Toxicological profiles - Acrylonitrile

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Toxicological Summary

If this is not possible, withdraw from the fire area and do not attempt to fight the fire. If a leak or spill has not ignited, use water spray in large quantities to disperse the vapours. Water spray can also be used to dilute spills to non-flammable mixtures and to flush spills away from ignition sources. Dike fire control water for appropriate disposal.

Solid streams of water may be ineffective and spread material. Tanks, drums or other containers should not be approached directly after they have been involved in a fire until they have completely cooled down. After the fire has been extinguished, explosive and toxic atmospheres may remain. Before entering such an area especially confined areas, check the atmosphere with an appropriate monitoring device while wearing full protective gear. Protection of Fire Fighters: Acrylonitrile is very toxic by inhalation and skin absorption and can form extremely toxic and flammable hydrogen cyanide gas during a fire.

Do not enter fire area without wearing specialized protective equipment suitable for the situation. Firefighter's normal protective clothing Bunker Gear will not provide adequate protection. A full-body encapsulating chemical protective suit with positive pressure self-contained breathing apparatus NIOSH approved or equivalent may be necessary.

NFPA - Flammability: 3 - Liquids and solids that can be ignited under almost all ambient temperature conditions. NFPA - Instability: 2 - Undergoes violent chemical change at elevated temperatures and pressures, or reacts violently with water, or may form explosive mixtures with water. Physical State: Liquid Melting Point: It is unstable polymerizes readily when moderately heated and exposed to light ultraviolet or sunlight , even if inhibited. Hazardous Polymerization: Acrylonitrile polymerizes violently, in the absence of an inhibitor and oxygen, if initiated by heat, light, pressure, peroxides, azo compounds, radicals, "Redox" catalysts or strong bases and acids.

Polymerization can occur in the liquid, solid and vapour phases. Even when inhibited, it will polymerize exothermically with generation of heat , at or above deg C. Many of these reactions can be done safely if specific control measures e. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.

Hazardous Decomposition Products: None reported. Conditions to Avoid: Heat, sparks, open flames, other ignition sources, sunlight, low inhibitor concentration, contamination. Eye Irritation: Acrylonitrile is a moderate to severe eye irritant. Application of 0. No effects were evident after 24 hours. Skin Irritation: Acrylonitrile is a severe skin irritant. No significant difference was noted in the severity of irritation between the intact and abraded skin. A hour exposure produced slight tissue death necrosis. Lethal inhalation or oral exposures with several different species have caused excitability and shallow, rapid breathing, changing to slow, gasping breathing followed by apnea and convulsions.

Vomiting has occurred, particularly for cats, and marked reddening of the skin of the ears, nose and feet has been noted. Dogs appear to be significantly more susceptible than other species. Inhalation and oral exposure has caused tearing, nasal discharge and salivation.

Oral exposure has caused incoordination and paralysis of hind limbs in rats. For example, high mortality was observed in rats following exposure to ppm for 8 hours, ppm for 4 hours, ppm for 2 hours or ppm for 1 hour. The initial response peaked within 0. The second phase produced central nervous system CNS effects including depression, convulsions and cyanosis starting 4 hours after administration.

Doses of 20, , or ppm in drinking water for 21 days had no effect on the liver. Acrylonitrile has caused harmful effects in the nervous systems of animals exposed by inhalation and ingestion to concentrations that are also capable of causing nervous system cancer. Inhalation of relatively low concentrations 20 ppm for 24 months has also caused degeneration and inflammatory changes in the nasal cavities of rats.

Mean body weights were significantly decreased in animals exposed to 80 ppm. More than 40 different organs and tissues were examined. Except for neoplastic findings, pathologic lesions showing dose-response relation to acrylonitrile exposure were observed only in the epithelium of the nasal mucosa. In animals inhaling 20 or 80 ppm, degeneration and inflammatory changes were observed in the respiratory epithelium of the nasal cavity.

In male rats, the incidence of hyperplasia was slightly, but not significantly increased at 20 ppm, but was at 80 ppm. The incidence of hyperplasia of mucous secreting cells was significantly increased. In female rats, inflammatory findings in the mucosa and squamous transformation in the respiratory epithelium was significantly increased at 20 and 80 ppm. This study demonstrates that repeated exposure to 20 ppm causes chronic inflammation of the nasal mucosa in rats. Mean body weights were significantly reduced in animals exposed to ppm. Two rats in the high dose group died.

