Ira Palminger Hallén

Total and Inorganic Mercury in Breast Milk and Blood in Relation to Fish Consumption and Amalgam Fillings in Lactating Women

Total mercury concentrations (mean +/- standard deviation) in breast milk, blood, and hair samples collected 6 wk after delivery from 30 women who lived in the north of Sweden were 0.6 +/- 0.4 ng/g (3.0 +/- 2.0 nmol/kg), 2.3 +/- 1.0 ng/g (11.5 +/- 5.0 nmol/kg), and 0.28 +/- 0.16 microg/g (1.40 +/- 0.80 micromol/kg), respectively. In milk, an average of 51% of total mercury was in the form of inorganic mercury, whereas in blood an average of only 26% was present in the inorganic form. Total and inorganic mercury levels in blood (r = .55, p = .003; and r = .46, p = .01 6; respectively) and milk (r = .47, p = .01; and r = .45, p = .018; respectively) were correlated with the number of amalgam fillings. The concentrations of total mercury and organic mercury (calculated by subtraction of inorganic mercury from total mercury) in blood (r = .59, p = .0006, and r = .56, p = .001; respectively) and total mercury in hair (r = .52, p = .006) were correlated with the estimated recent exposure to methylmercury via intake of fish. There was no significant between the milk levels of mercury in any chemical form and the estimated methylmercury intake. A significant correlation was found between levels of total mercury in blood and in milk (r = .66, p = .0001), with milk levels being an average of 27% of the blood levels. There was an association between inorganic mercury in blood and milk (r = .96, p < .0001); the average level of inorganic mercury in milk was 55% of the level of inorganic mercury in blood. No significant correlations were found between the levels of any form of mercury in milk and the levels of organic mercury in blood. The results indicated that there was an efficient transfer of inorganic mercury from blood to milk and that, in this population, mercury from amalgam fillings was the main source of mercury in milk. Exposure of the infant to mercury from breast milk was calculated to range up to 0.3 microg/kg x d, of which approximately one-half was inorganic mercury. This exposure, however, corresponds to approximately one-half the tolerable daily intake for adults recommended by the World Health Organization. We concluded that efforts should be made to decrease mercury burden in fertile women.

Lead and cadmium levels in human milk and blood

Lead and cadmium levels were determined (with AAS) in blood and milk obtained at 6 weeks after delivery from women living in the vicinity of a copper and lead metal smelter and in a control area. Analysis of lead and cadmium were also performed in blood samples obtained at delivery. Accuracy of the analysis was confirmed by the analysis of quality control samples. In general, blood and milk levels of lead and cadmium were low in both areas. At 6 weeks after delivery the lead levels in blood and milk were 32 +/- 8 and 0.7 +/- 0.4 micrograms Pb/l, respectively (total mean +/- S.D., n = 75). Cadmium levels in blood and milk were 0.9 +/- 0.3 and 0.06 +/- 0.04 microgram Cd/l, respectively (n = 75). At delivery the lead levels in blood of women in the smelter area were higher, 38.7 micrograms Pb/l, than the blood lead levels in women from the control area, 32.3 micrograms Pb/l, (P < 0.001). At 6 weeks after delivery there was no difference in blood lead levels between the two groups. In contrast, the lead levels in milk were higher in women from the smelter area, 0.9 microgram Pb/l, than in women from the control area, 0.5 microgram Pb/l, (P < 0.001). No differences in blood cadmium levels were found between the two groups. Milk cadmium levels in women from the control area, 0.07 microgram Cd/l, were somewhat higher (P < 0.01) than in women from the smelter area, 0.05 microgram Cd/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Exposure to toxic elements via breast milk

Breast milk is the ideal nutrient for the newborn, but unfortunately also a route of excretion for some toxic substances. Very little attention has been paid to breast milk as a source of exposure to toxic elements. The dose-dependent excretion is breast milk and the uptake in the neonate of inorganic mercury, methylmercury and lead were studied in an experimental model for rats and mice. The transfer of mercury from plasma to milk was found to be higher in dams exposed to inorganic mercury than to methylmercury. In contrast, the uptake of mercury from milk was higher in the sucklings of dams exposed to methylmercury than to inorganic mercury. Pre- and postnatal exposure to methylmercury resulted in increased numbers and altered proportions of the thymocyte subpopulation and increased lymphocyte activities in the offspring of mice and also effects on the levels of noradrenaline and nerve growth factor in the developing brain of rats. Mercury in blood and breast milk in lactating women in Sweden was studied in relation to the exposure to mercury from, fish and amalgam. Low levels were found; the mean levels were 0.6 ng g-1 in milk and 2.3 ng g-1 in blood. There was a statistically significant correlation between mercury levels in blood and milk, showing that milk levels were approximately 30% of the levels in blood. Inorganic mercury exposure from amalgam was reflected in blood and milk mercury levels. Recent exposure to methylmercury from consumption of fish was reflected in mercury levels in the blood but not in milk.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk assessment in relation to neonatal metal exposure

