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1.
Aquat Toxicol ; 225: 105524, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32610223

RESUMO

In the present research, the effects of exposure to a sublethal concentration of zinc (Zn) on metal and ion homeostasis, and the regulation and the localization of various Zn transporters (i.e., the Zrt-Irt Like Protein (ZIP) family of Zn transporters), were investigated in zebrafish (Danio rerio) during early development. Exposure to an elevated level of Zn [4 µM (high) vs. 0.25 µM (control)] from 0 day post-fertilization (dpf) resulted in a significant increase in the whole body content of Zn at 5 dpf. A transient decrease in the whole body calcium (Ca) level was observed in 3 dpf larvae exposed to high Zn. Similarly, whole body nickel (Ni) and copper (Cu) contents were also reduced in 3 dpf larvae exposed to high Zn. Importantly, the magnitude of reduction in whole body Ni and Cu contents following Zn exposure was markedly higher than that in Ca content, suggesting that internal Ni and Cu balance were likely more sensitive to Zn exposure in developing zebrafish. Exposure to high Zn altered the mRNA expression levels of specific zip transporters, with an increase in zip1 (at 3 dpf) and zip8 (at 5 dpf), and a decrease in zip4 (at 5 dpf). The expression levels of most zip transporters tended to decrease from 3 dpf to 5 dpf with the exception of zip4 and zip8. Results from in situ hybridization revealed that several zip transporters exhibited distinct spatial distribution (e.g., zip8 in the intestinal tract, zip14 in the pronephric tubules). Overall, our findings suggested that exposure to sublethal concentrations of Zn disrupts the homeostasis of essential metals during early development and that different ZIP transporters may play unique roles in regulating Zn homeostasis in various organs in developing zebrafish.


Assuntos
Proteínas de Transporte de Cátions/genética , Homeostase/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/genética , Peixe-Zebra , Zinco/toxicidade , Animais , Cálcio/metabolismo , Cobre/metabolismo , Relação Dose-Resposta a Droga , Larva/efeitos dos fármacos , Larva/metabolismo , Nível de Efeito Adverso não Observado , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/fisiologia , Zinco/metabolismo
2.
Chemosphere ; 261: 127682, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32711240

RESUMO

Neonicotinoid insecticides (NEOs) have become the most widely used insecticides worldwide, and they are ubiquitous in food (i.e., fruit juices). In the present study, occurrence of seven NEOs and four metabolites (m-NEOs) in 400 fruit juice samples were investigated. NEOs and m-NEOs were frequently detected (65%-86%) in fruit juice samples. The median residues of NEOs and m-NEOs were ranged from 0.06 ng/mL to 0.94 ng/mL. Seasonal variations in NEOs and m-NEOs in fruit juices were found, indicating that the target analyte residues during the dry season were remarkably higher than those of residues during wet season. The relative potency factor (RPF) method was used to integrate individual NEOs into a single metric [imidacloprid (IMIRPF)] representing the intakes of IMI equivalent to total NEOs for each fruit juice sample. The estimated daily intake (EDI) of total NEOs for the general Chinese population was obtained. The median IMIRPF for total fruit juices was 13.4 ng/g, and the median EDI of NEOs was 18.2 ng/kg bw/day for the general population. Although the EDIs in this study were considerably lower than the acceptable daily intake (60 µg/kg bw/day, ADI), the dietary exposure risks for total NEOs should not be ignored because of the increasing usage of NEOs and their ubiquitous presence in fruit juices in China. To the best of our knowledge, this report was the first time to document residues of NEO and m-NEO in fruit juice samples collected from China.


Assuntos
Exposição Dietética/estatística & dados numéricos , Sucos de Frutas e Vegetais/análise , Inseticidas/análise , Neonicotinoides/análise , Grupo com Ancestrais do Continente Asiático , China , Coleta de Dados , Frutas/química , Humanos , Nitrocompostos , Nível de Efeito Adverso não Observado , Projetos de Pesquisa , Estações do Ano , Verduras/química
3.
Environ Geochem Health ; 42(11): 3675-3701, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32488799

