RESUMO
There is a worldwide concern on adverse health effects of dietary exposure to acrylamide (AA) due to its presence in commonly consumed foods. AA is formed when carbohydrate rich foods containing asparagine and reducing sugars are prepared at high temperatures and low moisture conditions. Upon oral intake, AA is rapidly absorbed and distributed to all organs. AA is a known human neurotoxicant that can reach the developing foetus via placental transfer and breast milk. Although adverse neurodevelopmental effects have been observed after prenatal AA exposure in rodents, adverse effects of AA on the developing brain has so far not been studied in humans. However, epidemiological studies indicate that gestational exposure to AA impair foetal growth and AA exposure has been associated with reduced head circumference of the neonate. Thus, there is an urgent need for further research to elucidate whether pre- and perinatal AA exposure in humans might impair neurodevelopment and adversely affect neuronal function postnatally. Here, we review the literature with emphasis on the identification of critical knowledge gaps in relation to neurodevelopmental toxicity of AA and its mode of action and we suggest research strategies to close these gaps to better protect the unborn child.
Assuntos
Acrilamida/toxicidade , Exposição Dietética/efeitos adversos , Síndromes Neurotóxicas/embriologia , Acrilamida/farmacocinética , Animais , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Manipulação de Alimentos , Humanos , Troca Materno-Fetal , GravidezRESUMO
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium, and it is found in many foods. Acrylamide (AA) can be produced in foods treated at high temperatures. In this study, we investigated the combined toxicity of OTA and AA against human renal and hepatic cells in vitro. The concentration at which the synergistic effect of OTA and AA occurs was determined using the combination index obtained from the cell viability results for OTA and AA individually or in combination. The synergistic toxicity of both substances was evaluated by cell viability and the production of reactive oxygen species. In addition, apoptosis-related markers were significantly upregulated by OTA and AA individually or in combination. To determine the combined toxic effects of OTA and AA on the cells, the levels of enzymes involved in the phase I reaction and apoptosis-related markers were determined using quantitative (q)PCR and Western blot. The expression levels of CYP enzymes CYP1A1 and CYP1A2 involved in the phase I reaction significantly increased when the cells were treated with OTA and AA in combination. The expression of apoptosis-related markers, Bcl2-associated X protein (Bax) and caspase 3, also increased when the cells were treated with OTA and AA in combination. Therefore, the synergistic toxicity of OTA and AA suggests that such effects may contribute to nephrotoxicity and hepatotoxicity.
Assuntos
Acrilamida/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ocratoxinas/toxicidade , Acrilamida/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Culinária/métodos , Sinergismo Farmacológico , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Microbiologia de Alimentos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Temperatura Alta/efeitos adversos , Humanos , Rim/citologia , Fígado/citologia , Ocratoxinas/farmacocinética , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade AgudaRESUMO
Acrylamide (AA) is a food contaminant present in a wide range of frequently consumed foods, which makes human exposure to this toxicant unfortunately unavoidable. However, efforts to reduce the formation of AA in food have resulted in some success. This review aims to summarize the occurrence of AA and the potential mitigation strategies of its formation in foods. Formation of AA in foods is mainly linked to Maillard reaction, which is the first feasible route that can be manipulated to reduce AA formation. Furthermore, manipulating processing conditions such as time and temperature of the heating process, and including certain preheating treatments such as soaking and blanching, can further reduce AA formation. Due to the high exposure to AA, recognition of its toxic effect is necessary, especially in developing countries where awareness about AA health risks is still very low. Therefore, this review also focuses on the different toxic effects of AA exposure, including neurotoxicity, genotoxicity, carcinogenicity, reproductive toxicity, hepatotoxicity, and immunotoxicity.
