SEARCH · PubMed Health

Results for “Acrylamides”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed1981

Studies on in vitro metabolism of acrylamide and related compounds.

The in vitro biotransformations of acrylamide and ten related compounds in the hepatic enzyme system of the mouse were studied in order to learn more about their toxic actions in vivo. Of nine analogues, which could be analyzed quantitatively by gas chromatography, seven compounds--N-tert-butylacrylamide, diacetone acrylamide, N,N-dimethylacrylamide, N-isobutoxymethylacrylamide,--were metabolized in microsomal enzymes with NADPH generating system. One or two metabolites from each of the seven compounds, except for N-isobutoxymethylacrylamide were detected by gas chromatography. The metabolite of N-isopropylacrylamide was identified as acrylamide by gas chromatography-mass spectrometry. The metabolite of N,N-dimethylacrylamide showed a RT value identical with and a mass spectrum similar to N-methylacrylamide. No metabolites from the other four compounds have yet been identified. Acrylamide and crotonamide did not seem to be metabolized in the same system. Phenobarbital pretreatment of mice enhanced the metabolic reactions of the seven compounds, but did not elevate those of acrylamide and crotonamide. The Km value of N-isopropylacrylamide was 0.35 mM, which was the smallest of all the test analogues. All of the eleven analogues studied were found to be metabolized by hepatic glutathione S-transferases as well. This reaction was also elevated by the phenobarbital treatment of mice. The relationships between the in vitro metabolisms and the in vivo toxicities of acrylamide analogues are discussed.

Acrylamides↗

PubMed1997

Acrylamide and carbon disulfide treatments increase the rate of rat brain tubulin polymerization.

Acrylamide and carbon disulfide produce central-peripheral distal axonopathy in experimental animals and humans. The main feature of this disease is the focal swellings containing neurofilaments in distal axons, followed by nerve degeneration beyond these swellings. We studied the possible role of tubulin assembly kinetics in this disease. The rats were either administered acrylamide (50 mg/kg, ip, saline) or exposed to carbon disulfide (700 ppm, 9 h) via inhalation for 12 and 15 d, respectively. Tubulin, purified from both acrylamide-(10.37 +/- 0.3 vs 11.3 +/- 0.15) and carbon disulfide-treated (9.72 +/- 0.5 vs 11.18 +/- 0.25) rat brains showed increase in Vmax (OD/min x 10(3)) of its polymerization. However, only acrylamide treatment showed a decrease in time to Vmax, when brain supernatant was used for tubulin polymerization. In vitro addition of acrylamide (0.1-1 mM) to bovine brain tubulin also showed a decrease in time to Vmax (16-21%) of its polymerization. Carbon disulfide treatment of rats, on the other hand, showed a decrease in MAP-2 and an increase in a 120-kDa peptide concentration. The latter showed immunoreactivity with anti-MAP-2. The increase in the rate of tubulin polymerization by acrylamide and carbon disulfide treatment may alter the rate of transport of axonal constituents, including neurofilament, and contribute toward their accumulation in the focal swellings observed in this neuropathy.

Acrylamides↗

PubMed2005

Involvement of the extracellular signal-regulated protein kinase pathway in phosphorylation of p53 protein and exerting cytotoxicity in human neuroblastoma cells (SH-SY5Y) exposed to acrylamide.

