Francesca Larese

Nanoparticle dermal absorption and toxicity: a review of the literature

IntroductionNanotechnologies are among the fastest growing areas of scientific research and have important applications in a wide variety of fields. The data suggest that in the future workers and consumers exposed to nanoparticles will significantly increase.Dermal absorption and toxicity of nanoparticlesAt now there are gaps in understanding about the human and environmental risk that manufactured nanoparticles pose for occupational exposed people and for consumers. There is a need for assessing the health and environmental impacts, the nanoparticles life cycle, the human exposure routes, the behavior of nanoparticles in the body, and the risk for workers. Possible routes of entry into the body include inhalation, absorption through the skin or digestive tract, injection, and absorption or implantation for drugs delivery systems. In particular, dermal absorption and skin penetration of nanoparticles needs a better evaluation because few and contradictory data are present in the literature, mainly on titanium dioxide.ConclusionsThere are limited data on carbon-based nanoparticles and very few data on other metal nanoparticles increasingly used in industry. The article reviews the literature on the percutaneous absorption of nanoparticles and their effect on skin.

Allergic airway disease in Italian bakers and pastry makers.

A survey was carried out on respiratory symptoms and skin prick test response to common allergens (atopy), storage mites, and occupational allergens among 226 bakers and pastry makers from 105 small businesses in northern Italy. Atopy was present in 54 workers (23.4%); 40 workers (17.7%) were skin positive to at least one storage mite, 27 (11.9%) to wheat flour and 17 (7.5%) to alpha-amylase. Work related asthma was reported by 11 (4.9%) workers and rhinoconjunctivitis by 31 (17.7%); 22 workers (10.2%) complained of chronic bronchitis. The distribution of skin prick test results among bakers and among 119 white collar workers did not indicate (by logistic analysis) an increased risk for bakers to skin sensitisation to common allergens, storage mite, or to a group of five flours. Sensitisation to wheat flour, on the other hand, was present only among exposed workers. Skin sensitisation to occupational allergens was significantly associated with atopy (p < 0.001), smoking habit (p = 0.015), and work seniority (p = 0.027). The risk of work related symptoms was associated with sensitisation to wheat or alpha-amylase, and with atopy, but not with sensitisation to storage mites, work seniority, or smoking habit. The results of the study indicate that there is still a significant risk of allergic respiratory disease among Italian bakers. Not only wheat allergens, but also alpha-amylase must be considered as causative agents, although sensitisation to storage mites is not important in the occupational allergic response. Atopy must be regarded as an important predisposing factor for skin sensitisation to occupational allergens and for the onset of symptoms at work. The data confirm that for effective prevention, greater care should be taken not only in limiting environmental exposure, but also in identifying susceptible people.

Current patch test results with the European baseline series and extensions to it from the 'European Surveillance System on Contact Allergy' network, 2007-2008

Background. The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences.

Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line.

For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products designed to come in direct contact with the skin. In this study we investigated the effects of Ag NPs on skin using the human-derived keratinocyte HaCaT cell line model. Ag NPs caused a concentration- and time-dependent decrease of cell viability, with IC(50) values of 6.8 ± 1.3 μM (MTT assay) and 12 ± 1.2 μM (SRB assay) after 7 days of contact. A 24h treatment, followed by a 6 day recovery period in Ag NPs-free medium, reduced cell viability with almost the same potency (IC(50)s of 15.3 ± 4.6 and 35 ± 20 μM, MTT and SRB assays, respectively). Under these conditions, no evidence of induction of necrotic events (propidium iodide assay) was found. Apocynin, NADPH-oxidase inhibitor, or N(G)-monomethyl-L-argynine, nitric oxide synthase inhibitor, did not prevent NPs-induced reduction of cell viability. TEM analysis of cells exposed to NPs for 24h revealed alteration of nuclear morphology but only a marginal presence of individual NPs inside the cells. These results demonstrate that on HaCaT keratinocytes a relatively short time of contact with Ag NPs causes a long-lasting inhibition of cell growth, not associated with consistent Ag NPs internalization.

Liver function alterations in synthetic leather workers exposed to dimethylformamide.

