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The skin constitutes a protective barrier to external physical and chemical aggressions. Although it is constantly exposed to various xenobiotics, it is generally considered poorly permeable to them, as for example metal ions, becoming unfortunately an entry route of such substances. Metals may penetrate inside the skin inducing more or less local effects such as skin sensitization and potential metals diffusion into the bloodstream. The objective of the study was to investigate the percutaneous penetration of metals in vitro - ex vivo in Franz cell with intact as well damaged skin applying a road dust powder. Moreover, porcine and human skins were compared. This study demonstrated that, after the application of a road dust powder on the skin, metals can penetrate and permeate this cutaneous membrane. From this experimental analysis, in intact skin lead (Pb) achieved the highest skin absorption in both human and porcine skin, while skin absorption profile of cobalt (Co) was the lowest in human skin than the one in porcine model. The concentrations of Ni present in receiving solution were higher compared to other metals in all experiments performed. The present work, definitely shows that metals permeation through damaged skin is accelerated than intact skin, as a result of the weaker cutaneous barrier function. According to published data, pig skin appeared as a suitable model for human skin. Our results confirmed that skin absorption of metals can be relevant in environmental exposures.

Dermal exposure to Aluminium nanoparticles (AlNPs) can occur in occupationally- and non occupationally exposed- population, due to the use of Al salts-based antiperspirants. No AlNPs transdermal permeation data exists. Our study investigated in vitro the permeation of 30–60 nm Al2O3NPs dispersed in synthetic sweat (20 g/L) using excised human skin on Franz cells. Experiments were performed using intact (experiment 1) and needle-abraded skin (experiment 2). After 24 h traces of Al were detectable in receiving solution of exposed cells (35.0 ± 6.0 ng/cm2 for intact and 88.5 ± 34.2 ng/cm2 for damaged skin, mean and SD) and in blank cells (36.3 ± 7.0 ng/cm2), without statistical significance (p = 0.08, Mann-Whitney test). The average amount of Al into intact and damaged skin samples was 3.96 ± 0.20 μg/cm2 for intact and 4.36 ± 0.47 μg/cm2 for damaged skin (p = 0.08). Al content was similar in epidermal and dermal layers of intact and damaged skin (1.95 ± 0.13 μg/cm2 and 2.31 ± 0.12 μg/cm2 epidermal, 2.01 ± 0.25 μg/cm2 and 2.05 ± 0.35 μg/cm2 dermal). Al is a trace element in human body and the amount found in receiving solutions could be due as background impurity. This data suggest a reassuring transdermal permeation profile for Al2O3NPs.

Children are potentially exposed to products that contain nanoparticles (NPs). In particular, silver NPs are commonly present both in products used by and around children, primarily due to their antibacterial properties. However, very few data are available regarding the ability of silver NPs to penetrate through the oral mucosa in children. In the present work, we used baby porcine buccal mucosa mounted on vertical Franz diffusion cells, as an in vitro model to investigate penetration of silver NPs (19 �� 5 nm). Permeability experiments were performed using pristine physiologically-relevant saline solution in the receiver chamber and known concentrations of NPs or ions in the donor chamber; conditions mimicked the in vivo physiological pH conditions. After physicochemical characterization of silver nanoparticles dispersed in physiological solution, we evaluated the passage of ions and NPs through the mucosa, using single particle inductively coupled plasma mass spectrometry. A flux of 4.1 �� 1.7 ng cm���2 min���1 and a lag time of 159 �� 17 min were observed through mucosa exposed to silver nanoparticles. The latter suggests nanoparticle penetration through the baby porcine mucosa and release Ag+ ions in the receptor fluid, as confirmed by computational model. Due to physiological similarity between human and pig membranes it is reasonable to assume that a trans-oral mucosa penetration could occur in children upon contact with silver nanoparticles.