Using human neuroblastoma SH-SY5Y cells, effects of acrylamide on p53 protein and intracellular signal transducting pathways were examined. Acrylamide increased p53, phosphorylated p53, and p53-associated protein murine double minute 2 (MDM2). The phosphorylation of p53 was specific for the Ser15 site. Among mitogen-activated protein kinases (MAPKs), acrylamide caused phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38 but not c-Jun NH(2)-terminal kinase. Nevertheless, blocking p38 pathway by LL-Z1640-2 did not suppress the phosphorylation of p53 at Ser15. In contrast, a specific inhibitor of ERK kinase (U0126 or PD98059) could abolish the accumulation as well as the phosphorylation of p53 at Ser15. Elevation of MDM2 was also abolished by U0126. An inhibitor of phosphatidylinositol 3-kinase-related kinase (PIKK) pathway (wortmannin) suppressed the increase of p53 and its phosphorylation at Ser15. Hence, acrylamide increases p53 protein and its phosphorylation at Ser15 through ERK and/or PIKK pathways. On the other hand, U0126 and PD98059 suppressed to some extent the cytotoxicity of acrylamide evaluated by trypan blue exclusion and lactate dehydrogenase (LDH) leakage, whereas neither LL-Z1640-2 nor wortmannin was effective in suppressing the toxicity. Thus, ERK pathway seems to play a role both in causing the phosphorylation of p53 at Ser15 and in the cytotoxicity of acrylamide in SH-SY5Y cells.

Acrylamide↗

PubMed2006

Rapid determination of acrylamide contaminant in conventional fried foods by gas chromatography with electron capture detector.

Gas chromatography coupled with electron capture detector (GC-ECD) was successfully developed and applied for the rapid determination of acrylamide in conventional fried foods, such as potato crisps, potato chips, and fried chicken wings. The method included defatting with n-hexane, extraction with aqueous solution of sodium chloride (NaCl), derivatization with potassium bromate (KBrO3) and potassium bromide (KBr), and liquid-liquid extraction with ethyl acetate. The final acrylamide extract was analyzed by GC-ECD for quantification and by GC-MS for confirmation. The chromatographic analysis was performed on the HP-INNOWax capillary column, and good retention and peak response of acrylamide were achieved under the optimal conditions (numbers of theoretical plates N = 83,815). The limit of detection (LOD) was estimated to be 0.1 microg kg(-1) on the basis of ECD technique. Recoveries of acrylamide from conventional samples spiked at levels of 150, 500 and 1000 microg kg(-1) (n = 4 for each level) ranged between 87 and 97% with relative standard deviations (RSD) of less than 4%. Furthermore, the GC-ECD method showed that no clean-up steps of acrylamide derivative would be performed prior to injection and was slightly more sensitive than the MS/MS-based methods. Validation and quantification results demonstrated that this method should be regarded as a new, low-cost, and robust alternative for conventional investigation of acrylamide.

Acrylamide↗

PubMed2005

Risk assessment of dietary acrylamide intake in Flemish adolescents.

Acrylamide has recently been found in a range of heat treated food items. As it is a neurotoxic agent and a probable, human carcinogen (IARC 2A), human exposure to this chemical might constitute an important public health issue. The purpose of the study was to estimate the acrylamide intake in Flemish adolescents (based on 7-day food record) and to evaluate the possible health risks due to the exposure. The Belgian Federal Agency for the Safety of the Food Chain collected 150 food items from different supermarkets and restaurants to analyse the acrylamide level. The limit of quantitation was 30 microg acrylamide/kg foodstuffs. Exposure modelling was based on Monte Carlo simulations. The estimated dietary intake of acrylamide per person given as the 5th, 50th and 95th percentile were 0.19, 0.51 and 1.09 mircog/kg bw/d. Bread, despite its low acrylamide content, is relevant as a source of acrylamide exposure at the lower percentiles. At higher percentiles the contribution of French fries and crisps is more important. It must be emphasised that the exposure assessment has several limitations. Risk of neurotoxicity seems negligible. The relevance of current intake levels in terms of cancer risk remains a subject of debate.

Acrylamide↗

PubMed2005

Human exposure and internal dose assessments of acrylamide in food.

