Abstract  The Port Pirie Cohort Study is the first study to monitor prospectively the association between lifetime blood lead exposure and the prevalence of emotional and behavioral problems experienced by children. Lead exposure data along with ratings on the Child Behavior Checklist were obtained for 322 11--13-year-old children from the lead smelting community of Port Pirie, Australia. Mean total behavior problem score (95% confidence interval (CI)) for boys whose lifetime average blood lead concentration was above 15 ug/dl was 28.7 (24.6--32.8) compared with 21.1 (17.5--24.8) in boys with lower exposure levels. The corresponding mean scores (95% CI) for girls were 29.7 (25.3--34.2) and 18.0 (14.7--21.3). After controlling for a number of confounding variables, including the quality of the child's HOME environment (assessed by Home Observation for Measurement of the Environment), maternal psychopathology, and the child's IQ, regression modeling predicted that for a hypothetical increase in lifetime blood lead exposure from 10 to 30 ug/dl, the externalizing behavior problem score would increase by 3.5 in boys (95% CI 1.6--5.4), and by 1.8 (95% CI -0.1 to 11.1) in girls. Internalizing behavior problem scores were predicted to rise by 2.1 (95% CI 0.0--4.2) in girls but by only 0.8 (95% CI -0.9 to 2.4) in boys.

Abstract  An increase in erythrocyte protoporphyrin (EP) is one of the most useful indicators of adverse biological response to lead exposure. A nonlinear mathematical model relating EP to blood lead concentration (PbB) was fitted to data in a sample of 1677 U.S. children (ages 2-6 years) in the Second National Health and Nutrition Examination Survey (NHANES II). Iron status was defined by percentage transferrin saturation (PTS). The dose-response curves for EP vs PbB increased systematically with decreasing PTS, largely due to decrease of a parameter proportional to red cell lead-holding capacity with decreasing PTS.

Abstract  Lead has been shown to be associated with elevated blood pressure in males in the NHANES II survey and in numerous other studies. This study confirms the association in males aged 20 to 74 and documents a significant, although weaker, association in females as well. Prospective cardiovascular disease studies such as the Framingham study indicate that increases in blood pressure should be associated with increased risk of cardiovascular disease. Using electrocardiogram data from NHANES II, this study confirms the expected association of lead with left ventricular hypertrophy (p less than 0.01). Such an association with permanent cardiovascular changes adds weight to the blood pressure findings. The logistic risk coefficients from the Framingham study can be combined with the study's association between lead and blood pressure to examine its implication for more serious outcomes. The results suggest that a halving of the population mean blood lead level would reduce myocardial infarctions by approximately 24,000 events per year and incidence of all cardiovascular disease by over 100,000. These numbers suggest a small attributable risk compared to the vast incidence of cardiovascular disease in the U.S., but a large attributable risk compared to most environmental toxins. Several biological mechanisms have been identified, with different implications for the use of bone lead as an exposure measure.

Abstract  In 14 retired lead workers, followed for over 18 years after end of exposure, repeated analyses of lead levels in finger bone by an in vivo X-ray fluorescence method revealed a decrease of lead concentration. The data were analysed using an exponential retention model. For the whole group the biological half-time was 16 (asymptotic 95% confidence interval, CI 12,23) years. The median of the estimated bone lead levels at the end of exposure was 85 micrograms.g-1 above the "background" (3 micrograms.g-1). A simultaneous follow-up of blood lead levels displayed a decrease, which could be described by a tri-exponential retention model with group half-times of 34 (CI 29,41) days, 1.2 (CI 0.9,1.8) years, and 13 (CI 10,18) years, respectively. The median of the estimated blood lead levels at the end of exposure for the three components were 0.49, 0.61, and 1.1 mumol.l-1 above the "background" (0.38-0.56 mumol.l-1), respectively. The well-documented decrease of lead exposure in the general population over the years, urged the use of a decreasing "background" of blood lead during the time of the study. The slowest of the three components represented the skeleton (probably mainly cortical bone), as did mainly probably also the intermediate one (trabecular bone). The data show the rather slow turnover of lead in the skeleton, the usefulnes of in vivo skeletal lead measurements as a long-term exposure index, and the importance of bone as a source of "endogenous" lead exposure.

