Aims: To study whether exposure to nitrogen trichloride in indoor chlorinated pools may affect the respiratory epithelium of children and increase the risk of some lung diseases such as asthma. ...Methods: In 226 healthy children, serum surfactant associated proteins A and B (SP-A and SP-B), 16 kDa Clara cell protein (CC16), and IgE were measured. Lung specific proteins were measured in the serum of 16 children and 13 adults before and after exposure to NCl3 in an indoor chlorinated pool. Relations between pool attendance and asthma prevalence were studied in 1881 children. Asthma was screened with the exercise induced bronchoconstriction test (EIB). Results: Pool attendance was the most consistent predictor of lung epithelium permeability. A positive dose-effect relation was found with cumulated pool attendance and serum SP-A and SP-B. Serum IgE was unrelated to pool attendance, but correlated positively with lung hyperpermeability as assessed by serum SP-B. Changes in serum levels of lung proteins were reproduced in children and adults attending an indoor pool. Serum SP-A and SP-B were already significantly increased after one hour on the pool side without swimming. Positive EIB and total asthma prevalence were significantly correlated with cumulated pool attendance indices. Conclusions: Regular attendance at chlorinated pools by young children is associated with an exposure dependent increase in lung epithelium permeability and increase in the risk of developing asthma, especially in association with other risk factors. We therefore postulate that the increasing exposure of children to chlorination products in indoor pools might be an important cause of the rising incidence of childhood asthma and allergic diseases in industrialised countries. Further epidemiological studies should be undertaken to test this hypothesis.
Advances in proteomics have led to the identification of sensitive urinary biomarkers of renal dysfunction that are increasingly used in toxicology and epidemiology. Recent animal data show that ...combined exposure to inorganic arsenic (As) and cadmium (Cd) gives rise to more pronounced renal toxicity than exposure to each of the agents alone. In order to examine if similar interaction occurs in humans, renal dysfunction was studied in population groups (619 persons in total) residing in two metal contaminated areas in China: mainly a Cd contaminated area in Zhejiang province (Z-area) and mainly a As contaminated area in Guizhou province (G-area). Nearby control areas without excessive metal exposure were also included. Measurements of urinary β
2-microglobulin (UB2MG),
N-acetyl-β-glucosaminidase (UNAG), retinol binding protein (URBP) and albumin (UALB) were used as markers of renal dysfunction. Urinary Cd (UCd) and total As (UTAs) were analyzed by graphite-furnace atomic absorption spectrometry. Urinary inorganic As and its mono- and di-methylated metabolites (UIAs) were determined by Hydride generation.
Results. As expected, the highest UCd values occurred in Z-area (Geometric mean, GM 11.6 μg/g crea) while the highest UTAs values occurred in G-area (GM = 288 μg/g crea). Statistically significant increases compared to the respective control area were present both for UTAs, UCd and for UB2MG, UNAG and UALB in Z-area as well as in G-area. UIAs was determined only in Z area. In G-area, there was a clear dose–response pattern both in relation to UTAs and UCd for each of the biomarkers of renal dysfunction. An interaction effect between As and Cd was demonstrated at higher levels of a combined exposure to As and Cd enhancing the effect on the kidney. In Z-area an increased prevalence of B2MG-uria, NAG-uria and ALB-uria was found in relation to UCd, but no relationship to UTAs was found. A statistically significant relationship between UIAs and UB2MG was found among women in this area and an interaction between As and Cd was indicated for B2MG.
Conclusion. The present studies, which employed sensitive biomarkers of renal dysfunction, give support to the idea that human co-exposure to Cd and inorganic arsenic gives rise to more pronounced renal damage than exposure to each of the elements alone, but further studies are needed to establish and clarify this interaction.
