Abstract  The biological image of the transition element vanadium ferments a great deal of contradiction-from toxicity to essentiality. Importance of this element as micro-nutrient is yet to be unequivocally accepted by biologists and biomedical scientists. In spite of toxicity, it seems interesting to analyze the different biological roles of the element. Vanadium compounds have been proven to be associated with various implications in the pathogenesis of some human diseases and also in maintaining normal body functions. Salts of vanadium interfere with an essential array of enzymatic systems such as different ATPases, protein kinases, ribonucleases and phosphatases. While vanadium deficiency accounts for several physiological malfunctionings including thyroid, glucose and lipid metabolism, etc., several genes are regulated by this element or by its compounds, which include genes for tumor necrosis factor-alpha (TNF-alpha), Interleukin-8 (IL-8), activator protein-1 (AP-1), ras, c-raf-1, mitogen activated protein kinase (MAPK), p53, nuclear factors-kappaB, etc. All these seem to be not far from its recognition as an element of pharmacological and nutritional significance, which is revealed through its increasing therapeutic uses in diabetes. Vanadium is also emerging as a potent anti-carcinogenic agent. This review summarizes the developments related to vanadium biology as a whole by analyzing the general biochemical functions of vanadium.

Abstract  BACKGROUND: Occupational exposure to fuel-oil ash, with its high vanadium content, may cause respiratory illness. It is unclear, however, what early acute health effects may occur on the pathway from normal to compromised respiratory function. METHODS: Using a repeated measures design, we studied prospectively 18 boilermakers overhauling an oil-fired boiler and 11 utility worker controls. Subjects completed a respiratory symptom diary five times per day by using a 0-3 scale where 0=symptom not present, 1=mild symptom, 2=moderate symptom, and 3=severe symptom. Daily symptom severity was calculated by using the highest reported score each day for upper and lower respiratory symptoms. Daily symptom frequency was calculated by summing all upper or lower airway symptom reports, then dividing by number of reporting times. Respiratory symptom frequency and severity were analyzed for dose-response relationships with estimated vanadium and PM(10) doses to the lung and upper airway by using robust regression. RESULTS: During the overhaul, 72% of boilermakers reported lower airway symptoms, and 67% reported upper airway symptoms. These percentages were 27 and 36 for controls. Boilermakers had more frequent and more severe upper and lower respiratory symptoms compared to utility workers, and this difference was greatest during interior boiler work. A statistically significant dose-response pattern for frequency and severity of both upper and lower respiratory symptoms was seen with vanadium and PM(10) in the three lower exposure quartiles. However, there was a reversal in the dose-response trend in the highest exposure quartile, reflecting a possible healthy worker effect. CONCLUSIONS: Boilermakers experience more frequent and more severe respiratory symptoms than utility workers. This is most statistically significant during boiler work and is associated with increasing dose estimates of lung and nasal vanadium and PM(10).

Abstract  Two studies at three sites in the UK provided confirmation that systematic positive bias in NO2 diffusion tube measurement occurred because of changes to "within-tube" chemistry, rather than eddy diffusion at the mouth of the tube. In the first study in Cambridge, UK, sampler overestimation for 1 and 2 week exposures was compared to corresponding time-averaged monitor measurements (NO-NO2-NOx, O3) and weather variables. Noninearity between sampler and monitor NO2 measurements was interpreted in terms of spatial and temporal variations in relative and absolute availability of NO, NO2 and O3 at the site. A maximum overestimation occurred for an exposure mean NO2/NOx approximately 0.5. The separate contributions of reduced NO2 photolysis and eddy diffusion were compared in Study II using samplers of two materials, acrylic and quartz, and of different lengths (40, 55, 71 and 120 mm) at three sites: Norwich background, Cambridge intermediate, London kerbside. For compared sites, NO2 measured by acrylic samplers was significantly higher than for equivalent quartz samplers. For quartz samplers [NO2]mean was only just above the monitor at Norwich and London; sampler/monitor NO2 = 1.04 (P = 0.59) and 1.01(P = 0.76), respectively. For acrylic samplers the order of [NO2]mean was 40 mm > 120 mm > 71 mm > or = 55 mm. Excepting 40 mm samplers, this accords with a chemical bias where co-diffusing NO and 03 molecules in longer tubes have more time to react to form excess NO2. Bias in 40 mm samplers is discussed. Eddy diffusion is negligible for standard samplers because [NO2]mean was equivalent for 55 mm and 71 mm acrylic samplers and close to monitor NO2 for 71 mm quartz tubes. Both studies showed that sampler accuracy was dependent on location. Significantly, overestimation was greatest (approximately 3-4 ppb) where the NO2 annual mean was approximately 20 ppb, close to the UK and EU air quality standard of 21 ppb.

