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Biomedical subjects

R Lauwerys

Publications and source records attributed to R Lauwerys.

At least 181 records · Page 10Linked to original sources

[Biological aspects of occupational exposure to cadmium and several other metals].

We have performed several cross-sectional epidemiological surveys among workers exposed to cadmium, mercury vapour or manganese in order to assess : their early biological or functional effects; the biological tests allowing an assessment of the amount of metal absorbed or stored in the body; the acceptable exposure levels. Studies have also been carried out among persons exposed to inorganic arsenic in order to define its inactivation mechanism and to develop a biological test of exposure. The kidney is the main critical organ following long-term exposure to cadmium. To prevent the occurrence of renal changes in the majority of male workers exposed to cadmium, its concentration in renal cortex should not exceed 215 micrograms/g (wet weight), and that in urine : 10 micrograms/g creatinine. A blood cadmium level of 1 microgram/100 ml has been suggested as maximum tolerable level for long-term exposure. Prolonged exposure to mercury vapour may lead to renal and neurological disturbances. The preclinical signs of nephrotoxicity are correlated with the amount of mercury absorbed which may be assessed by monitoring the mercury level in urine. The neurotoxic effects (particularly tremor) are mainly related to the integrated exposure (duration and intensity). A maximal permissible level of 50 micrograms Hg/g urinary creatinine is proposed to prevent the occurrence of these toxic effects. An exposure to manganese dust for 7 years on the average at a level below the maximum allowable airborne concentration (5 mg/m3) recommended by the ACGIH in the USA may still lead to a slight reduction in psychomotor and spirometric performances and interfere with calcium metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Arsenicals↗

Preclinical toxic effects of manganese in workers from a Mn salts and oxides producing plant.

The results of the present epidemiological study among 141 workers (mean age: 34 years) from a Mn salts and oxides producing plant in Belgium suggest that preclinical perturbations (lung function, CNS, biological parameters) may occur in subjects exposed to airborne Mn levels (7 years on the average) usually lower (total dust, geometric mean about 1 mg/m3, 95th percentile 3.3 mg/m3) than the levels actually (5 mg/m3) tolerated.

Adult↗

Surveillance of workers exposed to mercury vapour:validation of a previously proposed biological threshold limit value for mercury concentration in urine.

A cross-sectional epidemiological study was carried out among subjects exposed to mercury (Hg) vapour, ie, a group of 131 male workers (mean age: 30.9 yr; average duration of exposure, 4.8 yr) and a group of 54 female workers (mean age, 29.9 yr; average duration of exposure 7 yr). The results were compared with those obtained in well-matched control groups comprising 114 and 48 male and female workers, respectively. The intensity of current Hg vapour exposure was rather moderate as reflected by the levels of mercury in urine (HgU) (mean and 95th percentile: males 52 and 147 micrograms/g creatinine; females 37 and 63 micrograms/g creatinine) and of mercury in blood (mean and 95th percentile: males 1.4 and 3.7 micrograms/dl; females 0.9 and 1.4 microgram/dl). Several symptoms mainly related to the central nervous system (memory disturbances, depressive feelings, fatigue, irritability) were more prevalent in the Hg-exposed subjects. They were, however, not related to exposure parameters. In both male and female Hg-exposed workers no significant disturbances were found in short-term memory (audioverbal), simple reaction time (visual), critical flicker fusion, and colour discrimination ability. Only slight renal tubular effects were detected in Hg-exposed males and females, ie, an increased urinary beta-galactosidase activity and an increased urinary excretion of retinol-binding protein. The prevalence of these preclinical renal effects was more related to the current exposure intensity (HgU) than to the duration of exposure and was detected mainly when HgU exceeds 50 micrograms/g creatinine. Changes in hand tremor spectrum recorded with an accelerometer were found in the Hg-exposed males only. The prevalence of abnormal values for some hand tremor parameters (total velocity and total displacement in the 2-50-Hz band) was mainly increased in male workers exposed for more than 10 yr. Unlike the renal tubular effects, the preclinical signs of tremor were more related to the integrated exposure than to the current exposure. Since the female workers, who have been exposed to Hg vapour levels usually insufficient to increase their HgU levels above 50 micrograms/g creatinine, did not exhibit any change in hand tremor pattern, the results of the present study tend to validate our previously proposed biological threshold limit value of a HgU of 50 micrograms/g creatinine for workers chronically exposed to mercury vapour.