Abstract  Triethyllead and the total lead were determind in the tissues in three acute fatal cases of tetraethyllead poisoning. In each case high concentrations of triethyllead were found (2.0–22.0 mgrg/g) being of the same range as the total lead content. The triethyllead content of the tissues showed a slightly decreasing trend with the length of the surviving period. High levels of the total lead were also found in blood (3.3–4.0 mgrg/ml), and urine (0.4–8.0 mgrg/ml), the highest values being observed after EDTA treatment. The triethyllead content in blood and urine was much lower.

Abstract  The biotic ligand model (BLM) is a mechanistic approach that greatly improves our ability to generate site-specific ambient water quality criteria (AWQC) for metals in the natural environment relative to conventional relationships based only on hardness. The model is flexible; all aspects of water chemistry that affect toxicity can be included, so the BLM integrates the concept of bioavailability into AWQC-in essence the computational equivalent of water effect ratio (WER) testing. The theory of the BLM evolved from the gill surface interaction model (GSIM) and the free ion activity model (FIAM). Using an equilibrium geochemical modeling framework, the BLM incorporates the competition of the free metal ion with other naturally occurring cations (e.g., Ca2+, Na+, Mg2+, H+), together with complexation by abiotic ligands [e.g., DOM (dissolved organic matter), chloride, carbonates, sulfide] for binding with the biotic ligand, the site of toxic action on the organism. On the basis of fish gill research, the biotic ligands appear to be active ion uptake pathways (e.g., Na+ transporters for copper and silver, Ca2+ transporters for zinc, cadmium, lead, and cobalt), whose geochemical characteristics (affinity = log K, capacity = Bmax) can be quantified in short-term (3-24 h) in vivo gill binding tests. In general, the greater the toxicity of a particular metal, the higher the log K. The BLM quantitatively relates short-term binding to acute toxicity, with the LA50 (lethal accumulation) being predictive of the LC50 (generally 96 h for fish, 48 h for daphnids). We critically evaluate currently available BLMs for copper, silver, zinc, and nickel and gill binding approaches for cadmium, lead, and cobalt on which BLMs could be based. Most BLMs originate from tests with fish and have been recalibrated for more sensitive daphnids by adjustment of LA50 so as to fit the results of toxicity testing. Issues of concern include the arbitrary nature of LA50 adjustments; possible mechanistic differences between daphnids and fish that may alter log K values, particularly for hardness cations (Ca2+, Mg2+); assumption of fixed biotic ligand characteristics in the face of evidence that they may change in response to acclimation and diet; difficulties in dealing with DOM and incorporating its heterogeneity into the modeling framework; and the paucity of validation exercises on natural water data sets. Important needs include characterization of biotic ligand properties at the molecular level; development of in vitro BLMs, extension of the BLM approach to a wider range of organisms, to the estuarine and marine environment, and to deal with metal mixtures; and further development of BLM frameworks to predict chronic toxicity and thereby generate chronic AWQC.

Abstract  The toxicity of all atomically stable metals in the periodic table, excluding Na, Mg, K, and Ca, was measured in one-week exposures using the freshwater amphipod Hyalella azteca in both Lake Ontario, Canada, and soft water (10% Lake Ontario). Metals were added as atomic absorption standards (63 metals), and also as anion salts for 10 metals. Lethal concentrations resulting in 50% mortality (LC50s) were obtained for 48 of the metals tested; the rest were not toxic at 1,000 Ág/L. The most toxic metals on a molar basis were Cd, Ag, Pb, Hg, Cr (anion), and Tl, with nominal LC50s ranging from 5 to 58 nmol/L (1 to 58 nmol/L measured). These metals were followed by U, Co, Os, Se (anion), Pt, Lu, Cu, Ce, Zn, Pr, Ni, and Yb with nominal LC50s ranging from 225 to 1,500 nmol/L (88û1,300 nmol/L measured). Most metals were similarly or slightly more toxic in soft water, but Al, Cr, Ge, Pb, and U were >17-fold more toxic in soft water; Pd was less toxic in soft water. Atomic absorption (AA) standards of As and Se in acid had similar toxicity as anions, Sb was more toxic as the AA standard, and Cr and Mn were more toxic as anions. One-week LC50s for H. azteca correlate strongly with three-week LC50s and three-week effect concentrations resulting in 50% reduction in reproduction (EC50s) in Daphnia magna.

