Quality and safety of South African hand sanitisers during the COVID-19 pandemic.

Health agencies recommend using hand sanitisers as protection against the coronavirus. Thus far, the emphasis on hand sanitiser studies is limited to an analysis of disinfectant content only. This study aims to provide an extended analysis of 60 off-the-shelf alcohol-based hand sanitisers by using gas chromatography to report on alcohol content and the presence of impurities, a recombinant yeast estrogen screen to assess estrogenic activity, and an investigation into labelling compliance with the South African National Standard. Fifty hand sanitisers had an alcohol content of ≥60% v/v alcohol; however, most contained skin irritants and substances that could harm human and environmental health. Estrogenic activity was detected in 29 hand sanitisers and none of the products complied with all the labelling requirements. Since off-the-shelf hand sanitisers in South Africa are not regulated and monitored, evidence-based public awareness programmes on hand sanitiser quality and safety should become a priority.

Quality of New Domestic Hand Sanitizer Drug Product Manufacturers During COVID-19.

The FDA initiated a cross-sectional, statistically based sampling and testing study to characterize the quality of marketed alcohol-based hand sanitizer (ABHS) by evaluating the alcohol content and impurities present in ABHS products manufactured by establishments that registered with the FDA during March-April 2020. A stratified sampling design divided the population of manufacturers into independent groups based on each establishment's level of experience with FDA oversight and its geographic location. ABHS products were collected and analyzed by spatially offset Raman spectroscopy and gas chromatography with mass spectrometry (GC-MS). The GC-MS results for 310 products, from 196 newly registered domestic manufacturers, showed that 71.6% (± 5.7%) of these manufacturers had violative products. In 104 (33.5%) cases, the alcohol content did not meet label claim assay specifications but still fell within CDC efficacy ranges. Ethanol ABHS products failed more often overall (assay and impurities) (84.3%) and for impurities (84.3%), than isopropanol ABHS products (11.2% and 6.2%, respectively). Differences in test results across active ingredients were statistically significant. Ethanol ABHS products often (63.5% of cases) failed due to the presence of acetal or acetaldehyde, particularly in products with pH ≤ 6. Other impurities were also detected in several ABHS products, suggesting the use of low-grade alcohol in the manufacture of these products. Evidence was insufficient to conclude that having experience manufacturing FDA-regulated products, or lack thereof, influenced product-level violative results. This study highlights the importance of sourcing and testing active pharmaceutical ingredients to produce quality drug products.

Toxicity of chemical-based hand sanitizers on children and the development of natural alternatives: a computational approach.

The unintended exposure of children to hand sanitizers poses a high risk of potentially fatal complications. Skin irritation, dryness, cracking, peeling, hypoglycemia, apnea, and acidosis are examples of unintended consequences of hand sanitizer. The sanitizer reportedly kills normal microbial flora on hands, which usually promotes innate immunity among children under 12. Children are more susceptible to the toxicity associated with the chemical constituents of marketed chemical-based hand sanitizers; however, the studies to develop sanitizer formulations for children are rudimentary. The adverse events limit the use of hand sanitizers specifically in children because of their sensitive and delicate skin. Additionally, it is reported that many chemical-based hand sanitizer formulations, especially alcohol-based ones may also contain contaminants like methanol, acetaldehyde, benzene, isopropanol, and ethyl-acetate. These contaminants are found to be hazardous to human health exhibiting toxicity on ingestion, inhalation, or dermal exposure, especially in children. Therefore, it is important to design novel, innovative, safer sanitizer formulations for children. The study aims to discuss the toxic contaminants in chemical-based sanitizer formulations and propose a design for novel herbal formulations with minimal toxicity and adverse effects, especially for children. The review focuses on ADMET analysis of the common contaminants in hand sanitizers, molecular docking, Lipinski's rule of five analysis, and molecular simulation studies to analyze the efficacy of interaction with the receptor leading to anti-microbial activity and drug-likeness of the compound. The in silico methods can effectively validate the potential efficacy of novel formulations of hand sanitizers designed for children as an efficient alternative to chemical-based sanitizers with greater efficacy and the absence of toxic contaminants.