This review provides a framework contributing to the risk assessment of acrylamide in food. It is based on the outcome of the ILSI Europe FOSIE process, a risk assessment framework for chemicals in foods and adds to the overall framework by focusing especially on exposure assessment and internal dose assessment of acrylamide in food. Since the finding that acrylamide is formed in food during heat processing and preparation of food, much effort has been (and still is being) put into understanding its mechanism of formation, on developing analytical methods and determination of levels in food, and on evaluation of its toxicity and potential toxicity and potential human health consequences. Although several exposure estimations have been proposed, a systematic review of key information relevant to exposure assessment is currently lacking. The European and North American branches of the International Life Sciences Institute, ILSI, discussed critical aspects of exposure assessment, parameters influencing the outcome of exposure assessment and summarised data relevant to the acrylamide exposure assessment to aid the risk characterisation process. This paper reviews the data on acrylamide levels in food including its formation and analytical methods, the determination of human consumption patterns, dietary intake of the general population, estimation of maximum intake levels and identification of groups of potentially high intakes. Possible options and consequences of mitigation efforts to reduce exposure are discussed. Furthermore the association of intake levels with biomarkers of exposure and internal dose, considering aspects of bioavailability, is reviewed, and a physiologically-based toxicokinetic (PBTK) model is described that provides a good description of the kinetics of acrylamide in the rat. Each of the sections concludes with a summary of remaining gaps and uncertainties.

Acrylamide↗

PubMed2004

Physicochemical investigation of acrylamide solubilization in sodium bis(2-ethylhexyl)sulfosuccinate and lecithin reversed micelles.

The state of acrylamide confined within dry sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and lecithin reversed micelles dispersed in CCl(4) has been investigated by FTIR and (1)H NMR spectroscopy. Measurements have been performed at 25 degrees C as a function of the acrylamide-to-surfactant molar ratio (R) at a fixed surfactant concentration (0.1 mol kg(-1)). The analysis of experimental data, corroborated by the results of SAXS measurements, is consistent with the hypothesis that acrylamide is quite uniformly distributed among reversed micelles mainly located in proximity to the surfactant head-group region and that its presence induces significant unidimensional growth of micellar aggregates. Moreover, the confinement of acrylamide within reversed micelles involves some changes of the typical H-bonded structure of pure solid acrylamide attributable to the establishment of system-specific acrylamide/surfactant head group interactions. Preliminary experiments showed that, by exposure to X-rays, the polymerization of acrylamide can be induced in the confined space of dry AOT and lecithin reversed micelles.

Acrylamide↗

PubMed2005

Transmitted mutational events induced in mouse germ cells following acrylamide or glycidamide exposure.

An increase in the germ line mutation rate in humans will result in an increase in the incidence of genetically determined diseases in subsequent generations. Thus, it is important to identify those agents that are mutagenic in mammalian germ cells. Acrylamide is water soluble, absorbed and distributed in the body, chemically reactive with nucleophilic sites, and there are known sources of human exposure. Here we review all seven published studies that assessed the effectiveness of acrylamide or its active metabolite, glycidamide, in inducing transmitted reciprocal translocations or gene mutations in the mouse. Major conclusions were (a) acrylamide is mutagenic in spermatozoa and spermatid stages of the male germ line; (b) in these spermatogenic stages acrylamide is mainly or exclusively a clastogen; (c) per unit dose, i.p. exposure is more effective than dermal exposure; and (d) per unit dose, glycidamide is more effective than acrylamide. Since stem cell spermatogonia persist and may accumulate mutations throughout the reproductive life of males, assessment of induced mutations in this germ cell stage is critical for the assessment of genetic risk associated with exposure to a mutagen. The two specific-locus mutation experiments which studied the stem cell spermatogonial stage yielded conflicting results. This discrepancy should be resolved. Finally, it is noted that no experiments have studied the mutagenic potential of acrylamide to increase the frequency of transmitted mutational events following exposure in the female germ line.

Acrylamide↗

PubMed2005

DNA adduction and mutagenic properties of acrylamide.

This review article summarizes our current knowledge on DNA damaging and mutagenic properties of acrylamide. Direct and indirect modes of interaction of acrylamide with DNA are discussed, and the resulting alkylating DNA adducts are highlighted. Emphasis is placed on glycidamide-DNA adducts generated via epoxidation of acrylamide presumably by cytochrome P4502E1. Dosimetry and mapping of acrylamide-induced DNA adducts in vitro and/or in vivo are described. Mutagenic potency and specificity of acrylamide in relation to its respective DNA adducts are discussed. Prospective views are provided on the potential applications of acrylamide-induced DNA adduct dosimetry/mapping and mutation frequency/spectrometry for biomonitoring purposes.

