Glycidamide

Glycidamide is part of the chemical group of amides and oxiranes, it is classified as a carcinogenic substance. It is associated with tobacco either as natural component, pyrolysis product in tobacco smoke or additive for one or more types of tobacco products. Glycidamide is formed from acrylamide. Acrylamide is an industrial chemical which is used in several ways, such as production of polyacrylamides for (waste)water treatment, textile, paper processing and cosmetics. It is also a product formed in certain foods prepared at high temperature frying, baking or roasting, such as fried potatoes, bakery products and coffee. Glycidamide is formed through the reaction of unsaturated fatty acids with oxygen. It is a dangerous substance, since it causes small mutations in cells which can result in several forms of cancer. Glycidamide is part of the chemical group of amides and oxiranes, it is classified as a carcinogenic substance. It is associated with tobacco either as natural component, pyrolysis product in tobacco smoke or additive for one or more types of tobacco products. Glycidamide is formed from acrylamide. Acrylamide is an industrial chemical which is used in several ways, such as production of polyacrylamides for (waste)water treatment, textile, paper processing and cosmetics. It is also a product formed in certain foods prepared at high temperature frying, baking or roasting, such as fried potatoes, bakery products and coffee. Glycidamide is formed through the reaction of unsaturated fatty acids with oxygen. It is a dangerous substance, since it causes small mutations in cells which can result in several forms of cancer. Two of the first researchers who acknowledged the existence of glycidamide were Murray and Cloke in 1934. They performed experiments on glycidamide formation (see Synthesis for more details). Since glycidamide is a metabolite of acrylamide, not much studies has been done on glycidamide on its own. Most of the studies focus on the effects of acrylamide, whereas less studies focus specifically on the effects of glycidamide. There are many studies that combine acrylamide and glycidamide, but the focus is still mainly on acrylamide. Glycidamide is a reactive epoxide metabolite from acrylamide. Glycidamides are fine crystals with lumps with a light orange color. It has an asymmetrical structure with electrophilic properties and can react with nucleophiles. This results in covalent binding of the electrophile. There is no data on the odor of glycidamide. Glycidamide gives a positive response in the Ames/Salmonella mutagenicity assay, which indicates that it can cause mutations in the DNA. Glycidamide is naturally formed by oxidation of acrylamide by cytochrome P450 2E1 (CYP2E1). This reaction follows Michaelis-Menten kinetics. Due to this reaction, glycidamide becomes critical to the genotoxicity of acrylamide. Saturated fatty acids protect the acrylamide from forming glycidamide. When during food processing, oil is used that contains unsaturated fatty acids, the amount of glycidamide formed is much higher. The first experiments on glycidamide formation were done by Murray and Cloke (1934). They tried to form glycidamides from α,β-ethylenic nitriles. In order to do so, they used the modified Radziszewski reaction. The Radziszewski reaction refers to a method for the preparation of amides, described by Radziszewski in 1885. The amides are prepared “by the action of 3% hydrogen peroxide on nitriles in the presence of alkali and at a temperature of 40 degrees Celsius”. The reaction was modified by adding methanol, ethanol and acetone. Some nitriles did indeed give glycidamides. Glycidamide reacts with DNA to form DNA adducts and is more reactive to DNA than acrylamide. Several glycidamide-DNA adducts have been characterized (Beland, 2015). The main DNA adducts are N7-(2-carbamoyl-2-hydroxyethyl)-guanine (or N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (or N3-GA-Ade). Glycidamide also reacts with haemoglobine (Hb) to form a cysteine adduct, S-(20hydroxy-2carboxyethyl)cysteine. With this reaction, N-terminal valine adducts are also formed. There are two isomers of this connection: (R)-Glycidamide and the mirror image (S)-Glycidamide. The racemate (RS)-Glycidamide is a 1:1 mixture of both isomers.