None of the animals developed any weakness in the hindlimbs or disturbances in gait. At 25 ppm, reductions in MCV were observed during the exposure period, but not with statistical significance until the 8-week follow-up; SCV was reduced at exposure week 24 and ASAP was reduced at week At ppm, significant MCV reductions were noted at weeks 16 and 24 of exposure; SCV was significantly reduced at weeks 12, 16, 20 and 24; and ASAP was reduced at weeks 16, 20, 24 and at the 8-week follow-up.

In all cases, maximal deficits were observed at the last week of exposure. Monkeys exposed to ppm were more susceptible than other species. Rats, rabbits and guinea pigs tolerated the lower exposures with minimal effects. At ppm, irritation of the eyes and nose, loss of appetite, gastrointestinal changes and reversible weakness of the hind limbs were observed. Autopsy showed kidney, spleen and liver changes cats only. Reported doses were 0, 3. Decreased water consumption, feed consumption and body weight suppression occurred within days of the study initiation and persisted throughout the study for all treatment groups.

The primary non-tumorous histopathologic effects occurred in the forestomach, with changes suggestive of chronic irritation occurring in a dose-related manner, and in the central nervous system, with gliosis in low and mid-dose females and in males, without statistical significance, but considered treatment related.

The CNS lesions were interpreted to be a tumour precursor. An olive oil control group was used. In the 8-week recovery period, the deficit in SCV persisted. There was degeneration of the adrenal glands and levels of some steroids in the blood were reduced, with a greater effect noted with gavage dosing. Increased cell growth in the stomach and duodenum was noted. Increased mortality was noted at ppm. Challenge tests with 0. Carcinogenicity: The International Agency for Research on Cancer IARC has concluded that there is sufficient evidence for the carcinogenicity of acrylonitrile to experimental animals.

Teratogenic and embryotoxic effects were seen at higher doses that also produced maternal toxicity e. At 25 ppm and higher, there was fetotoxicity reduced body weight with overt signs of maternal toxicity depressed body weight gain. No significant teratogenicity was observed. Minor changes in neurological chemistry were noted. There were no effects on the mothers. Reproductive Toxicity: There is insufficient information available to conclude that acrylonitrile is toxic to reproduction.

In two studies, reduced sperm count and testicular effects were observed, but reproductive outcome was not assessed. A dose-dependant decrease in body and testis weight was observed. Sperm count and sperm motility were significantly decreased. Exposure of rats to ppm led to decreased fertility and decreased viability of the young. Females developed progressive muscular weakness in the hind legs about weeks after weaning of the second litter.

In an unpublished 3-generation reproduction study, rats were exposed to 0, or ppm in drinking water. These effects were attributed to decreased water intake of the mothers. There were no changes in reproductive capacity at ppm. Mutagenicity: Numerous mutagenicity tests have been conducted, but none clearly show conclusively that acrylonitrile is mutagenic. In studies using live animals and routes of exposure relevant to human, test results have been negative unscheduled DNA synthesis, chromosomal aberrations and dominant lethal effects , in all but one study.

However, this dose is expected to have produced significant other toxicity in the animals. However, conclusions cannot be drawn due to weaknesses in the test protocol. Positive results have been obtained in tests using bacteria, usually but not exclusively in the presence of metabolic activation. Positive and negative results have been obtained in tests using fungi.

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A study of acute toxicity. Journal of Industrial Hygiene and Toxicology. Health effects of acrylonitrile in acrylic fiber factories. British Journal of Industrial Medicine. Effect of chronic exposure to acrylonitrile on subjective symptoms. Keio Journal of Medicine. Health profiles of workers exposed to acrylonitrile. Occupational contact dermatitis due to acrylonitrile.

Contact Dermatitis. Analysis of chromosomes of workers exposed to acrylonitrile. Archives of Toxicology. Evaluation of some biomonitoring markers in occupationally exposed populations to acrylonitrile. Teratogenesis, Carcinogenesis, and Mutagenesis. Part I of II.