Acrylamide↗

PubMed2005

DNA damage and DNA adduct formation in rat tissues following oral administration of acrylamide.

Acrylamide is present as a contaminant in the human diet in heated food products. It has been found to be carcinogenic in laboratory rats and has been classified as probably carcinogenic in humans. In order to clarify the possible involvement of a primary genotoxic mechanism in acrylamide-induced carcinogenicity, both the presence of DNA damage, measured by the comet assay, and the formation of N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (N3-GA-Ade), derived from reaction of the active metabolite glycidamide (GA) with the DNA, analyzed by LC/MS/MS, were assessed in selected rat tissues. Rats were administered with single oral doses of acrylamide (18, 36 or 54 mg/kg body weight (b.w.) and the organs (blood leukocytes, brain, bone marrow, liver, testes and adrenals) were sampled at different times after treatment. Results from GA-induced DNA adduct measurements indicated a relatively even organ distribution of the adducts in brain, testes and liver. Organ-specificity in acrylamide carcinogenesis can therefore not be explained by a selective accumulation of GA-DNA adducts in the target organs, at least not after a single dose exposure. The DNA adduct profiles and half-lives were similar in the different organs; except that the N3-GA-Ade adduct was more rapidly removed from tissues than the N7-GA-Gua adduct. Increased extent of DNA migration, as measured by the in vivo rat comet assay, was found in brain and testes, and these specific results seem to be in accordance with the known organ-specificity in acrylamide carcinogenesis in rat. Only weak and transient DNA damage was recorded in the liver, bone marrow and adrenals. The DNA-damaging effect of the compound observed in the blood leukocytes could be a simple biomarker of acrylamide exposure and genotoxicity.

Acrylamide↗

PubMed2026

Changes in the chick liver structure and blood plasma biochemical properties following in ovo administration of acrylamide.

This study analyzed the effects of acrylamide administration during the embryonic period on liver microstructure and blood plasma biochemical parameters in hatched chicks. On day 6 of incubation, 96 embryonated eggs per group were injected with acrylamide (ACR) at doses of 0.0, 0.25, 0.5, 1.0, 2.0 and 4.0 mg ACR/egg dissolved in 0.9% saline solution (100 µL). Embryo development, hatchability and quality of chicks were evaluated. The ten chicks per group (0.0, 0.25, 0.5 and 1.0 mg ACR/egg) were euthanized immediately after hatching, and blood and liver samples were collected for further analysis. Hatchability was 74.0, 67.7, 66.7 and 49.5% in groups treated with 0.0, 0.25, 0.5, 1.0 mg ACR/egg, respectively, while all embryos died in 2.0 and 4.0 mg ACR/egg groups. Acrylamide intoxication affected only a few biochemical parameters of blood, including a significant decrease in glucose and globulin levels in the group injected with a dose of 1 mg/egg and a significant increase in blood urea nitrogen concentration in the group treated with a dose of 0.5 mg/egg. However, this substance caused negative changes in the microarchitecture of the liver of one-day-old chicks, as indicated by the results of histomorphometric analysis, such as an increase in total hepatocyte nuclei, binucleated hepatocytes, cell nucleus size, collagen area, and other cells. Furthermore, abnormalities in liver structure were confirmed by trace elements content results. Thus, in individuals treated with acrylamide (0.25 and 0.5 mg/egg), a decrease in copper levels and (0.25 mg/egg) nickel and iron levels and an increase in cadmium levels were observed. An increase in lead content was similarly observed in the group exposed to acrylamide at a dose of 0.5 mg/egg, as well as an increase in zinc levels in groups administered various doses of this toxic substance. Overall, the results suggest an inconsistent and dose-dependent toxic effect of acrylamide on liver structure and selected blood plasma parameters in one-day-old chicks.

Acrylamide↗

PubMed1999

Effect of acrylamide on aldolase structure. I. Induction of intermediate states.

