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1.
Environ Toxicol Pharmacol ; 88: 103737, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34481063

RESUMO

Climatic conditions raise new concerns about the potential impact of heat on the absorption and kinetics of certain chemicals. The impact of 3 temperatures (21, 25 and 30 °C WBGT) on the toxicokinetics of toluene and acetone was therefore evaluated in five human subjects during controlled exposures in an inhalation chamber. Biological samples were collected and analyzed by GC-MS/MS. Increases between 4 and 85 % were observed for solvents concentrations in blood (30 vs 21 °C) while decreases in urine samples for acetone and o-cresol were measured at the end of the exposure period (4 h). Mean blood concentrations at 4 h are well correlated with temperature. Results suggest an increased absorption and/or a decreased elimination of volatile chemicals in the presence of heat. Higher increases of blood chemical concentrations were observed in heavier individuals. Further studies should include physiologically based toxicokinetic models to help in better understanding the mechanisms involved and their respective contribution.


Assuntos
Acetona/farmacocinética , Temperatura Alta , Solventes/farmacocinética , Tolueno/farmacocinética , Acetona/sangue , Acetona/urina , Adulto , Testes Respiratórios , Humanos , Exposição por Inalação , Masculino , Projetos Piloto , Absorção Cutânea , Tolueno/sangue , Tolueno/urina , Adulto Jovem
2.
Food Chem Toxicol ; 139: 111242, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32205228

RESUMO

INTRODUCTION: Exposures to volatile organic compounds and metals have previously been associated with liver diseases including steatohepatitis, although more data are needed. Benzene, toluene, ethylbenzene, xylenes, styrene (BTEXS) and metals were measured in blood samples collected between May 2012-July 2013 from volunteers participating in home visits for the Gulf Long-term Follow-up (GuLF) Study. This cross-sectional analysis evaluates associations of exposure biomarkers with serum liver injury and adipocytokine biomarkers in a sample of 214 men. METHODS: Adult nonsmoking men without a history of liver disease or heavy alcohol consumption were included. The serologic disease biomarkers evaluated were the hepatocellular injury biomarker, cytokeratin 18 [whole (CK18 M65) and caspase-cleaved fragment (CK18 M30)]; and adipocytokines. Confounder-adjusted beta coefficients were determined using linear regression models for the overall sample (primary endpoints) and for obesity-classified sub-groups (secondary endpoints). A product interaction term between the exposure of interest and a dichotomized indicator of obesity was included to determine the disease modifying effects of obesity on the biomarker associations. RESULTS: The study sample was 57% white and 51% obese. In the overall sample, lead was positively associated with CK18 M30 (ß = 21.7 ± 6.0 (SE), p = 0.0004); IL-1ß (ß = 32.8 ± 5.2, p < 0.0001); IL-6 (ß = 72.8 ± 18.3, p = 0.0001); and IL-8 (ß = 140.8 ± 42.2, p = 0.001). Cadmium exposures were associated with increased IL-1ß (ß = 77.8 ± 26.3, p = 0.003) and IL-8 (ß = 419.5 ± 201.2, p = 0.04). There were multiple significant interactions between obesity and exposure to lead, cadmium, benzene and toluene in relation to outcome biomarkers. Among obese participants (n = 108), benzene, lead, and cadmium were each positively associated with CK18 M30, IL-1ß, IL-6, and IL-8. In obese subjects, lead was also inversely associated with leptin, and toluene was positively associated with IL-1ß. CONCLUSION: For the overall sample, heavy metal exposures were associated with liver injury (lead only) and/or systemic inflammation (lead and cadmium). Obesity modified the associations between BTEXS and heavy metal exposures on several of the outcome variables. In the obesity subgroup, liver injury was positively associated with lead, cadmium and benzene exposures; systemic inflammation was increased with lead, cadmium, benzene, and toluene exposures; and leptin was inversely associated with lead exposures. The cross-sectional design of this study makes it difficult to determine causality, and all results should be interpreted cautiously. Nonetheless, the potential impact of exposures to lead, cadmium, benzene and toluene in steatohepatitis, an obesity-associated inflammatory liver disease, warrants further investigation.


