Marcella Mauro

Nanoparticles skin absorption: New aspects for a safety profile evaluation

Nanoparticles (NPs) skin absorption is a wide issue, which needs to be better understood. The attempt of this review is to summarize the scientific evidence concerning open questions, i.e.: the role of NPs intrinsic characteristics (size, shape, charge, surface properties), the penetration of NPs through the intact or impaired skin barrier, the penetration pathways which should be considered and the role of NPs interaction in physiological media. The outcomes suggest that one main difference should be made between metal and non-metal NPs. Both kinds have a secondary NPs size which is given after interaction in physiological media, and allows a size-dependent skin penetration: NPs⩽4nm can penetrate and permeate intact skin, NPs size between 4 and 20nm can potentially permeate intact and damaged skin, NPs size between 21 and 45nm can penetrate and permeate only damaged skin, NPs size>45nm cannot penetrate nor permeate the skin. Other aspects play an important role, mostly for metal NPs, i.e., dissolution in physiological media, which can cause local and systemic effects, the sensitizing or toxic potential and the tendency to create aggregates. This paper suggests a decision tree to evaluate the potential risk for consumers and workers exposed to NPs.

Titanium Dioxide Nanoparticle Penetration into the Skin and Effects on HaCaT Cells.

Titanium dioxide nanoparticles (TiO2NPs) suspensions (concentration 1.0 g/L) in synthetic sweat solution were applied on Franz cells for 24 h using intact and needle-abraded human skin. Titanium content into skin and receiving phases was determined. Cytotoxicity (MTT, AlamarBlue® and propidium iodide, PI, uptake assays) was evaluated on HaCat keratinocytes after 24 h, 48 h, and seven days of exposure. After 24 h of exposure, no titanium was detectable in receiving solutions for both intact and damaged skin. Titanium was found in the epidermal layer after 24 h of exposure (0.47 ± 0.33 μg/cm2) while in the dermal layer, the concentration was below the limit of detection. Damaged skin, in its whole, has shown a similar concentration (0.53 ± 0.26 μg/cm2). Cytotoxicity studies on HaCaT cells demonstrated that TiO2NPs induced cytotoxic effects only at very high concentrations, reducing cell viability after seven days of exposure with EC50s of 8.8 × 10−4 M (MTT assay), 3.8 × 10−5 M (AlamarBlue® assay), and 7.6 × 10−4 M (PI uptake, index of a necrotic cell death). Our study demonstrated that TiO2NPs cannot permeate intact and damaged skin and can be found only in the stratum corneum and epidermis. Moreover, the low cytotoxic effect observed on human HaCaT keratinocytes suggests that these nano-compounds have a potential toxic effect at the skin level only after long-term exposure.

Frequency weightings of hand-transmitted vibration for predicting vibration-induced white finger

OBJECTIVE The aim of this study was to investigate the performance of four frequency weightings for hand-transmitted vibration to predict the incidence of vibration-induced white finger (VWF). METHODS In a longitudinal study of vibration-exposed forestry and stone workers (N=206), the incidence of VWF was related to measures of vibration exposure expressed in terms of 8-hour frequency-weighted energy-equivalent root-mean-square (rms) acceleration magnitude [A(8)] and years of follow-up. To calculate A(8), the rms acceleration magnitudes of vibration were weighted by means of four frequency weightings: (i) W(h) (the frequency weighting specified in ISO 5349-1:2001); (ii) W(h-bl) (the band-limiting component of W(h)); (iii) W(hf) (a frequency weighting based on finger vibration power absorption); and (iv) W(hT) (a frequency weighting based on a Japanese study of VWF prevalence). The relations of VWF to alternative measures of vibration exposure were assessed by the generalized estimating equations (GEE) method to account for the within-subject dependency of the observations over time. RESULTS Data analysis with a GEE logistic model and a measure of statistical fit suggested that calculating A(8) by weighting the tool rms accelerations with W(h-bl)gave better predictions of the cumulative incidence of VWF than the other alternative measures of daily vibration exposure. Values of A(8) derived from the currently recommended ISO frequency weighting Wh produced poorer predictions of the incidence of VWF than those obtained with frequency weightings W(hf)or W(hT). CONCLUSIONS This prospective cohort study suggests that measures of daily vibration exposure which give relatively more weight to intermediate and high frequency vibration are more appropriate for assessing the probability of VWF.