RESUMO

Groundwater is one of the most important sources of water for drinking and cooking in rural India. A total of 382 groundwater samples were collected from 58 villages and analyzed for HMs and Sr by inductively coupled plasma mass spectrometer. The average concentrations of HMs and Sr in water was in the order of strontium (Sr) > arsenic (As) > chromium (Cr) > lead (Pb) > mercury (Hg) > cadmium (Cd). Out of 58 villages, 21, 37, 35, 35, 35 and 39 villages had Cr, As, Cd, Hg, Pb and Sr higher (WHO limit) than their respectively permissible levels. Health risk assessment of HMs and Sr for humans revealed that the non-carcinogenicity hazard quotients (HQi+d) for HMs and Sr were higher than unity for adult and children. The hazard index (HI) was 531.066 for adult and 902.926 for children. The HI > 1 was observed in 45 villages for adults and 56 villages for children. The lifetime cancer risk in adult for Asi, Asd, and Pbi in 36, 25 and 23 villages, whereas in children was 42, 20 and 22 villages, respectively. In conclusion, the health risks arising from consumption of groundwater containing HMs and Sr indicated that there is a significant carcinogenic risks for adult and children. This is the first attempt to provide information on the health risks of Sr in drinking water in India. The present findings can be useful for the development of potential strategies for risk control and management.


Assuntos
Exposição Dietética/efeitos adversos , Metais Pesados/análise , Estrôncio/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Adulto , Carcinógenos/análise , Carcinógenos/toxicidade , Criança , Culinária , Exposição Dietética/análise , Água Potável/análise , Água Subterrânea/química , Humanos , Índia , Metais Pesados/toxicidade , Nível de Efeito Adverso não Observado , Medição de Risco , Estrôncio/toxicidade
4.
Toxicol Lett ; 332: 181-191, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32473956

RESUMO

Trans-1233zd was developed as a refrigerant and propellant in consumer products; its toxicity has been studied extensively. The scope of this assessment is to apply the confirmed NOAEC to conduct Benchmark Dose Modeling (BMD) and determine the Point of Departure (POD). In a previously published 13-week inhalation study, a NOAEC was identified at 4000 ppm. Due to uncertainty concerning the cardiac lesion, an external pathology peer review of heart tissues was undertaken using published best practices and consistent nomenclature and diagnostic criteria. The cardiac lesion observed at 4000 ppm was considered to be spontaneous based on lesion location and microscopic features. BMD was applied to derive the BMDL05 and BMDL10; the more conservative BMDL05 was used as the POD for risk assessment to calculate the Reference Exposure Levels (RELs). The 2-Box Air Dispersion Model was used to calculate the exposure to consumer products. Both the acute and chronic exposure concentrations calculated were compared to the acute and chronic RELs. The acute and chronic exposure to trans-1233zd in the assessed consumer products are below the RELs and deemed safe for their intended uses.


Assuntos
Clorofluorcarbonetos de Metano/toxicidade , Clorofluorcarbonetos/toxicidade , Administração por Inalação , Animais , Benchmarking , Relação Dose-Resposta a Droga , Exposição Ambiental , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Exposição por Inalação , Masculino , Modelos Biológicos , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Medição de Risco
5.
Toxicol Lett ; 334: 117-144, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497562

RESUMO

This paper derives an occupational exposure limit for benzene using quality assessed data. Seventy-seven genotoxicity and 36 haematotoxicity studies in workers were scored for study quality with an adapted tool based on that of Vlaanderen et al., 2008 (Environ Health. Perspect. 116 1700-5). These endpoints were selected as they are the most sensitive and relevant to the proposed mode of action (MOA) and protecting against these will protect against benzene carcinogenicity. Lowest and No- Adverse Effect Concentrations (LOAECs and NOAECs) were derived from the highest quality studies (i.e. those ranked in the top tertile or top half) and further assessed as being "more certain" or "less certain". Several sensitivity analyses were conducted to assess whether alternative "high quality" constructs affected conclusions. The lowest haematotoxicity LOAECs showed effects near 2 ppm (8 h TWA), and no effects at 0.59 ppm. For genotoxicity, studies also showed effects near 2 ppm and showed no effects at about 0.69 ppm. Several sensitivity analyses supported these observations. These data define a benzene LOAEC of 2 ppm (8 h TWA) and a NOAEC of 0.5 ppm (8 h TWA). Allowing for possible subclinical effects in bone marrow not apparent in studies of peripheral blood endpoints, an OEL of 0.25 ppm (8 h TWA) is proposed.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Benzeno/toxicidade , Mutagênicos/toxicidade , Exposição Ocupacional/análise , Estudos Epidemiológicos , Humanos , Concentração Máxima Permitida , Nível de Efeito Adverso não Observado , Exposição Ocupacional/efeitos adversos , Medição de Risco , Níveis Máximos Permitidos
6.
Ecotoxicol Environ Saf ; 199: 110751, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446104

