2Methylaniline [factsheet]

2-METHYLANILINE

(o-TOLUIDINE)

Please Note: The main source of information for this fact sheet is EPA's Health and Environmental Effects Profile for 2-Methylaniline and 2-Methylaniline Hydrochloride. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure

* 2-Methylaniline has been found in tobacco smoke and in steam volatiles from the distillation of one type of tobacco leaves. (1)

* 2-Methylaniline has been detected in a variety of foods including fresh kale, celery and carrots, and in shelled peas, red cabbage, and black tea aroma. (2)

* Occupational exposure via inhalation or skin contact is possible in work environments utilizing 2-methylaniline. (2)

Assessing Personal Exposure

* There is a medical test available to determine whether someone has been exposed to

2-methylaniline via analysis of blood or urine. (3)

Health Hazard Information

Acute Effects:

* 2-Methylaniline is highly toxic to humans when absorbed through the skin, inhaled as vapor, or swallowed. 2-Methylaniline changes hemoglobin to methemoglobin and if intense, the methemoglobinemia results in severe damage to the cells of the central nervous system. (1,3,4)

* Tests involving acute exposure of animals, such as the LD₅₀ test in rats, have shown 2-methylaniline to have moderate acute toxicity. (5)

Chronic Effects (Noncancer):

* The long-term (chronic) effects experienced by workers exposed to 2-methylaniline include anemia, anorexia, weight loss, skin lesions, central nervous system depression including dizziness, headache, and confusion, and cyanosis and methemoglobinemia. (3)

* Animal studies indicate that chronic exposure to 2-methylaniline causes methemoglobinemia, reticulocytosis, and anemia. (2,3)

* EPA has not established an RfD or an RfC for 2-methylaniline.

Reproductive/Developmental Effects:

* Limited information regarding the reproductive or developmental effects of inhaled or ingested 2-methylaniline was located. One Russian study reported an increased number of offspring in mice following injection with 2-methylaniline during gestation. (8)

Cancer Risk:

* Epidemiological evidence clearly associates occupational exposure to 2-methylaniline with an increased risk of bladder cancer among workers. The risk of bladder cancer was greatest among workers with possible and definite exposures to 2-methylaniline and the risk increased with duration of exposure. (3)

* 2-Methylaniline*HCl (the hydrochloride of 2-methylaniline) was carcinogenic in both rats and mice. A cancer study reported increased incidences of skin tumors in rats along with hepatocellular or adenomas in female mice and hemangiosarcomas at all sites in male mice. (2,3)

* The International Agency for Research on Cancer (IARC) has stated that there is sufficient evidence for the carcinogenicity of 2-methylaniline*HCL in experimental animals. (1)

* EPA has classified 2-methylaniline as a Group B2, a probable human carcinogen. (2)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has ranked 2-methylaniline in the nonthreshold category. The 1/ED₁₀ value is 0.093 per (mg/kg)/d and this would place it in the low category under Superfund's ranking for carcinogenic hazard. (6)

Physical Properties

* 2-Methylaniline is a colorless to light yellow liquid. (2)

* 2-Methylaniline has an odor threshold of 0.25 ppm. (7)

* 2-Methylaniline is slightly soluble in water. (2)

* The chemical formula for 2-methylaniline is C₇H₉N, and it has a molecular weight of 107.15 g/mol. (2,8)

* The vapor pressure for 2-methylaniline is 0.317 mm Hg at 25 EC, and the log octanol/water partition coefficient (log K_ow) is 1.56. (9)

Uses

* The principal commercial use of 2-methylaniline is in the manufacture of dyes, rubber vulcanization accelerators, hypnotic and anesthetic pharmaceuticals, and the pesticide siduron. (1,2)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
1,000,000.0
_ _ _ _ 100,000.0
_ _ _ _ 10,000.0
_ _ _ _ 1,000.0
_ _ _ _ 100.0
_ _ _ _ 10.0		* OSHA PEL, MSHA (22 mg/m³)	2,5
_ _ _ _ 1.0		* ACGIH TLV (9 mg/m³)	2,5

ACGIH TLVCAmerican Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect.

MSHACMine Safety and Health Administration.

OSHA PELCOccupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.

^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice.

References

1. International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Volume 27. World Health Organization, Lyon. 1982.

2. U.S. Environmental Protection Agency. Health and Environmental Effects Profile for 2-Methylaniline and 2-Methylaniline Hydrochloride. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1987.

3. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, Bethesda, National Library of Medicine, MD. 1993.

4. G.D. Clayton and F.E. Clayton, Eds. Patty's Industrial Hygiene and Toxicology. Volume IIA. 3rd revised ed. John Wiley & Sons, New York. 1981.

5. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

6. U.S. Environmental Protection Agency. Technical Background Document to Support Rulemaking Pursuant to the Clean Air ActCSection 112(g). Ranking of Pollutants with Respect to Hazard to Human Health. EPAB450/3-92-010. Emissions Standards Division, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.

7. J.E. Amoore and E. Hautala E. Odor as an aid to chemical safety: Odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. Journal of Applied Toxicology, 3(6):272-290. 1983.

8. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck & Co., Inc., Rahway, NJ. 1989.

9. U.S. Environmental Protection Agency. Assessment Tools for the Evaluation of Risk (ASTER, online database). Environmental Research Laboratory, Duluth, MN. 1993.