Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys.

Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov-Smirnov test, P-value<10-15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (r S -values>-0.62), but in girls only 207 (41%) showed inverse correlation (r S -values>-0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.

Arsenic-induced suppression of kidney cell proliferation and the transcriptional coregulator MAML1.

Mastermind-like 1 (MAML1) is a transcriptional coregulator of diverse/multiple activators, such as Notch, p53, myocyte enhancer factor 2C, NF-κB, beta-catenin, papillomavirus E6 proteins, early growth response 1 and runt-related transcription factor 2. Thus, MAML1 functions in various signaling pathways, most of them connected to cell proliferation, which suggests that MAML1 might play a potential role as a cell proliferation marker. In this study we show that MAML1 expression in the kidney correlates in silico with established cell proliferation markers including PCNA, CDC2 and XRCC5 (Ku80). Over-expression of MAML1 increased proliferation of human embryonic kidney (HEK) 293 cells, while MAML1 downregulation by siRNA decreased cell proliferation. Exposure of HEK293 cells to inorganic arsenic (arsenite) showed reduced levels of MAML1, in combination with a decreased proliferation rate. Our findings provide evidence that arsenic can inhibit proliferation of embryonic kidney cells, possibly through reduction of MAML1 gene expression.

Critical windows of exposure for arsenic-associated impairment of cognitive function in pre-school girls and boys: a population-based cohort study.

BACKGROUND: Exposure to arsenic through drinking water has been associated with impaired cognitive function in school-aged children in a few cross-sectional studies; however, there is little information on critical windows of exposure. METHODS: We conducted a population-based longitudinal study in rural Bangladesh. We assessed the association of arsenic exposure, based on urinary arsenic (U-As; twice during pregnancy and twice in childhood), with the development of about 1700 children at 5 years of age using Wechsler Pre-school and Primary Scale of Intelligence [intelligence quotient (IQ)]. RESULTS: Median maternal U-As in pregnancy was 80 µg/l (10-90 percentiles: 25-400 µg/l). Children's urine contained 35 (12-155) µg/l and 51 (20-238) µg/l at 1.5 and 5 years, respectively. Using multivariable-adjusted regression analyses, controlling for all potential confounders and loss to follow-up, we found that verbal IQ (VIQ) and full scale IQ (FSIQ) were negatively associated with (log) U-As in girls. The associations were consistent, but somewhat stronger with concurrent arsenic exposure [VIQ: B = -2.4, 95% confidence interval (CI) = -3.8 to -1.1; FSIQ: B = -1.4, 95% CI = -2.7 to -0.1, n = 817), compared with that at 1.5 years (VIQ: B = -0.85, 95% CI = -2.1 to 0.4; FSIQ: B = -0.74, 95% CI = -1.9 to 0.4, n = 902), late gestation (VIQ: B = -1.52, 95% CI = -2.6 to -0.4; FSIQ: B = -1.35, 95% CI = -2.4 to -0.3, n = 874) and early gestation (VIQ: B = -1.23, 95% CI = -2.4 to -0.06; FSIQ: B = -0.92, 95% CI = -2.0 to -0.2, n = 833). In boys, U-As showed consistently low and non-significant associations with all IQ measures. An effect size calculation indicated that 100 µg/l U-As was associated with a decrement of 1-3 points in both VIQ and FSIQ in girls. CONCLUSION: We found adverse effects of arsenic exposure on IQ in girls, but not boys, at 5 years of age.

Assessment of early-life lead exposure in rural Bangladesh.

Lead is a well-known neurotoxic metal and one of the most toxic chemicals in a child's environment. The aim of this study was to assess early-life lead exposure in a pristine rural area of Bangladesh. The exposure was expected to be very low because of the absence of vehicle traffic and polluting industries. Lead was measured in erythrocytes, urine, and breast milk of 500 randomly selected pregnant women, participating in a randomized food and micronutrient supplementation trial in Matlab (MINIMat). Lead was also measured in urine of their children at 1.5 and 5 years of age, and in rice, well water, cooking pots, and materials used for walls and roof. All measurements were performed using ICPMS. We found that the women had relatively high median erythrocyte lead levels, which increased considerably from early pregnancy to late lactation (81-136microg/kg), probably due to release from bone. Urinary lead concentrations were unchanged during pregnancy (median approximately 3.5microg/L) and non-linearly associated with maternal blood lead levels. Children, at 1.5 and 5 years of age, had a median urinary lead concentration of 4microg/L, i.e., similar to that in their mothers. Rice, the staple food in Matlab, collected from 63 homes of the study sample, contained 1-89microg/kg (median 13microg/kg) dry weight and seems to be an important source of lead exposure. Other sources of exposure may be cooking pots and metal sheet roof material, which were found to release up to 380 and 4200microg/L, respectively, into acidic solutions. Based on breast milk lead concentrations (median 1.3microg/L) a median daily intake of 1.2microg was estimated for 3 months old infants. However, alternatives to breast-feeding are likely to contain more lead, especially rice-based formula. To conclude, lead exposure in women and their children in a remote unpolluted area was found to be surprisingly high, which may be due to their living conditions.

Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women--a prospective cohort study.

Experimental studies indicate that zinc (Zn) and calcium (Ca) status, in addition to iron (Fe) status, affect gastrointestinal absorption of cadmium (Cd), an environmental pollutant that is toxic to kidneys, bone and endocrine systems. The aim of this study was to evaluate how various nutritional factors influence the uptake of Cd in women, particularly during pregnancy. The study was carried out in a rural area of Bangladesh, where malnutrition is prevalent and exposure to Cd via food appears elevated. The uptake of Cd was evaluated by associations between erythrocyte Cd concentrations (Ery-Cd), a marker of ongoing Cd exposure, and concentrations of nutritional markers. Blood samples, collected in early pregnancy and 6 months postpartum, were analyzed by inductively coupled plasma mass spectrometry (ICPMS). Ery-Cd varied considerably (range: 0.31-5.4microg/kg) with a median of 1.1microg/kg (approximately 0.5microg/L in whole blood) in early pregnancy. Ery-Cd was associated with erythrocyte manganese (Ery-Mn; positively), plasma ferritin (p-Ft; negatively), and erythrocyte Ca (Ery-Ca; negatively) in decreasing order, indicating common transporters for Cd, Fe and Mn. There was no evidence of Cd uptake via Zn transporters, but the association between Ery-Cd and p-Ft seemed to be dependent on adequate Zn status. On average, Ery-Cd increased significantly by 0.2microg/kg from early pregnancy to 6 months postpartum, apparently due to up-regulated divalent metal transporter 1 (DMT1). In conclusion, intestinal uptake of Cd appears to be influenced either directly or indirectly by several micronutrients, in particular Fe, Mn and Zn. The negative association with Ca may suggest that Cd inhibits the transport of Ca to blood.

Early-life nutritional and environmental determinants of thymic size in infants born in rural Bangladesh.

AIM: The aim was to assess the impact of nutritional status and environmental exposures on infant thymic development in the rural Matlab region of Bangladesh. METHODS: In a cohort of N(max) 2094 infants born during a randomized study of combined interventions to improve maternal and infant health, thymic volume (thymic index, TI) was assessed by ultrasonography at birth and at 8, 24 and 52 weeks of age. Data on birth weight, infant anthropometry and feeding status were also collected. RESULTS: At all ages, TI was positively associated with infant weight and strongly associated with the month of measurement. Longer duration of exclusive breastfeeding resulted in a larger TI at 52 weeks. TI at birth and at 8 weeks correlated positively with birth weight, but by 24 and 52 weeks and when adjusted for infant weight this effect was no longer present. Thymic size was not affected by pre-natal maternal supplementation or by socioeconomic status but was correlated to arsenic exposure during pregnancy. CONCLUSION: In this population of rural Bangladeshi infants, thymic development is influenced by both nutritional and environmental exposures early in life. The long-term functional implications of these findings warrant further investigation.

Creatinine versus specific gravity-adjusted urinary cadmium concentrations.

