J. P. Buchet

Renal effects of cadmium body burden of the general population.

In a cross-sectional population study to assess whether environmental exposure to cadmium is associated with renal dysfunction, 1699 subjects aged 20-80 years were studied as a random sample of four areas of Belgium with varying degrees of cadmium pollution. After standardisation for several possible confounding factors, five variables (urinary excretion of retinol-binding protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin, aminoacids, and calcium) were significantly associated with the urinary excretion of cadmium (as a marker of cadmium body burden), suggesting the presence of tubular dysfunction. There was a 10% probability of values of these variables being abnormal when cadmium excretion exceeded 2-4 micrograms/24 h. Excretion reached this threshold in 10% of non-smokers. There was also evidence that diabetic patients may be more susceptible to the toxic effect of cadmium on the renal proximal tubule.

Renal excretion of proteins and enzymes in workers exposed to cadmium

Abstract. The proteinuria rate and the relative clearances of β2‐microglobulin, orosomucoid, albumin, transferrin and IgG were measured in forty‐two workers exposed to cadmium and in seventy‐seven control workers. A tubular type proteinuria with an increased excretion of β2‐microglobulin and often also a glomerular type proteinuria with an increased excretion of orosomucoid, albumin, transferrin and IgG were observed mainly in workers exposed to cadmium for more than 25 years and whose cadmium concentration in blood exceeded 1 μg Cd/100 ml and that in urine 10 μg Cd/g creatinine. The glomerular dysfunction was also suggested by an increased plasma level of β2‐microglobulin and creatinine. Both tubular and glomerular impairments occurred with the same prevalence and were not necessarily associated. The increased release of β‐galactosidase by the kidney suggested that cadmium can damage some epithelial cells.

Epidemiological survey of workers exposed to cadmium.

Pulmonary ventilatory function and various biological indices have been investigated in three groups of workers exposed to cadmium dust (women with less than 20 years’ exposure [E1], men with less than 20 years’ exposure [E2], and men with more than 20 years’ exposure [E3]) and in three matched control groups. The current airborne Cd dust concentration in the workrooms was below the actual American threshold limit value (200μg/cu m). A slight but significant reduction in forced vital capacity, in forced expiratory volume in one second, and in peak expiratory flow rate was found in E3 workers. Kidney damage was more prevalent than pulmonary ventilatory changes, since excessive proteinuria was observed in 15% of E2 workers and in 68% of E3 workers. The electrophoretic pattern of the urinary proteins suggests that the lesion is first glomerular and later becomes predominantly tubular (mixed proteinuria).

Low Bone Density and Renal Dysfunction Following Environmental Cadmium Exposure in China

Abstract This paper presents the main findings of a study on health effects of environmental cadmium pollution in China, performed in 1998, i.e. approximately 25 years after the first warnings of such effects were published in Ambio. Forearm bone mineral density (BMD) and renal dysfunction were assessed in population groups exposed to cadmium via rice. Decreased BMD was found in postmenopausal women with elevated urinary cadmium (CdU) or cadmium in blood (CdB) and among men with elevated CdB. Also, clear and statistically significant dose-effect and dose-response relationships were found between CdB or CdU and renal dysfunction (increased excretion of retinol-binding protein). This is the first report of bone effects among Cd-exposed population groups in Asia outside Japan. The report is also of interest since it demonstrates that bone effects, a comparatively severe adverse health effect of Cd, in combination with renal dysfunction, still occurs in environmentally exposed population groups in Asia. Recent reports on bone effects in Cd-exposed population groups in Europe are discussed.

Significance of cadmium concentration in blood and in urine in workers exposed to cadmium

Abstract All the workers (n = 11) occupied in a small factory producing cadmium salts were followed up during several months. Four of them were newly employed workers. At regular time intervals the workers were equipped with a personal air sampler and cadmium concentrations in blood and in urine were measured. The total airborne concentration of cadmium at the different work places was very high. The median values ranged from 110 to 2125 μg/m3. In view of the hygiene practice of the workers, ingestion of cadmium may also have played a role in the overall exposure. After the start of the exposure, cadmium concentration in blood increases linearly up to 120 days and then levels off. This suggests that when equilibrium is reached cadmium level in blood is a good indicator of the average intake during recent months. The interpretation of the cadmium levels in urine is more complex. In seven workers exposed for more than 250 days cadmium level in urine seemed to reflect mainly current exposure. Our results suggest also the existence of three phases in the evolution of the Cd levels in urine after the onset of high exposure. A first phase of very short duration (0–15 days) is observed during which cadmium level in urine increases rapidly to reach a value of about 15 μg/g creatinine. This is followed by a second phase (15–120 days) during which cadmium level in urine increases more slowly. After 120 days there is apparently a rapid increase of the cadmium level in urine (third phase). The results obtained during this study as well as our previous clinical observations on workers exposed to cadmium lead us to propose a tentative biological threshold of 10 μg Cd/g urinary creatinine. It should be stressed that this proposal applies only to adult males occupationally exposed to cadmium and not necessarily to other groups of the general population.

Characterization of the proteinuria in cadmium-exposed workers.

