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1.
Neurol India ; 70(5): 1953-1957, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352593

RESUMO

Background: Children aged 5 to 14 years are employed in the informal units of footwear making and are exposed to a mixture of organic solvents present in the adhesives. Organic solvents are reported to be toxic to the neurobehavioral system. Objective: The present study was undertaken among the working children of informal footwear units of Agra to assess neurobehavioral functions using neurobehavioral tests. Materials and Methods: The study included 151 working children and 157 school children. We used the interview technique to collect the data regarding demographic, occupational, personal, and clinical characteristics using a pre-designed and pre-tested proforma. Each study participant was then subjected to a neurobehavioral test battery that included digit symbol test, finger dexterity, tweezer dexterity, vocabulary test, picture completion, and maze completion test. Results: The mean age of working children was 10.8 ± 1.5 years and that of school children was 11.0 ± 1.5 years. Except for the vocabulary test scores, all other test scores were significantly lower among working children as compared with the school children. Conclusion: The study revealed that the working children in informal footwear making units are exposed to a mixture of chemicals that affect their neurobehavioral function as reflected by poor neurobehavioral test battery (NBT) scores.


Assuntos
Dedos , Exposição Ocupacional , Criança , Humanos , Destreza Motora , Solventes/toxicidade , Testes Neuropsicológicos
2.
Chemosphere ; 299: 134415, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35351475

RESUMO

Deep Eutectic Systems (DES) have emerged as a "green alternative" to organic solvents and have been coined as biocompatible and biodegradable. However, the number of studies concerning the real biodegradability and biocompatibility are scarce. Thus, to study the toxicity of certain DES, two different approaches were used: i) zebrafish exposure via water, where the system (DES) was tested at potentially realistic environmental concentrations and ii) via intraperitoneal injection, where the system was tested in different concentrations, relevant to the pharmaceutical industry. These studies were performed using zebrafish, a standardized animal model often used in biomedicine and toxicological assays. The results show low toxicity according to tested concentrations (up to 73.47 µM), when the system CA:T:W, with a 2:1:3 molar ratio, was tested through exposure via water and also in the intraperitoneal injection tests with concentrations up to 6000 µM. The activity of different enzymes involved in antioxidant pathways (glutathione S-transferase, catalase, glutathione peroxidase), the total antioxidant capacity (TAC) and lipoperoxidation (MDA content) were determined suggesting low toxicity of the tested system (DES). The promising results herein presented show that DES present the potential to be used as the new class of green solvents, not only for use in the pharmaceutical industry, but also in cosmetic and chemical engineering processes without causing negative impact on living organisms.


Assuntos
Solventes Eutéticos Profundos , Peixe-Zebra , Animais , Antioxidantes , Solventes/química , Solventes/toxicidade , Água/química
3.
J Appl Toxicol ; 40(5): 691-705, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32030785

RESUMO

Two proposition 65 no-significant-risk level (NSRL)-type values were derived for 2-nitropropane (2-NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2-NP during indoor application of paint from a spray can containing the solvent 1-nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2-NP single exposure inhalation studies in Sprague-Dawley rats. Several BMD models provided an acceptable fit for the male rat hepatocellular carcinoma incidence data (gamma, log-probit, log-logistic and multistage); therefore, the mean of the BMD lower limits from each model were used as the point of departure to derive the inhalation cancer potency. The oral human cancer potency was derived from the inhalation human cancer potency based on the ratio of the uptake factors for inhalation vs. oral routes. The derived inhalation and oral NSRLs are 67 µg/day and 32 µg/day, respectively. For the inhalation and dermal exposure assessment, three key factors were analyzed: the 2-NP residual concentration in the spray paint product, the mass of spray paint used and the frequency of use. Based on the screening exposure assessment, potential consumer inhalation and dermal exposure to 2-NP from indoor application of paint from a spray can does not exceed our proposed NSRLs, and a warning label is therefore not required for spray can products containing the solvent 1-nitropropane where 2-NP is a minor contaminant.


