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M Vahter

Publications and source records attributed to M Vahter.

At least 19 recordsLinked to original sources
PubMed2000

Genetic polymorphism in the biotransformation of inorganic arsenic and its role in toxicity.

Arsenic is a recognized human carcinogen, but experimental cancer studies are negative. There is a variation in susceptibility among individuals, which probably is related to variation in metabolism. Inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are less toxic and more readily excreted in urine than the inorganic arsenic. The rate of methylation of arsenic varies considerably between species. Most population groups studied so far have on average 10-30% inorganic, 10-20% MMA, and 60-70% DMA in urine, but there is a considerable inter-individual variation. Also, recent studies have identified groups with unusually low or high urinary excretion of MMA. Thus, there seems to be a genetic polymorphism in the biomethylation of arsenic. However, the methyltransferases involved in arsenic methylation have not been characterized.

Animals↗
PubMed2000

Metal-bone interactions.

Recent studies indicate that lead and cadmium may exert both direct and indirect actions on bone turnover, indirectly via kidney dysfunction, and directly on osteoblast and osteoclast function. Increased blood lead concentrations, most likely as a result of an increased bone turnover, have been detected in pregnant, lactating, and menopausal women. Lead exposure has also been negatively associated with children's growth in stature. Both lead and cadmium are nephrotoxic and can disturb vitamin D metabolism. Cadmium has been shown to induce kidney damage and osteoporosis/osteomalacia at long-term high-level exposure. A negative association between cadmium dose and bone mass has recently been detected in both occupationally and environmentally exposed people at relatively low cadmium exposure.

Adult↗
PubMed2000

Longitudinal study of methylmercury and inorganic mercury in blood and urine of pregnant and lactating women, as well as in umbilical cord blood.

We have investigated exposure to methylmercury (MeHg) and mercury vapor (Hg0) in pregnant women and their newborns in Stockholm. The women were followed for 15 months post delivery. MeHg, inorganic Hg (I-Hg), and total Hg (T-Hg) in maternal and cord blood were determined by automated alkaline solubilization/reduction and cold vapor atomic fluorescence spectrometry. T-Hg in urine was determined by inductively coupled plasma mass spectrometry. About 72% of the Hg in blood (n = 148) in early pregnancy was MeHg (median 0.94 microg/L, maximum 6.8 microg/L). Blood MeHg decreased during pregnancy, partly due to decreased intake of fish in accordance with recommendations to not eat certain predatory fish during pregnancy. Cord blood MeHg (median 1.4 microg/L, maximum 4.8 microg/L) was almost twice that in maternal blood in late pregnancy and was probably influenced by maternal MeHg exposure earlier and before pregnancy. Blood I-Hg (median 0.37 microg/L, maximum 4.2 microg/L) and urine T-Hg (median 1.6 microg/L, maximum 12 microg/L) in early pregnancy were highly correlated, and both were associated with the number of amalgam fillings. The concentrations decreased during lactation, probably due to excretion in milk. Cord blood I-Hg was correlated with that in maternal blood. The results show the importance of speciation of Hg in blood for evaluation of exposure and health risks.

Adult↗
PubMed2000

Toxic and essential elements in placentas of Swedish women.