Determination of ethanol, isopropyl alcohol and methanol in alcohol-based hand sanitiser to ensure product quality, safety and efficacy.

The Coronavirus Disease-2019 (COVID-19) outbreak is an unprecedented global pandemic, sparking grave public health emergencies. One of the measures to reduce COVID-19 transmissions recommended by the World Health Organization is hand hygiene, i.e., washing hands with soap and water or disinfecting them using an alcohol-based hand sanitiser (ABHS). Unfortunately, competing ABHSs with unknown quality, safety, and efficacy thrived, posing yet another risk to consumers. This study aims to develop, optimise, and validate a gas chromatography-mass spectrometry (GC-MS)-based analytical method to simultaneously identify and quantify ethanol or isopropyl alcohol as the active ingredient in ABHS, with simultaneous determination of methanol as an impurity. The GC-MS was operated in Electron Ionisation mode, and Selected Ion Monitoring was chosen as the data acquisition method for quantitation. The analytical method was validated for liquid and gel ABHSs, covering the specificity, linearity and range, accuracy, and precisions, including the limit of detection and the limit of quantitation. The specificity of each target analyte was established using the optimised chromatographic separation with unique quantifier and qualifier ions. The linearity was ascertained with a coefficient of determination (r2) of > 0.9994 over the corresponding specification range. Respectively, the accuracy and precisions were satisfactory within 98.99 to 101.09% and < 3.04% of the relative standard deviation. The method was successfully applied to 69 ABHS samples, where 14 contained insufficient amounts of the active ingredient. Alarmingly, four samples comprised a high amount of methanol ranging from 5.3 to 19.4% with respect to the active alcohol percentage, which may pose significant short- and long-term health issues, leading to life-threatening crises for consumers. The method established would benefit in protecting the public against the potential harm due to substandard or unsafe ABHS products, primarily due to the presence of hazardous impurities such as methanol.

COVID-19, Overzealous Sanitizer Use, and Hair Discoloration: Case Reports.

Proper hand hygiene is one of the top preventive measures against the Coronavirus Disease 2019 (COVID-19). In this study, we report the cases of four patients who presented with blonde discoloration of hair of the dorsal hands and distal forearms during the COVID-19 pandemic. The mean age of participants was 41.25±4.35 years, and 75% percent of them were men. Three patients were medical staff who had to use antiseptics frequently, and one of them was a housewife. In all participants, the primary color of hand hair was black. The duration of sanitizer use was approximately four months (Table 1). One of the patients, a 42-year-old male ophthalmologist, was examined due to the blonde discoloration of hairs of the dorsal hands and distal forearms (Figure 1). The color of the hand and forearms hair had changed to blonde. However, the underlying skin was unaffected. A dermoscopy examination showed lighter hair compared with the natural black hair of unaffected parts. In addition, the hair color of the scalp, upper arms, and other body parts was normal. The patient had frequently used a hand sanitizer that contained 70% ethanol and didecyl dimethyl ammonium chloride (DDAC) for the past five months. The three other patients also had blonde discoloration observable on the hair of dorsal hands. They all reported excessive use of various alcoholic sanitizers. However, they were unaware of other ingredients. In addition, the examination of hair shafts and underlying skin was normal. The COVID-19 pandemic caused an abrupt increase in the use of sanitizers. Hand disinfectants consist of two main categories: non-alcohol-based hand sanitizers and alcohol-based hand sanitizers. The alcohol-based type is an effective measure for the inactivation of enveloped viruses such as coronaviruses (1). It has been shown that percutaneous absorption of alcohol is possible through intact skin. The use of ethanol as a penetration enhancer for pharmaceutical purposes also confirms that ethanol can be absorbed via the skin and be systematically distributed in the body (2). Reisfield et al. observed that intensive use of ethanol-based sanitizers led to an increase in urinary ethanol biomarkers concentrations (3). Alcohols used in various types of gels and solutions are easily released during hand rubbing (4). Ethanol absorption by inhalation should therefore also be taken into account (5). Different pathways of ethanol metabolism can produce free radicals, which affect the antioxidant system (6). In addition, DDAC is also associated with cell growth inhibition and stress oxidative induction (7). Hair discoloration may be a voluntary cosmetic change or a result of chemical or metal exposure. Most unwanted hair discolorations are blonde or white (8). Previous data suggested that an increase in pro-oxidants and a decrease in antioxidants play an important role in hair discoloration. A study performed by Akin Belli et al. demonstrated that hair discoloration is closely related to factors such as emotional stress and alcohol consumption, which cause oxidative stress (9). Hair discoloration might therefore result from oxidative stress induced by ethanol and DDAC used in sanitizers. Golden hair discoloration has been associated with chloride in water. Hypochlorous acid in swimming pool water can penetrate the hair cortex through the cuticle, where it can oxidize and degenerate melanosomes (10). Another possible hypothesis is that the chloride compound in DDAC might be the culprit in sanitizer hair discoloration. Additionally, the bleaching compounds used in some hand disinfectants could be another possible cause of hair discoloration. To the best of our knowledge, this observation of hair discoloration was not previously reported during the COVID-19 outbreak. It is also noteworthy that most hair discoloration normalizes over time (8). The limitations of our study included the fact that the hand sanitizers used by the patients were unavailable and thus their ingredients could not be examined. Furthermore, as most of the sanitizers in this current pandemic are not standardized, they may have unknown ingredients with discoloration properties. Due to the overzealous use of various antiseptics during the pandemic, it is expected that this side-effect will be observed more and more often. Therefore, physicians must be aware of this presentation and reassure the patient regarding this phenomenon. Additionally, products free of such agents should be prescribed to avoid hair discoloration.

