Dual Exposure to E-Cigarette Vapour and Cigarette Smoke Results in Poorer Airway Cell, Monocyte, and Macrophage Function Than Single Exposure.

E-cigarette users predominantly also continue to smoke cigarettes. These Dual Users either consume e-cigarettes in locations where smoking is not allowed, but vaping is, or to reduce their consumption of cigarettes, believing it will lead to harm reduction. Whilst it is known that e-cigarette vapour is chemically less complex than cigarette smoke, it has a distinct chemical profile, and very little is known about the health impacts of exposure to both chemical profiles vs. either alone. We simultaneously exposed cells in vitro to non-toxic levels of e-cigarette vapour extract (EVE) and cigarette smoke extract (CSE) to determine their effects on 16HBE14o- airway epithelial cell metabolism and inflammatory response, as well as immune cell (THP-1 cells and monocyte-derived macrophages (MDM) from healthy volunteers) migration, phagocytosis, and inflammatory response. We observed increased toxicity, reduced metabolism (a marker of proliferation) in airway epithelial cells, and reduced monocyte migration, macrophage phagocytosis, and altered chemokine production after exposure to either CSE or EVE. These cellular responses were greater after dual exposure to CSE and EVE. The airway epithelial cells from smokers showed reduced metabolism after EVE (the Switcher model) and dual CSE and EVE exposure. When EVE and CSE were allowed to interact, the chemicals were found to be altered, and new chemicals were also found compared to the CSE and EVE profiles. Dual exposure to e-cigarette vapour and cigarette smoke led to worse functional outcomes in cells compared to either single exposure alone, adding to limited data that dual use may be more dangerous than smoking only.

An approach to quantify ortho-phthalaldehyde contamination on work surfaces.

Ortho-phthalaldehyde (OPA) is used as a high-level disinfectant for reusable medical devices in healthcare settings. The ACGIH recently adopted a Threshold Limit Value-Surface Limit (TLV-SL; 25 µg/100 cm2) for OPA surface contamination to prevent induction of dermal and respiratory sensitization following dermal exposure. However, there is no current validated method to measure OPA surface contamination. This study aimed to develop a standardized approach for sample collection and quantitative determination of OPA from work surfaces for use in risk assessment practices. The reported method utilises readily available commercial wipes to collect surface samples coupled with direct detection of OPA via liquid chromatography time of flight mass spectrometry (LC-ToF-MS). This approach avoided complex derivatization steps commonly required for the analysis of aldehydes. Method evaluation was conducted in accordance with the Occupational Safety and Health Administration (OSHA) surface sampling guidelines. Overall recoveries of 25 µg/100 cm2 of OPA from stainless steel and glass surfaces were 70% and 72%, respectively. The reported LOD for this method was 1.1 µg/sample and the LOQ was 3.7 µg/sample. OPA remained stable on the sampling medium for up to 10 days, when stored at 4 °C. The method was demonstrated in a workplace surface assessment at a local hospital sterilising unit, successfully detecting OPA on work surfaces. This method is intended to supplement airborne exposure assessment and provide a quantitative assessment tool for potential dermal exposure. When used in conjunction with a thorough occupational hygiene program that includes hazard communication, engineering controls, and personal protective equipment, skin exposure and consequent sensitization risks in the workplace can be minimized.

In vitro assessment of the dermal penetration potential of sodium fluoroacetate using a formulated product.

This paper presents experimental data on the skin absorption of sodium fluoroacetate from a formulated product using an in vitro approach and human skin. Sodium fluoroacetate is a pesticide, typically applied in formulation (1080) for the control of unwanted vertebrate invasive species. It has been assigned a Skin Notation by the ACGIH, and other international workplace health regulatory bodies, due to its predicted ability to permeate intact and abraded human skin. However, there is a distinct lack of experimental data on the skin absorption of sodium fluoroacetate to support this assignment. This study found that sodium fluoroacetate, as a formulated product, permeated the human epidermis when in direct contact for greater than 10 hr. A steady-state flux (Jss) of 1.31 ± 0.043 µg/cm2/hr and a lag time of 6.1 hr was calculated from cumulative skin permeation data. This study provides important empirical evidence in support of the assignment of a Skin Notation.

Rapid Assessment of Oxidative Damage Potential: A Comparative Study of Engineered Stone Dusts Using a Deoxyguanosine Assay.

