Biomedical subjects

J M Haguenoer

Publications and source records attributed to J M Haguenoer.

At least 19 recordsLinked to original sources

PubMed2006

Environmental lead exposure and its relationship to traffic density among Senegalese children: a cross-sectional study.

Leaded-gasoline is probably the primary source of lead (Pb) exposure in Dakar (Senegal). The present cross-sectional study was undertaken to investigate the levels of Pb in Senegalese children and to present helpful data on the relationship between Pb levels and changes in biological markers of heme biosynthesis and oxidative stress. A total of 330 children, living since birth either in rural or urban areas (ie, Khombole (n = 162) and Dakar (n = 168), respectively) were included. During this cross-sectional study, the mean blood (B)-Pb level in all children was 7.32 +/- 5.33 microg/dL, and was influenced by the area of residence and gender. In rural children, 27 subjects (16.7%), 18 boys (19.6%) and nine girls (12.9%), had a B-Pb level > 10 microg Pb/dL, whereas 99 urban children (58.9%), respectively, 66 boys (71.8%) and 33 girls (43.4%), had alarmingly high B-Pb levels. Accordingly, urine delta-aminolevulinic acid levels were higher in children living in the urban area than in the rural areas (P < 0.001), and closely correlated with the B-Pb levels (P < 0.01). Moreover, glutathione peroxidase (GPx) activity, selenium (Se) level, glutathione reductase (GR) activity, and glutathione status were significantly influenced by area of residence and/or by gender. GPx activity and Se level were not only negatively correlated with B-Pb levels, but also positively correlated together (P < 0.01). Taken together, the present results allow us to conclude that urban children have higher B-Pb levels than rural children, and that of these children, boys have higher B-Pb levels than girls, leading thereby to alterations of heme biosynthesis and pro-oxidant/antioxidant balance. We also suggest that exposure to Pb and the Pb-induced adverse effects merits attention and that the development of preventive actions are of increasing importance in Senegal.

Air Pollutants↗

PubMed2004

Exposure to glycol ethers in a population of French men evaluated by measurement of urinary alkoxycarboxylic acids.

OBJECTIVES: Glycol ethers are solvents that are present in a large number of products used commercially and domestically. During recent years, ethylene glycol ether derivatives, in particular ethylene glycol methyl ether and ethylene glycol ethyl ether, have been progressively replaced by propylene glycol ether derivatives, which are less toxic. The aim of this study was to estimate the level of exposure to glycol ethers in a sample population of French men employed by the Paris Municipality by measuring the amount of alkoxycarboxylic acid metabolites in their urine. METHODS: Urine samples were collected at the end of two different working weeks from 109 men, 54 of whom were judged to be occupationally exposed to glycol ether-containing products. Five alkoxyacetic acids (methoxyacetic, ethoxyacetic, n-propoxyacetic, phenoxyacetic, butoxyacetic acids) from ethylene glycol derivatives, and one alkoxypropionic acid (2-methoxypropionic) from a propylene glycol derivative, were simultaneously analysed by gas chromatography coupled to electron-capture detection. RESULTS: 2-Methoxypropionic was the most frequently found alkoxycarboxylic acid. The concentration of this metabolite reached 5.6 mmol/mol creatinine. The second most common alkoxycarboxylic acid was phenoxyacetic (up to 2.3 mmol/mol creatinine). The concentrations of the other alkoxycarboxylic acids were less than 1 mmol/mol creatinine. Although the concentration of alkoxycarboxylic acids was higher among men occupationally exposed to glycol ether-containing products than among unexposed men, the difference was significant only for butoxyacetic acid. CONCLUSIONS: Our data suggest that the use and exposure levels of glycol ethers have qualitatively and quantitatively changed dramatically over recent years. Particular attention should be paid in the future to alkoxypropionic acids derived from minor isomers of propylene glycol ether derivatives.

Adult↗

PubMed2003

Environmental lead exposure and its relationship to traffic density among Senegalese children: a pilot study.

