Effects of occupational lead and cadmium exposure on some immunoregulatory cytokine levels in man

The levels of serum interleukin-1beta (IL-1beta), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (gamma-IFN) were assessed in the workers who were occupationally exposed to lead and cadmium. The values were compared with the age-matched control group. Blood lead and cadmium levels were significantly raised. Our findings suggest that chronic lead and cadmium exposure in humans resulted in significant suppression of the serum IL-1beta level, but did not alter IL-2 and TNF-alpha levels. The gamma-IFN level was also reduced in lead workers. In contrast, a significant enhancement was observed in the cadmium-exposed group. We conclude from these results that lead and cadmium exposure at chronically high level may affect some cytokine levels in humans.     

Hemorheology in occupational lead exposure

OBJECTIVES: The purpose of this investigation was to study hemorheological parameters in occupationally lead exposed men. MATERIAL AND METHODS: For 15 clinically healthy lead-exposed male subjects [age 34.6 (SD 8) years] the viscous (epsilon') and elastic (epsilon") components of whole blood viscosity corrected for 45% hematocrit were measured for shear rates between 1.s-1-100.s-1 at 37 degrees C. Moreover, lead concentrations in blood and urine and the delta-aminolevulinic acid dehydrase level were determined. Fifteen unexposed age-matched men were used as referents. RESULTS: The mean lead concentration in the blood and urine of the lead-exposed men was 48.7 (SD 16.2) micrograms. dl-1 and 38.8 (SD 17.1) micrograms.g creatinine-1, respectively. While epsilon" was significantly increased only at low shear rates, epsilon' was elevated throughout the investigated shear range in comparison with the values of the unexposed referents. These results are characteristic of erythrocytes with enhanced rigidity. The aggregation and filtration index of erythrocytes were significantly elevated for the lead-exposed workers. A positive correlation existed between lead in blood and epsilon' or epsilon", whereas delta -aminolevulinic acid dehydrase and epsilon' or epsilon" were inversely correlated. No differences in plasma viscosity or in lipid status could be detected. CONCLUSION: Increased blood lead concentrations can be considered an additional risk factor for vascular diseases predisposing towards microvascular occlusion.     

Brain cancer and occupational exposure to lead

A recent report in the literature suggested a link between occupational exposure to lead and brain cancer. To explore the hypothesis, we applied a job-exposure matrix for lead to the occupation and industry codes given on the death certificate of 27,060 brain cancer cases and 108,240 controls who died of non-malignant diseases in 24 US states in 1984-1992. Brain cancer risk increased by probability of exposure to lead among Caucasian men and women with high-level exposure, with a significant twofold excess among Caucasian men with high probability and high level of exposure to lead (odds ratio = 2.1; 95% confidence interval, 1.1-4.0). Risks were also elevated in the low- and medium-probability cells for African-American men with high-level exposure to lead. Trend by intensity level was statistically significant among African-American men (all probabilities combined). Although exposure assessment was based solely on the occupation and industry reported on the death certificate, these results add to other epidemiologic and experimental findings in lending some support to the hypothesis of an association between occupational exposure to lead and brain cancer risk. Analytic studies are warranted to further test this hypothesis.     

Renal effects of environmental and occupational lead exposure

Environmental and industrial lead exposures continue to pose major public health problems in children and in adults. Acute exposure to high concentrations of lead can result in proximal tubular damage with characteristic histologic features and manifested by glycosuria and aminoaciduria. Chronic occupational exposure to lead, or consumption of illicit alcohol adulterated with lead, has also been linked to a high incidence of renal dysfunction, which is characterized by glomerular and tubulointerstitial changes resulting in chronic renal failure, hypertension, hyperuricemia, and gout. A high incidence of nephropathy was reported during the early part of this century from Queensland, Australia, in persons with a history of childhood lead poisoning. No such sequela has been found in studies of three cohorts of lead-poisoned children from the United States. Studies in individuals with low-level lead exposure have shown a correlation between blood lead levels and serum creatinine or creatinine clearance. Chronic low-level exposure to lead is also associated with increased urinary excretion of low molecular weight proteins and lysosomal enzymes. The relationship between renal dysfunction detected by these sensitive tests and the future development of chronic renal disease remains uncertain. Epidemiologic studies have shown an association between blood lead levels and blood pressure, and hypertension is a cardinal feature of lead nephropathy. Evidence for increased body lead burden is a prerequisite for the diagnosis of lead nephropathy. Blood lead levels are a poor indicator of body lead burden and reflect recent exposure. The EDTA lead mobilization test has been used extensively in the past to assess body lead burden. It is now replaced by the less invasive in vivo X-ray fluorescence for determination of bone lead content.     

