ABSTRACT
Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.
Subject(s)
Tobacco Smoke Pollution , Pregnancy , Humans , Female , Pregnant Women , 8-Hydroxy-2'-Deoxyguanosine , Brazil , Placenta/chemistry , Aniline Compounds/analysis , Amines/toxicity , Amines/urine , DNA Damage , Smoke/analysis , Azo Compounds , Life Style , Socioeconomic Factors , Genetic VariationABSTRACT
Azo dyes used in textile products contain aromatic amines (AAs), which may be released into the environment after skin bacteria cleavage the azo bond. In Europe, 22 carcinogenic AAs are regulated. Unfortunately, no information is available in many non-European countries, including Brazil. This study aimed to determine the concentrations of 20 regulated AAs in clothes marketed in Brazil and Spain. Generally, higher levels of regulated AAs were found in samples sold in Brazil than in Spain, which is linked to the lack of regulation. Sixteen AAs showed concentrations above 5 mg/kg in samples commercialized in Brazil, while 11 exceeded that threshold in Spain. Regulated AAs with levels above 5 mg/kg were more found in synthetic clothes of pink color. Concentrations in clothing were also used to evaluate the dermal exposure to AAs in 3 vulnerable population groups. The highest exposure corresponded to 2,4-diaminoanisole for toddlers in Brazil and 4,4-oxydianiline for newborns in Spain. Non-cancer risks associated with exposure to 4,4-benzidine by Brazilian toddlers was 14.5 (above the threshold). On the other hand, 3,3-dichlorobenzidine was associated with potential cancer risks for newborns and toddlers in Brazil. Given this topic's importance, we recommend conducting continuous studies to determine the co-occurrence of carcinogenic substances.
Subject(s)
Amines , Textiles , Infant, Newborn , Humans , Brazil , Spain , Amines/toxicity , Azo Compounds , Clothing , Coloring Agents/chemistryABSTRACT
Glyphosate (GLY) is the active ingredient of several herbicide formulations widely used to control weeds in agricultural and non-agricultural areas. Due to the intensive use of GLY-based herbicides and their direct application on soils, some of their components, including the active ingredient, may reach the aquatic environment through direct run-off and leaching. The present study assessed the acute toxicity and genotoxicity of the GLY-based formulation Atanor 48 (ATN) and its major constituents GLY, surfactant polyethoxylated tallow amine (POEA), as well as the main metabolite of GLY aminomethylphosphonic acid (AMPA) on non-target aquatic organisms. The toxic effects of these chemicals were evaluated in the fish embryo acute toxicity test with zebrafish (Danio rerio), while genotoxic effects were investigated in the comet assays with cells from zebrafish larvae and rainbow trout gonad-2 (RTG-2). GLY and AMPA caused no acute toxic effect, while ATN and POEA induced significant lethal effects in zebrafish (LC50-96 h 76.50 mg/L and 5.49 mg/L, respectively). All compounds were genotoxic in comet experiments with zebrafish larvae (LOEC 1.7 mg/L for GLY, ATN, AMPA and 0.4 mg/L for POEA). Unlike in vivo, only POEA induced DNA damage in RTG-2 cells (LOEC 1.6 mg/L), suggesting that it is a direct acting genotoxic agent. In summary, these data indicate that the lethal effects on zebrafish early-life stages can be ranked in the following order from most to least toxic: surfactant POEA > formulation ATN > active ingredient GLY ≈ metabolite AMPA. Genotoxic effects were observed in both RTG-2 cells (only POEA) and zebrafish (all test compounds) with the lowest tested concentrations. Therefore, it is important to evaluate different toxicological endpoints as well as use different non-target organisms to predict the hazards of GLY-based formulations and their components and breakdown product to aquatic biota.