Rapid changes in organ development and function occur during the neonatal period. During this period the central nervous system is in a rapid growth rate and highly vulnerable to toxic effects of, e.g., lead and methylmercury. Furthermore, the kinetics of many metals is age-specific, with a higher gastrointestinal absorption, less effective renal excretion as well as a less effective blood-brain barrier in newborns compared to adults. Due to their low body weight and high food consumption per kg of body weight, the tissue levels of contaminants can reach higher levels in newborns than in adults. Generally, there is a low transfer of toxic metals through milk when maternal exposure levels are low. However, knowledge is limited about the lactational transport of metals and the potential effects of metals in the mammary gland on milk secretion and composition. There are some data from rodents on the lactational transfer and the uptake in the neonate of inorganic mercury, methylmercury, lead and cadmium. Metal levels in human breast milk and blood samples from different exposure situations can give information on the correlation between blood and milk levels. If such a relationship exists, milk levels can be used as an indicator of both maternal and neonatal exposure. Better understanding of the neonatal exposure, including kinetics in the lactating mother and in the newborn, and effects of toxic metals in different age groups is needed for the risk assessment. Interactions with nutritional factors and the great beneficial value of breast-feeding should also be considered.

Placental and lactational transfer of lead in rats: a study on the lactational process and effects on offspring.

The effects of placental and lactational exposure to lead (Pb) were studied in suckling rats after long-term exposure of their dams to Pb in drinking water. Dams were given 12 mM Pb-acetate in the drinking water 8 weeks prior to mating and during gestation. One group of dams was also continuously exposed during lactation until day 15. Neonates from Pb-treated dams were cross-fostered at birth to control dams treated with Na-acetate (12 mM) in the drinking water. In the same way, neonates from dams receiving control water were in the same way cross-fostered to Pb-exposed dams. All animals were killed at day 15 of lactation, when measurements were performed. Continuous Pb exposure during gestation and lactation resulted in milk Pb levels approximately 2.5 times higher than the blood Pb levels. When Pb exposure was terminated at parturition the milk Pb levels were at a level similar to those of blood Pb at day 15 of lactation, and only 10% of the milk levels found after continuous Pb exposure. Exposure to Pb via placenta and milk in offspring from dams exposed continuously resulted in more than 6 times higher blood and brain Pb levels than in offspring exposed only via the placenta. Exposure only via milk in offspring from dams exposed to Pb until parturition resulted in higher blood Pb levels than in offspring exposed to Pb only via the placenta. This indicates that the lactational transfer after current or recent exposure of Pb in dams is considerably higher than placental transfer. Offspring in all the exposed groups had decreased ALAD activity in the blood. An exponential relationship between blood Pb levels and ALAD activity was demonstrated in the offspring. Due to the exponential decrease in ALAD activity at increasing blood Pb levels, ALAD is particularly sensitive in reflecting differences in Pb exposure within the lowest range of blood Pb levels. There was a slight effect on weight gain in the offspring. However, there was no effect on milk quality, as measued by milk lipid, protein and calcium concentrations, nor on milk production assessed by the mammary gland RNA and DNA content. This indicates that the effect on weight gain was a direct effect of Pb in the offspring.

Placental and lactational transfer of ochratoxin A in rats

The placental and lactational transfer of ochratoxin A (OA) was investigated in a cross-fostering study in rats. Dams were given 50 microg OA(-1) kg body weight by gastric intubations 5 times a week for 2 weeks before mating, during gestation and then 7 days a week during lactation. Neonates from OA-treated dams were cross-fostered at birth to control dams treated with only vehicle. In the same way, neonates from control dams were cross-fostered to OA-treated dams. Treatment with OA did not result in any effects on birth weight or growth development of the pups during the first 21 days of life. There were no effects on milk quality as measured by milk lipids, protein or lactose concentrations, or on milk production, assessed by the mammary gland content of RNA and DNA. A mean milk:blood ratio of approximately 0.6 was found. The dose of OA from milk to the suckling pup at 14 days of age can be calculated to about 50 microg kg(-1) body weight(-1) day, which is similar to the dose given to the dams. Pups exposed to OA only via milk had blood and kidney levels of OA approximately 3 times higher than their dams, indicating a high absorption and/or a low excretion of OA in the sucklings. At 14 days of age the highest blood and kidney levels of OA were found in offspring exposed both via placenta and milk, with the highest contribution from milk. Offspring exposed only via milk had about 4-5 times higher levels of OA in blood and kidney compared to offspring exposed only via placenta. As milk could be a significant source of OA exposure in newborns, adverse health effects resulting from postnatal exposure should be studied and evaluated in the risk assessment of OA.

