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1.
Regul Toxicol Pharmacol ; 120: 104860, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33406392

RESUMO

This study aimed to use a reverse dosimetry PBPK modeling approach to estimate toluene atmospheric exposure from urinary measurements of S-benzylmercapturic acid (BMA) in a small group of individuals and to evaluate the uncertainty associated to urinary spot-sampling compared to 24-h collected urine samples. Each exposure assessment technique was developed namely to estimate toluene air exposure from BMA measurements in 24-h urine samples (24-h-BMA) and from distributions of daily urinary BMA spot measurements (DUBSM). Model physiological parameters were described based upon age, weight, size and sex. Monte Carlo simulations with the PBPK model allowed converting DUBSM distribution (and 24-h-BMA) into toluene air levels. For the approach relying on DUBSM distribution, the ratio between the 95% probability of predicted toluene concentration and its 50% probability in each individual varied between 1.2 and 1.4, while that based on 24-h-BMA varied between 1.0 and 1.1. This suggests more variability in estimated exposure from spot measurements. Thus, estimating toluene exposure based on DUBSM distribution generated about 20% more uncertainty. Toluene levels estimated (0.0078-0.0138 ppm) are well below Health Canada's maximum chronic air guidelines. PBPK modeling and reverse dosimetry may be combined to interpret urinary metabolites data of VOCs and assess related uncertainties.


Assuntos
Acetilcisteína/análogos & derivados , Poluentes Atmosféricos/toxicidade , Biomarcadores Ambientais/efeitos dos fármacos , Monitoramento Ambiental/métodos , Modelos Biológicos , Tolueno/toxicidade , Acetilcisteína/urina , Adulto , Biomarcadores Ambientais/fisiologia , Humanos , Método de Monte Carlo
2.
J Appl Toxicol ; 39(7): 974-991, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30834571

RESUMO

This study aimed to assess the impact of multi-route co-exposures to chemicals on interindividual variability in toxicokinetics. Probabilistic physiologically based pharmacokinetic multi-route interaction models were developed for adults and four younger subpopulations. Drinking water-mediated multi-route exposures were simulated for benzene alone or in co-exposure with toluene, ethylbenzene and m-xylene, for trichloroethylene or vinyl chloride (VC), alone and in mixture. These simulations were performed for "low" and "high" exposure scenarios, involving respectively the US EPA's short-term drinking water health advisories, and 10 times these advisory values. Distributions of relevant internal dose metrics for benzene, trichloroethylene and VC were obtained using Monte Carlo simulations. Intergroup variability indexes (VI) were computed for the "low" (VIL ) and "high" (VIH ) exposure scenarios, as the ratio between the 95th percentile in each subpopulation over the median in adults. Thus, for benzene, parent compound's area under the curve-based VIL for single exposures vs. co-exposures correspondingly varied between 1.7 (teenagers) and 2.8 (infants) vs. 1.9 and 3.1 respectively. VIH varied between 2.5 and 3.5 vs. 2.9 and 4.1. Inversely, VIL and VIH for the amount of benzene metabolized via CYP2E1 pathway decreased in co-exposure compared to single exposure. For VC and trichloroethylene, similar results were obtained for the "high" exposure, but "low" co-exposures did not impact the toxicokinetics of individual substances. In conclusion, multi-route co-exposures can have an impact on the toxicokinetics of individual substances, but to an extent, that does not seem to challenge the default values attributed to the factors deemed at reflecting interindividual or child/adult differences in toxicokinetics.


Assuntos
Água Potável/química , Exposição Ambiental/análise , Modelos Biológicos , Compostos Orgânicos Voláteis/toxicidade , Poluentes Químicos da Água/toxicidade , Adolescente , Adulto , Fatores Etários , Exposição Dietética/efeitos adversos , Exposição Dietética/análise , Água Potável/normas , Exposição Ambiental/efeitos adversos , Humanos , Lactente , Exposição por Inalação/efeitos adversos , Exposição por Inalação/análise , Especificidade de Órgãos , Absorção Cutânea/efeitos dos fármacos , Toxicocinética , Compostos Orgânicos Voláteis/farmacocinética , Poluentes Químicos da Água/farmacocinética
3.
J Toxicol Environ Health A ; 81(20): 1066-1082, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30365389

