In vitro skin irritation assessment using EpiDerm™: applicability for updating toxicity information of oxybenzone and N,N-diethyl-m-toluamide.

A skin irritation test using in vitro reconstructed human epidermis (RhE) models was established for hazard identification of irritant chemicals in accordance with UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) category. In this study, EpiDerm™ was used to assess skin irritation by oxybenzone and N,N-diethyl-m-toluamide (DEET), which are widely used sunscreen and insect repellent components, respectively. EpiDerm™ was applied with oxybenzone and DEET, combined and sequentially with each single dose. Epidermal morphology and differentiation/proliferation were examined microscopically. Oxybenzone and sequential administration groups were determined as nonirritant with cell viability >50% and the morphology was comparable to the human epidermis. Contrastingly, the DEET and coadministration groups exhibited cell viability <50% and poor epidermal morphology. Interleukin (IL)-1α release from substance-treated EpiDerm™ increased inversely to cell viability, suggesting the pro-inflammatory reaction was initiated by DEET. CK-10, E-cadherin, Ki-67, laminin, and ceramide were identified as relevant markers to assess oxybenzone- or DEET-induced epidermal injury. In conclusion, these results may indicate to be aware of the possible skin irritation by indiscriminate use of oxybenzone and DEET without animal testing.

Insertion site assessment of peripherally inserted central catheters: Inter-observer agreement between nurses and inpatients.

INTRODUCTION: Many patients are discharged from hospital with a peripherally inserted central catheter in place. Monitoring the peripherally inserted central catheter insertion site for clinical and research purposes is important for identifying complications, but the extent to which patients can reliably report the condition of their catheter insertion site is uncertain. The aim of this study was to assess the inter-observer agreement between nurses and patients when assessing a peripherally inserted central catheter site. METHODS: The study was based on inpatients who were enrolled in a single-centre, randomised controlled trial comparing four different dressing and securement devices for peripherally inserted central catheter sites. A seven-item peripherally inserted central catheter site assessment tool, containing questions about the condition of the dressing and the insertion site, was developed. Assessment was conducted once by the research nurse and, within a few minutes, independently by the patient. Proportions of agreement and Cohen's kappa were calculated. RESULTS: In total, 73 patients agreed to participate. Overall, percentage agreement ranged from 83% to 100% (kappa = .65-.82). For important clinical signs (redness, swelling, ooze, pus and tracking), there were high levels of percentage agreement (99%-100%). CONCLUSION: The high level of agreement between nurse/patient pairs make the instrument useful for assessing peripherally inserted central catheter-associated signs of localised infection, allergic or irritant dermatitis or dressing dislodgement in a community setting.

Assessment of the in vitro dermal irritation potential of cerium, silver, and titanium nanoparticles in a human skin equivalent model.

Metal nanoparticles can potentially contact human skin during their manufacture and use in commercial products. This study examined the potential of metal nanoparticles to elicit irritant contact dermatitis in a human skin equivalent model (HSEM) derived from keratinocytes. Ag (10-100 nm), TiO2 (22-214 nm), and CeO2 (15-40 nm) nanoparticles were studied. The Ag particles were either coated/shelled with silica or capped with citrate or polyvinylpyrrolidone and were in water. The TiO2 and CeO2 particles were suspended in media containing 10% fetal bovine serum. The particles (1 mg/ml) were applied to the epidermal surface of the HSEM. Positive (5% sodium dodecyl sulfate (SDS)) and negative controls (saline or media) were included. After 1-h exposure at 37 °C, the HSEM was washed with saline to remove the nanoparticles. Following a 42-h incubation (37 °C), HSEM viability was assessed using the MTT assay. A test substance is considered a dermal irritant if the HSEM viability is < 50%. The mean viability for the SDS-treated HSEM was 7.8%. The viabilities of the nanoparticle-treated HSEM were 91% or greater. The Ag, TiO2, and CeO2 nanoparticles examined were not dermal irritants under the conditions used in this study. The stratum corneum of the HSEM may limit penetration of metal nanoparticles to induce toxicity.