Assuntos
Derivados de Benzeno/sangue , Benzeno/metabolismo , Hepatopatias/sangue , Fígado/diagnóstico por imagem , Metais Pesados/sangue , Estireno/sangue , Tolueno/sangue , Xilenos/sangue , Adipocinas/sangue , Adulto , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Benzeno/toxicidade , Derivados de Benzeno/toxicidade , Bilirrubina/sangue , Biomarcadores/sangue , Cotinina/sangue , Cotinina/toxicidade , Estudos Transversais , Citocinas/sangue , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental , Humanos , Inflamação , Queratina-18/sangue , Fígado/metabolismo , Hepatopatias/etiologia , Masculino , Metais Pesados/toxicidade , Pessoa de Meia-Idade , Estireno/toxicidade , Tolueno/toxicidade , Compostos Orgânicos Voláteis/sangue , Xilenos/toxicidade
3.
Environ Res ; 175: 100-107, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31108353

RESUMO

BACKGROUND: The chemicals benzene, toluene, ethylbenzene, and xylenes (BTEX) are neuroactive. Exposures often co-occur because they share common sources. We examined neurologic effects of environmental BTEX exposure among U.S. Gulf coast residents taking into account concomitant exposures. METHODS: We measured blood concentrations of BTEX in 690 Gulf state residents. Neurologic symptoms were ascertained via telephone interview. We used log-binomial regression to estimate associations between blood BTEX levels and self-reported neurologic symptoms independently for the presence of any neurologic, central (CNS), or peripheral nervous system (PNS) symptoms. We estimated associations in single chemical models mutually adjusted for co-occurring BTEX and used weighted quantile sum regression to model associations between the combined BTEX mixture and neurologic symptoms. RESULTS: Half (49%) of participants reported at least one neurologic symptom. Each BTEX chemical was associated with increased CNS and PNS symptoms in single-chemical models comparing the highest to lowest quartile of exposure. After adjusting for coexposures, benzene was associated with CNS symptoms among all participants (PR = 2.13, 95% CI: 1.27, 3.57) and among nonsmokers (PR = 2.30, 95% CI: 1.35, 3.91). After adjusting for coexposures, associations with toluene were apparent only for reporting multiple PNS symptoms (PR = 2.00, 95% CI: 0.96, 4.16). In mixture analyses, a one-quartile increase in BTEX exposure was associated with neurologic symptoms (OR = 1.47, 95% CI: 1.11, 1.98). The weighted quantile sum index weighted benzene most heavily, which was consistent with single chemical analyses. CONCLUSIONS: Increasing blood benzene concentration was associated with increased prevalence of CNS symptoms. In this sample, BTEX-associated neurologic effects are likely driven by exposure to benzene and, to a lesser extent, toluene.


Assuntos
Exposição Ambiental , Hidrocarbonetos Aromáticos , Doenças do Sistema Nervoso , Poluição por Petróleo , Adulto , Benzeno/efeitos adversos , Benzeno/análise , Derivados de Benzeno/efeitos adversos , Derivados de Benzeno/sangue , Feminino , Humanos , Hidrocarbonetos Aromáticos/efeitos adversos , Hidrocarbonetos Aromáticos/sangue , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/epidemiologia , Fatores Socioeconômicos , Tolueno/efeitos adversos , Tolueno/sangue , Xilenos/efeitos adversos , Xilenos/sangue
4.
Environ Sci Pollut Res Int ; 26(11): 10552-10561, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30761498

RESUMO

Few studies have examined the effects of environmental concentrations of benzene, toluene, ethylbenzene, and xylene (BTEX) on the hematologic system of residents near a petrochemical complex. This study evaluated the potential effects of blood BTEX concentrations on the hematologic parameters of residents in a community near a petrochemical complex (contaminated group) and another community free of known petrochemical pollution (control group). Volunteer residents were randomly recruited. Each participant completed a questionnaire and donated blood samples to evaluate blood BTEX concentrations and hematologic parameters. We found the mean concentrations of blood BTEX of the contaminated group were 1.2 to 6.7 times higher than the control group. Multiple hematologic parameters of participants were significantly different between the two study groups. Inverse associations were found for ln-transformed blood benzene concentrations with mean corpuscular hemoglobin concentration (MCHC) (ß = - 2.75) and platelet counts (ß = -8.18). Several weaker associations were also observed between other compounds and multiple hematologic parameters. Our results suggest that the residents living near petrochemical complexes have higher blood BTEX concentrations. Furthermore, the increased blood BTEX levels in residents are associated with the reduction in RBC counts, hemoglobin concentration, hematocrit, MCHC, and platelet counts. This study provided particularly important information for the health risk assessment of residents living near petrochemical complexes.