Exercise and cellular innate immune function

PURPOSE: To determine, in three-dimensions, the difference between prostate delineation in magnetic resonance (MR) and computer tomography (CT) images for radiotherapy treatment planning. PATIENTS AND METHODS: Three radiation oncologists, considered experts in the field, outlined the prostate without seminal vesicles both on CT, and axial, coronal, and sagittal MR images for 18 patients. To compare the resulting delineated prostates, the CT and MR scans were matched in three-dimensions using chamfer matching on bony structures. The volumes were measured and the interscan and interobserver variation was determined. The spatial difference between delineation in CT and MR (interscan variation) as well as the interobserver variation were quantified and mapped three-dimensionally (3D) using polar coordinates. A urethrogram was performed and the location of the tip of the dye column was compared with the apex delineated in CT and MR images. RESULTS: Interscan variation: CT volumes were larger than the axial MR volumes in 52 of 54 delineations. The average ratio between the CT and MR volumes was 1.4 (standard error of mean, SE: 0.04) which was significantly different from 1 (p < 0.005). Only small differences were observed between the volumes outlined in the various MR scans, although the coronal MR volumes were smallest. The CT derived prostate was 8 mm (standard deviation, SD: 6 mm) larger at the base of the seminal vesicles and 6 mm (SD 4 mm) larger at the apex of the prostate than the axial MRI. Similar figures were obtained for the CT and the other MRI scans. Interobserver variation: The average ratio between the volume derived by one observer for a particular scan and patient and the average volume was 0.95, 0.97, and 1.08 (SE 0.01) for the three observers, respectively. The 3D pattern of the overall observer variation (1 SD) for CT and axial MRI was similar and equal to 3.5 to 2.8 mm at the base of the seminal vesicles and 3 mm at the apex. CONCLUSION: CT-derived prostate volumes are larger than MR derived volumes, especially toward the seminal vesicles and the apex of the prostate. This interscan variation was found to be larger than the interobserver variation. Using MRI for delineation of the prostate reduces the amount of irradiated rectal wall, and could reduce rectal and urological complications.     

Improvement in semen quality associated with decreasing occupational lead exposure

BACKGROUND: Cross-sectional studies have suggested that occupational lead exposure may adversely affect sperm quality. METHODS: Sperm quality changes were prospectively assessed in 19 men employed at a car battery plant where efforts were made to decrease the exposure level. The participants delivered monthly samples of semen and venous blood during their employment at the factory. The factory then closed, and additional samples were obtained from 16 of the men. RESULTS: Average blood-lead concentrations decreased from 2.03 mumol/l to 0.96 mumol/l during the observation period. Concomitantly, significant improvements were seen in the proportion of motile cells both at sample delivery and after 24 hr, and in penetration. However, the sperm cell concentration and the proportion of morphological abnormalities did not change. CONCLUSIONS: These results support the notion that occupational lead exposure at currently acceptable levels has a small adverse effect on sperm quality, especially sperm motility, and that this effect is at least partially reversible.     

Association of cumulative lead and neurocognitive function in an occupational cohort.

Lead is a neurotoxicant that accumulates in bone with a half life of 25-30 years. To evaluate the association of lead biomarkers and cognitive function, a cohort of exposed and nonexposed workers who had been previously assessed in 1982 was retested approximately 22 years later. For the current assessment, both blood lead and tibia bone lead levels were determined. In addition, cognitive function was tested with the Pittsburgh Occupational Exposures Test battery, which had previously been administered in 1982. In exposed workers, bone lead level predicted lower current cognitive performance and cognitive decline over 22 years. In those lead-exposed workers older than age 55, higher levels of bone lead predicted poorer cognitive scores, suggesting vulnerability for older workers with higher past lead exposure. Finally, there was no association with bone lead level and recency of exposure, suggesting that cumulative body burden is most likely responsible for the progressive cognitive decrement evidenced with vulnerability because of aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lifetime lead exposure on spatial and temporal visual function in monkeys