Abstract  BACKGROUND: The Democratic National Convention (DNC) in Boston, Massachusetts in 2004 provided an opportunity to evaluate the impacts of a localized and short-term but potentially significant change in traffic patterns on air quality, and to determine the optimal monitoring approach to address events of this nature. It was anticipated that the road closures associated with the DNC would both influence the overall air pollution level and the distribution of concentrations across the city, through shifts in traffic patterns. METHODS: To capture these effects, we placed passive nitrogen dioxide badges at 40 sites around metropolitan Boston before, during, and after the DNC, with the goal of capturing the array of hypothesized impacts. In addition, we continuously measured elemental carbon at three sites, and gathered continuous air pollution data from US EPA fixed-site monitors and traffic count data from the Massachusetts Highway Department. RESULTS: There were significant reductions in traffic volume on the highway with closures north of Boston, with relatively little change along other highways, indicating a more isolated traffic reduction rather than an across-the-board decrease. For our nitrogen dioxide samples, while there was a relatively small change in mean concentrations, there was significant heterogeneity across sites, which corresponded with our a priori classifications of road segments. The median ratio of nitrogen dioxide concentrations during the DNC relative to non-DNC sampling periods was 0.58 at sites with hypothesized traffic reductions, versus 0.88 for sites with no changes hypothesized and 1.15 for sites with hypothesized traffic increases. Continuous monitors measured slightly lower concentrations of elemental carbon and nitrogen dioxide during road closure periods at monitors proximate to closed highway segments, but not for PM2.5 or further from major highways. CONCLUSION: We conclude that there was a small but measurable influence of DNC-related road closures on air quality patterns in the Boston area, and that a low-cost monitoring study combining passive badges for spatial heterogeneity and continuous monitors for temporal heterogeneity can provide useful insight for community air quality assessments.

Abstract  Vanadium is an important environmental and industrial pollutant whose concentrations have increased in the last decades. Due to its status as reproductive toxicant and a microtubule damaging agent, the present study investigated by immunohistochemistry the effect of the inhalation of vanadium pentoxide on gamma-tubulin within somatic and testicular germ cells. Male mice inhaled vanadium pentoxide (V2O5) (0.02 M) 1 h/twice a week for 12 weeks. Our results demonstrated that vanadium accumulates in the testes starting with the initial inhalation (24 h), and this pattern remained until the last week of treatment. In general, vanadium was capable of significantly decreasing the percentage of gamma-tubulin in all analyzed testicular cells (Sertoli, Leydig and germ cells) starting with the first week of treatment. For all cell types studied, regression analysis revealed a negative and significant relationship between the percentage of immunopositive cells to gamma-tubulin and exposure time, showing a time dependent response in all cases. Our findings suggest that alterations on this protein might imply changes in microtubule-involved function such as cell division, which in the testes might lead to damage in the spermatogenesis, leading probably to infertility.

Abstract  OBJECTIVES: Among other constituents, fuel oil ash contains vanadium pentoxide, a known respiratory irritant. Exposure to ambient vanadium pentoxide dust has been shown to produce irritation of the eyes, nose, and throat. The usefulness of nasal lavage in detecting an inflammatory response to exposure to fuel oil ash among 37 boilermakers and utility workers was investigated.

METHODS: A baseline lavage was performed on the morning of the first day back to work after an average of 114 days away from work (range 36 hours to 1737 days). A lavage was performed after exposure on the morning three days after the baseline lavage. Exposure to respirable particulate matter of diameter < or = 10 microns (PM10) and respirable vanadium dust were estimated with daily work diaries and a personal sampling device for respirable particulates. These estimates were made for each subject on each workday during the three days between lavages. For each subject, the adjusted change in polymorphonuclear cells was calculated by dividing the change in polymorphonuclear cell counts by the average of the counts before and after exposure. The association between the adjusted polymorphonuclear cell counts and exposure was assessed with multiple linear regression, adjusted for age and current smoking.