Assuntos
Derivados de Benzeno/sangue , Benzeno/análise , Exposição Ambiental/efeitos adversos , Tolueno/sangue , Xilenos/sangue , Idoso , Benzeno/toxicidade , Derivados de Benzeno/toxicidade , Contagem de Células Sanguíneas , China , Estudos Transversais , Feminino , Hematologia , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tolueno/toxicidade , Xilenos/toxicidade
5.
Int Arch Occup Environ Health ; 92(5): 699-707, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30683999

RESUMO

PURPOSE: To evaluate the effects of a chronic occupational exposure to toluene on color vision. METHODS: Color vision was tested in 51 workers exposed to pure toluene and in 51 matched control subjects. Current exposure was determined by biological monitoring. Blood samples were taken at the end of a Friday shift. Color vision ability was assessed using the Ishihara plates (to screen for congenital dyschromatopsia), the Farnsworth panel D-15 test, the Lanthony panel D-15 desaturated test, the Velhagen plates, and the Standard Pseudoisochromatic Plates Part 2. RESULTS: Median toluene concentration was 1.59 mg/l (quartiles 0.78 and 2.65). The whole group of workers did not perform worse than the controls. The same applies to 20 printers, who regularly assessed hues. Assessed with the most sensitive Lanthony panel D-15 desaturated test, color vision of 24 permanently exposed assistants was impaired (median color confusion index of the 1st eyes 1.08 vs. 1.02, p < 0.02; 2nd eyes 1.08 vs. 1.0, p < 0.05; sign test). The assistants made almost exclusively blue-yellow errors. The other color vision tests did not reveal any differences between the groups. CONCLUSION: Changes in the retina are a possible explanation for the observed blue-yellow dyschromatopsia.


Assuntos
Defeitos da Visão Cromática/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Tolueno/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/análise , Monitoramento Biológico , Cor , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Impressão , Tolueno/sangue
6.
Leg Med (Tokyo) ; 34: 48-57, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30172242

RESUMO

Toluene, a liquid aromatic hydrocarbon, is one of the most widely used industrial solvents, and is present in numerous paints, paint thinners, glues and other industrial and household products. It has become the most abused solvent in the world due to its rapid effects following inhalation. However, the numerous cases of fatal and non-fatal toluene-related intoxication reported in the literature have not yet been collected and discussed in the forensic setting. In this paper we aim to provide a review of the cases of toluene abuse and intoxication and the state of the art of the forensic toxicological analysis of toluene intoxications in the living and in the dead subject, from the early identification to the medico-legal interpretation of the toxicological result. We have identified a total of 45 papers regarding different aspects of toluene abuse, and divided them into three sections, namely sampling, storage and techniques of analysis, assessment in living subjects and post-mortem assessment. This article reports toluene concentrations in blood from 202 living subjects, 23 fatal toluene intoxications and 85 toluene related deaths. Toxicological results are discussed in relation to the clinical presentation (living subjects, including impaired drivers), and the manner of death according to the medical examiner reports (post-mortem examinations). Finally, we discuss the strengths and limitations of the review.


Assuntos
Medicina Legal/métodos , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Tolueno/efeitos adversos , Tolueno/sangue , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Solventes , Tolueno/envenenamento , Tolueno/toxicidade , Adulto Jovem
7.
Artigo em Chinês | MEDLINE | ID: mdl-30248740

RESUMO

Objective: The main purpose of this study was to ascertain whether (or not) exposure to benzene, toluene, xylene and ethylbenzene (BTXE) , under normal working conditions, was associated with any health effects. Methods: From January to December 2014, the workplaces concentrations of BTXE were measured of 71 enterprises in Suzhou Industrial Park. Occupational health examination were investigated on 764 employees who exposed to BTXE, as well as 4409 employees of the corresponding enterprises who unexposed to BTXE, and analyzed the data of the two groups. Results: A total of 6 monitoring sites in 3 enterprises BTXE concentrations excess of the standards, the unexposed group was under the limit of detection. The means of red blood cell count, hemoglobin, hematocrit, intermediate cell count and percentage of intermediate cells were significantly higher in exposed group than in unexposed group (P<0.05) . Conversely, platelet count was significantly lower in exposed group than in unexposed group (P<0.05) . The proportion of red blood cell volume, lymphocyte count and percentage of intermediate cells were significantly lower in exposed group than in unexposed group (P<0.05) . Both means and proportion of glutamic pyruvic transaminase and urea nitrogen were significantly higher in exposed group than in unexposed group (P<0.05) . The positive rate of protein, urine, urine red blood cell were significantly higher in exposed group than in unexposed group (P<0.05) . The abnormal rate of electrocardiogram, liver and kidney B scan were significantly higher in exposed group than in unexposed group (P<0.05) . Multivariate logistic regression analysis revealed that percentage of intermediate cells increased, urea nitrogen increased, urine protein positived, urine red blood cells positived in exposed group the OR values were 1.689, 3.291, 3.163 and 1.743 (P<0.05) . Conclusion: Occupational exposure to low concentrations of BTXE had a certain impact on the blood system and liver and kidney function of the employees, occupational health surveillance for such people should be strengthened.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Derivados de Benzeno/toxicidade , Benzeno/toxicidade , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Tolueno/toxicidade , Xilenos/toxicidade , Poluentes Ocupacionais do Ar/sangue , Benzeno/administração & dosagem , Benzeno/análise , Derivados de Benzeno/administração & dosagem , Derivados de Benzeno/sangue , Humanos , Fígado , Doenças Profissionais/sangue , Tolueno/administração & dosagem , Tolueno/sangue , Xilenos/administração & dosagem , Xilenos/sangue
8.
Xenobiotica ; 48(7): 684-694, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28783416

