nHexane [factsheet]

n-HEXANE

Please Note: The main source of information for this fact sheet is EPA's Integrated Risk Information System (IRIS), which contains information on inhalation chronic toxicity of hexane and the Reference Concentration (RfC). 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literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.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

* The most probable route of human exposure to hexane is by inhalation. Individuals are most likely to be exposed to hexane in the workplace. Monitoring data indicate that hexane is a widely occurring atmospheric pollutant. (1,2)

Assessing Personal Exposure

* No information was located regarding the measurement of personal exposure to hexane.

Health Hazard Information

Acute Effects:

* Acute (short-term) inhalation exposure of humans to high levels of hexane causes mild CNS depression and irritation of the mucous membranes. CNS effects include dizziness, giddiness, slight nausea, and headache in humans. (1-3)

* Acute exposure to hexane vapors may cause dermatitis and irritation of the eyes and throat in humans. (2)

* Acute animal tests, such as the LC₅₀ and LD₅₀ tests in rats, have demonstrated hexane to have low acute toxicity from inhalation and ingestion exposure. (4)

Chronic Effects (Noncancer):

* Chronic (long-term) inhalation exposure to hexane is associated with polyneuropathy in humans, with numbness in the extremities, muscular weakness, blurred vision, headache, and fatigue observed. (1,2,5,7)

* Rats, chronically exposed by inhalation, have exhibited neurotoxic effects. (5)

* Mild inflammatory, erosive, and degenerative lesions in the olfactory and respiratory epithelium of the nasal cavity have been observed in mice chronically exposed by inhalation. Pulmonary lesions have also been observed in chronically exposed rabbits. (5)

* The RfC for hexane is 0.2 mg/m³ based on neurotoxicity and epithelial lesions in the nasal cavity in humans. (5)

* EPA has medium confidence in the epidemiological study on which the RfC was based because the lowest-observed-adverse-effect level (LOAEL) in this study was based on neurotoxicology, and this endpoint is supported by numerous other subchronic inhalation studies in animals and by human occupational studies; medium confidence in the database because of the lack of long-term inhalation studies and appropriate reproductive studies; and, consequently, medium confidence in the RfC. (5)

* EPA has not established an RfD for hexane. (5)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has evaluated hexane for chronic toxicity and has given it a composite score of 13 (scores range from 1 to 100, with 100 being the most toxic). These scores are nonlinear and are the product of two ratings: a rating based on the minimal-effect-dose and a rating based on the type of effect. (6)

Reproductive/Developmental Effects:

* No information is available on the reproductive or developmental effects of hexane in humans.

* Testicular damage has been observed in male rats exposed to hexane via inhalation. (5)

* Teratogenic effects were not observed in the offspring of rats chronically exposed via inhalation in several studies. (3,5,8)

Cancer Risk:

* No information is available on the carcinogenic effects of hexane in humans or animals.

* EPA has classified hexane as a Group D, not classifiable as to human carcinogenicity, based on a lack of data concerning carcinogenicity in humans and animals. A carcinogenicity risk assessment is currently under review by EPA. (3,5)

Physical Properties

* The chemical formula for hexane is C₆H₁₄, and its molecular weight is 86.17 g/mol. (8)

* Hexane is a colorless volatile liquid that is insoluble in water and highly flammable. (2,8)

* The odor threshold for hexane is 130 ppm, with a faint peculiar odor reported. (8,9)

* The vapor pressure for hexane is 150 mm Hg at 25 EC. (3)

Uses

* Commercial grades of hexane are used as solvents for glues, varnishes, cements, and inks. (3)

* Hexane is also used as a solvent in the extraction of edible fats and oils. (2,3)

* Hexane is used as the liquid in low temperature thermometers. (2,8)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
1,000,000.0
_ _ _ _ 100,000.0	* LC₅₀ (rats) (169,168 mg/m³)		4
_ _ _ _ 10,000.0
_ _ _ _ 1,000.0
_ _ _ _ 100.0	* LOAEL^c (humans) (204 mg/m³)	* NIOSH REL (360 mg/m³) * OSHA PEL and ACGIH TLV (180 mg/m³)	5 4 4
_ _ _ _ 10.0
_ _ _ _ 1.0
_ _ _ _ 0.1	* RfC (0.2 mg/m³)		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.

LC₅₀ (Lethal Concentration₅₀)CA calculated concentration of a chemical in air to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population.

LOAELCLowest-observed-adverse-effect level.

NIOSH RELCNational Institute of Occupational Safety and Health's recommended exposure limit; NIOSH-recommended exposure limit for an 8- or 10-h time-weighted-average exposure and/or ceiling.

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.

RfCCReference concentration.

^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.

^c The LOAEL is from the critical study used as the basis for the EPA RfC.

References

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

2. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes Publications, Park Ridge, NJ. 1985.

3. U.S. Environmental Protection Agency. n-Hexane Health Advisory. Office of Drinking Water, Washington, DC. 1987.

4. 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.

5. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on n-Hexane. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 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. E.J. Calabrese and E.M. Kenyon. Air Toxics and Risk Assessment. Lewis Publishers, Chelsea, MI. 1991.

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

9. J.E. Amoore and E. Hautala. 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.