Belgium↗

Fertility of male workers exposed to mercury vapor or to manganese dust: a questionnaire study.

The fertility of male workers exposed to mercury vapor or to manganese dust was assessed with the use of the questionnaire developed by Levine et al [1980]. In the mercury group (concentration of mercury in urine ranging from 5.1 to 272.1 micrograms/g creatinine), no statistically significant difference was found between the observed number of children and that expected on the basis of the reproductive experience of a well-matched control group. On the contrary, by comparison with their corresponding controls, the manganese-exposed workers exhibited a statistically significant deficit in the number of children during their period of exposure to the metal. The airborne concentration of manganese dusts at the different workplaces ranged from 0.07 to 8.61 mg/m3 with a geometric mean of 0.94 mg/m3.

Adolescent↗

Study of inorganic arsenic methylation by rat liver in vitro: relevance for the interpretation of observations in man.

The biotransformation of inorganic arsenic by rat liver in vitro leads to the production of a monomethylated and a dimethylated arsenic derivative, measured by flameless atomic absorption as monomethylarsonic (MMA) and dimethylarsinic (DMA) acids respectively. The methylating activity is localized in the cytosol and accepts only As3+ as substrate. Its optimum pH lies between 7.5 and 8.0, and reduced glutathione (10(-2)M) is required for full activity. S-Adenosylmethionine is the essential methyl group donor and corrinoïd derivatives act synergistically. An excess of substrate and the addition of mercuric ions prevent the formation of the dimethylated arsenic derivative without affecting that of the monomethylated compound. This indicates that two different enzymatic activities are involved in the methylation of inorganic arsenic in mammals. Previous observations in man (Buchet et al. 1981 b, 1984) and the results of the present study suggest that DMA production results from the subsequent methylation of the MMA precursor, although the possibility that metabolites are also produced by two completely independent pathways cannot yet be conclusively rejected. The kinetics of MMA and DMA production provide an explanation for the observations that in volunteers given increasing amounts of As3+, the urinary excretion of DMA levels off faster than that of MMA and in patients acutely intoxicated with As3+, several days may elapse before DMA becomes the preponderant metabolite. The results of the present study also suggest that the reduction of MMA production associated with an increased synthesis of DMA found in patients with liver diseases given a standard dose of As3+ might be due to a reduction of As3+ uptake by the liver cells.

Animals↗

Erythrocyte pyrimidine 5'-nucleotidase activity in workers exposed to lead, mercury or cadmium.

The erythrocyte pyrimidine 5'-nucleotidase activity (P5N) was measured in workers exposed to lead, cadmium or inorganic mercury and the effect of lead on this enzyme activity was compared with that on the classical biological parameters (ALAD, ZPP, ALAU), reflecting the interference of this metal with the heme biosynthesis pathway. P5N is inhibited by lead but not by cadmium and mercury. The correlation coefficient between log P5N and lead in blood (PbB) amount to 0.79 (n = 278; PbB ranging from 4.9 to 73.5 micrograms/100 ml). The response of P5N to lead closely parallels that of ALAD.

5'-Nucleotidase↗

[Biological monitoring of exposure to industrial toxic substances. Present-day situation and prospects for development].