The aim was to assess how urinary creatinine is affected by age, gender, body size and meat intake, and to determine to what extent such factors might affect the creatinine adjustment of urinary cadmium. The study was based on three Swedish studies: (1) 67 non-smoking women aged 20-50 years (24-h urine samples); (2) 289 men and 434 women aged 16-81 years (spot urine samples); and (3) 98 men and 105 women aged 19-72 years (spot urine samples). The effects of age, body surface area (as an indicator of muscle mass), and meat intake on urinary creatinine and cadmium were analysed using multiple regression analyses. Gender- and age-related variations in urinary creatinine and cadmium adjusted for creatinine or specific gravity were compared by ANOVA or ANCOVA. In the multiple regression analyses, body surface area, gender, age and meat intake were the major determinants of urinary creatinine. Urinary cadmium adjusted for creatinine and specific gravity were also dependent on body size, gender and age. Urinary cadmium adjusted for creatinine was 15-92% higher in women or older individuals than in men or younger individuals. Women or older individuals had -3 to 79% higher urinary cadmium adjusted for specific gravity than men or younger individuals had, and such a difference between gender or age group was less obvious in specific gravity adjustment than in creatinine adjustment. Thus, urinary cadmium adjusted for creatinine is more affected by age, gender, body size and meat intake than is specific gravity adjustment. When comparing individuals or populations with large differences in muscle mass or meat intake, such effects can be especially important. In such studies, specific gravity adjustment seems to be more appropriate.

Exposure to methylmercury in non-fish-eating people in Sweden.

The extensive use of fish meal as a source of protein for poultry and swine may lead to additional exposure to methylmercury (MeHg). We determined the concentration of MeHg and inorganic mercury (I-Hg) in blood and total mercury (T-Hg) in hair in 27 persons (9 men and 18 women, 20-58 years of age) who stated that they had consumed no fish for a period of 2 years or more. The participants answered a food frequency questionnaire and reported their number of dental amalgam fillings. The MeHg concentrations in blood (median, 0.10 microg/L; range, 0.0-1.0 microg/L) were very low and did not constitute a concern for health effects. We also analyzed selenium (Se) in serum. The median concentration was 76 microg/L (range, 53-103 microg/L), which is in agreement with previous studies of the Swedish general population, indicating that the Se status of non-fish-eating individuals is not substantially lower than that of people who include fish in their diet. We found a significant association (P=0.002) between the number of dental amalgam fillings and the I-Hg concentration in blood (median, 0.09 microg/L; range, 0.03-0.57 microg/L). The T-Hg in hair (median, 0.06 mg/kg; range, 0.04-0.32 mg/kg) was significantly associated (R2=0.89; P<0.001) with the MeHg in blood, but not with the I-Hg in blood. Therefore, the T-Hg in hair seems to reflect MeHg exposure and not I-Hg exposure even in persons with no intake of fish.

Methyl mercury and inorganic mercury in Swedish pregnant women and in cord blood: influence of fish consumption.

We studied exposure to methyl mercury (MeHg) in Swedish pregnant women (total mercury [T-Hg] in hair) and their fetuses (MeHg in cord blood) in relation to fish intake. The women were recruited at antenatal care clinics in late pregnancy to participate in an exposure study of environmental pollutants. Fish consumption was evaluated using food frequency questionnaires including detailed questions on fish consumption. In addition, we determined inorganic mercury (I-Hg) and selenium (Se) in cord blood. On average, the women consumed fish (all types) 6.7 times/month (range 0-25 times/month) during the year they became pregnant. They reported less consumption of freshwater fish--species that might contain high concentrations of MeHg--during than before pregnancy. T-Hg in maternal hair (median 0.35 mg/kg; range 0.07-1.5 mg/kg) was significantly associated (R2 = 0.53; p < 0.001) with MeHg in cord blood (median 1.3 microg/L; range 0.10-5.7 microg/L). Both hair T-Hg and cord blood MeHg increased with increasing consumption of seafood (r = 0.41; p < 0.001 and r = 0.46; p < 0.001, respectively). Segmental hair analysis revealed that T-Hg closer to the scalp was lower and more closely correlated with MeHg in cord blood than T-Hg levels in segments corresponding to earlier in pregnancy. We found a weak association between Se (median 86 microg/L; range 43-233 microg/L) and MeHg in cord blood (r = 0.26; p = 0.003), but no association with fish consumption. I-Hg in cord blood (median 0.15 microg/L; range 0.03-0.53 microg/L) increased significantly with increasing number of maternal dental amalgam fillings.

Metals and women's health.