Abstract  Metallothionein, a protein of small molecular weight, isolated from equine renal cortex contains 2.9% of cadmium, 0.6% of zinc, and 4% of sulfur. The protein, homogeneous on ultracentrifugation, but containing minor impurities on electrophoresis, does not absorb radiation at and near 280 m'mu', corresponding to a very low content of aromatic amino acids. A large number of cysteine residues account for the high sulfur content. The stoichiometry between titratable --SH groups and metal atoms, the displacement of the metals by --SH specific agents, and the selective removal of zinc and cadmium by hydrogen ions, all suggest isomorphous binding of the two metals to the protein through mercaptide linkages. Although the biological function of metallothionein is not known thus far, the specific association of cadmium with this macromolecule suggests a biological role of this cadmium-containing protein.

Abstract  We report associations between serial measures of blood lead and intelligence in children age 10–12 years, half heavily exposed to lead from the prenatal period onward, and half relatively unexposed. For a subsample, we examine bone lead-IQ associations, comparing them with blood lead associations. Both blood and bone lead levels were associated with intelligence decrements, small relative to the contribution of social factors. For each doubling of Tib-Pb, Full Scale, Performance, and Verbal IQ decreased by an estimated 5.5, 6.2, and 4.1 points, respectively. Bone lead-IQ associations were stronger than those for blood lead, which nonetheless provide robust analogues. Current BPb, easy to obtain, provides a useful means for assessing Pb exposure/IQ associations.

Abstract  Aims: Chronic exposure to lead results in sustained hypertension in humans and experimental animals. We investigated the possible role of reactive oxygen species (ROS) and their impact on DNA damage in lead-induced hypertension. Further the effect of short-term supplementation of vitamin C is also demonstrated. Methods: Male Wistar rats were treated with either lead acetate (100 ppm) alone or lead acetate plus vitamin C (20 mg/rat/day). The control rats were fed regular rat chow. Blood pressure, antioxidants, total antioxidant status as measured by ferric-reducing antioxidant power, nitric oxide (NO) metabolites, malondialdehyde (MDA) and 8-hydroxy 2-deoxyguanosine were determined after 0, 1, 2 and 3 months. Results: The lead-exposed group showed a significant rise in blood pressure, lipid peroxidation (MDA) and a substantial oxidative damage to the DNA. A significant fall in NO metabolites, total antioxidant levels and ferric-reducing antioxidant power was also observed in this group. Concomitant administration of vitamin C ameliorated hypertension, normalized NO levels and abrogated lipid peroxidation. Also, it completely prevented oxidative damage to the DNA. Conclusions: These findings point to enhanced ROS-mediated inactivation and sequestration of NO which can potentially contribute to hypertension, lipid peroxidation, reduced antioxidant status and oxidative DNA damage. The beneficial effects of vitamin C on these parameters support the role of increased ROS activity in the pathogenesis of these abnormalities in this model.