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Follow-up biological and genotoxicological monitoring of acrylonitrile- and dimethylformamide-exposed viscose rayon plant workers. Environmental and Molecular Mutagenesis. Cyanides and nitriles: acrylonitrile. In Patty's industrial hygiene and toxicology. Edited by G. Clayton, et al. Part D. John Wiley and Sons, Last updated: 16 Willhite, C. Toxicology updates: acrylonitrile. Journal of Applied Toxicology. Toxicity and biochemical changes in rats after inhalation exposure to 1,1-dichlorethylene, bromobenzene, styrene, acrylonitrile or 2-chlorobutadiene.

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Acute nephrotoxic potential of acrylonitrile in Fischer rats. Research Communications in Chemical Pathology and Pharmacology. Assessment of the acute acrylonitrile-induced neurotoxicity in rats. Neurotoxicology and Teratology. The effects of acrylonitrile on hemoglobin and red cell metabolism. Journal Of Toxicology and Environmental Health. Acrylonitrile-induced gastrointestinal hemorrhage and the effects of metabolism modulation in rats. Limited hepatotoxic potential of acrylonitrile in rats. Studies of effects of daily inhalation. Carcinogenicity bioassays on rats of acrylonitrile administered by inhalation and by ingestion.

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Cancer Research, Vol. Association of American Railroads, Jan. EditDocument - Password required 41 Odor thresholds for chemicals with established occupational health standards. American Industrial Hygiene Association, In: Kirk-Othmer encyclopedia of chemical technology. In: Ullmann's encyclopedia of industrial chemistry. VCH Publishers, Version 3. Butterworth-Heinemann Ltd.

Edited by A. Spencer, et al. National Fire Protection Association, In: Chemical safety sheets: working safely with hazardous chemicals. Kluwer Academic Publishers, Electrostatic hazards: their evaluation and control. Translated by M. Verlag Chemie, Quick selection guide to chemical protective clothing. Lange's handbook of chemistry. McGraw-Hill, Inc.

Data compilation tables of properties of pure compounds. Surface tension of pure liquid compounds. In: Compilation of data of some pure liquid compounds. Journal of Physical and Chemical Reference Data. Corrosion resistance tables: metals, nonmetals, coatings, mortars, plastics, elastomers and linings, and fabrics. Part A, A-D. Marcel Dekker, Inc. National Association of Corrosion Engineers, Carcinogenicity and other health effects of acrylonitrile with reference to occupational exposure limit. Two-year toxicity and oncogenicity study with acrylonitrile incorporated in the drinking water of rats.

Skin sensitization to acrylonitril in the Albino guinea pig maximization-test. Unpublished report. June 23, 64 Chu, C. Allergic contact dermatitis from acrylonitrile. American Journal of Contact Dermatitis. Allergic contact dermatitis due to acrylonitrile. Contact Dermatitis Newsletter London. Cyanide poisoning: pathophysiology and treatment recommendations. Occupational Medicine. For rabbits, 4-h exposure to acrylonitrile at up to ppm produced slight to marked, but reversible, effects Dudley and Neal Monkeys exposed to acrylonitrile at 65 or 90 ppm for 4 h exhibited transient skin flushing and transient elevation of respiration rate Dudley and Neal The no-effect level was 12 ppm.

Although evidence of fetal toxicity e. In monkeys, slight or modest reversible effects transient skin flushing and elevation of respiration rates were observed after 4-h exposures at 65 or 90 ppm Dudley and Neal Slight transient effects ocular and nasal irritation, redness of skin were observed in rats following a 2-h exposure at ppm Dudley and Neal All effects resolved within 12 h postexposure. At higher concentrations or at longer exposure durations, effects were more severe rapid respiration, tremors, convulsions, and death.

A threshold for these more severe effects in the rat appears to be. That suggests that an intraspecies uncertainty factor of 2 would account for toxicokinetic variability in the human population. Data from occupational studies suggest that the AEGL-2 values are sufficiently protective. Occupational exposure data showed that routine exposure to acrylonitrile at ppm approximately tofold higher than the 8-h AEGL-2 resulted in complaints of headache, fatigue, nausea, and insomnia, which are neither irreversible nor escape-impairing effects Sakurai and Kusumoto ; Sakurai et al.

