Molecular mechanisms of nickel carcinogenesis: gene silencing by nickel delivery to the nucleus and gene activation/inactivation by nickel-induced cell signaling

We have summarized the molecular and cellular events involved in nickel (Ni) compound induced carcinogenesis. The major hypothesis for nickel carcinogenic action has involved the ability of the Ni compound to deliver high concentrations of Ni intracellularly, enter the nucleus and interact with chromatin. Ni has been found to selectively damage heterochromatin, and a major action of Ni is its ability to silence the expression of genes located near heterochromatin by inducing a loss of histone H4 and H3 acetylation and DNA hypermethylation. When Ni silences critical genes, such as tumor suppressor genes, the cell is altered to a greater state of neoplastic transformation. The carcinogenic hazard of Ni compounds has been directly related to the ability of that Ni compound to raise the intracellular Ni ions. The mechanisms of Ni-induced gene silencing will be discussed. However, recently it has been found that soluble Ni ions can interact with the cell surface receptors and activate cell signaling resulting in the induction of a variety of cellular genes. In particular, the Ca and hypoxia inducible factor pathway is activated in all cells exposed to soluble Ni ions. In the case of HIF-1 induction, a cell is now equipped with the expression of a variety of genes that will allow the cell to survive the lack of oxygen and thus should enable a previously initiated cancer cell to progress into a full malignant state and metastasize. These new findings support the view that soluble Ni ions exhibit carcinogenic potential by activating cell promotion and lend strength to the epidemiological data showing soluble Ni to be associated with cancer risk in Ni refinery workers.     

Radiographic evidence of pulmonary fibrosis and possible etiologic factors at a nickel refinery in Norway

Animal studies have shown that nickel compounds may induce pulmonary fibrosis, but so far only limited documentation in humans has been available. Radiographs of 1046 workers in a nickel refinery in Norway were read blindly and independently by three NIOSH certified B-readers, according to the ILO standards. Pulmonary fibrosis (PF) was defined as a median reading of ILO score > or = 1/0 and following this criterion, 47 cases (4.5%) were identified. In logistic regression models, controlling for age and smoking, there was evidence of increased risk of PF with cumulative exposure to soluble nickel or sulfidic nickel (p = 0.04 for both). For metallic nickel a p-value of 0.07 was found. For soluble nickel there was a dose-response trend for 4 categories of cumulated exposure. In the group with the highest cumulative exposure to soluble nickel (low exposure as reference), the crude odds ratio for PF was 4.34 (95% CI 1.75-10.77). The risk adjusted for age, smoking, asbestos and sulfidic nickel was 2.24 (0.82-6.16), with a dose-response trend. The corresponding figures for sulfidic nickel were 5.06 (1.70-15.09, crude) and 2.04 (0.54-7.70, adjusted for age, smoking, asbestos and soluble nickel). However, the dose-response trend was less clear for sulfidic nickel. Controlling for estimated asbestos exposure at the refinery tended to increase the odds ratios of soluble and sulfidic nickel. This study indicates that in addition to age and smoking exposure to soluble and sulfidic nickel compounds are risk factors of PF in humans. Since the number of cases identified in this study is small and undetected confounders may have been present, further studies in other cohorts are appropriate.     

X-ray diffraction spectrometric analysis of nickel refinery aerosols,process materials and particulates isolated from worker lung tissues

Results are reported of X-ray diffraction analysis of extracts derived from lungs of two nickel refinery workers and of three stationary air samples collected inside a nickel refinery. Since environmental samples from the 1950s and 1960s do not exist, two archived production control samples from that period were also analyzed. Because nickel has been found in respiratory tissue of workers retired for more than twenty years, it was likely that the residual nickel compounds must be rather insoluble. Preliminary surveys showed that sulfur was not present in the lung tissue deposits and thus water-soluble and sulfidic nickel were therefore extracted from the ten process samples before the X-ray analysis. A common compound that was found in all 10 samples was trevorite. This is a spinel-type mineral, much like magnetite where the divalent iron is replaced by nickel. It may be formed when trivalent iron reacts with nickel at 1100 degrees C. It has magnetic properties and is very insoluble. Samples from the lungs were obtained by burning off the organic tissue at 630 degrees C. Due to a relatively high detection limit for the X-ray diffraction technique, we were initially not able to detect any mineral nickel compound. But when particles extracted with a magnet were analyzed, a very clear diffraction pattern of trevorite was identified. The main residue after the magnetic separation had a low concentration of nickel (4 microg g(-1)), which suggests that trevorite was the dominating, if not the only, nickel compound present. In addition, chemical analyses were performed on 13 tissue samples from one single lung; one from each main bronchus, two from each lobe, and an additional one from the lower right lobe. Statistical testing showed a highly significant correlation between the five elements determined: Ni, Co, Cu, Fe and Cr. This suggests that these metals are isomorphous and substitute for each other in the mineral structure. These results may indicate that the nickel left in the lungs some years after exposure is trevorite, and may be biologically inert. However, further speciation of nickel compounds in the lungs seems warranted, and trevorite should be tested for its potential toxic effects.     

