RESUMEN

In Brazil, the favorable weather conditions and abundant land contribute to the thriving agricultural production. Brazilian crops extensively employ pesticides due to their high efficacy, cost-effectiveness, and permissive regulatory framework. However, pesticide use also endangers water resources, animal organisms, and human health. Due to the lack of data on pesticide use in the Amazonas forest-based Brazil, the present study aimed to assess the levels of twenty-one current-use pesticides (CUPs) from five different classes in river waters collected from urban and riverside areas in this region. Moreover, the non-carcinogenic risks associated with water consumption were also characterized. Thirteen CUPs were detected in concentrations above the limit of detection (LOD) in at least one of the water samples, and most pesticides were detected in riverside areas. In contrast, only 18% of the analyzed samples were considered "clean," with only one compound detected. Fenitrothion showed the highest concentration, with a mean value of 4.86 ng/mL (0.30-14.3 ng/mL). Up to 33% of the samples showed levels of fipronil above the LOD, an issue of environmental and human health concern, mainly because of the adverse effects observed in honeybees. Despite this, the human health risk assessment showed a target hazard quotient below one (HQ < 1) in adults for all substances, suggesting that pesticide exposure through water consumption should not mean risk for the riverside populations. Taking into account the large extension of Brazil, as well as its different agricultural practices throughout the country, it would be of great importance to conduct extensive research in other areas. It would help to gain knowledge in this field and to promote eco-friendly alternatives to mitigate pesticide use and, consequently, to reduce their potential adverse effects on human health and the ecosystems.

Asunto(s)

Monitoreo del Ambiente , Plaguicidas , Ríos , Contaminantes Químicos del Agua , Brasil , Medición de Riesgo , Plaguicidas/análisis , Contaminantes Químicos del Agua/análisis , Ríos/química , Humanos , Monitoreo del Ambiente/métodos , Ciudades

RESUMEN

Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI - 3.57 and 0.36 µg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84 % detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53 %. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.

Asunto(s)

Contaminantes Ambientales , Fórmulas Infantiles , Lactante , Femenino , Humanos , Fórmulas Infantiles/química , Contaminantes Ambientales/análisis , Cadmio , Brasil , Plomo/análisis , Leche Humana/química

RESUMEN

The Fundão Dam failure has been the most significant environmental disaster in Brazil. The catastrophe released large amounts of mining waste into the environment, including toxic metals/metalloids, which are recognized to induce carcinogenic effects. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG), a widely accepted oxidative stress and carcinogenesis biomarker, provide a potential tool for assessing the disaster's health implications. This study investigated the association between urinary levels of some toxic metals/metalloids and 8OHdG in Brazilian individuals living in areas affected by the Fundão dam failure. Urinary concentrations of arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), and lead (Pb) were determined using inductively coupled plasma mass spectrometry, while 8OHdG was analyzed by liquid chromatography-tandem mass spectrometry. Non-parametric bootstrap regression was used to estimate the associations between the urinary levels of toxic elements and 8OHdG. The results showed that except for Hg, urinary concentrations of all metals/metalloids analyzed here exceeded the reference ranges for the Brazilian population. The regression analysis revealed that As (0.337; CI 95%: 0.203; 0.474), Cd (0.268; CI 95%: 0.036; 0.520), and Ni (0.296; CI 950.108; 0.469) were positively associated with creatinine-adjusted urinary 8OHdG levels. Associations were not found for Hg (0.0122; CI 95%: -0.155; 0.183) and Pb (0.201; CI 95%: -0.040; 0.498). The current findings suggest that high exposure to toxic metals/metalloids might increase 8OHdG levels with potential adverse health effects. This study is the first one in which the relationship between toxic metals/metalloids and oxidative stress biomarkers is investigated in populations affected by environmental disasters. Further prospective studies are necessary to monitor exposure levels and explore additional health impacts.

Asunto(s)

Arsénico , Mercurio , Metaloides , Metales Pesados , Humanos , Metaloides/toxicidad , Cadmio , Brasil , 8-Hidroxi-2'-Desoxicoguanosina , Plomo , Estudios Prospectivos , Níquel , Estrés Oxidativo , Metales Pesados/toxicidad , Monitoreo del Ambiente/métodos

RESUMEN

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.

