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

Abstract

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)

Further scientific issues in determining an occupational standard for cadmium

“…We have each been involved in one survey of a factory using cadmium sulfide [Greenberg et al, 1986;Chettle, unpublished data]; in both cases, there was a lower incidence of renal dysfunction and lower cadmium body burdens than at apparently comparable plants handling cadmium oxides. In the latter case, some air monitoring data for cadmium were available and the ratio of body burden to cumulative exposure was less than in the survey reported by Mason et al [1988]. The difference, however, did not achieve statistical significance, due in part to wide inter-individual variation.…”

“…Data from a number of studies [Ellis et al, 1985; Mason et al, 1988; Roels et al, 1989; Thun et al, 19891 have made it clear that current regulatory standards for occupational exposure to cadmium and its compounds are ripe for review. Scientific issues which should undergird any change in policy have been addressed by the summary paper of Thun et al [ 19911. That paper presents an excellent summary and critique of data, particularly the human experience, relevant to determining appropriate regulatory standards for cadmium in air concentrations.…”

Using Ionizing Radiation to Determine Trace Element Content in Living Human Subjects

“…Although many studies were undertaken, those that had the greatest impact identified critical levels of Cd in the kidney 51) , the corresponding levels in liver and the cumulative Cd in air exposures that would result in these critical levels being reached. The results from entirely independent studies at Brookhaven 52) and at Birmingham 53) agreed very closely. Kidney dysfunction, as evidenced by increased urinary excretion of low molecular weight proteins, for 50% of an exposed group was associated with a cumulative Cd in air figure of 1,000 gCd.y/m 3 air.…”

Cadmium-Induced Renal Lipid Peroxidation in Rats and Protection by Selenium

“…Angerer, 1992). Following occupational or environmental exposure to Cd, the kidney is a primary target tissue (Piscator, 1986;Mason et al, 1988;Staessen et al, 1994). Numerous epidemiological studies on industrial workers or inhabitants in Cd-polluted areas have documented the adverse renal effects that may be produced by this heavy metal (Friberg, 1948;Buchet et al, 1990;Nogawa & Kido, 1993).…”