OBJECTIVES: To evaluate interactions between toxic and essential elements in the mother-fetus relationship and possible predictors of trace element concentrations in placenta and cord blood. DESIGN AND METHODS: A group of 106 Swedish women was investigated for concentrations of cadmium, lead, and several essential elements in placenta as well as cadmium, lead, zinc, and selenium in venous blood collected at gestational week (gw) 36 and umbilical cord blood. Relations between these elements and maternal and child's characteristics were examined. RESULTS: The concentrations of cadmium in placenta ranged from 10 to 170 nmol/kg, with the median value (Md) being 46 nmol/kg. Cord blood cadmium (Md of 0.19 nmol/L) was only about 10% of that in maternal blood. Smokers had significantly higher cadmium concentrations in blood (p < 0.001) and placenta (p = 0.001) than non-smokers. The median placental concentration of lead was 26 nmol/kg (range 0-630 nmol/kg). The lead levels in cord blood (Md of 54 nmol/L) were almost the same as in maternal blood. Statistically significant negative associations were found between cord blood lead, on one hand, and child's weight, length, and head circumference, on the other. The placental levels (medians and ranges) of the essential elements (micromol/kg) were 160 (120-280) for zinc, 2.4 (2.0-3.3) for selenium, 15 (10-20) for copper, 0.084 (0.02-0.32) for cobalt, 0.055 (0.03-0.12) for molybdenum, and 1.2 (0. 65-5.1) for manganese, respectively. Several of the essential elements in placenta correlated significantly with each other. Multiparous mothers had significantly lower concentrations of zinc (p = 0.002) and selenium (p = 0.049) in serum as well as zinc (p = 0. 001) and calcium (p = 0.004) in placenta than nulliparous ones. Also, cord blood zinc decreased with parity. CONCLUSIONS: The results showed that lead, but not cadmium crossed easily the placental barrier. There were no negative effects of cadmium on the zinc status. Cord blood lead, on the other hand, was a negative predictor of child's birth weight, length and head circumference, indicating that lead might have negative influence on growth in children even at very low exposure levels. There was a depletion of maternal stores of essential elements with increasing parity.

Cadmium↗
PubMed2000

Phlebotomy increases cadmium uptake in hemochromatosis.

The intestinal absorption of the nephrotoxic environmental pollutant cadmium increases markedly when iron stores are depleted. This may be mediated by an up regulation of the recently identified mucosal transporter DMT1 (Nramp2 or DCT1) for divalent cations. We tested whether the highly increased iron absorption in hereditary hemochromatosis (HH) was accompanied by an enhanced absorption of cadmium and lead. Cadmium and lead in blood and iron status markers were determined in 21 nonsmoking subjects with HH genetically tested for the HFE mutations and in 21 nonsmoking controls matched for age and sex. In subjects with HH on maintenance phlebotomy treatment, blood concentrations of cadmium, but not lead, were significantly higher than in paired controls. There was a strong age-independent positive association between blood cadmium and the number of years of phlebotomy treatment. Blood lead showed a similar but less pronounced consequence of treatment. All HH subjects with lower blood cadmium than the corresponding controls had either no mutation in the HFE gene, were not phlebotomized, or were phlebotomized for only a limited time. Our findings indicate that the treatment rather than the disease increased the cadmium uptake in homozygous HH. Further studies are needed to confirm whether the disease decreased cadmium absorption and whether the absorption was dependent on the genotype.

Absorption↗
PubMed2000

Both the environment and genes are important for concentrations of cadmium and lead in blood.

Concentrations of cadmium and lead in blood (BCd and BPb, respectively) are traditionally used as biomarkers of environmental exposure. We estimated the influence of genetic factors on these markers in a cohort of 61 monozygotic and 103 dizygotic twin pairs (mean age = 68 years, range = 49-86). BCd and BPb were determined by graphite furnace atomic absorption spectrophotometry. Variations in both BCd and BPb were influenced by not only environmental but also genetic factors. Interestingly, the genetic influence was considerably greater for nonsmoking women (h(2) = 65% for BCd and 58% for BPb) than for nonsmoking men (13 and 0%, respectively). The shared familial environmental (c(2)) influence for BPb was 37% for men but only 3% for women. The association between BCd and BPb could be attributed entirely to environmental factors of mutual importance for levels of the two metals. Thus, blood metal concentrations in women reflect not only exposure, as previously believed, but to a considerable extent hereditary factors possibly related to uptake and storage. Further steps should focus on identification of these genetic factors and evaluation of whether women are more susceptible to exposure to toxic metals than men.

Aged↗
PubMed1999

Lead in plasma and whole blood from lead-exposed children.

