Acrylonitrile carcinogen

Mechanisms of acrylonitrile carcinogenicity in experimental test systems... 

Acrylonitrile is beheved to behave similarly to hydrogen cyanide (enzyme inhibition of cellular metaboHsm) (150) and is befleved to be a potential carcinogen (151). It can also affect the cardiovascular system and kidney and Hver functions (150). Eurther information on the toxicology and human exposure to acrylonitrile is available (152—154) (see Acrylonitrile). 

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... 

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. 

Bio/dynamics. 1980a. A twenty-four month oral toxicity/carcinogenicity study of acrylonitrile administered to Spartan rats in the drinking water. Biodynamics, Inc., Division of Biology and Safety Evaluation, East Millstone, NJ. Project No. BDN-77-28. 

IARC. 1979. Acrylonitrile, acrylic and modacrylic fibres, and acrylonitrile-butadiene-styrene and styrene-acrylonitrile copolymers. IARC monographs on the evaluation of the carcinogenic risk of... 

Koerselman W, van der Graaf M. 1984. Acrylonitrile A suspected human carcinogen. Int Arch Occup Environ Health 54 317-324. 

Maltoni C, Ciliberti A, Di Maio V. 1977. Carcinogenicity bioassays on rats of acrylonitrile administered by inhalation and by ingestion. Med Lav 68 401-411. 

Sanner T, Rivedal E. 1985. Tests with the Syrian hamster embryo (SHE) cell transformation assay. In Ashby J, de Serres FJ, et al., eds. Progress in mutation research. Vol. 5. Evaluation of short-term tests for carcinogens. Amsterdam, The Netherlands Elsevier Science Publishers, 665-671. Sato M, Ishizu S, Momotuni H. 1975. [Determination of acrylonitrile, cyanide and thiocyanate in blood and urine.] Jap J Ind Health 17 99-105. (Japanese). 

Strother DE, Mast RW, Kraska RC, et al. 1988. Acrylonitrile as a carcinogen Research needs for better risk assessment. Ann NY Acad Sci 534 169-178. 

Styrene is a commercially important monomer that is used extensively in the manufacture of polystyrene resins and in co-polymers with acrylonitrile and 1,3-butadiene (reinforced plastics). Exposure to styrene occurs due to intake of food that has been in contact with styrene-containing polymers. lARC has determined that styrene is possibly carcinogenic to humans. There is no restriction on using styrene within the European Union (i.e., there is no SML). 

Toxicology. Acrylonitrile is an eye, skin, and upper respiratory tract irritant systemic effects are nonspecific but may include the central nervous, hepatic, renal, cardiovascular, and gastrointestinal systems. It is carcinogenic in experimental animals. 

The lARC has determined that there is sufficient evidence of carcinogenicity of acrylonitrile in animals and that it is probably carcinogenic to humans. ... 

The 2003 ACGIH threshold limit value-time-weighted average (TLV-TWA) for acrylonitrile is 2 ppm (4.3mg/m ) with an A3-confirmed animal carcinogen with unknown relevance to humans designation and a notation for skin absorption. 

Benzene is a clear, colorless, flammable liquid with a pleasant characteristic odor, bp 80.1°C, flash point -11.1°C, and ignition temperature 538°C. Benzene has been found to be very toxic and is on the list of Known to Be Human Carcinogens published every two years by the Department of Health and Human Services under the National Toxicology Program (NTP). There are four top 50 chemicals on this worst carcinogen list benzene 1,3-butadiene ethylene oxide and vinyl chloride. There are also four chemicals in the top 50 on the Reasonably Anticipated to Be Human Carcinogens list acrylonitrile, ethylene dichloride, formaldehyde, and propylene oxide. 

By-products of this reaction are acetonitrile, CH3-C=N, and hydrogen cyanide. This is now a major source of these two materials. Interestingly, the C2 by-product acetonitrile has a bp of 81.6 °C, whereas acrylonitrile with three carbons has a lower bp of 77.3 °C, quite an unusual reversal of this physical property s dependence on molecular weight. The TWA of acrylonitrile is 2 ppm and it is on the list of Reasonably Anticipated to Be Human Carcinogens. ... 

U.S. price trends show that cotton and polyester are the most popular for good reason they are the cheapest. Nylon and acrylic have had price increases over the last few years, part of which may be due to improvements and safeguards needed to manufacture their precursors acrylonitrile, butadiene, and benzene, which are on carcinogen lists. 

Polyacrylonitrile plastic bottles for soft drinks and beer were taken off the market as possible carcinogens because of migration of acrylonitrile into the drink. Now most plastic food containers of this type are poly(ethylene terephthalate). 

Since the monomers are carcinogenic, should the polymerization of styrene, acrylonitrile, and vinyl chloride be banned ... 

Acrylonitrile (vinyl cyanide) is produced by the ammoxidation of propylene. Again, since this monomer is carcinogenic, care must be taken to minimize exposure to it. 

Acrylonitrile. - Used widely in the polymer industry, acrylonitrile is considered to be a possible human carcinogen. DNA damage is believed to involve metabolism to an epoxide, followed by adduct formation with DNA. There is also evidence for radical-mediated damage to DNA. For example, Ohnishi et al. have trapped a nitrogen-centred radical derived from acrylonitrile, the formation of which was associated damage to DNA.22... 

An example of this type of a safer chemical is methacrylonitrile (1) compared with acrylonitrile (2) (Figure 1.1). Both compounds are a, 3-unsaturated aliphatic nitriles, and structurally very similar, but 2 causes cancer whereas 1 does not appear to do so. Among other applications, 2 is used in the production of acrylic and modacrylic fibers, elastomers, acrylonitrile-butadiene-styrene and styrene-acrylonitrile resins, nitrile rubbers, and gas barrier resins. In a study conducted by the US National Toxicology Program (NTP) in which 2 was administered orally to mice for 2 years, there was clear evidence that it caused cancer in the treated mice (in addition to causing other toxic effects), and is classified by the NTP as a probable human carcinogen [26]. 

Figure 1.1 Structures of methacrylonitrile (1) (noncarcinogenic) and acrylonitrile (2) (probably a human carcinogen).

Acrylonitrile is mutagenic, especially after bioactivation by a microsomal system. Since formation of DNA adducts with acrylonitrile in vitro is strongly increased by formation of its epoxide, it is very likely that the genotoxicity of acrylonitrile is mediated primarily by this metabolite. The epoxide, therefore, may be implicated in the carcinogenicity of acrylonitrile. 

There is inadequate evidence in humans for the carcinogenicity of acrylonitrile. 

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