RESUMO

1. Multiple exposures are ubiquitous in industrial environments. In this article, we highlight the risks faced by workers and complete the data available on the metabolic impact of a common mixture: toluene (TOL) and methylethylketone (MEK). 2. Rats were exposed by inhalation under controlled conditions either to each solvent individually, or to mixtures of the two. How the interaction between the two solvents affected their fate in the blood and brain, their main relevant urinary metabolites (o-cresol, benzylmercapturic acid for TOL and 2,3-butanediols for MEK) and their hepatic metabolism were investigated. 3. Although the cytochrome P450 concentration was unchanged, and the activities of CYP1A2 and CYP2E1 isoforms were not additively or synergistically induced by co-exposure, TOL metabolism was inhibited by the presence of MEK (and vice versa). Depending on the relative proportions of each compound in the mixture, this sometimes resulted in a large increase in blood and brain concentrations. Apart from extreme cases (unbalanced mixtures), the amount of o-cresol and benzylmercapturic acid (and to a lesser extent 2,3-butanediols) excreted were proportional to the blood solvent concentrations. 4. In a co-exposure context, ortho-cresol and benzylmercapturic acid can be used as urinary biomarkers in biomonitoring for employees to relatively accurately assess TOL exposure.


Assuntos
Butanonas/metabolismo , Butanonas/toxicidade , Exposição por Inalação , Tolueno/metabolismo , Tolueno/toxicidade , Animais , Bioensaio , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Butanonas/sangue , Butanonas/urina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos Endogâmicos BN , Tolueno/sangue , Tolueno/urina
9.
Environ Toxicol Pharmacol ; 56: 21-28, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28869856

RESUMO

Data from National Health and Nutrition Examination Survey were analyzed to evaluate detection rates, trend in and factors affecting the observed levels of 1,4-dichlorobenzene, benzene, ethylbenzene, o-xylene, styrene, toluene, and m/p-xylene among US adolescents and adults over 2005-2012. Over 2005-20102, among adolescents, detection rates declined by more than 50% for benzene, ethylbenzene, and o-xylene, and among adults, detection rates declined by more than 50% for ethylbenzene and o-xylene and by a little less than 50% for benzene. Among adults, adjusted levels of 1, 4-dichlorobenzene, benzene, ethylbenzene, o-xylene, toluene, and m/p-xylene decreased by 13.7%, 17.1%, 20%, 17.7%, 23.2%, and 18.7% respectively for every two-year survey cycle. Among adolescents, percentage decline in the levels of 1, 4-dichlorobenzene, benzene, ethylbenzene, o-xylene, styrene, toluene, and m/p-xylene was 15.2%, 21.4%, 19.3%, 16.1%, 47.8%, and 17.7% respectively for every two year survey period. The ratio of adjusted geometric means for adult smokers as compared to adult nonsmokers was 10.7 for benzene, 3.5 for ethylbenzene, 2.0 for o-xylene, 3.4 for styrene, 3.5 for toluene, and 2.2 for m/p-xylene. Among adolescents, gender did not affect the adjusted levels of any of the seven VOCs, and the order in which adjusted levels for 1, 4-dichlorobenzene by race/ethnicity was observed was: non-Hispanic white (0.038ng/mL)

Assuntos
Monitoramento Ambiental/métodos , Fumar/sangue , Compostos Orgânicos Voláteis/sangue , Adolescente , Adulto , Derivados de Benzeno/sangue , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Sensibilidade e Especificidade , Fumar/etnologia , Estireno/sangue , Tolueno/sangue , Estados Unidos/etnologia , Xilenos/sangue , Adulto Jovem
10.
Aust N Z J Public Health ; 41(1): 99-104, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27774705

