Urinary hexane diamine to assess respiratory exposure to hexamethylene diisocyanate aerosol: a human inhalation study

The use of urinary hexane diamine (HDA) as a biomarker to assess human respiratory exposure to hexamethylene diisocyanate (HDI) aerosol was evaluated. Twenty-three auto body shop workers were exposed to HDI biuret aerosol for two hours using a closed exposure apparatus. HDI exposures were quantified using both a direct-reading instrument and a treated-filter method. Urine samples collected at baseline, immediately post exposure, and every four to five hours for up to 20 hours were analyzed for HDA using gas chromatography and mass spectrometry. Mean urinary HDA (microg/g creatinine) sharply increased from the baseline value of 0.7 to 18.1 immediately post exposure and decreased rapidly to 4.7, 1.9 and 1.1, respectively, at 4, 9, and 18 hours post exposure. Considerable individual variability was found. Urinary HDA can assess acute respiratory exposure to HDI aerosol, but may have limited use as a biomarker of exposure in the workplace. [Authors]

Modélisation toxicocinétique du benzo(a)pyrène et 3-hydroxybenzo(a)pyrène pour l’interprétation des données de surveillance biologique de l’exposition chez les travailleurs

De nombreux travailleurs sont exposés aux hydrocarbures aromatiques polycycliques (HAP). Le benzo(a)pyrène (BaP) fait partie de ce groupe de polluants. Cette substance a été classée cancérogène reconnu chez l’humain. Pour évaluer l'exposition aux HAP cancérogènes, plusieurs chercheurs ont proposé d’utiliser la mesure du 3-hydroxybenzo(a)pyrène (3-OHBaP) dans l’urine des travailleurs exposés. Dans le cadre du présent projet, deux approches de modélisation ont été développées et appliquées pour permettre une meilleure compréhension de la toxicocinétique du BaP et son biomarqueur d’intérêt actuel, le 3-OHBaP, et pour aider à interpréter les résultats de surveillance biologique. Un modèle toxicocinétique à plusieurs compartiments a été développé sur la base des données préalablement obtenues sur le rat par notre groupe. Selon le modèle, le BaP injecté par voie intraveineuse est rapidement distribué du sang vers les tissus (t½ ≈ 4 h), avec une affinité particulière pour les poumons et les composantes lipidiques des tissus. Le BaP est ensuite distribué vers la peau et le foie. Au foie, le BaP est promptement métabolisé et le 3-OHBaP est formé avec une demi-vie de ≈ 3 h. Le métabolisme pulmonaire du BaP a également été pris en compte, mais sa contribution à la cinétique globale du BaP a été jugée négligeable. Une fois formé, le 3-OHBaP est distribué vers les différents organes presque aussi rapidement que la molécule mère (t½ ≈ 2 h). Le profil temporel du 3-OHBaP dans le rein montre une accumulation transitoire en raison de la différence observée entre le taux d’entrée (t½ = 28 min) et le taux de sortie (t½ = 4,5 h). La clairance totale de 3-OHBaP du corps est principalement gouvernée par le taux de transfert de la bile vers le tractus gastro-intestinal (t½ ≈ 4 h). Le modèle toxicocinétique à plusieurs compartiments a réussi à simuler un ensemble indépendant de profils urinaires publiés sur le 3-OHBaP. Ce modèle toxicocinétique à compartiments s'est avéré utile pour la determination des facteurs biologiques déterminants de la cinétique du BaP et du 3-OHBaP. Par la suite, un modèle pharmacocinétique à base physiologique (PCBP) reproduisant le devenir du BaP et du 3-OHBaP chez le rat a été construit. Les organes (ou tissus) représentés comme des compartiments ont été choisis en fonction de données expérimentales obtenues in vivo chez le rat. Les coefficients de partition, les coefficients de perméabilité, les taux de métabolisation, les paramètres d'excrétion, les fractions absorbées et les taux d'absorption pour différentes voies d’exposition ont été obtenus directement à partir des profils sanguins, tissulaires, urinaires et fécaux du BaP et du 3-OHBaP. Les valeurs de ces derniers paramètres ont été calculées par des procédures Monte-Carlo. Des analyses de sensibilité ont ensuite été réalisées pour s’assurer de la stabilité du modèle et pour établir les paramètres les plus sensibles de la cinétique globale. Cette modélisation a permis d’identifier les facteurs déterminants de la cinétique: 1) la sensibilité élevée des paramètres de la métabolisation hépatique du BaP et du 3-OHBaP ainsi que du taux d'élimination; 2) la forte distribution du BaP dans les poumons par rapport à d'autres tissus; 3) la distribution considérable du BaP dans les tissus adipeux et le foie; 4) la forte distribution du 3-OHBaP dans les reins; 5) le transfert limité du BaP par la diffusion tissulaire dans les poumons; 6) le transfert limité du 3-OHBaP par la diffusion tissulaire dans les poumons, les tissus adipeux et les reins; 7) la recirculation entéro-hépatique significative du 3-OHBaP. Suite à des analyses de qualité des ajustements des équations du modèle aux données observées, les probabilités que les simulations reproduisent les données expérimentales par pur hasard se sont avérées toujours inférieures à 10% pour les quatre voies d’exposition : intraveineuse, orale, cutanée et respiratoire. Nous avons extrapolé les modèles cinétiques du rat à l’humain afin de se doter d’un outil permettant de reconstituer les doses absorbées chez des travailleurs exposés dans diverses industries à partir de mesures de l'évolution temporelle du 3-OHBaP dans leur urine. Les résultats de ces modélisations ont ensuite été comparés à ceux de simulations obtenues avec un modèle toxicocinétique à compartiment unique pour vérifier l’utilité comparative d’un modèle simple et complexe. Les deux types de modèle ont ainsi été construits à partir de profils sanguins, tissulaires, urinaires et fécaux du BaP et du 3-OHBaP sur des rats exposés. Ces données ont été obtenues in vivo par voie intraveineuse, cutanée, respiratoire et orale. Ensuite, les modèles ont été extrapolés à l’humain en tenant compte des déterminants biologiques essentiels des différences cinétiques entre le rat et l’humain. Les résultats ont montré que l'inhalation n'était pas la principale voie d'exposition pour plusieurs travailleurs étudiés. Les valeurs de concentrations de BaP dans l’air utilisées afin de simuler les profils d’excrétion urinaire chez les travailleurs étaient différentes des valeurs de concentrations de BaP mesurées dans l’air. Une exposition au BaP par voie cutanée semblait mieux prédire les profils temporels observés. Finalement, les deux types de modélisation se sont avérés utiles pour reproduire et pour interpréter les données disponibles chez des travailleurs.

