Michael J. Korsch

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.

Sources of lead in soil and dust and the use of dust fallout as a sampling medium

Abstract Pilot investigations using stable lead isotope and scanning electron microscopic analyses have been undertaken in different environments ranging from mining and smelting to urban in order to better understand the source of, and relationships between, soil and house dust. House dust is characterised by vacuum cleaner dust and/or surface wipes and compared with long-term dust (dust fall) accumulations over a > 3-month interval or with airborne particulates. Finer grain sizes of soils have lead concentrations from 2 to 9 times those measured in the bulk fractions. In Broken Hill isotopic ratios show that the major source of lead in soils is from the orebody, with rare examples containing lead from paint sources. In inner Sydney, soil lead values vary from 37 to 2660 ppm Pb in bulk samples and up to 3130 ppm in the finer fractions. The lead may be from diverse sources such as gasoline or paint. Finer fractions of vacuum cleaner dust from both Broken Hill and Sydney may contain up to three times the amount of lead measured in the bulk samples. In Broken Hill, the percentages by weight of total lead in the −250-μm fraction range from 11 to 51%. Bulk vacuum cleaner dusts from Broken Hill contain up to 4490 ppm Pb. Bulk vacuum cleaner dusts from inner Sydney contain up to 2950 ppm Pb. Isotopic variations in fractions of vacuum cleaner dust containing > 1000 ppm Pb from inner Sydney indicate that the lead in dust has come from different sources and such differences lessen the usefulness of analyses of bulk vacuum cleaner dust. Our results reinforce the importance of analysing the finer fraction of soil and house dust, especially those in the −150-μm (or even −100-μm) fraction for soils and the −100-μm fraction for vacuum cleaner dust. Dust-fall accumulations have many advantages over more conventional methods for estimating lead in house dust, such as vacuum cleaner dust or surface wipes. These advantages include: low cost; no power source required; can be set up by a technician; minimal inconvenience to householder (i.e., no power required, no noise, out of the way, a few minutes to set up and collect); integrates lead flux over a specific period; usually unbiased (in contrast to vacuuming or wipes where the householder may clean prior to a sampling visit); easy to ‘control’ by placement of other dishes in the same house. For Broken Hill, a strong correlation ( r = 0.95) was obtained between the isotopic composition of lead in blood and dust-fall accumulation.

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 (~ 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 μg/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 μg lead (geometric mean, 145 μg lead) compared with 330 μg 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.

Lead Bioavailability in the Environment of Children: Blood Lead Levels in Children Can Be Elevated in a Mining Community

Lower blood lead averages in mining communities, compared with other child exposure settings, e.g., innercity areas of the United States and smelter communities, have been attributed to lower bioavailability of lead to children in the mining areas. Direct supporting evidence of the lower bioavailability has, however, generally been lacking. Elevated blood lead levels for approximately 85% of children with > 10 micrograms/dl have been reported from the Broken Hill mining community in Australia. Lead isotope, optical, and scanning electron microscope analyses on the lead species from soils and dusts show them to be derived mainly from weathered ore body material. Solubility tests using 0.1M HCl on the -53 + 38 microns fraction of soil and dust show the lead species to have a high degree of bioavailability. Ingestion of soil and dust, either directly or via mouthing activity, is the main source and pathway for elevated blood lead in children from this community.

Source of lead in humans from Broken Hill mining community.

This paper documents the first precise lead isotope measurements for men, women and children from the same family in an attempt to determine the source of lead in their blood. The subjects reside in one of the worlds largest lead mining cities, Broken Hill, NSW, Australia. Biological and environmental samples have been compared using isotopic compositions and lead contents. Adult males have isotopic profiles (or compositions) which appear to be related to their occupations. Adult females have low blood leads (<10 μg dL−1) and their main source of lead is not from the mine dumps around which the city is built but probably from a mixture of petrol, food and perhaps water. The blood lead contents in children from 1 to 14 years old vary and are partly dependent on age. There is a moderate correlation of blood lead and isotopic compositions (r = 0.73) indicating that a significant component of blood lead derives from the mine dumps in children with elevated blood leads. Some children with blood leads <20 μg dL−1, however, also have a dominant component of mine lead in their blood

Windblown Lead Carbonate as the Main Source of Lead in Blood of Children from a Seaside Community: An Example of Local Birds as “Canaries in the Mine”

