Acrylamide toxicity

Although the mechanism of acrylamide toxicity is unknown, glycidamide may mediate the genotoxicity associated with acrylamide exposure. While both acrylamide and glycidamide bind to hemoglobin in vivo, only glycidamide forms adducts with DNA. 

Doerge, D. R., Young, J. F., Chen, J. J., Dinovi, M. J., and Henry, S. H. (2008). Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity. J Agric Food Chem 56, 6031-6038. 

Polyacrylamide gels are made by polymerization of acrylamide (toxic) with N, -methylenebisacrylamide in the presence of free radicals generated from either ammonium persulfate (oxidative chemical initiator) or riboflavin-5 -phosphate (photochemical initiator). The reaction is controlled by equimolar concentrations of N,N,N, N -tetramethylethylene diamine (TEMED) as catalyst. 

The reaction with sodium sulfite or bisulfite (5,11) to yield sodium-P-sulfopropionamide [19298-89-6] (C3H7N04S-Na) is very useful since it can be used as a scavenger for acrylamide monomer. The reaction proceeds very rapidly even at room temperature, and the product has low toxicity. Reactions with phosphines and phosphine oxides have been studied (12), and the products are potentially useful because of thek fire retardant properties. Reactions with sulfide and dithiocarbamates proceed readily but have no appHcations (5). However, the reaction with mercaptide ions has been used for analytical purposes (13)). Water reacts with the amide group (5) to form hydrolysis products, and other hydroxy compounds, such as alcohols and phenols, react readily to form ether compounds. Primary aUphatic alcohols are the most reactive and the reactions are compHcated by partial hydrolysis of the amide groups by any water present. 

CAUTION Acrylamide is extremely TOXIC and precautions must be taken to avoid skin contact or inhalation. Use gloves and handle in a well ventilated fume cupboard... 

Bis-acrylamide (Af,Af -methylene bisacrylamide) [110-26-9] M 154.2, m >300 . Recrystd from MeOH (lOOg dissolved in 500mL boiling MeOH) and filtered without suction in a warmed funnel. Allowed to stand at room temperature and then at -15°C overnight. Crystals collected with suction in a cooled funnel and washed with cold MeOH). Crystals air-dried in a warm oven. TOXIC. 

The main disadvantage in using poly(acrylamide) systems is that they are not biodegradable and the monomers are toxic. Extensive purification is also required to remove the organic solvents, anionic surfactants, and residual monomers. Edman et al. [74] produced biodegradable poly(acryldextran) particles by incorporating dextran into the poly(acrylamide) chain. These particulate systems were metabolized and eliminated faster, both in vivo and in vitro, than poly(acrylamide) particles. 

EPA. 1986c. Final report on the evaluation of four toxic chemicals in an in vivo/in vitro toxicological screen Acrylamide, chlordecone, cyclophosphamide, and diethylstilbestrol. Research Triangle Park, NC U.S. Environmental Protection Agency, Health Effects Research Laboratory. EPA-600-1-86-002. 

Simmons JE, Berman E, Jackson M, et al. 1987. In vitro and in vivo toxicity A comparison of acrylamide, cyclophosphamide, chlordecone, and diethylstilbestrol. J Environ Sci Health A22(7) 639-64. 

Protective Effects of Linoleic acid on toxicity Caused by Acrylamide in Rats... 

Toxicology. Acrylamide causes central-peripheral axonopathy in laboratory animals it is carcinogenic and causes male reproductive toxicity. 

Sakamoto J, Hashimoto K Reproductive toxicity of acrylamide and related compounds in mice—effects on fertility and sperm morphology. Arch Toxicol 59 201-205, 1986... 

Chapin RE, Fail PA, George JD, et al The reproductive and neural toxicities of acrylamide and three analogues in Swiss mice, evaluated using the continuous breeding protocol. Fund Appl Toxicol 27(l) 9-24, 1995... 

Johnson KA, Gorzinski SJ, Bodner KM, et al Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats. Toxicol Appl Pharmacol 85 154-168, 1986... 

In addition to generation of toxic compounds in the frying oil, toxic molecules may be generated in foodstuff. In April 2002, Swedish scientists sounded an alarm when they discovered that certain cooked food, particularly potato chips and French fries, contained high levels of acrylamide, a chemical compound that is listed by the World Health Organization (WHO) as a probable human carcinogen (Mitka,... 

Stained, and cleared. In contrast, polyacrylamide does not permit the separation of many macromolecules, which cannot penetrate the gel. The polyacrylamide gels can only be used 12 or more hours after polymerization. Finally, acrylamide is known to be toxic to laboratory workers (SI). 

Caution Acrylamide is very toxic. Avoid inhalation of dust and wear gloves during manipulation with monomers ... 

Aciylamide is required in very large quantities as the pre-polymer of the polyacrylamide that is very widely used in polymer and flocculant apphcations. The chemical manufacture of acrylamide has been estabhshed for a long time. The original process involved treatment of acrylonitrile with sulphuric acid at 90°C. More recently processes have been introduced that require the use of copper catalysts and high temperatures (80-140°C), but result in the formation of large quantities of toxic waste, including HCN. The expensive copper catalyst used is difficult to regenerate. In addition the chemical process produces aciylamide that requires considerable purification, for instance because the... 

Friedman, M., Levin, C. E. (2008). Review of methods for the reduction of dietary content and toxicity of acrylamide. J. Agric. Food Chem., 56, 6113-6140. 

Nonmetallic neurotoxins are frequently used in industry in manufacturing of chemicals and resins or as solvents. Some examples are hydrogen sulfide (which paralyzes specifically the nervous centers that control respiratory movement), carbon disulfide, -hexane, methyl -butyl ketone, and acrylamide. Exposure to all of these substances may occur through inhalation of vapors. In addition, carbondisufide and acrylamide may enter the system by dermal absorption. -Hexane and methyl -butyl ketone are not toxic by themselves but are activated by cytochrome P-450 to the neurotoxic hexanedione (CH3COCH2CH2COCH3). 

More than a dozen biocompatible and biodegradable polymers have been described and studied for their potential use as carriers for therapeutic proteins (Table 13.5). However, some of the monomer building blocks such as acrylamide and its derivatives are neurotoxic. Incomplete polymerization or breakdown of the polymer may result in toxic monomer. Among the biopolymers, poly-lactide cofabricated with glycolide (PLG) is one of the most well studied and has been demonstrated to be both biocompatible and biodegradable [12]. PLG polymers are hydrolyzed in vivo and revert to the monomeric forms of glycolic and lactic acids, which are intermediates in the citric acid metabolic pathway. 

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