Occupational skin disease among Australian healthcare workers: a retrospective analysis from an occupational dermatology clinic, 1993-2014.

BACKGROUND: Healthcare workers (HCWs) are at risk of developing occupational skin disease (OSD). OBJECTIVES: To ascertain the causes of OSD in Australian HCWs in a tertiary referral clinic. METHODS: A retrospective review was performed of patients assessed at the Occupational Dermatology Clinic in Melbourne from 1993 to 2014. RESULTS: Of 685 HCWs assessed in the clinic over a period of 22 years, 555 (81.0%) were diagnosed with OSD. The most common diagnosis was irritant contact dermatitis (ICD) (79.1%), followed by allergic contact dermatitis (ACD) (49.7%). Natural rubber latex allergy was also relatively frequent (13.0%). The major substances causing ACD were rubber glove chemicals (thiuram mix and tetraethylthiuram disulfide), preservatives (formaldehyde, formaldehyde releasers, and isothiazolinones), excipients in hand cleansers, which are hard-to-avoid weak allergens, and antiseptics. ACD caused by commercial hand cleansers occurred more frequently than ACD caused by alcohol-based hand rubs (ABHRs). Occupational ICD was mostly caused by water/wet work and hand cleansers, and environmental irritants such as heat and sweating. CONCLUSIONS: Understanding the causes of OSD in HCWs is important in order to develop strategies for prevention. We suggest that skin care advice should be incorporated into hand hygiene education. The use of ABHRs should be encouraged, weak allergens in skin cleansers should be substituted, and accelerator-free gloves should be recommended for HCWs with OSD.

Predicting skin sensitisation using a decision tree integrated testing strategy with an in silico model and in chemico/in vitro assays.

There is a pressing need for non-animal methods to predict skin sensitisation potential and a number of in chemico and in vitro assays have been designed with this in mind. However, some compounds can fall outside the applicability domain of these in chemico/in vitro assays and may not be predicted accurately. Rule-based in silico models such as Derek Nexus are expert-derived from animal and/or human data and the mechanism-based alert domain can take a number of factors into account (e.g. abiotic/biotic activation). Therefore, Derek Nexus may be able to predict for compounds outside the applicability domain of in chemico/in vitro assays. To this end, an integrated testing strategy (ITS) decision tree using Derek Nexus and a maximum of two assays (from DPRA, KeratinoSens, LuSens, h-CLAT and U-SENS) was developed. Generally, the decision tree improved upon other ITS evaluated in this study with positive and negative predictivity calculated as 86% and 81%, respectively. Our results demonstrate that an ITS using an in silico model such as Derek Nexus with a maximum of two in chemico/in vitro assays can predict the sensitising potential of a number of chemicals, including those outside the applicability domain of existing non-animal assays.

Occupational skin disease in Victoria, Australia.

OBJECTIVES: To describe the characteristics of patients with occupational skin disease (OSD) in a tertiary referral clinic in Victoria, Australia. METHODS: A retrospective review was conducted of records from patients seen at the Occupational Dermatology Clinic in Melbourne, Australia between 1 January 1993 and 31 December 2010. RESULTS: Of the 2894 people assessed in the clinic during the 18-year period, 44% were women and 56% were men. In all, 2177 (75%) were diagnosed with occupational skin disease (OSD). Of the patients with a work-related skin condition, 45% (n = 979) were considered to be atopic. The most common diagnosis in those with OSD was irritant contact dermatitis (ICD) (44%), followed by allergic contact dermatitis (33%) and endogenous eczema (11%). Women were significantly more likely to have soaps and detergents (P < 0.001) and water/wet work (P < 0.001) as causes of their ICD than men. Men were significantly more likely to have oils and coolants (P < 0.001) and solvent exposures (P < 0.001) as causes of their ICD. Occupational groups with the highest incidence of OSD were the hair and beauty professions (70 per 100 000), followed by machine and plant operators (38 per 100 000) and health-care workers (21 per 100 000). CONCLUSION: We confirm the importance of occupational contact dermatitis as the most common cause of OSD, with ICD being the most common diagnosis. There are differences in the causes of ICD between our group of male and female workers. For the first time in Australia, rates of OSD in certain industries have been calculated.