Assuntos
Nitroparafinas/toxicidade , Propano/análogos & derivados , Solventes/toxicidade , Administração por Inalação , Administração Oral , Animais , Humanos , Masculino , Sprays Nasais , Nitroparafinas/administração & dosagem , Sprays Orais , Propano/administração & dosagem , Propano/toxicidade , Ratos Sprague-Dawley , Medição de Risco , Solventes/administração & dosagem , Toxicocinética
4.
J Appl Toxicol ; 40(4): 483-492, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31736102

RESUMO

Carrier solvents are used frequently in toxicity testing to assist hydrophobic chemicals into solution, but such solvents may have toxic effects on test subjects. Amphibians are model organisms in toxicity studies; however, little is known about the direct effects of solvents on native amphibians. Following modifications to standardized guidelines for native species, we used acute 96-hour exposures to assess the direct effects of three common solvents on survival, differences in morphology and occurrence of abnormalities of northern leopard frog larvae (Lithobates pipiens). The solvents, dimethyl sulfoxide (DMSO), ethanol (ETOH) and acetone (ACE) were used at nominal concentrations ranging from 1 to 100 µL/L. We also conducted a 30-day exposure to assess the direct chronic effects of DMSO at 1 and 5 µL/L, on larval growth, development and sex differentiation, but found no effects. Acute exposure to solvents also had no effect on the survival of larvae, but we found significant abnormalities in tadpoles acutely exposed to 100 µL/L ACE. Acute exposure to DMSO and ETOH had further concentration-dependent effects on larval morphological traits. Our study suggests that DMSO and ETOH at ≤20 µL/L may be used as solvents in amphibian ecotoxicological studies, but ACE should be limited to ≤50 µL/L in ecotoxicity studies and perhaps much less (≤10 µL/L) in studies with other amphibians, based on a review of existing literature. We emphasize pilot studies when using solvents on acute and chronic ecotoxicity tests, using native amphibians.


Assuntos
Acetona/toxicidade , Dimetil Sulfóxido/toxicidade , Ecotoxicologia , Embrião não Mamífero/efeitos dos fármacos , Etanol/toxicidade , Rana pipiens/embriologia , Solventes/toxicidade , Testes de Toxicidade , Animais , Relação Dose-Resposta a Droga , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Masculino , Medição de Risco , Diferenciação Sexual/efeitos dos fármacos , Fatores de Tempo
5.
Hum Reprod ; 34(5): 903-919, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30927411

RESUMO

STUDY QUESTION: Is there an association between maternal occupational exposure to solvents, pesticides and metals as assessed by expert-based assessment and congenital anomalies in the offspring? SUMMARY ANSWER: There is an association between maternal occupational exposure to solvents and congenital anomalies in the offspring, including neural tube defects, congenital heart defects and orofacial clefts. WHAT IS KNOWN ALREADY: One important environmental risk factor for development of congenital anomalies is maternal occupational exposure to chemicals in the workplace prior to and during pregnancy. A number of studies have assessed the association with often conflicting results, possibly due to different occupational exposure assessing methods. STUDY DESIGN, SIZE, DURATION: For this systematic review with meta-analysis, the search terms included maternal occupation, exposure, congenital anomalies and offspring. Electronic databases MEDLINE and EMBASE were searched for English studies up to October 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two reviewers independently screened all citations identified by the search. Case-control studies and cohort studies were included if (I) they reported on the association between maternal occupational exposure to solvents, pesticides or metals and congenital anomalies, and (II) assessment of occupational exposure was performed by experts. Data on study characteristics, confounders and odds ratios (ORs) were extracted from the included studies for four subgroups of congenital anomalies. Methodological quality was assessed using the Newcastle-Ottawa Scale. In the meta-analysis, random effects models were used to pool estimates. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 2806 titles and abstracts and 176 full text papers were screened. Finally, 28 studies met the selection criteria, and 27 studies could be included in the meta-analysis. Our meta-analysis showed that maternal occupational exposure to solvents was associated with neural tube defects (OR: 1.51, 95%CI: 1.09-2.09) and congenital heart defects (OR: 1.31, 95%CI:1.06-1.63) in the offspring. Also maternal occupational exposure to glycol ethers, a subgroup of solvents, was associated with neural tube defects (OR: 1.93, 95%CI: 1.17-3.18) and orofacial clefts (OR: 1.95, 95%CI: 1.38-2.75) in the offspring. Only one study investigated the association between maternal occupational exposure to solvents and hypospadias and found an association (OR: 3.63, 95%CI: 1.94-7.17). Results of the included studies were consistent. In our meta-analysis, we found no associations between occupational exposure to pesticides or metals and congenital anomalies in the offspring. LIMITATIONS, REASONS FOR CAUTION: A limited number of studies was included, which made it impossible to calculate pooled estimates for all congenital anomalies, analyse individual chemicals or calculate exposure-response relations. Bias could have been introduced because not all included studies corrected for potentially confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: Employers and female employees should be aware of the possible teratogenic effects of solvent exposure at the workplace. Therefore, is it important that clinicians and occupational health specialist provide women with preconception advice on occupational solvent exposure, to reduce the congenital anomaly risk. STUDY FUNDING/COMPETING INTEREST(S): NSp was paid by the Graduate School of Medical Sciences (MD/PhD program), UMCG, Groningen, the Netherlands. EUROCAT Northern Netherlands is funded by the Dutch Ministry of Health, Welfare and Sports. There are no competing interests. REGISTRATION NUMBER: CRD42017053943.