In Senegal, as in many developing countries, traffic density is increasing in urban areas; in Dakar more than 50% of vehicles use gasoline. Yet the extent and real magnitude of the problem has neither been recognized nor assessed in these countries. Systemic data assessment of lead pollution and people's exposure are not well known in Senegal. This study was also designed to determine the impregnation levels of the lead released by the exhaust of cars and the changes of some early biological markers in Senegalese children. Blood lead (BPb) levels showed that all the children enrolled were exposed. However, lead exposure levels (from 34.7 to 145.8 microg/L) were less important for children living in rural areas (60.9+/-18.3 microg/L) than for those living in urban areas (106.7+/-16.9 microg/L). These changes could be correlated to the difference in the automobile traffic between both these regions (P < 0.001). BPb mean levels found in boys were higher than those in girls (P < 0.05). Despite elevated BPb levels, all values for blood zinc protoporphyrin and urine delta-aminolevulinic acid were within physiological ranges. In addition, variations in some biological markers of oxidative stress and renal disorders were seen; however, they must be confirmed by a future epidemiological study.

Air Pollutants↗

PubMed2002

[Home environment and acute propylene glycol intoxication in a two-year old. An unusual case report].

BACKGROUND: Acute propylene glycol intoxication in a two-year-old toddler underlines the potentially serious toxicity in children of this chemical agent present as a diluent in many drugs and environmental products such as cosmetics, diapers, cleansing towels, despite a common consideration of safety and lack of toxicity. CASE REPORT: A two-years-old boy previously healthy was found in the morning by his parents in his cradle, lethargic, responsive only to sharp pain. On admission, vital signs were: temperature 38.5 degrees C, lethargy, polypnea; propylene glycol intoxication through disposable cleansing towels chewing was ascertained by anamnesis and blood urine analyses which revealed metabolic acidosis and serum propylene glycol peak. CONCLUSION: Environmental acute propylene glycol intoxication must be considered and searched for in front of a metabolic acidosis case of unknown origin in children.

Acidosis↗

PubMed2001

Environmental exposure to lead in a population of adults living in northern France: lead burden levels and their determinants.

As part of the assessment of a site in northern France polluted by metals from two smelters (in particular, lead, cadmium and mercury), a cross-sectional study was carried out which intended to estimate the levels of the lead burden of the adult population living on the site and the factors associated with these levels. The exposed zone included 10 municipalities in the Nord-Pas de Calais region, located in the vicinity of two non-ferrous metal smelters. The soils in these municipalities contained between 100 and 1700 ppm of lead. The non-polluted zone contained 20 municipalities from the same region, drawn randomly from those in the region of comparable size but free from any industrial lead exposure. The adult study population (301 men and 300 women) was stratified according to age, sex, employment status and exposure level. The inclusion criteria required subjects who were aged between 20 and 50 years and had been living in the exposed zone for at least 8 years; the exclusion criteria were pregnancy, cancer, kidney disease and diabetes. No more than 10% of the subjects participating could work at one of the two smelters. Data collection took place at home; visiting nurses interviewed subjects to complete a questionnaire and also took blood samples. The lead assay was performed by atomic absorption spectrometry. The geometric mean of the blood-lead levels was 74 microg/l, 95% CI = 69-80 among men and 49 microg/l, 95% CI = 46-53 among women. Blood-lead levels exceeding 100 microg/l were found among 30% of men and 12% of women. Several factors were associated with variation of the mean blood-lead level: the blood-lead level was significantly higher among the men for subjects living less than 1 km from the smelters (geometric mean x 1.3, 95% CI = 1.1-1.6), for those who drink alcoholic beverages (x 1.1, 95% CI = 1.0-1.2 for consumption of 30 g/day), those who smoke (x 1.2, 95% CI = 1.0-1.3 for 20 cigarettes/day), and for subjects with occupational exposure; among the women, for subjects living less than 1 km from the smelters (geometric mean x 1.5, 95% CI = 1.2-1.7), for those who drink alcohol (x 1.1, 95% CI = 1.1-1.2 for a daily consumption of 10 g), and for women living in a building constructed before 1948 (x 1.2, 95% CI = 1.0-1.4).

Adult↗

PubMed2001

Determinants of cadmium burden levels in a population of children living in the vicinity of nonferrous smelters.

