Search

Newly born infants (n = 15) were monitored for 6 months after birth or for longer periods to evaluate the changes in isotopic composition and lead concentration in infants as compared with that in women from the same population groups and to determine the clearance rates of lead from blood in the infants. These data represent the first published results for serial blood sampling in a relatively large cohort of newly born infants. Blood lead concentrations decrease from the cord to samples taken at 60 to 90 days and then increase by amounts varying from negligible to 166%. In spite of concern about individual susceptibility to lead pharmacokinetics, changes in isotopic ratio followed a smooth decrease over time for 9 of the 11 infants born to migrant parents, and the patterns of variation were quite reproducible. Data for 2 of 4 infants born to multigenerational Australian parents exhibited little change in isotopic ratio over time, and in the other two cases, the changes were attributed to diet. The rate of exchange (t1/2) for the migrant infants of lead in blood derived from the mother during pregnancy and the lead from the current environment was calculated by using a linear function and ranged from 65 to 131 (91+/-19, mean+/-SD) days. The half-lives for the exchange of skeletal and environmental lead for 7 of the 8 women before significant mobilization of lead from the maternal skeleton ranged from 50 to 66 (59+/-6) days. One explanation for the longer half-lives for infants as compared with the mothers may be the proportionally higher contribution of current environmental (Australian) lead in the infants at parturition. Exchanges of lead in infants are more complex than for the adults, reflecting inputs from sources such as maternal skeletal lead during breast feeding.

A cohort of 15 immigrant females to Australia and 7 native Australian controls were monitored on a monthly basis with high-precision lead isotopic methods during gestation and for 6 months after pregnancy to determine the extent of lead mobilization from the maternal skeleton. Quarterly environmental samples of house dust, drinking water, urban air, gasoline, and a 6-day duplicate diet were also measured. The geometric mean blood lead concentration for the immigrant females on arrival in Australia was 3.0 microg/dl (range: 1.9 to 20 microg/dl), and for the Australian controls was 3.1 gm/dl (range: 1.9 to 4.3 microg/dl). During gestation and after pregnancy, blood lead concentrations varied, with mean individual changes of -14% to 83%. For the immigrant subjects, the percentage change in blood lead concentration was significantly greater during the postpregnancy period than during the 2nd and 3rd trimesters (p < 0.001). Skeletal contribution to blood lead, based on the isotopic composition for the immigrant subjects, increased in an approximately linear manner during pregnancy. The mean increases for each individual during pregnancy varied from 26% to 99%. Skeletal lead contribution to blood lead was significantly greater (p < 0.001) during the postpregnancy period than during the 2nd and 3rd trimesters. The contribution of skeletal lead to blood lead during the postpregnancy period remained essentially constant at the increased level of lead mobilization, although the duration of breastfeeding varied from 1 week to more than 6 months. The increased contribution of skeletal lead to blood lead during the postpregnancy period is attributed to increased mobilization of lead from maternal skeletal stores during lactation. The increased contribution of skeletal lead both during pregnancy and in the postpregnancy period is consistent with increased bone resorption, and may be associated with an inadequate calcium intake observed in quarterly 6-day duplicate diets. Mobilization of skeletal lead stores represents a potentially important source of perinatal lead intake and accumulation in the developing fetus. Only two subjects consumed dietary supplements for calcium, and their mobilization of lead from the skeleton to the blood was the lowest of all the subjects. These two subjects' use of calcium supplements may have reduced mobilization of skeletal mineral stores to supply the calcium needs of pregnancy and lactation. Calcium supplementation may be an important means of limiting fetal exposure to lead.

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.

Public health and medical recommendations on prevention of lead toxicity rely on use of blood lead concentrations to assess lead exposure and predict onset of adverse health effects. Blood lead levels have generally been thought to reflect recent environmental lead exposures. However, tissue lead stores are accumulated over a long time period (i.e., years). These tissue stores, primarily from bone, can be remobilized as part of both normal physiologic and pathologic processes. Although chemical analyses do not differentiate lead isotopes, mass spectrometric determinations can differentiate the quantities of stable lead isotopes present in particular samples (e.g., lead 207, lead 206, lead 204, and lead 208). Selected geographic locations may have distinct isotopic profiles. For example, on mainland Australia the 206Pb/204Pb ratios reported in both environmental lead sources and blood samples are typically less than 17.0. By contrast, stable lead isotope profiles in blood samples of adult women immigrating from Eastern Europe and the former Soviet Union usually have 206Pb/204Pb ratios greater than 17.5 and as high as 18.5 on entry into Australia. Longitudinal monitoring of blood samples to determine stable lead isotope profiles by mass spectrometry and chemical analyses of blood samples for total lead content were conducted over a 300-day period. These data show that between 45% and 70% of lead in blood comes from long-term tissue lead stores. Recognition that the predominant source of lead in blood was tissue stores rather than the contemporaneous environment should greatly modify recommendations on use of blood lead to monitor occupational or environmental interventions. In addition, internal biokinetics of lead, documented through presence of tissue lead in blood, underlie the long-term health risks of lead exposure. Transfer of lead to the fetus from maternal tissue stores represents a special area of concern.

Male rats were exposed to dietary Pb (200 ppm), Cd (50 ppm), or As (50 ppm) as arsenate either alone or in combination for 10 weeks using a 2 x 2 x 2 factorial design. Cd and As reduced weight gain even when differences in food intake were taken into account, and administration of both Cd and As depressed weight gain more than did either metal alone. Pb did not adversely affect food consumption or weight gain. Increased RBCs were observed after administration of Pb, Cd, or As, and more cells were observed when two or three metals were concomitantly administered. Despite increased numbers of circulating RBCs, hemoglobin and hematocrit were reduced, especially with the Pb-Cd combination. Analysis of blood chemistries showed normal ranges for blood urea nitrogen, creatinine, cholesterol, calcium, albumin, total protein, and bilirubin. Uric acid was increased by Pb, but not by Cd or As. SGOT activity was reduced by As alone. Serum alkaline phosphatase was reduced by either As or Cd but not Pb. Combinations of As and Cd did not further reduce the activity of this enzyme. Kidney weight and kidney weight/body weight ratios were increased by Pb alone, but Cd or As alone or in combination had no effect. Liver weight/body weight ratios were reduced in animals fed Cd. Kidney histology showed predominantly Pb effects, i.e., intranuclear inclusion bodies and cloudy swelling. Ultrastructural evaluation of kidneys from Pb-treated animals disclosed nuclear inclusion bodies and mitochondrial swelling. Concurrent administration of Cd reduced total mean bone and kidney Pb levels by 50% and 60%, respectively, and this was associated with a decrease in kidney intranuclear inclusions. Cd exposure also reduced renal, femur, and liver concentrations of Fe by 33%, 43%, and 63%, respectively, decreased femur Zn by 27%, but increased renal Zn by 20%. Administration of As produced mild swelling of tubule cell mitochondria, increased mean total renal Cu to 200% of control, and increased liver Fe by 44%. Dietary Pb produced increased urinary excretion of ALA and coproporphyrin. Dietary exposure to As caused increased urinary excretion of uroporphyrin and to a lesser extent coproporphyrin, whereas dietary Cd caused no significant changes in urinary levels of any of the porphyrins measured. Pb plus As produced an additive effect on coproporphyrin excretion but not that of ALA or uroporphyrin. These studies indicate that interactions between common toxic elements do occur and are characterized by alterations in both tissue trace metal levels and toxicity.