Assuntos
Anormalidades Congênitas/epidemiologia , Exposição Materna/efeitos adversos , Exposição Ocupacional/efeitos adversos , Teratogênicos/toxicidade , Anormalidades Congênitas/etiologia , Anormalidades Congênitas/prevenção & controle , Feminino , Humanos , Exposição Materna/prevenção & controle , Exposição Materna/normas , Metais/normas , Metais/toxicidade , Exposição Ocupacional/prevenção & controle , Exposição Ocupacional/normas , Saúde Ocupacional/normas , Praguicidas/normas , Praguicidas/toxicidade , Prevalência , Solventes/normas , Solventes/toxicidade , Teratogênicos/normas
6.
Ecotoxicol Environ Saf ; 174: 455-458, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30852310

RESUMO

Due to various desirable physicochemical properties, ionic liquids (ILs) are still gaining in popularity. ILs have been recurrently considered green solvents. However, environmental, health and safety assessments of ILs have raised certain doubts about their benignness, and their greenness status is currently unclear. To clarify the situation on their greenness, we perform a comprehensive assessment of more than 300 commercially available ILs. We apply multicriteria decision analysis, the tool that allows ranking many alternatives according to relevant criteria. They are toxicity towards various organisms, biodegradability, hazard statements and precautionary measures during their handling. We incorporated organic solvents to rankings, as their greenness is better described, so they serve as greenness reference points. The ranking results obtained considering the whole set of criteria show that ILs are placed between recommended polar solvents and problematic/undesirable non polar organic solvents in terms of greenness. However, the exclusion of toxicity data due to unavailability of endpoints results in assessment of ILs as greener than most of organic solvents.


Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Líquidos Iônicos/toxicidade , Solventes/toxicidade , Biodegradação Ambiental , Técnicas de Apoio para a Decisão , Poluentes Ambientais/química , Química Verde , Líquidos Iônicos/química , Solventes/química
7.
Int J Toxicol ; 37(2): 125-143, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29357719

RESUMO

The National Academy of Science has recommended that a risk of bias (RoB; credibility of the link between exposure and outcome) assessment be conducted on studies that are used as primary data sources for hazard identification and dose-response assessment. Few applications of such have been conducted. Using trichloroethylene and congenital heart defects (CHDs) as a case study, we explore the role of RoB in chemical risk assessment using the National Toxicology Program's Office of Health Assessment and Translation RoB tool. Selected questions were tailored to evaluation of CHD and then applied to 12 experimental animal studies and 9 epidemiological studies. Results demonstrated that the inconsistent findings of a single animal study were likely explained by the limitations in study design assessed via RoB (eg, lack of concurrent controls, unvalidated method for assessing outcome, unreliable statistical methods, etc). Such limitations considered in the context of the body of evidence render the study not sufficiently reliable for the development of toxicity reference values. The case study highlights the utility of RoB as part of a robust risk assessment process and specifically demonstrates the role RoB can play in objectively selecting candidate data sets to develop toxicity values.