Asunto(s)

Contaminación por Humo de Tabaco , Embarazo , Humanos , Femenino , Mujeres Embarazadas , 8-Hidroxi-2'-Desoxicoguanosina , Brasil , Placenta/química , Compuestos de Anilina/análisis , Aminas/toxicidad , Aminas/orina , Daño del ADN , Humo/análisis , Compuestos Azo , Estilo de Vida , Factores Socioeconómicos , Variación Genética

RESUMEN

Over the years, humans have been continuously exposed to several compounds directly generated by industrial processes and/or present in consumed products. Polycyclic aromatic hydrocarbons (PAHs) are legacy pollutants ubiquitous in the environment and represent the main chemical pollutants in urban areas. Worldwide, studies that aim to understand the impacts of exposure to these chemicals have gained increasing prominence due to their potential toxicity profile, mainly concerning genotoxicity and carcinogenicity. Human biomonitoring (HB) is an analytical approach to monitoring population exposure to chemicals; however, these studies are still limited in Brazil. Thus, this work aimed to evaluate the exposure of Brazilian pregnant women to PAHs through HB studies. Besides, the risk characterization of this exposure was performed. For this purpose, urine samples from 358 Brazilian pregnant women were used to evaluate 11 hydroxylated metabolites of PAHs employing gas chromatography coupled to mass spectrometry. The 1OH-naphthol and 2OH-naphthol were detected in 100% of the samples and showed high levels, corresponding to 16.99 and 3.62 µg/g of creatinine, respectively. 2OH-fluorene (8.12 µg/g of creatinine) and 9OH-fluorene (1.26 µg/g of creatinine) were detected in 91% and 66% of the samples, respectively. Benzo(a)pyrene (BaP) metabolites were detected in more than 50% of the samples (0.58-1.26 µg/g of creatinine). A hazard index of 1.4 and a carcinogenic risk above 10-4 were found for BaP metabolites in the risk characterization. Therefore, our findings may indicate that exposure to PAHs poses a potential risk to pregnant women's health and a high probability of carcinogenic risk due to their exposure to BaP. Finally, this work shows the need for more in-depth studies to determine the sources of exposure and the implementation of health protection measures regarding the exposure of the Brazilian population to PAHs.

Asunto(s)

Contaminantes Ambientales , Hidrocarburos Policíclicos Aromáticos , Humanos , Femenino , Embarazo , Hidrocarburos Policíclicos Aromáticos/orina , Monitoreo Biológico , Brasil , Mujeres Embarazadas , Monitoreo del Ambiente/métodos , Naftoles/análisis , Creatinina , Contaminantes Ambientales/orina , Medición de Riesgo , Carcinógenos/análisis , Fluorenos/análisis

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) and toxic metals are widely spread pollutants of public health concern. The co-contamination of these chemicals in the environment is frequent, but relatively little is known about their combined toxicities. In this context, this study aimed to evaluate the influence of the co-exposure to PAHs and toxic metals on DNA damage in Brazilian lactating women and their infants using machine learning approaches. Data were collected from an observational, cross-sectional study with 96 lactating women and 96 infants living in two cities. The exposure to these pollutants was estimated by determining urinary levels of seven mono-hydroxylated PAH metabolites and the free form of three toxic metals. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the urine were used as the oxidative stress biomarker and set as the outcome. Individual sociodemographic factors were also collected using questionnaires. Sixteen machine learning algorithms were trained using 10-fold cross-validation to investigate the associations of urinary OH-PAHs and metals with 8-OHdG levels. This approach was also compared with models attained by multiple linear regression. The results showed that the urinary concentration of OH-PAHs was highly correlated between the mothers and their infants. Multiple linear regression did not show a statistically significant association between the contaminants and urinary 8OHdG levels. Machine learning models indicated that all investigated variables did not present predictive performance on 8-OHdG concentrations. In conclusion, PAHs and toxic metals were not associated with 8-OHdG levels in Brazilian lactating women and their infants. These novelty and originality results were achieved even after applying sophisticated statistical models to capture non-linear relationships. However, these findings should be interpreted cautiously because the exposure to the studied contaminants was considerably low, which may not reflect other populations at risk.

