Epsilon Open Archive

Abstract

This thesis comprises studies on the transfer of cadmium (Cd) from the lactating dam to the suckling and CNS effects of Cd during development, using rodents as a model. The purpose has been to conduct low–level exposure studies relevant for risk assessment of Cd. Cadmium is recognised as a toxic environmental contaminant with renal dysfunction considered as the critical effect after long-term exposure. For the non-smoking, non-occupationally exposed population, food, especially of vegetable origin, is the main source of cadmium exposure. Cd concentration in suckling pup kidney was strongly correlated with Cd in milk and kidney of the Cd exposed lactating rats, showing that cadmium is transferred to the pup via milk and absorbed in the suckling. This indicates that Cd in kidney can be used as a biomarker of the Cd dose in pups. A prominent uptake and retention of Cd was demonstrated in the mammary tissue, where Cd binding to metallothionein was indicated. Cd in milk was present mainly in the fat and casein fractions with a smaller part in the whey fraction. The serotonergic system in the developing brain was found to be susceptible to Cd. Hippocampal and cortical levels of serotonin and its metabolite, 5-hydroxyindoleacetic acid, were markedly reduced in animals exposed via milk. The exposure did not cause any detectable levels of Cd in the brain. A positive linear correlation was revealed between spontaneous locomotor activity and kidney cadmium concentrations in pups exposed via milk. There were no effects on learning, memory or anxiety due to treatment. Effects on the fatty acid composition after Cd exposure were found in the liver and milk of the dams, and a minor modification was detected in the brain of the pups. The long-chain polyunsaturated fatty acids, which are important for normal development of the CNS, were unaltered, as were zinc levels in the brain. Probably, the observed CNS effects are due to a direct effect of very low levels of Cd in the developing brain. The results indicate that neurochemical and neurobehavioral effects during development may be a more sensitive endpoint for cadmium toxicity than renal dysfunction.