The 1-h and 4-h AEGL-2 values are also below the lower end of the range of exposures estimated for occupational accidents over18 ppm Chen et al. Quantitative exposure-response data in humans regarding the lethality of acrylonitrile were not available. Lethality data in multiple laboratory species monkey, rat, dog, rabbit, guinea pig, and cat are available. Lethality in rats appears to occur at cumulative exposures of 1,, ppm-h for min to 6-h exposure durations, although for nose-only exposures it is notably higher about 3, ppm-h.

Lethal response data for monkeys were not available. Dogs were the most sensitive species, with lethality in 1 of 2 dogs observed following a 4-h exposure to acrylonitrile at 65 ppm. However, a 4-h exposure of four dogs to acrylonitrile at ppm resulted in no deaths, whereas exposure at ppm killed two of three dogs. Data from studies of rats were the most extensive. Dudley and Neal provided response data in rats exposed for 0. Thirty-minute exposure of rats to acrylonitrile concentrations as high as 2, ppm were without lethal effect.

A 4-h LC 50 of ppm was reported for rats Haskell At higher concentrations, rats died within h into the exposure period while deaths following exposure occurred between 7 min and 18 h; there was a day observation period. There were no deaths among 10 rats exposed to acrylonitrile at 1, ppm for 1 h Vernon et al. A two-generation study found weight decrements in the F 1 offspring of the ppm group, but no other evidence of exposure-related mortalities in adult animals, functional effects on reproduction or effects on reproductive organs, or toxicity in developing offspring at exposures up to 90 ppm Nemec et al.

Data for min, 1-h, 4-h, and 8-h AEGL-specific exposure periods are available from the reports by Appel et al. With the exception of the 4-h value, the resulting BMCL 05 values show a consistent duration-dependent relationship; therefore, the min, 1-h, and 8-h estimates were used to derive corresponding AEGL-3 values. Although the dog appeared to be the most sensitive species, the overall database for rats is more robust. This suggests that an intraspecies uncertainty factor of 2 would account for toxicokinetic variability in the human population. The AEGL-1 values are based on the absence of effects in male volunteer subjects exposed to acrylonitrile in a controlled-exposure study Jakubowski et al.

The difference reflects different end points used to derive the values. The ERPG-2 is based on reversible effects observed in dogs salivation observed at 35 ppm for 4 h , whereas the 1-h AEGL-2 value is based on a no-effect level for fetal toxicity in rats 12 ppm, 6 h, gestation days Data were adequate for the development of AEGL values for acrylonitrile. Human data were used for deriving AEGL-1 values for 10 min and 30 min durations; however, values for 1 h, 4 h and 8 h are not recommended because they. Data on developmental toxicity in rats, supported with more limited data in monkeys, were used for developing AEGL-2 values.

A robust data set in rats allowed for derivation of AEGL-3 values. The ERPG-1 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing other than mild, transient adverse health effects or without perceiving a clearly defined objectionable odor. The ERPG-2 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing or developing irreversi-.

The ERPG-3 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing or developing life-threatening health effects. Acrylonitrile is categorized as a confirmed animal carcinogen with unknown relevance to humans. A ceiling value should not be exceeded at any time. Emergency Response Planning Guidelines: Acrylonitrile. Appel, K. Peter, and H. Effect of potential antidotes on the acute toxicity of acrylonitrile.

Health 49 2 Peter, M. Bolt, and H. Interaction of acrylonitrile with hepatic microsomes of rats and men. Babanov, G. Kljuchikov, N. Karajeva, and Z. Clinical symptoms of chronic poisoning by acrylonitrile [in Russian]. Bader, M. Follow-up biomonitoring after accidental exposure to acrylonitrile- Implications for protein adducts as a dose monitor for short-term exposure.

Benz, F. Effect of cytochrome P inhibitors and anticonvulsants on the acute toxicity of acrylonitrile. Bergmark, E. Hemoglobin adducts of acrylamide and acrylonitrile in laboratory workers, smokers and nonsmokers. Beskid, O. Dusek, I. Solansky, and R. The effects of exposure to different clastogens on the pattern of chromosomal aberrations detected by FISH whole chromosome painting in occupationally exposed individuals.

