Nested case-control study of leukaemia, multiple myeloma, and kidney cancer in a cohort of petroleum workers exposed to gasoline.
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OBJECTIVES: This nested case-control study was based on data in a cohort study of more than 18,000 petroleum distribution workers exposed to gasoline, which contains about 2%-3% benzene. Risks of leukaemia, acute myeloid leukaemia, multiple myeloma, and kidney cancer were examined relative to exposure to gasoline. METHODS: For each case, up to five individually matched controls were selected. Analyses based on the Mantel-Haenszel procedure as well as univariate and multivariate conditional logistic regression were performed for each disease category. Jobs with similar exposures were grouped into homogeneous categories for analysis. Several quantitative indices of exposure to gasoline were used in the analyses: duration of exposure, cumulative exposure, frequency of peak exposure, and time of first exposure. RESULTS: No increased risks for the four cancers were found for any job category. Analyses with logistic regression models based on duration of exposure, cumulative exposure, and frequency of peak exposure did not show any increased risk or exposure-effect relation. Time of first exposure to gasoline was also found to be unrelated to the four diseases under investigation. CONCLUSION: Exposure to gasoline or benzene at the concentrations experienced by this cohort of distribution workers is not a risk factor for leukaemia (all cell types), acute myeloid leukaemia, multiple myeloma, or kidney cancer. (+info)
Analysis of chromosome loss and non-disjunction in cytokinesis-blocked lymphocytes of 24 male subjects.
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Chromosome malsegregation in peripheral blood lymphocytes of 24 healthy male subjects was analysed by means of fluorescence in situ hybridization with centromeric probes of chromosomes 7, 11, 18 and X. On the basis of the distribution of centromeric signals in cytokinesis-blocked cells, both loss (leading to centromere-positive micronuclei) and non-disjunction (resulting in an unbalanced distribution of signals in the main nuclei) of the hybridized chromosomes in vitro were identified. In addition, the incidence of binucleated cells with two hyperploid nuclei, possibly arising from mitotic division of trisomic types, was determined. In this way, the incidence of chromosome malsegregation in vivo and in vitro could be compared in the same cell samples. The results obtained show that ageing is positively correlated with the incidence of malsegregation of chromosome X in peripheral lymphocytes of male subjects and confirm the higher susceptibility of chromosome X to malsegregation in comparison with autosomes. A positive correlation between in vitro and in vivo malsegregation rates was observed for both chromosome X and for autosomes. Finally, relatively high frequencies of multiple malsegregation events, greater than expected for independent events, were recorded for both chromosome X and for autosomes, indicating that the abnormal segregation of chromosomes may be connected to a general dysfunction of the mitotic apparatus. The correlation observed between in vitro and in vivo malsegregation frequencies and the association of both parameters with ageing suggest that analysis of chromosome malsegregation in binucleated cells is a useful tool in the study of genomic instability in human populations. (+info)
Physiologically based toxicokinetic modeling of inhaled ethyl tertiary-butyl ether in humans.