Lead, cadmium, mercury, and arsenic are common environmental pollutants in industrialized countries, but their combined impact on children's health is little known. We studied their effects on two ...main targets, the renal and dopaminergic systems, in > 800 children during a cross-sectional European survey. Control and exposed children were recruited from those living around historical nonferrous smelters in France, the Czech Republic, and Poland. Children provided blood and urine samples for the determination of the metals and sensitive renal or neurologic biomarkers. Serum concentrations of creatinine, cystatin C, and $\beta_2-microglobulin$ were negatively correlated with blood lead levels (PbB), suggesting an early renal hyperfiltration that averaged 7% in the upper quartile of PbB levels (> $55 \mu g/L$; mean, $78.4 \mu g/L$). The urinary excretion of retinol-binding protein, Clara cell protein, and $N-acetyl-\beta-D-glucosaminidase$ was associated mainly with cadmium levels in blood or urine and with urinary mercury. All four metals influenced the dopaminergic markers serum prolactin and urinary homovanillic acid, with complex interactions brought to light. Heavy metals polluting the environment can cause subtle effects on children's renal and dopaminergic systems without clear evidence of a threshold, which reinforces the need to control and regulate potential sources of contamination by heavy metals.
By selecting specific decay reactions in high-energy collisions (60 keV/amu) of hydrogen cluster ions with a helium target (utilizing event-by-event data of a recently developed multicoincidence ...experiment) and by deriving corresponding temperatures for these microcanonical cluster ensembles (analyzing respective fragment distributions), we are able to construct caloric curves for H+3(H2)(m) cluster ions (6<or=m<or=14). All individual curves and the mean of these curves show a backbending in the plateau region, thus constituting direct evidence for a negative microcanonical heat capacity in the liquid-to-gas transition of these finite systems.
The clinical relevance of renal effects of cadmium in people exposed in the environment remains uncertain. This study examined the evolution of renal effects observed in a population exposed to ...cadmium in the environment.
208 men and 385 women surveyed in 1985–89 (Cadmium in Belgium study Cadmibel; baseline) were reexamined on average 5 years later (Public health and environmental exposure to cadmium study PheeCad; followup). Urinary and blood cadmium and markers of renal tubular dysfunction and glomerular effects were measured. The association between cadmium body burden and renal factors was examined by multivariate logistic and linear regression.
In men, mean urinary cadmium excretion and blood cadmium concentration measured at follow-up were 7·5 nmol/24 h (SD 1·9) and 6·1 nmol/L (2·2), reductions of 16% and 35% from baseline, respectively. In women, the corresponding values were 7·6 nmol/24 h (1·9) and 7·8 nmol/L (2·1), reductions of 14% and 28% from baseline. No indication of progressive renal damage was found and the overall results suggest that the effects of low environmental exposure to cadmium on the kidney are weak, stable, or reversible.
Subclinical renal effects that have been reported in Belgium in patients with increased cadmium body burden are not associated with progressive renal dysfunction and most likely represent non-adverse manifestations.
Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The effects of three organic vanadium compounds were studied in non‐ketotic, streptozotocin‐diabetic rats: ...vanadyl acetylacetonate (VAc), vanadyl 3‐ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple inorganic vanadium salt, vanadyl sulphate (VS) was also studied.
Oral administration of the three organic vanadium compounds (125 mg vanadium element l−1 in drinking fluids) for up to 3 months induced a faster and larger fall in glycemia (VAc being the most potent) than VS. Glucosuria and tolerance to a glucose load were improved accordingly.
Activities and mRNA levels of key glycolytic enzymes (glucokinase and L‐type pyruvate kinase) which are suppressed in the diabetic liver, were restored by vanadium treatment. The organic forms showed greater efficacy than VS, especially VAc.
VAc rats exhibited the highest levels of plasma or tissue vanadium, most likely due to a greater intestinal absorption. However, VAc retained its potency when given as a single i.p. injection to diabetic rats. Moreover, there was no relationship between plasma or tissue vanadium levels and any parameters of glucose homeostasis and hepatic glucose metabolism. Thus, these data suggest that differences in potency between compounds are due to differences in their insulin‐like properties.
There was no marked toxicity observed on hepatic or renal function. However, diarrhoea occurred in 50% of rats chronically treated with VS, but not in those receiving the organic compounds.
