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D Lison

Publications and source records attributed to D Lison.

At least 19 recordsLinked to original sources
PubMed2002

Quantitative determination of 5-hydroxy-N-methylpyrrolidone in urine for biological monitoring of N-methylpyrrolidone exposure.

The aim of this work was to validate a sensitive method for quantitative analysis of 5-hydroxy-N-methylpyrrolidone (5-HNMP) in urine. This compound has been recommended as a marker for biological monitoring of N-methylpyrrolidone (NMP) exposure. Different solvents and alternative methods of extraction including liquid-liquid extraction (LLE) on Chem Elut and solid-phase extraction (SPE) on Oasis HLB columns were tested. The most efficient extraction of 5-HNMP in urine was LLE with Chem Elut columns and dichloromethane as a solvent (consistently 22% of recovery). The urinary extracts were derivatized by bis(trimethylsilyl)trifluoroacetamide and analysed by gas chromatography-mass spectrometry (GC-MS) with tetradeutered 5-HNMP as an internal standard. The detection limit of this method is 0.017 mg/l urine with an intraassay precision of 1.6-2.6%. The proposed method of extraction is simple and reproducible. Four different m/z signal ratios of TMS-5-HNMP and tetralabelled TMS-5-HNMP have been validated and could be indifferently used in case of unexpected impurities from urine matrix.

Environmental Monitoring↗
PubMed2002

The Coca-Cola incident in Belgium, June 1999.

The present paper describes the outbreak of health complaints that occurred in Belgium, in June 1999, among schoolchildren and members of the general public in relation to the consumption of Coca-Cola and other soft drinks. The outbreak took place in the wake of a major food crisis, caused by PCB/dioxin contamination of animal feed, that had erupted shortly before. The clinical features (absence of serious poisoning) and epidemiological characteristics of the Coca-Cola outbreak pointed to mass sociogenic illness, and no subsequent toxicological or other data have refuted this hypothesis.

Abdominal Pain↗
PubMed2001

Investigations on the liver toxicity of a blend of HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane) and HCFC-124 (2-chloro-1,1,1,2-tetrafluoroethane) in guinea-pigs.

2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) has been developed as a substitute for ozone-depleting chlorofluorocarbons (CFCs). It is a structural analogue of halothane and similarities in the metabolic pathways and liver toxicity of both compounds have been described. The present study was initiated after an accidental outbreak of hepatitis in an industrial setting to examine whether concomitant exposure to 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), which is not hepatotoxic, could enhance the liver toxicity of HCFC-123. Male Hartley guinea-pigs were exposed for 4 h to 5,000 ppm HCFC-123 alone or blended with 5,000 ppm HCFC-124, either once (single exposure) or on 5 consecutive days (repeated exposure). The animals were killed either 24 or 48 h after the last exposure. A transient cytolytic action of HCFC-123 was evident by increased mean serum levels of alanine aminotransferase at 24 h and isocitrate dehydrogenase at 24 and 48 h, both after a single or repeated exposure. The liver toxicity of HCFC-123 was confirmed by pathological examination of liver tissue, which showed mild (foci of necrotic hepatocytes) to moderate (multifocal random degeneration and necrosis) damage. Steatosis was also observed and was more pronounced after repeated exposure than after single. One animal out of 6 that were repeatedly exposed to the blend and sacrificed at 24 h showed liver lesions similar to halothane hepatitis. Although a few other animals responded markedly in the blend-treated group, on average, no significant difference in the biochemical or pathological lesions was found between the groups treated with HCFC-123 alone or with the blend. Urinary excretion of trifluoroacetic acid and chlorodifluoroacetic acid increased dose-dependently upon exposure to HCFC-123 and indicated accumulation after repeated exposure. No difference in metabolite excretion was found between animals treated with HCFC-123 alone or blended with HCFC-124. Treatment with HCFC-123 depleted hepatic glutathione levels by about 40 and 25% after single and repeated exposure, respectively; the amplitude of this reduction was not modified by co-exposure to HCFC-124. In conclusion, this study confirmed the hepatotoxicity of HCFC-123, based on biochemical, histopathological and metabolite studies, and found only very limited indication of a potentiation by HCFC-124 of this hepatotoxic effect.