Contact dermatitis in construction workers (CWs) is frequent due to the widespread exposure to sensitizing substances and irritating agents and the wet and cold working conditions.Background: Contact dermatitis in construction workers (CWs) is frequent due to the widespread exposure to sensitizing substances and irritating agents and the wet and cold working conditions. Objective: Our objectives were to evaluate contact dermatitis characteristics among CWs who underwent patch test in northeastern Italy and to identify related allergens. Methods: Seven hundred ninety-five CWs were studied and their data were compared to 2.099 male white-collar workers. The associations between patch test results and occupations were assessed by multivariate logistic regression analysis. Incidence data were calculated from 1996 to 2016. Results: CWs with confirmed occupational dermatitis presented an increased risk to be sensitized to potassium dichromate [OR 3.1 (95%IC 2.0-4.8)], to thiurams [OR 8 .6 (95%IC 4.0-18.4)], and to epoxy resins [OR 12.7 (95%IC 6.1-26.4)]. Sensitization to chromate decreased significantly after 2004, following EU regulation of chromate content in concrete, while sensitization to epoxy resins and thiurams increased. The overall incidence of occupational contact dermatitis in CWs decreased significantly. Conclusion: Our study demonstrated the effectiveness of EU regulations in reducing chromate sensitization in CWs and the overall incidence of occupational contact dermatitis. However, sensitization to other haptens is increasing, though improvement of protective measures is compulsory.

"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM", Background: Clinical surveillance of the prevalence of contact allergy in consecutively patch tested patients is a proven instrument to continually assess the importance of contact allergens (haptens) assembled in a baseline series. Objectives: To present current results from the European Surveillance System on Contact Allergies, including 13 countries represented by 1 to 11 departments. Methods: Anonymized or pseudonymized patch test and clinical data from various data capture systems used locally or nationally as transferred to the Erlangen data centre were pooled and descriptively analysed after quality control. Results: In the 4 years (2015-2018), data from 51 914 patients patch tested with the European baseline series (EBS) of contact allergens were analysed. Contact allergy to nickel was most frequent (17.6% positive), followed by contact allergy to fragrance mix I (6.9%), methylisothiazolinone (MI; 6.2%), and Myroxylon pereirae resin (balsam of Peru; 5.8%). Conclusions: While the prevalence of MI contact allergy decreased substantially following regulatory intervention, the persistently high levels of allergy to metals, fragrances, other preservatives, and rubber chemicals point to problems needing further research and, potentially, preventive efforts. Results with national additions to the baseline series provide important information on substances possibly to be considered for inclusion in the EBS., Partial funding by EADV Grant PPRC-2018-8

Environmental nanoparticles or ultrafine particles (UFPs) are defined by their aerodynamic size

This study was aimed at the production and characterization of coated cotton textiles with luminescent ceramic nanophases doped with cationic Ir(III) tetrazole complexes. We confirmed that SiO2 nanoparticles (NPs) do not affect the phosphorescent properties of the complexes that maintain their emission (610 and 490 nm). For the first time we transferred the luminescence feature from nanosol to textile surface, highlighting the advantages of using nanosilica as an encapsulating and stabilizing matrix. The optimized Ir@SiO2 suspensions were homogenously applied onto the cotton surface by dip-pad-dry-cure technique, as proved by the 2p-fluorescence microscope analysis. Once we verified the self-marker properties of the Ir(III) complex, we observed an excellent washing fastness of the coating with a very limited release. SiO2 in the washing water was quantified at maximum around 1.5 wt% and Ir below the inductively coupled plasma optical emission spectrometry (ICP-OES) detection limit of 1 ppm. A Franz cell test was used to evaluate any possible ex-vivo uptake of Ir@SiO2 nanoparticles across human skin tissues, showing that epidermis and dermis stop over 99% of Ir, implying a reduced impact on human health. The light-induced antimicrobial potential of the Ir@SiO2 were assessed toward both Gram(&minus, ) and Gram(+) bacteria. The results encouraged further developments of such functional textiles coated by self-markers and antibacterial active nanophases.

MnFe2O4 nanoparticles (NPs) are commonly produced in some occupational settings and may reach high concentration in activities such as arc-welding or ferroalloy metallurgy. Manganese is an essential cofactor in enzyme activities but it has been demonstrated that long-term exposure to excessive levels can lead to “manganism”, a neurodegenerative disease resembling Parkinson features. Inhaled NPs deposit partially in pharynx and nasopharynx and may reach the central nervous system through the olfactory nerve, which is completely enveloped by the meningeal membranes throughout its course from the nasal cavity to the olfactory bulb or through the trigeminal nerves. This study investigated in vitro the transmeningeal absorption of 50 nm MnFe2O4NPs, using excised porcine meninges mounted on Franz diffusion cells. We tested two donor solutions: the first containing MnFe2O4NPs (2.0 g/L) and the second obtained by the ultrafiltration of the first one, in order to test only the NPs water soluble fraction. Each experiment was carried separately for 4 h. Results showed that no Mn flux permeation through the meninges occurred, since only trace of the metal was found in receivers solutions of cells exposed to MnFeNPs (5.5 ± 2.2 ng/cm2), ultrafiltered solution (3.5 ± 1.5 ng/cm2) and blank cells. (2.1 ± 0.6 ng/cm2) (mean and SE). Differences did not reach the statistical significance. Our study shows – for the first time - that MnFe2O4NPs penetrate the meningeal membrane in a negligible amount, thus making unlikely the hypothesis of a transcellular and paracellular absorption through the olfactory nerve but not excluding the hypothesis of an active intraneuronal absorption.