SummaryThe concentration of several protein (β2-microglobulin, orosomucoid, albumin, transferrin) and of total amino acids was determined in the urine of 18 cadmium-exposed workers and in a group of matched nonexposed workers. The results were compared with the electrophoretic pattern of urinary proteins on agarose gel.Ten of the cadmium-exposed workers had an abnormal electrophoretic pattern, eight of them excreted larger quantities of high and low molecular weight proteins, and the other two showed only an increased excretion of high molecular weight proteins. An increased β2-microglobulin excretion was found in five workers with a normal urinary protein electrophoresis whereas only the urine of three exposed workers were found to be normal. We have confirmed a previous observation that in the majority of the cadmium-exposed workers with an abnormal electrophoretic pattern or an increased total proteinuria, not only low molecular weight proteins (β2-microglobulin) are excreted in greater amount but also high molecular weight proteins such as albumin and transferrin.Furthermore, in cadmium-exposed workers proteinuria is more closely related to the concentrations of albumin and orosomucoid in urine than that of β2-microglobulin. The change in urinary concentration of total amino acids was less marked than that of protein. The determination of both low and high molecular weight proteins ought to be recommended for detecting renal damage due to cadmium.

Placental transfer of lead, mercury, cadmium, and carbon monoxide in women. II. influence of some epidemiological factors on the frequency distributions of the biological indices in maternal and umbilical cord blood.

Various epidemiological factors (smoking, residence, age, occupation, drinking habits, duration of pregnancy, and number of previous pregnancies) were investigated in 474 pregnant women (European) and their newborns to assess the effects of these factors on the presence of lead, mercury, cadmium, and carbon monoxide in blood of mothers and newborns. Smoking showed a statistically significant influence on carboxyhemoglobin level in mothers and newborns, and on cadmium concentration in maternal blood. In addition, low-birth-weight newborns and smoking mothers were associated. A slight but statistically significant effect of environmental pollution by lead (greater in urban/industrial populations and least in rural populations) on lead uptake by the pregnant mothers and its transfer to their fetuses was demonstrated. Some of these results suggest that during pregnancy, lead could be mobilized from maternal tissue deposits, but more work is required to confirm this hypothesis. No significant relationships were found among the other epidemiological parameters and the biological measurements made on maternal and cord blood.

Impact of Environmental Cadmium Pollution on Cadmium Exposure and Body Burden

The body burden of cadmium, as estimated from 24-h urine cadmium levels, was determined in 1,523 subjects who were not occupationally exposed and who lived in five areas of Belgium. Urinary cadmium levels differed significantly with place of residence. These differences persisted after standardization for the other significant determinants (i.e., age, body mass index, smoking habits, social class, alcohol consumption, and menopause). The highest 24-h urine cadmium levels were found in subjects who lived in areas that contained cadmium-polluted soils. The body burden overload has been attributed mainly to the consumption of locally grown vegetables and the use of contaminated well water for cooking and drinking. Blood cadmium levels were also dependent on place of residence. However, the geographical differences in blood cadmium did not parallel those of urine cadmium. Blood cadmium is more influenced by recent exposure; therefore, this latter observation might reflect the recent implementation of preventive measures in some areas.

Response of free erythrocyte porphyrin and urinary ? -aminolevulinic acid in men and women moderately exposed to lead

SummaryThe responses of various biological parameters of the haem biosynthesis pathway in a group of adult male and female workers moderately exposed to inorganic lead have been compared. The identical range of blood lead levels in both groups indicates a similar degree of exposure. Women, however, exhibit a larger increase in free erythrocyte porphyrin (FEP) and in urinary δ-aminolevulinic acid (ALA-U) than men.The earlier response in women is probably not due to a relative degree of anaemia (menstrual blood loss) as compared to men, since there is no significant correlation between haemoglobin (Hb) and FEP or ALA-U, and consequently standardization for the same Hb-content does not modify the independent effect of lead on the FEP and ALA-U responses. A greater susceptibility to Pb of the haem biosynthesis pathway in women has therefore been confirmed by the results of the present epidemiological survey among workers of both sexes.A preliminary and limited survey on children (11 to 12 years old) of schools situated at less than 1 km from a Pb-processing plant revealed increased FEP and blood lead concentrations and demonstrated that like women children exhibit an earlier biological response to Pb-B than adult men.

Mobilization of lead during pregnancy in rats.

SummaryLead was administered to three groups of 4 weeks-old female rats at the dose of 1 ppm in drinking water. The first group received lead continuously for 150 days before mating (with non-lead-treated male rats), during pregnancy and during 3 weeks after delivery. In the second group lead was also administered for 150 days before mating but was withdrawn during pregnancy and during the post natal period. In the third group lead was administered for 150 days; the animals were then kept without lead exposure during the 50 days before making them pregnant, during pregnancy and during the post natal period. A control group received only demineralized water.On day 21 after delivery the mothers and their newborns were sacrificed and various parameters of blood-lead concentration (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins concentration (FEP), σ-aminolevulina-ate dehydratase activity (ALAD) — and tissues — ALAD, free tissue porphyrins (FTP), lead concentration (Pb-T) - were determined.In mothers and in newborns lead concentration in blood and in soft tissues were increased over control values only in the group in which lead had been stopped for 50 days before pregnancy. This lead accumulation in soft tissues was associated with an increased FTP in liver, heart and brain of the mothers and in liver of the newborns. This observation suggests that lead stored in the organism can be mobilized during pregnancy.