Chronic effects on single and multiple oral and subcutaneous cadmium administrations on the testes of Wistar rats

Thirty mature male Wistar rats were administered cadmium as CdCl2 X 1H2O in single doses of 50 mg/kg p.o. or 2.5 mg/kg i.p. or 10 weekly doses of 5 mg/kg p.o. or 0.25 mg/kg i.p., respectively. Ten males, each treated correspondingly with the vehicle, served as control groups. Some of the animals were necropsied after 12 and 18 months, respectively, the remainder were kept for up to 30 months. In a supplementary study 25 males were each treated once with 200 mg/kg p.o. or 2 mg/kg s.c. and 35 males with 100 mg/kg p.o. This experiment was terminated after 6 months. Animals having received 1 X 100 or 1 X 200 mg/kg p.o. or 1 X 2.0 or 1 X 2.5 mg/kg s.c. showed severe lesions of the whole testicular parenchyma with massive calcification of the necrotic tubuli and pronounced fibrosis of the interstitium. All animals receiving 2.5 mg/kg s.c. had a Leydig cell tumor in at least one of the testes. In 5 out of 15 animals surviving 18 months these tumors were classified as malignant (mean time of induction: 858 +/- 77 days). All the other tumors detected were not regarded as causally related to treatment. The results of the supplementary study indicate that with very high oral cadmium dosages Leydig cell tumors may be induceable. Since the massive lesion of the testes appears to be the prerequisite for the occurrence of induced Leydig cell tumors, a non-genetic mechanism is to be assumed in respect to the formation of these tumors.