Assuntos
Acrilamida , Contaminação de Alimentos , Acrilamida/análise , Acrilamida/química , Acrilamida/farmacocinética , Acrilamida/toxicidade , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Fermentação , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Manipulação de Alimentos/métodos , Humanos , Concentração de Íons de Hidrogênio , Água/análiseRESUMO
The study was initiated with the intent to synthesize acrylamide grafted neem gum polymer (AAm-g-NG), and screen its drug release retardation ability both in vitro and in vivo. Different batches (NGP-1 to NGP-9) of tablet formulation were prepared by varying polymer concentration using propranolol HCl and compared with HPMC K100â¯M and marketed SR tablets. FTIR study proved the grafting phenomenon and showed no incompatibility between AAm-g-NG and propranolol HCl. AAm-g-NG showed significant swelling and water retention capacity than NG. AAm-g-NG was found to be biodegradable and exhibited no toxicity to Artemia salina. After 12â¯h, NGP-6 showed non-significant (pâ¯>â¯0.05; f2= â¼ 90) percent drug release (80.52⯱â¯3.41%) compare to marketed formulation (79.65⯱â¯4.08%). Significant swelling of the matrix caused slower diffusion of the drug. NGP-6 and marketed formulation in rabbits showed the non-significant difference between Cmax and Tmax, hence NGP-6 meets the requirement of sustained-release tablets.
Assuntos
Acrilamida , Azadirachta , Gomas Vegetais , Acrilamida/química , Acrilamida/farmacocinética , Acrilamida/toxicidade , Animais , Artemia/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/toxicidade , Liberação Controlada de Fármacos , Gomas Vegetais/química , Gomas Vegetais/farmacocinética , Gomas Vegetais/toxicidade , Coelhos , ComprimidosRESUMO
Acrylamide is included on the State of California's Proposition 65 list as a carcinogen. Acrylamide is found in cigarette smoke and in many types of foods, including breads, cereals, coffee, cookies, French fries, and potato chips. In 1990, California's Office of Environmental Health Hazard Assessment (OEHHA) established a no significant risk level (NSRL) of 0.2⯵g/day for acrylamide. Since then, multiple cancer studies have been published. In this report, we developed an updated NSRL for acrylamide. Using benchmark dose modeling and a weight-of-evidence, non-threshold approach to identify the most sensitive species, cancer slope factors (CSFs) were derived based on combined incidences of statistically significant neoplastic lesions in the Harderian gland, lung, and stomach in male mice. We then used a toxicokinetic (TK)-based scaling approach to convert the animal CSF to a human equivalent CSF, which served as the basis for the NSRL of 1.1⯵g/day at the cancer risk level of 1 in 100,000. This NSRL can be used in quantitative exposure assessments to assess compliance with Proposition 65 to ascertain either the need for or exemption from the Proposition 65 labeling requirement and drinking water discharge prohibition.
Assuntos
Acrilamida/toxicidade , Carcinógenos/toxicidade , Modelos Teóricos , Neoplasias/induzido quimicamente , Acrilamida/farmacocinética , Animais , Testes de Carcinogenicidade , Carcinógenos/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Camundongos , Ratos Endogâmicos F344 , Medição de Risco , ToxicocinéticaRESUMO
The endocrine system is highly sensitive to endocrine-disrupting chemicals (EDC) which interfere with metabolism, growth and reproduction throughout different periods of life, especially in the embryonic and pubertal stages, in which gene reprogramming may be associated with impaired development and control of tissues/organs even in adulthood. Acrylamide is considered a potential EDC and its main source comes from fried, baked and roasted foods that are widely consumed by children, teenagers and adults around the world. This review aimed to present some aspects regarding the acrylamide formation, its toxicokinetics, the occurrence of acrylamide in foods, the recent findings about its effects on different systems and the consequences for the human healthy. The challenges to characterize the molecular mechanisms triggered by acrylamide and to establish safe levels of consumption and/or exposure are also discussed in the present review.
Assuntos
Acrilamida/toxicidade , Disruptores Endócrinos/toxicidade , Sistema Nervoso/efeitos dos fármacos , Acrilamida/química , Acrilamida/farmacocinética , Animais , Criança , Disruptores Endócrinos/química , Disruptores Endócrinos/farmacocinética , Humanos , Sistema Nervoso/crescimento & desenvolvimento , Sistema Nervoso/metabolismo , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Reprodução/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismoRESUMO
The aim of present study was to develop controlled release formulation of pirfenidone using acrylamide grafted pullulan. Interpenetrating polymer network (IPN) microspheres were prepared using acrylamide grafted pullulan and PVA utilizing glutaraldehyde assisted water-in-oil emulsion crosslinking method. IPN microspheres were characterized by FTIR, solid state 13C NMR and XRD spectroscopy. In vitro enzymatic degradation study showed 34.30% degradation after 24 h with degradation rate constant of 0.0088 min-1. In vitro biocompatibility test showed no changes in cellular morphology and cell adherence to microspheres, indicating its biocompatible nature. The release exponent value of all formulations was less than 0.45, indicating the release mechanism to be Fickian diffusion. Finally, in vivo pharmacokinetic study showed longer Tmax (1.16 h) and greater AUC value (10037.76â¯ngâ¯h/mL,) as compared to Pirfenex® (Tmax = 0.5 h; AUCâ¯=â¯4310.45â¯ngâ¯h/mL,). The results indicated that the prepared formulation could successfully control the drug release for prolonged time period.