Abstract  The pattern of blood lead during pregnancy was investigated in a cohort of 195 women who, between October 1992 and February 1995, entered prenatal care at Magee-Womens Hospital in Pittsburgh, Pennsylvania, by week 13 of pregnancy. Blood was drawn as many as five times, once in each of the first two trimesters and a maximum of three times in the third trimester. Blood lead determinations were made by atomic absorption spectrophotometry. Potential sources or modifiers of lead exposure were collected by interviews, including sociodemographic, pregnancy history, occupational, and lifestyle data. Results confirmed a previously reported U-shaped curve in blood lead concentration during pregnancy as well as findings that blood lead levels increase with age, smoking, lower educational level, and African-American race and decrease with history of breastfeeding and higher intake of calcium. Additionally, interactions were found between time since last menstrual period and both maternal age and calcium. Specifically, older mothers showed steeper increases in blood lead concentrations during the latter half of pregnancy than did younger mothers, and intake of calcium had a protective effect only in the latter half of pregnancy, an effect that became stronger as pregnancy progressed. These findings provide further evidence that lead is mobilized from bone during the latter half of pregnancy and that calcium intake may prevent bone demineralization.

Abstract  BACKGROUND: Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR). OBJECTIVE: To develop an equation to predict GFR from serum creatinine concentration and other factors. DESIGN: Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease. PATIENTS: 1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample. METHODS: The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample. RESULTS: To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively. CONCLUSION: The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.

Abstract  We report 208Pb/207Pb and 206Pb/207Pb ratios for 1001 duplicate diets collected from mothers and children, 1304 samples of house dust and hand wipes, and 64 samples of aerosols that were taken in Omaha, Nebraska, during the period from 1990 to 1997. A plot of 208Pb/207Pb versus 206Pb/207Pb for the dust and hand wipes indicates that they contain lead from ores mined in Idaho, Missouri, and Mexico. The absence of lead from Utah suggests that this mixture is not representative of the whole country. The lead in the aerosols has a narrower range of isotope ratios and resembles aerosols collected elsewhere in the United States. Most dietary collections contain a large component of house dust. Some, especially those from infants, are dominated by uranogenic lead with high 206Pb/207Pb ratios. Its source is taken to be calcium-supplemented food where the calcium is derived from limestone. Another source of lead is thorogenic and is ascribed to lead in tin coatings. Agricultural lead, whether from soil (estimated from recently published analyses of sedimentary materials), fertilizer, or agricultural lime, could not be unambiguously identified in the diets. Lead derived from aerosols, if present at all, is insignificant.

Abstract  The aim of this study was to examine the effects of prenatal and postnatal chronic exposure to mercury (Hg), polychlorinated biphenyls (PCBs) and lead (Pb) on the neuromotor development of preschool children. The study population consisted of 110 preschool Inuit children from Nunavik (Canada). Blood Hg, PCBs and Pb concentrations were measured at birth (cord blood) and at the time of testing. Gross motor functions were evaluated and a neurological examination was performed. Fine neuromotor performance was assessed using quantitative measures of postural hand tremor, reaction time, sway oscillations, as well as alternating and pointing movements. Potential covariates were documented including demographic and familial characteristics, other prenatal neurotoxicants (alcohol, tobacco) and nutrients (selenium (Se), Omega-3 polyunsaturated fatty acids (n-3 PUFA)). Hierarchical multivariate regression analyses were performed, controlling for significant covariates. Gross motor development was not linked to prenatal exposures. However, significant associations were observed between blood Pb concentration at testing time and changes in reaction time, sway oscillations, alternating arm movements and action tremor. For some of these outcomes, neuromotor effects of Pb exposure are observed at blood concentrations below 10 μg/dl. Negative effects of PCBs on neuromotor development were not clearly observed, neither were the potential beneficial effects of n-3 PUFA and selenium. Tremor amplitude was related to blood Hg concentrations at testing time, which corroborate an effect already reported among adults.