Relación de exposición a polvos de carbón, sílice cristalina y neumoconiosis, en trabajadores de minas de socavón, Cundinamarca, 2014.

Objetivo: Determinar el nivel de riesgo de la exposición por fracción respirable a polvo de carbón y sílice cristalina y la prevalencia de neumoconiosis en trabajadores de minas de socavón del departamento de Cundinamarca. Métodos: estudio de corte transversal, en grupos de exposición similar (GES) en las minas seleccionadas, el tamaño muestral fue constituido por 11 empresas y 215 trabajadores en donde se realizó un muestreo ambiental para medir los niveles de polvo de carbón y sílice cristalina. Resultados: La edad promedio del grupo fue de 46±9,5 años y género masculino (97,2%), se encontró una asociación significativa entre polvo de carbón y neumoconiosis (p =0,050) y no fue significativa con exposición a sílice cristalina (p = 0,537). El modelo de regresión logística mostró asociación significativa con la escala de nivel de riesgo de carbón medio (OR=10.4, IC 95%:1.50, 71.41, p=0,02), ajustando con variables significativas como: tamaño de la empresa mediana (OR = 2,67, IC 95%:1.07, 6.66, p=0,04), antigüedad mayor o igual a 30 años (OR = 7,186, IC 95%:2.98, 17.29, p=0,001) y habito tabáquico por más de un año (OR = 4,437, IC 95%:2.06, 9.55, p=0,001) para sílice cristalina no hubo asociación en el modelo multivariado. Conclusión: El riesgo de exposición a carbón de nivel medio está relacionado con la prevalencia de neumoconiosis y otros factores adicionales como tamaño de la empresa mediana, antigüedad mayor o igual a 30 años y habito tabáquico por más de un año para los trabajadores de minería de socavón en Cundinamarca. Para los niveles de sílice cristalina no se encontró asociación significativa.