RESUMO

OBJECTIVE: Abuse of inhalants containing the volatile solvent toluene is a significant public health issue, especially for adolescent and Indigenous communities. Adolescent inhalant abuse can lead to chronic health issues and may initiate a trajectory towards further drug use. Identification of at-risk individuals is difficult and diagnostic tools are limited primarily to measurement of serum toluene. Our objective was to identify the effects of adolescent inhalant abuse on subsequent drug use and growth parameters, and to test the predictive power of growth parameters as a diagnostic measure for inhalant abuse. METHODS: We retrospectively analysed drug use and growth data from 118 Indigenous males; 86 chronically sniffed petrol as adolescents. RESULTS: Petrol sniffing was the earliest drug used (mean 13 years) and increased the likelihood and earlier use of other drugs. Petrol sniffing significantly impaired height and weight and was associated with meeting 'failure to thrive' criteria; growth diagnostically out-performed serum toluene. CONCLUSIONS: Adolescent inhalant abuse increases the risk for subsequent and earlier drug use. It also impairs growth such that individuals meet 'failure to thrive' criteria, representing an improved diagnostic model for inhalant abuse. Implications for Public Health: Improved diagnosis of adolescent inhalant abuse may lead to earlier detection and enhanced health outcomes.


Assuntos
Gasolina/envenenamento , Abuso de Inalantes/etnologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/psicologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Tolueno/sangue , Adolescente , Comportamento do Adolescente/etnologia , Comportamento do Adolescente/psicologia , Creatina Quinase/sangue , Insuficiência de Crescimento/sangue , Insuficiência de Crescimento/etnologia , Transtornos do Crescimento/sangue , Transtornos do Crescimento/etnologia , Humanos , Abuso de Inalantes/psicologia , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/etnologia , Tolueno/efeitos adversos
11.
J Occup Environ Med ; 58(1): 24-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26716845

RESUMO

OBJECTIVE: This study aimed to evaluate blood volatile organic compound (VOC) levels as biomarkers of occupational jet propulsion fuel 8 (JP-8) exposure while controlling for smoking. METHODS: Among 69 Air Force personnel, post-shift blood samples were analyzed for components of JP-8, including ethylbenzene, toluene, o-xylene, and m/p-xylene, and for the smoking biomarker, 2,5-dimethylfuran. JP-8 exposure was characterized based on self-report and measured work shift levels of total hydrocarbons in personal air. Multivariate regression was used to evaluate the relationship between JP-8 exposure and post-shift blood VOCs while controlling for potential confounding from smoking. RESULTS: Blood VOC concentrations were higher among US Air Force personnel who reported JP-8 exposure and work shift smoking. Breathing zone total hydrocarbons was a significant predictor of VOC blood levels, after controlling for smoking. CONCLUSIONS: These findings support the use of blood VOCs as a biomarker of occupational JP-8 exposure.


Assuntos
Poluentes Ocupacionais do Ar/análise , Hidrocarbonetos/química , Militares , Exposição Ocupacional/análise , Compostos Orgânicos Voláteis/sangue , Adolescente , Adulto , Medicina Aeroespacial , Derivados de Benzeno/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Tolueno/sangue , Xilenos/sangue , Adulto Jovem
12.
Toxicol Ind Health ; 32(6): 987-97, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25001206

RESUMO

Nickel (Ni) and Ni compounds are widely present in the urban air. The purpose of this study is to estimate exposure of individuals to Ni and the correlation between this exposure and the values of blood counts in outdoor workers. This study focused on a sample of 101 outdoor workers (55 male and 46 female; 65 nonsmokers and 36 smokers), all employed in the municipal police in a large Italian city. The personal levels of exposure to Ni were assessed through (a) environmental monitoring of Ni present in the urban air obtained from individual samples and (b) biological monitoring of urinary and blood Ni. The blood count parameters were obtained from the hemochromocytometric tests. Pearson correlation coefficients (r) were calculated to assess the association between the blood and urinary Ni and the complete blood count. Multiple linear regression models were used to examine the associations between the complete blood count and the independent variables (age, gender, years of work for current tasks, cigarette smoking habit (current and never smoker), values of airborne Ni, and blood and urinary Ni). Multiple linear regression analysis performed on the total group of 101 subjects confirms the association among the red blood cells count, the hematocrit, and the urinary Ni (R(2) = 0.520, p = 0.025 and R(2) = 0.530, p = 0.030). These results should lead to further studies on the effects of Ni in working populations exposed to urban pollutants. The possibility that the associations found in our study may be partially explained by other urban pollutants (such as benzene, toluene, and other heavy metals) not taken into consideration in this study cannot be ruled out.