Cerium oxide (CeO2) nanoparticles (NPs) are used in polishing products and absorbents, as promoters in wound healing, and as organopesticide decontaminants. While systemic bioaccumulation and organ toxicity has been described after inhalation, data on CeO2 NPs&rsquo, transdermal permeation are lacking. Our study was an in vitro investigation of the permeation of 17-nm CeO2 NPs dispersed in synthetic sweat (1 g L&minus, 1) using excised human skin on Franz cells. Experiments were performed using intact and needle-abraded skin, separately. The average amount of Ce into intact and damaged skin samples was 3.64 &plusmn, 0.15 and 7.07 &plusmn, 0.78 &micro, g cm&minus, 2, respectively (mean &plusmn, SD, p = 0.04). Ce concentration in the receiving solution was 2.0 &plusmn, 0.4 and 3.3 &plusmn, 0.7 ng cm&minus, 2 after 24 h (p = 0.008). The Ce content was higher in dermal layers of damaged skin compared to intact skin (2.93 &plusmn, 0.71 &micro, 2 and 0.39 &plusmn, 0.16 &micro, 2, respectively, p = 0.004). Our data showed a very low dermal absorption and transdermal permeation of cerium, providing a first indication of Ce skin uptake due to contact with CeO2.

Highlights After the introduction of the EU regulatory interventions, nickel sensitization decreased significantly in the group of females aged ≤25 years. Women born between 1966 and 1975 presented the higheest prevalence of sensitization to nickel, then prevalence of sensitization gradually decreased with a minimum in more recent years. Nickel sensitization is higher in Italian patients compared to people living in other EU coutries. Additional interventions are needed to address nickel sensitization.

The great antimicrobial action of copper oxide nanoparticles (CuO NPs) and their consequent use in many applications in the biomedical field have caused concern about the potentially negative effects of human skin exposure to CuO NPs. However, so far, very few studies have investigated the toxic action of CuO NPs toward humans, with a special focus on the skin penetration route of entry. This study considers for the first time the absorption of topically applied CuO NPs through the human skin, using a Franz static diffusion cell model. We characterised the colloidal behaviour and static dissolution of commercial bare CuO NPs, evaluating both intact and damaged skins. We tested physiological solutions as the receiving phase; as the donor phase, CuO NPs were dispersed in synthetic sweat and exposed to the outer surface of the skin (0.11 mg cm(-2)) for 24 hours. The Cu elemental analysis in the receptor fluid and in the exposed skin allowed us to quantify the copper translocation within the epidermis and dermis. The experimental data showed that the CuO NPs absorption through intact skin was negligible. However, in damaged skin, we observed an increasing permeation of copper. The latter would justify the capacity of CuO NPs to pass the first skin layers and release Cu2+ ions into the stratum corneum, reaching the receptor fluid in the in vitro diffusion cell system.

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.

Metals can penetrate the skin barrier and reach the viable epidermis and dermis, inducing allergic sensitization that can cause allergic contact dermatitis through a delayed-type hypersensitivity reaction. Moreover, metals can permeate the skin, reaching the general circulation with a potential for systemic intoxication that has been demonstrated only for extremely toxic metals, such as dimethylmercury. Penetration is related to many factors, such as applied dose, area involved, duration of contact, body site, thickness and integrity of the skin layers, sweating, temperature, humidity, physical activity, gender, race, age, characteristic of the substance, vehicles used, etc.

