The effects of low environmental cadmium exposure on bone density.

Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9; 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction (beta(2)M-U RBP, NAG), glomerular dysfunction (Alb-U and beta(2)M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone density.

The effects of environmental cadmium exposure on kidney function: the possible influence of age.

The study aimed to assess the possible influence of long-term environmental exposure to cadmium and age at the time of exposure on renal function. The study was a follow-up of the 1991-1994 project concerning 2000 inhabitants of a cadmium-contaminated area in the vicinity of a zinc smelter. Since the smelter was built in the late 1950s but was not operated until 1968, some of the inhabitants were not exposed to cadmium during childhood. For the follow-up, 308 persons who in 1993 presented with Cd-U levels > or = 0.5 microg/L adjusted for specific gravity (1.020) were selected in 2000. The study population included 136 people who were exposed to cadmium in childhood (former children) and 172 adults (unexposed adults) with no such exposure. These two groups were divided into subgroups according to Cd-U levels: < or =1 (group 1), 1-2 (group 2), and > or =2 microg/g creatinine (group 3). Urinary and blood cadmium and the markers of renal tubular dysfunction (beta2 M-U, RBP-U, NAG, NAG-A, NAG-B) and glomerular dysfunction (Alb-U and beta2 M-S) were measured. Persons with a history of occupational exposure to cadmium were excluded from this project. In group 3 of the unexposed adults, concentrations of RPB-U, NAG, NAG-B, and Alb-U were significantly higher than those in group 1. In former children, this could be observed only for RPB-U and Alb-U. Urine concentrations of these markers were higher in all of the subgroups of former children than in the groups of unexposed adults (except for NAG and its two forms). However, these differences were significant only for RBP-U in group 3. The findings indicate that early renal effects in the general population may occur at Cd-U concentrations above 2 microg/g creatinine and at lower levels for NAG-B. Moreover, cadmium exposure in childhood may have a stronger impact the renal function, particularly tubular reabsorption, than the exposure of a mature organism.

Reversibility of microproteinuria in nickel-cadmium battery workers after removal from exposure.

OBJECTIVES: The study was aimed at assessing the reversibility of renal tubule dysfunction in workers exposed to cadmium according to the severity of microproteinuria, concentrations of cadmium in urine (Cd-U), and the time since removal from exposure. METHODS: The study was carried out in a nickel-cadmium battery factory. Exposure to cadmium was formerly very high. In 1983 and in 1986-1988, geometric mean concentrations of cadmium in blood (Cd-B) of workers amounted to 23.3 micro g/l and 55.7 microg/l, respectively. Workers with determinations of Cd-B, Cd-U and retinol binding protein in urine (RBP-U) in the past were eligible for the study. Fifty-eight workers who had met this profile and had been removed from exposure to cadmium before 1998 were investigated in 1998-1999. They were divided into three groups according to their RBP-U concentrations in 1986-1988: <300 ( n=26); 301-1,501 ( n=25) and >1501 microg/g creatinine ( n=7). RESULTS: In 1999, the RPB-U levels were below 300 microg/g creatinine in 85%, 64% and 42% of persons from groups 1, 2 and 3, respectively. Statistical analysis of the results by means of multi-parametric logistic regression analysis revealed that, from the viewpoint of reversibility of tubular proteinuria, its severity in 1986-1988 was most important. Also, the time since the removal from exposure to cadmium and Cd-U levels seemed to play some role, but the influence of these parameters was not statistically significant. Significant correlation between beta(2)-microglobulin in serum (beta(2)M-S) and RBP-U concentrations measured in 1998-1999 with apparent lack of correlation between beta(2)M-S and RBP-U concentrations in 1986-1988 supports the hypothesis that the glomerular impairment induced by cadmium may be secondary to the tubular lesion rather than independent from tubular effect. CONCLUSIONS: The results show that the tubular proteinuria, and maybe also the decline in glomerular filtration rate, may be reversible, even in the case of relatively high past exposure. The results confirm the necessity for monitoring urinary levels of low-molecular-weight proteins during periodic examination of workers exposed to cadmium.

Biological monitoring of occupational exposure to arsenic by determining urinary content of inorganic arsenic and its methylated metabolites.

