Acrylamide

Acrylamide (2-propenamide) is a known neurotoxin[1][2] and carcinogen[3], present in heated foods (incl. bread) and cigarette smoke. Environmentally, it may be the result of decomposition of polyacrylamide (in herbicides). Acrylamide is industrially produced for various purposes (eg polymeres). It decomposes in the presence of acids, bases and oxidizing agents, rendering ammonia or nitrogen oxides. Endogenously, acrylamide is metabolized to glycidamide (a DNA-reactive expoxide[4]).

Acrylamide in food

Amides are derivates of ammonia or (carboxylated) amines. Particularly in heated (>120°C) plant foods, acrylamide is yielded by the reaction of a specific amino acid (asparagine) and carbonyls (eg yielded by lipid oxidation) or reducing sugars (sugars yielding aldehydes; such as glucose in starches, and other aldoses, as well as ketoses and fructose)[5]. In this reaction, glucans such as glucose, starch and cellulose are interchangeable.[6] Higher levels of reducing sugars results in higher levels of acrylamide.[7] Particularly deep-frying has great consequences, evoking various complex reactions such as oxidation, hydrolysis, isomerization, and polymerization.[8] Microwaving creates more acrylamide than roasting.[9] Elevated phenol levels in potatoes[10], and some antioxidants (vitamin C[11], vitamin E) decrease the level of acrylamide produced during food processing[12], but adding antioxidants to foods may increase the formation of acrylamide upon long-term heating if free sugar concentration is low and asparagine concentration is relatively high.[13] Eugenol in nutmeg, cinnamon and basil restores the acrylamide-induced reduction in glutathione (similar to selenium[14]) and dopamine levels, and reduces oxidative stress in the brain.[15]

• Potatoes may contain varying levels of acrylamide, varying per season[16], as storing below 10°C increases breakdown of starch to sucrose, ultimately cleaved by acid invertase to produce glucose and fructose[17]. The mean level of acrylamide content in all frozen potato products before preparation was found to be 322 μg/kg.[18] Even though potato crisps contain at least 10 fold more acrylamide (250 to 6700 mcg/kg) than acrolein (26 mcg/kg), 4 to 12 fold more acrolein- than acrylamide-related mercapturic acids are excreted in urine, which may indicate undetected varieties of acrolein.[19] A french study found on average 954 mcg/kg acrylamide in potato chips/crisps.[20] A Swiss study found 7000 mcg/kg acrylamide in one particular brand of potato chips.[21] A Chinese study found on average 1548 mcg/kg acrylamide in potato chips.[22]Another Chinese study found 604 mcg/kg acrylamide in fried potato.[23] In an Iranian study, levels of acrylamide in potato products varied between 244 and 1688 mcg/kg.[24] In a Canadian study the acrylamide concentration in potato chips varied from 106 to 4630 mcg/kg.[25]
• Cookies' acrylamide concentrations correspond with baking temperature and surface color. Steam-assisted baking results in lower levels.[26] Cookies baked at 150°C  for 25  minutes yielded 75 mcg/kg acrylamide, compared to 236 mcg/kg in cookies baked at 240°C  for 9 minutes.[27] Cookies baked in an oven at 205°C for 11 min yielded 107 mcg/kg acrylamide.[28] A Chinese study found on average 388 mcg/kg acrylamide in biscuits.[29]
• Cereals may contain from 50 to 347 mcg/kg[30] up to 1080 mcg/kg acrylamide.[31]
• Corn products were found to contain between 30 and 410 mcg/kg acrylamide [32].
• Crispbread / crackers may contain 845 mcg/kg[33] or 942 mcg/kg acrylamide.[34]
• Bread (wheat; up to 5 mcg/kg) and rye bread (7 to 23 mcg/kg) contain relatively little acrylamide when untoasted, but toasted wheat (11 to 161 mcg/kg) and rye bread slices (27 to 205 mcg/kg) contain much more.[35]
• Soybean-containing commercial bakery products contain higher levels of acrylamide than similar bakery products without soy.[36]
• In prawn strips, on average 341 mcg/kg and in rice crusts 201 mcg/kg acrylamide was found. Heated protein-rich food also showed some acrylamide content, ranging from 2 to 78 µg/kg.[37]
• Almonds roasted at 138°C for 22 min had acrylamide levels ranging from 117 to 221 μg/kg, with an average of 187 μg/kg.[38]
• Prune juice contains 186 to 916 µg/kg acrylamide. Strained prunes in babyfood may contain 75 to 265 µg/kg, baby apple/prune juice 33 to 61 µg/kg, and prunes 58 to 332 µg/kg. Prunes are produced industrially by dehydration of plums at temperatures of 85–90°C for 18 h. Prune juice is produced by boiling the prunes in water, and may include pasteurisation. Strained/pureed prunes in babyfoods contain up to 265 mcg/kg acrylamide, and apple-prune juice up 61 mcg/kg.[39]

Acrylamide food additives

• AF-2 or furylfuramide; 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide (widely used in Japan[40]), was first demonstrated to be mutagenic in Escherichia coli WP-2 and then proved to be carcinogenic in experimental animals [41][42][43] 5-nitro-2-furyl is a radical.
• 5-NFAA; 3-(5-nitro-2-furyl)acrylic acid proved to be more mutagenic than AF-2.[44]