RESUMO

Tonalide or acetyl hexamethyl tetralin (AHTN) is used as a fragrance additive in various household products. Recently, AHTN has drawn attention owing to its negative health effects on aquatic organisms. Data on AHTN toxicity toward aquatic species are limited. Therefore, this study tested the oxidative stress induced by AHTN exposure on the Rhodeinae sinensis Gunther and Macrobrachium nipponense. In this study, malonaldehyde (MDA) content and the activities of acetyl cholinesterase (AchE), superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase (CAT) in R. sinensis Gunther were tested after 30 days of exposure to 30.093, 34.005, 38.426, 43.421, 49.067, 55.444, 62.652, 70.800, and 80.000 µg/L AHTN, respectively. The MDA, AchE, SOD, GST and CAT in M. nipponense were tested after 40 days of exposure to 60.000, 72.000, 86.400, 103.680, 124.416, 149.299, 179.159, 214.991, and 257.989 µg/L AHTN, respectively. In addition, an integrated biomarker response (IBR) index was utilised to evaluate the integrated toxic effects of AHTN on R. sinensis Gunther and M. nipponense. Finally, the predicted no-effect concentrations (PNECs) of AHTN, based on reproduction, biochemistry, survival, chronic toxicity, and acute toxicity endpoints were derived. The results indicated that low concentrations of AHTN can induce significant changes of oxidative stress biomarkers. The no observed effect concentrations (NOECs) of SOD, GST, AchE, CAT, and MDA were 103.680, 72.000, <60.000, 72.000, and <60.000 µg/L for R. sinensis Gunther and 38.426, 43.421, 30.093, 30.093, and 38.426 µg/L for M. nipponense, respectively. The IBR calculation results showed that 149.299 µg/L AHTN caused the highest toxic effect on R. sinensis Gunther after 30 days of exposure, whereas 70.797 µg/L AHTN caused the greatest damage to M. nipponense after 40 days of exposure. The PNECs of AHTN based on the non-traditional endpoints of biochemistry and reproduction were 0.00145 µg/L and 0.000395 µg/L, respectively, which were significantly lower than the PNEC of 2.636 µg/L for traditional endpoint survival. Therefore, the protection of aquatic organisms based on non-traditional toxicity endpoints should be considered in ecological risk assessment.


Assuntos
Antioxidantes/metabolismo , Organismos Aquáticos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Palaemonidae/efeitos dos fármacos , Perfumes/toxicidade , Tetra-Hidronaftalenos/toxicidade , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Animais , Organismos Aquáticos/enzimologia , Catalase/metabolismo , Relação Dose-Resposta a Droga , Determinação de Ponto Final , Glutationa Transferase/metabolismo , Malondialdeído/metabolismo , Nível de Efeito Adverso não Observado , Palaemonidae/enzimologia , Valor Preditivo dos Testes , Superóxido Dismutase/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-32414159

RESUMO

Palm puree is rich in antioxidants and is produced via blending various proportions of mesocarp fibre and crude palm oil. The aim of this study was to assess the acute and subchronic toxicity of palm puree in male and female Sprague-Dawley rats. For the acute toxicity study, animals administered single palm-puree doses (2000 mg kg-1) by gavage were observed daily for 14 d. For the subchronic toxicity study, the rats were administered 500, 1000, or 2000 mg kg-1 palm puree daily for 28 d. We evaluated body and organ weights; performed haematological, biochemical, and histopathological analyses of blood and organ samples during and after treatment; and calculated the oral no-observed-adverse-effect level (NOAEL). The toxicity studies showed no signs of toxicity or mortality. The haematological, biochemical, and histopathological analyses and body and organ weights indicated no evidence of substantial toxicity at any dose of palm puree. The oral lethal dose and NOAEL for the palm puree were greater than 2000 mg kg-1 d-1 over 28 d. To the best of our knowledge, the present study is the first to confirm the safety of palm puree as a novel functional food. These encouraging results warrant further studies to elucidate its potential for pharmaceutical formulations.


