Empirical data in support of a skin notation for methyl chloride.

This article presents the first empirical experimental data on the skin absorption of methyl chloride gas using an in vitro technique and human skin. Methyl chloride is a commonly used industrial agent that is known to be an inhalational hazard but is also reported to be absorbed through human skin in amounts that contribute substantially to systemic intoxication. As a result, is has been assigned a skin notation by the ACGIH. Other than predictive models, there is a general paucity of experimental data on the skin absorption of methyl chloride and therefore a distinct lack of empirical evidence in the open literature to support the assignment of a skin notation for this chemical. This study found that methyl chloride permeates through human epidermis when exposed at high atmospheric concentrations within relatively short timeframes. Therefore, providing important initial empirical evidence in support of the assignment of a skin notation.

Dermal absorption of fumigant gases during HAZMAT incident exposure scenarios-Methyl bromide, sulfuryl fluoride, and chloropicrin.

Accidental or intentional releases of toxic gases or vapors are the most common occurrence in hazardous material (HAZMAT) incidents that result in human injuries. The most serious hazard from exposure to gases or vapors is via the respiratory system. Dermal uptake, as a secondary route, is still a concern, most acutely for the unprotected public. There is a limited evidence base describing skin absorption of toxic gases and vapors in HAZMAT exposure scenarios, which are relatively brief compared with traditional test periods for skin absorption studies. We describe research designed to provide experimental data to support decision-making by first responders regarding skin decontamination in HAZMAT-focused exposure scenarios involving toxic gases. We present findings for three common fumigants, methyl bromide, sulfuryl fluoride, and chloropicrin assessed using an Organization for Economic Co-operation and Development in vitro toxicology protocol utilizing human skin and gas/vapor exposures. Results indicate that for atmospheric concentrations that would be lethal via inhalation (LCLo), intact skin provides an excellent barrier to exposures up to 30 min, with little influence of common clothing fabric and high temperature and humidity conditions. The findings may challenge the current HAZMAT dogma requiring mass personal decontamination by strip and shower for short-term exposures to sulfuryl fluoride and chloropicrin gas/vapor.

Hydrogen sulphide and phosphine interactions with human skin in vitro.

Accidental or intentional releases of toxic gases can have significant public health consequences and emergency resource demands. Management of exposed individuals during hazardous material incidents should be risk and evidence based, but there are knowledge gaps in relation to dermal absorption of gases and management advice for potentially exposed individuals. Using a modified Organization for Economic Co-operation and Development (OECD) in vitro toxicology protocol with human donor skin, this article reports on two common and odorous chemicals, hydrogen sulphide and phosphine. Results show that undamaged human skin provides a good barrier to hydrogen sulphide (up to 800 ppm) and phosphine (up to 1000 ppm) penetration for up to 30 min exposures, with little variability in the presence of clothing or in elevated temperature and humidity conditions. A practical guideline template for skin decontamination has been developed, and implications of the research for first responders are outlined.

In-vitro methods for testing dermal absorption and penetration of toxic gases.

This technical note provides details of an experimental technique for in-vitro skin studies with atmospheric chemical challenge. There appear to be major evidence gaps in relation to dermal exposure of gases. We describe a modification of standard OECD protocols for an atmospheric delivery system which can be used to understand interaction of toxic gases and the skin. The system can be used to examine the mechanisms by which skin uptake occurs. Auxiliary components which allow for parameter variation such as temperature and relative humidity are also described. Methodology presented in this technical note uses examples of gas challenges (ammonia, chlorine) to illustrate its application to gases of differing physicochemical properties. This adapted protocol can be applied in the context of HAZMAT scenarios involving atmospheric toxic chemical release and dermal absorption potential under variable exposure conditions.

Implementation of a Standardized Premedication Bundle to Improve Procedure Success for Nonemergent Neonatal Intubations.

The American Academy of Pediatrics recommends premedication for all nonemergent neonatal intubations, yet there remains significant variation in this practice nationally. We aimed to standardize our unit's premedication practices for improved intubation success and reduced adverse events. Methods: The study workgroup developed educational material and protocol content. Process measures included premedication use, education, and audit form completion. Primary (success on first intubation attempt and adverse event rates) and secondary (trainee success) study outcomes are displayed using statistical process control charts and pre-post cohort comparisons. Results: Forty-seven percent (97/206) of nurses completed educational intervention before protocol release, with an additional 20% (42/206) following a staff reminder. Two hundred sixteen (216) patients were intubated per protocol with 81% (174/216) audit completion. Compared with baseline (n = 158), intubation attempts decreased from 2 (IQR, 1-2) to 1 (IQR, 1-2) (P = 0.03), and success on the first attempt increased from 40% (63/158) to 57% (124/216) (P < 0.01), with a notable improvement in trainee success from less than 1% (1/40) to 43% (31/72) (P < 0.01). The rate of severe and rare adverse events remained stable; however, there was a rise in nonsevere events from 30% (48/158) to 45% (98/216). The tachycardia rate increased with atropine use. There was no change in chest wall rigidity, number of infants unable to extubate following surfactant, or decompensation awaiting medications. Conclusions: Standardizing procedural care delivery reduced intubation attempts and increased the attempt success rate. However, this was accompanied by an increase in the rate of nonsevere adverse events.

