Johanna Sundberg

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.

Protein binding of mercury in milk and plasma from mice and man : a comparison between methylmercury and inorganic mercury

Inorganic mercury has previously been shown to be excreted to milk from plasma to a higher extent than methylmercury. Protein binding of mercury as methylmercury and inorganic mercury in whey and plasma from mouse and man was studied in order to get a better understanding of the transport of mercury into milk. Mice were administered a single i.v. dose of 0.25 mg Hg/kg body weight labelled with (CH3)203HgCl or 203HgCl2, resulting in 11 ng Hg/g milk and 38 ng Hg/g milk after 1 h, respectively. Milk and plasma from mice and man were also incubated with the respective radiolabelled compound (150 ng Hg/g milk or plasma). Casein, fat and whey fractions in milk from methylmercury treated mice were found to contain 11, 39 and 34%, respectively, and from inorganic mercury treated mice 31, 15 and 41%, respectively, of the total amount of mercury in milk. Serum albumin was a major mercury binding protein in whey and plasma from mice for both methylmercury and inorganic mercury, as demonstrated by FPLC gel filtration and anion-exchange chromatography and further characterised by SDS-PAGE for whey. In addition, anion-exchange chromatography indicated that inorganic mercury, but not methylmercury, in whey from mouse milk formed a dimer of serum albumin. The unbound fraction of mercury in whey and plasma from mice was very small (<0.7%), and somewhat higher in plasma and whey from man. It is concluded, that the unbound fraction in plasma cannot be a determining factor for the observed differences in milk excretion between the two mercury compounds. Instead, it is suggested that methylmercury and to some extent inorganic mercury are transferred from plasma into milk using albumin as a passive carrier.

Lead poisoning in cattle — transfer of lead to milk

The transfer of lead to milk in cattle in relation to blood lead levels and the uptake of lead in edible tissues was studied for an accidental exposure over 1 or 2 days to lead in excessive amounts from the licking of burnt storage batteries. The degree of exposure was monitored by determination of blood lead levels. Milk and blood samples were taken from eight cows, without acute symptoms of lead poisoning, during a period of 18 weeks. Two weeks after the accidental exposure, lead levels (mean +/- SD) in milk were 0.08 +/- 0.04 mg kg-1 and in blood 0.36 +/- 0.04 mg kg-1 in six of the cows. The relationship between lead concentration in blood and those in milk was found to be exponential and could be expressed by the equation: log y = 3.19x - 2.36 (r = 0.85, p less than 0.001), where y and x are the lead concentrations in milk and blood, respectively. The lead level in milk was relatively constant up to a blood lead level of 0.2-0.3 mg kg-1, and increased sharply at higher blood levels. The biological half-life of lead in blood was shown to be approximately 9 weeks. In eight acutely sick cows, which were emergency slaughtered, the range of lead levels in edible muscle tissue was 0.23-0.50 mg kg-1 wet weight. Very high concentrations were found in the kidneys, with a range of 70-330 mg kg-1, and in the livers, with a range of 10-55 mg kg-1. Four of the cows were pregnant, in the first or second month of gestation, during the episode of exposure. The lead exposure was not found to disturb the gestation or development of the fetuses.

Methyl mercury exposure via placenta and milk impairs natural killer (NK) cell function in newborn rats

The effect of methyl mercury (MeHg) exposure (3.9 micrograms/g diet) on the development of immune function was studied in the newborn Sprague-Dawley rat after MeHg exposure via placenta and/or milk. No consistent alterations were observed between control and treated offspring (at the age of 15 days) on the following parameters: body weights, lymphoid organ weights or cell number, and the lymphoproliferative response to B-cell mitogen. The lymphoproliferative response to T-cell mitogen was increased in thymocytes (by 30-48%), but decreased in splenocytes (by 30-32%). This decreased activity was only observed in the groups exposed during lactation. White blood cell counts (WBC) were increased in all groups. Natural killer (NK) cell activity was reduced (by 42%, P less than 0.01) in the group that was exposed both via placenta and milk. These results indicate that placental and lactational transfer of MeHg does adversely affect the developing immune system of the rat.

Immunomodulating effects after perinatal exposure to methylmercury in mice.