Assessment of quality of alcohol-based hand sanitizers used in Johannesburg area during the CoViD-19 pandemic.

Since the outbreak of the Coronavirus Disease 2019 (CoViD-19), the World Health Organization has recommended that, in absence of soap and water, alcohol-based hand sanitizer can be used to prevent the transmission of coronaviruses. Unfortunately, many media and anecdotal reports indicate that many alcohol-based hand sanitizers sold in South Africa are substandard and some contain potentially toxic ingredients. The study aimed to identify hand sanitizers used in the Johannesburg area during the CoViD-19 pandemic that do not contain the recommended alcohol concentration of at least 70% propanol or 60% ethanol, and contain traces of toxic ingredients. Hand sanitizers randomly collected from various traders around Johannesburg were analyzed using Agilent auto sampler coupled to a gas chromatograph utilizing flame ionisation detection. Of the 94 hand sanitizer samples collected, three preparations contained no alcohol, whereas the rest contained either ethanol, 2-propanol or 1-propanol or a combination of two alcohols. Of the alcohol-containing hand sanitizers, 37 (41%) contained less than 60% alcohol. Ethyl acetate, isobutanol and other non-recommended alcohols (methanol and 3-methyl-butanol) were also identified. Consumers are therefore warned that among the many brands of hand sanitizers found around Johannesburg, there are some substandard preparations and some that contain traces of toxic ingredients.

Aquatic Toxicity Effects and Risk Assessment of 'Form Specific' Product-Released Engineered Nanomaterials.

The study investigated the toxicity effects of 'form specific' engineered nanomaterials (ENMs) and ions released from nano-enabled products (NEPs), namely sunscreens, sanitisers, body creams and socks on Pseudokirchneriella subcapitata, Spirodela polyrhiza, and Daphnia magna. Additionally, risk estimation emanating from the exposures was undertaken. The ENMs and the ions released from the products both contributed to the effects to varying extents, with neither being a uniform principal toxicity agent across the exposures; however, the effects were either synergistic or antagonistic. D. magna and S. polyrhiza were the most sensitive and least sensitive test organisms, respectively. The most toxic effects were from ENMs and ions released from sanitisers and sunscreens, whereas body creams and sock counterparts caused negligible effects. The internalisation of the ENMs from the sunscreens could not be established; only adsorption on the biota was evident. It was established that ENMs and ions released from products pose no imminent risk to ecosystems; instead, small to significant adverse effects are expected in the worst-case exposure scenario. The study demonstrates that while ENMs from products may not be considered to pose an imminent risk, increasing nanotechnology commercialization may increase their environmental exposure and risk potential; therefore, priority exposure cases need to be examined.

