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Over the past decade, the primary focus of nanotoxicology and nanoenvironmental health and safety efforts has been largely on inhalation exposure to engineered nanomaterials, at the production stage, and much less on considering risks along the life cycle of nano-enabled products. Dermal exposure to nanomaterials and its health impact has been studied to a much lesser extent, and mostly in the context of intentional exposure to nano-enabled products such as in nanomedicine, cosmetics and personal care products. How concerning is dermal exposure to such nanoparticles in the context of occupational exposures? When and how should we measure it? In the first of a series of two papers (Larese Filon et al., 2016), we focused our attention on identifying conditions or situations, i.e. a combination of nanoparticle physico-chemical properties, skin barrier integrity, and occupations with high prevalence of skin disease, which deserve further investigation. This second paper focuses on the broad question of dermal exposure assessment to nanoparticles and attempts to give an overview of the mechanisms of occupational dermal exposure to nanoparticles and nano-enabled products and explores feasibility and adequacy of various methods of quantifying dermal exposure to NOAA. We provide here a conceptual framework for screening, prioritization, and assessment of dermal exposure to NOAA in occupational settings, and integrate it into a proposed framework for risk assessment., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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/cm(2)) 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/cm(2)). 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.

Gold nanoparticles (AuNPs) are produced for many applications but there is a lack of available data on their skin absorption. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. A physiological solution was used as receiving phase and 0.5 mL (1st exp) and 1.5 mL (2nd exp) of a solution containing 100 mg L⁻¹ of AuNPs (15 and 45 μg cm⁻², respectively) was applied as donor phase to the outer surface of the skin for 24 h. Skin absorption was dose dependent. Mean gold content of 214.0 ± 43.7 ng cm⁻² and 187.7 ± 50.2 ng cm⁻² were found in the receiving solutions of cells where the AuNPs solution was applied in higher concentration on intact skin (8 Franz cells) and on damaged skin (8 Franz cells), respectively. Twenty-four hours gold flux permeation was 7.8 ± 2.0 ng cm⁻² h⁻¹ and 7.1 ± 2.5 ng cm⁻² h⁻¹ in intact and damaged skin, respectively, with a lag time less than 1 hour. Transmission Electron Microscope analysis on skin samples and chemical analysis using Inductively Coupled Plasma-Mass Spectrometry demonstrated the presence of AuNPs into epidermis and dermis. This study showed that AuNPs are able to penetrate the human skin in an in vitro diffusion cell system.

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.

Objective: The aim of this study was to investigate the percutaneous penetration of lead oxide (PbO) powder and the effect of rapid skin decontamination with two different detergents., Methods: Franz cells were used to study in vitro PbO skin penetration through human skin during a 24-hour period. The tests were performed without or with decontamination using either Ivory Liquid soap or a new experimental cleanser 30 minutes after the start of exposure., Results: We confirm that PbO can pass through the skin with a median penetration of 2.9 ng/cm (25-75th percentiles 0.35-6). The cleaning procedure using Ivory Liquid soap significantly increased skin penetration with a median value of 23.6 ng/cm (25-75th percentiles 12-47.1; Mann-Whitney U test, P = 0.0002), whereas the new experimental cleanser only marginally increased penetration (7.1 ng/cm)., Conclusions: Our results indicate that it is necessary to prevent skin contamination from occurring because a short contact can increase skin content and penetration even if quickly followed by washing. This study demonstrated that PbO powder can pass through the skin and that skin decontamination done after 30 minutes of exposure did not decrease skin absorption occurring over 24 hours and stresses the need to prevent skin contamination when using toxic substances.