Administration, Inhalation↗
PubMed2001

Insertion polymorphism of CYP2E1 and urinary N-methylformamide after N,N- dimethylformamide exposure in Japanese workers.

OBJECTIVES: This study examined whether consideration of the *1C/*1D CYP2E1 insertion polymorphism is important for interpreting the biological monitoring of exposure to N,N-dimethylformamide (DMF) in Japanese workers. METHODS: The insertion genotype, airborne DMF exposure on the last day of a work week, and NMF in urine sampled just after the last workshift of the week were determined in 44 male and female Japanese workers. RESULTS AND CONCLUSIONS: The allelic frequency of this CYP2E1 polymorphism was 0.261 in this Japanese population of workers. The CYP2E1 insertion polymorphism did not contribute to NMF levels even after consideration of BMI or alcohol intake. The results indicate that CYP2E1 insertion polymorphism does not appear to be an important determinant for the interpretation of biological exposure to DMF by the measurement of urinary NMF.

Adult↗
PubMed2001

Update on the genotoxicity and carcinogenicity of cobalt compounds.

OBJECTIVE: To integrate recent understandings of the mechanisms of genotoxicity and carcinogenicity of the different cobalt compounds. METHOD: A narrative review of the studies published since the last IARC assessment in 1991 (genotoxicity, experimental carcinogenesis, and epidemiology). RESULTS: Two different mechanisms of genotoxicity, DNA breakage induced by cobalt metal and especially hard metal particles, and inhibition of DNA repair by cobalt (II) ions contribute to the carcinogenic potential of cobalt compounds. There is evidence that soluble cobalt (II) cations exert a genotoxic and carcinogenic activity in vitro and in vivo in experimental systems but evidence in humans is lacking. Experimental data indicate some evidence of a genotoxic potential for cobalt metal in vitro in human lymphocytes but there is no evidence available of a carcinogenic potential. There is evidence that hard metal particles exert a genotoxic and carcinogenic activity in vitro and in human studies, respectively. There is insufficient information for cobalt oxides and other compounds. CONCLUSION: Although many areas of uncertainty remain, an assessment of the carcinogenicity of cobalt and its compounds requires a clear distinction between the different compounds of the element and needs to take into account the different mechanisms involved.

Animals↗
PubMed2001

Interleukin-9 reduces lung fibrosis and type 2 immune polarization induced by silica particles in a murine model.

We examined the effect of interleukin (IL)-9, a cytokine active on B and T lymphocytes and associated with bronchial asthma, on the development of lung fibrosis induced by crystalline silica particles. Therefore, we compared the response to silica (1 and 5 mg/animal, intratracheally) in transgenic mice that constitutively express high levels of IL-9 (Tg5) and their wild-type counterparts (FVB). At 2 and 4 mo after treatment with silica, histologic examination and measurement of lung hydroxyproline content showed that the severity of fibrosis was significantly less important in Tg5 mice than in their wild-type counterparts. Intraperitoneal injection of IL-9 in C57BL/6 mice also reduced the amplitude of silica-induced lung fibrosis. The reduction of lung fibrosis by IL-9 was associated with a significant expansion of the B-lymphocyte population, both in bronchoalveolar lavage (BAL) and in the pulmonary parenchyma. In wild-type animals, silica-induced fibrosis correlated with markers of a T helper 2-like response such as upregulation of IL-4 levels in lung tissue and an increased immunoglobulin (Ig) G1/IgG2a ratio in BAL. Immunohistochemical studies demonstrated that the upregulation of IL-4 associated with the development of fibrosis was mainly localized in inflammatory alveolar macrophages. In transgenic mice, the level of IL-4 in lung homogenates was not significantly affected by silica treatment, and a reduced IgG1/IgG2a ratio was observed upon treatment with silica. The levels of interferon-gamma were significantly decreased after silica treatment in both strains. Together, these observations point to an antifibrotic effect of IL-9 in pulmonary fibrosis associated with a limitation of the type 2 polarization which accompanies lung fibrosis.