RESULTS: Personal sampling (one to 10 hour time weighted average) showed a range of PM10 concentrations of 50 to 4510 micrograms/m3, and respirable vanadium dust concentration of 0.10 to 139 micrograms/m3. In smokers the adjusted polymorphonuclear cell count was not significantly different from zero (-0.1%, P > 0.5), but in nonsmokers it was significantly greater than zero (+50%, P < 0.05). In both non-smokers and smokers, there was considerable variability in adjusted polymorphonuclear cell counts and a dose-response relation between these adjusted cell counts and either PM10 or respirable vanadium dust exposure could not be found.

CONCLUSION: A significant increase in polymorphonuclear cells in non-smokers but not smokers was found. This suggests that in non-smokers, exposure to fuel oil ash is associated with upper airway inflammation manifested as increased polymorphonuclear cell counts. The lack of an increase in polymorphonuclear cells in smokers may reflect either a diminished inflammatory response or may indicate that smoking masks the effect of exposure to fuel oil ash.

Abstract  Mechanism of lipid peroxidation triggered by vanadium in human term placental microsomes was reinvestigated in vitro. Production of lipid peroxyl radicals was estimated from co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol. Vanadyl(IV), but not vanadate(V) caused a dose-dependent co-oxygenation. Vanadate(V) required the presence of reduced nicotinamide adenine dinucleotide phosphate to trigger co-oxygenation of benzo(a)pyrene-7,8-dihydrodiol. To determine the role of pre-formed lipid hydroperoxides, the results obtained with partially peroxidized linoleic acid were compared with those of fresh linoleate. Superoxide dismutase inhibited the co-oxygenation of reaction when fresh linoleic acid was used. To further characterize the role of superoxide anion-radical in the vanadium redox cycling, the increase of optical density of vanadate(V) dissolved in Tris buffer was measured at 328 nm during the addition of KO2. The rate of this reaction producing peroxy-vanadyl complex was decreased by superoxide dismutase, especially, in the presence of catalase. It is suggested that vanadium catalyzes two separate processes, both leading to enhanced lipid peroxidation: (i) initiation, dependent on superoxide and triggered by peroxy-vanadyl; (ii) propagation, dependent on pre-formed lipid hydroperoxide not sensitive to superoxide dismutase. It is postulated that the vanadium-triggered initiation of lipid peroxidation may be crucial for toxicity in organs with limited endogenous lipid peroxidation.

Abstract  We prospectively investigated the lower airway response in boilermakers overhauling an oil-powered boiler. We studied 26 male boilermakers with a mean age (SD) of 43.3 (8.6) yr. Pre-exposure spirometry and methacholine challenge tests were performed before beginning the boiler overhaul; postexposure tests were performed after approximately 4 wk of work on the boiler. Exposure to particulates with an aerodynamic diameter of 10 microns and smaller (PM10) and respirable vanadium dust were estimated using daily work diaries and a personal sampling device for respirable particles. Using these estimates, we calculated average and peak exposure between pre- and postexposure tests for each subject. The average PM10 concentration ranged from 1.44 to 6.69 mg/m3, with a mean (SD) of 3.22 (1.42) mg/m3; the average vanadium concentration ranged from 2.2 to 31.3, with a mean (SD) of 12.2 (9.1) micrograms/m3. The mean postexposure fall in FEV1 was 140 +/- 160 ml (p < 0.01); 24 of 26 subjects had a drop in FEV1. For each subject, the adjusted change in FEV1 (delta FEV1.adj) was calculated by dividing the change in FEV1 by the average of the pre- and postexposure FEV1 values. The delta FEV1.adj was regressed, controlling age and current smoking status, on average and peak exposure to both PM10 and vanadium. There was a dose-response relationship between average and peak PM10 exposure and delta FEV1.adj: beta = -0.91% per mg/m3, p = 0.08 and beta = -1.03% per mg/m3, p = 0.03, respectively. However, there was no relationship between delta FEV1.adj and respirable vanadium dust concentration. Furthermore, there was no postexposure change in nonspecific airway responsiveness. In summary, we found a significant fall in FEV1 and a dose-response relationship between delta FEV1.adj and average and peak PM10 exposure. This across-job drop in FEV1 was not associated with a shift in bronchial responsiveness as measured by methacholine.