Detailed characterization of several aspects of visual function was performed in two groups of monkeys (Macaca fascicularis) exposed to lead continuously from birth. One group of four monkeys was dosed from birth onward with 500 microg/kg/day of lead as lead acetate, while another group of six monkeys was dosed with 2000 microg/kg/day. Blood lead levels peaked in the former group at 50 microg/dl early in life; the latter group had peak blood lead concentrations averaging 115 microg/dl during infancy. Blood lead concentrations decreased before one year of age to stable levels of 25 or 35 microg/dl in the low and high dose groups respectively. Spatial and temporal visual function was assessed using a psychophysical procedure at 7-9 years of age. Six age-matched controls were tested concurrently. Two treated monkeys had severe hyperopia: one was assessed on temporal vision only and the other was not assessed. Spatial data from a third monkey were considered suspect and excluded. Six of the nine treated monkeys in which temporal vision was assessed had thresholds below control values at low and/or middle frequencies under high luminance conditions. Low-luminance temporal vision was not affected. There was no evidence of impairment of spatial visual function in lead-exposed monkeys with normal refractive status at either high or low luminance. This study suggests that temporal visual function may be preferentially impaired as a result of lifetime exposure to a moderate body burden of lead, although these results require replication before definitive conclusions may be drawn.     

Effect of pentachlorophenol on immune function

The organochlorine compound, pentachlorophenol, was evaluated for effects on immune system function in male Fisher 344 rats. Pentachlorophenol was prepared in an olive oil vehicle and was administered by oral gavage twice weekly for 28 days at a dose of 2.0 mg/kg per treatment. Exposure to pentachlorophenol increased body weight gains (P=0.024) during the treatment period. Liver (P=0.034) and kidney (P=0.012) body weight ratios were also increased. Pentachlorophenol exposure enhanced T-lymphocyte blastogenesis induced by concanavalin A (Con A)(P=0.0001) and phytohemagglutinin (PHA)(P=0.048) evaluated using stimulation indices. Corresponding B-lymphocyte blastogenesis induced by lipopolysaccharide/dextran (LPS/dex)(P=0.0034) was also enhanced by pentachlorophenol exposure. Pentachlorophenol suppressed the antibody response against sheep red blood cells (SRBCs) by 39% when the response was expressed per viable spleen cell (P=0.006). This suppression was not evident when the response was expressed per spleen (P=0.22), suggesting that a compensatory mechanism or extramedullary splenic hemopoiesis was occurring minimizing the overall impact on humoral immunity. The enhanced B- and T-lymphocyte blastogenesis may also reflect compensatory or hemopoietic activity. Pentachlorophenol exposure had no effect on peritoneal macrophage phagocytosis (P=0.31) or lymphocyte cell surface antigen expression. The observed alterations in lymphocyte blastogenesis and humoral immunity subsequent to pentachlorophenol exposure do not appear to be associated with phagocytosis or lymphocyte cell surface antigen expression.     

Evolution of a state occupational lead exposure registry: 1986-1996

In the first 11 full years of operation (January 1, 1986, through December 31, 1996) of an adult lead registry in New Jersey, 23,456 reports of occupational lead toxicity (blood lead level > or = 1.21 mumol/L) in 4,011 workers, involving 496 workplaces, were received. The majority of the reports and workers were from the manufacturing and construction industries. Over the 11 years, the annual numbers of reports and workers declined, although the annual numbers of involved workplaces remained stable, as did the number of newly identified workers and workplaces. The decline occurred primarily in the manufacturing industry; the construction industry experienced an increase in reports and reported workers. For all years combined, 36% of reported workers had at least one blood lead level equal to or greater than 1.93 mumol/L, although in the most recent years the percentage dropped overall and in both the manufacturing and construction industries.     