The popularity of engineered stone (ES) has been associated with a global increase in occupational lung disease in workers exposed to respirable dust during the fabrication of benchtops and other ES products. In this study, the reactivity and subsequent oxidative reduction potential of freshly generated ES dusts were evaluated by (i) comparing different engineered and natural stones, (ii) comparing settled and respirable stone dust fractions and (iii) assessing the effect of ageing on the reactivity of freshly generated stone dust. An established cell-free deoxyguanosine hydroxylation assay was used to assess the potential for oxidative DNA damage. ES dust exhibited a higher relative reactivity than two of the three natural stones tested. Respirable dust fractions were found to be significantly more reactive than their corresponding settled fraction (ANOVA, p < 0.05) across all stone types and samples. However, settled dust still displayed high relative reactivity. The lower reactivity of the settled dust was not due to decay in reactivity of the respirable dust when it settled but rather a result of the admixture of larger nonrespirable particles. No significant change in respirable dust reactivity was observed for three ES samples over a 21-day time period, whereas a significant decrease in reactivity was observed in the natural stone studied. This study has practical implications for dust control and housekeeping in industry, risk assessment and hazard management.

Characterisation of dust emissions from machined engineered stones to understand the hazard for accelerated silicosis.

Engineered stones are novel construction materials associated with a recent upsurge in silicosis cases among workers in the stonemason industry. In order to understand the hazard for the short latency of lung disease among stonemasons, we simulated real-time dust exposure scenario by dry-machining engineered stones in controlled conditions, capturing and analysing the respirable dust generated for physical and chemical characteristics. Natural granite and marble were included for comparison. Cutting engineered stones generated high concentrations of very fine particles (< 1 µm) with > 80% respirable crystalline silica content, in the form of quartz and cristobalite. Engineered stones also contained 8-20% resin and 1-8% by weight metal elements. In comparison, natural stones had far lower respirable crystalline silica (4- 30%) and much higher metal content, 29-37%. Natural stone dust emissions also had a smaller surface area than engineered stone, as well as lower surface charge. This study highlighted the physical and chemical variability within engineered stone types as well as between engineered and natural stones. This information will ultimately help understand the unique hazard posed by engineered stone fabrication work and help guide the development of specific engineering control measures targeting lower exposure to respirable crystalline silica.

The role of formulation co-ingredients in skin and glove barrier protection against organophosphate insecticides.

BACKGROUND: Commercially formulated pesticide products are complex mixtures of one or more active ingredients and several co-ingredients. However, the modifying effect of co-ingredients on skin uptake and glove barrier protection has been poorly studied. The aim of this study was to understand the role of formulation co-ingredients in skin and glove barrier protection performance against organophosphate insecticides. RESULTS: We adapted standard in vitro diffusion cell methods to test permeation kinetics of two commonly used organophosphate insecticides: dimethoate and omethoate. For spray dilutions, dimethoate and omethoate did not reach breakthrough glove permeation rate (1 µg·cm-2 ·min-1 ) and no or little skin permeation was observed for up to 8 h, regardless of formulation. For exposure conditions involving highly concentrated products, significant differences in glove permeation were observed between different formulations of dimethoate (about 1.5-fold, P < 0.05) and of omethoate (184-fold, P < 0.001). In contrast, no difference (P > 0.05) was observed between formulations in terms of skin permeation. CONCLUSION: These results suggest that co-ingredients play a critical role in glove barrier protection against undiluted organophosphate insecticides, whereas their influence on skin uptake was insignificant within the exposure time tested. This implies that dermal exposure risk may vary between handling different formulated products of the same active ingredient hence recommending a common glove material for different formulations of the same chemical without careful consideration of co-ingredients and their permeation properties may not necessarily be appropriate. © 2021 Society of Chemical Industry.

Glove performance in a warming climate: The role of glove material and climate on permeation resistance to organophosphate insecticides.

