Acrylonitrile [factsheet]

ACRYLONITRILE

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System (IRIS), which contains information on inhalation chronic toxicity of acrylonitrile and the RfC and the carcinogenic effects of acrylonitrile including the unit cancer risk for inhalation exposure, EPA's Health Effects Assessment for Acrylonitrile, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for Acrylonitrile. Other secondary sources include 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literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.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

* Human exposure to acrylonitrile appears to be primarily occupational, via inhalation. (1)

* Acrylonitrile may be released to the ambient air during its manufacture and use. (1)

Assessing Personal Exposure

* Acrylonitrile can be detected in the blood to determine whether or not exposure has occurred. Metabolites may be detected in the urine, but some breakdown products are not specific to acrylonitrile. (1)

Health Hazard Information

Acute Effects:

* Acute (short-term) occupational exposure of workers to acrylonitrile via inhalation has been observed to cause low-grade anemia, cyanosis, leukocytosis, kidney irritation, mild jaundice, and irregular breathing, with symptoms that include mucous membrane irritation, headaches, dizziness, nausea, feelings of apprehension and nervous irritability, muscle weakness, and convulsions. (1-4)

* A child died after being exposed to acrylonitrile by inhalation, suffering from respiratory malfunction, lip cyanosis, and tachycardia before death. Several adults exposed to the same concentration of acrylonitrile exhibited eye irritation, but no toxic effects. (1,4)

* Acute dermal exposure may cause severe burns to the skin. (3)

* Acute animal tests, such as the LC₅₀ and LD₅₀ tests in rats, mice, rabbits, and guinea pigs, have demonstrated acrylonitrile to have high acute toxicity from inhalation and high to extreme acute toxicity from oral or dermal exposure. (5)

Chronic Effects (Noncancer):

* In one study, headaches, fatigue, nausea, and weakness were frequently reported in chronically (long-term) exposed workers. (6)

* Degenerative and inflammatory changes in the respiratory epithelium of the nasal turbinates and effects on brain cells have been observed in rats chronically exposed by inhalation. (1,4,6,7)

* The RfC for acrylonitrile is 0.002 mg/m³ based on degeneration and inflammation of nasal respiratory epithelium in rats. (4)

* EPA has medium confidence in the study on which the RfC was based because, although it was a well-conducted chronic study in an appropriate number of animals (100/sex/concentration), it was performed on only one species, did not identify a no-observed-adverse-effect level (NOAEL), was confounded by the early sacrifice of rats with large mammary gland tumors and the target organ (nasal turbinates) was examined only at the end of the study in relatively few animals (10-12/sex/concentration); medium to low confidence in the database because of the lack of chronic or subchronic inhalation data in a second species, the lack of reproductive data by the inhalation route and the existence of an oral study showing reproductive effects; and, consequently, medium to low confidence in the RfC. (4)

* The RfD for acrylonitrile is under review by EPA. (4)

Reproductive/Developmental Effects:

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

* Fetal malformations (including short tail, missing vertebrae, short trunk, omphalocele, and hemivertebra) have been reported in rats exposed to acrylonitrile by inhalation. (1,4)

* Offspring of rats exposed to acrylonitrile in their drinking water showed an increased incidence of cancer (astrocytoma and Zymbal gland). (4)

* In mice orally exposed to acrylonitrile, degenerative changes in testicular tubules and decreased sperm count were observed. (1)

Cancer Risk:

* A statistically significant increase in the incidence of lung cancer has been reported in several studies of chronically exposed workers. However, some of these studies contain deficiencies such as lack of exposure information, short followup, and confounding factors. (1,4,6,7)

* In several studies, an increased incidence of tumors has been observed in rats exposed by inhalation, drinking water, and gavage. Astrocytomas in the brain and spinal cord and tumors of the Zymbal gland (in the ear canal) have been most frequently reported, as well as tumors of the stomach, tongue, small intestine, and mammary gland (in females). (1-4,6,7)

* EPA has classified acrylonitrile as a Group B1, probable human carcinogen (cancer-causing agent). (4)

* EPA uses mathematical models, based on human and animal studies, to estimate the probability of a person developing cancer from breathing air containing a specified concentration of a chemical. EPA calculated an inhalation unit risk estimate of 6.8 H 10^-5 (Fg/m³)^-1. EPA estimates that, if an individual were to breathe air containing acrylonitrile at 0.01 m g/m³,* over his or her entire lifetime, that person would theoretically have no more than a one-in-a-million increased chance of developing cancer as a direct result of breathing air containing this chemical. Similarly, EPA estimates that breathing air containing 0.1 m g/m³ would result in not greater than a one-in-a-hundred thousand increased chance of developing cancer, and air containing 1.0 m g/m³ would result in not greater than a one-in-ten thousand increased chance of developing cancer. (4)

* 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 acrylonitrile in the nonthreshold category. The 1/ED₁₀ value is 2.3 per (mg/kg)/d and this would place it in the medium category under Superfund's ranking for carcinogenic hazard. (8)

Physical Properties

* The chemical formula for acrylonitrile is C₃H₃N, and its molecular weight is 53.06 g/mol. (1,7)

* Acrylonitrile occurs as a colorless liquid that is soluble in water. (1,7)

* Acrylonitrile has a pungent, onion- or garlic-like odor, with an odor threshold of 47 mg/m³. (1)

* The vapor pressure for acrylonitrile is 100 mm Hg at 22.8 EC, and its log octanol/water partition coefficient (log K_ow) is -0.92. (1)

Uses

* Acrylonitrile is primarily used in the manufacture of acrylic and modacrylic fibers. It is also used as a raw material in the manufacture of plastics (acrylonitrile-butadiene-styrene and styrene-acrylonitrile resins), adiponitrile, acrylamide, and nitrile rubbers and barrier resins. (1,7)

Health Data from Inhalation Exposure

Concentration (mg/m³)	Health numbers^a	Regulatory, advisory numbers^b	Reference
1,000.0
_ _ _ _ 100.0	* LC₅₀ (rats) (922 mg/m³)		5
_ _ _ _ 10.0	* LOAEL^c (rats) (43 mg/m³)	* MSHA standard (45 mg/m³)	4 5
_ _ _ _ 1.0		* ACGIH TLV (5 mg/m³) * NIOSH REL (2 mg/m³)	5 5
_ _ _ _ 0.1
_ _ _ _ 0.01
_ _ _ _ 0.001	* RfC (0.002 mg/m³)		4
_ _ _ _ 0.0001
_ _ _ _ 0.00001	* EPA Cancer Risk Level (1-in-a-million excess lifetime risk) = 0.00001 mg/m³		4

See notes on following page.

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.

MSHACMine Safety and Health Administration.

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.

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

2. International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some Monomers, Plastics and Synthetic Elastomers, and Acrolein. Volume 19. World Health Organization, Lyon. 1979.

3. U.S. Environmental Protection Agency. Health Assessment Document for Acrylonitrile (Revised Draft). EPA/600/8-82-007. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Research Triangle Park, NC. 1982.

4. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Acrylonitrile. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

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. Health Effects Assessment for Acrylonitrile. EPA/600/8-88/014. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1988.

7. U.S. Environmental Protection Agency. Health and Environmental Effects Profile for Acrylonitrile. EPA/600/x-85/372. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1985.

8. 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.