Bhooma, T. Padmavathi, and S. Effect of acrylonitrile on the procoagulant activity of rat lung. Blair, A. Stewart, D. Zaebst, L. Pottern, J. Zey, T. Bloom, B. Miller, E. Ward, and J. Mortality of industrial workers exposed to acrylonitrile. Work Environ. Health 24 suppl. Borba, H. Monteiro, M. Proenca, T. Chaveca, V.

Pereira, N. Lynce, and J. Evaluation of some biomonitoring markers in occupationally exposed populations to acrylonitrile. Buchter, A. Clinical toxicology of acrylonitrile. Burka, L. Sanchez, E. Ahmed, and B. Comparative metabolism and deposition of acrylonitrile and methacrylonitrile in rats. Butterworth, B. Eldridge, C. Sprankle, P. Working, K. Bentley, and M. Tissue-specific genotoxic effects of acrylamide and acrylonitrile. Campian, E. Cai, and F. Acrylonitrile irreversibly inactivates glyceraldehydephosphate dehydrogenase by alkylating the catalytically active cysteine Chang, C.

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China Occup. Cole, P. Mandel, and J. Acrylonitrile and cancer: A review of the epidemiology. Collins, J. Cheng, G. Buck, J. Zhang, M. Klebanoff, E. Schisterman, T. Scheffers, H. Ohta, K. Takaya, H. Miyauchi, M. Markowitz, B. Divine, and S. The feasibility of conducting a reproductive outcome study of Chinese acrylonitrile worker. Crespi, C. Ryan, G. Seixas, T. Turner, and B.

Tests for mutagenic activity using mutation assays at two loci in the human lymphoblast cell lines TK6 and AHH Ashby, F. Draper, M. Ishidate, Jr. Margolin, B. Matter, and M. Shelby, eds. Progress in Mutation Research Vol. New York: Elsevier. Crump, K. The multistage model with a time-dependent dose pattern: Applications to carcinogenic risk assessment. Risk Anal. Czeizel, A. Hegedus, and L. Congenital abnormalities and indicators of germinal mutations in the vicinity of an acrylonitrile producing factory.

Dahl, A. Metabolism of organonitriles and cyanide by rat nasal tissue enzymes. Xenobiotica 19 11 Davis, J. Davies, A. Rafonnelli, and G. Investigation of fatal acrylonitrile intoxications. Deichmann, ed. Delivanova, S. Popovski, and T. Blepharoconjunctivitis in workers in the manufacture of synthetic polyacrylonitrile fibers [in Serbian].

Skopje Poncelet, M. Roberfroid, and M. Mutagenicity of acrylonitrile. Toxicology 11 1 Dong, D. Wang, X. Ai, and H. EPA Document No. Microfiche No. Dorodnova, N. Drawbaugh, R. Interspecies differences in rhodanese thiosulfate sulfurtransferase, EC 2. Dudley, H. Toxicology of acrylonitrile vinyl cyanide.

Study of the acute toxicity. Sweeney, and J. Toxicology of acrylonitrile. Studies of effects of daily inhalation. Enikeeva, N. Ostrovskaja, L. Syso, Z. Podrez, L. Braginskaja, N. Gvozdev, N. Nesterova, A. Musserskaja, N. Suzdaltreva, and A. Industrial hygiene and health status of workers involved in the manufacture of the synthetic fibre Nitron [in Russian]. EPA U. Health Assessment Document for Acrylonitrile.

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Acrylonitrile CAS No. Integrated Risk information System, U. Environmental Protection Agency [online]. Fahmy, M. Evaluation of the genotoxicity of acrylonitrile in different tissues of male mice. Cytologia 64 1 Fan, W. Wang, S. Ding, Y. Zhou, and F. Application of micronucleus test of buccal mucosal cells in assessing the genetic damage of workers exposed to acrylonitrile [in Chinese]. Farooqui, M. In vivo interactions of acrylonitrile with macromolecules in rats.