There is a lack of information concerning whether environmental-related health effects are more or less prevalent or manifested differently in women compared to men. Previously, most research in the area of toxicology and environmental and occupational health involved male subjects. The present work aims at reviewing exposure and health effects of cadmium, nickel, lead, mercury, and arsenic manifested differently in women than in men. The gender difference in exposure to nickel results in a much higher prevalence of nickel allergy and hand eczema in women than in men. The internal cadmium dose is generally higher in women than in men, due to a higher gastro-intestinal absorption at low iron stores. This was probably one major reason why Itai-itai disease was mainly a woman's disease. Yet, data are sparse regarding the risk for women relative to men to develop cadmium-induced kidney damage in populations exposed to low levels of cadmium. Lead is accumulated mainly in bone and increased endogenous lead exposure has been demonstrated in women during periods of increased bone turnover, e.g., menopause. Both lead and mercury exposure in pregnant women has to be kept low in order to prevent neurodevelopment effects in the developing fetus and child. Limited data indicate that women are more affected than men following exposure to methylmercury at adult age, while males seem to be more sensitive to exposure during early development. Regarding arsenic, some data indicate gender differences in the biotransformation by methylation, possibly also in susceptibility to certain arsenic-related cancers. Obviously, gender-related differences in exposure and health effects caused by metals are highly neglected research areas, which need considerable focus in the future.

Role of metabolism in arsenic toxicity.

In humans, as in most mammalian species, inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by alternating reduction of pentavalent arsenic to trivalent and addition of a methyl group from S-adenosylmethionine. The methylation of inorganic arsenic may be considered a detoxification mechanism, as the end metabolites, MMA and DMA, are less reactive with tissue constituents, less toxic, and more readily excreted in the urine than is inorganic arsenic, especially the trivalent form (AsIII, arsenite). The latter is highly reactive with tissue components, due to its strong affinity for sulfhydryl groups. Thus, following exposure to AsV the first step in the biotransformation, i.e. the reduction to AsIII, may be considered a bioactivation. Also, reactive intermediate metabolites of high toxicity, mainly MMAIII, may be formed and distributed to tissues. Low levels of MMAIII and DMAIII have been detected in urine of individuals chronically exposed to inorganic arsenic via drinking water. However, the contribution of MMAIIIand DMAIII to the toxicity observed after intake of inorganic arsenic by humans remains to be elucidated. The major route of excretion of arsenic is via the kidneys. Evaluation of the methylation of arsenic is mainly based on the relative amounts of the different metabolites in urine. On average human urine contains 10-30% inorganic arsenic, 10-20% MMA and 60-80% DMA.

Prenatal exposure to methylmercury changes dopamine-modulated motor activity during early ontogeny: age and gender-dependent effects.

We have shown previously that prenatal exposure of rats to 0.5 mg/kg/day of methylmercury (MeHg) produces gender-dependent changes in motor activity in adulthood. In the present study we have investigated whether changes in motor activity could also be found during early ontogeny of the offspring. Pregnant rats were treated with MeHg from day 7 of pregnancy to day 7 of lactation. The habituation to a novel environment (spontaneous activity) and the response to stimulation of the dopaminergic system were studied on postnatal day 14 and 21. Measures of spontaneous activity showed a slight increase in MeHg-prenatal exposed male and female rats at 14 days, but not at 21 days. Following administration of U91356A, a selective dopamine D(2) receptor agonist, a significantly lower dopamine-mediated locomotor activity was observed in the 21 day old MeHg-treated males, but not in females. These results show that prenatal exposure to MeHg alters postjunctional dopaminergic activity during the period of maturation of the dopamine system in the brain. Moreover, the gender-dependent susceptibility previously found in adulthood is already evident at the prepubertal stage.

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.

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.

Impact of soil and dust lead on children's blood lead in contaminated areas of Sweden.

The impact of lead in soil and dust on blood lead concentrations in young children (i.e., 1-5 y of age, N = 202) and the risk of health effects were investigated in an urban and a mining area of Sweden. Blood, soil, and indoor dust, as well as information on lead-exposure factors, were collected. The blood lead concentrations (total range = 9-77 microg/l) the authors measured indicated a low risk for lead-induced health effects. Lead in soil (i.e., < 10-5,000 microg/g) and in dust (i.e., < 1-316 microg/g) had little effect on blood lead concentrations, given the present conditions and present concentration range--especially in the mining area. Urban children had significantly higher blood lead concentrations than children in the mining area, despite higher concentrations of lead in soil in the mining area. In the urban children, blood lead concentrations were influenced by parental smoking and lead in dust at day-care centers.

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.

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.

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.

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.

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.