Abstract  Lead (Pb) affects elements of humoral and cell-mediated immunity, and diminishes host resistance to infectious disease. Evidence is presented supporting a hypothesis of Pb-induced immunosuppression stemming from altered fatty acid metabolism, and mediated by eicosanoids and macrophages (M0). Chronic Pb exposure increases the proportion of arachidonate (ArA) among fatty acids in lipid from avian tissues, and this change provides precursors for eicosanoids, the oxygenated derivatives of ArA that mediate M0 acute inflammatory response. In the current study, we showed that the concentration of ArA in phospholipids of M0 elicited from turkey poults fed 100 ppm dietary Pb acetate was twice that of controls. In vitro production of eicosanoids by these M0 was substantially increased, and this effect was most pronounced following lipopolysaccharide stimulation: prostaglandin F2alpha was increased 11-fold, thromboxane B2 increased threefold, and prostaglandin E2 increased by 1.5 times. In vitro phagocytic potential of these M0 was suppressed, such that the percentage of M0 engulfing sheep red blood cell (RBC) targets was reduced to half that of control M0. In vivo susceptibility of Pb-treated and control birds to Gram-negative bacteria challenge was also evaluated. The morbidity of chicks inoculated with Salmonella gallinarum and fed either control or 200 ppm Pb acetate-supplemented diets was similar, except early in the course of the disease when mortality among Pb-treated birds was marginally greater. In these studies, effects of Pb that could influence immunological homeostasis were demonstrated for M0 metabolism of ArA, for production of eicosanoids, and for phagocytosis. There was also the suggestion that these in vitro indices of immune function are related to in vivo disease resistance.

Abstract  Lead, a ubiquitous environmental contaminant, has been shown to modulate various functions of the immune system and decrease host resistance to infectious disease. However, limited information is available concerning the direct effects of lead on the host immune response to an infectious agent after developmental exposure. The current study utilized chickens to examine the effect of embryonic lead exposure on immune and cellular responses during viral challenge. Sublethal doses of lead were introduced into fertilized Cornell K Strain White Leghorn chicken eggs via the air sac at day 5 or day 12 of embryonic development (designated as E5 and E12, respectively). Four-week-old female chickens were inoculated with infectious bronchitis virus (IBV) strain M41. Antibody titer to IBV, delayed-type hypersensitivity (DTH) response against bovine serum albumin (BSA), the absolute number and percentage of leukocyte subpopulations, and interferon-? (IFN-?)-like cytokine production by splenocytes were evaluated at 5û6 weeks of age. While antibody response to IBV in juvenile chicks was unaffected by the in ovo lead exposure, IFN-?-like cytokine production by splenocytes was significantly depressed following lead exposure at both developmental stages. In contrast with this pattern, the DTH response against BSA was unaffected following E5 exposure, but was significantly decreased after E12 exposure to lead. These changes were similar to those previously reported in chickens not exposed to IBV. While lead exposure at E5 induced significant changes in the percentage of circulating heterophils at 1 day postinfection (dpi), lead did not cause any change in relative leukocyte counts after E12 exposure. At 7 dpi, E5 lead exposure resulted in decreased absolute number and percentage of circulating lymphocytes, while total leukocyte counts, and the absolute number and percentage of circulating monocytes and heterophils were significantly reduced in E12 lead-exposed chickens. These results suggest that low-level exposure to lead has a direct effect on the developing chicken immune system, which is evident even during a postnatal infection. Furthermore, some of the changes were observed only when chicks were stressed by the viral infection. It appears that lead exposure during different stages of embryonic development is likely to result in different immunotoxic outcomes in juveniles.