Assuntos
Óleo de Palmeira , Administração Oral , Animais , Peso Corporal , Relação Dose-Resposta a Droga , Feminino , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão , Óleo de Palmeira/toxicidade , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
8.
Sci Total Environ ; 727: 138491, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32335449

RESUMO

Pesticides can potentially contribute to the development of numerous neurodegenerative diseases. This study evaluates the effects of a six-pesticide mixture at doses around the no-observed-adverse-effectlevels (0 × NOAEL, control) and 0.25, 1 and 5 × NOAEL on behavior of Wistar rats. After 3, 6 and 12 months, rats were observed for neurobehavioral changes using the techniques of elevated plus maze and universal problemchamber, and the experiment was conducted thrice. The 3-month exposure revealed a decrease in the cognitive ability at the dose of 5 × NOAEL, and a dose-dependent research activity and anxiety. The 6-month exposurerevealed non-monotonic effects on the cognitive ability, with a decrease by 0.25 and 5 × NOAEL, as well as non-monotonic effects on anxiety, withan increase by 0.25 and 1 × NOAEL. A decrease was also observed in research activity at 5 × NOAEL. However, the 12-month exposure resulted to an increase in cognitive ability by 0.25 × NOAEL and in anxiety by 1 × NOAEL, as well as to a dose-dependent research activity. Repeating the trial showed that the cognitive ability increased from one trial to another, while the researching activity decreased and the anxiety increased by 0× NOAEL. In the groups exposed to pesticides mixture, the trends were different, showing that the exposure to pesticides combined with repeated trials, also influence the response of the animals. The resultsdemonstrate the occurrence of several dose-dependent behavioral responses, with negative effects occurring at doses that are considered safe. This study provides novel insights about time-dependent mixtures biology, and an important perspective to consider when conducting risk assessments.


Assuntos
Praguicidas , Animais , Ansiedade , Nível de Efeito Adverso não Observado , Ratos , Ratos Wistar , Medição de Risco
9.
Aquat Toxicol ; 222: 105422, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32112996

RESUMO

The proliferations of cyanobacteria are increasingly prevalent in many rivers and water bodies due especially to eutrophication. This work aims to study in female medaka fish the toxicity, the transfer and the depuration of the anatoxin-a, a neurotoxin produced by benthic cyanobacterial biofilms. This work will provide answers regarding acute toxicity induced by single gavage by anatoxin-a and to the risks of exposure by ingestion of contaminated fish flesh, considering that data on these aspects remain particularly limited. The oral LD50 and NOAEL of a single dose of (±)-anatoxin-a were determined at 11.50 and 6.67 µg.g-1, respectively. Subsequently, the toxico-kinetics of the (±)-anatoxin-a was observed in the guts, the livers and the muscles of female medaka fish for 10 days. Anatoxin-a was quantified by high-resolution qTOF mass spectrometry coupled upstream to a UHPLC chromatographic chain. The toxin could not be detected in the liver after 12 h, and in the gut and muscle after 3 days. Overall, the medaka fish do not appear to accumulate (±)-anatoxin-a and to largely recover after 24 h following a single sub-acute oral liquid exposure at the NOAEL.


Assuntos
Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Oryzias/metabolismo , Tropanos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cianobactérias/metabolismo , Eutrofização , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Dose Letal Mediana , Fígado/efeitos dos fármacos , Fígado/metabolismo , Toxinas Marinhas/metabolismo , Modelos Teóricos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Neurotoxinas/metabolismo , Nível de Efeito Adverso não Observado , Rios/química , Toxicocinética , Tropanos/metabolismo , Poluentes Químicos da Água/metabolismo
10.
Aquat Toxicol ; 222: 105448, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32197184