Assuntos
Acrilamida/química , Materiais Biocompatíveis/química , Glucanos/química , Álcool de Polivinil/química , Piridonas/química , Acrilamida/farmacocinética , Animais , Materiais Biocompatíveis/farmacocinética , Sobrevivência Celular , Glucanos/farmacocinética , Células Hep G2 , Humanos , Cinética , Microesferas , Tamanho da Partícula , Álcool de Polivinil/farmacocinética , Piridonas/farmacocinética , Coelhos , Propriedades de Superfície , TemperaturaRESUMO
To investigate the association between dietary acrylanide and advanced prostate cancer, we examined acrylamide-gene interactions for advanced prostate cancer risk by using data from the Netherlands Cohort Study. Participants (n = 58,279 men) completed a baseline food frequency questionnaire (FFQ), from which daily acrylamide intake was calculated. At baseline, 2,411 men were randomly selected from the full cohort for case-cohort analysis. Fifty eight selected single nucleotide polymorphisms (SNPs) and two gene deletions in genes in acrylamide metabolism, DNA repair, sex steroid systems, and oxidative stress were analyzed. After 20.3 years of follow-up, 1,608 male subcohort members and 948 advanced prostate cancer cases were available for Cox analysis. Three SNPs showed a main association with advanced prostate cancer risk after multiple testing correction: catalase (CAT) rs511895, prostaglandin-endoperoxide synthase 2 (PTGS2) rs5275, and xeroderma pigmentosum group C (XPC) rs2228001. With respect to acrylamide-gene interactions, only rs1800566 in NAD(P)H quinone dehydrogenase 1 (NQO1) and rs2301241 in thioredoxin (TXN) showed a nominally statistically significant multiplicative interaction with acrylamide intake for advanced prostate cancer risk. After multiple testing corrections, none were statistically significant. In conclusion, no clear evidence was found for interaction between acrylamide intake and selected genetic variants for advanced prostate cancer risk.
Assuntos
Acrilamida/efeitos adversos , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Acrilamida/farmacocinética , Idoso , Catalase/genética , Estudos de Coortes , Ciclo-Oxigenase 2/genética , Proteínas de Ligação a DNA/genética , Alimentos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , NAD(P)H Desidrogenase (Quinona)/genética , Países Baixos , Neoplasias da Próstata/etiologiaRESUMO
Acrylamide (AA) is a highly reactive organic compound capable of polymerization to form polyacrylamide, which is commonly used throughout a variety of industries. Given its toxic effect on humans and animals, the last 20 years have seen an increased interest in research devoted to the AA. One of the main sources of AA is food. AA appears in heated food following the reaction between amino acids and reduced sugars. Large concentrations of AA can be found in popular staples such as coffee, bread or potato products. An average daily consumption of AA is between 0.3-2.0 microg/kg b.w. Inhalation of acrylamide is related with occupational exposure. AA delivered with food is metabolized in the liver by cytochrome P450. AA biotransformation and elimination result in formation of toxic glycidamide (GA). Both, AA and GA can be involved in the coupling reaction with the reduced glutathione (GSH) forming glutathione conjugates which are excreted with urine. Biotransformation of AA leads to the disturbance in the redox balance. Numerous research proved that AA and GA have significant influence on physiological functions including signal propagation in peripheral nerves, enzymatic and hormonal regulation, functions of muscles, reproduction etc. In addition AA and GA show neurotoxic, genotoxic and cancerogenic properties. In 1994, International Agency for Research on Cancer (IARC) classified acrylamide as a potentially carcinogenic substance to human.