The use of palladium (Pd) has grown in the last decades, commonly used in automotive catalytic converters, jewellery and dental restorations sectors. Both general and working population can be exposed to this metal, which may act as skin sensitizer. This study investigated in vitro palladium powders permeation through excised intact and damaged human skin using the Franz diffusion cell method and the effect of rapid skin decontamination using sodium laureth-sulphate. 1 mL of a 10 min sonicated suspension made of 2.5 g of Pd powder in 50 mL synthetic sweat at pH 4.5 and room temperature was applied to the outer surface of the skin membranes for 24 h. Pd permeation, assessed by ICP-MS, was higher when damaged skin was used (p = 0.03). Final flux permeation values and lag times were 0.02 ± 0.01 μg cm−2 h−1 and 6.00 ± 3.95 h for intact, and 0.10 ± 0.02 μg cm−2 h−1 and 2.05 ± 1.49 h for damaged skin samples, respectively. Damaged skin protocol enhances Pd skin penetration inside dermal layer (p = 0.04), thus making the metal available for systemic uptake. Pd penetration (p = 0.02) and permeation (p = 0.012) through intact skin decreased significantly when a cleaning procedure was applied. This study demonstrates that after skin exposure to Pd powders a small permeation of the metal happen both through intact and damaged skin and that an early decontamination with a common cleanser can significantly decrease the final amount of metal available forsystemic uptake.

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.

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 ?g/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 ?g/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. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

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.

SummaryBackground Occupational contact dermatitis is one of the most common occupational diseases in Europe. In order to develop effective preventive measures, detailed and up-to-date data on the incidence, main causes and professions at risk of occupational contact dermatitis are needed. Objectives To describe the pattern of patch test reactivity to allergens in the European baseline series of patients with occupational contact dermatitis in different occupations. Methods We analysed data collected by the European Surveillance System on Contact Allergy (ESSCA) network from 2002 to 2010, from 11 European countries. Results Allergens in the European baseline series associated with an at least doubled risk of occupational contact dermatitis include: thiuram rubber chemical accelerators, epoxy resin, and the antimicrobials methylchloroisothiazolinone/methylisothiazolinone, methyldibromo glutaronitrile, and formaldehyde. The highest risk of occupational contact dermatitis was found in occupations classified as ‘other personal services workers’, which includes hairdressers, nursing and other healthcare professionals, precision workers in metal and related materials, and blacksmiths, tool-makers and related trades workers. Conclusions In the planning and implementation of measures aimed at preventing occupational contact dermatitis, the focus should be on the identified high-risk occupational groups and the most common occupational allergies.

The role of the skin as a potential route of exposure to nanomaterials is described in the present chapter. We survey the existing literature on various types of nanomaterials with respect to their penetration through the skin and toxicological responses. Most studies suggest minimal skin penetration and little to no systemic exposure. However, studies have also shown that nanoparticle size, shape, charge, surface properties, and vehicle/solvent as well as the choice of animal species are important determinants as to whether or not nanoparticles traverse through the rate-limiting lipid barrier of the stratum corneum. Long-term in vivo studies in animals or humans are needed because in vitro systems and differences in animal species provide limitations for a complete understanding of nanoparticle penetration through the skin.

Growing warnings on health effects related to electronic cigarettes have met inconclusive findings at present. This study analyzed the in vitro percutaneous absorption of nicotine resulting by skin contamination with two e-liquids (refill 1 and 2) containing nicotine at 1.8%. Donor chambers of 6 Franz cells for each refill liquid were filled with 1 mL of nicotine e-liquid for 24 h; at selected intervals, 1.5 mL of the receptor solutions were collected for nicotine concentration analysis by mean gas chromatography–mass spectrometry (LOD: 0.01 μg/mL). The experiment was repeated removing the nicotine donor solution after 10 min from the application and rinsing the skin surface three times with 3.0 mL of milliQ water. A total of 12 cells with 24 h exposure and 12 cells washed were studied. The mean concentration of nicotine in the receiving phase at the end of the experiment was 54.9 ± 29.5 and 30.2 ± 18.4 μg/cm2 for refill 1 and 2 respectively and significantly lower in washed cells (4.7 ± 2.4 and 3.5 ± 1.3 μg/cm2). The skin absorption of nicotine can lead to minor health illness in vapers, while caution must be paid to dermal contamination by e liquids in children. The skin cleaning significantly reduced the transdermal absorption kinetic and intradermal deposition of nicotine.

