Multiple Targets of Toxicity in Environmental Exposure to Low-Dose Cadmium

Dietary assessment reports and population surveillance programs show that chronic exposure to low levels of environmental cadmium (Cd) is inevitable for most people, and adversely impacts the health of children and adults. Based on a risk assessment model that considers an increase in the excretion of beta(2)-microglobulin (beta M-2) above 300 mu g/g creatinine to be the critical toxicity endpoint, the tolerable intake level of Cd was set at 0.83 mu g/kg body weight/day, and a urinary Cd excretion rate of 5.24 mu g/g creatinine was considered to be the toxicity threshold level. The aim of this review is to draw attention to the many other toxicity endpoints that are both clinically relevant and more appropriate to derive Cd exposure limits than a beta M-2 endpoint. In the present review, we focus on a reduction in the glomerular filtration rate and diminished fecundity because chronic exposure to low-dose Cd, reflected by its excretion levels as low as 0.5 mu g/g creatinine, have been associated with dose-dependent increases in risk of these pathological symptoms. Some protective effects of the nutritionally essential elements selenium and zinc are highlighted. Cd-induced mitochondrial dysfunction is discussed as a potential mechanism underlying gonadal toxicities and infertility.

Automated summary

Dietary assessment reports and population surveillance programs have shown that chronic exposure to low levels of environmental cadmium adversely affects the health of both children and adults. This review assesses the current risk assessment model for cadmium and highlights alternative toxicity endpoints that are more relevant in deriving exposure limits. The review also discusses the association between low-dose cadmium exposure and reduced glomerular filtration rate and fertility, as well as the potential protective effects of selenium and zinc. Additionally, the review explores mitochondrial dysfunction as a potential mechanism underlying gonadal toxicities and infertility caused by cadmium.