Asunto(s)

Contaminantes Ambientales , Hidrocarburos Policíclicos Aromáticos , Humanos , Femenino , Lactante , Hidrocarburos Policíclicos Aromáticos/análisis , Estudios Transversales , Brasil , Lactancia , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/orina , 8-Hidroxi-2'-Desoxicoguanosina/orina , Daño del ADN , Biomarcadores/metabolismo , Estrés Oxidativo

RESUMEN

The staggering amount of chemicals in clothes and their harmful effects on human health and the environment have attracted the attention of regulatory agencies and the scientific community worldwide. Azo dyes are synthetic dyestuffs with widespread use in textile industries, currently classified as emerging pollutants of great health concern to consumers. These compounds may release one or more aromatic amines (AAs) after reductive cleavage of their azo bounds. Twenty-two AAs have already been regulated due to their carcinogenic effects. However, since information on their potential toxicity is not currently available, several AAs have not been still regulated by the European Union. Considering this gap, the present study aimed to assess the levels of forty non-regulated AAs in 240 clothing items from Spain and Brazil. The potential impact on the health of vulnerable population groups after dermal exposure to those garments was also evaluated. In Brazil, at least one AA was detected in the clothes, while in samples obtained in Spain, only two of them showed values below the limit of detection for AAs. In 75 clothes, at least one of the measured AAs was higher than the hazardous threshold (30 mg/kg), which can mean risks to human health since these compounds are suspected to be mutagenic. Aniline, the most common AA, showed a high detection rate (82%) in clothes, with significantly higher concentrations in items commercialized in Brazil (0.35 vs. 0.17 mg/kg; p = 0.032). Moreover, o-aminobenzenesulfonic and p-phenylenediamine, suspected mutagenic, were found at relevant concentrations in several clothes, mainly made of synthetic fibers. In this study, the hazard index associated with exposure to AAs through clothing was low (0.006-0.13) for all the population groups of both countries in the medium-bound scenario. However, its value was close to 1 for Brazilian pregnant women (0.998) when the maximum concentration value was considered under an upper-bound scenario. The risk of exposure to non-regulated AAs may be underestimated since only dermal exposure was considered for risk assessment. Moreover, the co-occurrence of other carcinogenic and non-carcinogenic substances present in skin-contact clothes should mean an additional source of potential risk.

Asunto(s)

Aminas , Evaluación del Impacto en la Salud , Embarazo , Humanos , Femenino , España , Brasil , Unión Europea

RESUMEN

Due to the increasing population worldwide, in recent years, an exponential increase in agricultural practices has occurred in order to attend to the growing demand for food. Unfortunately, this increase is not associated with the supply of foodstuffs free of environmental pollutants. In Brazil, agriculture is one of the most important economic pillars, making the country one of the largest consumers of pesticides around the world. The intense use of pesticides, mainly glyphosate, 2,4-D, and atrazine, constitutes an essential factor in the viability of this great agricultural productivity. Sugarcane, corn, soybean, and citrus crops consume around 66% of the total pesticides worldwide, representing 76% of the planted area. Pesticide residues have been frequently detected in food and the environment, becoming a significant concern for human health. Monitoring programs for pesticide use are essential to reduce the potential negative impacts on the environment and improve the overall efficiency and sustainability of their use. However, in Brazil, the approval status of pesticide-active ingredients is very discrepant compared to other agricultural countries. Moreover, the duality of benefits and risks of pesticide application creates an economic and toxicological conflict. In this paper, we have critically reviewed the duality of risks-benefits of the use of pesticides in agriculture and the current Brazilian legislation issues. We have also compared this flawed legislation with other countries with high economic potential. Due to the negative environmental impacts on soil and water by the high levels of pesticides, remediation techniques, sustainable agriculture, and the development of new technologies can be considered some viable alternatives to reduce the levels in these compartments. Besides, this paper includes some recommendations that can be included in the coming years.

Asunto(s)

Agricultura , Plaguicidas , Humanos , Brasil , Residuos de Plaguicidas/análisis , Plaguicidas/toxicidad , Plaguicidas/análisis , Medición de Riesgo

RESUMEN

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.

