Dietary zinc, calcium and nickel are associated with lower childhood blood lead levels.

The potential mitigation of elevated blood lead (PbB) levels with nutrient intake remains debatable. A comprehensive review by Kordas (2017) concluded that careful examination of the links between nutrition (nutritional status, nutrients, diet) and lead (Pb) exposure revealed limited and tenuous evidence. We have measured 20 elements including calcium (Ca), chromium (Cr), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), nickel (Ni), zinc (Zn), and Pb from 6-day duplicate diets of 108 young children over a 5-year period and expressed these as intakes per body weight. Bivariate analyses showed a weak positive association between the Pb content in the diets of the participants and the level of Pb in their blood, as might be expected. Weak, but negative, associations occurred between the other elements in the diet and PbB. The associations for Ca, Mg, Ni and Zn were statistically significant for both subject-based (between subjects) and within-subject effects: that is, as the levels of elements in diet increased, the PbB level decreased. The largest percentage of variance of PbB in the context of the bivariate model accounted for was 4.23% for Zn, followed by Ca (3.91%) and Fe (2.20%). Supplementary analyses indicated that the between- and within-subject effects did not vary with the age at which participants entered the study, or with the levels of elements at their first measurement. A multivariable analysis using Weighted Quantile Sum Regressions showed that a weighted composite comprised of all the dietary elements had a significant association with PbB when adjusted for Pb in the diet and other covariates and also when adjusted for Pb in house dust; the latter was found to have the strongest association with PbB in earlier analyses. The highest weights were for Ca (0.29), Ni (0.27) and Zn (0.22); these results are generally consistent with those from the mixed model analyses.

Revisiting mobilisation of skeletal lead during pregnancy based on monthly sampling and cord/maternal blood lead relationships confirm placental transfer of lead.

Lead (Pb) can be released from the maternal skeleton during pregnancy and lactation and transferred to the infant. Most support for this hypothesis comes from blood Pb (PbB) studies involving limited sampling during pregnancy, the maximum usually being five samplings, including at delivery. We provide longitudinal data for PbB concentrations and Pb isotopic ratios for three cohorts of pregnant females (n = 31), two of which are based on monthly sampling and the other on quarterly sampling. We also provide data for samples collected post-partum. The data are compared with changes observed in a matched, by country and age, non-pregnant control cohort (n = 5). The monthly data illustrate the variability between subjects, which is also apparent when the data are compared on a trimester basis. Mixed model analyses showed that, in the third trimester, the mean PbB level was significantly lower for women (n = 10) who took a calcium (Ca) supplement (PbB 1.6 µg/dL) than those whose Ca intake was low (low-Ca cohort; n = 15; PbB 2.5 µg/dL) because low Ca means more mobilisation is required for homoeostasis so that more Pb was mobilised from the skeleton. For women who took the supplement, post-partum PbB levels were significantly higher than those in the other periods (2.7 vs 1.4-1.6 µg/dL). For women in the low-Ca cohort, PbB levels were higher at post-partum than in pre-pregnancy and in the first and second trimesters (3.1 vs 1.8 µg/dL), while the levels in the third trimester were higher than those in the first and second trimesters. Importantly, the increase in PbB during gestation was delayed until the third trimester in the Ca-supplemented cohort compared with the low-Ca cohort. Regression analysis showed that the changes over trimester were very similar for PbB and the (206)Pb/(204)Pb ratio providing convincing evidence for extra mobilisation of Pb from the maternal skeleton during pregnancy and lactation. Isotopic ratios in the cord blood samples were similar to those in the maternal blood samples taken prior to parturition with an R (2) 0.94 for the migrant subjects and R (2) 0.74 for Australian subjects for (206)Pb/(204)Pb ratios, supporting the concept of placental transfer of mobilised skeletal stores of Pb.

Pathways of Pb and Mn observed in a 5-year longitudinal investigation in young children and environmental measures from an urban setting.