Assuntos
Acrilamida/farmacocinética , Acrilamida/intoxicação , Dano ao DNA , Análise de Alimentos/métodos , Contaminação de Alimentos/prevenção & controle , Nefropatias/fisiopatologia , Reprodução/efeitos dos fármacos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Contaminação de Alimentos/análise , Humanos , Nefropatias/induzido quimicamenteRESUMO
Acrylamide is classified as a probable carcinogen to humans and generated from Maillard reaction. Currently, the short-term exposure to acrylamide was evaluated via external diet sources in vitro or two main mercapturic acid metabolites: N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) in vivo. In the present work, we comprehensively profiled four mercapturic acid metabolites and evaluated their internal exposure in rats and Chinese adolescents. The cumulative excretion of mercapturic acid metabolites contributes 38.4-73.0 and 43.8-63.6 % of total in vivo metabolites of acrylamide in male and female rats, respectively, when 1, 10, and 50 mg/kg bw of acrylamide were orally administered. Toxicokinetic study revealed that the conversion of acrylamide into glycidamide and glutathione coupling process is highly related to the gender and oral gavage dose via evaluating kinetic parameters, accumulative excretion percentages, and molar ratios of oxidative to reductive metabolism. In human study, a total of 101 Chinese adolescents (41 men and 60 women) were enrolled and served with a meal of potato chips, corresponding to a single-dose (12.6 µg/kg bw) exposure to acrylamide. Toxicokinetic work showed that AAMA is an early and predominant metabolite appearing as a biomarker in urine. N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), an oxidative product from AAMA, exhibits a higher peak concentration than GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA) during the whole 48-h toxicokinetic period. The internal exposure via four mercapturic acid metabolites is associated with the gender and body mass index characteristics. Thus, current study aims at mercapturic acid metabolites as urinary biomarkers and provides comprehensive insights into the short-term internal exposure to acrylamide.
Assuntos
Acrilamida/toxicidade , Biomarcadores/urina , Acetilcisteína/análogos & derivados , Acetilcisteína/metabolismo , Acetilcisteína/urina , Acrilamida/farmacocinética , Acrilamida/urina , Animais , Exposição Ambiental , Feminino , Humanos , Masculino , Ratos Sprague-Dawley , Testes de Toxicidade/métodos , Adulto JovemRESUMO
A liberal amount of acrylamide (AA) is produced as a result of frying or baking foods in high temperatures, and individuals take certain amounts of AA everyday by consuming these food items. Pregnant women are also exposed to AA originating from food during pregnancy and their fetus are probably affected. The rats were divided into five different groups: control (C), corn oil (CO), vitamin E (Vit E), AA, and Vit E + AA, with eight pregnant rats in each group. On the 20th day of pregnancy, fetuses were removed and brain tissues of fetuses were examined for biochemical and histological changes. AA caused degeneration in neuron structures in fetal brain tissue and caused hemorrhagic damages; dramatically decreased brain-derived neurotrophic factor levels; increased malondialdehyde, total oxidant capacity levels; and decreased reduced glutathione and total antioxidant capacity levels (p < 0.05). On the other hand, it was determined that the Vit E, a neuroprotectant and a powerful antioxidant, suppressed the effects of AA on fetal development and fetal brain tissue damage for the above-mentioned parameters (p < 0.05). It is recommended to consume food containing Vit E as a protection to minimize the toxic effects of food-oriented AA on fetus development due to the widespread nature of fast-food culture in today's life and the impossibility of protection from AA toxicity.
Assuntos
Acrilamida/toxicidade , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Desenvolvimento Fetal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Organogênese/efeitos dos fármacos , Vitamina E/farmacologia , Acrilamida/farmacocinética , Animais , Encéfalo/embriologia , Encéfalo/patologia , Feminino , Exposição Materna/efeitos adversos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Ratos WistarRESUMO
Acrylamide (AA) is a heat-generated food toxicant formed when starchy foods are fried or baked. This study describes a simple and sensitive liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of AA and its active metabolite, glycidamide (GA) in rat plasma, urine, and 14 different tissues. The assay utilized a simple method of protein precipitation and achieved a lower limit of quantification of 5, 10 and 25 ng/mL of AA and 10, 20 and 100 ng/mL of GA for plasma, tissues and urine, respectively. The assay was fully validated to demonstrate the linearity, sensitivity, accuracy, precision, process recovery, and stability using matrix matched quality control samples. The mean intra- and inter-day assay accuracy was 91.6-110% for AA and 92.0-109% for GA, and the mean intra- and inter-day assay precisions were ≤ 10.9% for AA and ≤ 8.60% for GA. The developed method was successfully applied to a pharmacokinetic study of AA and GA following intravenous and oral administration of AA in rats. Tissue distribution characteristics of AA and GA were also determined under steady-state conditions.
