Agneta Oskarsson

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)

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.

Acid precipitation : effects on trace elements and human health

Environmental pollution by acid precipitation increases the solubilization and mobilization of toxic metals. Through the food chain, this may alter the intake of toxic and essential elements in man. Potential adverse health effects could follow after increased human exposure. For the general population, the exposure pattern and health effects caused by aluminium, cadmium, lead and mercury are of particular concern. Although there are several indications that the exposure to toxic elements (e.g. aluminium, cadmium, lead and methylmercury), as well as the intake of essential elements (e.g. selenium), may be affected by acid precipitation, there is presently no firm evidence of adverse health effects in man. However, the present data clearly indicate that the safety margins are small. Thus, the ongoing acidification in many areas must be stopped before such effects become evident. The effects on trace element status and human health by acid precipitation were discussed at the ISTERH (International Society for Trace Element Research in Humans) Conference in Stockholm, May, 1992. The main findings are briefly summarized here.

Influence of sodium selenite on 203Hg absorption, distribution, and elimination in male mice exposed to methyl203Hg.

To study the effects of long-term selenium supplementation on absorption, distribution, and elimination of methylmercury (MeHg) in mice, three groups of male mice (Balb/c CA) were exposed for 7 wk to 0, 0.6, and 3 ppm sodium selenite in tap water. They were then given a single oral dose of Me203Hg (2 μmol/kg) by gastric intubation, and elimination of203Hg was followed by whole-body counting for 49 d at the same Se exposure as previously. Twenty-four hours and 49 d after dosage, 6–7 animals/group were sampled for analysis of203Hg distribution in the body. Glutathione peroxidase (GSH-PX) activity in blood and selenium levels in the liver were used as measures of selenium status. Gastrointestinal absorption of Me203Hg was not influenced by the Se status of the animals. Selenium supplementation of MeHg-exposed mice caused an enhanced whole-body elimination of Hg, but selenium-supplemented animals did not have lower Hg levels in the brain and kidney than nonsupplemented animals. The effect of selenium on the accumulation, of Hg in the brain was dose-dependent, a high dose (3 ppm Se) causing a higher initial accumulation of Hg. The intracellular distribution of203Hg in the liver and kidney was not affected by Se. The results indicate that selenium treatment of MeHg-exposed mice may have a positive effection the health of the animals by decreasing the total body burden of MeHg.

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.

Mercury levels in the hair of pregnant women in a polluted area in Sweden.

Total mercury concentration in hair, sampled at delivery, was determined in women living in an area polluted with atmospheric emissions of mercury from a metal smelter, (n = 122) and in a control area (n = 75). Information on fish consumption was obtained at the 10th week of pregnancy. The average mercury concentration in hair was 0.27 mg/kg (range 0.07-0.96 mg/kg), which is somewhat lower than previously reported for pregnant women in Sweden and very low compared with levels in fish-eating populations in other parts of the world. Women living in the polluted area had significantly lower mercury levels in hair than women in the control area when comparing groups with quantitatively similar consumption of freshwater fish. Possibly, the population in the smelter area does not catch fish in the neighbourhood and/or the fish in the control area has elevated mercury levels. Consumption of freshwater fish > or = once a week resulted in approximately twice as high hair mercury levels as in those who did not eat freshwater fish at all. Also consumption of saltwater fish > or = once a week resulted in significantly higher hair mercury levels than in those consuming saltwater fish < once a month. Hair levels from the 10th week of pregnancy were similar to the levels at delivery in women with high (> or = once a week) consumption of freshwater fish but decreased during this period in women who did not eat freshwater fish at all, which could be explained by decreased exposure during pregnancy and measurement in recently formed hair.

Metal‐ and Metalloid‐Induced Porphyrinurias Relationships to Cell Injury

The value of correlating specific porphyrin excretion patterns with other data on cell and organelle functionality rests with providing better insight into the mechanism(s) of the porphyrinuria and delineating the biological significance of this phenomenon with regard to cell injury. The heme biosynthetic pathway enzymes 8-aminolevulinic acid synthetase (ALAS), coproporphyrinogen oxygenase, and ferrochelatase are localized in the mitochondrion,’-’ which also performs a number of other functions for the ce1L4 Furthermore, it is becoming increasingly clear that there is a close relationship between normal mitochondrial structure and biochemical functionality’ and that any physical perturbation of the mitochondria (such as osmotic swelling) will also disrupt essential processes (such as NAD-linked substrate oxidation).6 An example of the potential significance of this with respect to the heme biosynthetic pathway and the development of porphyrinurias concerns the dependence of ferrochelatase activity upon the reduction of ferric iron to ferrous iron by the mitochondrial electron transport chain during transport of this element across the membrane.’ Hence any disruption of mitochondrial respiration and the attendant flow of electrons will also influence the activity of this enzyme and perhaps the other mitochondrial enzymes with subsequent development of coproporphyrinuria. Similar arguments concerning the importance of organelle structure to biochemical function have also recently been madesv9 with regard to putative relationships between the metal-induced disruption of the structure of endoplasmic reticulum and the induction of microsomal heme oxygenase, the rate-limiting enzyme in the heme degradation pathway. The main point here is that there are abundant basic data from a number of laboratories that confirm a close set of interdependent relationships between the structure of organelles and the processes localized in organelles (such processes include mitochondrial respiration, microsomal drug metabolism, and the biosynthesis of heme). The following review will attempt to examine the effects of specific metals and metalloids on enzymes in the heme biosynthetic pathway in relation to perturbations in

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.