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Biomedical subjects

D Lison

Publications and source records attributed to D Lison.

At least 55 records · Page 3Linked to original sources
PubMed1997

Comparative evaluation of the in vitro micronucleus test and the alkaline single cell gel electrophoresis assay for the detection of DNA damaging agents: genotoxic effects of cobalt powder, tungsten carbide and cobalt-tungsten carbide.

Although it is well known that micronuclei may arise from either DNA breakage leading to acentric chromosome fragments or from chromosome/chromatid lagging in anaphase, the ratio between the amount of DNA breakage induced and the frequency of micronuclei expressed in the following interphase is unclear. With the development of the alkaline single cell gel electrophoresis assay, which measures single strand and/or double strand breaks in a cell by cell approach, it is new possible to address this question at the cellular level. We therefore compared the genotoxic potential of pure cobalt powder (Co) and a cobalt-containing alloy, cobalt-tungsten carbide (WC-Co), involved in specific lung disorders, in parallel with the alkaline single cell gel electrophoresis (SCGE) assay (comet assay) and the cytokinesis-blocked micronucleus (MN) test, both carried out in vitro on isolated human leukocytes. The comet assay indicated that the WC-Co mixture produced a higher level of DNA damage than Co alone; WC alone was not able to induce a dose-dependent DNA breakage effect as was seen for Co and WC-Co. Results from the MN test confirmed these observations. It was clear that the clastogenic property of Co-containing dust is significantly enhanced when the Co metal is mixed with WC and suggested that their physicochemical characteristics may act as one of the important parameters responsible for the increased incidence of lung cancers observed in the population of hard metal workers. In agreement with data obtained in the same laboratory on liposoluble chemicals (PCBs and chlorinated aliphatic hydrocarbons) and from the literature, the results indicate that both the comet assay and the micronucleus test were able to detect differences in the genotoxic potential of the compounds studied. Although the micronucleus test seemed to be less sensitive to assess a synergistic DNA damaging potential of the mixture involved, it detects chromosomal aberrations (chromosome/genome mutations) and not just repairable DNA breakage or alkali-labile sites. Combination of the comet assay and the in vitro MN test might therefore be recommended for genotoxins to understand the mechanisms underlying mutagenicity and to assess the lowest efficient dose.

Adult↗
PubMed1997

Reduction of the ex vivo production of tumor necrosis factor alpha by alveolar phagocytes after administration of coal fly ash and copper smelter dust.

We investigated the effect of intratracheally instilled coal fly ash (FA) and copper smelter dust (CU) on the lung integrity and on the ex vivo release of tumor necrosis factor alpha (TNF-alpha) by alveolar phagocytes. Groups of female NMRI mice received a single intratracheal administration of different particles normalized for the arsenic content (20 micrograms/kg body weight, i.e., 600 ng arsenic/mouse) and the particle load (100 mg/kg body weight, i.e., 3 mg/mouse). Mice received tungsten carbide (WC) alone (100 mg/kg), FA alone (100 mg/kg, i.e., 20 micrograms arsenic/kg), CU mixed with WC (CU, 13.6 mg/kg, i.e., 20 micrograms arsenic/kg; WC, 86.4 mg/kg) and Ca3(AsO4)2 mixed with WC (20 micrograms arsenic/kg; WC, 100 mg/kg). Animals were sacrificed at 1, 6, or 30 d posttreatment and analyzed by bronchoalveolar lavage for total protein (TP) content, inflammatory cell number and type, and TNF-alpha production. Additional mice were studied to evaluate particle retention by measuring total arsenic retention in the lung at appropriate times. Instillation of WC induced a mild and transient (d 1) inflammatory reaction characterized by an increase of TP and an influx of polymorphonuclear leukocytes in the alveolar compartment. Compared to WC, Ca3(AsO4)2 produced a significant increase of TP content in BALF. CU particles caused a severe but transient inflammatory reaction, while a persisting alveolitis (30 d) was observed after treatment with FA. Compared to control saline, a marked inhibition of TNF-alpha release was observed in response to LPS in all groups at d 1. Cytokine production was upregulated in WC- and Ca3(AsO4)1-treated animals after 6 and 30 d, respectively. However, a 90% inhibition of TNF-alpha production was still observed at d 30 after administration of CU and FA. Although arsenic was cleared from the lung tissue 6 d after Ca3(AsO4)2 administration, a significant fraction persisted (10-15% of the arsenic administered) in the lung of CU- and FA-treated mice at d 30. We hypothetize that suppression of TNF-alpha production is dependent upon the slow elimination of the particles and their metal content from the lung.