This report covers part of the assessment of a site in northern France polluted by industrial metal emissions. Our objectives were to assess the cadmium burden in children aged 8 to 11 years and look for factors that affected it. A cross-sectional population-based study took place in 1996-1997 and included 400 children (200 in the metal-polluted area). The geometric mean of the blood cadmium (CdB) levels of children living on the polluted site was 0.51 microg/L (95% CI=[0.49-0.53]); that of the nonexposed children was 0.47 microg/L (95% CI=[0.45-0.49]) (P<0.01). The geometric mean of the urinary cadmium (CdU) levels of children living on the polluted site was 1.16 microg/g creatinine (95% CI=[1.01-1.34]); that of the nonexposed children was 0.99 microg/g creatinine (95% CI=[0.86-1.14]) (P=0.10). Mean CdB was higher among children within 4 km of a zinc smelter and consuming > or =500 ml of tap water daily (x1.34; 95% CI=[1.14-1.51]) compared with children living more than 4 km away and consuming <500 ml of tap water daily. Independently of this association, consumption of fish and shellfish (> or =once a week vs. or =once daily vs. <once daily) was associated with higher mean CdB levels, respectively: x 1.14; 95% CI=[1.07-1.21] and x 1.25; 95% CI=[1.04-1.50]. Neither sex nor age was associated with CdB. Mean CdU was associated with paternal occupational cadmium exposure.

Animals↗

PubMed2001

Occupational and environmental risk factors of the myelodysplastic syndromes in the North of France.

Aetiological factors of the myelodysplastic syndromes (MDS) are largely unknown, with the exception of alkylating agents, ionizing radiation and benzene. Some other risk factors have been suggested by the few epidemiological studies reported (solvents, ammonia, exhaust gases, metals, pesticides, alcohol). We performed a case-control study to assess the relationship between occupational or environmental factors and MDS. Two hundred and four patients with newly diagnosed MDS, and 204 sex- and age-matched controls were included. Medical history, demographic data, lifetime exposure and hobbies were obtained. Qualitative and quantitative exposure to chemical and physical hazards were evaluated with the patients and reviewed by a group of experts in occupational exposure. The median age was 70 years and 62% of the patients were men. In univariate analyses, we found relationships between MDS and smoking habits, gardening, occupations such as health professionals, technical and sale representatives, machine operators, agricultural workers, textile workers, qualitative occupational exposures (exposed/non-exposed) to oil, solvents, ammonia, pesticides, fertilizers, cereal dusts, contact with poultry or livestock and infective risk, and lifetime cumulative exposure to solvents, oil, textile dust and infective risk. The main risk factors of MDS determined by multivariate analyses (conditional logistic regression) were, being an agricultural worker [odds ratio (OR) = 3.66; 95% confidence interval (CI) 1.9-7.0], textile operator (OR = 3.66; 95% CI 1.9-7.9), health professional (OR = 10.0; 95% CI 2.1-48.7), commercial and technical sale representative (OR = 4.45; 95% CI 1.4-14.6), machine operator (OR = 2.69; 95% CI 1.2-6.0), living next to an industrial plant (OR = 2.45; 95% CI 1.5-4.1), smoking (OR = 1.74; 95% CI 1.1-2.7) and lifetime cumulative exposure to oil (OR = 1.1; 95% CI 1.0-1.2). Further studies should be performed to assess specific exposures more precisely and it would be of interest to develop a map of haematological malignancies according to industrial background.

Aged↗

PubMed2001

Personal exposure of workers to atmospheric PAHs on gasworks sites--The SOLEX study.

The aim of the SOLEX study was to estimate the personal exposure of workers to atmospheric polycyclic aromatic hydrocarbons (PAHs) on former gasworks sites in the Paris metropolitan area. Devices to sample gas and particulate phases for 9 PAHs were carried during one working day of a study week in November 1997 by 24 workers and in June 1998 by 19 workers with contrasted job profiles involving different opportunities for contact with the soil; among these volunteers, some were active in the process of contaminated soil remediation during the November study period. PAH concentrations were measured by high-performance liquid chromatography. Subjects working on the site under remediation were clearly more exposed (684.1 ng/m3 for total PAHs in November 1997) than workers, without close contact with soil, whose PAH exposure was similar to that measured by fixed monitors in the ambient air in Paris. The contrasts were weaker in June 1998, when soil remediation had nearly been completed. Only subjects involved in activities with close contact with the ground were found with exposures exceeding background levels. Further investigations are needed to improve our understanding of the influence of the pollutants present in the soil.

