[Use of illicit substances in the workplace]. / Consommation de substances illicites en milieu professionnel.

The development of addictive behaviors is a source of worry and concern for workplace and occupational physicians. To estimate the prevalence of behaviors, two types of surveys can be carried out: self-assessment surveys and biological testing in the workplace. For the latter, when a settlement is within the company, the prevalence is often lower compared to those enterprises that have not adapted this policy. Very few investigations have been published in France to date. Data published by the United Nations Office against Drugs and Crime (UNODC) shows a stable consumption of illicit substances in recent years. They reported consumption in the world among the general population (all subjects aged 15 to 64). For France, were described a prevalence estimated in 2005 to 8.6%, 0.6% and 0.2% for cannabis, cocaine and amphetamine derivatives, respectively, and in 2007 to 4.6% for opiates. Some prevalence in the workplace have been reported in Europe in chemical, petrochemical, metallurgical, automotive, in the transport sector and in medical and military fields. However, it appears that few surveys in the workplace have been published in France, this lack may be explained by a desire for anonymity on the subject at the level of company management and doctors work that focus on individual support with the problem of addiction. Screening for illicit substances is necessary because these psychotropic substances affect alertness and pose risks in the workplace, especially such that the association cannabis-alcohol further increases the risk. Knowledge of consumption is, moreover, an important factor in job security. It may be acquired if reliable methods, inexpensive to allow routine screening. Publication of results will reveal the extent of the problem and implement more effective campaigns of information and prevention in the workplace.

Glycol ethers and semen quality: a cross-sectional study among male workers in the Paris Municipality.

OBJECTIVES: Apparent increases in human male reproductive disorders, including low sperm production, may have occurred because of increased chemical exposure. Various glycol ether-based solvents have pronounced adverse effects on sperm production and male fertility in laboratory animals. The authors investigated the effects of past and current exposure to glycol ether-containing products on semen quality and reproductive hormones among men employed by the Paris Municipality. METHODS: Between 2000 and 2001 the authors recruited 109 men who gave semen, blood and urine samples and underwent an andrological examination. Information on lifestyle, occupation, exposure and medical history was obtained by interview. According to their job and chemical products used during the period 1990-2000, men were classified as either occupationally exposed or non-exposed. Current exposure levels to glycol ethers at the time of the study were evaluated by biological monitoring of six urinary metabolites. RESULTS: Previous exposure to glycol ethers was associated with an increased risk for sperm concentration, for rapid progressive motility and for morphologically normal sperm below the World Health Organization semen reference values. No effect of previous glycol ether exposure on hormones levels was observed. By contrast, current glycol ether exposure levels were low and not correlated with either seminal quality or hormone levels. CONCLUSIONS: This study suggests that most glycol ethers currently used do not impact on human semen characteristics. Those that were more prevalent from the 1960s until recently may have long lasting negative effects on human semen quality.

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.

Exposure to occupational and environmental factors in myelodysplastic syndromes. Preliminary results of a case-control study.

We performed a case-control study of occupational and environmental risk factors in myelodysplastic syndromes (MDS) diagnosed at our institution, using the method of Siemiatycki. A control for each MDS case, matched for age, sex, and residence area was chosen. The questionnaire asked demographic data, medical history, and information on life-time environmental and occupational exposures. Occupational exposures were first assessed by job titles, then by evaluating exposure to a list of 70 chemicals, and the level and duration of exposure to those chemicals (exposure index). In the first 100 cases and controls analyzed, a significantly higher incidence of smokers or ex-smokers was seen in MDS cases (odds ratio, OR = 1.83, P = 0.03). A significant excess of MDS was found in male patients with jobs (or previous jobs) generally exposing to chemical compounds, including plant and machine operators and assemblers (odds ratio, OR = 3.73, P = 0.014) whereas, on the contrary, technicians and associate professionals were more often seen in controls (OR = 0.17, P = 0.002). In males, there was also a trend for more skilled agricultural workers and coal miners in MDS cases. In females, there was a non-significant trend for more professionals in controls. After adjusting for sex, age and smoking habits, significantly more frequent exposure to stone dusts (OR = 3.06, P = 0.011), and cereal dusts (OR = 2.27, P = 0.04) was found. There was also a trend for higher incidence of exposure to exhaust gases and nitro-organic explosives. In addition, significantly higher exposure indices to petrol and diesel derivatives (P = 0.03) and to fertilizers (P = 0.003) were seen in MDS cases, as compared to controls. No significant difference in exposure to other chemicals was seen between MDS cases and controls. These preliminary results of our study, which is accruing more cases, suggest, as two previously published case-control studies of risk factors in MDS, that exposure to some chemicals may be involved in the pathogenesis of MDS.