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A physiologically based toxicokinetic (PBTK) model was developed for evaluation of inhalation exposure in humans to the gasoline additive, ethyl tertiary-butyl ether (ETBE). PBTK models are useful tools to relate external exposure to internal doses and biological markers of exposure in humans. To describe the kinetics of ETBE, the following compartments were used: lungs (including arterial blood), liver, fat, rapidly perfused tissues, resting muscles, and working muscles. The same set of compartments and, in addition, a urinary excretion compartment were used for the metabolite tertiary-butyl alcohol (TBA). First order metabolism was assumed in the model, since linear kinetics has been shown experimentally in humans after inhalation exposure up to 50 ppm ETBE. Organ volumes and blood flows were calculated from individual body composition based on published equations, and tissue/blood partition coefficients were calculated from liquid/air partition coefficients and tissue composition. Estimates of individual metabolite parameters of 8 subjects were obtained by fitting the PBTK model to experimental data from humans (5, 25, 50 ppm ETBE, 2-h exposure; Nihlen et al., Toxicol. Sci., 1998; 46, 1-10). The PBTK model was then used to predict levels of the biomarkers ETBE and TBA in blood, urine, and exhaled air after various scenarios, such as prolonged exposure, fluctuating exposure, and exposure during physical activity. In addition, the interindividual variability in biomarker levels was predicted, in the eight experimentally exposed subjects after a working week. According to the model, raising the work load from rest to heavy exercise increases all biomarker levels by approximately 2-fold at the end of the work shift, and by 3-fold the next morning. A small accumulation of all biomarkers was seen during one week of simulated exposure. Further predictions suggested that the interindividual variability in biomarker levels would be higher the next morning than at the end of the work shift, and higher for TBA than for ETBE. Monte Carlo simulations were used to describe fluctuating exposure scenarios. These simulations suggest that ETBE levels in blood and exhaled air at the end of the working day are highly sensitive to exposure fluctuations, whereas ETBE levels the next morning and TBA in urine and blood are less sensitive. Considering these simulations, data from the previous toxicokinetic study and practical issues, we suggest that TBA in urine is a suitable biomarker for exposure to ETBE and gasoline vapor. (+info)
Mass psychogenic illness attributed to toxic exposure at a high school.
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BACKGROUND AND METHODS: Mass psychogenic illness may be difficult to differentiate from illness caused by bioterrorism, rapidly spreading infection, or toxic substances. We investigated symptoms attributed to exposure to toxic gas at a high school in Tennessee. In November 1998, a teacher noticed a 'gasoline-like' smell in her classroom, and soon thereafter she had a headache, nausea, shortness of breath, and dizziness. The school was evacuated, and 80 students and 19 staff members went to the emergency room at the local hospital; 38 persons were hospitalized overnight. Five days later, after the school had reopened, another 71 persons went to the emergency room. An extensive investigation was performed by several government agencies. RESULTS: We were unable to find a medical or environmental explanation for the reported illnesses. The persons who reported symptoms on the first day came from 36 classrooms scattered throughout the school. The most frequent symptoms (in this group and the group of people who reported symptoms five days later) were headache, dizziness, nausea, and drowsiness. Blood and urine specimens showed no evidence of carbon monoxide, volatile organic compounds, pesticides, polychlorinated biphenyls, paraquat, or mercury. There was no evidence of toxic compounds in the environment. A questionnaire administered a month later showed that the reported symptoms were significantly associated with female sex, seeing another ill person, knowing that a classmate was ill, and reporting an unusual odor at the school. CONCLUSIONS: The illness attributed to toxic exposure had features of mass psychogenic illness - notably, widespread subjective symptoms thought to be associated with environmental exposure to a toxic substance in the absence of objective evidence of an environmental cause. Alleviation of the anxiety surrounding an episode of mass psychogenic illness requires prompt recognition and a detailed investigation. (+info)
Analysis of a petrol plume over England: 18-19 January 1997.
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OBJECTIVES: About 7000 tonnes of unleaded petrol were discharged into the English Channel after a tanker collision off Ostend on Saturday 18 January 1997. The petrol evaporated and the vapour plume was carried across the central part of England to Wales, resulting in reports of unidentified odours, and irritation of the eyes, skin, and upper respiratory tract. This work uses this incident to show how marine and atmospheric dispersion modelling together with routine air quality monitoring can assist in identifying hazards to the population at risk from chemical incidents. METHODS: Public health surveillance and results from environmental sampling were compared with the behaviour of the plume as predicted by computer modelling. RESULTS: The predicted plume path and dispersion were shown to correlate well with the results from surveillance and environmental analysis. CONCLUSIONS: There is a need for public health professionals to interact with medical toxicologists, atmospheric and marine scientists and engineers, and other environmental experts in managing events of this nature. (+info)
Analysis of incidence of childhood cancer in the West Midlands of the United Kingdom in relation to proximity to main roads and petrol stations.