Effects of Ochratoxin A on the rat immune system after perinatal exposure

Effects on the immune system after perinatal exposure to ochratoxin A (OA) were studied in Sprague-Dawley rats after single or repeated exposure of the dams. In a short-term study, dams with litters were given a single dose of OA (0, 10, 50 or 250 micrograms/kg body weight) on day 11 of lactation. The effects on cell numbers in spleen and thymus añd on the mitogen responses of lymphocytes were evaluated in the suckling pups on day 14 of lactation. The proliferative response of splenocytes to the T-cell mitogen Concanavalin A (Con A) was significantly stimulated in pups from dams given 10 or 50 micrograms OA/kg body weight as compared to control pups. In addition, proliferation of thymocytes in response to Con A was stimulated in pups from dams exposed to 50 micrograms OA/kg body weight. In a long-term, cross-fostering study comparing pre- and postnatal exposure, half of the dams received 50 micrograms OA/kg body weight 5 days a week by gastric intubation 2 weeks before mating, during gestation and then 7 days a week until weaning. Effects on immune parameters were studied in the pups on day 14 of lactation and at 13 weeks of age. Suppressed mitogenic responses were seen to both lipopolysaccharide (LPS) and Con A in prenatally exposed pups sampled on day 14 of lactation. At 13 weeks the response of splenocytes to LPS was still impaired. The primary antibody response to a viral antigen was also lower in the prenatally exposed pups than in the control pups. These effects on the immune response were not seen in the groups of pups exposed postnatally or both pre- and postnatally, although blood concentrations of OA were higher in these groups at the time of the first sampling. This indicates that the decrease in proliferation and antibody production resulted from prenatal modulation of the immune system. The results show that prenatal exposure to relatively low doses of OA may induce immunosuppression. In contrast, short-term exposure of suckling pups to OA via the milk stimulates the proliferative responses of lymphocytes to polyclonal activation.

Bioavailability of lead from various milk diets studied in a suckling rat model

The bioavailability of lead from various milk diets was studied in 14 day old suckling rats. Human milk, infant formula, cows milk, rat milk and deionized water labeled with 203Pb were given to rat pups by gastric intubation. Animals were killed after 2 or 6 h and the radioactivity in the tissues was measured. At 2 h after administration the lead bioavailability, defined as lead uptake in the body, excluding the gastrointestinal tract, was 47% from water, 42% from human milk, 40% from infant formula, 31% from cows milk and 11% from rat milk. After 6 h the bioavailability of lead was about 50% from water and human milk, 45% from infant formula and cows milk, and 36% from rat milk. The blood lead levels in the pups reflected the total body uptake and were also correlated to the brain lead levels. Thus, rat pups given lead in human milk had approximately twice as high lead levels in blood and brain than pups given lead in rat milk. The intestinal absorption of lead was dependent on the milk diet given to the sucklings. In duodenum, the highest uptake of lead was found in rats given water or human milk, whereas in rats given rat or cows milk the highest uptake of lead was found in ileum. The distribution of lead in cream, whey and casein fractions of the milk diets after in vitro labeling with 203Pb was also studied. The casein fraction in cows and rat milk contained 90–96% of the total amount of lead in the diet. In infant formula and human milk, 77 and 56% lead was found in the casein fraction, respectively. The higher lead bioavailability observed in the suckling rat fed human milk than in those fed rat and cows milk may partly be explained by a lower proportion of lead bound to casein in human milk.

Distribution of lead in lactating mice and suckling offspring with special emphasis on the mammary gland

The distribution of lead in lactating mice and suckling offspring was studied with whole body autoradiography at 4 and 24 h after a single intravenous injection of 203Pb (50 nmol Pb/kg) to the dams. In the lactating mice on day 14 of lactation, the highest uptake of radioactivity at 4 h after administration was recorded in renal cortex, skeleton and liver. A high uptake was also evident in the mammary gland. At 24h after administration, the radioactivity had decreased in most organs except in the skeleton. In the suckling pups, exposed to lead only via dams’ milk for 24 h, the highest level of radioactivity was present in the intestinal mucosa and a much lower level of radioactivity was present in the skeleton. The mammary glands from mice given three daily intravenous injections of 240 μmol Pb/kg were examined with X-ray microanalysis. At 4 h after the last injection, lead was found associted with casein micelles both inside the alveolar cell and in the milk lumen, indicating that lead is excreted into the milk, bound to casein, via the Golgi secretory system.