Asunto(s)

Aminas , Textiles , Recién Nacido , Humanos , Brasil , España , Aminas/toxicidad , Compuestos Azo , Vestuario , Colorantes/química

RESUMEN

The presence of phthalates constitutes a risk to the health of aquatic environments and organisms. This work aimed to evaluate the toxic effects of di-iso-pentyl-phthalate (DiPeP) at environmentally relevant concentrations of 5, 25, and 125 µg/L in Danio rerio after subchronic exposure for 14 days. DiPeP altered the antioxidant system in the liver (125 µg/L), intestine (25 µg/L), brain, and gills in all concentrations tested. In animals exposed to 125 µg/L, DNA damage was identified in the gills. In addition, loss of cell boundary of hepatocytes, vascular congestion, necrosis in the liver, and presence of immune cells in the intestinal lumen were observed. Erythrocytic nuclear alterations in the blood occurred in animals exposed to 25 µg/L. DiPeP was quantified in muscle tissue at all exposure concentrations, appearing in a concentration-dependent manner. Contaminants such as DiPeP will still be used for a long time, mainly by industries, being a challenge for industry versus environmental health.

Asunto(s)

Ácidos Ftálicos , Contaminantes Químicos del Agua , Animales , Pez Cebra/fisiología , Ácidos Ftálicos/toxicidad , Hígado , Modelos Teóricos , Contaminantes Químicos del Agua/toxicidad

RESUMEN

Polybrominated diphenyl ethers (PBDEs) are ubiquitous flame retardants and are environmentally persistent. PBDEs show endocrine disruption, neurotoxicity, and lower birth weight in infants, and their human body burden has become a public health concern. The infants' exposure begins in the prenatal period and continues via breast milk ingestion, although, little is known about the factors that may influence this exposure. In this study, PBDE levels in Brazilian breast milk were assessed in 200 lactating women. The risk assessment of infants' exposure to PBDE was performed through the estimated daily intake (EDI) calculation. The geometric mean (GM) of ∑PBDEs levels was 2.33 (0.14-6.05) ng/g wet weight. At least one PBDE congener was detected in the samples, and the 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) showed a 100% of detection rate (GM of 1.05 ng/g). Location of residence, maternal level education, monthly salary, and race were positively associated with PBDE levels (p < 0.05). The EDI of BDE-47 was higher in Belo Horizonte (8.29 ng/kg/day) than in Viçosa (6.36 ng/kg/day), as well as for the ∑PBDEs (19.77 versus 12.78 ng/kg/day) (p < 0.05). Taking the high detection rate of PBDEs in breast milk and their toxicity, continuous studies on infant exposure, fetal growth, and child neurodevelopment are requested.

Asunto(s)

Contaminantes Ambientales , Retardadores de Llama , Brasil , Niño , Contaminantes Ambientales/análisis , Femenino , Retardadores de Llama/análisis , Éteres Difenilos Halogenados/análisis , Humanos , Lactante , Lactancia , Exposición Materna , Leche Humana/química , Embarazo

RESUMEN

Bisphenols (BPs) and phthalate esters (PAEs) are extensively used in toys and childcare products. Therefore, children may be exposed to these compounds, causing potential adverse effects. Despite the strict control of the levels of these contaminants in toys by some nations, routine testing in Brazil is very scarce. The present study was aimed at determining the concentrations of PAEs and BPs in toys commercialized in Brazil, employing GC-MS and LC-MS/MS, respectively. Furthermore, the migration capacity of PAEs into saliva and the daily intake (EDI) were also estimated. Di-2-ethylhexyl phthalate (DEHP) was the PAE with the highest detection rate (93%) and migration rate (0.26 µg/min). Moreover, the levels of DEHP in some samples were above the threshold values set by the European Commission and the Brazilian Institute of Metrology, Standardization, and Industrial Quality. Among the BPs analogs, BPA and BPS presented the highest positive detection rates (72% and 30%, respectively). However, their levels were below the permitted values in all analyzed samples. A daily intake of DEHP was estimated at 29.8 µg/kg bw/day, being this exposure similar to those found in other countries and below the EFSA acceptable intake limit (50 µg/kg bw/day). However, our data are referred to exposure through oral contact with the analyzed toys, while the contribution of other potential sources, such as food consumption, were not here considered. To the best of our knowledge, this is the first study estimating the exposure of Brazilian children to PAEs and BPs, considering toys as the exposure source. These preliminary data may become a valuable guide for the control of EDC levels in toys commercialized in Brazil, as well as for future studies regarding estimation of exposure to EDCs by children taking into account multiple potential sources.