Perspectives of compounding pharmacists on alcohol-based hand sanitizer production and utilization for COVID-19 prevention in Addis Ababa, Ethiopia: A descriptive phenomenology study.

BACKGROUND: Globally, the safety of patients and healthcare providers is at risk due to health care-associated infections (HCAIs). World Health Organization and the Centers for Disease Control and Prevention recommend using alcohol-based hand rub (ABHR) for hand hygiene in healthcare settings to prevent HCAIs. Irrational use of ABHR will have undesirable consequences including wastage of products, exposure of healthcare providers to infections and emergence of microbial resistance to the alcohol in hand sanitizers. This study aimed to explore the perspective and experiences of compounding pharmacists on production and utilization of ABHR solution for coronavirus disease in 2019 (COVID-19) prevention in public hospitals of Addis Ababa, Ethiopia. METHODS: A descriptive qualitative study using in-depth interview of 13 key-informants serving as compounding pharmacists in public hospitals of Addis Ababa, Ethiopia, was conducted. The study participants were identified and selected by purposive sampling. All transcribed interviews were subjected to thematic analysis and transcripts were analyzed manually. FINDINGS: The compounding pharmacists in this study had a mean age of 30.6 (±3.1) years and nine of the thirteen participants were men. Ten participants believed that the compounding practice in their respective sites followed the principles of good compounding practice. More than half of the participants did not believe that ABHR products were used rationally in health facilities. They argued that users did not have enough awareness when and how to use sanitizers. Most of the interviewees reported that compounding personnel had no formal training on ABHR solution production. Study participants suggested incentive mechanisms and reimbursements for experts involved in the compounding of ABHR solutions. CONCLUSION: Three of the compounding pharmacists indicated that ABHR production in their setting lack compliance to good compounding practice due to inadequate compounding room, quality control tests, manpower and equipment. Despite this, most study participants preferred the in-house ABHR products than the commercially available ones. Thus, training, regular monitoring and follow-up of the hospital compounding services can further build staff confidence.

Death by hand sanitizer: syndemic methanol poisoning in the age of COVID-19.

BACKGROUND: The advent of COVID-19 increased attention to hand hygiene in prevention of disease transmission. To meet the increased demand for hand sanitizer during the pandemic, the US FDA issued an Emergency Use Authorization allowing new manufacturers and importers to enter the market. Some of the newly introduced hand sanitizer products contained methanol in lieu of ethanol or isopropanol. We describe five patients with fatal methanol poisoning resulting from hand sanitizers improperly containing methanol. CASE SUMMARY: Comparing a 5-month period from 2019 to the same time frame in 2020, the Arizona Poison and Drug Information Center has seen an increase of 124% in exposures to hand sanitizer. Of these cases, 28% involved methanol-contaminated hand sanitizer. Five of these patients died from methanol poisoning. All five cases had similar clinical features with severe high anion gap metabolic acidosis and, in four patients, elevated osmolal gap. Methanol concentrations were consistently very elevated, but these results were not available before the patients succumbed. Four of the patients received fomepizole and adjunctive care. Two patients received emergency extracorporeal therapy. All five died despite maximal treatment efforts. CONCLUSION: During the pandemic in 2020, there was a proliferation of alcohol-based hand sanitizers which contained methanol. Exposure to these products, which failed to meet regulatory standards, led to increased harm and death. Challenges to treatment of methanol poisoning, especially in rural areas, include lack of access to timely laboratory measurement of methanol concentrations and lack of available emergency hemodialysis without transfer of the patient.

Allergenic Ingredients in Health Care Hand Sanitizers in the United States.