Abstract  Macrophages (M phi) can be induced to produce nitric oxide (NO), which has been suggested to be important for macrophages to exercise various functions. We have previously reported that an environmental toxicant, lead (Pb), can significantly inhibit NO production by murine splenic M phis. Herein, eight additional metal ions, gold (Au), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), and zinc (Zn), were assessed. In addition to Pb, Hg and Cd significantly suppressed NO production by cytokine (interferon-gamma and tumor necrosis factor-alpha)-stimulated murine M phis. Au and Cu also were inhibitory, but less than Pb, Hg, and Cd. In contrast, Cr and Zn were not modulatory, and Ni and Co significantly enhanced NO production by cytokine-stimulated M phis. The enhancement by Ni and Co was inhibited by the arginine analog N-monomethylarginine. The metals showed different activating/inhibiting profiles when added to a cell-free (activated M phi lysate) NO-producing-system in which inducible NO synthase (iNOS) is already expressed. Cr, Cu, Pb, and Zn moderately suppressed iNOS, which suggests that they may directly modify enzyme or cofactor activity. Cd, Hg, Mg, Ni, or Co did not produce any significant effect on NO production by the cell-free system. Inhibition of NO production by Pb-exposed M phis was not due to decreased expression of iNOS nor limited to its modest direct inhibition of iNOS; thus, other mechanism(s) must be accountable for the efficient Pb-induced inhibition of NO production by M phi. Ni or Co did induce a substantial increase of iNOS protein. Overall, these observations provide additional insight into the means by which metals via inhibition or enhancement of NO production may be pathogenic, by suppression of defense mechanisms or induction of hypersensitivity, respectively.

Abstract  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.

Abstract  OBJECTIVES: The purpose of this study was to monitor blood lead in a northern Swedish cohort of mothers and children during pregnancy and at birth. METHODS: Blood lead was analyzed during pregnancy and in the umbilical cords of 290 women living near a smelter and in 194 control subjects. RESULTS: During pregnancy, there were statistically significant overall increases in blood lead concentrations by 20% and 15% in the smelter and reference areas, respectively. Mean maternal blood lead concentrations at delivery were 0.15 mumol/L (3.11 micrograms/dL) in the smelter area and 0.13 mumol/L (2.69 micrograms/dL) in the control area. Umbilical cord blood lead levels were 80% to 87% of the maternal levels. Blood lead levels were influenced by place of residence, employment at the smelter, smoking, and wine consumption. Maternal serum calcium levels decreased during pregnancy and were significantly lower than those of the newborns. CONCLUSIONS: An increase in blood lead concentrations was found during pregnancy, despite increased blood volume and unchanged or decreasing environmental lead levels. The mobilization of lead from bone during pregnancy may explain the increase.

Abstract  To investigate associations between the timing of lead (Pb) exposure on early intelligence, we examined the results of psychometric evaluations at ages 3, 4, 5, and 7 years, from 442 children whose mothers were recruited during pregnancy from a smelter town and a non-lead-exposed town in Yugoslavia. We compared the relative contribution of prenatal blood lead (BPb) with that of relative increases in BPb in either the early (0û2 years) or the later (from 2 years on) postnatal period to child intelligence measured longitudinally at ages 3 and 4 (McCarthy GCI), 5 (Wechsler Preschool and Primary Scale of Intelligence-Revised, WPPSI-R IQ), and 7 (Wechsler Intelligence Scale for Children-version III, WISC-III IQ), controlling for: Home Observation for Measurement of the Environment (HOME) quality; maternal age, intelligence, education, and ethnicity; and birthweight and gender. Elevations in both prenatal and postnatal BPb were associated with small decrements in young children's intelligence.

Abstract  Average concentration of Pb in atmospheric air particulates in different suburbs of Mumbai was studied for almost a decade and its spatial and temporal profiles are discussed in relation to emission sources. In general the concentration of Pb in all the residential suburban atmosphere is well below the Central Pollution Control Board (CPCB, 1994) prescribed limit of 1.5 microg m(-3) barring a few exceptions for some residential/industrial sites, such as those of Thane and Kurla scrap yards. The correlation between blood lead of children and air lead reveals that the blood Pb level in children could increase by 3.6 microg dl(-1) for an incremental rise of 1.0 microg Pb m(-3) of air. The temporal profile of air Pb values indicates a decreasing trend in residential suburbs (Khar: 1984, 0.39 microg m(-3); 1996, 0.17 microg m(-3)) as well as in suburban residential areas with low traffic (Goregaon: 1984, 0.53 microg m(-3); 1996, 0.30 microg m(-3)).