Assuntos
Poluentes Atmosféricos/sangue , Poluentes Atmosféricos/urina , Níquel/sangue , Níquel/urina , Exposição Ocupacional/efeitos adversos , Adulto , Benzeno , Contagem de Células Sanguíneas , Cidades , Monitoramento Ambiental , Feminino , Hematócrito , Humanos , Itália , Limite de Detecção , Modelos Lineares , Masculino , Metais Pesados/sangue , Pessoa de Meia-Idade , Polícia , Fumar/efeitos adversos , Estresse Fisiológico , Tolueno/administração & dosagem , Tolueno/sangue
13.
Pharmacology ; 94(3-4): 135-42, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25247698

RESUMO

BACKGROUND/AIMS: The study objective was to investigate and compare the pharmacokinetics of a single oral dose of ACT-077825, a novel direct renin inhibitor, in young and elderly, male and female healthy subjects and to evaluate the safety and tolerability of ACT-077825 in these population groups. METHODS: A total of 32 healthy subjects were included in this single-center, open-label study. The subjects were divided into 4 groups, including 8 young male, 8 young female, 8 elderly male and 8 elderly female subjects. Each participant received a single 200-mg dose of ACT-077825. Blood samples were taken over 5 days (120 h) to determine the plasma levels of ACT-077825. Safety and tolerability were monitored using standard assessments before drug administration, on the administration day and at the end of the blood sampling period. RESULTS: Upon pooling male and female subjects, exposure was higher in elderly compared to young subjects, showing an increase of 65% for AUC0-∞, 40% for Cmax and 38% for t1/2. While young male and female subjects showed similar plasma profiles and exposure, a significant increase in exposure occurred with age in both sexes compared to younger subjects. The difference was largest between young and elderly females. Furthermore, the exposure to ACT-077825 was around 30% higher in elderly female compared to elderly male subjects. ACT-077825 was well tolerated by all groups, including the elderly females who showed the highest exposure. CONCLUSIONS: ACT-077825 exposure is moderately increased in elderly subjects. The clinical relevance of this observation should be explored in the context of further studies.


Assuntos
Anti-Hipertensivos/farmacocinética , Tolueno/análogos & derivados , Adulto , Fatores Etários , Idoso , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/sangue , Feminino , Humanos , Masculino , Renina/antagonistas & inibidores , Fatores Sexuais , Tolueno/efeitos adversos , Tolueno/sangue , Tolueno/farmacocinética
14.
Drug Chem Toxicol ; 37(1): 69-75, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23841515

RESUMO

Occupational exposure to organic solvents present in paints is responsible for an increased production of reactive species, thus enabling the development of several diseases. Besides, both exo- and endogenous antioxidant defense systems are necessary to avoid oxidative tissue damage. This study investigated possible protective effects of the exo- and endogenous antioxidants on oxidative damage in painters occupationally exposed to organic solvents (n = 42) and controls (n = 28). Retinol, lycopene and ß-carotene were significantly lower in the exposed group. Despite the fact that blood toluene was below the biological exposure limits, malondialdehyde levels and antioxidant enzyme activities were increased, whereas reduced glutathione levels were decreased in painters, compared to nonexposed subjects. Moreover, multivariate regression models showed that reduced glutathione and carotenoids (mainly ß-carotene) have the major influence on lipid peroxidation (LPO). The present work suggests that the exogenous antioxidants, such as carotenoids, could protect occupationally exposed subjects to xenobiotics from LPO.


Assuntos
Antioxidantes/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Exposição Ocupacional , Pintura/análise , Solventes/toxicidade , Adulto , Carotenoides/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Licopeno , Masculino , Malondialdeído/sangue , Pintura/toxicidade , Análise de Regressão , Tolueno/sangue , Vitamina A/sangue , alfa-Tocoferol/sangue , beta Caroteno/sangue
15.
Xenobiotica ; 44(3): 217-28, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24015909

RESUMO

1. Toluene (TOL) is widely used in industry. Occupational exposure to TOL is commonly assessed using TOL in blood, hippuric acid and ortho-cresol. Levels of these biomarkers may depend on factors potentially interfering with TOL biotransformation, such as the presence of other solvents in the workplace. Mercapturic acids (MAs) could be an alternative to the "traditional" TOL biomarkers. 2. This study aims (1) to investigate in rat the effects of an exposure to vapours mixtures on the TOL metabolism, and (2) to assess how well MAs performed in these contexts compared to the traditional TOL biomarkers. 3. Rats were exposed by inhalation to binary mixtures of TOL with n-butanol (BuOH), ethyl acetate (EtAc), methyl ethyl ketone (MEK) or xylenes (XYLs); biological exposure indicators were then measured. 4. Depending on the compounds in the mixture and their concentrations, TOL metabolism was accelerated (with BuOH), unchanged (with EtAc) or inhibited (with XYLs and MEK). Inhibition leads to an increase in blood TOL concentrations, even at authorized atmospheric concentrations, which may potentiate the effect of TOL. 5. MAs excretions are little affected by coexposure scenarios, their levels correlating well with atmospheric TOL levels. They could thus be suitable bioindicators of atmospheric TOL exposure.


