Low level exposure to cadmium and early kidney damage: the OSCAR study.

OBJECTIVES: To study the dose-response relation between cadmium dose and renal tubular damage in a population of workers and people environmentally or occupationally exposed to low concentrations of cadmium. METHODS: Early kidney damage in 1021 people, occupationally or environmentally exposed to cadmium, was assessed from cadmium in urine to estimate dose, and protein HC (alpha(1)-microglobulin) in urine to assess tubular proteinuria. RESULTS: There was an age and sex adjusted correlation between cadmium in urine and urinary protein HC. The prevalence of tubular proteinuria ranged from 5% among unexposed people to 50% in the most exposed group. The corresponding prevalence odds ratio was 6.0 (95% confidence interval (95% CI) 1.6 to 22) for the highest exposure group, adjusted for age and sex. Multiple logistic regression analysis showed an increasing prevalence of tubular proteinuria with urinary cadmium as well as with age. After adjustment to the mean age of the study population (53 years), the results show an increased prevalence of 10% tubular proteinuria (taking into account a background prevalence of 5%) at a urinary cadmium concentration of 1.0 nmol/mmol creatinine. CONCLUSION: Renal tubular damage due to exposure to cadmium develops at lower levels of cadmium body burden than previously anticipated.

Low-level cadmium exposure and osteoporosis.

Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia. We have examined whether long-term low-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16-81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age. There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose category (> or = 3 nmol/mmol creatinine) compared with the lowest dose group (< 0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose group 0.5-3 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.

Mortality and cancer incidence in Swedish battery workers exposed to cadmium and nickel.

OBJECTIVE: To follow up cancer incidence and mortality in a group of Swedish battery workers exposed to nickel hydroxide and cadmium oxide. METHODS: 869 workers, employed at least one year between the years 1940 and 1980 were followed up until 1992. Vital status and causes of death were obtained from the Swedish cause of death registry. Cancer morbidity was retrieved from the Swedish cancer registry. Regional reference rates were used to compute the expected numbers of deaths and cancers. RESULTS: Up to 31 December, 1992, a total of 315 deaths (292 in men and 23 in women) had occurred in the cohort. For men, the overall standardised mortality ratio (SMR) was 106 (95% confidence interval (95% CI) 93.7 to 118) and for women 83.8 (95% CI 53.1 to 126). The SMRs for total cancer mortality were 125 (95% CI 98.2 to 157) for men and 69.5 (95% CI 25.5 to 151) for women. The SMR for lung cancer in men was 176 (95% CI 101 to 287). No lung cancers were found among female workers. Up to 31 December, 1991, a total of 118 cancers had occurred in the cohort. A significantly increased standardised incidence ratio (SIR) was found for cancer of the nose and nasal sinuses in men, three cases v 0.36 expected, yielding an SIR of 832 (95% CI 172 to 2430). Applying a 10 year latency period in cohort members exposed to > or = 1000 micrograms cadmium/m3, the SIR was 1107 (95% CI 134 to 4000). Similarly, for cohort members exposed to 2000 micrograms nickel/m3, the SIR was 1080 (95% CI 131 to 3900). CONCLUSION: There was an increased overall risk for lung cancer, but no exposure-response relation between cumulative exposure to cadmium or nickel and risk of lung cancer. There was a highly significant increased risk of cancer of the nose and nasal sinuses, which may be caused by exposure to nickel or cadmium or a combination of both exposures.

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.

Cadmium concentration in the kidney cortex of occupationally exposed workers measured in vivo using X-ray fluorescence analysis.

A method for in vivo X-ray fluorescence analysis of the cadmium concentration in the kidney cortex has been improved and tested in 20 selected male occupationally cadmium-exposed workers (duration of exposure 7-39 years). The concentration of cadmium in kidney cortex ranged from 47 to 317 (median 141) micrograms/g. The concentration of cadmium in blood was 32-160 (median 64) nmole/liter, cadmium in urine was 2.5-13 (median 5.4) nmole/mmole creatinine, and beta 2-microglobulin in urine was 3.3-68 (median 14) micrograms/mmole creatinine. In individuals, the relationship between duration of exposure, time-integrated exposure, and cadmium level in urine on the one hand and cadmium level in the kidney on the other varied considerably. Direct in vivo analysis of the concentration of cadmium in the kidney cortex is therefore valuable as a complement to the other tests when monitoring cadmium exposure. Our method is sensitive, practically free from risk, and can b performed by routine at low costs.

Biological monitoring, by in vivo XRF measurements, of occupational exposure to lead, cadmium, and mercury.

In vivo X-ray fluorescence (XRF) techniques were used for biological monitoring of lead, cadmium, and mercury. Lead accumulates in bone, the level of which may thus be used for monitoring of exposure. However, there was no close association between lead levels in bone and exposure time, partly because of differences in exposure patterns and partly, probably, because of variations in the toxicokinetics of lead. There are at least two separate bone lead compartments. The average over-all half-time is probably 5-10 yr. The finger bone level may be an index of the lead status of the total skeleton. In lead workers, the mobilization of bone lead causes an "internal" lead exposure and affects the blood lead level considerably. In cadmium workers, in vivo XRF is a sensitive and risk-free method for assessment of accumulation in kidney cortex, the critical tissue as to toxic effects; workers displayed increased levels. However, there was no clear association with duration and intensity of exposure, cadmium levels in urine, or microglobulinuria. Determinations of kidney cadmium may add important information on the state of accumulation and, thus, risk of kidney damage. Workers exposed to elemental mercury vapor, as well as fishermen exposed to methyl mercury, had mercury levels in bone below the detection limit of the XRF method.

Cancer mortality of cadmium workers.

Several epidemiological studies of workers exposed to cadmium indicate an increased risk of lung and prostatic cancer. The increase is statistically significant in some of the studies but the SMR is greater than 100 in almost all. A cohort study of the mortality among 522 Swedish workers exposed to cadmium for at least one year in a nickel-cadmium battery plant support the earlier findings. The SMR for lung and prostatic cancer increased with increasing dose and latency but did not obtain statistical significance. A combination of all the available data from the most recent follow up of causes of death among cadmium workers in six different cohorts shows 28 cases of prostatic cancer (SMR = 162) and 195 cases of lung cancer (SMR = 121). This new analysis suggests that long term, high level exposure to cadmium is associated with an increased risk of cancer. The role of concomitant exposure to nickel needs further study.