Abstract
In rats of the present (re-derived) Wistar-Porton strain that are dosed either intravenously (i.v.), or intraperitoneally (i.p.) with Cd (1.25 mg/kg body weight) on day 12 of gestation (gd 12), foetal uptake of Cd is at least 6-fold greater than that reported in an earlier study (Webb and Samarawickrama 1981). Higher doses (1.5 and 2.0 mg/kg body weight) are lethal to the maternal animal when administered i. v., but not if given ip. The foetotoxicity of i.p. injected Cd, however, increases with the dose over the range 1.25–2.0 mg Cd/kg body weight. The teratogenic response, which is also wider than that observed previously, is maximal after the injection of 1.25 mg Cd/kg body weight i.v. on gd 10 and i.p. on gd 12. Whilst the incidences of hydrocephalus, urogenital abnormalities, cleft palate and other less common defects are similar after dosing by both routes, the incidence, range and severity of skeletal malformations are greater after i. p. than after i.v. administration of Cd on gd 12. This difference in response is unlikely to be explained by a difference in either foetal, or placental uptake of the metallic ion since, at 4 h after i.p. dosing, the foetal concentration of Cd is not significantly different from that after i.v. injection, whilst the placental concentration is about 33% less. It is suggested that damage to the maternal liver, which is more severe after the i.v. injection of the optimum dose, may be an additional factor that, in conjunction with the inhibition of transport in the placenta and biosynthetic processes in the embryo/foetus, contributes to the teratogenic effects of Cd in the pregnant rat.
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References
Barr M (1973) The teratogenicity of cadmium chloride in two stocks of Wistar rats. Teratology 7: 237–242
Christley J, Webster WS (1983) Cadmium uptake and distribution in mouse embryos following maternal exposure during the organogenic period: a scintillation and autoradiographic study. Teratology 27: 305–312
Danielsson BRG, Dencker L (1984) Effect of cadmium on the placental uptake and transport to the fetus of nutrients. Biol Res Pregnancy 5: 93–101
Dencker L (1975) Possible mechanisms of cadmium fetotoxicity in golden hamsters and mice: uptake by the embryo, placenta and ovary. J Reprod Fertil 44: 461–471
Dudley RE, Svoboda DJ, Klaassen CD (1982) Acute exposure to cadmium causes severe liver injury in rats. Toxicol Appl Pharmacol 65: 303–313
Ferm VH (1971) Developmental malformations induced by cadmium. A study of timed injections during embryogenesis. Biol Neonate 19: 101–107
Ferm VH, Carpenter SJ (1967) Teratogenic effect of cadmium and its inhibition by zinc. Nature 216: 1123
Ferm VH, Hanlon DP, Urban J (1969) The permeability of the hamster placenta to radioactive cadmium. J Embryol Exp Morphol 22: 107–113
Feuston MH, Scott WJ (1985) Cadmium-induced forelimb ectrodactyly: A proposed mechanism of teratogeneses. Teratology 32: 407–419
Holt D, Webb M (1986a) Comparison of some biochemical effects of teratogenic dose of mercuric mercury and cadmium in the pregnant rat. Arch Toxicol 58: 249–254
Holt D, Webb M (1986b) The toxicity and teratogenicity of mercuric mercury in the pregnant rat. Arch Toxicol 58: 243–248
Ishizu S, Minami M, Suzuki A, Yamada M, Sato M, Yamamura K (1973) An experimental study on the teratogenic effect of cadmium. Ind Health 11: 127–139
Khera KS (1985) Maternal toxicity: A possible etiological factor in embryo-fetal deaths and fetal malformations in rodent-rabbit species. Teratology 31: 129–153
Klein NW, Vogler MA, Chatot CL, Pierro LJ (1980) The use of cultured rat embryos to evaluate the teratogenic activity of serum: cadmium and cyclophosphamide. Teratology 21: 199–208
Layton WM, Layton MW (1979) Cadmium induced limb defects in mice: Strain associated differences in sensitivity. Teratology 19: 229–236
Levin AA, Miller RK (1980) Fetal toxicity of cadmium in the rat: Maternal vs fetal injections. Teratology 22: 1–5
Messerle K, Webster WS (1980) Teratogenic and cellular effects of cadmium on the embryonic mouse. J Anat 130: 212–213
Messerle K, Webster WS (1982) The classification and development of cadmium-induced limb defects in mice. Teratology 25: 61–70
Record IR, Dreosti IE, Manuel SJ (1982a) Inhibition of rat yolk sac pinocytoisis by cadmium and its reversal by zinc. J Nutr 112: 1194–1998
Record IR, Dreosti IE, Manuel SJ, Buckley RA (1982b) Interactions of cadmium and zinc in cultured rat embryos. Life Sci 31: 2735–2743
Samarawickrama GP (1979) Biological effects of cadmium in mammals. In: Webb M (ed) The chemistry, biochemistry and biology of cadmium. Elsevier/North Holland, Amsterdam, pp 341–421
Samarawickrama GP, Webb M (1979) Acute effects of cadmium on the pregnant rat and embryo-fetal development. Environ Health Perspect 28: 245–249
Samarawickrama GP, Webb M (1981) The acute toxicity and teratogenicity of cadmium in the pregnant rat. J Appl Toxicol 1: 264–269
Sonawane BR, Nordberg M, Nordberg GF, Lucier GW (1975) Placental transfer of cadmium in rats: Influence of dose and gestational age. Environ Health Perspect 12: 97–102
Warner CW, Sadler TW, Tulis SA, Smith MK (1984) Zinc amelioration of cadmium-induced teratogenesis in vitro. Teratology 30: 47–53
Webb M, Samarawickrama GP (1981) Placental transport and embryonic utilization of essential metabolites in the rat at the teratogenic dose of cadmium. J Appl Toxicol 1: 270–277
Webb M, Verschoyle RD (1976) An investigation of the role of metallothioneins in protection against the acute toxicity of the cadmium ion. Biochem Pharmacol 25: 673–679
Webster WS, Messerle K (1980) Changes in the mouse neuroepithelium associated with cadmium-induced neural tube defects. Teratology 21: 79–88
Wolkowski RM (1974) Differential cadmium-induced embryotoxicity in two inbred mouse strains. I Analysis of inheritance of the response to cadmium and of the presence of cadmium in fetal and placental tissues. Teratology 10: 243–262
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Holt, D., Webb, M. Teratogenicity of ionic cadmium in the Wistar rat. Arch Toxicol 59, 443–447 (1987). https://doi.org/10.1007/BF00316212
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DOI: https://doi.org/10.1007/BF00316212