A cross-sectional study of the prevalence of chronic liver function alterations was performed in 75 workers employed in a synthetic leather factory, exposed to dimethylformamide (DMF) air concentrations below threshold limit values (30 mg/m3). Biological monitoring among workers revealed acceptable urine levels of monomethylformamide (NMF) on average, but the very wide range indicated that occasional overexposure was possible. The worker survey showed a high percentage of disulfiram-like symptoms (50%) and liver function abnormalities (22.7%), compared with a demographically similar group of unexposed workers. Covariance analysis (ANCOVA) revealed that enzyme levels were significantly higher in exposed workers than in controls after data were corrected for age, alcohol consumption, body mass index, and cholesterol levels. The authors conclude that DMF can cause liver diseases even if air TLVs are respected, because accidental contact with liquid DMF can significantly increase DMF uptake. In this situation, air monitoring is no longer sufficient to evaluate worker exposure.

Sensitization to green coffee beans and work-related allergic symptoms in coffee workers

BACKGROUND Occupational respiratory allergy to green coffee beans (GCB) and to castor beans (CB) was studied in 112 workers in a modern coffee manufacturing plant of Trieste (Italy), where the process is completely automatic, the environmental conditions are good and where exposure to CB can be considered absent because since 1970, only new sacks have been used for coffee transportation. METHODS All subjects were interviewed by a trained doctor using a questionnaire to investigate allergic symptoms and predisposing factors. Sensitization to GCB and to common allergens (pollens, molds, house dust mites) were evaluated by the skin-prick test. The serum of subjects with a positive skin-prick test to CGB or who had symptoms at work was tested for specific IgE (RAST) for GCB and CB. Lung function was evaluated by a Ponigraph spirometer. RESULTS Sensitization to GCB was found in 25.8% of green coffee workers (31 cases), in 2.7% of roasted coffee workers (37 cases) and in 4.5% of the clerks (44 cases), p < 0.01. The evaluation of IgE specific for CB gave positive results only in 3 of 10 subjects sensitized to GCB. A total of 20% of GCB workers (6 cases) complained of work-related respiratory symptoms (asthma and/or rhinitis) compared with only one subject in the roasted coffee group and one in the control group (p < 0.01). Asthma was reported by 2/31 of the green coffee workers and by 1/44 of roasted coffee workers. CONCLUSIONS There was a significant correlation between sensitization to GCB and work related symptoms (p < 0.01), common allergic symptoms (p < 0.05) and atopy by prick test (< 0.01). These results point to the need to evaluate atopic status in workers and identify the most susceptible subjects, with the aim of informing them of their at-risk status and monitoring their progress. This makes it possible to diagnose sooner those symptoms possibly indicative of a work-related disease, because even in presence of good environmental conditions and even when symptoms are mild, it is almost always the atopic subjects who are affected.

Allergic contact sensitivity in elderly patients

Background and aims: Aging has been shown to be correlated with the rate and type of contact sensitization, but only a few studies have evaluated patch test reactivity in elderly subjects with an adequately large population. Methods: The response patterns to patch testing in 1444 elderly subjects (>65 years) with suspected allergic contact dermatitis were studied, and the results compared with a control group of individuals with suspected allergic contact dermatitis, aged between 20 and 40 years. Results: The prevalence of the positive patch test to at least one hapten was significantly lower in the group of elderly patients compared with adult patients (40.7 vs 47.8%, p<0.0001). However, some allergens, i.e., primin, diaminodiphenylmethane, neomycin, lanolin alcohols, paraben mix, Euxyl K400 and quinoline mix, showed an increased sensitization rate in elderly patients compared with adult patients. These allergens are now less frequently employed in the workplace, or are substances particularly used in the formulation of topical treatment of age-related diseases, i.e., leg ulcer and xerosis. It was also found that the intensity of positive patch test reactions was significantly lower in elderly patients compared with younger subjects, with higher proportions of weak (+) positive reactions. Moreover, elderly patients showed a dynamic pattern of increasing intensity of patch test reactions at the second reading after 3 days compared with the first reading after 2 days more frequently than younger patients (60 vs 53%, p<0.0001 ). Conclusions: These findings suggest an age-dependent decline of overall positive patch test reactions, but a higher sensitization rate to some allergens frequently used in the composition of topical treatments. The development of an allergic response in elderly patients was found to be delayed, and this may require an additional reading after 7 days and the interpretation of even weak reactions as valid positive patch test reactions.