We monitored 108 children ≤5 years on a 6-month basis for up to 5 years in a major urban setting. Samples (n ∼ 7000) included blood, urine, handwipes (interior, and after exterior playing), 6-day duplicate diet, drinking water, interior house and day care dust-fall accumulation using petri dishes, exterior dust-fall accumulation, exterior dust sweepings, paint, soil and urban air. The geometric mean blood Pb (PbB) was 2.1 µg/dL and blood Mn (MnB) was 10.0 µg/L. Following a path modelling approach, mixed model analyses for a fully adjusted model showed the strongest associations for PbB were with interior house dust and soil; for MnB there were no significant associations with any predictors. Predictor variables only explained 9% of the variance for Pb and 0.7% for Mn. Relationships between environmental measures and PbB in children are not straightforward; soil and dust sweepings contribute only about 1/5th of the amounts to PbB found in other studies.

Longitudinal monitoring of selected elements in blood of healthy young children.

There are limited data on essential nutrients in the whole blood of young children. As part of a longitudinal study of the impact on young children and the environment from the introduction of an organic Mn compound into unleaded gasoline in Australia, we have measured a suite of elements in whole blood. The children, aged between 6 and 31 months at recruitment, have been monitored at 6-month intervals for up to 5 years. Blood samples were analysed by inductively coupled plasma mass spectrometry for Ca, Mg, Fe, Mn, Cu, Zn and Pb. Mixed model analyses of 665 blood samples using backward elimination showed significant positive relationships between Ca, Mg and Zn and season, variable relationships with time, but no association with gender or traffic exposure. The elements Ca, Mg and Zn showed higher concentrations in summer compared with winter, whereas Fe and Pb showed lower concentrations in summer compared with winter. Concentrations of all elements except Fe showed significant effects over time: Ca, Cu, Mg, Pb and Mn showed decreases over time, whereas Zn showed an increase. The mixed model analyses with the individual elements as the dependent variable showed some interesting relationships and require further follow-up as some of these appear to conflict with pre-existing concepts, although the multi-element data on which these concepts are based are limited. The variance for blood Pb and blood Mn arising from the other elements was small with 0.5% in the case of blood Pb and 3.7% for blood Mn.

Comparison of lead isotopes with source apportionment models, including SOM, for air particulates.

We have measured high precision lead isotopes in PM(2.5) particulates from a highly-trafficked site (Mascot) and rural site (Richmond) in the Sydney Basin, New South Wales, Australia to compare with isotopic data from total suspended particulates (TSP) from other sites in the Sydney Basin and evaluate relationships with source fingerprints obtained from multi-element PM(2.5) data. The isotopic data for the period 1998 to 2004 show seasonal peaks and troughs that are more pronounced in the rural site for the PM(2.5).samples but are consistent with the TSP. The Self Organising Map (SOM) method has been applied to the multi-element PM(2.5) data to evaluate its use in obtaining fingerprints for comparison with standard statistical procedures (ANSTO model). As seasonal effects are also significant for the multi-element data, the SOM modelling is reported as site and season dependent. At the Mascot site, the ANSTO model exhibits decreasing (206)Pb/(204)Pb ratios with increasing contributions of fingerprints for "secondary smoke" (industry), "soil", "smoke" and "seaspray". Similar patterns were shown by SOM winter fingerprints for both sites. At the rural site, there are large isotopic variations but for the majority of samples these are not associated with increased contributions from the main sources with the ANSTO model. For two winter sampling times, there are increased contributions from "secondary industry", "smoke", "soil" and seaspray with one time having a source or sources of Pb similar to that of Mascot. The only positive relationship between increasing (206)Pb/(204)Pb ratio and source contributions is found at the rural site using the SOM summer fingerprints, both of which show a significant contribution from sulphur. Several of the fingerprints using either model have significant contributions from black carbon (BC) and/or sulphur (S) that probably derive from diesel fuels and industrial sources. Increased contributions from sources with the SOM summer fingerprints could explain the summer-time peaks in isotopic ratio at both sites and, at the rural site, be associated with meteorological influences. Nevertheless, the SOM results indicate that there are multiple overlapping 'weak' sources.