Background In late 2006, the seaside community in Esperance, Western Australia, was alerted to thousands of native bird species dying. The source of the lead was thought to derive from the handling of Pb carbonate concentrate from the Magellan mine through the port of Esperance, begun in July 2005. Concern was expressed for the impact of this process on the community. Objective This study was designed to evaluate the source of Pb in blood of a random sample of the community using Pb isotope ratios. Methods The cohort comprised 49 children (48 < 5 years of age) along with 18 adults (> 20 years of age) with a bias toward higher blood lead (PbB) values to facilitate source identification. Results Mean PbB level of the children was 7.5 μg/dL (range, 1.5–25.7 μg/dL; n = 49; geometric mean, 6.6 μg/dL), with four children whose PbB was > 12 μg/dL. The isotopic data for blood samples lay around two distinct arrays. The blood of all children analyzed for Pb isotopes contained a contribution of Pb from the Magellan mine, which for young children ranged from 27% up to 93% (mean, 64%; median, 71%). Subtraction of the ore component gave a mean background PbB of 2.3 μg/dL. Several children whose PbB was > 9 μg/dL and most of the older subjects have complex sources of Pb. Conclusions The death of the birds acted as a sentinel event; otherwise, the exposure of the community, arising from such a toxic form of Pb, could have been tragic. Isotopic data and mineralogic and particle size analyses indicate that, apart from the recognized pathway of Pb exposure by hand-to-mouth activity in children, the inhalation pathway could have been a significant contributor to PbB for some of the very young children and in some parents.

Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing.

In a pilot study to determine if zinc (Zn) from zinc oxide nanoparticles in sunscreen can penetrate human skin in vivo, nanoparticles (~30nm) of a stable isotope (52% (68)Zn enrichment) were incorporated into an essentially phytochemical-based formulation and applied to the backs of 3 human subjects twice daily for 5 days during the Southern Hemisphere winter. Blood and urine were collected prior to application and at regular intervals and up to 50 days. As observed in a larger outdoor trial following this pilot study but with a different formulation and with UV exposure: values of (68)Zn in blood continued to increase beyond the 5 day application phase with the highest measurement at 14 days after the first application; variable amounts of the (68)Zn tracer were observed in urine; and the amounts of extra Zn added to blood were small and indicate very low levels of absorption (minimal estimate <0.01% of the applied dose) through the skin. Reasons for differences in absorption detected in the stable isotope trials and previous investigations include: the sensitivity of the stable isotope method; the duration of the investigations; the number of applications of sunscreen formulation; in vitro methods with excised skin; lack of measurement of blood and urine; no skin flexing; and lack of UV exposure.

Stable lead isotope profiles in smelter and general urban communities: a comparison of environmental and blood measures

High-precision lead isotope ratios and lead concentrations have been compared statistically and graphically in women of child-bearing age (n = 77) from two smelter communities and one general urban community to evaluate the relative contributions to blood lead of tissue lead stores and lead from the contemporaneous environment (soil, floor dust, indoor airborne dust, water, food). Blood lead (PbB) contents were generally low (e.g. <10 μg dL−1). Statistically significant isotopic differences in blood and environmental samples were observed between the three cities although isotopic differences in blood for individual subjects living in close proximity (∼200 m radius) was as large as the differences within a city. No single environmental measure dominated the biological isotope profile and in many cases the low levels of blood lead meant that their isotopic profiles could be easily perturbed by relatively small changes of environmental exposure. Apportioning of sources using lead isotopes is possibly not feasible, nor cost effective, when blood lead levels are <5 μg dL−1. Interpretations based on statistical analyses of city-wide data do not give the same conclusions as when the houses are considered individually. Aggregating data from multiple subjects in a study such as this obscures potentially useful information. Most of the measures employed in this study, and many other similar studies, are markers of only short-to-medium integration of lead exposure. Serial sampling of blood and longer sampling times, especially for household variables, should provide more meaningful information.

Nd and Pb isotopic studies of an Archaean layered mafic-ultramafic complex, Western Australia, and implications for mantle heterogeneity

Abstract Nd and Pb isotopic ratios have been measured on the same samples from the Archaean layered Millindinna Complex in the western Pilbara Block of Western Australia. The Sm-Nd whole rock/mineral age is 2830 ± 20 Ma (2σ) and the initial 143 Nd 144 Nd ratio is 0.50892 ± 0.00002 ( ϵNd −0.7 ± 0.4). The dispersion in lead isotopic ratios is limited and the resulting Pb-Pb whole rock age is 2960 ± 20 Ma (2σ) with a calculated Mi of 8.3. Variations in calculated solTh U and initial 208 Pb 206 Pb ratios preclude a single source for this complex. Comparison with other Nd-Pb investigations of mafic/ultramafic complexes, particularly those in the time span from 2600–2900 Ma, reveals a trend from positive ϵNd and low μ (7.7–7.9) values in Ontario (Munro Township, Alexo, Newton) to negative ϵNd and higher μ values in the Suomussalmi, Millindinna and Stillwater Complexes. Although this trend could be the result of either mantle heterogeneity and/or crustal contamination, at the present time we favour crustal contamination.

Importance of monitoring family members in establishing sources and pathways of lead in blood

High precision lead isotope measurements were undertaken to establish the sources and pathways in blood and environmental samples of five families from the Broken Hill lead mining community, New South Wales, Australia. The five families were selected from 27 families investigated to illustrate the different sources and pathways of lead into blood and the importance of monitoring the whole family. The results illustrate that although the major source of lead is from the orebody, paint and petrol can be significant contributors to both house dust and blood leads. The results also show that the sources and pathways can be from the fathers occupation and hence monitoring of families is important, especially in high risk locations. In two cases, the elevated blood leads in the children did not derive from their current residence but from other residences in the community.