Effect of a metal mixture in diet on the toxicokinetics and toxicity of cadmium, mercury and manganese in rats.

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.

Age and intestinal retention of mercury and cadmium in rats.

The site of cadmium and mercury retention in the intestine was determined in 6-day-old sucklings and 6-week-old weaned rats 6 days after oral administration of 115mCd and 203Hg. The ileum was found to be the main site of intestinal retention of both cations in sucklings but not in weaned rats. Other age- and element-specific differences in the site of metal retention in the intestine were also found. These differences indicate that even in neonates, metal absorption might be a more specific process than previously assumed.

The effect of chemotherapy for mixed fission products on the toxicokinetics of cadmium and mercury in rats.

The mixture of calcium alginate, ferrihexacyanoferrate(II) and potassium iodide, which efficiently decreases fission product retention, had no influence on 115mCd toxicokinetics in rats. This mixture, however, caused increased whole body retention of 203Hg after oral administration. It is assumed that iodine in the mixture might be responsible for this effect.

Chronic and reproduction studies in rats exposed to gasifier ash leachates.

Ash from the coal gasification process contains a broad spectrum of elements which through leaching (gasifier ash leachates) may enter into the environment. The health effect of such leachates i.e. complex mixtures of inorganic elements is insufficiently known. We investigated the effect of gasifier ash leachates in a chronic-(9-month) and in a three-generation reproduction study. The leachates were prepared weekly by water extraction of ash from a Lurgi coal gasification plant in Yugoslavia, and given to experimental animals instead of drinking water. In the chronic experiment exposed animals showed no changes in mortality rate, haematological findings, concentration of Fe, Zn, Mn in kidneys, liver, testicles and femur, as well as in femur composition and morphometry, gross pathology and organ histology. In the reproduction study the number of pregnancies, weight and number of newborns, and concentration of Fe, Zn, Mn in carcasses of sucklings were the same in control and experimental animals.

Simultaneous reduction of radioactive strontium, caesium and iodine retention by single treatment in rats.

The effect of a mixture of calcium alginate, iron (III) ferrocyanide and potassium iodide added to rat diet on 85Sr, 137Cs and 131I metabolism and health was investigated in female rats after four weeks of treatment. The retention of these radioisotopes was determined in the whole body and critical organs six days after 85 Sr and 137CS and one day after 131I oral administration. The health effect of the mixture was evaluated by measuring body weights, haematological parameters, concentrations of iron, zinc and manganese in the kidneys, liver and femur, bone parameters (femur composition and morphometry) and by a histopathological examination. The mixture reduced 85Sr retention in the femur 11 times, 137Cs retention in the thigh muscle 102 times and 131I retention in the thyroid 134 times. Treated animals were in good health and the only differences found between the control and experimental rats were slightly lower haemoglobin values in the blood and a slightly lower iron concentration in the liver. It is concluded that the mixture was very efficient for decreasing body retention of three important fission products and that it can be used over long periods without causing adverse health effects.

Bioavailability of cadmium in rats fed various diets.

Six-week-old female albino rats were fed rat diet or human foods: meat, bread or milk--3 days before and 6 days after a single oral dose of 115m Cd. All animals were killed 6 days after administration and the radioactivity in the whole body and in the gut-free carcass were determined in a double scintillation counter. Gut retentions were calculated as the difference: whole body minus carcass. All animals fed meat, bread or milk had much higher body retentions than animals fed rat diet (whole body 4-5 times, carcass about 3 times and gut 10-14 times). Our results point out the importance of nutritional factors in metal metabolism and toxicity.

Chronic studies in rats exposed to liquid effluent from coal gasification process.

The health effects of the E-effluent (water for quenching ash) from a coal gasification plant were assayed in a chronic experiment (16 month exposure) and a three generation reproduction study. Animals exposed to 100% E-effluent had an increased daily intake of various inorganic elements (Fe, Cu, K, I, Se, Cd, Hg, Pb, As, F and Cr). In spite of that, the exposed and control animals had the same mortality rate, haematological findings, urinary protein excretion, trace element concentrations in kidneys, liver and femur, bone composition and morphometry, and histological findings. The pre- and post-natal development and growth was unchanged during three generations. It is concluded that the higher intake of various inorganics caused no change in the parameters measured.