RESUMO

Pyriproxyfen (PPF) is a synthetic substance and an insect juvenile hormone agonist with growth regulating effect. It is used worldwide as a pesticide in agriculture and public health campaigns, including the control of Aedes aegypti proliferation. It has low volatility, high Kow value and high lability in aerobic aquatic systems but is considered persistent in anaerobic systems, with a half-life of 288.9 days. The objective of this study is to survey the environmental contamination by pyriproxyfen in aquatic environmental matrices, to review the acute and chronic toxicity in non-target aquatic organisms and to make a risk assessment for the organisms addressed in the bibliographic survey. Pyriproxyfen quantification studies in aquatic environmental matrices are quite scarce and punctual-not representative of regional and global contamination. The water of the River Júcar (Spain) presented the highest concentration of PPF (99.59 ng L-1) among the matrices analysed, which is equivalent to 1% of the maximum dose allowed by the World Health Organization for use in drinking water. Acute and chronic aquatic toxicity studies with LC50, EC50, LOEC and NOEC values of PPF were compiled and interpreted to evaluate possible risks to non-target aquatic organisms. Pyriproxyfen caused a high risk at concentrations detected in aquatic environments for Daphnia magna, with probable reproductive effects and occasional survival risk. This species was the most sensitive to the pesticide, with the lowest estimated concentration of 50 % of effect values, followed by a freshwater fish (Xiphophorus maculatus) and estuarine crustaceans (Eurytemora affinis and Leander tenuicornis). The most resistant organisms to PPF within the endpoints addressed in this review were Danio rerio (zebrafish) and Capitella sp. (polychaete). Through the species sensitivity distribution (SSD), it was possible to estimate HC5 at 0.214 µg L-1 and that 2.3 % of the species present high sensitivity to pyriproxyfen in the environmental concentration detected in river water and 25.82 % of the species are affected in the concentration allowed for lavicidal use. In order to obtain more accurate risk estimates, we suggest ecotoxicological assessments in other species, covering various taxa, with emphasis on microcrustaceans due to their fundamental role in the aquatic food web and taxonomic proximity to pesticide target organisms. Furthermore, additional studies of contamination in aquatic environmental matrices are required, with particular attention to freshwater and estuarine environments due to the proximity to the sources of pyriproxyfen and environmental characteristics suggesting high accumulation. Thus, it will be possible to estimate realistic exposure levels and risks in different environments, contributing to effective and safe decision making, integrating development, public health and environmental policy.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Praguicidas/toxicidade , Piridinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Ciprinodontiformes/crescimento & desenvolvimento , Daphnia/efeitos dos fármacos , Ecotoxicologia , Dose Letal Mediana , Nível de Efeito Adverso não Observado , Medição de Risco , Rios/química , Espanha , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Peixe-Zebra/crescimento & desenvolvimento
11.
J Toxicol Sci ; 45(3): 151-162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32147638

RESUMO

Information on the safety of chemical substances in patients with various preexisting conditions remains limited. Acetaminophen was added to the basal diet at 0, 80, 253, 800, 2530, or 8000 ppm and administered to type 2 diabetes mellitus rats (GK/Jcl) and the control male rats (Wistar) for 13 weeks. Both strains treated with 8000 ppm acetaminophen (561.4 and 567.7 mg/kg body weight/day, GK/Jcl and Wistar rats, respectively) showed decreased levels of red blood cell counts, blood urea nitrogen, creatinine, and total bilirubin compared to those of non-treated rats. Treatment with 8000 ppm of acetaminophen reduced the blood glucose and hemoglobin A1c levels of GK/Jcl rats. An increase in the relative weights of the kidneys and liver, and a decrease in the weight of the salivary glands were observed in both GK/Jcl and Wistar rats treated with 8000 ppm acetaminophen relative to those of non-treated control rats. Microscopically, both strains treated with 2530 (174.3 and 164.2 mg/kg body weight/day, GK/Jcl and Wistar rats, respectively) or 8000 ppm acetaminophen showed hepatocellular hypertrophy and degenerative lesions in the salivary glands, whereas similar lesions were not observed in non-treated rats. In conclusion, the no-observed-adverse-effect-level of acetaminophen was 800 ppm in both diabetic and control rats.


Assuntos
Acetaminofen/toxicidade , Diabetes Mellitus Tipo 2/fisiopatologia , Nível de Efeito Adverso não Observado , Animais , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Hipertrofia , Masculino , Ratos Wistar
12.
Toxicon ; 177: 16-24, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32056831

RESUMO

Palytoxin is an emergent toxin in Europe and one of the most toxic substances know to date. The toxin disrupts the physiological functioning of the Na+/K+-ATPase converting the enzyme in a permeant cation channel. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Several reports have previously investigated the oral and intraperitoneal toxicity of PLTX in mice. However, in all cases short observation periods (24 and 48 h) after toxin administration were evaluated. In this work, single oral or intraperitoneal doses of PLTX were administered to healthy mice and surviving animals were followed up for 96 h. The data obtained here allowed us to calculate the oral and intraperitoneal lethal doses 50 (LD50) which were in the range of the values previously described. Surprisingly, the oral NOAEL for PLTX was more than 10 times lower than that previously described, a fact that indicates the need for the reevaluation of the levels of the toxin in edible fishery products.


