Jean-Pierre Buchet

Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust.

The prevalence of neuropsychological and respiratory symptoms, lung ventilatory parameters, neurofunctional performances (visual reaction time, eye-hand coordination, hand steadiness, audioverbal short term memory), and several biological parameters (calcium, iron, luteinising hormone (LH), follicle stimulating hormone (FSH), and prolactin concentrations in serum, blood counts, manganese (Mn) concentration in blood and in urine) were examined in a group of workers (n = 92) exposed to MnO2 dust in a dry alkaline battery factory and a matched control group (n = 101). In the battery plant, the current exposure of the workers to airborne Mn was measured with personal samplers and amounted on average (geometric mean) to 215 and 948 micrograms Mn/m3 for respirable and total dust respectively. For each worker, the lifetime integrated exposure to respirable and total airborne Mn dust was also assessed. The geometric means of the Mn concentrations in blood (MnB) and in urine (MnU) were significantly higher in the Mn exposed group than in the control group (MnB 0.81 v 0.68 microgram/100 ml; MnU 0.84 v 0.09 microgram/g creatinine). On an individual basis, MnU and MnB were not related to various external exposure parameters (duration of exposure, current exposure, or lifetime integrated exposure to airborne Mn). On a group basis, a statistically significant association was found between MnU and current Mn concentrations in air. No appreciable difference between the exposed and the control workers was found with regard to the other biological measurements (calcium, LH, FSH, and prolactin in serum). Although the erythropoietic parameters and serum iron concentration were in the normal range for both groups, there was a statistically significant trend towards lower values in the Mn exposed workers. The prevalences of reported neuropsychological and respiratory symptoms, the lung function parameters, and the audioverbal short term memory scores did not differ between the control and exposed groups. The Mn workers, however, performed the other neurofunctional tests (visual reaction time, eye-hand coordination, hand steadiness) less satisfactorily than the control workers. For these tests, the prevalences of abnormal results were related to the lifetime integrated exposure to total and respirable Mn dust. On the basis of logistic regression analysis it may be inferred that an increased risk of peripheral tremor exists when the lifetime integrated exposure to Mn dust exceeds 3575 or 730 micrograms Mn/m3 x year for total and respirable dust respectively. The results clearly support a previous proposal by the authors to decrease the current time weighted average exposure to Mn dust.

Exposure To Lead By the Oral and the Pulmonary Routes of Children Living in the Vicinity of a Primary Lead Smelter

Abstract Yearly from 1974 to 1978, a medical survey was carried out among 11-year-old children attending schools situated less than 1 and 2.5 km from a lead smelter. Age-matched control children from a rural and urban area were examined at the same time. The blood lead levels (PbB) of the children living in the smelter area (mainly those attending schools located less than 1 km from the smelter) were higher than those of rural and urban children. The mean PbB levels were usually lower in girls than in boys, especially in the smelter area. Despite a slightly decreasing trend in the annual mean airborne lead concentration at less than 1 km (mean PbA: from 3.8 μg/m3 in 1974 to 2.3 μg/m3 in 1978) the PbB levels there did not improve, whereas 2.5 km from the plant a significant tendency to normalization of PbB became apparent. Therefore, in the third survey, the medical examination was combined with an environmental study which demonstrated that lead in school-playground dust and in air strongly correlated. Lead on the childrens hands (PbH) was also significantly related to lead in air or lead in dust. Less than 1 km from the factory boys and girls had on the average 436 and 244 μg Pb/hand, respectively, vs 17.0 and 11.4 μg Pb/hand for rural boys and girls, respectively. Partial correlations between PbB, PbA, and PbH indicated that in the smelter area the quantitative contribution of PbA to the childrens PbB is negligible compared to that of PbH. Thus, the control of airborne lead around the lead smelter is not sufficient to prevent excessive exposure of children to environmental lead. In view of the importance of lead transfer from dust and dirt via hands to the gastrointestinal tract remedial actions should be directed simultaneously against the atmospheric emission of lead by the smelter and against the lead particulates deposited on soil, dust, and dirt.

