The metabolism and toxicity of lead, cadmium, mercury, and manganese in the postnatal period was studied in rats. Absorption, whole body retention, and organ distribution of 203Pb, "1115Cd, 203Hg, and 54Mn were determined after oral and parenteral administration of these radioisotopes. The acute oral toxicity (LD50) was determined after a single application of metal chlorides. The results obtained in sucklings show a very high intestinal absorption of all metals which is partly attributed to milk diet; a higher whole body retention, higher blood levels and a much higher accumulation in the brain; and a higher oral toxicity.These results indicate age specific differences in the pharmacokinetics of metals in sucklings. It seems reasonable to consider the early neonatal age as a critical period for metal accumulation and therefore for metal toxicity.The results are interpreted on the basis of current concepts of developmental physiology and pharmacology and suggestions for future research trends are made.All environmental chemicals which enter into the biological cycle have the potential of entering into the human body at all stages of its development. Metals represent a group of special concern, since the concentration of some toxic metals in the environment has already reached levels which might be harmful especially if combined with other factors which increase the metals' absorption, retention and toxicity. The question is raised whether the young, from birth and onward, might be more sensitive to toxic metals in the environment than are adults. A conclusive answer is difficult to give since for ethical reasons most of the data available at present have been obtained on animals. Moreover, many stages in the mammalian development cycle can be considered as "critical" in themselves, so that to assess the possible effects of an exposure in terms of the chemical form, dose, or route of administration of a metal is extremely difficult. A new field of developmental toxicology will have to be established in order to elucidate critical biochemical processes in the immature organism that might be responsible for differences in the metabolism and August 1978 toxicity of metals in these members of the population as compared to adults.The transfer of metals from mother to embryo and fetus and the gametotoxic, embryotoxic and fetotoxic properties of lead, cadmium, and mercury have been adequately reviewed in publications from earlier meetings of the Scientific Committee on the Toxicology of Metals (1-3). It is, however, astonishing how little information is available on the pharmacokinetics and effects of metals during the immediate postnatal period. This period, in which rapid changes in organ function and development occur and in which milk is the only nutritional source, has been neglected from the standpoints of both pharmacology (4) and environmental toxicology. The realization that exposure to toxic metals during the early neonatal period might cause irreversible behavioral (5, 6) and other changes seems at least to b...

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The purpose of this work was to determine whether a metal mixture added to diet influences the toxicokinetics and toxicity of some elements. The metal mixture (MM) used in these experiments was ash (slag) from a coal gasification plant. The effect of this mixture (5 percent in diet) on the toxicokinetic and on the acute or subchronic toxicity of Cd, Hg, Mn was determined in rats of different ages. Rats were exposed for five weeks in toxicokinetic and six weeks in acute toxicity experiments. Sucklings were exposed through their mothers, which received the MM in diet over the pregnancy and lactation period. In toxicokinetic studies, half of the animals additionally received Cd, Hg or Mn (100, 50 or 2000 ppm, respectively) in drinking water. In subchronic experiments, six-week-old albino rats of both sexes were given MM in the diet and Cd, Hg or Mn in drinking water for 16 weeks. In toxicokinetic studies, 115mCd, 203Hg or 54Mn were administered orally or intraperitoneally to mothers and pups. Exposure to MM had no effect on the absorption, retention and organ distribution of these elements determined six days after radioisotope administration. In acute toxicity studies, exposure to MM in diet had no effect on LD50 values obtained eight days after oral administration of Cd, Hg or Mn to rats of different ages. In subchronic experiments, the effect of individual metals (Cd, Hg or Mn) was similar in animals with and without simultaneous exposure to the metal mixture (only a slight potentiation of a few health-effect parameters of cadmium was noticed in some animals). It is concluded that oral exposure to MM in the diet had almost no effect on the toxicokinetics and toxicity of Cd, Hg and Mn. This could be explained by the low level or low bioavailability of elements from MM, by the metal-metal interaction within the mixture or by the choice of health effect indicators determined. These results are presented as one of the potential approaches for studying the health effect of a metal mixture as occurring in the environment.