Abstract  Exposure to environmental pollutants has been linked to various airway diseases and disease exacerbations. Almost all chronic airway diseases such as chronic obstructive pulmonary disease and asthma are caused by complicated interactions between gene and environment. One of the major hallmarks of those diseases is airway mucus overproduction (MO). Excessive mucus causes airway obstruction and significantly increases morbidity and mortality. Metals are major components of environmental particulate matters (PM). Among them, vanadium has been suggested to play an important role in PM-induced mucin production. Vanadium pentoxide (V(2)O(5)) is the most common commercial source of vanadium, and it has been associated with occupational chronic bronchitis and asthma, both of which are MO diseases. However, the underlying mechanism is not entirely clear. In this study, we used both in vitro and in vivo models to demonstrate the robust inductions of mucin production by V(2)O(5). Furthermore, the follow-up mechanistic study revealed a novel v-raf-1 murine leukemia viral oncogene homolog 1-IKK-NF-κB pathway that mediated V(2)O(5)-induced mucin production. Most interestingly, the reactive oxygen species and the classical mucin-inducing epidermal growth factor receptor (EGFR)-MAPK pathway appeared not to be involved in this process. Thus the V(2)O(5)-induced mucin production may represent a novel EGFR-MAPK-independent and environmental toxicant-associated MO model. Complete elucidation of the signaling pathway in this model will not only facilitate the development of the treatment for V(2)O(5)-associated occupational diseases but also advance our understanding on the EGFR-independent mucin production in other chronic airway diseases.

Abstract  Residual oil fly ash (ROFA) is a chemically complex mixture of compounds, including metals that are potentially carcinogenic because of their ability to cause oxidative injury. In this study, we investigated the association between exposure to particulate matter with an aerodynamic mass median diameter

Abstract  There is no general agreement yet about the teratogenic effects or developmental toxicity of vanadium in animal studies. This is a report on developmental toxicity in NIH mice following injection of vanadium pentoxide (V2O5, 5 mg/kg body weight, i.p.) at different times of gestation (on days 1-5, 6-15, 7, 8, 9, 10, 11, 14-17 of gestation). No adverse effects of V2O5 on pre-implantation and implantation were noted, and neither were teratogenicity and premature birth. However, there was toxic effect on embryofetus. Increased frequency of resorption or fetal death on days 6-15, 7, 14-17 of gestation were observed. Delayed ossification of bones was noted on days 6-15, 8, 10, 14-17 of gestation. These results suggest that V2O5 may be a weak developmental toxicant but not a teratogen in NIH mice. In addition, this paper reports the developmental toxicity, especially teratogenicity of N, N'-methylene-bis (2-amino-1, 3, 4-thiadiazole) which was used as the positive control in NIH mice.

Abstract  Vanadium was determined in urine and blood of two workers (Worker Nos. 1 and 2 with direct exposure to vanadium pentoxide) and 13 fellow workers (with indirect or no vanadium exposure), and the results were compared by means of personal and stationary sampling of vanadium in air. Worker No. 1, a foreman with the heaviest exposure to vanadium, had a green tongue, complained of frequent productive coughing, and excreted 47 to 124 ng/ml vanadium in his late morning and mid-afternoon urine. Worker No. 2, a helper to the foreman with less exposure, had no green tongue or subjective complaints, and excreted no vanadium at a measurable level even in his mid-shift urine. No vanadium was detected in urine samples from other workers, nor in blood from all workers including Worker Nos. 1 and 2. Application of inductively coupled plasma emission spectrometry to measurement of vanadium in biological materials is discussed.