Remarkable dynamics of nanoparticles in the urban atmosphere

Nanoparticles emitted from road traffic are the largest source of respiratory exposure for the general public living in urban areas. It has been suggested that the adverse health effects of airborne particles may scale with the airborne particle number, which if correct, focuses attention on the nanoparticle (less than 100 nm) size range which dominates the number count in urban areas. Urban measurements of particle size distributions have tended to show a broadly similar pattern dominated by a mode centred on 20–30 nm diameter particles emitted by diesel engine exhaust. In this paper we report the results of measurements of particle number concentration and size distribution made in a major London park as well as on the BT Tower, 160 m high. These measurements taken during the REPARTEE project (Regents Park and BT Tower experiment) show a remarkable shift in particle size distributions with major losses of the smallest particle class as particles are advected away from the traffic source. In the Park, the traffic related mode at 20–30 nm diameter is much reduced with a new mode at <10 nm. Size distribution measurements also revealed higher number concentrations of sub-50 nm particles at the BT Tower during days affected by higher turbulence as determined by Doppler Lidar measurements and indicate a loss of nanoparticles from air aged during less turbulent conditions. These results suggest that nanoparticles are lost by evaporation, rather than coagulation processes. The results have major implications for understanding the impacts of traffic-generated particulate matter on human health.

Remarkable dynamics of nanoparticles in the urban atmosphere

Nanoparticles emitted from road traffic are the largest source of respiratory exposure for the general public living in urban areas. It has been suggested that adverse health effects of airborne particles may scale with airborne particle number, which if correct, focuses attention on the nanoparticle (less than 100 nm) size range which dominates the number count in urban areas. Urban measurements of particle size distributions have tended to show a broadly similar pattern dominated by a mode centred on 20–30 nm diameter emitted by diesel engine exhaust. In this paper we report the results of measurements of particle number concentration and size distribution made in a major London park as well as on the BT Tower, 160 m aloft. These measurements taken during the REPARTEE project (Regents Park and BT Tower experiment) show a remarkable shift in particle size distributions with major losses of the smallest particle class as particles are advected away from the traffic source. In the Park, the traffic related mode at 20–30 nm diameter is much reduced with a new mode at <10 nm. Size distribution measurements also revealed higher number concentrations of sub-50 nm particles at the BT Tower during days affected by higher turbulence as determined by Doppler Lidar measurements and are indicative of loss of nanoparticles from air aged during less turbulent conditions. These results are suggestive of nanoparticle loss by evaporation, rather than coagulation processes. The results have major implications for understanding the impacts of traffic-generated particulate matter on human health.

Avaliação de equipamentos de aplicação de herbicidas em operação de repasse em cana-de-açúcar e segurança para o trabalhador