In conclusion, organic vanadium compounds, in particular VAc, correct the hyperglycemia and impaired hepatic glycolysis of diabetic rats more safely and potently than VS. This is not simply due to improved intestinal absorption, indicating more potent insulin‐like properties.
British Journal of Pharmacology (1999) 126, 467–477; doi:10.1038/sj.bjp.0702311
In a cross-sectional population study to assess whether environmental exposure to cadmium is associated with renal dysfunction, 1699 subjects aged 20-80 years were studied as a random sample of four ...areas of Belgium with varying degrees of cadmium pollution. After standardisation for several possible confounding factors, five variables (urinary excretion of retinol-binding protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin, aminoacids, and calcium) were significantly associated with the urinary excretion of cadmium (as a marker of cadmium body burden), suggesting the presence of tubular dysfunction. There was a 10% probability of values of these variables being abnormal when cadmium excretion exceeded 2-4 micrograms/24 h. Excretion reached this threshold in 10% of non-smokers. There was also evidence that diabetic patients may be more susceptible to the toxic effect of cadmium on the renal proximal tubule.
OBJECTIVES: This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role ...of arsenicals present in food and of the element present in drinking water. METHODS: 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. CONCLUSIONS: To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.
On the basis of studies of the prevalence of skin cancer among users of As-rich well water in Taiwan, WHO experts recommended in 1984 a maximum As concentration of 50
μg/litre in drinking water. ...Since that time, a plethora of non-cancer as well as cancer effects has been observed in several other populations sustaining a chronic exposure to various As concentrations in drinking water. This prompted a revision of the standard and a provisional guideline of 10
μg/litre was recommended in 1993. While the uncertainty linked to the statistical inferences leading to the guideline are reduced by the fact that they are directly estimated from human data and result from extrapolations made relatively close to observed exposure levels, developed guideline depends strongly on the choice of the dose–response model (linear, quadratic, hockey-stick) and the accuracy of the exposure data. The potential exposure to As sources other than drinking water, dietary habits and genetic characteristics of the populations may also make more difficult the inference of a recommendation for As concentration in drinking water. Owing to the huge cost of strongly reducing the current As in water standard, many efforts are presently made to clarify the quantitative aspects of As-induced cancers, particularly at low dose levels. New data on the metabolism and carcinogenic mechanism of As in humans along with the results of epidemiological studies presently under way in several countries will help to reduce the uncertainty in the risk assessment of As.
Selenium is a trace element that exerts certain insulin-like actions in vitro. In this study, we evaluated its in vivo effects on the glucose homeostasis of rats made diabetic and insulin-deficient ...by streptozotocin. Na2SeO4 was administered ad libitum in drinking water and/or food for 10 weeks. The elevated plasma glucose levels (approximately 25 mmol/l) and glucosuria (approximately 85 mmol/day) of untreated rats were decreased by 50 and 80%, respectively, by selenate treatment. The beneficial effect of selenate was also evident during oral and intravenous glucose tolerance tests: the integrated glucose responses were decreased by 40-50% as compared to those in untreated rats. These effects were not due to an increase in plasma insulin levels. Compared to non-diabetic rats, pancreatic insulin reserves were reduced by more than 90% in treated and untreated diabetic rats. The hepatic activities and mRNA levels of two key glycolytic enzymes, glucokinase and L-type pyruvate kinase were blunted in diabetic rats. They increased approximately two- to threefold after selenate treatment, to reach 40-75% of the values in non-diabetic rats. In contrast, elevated activity and mRNA levels of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase, were reduced by 40-65% after selenate administration. Since selenate induced a moderate decrease in body weight due to an anorexigenic effect, we checked that there was no improvement of glucose homeostasis or hepatic glucose metabolism in an additional group of calorie-restricted diabetic rats, which was weight-matched with the selenate group. In addition, no obvious toxic side-effects on the kidney or liver were observed in the rats receiving selenate. In conclusion, selenate induces a sustained improvement of glucose homeostasis in streptozotocin-diabetic rats by an insulin-like action, which involves partial correction of altered pretranslational regulatory mechanisms in liver metabolism.
PDF