Occupational Contact Dermatitis: Workers' Compensation Patch Test Results of Portland, Oregon, 2005-2014.

BACKGROUND: Workers are exposed to potential irritants and allergens with constant introduction of new industrial chemicals in the workplace. OBJECTIVE: Characterize the final diagnoses, demographics, occupations, exposures, clinical presentations, patch test results, dermatologic histories, and risk factors of workers evaluated for suspected work-related allergic contact dermatitis (ACD). METHODS: A retrospective chart review of 310 workers' compensation independent medical examinations evaluated for suspected work-related ACD was performed. Workers were seen in a community dermatology clinic in Portland, Oregon, from 2005 to 2014. Evaluation included history, physical examination, patch testing, and further diagnostic workup when indicated. RESULTS: Hand dermatitis was the most common presentation (n = 148, 47.7%). Prevalent occupations included health care workers (n = 51, 16.5%), custodial staff (n = 41, 13.2%), and machinists (n = 36, 11.6%). Allergic contact dermatitis (47.5%) was more common than irritant contact dermatitis (ICD) (38.9%) in those diagnosed as having occupational skin disease (n = 185). The highest-frequency work-related allergens were thiuram mix (21 of 88, 23.9%), carba mix (20 of 88, 22.7%), potassium dichromate (9 of 88, 10.2%), and epoxy resin (9 of 88, 10.2%). CONCLUSIONS: Allergic contact dermatitis and ICD are common occupational skin disorders. In this population of workers' compensation referrals, ACD was more common, with 73.3% of those cases work related, compared with 86.7% of ICD. Blue collar work and wet work were risk factors for the development of ACD and ICD.

An Exploratory Study of Skin Problems Experienced by UK Nursing Home Residents Using Different Pad Designs.

PURPOSE: The primary aim of this study was to determine whether the severity of incontinence-associated dermatitis (IAD) among nursing home-based incontinence pad users varies between pad designs. A second aim was to examine the utility of a simple method for reporting skin health problems in which healthcare assistants were asked to record basic observational data at each pad change. STUDY DESIGN: Randomized, multiple crossover, observational, exploratory. SUBJECTS AND SETTING: Twenty-one men and 57 women using absorbent continence products to contain urinary and/or fecal incontinence were recruited from 10 nursing homes in London and the south of England. METHODS: A day-time variant and a night-time variant of each of the 4 main disposable pad designs on the market for moderate/heavy incontinence were tested: (1) insert pads with stretch pants; (2) 1-piece all-in-one diapers; (3) pull-up pants; and (4) belted/T-shape diapers. All pad variants for day-time use had an absorption capacity of 1900 mL ± 20% (measured using ISO 11948-1 International Standards Organization) while the capacity of night-time variants was 2400 mL ± 20%. Each resident used each of the 4 pad designs (day-time and night-time variants) for 2 weeks and the order of testing was randomized by nursing home. Skin health data were collected using 2 methods in parallel. Method 1 comprised visual observation by researchers (1 observation per pad design; 4 observations in total over 8 weeks). In method 2, healthcare assistants logged observational data on skin health at every pad change for the 8 weeks. The primary outcome variable was severity of the most severe skin problem noted by the researcher for each resident, and for each pad design (method 1). Descriptive data on skin care methods used in the nursing homes were also collected using short questionnaires and researcher observation. RESULTS: No significant differences in the severity or incidence of skin problems were found between observations using the 4 pad designs. However, a wide range of skin conditions was recorded that made classification difficult; the skin was often marked with creases from absorbent products, temporary marks, and pink/purple discoloration. We observed few cases of the severe erythema, rashes, and vesicles that are commonly used descriptors in previous skin tools. Nevertheless, the collected data reflect an abundance of skin problems that were difficult to categorize neatly. Researcher observations (method 1) showed that nearly all the residents (96%) had at least 1 IAD skin problem recorded over the 8-week period and 64% of residents had at least 1 problem that was rated as maximum severity. Healthcare assistants logged skin problems on 6.1% of pad changes. The discrepancy between researcher and healthcare assistant data appears to be largely due to healthcare assistants sometimes discounting low-grade IAD as normal for that population. CONCLUSION: Incontinence-associated dermatitis is common among nursing home residents who use incontinence pads, and it is often severe. No evidence was found that any design of pad was more likely than any others to be associated with skin problems. The method devised to enable healthcare assistants to record basic observational data on skin health in the diaper area at each pad change (Method 2) proved simple to use but still resulted in substantial underreporting of IAD, suggesting that further work is needed to develop a tool that more successfully encourages them to log and treat IAD problems.

