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Biomedical subjects

L Järup

Publications and source records attributed to L Järup.

32 records · Page 2Linked to original sources

Enzymuria in a population living near a cadmium battery plant.

OBJECTIVES: To study the body burden of cadmium and signs of tubular dysfunction in a rural population living near a closed nickel cadmium battery plant. METHODS: Cadmium and N-acetyl-beta-glucosaminidase (NAG) in urine were measured in 72 subjects who lived close to the plant. RESULTS: Residents living close to the plant had higher median urinary cadmium concentrations than those living farther away (1.01 v 0.46 nmol/mmol creatinine) and than a control group (0.2 nmol/mmol creatinine). There was a significant correlation between urinary cadmium and the excretion of NAG in urine as well as signs of tubular dysfunction in residents who excreted urinary cadmium above 0.5 nmol/mmol creatinine. CONCLUSION: Tubular dysfunction may appear in environmentally exposed subjects at lower cadmium body burdens than previously anticipated.

Acetylglucosaminidase↗

Decreased glomerular filtration rate in solderers exposed to cadmium.

OBJECTIVES: to evaluate the degree of cadmium induced glomerular impairment and to assess the dose-response relation between cadmium dose and the prevalence of glomerular dysfunction. METHODS: A comparison of glomerular filtration rates (GFR) assessed by Cr-EDTA clearance was made in 42 solderers previously exposed to cadmium for at least five years. Blood and urine data were collected at health examinations in 1984, 1989, and 1993. Individual doses of cadmium were estimated by analysing cadmium in blood. RESULTS: Glomerular lesions induced by cadmium are irreversible and the GFR decreases with the degree of tubular damage. The GFR also decreases with cadmium dose and there is a dose-response relation between blood cadmium and prevalence of glomerular damage with 3.4% prevalence at blood cadmium concentrations below 50 nmol/l, 33% at blood cadmium concentrations between 50 and 75 nmol/l and 100% prevalence of glomerular damage when cadmium in blood exceeds 75 nmol/l. CONCLUSIONS: The kidney lesions induced by cadmium are irreversible and the prevalence of those lesions are dose dependent. There is also evidence of a dose related decrease in GFR even a long time after the end of exposure. Exposure to cadmium should therefore be minimised and workers exposed to cadmium should be examined regularly for many years after the end of exposure.

Cadmium↗

Dose-response relations between urinary cadmium and tubular proteinuria in cadmium-exposed workers.

Cadmium in urine reflects the body burden in cadmium-exposed individuals. Urinary beta 2-microglobulin is frequently used as a marker of tubular proteinuria with an arbitrarily chosen value (34 micrograms/mmole creatinine) as the cut-off limit. Both this cut-off level and a lower limit (25 micrograms/mmole creatinine) were used in a study of the relationship between urinary cadmium and beta 2-microglobulin in 561 cadmium-exposed battery workers. There was a clear dose-response relation between the urinary cadmium level and the prevalence of tubular proteinuria ranging from 0.8% in the lowest exposure group, excreting less than 1 nmole cadmium/mmole creatinine, to 46.4% (50.0 for the lower cut-off level) in the highest exposure group with a mean urinary cadmium of 15 nmole/mmole creatinine. The relation between urinary cadmium and tubular proteinuria was also assessed using probit analysis. There was a 10% response at a urinary cadmium of 3 nmole/mmole creatinine. The impact of age on the dose-response relation was explored in two age groups with the cut-off point at 60 years of age, showing a 10% prevalence of tubular proteinuria at urinary cadmium levels of 1.5 nmole/mmole creatinine in this older age group and 5.0 nmole/mmole creatinine in the category under 60 years of age. The study thus indicates that the present health-based limit (10 nmole/mmole creatinine) proposed by the World Health Organization (WHO) is too high and it is suggested that a new limit should be set to 3 nmole/mmole creatinine.

Aged↗

Incidence of renal stones among cadmium exposed battery workers.

The health effects of occupational exposure to cadmium were studied in a group of 902 workers employed for at least one year in a Swedish battery factory between 1931 and 1982. Data on air cadmium concentrations for different periods were combined with company employment records to obtain individual cumulative exposure estimates. A questionnaire including questions on the occurrence of kidney stones was sent to all 601 living workers and to the next of kin of 267 of the deceased workers. The response rate was 88%. 73 workers reported renal calculi that appeared after initial employment. A dose-response relation was found between cumulative exposure to cadmium and age standardised cumulative incidence. Incidence rate ratios (IRRs) were then computed for three exposure categories (< 250, 250- < 5000, and 5000 micrograms/m3 x years) standardised for calendar time, age, and smoking with the low exposure group as reference level. The IRRs were 1.0, 1.6 [95% confidence interval (95% CI) 0.7-3.4], and 3.0 (95% CI 1.3-6.8) respectively. beta 2 Microglobulin measurements were available for 33 workers who formed stones; 13 of these workers had tubular proteinuria (beta 2 microglobulin > or = 34 micrograms/mmole creatinine)--that is, a prevalence of 39%. There was also an indication of a steeper dose-response relation among workers with tubular proteinuria.

Age Factors↗

Renal function impairment in workers previously exposed to cadmium.

Cadmium-induced renal effects were followed (1989) in 16 workers previously exposed to cadmium, who had been shown 5 years earlier to have had tubular damage; all but 1 worker had persistent tubular damage (beta 2-microglobulin > 60 micrograms/mmol creatinine). The mean glomerular filtration rate (GFR) decreased from 77.3 to 71.7 ml/min/1.73 m2, which is 2.0 ml/min more than would have been expected from aging only. There was a negative correlation between loss of tubular function (relative clearance of beta 2-microglobulin) and the ratio of observed versus reference GFRs in accordance with a 1984 study. The results confirm that cadmium-induced tubular damage is irreversible. They also suggest that the glomerular dysfunction after cadmium exposure is irreversible and progressive also after exposure stops. A nonsignificant correlation was found between cumulative cadmium exposure and decreased GFR.