Abstract  Vanadium was determined by both instrumental neutron activation analysis (INAA) and NAA with radiochemical separation (RNAA) in hair of normal children and of children potentially exposed by accidental drinking of vanadium contaminated water (long-term, low-dose exposure). Vanadium hair levels in the two groups did not differ significantly and were in the range 46-313 micrograms/kg (median 98 micrograms/kg) and 24-235 micrograms/kg (median 88 micrograms/kg for the normal and exposed groups, respectively. Using RNAA with proven reliability at the ultratrace level, vanadium was determined in whole blood of the exposed and normal children, normal adults and workers professionally exposed to vanadium in a factory producing vanadium pentoxide. Significantly increased vanadium concentrations were found in blood of exposed children (range 0.018-0.239 micrograms/l, median 0.078 micrograms/l) compared to normal children (range 0.024-0.226 micrograms/l, median 0.042 micrograms/l), while no differences could be detected between blood vanadium levels of normal children and normal adults (range 0.032-0.095 micrograms/l, median 0.056 micrograms/l). Preliminary results for vanadium in blood of occupationally highly exposed persons showed values 2-4 orders of magnitude higher than in normal adults.

Abstract  8 men who had been maintaining a very large oil-fired boiler for a few weeks suffered acute respiratory and other symptoms. The crude oil used contained a small amount of vanadium as an impurity. Work was done inside the boiler and in the deadspace at the top. The workers inside the boiler were in close contact with scale contaminated by condensed vanadium pentoxide. Samples of scale from 3 areas inside the boiler contained 14.2, 10, and 5.8% vanadium pentoxide. There were no residual health effects. Protective clothing had not been worn. Recommendations are made concerning: pre-employment and other medical examinations; selection of breathing and eye protection; general protective clothing; biological monitoring of urine samples; dust measurement. The literature is reviewed.

Abstract  Vanadium pentoxide (V(2)O(5)) is a cause of occupational asthma and bronchitis. We previously reported that intratracheal instillation of rats with V(2)O(5) causes fibrosis of the lung parenchyma (J. C. Bonner, P. M. Lindroos, A. B. Rice, C. R. Moomaw, and D. L. Morgan. Am. J. Physiol. Lung Cell. Mol. Physiol. 274: L72-L80, 1998). In this report, we show that intratracheal instillation of V(2)O(5) induces airway remodeling similar to that observed in individuals with asthma. These changes include airway smooth muscle cell thickening, mucous cell metaplasia, and airway fibrosis. The transient appearance of peribronchiolar myofibroblasts, which were desmin and vimentin positive, coincided with a twofold increase in the thickness of the airway smooth muscle layer at day 6 after instillation and preceded the development of airway fibrosis by day 15. The number of nuclear profiles within the smooth muscle layer also increased twofold after V(2)O(5) instillation, suggesting that hyperplasia accounted for thickening of the smooth muscle layer. The majority of cells incorporating bromodeoxyuridine at day 3 were located in the connective tissue surrounding the airway smooth muscle wall that was positive for vimentin and desmin. These data suggest that myofibroblasts are the principal proliferating cell type that contributes to the progression of airway fibrosis after V(2)O(5) injury.

Abstract  Platelet-derived growth factor (PDGF) is a potent mitogen for mesenchymal cells. Induction of the PDGF receptor-alpha (PDGF-R alpha) in vitro enhances PDGF-induced mitogenesis and chemotaxis. Thus we investigated whether the PDGF-R alpha is induced in vivo during pulmonary fibrogenesis using a vanadium pentoxide (V2O5) model of lung injury. PDGF-R alpha mRNA expression was induced 24 h postinstillation. PDGF-R beta mRNA was constitutively expressed and did not increase. Western blotting showed upregulation of PDGF-R alpha protein by 48 h, and immunohistochemical analysis localized PDGF-R alpha primarily in mesenchymal cells residing within fibrotic lesions. Upregulation of PDGF-R alpha in vivo preceded mesenchymal cell hyperplasia (3-7 days) and collagen deposition by day 15. Supernatants from alveolar macrophages treated with V2O5 in vitro released upregulatory activity for PDGF-R alpha on cultured lung myofibroblasts, and this activity was blocked by the interleukin-1-receptor antagonist. These data suggest that interleukin-1 beta-mediated induction of PDGF-R alpha in vivo is important to lung myofibroblast hyperplasia during fibrogenesis.