Asunto(s)

Dietilhexil Ftalato , Ácidos Ftálicos , Brasil , Niño , Cromatografía Liquida , Exposición a Riesgos Ambientales/análisis , Ésteres , Humanos , Saliva , Espectrometría de Masas en Tándem

RESUMEN

Monitoring human exposure to polycyclic aromatic hydrocarbons (PAHs) is a public health concern. Children are a vulnerable subgroup of the population with limited human biomonitoring data worldwide. Thus, this study aimed to measure the levels of seven PAH metabolites in urine from Brazilian children and provide risk assessment values for this exposure. Our data show naphthalene was the major contributor to children's exposure to PAHs, with a 100% detection rate. Children in urban regions presented higher exposure to PAHs, with higher concentrations of 2-naphthol in the southeast (1.09 ng/mL, p < 0.05). Furthermore, the highest concentration of 2-naphthol was found in older children (p = 0.02), suggesting a possible difference in dietary habits. Exposure to the carbaryl insecticide is suggested based on the high concentrations of 1-naphthol (1.29 ng/mL) and considering the ratio 1-naphthol/2-naphthol (1.78). Moreover, the positive correlation between the metabolites of fluorine and pyrene also suggests exposure to PAHs by petrol combustion. The risk assessment of the PAH exposure was evaluated using the estimated daily intake (EDI) for two naphthalene metabolites in the study with a 100% detection rate. The EDI was 14.47 ng/kg BW/day. The risk assessment to the PAH exposure revealed a non-carcinogenic risk profile, with a hazard quotient of 0.71. To the best of our knowledge, this study is the first to provide levels of PAHs in Brazilian children.

Asunto(s)

Hidrocarburos Policíclicos Aromáticos , Monitoreo Biológico , Biomarcadores/orina , Brasil , Niño , Monitoreo del Ambiente , Humanos , Naftalenos , Hidrocarburos Policíclicos Aromáticos/análisis , Medición de Riesgo

RESUMEN

Organophosphates (OPPs) are an important element of modern agriculture; however, because they are being used excessively, their residues are leaching and accumulating in the soil and groundwater, contaminating aquatic and terrestrial food chains. An important OPP called disulfoton is frequently used to eradicate pests from a wide range of crops, including Brazil's coffee crops. Additionally, it does not easily degrade in the environment, and as such, this compound can slowly build up in living organisms such as humans. Moreover, this compound has been classified as "extremely hazardous" by the World Health Organization. This study evaluated the degradation efficiency of disulfoton using a Fenton-like reaction catalyzed by magnetite nanoparticles and determined the toxicity of the by-products of the degradation process using the bioindicator Allium cepa. Further, the removal efficiency of disulfoton was determined to be 94% under optimal conditions. On the other hand, the Allium cepa bioassay showed different toxic, cytotoxic, genotoxic, and mutagenic outcomes even after the remediation process. In conclusion, the Fenton process catalyzed by magnetite nanoparticles presents great efficiency for the oxidation of disulfoton. However, it is important to highlight that the high degradation efficiency of the Fenton-based process was not sufficient to achieve detoxification of the samples.

Asunto(s)

Agricultura , Disulfotón , Humanos , Disulfotón/metabolismo , Oxidación-Reducción , Suelo/química , Productos Agrícolas/metabolismo

RESUMEN

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants, commonly used as flame retardants in a wide variety of products. In the last years, the concentration of PBDEs is increasing in the environment, turning human exposure more common. Since the diet is the primary source of human exposure, several surveys evaluate the levels of PBDEs in foods to estimate the dietary intake and the hazard index (HI). However, this data is limited in Brazil. Thus, this study aims to determine the level of seven PBDE congeners (BDE-28, 47, 99, 100, 153, 154, 183) in Brazilian food of animal origin. The total concentration of PBDE (∑PBDE) determined in the food samples were 2.29 (0.92-4.85) ng/g wet weight (ww), 1.98 (1.23-3.12) ng/g ww, 1.91 (1.23-3.12) ng/g ww, and 4.42 (1.26-8.42) ng/g ww in eggs, fish, seafood, and milk, respectively. BDE-47 was the most abundant compound. Based on consumer habits and the found levels of PBDEs in Brazilian food, we estimated the daily intake of ∑PBDEs as 3.25 (0.02-2.19) ng/kg bw per day. Surprisingly, the PBDE levels in milk samples were higher than those found in reported studies in other countries, and the consumption of milk products give a higher relative contribution to PBDEs exposure. The HI was <1. A complete risk assessment of the human exposure to PBDEs most likely could be evaluated considering all commercial PBDEs congeners and other exposure sources of these contaminants.

