Acrylonitrile toxicity

Hepatic Effects. Acrylonitrile is metabolized in the liver to potentially toxic metabolites (see Section 2.3). There are limited indications that the liver is a target organ for acrylonitrile toxicity. 

The increased metabolism of acrylonitrile to 2-cyanoethylene oxide has significant implications in acrylonitrile toxicity. 2-Cyanoethylene oxide has been shown to react with cell macromolecules (including nucleic acids) both in vivo and in vitro (Guengerich et al. 1981 Hogy and Guengerich 1986). This metabolite may be responsible for the carcinogenic effects of acrylonitrile. 

Developmental Toxicity. No information is available on developmental effects of acrylonitrile in humans by any route of exposure. Acrylonitrile is teratogenic and embryotoxic in rats both by the oral and inhalation routes of exposure. Developmental studies on other animal species have not been conducted. Because species differences for acute acrylonitrile toxicity and metabolism have been demonstrated, additional developmental studies in other species using various dose levels would be valuable in evaluating the potential for acrylonitrile to cause developmental effects in humans. Because the available oral study was conducted by gavage, additional studies are needed to determine if these effects will occur following ingestion of drinking water or food. 

Cote IL, Bowers A, Jaeger RJ. 1983. Induced tolerance to acrylonitrile toxicity by prior acrylonitrile exposure. Res Commun Chem Pathol Pharmacol 42 169-172. 

In animal studies acetone has been found to potentiate the toxicity of other solvents by altering their metabolism through induction of microsomal enzymes, particularly cytochrome P-450. Reported effects include enhancement of the ethanol-induced loss of righting reflex in mice by reduction of the elimination rate of ethanol increased hepatotoxicity of compounds such as carbon tetrachloride and trichloroethylene in the rat potentiation of acrylonitrile toxicity by altering the rate at which it is metabolized to cyanide and potentiation of the neurotoxicity of -hexane by altering the toxicokinetics of its 2,4-hexane-dione metabolite.Because occupationally exposed workers are most often exposed to a mixmre of solvents, use of the rule of additivity may underestimate the effect of combined exposures. ... 

Target organs of acrylonitrile toxicity in experimental animals are listed in Table 7. 

In a human neuroblastoma cell line, Cova et al. (1992) found acrylonitrile to be highly toxic, showing an EC50 of 72.5 nM for cytotoxicity. The cytotoxic potency of potassium cyanide was 2.5 J,M, thus acrylonitrile toxicity in these cells cannot be attributed to its metabolism to cyanide. 

Methylacrylonitrile is a moderate to severe acute toxicant. The degree of toxicity varied with toxic routes and species. Inhalation, ingestion, and skin application on test subjects produced convulsion. Exposure to high concentrations can result in asphyxia and death. The lethal concentrations varied among species from 50 to 400 ppm over a 4-hour exposure period. The clinical symptoms observed in rats suggested a toxic activity of metabolically formed cyanide (Peter and Bolt 1985). This finding was in contrast with acrylonitrile toxicity in the same species, where formation of metabolic cyanide played a minor role. 

Acrylonitrile toxic product, flammable and explosive. Gives off toxic fumes (HCN) in the event of fire. 

Pure acrylonitrile boils at 78°. Acrylonitrile vapour is highly toxic it should therefore be handled with due caution and all operations with it should be conducted in a fume cupboard provided with an efficient draught. Acrylonitrile forms an azeotropic mixture with water, b.p. 70-5° (12-5 per cent, water). The commercial product may contain tte polymer it should be redistilled before use and the fraction b.p. 76 -5-78° collected separately as a colourless liquid. 

Acrylonitrile is combustible and ignites readily, producing toxic combustion products such as hydrogen cyanide, nitrogen oxides, and carbon monoxide. It forms explosive mixtures with air and must be handled in weU-ventilated areas and kept away from any source of ignition, since the vapor can spread to distant ignition sources and flash back. 

Federal regulations (40 CFR 261) classify acrylonitrile as a hazardous waste and it is Hsted as Hazardous Waste Number U009. Disposal must be in accordance with federal (40 CFR 262, 263, 264), state, and local regulations only at properly permitted faciUties. It is Hsted as a toxic pollutant (40 CFR 122.21) and introduction into process streams, storm water, or waste water systems is in violation of federal law. Strict guidelines exist for clean-up and notification of leaks and spills. Federal notification regulations require that spills or leaks in excess of 100 lb (45.5 kg) be reported to the National Response Center. Substantial criminal and civil penalties can result from failure to report such discharges into the environment. 

SAN resins themselves appear to pose few health problems in that they have been approved by the EDA for beverage botde use (149). The main concern is that of toxic residuals, eg, acrylonitrile, styrene, or other polymerization components such as emulsifiers, stabilizers, or solvents. Each component must be treated individually for toxic effects and safe exposure level. 