Due to the increased production and use of nanoparticles (NPs), there are workers and consumers that can be exposed to NPs. There is a debate among scientists to define possible effects related to this exposure and there are more open questions. The review evaluates the recent knowledge on this topic trying to classify NPs in relation to their hazard for skin exposure, both for workers and consumers. While the same kind of NPs can be safe for skin contact (such as titanium dioxide and zinc oxide), others can exert a sensitization effect such as NPs that can release sensitizing metals (i.e., Ni, Pd, Co), as well as a toxic effects for NPs that can release toxic metals such as Cd or As.

BACKGROUND: Formaldehyde is a widely used organic compound, used in several applications (hard thermoset resins, adhesives, disinfectants, tissue fixatives, etc), in its free form or released by formaldehyde releaser products. Its use is under control due to its toxic, carcinogenic, and allergenic properties. OBJECTIVE: The aim of this study was to investigate the frequency of formaldehyde sensitization, time trend, and correlation to occupations. METHODS: This study is a cross-sectional study on a population of 23,774 patients tested from 1996 to 2012 in Northeastern Italy. RESULTS: Frequency of sensitization was 3.3%, without any significant time trend. Hands (39.8% overall) and face (25.6% females, 15.5% males) were mainly involved. We found a trend toward decrease by age in females (3.11% in first quintile [14-26 years], 2.29% in fifth quintile [59-97 years], P < 0.01). On a logistic regression analysis (control group: white-collar workers), we found associations in health care (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.04-1.81), wood (OR, 2.14; 95% CI, 1.30-3.51), and textile (OR, 1.79; 95% CI, 1.14-2.79) sectors and professional drivers (OR, 1.94; 95% CI, 1.05-3.60). We found a high rate of cosensitization to formaldehyde in patients with positive patch test reactions to quaternium-15 (OR, 18.7; 95% CI, 12.6-27.7). CONCLUSIONS: Sensitization to formaldehyde is relevant in our population, especially in the health care sector, wood and textile industries, and professional drivers. No significant time trend was found.

Silver nanoparticles (AgNPs) are commonly used in antiseptic sprays and mist and can easily come in contact with the mucosa of the upper airways. The intranasal pathway represents the only direct connection between the external environment and the brain structures, which traditionally are considered well protected. Much is known regarding drugs absorption through this route, but toxicological knowledge is scant. The olfactory bundles are surrounded by meningeal sheets in their course from the nasal mucosa to the olfactory bulb. This study investigated in vitro the transmeningeal absorption of 19 nmAgNPs, using excised porcine meninges mounted on Franz diffusion cells. We used two donor solutions: the first containing AgNPs (0.5 g/L) and the second containing only the water-soluble silver species derived from the ultrafiltration of the first one. Each experiment was carried separately for 2 hours. Results showed silver flux permeation through the meninges, with similar values in both experiments (0.78 ± 0.71 ng cm-2 h-1 and 0.73 ± 0.43 ng cm-2 h-1, for AgNPs and Ag ions respectively, mean and SD). Our study demonstrate that the meningeal barrier is permeable to silver and silver ions, when is applied in the nanoparticles form. This could lead to neurotoxic and neurodegenerative effects, which are now emerging in the scientific literature. Metal nanoparticles are commonly encountered in working scenarios, but their behavior in physiological media is different. Therefore the toxicological potential of metal NPs is heterogeneous and requires further efforts to be assessed on a case by case basis.

Background: Exposure to nickel, cobalt and chromate are important causes of occupational contact dermatitis. Objectives: To estimate the prevalence of nickel, cobalt and chromate allergy in a population of consecutive patients and to investigate the possible association with individual and occupational risk factors. Patients/Methods: A total of 14 464 patients (67.6% women and 32.4% men) with suspected allergic dermatitis underwent patch tests. The associations between patch test results and occupations were studied by multivariate logistic regression analysis. Results: About 24.6% of the patients reacted positively to nickel sulphate, 10.2% to cobalt chloride and 8.7% to potassium dichromate. Nickel sensitization was higher in women aged 26–35 years in comparison with the youngest group (15–25 years) and the older group (> 45 years). In women, the prevalence of positive reactions to nickel was positively associated with metal and mechanical work (OR 1.54; 95%, CI 1.16–2.05). Chromate sensitization was more prevalent in building trade workers for both women (OR 1.58; 95% CI 1.00–2.49) and men (OR 2.24; 95% CI 1.55–3.22). Cobalt sensitization was associated with textile and leather work in women (OR 1.52; 95% CI 1.09–2.12) and with cleaning work in men (OR 1.86; 95% CI 1.18–2.93). Conclusions: Our study showed interesting associations between some occupations and nickel, chromate and cobalt allergy.

