Toxicokinetics - trdoer40174

The lungs and kidneys are the main target organs for cadmium toxicity

following intermediate or chronic duration exposure by the inhalation or oral

routes. The earliest clinical signs of cadmium poisoning are proteinuria,

glucosuria, and aminoaciduria (USEPA 1985a). Cadmium damages the renal

tubules and results in an inhibition of tubular reabsorption but rarely results in

renal failure (ATSDR 1992). Prolonged exposure to cadmium which causes

renal dysfunction can lead to painful and debilitating bone disease after

inhalation or oral exposure as a result of the cadmium effect on calcium

metabolism (ATSDR 1992).

A toxicokinetic model is available to determine the level of chronic human

oral exposure which results in 200 ug Cd/g wet human renal cortex (the highest

renal level not associated with significant proteinuria, the NOAEL). The model

assumes a 2.5 percent absorption of Cd from food or 5 percent from water, and

that 0.01 percent of the Cd body burden is eliminated per day (USEPA 1985b).

The model predicts that the NOAEL for chronic Cd exposure is 0.005 and

0.01 mg Cd/kg/day from water and food, respectively. Thus, based on an

estimated NOAEL of 0.005 mg Cd/kg/day for Cd in drinking water, an oral RfD

of 0.0005 mg Cd/kg/day (water) was calculated; an equivalent oral RfD for Cd in

food is 0.001 mg Cd/kg/day. A risk assessment for an inhalation RfD for

cadmium is under review by a USEPA work group.

USEPA has classified cadmium as a Group B1 or probable human

carcinogen. This classification is based on occupational epidemiology studies

that have shown an increased risk of lung cancer in workers exposed to cadmium

via inhalation. A two-fold excess risk of lung cancer was observed in cadmium

smelter workers (USEPA 1985b). USEPA has estimated a cancer potency factor

(CPF) of 6.1 (mg/kg/day)-1 through inhalation route only. The CPF is based on

several animal studies (Takenaka et al. 1983; Sanders and Mahaffey 1984).

Toxicokinetics

Cadmium compounds are poorly absorbed from the skin and intestinal tract

but are relatively well absorbed from the respiratory tract. Following ingestion or

inhalation, cadmium is distributed to most tissues of the body. Initially, highest

levels are found in the liver. Later, relocation occurs and highest concentrations

appear in the renal cortex (ATSDR 1992). In a study exposing rats daily to

cadmium fumes, the distribution of Cd in the tissue was kidney > lung > liver >

spleen > aorta > blood (ATSDR 1992). Blood levels in the exposed animals were

no different from those of unexposed animals. Similar distributions were found

using guinea pigs and monkeys.

Following oral administration, 1 to 5 percent of the dose is absorbed.

Variations in absorption are induced by many factors such as age, dietary

calcium, and dietary protein levels. Excretion occurs primarily via the kidney at

a very slow rate. The biological half-life of cadmium is estimated to be on the

order of decades in humans (ATSDR 1992).

D22

Appendix D Toxicological Profiles