Correlation of urinary nickel excretion with observed 'total' and inhalable aerosol exposures of nickel refinery workers

An investigation of the relationship between observed nickel aerosol exposures and urinary nickel excretion was undertaken at a Scandinavian nickel refinery. The goal of the study was to assess the impact of nickel aerosol speciation, the use of particle size-selective sampling instrumentation and adjustment of urinary levels for creatinine excretion on the usefulness of urinary nickel excretion as a marker for exposure. Urinary nickel measurements and paired 'total' and inhalable aerosol exposure measurements were collected each day for one week from refinery workers in four process areas. The mean observed urinary nickel concentration was 12 micrograms L-1 (11 micrograms of Ni per g of creatinine). The strongest relationships between urinary excretion and aerosol exposure were found when urinary nickel levels were adjusted for creatinine excretion and when exposure to only soluble forms of nickel aerosol was considered. No significant difference was observed between measures of 'total' and inhalable aerosol in the ability to predict urinary excretion patterns. In the light of these results, it is recommended that consideration be given to the chemical species distribution of nickel aerosol in the use of urinary nickel measurements as a screening tool for cancer risk in occupationally-exposed populations.     

Probabilistic human health risk of PCDD/F exposure: a socioeconomic assessment

The aim of the present study was to assess the human health risks (carcinogenic and non-carcinogenic) of PCDD/F exposure for the adult population living in two different areas (industrial and residential) of Tarragona (Catalonia, Spain), as well as to compare these risks according to the socioeconomic status of the population. Two pathways were considered for PCDD/F exposure: direct (air inhalation, dermal contact and ingestion from soils and dust) and dietary. Although environmental exposure was higher for the population living in the neighborhood of the industrial area (mainly lower socioeconomic group subjects), it only accounted 1.05%. On the other hand, PCDD/F exposure through dietary intake was more important for those individuals of an upper socioeconomic level. This was due to the fact that their diet is richer in those foodstuffs containing higher PCDD/F concentrations. Consequently, taking together direct and dietary exposure to PCDD/Fs, the result is that upper socioeconomic group populations are more exposed to these toxic pollutants. In any case, the current levels of PCDD/F exposure would not mean significant carcinogenic and non-carcinogenic risks for the population living in the industrial and residential areas of Tarragona.     

Multi-component assessment of worker exposures in a copper refinery. Part 1. Environmental monitoring

The exposure characterisation described in this paper for 135 copper refinery workers (45 females, 90 males) focuses on the concentrations of copper, nickel and other trace elements in the inhalable aerosol fractions, as well as in the water-soluble and water-insoluble subfractions. Some information is also provided on the thoracic and respirable aerosol fractions. Further, results are presented for volatile hydrides of arsenic and selenium released in the copper purification steps of the electrorefining process. For the pyrometallurgical operations, a comparison of the geometric means for the inhalable aerosol fraction indicated that water-soluble copper levels were on average 19-fold higher compared to nickel (p < 0.001) and a significant association was evident between them (r = 0.87, p < 0.001); for the insoluble subfraction, the copper : nickel ratio was 12.5 (p < 0.001) and the inter-element correlation had r = 0.98 and p < 0.001. Although for the electrorefinery workers the relative inhalable concentrations of copper and nickel were not significantly different (p > 0.05), the corresponding inter-element associations were: slope of 7.7, r= 0.54, p < or =0.001 for the water-soluble subfraction and slope of 1.3, r = 0.71 and p < or =0.001 for the water-insoluble subfraction. On average, a good proportion of the inhalable copper and nickel were found in the thoracic (40%) and respirable (20%) aerosol fractions. Cobalt air concentrations were generally low with geometric means and 95% confidence intervals of 3.1 (2.4-4.2)microg m(-3) (pyrometallurgical workers) and 0.3 (0.4-0.5) microg m(-3)(electrorefinery workers). Similarly, the maximum concentrations of cadmium and lead were low, respectively 4 and 25 microg m(-3). Of the hydrides, tellurium and antimony could not be detected, but for the arsenic (arsine) and selenium hydrides measurable exposure occurred for almost all electrorefinery workers, although the levels were generally low at 0.2 microg m(-3).     