Assuntos
Cardiopatias Congênitas , Revisões Sistemáticas como Assunto , Tricloroetileno , Animais , Feminino , Humanos , Gravidez , Viés , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/epidemiologia , Troca Materno-Fetal , Medição de Risco/métodos , Solventes/toxicidade , Tricloroetileno/toxicidade
8.
Regul Toxicol Pharmacol ; 92: 439-457, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29069582

RESUMO

The European chemical control regulation (REACH) requires that data on physical/chemical, toxicological and environmental hazards be compiled. Additionally, REACH requires formal assessments to ensure that substances can be safely used for their intended purposes. For health hazard assessments, reference values (Derived No Effect levels, DNELs) are calculated from toxicology data and compared to estimated exposure levels. If the ratio of the predicted exposure level to the DNEL, i.e. the Risk Characterization Ratio (RCR), is less than 1, the risk is considered controlled; otherwise, additional Risk Management Measures (RMM) must be applied. These requirements pose particular challenges for complex substances. Herein, "white spirit", a complex hydrocarbon solvent, is used as an example to illustrate how these procedures were applied. Hydrocarbon solvents were divided into categories of similar substances. Representative substances were identified for DNEL determinations. Adjustment factors were applied to the no effect levels to calculate the DNELs. Exposure assessments utilized a standardized set of generic exposure scenarios (GES) which incorporated exposure predictions for solvent handling activities. Computer-based tools were developed to automate RCR calculations and identify appropriate RMMs, allowing consistent communications to users via safety data sheets.


Assuntos
Exposição Ambiental/efeitos adversos , Substâncias Perigosas/toxicidade , Exposição Ocupacional/efeitos adversos , Monitoramento Ambiental/métodos , União Europeia , Humanos , Hidrocarbonetos/toxicidade , Valores de Referência , Medição de Risco , Solventes/toxicidade
9.
Water Res ; 125: 237-248, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28865373

RESUMO

Ionic liquids (ILs) are much known for their promising alternative for volatile solvents in industries and gained popularity as a greener solvent, however industrial effluent discharge containing ILs are also increasing. There is a scarcity of information on the toxicity of ILs; the present study will explore different facts about their harmfulness. The toxic effects of five different ILs: [C4MIM]Br, [Hx3PC14]N(CN)2, [C10MIM]BF4, [BTDA]Cl and [C4MPY]Cl were analysed on bacteria, fungi, plant and animal cells. Both Gram positive and negative bacteria were found to be more susceptible to [C10MIM]BF4 and [BTDA]Cl than [C4MIM]Br, [Hx3PC14]N(CN)2 and [C4MPY]Cl, whereas fungi revealed quite a resistance to all ILs. All ILs were toxic towards Triticum aestivum affecting their roots and shoots, however [C10MIM]BF4 and [BTDA]Cl were more toxic amongst them. Studies on Allium cepa described their toxic behaviour at the genetic level by altering cell division and nuclear material. Furthermore, studies on human red blood cells described by % haemolysis in which [Hx3PC14]N(CN)2 and [BTDA]Cl exhibited higher toxicity at very lower concentrations. While the genotoxic effect on blood lymphocytes exerted by [Hx3PC14]N(CN)2, [C10MIM]BF4 and [BTDA]Cl confirmed their toxic effects on human cells.


Assuntos
Monitoramento Ambiental , Líquidos Iônicos/toxicidade , Solventes/toxicidade , Triticum/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Líquidos Iônicos/análise , Líquidos Iônicos/química , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/efeitos dos fármacos , Medição de Risco , Solventes/análise , Solventes/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química
10.
Toxicol Mech Methods ; 26(4): 238-42, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26998723

RESUMO

Occupational exposure as a painter is associated with DNA damage and development of cancer. Comet assay has been widely adopted as a sensitive and quantitative tool for DNA damage assessment at the individual cell level in populations exposed to genotoxics. The aim of this study was to assess the application of the high-throughput comet assay, to determine the DNA damage in car spray painters. The study population included 52 car spray painters and 52 unexposed subjects. A significant increase in the %TDNA median (p < 0.001) was observed in the exposed group in comparison to the unexposed group. Neither age (%TDNA: p = 0.913) nor time of exposure (%TDNA: p = 0.398) were significantly correlated with DNA damage. The car spray painters who consumed alcohol did not show a significant increase in DNA damage compared to nonalcohol consumers (p > 0.05). The results showed an increase in DNA breaks in car spray painters exposed to organic solvents and paints; furthermore, they demonstrated the application of high-throughput comet assay in an occupational exposure study to genotoxic agents.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Dano ao DNA , Linfócitos/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Pintura/análise , Solventes/toxicidade , Estudos de Casos e Controles , Ensaio Cometa , Estudos Transversais , Ensaios de Triagem em Larga Escala , Humanos , Linfócitos/patologia , Masculino , Exposição Ocupacional/análise
11.
Toxicol Ind Health ; 31(12): 1252-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23788394

