Francesca Larese Filon

Human skin penetration of cobalt nanoparticles through intact and damaged skin

Cobalt nanoparticles (CoNPs) are produced for several industrial and biomedical applications but there is a lack of data on human cutaneous absorption. Cobalt is also a skin sensitizer that can cause allergic contact dermatitis. Co applied as NPs, due to their small size and high surface, can penetrate into the skin in higher amount that bulk material. The aim of this study was to evaluate the absorption of Co applied as NPs in both intact and damaged skin. Experiments were performed using Franz cells and 1.0 mg cm(-2) of CoNPs was applied as donor phase for 24h. Mean Co content of 8.5 ± 1.2 ng cm(-2) and 1.87 ± 0.86 μg cm(-2) were found in the receiving solutions of Franz cells when 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 ± 2.1h. This study suggests that Co applied as NPs is able to penetrate the human skin in an in vitro diffusion cell system.

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.

Human skin penetration of gold nanoparticles through intact and damaged skin.

Abstract 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 mgL-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.

In vitro absorption of metal powders through intact and damaged human skin.

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.

Nickel, cobalt and chromate sensitization and occupation*

Background: Exposure to nickel, cobalt and chromate are important causes of occupational contact dermatitis.

Skin absorption of inorganic lead (PbO) and the effect of skin cleansers.

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/cm2 (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/cm2 (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/cm2). 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.

Patch test results of the European baseline series among patients with occupational contact dermatitis across Europe - analyses of the European Surveillance System on Contact Allergy network, 2002-2010.

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.

Associations between two job stress models and measures of salivary cortisol

PurposeTo investigate the association between two job stress models—the job demand-control model and the effort-reward imbalance model—and repeated measures of salivary cortisol among male and female call-centre operators.MethodsDaily cortisol profiles consisting of seven time points were measured across two workdays and one leisure day to determine the cortisol awakening response and the cortisol output in the day in 104 volunteers. The employees completed two self-administered questionnaire—the Karasek’s demand-control questionnaire and the Siegrist’s effort-reward imbalance questionnaire—to assess psychosocial hazards at work. The relations between the perceived workload measures and salivary cortisol levels were analyzed by means of generalized estimating equations method after adjusting for potential confounders (gender, age, educational level, marital status, morning awakening time, sleep duration and quality, weekdays, work schedule, adherence to sampling procedure).ResultsThe total cortisol amount excreted in the awakening period was positively associated with the job strain measures (high strain vs. low strain: 1.4 (2.4–0.3) nmol/l). In contrast, individuals scoring higher in effort-reward imbalance at work had both lower cortisol awakening response (high imbalance vs. low imbalance: −0.7 (−1.3 to −0.2) nmol/l) and lower diurnal secretory activity (−9.2 (−17.7 to −0.7) nmol/l). Gender, weekday and adherence to sampling schedule significantly influenced the cortisol excretion in the morning period.ConclusionsOur results indicate that the two work stress models differentially affect salivary cortisol output. This finding suggests that combining the information from two complementary job stress models results in improved knowledge on the psychobiological correlates of the psychosocial work environment.

Salivary Cortisol and Psychosocial Hazards at Work

BACKGROUND Experimental and clinical evidence suggest that stress can lead to ill-health through the disregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Studies to date have produced equivocal results likely due to different methodologies and failure to account for confounding factors. This investigation aimed to assess the relation between self-reported work-related stressors and salivary cortisol and to clarify the role of the potential confounders. METHODS Thirty-six call-handlers completed a self-administered job content questionnaire and collected seven daily salivary samples on two workdays and a weekend. The diurnal salivary cortisol output was expressed as cortisol awakening response (CAR), and cortisol output in the rest of the day. Salivary cortisol data were normalized by means of square root transformation. The generalized estimating equations method was used to assess the relation between job strain and cortisol levels after adjusting for gender, weekdays and adherence to the sampling schedule. RESULTS Job strain significantly influenced the total amount of cortisol response to waking (high strain vs. low strain: 1.1 (0.3-2.0) nmol/L). The cortisol response to waking showed gender-specific differences [women excreting greater cortisol than men: 1.1 (0.3-1.9) nmol/L], and weekday differences [workdays vs. weekend: 1.0 (0.3-1.6) nmol/L]. Non-compliance with the sampling protocol was associated with lower salivary cortisol than in adherent subjects. CONCLUSIONS Our results provide further evidence for the HPA axis involvement in the physiological response to work stress. The measure of the CAR showed to be the sensitive index to assess the physiological response to psychosocial factors. Gender, weekday, and protocol compliance were confounding factors.

Sensitization to palladium chloride: a 10-year evaluation.

BACKGROUND Palladium is increasingly used in industry, jewelry, and dentistry and is becoming more common since the European directive restricting the use of nickel in all products placed in direct and prolonged contact with the skin. OBJECTIVE The role of palladium sensitization is still unclear, and the aim of our study is to evaluate the trend of sensitization in a contact dermatitis clinic population during a 10-year period. METHODS We report our experience with 4,446 patients (3,077 female, 1,369 male; mean age, 40.1 +/-13.7 years) with suspected contact dermatitis patch-tested during the period of 1991 to 2000. RESULTS A positive patch-test result to palladium chloride 1% was indicated in 236 patients (5.3%), with a higher percentage in females (6.7%) than in males (2.3%), and the sensitization to this metal has increased over the specified period, to a maximum in the year 2000 (9.7%). In the majority of cases, subjects were polysensitized (92.8%), but 7.2% of subjects were patch-test positive only to palladium. Of palladium-sensitized patients, 40.5% complained of hand dermatitis, 47.4% complained of body dermatitis, and 1.7% complained of burning mouth syndrome. Palladium sensitization is significantly related to female sex (OR = 3.08; 95% CI, 2.07-4.61) and to sensitization to other metals, with a maximum for nickel sulfate (OR = 32.9; 95% CI, 21.3-51.5). CONCLUSION Sensitization to palladium is increasing by the year, reaching high values, but its role in reducing sensitization and symptoms is still unclear because of the frequent cosensitization with nickel and the low number of monosensitized patients with relevant sensitizations. We need to follow palladium sensitization in future years to verify an increase of sensitization due to the increasing use of this metal.