Partitioning between soluble and insoluble fractions of major and trace elements in size-classified airborne particulate matter collected in Tokyo

Airborne particulate matter (APM) is a major air pollutant, and the effect on human health of fine APM (PM2.5) deposited deep inside the lungs has recently become a serious concern. Moreover, soluble constituents may leach from APM, and intensify some health disorders. To identify the soluble chemical constituents of APM, size-classified APM was sampled in central Tokyo, and the elemental compositions of the water-soluble, acid-soluble and insoluble fractions were investigated. The extraction procedure was validated by calculating the mass balance of soluble and insoluble fractions of a standard APM reference material (NIST SRM 1648). Among the major elements, Fe and Ti in APM of all size classes and K in coarse APM were distributed primarily in the insoluble fraction and were inferred to be present as oxides or silicates, whereas Na and Mg in all size classes and K in fine APM were primarily in the water-soluble fraction and were inferred to be have originated mainly from sea salt. Among the trace elements, Zn and Cd in the fine APM (d < 2 microm) had large enrichment factors, indicating an anthropogenic origin, and were distributed primarily in the water-soluble fraction. When fine anthropogenic APM enters into the lungs, leached toxic elements, such as Cd, may adversely affect health. The higher the bonding energy of the monoxide molecule of the element was, the higher its distribution ratio was in the water-soluble fraction. Therefore, many metallic elements in APM were inferred to be present as oxygen-bonded compounds.     

Manganese air exposure assessment and biological monitoring in the manganese alloy production industry

One hundred workers carried personal air sampling equipment during three days to assess exposure to inhalable and respirable Mn. A novel four-step chemical fractionation procedure developed for the speciation of Mn in workroom aerosols was applied for selected aerosol filters. Blood and urine samples were analysed for Mn. The geometric mean (GM) concentrations of inhalable (n = 265) and respirable (n = 167) Mn determined in all filters were 254 microg m(-3) and 28 microg m(-3) respectively. Only 10.6% (95% CI 8.9-12.5) respirable Mn was found in the inhalable fraction when inhalable and respirable samples collected in parallel were considered (n = 153 pairs). There was a high correlation (Pearson's r = 0.70; p < 0.001) between respirable and inhalable Mn. The largest amounts of Mn in the inhalable aerosol fraction were found as Mn0 and Mn2+ (47.4%), whereas 28% was practically "insoluble". The associations between B-Mn and aerosol concentrations of Mn were weak, but an association was found between U-Mn and respirable Mn; Pearson's r being 0.38 between "soluble" respirable Mn and U-Mn. No significant association was found between the "insoluble" components (probably SiMn) and Mn in biological samples.     

Welding fumes from stainless steel gas metal arc processes contain multiple manganese chemical species