Asunto(s)

Huevos/análisis , Contaminantes Ambientales/toxicidad , Éteres Difenilos Halogenados/toxicidad , Leche/química , Alimentos Marinos/análisis , Animales , Brasil , Contaminantes Ambientales/administración & dosificación , Contaminantes Ambientales/química , Peces , Análisis de los Alimentos , Contaminación de Alimentos , Éteres Difenilos Halogenados/administración & dosificación , Éteres Difenilos Halogenados/química , Humanos

RESUMEN

Research pertaining to exposure of humans to per- and polyfluorinated alkyl substances (PFASs) has received considerable public and regulatory attention in recent years. Although several studies have reported exposure to PFASs by populations in North America and western Europe, such information is still scarce in Latin America, including Brazil. In this study, concentrations of thirteen PFASs were determined in whole blood collected during the second trimester from 252 pregnant Brazilian women. This is a nested case-control study within the Brazilian Ribeirao Preto and Sao Luiz Birth Cohort Study (BRISA) with selected birth outcomes cases (n = 63) and matched controls (n = 189). PFASs concentrations were associated with conditions including preeclampsia, birth weight (BW), preterm birth, and intrauterine growth restriction (IUGR). Among PFASs measured, perfluorooctane sulfonate (PFOS) was found at the highest concentration (range: 1.06-106 ng mL-1 with a median value of 3.41 ng mL-1) which was followed by perfluorooctanoic acid (PFOA, range: 0.11-2.77 ng mL-1 with a median value of 0.20 ng mL-1). A significant positive association of PFOS and PFOA concentrations with fetal growth restriction (p < 0.05) was found. This is the first study to assess whole blood concentrations of PFASs and their effect on fetal growth in pregnant Brazilian women.

Asunto(s)

Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Nacimiento Prematuro , Brasil , Caprilatos/toxicidad , Estudios de Casos y Controles , Estudios de Cohortes , Europa (Continente) , Femenino , Desarrollo Fetal , Fluorocarburos/toxicidad , Humanos , Recién Nacido , América del Norte , Embarazo

RESUMEN

Bupivacaine, a local anesthetic, is commercialized as a racemic mixture of R-bupivacaine and S-bupivacaine enantiomers. HIV infection increases the expression of placental P-glycoprotein (P-gp), and antiretroviral (ARV) therapy inhibits cytochrome P450 3A and P-gp. The present study evaluates the kinetic disposition of bupivacaine enantiomers in HIV-infected parturient women on ARV therapy. In this study, HIV-infected parturient women (n = 10) treated with zidovudine, lamivudine, lopinavir, and ritonavir were investigated. Anesthesia and/or analgesia was achieved by the administration of 0.5% racemic bupivacaine hydrochloride with 1:200000 epinephrine in the epidural space at doses of 2.5 to 22.5 mg. Maternal serial blood samples were obtained at the time immediately before and 5, 15, 30, 45, and 60 minutes and 2, 4, 6, 8, 10, 12, and 14 hours after administration of the bupivacaine. At the time of delivery, samples of maternal and umbilical cord vein blood were also collected. The results suggest that bupivacaine pharmacokinetics are enantioselective, revealing higher maternal plasma concentrations of the R-bupivacaine enantiomer (area under the total plasma concentration-time curve was calculated by the trapezoid method with extrapolation to infinity/dose(S)/(R) = 0.91; P < .05). The plasma unbound fraction of the drug (0.09 vs 0.06) and the umbilical cord vein/maternal plasma ratio (0.47 vs 0.39) were higher for the R-bupivacaine enantiomer than the S-bupivacaine enantiomer (P < .05). ARV therapy with ritonavir confers an enantioselective interaction between the enantiomers of bupivacaine and placental P-gp, producing greater inhibition of efflux transport of the R-bupivacaine enantiomer. Possible changes in the well-being of the fetuses of mothers under analgesia may be a consequence of the increased placental transfer of bupivacaine enantiomers to the fetal circulation.