In 31 children exposed to lead and 13 considerably less exposed children ("unexposed"), the plasma (Pb-P) concentrations ranged from 0.46 to 18.4 (median, 2.4) and from 0.14 to 0.38 (median, 0.21) microg/L, respectively. Corresponding whole-blood concentrations (Pb-B) were 99-920 (median, 370) and 39-120 (median, 66) microg/L, respectively. The relation between Pb-B and Pb-P was nonlinear; when Pb-P rose, the Pb-B increased relatively less. There was a close association between Pb-B and log Pb-P (r=0.95; P=0.0001). When these data were compared to previous data on adults, there was no major difference between children and adults in the Pb-B/Pb-P relation. Free erythrocyte protoporphyrins in blood were associated with Pb-P (r=0.75; P=0.0001) and Pb-B (r=0.90; P=0.0001). Also, there was an association between blood-hemoglobin concentration and Pb-P in both exposed (r=-0.67; P=0.0001) and unexposed (r=-0.67; P=0.01) children; the corresponding figures for Pb-B were r=-0.42; P=0.02, and r=-0.80; P=0.001, respectively. Thus, at least with regard to toxicity on hematopoiesis at high lead levels, Pb-P may be a more relevant indicator of exposure and risk than Pb-B. Because the curved Pb-B/Pb-P relation indicates a saturation of binding sites for lead in red cells, exposure and risk at high lead levels may easily be underestimated from Pb-B data.

Adolescent↗
PubMed1999

Lead exposure and hearing effects in children in Katowice, Poland.

The objective of the study was to investigate the relationship between lead exposure and hearing in children in the Katowice region, an industrial area in Poland. Blood lead was determined using inductively coupled plasma mass spectrometry, with appropriate quality control. The concentrations of lead in blood (B-Pb) in 155 children, aged 4-14, ranged from 19 to 281 microg/L (0.09 to 1.4 micromol/L), with a median of 72 microg/L (0.34 micromol/L). The hearing thresholds increased significantly with increasing blood lead levels at all investigated frequencies (0.5, 1, 2, 4, 6, and 8 kHz). The relationship also remained significant for B-Pb below 100 microg/L (0.48 micomol/L; n=107). The brainstem auditory evoked potential latency of wave I was significantly increased (also after adjustment for age) in the group of children with the highest blood lead levels (B-Pb above 100 microg/L, 0.48 micromol/L; n=51), compared to the group with the lowest ones (B-Pb below 46 microg/L, 0.22 micromol/L; n=51). The audiometric results clearly indicate that auditory function in children is impaired at a blood lead concentration even below 100 microg/L (0.5 micromol/L).

Adolescent↗
PubMed1999

Variation in blood concentrations of cadmium and lead in the elderly.

This study aims at characterizing blood concentrations of cadmium (B-Cd) and lead (B-Pb) in a group of 176 men and 248 women, 49-92 years of age (mean 68 years), selected from the Swedish Twin Registry. Metal concentrations were determined using graphite furnace atomic absorption spectrophotometry. B-Cd ranged from 0.05 to 6.8 microg Cd/L (median 0.36 microg Cd/L) and B-Pb from 5.6 to 150 microg Pb/L (median 27 microg Pb/L). As expected, smokers had higher B-Cd than nonsmokers (median 1.3 versus 0.32 microg Cd/L), while B-Pb was not significantly related to smoking habits. Among nonsmokers, women had higher B-Cd than men (median 0.35 versus 0.25 microg Cd/L). In men, but not women, B-Cd increased with age and consequently the gender-related difference in B-Cd was most obvious in the youngest age group. On the other hand, women had lower B-Pb than men (median 24 versus 30 microg Pb/L). In both men and women, B-Pb decreased between 50 and 70 years of age, perhaps reflecting decreased energy intake. In women, the highest B-Pb in the 50-55 years age group is probably related to an increased release of Pb from the skeleton during postmenopausal bone demineralization. After about 70 years, B-Pb tended to increase, which probably is a cohort effect due to much higher Pb exposure 10-30 years ago when leaded gasoline was used.

Aged↗
PubMed1999

A method to compensate for incomplete 24-hour urine collections in nutritional epidemiology studies.