Acrylamide exposure

• Though Guideline-base diets contain less acrylamide contributed by French fries and potato chips, overall acrylamide intake is yet relatively high due to more frequent breakfast cereal intake.[45]
• In a Californian study, non-cancer benchmarks for acrylamide were exceeded by >95% of preschool-age children, most of the acrylamide coming from chips, cereal, crackers, and other processed carbohydrate foods.[46]
• In Poland, the daily exposure of infants aged 6-12 months of life was estimated at the minimum level in the range from 0.41 to 0.62 μg/kg bodyweight (bw), and at the average level - from 2.10 to 4.32 μg/kg bw. For the worst case scenario the exposure ranged from 7.47 to 12.35 μg/kg bw and was more than a dozen times and even several dozen times higher than the exposure estimated for the average total population.[47]
• In a French study mean daily acrylamide exposure was assessed to be 0.43 μg/kg of body weight for adults and 0.69 μg/kg for children.[48]
• In Finland, the most important source of acrylamide exposure was coffee, followed by casseroles rich in starch, then rye bread. Among children, the most important sources were casseroles rich in starch and then biscuits and, finally, chips and other fried potatoes. Daily acrylamide exposure per kg bodyweight was highest among the 3-year-old children (1.01 µg/kg) and lowest among 65-74-year-old women (0.31 µg/kg).[49]
• In Norway the dietary exposure of 119 pregnant women to acrylamide was estimated at 0.3 mcg/kg bodyweight.[50]
• In Belgium, the daily average acrylamide exposure was calculated to be 0.4 mcg/kg bodyweight, and the main contributors being chips (23%), coffee (19%), biscuits (13%), and bread (12%).[51]

Health effects

• Acrylamide induces hepatic ornithine decarboxylase (ODC)[52] and affects behaviour by influencing hepatic mechanisms or central dopaminergic function.[53]
• Acrylamide and its metabolite glycidamide bind with proteins to form protein adducts in metabolic processes.[54]
• Acrylamide increases expression of nitric oxide synthase (iNOS) and cycloogenase-2 (Cox-2) and NOS activity in breast epithelial cells.[55] These are known to be early molecular changes in disease formation.
• The placenta gives negligible protection of the fetus to exposure from acrylamide[56]. Maternal dietary exposure to acrylamide is associated with reduced birth weight and head circumference.[57][58]
• In mice, acrylamide altered the morphology and histology of the small intestinal wall, decreasing proliferation, myenteron and submucosal thicknesses, villus length, fractal dimension, crypt depth, crypt number, and the small intestinal absorptive surface. Conversely, apoptosis, hemoglobin adduct levels, intensity of epithelium staining, enterocyte number, villus epithelial thickness, and crypt width and parameters associated with nerve ganglia were increased. These effects were inhibted by potato fiber.[59]
• In pregnant mice, both acrylamide and fried potato chips increased the rate of abortion and neonatal mortality and decreased the total number, body weight, size, and crown-rump length of the offspring before and after birth. Fried potato chips induced higher rates of congenital malformations than acrylamide alone.[60]
• In rat pups, acrylamide administration induced neurotoxic symptoms, including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Acrylamide treatment caused a significant alteration in the expression of a few genes that are involved in muscle contraction, pain, and dopaminergic neuronal pathways.[61]
• In rats, acrylamide exposure of 2500 μg/kg bodyweight caused significant changes in serum hormones, histopathology, testicular gene expression, and cell proliferation.[62]
• In weaning male rats, acrylamide has a toxicological effect on the reproductive system.[63]
• In rats, at a dose of 1 μg/kg bodyweight, adducts (DNA adducts, primarily at N7 of guanine) were found in kidney and lung, but not in liver. At 10 μg/kg bw, adducts were found in all three organs, at levels close to those found at 1 μg acrylamide/kg.[64]
• Human epidemiological studies show a lack of relationship between acrylamide intake and various types of cancer.[65][66] Given the consistent relationship between dietary carcinogenic heterocyclic amines (HCAs) and various types of cancer, and that dietary acrylamide mainly comes from processed plant (starchy) foods, and that dietary carcinogenic HCAs mainly come from processed animal foods, a high plant food intake (vs high animal food intake) is indeed unlikely to increase exposure to dietary carcinogens (acrylamide intake will be the expense of HCA intake).

Acetamide in food

Amides are derivates of ammonia or (carboxylated) amines. Acetamide is a carcinogenic derived from acetic acid, by dehydrating ammonium acetate[67], or by hydrolysis of acetonitrile[68]. Thermal degradation (>200°C) of chitin also yields acetamide.[69] Chitin is a good inducer for defense mechanisms in plants[70], and present in fungi, the exoskeletons of crustaceans such as crabs, lobsters and shrimps, in mollusks, and in the internal shells of squid and octopus. Acetamide is also a byproduct of thermochemical treatment of lignocellulosic biomass.[71]

3-MCPD

3-monochloropropane-1,2-diol (3-MCPD).