Animals↗
PubMed1997

Reversibility of microproteinuria in cadmium workers with incipient tubular dysfunction after reduction of exposure.

The study aimed at assessing the evolution of cadmium (Cd)-induced renal tubular dysfunction in Cd workers according to the severity of the microproteinuria observed at the time the exposure was substantially decreased. Male workers employed in the Cd production industry for whom formerly high exposure had markedly decreased by 1984 and for whom standardized medical data were available during two observation periods (1980-1984 and 1990-1992) were eligible for the study. A total of 32 Cd workers fulfilling this profile were divided into two groups on the basis of historical records of urinary Cd concentration (Cd-U) covering the period until 1984. The workers with Cd-U values of > 10 micrograms Cd/g creatinine were subdivided further on the basis of the urinary concentration of beta 2-microglobulin (beta 2 MG-U) measured during the first observation period (1980-1984). In each group, the tubular microproteinuria as reflected by beta 2 MG-U and the concentration of retinol-binding protein in urine as well as the internal Cd dose as reflected by the concentration of Cd in blood and urine were compared between the first and second (1990-1992) observation periods. Increased microproteinuria was often diagnosed in cases with Cd-U values of > 10 micrograms Cd/g creatinine. The evolution of tubular renal function has been found to depend on the extent of the body burden of Cd (as reflected by Cd-U) and the severity of the initial microproteinuria at the time high Cd exposure was reduced or ceased. When reduction of Cd exposure took place while beta 2 MG-U did not exceed the upper reference limit of 300 micrograms/g creatinine, the risk of developing tubular dysfunction at a later stage was likely to be low, even in cases with historical Cd-U values occasionally > 10 but always < 20 micrograms Cd/g creatinine. When the microproteinuria was mild (beta 2 MG-U > 300 and < or = 1,500 micrograms/g creatinine) at the time exposure was reduced, and the historical Cd-U values had never exceeded 20 micrograms Cd/g creatinine, there was indication of a reversible tubulotoxic effect of Cd. When severe microproteinuria (beta 2 MG-U > 1,500 micrograms/g creatinine) was diagnosed in combination with historical Cd-U values exceeding 20 micrograms Cd/g creatinine, Cd-induced tubular dysfunction was progressive in spite of reduction or cessation of Cd exposure.

Analysis of Variance↗
PubMed1997

Influence of the route of administration and the chemical form (MnCl2, MnO2) on the absorption and cerebral distribution of manganese in rats.