Abstract  Using neutron activation analysis, vanadium was analysed in a range of foods, human body fluids and tissues. On the basis of these results and those of other workers, it was concluded that daily dietary intake amounts to some tens of micrograms. Analysis of body fluids (including milk, blood and excreta) and organs and tissues provided an estimate for the total body pool of vanadium in man of about 100 microgram. Vanadium was not detectable in blood and urine at the level of 0.3 ng/g, while low levels were found in muscle, fat, bone, teeth and other tissues. The relationship between dietary intake to pulmonary absorption is discussed in relation to the occurrence of vanadium in man-made air particulates. The very low levels found in milks and eggs suggest minimal vanadium requirements in growth. The findings are discussed in the light of previous results and also in relation to the possible essentiality of vanadium.

Abstract  Radiolabeled vanadium as either vanadyl ion or vanadate ion was injected intravenously into adult beagle dogs, and blood samples were collected at various times up to 48 hr post injection. For each sample, the distribution of vanadium between the cells and the plasma was determined, and the plasma was analyzed by electrophoresis to identify specific vanadium-binding proteins. Initially, vanadyl ion left the bloodstream more rapidly than vanadate, but the rates equalized after about 5 hr. A significant fraction of the vanadium in blood was associated with the cellular component following injection of both forms of vanadium. About 77% of the plasma vanadium was eventually bound by the serum iron transport protein transferrin, regardless of the vanadium species initially injected. For both vanadyl and vanadate, about 30 hr were required to reach the maximum degree of transferrin binding.

Abstract  By using the method of radioactive isotopes on albino rats, we studied the rate and degree of absorption of vanadium in to the blood, the time of its retention in the organs and the kinetics of its excretion, the influence of stable vanadium on the generative function and the correlation between the carrier state in workers who are in contact with vanadium in its production and the levels of exposure. Varying rates of absorption in to the blood in dependence on the route of administration, accumulation of vanadium in the kidneys, bone tissue, liver, lungs, placenta, testicles and the mammary gland, predominant elimination by the kidneys during the first two days, the gonodotoxic and embryotoxic effects were established. Correlation was revealed between the content of vanadium in the urine of workers and the levels of exposure.

Abstract  Vanadium pentoxide (V2O5) is the most toxic form of vanadium for mammals, presumably because of its inhibitory effects on several enzymes. We have previously demonstrated an increase in polyploid cell frequency and a decrease in the mitotic index of human lymphocytes treated in vitro with V2O5. The administration of metavanadate to adult rats induced impairment of spermatogenesis, and a decrease in the mobility of spermatozoa, while its administration to pregnant rats increased the mortality rate of embryos. In vitro orthovanadate inhibited luteinising: hormone-induced cyclic adenosine monophosphate (cAMP) in isolated corpora lutea from psuedopregnant rats. Since puberty is the result of several modifications in the mechanisms controlling gonadotrophin secretion and gonadal reactivity to them, we decided to compare the effects of V2O5 administered to male and female prepubertal rats.

Abstract  Tissue vanadium levels were determined in rats of different age by neutron activation analysis. The vanadium concentrations in the tissues of rats 21 days old are of the order of few tens of ng/g. Significant depletions of these concentrations were observed in kidney, liver lung and spleen at 115 days postnatal period. At this time the vanadium content in all tissues analysed did not exceed 10 ng/g.

Abstract  This guideline summarizes pertinent information about vanadium pentoxide dust for workers and employers as well as for physicians, industrial hygienists, and other occupational safety and health professionals who may need such information to conduct effective occupational safety and health programs. Recommendations may be superseded by new developments in these fields; readers are therefore advised to regard these recommendations as general guidelines and to determine periodically whether new information is available.

Abstract  For efficient detection and evaluation of environmental chemical mutagens, the assay procedures must be simple and inexpensive. By the use of microorganisms as the repair test, chemicals that damage DNA may be selected very quickly. These DNA-damaging chemicals are likely to be mutagenic and carcinogenic, as well as effectors of chromosome aberrations. Recent developments in techniques and mutagen screening by the rec-assay system using recombination-proficient and -deficient strains of Bacillus subtilis are reviewed in this chapter.