Subject(s)
Aquatic Organisms/drug effects , Glycine/analogs & derivatives , Herbicides/toxicity , Water Pollutants, Chemical/toxicity , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/toxicity , Amines/toxicity , Animals , Comet Assay/methods , DNA Damage/drug effects , Female , Glycine/toxicity , Larva/drug effects , Male , Mutagens/toxicity , Oncorhynchus mykiss , Organophosphorus Compounds/toxicity , Zebrafish , GlyphosateABSTRACT
The surfactant polyoxyethylene amine (POEA) is added to several formulations of glyphosate herbicides that are widely used in agriculture and can contaminate aquatic ecosystems. In the present study, an integrated approach examining genotoxic, biochemical and physiological parameters was employed to evaluate acute effects of POEA on the Neotropical fish Prochilodus lineatus. Juvenile fish were exposed to 0.15 mg·L(-1) (POEA 1), 0.75 mg·L(-1) (POEA 2) and 1.5 mg·L(-1) (POEA 3) of POEA or only water (CTR), and after 24h exposure samples of blood and liver were taken. Compared with CTR, liver of fish exposed to POEA 2 and POEA 3 showed increased activity of 7 ethoxyresorufin-O-deethylase and increased content of glutathione, whereas the activity of glutathione-S-transferase was diminished. On the other hand, fish of the group POEA 1 showed an increase in the activity of superoxide dismutase and in the occurrence of lipid peroxidation. Fish exposed to POEA 3 presented increased hepatic activity of glutathione peroxidase and reduced plasma cortisol. The exposure to POEA at all concentrations tested caused an increase in plasma lactate and a decrease in the hepatic activity of catalase, in the number of red blood cells and in hemoglobin content. The comet assay used for analyzing DNA damage in blood cells indicated the genotoxicity of the surfactant at all concentrations tested. Taken together these results show that POEA can cause effects at various levels, such as hemolysis, DNA damage and lipid peroxidation, which are directly related to an imbalance in the redox state of the fish.
Subject(s)
Amines/toxicity , Fishes/genetics , Fishes/metabolism , Polyethylene Glycols/toxicity , Surface-Active Agents/toxicity , Water Pollutants, Chemical/toxicity , Animals , Cytochrome P-450 CYP1A1/metabolism , DNA Damage/drug effects , DNA Damage/genetics , Fresh Water , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Hydrocortisone/metabolism , Lipid Peroxidation/drug effects , Lipid Peroxidation/genetics , Liver/drug effects , Liver/metabolism , Mutagenicity Tests/methods , Superoxide Dismutase/metabolismABSTRACT
This work describes the mutagenic response of Sudan III, an adulterant food dye, using Salmonella typhimurium assay and the generation of hazardous aromatic amines after different oxidation methods of this azo dye. For that, we used metabolic activation by S9, catalytic oxidation by ironporphyrin and electrochemistry oxidation in order to simulate endogenous oxidation conditions. The oxidation reactions promoted discoloration from 65% to 95% of Sudan III at 1 × 10(-4)molL(-1) and generation of 7.6 × 10(-7)molL(-1) to 0.31 × 10(-4)molL(-1) of aniline, o-anisidine, 2-methoxi-5-methylaniline, 4-aminobiphenyl, 4,4'-oxydianiline; 4,4'-diaminodiphenylmethane and 2,6-dimethylaniline. The results were confirmed by LC-MS-MS experiments. We also correlate the mutagenic effects of Sudan III using S. typhimurium with the strain TA1535 in the presence of exogenous metabolic activation (S9) with the metabolization products of this compound. Our findings clearly indicate that aromatic amines are formed due to oxidative reactions that can be promoted by hepatic cells, after the ingestion of Sudan III. Considering that, the use of azo compounds as food dyestuffs should be carefully controlled.
Subject(s)
Amines/metabolism , Azo Compounds/metabolism , Azo Compounds/toxicity , Coloring Agents/metabolism , Cytochrome P-450 Enzyme System/metabolism , Amines/analysis , Amines/toxicity , Animals , Azo Compounds/chemistry , Catalysis , Coloring Agents/chemistry , Coloring Agents/toxicity , Electrochemical Techniques , Food Coloring Agents/toxicity , Isoenzymes/metabolism , Liver/enzymology , Metalloporphyrins/chemistry , Metalloporphyrins/metabolism , Mutagenicity Tests/methods , Mutation , Oxidation-Reduction , Rats , Rats, Sprague-Dawley , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Tandem Mass SpectrometryABSTRACT
Arylamines are well-known as widespread industrial and environmental mutagens and carcinogens. Their bioactivity stems from enzymatic metabolic activation to reactive and highly electrophilic intermediates. In this work, computational investigations related to the biological activity of these compounds have been reviewed, especially focusing on studies reporting results from quantum-mechanical calculations. Correlations between relative mutagenicities and structural and electronic features of the parent amines and of their derived nitrenium ion intermediates were examined, with the aim of achieving a clearer comprehension of the main factors determining the genotoxic potential of this type of compounds.