More data on mercury absorption in relation to dietary treatment in rats.

The kinetics of mercury (Hg) absorption in relation to diet by determining whole body (WB), carcass (C) and gut (G) retention in control and milk-fed rats 6, 9, 12 and 15 days after oral administration of 203Hg have been studied. All retention values were higher in the milk-fed than in control rats during the experimental period. The higher WB retention in the milk-fed animals was primarily due to increased G retention especially at shorter time intervals. Animals on the milk diet had in the C, higher retention values, and in the G, higher retention and longer residence time. There was no evidence that Hg from the gut compartment entered into other parts of the body within the observation period. More evidence is needed about the effect of other dietary treatments on Hg metabolism.

Toxicologic studies of emissions from coal gasification process. I. Subchronic feeding studies.

The increasing use of new sources of energy may result in additional contamination of the human environment with inorganic and organic pollutants which are not yet adequately investigated with regard to their potential impact on human health. However, some evidence exists that several trace inorganic and organic contaminants found in coal processing residues may constitute potential health problems. Therefore, the comparative biological hazards of solid wastes and effluents from a Lurgi coal gasification plant were initially evaluated using acute and chronic feeding experiments in male and female rats. In the subchronic experiment, six-week old animals were fed diets wih various levels of ash (slag) additive (0.5%, 1%, and 5%) for period of 16 weeks. Following exposure, blood samples were taken and 22-hour urine samples were collected. Livers and kidneys, and testicles in males, were taken for trace element analysis or histologic examination. The urinary values, erythrocyte and leucocyte count, hemoglobin, packed cell volume, and concentration of trace elements in exposed animals were determined. The addition of ash (slag) to the diet in concentrations much higher than expected in conditions of environmental contamination had no measurable health effects. Although these initial results obtained in relatively short-term experiments cannot be directly extrapolated to human health effects, particularly not for carcinogenic assessment, there is an indication that exposure to solid wastes from the coal gasification plant may not be toxic.

Effect of milk on mercury absorption and gut retention in rats.

The retention of 203Hg was studied six days after a single oral or intraperitoneal administration to six week old female albino rats fed rat's diet or milk. After oral administration rats on milk diet had a two times higher retention of mercury in the gut-free carcass and a 23 times higher retention in the gut than animals on rat's diet. Changes in diet had very little influence on mercury retention after intraperitoneal administration. The higher gut and carcass rentions of mercury in animals on milk diet could be prevented or reduced by transferring rats from milk diet to rat's diet several days after an oral dose of mercury. These results might be relevant for interpreting high gut and carcass retention after oral administration of some metals in suckling and changes which occur at weaning.

Influence of some factors on cadmium pharmacokinetics and toxicity.

Cadmium metabolism in the young and in conditions of dietary contamination with ash from coal gasification were investigated. The experiments were performed in adult rats which received ash in the diet (5%) and/or cadmium in drinking water (100 ppm) over a period of five weeks and in sucklings whose mothers were given the same treatment throughout pregnancy and lactation. In pharmacokinetic studies, (115m)Cd was administered orally or intraperitoneally to determine the intestinal absorption, retention, and distribution. Cadmium toxicity (LD(50)) was determined in different age groups of animals treated with ash for five weeks before a single oral or intraperitoneal administration of cadmium chloride. After intraperitoneal administration, (115m)Cd body retention decreased with age and was independent of the dietary treatment. Sucklings had a higher retention in the blood, carcass, and gut than adults. After oral administration, sucklings had a much higher body retention than adults regardless of the dietary treatment of their mothers. Cadmium toxicity was also independent of the dietary treatment. Most striking was a very high oral toxicity of cadmium in sucklings. It is concluded that the young might be at a special risk at the same level of environmental cadmium exposure because of the high oral cadmium toxicity at this age which is most probably due to a high cadmium retention in the gut. It is also concluded that the mixture of elements contained in ash is not likely to influence cadmium metabolism and toxicity in conditions of dietary exposure.

Influence of age on metal metabolism and toxicity.

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, 115mCd, 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.