Assuntos
Acrilamida/análise , Acrilamida/farmacocinética , Cromatografia Líquida/métodos , Compostos de Epóxi/análise , Compostos de Epóxi/farmacocinética , Espectrometria de Massas em Tandem/métodos , Acrilamida/administração & dosagem , Administração Oral , Animais , Compostos de Epóxi/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Soro/química , Distribuição Tecidual , UrináliseRESUMO
Acrylamide (AA) was firstly detected in food in 2002, and since then, studies on AA analysis, occurrence, formation, toxicity, risk assessment and mitigation have been extensively carried out, which have greatly advanced understanding of this particular biohazard at both academic and industrial levels. There is considerable variation in the levels of AA in different foods and different brands of the same food; therefore, so far, a general upper limit for AA in food is not available. In addition, the link of dietary AA to human cancer is still under debate, although AA has been known as a potential cause of various toxic effects including carcinogenic effects in experimental animals. Furthermore, the oxidized metabolite of AA, glycidamide (GA), is more toxic than AA. Both AA and GA can form adducts with protein, DNA, and hemoglobin, and some of those adducts can serve as biomarkers for AA exposure; their potential roles in the linking of AA to human cancer, reproductive defects or other diseases, however, are unclear. This review addresses the state-of-the-art understanding of AA, focusing on risk assessment, mechanism of formation and strategies of mitigation in foods. The potential application of omics to AA risk assessment is also discussed.
Assuntos
Acrilamida/toxicidade , Biomarcadores/análise , Carcinógenos/toxicidade , Medição de Risco/métodos , Acrilamida/farmacocinética , Animais , Asparagina/química , Asparagina/metabolismo , Carcinógenos/farmacocinética , Água Potável/química , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Compostos de Epóxi/toxicidade , Inocuidade dos Alimentos , Humanos , Testes de Mutagenicidade , Reprodução/efeitos dos fármacosRESUMO
α,ß-Unsaturated aliphatic carbonyl compounds are naturally widespread in food, but are also formed during the thermal treatment of food. This applies, for example, to the genotoxic carcinogen acrylamide (AA), but also to acrolein (AC), the simplest α,ß-unsaturated aldehyde. First observations indicate that human exposure to AC may be higher than the exposure to AA. The DFG Senate Commission on Food Safety therefore compared data on AC and AA available in the scientific literature, evaluating current knowledge on formation, occurrence, exposure, metabolism, biological effects, toxicity, and carcinogenicity and defined knowledge gaps as well as research needs in an opinion on November 19, 2012, in German. The English version was agreed on April 17, 2013.
Assuntos
Acroleína/química , Acroleína/toxicidade , Acrilamida/química , Acrilamida/toxicidade , Contaminação de Alimentos/análise , Inocuidade dos Alimentos , Acroleína/farmacocinética , Acrilamida/farmacocinética , Animais , Exposição Ambiental/análise , Alemanha , Órgãos Governamentais , Calefação , Humanos , Testes de ToxicidadeRESUMO
Estimates of internal dosimetry for acrylamide (AA, 2-propenamide; CASRN: 79-06-1) and its active metabolite glycidamide (GA) were compared using either biomarkers of internal exposure (hemoglobin adduct levels in rats and humans) or a PBTK model (Sweeney et al., 2010). The resulting impact on the human equivalent dose (HED, oral exposures), the human equivalent concentration (HEC, inhalation), and final reference values was also evaluated. Both approaches yielded similar AA HEDs and HECs for the most sensitive noncancer effect of neurotoxicity, identical oral reference doses (RfD) of 2×10(-3) mg AA/kg bw/d, and nearly identical inhalation reference concentrations (RfC=0.006 mg/m(3) and 0.007 mg/m(3), biomarker and PBTK results, respectively). HED and HEC values for carcinogenic potential were very similar, resulting in identical inhalation unit risks of 0.1/(mg AA/m(3)), and nearly identical oral cancer slope factors (0.4 and 0.5/mg AA/kg bw/d), biomarker and PBTK results, respectively. The concordance in estimated HEDs, HECs, and reference values from these two diverse methods increases confidence in those values. Advantages and specific application of each approach are discussed. (Note: Reference values derived with the PBPK model were part of this research, and do not replace values currently posted on IRIS: http://www.epa.gov/iris/toxreviews/0286tr.pdf.).
