Brian L. Gulson

Pregnancy increases mobilization of lead from maternal skeleton

The question of the extent of lead mobilization from the maternal skeleton during pregnancy and lactation is one of the most outstanding problems of lead toxicity. We have undertaken a longitudinal cohort study in an urban environment of European female immigrants of child-bearing age (18 to 35 years) to Australia whose skeletal lead isotopic composition has been determined to be different from that in their current environment. The cohort was to consist of 100 immigrants anticipated to provide 20 pregnant subjects who would be compared with two groups of control subjects: a matched immigrant nonpregnant control group and second-generation Australian pregnant control subjects. Pregnant subjects also serve as their own controls for a comparison of changes during gestation with those before conception. High-precision lead isotopic compositions and lead concentrations are measured in maternal blood and urine prenatally, monthly during gestation, and postnatally for 6 months; they are also measured in infant blood and urine for 6 months; environmental measures are sampled quarterly for 6-day duplicate diet, house dust and water, and urban air and gasoline. Because of continuing public health concerns about lead exposure, interim findings from this cohort are being reported. To date there have been 13 conceptions in immigrant subjects, with 7 births, in addition to 3 conceptions in the Australian control group, with 2 births. PbBs have been generally low, with a geometric mean of 3.0 microg/dl, and have ranged from 1.9 to 20 microg/dl. Increases in PbB of approximately 20% during pregnancy have been detectable even in subjects with low blood lead levels. The skeletal contribution to blood lead level, based on isotopic measurements, has exhibited a mean increase (and standard deviation) of 31% +/- 19% with a range from 9% to 65%. Earlier studies that used lead concentrations only have suggested that blood lead levels increased only during the second half of pregnancy. This increase in blood lead levels has also been observed in the present study. However, in two subjects the increases in total blood lead were also detected in the first 2 months of pregnancy. Changes in isotopic composition and blood lead during gestation for Australian pregnant controls were negligible. The ratio of cord/maternal blood lead levels varied from 0.54 to 1.05, and the ratio for the isotopic composition was 0.993 to 1.002. Results of this study confirm that lead is mobilized from skeletal stores at an accelerated rate during pregnancy and is transferred to the fetus. These results also show that mobilization from long-term stores (i.e., bone) contributes significantly to blood lead levels during pregnancy. Furthermore, exposure of the fetus to lead during pregnancy has implications for interpretations of neurobehavioral disorders attributed to only postnatal exposure. Even after 800 days of residence in Australia, the contribution of European skeletal lead to blood lead in nonpregnant subjects can be on the order of 50%, but the current PbB may give no indication of the former high skeletal lead burden.

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.

Use of lead isotopes in soils to identify the source of lead contamination near Adelaide, South Australia.

Soil profiles from an urban-rural transect near Adelaide, South Australia, have been analyzed by using lead isotopes as a discriminant for the source of soil lead. Analyses of the top 10 cm of soil profiles taken from sites up to 50 km from Adelaide show that this surface horizon mainly contains Precambrian lead, such as that found in the Broken Hill or Mount Isa deposits. There is also a small amount of younger lead present, similar to that derived from Missouri and young Canadian deposits. Both types of lead are used in the manufacture of tetraethyllead for Adelaide gasoline. Natural soil lead, derived from parent rock, occurs throughout the profiles; however, it is only a relatively minor component in the surface horizons but is the major component a t depths greater than 30-40 cm. Assessment of the data suggests that orchard sprays, power stations, and smelters are not the main source of lead in the surface horizons-rather, contamination derived from tetraethyllead from gasoline is indicated.

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.

Petrogenesis of Late Cenozoic volcanic rocks from the Taupo Volcanic Zone, New Zealand, in the light of new lead isotope data

Abstract Lead isotopes and U Pb concentrations have been measured for a wide range of volcanic rocks from the Taupo Volcanic Zone (TVZ), New Zealand. Combined geochemical and isotope plots suggest that the majority of mafie-intermediate volcanic rocks result from contamination (AFC) of primitive basalt by Mesozoic metasedimentary basement. Lead isotope data indicate that some previously published petrogenetic models require modification, notably in the choice of parental magma and in the composition and proportion of the crustal assimilant. Evidence is also presented to show that the voluminous ignimbrites and rhyolites of the TVZ could be derived by melting of early-formed andesites (with accompanying minor crustal contamination) and rule out previous models such as direct melting of Mesozoic basement rocks or contamination of mantle derived melts.

History of Lead Exposure in Children Revealed from Isotopic Analyses of Teeth

A pilot study to evaluate the efficacy of using high precision lead isotopes as an indicator of previous lead exposure in children was undertaken on deciduous teeth from 10 children in a lead-mining city. The present study illustrates the applicability of the method and provides data from two subjects who had different exposure to lead during early childhood. Teeth were examined by slicing the crowns into upper and lower sections and/or by selective dissolution with different mineral acids. Different exposures to mine lead and other sources, such as food, water, air (gasoline), are readily detected in any tooth from an individual.