Impairment of Renal Function with Increasing Blood Lead Concentrations in the General Population

BACKGROUND Nephropathy is known to occur in persons with heavy exposure to lead. Whether exposure to lead in the general population leads to impaired renal function is not known. METHODS We studied renal function and indexes of lead exposure in a random population sample of 965 men and 1016 women (age range, 20 to 88 years). In all the subjects we measured creatinine clearance and blood concentrations of lead and zinc protoporphyrin (an indirect measure of blood lead level). RESULTS The mean (+/- SD) creatinine clearance rate was 99 +/- 30 ml per minute in the men and 80 +/- 25 ml per minute in the women. In the men the geometric mean blood lead concentration was 114 micrograms per liter (0.55 mumol per liter) (range, 23 to 725 micrograms per liter [0.11 to 3.5 mumol per liter]), and in the women 75 micrograms per liter (0.36 mumol per liter) (range, 17 to 603 micrograms per liter [0.08 to 2.9 mumol per liter]); the zinc protoporphyrin values in blood averaged 1.0 and 1.1 micrograms per gram of hemoglobin, respectively. The creatinine clearance rate was inversely correlated with blood lead and zinc protoporphyrin values in the men and the women both before and after adjustments for age, bodymass index, and diuretic treatment. A 10-fold increase in blood lead concentration was associated with a reduction of 10 to 13 ml per minute in creatinine clearance. We also found a positive correlation between serum beta 2-microglobulin (which is inversely related to the glomerular filtration rate) and blood lead in men, between serum beta 2-microglobulin and zinc protoporphyrin in both sexes, and between serum creatinine and zinc protoporphyrin in men. CONCLUSIONS Exposure to lead may impair renal function in the general population. The alternative hypothesis that renal impairment may lead to an increase in the blood lead concentration cannot be excluded, however.

Placental transfer of lead, mercury, cadmium, and carbon monoxide in women: I. Comparison of the frequency distributions of the biological indices in maternal and umbilical cord blood

500 pregnant women living in different areas in Belgium were surveyed to evaluate the extent of environmental exposure to heavy metals (lead, cadmium, and mercury) during fetal life, possible biological effects of such exposure, and various epidemiological significances which may influence such exposure. In addition carboxyhemoglobin level was determined. And frequency distributions of these various hematological indexes were compared. Maternal and umbilical cord blood levels of these hematological parameters indicate that the 3 metals do cross the placenta, but the transfer rate differs for each heavy metal. No barrier was demonstrated for mercury transfer. A slight barrier seemed present for lead. A barrier of some importance was demonstrated for cadmium. Statistical correlations bear out these contentions; there was a lower correlation between maternal blood cadmium and umbilical blood cadmium concentrations (r + .38) than for the other 2 metals (r .6). Carboxyhemoglobin levels of mother and newborn are highly correlated (P .001), and in mothers carboxyhemoglobin levels are also associated with cadmium concentration in blood, suggesting that the source of these pollutants is the same, namely smoking. There were no significant correlations observed between blood lead concentrations and erythrocyte prophyrin level; rather, because of its high sensitivity to lead, the erythrocyte enzyme ALAD was negatively correlated with blood lead in mother and newborn.

Markers of early renal changes induced by industrial pollutants. II. Application to workers exposed to lead.

The present study has been carried out in the framework of a collaborative research project on the development of new markers of nephrotoxicity. A battery of more than 20 potential indicators of renal changes has been applied to 50 workers exposed to lead (Pb) and 50 control subjects. After application of selection criteria 41 exposed and 41 control workers were eventually retained for the final statistical analysis. The average blood Pb concentration of exposed workers was 480 micrograms/l and their mean duration of exposure was 14 years. The battery of tests included parameters capable of detecting functional deficits (for example, urinary proteins of low or high molecular weight), biochemical alterations (for example, urinary eicosanoids, glycosaminoglycans, sialic acid) or cell damage (for example, urinary tubular antigens or enzymes) at different sites of the nephron or the kidney. The most outstanding effect found in workers exposed to Pb was an interference with the renal synthesis of eicosanoids, resulting in lower urinary excretion of 6-keto-PGF1 alpha and an enhanced excretion of thromboxane (TXB2). The health significance of these biochemical alterations, detectable at low exposure to Pb is unknown. As they were not associated with any sign of renal dysfunction, they may represent reversible biochemical effects or only contribute to the degradation of the renal function from the onset of clinical Pb nephropathy. The urinary excretion of some tubular antigens was also positively associated with duration of exposure to Pb. Another effect of Pb that might deserve further study is a significant increase in urinary sialic acid concentration.