Adult↗

PubMed2000

Feasibility of assessing dermal exposure to PAHs of workers on gaswork sites--the SOLEX study.

Population exposure to pollutants in soil is an important public health concern. Difficult to measure, it is usually estimated using multimedia models. Modeling data predict that the skin surface is a predominant exposure route in roughly 15% of the US Superfund sites. Nonetheless, no study has confirmed these predictions. The SOLEX study was an opportunity to study the feasibility of estimating the cutaneous polycyclic aromatic hydrocarbons (PAHs: all 16 of the United States Environmental Protection Agency list) load of workers at three former manufactured gas sites, one of those being under remediation. Over two measurement periods (November 1997 and June 1998), 30 and 28 volunteers, respectively, were equipped for a single day work with five pads that collected soil particles and were placed at the neck, shoulder, wrist, groin, and ankle. Pad contamination was observed for six of the nine workers on the site being remediated but not on other sites. The wrist pad was most often affected, followed by the neck pad, these are, the exposed regions of the body. The PAHs most frequently identified were anthracene, fluoranthene, naphthalene, phenanthrene, and pyrene, at concentrations relatively high. In conclusion, this study showed that estimating skin exposure to soil pollutants is feasible. Secondly, it suggested that only subjects in close contact with the soil had a detectable exposure to PAHs. Extension of this approach to other exposure settings is warranted, especially among children playing in polluted public or private gardens, because their games lead to frequent contact with the soil.

Administration, Cutaneous↗

PubMed2000

Environmental lead exposure in a population of children in northern France: factors affecting lead burden.

BACKGROUND: This study is part of the assessment of a site in northern France polluted by lead from industrial emissions. Our objectives were to look for the factors that influence lead burden in children aged 8-11 years. METHODS: A cross-sectional population-based study took place in 1996-97 and included 400 children (200 of whom lived on the metal-polluted site). RESULTS: The geometric mean of the blood-lead levels of children living on the polluted site was 39.5 microg/l (95% CI = 36.3-43.1); that of the non-exposed children was 30.6 microg/l (95% CI = 27.8-33.6) (P < 0.0001). Analysis of the variations in the mean blood-lead levels showed associations with: distance from the smelting plants (mean blood-lead level fell by a factor of 1/1.3 (95% CI = 1/1.2-1/1.4) for each km from the smelter over the range of 1-3 km and was constant thereafter) and consumption of tap water (when the water pipes were made of lead, the mean blood-lead level of children who drank tap water was twice as high (95% CI = 1.2-3.4) as that of children who did not). CONCLUSIONS: The children's blood-lead levels were essentially linked to two factors: proximity to the smelters and drinking tap rather than bottled water.

Body Burden↗

PubMed2000

Urinary 1-hydroxypyrene as a biomarker of polycyclic aromatic hydrocarbons exposure of workers on a contaminated site: influence of exposure conditions.

The aim of the study was to determine the exposure levels of workers to polycyclic aromatic hydrocarbons on gasworks sites by the measurement of urinary 1-hydroxypyrene. Start-shift and end-shift urine samples were taken every day during an entire week (Monday to Friday), once in November and a second time in June. Four groups of workers were selected according to their activity. Increased exposure was only found among volunteers involved in the remediation of a site, 0.16 to 2.31 mumol/mol creatinine in non-smokers. The median of the non-smoker referent group was 0.02 mumol/mol creatinine (95% confidence interval, 0.01 to 0.04). Smokers had greater exposure levels than non-smokers in every group. Within and between variability was around 200%. Assessment of the exposure of persons on contaminated soil is possible, with the condition that the exposed subjects come in direct contact with the soil.

Analysis of Variance↗

PubMed2000

Acute respiratory effects of exposure to stainless steel and mild steel welding fumes.