Assuntos
Acrilamida/administração & dosagem , Biomarcadores/metabolismo , Modelos Biológicos , Acrilamida/farmacocinética , Animais , Área Sob a Curva , Feminino , Humanos , Masculino , RatosRESUMO
Acrylamide (AA), classified as class 2A carcinogen (probably carcinogenic to humans) by the International Agency for Research on Cancer (IARC), is formed during heating of food from reducing carbohydrates and asparagine by Maillard reaction chemistry. After dietary uptake, AA is in part metabolically converted into the proximate genotoxic phase I metabolite glycidamide (GA). GA reacts with nucleophilic base positions in DNA, primarily forming N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) adducts. In a competing phase II biotransformation pathway AA, as well as its phase I metabolite GA, is coupled to glutathione (GSH). The GSH coupling products are further biotransformed and excreted via urine as mercapturic acids (MA), N-acetyl-S-(2-carbamoylethyl)cysteine (AAMA), and N-acetyl-S-(2-hydroxy-2-carbamoylethyl)cysteine (GAMA). In the present study, hepatic biotransformation pathways and DNA adduct formation were studied in primary rat hepatocytes, incubated with AA (0.2-2,000 µM) for up to 24 h. Contents of AA-GSH, GA, AAMA, and GAMA were measured in the cell culture medium after solid phase extraction (SPE). N7-GA-Gua adducts in DNA of hepatocytes were determined by HPLC-ESI-MS/MS after lysis of the cells and neutral thermal hydrolysis. Formation of AA-GSH was linear with AA concentration and incubation time and became detectable already at 0.2 µM (4 h). In contrast to AA, GA was not detected before 16 h incubation at 10-fold higher AA concentration (2 µM). In summary, the rate of AA-GSH formation was found to be about 1.5-3 times higher than that of GA formation. N7-GA-Gua adducts were found only at the highest AA concentration tested (2,000 µM).
Assuntos
Acrilamida/farmacocinética , Compostos de Epóxi/metabolismo , Glutationa/metabolismo , Hepatócitos/efeitos dos fármacos , Acetilcisteína/análogos & derivados , Acetilcisteína/análise , Acetilcisteína/metabolismo , Acrilamida/metabolismo , Acrilamida/toxicidade , Animais , Biomarcadores/análise , Carcinógenos/metabolismo , Carcinógenos/farmacocinética , Células Cultivadas , Cromatografia Líquida de Alta Pressão/métodos , Meios de Cultura/química , Cisteína/análogos & derivados , Cisteína/metabolismo , Adutos de DNA , Compostos de Epóxi/toxicidade , Hepatócitos/metabolismo , Inativação Metabólica , Masculino , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
The present study aimed to study the reaction conditions of grafting of acrylamide on xanthan gum. It was analyzed the influence of reaction conditions, mainly type of initiator activation, initiator concentration and initiator/acrylamide ratio, on graft parameters and copolymer properties. Potassium persulfate was employed as an initiator and heating or N,N,N',N'-tetramethylethylenediamine was used to activate the initiator. Reaction time and initiator concentration were varied and final values for grafting percentage and grafting efficiency were the same for both methods, whereas speed in reaching these values differs from one technique to another. We found that reaction time was inversely proportional to intrinsic viscosity, likely due to main chain degradation promoted by potassium persulfate (KPS); furthermore, the increasing in the KPS concentration lowers grafting percentage, acrylamide conversion and chain degradation, possibly as a result of O(2) formation at high KPS concentrations.
