The incidence of “acid attacks” (vitreolage) is a global concern, with those affected often receiving lifelong medical care due to physical and psychological damage. The purpose of this study was to evaluate the effectiveness of several emergency skin decontamination approaches against concentrated (>99 %) sulphuric acid and to identify the effective window of opportunity for decontamination. The effects of four decontamination methods (dry, wet, combined dry & wet and cotton cloth) were assessed using an in vitro diffusion cell system containing dermatomed porcine skin. Sulphuric acid (H2SO4) was applied to the skin with decontamination protocols performed at 10 s, 30 s, 8 min, and 30 min post exposure. Skin damage was quantified by tritiated water (3H2O) penetration, receptor fluid pH and photometric stereo imaging (PSI), with quantification of residual sulphur (by SEM-EDS) to determine overall decontamination efficiency. Skin translucency (quantified by PSI) demonstrated a time-dependent loss of dermal tissue integrity from 10 s. Quantification of dermal sulphur content confirmed the rapid (exponential) decrease in decontamination efficiency with time. The pH of the water effluent indicated complete neutralisation of acid from the skin surface after 90 s of irrigation. Wet decontamination (either alone or immediately following dry decontamination) was the most effective intervention evaluated, although no decontamination technique was statistically effective after 30 s exposure to the acid. These data demonstrate the time-critical consequences of dermal exposure to concentrated sulphuric acid: we find no practical window of opportunity for acid decontamination, as physical damage is virtually instantaneous.

This chapter reviews the causes of both accidental and deliberate release of hazardous chemical, biological, radiological and nuclear (CBRN) substances; general principles of identification and contact tracing; the initial operational response to exposure; management of fatalities; and, practicalities for health care response.

EFSA Supporting PublicationsVolume 12, Issue 2 760E External scientific reportOpen Access Preparatory work to support the re-evaluation of botanically defined feed flavouring additives K.A. Lewis, K.A. Lewis Agriculture and Environment Research Unit (AERU), University of Hertfordshire, UKSearch for more papers by this authorJ. Tzilivakis, J. Tzilivakis Agriculture and Environment Research Unit (AERU), University of Hertfordshire, UKSearch for more papers by this authorA. Green, A. Green Agriculture and Environment Research Unit (AERU), University of Hertfordshire, UKSearch for more papers by this authorD.J. Warner, D.J. Warner Agriculture and Environment Research Unit (AERU), University of Hertfordshire, UKSearch for more papers by this authorD. Naseby, D. Naseby Microbiology and Biotechnology Research Unit, University of Hertfordshire, UKSearch for more papers by this authorJ.A. Stedman, J.A. Stedman Private consultant, UKSearch for more papers by this authorR.P. Chilcott, R.P. Chilcott Department of Pharmacy, University of Hertfordshire, UKSearch for more papers by this author K.A. Lewis, K.A. Lewis Agriculture and Environment Research Unit (AERU), University of Hertfordshire, UKSearch for more papers by this authorJ. Tzilivakis, J. Tzilivakis Agriculture and Environment Research Unit (AERU), University of Hertfordshire, UKSearch for more papers by this authorA. Green, A. Green Agriculture and Environment Research Unit (AERU), University of Hertfordshire, UKSearch for more papers by this authorD.J. Warner, D.J. Warner Agriculture and Environment Research Unit (AERU), University of Hertfordshire, UKSearch for more papers by this authorD. Naseby, D. Naseby Microbiology and Biotechnology Research Unit, University of Hertfordshire, UKSearch for more papers by this authorJ.A. Stedman, J.A. Stedman Private consultant, UKSearch for more papers by this authorR.P. Chilcott, R.P. Chilcott Department of Pharmacy, University of Hertfordshire, UKSearch for more papers by this author First published: 13 February 2015 https://doi.org/10.2903/sp.efsa.2015.EN-760 The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. Published date: 13 February 2015 Question number: EFSA-Q-2013-00297 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References EFSA (European Food Safety Authority), 2012. Compendium of botanicals reported to contain naturally occurring substances of possible concern for human health when used in food and food supplements. EFSA Journal 2012; 10(5):2663. [ 60 pp.] doi:10.2903/j.efsa.2012.2663. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2012a. Guidance for the preparation of dossiers for nutritional additives. EFSA Journal, 2012; 10(1):2535, 14 pp. doi:10.2903/j.efsa.2012.2535 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2012b. Guidance for the preparation of dossiers for zootechnical additives. EFSA Journal, 2012; 10(1):2536, 19 pp. doi:10.2903/j.efsa.2012.2536 EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed), 2012c. Guidance for the preparation of dossiers for sensory additives. EFSA Journal 2012; 10(1):2534, 26 pp. doi:10.2903/j.efsa.2012.2534 Volume12, Issue2February 2015760E ReferencesRelatedInformation