Assuntos
Acrilamidas/toxicidade , Venenos de Cnidários/toxicidade , Testes de Toxicidade Aguda , Animais , Humanos , Dose Letal Mediana , Camundongos , Nível de Efeito Adverso não Observado , ATPase Trocadora de Sódio-Potássio/metabolismo
13.
J Toxicol Sci ; 45(2): 95-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32062621

RESUMO

We present a systematic, comprehensive and reproducible weight-of-evidence approach for predicting the no-observed-adverse-effect level (NOAEL) for systemic toxicity by using read-across and quantitative structure-activity relationship (QSAR) models to fill gaps in rat repeated-dose and developmental toxicity data. As a case study, we chose valproic acid, a developmental toxicant in humans and animals. High-quality in vivo oral rat repeated-dose and developmental toxicity data were available for five and nine analogues, respectively, and showed qualitative consistency, especially for developmental toxicity. Similarity between the target and analogues is readily defined computationally, and data uncertainties associated with the similarities in structural, physico-chemical and toxicological properties, including toxicophores, were low. Uncertainty associated with metabolic similarity is low-to-moderate, largely because the approach was limited to in silico prediction to enable systematic and objective data collection. Uncertainty associated with completeness of read-across was reduced by including in vitro and in silico metabolic data and expanding the experimental animal database. Taking the "worst-case" approach, the smallest NOAEL values among the analogs (i.e., 200 and 100 mg/kg/day for repeated-dose and developmental toxicity, respectively) were read-across to valproic acid. Our previous QSAR models predict repeated-dose NOAEL of 148 (males) and 228 (females) mg/kg/day, and developmental toxicity NOAEL of 390 mg/kg/day for valproic acid. Based on read-across and QSAR, the conservatively predicted NOAEL is 148 mg/kg/day for repeated-dose toxicity, and 100 mg/kg/day for developmental toxicity. Experimental values are 341 mg/kg/day and 100 mg/kg/day, respectively. The present approach appears promising for quantitative and qualitative in silico systemic toxicity prediction of untested chemicals.


Assuntos
Ácido Valproico/toxicidade , Feminino , Previsões , Humanos , Masculino , Nível de Efeito Adverso não Observado , Relação Quantitativa Estrutura-Atividade
14.
Environ Int ; 137: 105505, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32014789

RESUMO

In line with the 3R concept, nanotoxicology is shifting from a phenomenological to a mechanistic approach based on in vitro and in silico methods, with a consequent reduction in animal testing. Risk Assessment (RA) and Life Cycle Assessment (LCA) methodologies, which traditionally rely on in vivo toxicity studies, will not be able to keep up with the pace of development of new nanomaterials unless they adapt to use this new type of data. While tools and models are already available and show a great potential for future use in RA and LCA, currently none is able alone to quantitatively assess human hazards (i.e. calculate chronic NOAEL or ED50 values). By highlighting which models and approaches can be used in a quantitative way with the available knowledge and data, we propose an integrated pathway for the use of in vitro data in RA and LCA. Starting with the characterization of nanoparticles' properties, the pathway then investigates how to select relevant in vitro human data, and how to bridge in vitro dose-response relationships to in vivo effects. If verified, this approach would allow RA and LCA to stir up the development of nanotoxicology by giving indications about the data and quality requirements needed in risk methodologies.