Povidone iodine is a water-soluble complex used to disinfect the skin surface and it exerts prolonged germicidal action against a broad spectrum of germs. Indeed, it is often applied on burned skin, large wounds, deep tissues or mucosa. Notably some surgical hand-scrub solutions, which are considered safe antiseptics, contain large amounts of iodine that can be absorbed by skin. The aim of present study was to study the skin absorption of iodine after the application on the skin of povidone-iodine solution, used by health care workers during surgical procedure. We use Franz diffusion static cells with human skin. After 24 h from the beginning of our measurement the iodine concentration in the receiving compartment was 11.59 ± 6.3 μg/cm 2 . The medium flux calculated was 0.73 ± 0.33 μg/cm 2 /h with a lag time of 8.9 ± 1.5 h. These in vitro results confirmed that povidone iodine could pass through the skin in a relevant amount that can explain the clinical findings in burned or surgically treated patients. In professional use the repetitive contact with povidone iodine, also as soap, can cause iodine skin permeation that must be considered when the washing procedures are repeated more than 20 times a day.

The aim of the study was to evaluate percutaneous penetration of platinum and rhodium nanoparticles (PtNPs: 5.8 ± 0.9 nm, RhNPs: 5.3 ± 1.9 nm) through human skin. Salts compounds of these metals are sensitizers and some also carcinogenic agents. In vitro permeation experiments were performed using Franz diffusion cells with intact and damaged skin. PtNPs and RhNPs, stabilized with polyvinylpyrrolidone, were synthesized by reduction of Na2PtCl6 and RhCl3·3H2O respectively. Suspensions with a concentration of 2.0 g/L of PtNPs and RhNPs were dispersed separately in synthetic sweat at pH 4.5 and applied as donor phases to the outer surface of the skin for 24 h. Measurements of the content of the metals in the receiving solution and in the skin were performed subsequently. Rhodium skin permeation was demonstrated through damaged skin, with a permeation flux of 0.04 ± 0.04 μg cm−2 h−1 and a lag time of 7.9 ± 1.1 h, while no traces of platinum were found in receiving solutions. Platinum and rhodium skin- analysis showed significantly higher concentrations of the metals in damaged skin. Rh and Pt applied as NPs can penetrate the skin barrier and Rh can be found in receiving solutions. These experiments pointed out the need for skin contamination prevention, since even a minor injury to the skin barrier can significantly increase penetration.

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 6 4 nm can penetrate and permeate intact skin, NPs size between 4 and 20 nm can potentially permeate intact and damaged skin, NPs size between 21 and 45 nm can penetrate and permeate only damaged skin, NPs size > 45 nm 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.

Cobalt nanoparticles (CoNPs) are produced for many applications but there is a lack of data on human absorption. The aim of our study was to evaluate the CoNPs skin absorption. Experiments were performed using Franz cells with human skin. Physiological solution was used as receiving phase and 1.0 mg cm-2 of CoNPs was applied as donor phase for 24 h. Mean Co content of 8.3 ± 1.5 ng cm-2 and 1.87 ± 0.86 ug cm-2 were found in the receiving solutions of cells where the CoNPs suspension was applied on intact skin and on damaged skin respectively. Twenty-four hours Co flux permeation was 76 ± 49 ng cm-2 h-1 in damaged skin with a lag time of 2.8 ± 2.1 hours. Transmission Electron Microscope analysis on skin samples and spectroscopic analysis demonstrated the presence of CoNPs into epidermis. This study showed that CoNPs are able to penetrate the human skin in an in-vitro diffusion cell system., JRC.I.4-Nanobiosciences