Animals↗
PubMed2001

Interstitial lung disease induced by exogenous agents: factors governing susceptibility.

The purpose of this review is to describe the present state of knowledge regarding host susceptibility factors that may determine the occurrence, development and severity of interstitial lung disease (ILD) caused by exogenous agents. First, host susceptibility may pertain to differences in the delivery and/or persistence of the noxious agent in the lung. The deposition and clearance of inhaled particles or fibres may vary depending on innate anatomical or physiological characteristics, and on acquired changes, such as nasal disease or smoking-induced alterations. Genetically- or environmentally-induced interindividual differences in the expression of pulmonary biotransformation enzymes may form the basis for, or contribute to the risk of, drug-induced interstitial lung disease. Secondly, there are genetic and acquired variations in various enzymatic and nonenzymatic defence systems that protect cells and tissues against oxidative stress, which is often involved in the pathogenesis of interstitial lung disease caused by particles, fibres, metals, organic agents and drugs. Thirdly, the occurrence of immunological sensitization is dependent on both genetic and environmental factors. This has been demonstrated in chronic beryllium lung disease and in hypersensitivity pneumonitis. Fourthly, the propensity of individuals to develop particular types of inflammation, such as granulomas, is probably under genetic control. The regulation and resolution of inflammation and fibrogenesis caused by dust particles are also partly determined by genetic factors, involving cytokine networks and growth factors. In conclusion, although the issue of genetics pervades the entire discussion of host susceptibility, genes are not the only determinants of health and disease. Environmental factors may be equally important in shaping host susceptibility. Therefore, research must be focused on both the genetic bases and the environmental determinants of interstitial lung disease, in order to provide mechanism-based prevention strategies, early detection of, and improved therapy for these conditions.

Air Pollutants↗
PubMed2000

Absence of significant genotoxicity in lymphocytes and urine from workers exposed to moderate levels of cobalt-containing dust: a cross-sectional study.

Mortality studies have shown that, in the past, lung cancer occurred after exposure to mixtures of cobalt metal and metallic carbide particles, the main constituents of hard metals, but apparently not when exposure was to cobalt alone. The major objective of this biomonitoring study was to assess genotoxic effects as a measure for carcinogenic risk in workers from cobalt refineries and hard metal plants currently exposed to the threshold limit value/time-weighted average (TLV-TWA) for cobalt-containing dust. The study comprised three groups of workers: 35 workers exposed to cobalt dust from three refineries, 29 workers exposed to hard metal dust from two producing plants, and 35 matched control subjects recruited from the respective plants. The study design integrated complementary methodologies to assess biomarkers of effects that represent both initial DNA damage (8-hydroxydeoxyguanosine [8-OHdG] in urine and comet assay on lymphocytes) and definitive chromosome breakage/loss (micronuclei in lymphocytes). Cobalt and cotinine were determined in urine as a measure for cobalt exposure and recent smoking, respectively. No significant increase of genotoxic effects was detected in workers exposed to cobalt-containing dust as compared to controls. No difference in any genotoxicity biomarker was found between workers exposed to cobalt and hard metal dusts. Multiple regression analysis indicated that workers who smoked and were exposed to hard metal dusts had elevated 8-OHdG and micronuclei values. Because this observation is in line with a previous epidemiological study of an increased risk of dying from lung cancer in workers from the hard metal industry who smoked, it is concluded that this specific occupational group needs closer medical surveillance.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Clues and uncertainties in the risk assessment of arsenic in drinking water.