Assuntos
Simulação por Computador , Nanoestruturas , Medição de Risco , Animais , Humanos , Nanoestruturas/toxicidade , Nível de Efeito Adverso não Observado , Testes de Toxicidade
15.
Environ Geochem Health ; 42(9): 2943-2962, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32067195

RESUMO

Metallurgical industrial processes have been reported to cause higher aluminium (Al) exposure in humans through plant food intake due to higher soil Al content and acidification of soil resulted from industrial acid rains. Mandi-Gobindgarh is critically environmentally polluted steel industrial town in India in which Al is used for deoxidation, grain refining and alloying in steel production. The Al processing has been reported to release Al into the environment, and therefore present study was undertaken to investigate the dietary Al exposure in children and adult population of Mandi-Gobindgarh from consumption of vegetable food stuffs grown in the fields around steel industries. Thirteen vegetable types including fruit vegetables, root vegetables, and leafy vegetables (LVs) along with soil samples were collected from agricultural fields around M-site (Mandi-Gobindgarh industrial site) and C-site (control non-industrial site) and analysed for Al on WD-XRF. Higher vegetable Al content was reported due to higher soil Al content and higher acidic soil pH at M-site than C-site. Correlation coefficient data have shown positive correlation of plant/vegetable Al with soil Al whereas negative correlation with soil pH at both the sites. Hierarchical cluster analysis based on vegetable Al content and bioaccumulation factor depicted higher number of clusters of vegetables at M-site (3-clusters) than C-site (2-clusters). The hazard quotients for Al intake in children and adults were found less than one. However, the weekly dietary Al exposure data have shown more than provisional tolerable weekly intake of 2 mg/kgbw/week in them from two LVs (Spinach and Brassica) from M-site than C-site which increases health concerns in humans from Mandi-Gobindgarh.


Assuntos
Alumínio/análise , Alumínio/toxicidade , Exposição Dietética/efeitos adversos , Contaminação de Alimentos/análise , Verduras/química , Adulto , Criança , Cidades , Análise por Conglomerados , Frutas/química , Humanos , Índia , Metalurgia , Nível de Efeito Adverso não Observado , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidade
16.
Artigo em Inglês | MEDLINE | ID: mdl-31947699

RESUMO

OBJECTIVE: This study was conducted to evaluate the acute and subchronic toxicity of gardenia yellow, a natural colorant widely used in China and other Asian countries. An acute toxicity test was performed in S-D rats of both genders and the lethal dose (LD50) of per oral gardenia yellow was estimated to be more than 15.0 g/kg·bw. In the subchronic study, gardenia yellow was orally administered to rats by gavage at doses of 0, 0.50, 1.50 and 4.50 g/kg·bw/day for 90 days followed by a recovery period of 28 days. No appreciable toxic-related changes were observed in the 0.50 g/kg·bw/day group. When the animals received gardenia yellow at 1.50 g/kg·bw/day or more, body weight loss was observed, and pigments began to deposit in several vital organs, resulting in significant changes of several hematological and biochemical indicators related to the nutritional status of the body, liver and kidney function, more severe in the high dose group. In the recovery period, the alterations of the clinical symptoms and parameters were relieved a lot. Based on the results of the current study, the no observed adverse effect level (NOAEL) of gardenia yellow E500 in rats was set to be 0.50 g/kg·bw/day.


Assuntos
Gardenia/toxicidade , Extratos Vegetais/toxicidade , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Dose Letal Mediana , Fígado/efeitos dos fármacos , Masculino , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
17.
Food Chem ; 313: 126156, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31931426

RESUMO

Low calorie foods are products designed to replace complete meals or to control snacking in many hypocaloric diets. These products provide many nutrients to the human diet, but little is known about their mineral elements composition. Here we study the mineral profile of weight loss related products, including the analysis of 22 elements (As, Ba, Be, Bi, Cd, Co, Cr, Cu, K, Mn, Mo, Na, Ni, P, Pb, Th, Tl, Sb, U, V, Y and Zn) in 73 commercial products marketed in Spain. In general a portion of these products provide up to 20-30% of the daily dietary reference intake of essential trace minerals like Cr or Mo. On the contrary, some of these foods have large concentrations of toxic minerals like As, Cd or Pb. In fact, the intake of those products with higher concentrations of toxic elements during a weight loss program could pose a risk to human health.