BACKGROUND: Cosensitization to nickel, cobalt and chromium occurs in the general population and in some occupational groups. OBJECTIVES: To estimate the isolated and concurrent occurrence of nickel, cobalt and chromium contact sensitization and their association with individual and occupational risk factors. PATIENTS/METHODS: Twelve thousand four hundred and ninety-two patients were patch tested with the European baseline series between 1997 and 2004 in north-eastern Italy. The associations between patch test results and patient characteristics and occupations were investigated by means of multinomial logistic regression analysis. RESULTS: Of the patients, 34.7% (4334 patients) had one or more positive patch test reactions to metals. As compared with those with negative reactions to all three metals, nickel sensitization was significantly higher in females than in males, not only as monosensitization, but also as cosensitization with cobalt, with chromium, or with both metals. Building and related trades workers showed positive reactions to chromium + nickel [odds ratio (OR) 1.99; 95% confidence interval (CI) 1.05-3.76) and chromium + cobalt (OR 2.61; 95% CI 1.46-4.67]. Cleaning workers showed a high prevalence of nickel, chromium, nickel + chromium and nickel + cobalt + chromium cosensitization (ORs 1.29, 1.66, 2.11, and 1.79, respectively). An excess risk for cosensitization to all three metals was found in textile and leather workers (OR 2.19; 95% CI 1.10-4.33), and in bartenders (OR 2.10; 95% CI 1.03-4.26). CONCLUSIONS: Some occupational groups are more likely to develop nickel, cobalt and chromium cosensitization.

Background. Sensitization to nickel, cobalt and chromium is frequent in patch test populations. The prevalence is affected by geographical and socio-cultural factors. Objectives. To investigate the temporal trend of nickel, cobalt and chromium contact sensitization between 1996 and 2010 in north-eastern Italy. Patients/methods. Nineteen thousand and eighty-eight patients (67.2% women and 32.8% men) with suspected allergic dermatitis underwent patch testing with the European baseline series. The associations between nickel, cobalt and chromium sensitization and patient age (in quintiles) and year of patch testing were investigated by means of multivariate logistic regression analysis. Results. The prevalence of nickel sensitization decreased significantly among younger women (≤26 years), from 38.3% (1996–1998) to 31.9% (2002–2004), 28.3% (2005–2007) and 29.0% (2008–2010), whereas an increase was observed in the 36–45-year and 46–58-year age groups. The overall prevalence of chromium sensitization dropped from 10.2% (1996–1998) to 4.6% (2008–2010) among women, and from 11.3% (1996–1998) to 5.9% (2008–2010) among men. The prevalence of cobalt sensitization increased among younger men (≤26 years), from 2.7% (1996–1998) to 7.3% (1999–2001), 9.6% (2002–2004), and 6.6% (2005–2007). Conclusions. Our study showed a decreasing trend of nickel sensitization (only among younger women) and of chromium sensitization in both sexes.

The bioavailability of metals, which are known as important contact allergens, is decisive for the development and the maintenance of contact dermatitis. The aim of this study was to evaluate the percutaneous penetration of metal powders of cobalt (Co), nickel (Ni) and chromium (Cr) and the effect of skin lesions on skin absorption. In vitro permeation experiments were performed using the Franz diffusion cells with intact and damaged human skin. Physiological solution was used as receiving phase and metal powders (Co, Ni and Cr) dispersed in synthetic sweat at pH 4.5 were applied as donor phase to the outer surface of the skin for 24h. The amount of each metal permeating the skin was analysed by electro-thermal atomic absorption spectroscopy (ETAAS). Donor solution analysis demonstrated that metals were present as ions. Measurements of metals skin content were also exploited. Median Co and Ni concentrations found in the receiving phase were significantly higher when Co and Ni powders were applied on the abraded skin than after application on the intact skin (3566 and 2631ngcm(-2) vs. 8.4 and 31ngcm(-2), respectively). No significant difference was found in Cr permeation through intact and damaged skin. The measurement of metals skin content showed that Co, Ni and Cr concentrations were significantly higher in the damaged skin than in the intact skin. Co and Ni ions concentrations increased significantly when the donor solutions were applied on the damaged skin, while Cr ions concentrations did not increase. This study demonstrated that Co and Ni powders can permeate through damaged skin more easily than Cr powder, which has probably a stronger skin proteins binding capacity. Therefore, our results suggest that is necessary to prevent skin contamination when using toxic substances because a small injury to the skin barrier can significantly increase skin absorption.