On the basis of studies of the prevalence of skin cancer among users of As-rich well water in Taiwan, WHO experts recommended in 1984 a maximum As concentration of 50 microg/litre in drinking water. Since that time, a plethora of non-cancer as well as cancer effects has been observed in several other populations sustaining a chronic exposure to various As concentrations in drinking water. This prompted a revision of the standard and a provisional guideline of 10 microg/litre was recommended in 1993. While the uncertainty linked to the statistical inferences leading to the guideline are reduced by the fact that they are directly estimated from human data and result from extrapolations made relatively close to observed exposure levels, developed guideline depends strongly on the choice of the dose-response model (linear, quadratic, hockey-stick) and the accuracy of the exposure data. The potential exposure to As sources other than drinking water, dietary habits and genetic characteristics of the populations may also make more difficult the inference of a recommendation for As concentration in drinking water. Owing to the huge cost of strongly reducing the current As in water standard, many efforts are presently made to clarify the quantitative aspects of As-induced cancers, particularly at low dose levels. New data on the metabolism and carcinogenic mechanism of As in humans along with the results of epidemiological studies presently under way in several countries will help to reduce the uncertainty in the risk assessment of As.

Arsenic↗
PubMed2000

Epidemiological survey of workers exposed to inorganic germanium compounds.

OBJECTIVES: To assess occupational exposure to inorganic germanium (Ge) in workers from a producing plant, and to assess the health of these workers, with a special focus on respiratory, kidney, and liver functions. METHODS: Cross sectional study of 75 workers exposed to Ge and 79 matched referents. Exposure was characterised by measuring air and urine concentrations of the element during a typical working week, and health was assessed by a questionnaire, clinical examination, lung function testing, chest radiography, and clinical chemistry in serum and urine, including high and low molecular weight urinary proteins. RESULTS: Airborne concentrations of Ge (inhalable fraction) ranged from 0.03 to 300 micrograms/m, which was reflected by increased urinary excretion of Ge (0.12-200 micrograms/g creatinine, after the shift at the end of the working week). Lung, liver, and haematological variables were not significantly different between referents and workers exposed to Ge. A slightly higher urinary concentration of high molecular weight proteins (albumin and transferrin) was found in workers exposed to Ge, possibly reflecting subclinical glomerular changes. No relation was found between the intensity or duration of exposure and the urinary concentration of albumin. No difference between referents and workers exposed to Ge was found for other renal variables. CONCLUSIONS: Measurement of urinary Ge can detect occupational exposure to inorganic Ge and its compounds. It is prudent to recommend the monitoring of renal variables in workers exposed to Ge.

Adult↗
PubMed2000

Erratum

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Journal Article↗
PubMed1999

Renal effects of low-level environmental cadmium exposure: 5-year follow-up of a subcohort from the Cadmibel study.

BACKGROUND: The clinical relevance of renal effects of cadmium in people exposed in the environment remains uncertain. This study examined the evolution of renal effects observed in a population exposed to cadmium in the environment. METHODS: 208 men and 385 women surveyed in 1985-89 (Cadmium in Belgium study [Cadmibel]; baseline) were re-examined on average 5 years later (Public health and environmental exposure to cadmium study [PheeCad]; follow-up). Urinary and blood cadmium and markers of renal tubular dysfunction and glomerular effects were measured. The association between cadmium body burden and renal factors was examined by multivariate logistic and linear regression. FINDINGS: In men, mean urinary cadmium excretion and blood cadmium concentration measured at follow-up were 7.5 nmol/24 h (SD 1.9) and 6.1 nmol/L (2.2), reductions of 16% and 35% from baseline, respectively. In women, the corresponding values were 7.6 nmol/24 h (1.9) and 7.8 nmol/L (2.1), reductions of 14% and 28% from baseline. No indication of progressive renal damage was found and the overall results suggest that the effects of low environmental exposure to cadmium on the kidney are weak, stable, or reversible. INTERPRETATION: Subclinical renal effects that have been reported in Belgium in patients with increased cadmium body burden are not associated with progressive renal dysfunction and most likely represent non-adverse manifestations.