Over the past few years, many studies, including one on our previous work, have examined the chronic effects of fumes from stainless steel (SS) welding on the health of welders. These chronic effects have been related to concentrations of chromium and nickel in SS welding fumes. The present study examined the acute respiratory effects of welding fumes in the workplace by measuring the across-shift changes in a population of 144 SS and mild steel (MS) welders and 223 controls. Manual Metal Arc, Metal Inert Gas, and Tungsten Inert Gas welding processes were studied. Pulmonary function tests were performed at the start (ante, or A) and at the end (post, or P) of the work shift. The study of sensitization to harmful respiratory effects of welding was based on the study of the (P-A)/A ratio (%) of the spirometric variations during the shift. The means of these ratios in the control subjects were used to account for the circadian effect. In SS welders we observed a significant decrease in forced vital capacity (FVC) during the shift. Significant across-shift decrements in forced expiratory volume in 1 second (FEV1) and FVC were related to the SS welding exposure compared with MS welding. Moreover, the across-shift decreases in FEV1, FVC, and peak expiratory flow (PEF) were significantly related to the Manual Metal Arc welding process, compared with Metal Inert Gas techniques (respectively, PEF = -2.7% of baseline values [SD, 11.9] vs 2.0% of baseline values [SD, 7.7] P = 0.04; FVC = -1.5% of baseline values [SD, 4.8] vs 0.2% of baseline values [SD, 4.5] P = 0.05). We also demonstrated the influence of duration of SS welding exposure on the course of lung function during the work shift. After 20 years of SS welding activity, SS welders had more significant across-shift decreases than MS welders with a similar MS exposure duration (respectively, FEV1 = -2.7% of baseline values [SD, 5.9] vs 0.7% of baseline values [SD, 4.2] P = 0.008; PEF = -3.8% of baseline values [SD, 9.6] vs 2.3% of baseline values [SD, 6.5] P = 0.04). We concluded that welding-related lung function responses are seen in SS compared with MS welders and in those with a longer lifetime welding history.

Adult↗

PubMed1998

Respiratory symptoms and pulmonary function among stainless steel welders.

In the last few years, many studies have been carried out concerning the effects of fumes from stainless steel (SS) welding on the health of welders. The respiratory effects of exposure to SS welding fumes have already been studied, but the results of lung function investigations have not been consistent. However, the main factor of risk for the welders' health seems to be related to the great concentration of chromium and nickel contained in fumes coming from SS welding. The aim of this study was to detect the chronic effects of SS welding exposure on pulmonary symptoms and ventilatory function tests. Respiratory symptoms and lung function tests were studied in 134 SS welders and 252 controls (C). Welders and controls were of similar average age, height, and duration in employment. The smoking habits of the groups were also similar. The medical questionnaire on respiratory symptoms was a version of the Medical Research Council questionnaire, modified by the British Occupational Hygiene Society. The flow-volume curves were performed with a calibrated pneumotachograph spirometer before each subject started working. After adjustment for tobacco habits, the SS welders presented a higher prevalence of bronchial irritative symptoms such as cough (P = 0.01) or sputum production (P = 0.02) than the controls. On the other hand, chronic bronchitis appeared to be significantly linked to tobacco consumption. The pulmonary function analysis underscored no significant difference between stainless steel welders and controls (forced expiratory volume in one second, observed/predicted: SS = 0.99 vs C = 0.98; maximal midexpiratory flow, observed/predicted: SS = 0.90 vs C = 0.92; maximal expiratory flow at 50 % of the forced vital capacity, observed/predicted: SS = 0.95 vs C = 0.95). On the other hand, by the mean of the two-ways analysis, a significant tobacco effect was found, without exposure or interaction of tobacco-exposure effects. There was no influence of the specific welding processes on the spirographic parameters, but a decrease in spirographic values after 25 years of welding activity was evident. The results of multiple regression indicated that age was not a confounding factor.

Adult↗

PubMed1997

Assessment of biological chromium among stainless steel and mild steel welders in relation to welding processes.