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OBJECTIVES: To investigate whether there is an excess of leukaemias in 0-15 year old children among those living in close proximity (within 100 m) of a main road or petrol station. METHODS: Data for 0-15 year old children diagnosed between 1990 and 1994 in the United Kingdom West Midlands were used. Postcode addresses were used to locate the point of residence which was compared with proximity to main roads and petrol stations separately, and to both together. Odds ratios (ORs) were calculated with solid tumours as a control, and incidence ratios (IRs) with population density as a control. RESULTS: The method based on solid tumours as a control showed ORs of 1.61 (95% confidence interval (95% CI) 0.90 to 2.87) and 1.99 (95% CI 0.73 to 5.43), for those living within 100 m of a main road or petrol station respectively. When population was used as a control, the estimated IRs for leukaemia were 1.16 (95% CI 0.74 to 1.72) and 1.48 (95% CI 0.65 to 2.93) for residence within 100 m of a main road or petrol station respectively, but neither reached significance at the 95% level. Results for residence in close proximity to both a main road and petrol station were inconsistent, but there were few. The influence of socioeconomic factors as represented by the Townsend deprivation index on leukaemia incidence was not significant and the results were not explicable on the basis of impact of social class. CONCLUSIONS: The results are suggestive of a small increase in risk of childhood leukaemia, but not solid tumours, for those living in close proximity to a main road or petrol station. This increase in risk is not, however, significant and a larger study is warranted to establish the true risk and causes of any increase in risk. (+info)
Diesel exhaust particles up-regulate expression of intercellular adhesion molecule-1 (ICAM-1) in human bronchial epithelial cells.
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Epidemiological and experimental studies suggest that diesel exhaust particles (DEP) may play an active role in the increased respiratory mortality and morbidity. We have shown that DEP augmented the production of inflammatory cytokines by human airway epithelial cells in vitro. ICAM-1 has been shown to play an important role in the local accumulation of inflammatory cells. We studied the effect of DEP on ICAM-1 gene expression and surface expression in human bronchial epithelial cell line BEAS-2B. DEP (5-50 microg/ml) showed a stimulatory effect on ICAM-1 mRNA levels as evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometric analysis demonstrated an increased ICAM-1 expression on the epithelial cell surfaces. The soluble form of ICAM-1 molecules was also increased by the stimulation of DEP. In vitro neutrophil attachment onto DEP-stimulated epithelial cells was augmented, which was partially blocked by anti-ICAM-1 neutralizing antibody. Finally, these events were significantly inhibited by pretreatment with anti-oxidants pyrrolidine dithiocarbamate and N-acetyl cysteine, and p38 mitogen activated protein kinase (MAPK) inhibitor SB203580. These findings suggested that DEP induced up-regulation of ICAM-1 gene, and this process might be largely dependent on oxidant-mediated NF-kappaB activation and p38-MAPK pathways. (+info)
A Mycobacterium strain with extended capacities for degradation of gasoline hydrocarbons.
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A bacterial strain (strain IFP 2173) was selected from a gasoline-polluted aquifer on the basis of its capacity to use 2,2, 4-trimethylpentane (isooctane) as a sole carbon and energy source. This isolate, the first isolate with this capacity to be characterized, was identified by 16S ribosomal DNA analysis, and 100% sequence identity with a reference strain of Mycobacterium austroafricanum was found. Mycobacterium sp. strain IFP 2173 used an unusually wide spectrum of hydrocarbons as growth substrates, including n-alkanes and multimethyl-substituted isoalkanes with chains ranging from 5 to 16 carbon atoms long, as well as substituted monoaromatic hydrocarbons. It also attacked ethers, such as methyl t-butyl ether. During growth on gasoline, it degraded 86% of the substrate. Our results indicated that strain IFP 2173 was capable of degrading 3-methyl groups, possibly by a carboxylation and deacetylation mechanism. Evidence that it attacked the quaternary carbon atom structure by an as-yet-undefined mechanism during growth on 2,2,4-trimethylpentane and 2,2-dimethylpentane was also obtained. (+info)