Assuntos
Acrilamida/farmacologia , Polímeros/síntese química , Polissacarídeos Bacterianos/química , Acrilamida/química , Acrilamida/farmacocinética , Adsorção , Varredura Diferencial de Calorimetria , Catálise , Etilenodiaminas/farmacologia , Concentração Osmolar , Polímeros/química , Polímeros/metabolismo , Polissacarídeos Bacterianos/metabolismo , Compostos de Potássio/farmacologia , Reologia , Espectrofotometria Infravermelho , Sulfatos/farmacologia , ViscosidadeRESUMO
Prohibited substances in cosmetics refer to substances which must not be among the raw material ingredients of cosmetic products. These substances are absorbed mostly through skin, as well as via lung and gastrointestinal tract. Polyacrylamide is ubiquitously used in industry and its decomposition residue acrylamide (ACR) easily finds its way into cosmetic products. ACR can either be oxidized to epoxide glycidamide or conjugated with glutathione, hemoglobin or DNA; ultimately it is excreted in urine. ACR causes neurotoxicity, reproductive toxicity and tumors in rodents. Occupational exposure to ACR causes neurotoxicity in humans; however, epidemiological evidence have not unambiguously answered the question of whether ACR exposure can increase cancer risk for humans.
Assuntos
Acrilamida/toxicidade , Cosméticos/química , Acrilamida/metabolismo , Acrilamida/farmacocinética , Resinas Acrílicas/química , China , HumanosRESUMO
Acrylamide (AA) is formed during the heating of food and is classified as a genotoxic carcinogen. The margin of exposure (MOE), representing the distance between the bench mark dose associated with 10% tumor incidence in rats and the estimated average human exposure, is considered to be of concern. After ingestion, AA is converted by P450 into the genotoxic epoxide glycidamide (GA). GA forms DNA adducts, primarily at N7 of guanine (N7-GA-Gua). We performed a dose-response study with AA in female Sprague-Dawley (SD) rats. AA was given orally in a single dosage of 0.1-10 000 µg/kg bw. The formation of urinary mercapturic acids and of N7-GA-Gua DNA adducts in liver, kidney, and lung was measured 16 h after application. A mean of 37.0 ± 11.5% of a given AA dose was found as mercapturic acids (MAs) in urine. MA excretion in urine of untreated controls indicated some background exposure from endogenous AA. N7-GA-Gua adduct formation was not detectable in any organ tested at 0.1 µg AA/kg bw. At a dose of 1 µg/kg bw, adducts were found in kidney (around 1 adduct/10(8) nucleotides) and lung (below 1 adduct/10(8) nucleotides) but not in liver. At 10, respectively, 100 µg/kg bw, adducts were found in all three organs, at levels close to those found at 1 µg AA/kg, covering a range of about 1-2 adducts/10(8) nucleotides. As compared to DNA adduct levels from electrophilic genotoxic agents of various origin found in human tissues, N7-GA-Gua adduct levels within the dose range of 0.1-100 µg AA/kg bw were at the low end of this human background. We propose to take the background level of DNA lesions in humans more into consideration when doing risk assessment of food-borne genotoxic carcinogens.
Assuntos
Acrilamida/toxicidade , Carcinógenos/toxicidade , Adutos de DNA/metabolismo , Compostos de Epóxi/metabolismo , Guanina/metabolismo , Acrilamida/farmacocinética , Acrilamida/urina , Animais , Carcinógenos/farmacocinética , Dieta , Relação Dose-Resposta a Droga , Compostos de Epóxi/urina , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Acrylamide (AA), a neurotoxic, testicular toxic, genotoxic and carcinogenic chemical, has been reported to be formed in processed food, and sensitivity to AA intoxication in childhood is a concern. In the present study, to clarify the general toxicological profile of AA in juvenile rats, subchronic toxicity was evaluated in F344 rats administered AA in the drinking water at 0 (control), 10, 20 and 40 ppm, presented to the dams (three per group) immediately after the birth of their litters, through lactation (3 weeks), and directly to the offspring in their drinking water after weaning for a further 9 weeks (12 weeks total). Treatment with AA caused a decrease in body weights in 20 and 40 ppm F(1) females, compared with the controls. Average AA intake throughout the treatment period for the 10, 20 and 40 ppm groups after weaning was equivalent to 1.0, 2.1 and 4.4 mg kg(-1) body weight per day, respectively, in males and 1.2, 2.5 and 4.9 mg kg(-1) body weight per day, respectively, in females. No toxicologically significant organ weight changes were observed. AA-induced histopathological changes were limited to focal degeneration and necrosis of the seminiferous epithelium in the testes and desquamated epithelium in the ducts of epididymides, noted only in 40 ppm males. Taken together with previous reports, juvenile rats are not necessarily more susceptible to AA-induced toxicity as compared with young adults.