BACKGROUND: Health care workers with occupational contact dermatitis often attribute their symptoms to frequent use of alcohol-based hand sanitizers. However, ingredient lists are difficult to obtain, and safe alternatives typically must accommodate brands utilized by a particular hospital system. OBJECTIVE: The aims of this study were to investigate allergenic ingredients present within health care hand sanitizers and to provide a comprehensive product list to assist with allergen avoidance. METHODS: Five major hospitals in Minnesota and 20 hospitals across the United States were called to obtain a product list. The National Library of Medicine's DailyMed Web site was searched to retrieve ingredients. Ingredients were compared with the American Contact Dermatitis Society 2017 Core Allergen Series and cross-reactors. RESULTS: The most common brands included Purell, Ecolab, DebMed, and Avagard. Active ingredients consisted of ethyl alcohol (85.0%), benzalkonium chloride (8.8%), or isopropyl alcohol (2.5%). Top 5 allergens included tocopherol (51.3%), fragrance (40.0%), propylene glycol (27.5%), benzoates (25.0%), and cetyl stearyl alcohol (12.5%). Four sanitizers were free of all American Contact Dermatitis Society allergens; 15 products contained only tocopherol or propylene glycol as allergens. CONCLUSIONS: We identified 19 low-allergen hand sanitizers within the most common brands utilized by US hospital systems. This product list will be useful for patients and health care workers seeking allergen avoidance.

The pandemic of COVID-19 and its implications for the purity and authenticity of alcohol-based hand sanitizers: The health risks associated with falsified sanitizers and recommendations for regulatory and public health bodies.

With the beginning of the pandemic of COVID-19 throughout the world, the demand and consumption of hand sanitizers has increased, which had led to a sharp crunch in these products at all levels. This shortage has led to an increase in the prevalence of falsified alcohol-based hand sanitizers, including the illegal addition of methanol to hand sanitizers and the production of hand sanitizers with an alcohol concentration of less than 60%. These findings indicate that regulatory and public health bodies should take an active role in ensuring the safety and quality of antimicrobial products such as alcohol-based hand sanitizers at every stage of the products' lifecycle, including distribution, manufacture and import.

Changes in workflow to a University Pharmacy to facilitate compounding and distribution of antiseptics for use against COVID-19.

This article is a report from an experience about a work developed by Farmácia Universitária at UFRJ (FU-UFRJ) during the nCov-19 pandemic period. The aim of this work was to describe its contribution in the production of antiseptic supplies used to prevent contagion by the new coronavirus. The work routine at the pharmacy has been changed to allow the implementation of local workflow during the pandemic, and to adapt the protection rules to meet the safety measures. FU-UFRJ started to manipulate two antiseptic formulations: 70% ethyl alcohol and gel alcohol, which are included in the National Form, manufacturing around 100 L of these formulations, weekly, to donate to different health units. The experience enabled the adaptation to emergency health standards, planning and meaningful guidance to pharmacists and technicians to attend clinics at university hospitals, vaccination center and UFRJ city hall, in order to facilitate the access to adequate hand hygiene to the population.

Antimicrobial properties of diethylamine NONOate, a nitric oxide donor, against Escherichia coli: a pilot study.

The emergence of SARS-CoV-2, the causative agent of COVID-19, highlights the increasing need for new and effective antiviral and antimicrobial agents. The FDA has recently banned several active ingredients used in hand sanitizers, including triclosan and benzethonium chloride. Nitric oxide (NO) is involved in the innate immune response and is a major component of macrophage-mediated attack on foreign viruses and bacteria. The specific aim of this study was to assess the antibacterial effects of 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NONOate) against Escherichia coli (E. coli). A bacterial growth assay was compared to an adenosine triphosphate (ATP) activity assay at various time points to assess effects of DEA-NONOate on E. coli growth. A UV/Vis spectrophotometer was used to determine concentration of E. coli by measuring optical density (OD) at 630 nm. A luminescent assay was used to measure ATP activity correlating to viable cells. DEA-NONOate at a concentration of 65 mM was able to inhibit the growth of E. coli with the same efficacy as 1 µg ml-1 concentration of ciprofloxacin. Both the OD and ATP assays demonstrated a 99.9% reduction in E. coli. Both a 1 µg ml-1 concentration of ciprofloxacin and a 65 mM concentration of DEA-NONOate achieved 99.9% inhibition of E. coli, verified using both optical density measurement of bacterial cultures in 96 well plates and a luminescent ATP activity assay. The bactericidal effects of DEA-NONOate against E. coli is proof-of-concept to pursue evaluation of nitric oxide-based formulations as antimicrobial and antiviral agents as hand sanitizers.