Assuntos
Biomarcadores/sangue , Exposição Ocupacional/análise , Tolueno/metabolismo , 1-Butanol , Acetatos , Acetilcisteína/sangue , Análise de Variância , Animais , Butanonas , Cresóis/sangue , Relação Dose-Resposta a Droga , Hipuratos/sangue , Masculino , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Tolueno/sangue , Tolueno/química , Xilenos
16.
Xenobiotica ; 43(8): 651-60, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23278281

RESUMO

1. Toluene (TOL) is a neurotoxic, ototoxic and reprotoxic solvent which is metabolized via the glutathione pathway, producing benzylmercapturic, o-, m- and p-toluylmercapturic acids (MAs). These metabolites could be useful as biomarkers of TOL exposure. 2. The aims of this study were (1) to provide data on MAs excretion in rat urine following TOL exposure by inhalation, (2) to compare them to data from traditional TOL biomarkers, i.e. TOL in blood (Tol-B), and urinary hippuric acid (HA) and o-cresol (oCre) and (3) to establish a relationship between these different indicators and the airborne TOL concentration (Tol-A). 3. Sprague-Dawley rats were exposed to a range of TOL concentrations. Blood and urine were collected and analyzed to determine biomarker levels. 4. Levels of the four MAs correlate strongly with Tol-A (comparable to the correlation with Tol-B). 5. MAs are thus clearly superior to oCre and HA as potential markers of exposure to TOL.


Assuntos
Acetilcisteína/sangue , Acetilcisteína/urina , Cresóis/urina , Exposição Ambiental/análise , Hipuratos/urina , Tolueno/sangue , Acetilcisteína/química , Poluição do Ar/análise , Animais , Biomarcadores/sangue , Biomarcadores/urina , Humanos , Isomerismo , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Análise de Regressão , Tolueno/química
17.
J Forensic Sci ; 58(2): 552-5, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23278468

RESUMO

We describe a case of an acute lethal poisoning with hydrocarbons resulting from massive accidental inhalation of gasoline vapors. The victim, a 50-year-old man was found unconscious inside a control room for the transport of unleaded fuel. Complete autopsy was performed and showed evidence of congestion and edema of the lungs. Toxicological investigation was therefore fundamental to confirm exposure to fumes of gasoline. Both venous and arterial blood showed high values of volatiles in particular for benzene (39.0 and 30.4 µg/mL, respectively), toluene (23.7 and 20.4 µg/mL), and xylene isomers (29.8 and 19.3 µg/mL). The relatively low values found in the lungs are consistent with the fact that the subject, during the rescue, underwent orotracheal intubation followed by resuscitation techniques, while the low concentrations for all substances found in urine and kidneys could point to a death that occurred in a very short time after first contact with the fumes of gasoline.


Assuntos
Poluentes Atmosféricos/envenenamento , Gasolina/envenenamento , Benzeno/análise , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Tolueno/sangue , Volatilização , Xilenos/sangue
18.
Chemosphere ; 87(7): 813-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22297198

RESUMO

OBJECTIVES: This is the first research study to compare among female, non-smoker workers: (a) the exposure to benzene, toluene and xylenes (BTXs) in urban air during work in the street (traffic policewomen, TP) vs. work in vehicles (police drivers, PD); (b) the exposure to BTXs in urban environments (in street and in car) vs. rural environments (roadwomen, RW); (c) the values of blood benzene, urinary trans, trans muconic acid (t,t-MA) and urinary S-phenylmercapturic acid (S-PMA) in urban areas (in street and in car) vs. rural areas. METHODS: Passive personal samplings and data acquired using fixed monitoring stations located in different areas of the city were used to measure environmental and occupational exposure to BTXs during the work shift in 48 TP, 21 PD and 22 RW. In the same study subjects, blood benzene, t,t-MA and S-PMA were measured at the end of each work shift. RESULTS: Personal exposure of urban workers to benzene seemed to be higher than the exposure measured by the fixed monitoring stations. Personal exposure to benzene and toluene was (a) similar among TP and PD and (b) higher among urban workers compared to rural workers. Personal exposure to xylenes was (a) higher in TP than in PD and (b) higher among urban workers compared to rural workers. Blood benzene, t,t-MA and S-PMA levels were similar among TP and PD, although the blood benzene level was significantly higher in urban workers compared to rural workers. In urban workers, airborne benzene and blood benzene levels were significantly correlated. CONCLUSIONS: Benzene is a human carcinogen, and BTXs are potential reproductive toxins at low dose exposures. Biological and environmental monitoring to assess exposure to BTXs represents a preliminary and necessary tool for the implementation of preventive measures for female subjects working in outdoor environments.