Incontinence-associated dermatitis (IAD) is a painful yet preventable form of cumulative skin irritation prevalent amongst those with limited movement. Consequently, it has a significant impact on the quality of life for those affected as well as substantial cost implications. Prevention and intervention is typically through good skin hygiene regimes and regular use of barrier products. In this paper, we describe the development of an in vivo model of IAD in healthy volunteers by occluded application of alkaline synthetic urine to the volar aspect of volunteer’s forearms for 6 h per day over a five-day period to reproduce the moist and irritant conditions causative of IAD. Irritation was assessed and quantified on a daily basis by a series of non-invasive biophysical measurements and compared to a contralateral saline-treated (control) site. Dermal irritation was assessed by subjective (visual) and objective measurements (laser Doppler and polarisation spectroscopic imaging, infrared thermography, skin reflectance spectroscopy, transepidermal water loss and skin surface pH). The provocation of reproducible, cumulative skin irritation was successfully demonstrated and quantified. This five-day model of irritation is considered appropriate for the initial clinical assessment of topical products to prevent or treat IAD.

Regulatory guidelines are generally written with great attention to detail in order to promote an unambiguous understanding of requirements. However, the necessarily comprehensive and rigorous nature of such documentation can paradoxically lead to misinterpretation and, consequently, submissions which may not meet the expectations of regulatory organisations.

The efficient removal of contaminants from the outer surfaces of the body can provide an effective means of reducing adverse health effects associated with incidents involving the accidental or deliberate release of hazardous materials. Showering with water is frequently used by first responders as a rapid method of mass casualty decontamination (MCD). However, there is a paucity of data on the generic effectiveness and safety of aqueous decontamination systems. To address these issues, we have developed a new in vitro skin diffusion cell system to model the conditions of a common MCD procedure ("ladder pipe system"). The new diffusion cell design incorporates a showering nozzle, an air sampling port for measurement of vapour loss and/aerosolisation, adjustable (horizontal to vertical) skin orientation and a circulating manifold system (to maintain a specified flow rate, temperature and pressure of shower water). The dermal absorption characteristics of several simulants (Invisible Red S, curcumin and methyl salicylate) measured with the new in vitro model were in good agreement with previous in vitro and in vivo studies. Moreover, these initial studies have indicated that whilst flow rate and water temperature are important factors for MCD, the presence of clothing during showering may (under certain circumstances) cause transfer and spreading of contaminants to the skin surface.

Collection and analysis of skin surface lipids or sebum has been reported in several previous studies where Sebutape™, polyurethane foam, cigarette paper and organic solvents were used to acquire samples, analysis of which was performed by thin layer chromatography, gas chromatography and infra-red spectroscopy. However, there is great variation in the reported quantity of sebum present on the skin surface as well as its composition.