Non-Beverage Alcohol Consumption In Izhevsk: 15 Years Later.

AIMS: Non-beverage alcohol was a major cause of preventable mortality of working-age males in Izhevsk (Russia) in 2003-2004. The Russian government has since taken measures to reduce availability of non-beverage alcohol. Yet, some types of non-beverage alcohol still remain available for consumers. The aim of this study was to assess the availability and sources of non-beverage alcohol in Udmurtia. METHODS: A survey of adults on the streets of Izhevsk and its environs was performed on workdays to assess non-beverage drinking patterns in 2018. The questionnaire included questions about socio-demographic status and alcohol use, including non-beverage alcohol consumption and drinking patterns. RESULTS: One hundred and sixty-eight people were questioned, of whom, 28% reported consuming non-beverage alcohol. Non-beverage alcohol consumers were more likely to be single, unemployed or retired, younger or older than 19-29 years, have lower educational status and income, have hangovers and drink moonshine. CONCLUSION: Non-beverage alcohol consumption still took place at Izhevsk, a typical Russian city, in 2018, and its availability was still high. Untaxed and cheap medicinal non-beverage alcohol consumption seems to have become the major source of non-beverage alcohol consumption. Further regulation of non-beverage alcohol may be required in Russia.

Alcohol-free hand sanitizer and other quaternary ammonium disinfectants quickly and effectively inactivate SARS-CoV-2.

BACKGROUND: SARS-CoV-2 is the virus responsible for the current global pandemic, COVID-19. Because this virus is novel, little is known about its sensitivity to disinfection. METHODS: We performed suspension tests against SARS-CoV-2 using three commercially available quaternary ammonium compound (Quat) disinfectants and one laboratory-made 0.2% benzalkonium chloride solution. FINDINGS: Three of the four formulations completely inactivated the virus within 15 s of contact, even in the presence of a soil load or when diluted in hard water. CONCLUSION: Quats rapidly inactivate SARS-CoV-2, making them potentially useful for controlling SARS-CoV-2 spread in hospitals and the community.

Virucidal activity of three ethanol-based hand rubs against murine norovirus in a hand hygiene clinical simulation study.

Aim: We evaluated the efficacy of three ethanol-based hand rubs against murine norovirus in a proposed clinical simulation test (prEN 17430). Materials & methods: Virucidal activity was determined in 18 volunteers using three hand rubs: ethanol 72.4 and 89.5% v/v solutions, and 86% v/v gel. Subjects underwent testing with each product (3/6 ml for 15/30 s) and a reference solution (6 ml 70% v/v ethanol for 60 s). Results: Against murine norovirus, the reduction factors (RF; RF mean ± standard deviation log10 reduction of postsampling) for ethanol gel 86% v/v (RF 1.96 ± 0.64), ethanol 89.5% v/v (RF 2.49 ± 0.59) and ethanol 72.4% v/v (RF 2.61 ± 0.50), were all significantly superior to that of the reference solution. Conclusion: All three hand rubs passed the criteria set out in prEN 17430 and exhibited excellent virucidal efficacy.

Alcohol-based hand sanitisers as first line of defence against SARS-CoV-2: a review of biology, chemistry and formulations.

The pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a serious global public health issue. Since the start of the outbreak, the importance of hand-hygiene and respiratory protection to prevent the spread of the virus has been the prime focus for infection control. Health regulatory organisations have produced guidelines for the formulation of hand sanitisers to the manufacturing industries. This review summarises the studies on alcohol-based hand sanitisers and their disinfectant activity against SARS-CoV-2 and related viruses. The literature shows that the type and concentration of alcohol, formulation and nature of product, presence of excipients, applied volume, contact time and viral contamination load are critical factors that determine the effectiveness of hand sanitisers.