Identification of secondary lead sources in the air of an urban environment

High precision lead isotopic data have been measured from particulates deposited on filters from two suburbs of Sydney (NSW, Australia) and gasoline from two main brands to evaluate the source of lead in air following the phasing out of leaded gasoline in Sydney in 1986 and a 25% reduction of lead in leaded gasoline in 1994. These measures have resulted in a 75% reduction of lead in Sydney air nowadays. Despite these positive figures, our results indicate that gasoline still accounts for more than 90% of the lead in the atmosphere of this city. However, when compared with an earlier investigation carried out in the period 1979–1981, our data show that a background source with a 206Pb/204Ph isotopic ratio higher than petrol has become detectable. We have used a best fitting mathematical procedure to identify the isotopic ratio and percentage contribution of this source to the air. The values that we have obtained are ∼ 18.2 and ∼7%, respectively, for the 206Pb204Pb ratio and the percentage contribution. Several local background sources are considered, including natural lead from soils, wood burning, coal burning in power stations and aircraft profellants. We also draw attention to the similarity of the background isotopic composition in Sydney air aid isotopic ratios measured in snows of Antarctica.

Identification of historical lead sources in roof dusts and recent lake sediments from an industrialized area: indications from lead isotopes

X-ray fluorescence and stable lead (Pb) isotopic analyses have been undertaken on dusts, known from microscopic investigation to contain significant quantities of industrially- and urban-derived particulate matter, present in the roof cavities of houses in the Illawarra region (N.S.W., Australia), with the objective of examining the historic record of Pb pollution. All investigated houses contained in excess of 250 micrograms g-1 Pb, with dwellings close to a copper smelter, in a large industrial complex including a major steelworks, containing higher (> 2500 micrograms g-1) Pb concentrations. The isotopic composition in the dusts, expressed here as 206Pb/204Pb, is relatively constant at 17.0, irrespective of dwelling age or distance from the industrial complex. Contamination of the dusts by Pb sourced from paint cannot explain the isotopic uniformity of the dust samples. Isotopic modelling indicates that the dusts contain Pb derived from the copper smelter, gasoline-air Pb and a minor contribution from coal-utilising sources. Lead loading was also investigated in the adjacent lagoon, which acts as a natural sink for particulate matter in the Illawarra region. Isotopic data and modelling indicate that one natural and four anthropogenic sources contribute to the Pb burden of this lagoon. The natural source consists of Permian rocks cropping out in the catchment area which have a 206Pb/204Pb of approximately 18.7. The suggested anthropogenic sources are an old disbanded base-metal (Pb) smelter (206Pb/204Pb approximately 16.2-16.3), the copper smelter (206Pb/204Pb approximately 17.9), gasoline-air derived Pb (206Pb/204Pb approximately 16.4-16.5) and industries utilising coal, for example the recently closed thermal coal-fired power station (206Pb/204Pb approximately 18.9). The relative contributions of the base-metal (mainly lead) smelter and gasoline-air Pb in the sediment can only be partly assessed due to the isotopic similarity of these sources. Likewise the natural background and coal source (e.g. power station) contributions can only be estimated from historical data. Age estimations for sediment cores, using 137Cs, provide some control on these assessments. Near surface sediments in the lagoon have a relatively constant 206Pb/204Pb of 17.6-17.7, irrespective of sample location. Isotopic calculations, together with records of particulate matter pollution emissions, indicate a link between the Pb in roof dusts (206Pb/204Pb approximately 17.0) and Pb contamination of the near surface (upper 20 cm) lagoonal sediments via a homogeneous, non-unique source of lead whose isotopic composition closely matches that of the dusts. Over the last 5 decades, atmospheric fallout of Pb-bearing particulate matter appears to have been the dominant pathway for addition of Pb to the lagoon and dwellings in the Illawarra region.

Percutaneous absorption of inorganic lead compounds

In vivo experiments with the stable lead isotope, 204Pb, have confirmed that inorganic lead compounds can be absorbed through the skin. Three different analytical techniques--thermal ionization mass spectrometry, inductively coupled plasma mass spectrometry and anodic stripping voltammetry--showed that lead, as lead nitrate or lead acetate, was rapidly absorbed through the skin and detectable in sweat, blood and urine within 6 h of skin application. Of the 4.4 mg of lead applied to the skin in one experiment, 1.3 mg was absorbed within 24 h. Initial rapid uptake was probably via sweat glands and hair follicles, followed by slower absorption via the transepidermal route. While increases in 204Pb concentration and abundance were observed, no increase in total lead in blood or urine was found. It is possible that the physicochemical form of skin-absorbed lead partitions strongly into extracellular fluid, but has a low affinity for erythrocytes. There was no significant difference in uptake of lead into erythrocytes (in vitro) from normal saline, synthetic sweat or sauna sweat. Ultrafiltration of sweat showed that up to 70% of lead in sweat was associated with > 30,000 MW particles. It is possible that percutaneous absorption of lead could contribute significantly to lead body burden, particularly from occupational exposure to lead in dust. Moreover, because lead absorbed through the skin was only just detectable in blood, and blood lead is the main criterion by which industry determines exposure, skin-absorbed lead may remain undetected.