Objetivou-se com este trabalho classificar em seguras ou inseguras as condições de trabalho de aplicação da formulação comercial de paraquat a 0,5% e de abastecimento dos tanques em operação de repasse em cultura de cana-de-açúcar com os pulverizadores costal manual, costal pressurizado e Pulmipur manual; determinar o efeito das variações na operação de repasse em quatro usinas de açúcar e álcool com o pulverizador costal pressurizado sobre as exposições dos trabalhadores ao paraquat; determinar a eficácia de equipamentos de proteção individual nessas condições de trabalho; e avaliar a intensidade da deriva e a eficácia de acessórios protetores de deriva. As exposições dérmicas e respiratórias dos trabalhadores foram avaliadas e utilizadas para calcular a margem de segurança (MS). Os valores de MS foram utilizados para classificar essas condições de trabalho em seguras (MS > 1) ou em inseguras (MS < 1). Para avaliar a deriva das aplicações na cultura e a eficácia dos protetores de deriva, foram estudados os tratamentos: formulação comercial de paraquat a 0,5% na calda, aplicada com o costal manual, sem e com o chapéu de proteção de deriva; com o costal pressurizado, sem e com a planilha de proteção de deriva; formulação comercial de paraquat pura com o Pulmipur; formulação comercial de glyphosate a 1% com o costal pressurizado e com a planilha, e puro com o Pulmipur; e testemunha sem aplicação. As duas atividades com o Pulmipur proporcionam as maiores exposições dérmicas, devido ao manuseio da formulação, e são inseguras sem o uso dos EPIs e seguras com estes. As atividades com o pulverizador costal manual ou pressurizado são seguras com ou sem os EPIs. As grandes diferenças nas EDs dos trabalhadores se devem às diferenças no tempo de trabalho diário e no número de trabalhadores nas equipes entre as usinas de açúcar e álcool. O protetor de deriva tipo chapéu é eficaz no controle da deriva na aplicação do paraquat, e a planilha, não.

Eficiência de vestimentas hidrorrepelentes novas na proteção do tratorista em pulverizações de agrotóxicos em goiaba com o turbopulverizador

Os objetivos do trabalho foram: quantificar as exposições dérmicas e respiratórias potenciais proporcionadas ao tratorista em pulverizações de agrotóxicos, na cultura de goiaba, com o turbopulverizador; avaliar a eficiência de duas vestimentas de proteção individual; avaliar a segurança e classificar estas condições de trabalho em seguras ou inseguras para cada agrotóxico considerado. A exposição dérmica potencial proporcionada ao tratorista pela condição de trabalho foi de 3.807,3 mL de calda/7h. A eficiência do conjunto de proteção individual Agro Light foi de 96,7 %, e a do Azeredo, 96,2 %. A exposição dérmica potencial nas regiões do corpo mais expostas do tratorista à pulverização, em ordem decrescente, foram os pés, os braços, as coxas+pernas-frente e o tronco-atrás. A exposição dérmica não-controlada pelos conjuntos de proteção individual foi igualmente distribuída em todas as regiões do corpo do tratorista devido aos controles das exposições dérmicas que proporcionaram às regiões mais expostas do corpo. Foram classificadas como seguras as pulverizações de três dos 17 agrotóxicos considerados e sete com o uso das vestimentas de proteção individual. As demais foram classificadas como inseguras.

Segurança no trabalho de preparo de calda no tanque de 2.000l do turbopulverizador com formulações líquidas de agrotóxicos registradas para a cultura de goiaba

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Controle de Aedes aegypti: período residual de temefós na água em recipientes de plástico, vidro e borracha, ação larvicida residual em recipientes de borracha e segurança das condições de trabalho na nebulização de malathion

Pós-graduação em Agronomia (Entomologia Agrícola) - FCAV

Segurança no trabalho de aplicação de agrotóxicos com o pulverizador de pistolas em citros

The purpose of this study envisaged the quantification of skin and respiratory exposures occasioned by work conditions during pesticide spraying of citrus fruits using hand gun sprayers; the evaluation of the efficiency of individual and group protection measures for the workers; the determination of workers' most exposed body regions; and the classification of work conditions, with and without the tested work-safety protection measures as recommended for the registered pesticides used to control the main pests and diseases that attack these types of trees and fruits. The AZR protection equipment proved to be the most efficient for the tractor driver, when spraying using pistol sprayers. The two sets of individual protection equipment that were checked also proved to be efficient. The most exposed regions of the tractor driver's body were the thighs, the front of the legs, the feet and hands. The most exposed regions of the individual sprayer working on foot were the hands and feet.

