Luca Fontana

The Effects of Nanomaterials as Endocrine Disruptors

In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited.

Exposure of rome city tram drivers to airborne platinum, rhodium, and palladium

Objective: To investigate the exposure of tram drivers of Rome to Pt, Rh, and Pd in total suspended particulate, PM10, and PM2.5 fractions. Methods: Sampling was performed on a tram running on about 15-km pathway characterized by a medium-high traffic car density. The analytical determination of metals was performed using inductively coupled plasma mass spectrometry. Results: Mean element values (in pg/m3) total suspended particulate, PM10, and PM2.5, were Pt, 20.3, 14.1, and 8.86, Rh, 3.99, 2.83, and 1.94, and Pd, 82.1, 58.0, and 15.2, respectively. Conclusions: Although the Pt, Rh and Pd levels in urban air were found to be still 8 to 11 orders of magnitude below the values thought to cause adverse effects on adult worker health, periodic environmental monitoring would be necessary to detect possible increments which could affect occupational exposure of tram drivers.

The effects of nanoparticles on the renal system

Abstract Through a process of translocation across biological barriers, nanoparticles can reach and deposit in secondary target organs where they may induce adverse biological reactions. Therefore, a correct assessment of nanoparticle-induced adverse effects should take into account the different aspects of toxicokinetics and tissues that may be targeted by nanoparticles. For this reason, a comprehensive evaluation of renal nanotoxicity is urgently needed as kidneys are particularly susceptible to xenobiotics and renal excretion is an expected and possible elimination route of nanoparticles in living organisms. On one hand, summarizing the findings of in vitro and in vivo studies that have investigated the adverse effects of nanoparticles on the kidney, this review intends to provide a thorough insight into the nephrotoxicity of these substances. The evaluation of the in vitro studies revealed that different types of nanoparticles (carbon, metal and/or silica nanoparticles) are able to exert significant cytotoxic effects (i.e., decreased cell viability, induction of oxidative stress, mitochondrial or cytoskeleton dysfunction and cell membrane and DNA damage). On the other hand, in vivo studies demonstrated that nanoparticles exhibited an important nephrotoxic potential both at tubular (i.e., degeneration of tubular epithelial cell, cellular fragments and proteinaceous liquid in tubule lumen, renal interstitial fibrosis) and glomerular level (i.e., swollen glomeruli, changes in Bowman’s space and proliferation of mesangial cells). Although the data currently available indicate that nanoparticles may adversely impact the renal system, further studies are needed in order to clarify all the potential molecular mechanisms of nephrotoxicity induced by these xenobiotics, in particular at glomerular level.

Effects of sub-chronic exposure to palladium (as potassium hexachloro-palladate) on cytokines in male Wistar rats.

Palladium (Pd) is a heavy metal belonging to the platinum group elements. It has been shown that Pd and its compounds can cause sensitization, asthma and dermatologic disorders. In this study, Wistar rats were exposed for 3 months to 0, 1, 10, 100, and 250 ng/ml of Pd (as potassium hexachloro-palladate) in drinking water. At the end of exposure, possible changes in two type-1 cytokines [interleukin (IL)-2, interferon (INF)-γ] and one type-2 cytokine (IL-4) in the serum were measured. After the sub-chronic exposure, analysis of variance of IL-2 and INF-γ response shows that the difference between mean values in the groups of animals exposed reaches statistical significance for IL-2 (P = 0.001), showing a J-shaped dose–response relationship. At the higher dose of 250 ng/ml Pd, it was observed a significant increase in IL-2 production when compared with the controls. Furthermore at 1 and 10 ng/ml of Pd we observed an increase of INF-γ production that was significant at 100 ng/ml of Pd, while at the higher dose of 250 ng/ml of Pd the response was indistinguishable from the control. At the doses investigated, Pd has been shown not to determine a modification of IL-4 response (P = 0.10). These preliminary findings indicate the need to carry out further investigations regarding the effect of other Pd compounds and the measurement of other types of cytokines both in the animal model used in our study and other models.

Distribution and elimination of palladium in rats after 90-day oral administration.