The present study tried to investigate, using a synthetic sweat at pH 4.5, whether metallic chromium can pass through the skin (in vitro) and the effect of rapid skin decontamination with a common detergent. A suspension of chromium powder in synthetic sweat at pH 4.5 was prepared and shaken with a stirring plate at room temperature for 30 min. Human skin membranes were set up in Franz-diffusion cells and 1 ml of the freshly made suspension was applied to the outer surface of the skin for 24h. The tests were performed without and with decontamination using the cleanser 30 min after the start of exposure. The appearance of metal ions in the aqueous receptor phase was quantified by Electro Thermal Atomic Absorption Spectroscopy (ETAAS) and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES). Speciation analysis and measurements of chromium skin content were also performed. Chromium skin permeation was demonstrated in in vitro experiments using the Franz cell system, giving a permeation flux of 0.84+/-0.25 ng cm(-2)h(-1) and a lag time of 1.1+/-0.7h. The cleaning procedure stop Cr permeation but its concentration into the skin significantly increased (Mann-Whitney U test P

Polycyclic aromatic hydrocarbons have mutagenic and carcinogenic properties and some of them are classified as probable or possible human carcinogens. Aim of this study was to evaluate the genotoxic risk in workers exposed to diesel exaust. Environmental and biological monitoring exposure to polycyclic aromatic hydrocarbons was carried out on fifty-two workers exposed to diesel exhaust. Urinary 1-hydroxypyrene was employed as a biomarker of internal dose. Significant urinary 1-hydroxypyrene differences between smokers and non-smokers were found. Twenty per cent of urinary 1-hydroxypyrene values exceeded benchmark level for genotoxic effect, while the results of environmental monitoring excluded the existence of exposure to polycyclic aromatic hydrocarbons. In the absence of greater knowledge about the relationship between urinary 1-hydroxypyrene and genotoxic effects under the conditions of very low exposure, extreme caution is recommended when this biomarker of internal dose is employed as an indicator of genotoxic risk. Toxicology and Industrial Health 2007; 23: 55—59.

Objectives To evaluate skin absorption of cobalt powder in an in vitro system. Experiments with volunteers show that cobalt powder can permeate through the skin, but there are no data with regard to the mechanism or the amount of permeation. Methods Skin permeation was calculated by the Franz diffusion cell method with human skin. A physiological solution was used as receiving phase and the cobalt powder was dispersed in synthetic sweat. The amount of metal passing through the skin was analysed by electro-thermal atomic absorption spectrometry (ETAAS). Parallel polarographic analysis (differential pulse polarography—DPP) allowed evaluation of cobalt present as ions (Co2+) in donor and receiving phases. Measurements of cobalt skin content were also performed. Results Evaluation of metal in the receiving phase allowed us to demonstrate the permeation of cobalt through the skin. Steady-state flow of percutaneous cobalt permeation was calculated as 0.0123±0.0054 mgrg cm–2 h–1, with a lag time of 1.55±0.71 h. Conclusions The experiments show that cobalt powder can pass through the skin when applied as a dispersion in synthetic sweat, oxidising metallic cobalt into ions, which permeate the skin. These experiments show for the first time how cobalt can permeate the skin.

s / Toxicology Letters 229S (2014) S40–S252 S239 were administered by gavage at the doses of 125mgkg−1 of PQ and 125mgkg−1 of PQ+316mgkg−1 of LAS, respectively. The obtained results showed that LAS improves the safety of PQ formulation by increasing its elimination and preventing lung and kidney injury. LAS prevented the biochemical and histological alterations in lung induced by PQ at the end of 24h and 48h. This was evidenced by a significant reduction in lipid peroxidation, the maintenance of reduced glutathione levels and decreased levels of oxidized glutathione, as well as the normalization of the urinary biomarkers, creatinineandN-acetyl-glucosaminidase. LAS treatmentalso caused a significant reduction in PQ-induced activation of nuclear factor kappa B (NFB) in the lung. The results allow us to conclude that lysine acetylsalicylate improves the safety of PQ formulation in rats by increasing its elimination andpreventing lung and kidney injury. http://dx.doi.org/10.1016/j.toxlet.2014.06.797

Background: Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) techniques have been used in various fields of medical research, including different pathologies of the nails; however, no studies have focused on obtaining high-resolution microscopic images and elemental analysis of disorders caused by synthetic nails and acrylic adhesives. Methods: Damaged/injured fingernails caused by the use of acrylate glue and synthetic nails were investigated using SEM and EDX methods. Results: SEM and EDX proved that synthetic nails, acrylic glue, and nails damaged by contact with acrylate glue have a different morphology and different composition compared to healthy human nails. Conclusions: SEM and EDX analysis can give useful information about the aspects of topography (surface sample), morphology (shape and size), hardness or reflectivity, and the elemental composition of nails.