Subject(s)
Amines/chemistry , Amines/toxicity , Carcinogens/chemistry , Carcinogens/toxicity , Mutagens/chemistry , Mutagens/toxicity , Amines/metabolism , Aniline Compounds/chemistry , Aniline Compounds/metabolism , Aniline Compounds/toxicity , DNA Damage , Mutagens/metabolism , Quantum Theory , Structure-Activity RelationshipABSTRACT
Aromatic amines are a group of chemicals whose ubiquitous presence in the environment is a result of the multitude of sources from which they originate. These compounds are widely used as raw materials or at intermediate stages in the manufacturing of industrial chemicals such as pesticides, medicines, dyestuffs, polymers, surfactants, cosmetics and corrosion inhibitors, especially in dyestuff factories. As with most chemical carcinogens, aromatic amines need to be metabolized into reactive electrophiles in order to exert their carcinogenic effects. This activation typically involves N-oxidation of arylamines to yield N-hydroxyarylamines. Since these amines are potential carcinogenic agents and are discharged into the atmosphere, water and soil, they constitute an important class of environmental pollutants of enormous concern due to the potential for human exposure.
Subject(s)
Amines/toxicity , Environmental Pollutants/toxicity , Amines/metabolism , Amines/pharmacokinetics , Biotransformation , Risk AssessmentABSTRACT
Fifteen quantitative structure-activity relationship (QSAR) models developed by various authors for the prediction of mutagenicity of aromatic and heteroaromatic amines were analyzed and thirteen of them, based on 95 amines, were compared using their respective statistics and order theory (Hasse Diagram Technique, HDT) to obtain an ordering of QSAR models. The technique of Formal Concept Analysis (FCA) was applied to the set of 95 amines to extract concepts and, in general, knowledge about the relationship between structural attributes and mutagenicity. HDT may be useful as a general tool for the comparison of different classes of QSAR models. FCA turns out to be a novel mathematical technique for seeking for relationships between molecular structure and activity.
Subject(s)
Amines/chemistry , Amines/pharmacology , Hydrocarbons, Aromatic/chemistry , Hydrocarbons, Aromatic/pharmacology , Mutagens/chemistry , Mutagens/pharmacology , Quantitative Structure-Activity Relationship , Amines/toxicity , Animals , Humans , Hydrocarbons, Aromatic/toxicity , Models, Genetic , Models, Statistical , Mutagenicity Tests , Mutagens/toxicityABSTRACT
Carbamazepine (CBZ), phenytoin (PHT), and gabapentine (GBP) are classical antiepileptic drugs (AEDs) that act through a variety of mechanisms. We have tested the in vitro effects of CBZ, PHT, and GBP at different concentrations on ectonucleotidase and acetylcholinesterase activities in zebrafish brain. CBZ inhibited ATP hydrolysis at 1000 microM (32%) whereas acetylcholine hydrolysis decreased at 500 microM (25.2%) and 1000 microM (38.7%). PHT increased AMP hydrolysis both at 500 microM (65%) and 1000 microM (64.8%). GBP did not promote any significant changes on ectonucleotidase and acetylcholinesterase activities. These results have shown that CBZ can reduce NTPDase (nucleoside triphosphate diphosphohydrolase) and PHT enhance ecto 5'-nucleotidase activities. Therefore, it is possible to suggest that the AEDs induced-effects on ectonucleotidases are related to enzyme anchorage form. Our findings have also shown that high CBZ concentrations inhibit acetylcholinesterase activity, which can induce an increase of acetylcholine levels. Taken together, these results showed a complex interaction among AEDs, purinergic, and cholinergic systems, providing a better understanding of the AEDs pharmacodynamics.