Occupational risk assessment and irritant contact dermatitis.

Dermatological disorders are a common workplace injury. Workers in many occupations are at increased risk of developing dermatological skin disorders due to chemical and physical hazards in the workplace. Contact irritant dermatitis can have adverse health effects on workers and may cause permanent scarring and disability. An occupational risk assessment may identify those workers at risk, and provide strategies to decrease the risk of developing contact irritant dermatitis and treatment options.

Safety assessment of animal- and plant-derived amino acids as used in cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of animal- and plant-derived amino acid mixtures, which function as skin and hair conditioning agents. The safety of α-amino acids as direct food additives has been well established, based on extensive research through acute and chronic dietary exposures and the Panel previously has reviewed the safety of individual α-amino acids in cosmetics. The Panel focused its review on dermal irritation and sensitization data relevant to the use of these ingredients in topical cosmetics. The Panel concluded that these 21 ingredients are safe in the present practices of use and concentration as used in cosmetics.

Safety Assessment of PEGylated oils as used in cosmetics.

PEGylated oil is a terminology used to describe cosmetic ingredients that are the etherification and esterification products of glycerides and fatty acids with ethylene oxide. The Cosmetic Ingredient Review Expert Panel (Panel) considered the safety of PEGylated oils, which function primarily as surfactants in cosmetic products. The Panel reviewed relevant animal and human data provided in this safety assessment and concluded that the 130 chemically related PEGylated oils were safe as cosmetic ingredients in the present practices of use and concentration when formulated to be nonirritating.

Safety assessment of nylon as used in cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of nylon polymers, which function in cosmetics primarily as bulking and opacifying agents. The Panel reviewed relevant animal and human data related to these large polymers and determined that they are not likely to penetrate the skin. Whatever residual monomers may be present were not present at a sufficient level to cause any reactions in test subjects at the maximum ingredient use concentration. Accordingly, the Panel concluded that these ingredients are safe in the present practices of use and concentration.

Safety assessment of Tin(IV) oxide as used in cosmetics.

Tin(IV) oxide functions as an abrasive, bulking, and opacifying agent in cosmetic products and is used at concentrations up to 0.4% in rinse-off products and up to 1.3% in leave-on products. The Cosmetic Ingredient Review Expert Panel (Panel) noted that tin(IV) oxide is a water-insoluble inorganic metal compound and should not be percutaneously absorbed; therefore, systemic exposure is not likely. Studies of dermal application of tin(IV) oxide were considered to determine toxicity at the site of application. The Panel concluded that tin(IV) oxide is safe in the present practices of use and concentration.

Occupational allergic contact dermatitis diagnosed by a systematic stepwise exposure assessment of allergens in the work environment.