The absorption and cerebral distribution of manganese (Mn) have been studied with respect to the route of administration and the chemical form of the Mn compound. Different groups of adult male rats received either MnCl2, 4H2O or MnO2 once a week for 4 weeks at a dose of 24.3 mg Mn/kg body wt. (b.w.) by oral gavage (g.) or 1.22 mg Mn/kg b.w. by intraperitoneal injection (i.p.) or intratracheal instillation (i.t.). Control rats were treated with 0.9% saline. Four days after the last administration the rats were killed and the concentration of Mn measured in blood, hepatic and cerebral tissues (cortex, cerebellum, and striatum). The liver Mn concentration was not affected by the treatments whatever the chemical form or the route of administration of the Mn compound. Administration of MnCl2 by g., i.p., and i.t. routes produced equivalent steady-state blood Mn concentrations (about 1000 ng Mn/100 ml), representing increases of 68, 59, and 68% compared with controls, respectively. Mn concentrations were significantly increased in the cortex but to a lesser extent (g., 22%; i.p., 36%; i.t., 48%) and were higher in the cerebellum after i.p. and i.t. administrations than after oral gavage. Rats treated i.t. with MnCl2 showed an elective increase of the striatal Mn concentration (205%). In contrast, MnO2 given orally did not significantly increase blood and cerebral tissue Mn concentrations; the low bioavailability is most likely due to the lack of intestinal resorption. Administration of MnO2 i.p. and i.t., however, led to significant increases of Mn concentrations in blood and cerebral tissues. These increments were not significantly different from those measured after MnCl2 administration, except for striatal Mn after i.t. which was markedly less (48%) after MnO2 administration. A comparison of the blood Mn kinetics immediately after g. and i.t. treatment with MnCl2 or MnO2 indicated that the higher elevation of blood Mn concentration (> 2000 ng Mn/100 ml) after i.t. administration of MnCl2 could account for the elective uptake of Mn in the striatum observed in repeated dosing experiments. It is concluded that the modulation of Mn distribution in brain regions according to the route of administration and the chemical form of the Mn compound may be explained on the basis of different blood Mn kinetics and regional anatomic specificities of the striatal region.

Animals↗
PubMed1997

Effect of sulphur mustard on the expression of urokinase in cultured 3T3 fibroblasts.

The expression of plasminogen activator (PA), a serine proteinase involved in the degradation of extracellular matrix proteins, has been investigated in 3T3 fibroblasts after in vitro exposure to sulphur mustard (SM). Expression of the cell-associated enzyme has been assessed with a synthetic substrate assay and at the mRNA level. Twenty-four hours after 100 microM SM, cell viability (monitored by MTT assay) was not significantly affected, but protein synthesis (tritiated leucine incorporation) was reduced to < 20% of the control value. PA activity was significantly increased compared to control cells with a 20-fold increase after 24 h. This up-regulation was independent of the cell density, occurred maximally between days 1 and 4 and persisted for at least 6 days after exposure. Lower concentrations of SM (< or = 10 microM) did not significantly affect PA activity. Northern blotting experiments revealed an increased expression of urokinase (u-PA) transcripts in cells treated with 100 microM SM, with a peak at 10 h after exposure. Conditioned culture medium from cell cultures treated with 100 microM SM did not affect the expression of PA activity in naive or SM-treated cultures. Thiodiglycol (100 microM), the main metabolite of SM, did not influence the expression of PA in the same system. Different compounds were tested for modulation of the PA upregulation after SM exposure. Nicotinamide (5 mM), vitamin D3 (10(-10)M), extracellular calcium (2 mM) or EGTA (5 mM) had no effect. Ryanodine (10 microM) amplified the PA up-regulation by a factor of 2 and vanadate (500 microM) reduced it by approximately 50%. Dexamethasone (1 microM) added directly after SM treatment almost completely prevented the induction of PA at both the protein and mRNA levels. Overall these results demonstrate an up-regulation of urokinase in 3T3 fibroblasts after treatment with SM, which is possibly mediated by intracellular calcium mobilization. Further studies are needed to identify the significance of this proteolytic response in the pathogenesis of blistering and/or DNA repair mechanisms.

3T3 Cells↗
PubMed1997

Influence of particle surface area on the toxicity of insoluble manganese dioxide dusts.