Assuntos
Poluentes Ocupacionais do Ar/sangue , Benzeno/metabolismo , Exposição Ocupacional/estatística & dados numéricos , Tolueno/sangue , Xilenos/sangue , Acetilcisteína/análogos & derivados , Acetilcisteína/urina , Adulto , Poluentes Ocupacionais do Ar/urina , Monitoramento Ambiental , Feminino , Humanos , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Polícia , População Rural , Ácido Sórbico/análogos & derivados , Ácido Sórbico/metabolismo , Emissões de Veículos/análise
19.
Toxicol Lett ; 210(2): 254-63, 2012 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-22342293

RESUMO

UNLABELLED: CYP2E1, an inducible enzyme present in different human tissues, metabolizes several potentially toxic substances including many volatile organic compounds (VOCs). One indirect way to monitor exposure to VOCs may be, therefore, the assessment of CYP2E1 activity in vivo using the chlorzoxazone (CHZ) test. GOAL: To compare CYP2E1 activity in two groups of workers: one with a known occupational exposure to VOCs (exposed group) and the other employed in administrative tasks at two universities (control group) from the city of León, Guanajuato, México. MATERIAL AND METHODS: (1) Passive diffusion monitors were used to evaluate individual levels of exposure to toluene, benzene and ethylbenzene in 48 persons (24 tannery workers and 24 administrative controls) during a 8h work shift; (2) after 12h fasting 500mg CHZ, a selective probe for assessing CYP2E1 activity, was orally administered and, after 2h, a venous blood sample was collected for HPLC plasmatic quantitative determination of CHZ and its mean metabolite 6-hydroxychlorzoxazone. RESULTS: Toluene mean exposure levels were higher in the exposed group (2.86±2ppm vs. 0.05±0.005ppm; p<0.001). Also, in this group CYP2E1 activity was lower (p<0.05) and it decreased as the accumulated months of labor exposure increased (negative correlation, p<0.05). These results are in line with previous findings obtained from shoemakers exposed to various solvents but, interestingly, they are partly in contrast with those of another study in printers. CONCLUSION: In spite of the relatively low levels of toluene exposure found for tannery workers, an effect on CYP2E1 activity was evident. Although the mechanism of this interaction is still unknown, the decrease in CYP2E1 activity per se might represent a health risk, considering that these workers may be less protected against other CYP2E1 substrates present in the labor setting or derived from an intentional exposure.


Assuntos
Citocromo P-450 CYP2E1/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Exposição Ocupacional/análise , Tolueno/metabolismo , Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Biomarcadores , Citocromo P-450 CYP2E1/sangue , Citocromo P-450 CYP2E1/genética , Monitoramento Ambiental/métodos , Hipuratos/urina , Humanos , México , Fumar , Curtume , Tolueno/sangue , Tolueno/química
20.
Med Tr Prom Ekol ; (12): 19-24, 2012.
Artigo em Russo | MEDLINE | ID: mdl-23461184

RESUMO

The article deals with data on levels of biochemical markers of response to chemical risk factors (benzol, toluene) of cardiovascular diseases in workers engaged into oil and gas extraction. Findings are reliable differences between the workers groups in serum benzol and toluene levels, in classic biochemical effect markers of cardiovascular diseases (total cholesterol level, low density lipoproteins, uric acid), in activity of lipid peroxidation products deteriorating endothelial dysfuction.


Assuntos
Benzeno/análise , Doenças Cardiovasculares , Indústrias Extrativas e de Processamento , Gás Natural/toxicidade , Doenças Profissionais , Exposição Ocupacional/efeitos adversos , Petróleo/toxicidade , Tolueno/sangue , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Monitoramento Ambiental/métodos , Indústrias Extrativas e de Processamento/normas , Indústrias Extrativas e de Processamento/estatística & dados numéricos , Feminino , Humanos , Masculino , Doenças Profissionais/sangue , Doenças Profissionais/diagnóstico , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Fatores de Risco , Federação Russa/epidemiologia
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