Fumes from a group of gas metal arc welding (GMAW) processes used on stainless steel were generated using three different metal transfer modes and four different shield gases. The objective was to identify and measure manganese (Mn) species in the fumes, and identify processes that are minimal generators of Mn species. The robotic welding system was operated in short-circuit (SC) mode (Ar/CO2 and He/Ar), axial spray (AXS) mode (Ar/O2 and Ar/CO2), and pulsed axial-spray (PAXS) mode (Ar/O2). The fumes were analyzed for Mn by a sequential extraction process followed by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis, and by X-ray diffraction (XRD). Total elemental Mn, iron (Fe), chromium (Cr) and nickel (Ni) were separately measured after aqua regia digestion and ICP-AES analysis. Soluble Mn2+, Fe2+, Fe3+, and Ni2+ in a simple biological buffer (phosphate-buffered saline) were determined at pH 7.2 and 5.0 after 2 h incubation at 37 C by ion chromatography. Results indicate that Mn was present in soluble form, acid-soluble form, and acid-soluble form after reduction by hydroxylamine, which represents soluble Mn0 and Mn2+ compounds, other Mn2+ compounds, and (Mn3+ and Mn4+) compounds, respectively. The dominant fraction was the acid-soluble Mn2+ fraction, but results varied with the process and shield gas. Soluble Mn mass percent in the fume ranged from 0.2 to 0.9%, acid-soluble Mn2+ compounds ranged from 2.6 to 9.3%, and acid plus reducing agent-soluble (Mn3+ and Mn4+) compounds ranged from 0.6 to 5.1%. Total Mn composition ranged from 7 to 15%. XRD results showed fumes had a crystalline content of 90-99% Fe3O4, and showed evidence of multiple Mn oxides, but overlaps and weak signals limited identification. Small amounts of the Mn2+ in the fume (<0.01 to ≈ 1% or <0.1 to ≈ 10 microg ml(-1)) and Ni2+ (<0.01 to ≈ 0.2% or <0.1 to ≈ 2 mg ml(-1)) ions were found in biological buffer media, but amounts were highly dependent on pH and the welding process. Mn generation rates for the fractions were tabulated, and the influence of ozone is discussed. The conclusions are that exposures to welding fumes include multiple Mn species, both soluble and insoluble, and that exposures to Mn species vary with specific processes and shield gases.     

Evaluation of a standardized method for determining soluble silver in workplace air samples

Several occupational exposure limits and guidelines exist for silver, but the values for each depend on the chemical form of the silver compound in question. In the past, it generally was not possible, without prior knowledge of the work process, to distinguish soluble silver from insoluble silver compounds collected in workplace air samples. Therefore, analytical results were historically reported as total silver. In this study, work was conducted to evaluate a method to differentiate between the quantities of water-soluble silver compounds and total silver collected on filters. The investigation entailed an evaluation of an International Organization for Standardization method to determine soluble silver in airborne particulate matter. The study design incorporated laboratory experiments to evaluate analytical figures of merit, such as selection of appropriate filter media and extraction solution, analytical recovery, and sample stability during storage. Polytetrafluoroethylene (PTFE) filters (2 microm, 37 mm) in opaque cassettes were either spiked with known amounts of silver nitrate or contained a known mass of solid silver nitrate. Results showed that over 90% of the silver was recovered from PTFE filters. Also, field studies were conducted in which workplace air samples were collected in two silver refineries. Some of these samples were analyzed only for soluble silver while others were sequentially extracted and analyzed, first, for soluble silver, then for total silver. The mass fractions of soluble silver, as compared to total silver, were approximately 2% or less. This investigation served to validate an international standard procedure for the determination of soluble silver in workplace air samples.     

Intercommunity and temporal variation of eleven essential and five toxic elements in human placentas from deliveries in thirteen arctic and sub-arctic areas of Russia and Norway

Research is described that constitutes an extension of an earlier paper (J. Environ. Monit., 2001, 3, 177-184), in which concentrations were measured in 263 human placentas of 11 essential elements (P, Ca, Mg, Cu, S, Na, Fe, Zn, K, Se, Mn) and 5 toxic elements (Ba, Sr, Pb, Ni, Cd). The additional data considered derive from earlier visits to 4 of the original 6 communities and 3 others, all but one of which are located in northern Norway and neighbouring areas of Russia. This more than doubled the number of placental samples available (263 to 571). Unfortunately, the personal, life-style and morphometric information obtained for the first study group was not available for the additional mothers. Country differences were evident for all elements except Ba, Fe and Zn; Cd, Cu, Mn, Na, Se, Ni, Pb, Sr and S were higher and K, P, Ca and Mg were lower in Russia (p < 0.03). Not unexpectedly, the highest median lead concentration was observed for the largest city in the western arctic region of Russia, namely Murmansk. Similarly, the higher median nickel level observed for Russia reflects the established observation that urinary nickel concentrations are higher in the Russian than in the Norwegian communities. Even though sampling was performed at different times of the year and before and after a 3-year interval in four centres, inter-collection differences were of relatively small magnitude and appear not to be linked to seasonal or temporal changes. Principal component analysis (PCA) confirmed the prominence of Factor 1, which grouped those metals that are known to form insoluble phosphate complexes and whose concentrations showed a dependence on gestational age and maternal smoking in the earlier study. It is concluded that PCA is a powerful statistical tool for exploring and identifying fundamental pathways and processes involved in governing the inorganic elemental composition of placental tissue. It also has the potential of identifying study limitations and quality assurance shortfalls. Further our findings show promise that placental concentrations of toxic elements may serve as an index of exposure and of nutritional intake for selected essential micro-elements.     