RESUMO

Biomonitoring might provide useful estimates of population exposure to environmental chemicals. However, data uncertainties stemming from interindividual variability are common in large population biomonitoring surveys. Physiologically based pharmacokinetic (PBPK) models might be used to account for age- and gender-related variability in internal dose. The objective of this study was to reconstruct air concentrations consistent with blood toluene measures reported in the third Canadian Health Measures Survey using reverse dosimetry PBPK modeling techniques. Population distributions of model's physiological parameters were described based upon age, weight, and size for four subpopulations (12-19, 20-39, 40-59, and 60-79 years old). Monte Carlo simulations applied to PBPK modeling allowed converting the distributions of venous blood measures of toluene obtained from CHMS into related air levels. Based upon blood levels observed at the 50th, 90th and 95th percentiles, corresponding air toluene concentrations were estimated for teenagers aged 12-19 years as being, respectively, 0.009, 0.04 and 0.06 ppm. Similarly, values were computed for adults aged 20-39 years (0.007, 0.036, and 0.06 ppm), 40-59 years (0.007, 0.036 and 0.06 ppm) and 60-79 years (0.006, 0.022 and 0.04 ppm). These estimations are well below Health Canada's maximum recommended chronic air guidelines for toluene. In conclusion, PBPK modeling and reverse dosimetry may be combined to help interpret biomonitoring data for chemical exposure in large population surveys and estimate the associated toxicological health risk.


Assuntos
Monitoramento Ambiental/métodos , Poluentes Ambientais/farmacocinética , Tolueno/farmacocinética , Adolescente , Adulto , Idoso , Canadá , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Método de Monte Carlo , Adulto Jovem
4.
New Solut ; 26(2): 253-70, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27231011

RESUMO

Most in the Economic Community of West African States region are employed in the informal sector. While the informal sector plays a significant role in the region's economy, policymakers and the scientific community have long neglected it. To better understand informal-sector work conditions, the goal here is to bring together researchers to exchange findings and catalyze dialogue. The article showcases research studies on several economic systems, namely agriculture, resource extraction, transportation, and trade/commerce. Site-specific cases are provided concerning occupational health risks within artisanal and small-scale gold mining, aggregate mining, gasoline trade, farming and pesticide applications, and electronic waste recycling. These cases emphasize the vastness of the informal sector and that the majority of work activities across the region remain poorly documented, and thus no data or knowledge is available to help improve conditions and formulate policies and programs to promote and ensure decent work conditions.


Assuntos
Saúde Ambiental , Saúde Ocupacional , África Ocidental , Agricultura , Comércio , Humanos , Setor Informal , Reciclagem , Meios de Transporte
5.
Int J Environ Health Res ; 25(2): 149-61, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24861281

RESUMO

To examine the relation between BTEX exposure levels and common self-reported health problems in 140 gasoline sellers in Cotonou, Benin, a questionnaire documenting their socioeconomic status and their health problems was used, whereas 18 of them went through semi-directed qualitative individual interviews and 17 had air samples taken on their workplace for BTEX analysis. Median concentrations for BTEX were significantly lower on official (range of medians: 54-207 µg/m³, n = 9) vs unofficial (148-1449 µg/m³, n = 8) gasoline-selling sites (p < 0.05). Self-reported health problems were less frequently reported in sellers from unofficial vs official selling sites (p < 0.05), because, as suggested by the semi-directed interviews, of their fear of losing their important, but illegal, source of income. Concluding, this study has combined quantitative and qualitative methodological approaches to account for the complex socioeconomic and environmental conditions of the investigated sellers, leading to their, in some cases, preoccupying BTEX exposure.


Assuntos
Poluentes Atmosféricos/análise , Derivados de Benzeno/análise , Benzeno/análise , Exposição Ocupacional , Adulto , Benin , Estudos Transversais , Monitoramento Ambiental , Feminino , Humanos , Masculino , Autorrelato , Emissões de Veículos/análise
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