The objective of this study was to examine the influence of specific surface area on the biological activity of insoluble manganese dioxide (MnO2) particles. The biological responses to various MnO2 dusts with different specific surface area (0.16, 0.5, 17 and 62 m2/g) were compared in vitro and in vivo. A mouse peritoneal macrophage model was used to evaluate the in vitro cytotoxic potential of the particles via lactate dehydrogenase (LDH) release. In vivo, the lung inflammatory response was assessed by analysis of bronchoalveolar lavage after intratracheal instillation in mice (LDH activity, protein concentration and cellular recruitment). In both systems, the results show that the amplitude of the response is dependent on the total surface area which is in contact with the biological system, indicating that surface chemistry phenomena are involved in the biological reactivity. Freshly ground particles with a specific surface area of 5 m2/g were also examined in vitro. These particles exhibited an enhanced cytotoxic activity, which was almost equivalent to that of 62 m2/g particles, indicating that undefined reactive sites produced at the particle surface by mechanical cleavage may also contribute to the toxicity of insoluble particles. We conclude that, when conducting studies to elucidate the effect of particles on the lung, it is important for insoluble particles such as manganese dioxide to consider the administered dose in terms of surface area (e.g. m2/kg) rather than in gravimetric terms (e.g. mg/kg).

Animals↗
PubMed1997

Biological monitoring of workers exposed to low levels of 2-butoxyethanol.

OBJECTIVES: (1) To assess the value of urinary butoxyacetic acid (BAA) measurement for the monitoring of workers exposed to low concentration of 2-butoxyethanol (BE); (2) to evaluate the in vivo effect of low occupational BE exposure on the erythrocyte lineage; and (3) to test the possible influence of genetic polymorphism for cytochrome P450 2E1 (CYP 2E1) on urinary BAA excretion rate. METHODS: Thirty-one male workers exposed to BE in a beverage package production plant were examined according to their external (BE) and internal (BAA) solvent exposure. The effect of this exposure on erythrocyte lineage [red blood cell numeration (RBC), hemoglobin (Hb), hematocrit (Htc), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), haptoglobin (Hp), reticulocyte numeration (Ret) and osmotic resistance (OR)], hepatic [aspartate aminotransferase (GOT), alanine aminotransferase (GPT)] and renal [plasmatic creatinine, urinary retinol binding protein (RBP)] parameters was also investigated. DNA purified from whole blood was used for CYP 2E1 genotyping. RESULTS: Average airborne concentration of BE was 2.91 mg/m3 (0.59 ppm) with a standard deviation of 1.30 mg/m3 (0.27 ppm). There was a relatively good correlation between external and internal exposure estimated by measuring BAA in post-shift urine samples (average 10.4 mg/g creatinine; r = 0.55; P = 0.0012). Compared with a matched control group (n = 21) exposed workers had a statistically significant decrease (3.3%; P = 0.03) in Hct while MCHC was increased (2.1%; P = 0.02). No significant difference was observed either in other erythroid parameters or in hepatic and renal biomarkers. One exposed individual exhibited a mutant allele with increased cytochrome P450 oxidative activity which coincided with a very low urinary BAA excretion. CONCLUSIONS: Single determination of BAA in post-shift urine samples can be used to assess exposure to low levels of BE. A slight but significant effect on erythroid parameters suggesting membrane damage was observed in exposed workers. The influence of the genetic polymorphism for CYP 2E1 deserves further investigation for the interpretation of urinary BAA measurements.

Adult↗
PubMed1997

In vitro genotoxic effects of hard metal particles assessed by alkaline single cell gel and elution assays.

Hard metals (WC-Co) are made of a mixture of cobalt metal (Co, 5-10%) and tungsten carbide particles (WC, >80%). Excessive inhalation of WC-Co is associated with the occurrence of different lung diseases including an excess of lung cancers. The elective toxicity of hard metal is based on a physico-chemical interaction between cobalt metal and tungsten carbide particles to produce activated oxygen species. The aim of the present study was to assess the genotoxic activity of hard metal particles as compared with Co and WC alone. In human peripheral lymphocytes incubated with Co or WC-Co, a dose- and time-dependent increased production of DNA single strand breaks (ssb) was evidenced by alkaline single cell gel electrophoresis (SCGE) and modified alkaline elution (AE) assays. Addition of 1 M formate, a hydroxyl radical scavenger, had a protective effect against the production of ssb by both WC-Co or Co alone. On the basis of an equivalent cobalt-content, WC-Co produced significantly more ssb than Co. WC alone did not produce DNA ssb detectable by the AE assay, but results obtained with the SCGE assay may suggest that it either allows some uncoiling of the chromatin loops or induces the formation of slowly migrating fragments. Overall, this in vitro study is the first demonstration of the clastogenic property of cobalt metal-containing dusts. The results are consistent with the implication of an increased production of hydroxyl radicals when Co is mixed with WC particles. The SCGE results also suggest that WC may modify the structure of the chromatin, leading to an increased DNA sensitivity to clastogenic effects. Both mechanisms are not mutually exclusive and may concurrently contribute to the greater clastogenic activity of WC-Co dust. This property of WC-Co particles may account for the excess of lung cancers observed in hard metal workers.