Studies of the percutaneous reservoir of sulphur mustard (HD) formed during absorption carried out during WWI and WWII are inconclusive. More recent studies have indicated that a significant amount of unreacted HD remains in human epidermal membranes during percutaneous penetration studies in vitro. The present study investigated the nature and persistence of the HD reservoir formed during in vitro penetration studies using dermatomed slices of human and pig skin (0.5mm thick). Amounts of (14)C-HD that (a) penetrated, (b) remained on the surface, (c) were extractable from and (d) remained in the skin after extraction were estimated by liquid scintillation counting (confirmed using GC-MS analysis). The results demonstrated that there is a reservoir of HD in human and pig skin for up to 24 h after contamination of the skin surface in vitro with liquid agent. At least some of this reservoir could be extracted with acetonitrile, and the amounts of extracted and unextracted HD exceed the amount required to produce injury in vivo by at least 20 fold. The study demonstrated the presence of a reservoir whether the skin was covered (occluded) or left open to the air (unoccluded). The study concluded that the extractable reservoir was significant in terms of the amount of HD required to induce a vesicant response in human skin. The extractable reservoir was at least 20 times the amount required per cm(2) estimated to cause a response in all of the human population, as defined by studies carried out in human volunteers during the 1940s.

Percutaneous vapor dosing studies have generally used saturated vapor concentration (SVC) measurements to estimate the exposure dose (Ct) of vapor produced from a volatile liquid within a closed system. The purpose of this study was to clarify whether the assumption was valid when translated to a biological system (pig skin) using sulfur mustard (SM) as a model skin penetrant. Three systems were evaluated, two containing skin and a control system (without skin). At set time points, samples from the headspace of each dosing system were extracted using a gas-tight syringe and analyzed by gas chromatography in conjunction with a flame-ionization detector. This demonstrated the rapid achievement of a constant vapor concentration within the biological and control systems and enabled a comparison with previously determined SVCs attained under ideal conditions. All three systems attained a constant vapor concentration within 2 min of exposure to SM. The control system reached an equilibrium vapor concentration of 1179 +/- 164 mg/m3, a value not significantly different from that derived from the SVC (1363 mg/m3). Because of absorption in the skin systems, SM vapor concentrations were significantly lower than that derived from the SVC and were dependent on the skin surface area within the dosing chamber (592 +/- 246 mg/m3 for a surface area of 10.15 cm2 and 740 +/- 224 mg/m3 for a surface area of 2.54 cm2). The assumption that SVC gives an acceptable measure of the Ct was shown to be valid by comparison with sulfur mustard recovered from the skin.

The purpose of this study was to characterize the skin absorption and distribution of VX (Oethyl–S–[2(diisopropylamino)ethyl] methylphosphonothioate) in the domestic pig in order to evaluate the animal as a potential model for assessing pretreatments against toxic anti–cholinesterase compounds. A liquid droplet (equivalent to a 2 LD 50 dose) of radiolabelled VX was applied to the inner ear–skin of each anaesthetized animal. Blood and tissue samples (liver, lung, kidney, heart and skin exposure sites) were obtained post–mortem. The amount of radioactivity in each sample was measured by liquid scintillation counting, from which the skin absorption rate and dose distribution of VX were calculated. A substantial proportion (229±3%) of the applied dose remained within the skin at the site of application. It is conceivable that strategies to minimize or remove this reservoir may be of benefit in the early treatment of VX–exposed casualties. Image analysis of autoradiographs of exposed skin sites indicated that each milligram of radioactive VX covered an area of 1.29±0.5 cm 2 . The average skin absorption rate of 14 C-VX was 6619±126 mg/cm 2 per hour. Comparison of these data with previous studies suggests that human skin is less permeable to VX than pig skin, but VX spreads over a greater surface area when applied to human skin. Thus, paradoxically, while pig-ear skin is more permeable than human skin, the difference in skin surface spreading may lead to the absorption of an equivalent systemic dose.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.

Nerve agents are a class of organophosphorus chemicals that inhibit certain cholinesterase enzymes (ChE). If untreated, percutaneous exposure to nerve agents, such as VX (O-ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate) can cause paralysis, apnoea and death. Much of the information concerning the percutaneous absorption and subsequent toxicity of nerve agents has been obtained using various rodent models. However, the most relevant ‘skin model’ is arguably the pig. Therefore, the purpose of this study was to examine the clinical manifestations of VX intoxication in the domestic white pig following a 2 LD50 (120 mg/kg) percutaneous challenge. There was a consistent onset of signs (where present) in each animal: mastication was followed by miosis, salivation, fasciculations and apnoea. Whilst ChE activity did not correlate with the onset of signs, there was a qualitative relationship in that mastication preceded substantial ChE inhibition, miosis lagged behind the linear decrease in acetylcholinesterase (AChE) activity and fasciculations and apnoea occurred after maximum ChE inhibition had been attained (5 / 10% of normal). These observations may be of use for the triage of patients exposed to VX. In comparison with similar studies with GD, VX did not affect glucose utilization. However, VX was similar to GD in that it caused a mild hyperkalaemia and hyperphosphataemia, although the significance of this observation was not clear. There was substantial lateral diffusion of the initial droplet of VX over the application site, indicating that, when decontaminating exposed skin, attention should also be directed to areas peripheral to the original site of exposure.