Adult↗

Arsenic exposure, smoking, and lung cancer in smelter workers--a case-control study.

A cohort of 3,916 Swedish copper smelter workers employed for at least 3 months between 1928 and 1967 was followed up through 1981. Arsenic exposure was estimated for different time periods at each workplace within the smelter. Detailed job records were linked to the exposure matrix, thus forming individual cumulative arsenic exposure measures for each smelter worker. Smoking history was collected for 107 lung cancer cases and 214 controls from the cohort. Lung cancer risks were positively related to cumulative arsenic exposure with smoking standardized relative risks ranging from 0.7 to 8.7 in different exposure groups. A negative confounding by smoking was suggested in the higher exposure categories. The interaction between arsenic and smoking for the risk of developing lung cancer was intermediate between additive and multiplicative and appeared less pronounced among heavy smokers.

Arsenic↗

Cumulative arsenic exposure and lung cancer in smelter workers: a dose-response study.

The cause-specific mortality was followed through 1981 in a cohort of 3,916 male Swedish smelter workers employed for at least 3 months from 1928 through 1967. Arsenic levels in the air of all workplaces within the smelter were estimated for three different time periods. Using this exposure matrix and detailed information of the work history, cumulative arsenic exposure could be computed for each worker. Standardized mortality ratios (SMRs) were calculated for several dose categories using age-specific mortality rates from the county where the smelter was situated. A positive dose-response relationship was found between cumulative arsenic exposure and lung cancer mortality with an overall SMR of 372 (304-450, 95% confidence interval). The lung cancer mortality was related to the estimated average intensity of exposure to arsenic but not to the duration. No positive dose-response relationship was found between arsenic and ischemic heart disease or cerebrovascular disease. There was also no evident dose-response relationship between estimated exposure to sulfur dioxide and lung cancer.

Adult↗

Cumulative blood-cadmium and tubular proteinuria: a dose-response relationship.

Biological monitoring, i.e. using individual measures of exposure such as cadmium in blood, is supposed to reflect the real dose better than the more commonly used external measures such as air-cadmium. In order to investigate this, cumulative cadmium doses were estimated individually for 440 workers in a battery factory. Cumulative air-cadmium dose as well as two different cumulative blood-cadmium doses were computed for each study individual. Forty workers had evidence of tubular proteinuria and a clear dose-response relationship was found for each of the dose estimates. Our results suggest that cumulative blood-cadmium is a more sensitive indicator of cadmium-induced renal dysfunction than cumulative air-cadmium.

Air Pollutants, Occupational↗

A suggestion on how to use measurements of cadmium in blood as a cumulative dose estimate.

The individual cumulative cadmium dose was estimated for 44 smelter workers in a cadmium-copper alloy plant. Two different principles were used: cumulative respiratory dose and cumulative average annual blood-cadmium dose. Out of eight workers with a cumulative respiratory dose exceeding 500 mg Cd . h/m3, two of them (25%) had signs of a cadmium-induced renal dysfunction. These two men were the only workers that had a cumulative average annual blood cadmium dose exceeding 200 micrograms Cd . year/l. Our results suggest that measurements of cadmium in the blood can be used as an indicator of the cadmium exposure of each individual and that, in order to prevent renal dysfunction, the average blood-cadmium concentration should not exceed 10 micrograms Cd/l over periods of many years (decades).

Adult↗

Biological half-time of cadmium in the blood of workers after cessation of exposure.

The biological half-time of cadmium in the blood of previously exposed workers was estimated after the cessation of exposure. Five men were followed for a period of 10 to 13 years. One-compartment and two-compartment exponential elimination models were used to describe the decrease in blood cadmium levels over time. The best fit to the observed data was obtained with a two-compartment model. The half-times estimated from this model ranged from 75 to 128 d for the fast component and from 7.4 to 16.0 years for the slow component. The results confirm that there is a very long whole-body biological half-time for cadmium, and the estimated half-times are similar to those obtained with different methods.

Adult↗

Creatinine versus specific gravity-adjusted urinary cadmium concentrations.

The aim was to assess how urinary creatinine is affected by age, gender, body size and meat intake, and to determine to what extent such factors might affect the creatinine adjustment of urinary cadmium. The study was based on three Swedish studies: (1) 67 non-smoking women aged 20-50 years (24-h urine samples); (2) 289 men and 434 women aged 16-81 years (spot urine samples); and (3) 98 men and 105 women aged 19-72 years (spot urine samples). The effects of age, body surface area (as an indicator of muscle mass), and meat intake on urinary creatinine and cadmium were analysed using multiple regression analyses. Gender- and age-related variations in urinary creatinine and cadmium adjusted for creatinine or specific gravity were compared by ANOVA or ANCOVA. In the multiple regression analyses, body surface area, gender, age and meat intake were the major determinants of urinary creatinine. Urinary cadmium adjusted for creatinine and specific gravity were also dependent on body size, gender and age. Urinary cadmium adjusted for creatinine was 15-92% higher in women or older individuals than in men or younger individuals. Women or older individuals had -3 to 79% higher urinary cadmium adjusted for specific gravity than men or younger individuals had, and such a difference between gender or age group was less obvious in specific gravity adjustment than in creatinine adjustment. Thus, urinary cadmium adjusted for creatinine is more affected by age, gender, body size and meat intake than is specific gravity adjustment. When comparing individuals or populations with large differences in muscle mass or meat intake, such effects can be especially important. In such studies, specific gravity adjustment seems to be more appropriate.

Adult↗