Female CF1 mice were bred for 6 consecutive, 42-d rounds of gestation-lactation. Their purified diets contained cadmium added at either 0.25, 5.0, or 50.0 ppm Cd; at each cadmium level, the diets were either sufficient or deficient in certain vitamins, minerals, and fat. The deficient diet at 5 ppm cadmium was designed to simulate conditions implicated in the etiology of itai-itai disease among multiparous women in Japan. Fertility, litter size, pup survival, and pup growth (weaning weight) are reported for mice on the six diets during each of the six rounds of gestation/lactation. Except for fertility, decreases in reproductive measures that occurred in response to dietary deficiencies or cadmium during round 1 of reproduction were repeated, unchanged in magnitude, in each successive round. For sufficient diet groups, 50 ppm cadmium had no effect on fertility or pup survival during lactation, but caused a 15% decrease in litter size at birth and a 25% decrease in pup growth. Dietary deficiencies alone decreased all four measures of reproductive performance: fertility by 12%, litter size by 30%, pup survival by 18%, and pup growth by 42%. In addition, dietary deficiencies strikingly decreased the incidence of consecutive pregnancies. Combined effects of 50 ppm cadmium and dietary deficiencies were additive for all reproductive measures except fertility; for fertility, cadmium caused no decrease in the fertility of sufficient-diet animals, but caused a striking 45% decrease in deficient-diet animals. Relating our results to humans, women who contracted itai-itai disease (analogous to mice on the deficient, 5 ppm cadmium diet), in addition to their characteristic bone disease, could have experienced decreases in fertility and in growth of their offspring related to their dietary deficiencies. In addition, their diet-related decreases in fertility could have been enhanced by their combined exposure to cadmium.

A new approach to the estimation of plutonium (Pu) levels in the skeleton based on measurements of Pu excretion in the feces following treatment with diethylenetriaminepentaacetic acid (DTPA) is presented. The estimation method was tested in groups of mice receiving either 0.5 or 5 pCi/kg of *'*u(IV) citrate, and treated with Na3[CaDTPA] starting either at 1 hr or 24 hr after Pu administration. In the case of DTPA treatment begun at 1 hr, the ratio of skeletal Pu content at 1 hr, S, to DTPA-induced fecal excretion of Pu, F, was 1.08+0.03. When DTPA treatment was begun at 24 hr, the corresponding S/F ratio was 1.68 + 0.08 and was independent of Pu injection level. In the mouse, therefore, a reasonable estimate of skeletal Pu content just prior to treatment can be determined from the amount of Pu measured in the feces following DTPA therapy. Application of this method to species other than the mouse is examined, with anticipation that the method might be applicable to cases of human exposure.

Substantial adsorption of Pu, Cd and Pb onto mouth surfaces of mice occurs during consumption of drinking water that contains these elements. If this adsorption is not taken into account, the amounts deposited in the eviscerated carcass (muscle plus skeleton) after gastrointestinal absorption are overestimated by 2-9 times for the experiments described. An evaluation of data indicate that significant adsorption can also occur during gavage administration. Methods are described for estimation of amounts deposited in the carcass after exposure of mice to these metals via drinking water or gavage.