Hands and forearms are the principal sites of dermal exposure to organophosphate insecticides, which makes glove use one of the most important components of an exposure control strategy. However, the selection of suitable gloves depends on issues such as task, type, and concentration of organophosphate as well as cost. In addition, chemical protection performance of gloves may be temperature dependent, which is of increasing concern in a warming climate. Two recommended reusable glove materials (polyvinylchloride and nitrile butadiene rubber) and one single-use glove (nitrile/neoprene) were tested for permeation resistance to actual formulations of organophosphate insecticides with active ingredients dimethoate and malathion. Chemical resistance parameters were measured using American society for testing and materials permeation test cells and compared across glove, organophosphate type, and temperature. The three gloves demonstrated comparable and adequate chemical resistance (less than one µg cm-2 min-1 for up to 8 hr exposure; 25-60 °C) for dilute forms of dimethoate and malathion, used during spraying activities. However, the single-use nitrile/neoprene glove is not designed to fully cover the elbow which limits its suitability. In permeation tests that reflect "worst case" exposure scenario to concentrated (neat) organophosphate formulations, as in mixing/loading tasks, a significant variation in chemical resistance between gloves was observed. While polyvinylchloride offered the maximum resistance, physical degradation of nitrile butadiene rubber after 3 hr of continuous exposure makes it unsuitable for handling neat dimethoate. The single-use nitrile/neoprene glove material had considerably poorer permeation resistance (up to 155-fold greater permeation and 6-fold shorter breakthrough) against neat formulations. Overall, elevated temperature (>40 °C) was shown to result in significantly greater (P < 0.05) cumulative permeation of neat formulation insecticides. This work demonstrates the variation in glove performance and potential for greater exposure risk particularly when mixing concentrated pesticides at elevated temperature conditions such as an occluded human skin or hot greenhouses. Training and guidance on testing, selection, use, and storage of gloves should consider in-use exposure scenarios and temperature-induced reduction in chemical protective performance.

Effects of E-cigarette E-liquid components on bronchial epithelial cells: Demonstration of dysfunctional efferocytosis.

BACKGROUND AND OBJECTIVE: E-cigarettes are often marketed and thought of as emitting harmless vapour; however, verification of their safety for non-smokers is scarce. We have previously shown that E-cigarettes cause decreased phagocytosis of bacteria by macrophages via reductions in surface bacterial recognition receptors. This study assessed the effect of E-cigarette constituents, 3 E-liquid apple flavours, nicotine, vegetable glycerine and propylene glycol, on bronchial epithelial cell viability, apoptosis and cytokine secretion and macrophage phagocytosis of apoptotic airway cells and phagocytic recognition molecules. METHODS: Cell necrosis and apoptosis were measured by Sytox Green stain and Annexin V. Efferocytosis was measured by internalization of pHrodo Green labelled apoptotic airway cells by macrophages. Expression of macrophage cell surface apoptotic cell receptors was measured by flow cytometry. Cytokine release by E-cigarette-exposed airway cells was measured by cytokine bead array. RESULTS: E-cigarette vapour increased primary bronchial epithelial necrosis and apoptosis. E-cigarette vapour reduced efferocytosis (lowest flavour 12.1%) versus control (20.2%, P = 0.032). The efferocytosis receptor CD44 was reduced by one flavour (MFI 1863 vs 2332 control, P = 0.016) and all components reduced expression of CD36, including the glycol bases (MFI 1067-12 274 vs 1415 control). Reduced secretion of TNF-α, IL-6, IP-10, MIP-1α and MIP-1ß was observed for all flavour variants. CONCLUSION: E-cigarettes can cause bronchial epithelial apoptosis and macrophage efferocytosis dysfunction via reduced expression of apoptotic cell recognition receptors. These data further show that E-cigarettes should not be considered harmless to non-smokers and their effects may go far beyond cytotoxicity to cells.

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.

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.

Exposure of Agriculture Workers to Pesticides: The Effect of Heat on Protective Glove Performance and Skin Exposure to Dichlorvos.