RESUMO

Nowadays, there are increasing numbers of studies about synthetic chemicals according to the supply demands of bioactive chemicals. The current study aims to investigate genotoxic potential of bioactive synthetic pyridine compounds, phenyl-3-pyridinylmethanone (1), p-tolyl-3-pyridinylmethanone (2), and 4-methoxyphenyl-3-pyridinylmethanone (3), using Ames/Salmonella and Escherichia coli WP2 bacterial reversion mutagenicity test systems. The mutant bacterial tester strains sodium azide-sensitive Salmonella typhimurium TA1535, 9-aminoacridine-sensitive S. typhimurium TA1537, and N-methyl-N'-nitro-N-nitrosoguanidine-sensitive E. coli WP2uvrA were used to detect the mutagenic potential of the test compounds. The results indicated that none of the test substances showed significant mutagenic activity on S. typhimurium TA1535, TA1537, and E. coli WP2uvrA bacterial strains up to 1 µg/plate concentrations.


Assuntos
Cetonas/toxicidade , Mutagênese/efeitos dos fármacos , Mutagênicos/toxicidade , Piridinas/toxicidade , Solventes/toxicidade , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Viabilidade Microbiana/efeitos dos fármacos , Testes de Mutagenicidade , Concentração Osmolar , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Salmonella typhimurium/crescimento & desenvolvimento , Salmonella typhimurium/metabolismo , Turquia
12.
Environ Sci Technol ; 48(18): 10821-8, 2014 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-25167095

RESUMO

Carbon dioxide (CO2) absorption with aqueous amine solvents is a method of carbon capture and sequestration (CCS) from flue gases. One concern is the possible release of amine solvents and degradation products into the atmosphere, warranting evaluation of potential pulmonary effects from inhalation. The CCS amines monoethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP) underwent oxidative and CO2-mediated degradation for 75 days. C57bl/6N mice were exposed for 7 days by inhalation of 25 ppm neat amine or equivalant concentration in the degraded mixture. The aqueous solutions were nebulized to create the inhalation atmospheres. Pulmonary response was measured by changes in inflammatory cells in bronchoalveolar lavage fluid and cytokine expression in lung tissue. Ames mutagenicity and CHO-K1 micronucleus assays were applied to assess genotoxicity. Chemical analysis of the test atmosphere and liquid revealed complex mixtures, including acids, aldehydes, and other compounds. Exposure to oxidatively degraded MEA increased (p < 0.05) total cells, neutrophils, and lymphocytes compared to control mice and caused inflammatory cytokine expression (statistical increase at p < 0.05). MEA and CO2-degraded MEA were the only atmospheres to show statistical (p < 0.05) increase in oxidative stress. CO2 degradation resulted in a different composition, less degradation, and lower observed toxicity (less magnitude and number of effects) with no genotoxicity. Overall, oxidative degradation of the amines studied resulted in enhanced toxicity (increased magnitude and number of effects) compared to the neat chemicals.


Assuntos
Aminas/toxicidade , Sequestro de Carbono , Carbono/análise , Solventes/toxicidade , Testes de Toxicidade , Administração por Inalação , Aminas/química , Animais , Cromatografia Líquida , Etanolamina/química , Etanolamina/toxicidade , Pulmão/metabolismo , Masculino , Espectrometria de Massas , Camundongos Endogâmicos C57BL , Mutagênicos/toxicidade , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
13.
J Occup Health ; 56(3): 205-14, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24739373