Acrylamide is a fluorescence quencher frequently applied for analysis of protein fluorophores exposure with the silent assumption that it does not affect the native structure of protein. In this report, it is shown that quenching of tryptophan residues in aldolase is a time-dependent process. The Stern-Volmer constant increases from 1.32 to 2.01 M-1 during the first 100 s of incubation of aldolase with acrylamide. Two tryptophan residues/subunit are accessible to quenching after 100 s of aldolase interaction with acrylamide. Up to about 1.2 M acrylamide concentration enzyme inactivation is reversible. Independent analyses of the changes of enzyme activity, 1ANS fluorescence during its displacement from aldolase active-site, UV-difference spectra and near-UV CD spectra were carried out to monitor the transition of aldolase structure. From these measurements a stepwise transformation of aldolase molecules from native state (N) through intermediates: I1, T, I2, to denatured (D) state is concluded. The maxima of I1, T, I2 and D states populations occur at 0.2, 1.0, 2.0 and above 3.0 M of acrylamide concentration, respectively. Above 3.5 M, acrylamide aldolase molecules become irreversibly inactivated.

Acrylamide↗

PubMed1999

Effect of acrylamide on aldolase structure. II. Characterization of aldolase unfolding intermediates.

Molecules of muscle aldolase A exposed to acrylamide change their conformation via I1, T, I2, D intermediates [1] and undergo a slow irreversible chemical modification of thiol groups. There is no direct correlation between activity loss and thiol groups modification. In the native enzyme two classes of Trp residues of 1. 8 ns and 4.9 ns fluorescence lifetime have been found. Acrylamide (0. 2-0.5 M) increases lifetime of longer-lived component, yet the transfer of aldolase molecules even from higher (1.0 M) perturbant concentration to a buffer, allows regain original Trp fluorescence lifetime. I1, detected at about 0.2 M acrylamide, represents low populated tetramers of preserved enzyme activity. T, of maximum population at about 0.7-1.0 M acrylamide, consists of meta-stable tetramers of partial enzymatic activity. These molecules are able to exchange their subunits with aldolase C in opposition to the native molecules. At transition point for I2 appearance (1.8 M acrylamide), aldolase becomes highly unstable: part of molecules dissociate into subunits which in the absence of perturbant are able to reassociate into active tetramers, the remaining part undergoes irreversible denaturation and aggregation. Some expansion of aldolase tetramers takes place prior to dissociation. D, observed above 3.0 M acrylamide, consists of irreversibly denatured enzyme molecules.

Acrylamide↗

PubMed2000

Cutaneous nerve degeneration induced by acrylamide in mice.

Acrylamide is a neurotoxin producing distal axonopathy. Previous studies mainly focused on large-diameter motor and sensory nerves, and the influences of acrylamide neurotoxicity on small-diameter sensory nerves in the skin remained elusive. We investigated skin innervation in mice intoxicated by acrylamide. Small-diameter sensory nerves in the skin degenerated after acrylamide intoxication. Epidermal nerve swelling was the earliest sign of acrylamide intoxication, with 29.5+/-2.4% of swollen epidermal nerves in the initial stage (P<0.001). There was a trend of progressive loss of epidermal nerves with a significantly reduced epidermal nerve density in the late stage (P<0.003). In the mean time, degenerating dermal nerves exhibited a beaded appearance. These results suggest the scenario of small-diameter cutaneous nerve degeneration in acrylamide neurotoxicity: beginning with epidermal nerve terminal swelling in the initial stage and resultant epidermal nerve depletion in the late phase.

Acrylamide↗

PubMed2001

Determination of acrylamide and glycidamide in rat plasma by reversed-phase high performance liquid chromatography.