Dichlorvos is a toxic organophosphate insecticide that is used in agriculture and other insecticide applications. Dermal uptake is a known exposure route for dichlorvos and chemical protective gloves are commonly utilized. Chemical handling and application may occur in a variety of thermal environments, and the rates of both chemical permeation through gloves and transdermal penetration may vary significantly with temperature. There has been no published research on the temperature-dependent kinetics of these processes for dichlorvos and thus, this study reports on the effects of hot conditions for the concentrated and application strength chemical. Dichlorvos breakthrough times for non-disposable polyvinyl chloride (PVC) gloves at 60 °C were approximately halved compared to 25 °C for the concentrate (2 vs. 4 h) and more than halved at application strength (3 vs. >8 h). From permeation experiments covering 15-60 °C, there was a 460-fold increase in cumulative permeation over 8 h for the concentrated dichlorvos and the estimated activation energy halved. Elevated temperature was also shown to be a significant factor for human skin penetration increasing the cumulative penetration of concentrate dichlorvos from 179 ± 37 to 1315 ± 362 µg/cm2 (p = 0.0032) and application strength from 29.8 ± 5.7 to 115 ± 19 µg/cm2 (p = 0.0131). This work illustrates the important role temperature plays in glove performance and health risk via dermal exposure. As such, it is important to consider in-use conditions of temperature when implementing chemical hygiene programs.

The greenhouse work environment: a modifier of occupational pesticide exposure?

Greenhouses are enclosed structures which have various characteristics that enhance crop productivity, but the implications for workers' pesticide exposure and uptake are not well understood. A narrative literature review was conducted to explore the mechanism/s of interactions between greenhouse characteristics and occupational pesticide exposure. Using a "work", "worker" and "workplace" conceptual framework, the greenhouse environment (hot and humid microclimate, limited space and dense crop arrangements) combines with work characteristics (high work and pesticide use intensity, multi-tasking, predominantly manual spraying techniques and quick reentry to treated farms) to potentially increase occupational pesticide exposure, compared with open field farming. Greenhouse environments, are variable but have been shown to influence pesticide availability, route, pathways and frequency of exposure, deposition and distribution on a worker's body as well as use and performance of exposure control methods. Training programs can emphasize the differences in exposure potential between greenhouse and open field farming. Development of tailored guidelines for exposure control strategies to better suit the level of uniqueness of greenhouse agriculture seems warranted.

Skin Notations for Low-Molecular-Weight Amines: Development of a Testing Protocol with Isopropylamine as an Example.

Owing to their volatility, the most important occupational exposure route for low-molecular-weight amines is considered to be inhalation. However, dermal exposure is also possible in many workplace situations. There are limited data available on the dermal uptake of these amines through human skin, and existing exposure standard skin notations are typically based on acute toxicity animal studies or by chemical analogy. This gap in knowledge is in part due to a lack of standardized approach for assessing dermal uptake. We describe a relatively simple protocol for the determination of permeation of low-molecular-weight amines through human skin in vitro. Using isopropylamine as a test amine, it was found that isopropylamine vapour has limited capacity to absorb into, or penetrate through, the epidermal layer of human skin, even at lethal atmospheric concentrations. This protocol can be adapted for a range of exposure scenarios, including clothing effects, and may be used to determine whether skin notations are warranted.

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.

On-chip capacitively coupled contactless conductivity detection using "injected" metal electrodes.

We demonstrate the use of injected gallium electrodes for capacitively coupled contactless conductivity detection (C(4)D) within a microchip electrophoresis device. Evaluation of the electrodes for quantitative detection of electrophoretically separated lithium, sodium and potassium ions showed the system offers competitive detection limits of 6.1 × 10(-6) M, 6.7 × 10(-6) M and 8.5 × 10(-6) M, respectively. The fabrication process is fast, highly reproducible, and eliminates difficulties with electrode alignment. Using this approach C(4)D can be readily achieved in any microchip by simply adding extra 'electrode' channels to the microchip design.

DNA capture-probe based separation of double-stranded polymerase chain reaction amplification products in poly(dimethylsiloxane) microfluidic channels.

Herein, we describe the development of a novel primer system that allows for the capture of double-stranded polymerase chain reaction (PCR) amplification products onto a microfluidic channel without any preliminary purification stages. We show that specially designed PCR primers consisting of the main primer sequence and an additional "tag sequence" linked through a poly(ethylene glycol) molecule can be used to generate ds-PCR amplification products tailed with ss-oligonucleotides of two forensically relevant genes (amelogenin and human c-fms (macrophage colony-stimulating factor) proto-oncogene for the CSF-1 receptor (CSF1PO). Furthermore, with a view to enriching and eluting the ds-PCR products of amplification on a capillary electrophoretic-based microfluidic device we describe the capture of the target ds-PCR products onto poly(dimethylsiloxane) microchannels modified with ss-oligonucleotide capture probes.