Relationships of Neurosensory Disorders and Reduced Work Ability to Alternative Frequency Weightings of Hand-Transmitted Vibration

OBJECTIVE This cohort study aims to compare the performance of alternative frequency weightings of hand-transmitted vibration (HTV) for the assessment of the exposure-response relationships for neurosensory disorders and reduced work ability among HTV-exposed workers. METHODS In a 3-year follow up study, the occurrence of neurosensory symptoms and reduced work ability, and the response to quantitative sensory testing (grip force, manipulative dexterity, touch sensation) were investigated in 249 HTV-exposed workers and 138 healthy controls. Among the HTV-exposed workers, the sensory outcomes were related to measures of daily vibration exposure expressed in terms of 8-hour energy-equivalent frequency-weighted acceleration magnitude [A(8)]. To calculate A(8), the acceleration magnitudes of vibration were weighted by means of four alternative frequency weightings of HTV. RESULTS The occurrence of neurosensory symptoms, reduced work ability, and abnormalities of sensory tests was greater among the HTV-exposed workers than the controls. Among the HTV-exposed workers, the deterioration of neurosensory outcomes and the reduction of work ability increased on par with the measures of vibration exposure. Exposure-response models revealed that the four alternative frequency weightings of HTV provided the same predictions for the probability of finger numbness among the exposed workers (observed 36% versus predicted 32%). CONCLUSIONS The findings of this study revealed significant dose-response relationships between measures of vibration exposure, sensory disorders, and reduced work ability among the HTV-exposed workers. There were no differences in the prediction of finger numbness between measures of vibration exposure calculated with alternative frequency weightings of HTV.

Cobalt Oxide Nanoparticles: Behavior towards Intact and Impaired Human Skin and Keratinocytes Toxicity

Skin absorption and toxicity on keratinocytes of cobalt oxide nanoparticles (Co3O4NPs) have been investigated. Co3O4NPs are commonly used in industrial products and biomedicine. There is evidence that these nanoparticles can cause membrane damage and genotoxicity in vitro, but no data are available on their skin absorption and cytotoxicity on keratinocytes. Two independent 24 h in vitro experiments were performed using Franz diffusion cells, using intact (experiment 1) and needle-abraded human skin (experiment 2). Co3O4NPs at a concentration of 1000 mg/L in physiological solution were used as donor phase. Cobalt content was evaluated by Inductively Coupled–Mass Spectroscopy. Co permeation through the skin was demonstrated after 24 h only when damaged skin protocol was used (57 ± 38 ng·cm−2), while no significant differences were shown between blank cells (0.92 ± 0.03 ng cm−2) and those with intact skin (1.08 ± 0.20 ng·cm−2). To further investigate Co3O4NPs toxicity, human-derived HaCaT keratinocytes were exposed to Co3O4NPs and cytotoxicity evaluated by MTT, Alamarblue® and propidium iodide (PI) uptake assays. The results indicate that a long exposure time (i.e., seven days) was necessary to induce a concentration-dependent cell viability reduction (EC50 values: 1.3 × 10−4 M, 95% CL = 0.8–1.9 × 10−4 M, MTT essay; 3.7 × 10−5 M, 95% CI = 2.2–6.1 × 10−5 M, AlamarBlue® assay) that seems to be associated to necrotic events (EC50 value: 1.3 × 10−4 M, 95% CL = 0.9–1.9 × 10−4 M, PI assay). This study demonstrated that Co3O4NPs can penetrate only damaged skin and is cytotoxic for HaCat cells after long term exposure.

In vitro permeability of silver nanoparticles through porcine oromucosal membrane

Silver nanoparticles (AgNPs) can come in contact with human oral mucosa due to their wide use in food industry and hygiene devices. We evaluate transmucosal absorption of 19 nm AgNPs using excised porcine buccal mucosa applied on Franz diffusion cells. Two donor solutions were used: one containing AgNPs (0.5 g/L) and one derived from the ultrafiltration of the former and containing only Ag in its soluble form. Experiments were carried out separately for 4 h. Silver flux permeation was demonstrated through oral mucosa, showing similar values for AgNPs (6.8±4.5 ng cm(-2) h(-1)) and Ag ions (5.2±4.3 ng cm(-2) h(-1)). Our study demonstrates that silver can permeate the oromucosal barrier and that absorption is substantially due to Ag ions, since no permeation difference was found using the two solutions. Mucosal absorption has to be considered in further risk assessment studies.

In vitro dermal penetration of nickel nanoparticles.