Assuntos
Fármacos Antiobesidade/química , Dieta Redutora , Contaminação de Alimentos/análise , Minerais/análise , Fármacos Antiobesidade/análise , Análise de Alimentos , Humanos , Metais/análise , Nível de Efeito Adverso não Observado , Medição de Risco , Espanha , Oligoelementos/análise
18.
Food Chem ; 313: 126135, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31951883

RESUMO

Persistent halogenated compounds (PHCs) contamination has become a major concern over the world. Here we investigated occurrence, spatial distributions, congener profiles, as well as health risks of PHCs in farmed golden pompano in China using gas chromatography/mass spectrometry (GC/MS). The concentrations of PCBs, PBDEs and OCPs were in the range of 0.78-4.79 ng/g wet weight (ww), not detected (nd)-1.14 ng/g ww and 1.1-38.8 ng/g ww, respectively. Furthermore, ρ,ρ'-DDT, ο,ρ'-DDT and PCB 101 were the dominant PHC contaminants. The estimated daily intakes of PHCs through consumption of golden pompano were up to 12.86 and 131.34 ng/kg body weight/day based on the mean and 95th concentrations determined in golden pompano, respectively. Risk-based analysis indicates that target PHCs in golden pompano would not pose risks to human. Our study presents the first report of a nationwide survey of PHCs contamination in farmed golden pompano in China.


Assuntos
Contaminação de Alimentos/análise , Hidrocarbonetos Clorados/análise , Perciformes , Poluentes Químicos da Água/análise , Animais , Aquicultura , Peso Corporal , China , Produtos Pesqueiros/análise , Cromatografia Gasosa-Espectrometria de Massas , Éteres Difenil Halogenados/análise , Humanos , Nível de Efeito Adverso não Observado , Praguicidas/análise , Bifenilos Policlorados/análise
19.
Toxicol Lett ; 322: 111-119, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31981686

RESUMO

The increasing concern of possible adverse effects on human health derived from occupational engineered nanomaterials (ENMs) exposure is an issue addressed by entities related to provide guidelines and/or protocols for ENMs regulation. Here we analysed 17 entities from America, Europe and Asia, and some of these entities provide limits of exposure extrapolated from the non-nanosized counterparts of ENMs. The international landscape shows that recommendations are mostly made for metal oxide based ENMs and tonnage is one of the main criteria for ENMs registration, however, sub-nanometric ENMs are emerging and perhaps a novel category of ENMs will appear soon. We identify that besides the lack of epidemiological evidence of ENMs toxicity in humans and difficulties in analysing the toxicological data derived from experimental models, the lack of information on airborne concentrations of ENMs in occupational settings is an important limitation to improve the experimental designs. The development of regulations related to ENMs exposure would lead to provide safer work places for ENMs production without delaying the nanotechnology progress but will also help to protect the environment by taking opportune and correct measures for nanowaste, considering that this could be a great environmental problem in the coming future.


Assuntos
Nanoestruturas/efeitos adversos , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Animais , Relação Dose-Resposta a Droga , Guias como Assunto , Humanos , Nível de Efeito Adverso não Observado , Exposição Ocupacional/legislação & jurisprudência , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/normas , Saúde do Trabalhador/legislação & jurisprudência , Saúde do Trabalhador/normas , Formulação de Políticas , Medição de Risco , Fatores de Risco , Níveis Máximos Permitidos
20.
Food Chem Toxicol ; 137: 111128, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31952986

RESUMO

The pathogenesis of Parkinson's disease has not been fully clarified yet but its cause is known to be multifactorial. One of these factors is oxidative stress induced by exposure to environmental toxifiers. We studied the effect of Bisphenol A (BPA) at concentrations of 0.5 mM and 1 mM, the concentration of 1 mM corresponding to Lowest Observed Adverse Effect Level (LOAEL) for humans in adult Drosophila melanogaster. The BPA induced oxidative stress was established by increased levels of malondialdehyde, reactive species, and decreased activity of the antioxidant enzymes superoxide dismutase and catalase, and detoxificant enzyme glutathione-S-transferase. Associated with oxidative stress, there was a reduction of acetylcholinesterase activity and a reduction of dopamine levels, which are related to the decreased locomotion activity as observed in negative geotaxis, open field and equilibrium behaviors in group exposed to 1 mM of BPA. Oxidative stress also impaired mitochondrial and cellular metabolic activity in the head causing an increase in the mortality of flies exposed to both BPA concentrations. Therefore, BPA induced Parkinsonian-like changes in flies and it is possible that the oxidative stress is closely related to this effect, providing new insights for future studies.


Assuntos
Compostos Benzidrílicos/toxicidade , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/crescimento & desenvolvimento , Doença de Parkinson/etiologia , Fenóis/toxicidade , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Feminino , Glutationa Transferase/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nível de Efeito Adverso não Observado , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
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