OBJECTIVE: To develop a method to make use of incomplete 24-hour urinary samples in nutritional epidemiology, especially when validating the dietary intake of nitrogen (protein), sodium and potassium. DESIGN: Urinary data for men and women collected in three different studies were evaluated. The concentration of para-aminobenzoic acid (PABA) in one 24-hour urine sample per person was compared with the concentrations of nitrogen, sodium, potassium and creatinine. SETTING: Men and women living in Cambridge, UK and women living in the town of Varberg, Sweden. SUBJECTS: In total, this study consists of data from 73 Swedish women (20-50 years of age), 165 UK women (50-65 years) and 75 UK men (55-88 years). RESULTS: On average four out of 10 people in this study had a PABA recovery below 85%. The linear regression equations for urinary excretion of nitrogen, sodium and potassium in relation to PABA recovery were y=2.3 + 0.088 x chi (r=0.99), y=45 + 0.82 x chi (r= 0.87) and y = 19 + 0.60 x chi (r= 0.93), respectively. CONCLUSIONS: The linear regression equations can be used for adjusting urinary nitrogen, sodium and potassium in urinary collections in cases where the PABA recovery is below 85%. Since it is common to obtain 24-hour urine collections with a PABA recovery below 85%, this method should increase the usefulness of biological markers of food intake in nutritional epidemiological studies and also increase the possibilities to study people that previously have been part of the drop-out group or the group with low motivation and cooperation. It is important to stress that we have not studied the relationship between PABA recovery and various urinary variables below the PABA recovery of 50%. Thus, in a case of PABA recovery below 50%, we do not recommend the use of this method to compensate for incomplete collections.

4-Aminobenzoic Acid↗
PubMed1999

Evaluation of kits for measurement of the soluble transferrin receptor.

Three commercially available kits for determination of the soluble serum transferrin receptor (sTfR), R&D Systems, UK, Ramco Laboratories, USA and Orion, Finland were compared with respect to practicability, comparability and ability to discriminate between iron deficient and non-iron deficient subjects. Serum samples representing different concentrations of sTfR were tested. The three kits involved virtually the same laboratory procedures except for a predilution step for Ramco. Both the absolute amounts and the units (mg/L and nmol/L) differed among the kits, emphasizing the need for internationally accepted reference material and comparable units. The correlation coefficients were 0.974 (Ramco and R&D), 0.769 (R&D and Orion) and 0.759 (Ramco and Orion), indicating a lower comparability for Orion compared to the other two kits. The differences between the kits may be attributed to uncertainties in the reference intervals and to variations in kit format. This may have implications for studies of the usefulness of sTfR as a marker of iron deficiency.

Calibration↗
PubMed1999

Methylation of inorganic arsenic in different mammalian species and population groups.

Thousands of people in different parts of the world are exposed to arsenic via drinking water or contaminated soil or food. The high general toxic of arsenic has been known for centuries, and research during the last decades has shown that arsenic is a potent human carcinogen. However, most experimental cancer studies have failed to demonstrate carcinogenicity in experimental animals, indicating marked variation in sensitivity towards arsenic toxicity between species. It has also been suggested that there is a variation in susceptibility among human individuals. One reason for such variability in toxic response may be variation in metabolism. Inorganic arsenic is methylated in humans as well as animals and micro-organisms, but there are considerable differences between species and individuals. In many, but not all, mammalian species, inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are more rapidly excreted in urine than is the inorganic arsenic, especially the trivalent form (AsIII, arsenite) which is highly reactive with tissue components. Absorbed arsenate (AsV) is reduced to trivalent arsenic (AsIII) before the methyl groups are attached. It has been estimated that as much as 50-70% of absorbed AsV is rapidly reduced to AsIII, a reaction which seems to be common for most species. In most experimental animal species, DMA is the main metabolite excreted in urine. Compared to human subjects, very little MMA is produced. However, the rate of methylation varies considerably between species, and several species, e.g. the marmoset monkey and the chimpanzee have been shown not to methylate inorganic arsenic at all. In addition, the marmoset monkey accumulates arsenic in the liver. The rat, on the other hand, has an efficient methylation of arsenic but the formed DMA is to a large extent accumulated in the red blood cells. As a result, the rat shows a low rate of excretion of arsenic. In both human subjects and rodents exposed to DMA, about 5% of the dose is excreted in the urine as trimethylarsine oxide. It is obvious from studies on human volunteers exposed to specified doses of inorganic arsenic that the rate of excretion increases with the methylation efficiency, and there are large inter-individual variations in the methylation of arsenic. Recent studies on people exposed to arsenic via drinking water in northern Argentina have shown unusually low urinary excretion of MMA. Furthermore, children had a lower degree of methylation of arsenic than adults. Some studies indicate a lower degree of arsenic methylation in men than in women, especially during pregnancy. Whether the observed differences in methylation of arsenic are associated with variations in the susceptibility of arsenic remains to be investigated.

