Effects of dietary cadmium on rhesus monkeys

Abstract

Ten male rhesus monkeys, each weighing 3.5 kg, were divided into four groups of 3, 3, 2, and 2, and were fed daily with 100 g pelleted food containing 300, 30, 3, and 0 ppm cadmium, respectively. Urine samples were collected every 2 weeks and blood samples every 4 weeks. One monkey each of the 300 and 30 ppm groups was autopsied for pathological examination and tissue cadmium determination at the week 24 of the experiment; the remaining 8 animals were killed after 55 weeks.The lowest exposed group (3 ppm) did not show any specific biological response to cadmium over a period of 55 weeks. In the 30 ppm group, no significant changes were observed for up to 24 weeks, although cadmium concentration in the renal cortex and urine at 24 weeks were 300 /.g/g wet weight and 18 ,g/l., respectively. Plasma urea nitrogen and urine protein (quantitative determination) increased after 30 and 36 weeks. At 55 weeks of the experiment, qualitative tests were negative for low molecular weight proteinuria and glycosuria, and the results remained normal for renal and liver function tests and blood analysis, although cadmium concentrations in the renal cortex of two monkeys were 460 and 730 ,ug/g wet weight and those in the liver were 110 and 160 ,ug/g wet weight, respectively.In the highest exposure group (300 ppm), urine cadmium increased to 250,ug/l. by 11 weeks, and urine retinol-binding protein, plasma GOT, GPT, and LDH increased after 12 weeks. Proteinuria (quantitative determination), glycosuria, aminoaciduria (panaminoaciduria), and erythrocytopenia were observed after 16 weeks, when urine cadmium was 500-900, 1g/l. Hypohemoglobinopathy and proteinuria (qualitative determination) were observed after 20 and 24 weeks, while cadmium concentrations in the renal cortex and the liver were 760 and 430 ,lg/g wet weight at 24 weeks, respectively. Slightly depressed tubular reabsorption of phosphate, increased urine 832-microglobulin, increased plasma urea nitrogen, and increased plasma a2-globulin fraction (electrophoresis) were observed between 28 and 30 weeks of the experiment. Creatinine clearance and plasma cholinesterase decreased after 47 and 54 weeks, respectively. Cadmium concentrations in the renal cortex and the liver of two monkeys at 55 weeks were 350 and 580 ,ug/g wet weight and 410 and 630 ,g/g wet weight, respectively. Pathological examinations revealed denaturation, destruction, and regeneration of the epithelial cells in renal proximal tubules, but no pathological changes in osseous tissues.Critical cadmium concentration in the renal cortex was estimated to be 380 ,uLg/g wet weight for low molecular weight proteinuria and 470 ,ug/g wet weight for proteinuria, glycosuria, and aminoaciduria. Critical concentration in the liver was also estimated to be 210 ,tg/g wet weight. The apparent biological half-time of cadmium in monkeys at autopsied stage was calculated to be 0.66, 6.4, 5.2, and 22.4 years for the 300, 30, 3, and 0 ppm groups, respectively.

Chronic health effects of orally administered cadmium in dogs

“…In other oral administration experiments, dogs given cadmium up to 30 ppm for a period of three months did not show any evidence of damage to the liver [35]. The observed effects of dietary cadmium in monkeys at doses of 0, 3,30 and 300 ppm for up to 54 weeks show that hepatic dysfunction appeared early in the highest exposure group [8]. The plasma GOT, GPT and LDH increased after 12 weeks in the 300 ppm group and the elevations of plasma enzyme activities appeared earlier than renal dysfunction.…”

“…Loeser and Lorke [35] reported the health effects of cadmium administered to dogs in their food at concentrations of 0,1.3,10 and 30 ppm over a period of three months. The effects of dietary cadmium on monkeys at dose levels of 0,3,30 and 300 ppm for up to nine years have been reported in Japan [8]. Nomiyama et al have also reported the toxicity of cadmiumcontaminated rice which was administered orally to monkeys for six years [36], In our present experiment, the health effects on beagles given cadmium orally in doses of 1,3,10,50 and 100 mg/day/animal (corresponding to 3,10,33,165, 333 ppm in food) over a period of eight years are reported.…”

“…The effects of dietary cadmium on monkeys at dose levels of 0,3,30 and 300 ppm for up to nine years have been reported in Japan [8]. Nomiyama et al have also reported the toxicity of cadmiumcontaminated rice which was administered orally to monkeys for six years [36], In our present experiment, the health effects on beagles given cadmium orally in doses of 1,3,10,50 and 100 mg/day/animal (corresponding to 3,10,33,165, 333 ppm in food) over a period of eight years are reported. In our dog study, behavior and body weight development were not affected by cadmium administration except for the male dog given 100 mg Cd/day (Figure 1).…”

“…Decreased hemoglobin levels have been observed in cadmium-exposed workers [37,38] and in other animal experiments [39,40,41]. In long-term oral experiments on monkeys, anemia appears at an early stage in monkeys given 300 ppm Cd [8]. Anemia has many causes, therefore, it is very difficult to say definitely whether cadmium exposure caused anemia in experimental animals or humans.…”

“…Considering these facts, the results obtained by these animal experiments are not always directly applicable to estimating the health effects of cadmium on humans. Because only a few papers have reported the chronic oral toxicity of cadmium in large animals [8,9], we conducted a long-term experiment using beagles to investigate the chronic health effects of cadmium.…”