Cobalt↗
PubMed1996

Exogenous catalase may potentiate oxidant-mediated lung injury in the female Sprague-Dawley rat.

Enhancement of lung antioxidant capacity has been proposed in the therapy of acute lung injuries involving local accumulation of reactive oxygen species (ROS). We have studied in the female Sprague-Dawley rat the effect of intratracheal administration of catalase (CAT) on the acute lung response induced by different ROS generating systems. The lung response was assessed at several time intervals (60-360 min) by monitoring in bronchoalveolar fluid (BALF) the activity of lactate dehydrogenase and the levels of total protein, albumin, and glucose. While CAT (50,000 IU/rat) significantly reduced the biochemical changes induced by hydrogen peroxide produced by a glucose/glucose oxidase system, it markedly exacerbated the lesions induced by phorbol myristate acetate (PMA). Several observations indicate that a particular chemical species formed during the catalase inactivation process is responsible for this effect. Parallel to the development of the lung damage, we noted a rapid reduction of CAT activity (80%) in the BALF of animals treated with PMA and CAT. In vitro an inhibition of CAT activity was observed in the presence of a superoxide anion generating system, and this inhibition was prevented by superoxide dismutase (SOD). A dose of 10,000 IU superoxide dismutase did not prevent the development of the lung lesions induced by PMA plus CAT. Administered alone or in association with PMA, CAT inactivated by heat or 3-aminotriazole also caused severe lung damage. In conclusion, the present study indicates that exogenous catalase may not always protect against the inflammatory reaction resulting from an oxidative stress. In the presence of superoxide anions, catalase may aggravate the lesions, and this possibility should be kept in mind when considering an antioxidant therapy.

Albumins↗
PubMed1996

Evaluation of three methods for the detection of DNA single-strand breaks in human lymphocytes: alkaline elution, nick translation, and single-cell gel electrophoresis.

The aim of this study is to assess the ability of three methods, alkaline elution (AE), nick translation (NT), and single-cell gel electrophoresis (SCGE), to detect DNA single-strand breaks (ssb) in human peripheral blood lymphocytes (HPBL) exposed in vitro to three genotoxic agents; gamma-rays, ethyl methanesulfonate (EMS) and benzo[a]pyrene diol epoxide (BPDE). The ultimate objective is to select the most feasible, sensitive, and reproducible method for the monitoring of populations exposed to genotoxic agents. AE and NT do not seem suitable assays. AE is able to detect DNA lesions induced by the three compounds, but only at relatively high doses (2 Gy, 5 mM EMS and 20 microM BPDE). With NT, DNA alterations induced by gamma-rays are not detected and ssb are only evidenced after exposure to EMS (80 mM), which already alters the viability of the lymphocytes. Nick translation is able to detect ssb induced by 10 microM BPDE. Compared to the other assays, the sensitivity of the SCGE assay is significantly higher since statistically significant changes were detected after incubation with 0.5 mM EMS and 1.25 microM BDPE. SCGE is a relatively simple method, not time-consuming and applicable to a large number of samples per working day. In conclusion, on the basis of the results of this in vitro comparison, SCGE seems a promising method for the monitoring of populations exposed to genotoxic chemicals.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1996

The practice of occupational and environmental health in Belgium.