Is the skin an important exposure route for workers during cyanogen fumigation?

BACKGROUND: Cyanogen is a toxic flammable gas used as a fumigant in numerous industries. Occupational exposure to cyanogen can occur during its production and use. The most serious human health risk from exposure to cyanogen is via the respiratory system. However, there is also potential for skin exposure in many workplace situations. The extent of skin absorption under occupational exposure scenarios has not been directly assessed. Understanding skin uptake potential may inform risk assessment and exposure control measures. RESULTS: We describe an in vitro experimental system using human epidermis and dynamic atmosphere exposure to cyanogen to mimic potential workplace exposures. The influence of clothing and ventilation on skin permeation outcomes were also assessed. No evidence of transdermal permeation was found at 100 or 1000 ppm exposures, while permeation of 0.99 ± 0.38 µg cm-2 was observed after 60 min exposure to 10 000 ppm. Fabric on skin and skin ventilation had no additional influence on transdermal permeation compared with naked skin, but fabric provided a reservoir for potential secondary exposures. CONCLUSION: Results show dermal uptake following cyanogen exposure is possible, but only at very high atmospheric concentrations (10 000 ppm after >15 min exposure). Importantly, this could have implications for fumigant applicators who may only be wearing personal respiratory protection. These empirical data may be used in conjunction with other relevant toxicological information in determining whether a Skin Notation is warranted for Workplace Exposure Standard setting. © 2019 Society of Chemical Industry.

Understanding skin absorption of common aldehyde vapours from exposure during hazardous material incidents.

The toxic release of aldehyde vapours during a hazardous material (HAZMAT) incident primarily results in respiratory concerns for the unprotected public. However, skin absorption may be an important concurrent exposure route that is poorly understood for this scenario. This study provides experimental data on the skin absorption properties of common aldehydes used in industry, including acetaldehyde, acrolein, benzaldehyde and formaldehyde, in gaseous or vapour form using an adapted in vitro technique. Two of the four tested aldehydes were found to penetrate the skin in appreciable amounts following 30-min exposure at HAZMAT relevant atmospheric concentrations: acetaldehyde (5.29 ± 3.24 µg/cm2) and formaldehyde (3.45 ± 2.58 µg/cm2). Whereas only low levels of acrolein (0.480 ± 0.417 µg/cm2) and benzaldehyde (1.46 ± 0.393 µg/cm2) skin penetration was noted. The aldehydes demonstrated differing levels of interaction with fabric. Formaldehyde and acetaldehyde adsorbed strongly to denim, whereas benzaldehyde and acrolein displayed no sink properties. However, denim was shown to be an initial protective barrier and reduced penetration outcomes for all aldehydes. This study provides important information to assist first responders and confirms the relevance of using physicochemical properties (e.g. solubility, molecular weight, partition coefficient) to predict skin permeation potential in the absence of empirical data during HAZMAT incidents involving different types of aldehydes.

Skin permeation of oxides of nitrogen and sulfur from short-term exposure scenarios relevant to hazardous material incidents.

Permeation of oxides of nitrogen and sulfur gases through skin and the consequences of dermal exposure are still poorly understood. We measured the penetration profile of three common industrial gases through skin, for short-term exposures relevant to HAZMAT scenarios. Time variations of gas concentration, clothing effects, temperature and humidity on epidermal absorption and penetration were assessed. Fabric off-gassing profiles were also investigated. The results show oxides of nitrogen (NO and NO2) at airborne concentrations up to lethal inhalation levels (e.g. 3000 ppm) have little skin penetration ability. Skin absorption and reservoir effects were noted. Skin exposed to SO2 (3000 ppm/30 min) shows negligible skin absorption or penetration. Fabric on skin marginally increased SO2 absorption and subsequent ventilation did not reduce the absorbed fraction. Increased temperature and humidity had limited additional effect on skin penetration. Importantly, clothing demonstrated sink properties, especially for SO2. Short-term skin exposure relevant to accidents will not significantly contribute to body burden. The greatest concern will likely be off-gassing of chemical-laden fabric for asthma suffers. The risk-based management approach is to avoid potential secondary inhalation from fabric off-gassing by removal of outer layer of bulky clothing. Decontamination and moving into an area of enhanced ventilation may also be advised.

Determination of threshold concentrations of multiple allergenic extracts for equine intradermal testing using normal horses in three seasons.