Low blood lead levels do not appear to be further reduced by dietary supplements.

OBJECTIVE: Our objective was to evaluate the association of dietary intakes of selected micronutrients and blood lead (PbB) concentrations in female adults and in children. DESIGN: With longitudinal monitoring, we measured daily intakes of the micronutrients calcium, magnesium, sodium, potassium, barium, strontium, phosphorus, zinc, iron (limited data), and copper from 6-day duplicate diets (2-13 collections per individual) and PbB concentrations. Participants were three groups of females of child-bearing age (one cohort consisting of 21 pregnant subjects and 15 nonpregnant controls, a second cohort of nine pregnant migrants), and one group of 10 children 6-11 years of age. RESULTS: Mean PbB concentrations were <5 microg/dL. A mixed linear model that included only group and time accounted for 5.9% of the variance of the PbB measurements; neither the effect of time nor the effect of group was significant. The model containing all of the micronutrients (except iron, for which there was a great deal of missing data), along with time and group, accounted for approximately 9.2% of the variance of PbB; this increase was not statistically significant. There was, however, a significant association of PbB with phosphorus, magnesium, and copper when all micronutrients were included in the statistical analysis, perhaps reflecting a synergistic effect. CONCLUSIONS: In contrast to most previous studies, we found no statistically significant relationships between the PbB concentrations and micronutrient intake. In adults and older children with low PbB concentrations and minimal exposure to Pb, micronutrient supplementation is probably unnecessary.

Changes in manganese and lead in the environment and young children associated with the introduction of methylcyclopentadienyl manganese tricarbonyl in gasoline--preliminary results.

A 4-year longitudinal study is being conducted to evaluate potential changes to the environment and exposure of young children associated with the introduction of methylcyclopentadienyl manganese tricarbonyl (MMT) into Australia in 2001. The cohort consists of 57 females and 56 males, with an age range of 0.29-3.9 years. Samples are collected every 6 months from children in residences located at varying distances from major traffic thoroughfares in Sydney. Environmental samples include air, house, and daycare center dustfall, soil, dust sweepings, and gasoline; samples from the children include blood, urine, handwipes prior to and after playing outdoors, and a 6-day duplicate diet. All samples are analyzed for a suite of 20 elements using inductively coupled plasma methods. Results are presented for the first three 6-month sampling periods for lead (Pb) and manganese (Mn). For dustfall accumulation, expressed as metal concentration/m2/30 days, there was no significant difference between homes and daycare centers for either Pb or Mn, no significant change over the three sampling periods (time) for Pb or Mn, and a positive relationship between "traffic exposure" (traffic volume and proximity to the road) and Pb but not Mn. Lead concentrations in soil was a significant predictor for Pb in the house dustfall. For handwipes, the concentrations of Pb and Mn in wipes taken from children after playing outdoors was usually significantly greater than those for wipes taken prior to playing. There was no significant association between the concentrations of either Pb or Mn in handwipes and traffic exposure, and there was no significant association between Pb concentrations in the handwipes and gender, although the latter showed a marginally significant association for Mn (P = 0.053). Age was related to Pb level in the handwipes, with older subjects having higher Pb levels, and there were significant decreases in Pb and Mn concentrations over time. Dustfall accumulation was a significant predictor for Pb in the handwipes, and dust sweepings were a significant predictor of Mn in handwipes. Blood lead (PbB) concentrations ranged from 0.6 to 19 microg/dL (GM 2.6) (n = 269), and manganese in blood (MnB) ranged from 1.8 to 45 microg/L (GM 11.6) (n = 254). There was no significant difference between females and males for either mean PbB or MnB; over time there was a significant decline in PbB but no significant change in MnB. The only significant predictor for PbB was dustfall accumulation, although dietary intake may also be important, and the only significant predictor for MnB was Mn in handwipes prior to playing. At this early stage of the investigation we have not been able to detect any increases in Mn in these environmental samples or blood samples potentially associated with the use of MMT; in fact the Mn levels in handwipes declined over time.