Occupational medicine and occupational health regulations in Belgium are succinctly presented. Since 1970 a minimum level of appropriate training has been required for conferral of a certificate in occupational medicine. At some universities this training is integrated into a larger programme which meets the requirements of EEC Directive 89/594. The current Belgian legislation relating to the prevention of occupational diseases and injuries is detailed in the Règlement pour la Protection du Travail, first published in 1946 and constantly updated. The occupational physician is supposed to provide advice on the risks to which workers are exposed and the adaptation of working conditions in accordance with the state of health or the abilities of the worker. Employers are obliged by law to cover the risks of accident by subscribing to a private insurance policy which covers any related costs. They also contribute financially to the Fonds des Accidents du Travail (Occupational Accidents Fund) and the Fonds des Maladies Professionnelles (Occupational Diseases Fund). Occupational diseases are recognised and may be financially compensated by the Fonds des Maladies Professionnelles.

Belgium↗
PubMed1996

Assessment of exposure to inorganic arsenic, a human carcinogen, due to the consumption of seafood.

To assess whether regular consumption of seafood, particularly fish and shellfish, by humans may lead to an overexposure to inorganic arsenic, a well-established human carcinogen, the urinary excretion of the relevant As metabolites (Asi, inorganic form; MMA, monomethylarsonic acid; DMA, dimethylarsinic acid) was compared in groups of subjects with different seafood consumption habits and in volunteers after ingestion of a known amount of seafood arsenicals. Studies of Italian cohorts, involving five groups of +/-30 subjects with different seafood consumption habits, and balance studies in Belgian volunteers failed to show a biologically significant absorption of inorganic arsenic either present as such in the food or formed from organoarsenicals during cooking or digestion. The results suggest that the digestion of some seafood, especially mussels, may increase the urinary excretion of the dimethylated arsenic metabolite. Therefore, the biological monitoring of exposure to inorganic arsenic in an industrial context should mainly rely upon specific measurement of the unmetabolized form when recent ingestion of seafood cannot be excluded.

Arsenic↗
PubMed1996

Determination of toluenediamines in urine of workers occupationally exposed to isocyanates by high-performance liquid chromatography.

In recent years, epidemiological evidence that exposure to toluene diisocyanate (TDI) is associated with adverse health effects has led to the development of useful analytical methods for the biological monitoring of TDI. In this paper, an HPLC method is presented that allows accurate determinations of toluenediamines (TDA), urinary metabolites of TDI, in hydrolysed human urine without complicated or time-consuming sample treatment. The procedure requires 5.0 ml of urine and involves the extraction with toluene of TDA and the hydrolysable conjugate fraction followed by further purification with a strong cation-exchange sorbent. Strongly alkaline conditions are chosen for the hydrolysis of urine samples and phenylene-1,3-diamine is used as internal standard to control the sample extraction and clean-up. Separation is performed on a base-deactivated octadecyl reversed-phase column by either ion-suppression or ion-pair chromatography. Chromatographic analysis is complete in less than 20 min and chromatograms with no interfering peaks are obtained. High sensitivity and selectivity are achieved by using electrochemical detection: 2,6- and 2,4-TDA can be detected at the 0.1 and 0.15 microgram l-1 levels, respectively. Absolute recoveries of the method tested with urine samples spiked at 10 micrograms l-1 with phenylene-1,3-diamine and from 1 to 25 micrograms l-1 with 2,6-and 2,4-TDA are greater than 87.6% and 88.3%, respectively. The assay is linear from 0 to 50 micrograms l-1. Within-run precisions evaluated on 10 urine samples ranging from 0 to 10 micrograms l-1 are 7.9% and 5.3% for 2,6- and 2,4-TDA, respectively. Results obtained with urine samples from 12 controls and 15 exposed workers from a flexible polyurethane foam factory indicate that the method is appropriate for the biological monitoring of occupational exposure to TDI.