RESUMO

OBJECTIVE: Occurrence of cholangiocarcinoma was recently reported at a high incidence rate among the employees working for an offset printing company in Osaka, Japan. 1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are suspected to be the causes of the cancer, as they had been used as ink cleaners in large amounts. However, it is not clear whether these chlorinated organic solvents played a role in the occurrence of cholangiocarcinoma or why the incidence rate is so high among the workers in this industry. To provide possible evidence for this severe occupational problem, we investigated the genotoxic effects of 1,2-DCP and DCM. METHODS: Male B6C3F1 and gpt Delta C57BL/6J mice were exposed by inhalation to the individual solvents or both solvents at multiple concentrations including the levels that were possibly present in the workplaces. The genotoxicity was analyzed by Pig-a gene mutation and micronuclei assays in peripheral blood and gpt mutation and comet assays in the livers of mice after repeated inhalation of 1,2-DCP or/and DCM. RESULTS: The Pig-a mutant frequencies and micronuclei incidences were not significantly increased by exposure of either 1,2-DCP or/and DCM at any concentration, suggesting there was no genotoxic potential in bone marrow for both solvents. In the liver, DNA damage, as measured by the comet assay, was dose dependently increased by 1,2-DCP but not by DCM. The gpt mutant frequency was 2.6-fold that of the controls in the co-exposure group. CONCLUSIONS: These results indicate that 1,2-DCP showed stronger genotoxicity in the liver and that the genotoxic effects were greatly enhanced by simultaneous exposure to DCM.


Assuntos
Cloreto de Metileno/toxicidade , Mutagênicos/toxicidade , Propano/análogos & derivados , Solventes/toxicidade , Animais , Medula Óssea/efeitos dos fármacos , Dano ao DNA , Exposição por Inalação , Fígado/efeitos dos fármacos , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Propano/toxicidade
14.
Regul Toxicol Pharmacol ; 69(1): 78-90, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24613484

RESUMO

The availability of experimental data suitable as a basis to quantify human variability in response to chemical exposure has increased in recent years. It has enabled scientifically based, data driven adjustment factors (AF) to be deployed in the risk assessment process. As part of this development, we derive AF for human toxicokinetic variability (HK) for three lipophilic organic solvents; toluene, styrene and methyl chloride using physiologically based pharmacokinetic (PBPK) models in a population framework. The Monte Carlo simulations cover the influence of age and gender on toxicokinetic variability in the general population, as well as workplace ventilation rates and fluctuations in exposure level and workload in adult male and female workers. The derived AFHK are below 2.2 (95th percentile) for all subpopulations, exposure scenarios and chemicals, except for markers of acute effects in workers, where the factors are up to 5.0.


Assuntos
Cloreto de Metila/toxicidade , Estireno/toxicidade , Tolueno/toxicidade , Adolescente , Adulto , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Método de Monte Carlo , Exposição Ocupacional/análise , Medição de Risco , Solventes/toxicidade , Toxicocinética , Ventilação , Local de Trabalho
15.
Regul Toxicol Pharmacol ; 68(3): 387-401, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24491968

RESUMO

1,4-Dioxane is found in consumer products and is used as a solvent in manufacturing. Studies in rodents show liver tumors to be consistently reported after chronic oral exposure. However, there were differences in the reporting of non-neoplastic lesions in the livers of rats and mice. In order to clarify these differences, a reread of mouse liver slides from the 1978 NCI bioassay on 1,4-dioxane in drinking water was conducted. This reread clearly identified dose-related non-neoplastic changes in the liver; specifically, a dose-related increase in the hypertrophic response of hepatocytes, followed by necrosis, inflammation and hyperplastic hepatocellular foci. 1,4-Dioxane does not cause point mutations, DNA repair, or initiation. However, it appears to promote tumors and stimulate DNA synthesis. Using EPA Guidelines (2005), the weight of the evidence suggests that 1,4-dioxane causes liver tumors in rats and mice through cytotoxicity followed by regenerative hyperplasia. Specific key events in this mode of action are identified. A Reference Dose (RfD) of 0.05mg/kgday is proposed to protect against regenerative liver hyperplasia based on a benchmark dose (BMD) approach. Based on this RfD, a maximum contaminant level goal of 350µg/L is proposed using a default relative source contribution for water of 20%.