Changes in the lead isotopic composition of blood, diet and air in Australia over a decade: globalization and implications for future isotopic studies.

Source apportionment in biological or environmental samples using the lead isotope method, where there are diverse sources of lead, relies on a significant difference between the isotopic composition in the target media and the sources. Because of the unique isotopic composition of Australian lead, source apportionment has been relatively successful in the past. Over the period of a decade, the 206Pb/204Pb ratio for Australian (mainly female) adults has shown an increase from a geometric mean of 16.8-17.3. Associated with this increase, there has been a decrease in mean blood lead concentration from 4.7 to 2.3 microg/dL, or about 5% per year, similar to that observed in other countries. Lead in air, which up until 2000 was derived largely from the continued use of leaded gasoline, showed an overall increase in the 206Pb/204Pb ratio during 1993-2000 from 16.5 to 17.2. Since 1998 the levels of lead in air were less than 0.2 microg/m3 and would contribute negligibly to blood lead. Over the 10-year period, the 206Pb/204Pb ratio in diet, based mainly on quarterly 6-day duplicate diets, increased from 16.9 to 18.3. The lead concentration in diet showed a small decrease from 8.7 to 6.4 microg Pb/kg although the daily intake increased markedly from 7.4 to 13.9 microg Pb/day during the latter part of the decade probably reflecting differences in demographics. The changes in blood lead from sources such as lead in bone or soil or dust is not dominant because of the low 206Pb/204Pb ratios in these media. Unless there are other sources not identified and analysed for these adults, it would appear that in spite of our earlier conclusions to the contrary, diet does make an overall contribution to blood lead, and this is certainly the case for specific individuals. Certain population groups from south Asia, south-east Asia, the Middle East and Europe (e.g. UK) are unsuitable for some studies as their isotopic ratios in blood are converging towards the increasing Australian values. The increases in blood 206Pb/204Pb ratio combined with globalization, which has resulted in the increases in 206Pb/204Pb ratio for diet, means that isotopic studies undertaken with a high degree of certainty of outcomes over a decade ago, are now considerably more difficult, not only in Australia but also in other countries where the isotopic differences are even less than in Australia.

The effect of exposure to employees from mining and milling operations in a uranium mine on lead isotopes--a pilot study.

Potential exposure during mining and milling of uranium ore has resulted in the industry being highly regulated. Exposure can arise from inhalation of the daughter product radioactive gas radon (222Rn), inhalation of radioactive dust particles from mining and milling, direct irradiation from outside the body, and ingestion of radionuclides (e.g. uranium or radium) in food or water. Making use of the highly unusual lead isotopic signature for uranium ores (high 206Pb/204Pb from the high uranium content, low 208Pb/204Pb from the low Th/U ratio), we undertook a pilot study of nine male mine employees and three controls from the Ranger uranium mine in the Northern Territory Australia to determine if it was feasible to use lead isotopes in blood to identify exposure to uranium-derived materials. The lead isotopic data for the mine employees and controls plot in two distinct fields which are consistent with predicted isotopic patterns. Assuming retention of 10% of the ingested lead, then the increases seen in 206Pb represent intakes of between 0.9 and 15 mg, integrated over the years of exposure. The small amount of lead does not affect blood lead concentrations, but appears to be sufficient to be detectable with sensitive isotopic methods. Further studies, including those on urine, should be undertaken to confirm the veracity of the lead isotope method in monitoring exposure of uranium industry employees.

Blood lead changes during pregnancy and postpartum with calcium supplementation.