Segurança no trabalho com agrotóxicos em citros: aplicação com o turbopulverizador e preparo de calda em tanque de 2.000 L

The objectives of this study were: a) to quantify dermal and respiratory exposure resulting from work conditions in the application of pesticides on citrus crops using a air-assisted sprayer and by preparing the spray in a tank with a capacity of2.000 L; b) to evaluate the measures of individual protection for these workers; c) to determine the areas of the worker's body most exposed; and d) to classify the work conditions with and without the protective measures tested, with regard to the occupational safety of the recommendations for the pesticides used in controlling the main pests and diseases of this crop. It was shown that for the tractor driver and sprayer operator applyng pesticides on citrus trees, the most efficient protective measures were the AZR ensemble and the Real cabin. The AZR ensemble was effective in controlling exposure of the spray preparer, because it was sufficient to turn work conditions from unsafe to safe. The area of the body most exposed under the two work conditions studied was the hands of the workers.

Respiratory infection, exposure to mouse allergen and breastfeeding: role in recurrent wheezing in early life

Background: Environmental factors may influence the development of allergen sensitization and asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life as a risk factor for recurrent wheezing. Methods: One hundred and four infants from low-income families, at high risk of asthma, were enrolled at birth. Dust samples were collected from the bedding and bedroom floor within 6 months after birth. Recurrent wheezing was defined as 3 or more wheezing episodes in the past year. Endotoxin was determined by Limulus amebocyte lysate assay, and major indoor allergens were quantitated by ELISA in dust extracts. IgE antibodies were measured by ImmunoCAP at 30 months of age. Results: At 30 months, 51 of the 99 infants who completed the study (51.5 per cent) had recurrent wheezing. Respiratory infection was strongly associated with recurrent wheezing (OR 6.67, 95 per cent CI 1.96-22.72), whereas exclusive breastfeeding for at least 1 month was a protective factor (OR 0.09, 95 per cent CI 0.01-0.51). Exposure to high levels of mouse allergen was more frequent among non-recurrent wheezers, approaching significance (OR 0.12, 95 per cent CI 0.01-1.13; p = 0.064). None of the children were sensitized to mouse. Sensitization to mite was found in 26/90 (28.8 per cent) children, with no association with recurrent wheezing. Conclusion: Respiratory infection was strongly associated with recurrent wheezing in the first 30 months of life, in children at high risk of asthma, living in a socially deprived community in Brazil

Effects of Chronic Exposure to Crack Cocaine on the Respiratory Tract of Mice

Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.

Respiratory Infection, Exposure to Mouse Allergen and Breastfeeding: Role in Recurrent Wheezing in Early Life

Background: Environmental factors may influence the development of allergen sensitization and asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life as a risk factor for recurrent wheezing. Methods: One hundred and four infants from low-income families, at high risk of asthma, were enrolled at birth. Dust samples were collected from the bedding and bedroom floor within 6 months after birth. Recurrent wheezing was defined as 3 or more wheezing episodes in the past year. Endotoxin was determined by Limulus amebocyte lysate assay, and major indoor allergens were quantitated by ELISA in dust extracts. IgE antibodies were measured by ImmunoCAP at 30 months of age. Results: At 30 months, 51 of the 99 infants who completed the study (51.5%) had recurrent wheezing. Respiratory infection was strongly associated with recurrent wheezing (OR 6.67, 95% CI 1.96-22.72), whereas exclusive breastfeeding for at least 1 month was a protective factor (OR 0.09, 95% CI 0.01-0.51). Exposure to high levels of mouse allergen was more frequent among non-recurrent wheezers, approaching significance (OR 0.12, 95% CI 0.01-1.13; p=0.064). None of the children were sensitized to mouse. Sensitization to mite was found in 26/90 (28.8%) children, with no association with recurrent wheezing. Conclusion: Respiratory infection was strongly associated with recurrent wheezing in the first 30 months of life, in children at high risk of asthma, living in a socially deprived community in Brazil. Copyright (C) 2009 S. Karger AG, Basel