Air quality and deposition of trace elements in Didouche Mourad, Algeria

Total suspended particulate matter and deposition fluxes of particles were investigated in the town of Didouche Mourad which is located 13 km north of Constantine. Samples of air particulate matter were collected at one site located in the heart of the town and situated 3 km north of a cement plant. Samples were collected from 2 November 2002 to 28 April 2003 every 3 days using a high volume air sampler. Sampling intervals were 24 h in all cases. During the same period, samples of dust fallout were collected at the same site. Samples were collected at 30-day intervals. Lead, chromium, manganese, nickel, copper, cobalt and cadmium deposition fluxes were measured and both the soluble and insoluble fractions were determined. Furthermore, the information gathered by this study was correlated with the corresponding hourly weather data provided by a weather station installed at the study station. The possible sources for dust and trace metals were analyzed by comparing average contributions of wind aspects to the concentrations and depositions of mass and chemical species with the average frequencies of wind direction. The mean concentration was 300 μg/m³. The average dust deposition rate through the period of study was 221 mg/(m².day). Results indicate that anthropogenic sources contribute greatly to trace elements. An exposure assessment to the heavy metals taking into account the inhalation route and soil dust ingestion was carried out and allowed direct comparison of trace metal intakes via these routes.     

Is benzene exposure from gasoline carcinogenic?

This article questions the basis for benzene as the carcinogenic surrogate in deriving health risk-based 'clean-up levels' for gasoline-impacted soil and groundwater at leaking underground storage tank properties. The epidemiological evidence suggests that acute myelogenous leukemia (AML) associated with chronic occupational benzene exposure can be best described by sigmoid dose-response relationships. A review of the molecular toxicology and kinetics of benzene points to the existence of threshold mechanisms in the induction of leukemia. The toxicological and epidemiological literature on chronic exposure to unleaded gasoline indicates that the benzene exposures required to induce a measurable carcinogenic response are substantially greater than exposures likely to be encountered from exposure to gasoline at contaminated properties. Thus, assuming that theoretical cancer risks associated with exposure to benzene from gasoline reflect actual health risks associated with such environmental exposures to gasoline and using these theoretical cancer risks and cancer potency factors for benzene to dictate soil and groundwater clean up of gasoline are not scientifically defensible.     

Environmental monitoring of the role of phosphate compounds in enhancing immobilization and reducing bioavailability of lead in contaminated soils

Lead is a highly toxic element and forms stable compounds with phosphate, which is commonly used to immobilize Pb in soils. However, few studies have monitored the long-term stability of immobilized Pb, which is a critical factor in determining the effectiveness of the in situ stabilization technique. Both soluble and insoluble phosphate compounds were tested for Pb immobilization, and its subsequent mobility and bioavailability in a contaminated soil from a shooting range. Adding tricalcium phosphate, hydroxyapatite, rock phosphate and potassium dihydrogen phosphate reduced the concentration of ammonium-nitrate-extractable Pb in the contaminated soil by 78.6%, 48.3%, 40.5% and 80.1%, respectively. Insoluble phosphate amendments significantly reduced leached Pb concentration from the column while soluble potassium dihydrogen phosphate compound increased P and Pb concentrations in the leachate. Rock phosphate reduced Pb accumulation in earthworms by 21.9% compared to earthworms in the control treatment. The long-term stability of immobilized Pb was evaluated after 2 years' incubation of the contaminated soil with rock phosphate or soluble phosphate compounds. Bioavailable Pb concentration as measured by simple bioavailability extraction test (SBET) showed the long-term stability of immobilized Pb by P amendments. Therefore, Pb immobilization using phosphate compounds is an effective remediation technique for Pb-contaminated soils.     