Adult↗
PubMed1999

Environmental health in the Baltic region--toxic metals.

Recent reports on concentrations of lead, cadmium, methylmercury, arsenic and nickel in some biological media in populations in the Baltic region are reviewed. In particular, children in parts of Poland, the Czech Republic, and Germany have uptakes of lead sufficient to cause adverse effects on the central nervous system and kidneys. Cadmium exposure is also high in Poland. Slight cadmium-induced effects on the kidneys have been reported from Germany and Sweden. Methylmercury uptake is dependent upon the intake of fish, in particular from contaminated lakes and rivers in Sweden and Finland, as well as the eastern coast of the Baltic Sea. There are some indications of immunotoxic effects associated with the intake of such fish. However, fish also contain other immunomodulating agents. Exposure to arsenic seems to be low everywhere in the Baltic region. There is high nickel exposure in northern Russia.

Adolescent↗
PubMed1998

Exposure to inorganic arsenic metabolites during early human development.

Because of the lack of data on the exposure to and toxic effects of inorganic arsenic during early human development, the transfer of arsenic to the fetus and suckling infant was studied in a native Andean population, living in the village San Antonio de los Cobres in the North west of Argentina, where the drinking water contains about 200 micrograms/liter. The concentration of arsenic in cord blood (median, 9 micrograms/liter) was almost as high as in maternal blood (median, 11 micrograms/liter), and there was a significant correlation between the two. Thus, at least in late gestation, arsenic is easily transferred to the fetus. The median concentration of arsenic in the placenta was 34 micrograms/kg, compared with 7 micrograms/kg previously reported for nonexposed women. Interestingly, essentially all arsenic in the blood plasma of both the newborns and their mothers was in the form of dimethylarsinic acid (DMA), the end product of inorganic arsenic metabolism. Similarly, about 90% of the arsenic in the urine of both the newborns and mothers in late gestation was present as DMA, compared with about 70% in nonpregnant women (p < 0.001). This may indicate that methylation of arsenic is increased during pregnancy and that DMA is the major form of arsenic transferred to the fetus. The increased methylation in late gestation was associated with lower arsenic concentrations in blood and higher concentrations in urine, compared with a few months postpartum. The arsenic concentrations in the urine of the infants decreased from about 80 micrograms/liter during the first 2 days of life to less than 30 micrograms/liter at 4.4 months (p = 0.025). This could be explained by the low concentrations of arsenic in the breast milk, about 3 micrograms/kg.

Arsenic↗
PubMed1998

Low-level arsenic excretion in breast milk of native Andean women exposed to high levels of arsenic in the drinking water.

OBJECTIVE: To investigate the excretion of arsenic in breast milk of lactating native Andean women living in a village in northwestern Argentina with high concentrations of arsenic in the drinking water (about 200 micrograms/l) and to assess the exposure of children to arsenic during the very first period of life. METHODS: The study included ten lactating women and two nursing babies. Hydride-generation atomic absorption spectrometry (HG-AAS) was used to determine the concentration of arsenic in samples of human milk, drinking water, blood, and urine. RESULTS: The concentrations of arsenic detected in maternal blood (total arsenic) and urine (metabolites of inorganic arsenic) were high, averaging 10 and 320 micrograms/l, respectively. In subjects without known exposure to arsenic the average concentrations found in blood and urine are 1-2 and about 10 micrograms/l, respectively. The metabolites of inorganic arsenic constituted more than 80% of the total arsenic in the urine, which shows that inorganic arsenic was the main form of arsenic ingested. The average concentration of arsenic detected in human milk was 2.3 micrograms/kg fresh weight (range 0.83-7.6 micrograms/kg). Although data on background levels of arsenic in human breast milk are scarce, the present concentrations seem to be slightly elevated. However, considering the high levels of arsenic exposure in the mothers, the total arsenic concentrations measured in human milk were low. In concordance with the low concentrations of arsenic found in the milk, the concentrations of arsenic metabolites measured in the urine of two of the nursing babies were low: 17 and 47 micrograms/l, respectively. CONCLUSIONS: The low concentrations of arsenic detected in the breast milk and urine of the two nursing babies in relation to the high level of maternal exposure to arsenic indicate that inorganic arsenic is not excreted in breast milk to any significant extent. This is a very important reason for long breast-feeding periods.