The influence of methylmercury on the developing immune system was studied in offspring from Balb/c mice exposed to 0, 0.5 or 5 mg Hg/kg as methylmercury in the diet. Dams were exposed for 10 weeks prior to mating, during gestation and lactation. Pups were exposed to mercury until day 15 of lactation, thereafter the pups were given control milk and control diet. Samples for mercury analysis were collected from the pups on days 22 and 50, and for immunological studies on days 10, 22 and 50. The exposure resulted in significantly increased total Hg concentrations in whole blood on day 22 and 50 in offspring from the 5 mg Hg/kg group, and in offspring from the 0.5 mg Hg/kg group on day 22. On day 50, blood mercury levels had decreased to background levels in the 0.5 mg Hg/kg group. Increased numbers of splenocytes and thymocytes were found in offspring from the 0.5 mg Hg/kg group. Flow cytometry analysis of thymocytes revealed increased numbers and altered proportions of lymphocyte subpopulations within the thymus in offspring from both of the exposed groups. The proliferative response of splenocytes to the B-cell mitogen LPS was increased in offspring from dams exposed to 5 mg Hg/kg, and the primary antibody response to a viral antigen was stimulated in pups from dams exposed to 0.5 mg Hg/kg. The present results indicate that placental and lactational transfer of mercury affects thymocyte development and stimulates certain mitogen- or antigen-induced lymphocyte activities in mice.

Methylmercury exposure during lactation: Milk concentration and tissue uptake of mercury in the neonatal rat

In recent years toxicological interest in mercury has predominantly been focused on the effects of prenatal exposure to methylmercury on the physical and mental development of children. Thus, there has been a general concern to limit the exposure of pregnant women to methylmercury. Much less attention has been paid to postnatal exposure to mercury. However, there is also a possibility of elevated mercury exposure in the newborn due to exposure via breast milk. There is a lack of data from both humans and animals on lactational transfer of many metals. However, metabolic evidence suggests that during the neonatal period the infant is sensitive to effects of these compounds. Thus, the gastrointestinal absorption and the retention of metals is higher during this period than adult life. In the present study the dose-dependent transfer of mercury into milk was studied in lactating rats treated with methyl-mercury. The uptake of mercury in tissues and blood was followed in the offspring exposed via milk.

Effects of long-term treatment with methyl mercury on the developing rat brain

Sprague-Dawley rats were exposed to low doses of methyl mercury (3.9 mg mercury/kg diet), via their dams during gestation and lactation and directly via their diet until sacrifice at 50 days postpartum, in order to study possible detrimental effects on CNS development. The methyl mercury exposure of the rats resulted in a brain concentration of 1.45 +/- 0.06 mg mercury/kg wet weight (mean +/- SEM). No general toxic effects were observed; body weight was not affected, brain weight was only slightly increased. No discernible general morphological alterations were seen in the brain as evaluated using cresyl violet histology. Furthermore, no effects on GFA-positive astrocytes in brain sections were observed and computerized morphometry of smeared astrocytes from frontal cortex, hippocampus, and cerebellum did not reveal any effects of the methyl mercury treatment. The noradrenaline (NA) and dopamine (DA) systems were also studied. In cerebellum the NA levels were increased (117% of controls, P = 0.008), whereas in other regions analyzed NA and DA levels were unchanged. Thus, long-term low-dosage exposure of methyl mercury in rats during development does not appear to exert any major effects on the morphological maturation of neurons and astrocytes. However, the results indicate that effects may occur in specific transmitter-identified systems, such as the NA input to cerebellum. The results therefore underline the need for detailed biochemical analyses to study the effects of long-term low-dosage exposure to neurotoxic compounds.

Milk transfer of inorganic mercury to suckling rats : interaction with selenite

The transport of mercury into rat milk, and uptake in the suckling offspring was studied after peroral administration of inorganic mercury to lactating control rats, and to rats fed selenite in the diet. On day 8, 9, 10, or 11 of lactation, dams were administered a single oral dose of 0.1, 0.4, 0.7, 1.3, or 5.8 mg Hg/kg bw labeled with203mercuric acetate. There was a linear relationship between mercury concentrations in dams plasma and milk. The level of mercury in milk was approximately 25% of the level in plasma. After 3 d, milk levels were reduced to half the levels at 24 h. In the suckling off-spring, exposed to mercury via milk during 3 d, the mercury level in blood was approximately 1% of the level in maternal blood. Mercury concentration in milk was linearly correlated to the levels in kidney, liver, and brain in the suckling offspring after 3 d exposure to mercury via milk. Selenite treatment of rats, 1.3 μg Se/g diet for 5 mo, resulted in increased transport of mercury to milk, probably because of increased plasma levels of mercury. However, selenite treatment of the dams did not cause any increased tissue levels of mercury in the suckling offspring.