The hygroscopic behaviour of individual aerosol particles in nickel refineries as investigated by environmental scanning electron microscopy

The hygroscopic properties of individual aerosol particles (1-35 microm equivalent projected area diameter) from the Roasting, Anode Casting and Electrorefining Departments of two Ni refineries were studied by environmental scanning electron microscopy (ESEM) and energy-dispersive X-ray microanalysis (EDX) at a relative humidity of 96-98% (at a temperature of 5 degrees C). In the Roasting and Anode Casting Departments, most particles (60-85% by number) showed no visible change in size or surface morphology when exposed to high relative humidity. Approximately 15-30% of the particles developed a thin water film (growth factors between 1.006 and 1.06) indicating the presence of thin surface coatings of sulfates. About 10% of the particles in the Roasting Department formed droplets (growth factors between 1.1 and 2.6) which always contained a large portion of insoluble material. In the Electrorefining Department, most particles (approximately 60%) were residues from the electrolysis bath solution. At a relative humidity of 96-98% these particles formed a solution which contained only small insoluble inclusions. About 30% of the particles in the Electrorefining Department developed thin water films. As only a small fraction of the particles increased substantially in size when exposed to high relative humidity, the deposition pattern of the total aerosol mass fraction will not be changed substantially by hygroscopic growth. The frequent occurrence of thin surface coatings of soluble material on insoluble Ni compounds has to be considered for health assessment purposes.     

Bioluminescent yeast estrogen assay (BLYES) as a sensitive tool to monitor surface and drinking water for estrogenicity

Estrogenic Endocrine Disrupting Chemicals (EDCs) are a concern due to their ubiquity and recognized adverse effects to humans and wildlife. Methods to assess exposure to and associated risks of their presence in aquatic environment are still under development. The aim of this work is to assess estrogenicity of raw and treated waters with different degrees of pollution. Chemical analyses of selected EDCs were performed by liquid chromatography-tandem mass spectrometry, and estrogenic activity was evaluated using in vitro bioluminescent yeast estrogen assay (BLYES). Most raw water samples (18/20) presented at least one EDC and 16 rendered positive in BLYES. When EDCs were detected, the bioassay usually provided a positive response, except when only bisphenol A was detected at low concentrations. The highest values of estrogenic activity were detected in the most polluted sites. The maximum estrogenic activity observed was 8.7 ng equiv. of E2 L(-1). We compared potencies observed in the bioassay to the relative potency of target compounds and their concentrations failed to fully explain the biological response. This indicates that bioassay is more sensitive than the chemical approach either detecting estrogenic target compounds at lower concentrations, other non-target compounds or even synergistic effects, which should be considered on further investigations. We have not detected either estrogenic activity or estrogenic compounds in drinking water. BLYES showed good sensitivity with a detection limit of 0.1 ng equiv. E2 L(-1) and it seems to be a suitable tool for water monitoring.     

Statistical methods to apportion the sources of particles in the industrial region of Estarreja—Portugal

Factor analysis models are very attractive for source apportionment and have been widely applied. They do not require a priori knowledge of the number and composition of the sources, and they can actually uncover previously unsuspected sources and estimate the composition of the sources using only ambient monitoring data.Aerosol particles were collected from an industrial atmosphere and analyses for water soluble and carbon components. Principal components analysis permitted the evaluation of the contribution due to industries, soil fraction, secondary pollutants and sea spray particles of the total suspended aerosol mass.It can be concluded that the atmospheric aerosol in the Industrial Area of Estarreja (Portugal) contains a relative important fraction that is water soluble. Ammonium sulphates and nitrates are the main components of this fraction. Carbon compounds constitute about 30% of the total aerosol mass. These compounds are mainly formed by organic matter emitted by the industries. Due to the mutagenic and carcinogenic characteristics of some organic compounds processed in the Industrial Area (vinyl chloride, benzene, aniline, etc.), the concern exists of negative human health effects as a result of prolonged inhalation. Soil compounds is another important fraction of the aerosol mass, mainly in summer with dry, sunny and windy weather conditions.A more conclusive idea of the sources and effects of aerosol matter can only be obtained with the specific analysis of organic compounds and the determination of trace elements, characteristic of each particular source.     