In 1977, consumption of PET resin in bottie appHcations was dramatically increased when the EDA banned competing acrylonitrile resins owing to toxicity considerations (recentiy rescinded) (69) and when the 2 L bottie was accepted for beverage sales worldwide (70). The carbon dioxide barrier properties of PET are sufficient to provide the six-month shelf life necessary for carbonated beverages (qv) (see also Barrier polymers). 

The surface area of a spill should be minimized for materials that are highly toxic and have a significant vapor pressure at ambient conditions, such as acrylonitrile or chlorine. This will make it easier and more practical to collect vapor from a spill or to suppress vapor release with foam. This may require a deeper nondrained dike area than normal or some other design that wilfminimize surface area, in order to contain the required volume. It is usually not desirable to cover a diked area to restric t loss of vapor if the spill consists of a flammable or combustible material. 

Acrylonitrile (Vinyl cyanide) CH,CHCN Closely resembles HCN in toxic action Poisonous by inhalation, ingestion or skin absorption Emits cyanides when heated or contacted by acids or acid fumes Symptoms flushed face, irritation of eyes and nose, nausea etc. Colourless flammable liquid with mild, faintly pungent odour Elash point 0°C. Dilute water solutions also have low flash points... 

Polymerization Exothermic reaction which, unless carefully controlled, can run-away and create a thermal explosion or vessel overpressurization Refer to Table 7.20 for common monomers Certain processes require polymerization of feedstock at high pressure, with associated hazards Many vinyl monomers (e.g. vinyl chloride, acrylonitrile) pose a chronic toxicity hazard Refer to Table 7.19 for basic precautions... 

Hydrogen cyanide (hydrocyanic acid) is a colorless liquid (b.p. 25.6°C) that is miscible with water, producing a weakly acidic solution. It is a highly toxic compound, but a very useful chemical intermediate with high reactivity. It is used in the synthesis of acrylonitrile and adiponitrile, which are important monomers for plastic and synthetic fiber production. 

Many vinyl monomers (e.g. vinyl chloride, acrylonitrile) pose a chronic toxicity hazard... 

Acrylonitrile (Vinyl cyanide, propenenitrile) CH2 CHCN 0 481 3.0-17.0 0.8 1.8 77 Colourless, partially water soluble liquid Experimental carcinogen Polymerizes violently with organic peroxides or concentrated caustic alkalis Highly toxic Usually inhibited... 

In humans, acute exposure to acrylonitrile results in characteristics of cyanide-type toxicity. Symptoms in humans associated with acrylonitrile poisoning include limb weakness, labored and irregular breathing, dizziness and impaired judgment, cyanosis, nausea, collapse, and convulsions (Baxter 1979). However, the doses that produce these effects were not clearly defined. Workers exposed to 16 to 100 ppm for 20 to 45 minutes complained of headaches and nausea, apprehension and nervous irritation (Wilson et al. 1948). The workers exposed to acrylonitrile vapors fully recovered. In a study with human volunteers exposed to acrylonitrile at doses of 2.3 and 4.6 ppm, no symptoms attributable to effects on the nervous system were observed (Jakubowski et al. 1987). 

In a three - generation reproduction study in rats, Beliles et al. (1980) found that exposure of animals to acrylonitrile in drinking water at 70 mg/kg/day resulted in reduced viability and lactation indices in all generations. The authors considered the reduced pup indices to be the result of maternal toxicity, possibly related to reduced milk production due to decreased water intake by the dams. Fostering of pups on untreated dams lessened pup mortality. Measurement of acrylonitrile in the pups was not performed. 

In animals, deaths from acrylonitrile have been reported in several species following inhalation, oral or dermal exposure. In most species, death appears to be related to cyanide poisoning. That the cyanide moiety is involved in human toxicity of acrylonitrile has been reported in a case study in which a human male was sprayed with acrylonitrile when a valve burst (Vogel and Kirkendall 1984). This individual suffered symptoms characteristic of cyanide poisoning, and treatments designed to reduce cyanide levels in the blood were required in order to save his life. 

Developmental Effects. There are no data available on developmental effects of acrylonitrile in humans however, two well-conducted studies in rats have shown that acrylonitrile is teratogenic in animals by both inhalation and oral exposure (Murray et al. 1978). Fetal malformations occurred in a dose-related manner. When administered orally, malformations were present even at doses in which no maternal or fetal toxicity was apparent. 

Acrylonitrile alone has little tendency to produce duodenal ulcers in animals, but pretreatment with phenobarbital or Aroclor results in a marked increase in the incidence of such ulcers (Szabo et al. 1983, 1984). Although the mechanism of the ulcerogenic effect is not obvious, these data indicate that agents which enhanced mixed-function oxidase activity may also increase the toxicity of acrylonitrile. 

Studies in animals indicate that acrylonitrile can produce teratogenic effects at doses that have little maternal toxicity, suggesting that pregnant women may also be susceptible. It also seems likely that individuals in poor health or with respiratory problems might be particularly susceptible to acrylonitrile, but there are no data on this point. 

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