Adolescent↗
PubMed1998

Exposure to lead and other metals in children from Katowice district, Poland.

OBJECTIVES: To assess the exposure to toxic metals and to evaluate its possible association with essential elements and socioeconomic status in children from the town of Bytom in the Katowice area; this area is one of the most polluted industrialized regions in Poland. METHODS: Concentrations of lead, cadmium, mercury, selenium, magnesium, copper, and zinc were determined in whole blood of 211 children aged 9 years. The samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Information on socioeconomic factors was collected using questionnaires. Concentrations of trace elements in the blood of 24 Swedish children aged 9-10 years were used for comparisons. RESULTS: The concentrations of lead detected in the blood of the Polish children ranged from 0.09 to 1.9 mumol/l, with the median value being 0.27 mumol/l. Statistically significant associations were found between lead and such socioeconomic factors as the number of siblings, trips outside the region, maternal smoking, playing outdoors, and apartment standard. The average blood lead level was about 3 times higher in the Polish children than in the Swedish group. The median blood concentration of cadmium found in the Polish children was 3.4 nmol/l (range 1.1-41 nmol/l; almost 3 times higher than that detected in the Swedish children), and that of mercury was 3 nmol/l (range 0.5-11 nmol/l). The median blood levels and ranges of the essential elements were 1.1 (0.7-2.0) mumol/l for selenium, 1.5 (1.2-1.9) mmol/l for magnesium, 17 (13-22) mumol/l for copper, and 78 (54-104) mumol/l for zinc, respectively. The concentrations of selenium and magnesium were significantly lower in the Polish group as compared with the Swedish children. CONCLUSIONS: In all, 7% of the Polish children had blood lead levels exceeding 0.5 mumol/l, the concentration above which negative effects on mental development have been reported. However, the findings indicate a decrease in lead exposure during recent years among the Bytom children.

Child↗
PubMed1998

Interactions between essential and toxic elements in lead exposed children in Katowice, Poland.

OBJECTIVES: To determine the influence of the essential element status on blood concentrations of lead and other toxic metals. DESIGN AND METHODS: A group of 157 children from Katowice, an industrial area in Poland, was investigated for concentrations of lead and cadmium in whole blood, and mercury, selenium, zinc, copper, and magnesium in whole blood and serum. Relations between these elements, serum ferritin, hematological parameters, as well as serum selenoprotein P and glutathione peroxidase (GSH-px) were examined. Conversion factors for element concentrations (mumol to microgram): lead 207.19, cadmium 112.41, mercury 200.59, selenium 78.96, magnesium 24.31, copper 63.55, and zinc 65. RESULTS: Blood lead was negatively associated with concentrations of selenium in whole blood and serum as well as selenoprotein P and glutathione peroxidase in serum. The association was mainly apparent at low blood lead concentrations, which may indicate an influence of selenium on the kinetics of lead, rather than an effect of lead on the selenium status. Children with low serum ferritin levels had statistically higher blood cadmium levels and a tendency for higher blood lead levels, indicating increased gastrointestinal absorption of these metals at reduced iron stores. Blood lead was negatively correlated with mean corpuscular hemoglobin concentration, which may reflect the effect of lead on hemoglobin synthesis. There was an association between blood mercury and selenium, indicating a common source of intake through fish consumption. CONCLUSIONS: The results indicate that selenium and iron status may influence the kinetics of lead.

Adolescent↗