Effect of deoxycholate on immunoglobulin G concentration in bile: studies in humans and pigs

Because an increase in biliary deoxycholate levels seems to be a risk factor for cholesterol gallstone formation, we determined the relationship between deoxycholate levels and levels of the pronucleating protein, immunoglobulin G (Ig) in human gallbladder bile. Patients with cholesterol gallstones had a higher concentration of biliary IgG compared with a pigmented stone group and control patients. This was associated with the simultaneous presence of two conditions in the cholesterol stone group, supersaturated bile and a high deoxycholate/cholate ratio. The other patient groups met only one of the two conditions. Next, animal studies were performed to determine if model biles mimicking the two conditions could affect IgG secretion by the gallbladder. Gallbladders were exposed in vivo and then in an Ussing chamber to model biles. The voltage clamp technique was used to monitor functional integrity of the preparation. Three different model biles were tested: (1) taurodeoxycholate (TDC), 80%; taurocholate (TC), 20%; and cholesterol saturation index (CSI), 1.2; (2) TDC, 20%; TC, 80%; and CSI, 1.2; and (3) TDC, 80%; TC, 20%; and CSI, 0.6. IgG concentrations became significantly higher in group 1 than in the other two groups. The concentration of mucous glycoprotein was also significantly greater in group 1 when compared with group 2. Plasma cells were increased in number in mucosal and submucosal layers in group 1. We conclude that cholesterol supersaturated model bile with high content of TDC induces gallbladder epithelial alterations, which increase the luminal concentration of IgG and mucous glycoprotein.     

Effect of contralateral noise exposure on otoacoustic distortion product emissions in man

The influence of contralateral white noise with levels of 50 and 60 dBnHL on the amplitude of distortion-product otoacoustic emissions (DPOAE) was measured. Thirty ears of normally hearing adults (17 women, 13 men, mean age 26.5 +/- 5.3 years) were examined. Two representative DPOAE frequencies 2f1-f2 = 1342 Hz and 6341 Hz were compared. The lower DPOAE frequency was placed in the frequency region where middle-ear pressure has a strong influence on DPOAE amplitudes, the higher DPOAE frequency respectively in the region where lesser influence is exerted by middle-ear pressure. During the application of contralateral white noise a statistically significant total of 85% of DPOAE amplitudes was reduced, although there was some variation in the individual behaviour of DPOAE amplitudes. In general the higher DPOAE frequency (6341 Hz) was reduced distinctly less than the lower DPOAE frequency (1342 Hz). The reaction of DPOAE amplitude depended closely on the time course of the contralateral stimulus and amplitude reductions were present over 10 minutes without adaptation or fatigue. It is not possible to differentiate between middle-ear or inner-ear mediate effects but the middle ear is at least involved. Based on the presence of those DPOAE amplitude reductions over ten minutes without adaptation or fatigue and the fact that lower frequencies are influenced much more than higher frequencies a synergistic effect--middle-ear and efferent mediated--is suggested.     

Effect of rat placental culture supernatants on cellular and humoral immune responses

PROBLEM: To evaluate the effect of rat placental culture supernatants (PS) on spontaneous, mitogen- and alloantigen-induced lymphoproliferation, antibody synthesis regulation, and symmetric/asymmetric antibody ratio. METHOD OF STUDY: The effect of PS was determined: (a) on cell proliferation of murine hybridoma cells and on spontaneous or ConA-induced proliferation of murine and rat splenocytes by thymidine incorporation; (b) on rat or mouse cell-mediated cytotoxicity (CMC) by 51Cr release; and (c) on antibody synthesis by enzyme-linked immunoadsorbent assay (ELISA). RESULTS: With 20% PS, hybridoma cell inhibition was 37% and that of splenocytes up to 60%, whereas it was 75 and 43%, respectively, in the presence of ConA. Despite marked cell death, hybridoma proliferation index increased significantly. There was a drop in total antidinitrophenylated (DNP) immunoglobulin G1 (IgG1) antibody production and an increase in asymmetric antibody percentage, correlating with placental supernatant concentration. CONCLUSIONS: Rat placental culture supernatants inhibit cell proliferation in all cases, diminish total antibody production, and increase the percentage of asymmetric antibodies by the hybridoma, and they increase antibody production by rat splenocytes.     

Effect of olive oil on immune function in middle-aged men

Autocrine motility factor is a tumor-secreted cytokine which regulates cellular growth and motility by a receptor-mediated pathway. In the accompanying report (Part I of II), it was demonstrated that high (K1735-M1) and low (K1735-C1.11) metastatic murine melanoma cells display distinct adhesion and spreading characteristics which correlate with their differential spontaneous and stimulated migrations on the extracellular matrix components fibronectin, laminin and collagen IV. These parameters were further related to discrete profiles of focal adhesion plaque integrity and reorganization. Here we describe unique migration patterns observed in these murine melanoma cells which reflect differences in degradation and/or remodeling of the cellular substratum. These profiles of matrix interaction were influenced distinctly by autocrine motility factor and dictated by both substrate composition and cellular phenotype. Since activation of the autocrine motility factor receptor stimulates invasion of a reconstituted basement membrane and enhances experimental metastasis by high- but not low-metastatic K1735 cells, differences in the invasive phenotypes of these cells may be due in part to their differential responses to external stimuli coupled with internal propensities toward either matrix degradation and migration (high-metastatic cells) or matrix remodeling and stasis (low-metastatic cells).     