Silver percutaneous absorption after exposure to silver nanoparticles: A comparison study of three human skin graft samples used for clinical applications

Silver nanoparticles (AgNPs) are increasingly applied to a wide range of materials for biomedical use. These enable a close contact with human skin, thanks to the large release of silver ions that is responsible for a broad spectrum of antimicrobial activity. Silver can permeate the skin; however, there are no data available on silver permeation through skin grafts commonly used in burns recovery. The aim of our study was to evaluate silver penetration using fresh, cryopreserved, and glycerolized human skin grafts after exposure to a suspension of AgNPs in synthetic sweat using a Franz diffusion cell apparatus for 24 h. Silver permeation profiles revealed a significantly higher permeation through glycerolized skin compared with both fresh and cryopreserved skin: 24-h silver flux penetration was 0.2 ng cm(-2) h(-1) (lag time: 8.2 h) for fresh skin, 0.3 ng cm(-2) h(-1) (lag time: 10.9 h) for cryopreserved skin, and 3.8 ng cm(-2) h(-1) (lag time: 6.3 h) for glycerolized skin. Permeation through glycerolized skin is significantly higher compared to both fresh and cryopreserved skin. This result can generate relevant clinical implications for burns treatment with products containing AgNPs.

In vitro percutaneous penetration and characterization of silver from silver-containing textiles.

The objective of this study was to determine the in vitro percutaneous penetration of silver and characterize the silver species released from textiles in different layers of full thickness human skin. For this purpose, two different wound dressings and a garment soaked in artificial sweat were placed in the donor compartments of Franz cells for 24 hours. The concentration of silver in the donor phase and in the skin was determined by an electrothermal atomic absorption spectrometer (ET-AAS) and by inductively coupled plasma mass spectrometer (ICP-MS). The characterization of silver species in the textiles and in the skin layers was made by scanning electron microscopy with integrated energy dispersive X-ray spectroscopy (SEM-EDX). Additionally, the size distribution of silver nanoparticles in the textiles was performed by atomic force microscopy (AFM). On the surface of all investigated materials, silver nanoparticles of different size and morphology were found. Released silver concentrations in the soaking solutions (ie, exposure concentration) ranged from 0.7 to 4.7 μg/mL (0.6–4.0 μg/cm2), fitting the bactericidal range. Silver and silver chloride aggregates at sizes of up to 1 μm were identified both in the epidermis and dermis. The large size of these particles suggests that the aggregation occurred in the skin. The formation of these aggregates likely slowed down the systemic absorption of silver. Conversely, these aggregates may form a reservoir enabling prolonged release of silver ions, which might lead to local effects.

Pre-employment screening among trainee bakers.

OBJECTIVES--To assess the prevalence of atopy in a vocational school so as to evaluate the feasibility of pre-employment screening. METHODS--The prevalence of atopy by family diathesis, prick tests, immunoglobulin E (IgE) concentrations, and personal history of allergic respiratory diseases was investigated in 144 trainee bakers and 81 students on a graphic artists course (mean age 15.4 years). Skin sensitisation to wheat, rye, and barley flours, to alpha amylase, and to storage mites was also evaluated. RESULTS--Personal allergic symptoms were reported by 13.2% of the bakers and 14.7% of the graphic artists and there was a significant association between symptoms and atopy by prick tests (odds ratio (OR) 17.2; 95% confidence interval (95% CI) 5.27-56.4) and by family history (OR 3.11; 95% CI 1.02-9.53). When bakers were grouped according to the presence of allergic symptoms and results of immunological tests, 6.9% had asthma, 6.3% had rhinoconjunctivitis, and a high percentage (28.5%) were without symptoms but scored positive on prick tests or family symptoms. Skin sensitisation to storage mites had similar prevalences (16%) in the two groups of trainees and occurred nearly always in atopic people. Positive skin tests to wheat flour (3.5%), rye (0.7%), and alpha amylase (0.7%) were specific to bakers. CONCLUSIONS--Pre-employment screening is a useful source of medical information and allows for counseling. The presence of asthma, or of another allergic disease in a severe form, is suggested as a criterion for excluding students of a vocational school from training as bakers. Student bakers without allergic symptoms but atopic by other criteria should be informed about their risks of developing occupational asthma, and periodic check ups must be recommended. Screening studies in vocational school provide a better understanding of specificity of skin sensitisation to occupational allergens.