Biological monitoring of exposure to an industrial chemical may be defined as the evaluation of the internal dose (internal exposure) by a biological method with the view of assessing the associated health risk. Depending on the biological parameter selected and on the time of sampling, internal dose may mean the amount of chemical recently absorbed, the amount stored in one or several compartments of the organism, or, under ideal conditions, the amount bound to the sites of action. The estimation of the internal dose has usually relied on two categories of tests: those based on the determination of the chemical and/or its metabolites in various biological media (eg, alveolar air, blood, urine) and those based on the quantification of a nonadverse biological effect, the intensity of which is related to the internal dose. Biological tests providing information on the amount of active chemical bound to the critical sites of action (target dose) and noninvasive analytical methods which measure the amount of cumulative toxins stored in certain body compartments (eg, bone, liver, kidney) are currently being developed. The main criteria to be considered in the selection of the most appropriate biological monitoring test of exposure are the specificity of the parameter and its sensitivity with respect to the exposure level, the analytical and biological applicability, the convenience for the workers, the possible risks associated with its application, and, of course, the accuracy of the exposure and/or health risk evaluation. Normally, the biological approach of exposure monitoring is reserved for chemicals which enter the organism and may exert systemic toxic effects. When a biological monitoring test of exposure is applicable, it offers several advantages over ambient air monitoring. A biological parameter reflecting the internal dose is necessarily more closely related to the systemic adverse effect(s) than any environmental measurement. Biological monitoring of exposure integrates the exposure by all routes (pulmonary, oral, and cutaneous) and sources. It may also take into account several factors which determine the uptake and the absorption of the chemical (individual variability, work load, hygiene habits, etc). However, contrary to ambient monitoring, biological monitoring is applicable only when sufficient information has been gathered on the metabolism of the chemical, its toxicity or that of its metabolites, and when some of the relationships between external exposure, internal dose and adverse effects have been assessed.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Kidney disorders and hematotoxicity from organic solvent exposure.

Short-term exposure to certain solvents, such as several halogenated hydrocarbons, petroleum distillates, ethylene glycol, ethylene glycol ethers, and diethylene glycol, may cause renal tubular necrosis. Tubular lesions with metabolic acidosis have been reported in addicts inhaling solvent vapor (eg, toluene). A Goodpasture's syndrome may be induced by acute or subacute exposure to solvents, but its incidence is rare. No adequate proof is yet available that repeated exposure to nonsubstituted organic solvents may lead to the development of different types of chronic glomerulonephritis, but the available epidemiologic data are suggestive of the existence of such an association. Only a few solvents have been reported to act on the hematopoietic system of humans. The hematotoxicity (aplastic anemia, leukemia) of benzene is well established. Some ethylene glycol ethers are also toxic to bone marrow.

Adult↗

[Biological markers of exposure to toxic agents].

Exposure to chemical agents may be assessed either qualitatively or semi-quantitatively with the help of a questionnaire (type of exposure and duration) or quantitatively either by the measurement of the concentration of the xenobiotics in the environment (ambient monitoring) or by the measurement of biological parameters related to the internal doses (biological monitoring of exposure). In industry, ambient monitoring usually implies the measurement of chemicals in air with static or personal samplers. The internal doses may be assessed either by measuring the chemical or its biotransformation products in biological media or by measuring some biological effects caused by the chemical. Depending on the selected biological parameter and the time of sampling, the result may reflect the amount of chemical recently absorbed, the amount stored in the organism (body burden) or the amount of active metabolites bound to the site of action. The biological parameter of exposure is more directly related to the adverse health effects that one attempts to prevent than any environmental measurement. Biological monitoring may take into consideration absorption by all the routes and from all sources (occupational and environmental), interindividual differences in toxicokinetic and in hygiene habits. The application of a biological test requires the critical evaluation of several factors, namely the sensitivity and the specificity of the test, the precision and the accuracy of the analytical method and eventually ethical aspects.

Biotransformation↗

Turbidimetric latex immunoassay for serum ferritin.

A sensitive immunoassay based on latex particle agglutination (latex immunoassay) has been developed for the determination of serum ferritin. Polystyrene particles (0.8 micron) to which anti-ferritin antibody is adsorbed are incubated with serum for 30 min with shaking or 60 min without shaking. The resulting agglutination is quantified by measuring the decrease of absorbance of the latex suspension at 360 nm. Pretreatment of the serum is required to prevent interference from complement, rheumatoid factor and chylomicrons. The lowest detectable concentration of ferritin in serum is about 5 micrograms/l. Within-runs and between-runs coefficients of variation, based on analysis of samples containing 14-820 micrograms/l ferritin, ranged from 3.6 to 13.8%. A correlation coefficient of 0.95 between latex immunoassay and radioimmunoassay was obtained for the determination of ferritin in 46 sera.

Ferritins↗

The influence of liver disease on the methylation of arsenite in humans.