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Kedderis, and S. Urinary metabolites of [1,2,C]acrylonitrile in rats and mice detected by 13C nuclear magnetic resonance spectroscopy. MacNeela, R. Morris, M. Watson, C. Thompson, and D. Hemoglobin adducts from acrylonitrile and ethylene oxide in cigarette smokers: Effects of glutathione S-transferase T1-null and M1-null genotypes. Cancer Epidemiol. Biomarkers Prev. Gargas, M. Anderson, S. Teo, R. Batra, T. Fennell, and G. A physiologically-based dosimetry description of acrylonitrile and cyanoethylene oxide in the rat.

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Assessment of the acute acrylonitrile-induced neurotoxicity in rats. Gincheva, N. Stamova, L. Hinkova, and S. Kyurktchiev, M. Spasovski, A. Bainova, M. Muhtarova, and V. Study of the health status of workers from the acrylonitrile department. Grunske, F. Ventox and Ventox intoxication [in German]. Haber, F. On the history of the gas war. Berlin, Germany: Verlag von Julius Springer. Haskell Laboratory. Toxicity of Vinyl Cyanide. Medical Research Project No.

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March 25, Ivanescu, M. Berinde, and L. Testosterone in sera of workers exposed to acrylonitrile. Endocrinologie 28 Jakubowski, M. Linhart, G.

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Toxicology 65 Vogel, R. Acrylonitrile vinyl cyanide poisoning: A case report. Wakata, A. Miyamae, S. Sato, T. Suzuki, T. Morita, N. Asano, T. Awogi, K. Kondo, and M. Environonmental Health Criteria. Geneva: World Health Organization [online]. WIL Research Laboratories. Willhite, C. The role of cyanide liberation in the acute toxicity of aliphatic nitriles. Ferm, and R. Teratogenic effects of aliphatic nitriles. Teratology 23 3 Marin-Padilla, V. Morphogenesis of axial skeletal dysraphic disorders induced by aliphatic nitriles.

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The LOA should help chemical emergency responders in assessing the public awareness of the exposure due to odor perception. The LOA derivation follows the guidance of van Doorn et al. The odor detection threshold OT 50 for acrylonitrile was reported to be 8. OT 50 for acrylonitrile: 8. The resulting concentration is multiplied by an empirical field correction factor.

It takes into account that in everyday life factors such as sex, age, sleep, smoking, upper airway infections, and allergies, as well as distraction, may increase the odor detection threshold by a factor of 4. In addition, it takes into account that odor perception is very fast about 5 seconds , which leads to the perception of concentration peaks.

Carcinogenicity assessments for lifetime exposure to inhaled acrylonitrile have been conducted by EPA and Felter and Dollarhide On the basis of these assessments, two calculations for cancer risk are presented below. In a cohort of 1, male textile workers exposed to acrylonitrile at ppm estimated for at least 10 years, 25 cases of cancer, including eight cases of respiratory cancer, were reported.

A positive trend was observed for increased cancer incidence with increased exposure duration and increased duration of followup time. To transform the unit risk for continuous lifetime exposure derived by EPA to a single h exposure estimate, default procedures linear transformation and correction by a factor of 6 to account for the relevance of sensitive stages in development were applied, as recommended in the standing operating procedures for AEGL development NRC , see Appendix A.

On the basis of the inhalation unit risk of 6. To convert the year exposure to a h exposure, the concentration associated with a 1 in 10, risk level is multiplied by 25, the number of days in 70 years :. To account for uncertainty regarding variability in the stage of cancer process that acrylonitrile or its metabolites may act, a multistage factor of 6 is applied Crump and Howe :. Therefore, on the basis of the potential carcinogenicity of acrylonitrile, an acceptable h exposure would be 2.

Extrapolation to 10 min was not calculated due to unacceptably large inherent uncertainty.

Toxicological profiles - Acrylonitrile Toxicological profiles - Acrylonitrile
Toxicological profiles - Acrylonitrile Toxicological profiles - Acrylonitrile
Toxicological profiles - Acrylonitrile Toxicological profiles - Acrylonitrile
Toxicological profiles - Acrylonitrile Toxicological profiles - Acrylonitrile
Toxicological profiles - Acrylonitrile Toxicological profiles - Acrylonitrile
Toxicological profiles - Acrylonitrile Toxicological profiles - Acrylonitrile
Toxicological profiles - Acrylonitrile Toxicological profiles - Acrylonitrile

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