A study was undertaken to assess the relationship between inhalation exposure to arsenic in copper smeltery workers and urinary excretion of total inorganic arsenic metabolites (Asitm), including inorganic arsenic (Asi), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). The methods applied made it possible, in principle, to determine all forms of airborne arsenic and to eliminate the influence of seafood-derived organoarsenicals on the level of urinary Asitm. Air samples were collected on the second day of work after the weekend break. Urine samples were collected just after shift-end on the same workday. The time-weighted average (TWA) concentrations of arsenic in the workers' breathing zone varied between 1 and 746 microg/m3 and Asitm concentrations in urine between 2 and 850 microg/l (s.g. 1.024). The urine samples with a specific gravity of lower than 1.010 and higher than 1.030 were not considered; neither were those subjects with an Asitm excretion efficiency of higher than 100% of the dose absorbed during the day of measurement. In total, 53 air samples and corresponding urine samples were obtained. The correlation coefficient between the airborne arsenic concentration in microg/m3 (X) and the concentration of urinary Asitm in microg/l, s.g. 1.024 (Y), was 0.723. The relation between the two variables can be presented using the following formula: Y = 6.29 x X0.616. According to the findings of this study, as well as the results of three other studies based on similar principles, the daily exposure to arsenic concentrations of 10 microg/m3 and 50 microg/m3 led to concentrations of Asitm in urine of about 30 microg/l and 70 microg/l (s.g. 1.024), respectively.

Blood lead levels in industrial workers in Poland.

Occupational exposure to lead occurs in about 1,300 enterprises in Poland. According to the 1994 data, based on the reports of the State Sanitary Inspectorate, 1,970 persons were employed at that time under conditions of exposure exceeding the Polish MAC level of 0.050 mg/m3. The measurements of workers' blood lead concentrations (Pb-B) were carried out only in 90 factories. In 1996, the Minister of Health and Social Welfare issued a directive stating that the Pb-B determinations in employees occupationally exposed to lead are compulsory. The aim of the present study was to assess lead exposure of workers employed in different branches of the Polish economy, based on Pb-B determinations. The measurements were performed on 2,324 male and 165 female workers of 13 different types of industry, including manufacture of crystal glass, battery industry, copper and zinc smelters, welding in a repair shipyard and some other workposts under conditions of lead exposure. The results of the determinations indicate that exposure to lead continues to be a serious problem in Polish industry. Pb-B concentrations exceeded the newly introduced Polish biological exposure index (BEI) value of 500 micrograms/l for men workers in about 30% of workers examined in 1996. In about 65% of females under 45 years of age the Pb-B concentrations were higher than 300 micrograms/l recommended as BEI for this age group. Considering the WHO-recommended health-based maximum individual biological action level of 400 micrograms/l, the percentage of the employees for whom higher values were found amounted to about 45% for men workers. The results point to the necessity of enforcing the implementation of Pb-B determinations according to the ministerial ordinance as well as of removing from exposure the workers with Pb-B levels exceeding the present BEI values. The improvement of working conditions and the implementation of health education for workers are also the actions to be promptly undertaken. In order to achieve these goals a close cooperation is required between the State Sanitary Inspectorate, the institutes of occupational health as well as the employers and trade unions.

Blood lead in the general population in Poland.

Lead concentration in venous blood (Pb-B) was investigated in 1122 inhabitants (including 555 children under 10 years of age) of five Polish towns with no large industrial lead emitters (group I) and in 1246 persons (707 children under 10 years of age) living in the vicinity of zinc and copper mills (group II). The samples were analysed using electrothermal atomic absorption spectrometry (ETAAS) and the performing laboratory participated in the external quality control scheme during the study period (1992-1994). In group I the mean geometric Pb-B concentrations ranged from 23.8 to 48.3 micrograms/l in females, from 42.5 to 76.8 micrograms/l in males and from 29.9 to 62.5 micrograms/l in children. In group II, the mean geometric Pb-B concentrations were significantly higher and ranged from 49.4 to 105 micrograms/l in females, from 98.5 to 149 micrograms/l in males and from 73.7 to 114 micrograms/l in children, the values decreasing as the distance from the source of emission increased. Cigarette smoking was found to bring about a significant increase in Pb-B levels for both males and females. A significant correlation was noted between Pb-B concentrations in mothers and children. The ratio between child and maternal Pb-B concentrations amounted to approximately 1.0 for group I and to about 0.5 for group II. These findings indicate the necessity of undertaking preventive activities over the lead-contaminated areas. However, the lead hazard in Poland seems to be associated with point sources of emission and hence does not concern the whole population.