Assuntos
Dioxanos/toxicidade , Neoplasias Hepáticas/induzido quimicamente , Fígado/efeitos dos fármacos , Solventes/toxicidade , Administração Oral , Animais , Dioxanos/normas , Relação Dose-Resposta a Droga , Água Potável/normas , Feminino , Hiperplasia/induzido quimicamente , Hiperplasia/patologia , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Modelos Biológicos , Medição de Risco , Solventes/normas
16.
Toxicol Mech Methods ; 24(4): 243-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24236478

RESUMO

Paint thinners are organic-solvent complex mixtures frequently used by car painters around the world in industries and shops. Some studies have revealed the oxidative effect induced by thinner inhalation; however, its genotoxic effect is poorly studied. The aim of this study was to assess the cytotoxicity, genomic damage and DNA repair in vitro induced by commercial paint thinner 0.14 in human lymphocytes. Cytotoxicity was determined by cell-viability analysis with trypan blue after 4 h treatment with different thinner concentrations (0.025 to 1.2 µL/mL). Genomic damage was evaluated by means of the alkaline single-cell gel electrophoresis (SCGE; pH > 13) in treated cultures after 1 h with three low-cytotoxic thinner concentrations (0.05, 0.1 and 0.2 µL/mL). In order to evaluate the genomic DNA repair, one set of SCGE slides was prepared immediately after treatment, and another one was prepared after 4 h of liquid-holding recovery. A significant level of cytotoxicity was observed over the entire concentration range of paint thinner in lymphocytes (F = 175.98; p ≤ 0.001). In the SCGE % tail DNA assessment, a significant increase of lymphocyte genomic damage was evidenced (F = 72.32; p < 0.001). In addition, we found a significant decrease in the % tail DNA in thinner-treated cells after liquid-holding recovery period (all p < 0.05), demonstrating that DNA primary lesions induced by low-cytotoxic thinner concentrations are efficiently repaired. In conclusion, thinner components induce cytotoxicity and genomic damage in human lymphocytes under the study conditions, possibly by oxidative and alkylative DNA damage.


Assuntos
Reparo do DNA , Linfócitos/efeitos dos fármacos , Solventes/toxicidade , Ensaio Cometa , Humanos , Técnicas In Vitro , Linfócitos/metabolismo
17.
Environ Sci Pollut Res Int ; 21(5): 3534-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24271731

RESUMO

Dimethylformamide (DMF) is a broad solvent used in the production of synthetic leather. Decades of year's research have been focused on workers in leather factories suffering from the release of DMF. However, little attention was paid on general population. Here, we examined the relationship between consistent DMF exposure and annual hospitalizations of local residents in Longwan, China, in 2008. We found a positive correlation with a relative risk (RR) increase of 1.110 for total hospitalizations. When the data were stratified by sex, we observed a higher correlation for female hospitalizations than for male hospitalizations, with RR values of 1.55 and 1.084, respectively. This might be attributed to the differences in genotypes of oxidant enzyme between gender. The significance of the correlations did not disappear after we excluded the extreme value of DMF or adjusted for SO2, NO2, and PM10. Population living near the leather factory has experienced almost constant DMF exposure, and real concern should be raised regarding such exposure. Governments should take responsibility for the protection of not only occupational workers but also residents, especially women.


Assuntos
Poluentes Atmosféricos/toxicidade , Dimetilformamida/toxicidade , Exposição Ambiental/efeitos adversos , Solventes/toxicidade , Têxteis , China/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Risco , Medição de Risco
18.
Inhal Toxicol ; 25 Suppl 2: 64-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24341848

RESUMO

CONTEXT: Manufacture of cigarettes results in tobacco by-products, some of which can be processed and added back to cigarettes. Such additions (known as reconstituted tobacco or reconstituted leaf) have been shown to reduce tar yields. A new process (termed "Deli" cast sheet) is a potential refinement of the reconstitution process. OBJECTIVE: Compare toxicity of smoke from experimental cigarettes made with reconstituted leaf with that from cigarettes made with Deli cast sheet. MATERIALS AND METHODS: Analytical chemistry, Salmonella mutagenicity and cytotoxicity assays were used to evaluate the composition biological activity of mainstream smoke from experimental cigarettes made with Deli cast sheet or with reconstituted leaf. The effect of different amounts of guar and propylene glycol in Deli cast sheet was also evaluated. RESULTS: Small increases in the amount of nitrogen oxides were found as a result of inclusion of the Deli cast sheet when compared with reconstituted leaf; no differences in cytotoxicity or mutagenicity were found. CONCLUSION: The Deli process neither significantly modified chemical composition of smoke nor affected its biological activity, as measured by the mutagenicity and cytotoxicity assays used here.