Abstract  An oligoclonal utilization of V"beta" 's has been reported for pathogenesis of several autoimmune diseases, anti-tumorigenic activity, and superantigen-regulation of thymic T cell development. Altered ratios of Th1 and Th2 cells also are observed in immunodysregulations, leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant immunity that could culminate with an autoimmune disease. Lead (Pb) and mercury (Hg) are known pollutants with immunodisrupting activities; Hg is known to cause autoimmune glomerulonephritis. Both metals are known to suppress host resistance to pathogens. To further evaluate the manner by which these metals causein vivoimmunomodulation, theirin vivoeffects on V"beta" expression were evaluated along with the Th1 and Th2 frequency. Exposure of BALB/c mice to PbCl2or HgCl2induced an oligoclonal response with increases of V"beta" 5+, V"beta" 7+, and V"beta" 13+CD4+splenic, but not thymic, T cells. A significantly skewed frequency of Pb-induced splenic Th2 cells expressing V"beta" 7 or V"beta" 13 over Th1 cells was determined by limiting dilution analysis, but this Th2 predominance was not observed with CD4+T cells expressing V"beta" 8. DO11.10 transgenic mouse exposed to Pb and antigen also demonstrated a skewed type-2 response evidenced by significantly increased IgE levels, lowered IFN-"gamma" levels, and increased IgG1 and lowered IgG2a anti-OVA levels. Even in the absence of specific T cell responses to a Pb-induced antigen, due to the restricted T cell specificity in the transgenic mouse model, Pb still was able to skew the response toward type-2 reactivity. However, this skewing occurred only in the presence of antigen. Therefore, the Pb-induced oligoclonal T cell response in BALB/c mice which must be initiated by self-antigens and was predominately type-2 may be responsible for autoantibody production and the detrimental health effects associated with Pb exposure.

Abstract  It has been repeatedly shown that the heavy metal mercury can induce or exacerbate lupus like autoimmunity in susceptible strains of rats and mice. A hallmark of such autoimmune induction is the accompaniment of an immune shift, in which there is usually an initial skewing toward a Th2-like immune environment. Another heavy metal, lead (Pb), has also been found to induce a Th2 shift in mice. However, exposure of normal mouse strains to Pb does not appear to induce autoimmunity. In order to investigate whether mice genetically predisposed to murine systemic lupus erythematosus (SLE) are susceptible to a Pb-induced exacerbation of lupus, males and females of four New Zealand mixed (NZM) mouse strains, along with BALB/c and C57Bl/6 controls, were administered three 100-microliter intraperitoneal injections of either 1.31 mM lead or sodium acetate per week for 3 wk. The four NZM strains chosen, NZM391, NZM2328, NZM88, and NZM2758, have differential genetic penetrance for SLE with variances in certain manifestations of the disease, but all of these strains naturally develop glomerulonephritis and produce high titers of anti-nuclear autoantibodies. The mice were prebled for baseline values and were bled directly after the injection period (d 1) and monthly thereafter for 5 mo. Sera were assessed for anti-double-stranded DNA titers, urea nitrogen levels, and creatine kinase activity, as well as four total immunoglobulin (Ig) G2a and IgG1 levels. Mortality and morbidity of the mice were also recorded. All NZM strains showed an acute, non-gender-based, susceptibility to Pb at d 1, but the control strains were unaffected. Over time, it became apparent that the strains diverged: The NZM391 strain showed gender-independent susceptibility to Pb enhancement of lupus manifestations and mortality; the NZM2328 strain exhibited gender-independent Pb susceptibility to manifestations, although only females had increased mortality; the NZM2758 strain exhibited non-gender-based elevations in urea nitrogen and creatine kinase activity levels; and the NZM88 strain displayed male susceptibility to anti-DNA and life span. Surprisingly, Pb increased the longevity of NZM88 and NZM2758 females. These results indicate that Pb indeed can exacerbate SLE in lupus-prone mice; however, even among lupus-prone strains, genetic differences determine the degree of exacerbation. Using the known phenotype and genetic differences, one can identify and characterize possible traits and loci associated with Pb susceptibility.