Air and biological monitoring were used for assessing external and internal chromium exposure among 116 stainless steel welders (SS welders) using manual metal arc (MMA), metal inert gas (MIG) and tungsten inert gas (TIG) welding processes (MMA: n = 57; MIG: n = 37; TIG: n = 22) and 30 mild steel welders (MS welders) using MMA and MIG welding processes (MMA: n = 14; MIG: n = 16). The levels of atmospheric total chromium were evaluated after personal air monitoring. The mean values for the different groups of SS welders were 201 micrograms/m3 (MMA) and 185 micrograms/m3 (MIG), 52 micrograms/m3 (TIG) and for MS welders 8.1 micrograms/m3 (MMA) and 7.3 micrograms/m3 (MIG). The curve of cumulative frequency distribution from biological monitoring among SS welders showed chromium geometric mean concentrations in whole blood of 3.6 micrograms/l (95th percentile = 19.9), in plasma of 3.3 micrograms/l (95th percentile = 21.0) and in urine samples of 6.2 micrograms/l (95th percentile = 58.0). Among MS welders, mean values in whole blood and plasma were rather more scattered (1.8 micrograms/l, 95th percentile = 9.3 and 1.3 micrograms/l, 95th percentile = 8.4, respectively) and in urine the value was 2.4 micrograms/l (95th percentile = 13.3). The analysis of variance of chromium concentrations in plasma previously showed a metal effect (F = 29.7, P < 0.001), a process effect (F = 22.2, P < 0.0001) but no metal-process interaction (F = 1.3, P = 0.25). Concerning urinary chromium concentration, the analysis of variance also showed a metal effect (F = 30, P < 0.0001), a process effect (F = 72, P < 0.0001) as well as a metal-process interaction (F = 13.2, P = 0.0004). Throughout the study we noted any significant differences between smokers and non-smokers among welders. Taking in account the relationships between chromium concentrations in whole, plasma or urine and the different welding process. MMA-SS is definitely different from other processes because the biological values are clearly higher. These higher levels are due to the very significant concentrations of total soluble chromium, mainly hexavalent chromium, in welding fumes.

Adult↗

PubMed1997

Assessment of potential damage to DNA in urine of coke oven workers: an assay of unscheduled DNA synthesis.

OBJECTIVES: A study was conducted in coke oven workers to evaluate the biological consequences of the exposure of these workers, particularly production of potential genotoxic factors. METHODS: 60 coke oven workers and 40 controls were recruited in the same iron and steel works. Exposure to polycyclic aromatic hydrocarbons (PAHs) was assessed by job and measurement of 1-hydroxypyrene (1OHP) in urine samples. An unscheduled DNA synthesis assay was performed on rat pleural mesothelial cells used as a test system to evaluate the effect of the workers' filtered urine on the DNA repair capacity of rat cells to determine whether DNA damaging agents are present in the urine of these workers. RESULTS: Urinary concentrations of 1OHP ranged from 0.06 to 24.2 (mean (SD) 2.1 (3.6)) mumol/mol creatinine in exposed coke oven workers, and from 0.01 to 0.9 in controls (0.12 (0.15)). These high concentrations in coke oven workers reflected recent exposure to PAHs and were in agreement with the assessment of exposure by job. No significant difference was found between coke oven workers and controls in the DNA repair level of rat cells treated with urine samples. However, the rat cell repair capacity decreased with increasing 1OHP concentrations in the exposed population (r = -0.28, P < 0.05). CONCLUSIONS: As high concentrations of 1OHP were found in the urine of some workers, a more stringent control of exposures to PAHs in the workplace is required. Exposure to PAHs was not associated with a clear cut modification of the urinary excretion of DNA damaging factors in this test, as shown by the absence of increased unscheduled DNA synthesis in rat cells. However, impairment of some repair mechanisms by urinary constituents is suspected.

Adult↗

PubMed1996

Dose-dependent elimination kinetics for mercury in urine: observations in subjects with brief but high-level exposure.

OBJECTIVES: To study the elimination kinetics for mercury in urine (U-Hg) after brief but high-level exposure. METHODS: U-Hg was examined in 11 workers after 2-10 days of exposure to inorganic Hg and after symptoms and signs of Hg intoxication had appeared. Initial U-Hg excretion varied between 60 and 2360 micrograms/g creatinine. The subjects were followed up for 1-11 months. In each subject, one- and two-compartment models were fitted to the U-Hg values, assuming an exponential decrease, by weighted non-linear least-squares regression (weight = 1/U-Hg). RESULTS: The data indicated two elimination phases in subjects with initial U-Hg above 600 micrograms/g. In the two-compartment models, there was a fast phase with a half-time of 2-16 days, and a slow phase with a half-time of more than a month. The fast phase contributed 70-90% to the sum of the Y intercepts. CONCLUSIONS: The kinetics of U-Hg excretion after cessation of exposure seems to be dose-dependent and, at least in certain cases, to have two phases. The explanation for the fast phase may be that the capacity of certain binding sites in the kidney was exceeded.