In vivo measurement of liver and kidney cadmium in workers exposed to this metal: Its significance with respect to cadmium in blood and urine

Abstract The cadmium concentration in liver (CdL) and in kidney is measured in vivo by neutron capture γ-ray analysis in 309 male workers occupied in two Belgian zinc-cadmium plants. At the same time, blood cadmium (CdB) and the urinary excretion of β 2 -microglobulin, albumin, total protein, calcium, and cadmium (CdU) is also determined. Among the 264 subjects retained for the statistical analysis 236 are still active at the plants (group A) while 28 others are retired Cd workers or workers removed from Cd exposure (group R). Group A comprises 149 subjects with normal renal function who are engaged in jobs not directly related to Cd production (subgroup Ala) and 87 Cd workers daily occupied with Cd production of whom 72 subjects (subgroup Alb) have not and 15 (subgroup A2) have sign(s) of renal dysfunction. Group R is subdivided into subgroups R1 ( n = 10) and R2 ( n = 18), subjects without and with renal dysfunction, respectively. Examination of the cumulative frequency distributions and the correlations between the various biological parameters in the different subgroups leads to the following conclusions: (a) calciuria is not much different among the subgroups, (b) CdB mainly reflects recent exposure to cadmium in the absence of Cd-induced renal damage, (c) CdU follows the body burden of cadmium but increases proportionately much more in workers with renal dysfunction particularly when signs of tubular dysfunction are present, (d) CdL is proportional to duration and intensity of Cd exposure in workers without as well as with renal dysfunction, (e) renal cortical cadmium (CdKc) is higher in subgroup Alb and Rl than in subgroup Ala but does not differ between Cd workers without (subgroup Alb) and with (subgroups A2 and R2) renal dysfunction. The latter finding can be explained by a progressive decrease of CdKc after the onset of the renal damage. This hypothesis is supported by the observations that in Cd workers from subgroup R2. CdKc negatively correlates with years of past exposure to Cd ( r = −0.59), that Cd workers with renal dysfunction (subgroups A2 and R2) excrete significantly more cadmium in urine, and that they show a much lower slope of CdKc versus CdL than those with normal renal function (subgroup Alb). The results of this investigation suggest that there exists a range of critical CdKc levels , i.e., approximately from 160 to 285 ppm. Beyond a CdKc of 285 ppm the probability is very high that all persons will show sign(s) of renal dysfunction. It has been found that kidney dysfunction is likely to develop in workers with CdL between 30 and 60 ppm and that almost all the Cd workers with CdL above 60 ppm evidence renal dysfunction. This study also demonstrates that in the absence of kidney dysfunction. CdU is correlated with the body burden of cadmium ( r = 0.59), but that CdB is not. On the basis of the interrelationships among CdL, CdKc, CdU, and the indicators of renal function, it can be concluded that the probability of developing Cd-induced renal dysfunction in male Cd workers appears to be very low when the critical CdU level of 10 μg/g creatinine is not regularly exceeded. This CdU level corresponds to an average cadmium body burden of 160–170 mg.

Evaluation of exposure to polycyclic aromatic hydrocarbons in a coke production and a graphite electrode manufacturing plant: assessment of urinary excretion of 1-hydroxypyrene as a biological indicator of exposure.