The capacity for inorganic arsenic (ASi) methylation in 13 healthy volunteers and in 30 patients with different types of liver disease has been assessed by measuring the amount of unmetabolized ASi, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) excreted in urine within 24 h after the IV injection of 7.14 micrograms/kg ASi. Liver disease does not affect the percent of the injected dose excreted within 24 h but has striking and opposite effects on the proportions of MMA and DMA. MMA excretion is highly correlated with the 14C-aminopyrine breath test (r = 0.73; P less than 0.05). The reduction in the proportion of MMA excreted in urine and the increase in that of DMA are similar with regard to sensitivity and specificity for detecting liver impairment. Unlike the 14C-aminopyrine breath test, the inorganic arsenic methylation test offers the advantage of being unaffected by treatment with microsomal enzyme inducers.

Adult↗

Cadmium, analgesics, and the chronic progressive nephrosis in the female Sprague-Dawley rat.

Female Sprague-Dawley rats received phenacetin or aspirin at average daily doses of 135 and 27 mg/kg respectively in the diet and either demineralized water (DMW) or a 100 ppm cadmium (Cd) solution as their drinking water for 12 months. This dose of Cd produced borderline tubular toxicity, as measured by the excretion of IV-injected human beta 2-microglobulin. The kidney accumulation of Cd just reached the critical level of 200 ppm in all groups at the end of the study. The various treatments did not significantly affect growth, creatinine clearance, urine osmolality and the urinary excretion of beta-N-acetyl-D-glucosaminidase and aminoacids. No interaction resulted from the concomitant administration of analgesics and Cd. Both aspirin subgroups (receiving DMW or Cd) showed an attenuation of the age-related decline of the renal function as revealed by a lower urinary excretion of albumin and total protein. The accentuation of the mesangial matrix seen upon aging was also partly inhibited in the aspirin rats.

Acetylglucosaminidase↗

In vivo metabolism of dimethylformamide and relationship to toxicity in the male rat.

After in vivo administration of dimethylformamide (DMF) to male rats, about 50% of the dose is excreted in urine as N-hydroxymethyl-N-methylformamide (DMF-OH) and about 4% as N-methylformamide (NMF). NMF is not a product of DMF-OH biotransformation but is directly formed from DMF. Comparison of the acute toxicity of DMF, DMF-OH and NMF shows that NMF is more toxic than DMF-OH, which is itself more toxic than DMF. This study explains the different toxicity profile of DMF and NMF which until recently was believed to represent the main metabolite of DMF.

Animals↗

Cytogenetic examination of leucocytes of workers exposed to mercury vapour.

Cytogenetic observations have been performed on male subjects occupationally exposed to elemental mercury in a plant where mercury is amalgamated with zinc and in a chloralkali plant [n = 22; average level of mercury in urine was 117 micrograms/g creatinine and of mercury in blood 3.1 micrograms/100 ml; mean duration of Hg exposure 4 years (range: 0.3-15.3)]. The exposure to mercury vapour did not result in an increased yield of structural chromosomal aberrations in peripheral blood lymphocytes of the workers. These negative results are in agreement with the findings reported for other eukaryotic systems and confirm that population monitoring based on cytogenetic examination of peripheral blood lymphocytes does not always represent a good indicator of damage to genetic material produced by a chemical.

Adult↗

In vivo and in vitro oxidative biotransformation of dimethylformamide in rat.

In rats and in humans, dimethylformamide (DMF) is mainly metabolized into N-hydroxymethyl-N-methylformamide (DMF-OH). The in vitro oxidation of DMF by rat liver microsomes is decreased in the presence of catalase and superoxide dismutase. The radical scavengers, dimethylsulfoxide (DMSO), tertiary butyl alcohol (t-butanol), aminopyrine, hydroquinone and trichloroacetonitrile reduce the oxidation of DMF to DMF-OH in vitro and in vivo. Conversely, DMF inhibits the demethylation of DMSO, t-butanol and aminopyrine. The addition of iron-EDTA to the incubation system induces the production of N-methylformamide (NMF) from DMF. These results support the hypothesis that the metabolic pathway leading from DMF to DMF-OH and NMF involves hydroxyl radicals. Superoxide radical and hydrogen peroxide take part in the metabolic process. DMF is preferentially metabolized into DMF-OH. NMF appears mainly when the production of hydroxyl radicals is stimulated, the methyl group being recovered as formic acid.

Animals↗