Acrylamide is a widely used monomer that produces peripheral neuropathy. It is metabolized to the epoxide, glycidamide, which is also considered to be neurotoxic. A new reversed-phase high-performance liquid chromatography (HPLC) method is described that permits simultaneous determination of acrylamide and glycidamide in rat plasma. Samples were deproteinized with acetonitrile and chromatography was performed using isocratic elution and UV absorption detection. The limits of detection for acrylamide and glycidamide were 0.05 and 0.25 microg/ml in plasma, respectively, and recovery of both analytes was greater than 90%. The assay was linear from 0.1 to 100 microg/ml for acrylamide and from 0.5 to 100 microg/ml for glycidamide. Variation over the range of the standard curve was less than 15%. The method was used to determine the concentration-time profiles of acrylamide and glycidamide in the plasma of acrylamide-treated rats.

Acrylamide↗

PubMed1982

Fluorescence quenching of liver alcohol dehydrogenase by acrylamide.

The quenching of the fluorescence of liver alcohol dehydrogenase by acrylamide has been studied as a function of excitation and emission wavelength. Downward curving Stern-Volmer plots are found, providing further support for the notion that Trp-15 of the protein is surface exposed and that Trp-314 is extensively buried within the protein. The acrylamide quenching of the binary complex formed between the protein and NAD+ was also studied. The quenching pattern in this case is found to be complicated due to the interaction of acrylamide with the binary complex. Independent evidence for the fact that acrylamide binds to the binary complex is obtained from enzyme inhibition studies and from NAD+ binding studies showing acrylamide to bind with positive cooperativity with respect to the coenzyme. When the interaction of acrylamide with the binary complex is taken into consideration, however, the quenching data can be interpreted as indicating that the binding of NAD+ to the protein does not induce a conformational change that leads to the exposure of Trp-314.

Acrylamides↗

PubMed2003

Acrylamide in foods: occurrence, sources, and modeling.

Acrylamide in food products-chiefly in commercially available potato chips, potato fries, cereals, and bread-was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Samples were homogenized with water/dichloromethane, centrifuged, and filtered through a 5 kDa filter. The filtrate was cleaned up on mixed mode, anion and cation exchange (Oasis MAX and MCX) and carbon (Envirocarb) cartridges. Analysis was done by isotope dilution ([D(3)]- or [(13)C(3)]acrylamide) electrospray LC-MS/MS using a 2 x 150 mm (or 2 x 100 mm) Thermo HyperCarb column eluted with 1 mM ammonium formate in 15% (or 10% for the 2 x 100 mm column) methanol. Thirty samples of foods were analyzed. Concentrations of acrylamide varied from 14 ng/g (bread) to 3700 ng/g (potato chips). Acrylamide was formed during model reactions involving heating of mixtures of amino acids and glucose in ratios similar to those found in potatoes. In model reactions between amino acids and glucose, asparagine was found to be the main precursor of acrylamide. Thus, in the reaction between nitrogen-15 (amido)-labeled asparagine and glucose, corresponding (15)N-labeled acrylamide was formed. The yield of the model reaction is approximately 0.1%.

Acrylamide↗

PubMed2003

Why asparagine needs carbohydrates to generate acrylamide.

Structural considerations dictate that asparagine alone may be converted thermally into acrylamide through decarboxylation and deamination reactions. However, the main product of the thermal decomposition of asparagine was maleimide, mainly due to the fast intramolecular cyclization reaction that prevents the formation of acrylamide. On the other hand, asparagine, in the presence of reducing sugars, was able to generate acrylamide in addition to maleimide. Model reactions were performed using FTIR analysis, and labeling studies were carried out using pyrolysis-GC/MS as an integrated reaction, separation, and identification system to investigate the role of reducing sugars. The data have indicated that a decarboxylated Amadori product of asparagine with reducing sugars is the key precursor of acrylamide. Furthermore, the decarboxylated Amadori product can be formed under mild conditions through the intramolecular cyclization of the initial Schiff base and formation of oxazolidin-5-one. The low-energy decarboxylation of this intermediate makes it possible to bypass the cyclization reaction, which is in competition with thermally induced decarboxylation, and hence promote the formation of acrylamide in carbohydrate/asparagine mixtures. Although the decarboxylated Amadori compound can be formed under mild conditions, it requires elevated temperatures to cleave the carbon-nitrogen covalent bond and produce acrylamide.

Acrylamide↗