[Methods for determining lead and cadmium in blood; cadmium, copper, nickel and chromium in urine using flameless atomic absorption spectrometry]. / Metody oznaczania kadmu i olowiu we krwi, kadmu, miedzi, niklu i chromu w moczu technika bezplomieniowej absorpcyjnej spektrometrii atomowej.

The estimation of environmental and occupational exposure to metals is based on the determination of metal concentrations in biological material. This paper describes methods for determining lead and cadmium in blood, and cadmium, copper, nickel and chromium in urine. The methods are evaluated in view of their linearity, precision, repeatability, reproducibility and detectability. The reliability of the methods was verified by determining lyphilized standards of known metal concentrations (Behring). The reproducibility expressed by the value of relative standard deviation ranged from 1.2% to 7.8%. In the case of lead and cadmium determinations, the reliability of results was confirmed due to the participation of our laboratory in the UK NEQAS external control project, the Queen Elizabeth Hospital, Birmingham. The results of external quality control (MR VIS = 19 for lead, as compared with the mean = 41 for all the project participants and MR VIS = 29 for cadmium, mean = 62) prove undoubtedly correctness of the methods applied. A small volume of sample to be analyzed is their major advantage, and due to adopted analytical parameters the methods can be used to determine metals in biological material in order to assess occupational or environmental exposure.

Urinary excretion of chromium as an indicator of exposure to various chromium forms in MMA/SS welders.

Increased levels of Cr discharged with urine after working shift, Cr-U (arithmetic mean 15.8 mu g/g creatinine), and Cr buildup during working shift, DeltaCr-U (arithmetic mean 3.8 mu g/g creatinine), were observed in 15 MMA/SS welders exposed during the working week to welding fumes containing Cr VI (33-56%) - mainly soluble (87%) and Cr III (44-67%) - mainly insoluble (72%). The highest correlation coefficients were obtained for DeltaCr-U vs. Cr total (r = 0.58), Cr VI (r = 0.56) and soluble Cr III in the air. Increased DeltaCr-U value for exposures at MAC Cr VI (16.8 mu g/g creatinine) was demonstrated in welders employed longer than 7 years and exposed to Cr VI below MAC level, which might suggest that the duration of employment affects that value within the low range of concentration of Cr VI in the air (< 0.03 mg/m3). Nevertheless, linear relationship between DeltaCr-U for exposures to Cr VI at MAC levels and duration of employment was not confirmed for wide range of air Cr VI (0.005-0.4 mg/m3). Similar DeltaCr-U values at MAC for Cr VI (6.4 and 6.6 mu g/g creatinine) were obtained for all welders, and those employed over 7 years, respectively, which may suggest that this parameter can be misleading.

[Biological monitoring of lead: system and quality control]. / Monitoring biologiczny olowiu: system i kontrola jakosci.

The assessment of health effects of lead exposure is based on the determination of lead blood concentrations. The correctness of predicting these effects depends on the reliability of determination results. The latter can be confirmed only if the laboratory participates in the quality assurance programme for chemical analyses. The aim of the present study was to investigate the systems in use for quality control, methods of determining lead blood concentration and the results of a project on quality control for lead determination in Poland (project coordinated by the Nofer Institute of Occupational Medicine, Lodz, Poland). The paper discusses the principles of the quality assurance programme implemented in Poland, elements of good laboratory practice with respect to blood sampling, analytical equipment and the use of flameless AAS for determining lead blood concentration. The quality assurance programme for lead determinations covers nine laboratories. The initial stage of its implementation revealed that only 50% of the determinations were correct. Consequently, a series of audits was made at the laboratories and some training provided for the staff. The last round indicated an increase in the percentage of correct results of up to 80%. Proper performance of lead determinations carried out routinely for the assessment of industrial exposure to lead is of extreme importance in view of the fact that lead determinations in blood are planned to be made compulsory and to replace urinary determinations of the metal.