Nickel nanoparticles (NiNPs) represent a new type of occupational exposure because, due to the small size/high surface, they can release more Ni ions compared to bulk material. It has been reported a case of a worker who developed sensitization while handling nickel nanopowder without precautions. Therefore there is the need to assess whether the skin absorption of NiNPs is higher compared to bulk nickel. Two independent in vitro experiments were performed using Franz diffusion cells. Eight cells for each experiment were fitted using intact and needle-abraded human skin. The donor phase was a suspension of NiNPs with mean size of 77.7 ± 24.1 nm in synthetic sweat. Ni permeated both types of skin, reaching higher levels up to two orders of magnitude in the damaged skin compared to intact skin (5.2 ± 2.0 vs 0.032 ± 0.010 μg cm(-2), p = 0.006) at 24 h. Total Ni amount into the skin was 29.2 ± 11.2 μg cm(-2) in damaged skin and 9.67 ± 2.70 μg cm(-2) in intact skin (mean and SD, p = 0.006). Skin abrasions lead to doubling the Ni amount in the epidermis and to an increase of ten times in the dermis. This study demonstrated that NiNPs applied on skin surface cause an increase of nickel content into the skin and a significant permeation flux through the skin, higher when a damaged skin protocol was used. Preventive measures are needed when NiNPs are produced and used due to their higher potential to enter in our body compared to bulk nickel.

Pilot study on in vitro silver nanoparticles permeation through meningeal membrane

Silver nanoparticles (AgNPs) are used as a common ingredient in antiseptic sprays and mists; they can easily come into contact with the upper-airway mucosa. The intranasal pathway represents the only direct connection between the external environment and brain structures, which are generally considered to be well protected. Drugs absorption through this route has been widely studied, but toxicological knowledge is scant. The olfactory bundles are surrounded by meningeal sheets in their path from the nasal mucosa to the olfactory bulb. This study investigated the transmeningeal absorption of 19nm AgNPs, using excised porcine meninges mounted on Franz diffusion cells in vitro. Two donor solutions were used: one containing AgNPs (0.5gL(-1)), and another containing only the water-soluble silver species derived from the ultrafiltration of the first one. Each experiment was carried out separately for 2h. Results showed silver flux permeation through the meninges, with similar values in both experiments (0.78±0.71ngcm(-2)h(-1) and 0.73±0.43ngcm(-2)h(-1), for AgNPs and Ag ions respectively, mean and SD). This study demonstrates that the meningeal barrier is permeable to silver and silver ions, when it is exposed to this metal in nanoparticular form; this might lead to neurotoxic and neurodegenerative effects, as recently shown by other studies. Silver nanoparticles are used by workers and consumers, and potential penetration through meningeal membrane needs to be considered and prevented when it is possible an inhalation exposure.

Lombalgia ed esposizione occupazionale a vibrazioni trasmesse al corpo intero e a shock meccanici: considerazioni sullo stato dell’arte

This paper offers an overview of the relation of low back pain (LBP) to occupational exposures to whole-body vibration (WBV) and mechanical shocks. LBP is a condition of multifactorial origin and is a very common health problem in the general population. Among occupational risk factors, epidemiological studies of driving occupations have provided evidence for strong associations between LBP and occupational exposures to WBV and mechanical shocks. Since it is hard to separate the contribution of WBV exposure to disorders in the lower back from that of other individual, ergonomic or psychosocial risk factors, a quantitative exposure-response relationship for WBV cannot be outlined precisely. Experimental research has provided biodynamic support to the findings of epidemiological studies, showing that in controlled laboratory conditions exposure to WBV can cause mechanical overload to the human spine. The EU Directive on mechanical vibration has established daily exposure action and limit values to protect the workers against the risk from WBV. There is some evidence that the EU exposure limit values are excessive, so much so that an elevated risk of LBP has been found for WBV exposures beneath the EU limit values. In the Italian arm of the EU VIBRISKS prospective cohort study of professional drivers, measures of internal lumbar load (compressive and shear peak forces), calculated by means of anatomy-based finite-element models, were found better predictors of the occurrence over time of low back disorders than the metrics of external exposure suggested by the EU Directive on mechanical vibration. Further biodynamic and epidemiological studies are needed to validate the findings of the VIBRISKS study.

Effectiveness of a secondary prevention protocol for occupational contact dermatitis

Occupational skin diseases are often responsible for sick leave or job changes, affect mostly young subjects, are costly to society and have been reported as significant predictor of unemployment.