Subject(s)
5'-Nucleotidase/metabolism , Acetylcholinesterase/metabolism , Anticonvulsants/toxicity , Brain/enzymology , Amines/toxicity , Animals , Brain/drug effects , Carbamazepine/toxicity , Cyclohexanecarboxylic Acids/toxicity , Dose-Response Relationship, Drug , Gabapentin , Phenytoin/toxicity , Zebrafish/metabolism , gamma-Aminobutyric Acid/toxicitySubject(s)
Humans , Thermic Treatment , Amines/toxicity , Polycyclic Aromatic Hydrocarbons , Hydrocarbons/toxicityABSTRACT
Amostras de seis lotes de sete marcas de salames tipo italiano foram analisadas quanto a aminas bioativas e características físico-químicas de qualidade. Oito das 10 aminas pesquisadas foram detectadas em todas as amostras com teores totais de 28,33 a 53,27mg/100g. A tiramina foi a amina predominante seguida da putrescina e da cadaverina. Todas as marcas apresentaram teores de tiramina capazes de causar efeito tóxico em indivíduos sensíveis dependendo da quantidade ingerida. Duas marcas apresentaram também teores potencialmente tóxicos de histamina e de feniletilamina. Nenhuma das marcas atendeu à legislação em pelo menos um parâmetro físico-químico. Os teores de umidade e de açucares totais foram as características com maior percentual de não-atendimento. Os teores de cinzas variaram de 5,54 a 7,12g/100g, sendo os cloretos 66 a 79% desses teores. As amostras apresentaram valores de pH de 4,86 a 5,78, acidez de 16,61 a 55,03ml NaOH N/100g e índice de peróxidos de não detectado a 334,82mEq/kg.(AU)
Six batches of seven brands of Italian sausages purchased in Belo Horizonte, MG were analyzed for bioactive amines and physico-chemical characteristics. Eight out of 10 amines investigated were detected in every sample with total levels varying from 28.33 to 53.27mg/100g. Tyramine was the predominant amine followed by putrescine and cadaverine. Every brand contained toxic tyramine levels for sensitive individuals depending on the amount of sausage consumption. Two brands also contained toxic levels of histamine and phenylethylamine. No brand was in conformity to legislation levels for at least one physico-chemical parameter. The highest discrepancies to legislation levels were observed for moisture and total sugar contents. The levels of ash varied from 5.54 to 7.12g/100g, with chlorides representing 66 to 79% of the levels.The pH varied from 4.86 to 5.78, acidity from 16.61 to 55.03ml NaOH N/100g and peroxide values from 0.0 (no detected) to 334.82mEq/kg.(AU)
Subject(s)
Quality Control , Chemical Phenomena/methods , Food Analysis/methods , Food/toxicity , Amines/toxicityABSTRACT
Amostras de seis lotes de sete marcas de salames tipo italiano foram analisadas quanto a aminas bioativas e características físico-químicas de qualidade. Oito das 10 aminas pesquisadas foram detectadas em todas as amostras com teores totais de 28,33 a 53,27mg/100g. A tiramina foi a amina predominante seguida da putrescina e da cadaverina. Todas as marcas apresentaram teores de tiramina capazes de causar efeito tóxico em indivíduos sensíveis dependendo da quantidade ingerida. Duas marcas apresentaram também teores potencialmente tóxicos de histamina e de feniletilamina. Nenhuma das marcas atendeu à legislação em pelo menos um parâmetro físico-químico. Os teores de umidade e de açucares totais foram as características com maior percentual de não-atendimento. Os teores de cinzas variaram de 5,54 a 7,12g/100g, sendo os cloretos 66 a 79 por cento desses teores. As amostras apresentaram valores de pH de 4,86 a 5,78, acidez de 16,61 a 55,03ml NaOH N/100g e índice de peróxidos de não detectado a 334,82mEq/kg.
Six batches of seven brands of Italian sausages purchased in Belo Horizonte, MG were analyzed for bioactive amines and physico-chemical characteristics. Eight out of 10 amines investigated were detected in every sample with total levels varying from 28.33 to 53.27mg/100g. Tyramine was the predominant amine followed by putrescine and cadaverine. Every brand contained toxic tyramine levels for sensitive individuals depending on the amount of sausage consumption. Two brands also contained toxic levels of histamine and phenylethylamine. No brand was in conformity to legislation levels for at least one physico-chemical parameter. The highest discrepancies to legislation levels were observed for moisture and total sugar contents. The levels of ash varied from 5.54 to 7.12g/100g, with chlorides representing 66 to 79 percent of the levels.The pH varied from 4.86 to 5.78, acidity from 16.61 to 55.03ml NaOH N/100g and peroxide values from 0.0 (no detected) to 334.82mEq/kg.
Subject(s)
Food/toxicity , Amines/toxicity , Chemical Phenomena/methods , Food Analysis/methods , Quality ControlABSTRACT
A carne de frango é um produto susceptível à deterioraçäo, devido à açäo de algumas enzimas e, também, da microbiota eventualmente presente ou adicionada. Tal fato causa o aparecimento de metabólitos que alteram as características do produto, tornando-o indesejável ou inaceitável. Dentre estas substâncias, as aminas biotivas, bases orgânicas de baixo peso molecular, têm sido propostas como um indicador de qualidade para a carne e produtos cárneos.