Renal kallikrein excretion as a distal nephrotoxicity marker during cadmium exposure in rats.

Cadmium exposure is known to induce hypertension, but development of hypertension is not universal in exposed animals. However, the cellular uptake of cadmium could also exert renal cytotoxic effects which have been, until now, essentially only studied at the proximal tubule level. Kallikrein is an enzyme synthetized in renal cortex and excreted in the urine in the distal tubule. Therefore, to evaluate the distal renal effect of cadmium, we studied the daily urinary kallikrein excretion (UKE) in conscious unrestrained female Brown Norway rats during long-term chronic exposure to 2 dosages of cadmium given subcutaneously 3 times a week, a low dose (LD): 0.25 mg/kg and a high dose (HD): 1 mg/kg. Neither dose of cadmium was able to induce significant hypertension in the treated animals. HD administration for 24 weeks resulted in a decreased UKE associated with an increase in plasma renin activity and sodium and potassium excretions. LD administration had no significant effect on UKE. Twenty weeks after stopping cadmium administration, a persistent reduction in UKE was still observed; furthermore, the group which had been previously administered a LD of cadmium, now also exhibited a reduced UKE. During this re-examination period in both groups, the UKE reductions were associated with normal systolic blood pressure, glycosuria, natriuresis. Our data show that cadmium administration can influence UKE, plasma renin activity, plasma aldosterone concentration and electrolyte excretion without inducing any variation of blood pressure. This may reflect a nephrotoxic, non-hypertensive effect. Since this effect persisted after stopping cadmium administration, it may indicate a prolonged irreversible nephrotoxic effect at the distal nephron level. Thus, UKE may be a useful non-invasive index to evaluate distal nephrotoxicity.

Toxic action of ethylene oxide on pulmonary cells (L132) cultured under aerobic conditions.

In environmental health, inhalation is the most prominent route of ethylene oxide (EO) exposure. In the current study, human embryonic pulmonary epithelial cells (L132 cell line) were exposed to EO following a prior adaptation to atmospheric conditions. A comparative study between two EO exposure conditions (0.07 and 0.18 g/m3 gas injections) was carried out after a 1-h incubation. Whereas control cells were exposed to a pure air stream. The EO cytotoxicity was established by electron microscopy and LDH and ATP determinations after 1, 3, 6 and 24 h following the exposure. The ultrastructural examination revealed a remarkable vacuolisation of the exposed cells leading to cell death. In spite of this modification, the number of mitochondria and the content of endoplasmic reticulum increased in the L132 cells. For both exposure concentrations LDH was released into the extracellular milieu. In the presence of the high EO concentration, LDH activity increased with respect to the post-exposure time involving alteration of the membrane and permeability. For low EO exposure, ATP synthesis was significantly increased after 1 h of post-exposure (P < 0.01) and decreased to normal levels after 6 h. For the high EO concentration, however, ATP continually increased with respect to the post-exposure time. This indicates cellular stimulation and suggests the activation of a defense mechanism. This study shows a direct EO cytotoxicity on L132 cells cultured in atmospheric conditions.

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.

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.

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.

Determination by hplc of trifluoroacetate levels in plasma and urine of patients anaesthetized with halothane.

A new method is described for determination of trifluoroacetic acid (TFA) in biological fluids. Optimum extraction is achieved by addition of 18-crown-6 ether and acidification of the sample. The 4-bromomethyl-7-methoxycoumarin derivatives of the carboxylic acid are prepared and a sample is subjected to HPLC. A linear analytical curve of peak area against TFA concentrations ranging between 0.2 and 20 mug ml is obtained, and the minimum detectable concentration is estimated to be 0.1 mug ml .

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).

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.

Development and evaluation of immunochromatographic rapid tests for screening of cannabinoids, cocaine, and opiates in urine.