BACKGROUND: Information on the presence of contact allergens and irritants is crucial for the diagnosis of occupational contact dermatitis. Ingredient lists and Material Safety DataSheets (MSDSs) may be incomplete. OBJECTIVES: To evaluate the workability of a systematic exposure assessment in consecutive patients with suspected occupational contact dermatitis, and to study how it could potentially aid correct diagnostic classification. METHODS: A tool for systematic stepwise assessment of exposures in the work environment was developed, consisting of six steps spanning medical history and workplace visits. The programme included 228 consecutive patients diagnosed with occupational contact dermatitis; all patients underwent a clinical examination, the stepwise exposure assessment, and extensive patch and prick testing. RESULTS: Of the participants, 48.2% were classified as having occupational allergic contact dermatitis. The diagnosis was made at the stepwise exposure assessment for 50.0% of patients at Step 1 (medical history) and for 34.5% at Step 2 (ingredient labelling/MSDS). We found 132 different occupational allergens of relevance to the patients' eczema, of these, 78.0% were allergens not included in the European baseline series. CONCLUSIONS: Systematic stepwise exposure assessment provides information that results in the identification of occupational allergies caused by allergens not included in the European baseline series in a substantial number of patients.

Skin irritation and sensitization: mechanisms and new approaches for risk assessment. 1. Skin irritation.

Cutaneous irritation presents a major health problem with serious social and occupational impact. The interaction between an irritant and the human skin depends on multiple factors: the intrinsic properties and the nature of the irritant itself, and specific individual- and environment-related variables. The main pathological mechanisms of irritancy include skin barrier disruption, induction of a cytokine cascade and involvement of the oxidative stress network; all of them resulting in a visible or subclinical inflammatory reaction. In vivo, different non-invasive parameters for the evaluation of skin irritation and irritant potential of compounds and their specific formulations have been introduced, such as epidermal barrier function, skin hydration, surface pH, lipid composition, skin colour and skin blood flow. The diverse physiological changes caused by irritating agents require implementation of a multiparametric approach in the evaluation of cutaneous irritancy.

Skin irritation and sensitization: mechanisms and new approaches for risk assessment.

Allergic contact dermatitis (ACD) is a common skin disease with a significant social and economic impact. In contrast to irritation, skin sensitization is a response of the adaptive immune system, in which there is a delayed T-cell-mediated allergic response to chemically modified skin proteins. The chemicals that can covalently modify the skin proteins and trigger an allergic reaction are referred to as haptens or sensitizers. Attempts have been made in many countries to reduce the problems of ACD by the implementation of legislations related to skin-sensitizing chemicals, as well as by the early detection and risk assessment of substances with sensitizing properties. For many years, the simple identification of sensitizing chemicals was performed in guinea pig tests. A murine test, the local lymph node assay (LLNA), has been validated as a replacement for the guinea pig tests. Despite the recent introduction of in vitro methods for the identification of sensitizing chemicals, the LLNA results (when coupled with good exposure data) can be used as the starting point for a quantitative risk assessment. The quantitative risk assessment is aimed to identify the safe use thresholds for any potential skin sensitizer.

Skin exposure in geriatric care - a comparison between observation and self-assessment of exposure.

The aim of this study was to compare observation and self-assessment of skin exposure to irritants during a working day in nursing in geriatric care. The study group consisted of 40 volunteers, 13 nurses, and 27 assistant nurses. Before the start of a working day, the participants completed a questionnaire regarding skin exposure to water, gloves, hand disinfection, and moisturizers. Observers subsequently used a hand-held computer to register the time and frequency of each exposure. The total mean skin exposure time was 96 min per working day, including glove use. The mean exposure time to water was 9 min per working day. A tendency to overestimate was found for all exposures. A strong correlation between self-reports and observations was found for hand disinfection and moisturizers, while a moderate correlation was found for gloves and number of water exposures and a weak correlation for total time of water exposure. Despite the differences between self-assessment and observation of the exposure, we consider the questionnaire to be useful for surveying skin exposure in nursing. Furthermore, the observations in this study suggest that nursing work in geriatric care may comprise limited exposure to water.