Subject(s)
Amines/toxicity , Chickens , Poultry Products , Food PreservationABSTRACT
CoASAc-dependent N-hydroxyarylamine O-acetyltransferase (OAT) is an enzyme involved in the intracellular metabolic activation of N-hydroxyarylamines derived from mutagenic nitroarenes and aromatic amines. The oat gene encoding the enzyme of S. typhimurium TA98 and TA100 was specifically disrupted and the sensitivities of the resulting strains, i.e., YG7130 and YG7126, to mutagens were compared with those of the conventional oat-deficient strains, i.e., TA98/1,8DNP6 and TA100/1,8DNP, respectively. The new oat-deficient strains and the conventional strains exhibited similar sensitivity against most of the chemicals tested: both strains YG7130 and strain TA98/1,8-DNP6 were resistant to mutagenicity by 1,8-dinitropyrene (1, 8-DNP), 1-nitropyrene, 2-amino-6-methyldipyrido[1,2-alpha:3', 2'-d]imidazole (Glu-P-1) and 2-amino-3-methyl-3H-imidazo[4, 5-f]quinoline (IQ); neither strain YG7130 nor strain TA98/1,8-DNP6 was resistant to the mutagenicity of 3-amino-1-methyl-5H-pyrido[4, 3-b]indole (Trp-P-2); strain YG7126 and strain TA100/1,8-DNP were refractory to the mutagenicity of 1,8-DNP. However, the order of the sensitivity against 2-nitrofluorene (2-NF) was TA98>YG7130>TA98/1, 8-DNP6 and TA100>YG7126>TA100/1,8-DNP. Since the strains YG7130 and YG7126 have chloramphenicol resistance (Cmr) gene in place of the chromosomal oat gene for gene disruption, the possible involvement of chloramphenicol acetyltransferase (CAT) encoded by the Cmr gene in the activation of 2-NF was examined. Strikingly, introduction of plasmid pACYC184 carrying the Cmr gene alone substantially enhanced the sensitivity of the conventional oat-deficient strains to 2-NF. These results suggest that the new strains as well as the conventional strains are useful to assess the roles of OAT in the metabolic activation of nitroaromatics and aromatic amines in S. typhimurium, and also that CAT has the ability to activate N-hydroxy aromatic amines to mutagens.
Subject(s)
Acetyltransferases , Acyltransferases/genetics , Amines/toxicity , Mutagens/toxicity , Nitro Compounds/toxicity , Salmonella typhimurium/genetics , Animals , Biotransformation , Escherichia coli/genetics , Mutagenicity Tests , Plasmids , Rats , Salmonella typhimurium/enzymologySubject(s)
Amines/metabolism , Amines/toxicity , Carcinogens/metabolism , Carcinogens/toxicity , DNA Adducts/biosynthesis , DNA Adducts/chemistry , Polycyclic Compounds/metabolism , Polycyclic Compounds/toxicity , Animals , DNA/drug effects , DNA/metabolism , Humans , Neoplasms/chemically induced , Neoplasms, Experimental/chemically inducedABSTRACT
Se ha efectuado un estudio cualitativo, usando una serie de reacciones para el reconocimiento y diferenciacion de los distintos tipos de aminas, así como el estudio comparativo entre los métodos volumétricos para la cuantificación de aminas, aprovechando su propiedad básica y el diferente comportamiento del grupo funcional amino frente a algunos reactivos. Se usaron métodos acidimétricos, basados en la titulación de las muestras como base, propiedad que en ciertas condiciones en cuantitativa. Los resultados obtenidos muestran que los métodos basados en reacciones de acilación, son los más convenientes para ser aplicadas a todas las aminas primarias y secundarias ensayadas.
Subject(s)
Amines/analysis , Amines/chemical synthesis , Amines/chemistry , Amines/pharmacokinetics , Amines/pharmacology , Amines/toxicitySubject(s)
Amines/toxicity , Environmental Monitoring , Micronuclei, Chromosome-Defective/drug effects , Adult , Carcinogens , Environmental Exposure , Humans , Male , Mutagens , Occupational Diseases/chemically induced , Occupational Diseases/genetics , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/geneticsABSTRACT
As a consequence of human exposure to carcinogenic aromatic amines, biochemical approaches to risk assessment have emphasized metabolic determinants of individual susceptibility and quantification of arylamine-macromolecular adducts. A known genetic polymorphism in humans, hepatic arylamine acetyltransferase activity, has been associated with differences in individual susceptibility to urinary bladder (slow acetylators) and colorectal (rapid acetylators) cancers. Similarly, the high specificity of an inducible human cytochrome P450 towards the N-oxidation of 4-aminobiphenyl and other aromatic amines is consistent with metabolic differences that can be used to predict relative human risk. Exposure to aromatic amines has also been documented, primarily by quantification of adducts with protein or DNA. Using 32P-postlabelling methods and a competitive avidin/biotin-amplified enzyme-linked immunoassay, we have estimated 4-aminobiphenyl-DNA adduct levels in surgical samples of human peripheral lung and urinary bladder epithelium and report values ranging from 2 to 97 adducts per 10(8) nucleotides.