The test principle and the optimization of the reactive ingredients are described for the one-step dip and-read immunochromatographic FRONTLINE rapid tests for drugs-of-abuse testing in urine samples. In a multicenter evaluation the rapid tests were compared with FPIA and EMIT immunoassays. Discrepant results were further analyzed by gas chromatography-mass spectrometry methods. In the comparison of the cannabinoids rapid tests versus both immunoassays using clinical and forensic urine samples (399 versus FPIA and 755 versus EMIT), sensitivities and specificities were 97% or better for both comparisons. For cocaine, a sensitivity of 100% versus both routine technologies was obtained, whereas the specificity was reduced somewhat to 91% because of some cross-reactivity with metabolites of methadone and of clozapine. Specificity was very high for the cocaine rapid tests (98-100%) when applied to urine samples of persons not in a methadone maintenance program. Sensitivities and specificities for the opiates rapid tests were 99% or better at all sites when compared with the routine methods. In the screening of about 1200 clinical urine samples for cannabinoids, cocaine or opiates misuse only six samples would have stayed undetected by rapid test analyzes. These results show the FRONTLINE assays allow a reliable and immediate screening for drugs of abuse.

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.

Gas-chromatographic determination of levamisole in human plasma-normalization and reliability of the method.

Levamisole has been used by many authors as an immunostimulant agent but the relationship between oral doses, plasma level and the therapeutic effects were not known. For such a study it was necessary to establish an accurate and reproducible method of measurement. We describe a modification of the gas chromatographic method of Wynants et al. (1975). The normalization of the extraction of the extraction process leads to greater reliability and accuracy (4 ng +/- 7.6%). Reproducibility was established using a series of 30 determinations from standard solutions and plasmas supplemented with Levamisole. The relative standard deviation in K evaluation was varied between 0.9 and 1.8%, 3.7 and 6.1% for standard solutions and plasmas respectively. Consequently this method was adopted for this pharmacokinetic study which was carried out on healthy and cancer patients.

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.

Toxicity of iron oxides and metabolites of benzo[a]pyrene alone or in combination in cells culture and identification by laser microprobe mass spectrometry.

The goal of the gas-phase studies of well-characterized transition-metal systems is to enhance our understanding of the chemistry and sometimes of the toxic, carcinogenic effects of transition metal oxide clusters and compounds. The analysis of inorganic solids by time of flight laser microprobe mass spectrometry (TOF-LMMS) shows the formation of clusters in the mass spectra which can be used for the identification of inorganic particles. First, we have applied non-resonance ionization (delta = 226 nm) or resonant ionization (delta = 293.7 nm) of iron to study the non stoichiometric Fe1-xO, Fe3O4, Fe2O3 compounds in positive mode by TOF-LMMS. The positive mass spectra are characterized by many differences between the clusters detected and their intensities. Then, we have analysed the benzo[a]pyrene (BaP), the 1-hydroxbenzo[a]pyrene (1-OH-BaP) and the 3-hydroxybenzo[a]pyrene (3-OH-BaP) of TOF-LMMS and by Fourier Transform Irons Cyclotron Resonance Mass Spectrometry (FT-ICR-MS). It is possible to distinguish these different compounds by their respective fingerprint. Later on, we have studied toxic effects of iron oxides (Hematite Fe2O3 and Magnetite Fe3O4), benzo[a]pyrene (BaP) and Pyrene, alone or in combination. The LC50 was appreciated by colony-forming cell culture method. Cells were observed by electron microscopy and the valence of particles was analysed by TOF-LMMS. With Fe2O3 we have observed a significant decrease (20%) at higher concentration (0.5 mmol/l) and smaller quantities of BaP were highly toxic. The association of BaP at the LC10 dose (0.05 mumol/l) with growing doses of Fe2O3 or Fe3O4 (0.0125; 0.025; 0.05; 0.1; 0.2 mmol/l), appeared to increase the toxic effect of BaP 3 to 4 times. These results suggest that Fe2O3 and Fe3O4 alone are not very toxic but the association of one of these compounds with BaP increases the toxicity of the latter. On the other hand, TOF-LMMS seems to show a metabolization of iron oxide into reduced form. But, it is necessary to raise the ambiguity about the iron which is always in the cells present. For that purpose, studies with iron oxides enriched by 54Fe isotope have begun.

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.

[Home environment and acute propylene glycol intoxication in a two-year old. An unusual case report]. / Environnement domestique et intoxication aiguë au propylène glycol chez un nourrisson de deux ans. A propos d'une observation inhabituelle.

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.