Effects of prolonged exposure to morphine and methadone on in vivo parameters of immune function in rats

In rats, two 6-week repeated dose oral toxicity studies were performed with morphine (250 and 500 mg/kg food) and methadone (200 and 400 mg/kg food), respectively. Alterations in immune function were studied by assessing primary and secondary immune responses to sheep red blood cells. In addition, the ability to resist challenge with infectious agents was measured in host resistance models employing the parasite Trichinella spiralis and the bacterium Listeria monocytogenes. The primary and secondary antibody responses to sheep red blood cells were not affected by treatment with either morphine or methadone. The clearance of L. monocytogenes bacteria in the spleen was not affected either. Prolonged treatment with morphine, however, resulted in a decrease in host resistance to T. spiralis infection, as indicated by a 1.5-fold increase in numbers of muscle larvae counted in the carcass, but did not affect the T. spiralis-specific IgM, IgG and IgE antibody responses. In contrast to morphine, the methadone-treated animals did not show a significant change in host resistance to T. spiralis. Total serum IgG levels, however, were increased in high-dose methadone-treated animals. Apparently, prolonged administration of morphine to rats resulted in immune suppression, mediating a slight, though biologically relevant, exacerbation of the T. spiralis infection, whereas methadone did not.     

Effect of acute and chronic lead exposure on the level of sulfhydryl groups in rat brain

Lead is known to be a potent neurotoxic agent. The interactions of lead with proteins are considered to be at least one of the mechanisms due to which lead exerts its toxicity. In the present work we demonstrate that acute and chronic models of exposure to lead affected the level of total and protein-bound SH groups in homogenates and synaptosomes obtained from rat brains. The concentrations of SH groups were lowered significantly (P < 0.05) in both types of poisoning. Different classes of cellular proteins were considered to play a role in high affinity binding of lead to these ligands.     

Effect of long-term lead exposure on hematology, blood biochemistry, and growth curves in monkeys

A total of 90 monkeys (Macaca fascicularis), comprising four study cohorts born over a seven-year period, were hand reared and dosed orally with lead or vehicle according to one of several protocols, in most cases from birth to 9-14 years. Blood lead concentrations of lead-exposed groups ranged from 10 to 90 micrograms/dl depending on dose and age. Routine hematology and blood biochemistry analyses were performed regularly. Comparison of treated groups at various ages to the appropriate control group revealed no strong indication of lead-related effects. In addition, body weight increase was modeled from days 30-3500 of age in subset of this larger group, including 52 monkeys exposed to vehicle or lead during development according to one of four regimens: vehicle, lead from birth onward, lead to 400 days of age, or lead beginning at 300 days of age. No effect of lead on body weight was found. These results suggest that lead exposure beginning early in life and continuing for as long as 14 years resulted in no overt toxicity, as measured by these parameters.     

The politics of reproductive hazards in the workplace: class, gender, and the history of occupational lead exposure

Over the past two decades, several U.S. companies have sought to bar women from jobs that expose them to potential reproductive hazards, justifying these exclusionary policies by their professed concerns for the well-being of unborn children and potential liability. Although recent court cases have stimulated academic interest in this issue, a historical review of the public health and medical literature reveals that this debate is not new. To understand the logic behind the emergence of "fetal protection" policies, one must examine the scientific history of occupational teratogens and the socio-political and economic forces that have driven scientific research in this field. Using lead as an example, the author argues that research on the reproductive hazards of employment has historically emphasized the risks to women and downplayed the risks to men. This results in environmental health policies that do not uphold the ultimate goal of occupational safety for all workers, but rather reinforce the systemic segregation of men and women in the workplace. Although the political struggle over exclusionary policies has a feminist orientation, it also has important class dimensions and ultimately must be viewed within the broader context of American capitalist production.