Adult↗
PubMed1999

Sulfur mustard upregulates the expression of interleukin-8 in cultured human keratinocytes.

Although the morphological description of sulfur mustard (SM) injury is well characterised, little is known of the molecular mediators involved in cutaneous toxicity. Since infiltration by lymphocytes and PMNs represents one of the very first events observed in vivo upon exposure to SM, this study examined whether SM exposure can modify the expression by cultured human keratinocytes of interleukin-8, one of the most important chemoattractants for polymorphonuclear leukocytes (PMNs) in humans. Conditioned medium harvested from control keratinocyte cultures showed a gradual accumulation of this cytokine over time followed by a levelling off after 12 hours. Upon treatment with 10(-6) and 10(-5) M SM, no significant difference compared to the control situation was observed. After 6 h, a significantly higher amount of IL-8 was secreted by human keratinocytes treated with 10(-4) M SM and the accumulation of the cytokine persisted up to 24 h after exposure. The expression of IL-8 mRNA was assessed semi-quantitatively (RT-PCR) at the same time points in control and SM-treated (10(-4) M) human keratinocytes. When compared to control cultures, a clear upregulation of IL-8 mRNA levels was observed 6 and 12 h after SM exposure, which is consistent with the secretion pattern of the protein. The present observation indicates that increased secretion of IL-8 by human keratinocytes represents an early event of the inflammatory reaction following SM which is coherent with the reported delay in the recruitment of lymphocytes and PMNs observed in vivo.

Animals↗
PubMed1999

Importance of biotransformation pathways for interpreting biological monitoring of exposure.

A detailed characterisation of the biotransformation pathways followed by the chemical of interest is, evidently, of primordial importance to design reliable biomonitoring programs. This short overview discusses some recent studies that are of potential interest for the development of new avenues of research. Four topics are addressed: tissue localisation of the metabolic process; importance of speciation; metabolic interactions and polymorphism and interindividual variability. While some of these studies offer new data that is directly useful for practical application, others raise mainly questions and indicate that there is still a large effort of research to be performed to improve the design and the interpretation of biomonitoring programs.

Biomarkers↗
PubMed1999

Coal fly ash- and copper smelter dust-induced modulation of ex vivo production of tumor necrosis factor-alpha by murine macrophages: effects of metals and overload.

The objective of this study was to assess the effect of two arsenic-containing particles, coal fly ash (FA) and copper smelter dust (CU), on lung integrity and on the ex vivo release of tumor necrosis factor alpha (TNF-alpha) by alveolar phagocytes. Particle effects were compared in nonoverload condition on the basis of a low but identical volume load and arsenic content intratracheally instilled in the mouse lung (273 nl/mouse and 186 ng arsenic/mouse; FAL and CUL groups). Other mice received 600 ng arsenic/mouse in amounts of particles leading to different volume loads (FAH and CUH groups: 880 and 273 nl/mouse, respectively). Animals were sacrificed at 1, 6, 30, or 120 d (FAL and CUL groups) or at 6 and 120 d posttreatment (FAH and CUH groups). Biochemical markers and inflammatory cell number and type were analyzed in bronchoalveolar lavage, ex vivo TNF-alpha production by alveolar phagocytes was assessed, and measurement of arsenic lung content and histopathological examinations were performed. Our results show that coal fly ash and copper smelter dust bear distinct inflammatory properties. At the end of the observation period (d 120), the high CU dose (CUH) produced a fibrotic reaction whereas the high dose of FA particles (FAH) generated a delayed and persistent lung inflammatory reaction associated with lymphoid noduli. Marked differences in TNF-alpha production were observed within the CU and FA groups. CU particles, conceivably through their metal content, decreased TNF-alpha production by alveolar phagocytes. Due to their low arsenic content, considerably higher FA particle doses needed to be administered to produce an inhibition of TNF-alpha production. Since high doses of FA (FAH) caused an overload condition, our results do not allow us to decide whether FA-mediated TNF-alpha reduction is due to the load administered or to the metallic content.

Animals↗