SUBSTANCE PROFILES

o-Nitroanisole 

CAS No. 91-23-6

Reasonably anticipated to be a human carcinogen

First Listed in the Eighth Report on Carcinogens (1998)

Carcinogenicity

o-Nitroanisole 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

(NTP 1993). 

When administered in the diet to male and female rats,

o-nitroanisole induced increased incidences of mononuclear cell

leukemia and neoplasms of the urinary bladder, kidney, and large

intestine. When administered in the diet to mice, o-nitroanisole

induced increased incidences of benign and malignant hepatocellular

neoplasms in males and increased incidences of hepatocellular

adenomas in females.

No adequate human studies of the relationship between exposure

to o-nitroanisole and human cancer have been reported (IARC 1996).

Additional Information Relevant to Carcinogenicity

o-Nitroanisole is genotoxic in a wide variety of bacteria and

mammalian cellular assays, and mutagenic and carcinogenic

metabolites have been described (NTP 1993, IARC 1996). 

No data were available that would suggest that the mechanisms

thought to account for tumor induction by o-nitroanisole in

experimental animals would not also operate in humans.

Properties

o-Nitroanisole is a colorless to slightly yellow liquid with a boiling point

of 277°C and a melting point of 9.4°C. It is insoluble in water but is

soluble in most organic solvents, including alcohol and ether (HSDB

2001).

Use

o-Nitroanisole is used primarily as a precursor to o-anisidine, which is

prepared by direct nitro-reduction. o-Anisidine is used extensively in

the synthesis of azo dyes either directly after being converted to a

diazonium salt or as a precursor for the preparation of dianisidine,

which is diazotized and coupled. Directly or indirectly, o-anisidine is

used in the manufacture of over 100 azo dyes (NTP 1993).

o-Nitroanisole has also been used as an intermediate for pharmaceutical

preparation (IARC 1996).

Production

o-Nitroanisole is produced by treating 2-chloronitrobenzene with

sodium methoxide under heat and pressure. The product separates as

an oil after dilution with water (IARC 1996). Of the 5 U.S. plants

reporting production or import use of o-nitroanisole in the 1977

TSCA Inventory, the one known manufacturer reported a production

volume of 100,000 to 1,000,000 lb/year (TSCAPP 1983), the three

known importers did not report volume information, and one plant’s

role was unknown. In 1976 and 1978, imports of the compound

through principal U.S. customs districts were reported to total

702,643 and 541,850 lb, respectively (HSDB 2001). No current data

on imports or exports of o-nitroanisole are available. Chem Sources

(2001) identified 10 U.S. suppliers of o-nitroanisole.

Exposure

The primary routes of potential human exposure to o-nitroanisole are

dermal contact, ingestion, and inhalation. Human exposure might be

associated with its widespread use in the manufacture of azo dyes

(NTP 1993). o-Nitroanisole was not included in the National

Occupational Hazard Survey or the National Occupational Exposure

Survey conducted by NIOSH (1990). o-Nitroanisole may be released

into the environment through various waste streams by dyes and

pharmaceutical manufacturing facilities. o-Nitroanisole has been

found in drinking water. Neither volatilization nor biodegradation

are expected to be important processes. When released into water, onitroanisole may adsorb to sediments and suspended solids.

Volatilization is very slow, as the half-life from a model river was

approximately 105 days and from a model pond was approximately

772 days. o-Nitroanisole will not bioaccumulate in aquatic organisms

and has moderate mobility when released to soil. o-Nitroanisole will

remain in vapor phase in the ambient atmosphere. It is degraded in

the atmosphere by reactions with photochemically produced

hydroxyl radicals, with an estimated half-life of 109 hr (HSDB

2001). 

Regulations

DOT

Nitroanisole is considered a hazardous material and special requirements have been

set for marking, labeling, and transporting this material

EPA

Clean Air Act

NSPS: Manufacture of substance is subject to certain provisions for the control of

Volatile Organic Compound (VOC) emissions

REFERENCES

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

HSDB. 2001. Hazardous Substances Data Base. National Library of Medicine. http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?HSDB.

IARC. 1996. Printing Processes and Printing Inks, Carbon Black and Some Nitro Compounds. IARC

Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 65. Lyon, France:

International Agency for Research on Cancer. 578 pp.

NIOSH. 1990. National Occupational Exposure Survey (1981-83). Unpublished provisional data as of 7/1/90.

Cincinnati, OH: U. S. Department of Health and Human Services.

NTP. 1993. Toxicology and Carcinogenesis Studies of o-Nitroanisole (CAS No. 91-23-6) in F344 Rats and

B6C3F1 Mice (Feed Studies). Technical Report Series No 416. NIH Publication No. 93-3147. Research

Triangle Park, NC and Bethesda, MD: National Toxicology Program. 482 pp.

TSCAPP. 1983. Toxic Substances Control Act Plant and Producers. Database available on the Chemical

Information System, Version 5.0/2.0.

O

CH3

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REPORT ON CARCINOGENS, ELEVENTH EDITION