OBJECTIVES--Characterisation of the airborne concentration of 13 polycyclic aromatic hydrocarbons (PAHs) at various workplaces in a graphite electrode and a coke production plant. Validation of the urinary excretion of 1-hydroxypyrene (hydroxypyrene) as a biological marker of exposure to PAH. DESIGN--Cross sectional study of workers exposed to PAHs (106 in the graphite electrode producing plant and 16 in the coke works). METHODS--Personal air sampling during at least six hours per workshift using a glass fibre filter and a Chromosorb 102 solid sorbent tube and analysis of PAHs by high performance liquid chromatography (HPLC) and spectrofluorometric detection (SFD). Collection of spot urine samples before and after the shift and analysis of 1-hydroxypyrene by HPLC and SFD. RESULTS--The workers most exposed to PAHs were those occupied at the topside area of the coke oven plant and those working in the blending and impregnation areas of the graphite electrode producing plant (mean airborne concentration of total PAHs: 199 and 223 micrograms/m3 respectively). Except for naphthalene and perylene, the relative proportion of the different PAHs did not differ between the plants. Pyrene concentration in air was highly correlated with the total airborne PAH concentration (r = 0.83, p < 0.0001) and the correlation coefficients between hydroxypyrene concentration in postshift urine samples and pyrene or total PAHs in air were 0.67 (p < 0.0001) and 0.72 (p < 0.0001) respectively. Excretion of hydroxypyrene doubled when the exposure to pyrene in air increased 10-fold. The half life for the urinary excretion of hydroxypyrene was around 18 hours (95% confidence interval 16.1-19.8). Smoking habits only explained 2.3% of the variance in hydroxypyrene excretion compared with 45% for the pyrene concentration in air. CONCLUSION--The determination of the urinary excretion of hydroxypyrene in postshift urine samples can be used as a suitable biomarker to assess individual exposure to PAHs in coke ovens and in graphite electrode manufacturing plants.

Effects of vanadium complexes with organic ligands on glucose metabolism: a comparison study in diabetic rats.

Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The effects of three organic vanadium compounds were studied in non‐ketotic, streptozotocin‐diabetic rats: vanadyl acetylacetonate (VAc), vanadyl 3‐ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple inorganic vanadium salt, vanadyl sulphate (VS) was also studied. Oral administration of the three organic vanadium compounds (125 mg vanadium element l−1 in drinking fluids) for up to 3 months induced a faster and larger fall in glycemia (VAc being the most potent) than VS. Glucosuria and tolerance to a glucose load were improved accordingly. Activities and mRNA levels of key glycolytic enzymes (glucokinase and L‐type pyruvate kinase) which are suppressed in the diabetic liver, were restored by vanadium treatment. The organic forms showed greater efficacy than VS, especially VAc. VAc rats exhibited the highest levels of plasma or tissue vanadium, most likely due to a greater intestinal absorption. However, VAc retained its potency when given as a single i.p. injection to diabetic rats. Moreover, there was no relationship between plasma or tissue vanadium levels and any parameters of glucose homeostasis and hepatic glucose metabolism. Thus, these data suggest that differences in potency between compounds are due to differences in their insulin‐like properties. There was no marked toxicity observed on hepatic or renal function. However, diarrhoea occurred in 50% of rats chronically treated with VS, but not in those receiving the organic compounds. In conclusion, organic vanadium compounds, in particular VAc, correct the hyperglycemia and impaired hepatic glycolysis of diabetic rats more safely and potently than VS. This is not simply due to improved intestinal absorption, indicating more potent insulin‐like properties.

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

Abstract  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.

Kidney Disorders and Hematotoxicity From Organic-solvent Exposure

Although the kidney is the critical organ limiting occupational exposure to soluble uranium compounds, there have been no adequate studies evaluating renal tubular dysfunction in chronically exposed workers. The present investigation evaluated kidney function among 39 uranium mill workers and 36 local cement plant workers of equivalent age, sex, and race. The uranium workers showed a significantly higher excretion of beta-2-microglobulin and five amino acids than the reference group. Although the levels of tubular proteinuria were mild, a dose-effect relation existed between the clearance of beta-2-microglobulin, relative to that of creatinine, and the length of time that the uranium workers had spent in the yellowcake drying and packaging area, the work area with the highest exposures to soluble uranium. Age did not account for this relationship. Glomerular function was significantly better among the uranium workers than among the referents, though this may have been the result of differences in the physical activity of the groups during the collection period. The data presented suggest reduced renal proximal tubular reabsorbtion of amino acids and of low molecular weight proteins, consistent with uranium nephrotoxicity.