RESUMEN

Bupivacaine, a drug used in obstetric anesthesia and analgesia, is commercially available as a racemic mixture of the R-bupivacaine and S-bupivacaine enantiomers, which show differences in pharmacokinetics, efficacy and toxicity. Changes in bupivacaine plasma protein binding is of clinical relevance considering its high protein binding (approximately 95%) and its classification as an intermediate hepatic extraction ratio drug (E = 0.38). Furthermore, the plasma protein binding of bupivacaine is also of clinical relevance considering that pregnancy is a physiological condition associated with reduced plasma albumin concentration. Also, different pathological conditions, such as pre-eclampsia, can reduce the maternal plasma protein concentrations and consequently increase the bupivacaine placental transfer. This report describes the development and validation of analytical methods for the sequential analysis of the total and unbound concentrations of bupivacaine enantiomers in human plasma using liquid chromatography coupled to mass spectrometry (LC-MS/MS) with a sensitivity compatible with application in pharmacokinetic studies including placental transfer. Aliquots of 200 µL of plasma or plasma ultra-filtrate were extracted with n-hexane in alkaline medium after the deproteinization of the matrix with acetonitrile and water. The separation of bupivacaine enantiomers was obtained on a Chirex® 3020 chiral stationary phase column using as a mobile phase a mixture of 95% n-hexane:ethanol (80:20, v/v) at a flow rate of 0.8 mL/min. The lower limit of quantification was 0.25 ng of each enantiomer/mL of plasma as the total concentration and 0.125 ng of each enantiomer/mL of plasma as the unbound concentration. The methods were applied to study the pharmacokinetics of bupivacaine enantiomers after the administration of 2.5 mg of 0.5% racemic bupivacaine hydrochloride with 1:200,000 epinephrine via the epidural route to an HIV-positive parturient woman undergoing antiretroviral treatment. The parturient showed lower AUC0-∞ (25.42 vs. 30.57 ng.h/mL) and higher volume of distribution (841.96 vs 655.05 L) and total clearance (98.34 vs 81.79 L/h) for the R-bupivacaine enantiomer. The pharmacokinetics of bupivacaine were enantioselective displaying a lower plasma proportion of the enantiomer R-bupivacaine (AUC(R)/(S) ratio equal to 0.83). The placental transfer was approximately 60% for both bupivacaine enantiomers. The unbound fraction (Fu) for the R-bupivacaine enantiomer was higher (10.84%) than the eutomer S-bupivacaine (6.29%).

Asunto(s)

Anestésicos Locales/sangre , Proteínas Sanguíneas/metabolismo , Bupivacaína/sangre , Intercambio Materno-Fetal , Equilibrio Ácido-Base/efectos de los fármacos , Anestesia Epidural/efectos adversos , Anestesia Epidural/métodos , Anestesia Obstétrica/efectos adversos , Anestesia Obstétrica/métodos , Anestésicos Locales/química , Anestésicos Locales/farmacocinética , Bupivacaína/química , Bupivacaína/farmacocinética , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Femenino , Feto/efectos de los fármacos , Feto/metabolismo , Voluntarios Sanos , Humanos , Embarazo , Unión Proteica , Estereoisomerismo , Espectrometría de Masas en Tándem/instrumentación , Espectrometría de Masas en Tándem/métodos

RESUMEN

ABSTRACT Different solid forms of an active pharmaceutical ingredient can have distinct chemical and physical characteristics. In this work, we studied the solubility and dissolution properties of the described tibolone polymorphic forms (I and II). Both forms were successively recrystallized and characterized by powder X-ray diffraction and attenuated total reflection infrared spectroscopy. Equilibrium solubility and dissolution profiles were performed for both forms. Solubility studies demonstrated that form II is statistically more soluble in water, 0.01 mol L-1 HCl and pH 4.5 acetate buffer. The solubility of forms I and II were explained in terms of crystal packing. Dissolution tests of tablets showed a lower release of polymorphic form II than form I from tablets. The results showed an impact of polymorphism on the quality of tibolone tablets and suggest that tibolone forms I and II can show distinct interactions with pharmaceutical excipients used in tablets. Therefore, only form I is acceptable for the preparation of tablet forms. Based on our results, we propose the quality control on tibolone raw materials using X-ray diffraction analysis and attenuated total reflection infrared spectroscopy.

Asunto(s)

Solubilidad/efectos de los fármacos , Disolución/análisis , Análisis Espectral , Comprimidos/normas , Difracción de Rayos X/métodos , Preparaciones Farmacéuticas/normas