Pregnancy and lactation are times of physiologic stress during which bone turnover is accelerated. Previous studies have demonstrated that there is increased mobilization of lead from the maternal skeleton at this time and that calcium supplementation may have a protective effect. Ten immigrants to Australia were provided with either calcium carbonate or a complex calcium supplement (approximately 1 g/day) during pregnancy and for 6 months postpartum. Two immigrant subjects who did not conceive acted as controls. Sampling involved monthly venous blood samples throughout pregnancy and every 2 months postpartum, and quarterly environmental samples and 6-day duplicate diets. The geometric mean blood lead at the time of first sampling was 2.4 microg/dL (range, 1.4-6.5). Increases in blood lead during the third trimester, corrected for hematocrit, compared with the minimum value observed, varied from 10 to 50%, with a geometric mean of 25%. The increases generally occurred at 6-8 months gestation, in contrast with that found for a previous cohort, characterized by very low calcium intakes, where the increases occurred at 3-6 months. Large increases in blood lead concentration were found during the postpartum period compared with those during pregnancy; blood lead concentrations increased by between 30 and 95% (geometric mean 65%; n = 8) from the minimum value observed during late pregnancy. From late pregnancy through postpartum, there were significant increases in the lead isotopic ratios from the minimum value observed during late pregnancy for 3 of 8 subjects (p < 0.01). The observed changes are considered to reflect increases in mobilization of lead from the skeleton despite calcium supplementation. The identical isotopic ratios in maternal and cord blood provide further confirmation of placental transfer of lead. The extra flux released from bone during late pregnancy and postpartum varies from 50 to 380 microg lead (geometric mean, 145 microg lead) compared with 330 microg lead in the previous cohort. For subjects replete in calcium, the delay in increase in blood lead and halving of the extra flux released from bone during late pregnancy and postpartum may provide less lead exposure to the developing fetus and newly born infant. Nevertheless, as shown in several other studies on calcium relationships with bone turnover, calcium supplementation appears to provide limited benefit for lead toxicity during lactation.

Identification of sources of lead in children in a primary zinc-lead smelter environment.

We compared high-precision lead isotopic ratios in deciduous teeth and environmental samples to evaluate sources of lead in 10 children from six houses in a primary zinc-lead smelter community at North Lake Macquarie, New South Wales, Australia. Teeth were sectioned to allow identification of lead exposure in utero and in early childhood. Blood lead levels in the children ranged from 10 to 42 micro g/dL and remained elevated for a number of years. For most children, only a small contribution to tooth lead can be attributed to gasoline and paint sources. In one child with a blood lead concentration of 19.7 microg/dL, paint could account for about 45% of lead in her blood. Comparison of isotopic ratios of tooth lead levels with those from vacuum cleaner dust, dust-fall accumulation, surface wipes, ceiling (attic) dust, and an estimation of the smelter emissions indicates that from approximately 55 to 100% of lead could be derived from the smelter. For a blood sample from another child, > 90% of lead could be derived from the smelter. We found varying amounts of in utero-derived lead in the teeth. Despite the contaminated environment and high blood lead concentrations in the children, the levels of lead in the teeth are surprisingly low compared with those measured in children from other lead mining and smelting communities.

Mobilization of lead from human bone tissue during pregnancy and lactation--a summary of long-term research.