Chromatography, High Pressure Liquid↗
PubMed1996

Experimental research into the pathogenesis of cobalt/hard metal lung disease.

In recent years clinical, epidemiological and experimental evidence has accumulated indicating that cobalt metal particles, when inhaled in association with other agents such as metallic carbides (hard metals) or diamond dust, may produce an interstitial lung disease termed "hard metal disease" or "cobalt lung". This article summarizes the progress accomplished in our two laboratories to understand the pathogenesis of this disease. Gaps and weaknesses in our current knowledge have also been highlighted in order to suggest potential avenues for further research. Whilst animal models have proved useful for the demonstration of the toxic synergy between cobalt and carbides (e.g. tungsten carbide), most animal models have remained descriptive and have not provided information on the mechanism for this synergy. In particular, the bizarre multinucleated giant cells which are an important hallmark of the human disease, have not been reproduced consistently in experimental animals. Since cobalt is a known sensitizer, there may also be a need to develop experimental models to test the possible involvement of immunological mechanisms in the pathogenesis of the interstitial disease. In vitro systems including macrophage cell cultures and physico-chemical tests have been useful to investigate the mechanism underlying the toxic synergy. The recent finding that, in vitro, cobalt and metallic carbides interact with oxygen to produce toxic activated oxygen species opens a new avenue of research and may offer an alternative interpretation of the fact that only a limited proportion of exposed workers develop interstitial disease. Besides the possible involvement of immunological mechanisms, it may be speculated that individuals with a lower antioxidant defence are more susceptible to the toxic effect of activated oxygen species produced by cobalt-containing dusts from hard metal.

Administration, Inhalation↗
PubMed1996

Occupational hazards for the male reproductive system.

The etiology of male infertilities is largely undetermined, and our knowledge of exogenous factors affecting the male reproductive system is still limited. In particular, the role of specific environmental and occupational factors is incompletely elucidated. Various occupational (physical and chemical) agents have been shown to affect male reproductive functions in animals, but large differences in reproductive function and/or xenobiotic handling between species limit extrapolation to humans. When available, human data are often conflicting and, except in a few instances, usually refer to broad and heterogenous occupational categories or to groups of agents (e.g., solvents). It is often difficult to elucidate the role of a single agent because occupational exposure conditions are often complex and various confounding factors related to lifestyle (smoking, alcohol, and diet) or socioeconomic state may also affect sperm quality, fertility, or pregnancy outcomes. The objective of this work is to summarize the main epidemiological and, where relevant, experimental findings pertaining to agents (physical and chemical) encountered in the occupational environment that might affect the male reproductive system (sperm count, motility and morphology, libido, and fertility) and/or related pregnancy outcomes (spontaneous abortion, stillbirth, low birth weight, and birth defects and childhood malignancy in offspring). Some methodological issues related to research on the reproductive effects of toxicants are also discussed briefly.

Anesthetics↗
PubMed1996

Human toxicity of cobalt-containing dust and experimental studies on the mechanism of interstitial lung disease (hard metal disease).

In the industry, the potential for exposure to cobalt metal dust is particularly important during the production of cobalt powder and the processing and use of hard metals and other cobalt-containing alloys. The different adverse health effects reported in these workers are reviewed. One of the main target organs is the respiratory tract, and this article concentrates on the lung parenchymal reactions induced by cobalt-containing dust. Clinical and epidemiological data indicate that this manifestation is rarely, if ever, induced by pure cobalt metal dust alone, but requires the concomitant inhalation of other compounds such as tungsten carbide in the hard metal industry (hard metal disease). Experimental studies demonstrate that cobalt metal and metallic carbides interact to produce an elective lung toxicity. Recent work on the mechanism of this interaction, which is based on the production of activated oxygen species, is reviewed. A practical implication in industrial hygiene should be that permissible exposure levels to Co dust might have to be different when exposure is to pure Co particles or an association with carbides.

Cobalt↗