinogenesis 5(11): 1449-52.

El-Bayoumy, K., A. Rivenson, B. Johnson, J. DiBello, P. Little and S. S. Hecht. 1988. Comparative tumorigenicity of 1-nitropyrene, 1-nitrosopyrene, and 1-aminopyrene administered by gavage to SpragueDawley rats. Cancer Res 48(15): 4256-60.

Hirose, M., M. S. Lee, C. Y. Wang and C. M. King. 1984. Induction of rat mammary gland tumors by 1-

nitropyrene, a recently recognized environmental mutagen. Cancer Res 44(3): 1158-62.

HSDB. 2003. Hazardous Substances Database. 1-Nitropyrene. National Library of Medicine.

http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB and search CAS number. Last accessed:

12/15/03.

IARC. 1989. Diesel and Gasoline Engine Exhausts and Some Nitroarenes. IARC Monographs on the

Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 46. Lyon, France: International Agency

for Research on Cancer. 458 pp.

Imaida, K., M. Hirose, L. Tay, M. S. Lee, C. Y. Wang and C. M. King. 1991. Comparative carcinogenicities

of 1-, 2-, and 4-nitropyrene and structurally related compounds in the female CD rat. Cancer Res

51(11): 2902-7.

Imaida, K., M. S. Lee, S. J. Land, C. Y. Wang and C. M. King. 1995. Carcinogenicity of nitropyrenes in the

newborn female rat. Carcinogenesis 16(12): 3027-30.

Moon, R. C., K. V. Rao and C. J. Detrisac. 1990. Respiratory carcinogenesis of nitroaromatics. Res Rep

Health Eff Inst (32): 1-29.

SRI. 1992. Directory of Chemical Producers, United States, 1992. Stanford Research Institute, Menlo Park,

CA: SRI International. 

Wislocki, P. G., E. S. Bagan, A. Y. Lu, K. L. Dooley, P. P. Fu, H. Han-Hsu, F. A. Beland and F. F. Kadlubar.

1986. Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and

benzo[a]pyrene in the newborn mouse assay. Carcinogenesis 7(8): 1317-22.

O2N

REPORT ON CARCINOGENS, ELEVENTH EDITION
SUBSTANCE PROFILES

REPORT ON CARCINOGENS, ELEVENTH EDITION

Nitroarenes (Selected) 

4-Nitropyrene

CAS No. 57835-92-4

Reasonably anticipated to be a human carcinogen

First Listed in the Eighth Report on Carcinogens (1998)

Carcinogenicity

4-Nitropyrene is reasonably anticipated to be a human carcinogen based

on sufficient evidence of malignant tumor formation at multiple tissue

sites in multiple species of experimental animals (IARC 1989).

Intraperitoneal injections of 4-nitropyrene caused an increased

incidence of liver tumors in male mice, lung tumors in male and

female mice (Wislocki et al. 1986), and mammary adenocarcinomas in

female rats (Imaida et al. 1991). When administered by subcutaneous

injections, 4-nitropyrene induced sarcomas at the injection site, and

increased incidences of mammary adenocarcinomas, leukemia, and

tumors of the Zymbal gland in female rats (Imaida et al. 1995, IARC

1989). In two studies, female rats receiving mammary gland injections

of 4-nitropyrene showed an increased incidence of mammary tumors

(Imaida et al. 1991, El-Bayoumy et al. 1993).

No data were available to evaluate the carcinogenicity of 4-

nitropyrene in humans.

Additional Information Relevant to Carcinogenicity

Although not as reactive or potent as some of the mononitro- or

dinitropyrenes, 4-nitropyrene is genotoxic in bacterial cells and

induces cell transformation in BALB cells in vitro. Metabolic pathways

for 4-nitropyrene, leading to mutagenic and likely DNA adducts, have

also been described (IARC 1989). 

No data were available that would suggest that the mechanisms

thought to account for tumor induction by 4-nitropyrene in

experimental animals would not also operate in humans.

Properties

4-Nitropyrene occurs as slender orange needles. It has a melting point

of 190°C to 192°C (IARC 1989). When heated to decomposition, 4-

nitropyrene emits toxic fumes of nitrogen oxides.

Use

4-Nitropyrene is used only as a laboratory chemical. There is no

evidence that 4-nitropyrene has ever been used for commercial

applications (IARC 1989).

Production

No evidence has been found that 4-nitropyrene has been produced for

other than laboratory use (IARC 1989). One U.S. producer (SRI

1992) and one U.S. supplier (Chem Sources 2001) were identified.

No data on imports or exports of 4-nitropyrene were available.

Exposure

The primary route of potential human exposure to 4-nitropyrene is

inhalation. Low concentrations of 4-nitropyrene were found in ambient

airborne particulates in one study. Prior to 1980, some carbon black

samples, known to be used in photocopy machines, were found to

contain considerable quantities of nitropyrenes (IARC 1989).

4-Nitropyrene is not listed in the National Occupational Exposure

Survey or the National Occupational Hazard Survey conducted by

NIOSH.

Regulations and Guidelines

No specific regulations or guidelines relevant to reduction of exposure to 4-nitropyrene

were identified.

REFERENCES

ChemSources. 2001. Chemical Sources International, Inc. http://www.chemsources.com.

El-Bayoumy, K., A. Rivenson, P. Upadhyaya, Y. H. Chae and S. S. Hecht. 1993. Induction of mammary

cancer by 6-nitrochrysene in female CD rats. Cancer Res 53(16): 3719-22.

IARC. 1989. Diesel and Gasoline Engine Exhausts and Some Nitroarenes. IARC Monographs on the

Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 46. Lyon, France: International Agency

for Research on Cancer. 458 pp.

Imaida, K., M. Hirose, L. Tay, M. S. Lee, C. Y. Wang and C. M. King. 1991. Comparative carcinogenicities

of 1-, 2-, and 4-nitropyrene and structurally related compounds in the female CD rat. Cancer Res

51(11): 2902-7.

Imaida, K., M. S. Lee, S. J. Land, C. Y. Wang and C. M. King. 1995. Carcinogenicity of nitropyrenes in the

newborn female rat. Carcinogenesis 16(12): 3027-30.

SRI. 1992. Directory of Chemical Producers, United States, 1992. Stanford Research Institute, Menlo Park,

CA: SRI International. 

Wislocki, P. G., E. S. Bagan, A. Y. Lu, K. L. Dooley, P. P. Fu, H. Han-Hsu, F. A. Beland and F. F. Kadlubar.

1986. Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and

benzo[a]pyrene in the newborn mouse assay. Carcinogenesis 7(8): 1317-22.

NO2