Accidents, Occupational↗

PubMed1996

Interactive effects of polycyclic aromatic hydrocarbons and iron oxides particles. Epidemiological and fundamental aspects.

Iron oxides are present in many occupational atmospheres mainly in iron ore mines and in steel industry. Among these workers, epidemiological studies indicated an excess of lung cancer deaths. In mines, it was difficult to involve iron oxides exposure because there are other possible causes as radon, polycyclic aromatic hydrocarbon (PAH) present in diesel exhausts, silicosis or siderosis. The contradictory results of these studies are due to the differences of exposure levels or to the presence or not of these cofactors or of a sufficient prevention. But generally the results agree with an interaction of iron oxide dusts and smoking habits. It is unclear if this interaction supports an additive or multiplicative risk of lung cancer. Experimental studies with Fe2O3 showed that these particles are able to induce lung cancers only in the presence of PAH when administered to animals. In vitro studies permitted to observe an interaction in the metabolism of benzo(a)pyrene (BaP) leading to a higher level of precursors of the ultimate carcinogen. As this metabolism of BaP is known to be enhanced during lipoperoxidation, it is possible to involve this mechanism with Fe2O3. After phagocytosis and dissolution with production of ferric ions, Fe2O3 can enhance the production of reactive oxygen species responsible of damaging both lipidic constituents and DNA. Fe3O4 and mainly FeO may be more toxic, introducing directly ferrous ions in the cells after dissolution, but the cancerogenicity of the these compounds is unknown, making necessary to develop research.

Animals↗

PubMed1996

Toxicity of ferric oxide and benzo[a]pyrene alone or in combination in respiratory tract of Sprague Dawley rats.

The association of small quantities of ferric oxide with Benzo[a]Pyrene (BaP) appears to increase in vivo the toxic effect of BaP. The effect of Fe2O3 may be mediated by the recruitment of alveolar macrophages. These cells would contribute to the production of toxic and carcinogenic BaP metabolites and would stimulate development of tumors by producing cellular mediators of inflammation. In order to understand the mechanism of the synergic effect, we have instillated male Sprague Dawley rats 3 weeks of age with a single dose: Fe2O3 (3 mg) or BaP (3 mg)/combination Fe2O3-BaP (3 mg-3 mg) in 200 microliters of physiological saline solution. Control group of identical size (treated with physiological saline solutions and untreated) were used for this study. Animals were sacrificed 48 hours after instillation and a bronchoalveolar lavage (BAL) was performed. With each BAL we have obtained protein measurement, cells were stained with May-Grünwald-Giemsa method and slides were studied with polarised light. The malonaldehyde (MDA) was measured by High Performance Liquid Chromatography. The PMN elastase determination was performed by IMAC (immuno-activation) technology. An automated kinetic method for measuring cathepsins B and L was carried out using a fluorogenic substrate: Z-Phe-Arg-AMC, a specific inhibitor E64 and AMC as an internal standard. After a quantitative Dot-Blot of the samples of BAL, an immunodetection of alpha(1)-antitrypsin (alpha(1)AT) was performed. The inhibitory capacity of alpha(1)AT was determined by an enzymatic reaction with porcine pancreatic elastase. We have observed an increased MDA level for rats intoxicated with Fe2O3 (123%), BaP (31%) and Fe2O3 + BaP (56%). The levels of PMN elastase and cathepsin B and L were increased: Fe2O3 (51-58%), BaP (52-27%). This effect was not seen for rats intoxicated by Fe2O3 + BaP. The free alpha(1)AT was decreased with the three toxics (Fe2O3: 44%--BaP: 42%--Fe2O3: 41%). The inhibitory capacity of alpha(1)AT was lower in groups of rats instilled with toxics.

Animals↗