The purpose of this study was to investigate the relationship between transepidermal water loss and skin permeability to tritiated water (3H2O) and the lipophilic penetrant sulfur mustard in vitro. No correlation was found between basal transepidermal water loss rates and the permeability of human epidermal membranes to 3H2O (p = 0.72) or sulfur mustard (p = 0.74). Similarly, there was no correlation between transepidermal water loss rates and the 3H2O permeability of full-thickness pig skin (p = 0.68). There was no correlation between transepidermal water loss rate and 3H2O permeability following up to 15 tape strips (p = 0.64) or up to four needle-stick punctures (p = 0.13). These data indicate that transepidermal water loss cannot be unconditionally ascribed to be a measure of skin barrier function. It is clear that further work should be conducted to interpret the significance of measuring transepidermal water loss by evaporimetry.

The purpose of this study was to develop a method for habituating pigs ( Sus scrofa domestica, middle white strain) to enable non-invasive, biophysical measurements of dorsal skin to be obtained on a daily basis over a 7-week period, thus eliminating the need for anaesthesia or restraint. This was accomplished by associating measurements of transepidermal water loss (TEWL) and skin reflectance spectroscopy (SRS) with feeding times, and with positive reinforcement by allowing exercise outside the home pen. During the pig habituation period, a well-defined series of behavioural changes were observed that included dominant/submissive leadership changes. Values of TEWL (6.29 ± 1.25 g.m -2 .h -1 ) were in agreement with previous studies (7.56 ± 2.90 g.m -2 .h -1 ) obtained from unrestrained Yucatan hairless micro-pigs (Gabard et al. 1995). The coefficient of variance of TEWL and SRS measurements were comparable with those reported previously using anaesthetized pigs (Chilcott et al. 2000). These data imply that biophysical skin measurements obtained from unrestrained, conscious animals are comparable to those obtained from anaesthetized pigs and therefore, support the use of unrestrained pigs for non-invasive biophysical skin measurements. Habituating animals for in-pen, non-invasive, biophysical measurements has substantial implications for reducing and refining laboratory animal experiments in dermatological research without compromising animal welfare.

The aim of this study was to evaluate the use of an in vitro skin diffusion cell system as a model for assessing decontaminants against the chemical warfare agent sulphur mustard (SM). The in vitro absorption rates of SM through heat-separated human (157 +/- 66 microg cm(-2) h(-1)) and pig-ear (411 +/- 175 microg cm(-2) h(-1)) epidermal membranes were in agreement with previous in vivo studies that quoted skin absorption rates of 150 and 366 microg cm(-2) h(-1), respectively. Decontaminants (fuller's earth, Ambergard and BDH spillage granules) were ranked in order of effectiveness by measuring the skin absorption rates and the percentage of applied dose of SM that penetrated human and pig-ear epidermal membranes. The effectiveness of fuller's earth measured in this in vitro study using human epidermal membranes was in agreement with a previous in vivo human volunteer study. Similarly, the effectiveness of fuller's earth and Ambergard measured in vitro with pig-ear epidermal membranes was in agreement with a previous in vivo study conducted on rats. However, there was complete disparity in the ranking of decontaminants between human and pig-ear epidermal membranes measured in vitro. Thus, although pig-ear skin may be a relatively good model for predicting the human skin absorption of SM, it is a poor model for testing decontamination systems. The results of this study further validate the use of Franz-type glass diffusion cells containing human epidermal membranes as a model for predicting in vivo human skin absorption.