Monitoring of polychlorinated biphenyl contamination and estrogenic activity in water, commercial feed and farmed seafood

We evaluated the concentration and congener distribution of seven "target" polychlorinated biphenyls (PCBs) present in water collected in different aquaculture farms of the Mediterranean area, commercial feeds, and farmed seafood. PCBs were present in feed and in tissues of all the analysed organisms at levels ranging from 1.96 ng g(-1) to 124.00 ng g(-1) wet weight, and in 10.5% of the water samples, at levels from under detection limit to 33.0 ng l(-1) with total PCB concentrations significantly higher in samples from the Tyrrhenian Sea than the Adriatic Sea. PCB congener distribution in tissues resembled that of feed, suggesting that commercial feed is an important source of PCBs. The estrogenicity of organic extracts of the samples was also evaluated by using an in vitro yeast reporter assay. Estrogenic activity higher than 10% of the activity induced by 10 nM 17 beta-estradiol was observed in 20.0% of seafood samples and 15.8% of water samples. Seafood and water samples from the Tyrrhenian Sea were more frequently estrogenic than the Adriatic ones (16.45 versus 4.08%). A significant correlation of total PCB concentrations on biological activity was observed for sea bass and mussels from the Adriatic Sea (p < 0.045 and p < 0.04, respectively), and for sea bass of the Tyrrhenian Sea (p = 0.05). These results indicate the need of an integral approach in the exposure assessment to potential toxic compounds for human via food.     

In utero and post-natal accumulation of organochlorine compounds in children under different environmental conditions

A study of intake of organochlorine compounds (OCs) in children both in utero and at the age of four years has been performed in two cohorts. One encompasses children born in Menorca Island between 1997 and 1998, and the other those born between 1997-1999 in Ribera d'Ebre, an in-land industrial-agricultural area of Catalonia. Comparison of the OC concentrations in serum samples from both populations, including those obtained from cord blood and blood collected at four years, provides information on the influence of local pollution sources in the accumulation of these compounds. Statistically significant differences (p < 0.01) have been found for hexachlorobenzene, indicating that chronic airborne contamination to this compound in Ribera d'Ebre involved higher in utero exposure, which increased in the first four years of growth. Similarly, in the cohort of Menorca, higher in utero exposure to PCBs was observed and this increased subsequently in the first four years of growth. Other compounds encompassing temporal contamination episodes such as gamma-HCH involved higher in utero exposure but strongly diminished in the first four years of growth. Overall, it can be concluded that local chronic pollution by OCs has a direct effect in children living in the surrounding areas. This influence is reflected in higher exposure, both in utero and in the first years of growth, that significantly stands out over the background contamination due to the ubiquity of these compounds.     

Lung cancer incidence among Norwegian nickel-refinery workers 1953-2000

Among workers employed at a nickel refinery in Norway between 1910 and 1977 an elevated risk of lung cancer has been demonstrated. A dose-related effect from nickel exposure has been identified, with the strongest gradient for water-soluble nickel. This pattern was recently confirmed in a nested case-control study with adjustment for smoking and potential occupational confounders. In the present study, updated cancer data were used to explore the risk by duration of work at the refinery and by exposure to different forms of nickel. Comparisons were made with the national male population (standardised incidence ratios) as well as internal reference groups (Poisson regression) under adjustment for age and smoking. The results confirmed earlier findings of a strong dose-related risk dependent on duration of work in production departments and cumulative exposure to nickel, most clearly seen for water-soluble nickel. Only slightly elevated risks were found among the unexposed and in the group with no experience from production or maintenance work. The risk associated with exposure to nickel chloride was similar to that for nickel sulfate. Analyses restricted to men exposed after 1967, with estimates based on personal monitoring of nickel in the breathing zone, showed the same risk pattern as for earlier years. Elevated lung cancer incidence was even suggested for workers with their first employment after 1978 when a lot of high exposure jobs were abandoned. The combined effect of exposure to nickel and smoking seemed to be in agreement with a multiplicative risk pattern.