Forty-one normal horses were evaluated for reactivity to intradermally injected aqueous allergens to determine allergen threshold concentrations (TC), with potential relevance to equine intradermal testing (IDT). Horses were tested three times over 1 year to assess seasonal variation in reactivity, using three to five serial dilutions of 27 allergens each time. Injection sites were evaluated after 15 min, 1 h, 4 h and 24 h. The highest allergen concentration at which < 10% of horses demonstrated positive reactivity (subjective score of > or = 2, scale of 0 to 4) at 15 min was considered the TC. The TC was determined for nine pollens (2000 to > 6000 PNU mL(-1)), four moulds (4000 to > 6000 PNU mL(-1)), seven insects (ant, horse fly 125 PNU mL(-1); house fly, cockroach 250 PNU mL(-1); moth 60 PNU mL(-1); mosquito 1000 PNU mL(-1); Culicoides nebeculosis 1 : 5000 w v(-1)) and three of four storage mites (1 : 10,000 w v(-1)). The TC was not determined due to excessive reactivity at the lowest concentrations tested for dust mites (Dermatophagoides farinae [< 1 : 12,000 w v(-1)], D. pteronyssinus [< 1 : 30,000 w v(-1)]), and Acarus siro (< 1 : 10,000 w v(-1)). Minor variation in the TC for specific allergens occurred in different seasons. Progressive sensitization with repeat testing occurred for grain mill dust mix. Positive reactivity at 1 h and 4 h occurred in > 10% of horses for nine of 19 allergens (pollens, mosquito, storage mites) at their determined TC. Positive reactivity was rare at 24 h. This study in normal horses suggests that appropriate testing concentrations of allergens for equine IDT in atopic horses may be > or = 1000 PNU mL(-1) for pollens and moulds, 60 to 250 PNU mL(-1) for most insects and < 1 : 12,000 w v(-1) for dust mites; and that reactions at 1-4 h may be insignificant.

Skin Absorption of Ethylene Oxide Gas Following Exposures Relevant to HAZMAT Incidents.

Ethylene oxide (EO) is a reactive gas used by numerous industries and medical facilities as a sterilant, a fumigant, and as a chemical intermediate in chemical manufacturing. Due to its common use, EO has been involved in a number of leaks and explosive incidents/accidents requiring HAZMAT response. However, the extent of skin absorption under short-term HAZMAT conditions has not been directly assessed. Such data would assist decision making by first responders regarding skin decontamination in EO HAZMAT incidents. An in vitro test protocol with human skin was used for EO exposures at 800 ppm and 3000 ppm. No evidence of dermal penetration was seen for 800 ppm EO during a 30-min challenge. For 3000 ppm, EO penetration was observed after 20 min and was greater under higher temperature/humidity conditions. Fabric (heavy cotton) on skin enhanced penetration 5-fold compared with naked skin. Off gassing from exposed fabric was rapid. The results show dermal uptake of EO vapour from exposure at 3000 ppm is small but clothing may contribute to further dermal absorption/penetration over time. For exposed, but asymptomatic, persons in EO HAZMAT incidents first responders should remove bulky clothing to prevent potential skin damage and further uptake.

Chlorine and hydrogen cyanide gas interactions with human skin: in vitro studies to inform skin permeation and decontamination in HAZMAT incidents.

Accidental or intentional toxic gas releases may result in significant public health and psychological consequences. Management of exposed individuals during HAZMAT incidents should be risk-based and supported by a suitable scientific evidence base. There appear to be large evidence gaps in relation to dermal absorption of gases, as well as management advice for potentially exposed individuals. Chlorine and hydrogen cyanide are two common HAZMAT gases and this paper addresses the need for experimental data tailored to HAZMAT scenarios and first responders. In addition to time variations of gas concentration, the modifying effects of clothing, temperature, and oil-based sunscreen on epidermal absorption and penetration are assessed. Results for chlorine show little penetration up to 500 ppm but with small enhancing effects due to heavy cotton and oil-based sunscreen. Hydrogen cyanide up to 800 ppm shows minor penetration consistent with previous studies, with little variability in the presence of sunscreen and clothing. Practical guidelines to support the decision-making of emergency responders with regard to personal decontamination have been derived.

Application of skin contamination studies of ammonia gas for management of hazardous material incidents.

In an atmospheric HAZMAT release unprotected public dermal exposure is often of short duration, but with potential secondary exposure if not decontaminated promptly. Mass decontamination is resource intensive and needs to be justified. For many HAZMAT agents there is no evidence-base on which to provide guidance on decontamination, particularly for non-symptomatic worried well. It is important to understand the influence of street clothing and environmental and other factors. Ammonia is a common HAZMAT agent and was selected for in vitro human skin studies of absorption, penetration and off-gassing at test concentrations up to 2000 ppm, incorporating primary and secondary exposure combinations up to 60 min. Intact skin provided a good barrier to ammonia penetration. Heavy street clothing such as denim was found to act as an initial barrier to skin absorption but subsequently as a reservoir for secondary exposure, under variable temperature and humidity conditions. Rapid off-gassing was observed for lighter fabrics including polyester and cotton. The findings here have been summarized as a set of practical guidelines for emergency responders who are required to make decisions about ammonia decontamination including for non-symptomatic individuals. This evidence-based diagrammatic approach allows for specific actions based on different atmospheric ammonia concentrations and other parameters.