The use of multiple parameters to characterize cadmium-induced renal dysfunction resulting from occupational exposure.

Renal function has been examined in a group of 77 subjects occupationally exposed to cadmium fume and dust, together with a referent group of 103 age- and socioeconomically matched subjects. Fourteen biochemical parameters were measured on each subject. Three different ways of combining the information from all 14 tests were used to identify those subjects with renal dysfunction. These were first to count the number of parameters in which a subject recorded an abnormal test result. Second, the z value was computed for each parameter for each person by comparison with the mean and standard deviation of a derived normal population; these z scores were then summed. Lastly a multivariate distance measure, Mahalanobis D2, was determined for each subject from the distribution of normal subjects. The three approaches showed a considerable degree of agreement in identifying subjects with renal dysfunction, but they also displayed complementary strengths and weaknesses. The consensus of the three techniques was then taken to define truly dysfunctional subjects and each of the 14 parameters, and some combinations of pairs of parameters were tested as to their sensitivity and specificity. For this group of subjects, it was not possible to improve greatly on the use of retinol binding protein on its own. Were a second parameter to be chosen, it would be desirable to choose one reflecting the glomerular filtration rate, but the absence of a suitable sensitive biological monitoring parameter precludes a firm recommendation.

In vivo neutron activation analysis of organ cadmium burdens. Referent levels in liver and kidney and the impact of smoking.

In vivo neutron activation measurements of liver and kidney cadmium have been made in 77 exposed workers and 101 referents. Cadmium levels were higher in exposed workers than in referents; both in liver, 25.7 cf. 0.6 micrograms/g, and kidney, 17.9 cf. 2.7 mg. The 19 referents who never smoked had lower mean organ cadmium burdens than the other referents, the difference achieving statistical significance in the kidney, p less than .01. Cigarette smoking was estimated to increase cadmium body burden by 370 +/- 140 micrograms/pack year. These referent cadmium levels are similar to, although slightly below, previous in vivo and autopsy data.

Relations between liver cadmium, cumulative exposure, and renal function in cadmium alloy workers.

Detailed biochemical investigations of renal function were made on 75 male workers exposed to cadmium and an equal number of referents matched for age, sex, and employment status. The exposed group consisted of current and retired workers who had been employed in the manufacture of copper-cadmium alloy at a single factory in the United Kingdom for periods of up to 39 years and for whom cumulative cadmium exposure indices could be calculated. In vivo measurements of liver and kidney cadmium burden were made on exposed and referent workers using a transportable neutron activation analysis facility. Significant increases in the urinary excretion of albumin, retinol binding protein, beta 2 microglobulin, N-acetylglucosaminidase (NAG), alkaline phosphatase, gamma-glutamyl transferase and significant decreases in the renal reabsorption of calcium, urate, and phosphate were found in the exposed group compared with the referent group. Measures of glomerular filtration rate (GFR) (creatinine clearance, serum creatinine, and beta 2 microglobulin) indicated a reduction in GFR in the exposed population. Many of these tubular and glomerular function indicators were significantly correlated with both cumulative exposure index and liver cadmium burden. Using cumulative exposure index and liver cadmium as estimates of dose, a two phase linear regression model was applied to identify an inflection point signifying a threshold level above which changes in renal function occur. Many biochemical variables fitted this model; urinary total protein, retinol binding protein, albumin, and beta 2 microglobulin gave similar inflection points at cumulative exposure levels of about 1100 y.micrograms/m3 whereas changes in the tubular reabsorption of urate and phosphate occurred at higher cumulative exposure indices. Measures of GFR, although fitting the threshold model did not give well defined inflection points. Fewer variables fitted the two phase model using liver cadmium; those that did gave threshold levels in the range 20.3-55.1 ppm. When cadmium workers with cumulative exposure indices of less than 1100 y.micrograms/m3 were compared with their respective referents only serum beta 2 microglobulin and urinary NAG were significantly increased in the exposed group and these differences were not related to the degree of cadmium exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadmium fume inhalation and emphysema.

Lung function and chest radiographs of 101 men who had worked for 1 or more years manufacturing copper-cadmium alloy were compared with those of a referent group matched for age, sex, and employment status. Cigarette consumption was similar in the two groups. The cadmium workers had an excess of abnormalities of lung function and of radiographic changes consistent with emphysema. Classification of the cadmium workers by exposure categories based on either estimated cumulative cadmium exposure or liver cadmium measured by neutron activation analysis showed that abnormalities of lung function were greatest in those with the highest cumulative cadmium exposure or liver cadmium. The difference in the transfer coefficient (KCO) between cadmium workers and referents increased linearly with increasing cumulative exposure without evidence for a threshold. The estimated mean decrement in KCO for a cadmium worker employed 5 or more years with a cumulative exposure of 2000 yr.microgram.m-3 (exposure to the current UK control limit of 50 micrograms.m-3 for a working lifetime of 40 yr) lies between 0.05 and 0.3 mmol.min-1.kPa-1.l-1 (95% confidence interval). This decrement is consistent with the functional and radiological changes of emphysema observed in this group of workers.

In-vivo and in-vitro measurements of lead and cadmium.

Tibia lead is measured in vivo using X-ray fluorescence. A(109)Cd source is used to excite Pb K X-rays, and this signals is normalized to that from Rayleigh scattering to remove geometrical variations. The lower limit of detection is 10 µg/g for a mean absorbed dose, to the exposed section of the leg, of 100 µGy. Tibia lead correlated positively with age in normal volunteers (r=0.615,p=0.004) and with duration of exposure in occupationally exposed subjects (r=0.847,p=0.0001). When the X-ray fluorescence technique was applied to autopsy specimens previously analyzed by atomic absorption spectrometry there was excellent agreement between measurement techniques.Cadmium is measured in vivo by neutron activation analysis. The detection limit in liver is 6.5 µg/g for a local skin dose equivalent of 0.5 mSv and in kidney is 6.4 mg for a dose equivalent of 0.9 mSv to the skin. Detailed analysis of the γ-ray spectrum will produce only slight improvements in detection limit. Uncertainties in organ position during measurement, even after ultrasonic localization, are likely to produce uncertainties of 20-25% in cadmium measurement. Autopsy samples were measured, using a fast neutron activation method, from people previously measured in vivo. The results are broadly consistent, but show differences greater than those accounted for by counting statistics.