Assuntos
Qualidade de Produtos para o Consumidor , Resíduos Industriais/efeitos adversos , Nicotiana/toxicidade , Folhas de Planta/toxicidade , Fumaça/efeitos adversos , Produtos do Tabaco/efeitos adversos , Animais , Células 3T3 BALB , Sobrevivência Celular/efeitos dos fármacos , Galactanos/química , Galactanos/toxicidade , Resíduos Industriais/análise , Resíduos Industriais/economia , Mananas/química , Mananas/toxicidade , Teste de Materiais , Camundongos , Testes de Mutagenicidade , Mutagênicos/análise , Mutagênicos/química , Mutagênicos/toxicidade , Gomas Vegetais/química , Gomas Vegetais/toxicidade , Folhas de Planta/química , Propilenoglicol/química , Propilenoglicol/toxicidade , Fumaça/análise , Solventes/química , Solventes/toxicidade , Nicotiana/química , Indústria do Tabaco/economia , Produtos do Tabaco/análise , Produtos do Tabaco/economia , Testes de Toxicidade
19.
Chemosphere ; 93(2): 455-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23820537

RESUMO

In this work, the cytotoxicity and toxicity of phosphonium-based deep eutectic solvents (DESs) with three hydrogen bond donors, namely glycerine, ethylene glycol, and triethylene glycol were investigated. The cytotoxicity effect was tested using brine shrimp (Artemia salina). The toxicity was investigated using the two Gram positive bacteria Bacillus subtilis and Staphylococcus aureus, and two Gram negative bacteria Escherichia coli and Pseudomonas aeruginosa. The cytotoxicity of tested DESs was much higher than that of their individual components, indicating their toxicological behavior was different. It was also found that there was toxic effect on the studied bacteria, indicating their potential application as anti-bacterial agents. To the best of our knowledge, this is the first time the cytotoxicity and toxicity of phosphonium-based DESs were studied.


Assuntos
Citotoxinas/química , Citotoxinas/toxicidade , Compostos Organofosforados/química , Solventes/química , Solventes/toxicidade , Testes de Toxicidade , Animais , Artemia/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Ligação de Hidrogênio
20.
Ann Ig ; 25(2): 125-36, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23471450

RESUMO

OBJECTIVES: The use of organic solvents has been linked to pathologies of different apparatuses. The purpose of this study is to analyze the liver damage induced by organic solvents. MATERIALS AND METHODS: We analyzed 556 workers, 278 exposed to organic solvents (group 1) and 278 not exposed to organic solvents (group 2). The exposed group was further divided into 2 subgroups: group 1A (139 workers exposed to considerable doses) and group 1B (139 workers exposed to negligible doses). Mean and standard deviation of some liver parameters was calculated. Statistically significant differences between the liver parameters in the different groups and subgroups were detected using the t-test. Multiple linear regression models were used to examine the associations between laboratory parameters and the independent variable. RESULTS: The data so far obtained showed the existence of statistically significant differences with regard to the total protein, total bilirubin, transaminase GOT and GPT, Gamma Glutamyl Transferase (gamma-GT). CONCLUSIONS: Our results confirm that exposure to solvents can alter some liver parameters. The blood tests we used can be useful tool for the assessment of the actual occupational hazards and to verify the effectiveness of the measures taken for the prevention and protection.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Poluição do Ar em Ambientes Fechados/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Pessoal de Laboratório , Fígado/efeitos dos fármacos , Doenças Profissionais/etiologia , Exposição Ocupacional , Recursos Humanos em Hospital , Solventes/toxicidade , Compostos Orgânicos Voláteis/toxicidade , Adulto , Alanina Transaminase/sangue , Consumo de Bebidas Alcoólicas/epidemiologia , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Laboratórios Hospitalares , Pessoal de Laboratório/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/sangue , Doenças Profissionais/epidemiologia , Recursos Humanos em Hospital/estatística & dados numéricos , Fumar/epidemiologia , gama-Glutamiltransferase/sangue
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