This study determined the distribution in internal organs and the elimination routes in rats after oral administration of potassium hexachloro-palladate. Forty male Wistar rats were exposed for 90 days to 0, 10, 100 and 250 ng/mL of the palladium (Pd) salt in drinking water. Samples of urine and feces were collected on days 1, 30, 60 and 90, while organs (kidney, liver, lung, spleen and bones) and blood were collected at the end of the experiment. Quantification method was based on the sector-field inductively coupled plasma mass spectrometry. Results indicated that Pd ions were rapidly eliminated from the body. The principal excretion was through the feces (650 ± 72.7 ng/g dry weight, at the Pd dose of 250 ng/mL), but at the higher dosing Pd was also eliminated through the urine (6.16 ± 1.91 ng/mL for the Pd intake of 250 ng/mL). A clear relationship between the Pd ingested dose and the Pd excretion amount was observed mainly in the feces. Absorbed Pd was mostly found in the kidney of rats (124.4 ± 23.0 ng/g dry weight, following the highest dose), while liver, lung, spleen and bones did not accumulate the metal. At the higher dosing, Pd content in the kidney raised proportionally with the Pd dose. Our findings may be useful to help in the understanding of the health impact of Pd dispersed in the environment as well as in identifying appropriate biological indices of Pd exposure.

The effects of iridium on the renal function of female Wistar rats

Despite the widespread use of iridium (Ir) in catalytic converters for improved capacity for reducing carbon monoxide (CO), hydrocarbon (HC) and nitrogen oxide (NO(x)) emissions, there is a lack of studies that have assessed possible toxicological hazards of exposure to Ir. The present investigation indicates that female Wistar rats exposed to Ir in the drinking water for 90 days displayed renal toxicity based on the elevated urinary retinol binding protein (RBP) and albumin. The RBP was more sensitive to albumin, showing significant increases at 0.01 mg/L.

Iridium alters immune balance between t helper 1 and t helper 2 responses

The recent introduction of iridium (Ir) into the catalytic converter has resulted in an increase of Ir levels into the environment, especially ambient air and soil. These observations suggested the need to evaluate potential toxicity due to Ir exposure. Since Ir compounds have been previously shown to cause immune sensitization in humans, the effects of Ir via drinking water for 90 days was assessed in adult female Wistar rats with respect to selected immune parameters. The Ir exposure induced dose-dependent decrease (p < .01) in T helper 1 (Th1) cytokines and increase (p < .001) in a T helper 2 (Th2) cytokine. The findings show that the Ir exposure affects an immune imbalance with a skewing toward a Th2 bias, a risk factor for asthma.

Palladium: Exposure, Uses, and Human Health Effects

Palladium (Pd) is a precious metal that, together with iridium (Ir), platinum (Pt), rhodium (Rh), ruthenium (Ru), and osmium (Os), belongs to the platinum group elements (PGEs). Pd is one of the rarest elements in the earths crust and its main ore deposits are found in the Russian Federation and South Africa. The unique chemical and physical properties of palladium account for its widespread use in many industrial sectors like chemical and petroleum industry, production of automobile catalysts, electronic devices, dental applications, and fine jewelry. A significant increase in the industrial use of Pd in the past 20 years has resulted in higher environmental levels of this metal, particularly in road dust, airborne particulate, soil, and groundwater tables. Therefore, it is clear that in recent years there has been a notable increase in Pd exposure both in the general population and in occupationally exposed subjects. Exposure to Pd can cause acute toxicity or hypersensitivity with respiratory symptoms, urticaria and, less frequently, contact dermatitis. Epidemiological studies have demonstrated that, among metals, Pd ions are one of the most frequent reacting sensitizers. This effect on the immune system represents the most important health hazard to humans.

Nanoparticle Exposure and Hormetic Dose–Responses: An Update

The concept of hormesis, as an adaptive response of biological systems to moderate environmental challenges, has raised considerable nano-toxicological interests in view of the rapid pace of production and application of even more innovative nanomaterials and the expected increasing likelihood of environmental and human exposure to low-dose concentrations. Therefore, the aim of this review is to provide an update of the current knowledge concerning the biphasic dose–responses induced by nanoparticle exposure. The evidence presented confirmed and extended our previous findings, showing that hormesis is a generalized adaptive response which may be further generalized to nanoscale xenobiotic challenges. Nanoparticle physico-chemical properties emerged as possible features affecting biphasic relationships, although the molecular mechanisms underlining such influences remain to be fully understood, especially in experimental settings resembling long-term and low-dose realistic environmental exposure scenarios. Further investigation is necessary to achieve helpful information for a suitable assessment of nanomaterial risks at the low-dose range for both the ecosystem function and the human health.

Effects of sub-acute exposure to rhodium (as Rh (III) chloride hydrate) on cytokines in female Wistar rats.

Quantitative changes in different cytokines were determined in serum of female Wistar rats exposed to Rhodium (III) chloride hydrate to evaluate its early effects on the immune system. Findings revealed an inhibitory effect of Rh salt since each cytokine, with the exceptions of IL-1α and IL-2 levels observed at the highest doses of exposure, was reduced compared to the controls and interestingly, the lowest doses induced the greatest inhibition. This generalized decrease of cytokine levels was not related to a specific cytokine pathway, and may suggest an anti-inflammatory role of Rh salt.