The skeleton is potential endogenous source of lead during pregnancy and lactation. We have undertaken a longitudinal investigation into the mobilization of lead from the human maternal skeleton to determine whether lead is mobilized from the maternal skeleton during pregnancy and lactation, and if so, when and how much is released. Subjects in the study were migrants to Australia (n=15) whose skeletal lead isotopic composition (endogenous lead) was different to that prevailing in the Australian environment (exogenous lead). This migrant cohort was compared with 6 multi-generational Australian controls. Biological and environmental samples were taken pre-pregnancy where possible, throughout pregnancy and postpartum for at least 6 months. Newly-born infants of the migrant and Australian mothers were monitored for 6 months. Blood lead concentrations for the migrant mothers ranged from 1.5 to 20 microg/dl (geometric mean 2.8) and for Australian mothers ranged from 1.9 to 4.3 microg/dl (geometric mean 2.9). There was minimal change in lead isotopic composition of the Australian pregnant controls although there were increases of approximately 40% in blood lead concentration in 3 of 6 cases during the postpartum period and from 0 to 12% in the other 3. In the migrant pregnant subjects, the geometric mean skeletal lead contribution to blood lead using the isotopic composition was approximately 33% (range 10-88%) for 14 subjects using a revised estimate for exogenous lead. Skeletal contribution to blood lead during the postpartum period was significantly greater than during pregnancy (P<0.001). The skeletal contributions to blood lead are higher and the changes are more consistent in those subjects who conceived within 100 days of arrival in Australia compared with those who conceived longer than 100 days. In the migrant subjects, changes in blood lead concentration during pregnancy and postpartum varied from subject to subject with an overall 20% increase; the increases during the postpartum period were greater than during pregnancy (P<0.001). It was estimated that the amount of maternal skeletal lead mobilized during pregnancy and transferred to the infant via cord blood averaged approximately 79%. The increased skeletal contribution to blood lead is attributed to a low daily calcium intake of approximately 500 mgCa/day, a condition which was present in both migrant and Australian subjects. An ongoing clinical trial is providing a new cohort with calcium supplements. A summary of other aspects of the study is included and covers: additional flux released from the skeleton during pregnancy and postpartum; XRF bone lead results; urinary excretion of lead during pregnancy and postpartum; dietary contribution to blood lead in female adults and children; comparison of rates of exchange of lead in blood of newly-born infants and mothers; relationships of lead in breast milk to lead in blood, urine and diet of the infant and mother; changes in blood lead after cessation of breastfeeding; urinary lead isotopes during pregnancy and postpartum indicate no preferential partitioning of endogenous lead into plasma; a comparison of some aspects of the nonhuman primate and human pregnancy studies.

Skeletal lead release during bone resorption: effect of bisphosphonate treatment in a pilot study.

There has been renewed interest in impacts on physiologic systems in the middle and older age groups, especially from fractures and hypertension. Increased blood lead (BPb) levels in postmenopausal females, which are thought to arise from bone demineralization, may also relate to other health effects including hypertension. Taking advantage of natural differences in lead isotope signature between Australian sources of lead and those from other countries, a 2-year pilot study was performed in premenopausal and postmenopausal females and male partners in which the subjects were administered a bisphosphonate, alendronate, for 6 months. The aim of the study was to determine how lead isotopes and lead concentrations changed in relation to bone remodeling processes. Premenopausal subjects were a woman (and male partner) from Bosnia and two women from Colombia. The postmenopausal subject was a woman from Russia. Her male partner and one man from Sri Lanka were included. Multigenerational Australian subjects were 2 perimenopausal women and 1 postmenopausal woman. Each subject had blood and urine samples collected for markers of bone turnover and for lead isotope studies monthly for 7-9 months before, for 3 months during, and for up to 6 months after treatment with alendronate to inhibit bone resorption. Each subject thus acted as his or her own control. As predicted, there were significant decreases in the lead isotope ratio, (206)Pb/(204)Pb, for the migrant subjects during treatment compared with the pretreatment period (p < 0.01). After cessation of treatment, an increasing isotope ratio for the postmenopausal subject (and older male partner) occurred later than for premenopausal subjects, indicative of prolonged efficacy of the alendronate for the older subjects. The average BPb concentrations in migrant subjects decreased by about 20% during the treatment compared with the pretreatment period (p < 0.01). To our knowledge, these are the first BPb concentrations reported over monthly to quarterly intervals for environmentally exposed adults over an extended period. The changes in lead isotopic composition and lead concentration are consistent with a decrease in bone resorption and associated mobilization of lead during alendronate therapy. Older subjects at risk of fractures may benefit from treatment with antiresorptive therapy, such as the potent bisphosphonates, with the added bonus of lower release of lead from bones and thus less risk of the potential adverse health effects of increased BPb levels.