Integrated index of occupational exposure to cadmium as a predictor of kidney dysfunction.

In a study carried out in an alkaline battery factory, the study group consisted of 141 factory workers exposed to cadmium, while 206 workers in the textile industry constituted the control group. Cadmium in blood (Cd-B), cadmium in urine (Cd-U) as well as beta 2-microglobulin and retinol-binding protein (RBP) in urine were determined. Exposure to cadmium in the factory was high. In 1988, Cd-B concentrations in different departments averaged 11.2-29.9 micrograms/l. To evaluate the admissible period of occupational exposure to cadmium, an integrated exposure index [Cd-B (micrograms/l) x years of exposure] is proposed. According to the dose-response relationship, an increase in low molecular weight protein excretion in urine can be expected in 10% of subjects at an integrated exposure index of about 300 micrograms/l x years of exposure. The data obtained confirmed the validity of the recommended health-based limits for occupational exposure of 10 micrograms/l and 10 micrograms/g creatinine for Cd-B and Cd-U respectively.

Effects of Na2CaEDTA on lead deposits in rabbit osseous tissue.

Radiochemical and autoradiographic methods were used for 210Pb determination after Na2CaEDTA administration to rabbits. 210Pb was determined in soft tissues, compact and trabecular bones and growing microareas on the endosteum of the long bone. After Na2CaEDTA injection lead was depleted from 'new' deposits mainly on the growing surface of both trabecular and compact bones.

Effect of cadmium on arterial blood pressure and lipid metabolism in rats.

A total dose of 8 mg cadmium acetate/kg body weight was administered by repeated i.p. injection to female Wistar rats for 12 weeks. Slight, but significant, increases in blood pressure were recorded. The lipid concentration in serum and other tissues examined was not significantly affected, apart from a decrease in hepatic triglyceride. The blood cadmium (Cd) concentration was increased 10 times and Cd in the aortic wall was 4 times higher in treated rats. Cd affects hepatic lipid metabolism and it is considered that the increase in blood pressure is associated with accumulation of Cd in the arterial walls.

Effect of inhalation exposure to cadmium oxide on arterial blood pressure, lipid metabolism and tissue cadmium concentration in rats.

The arterial blood pressure, lipid content in serum and some organs, cadmium level in blood, aorta wall, lung and liver have been examined in rats repeatedly exposed to cadmium oxide fume 5 hours daily, 5 days a week, during 6 months. The blood pressure in rats exposed to cadmium oxide at concentration 0.02 mg Cd/m3 and 0.16 mg Cd/m3 was not changed, but it was slightly lowered at concentration 1.0 mg Cd/m3, which has been found lethal for rats. The concentration of total cholesterol, phospholipids and cholesterol esters in serum of female rats exposed at concentration of 0.16 mg Cd/m3 for 3 months was decreased, but was not affected after 6 months of exposure. The content of cholesterol and triglycerides in aorta wall, heart and liver was unchanged, although the content of cholesterol was decreased in adrenals of rats exposed for 3 months at concentration of 0.16 mg Cd/m3. Inhalation of cadmium oxide brought about the marked increase of Cd content in lung and kidney of rats exposed at all concentrations an increase of Cd blood level in rats exposed at concentrations of 0.16 mg Cd/m3 and 1.0 mg Cd/m3 and no increase of Cd content in aorta wall.

Teratogenicity, fetal toxicity and tissue concentration of cadmium administered to female rats during organogenesis.

Cadmium chloride was administered by gavage to pregnant rats from day 7 to day 16 of gestation. Cadmium, when administered at a dose of 40 mg Cd per kg per day, was associated with significant maternal toxicity, placental injury and an increased fetal burden of cadmium. At lower dose levels (2-20 mg Cd per kg per day), fetal development was retarded. Teratogenic effects were not observed and the fetal cadmium concentrations did not differ significantly from the controls, despite the marked cadmium accumulation in the placenta and maternal tissues. The body-weight gain during gestation of all cadmium-treated females was reduced and an absolute weight of adrenals in females given cadmium at doses 4 mg kg-1 and higher was significantly increased. The obtained results indicate that cadmium-induced fetal toxicity is associated with concomitant maternal toxicity and alteration in placental function.