The teratogenicity of cadmium chloride in two stocks of Wistar rats.

The teratogenicity of cadmium chloride (16 pM/kg Cd++) was studied in Wistar rats from two commercial sources. Subcutaneous cadmium was not teratogenic. Intraperitoneal cadmium was highly teratogenic in both stocks when given on day 9, 10, or 11 of gestation. There were marked differences between the two stocks in fetal mortality and the incidence and types of malformations produced. Cadmium on day 9 produced an attenuation of the abdominal wall in 13-16% of the term fetuses. In one stock of rats, cadmium on day 10 produced reduction deformities of one forelimb similar to the previously reported acetazolamide syndrome in rats. In recent years the presence of cadmium as an environmental contaminant has aroused concern because of its marked toxicity in man (Flick et al., '71). Both acute and chronic forms of cadmium poisoning have been reported in man but the role of cadmium in human teratogenesis remains unresolved. In mice orally administered cadmium salts produce fetal mortality, runting, and malformation (Schroeder and Mitchener, '71). Intravenous cadmium sulfate in hamsters produces malformation, particularly of the face (MulvihiU et al., '70). Preliminary studies in this laboratory have shown that intraperitoneal cadmium sulfate is teratogenic in rats (Barr, '72), but the spectrum of malformations is quite different from that reported in hamsters. Further investigation showed that both the incidence and variety of malformations caused by cadmium in rats depend a great deal on the particular stock of animals used. This study reports the teratogenic effects of cadmium chloride in two stocks of Wistar rats. MATERIALS AND METHODS Virgin female and male Wistar rats were purchased from two commercial sources and designated as the C and S stocks.2 The rats were maintained in one room with a controlled environment and allowed Rockland rat diet and tap water ad libitum. Nonpregnant females were housed TERATOLOGY, 7: 237-242. 4-6 per cage; pregnant females were caged individually. Males and females were bred in pairs overnight and the presence of sperm in a vaginal smear was assumed to indicate day 0 of pregnancy. The dose used in this study was 16 p iu / kg Cd++, as cadmium chloride, in 2.0 ml isotonic saline. Injections were given intraperitoneally (ip) and in some cases subcutaneously (sc). Controls received ip injections of isotonic saline. All injections were given at 8-9 AM on day 9, 10, or 11 of gestation. Six rats were bred successfully 14-31 days after receiving an ip dose of cadmium chloride. On day 21 of gestation pregnant rats were killed by ether overdose and the number and intrauterine positions of fetuses and resorption sites were noted. The fetuses were separated from their placentas, cleaned, and promptly weighed. After fixation in Bouin's fluid the fetuses were examined for malformation by the razor-blade dissection technique (Wilson, '65). In the statistical treatment of the data, means, errors, and rates were calculated from subgroup totals and from litter means. There was little difference between the results of the two methods of calculation and the results reported are those calculated from subgroup totals, ignoring Received Dec. 7, '72. Accepted Mar. 5, '73. 1 Supported by NIH grant 5-Sol-RR05383 to the Uni2 C stock from Carworth, New City, N. Y . , S stock versity of Michigan. 6.om Simonsen Laboratories, Gilroy, California.