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.

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.

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.

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.

Both Handwashing and an Alcohol-Based Hand Sanitizer Intervention Reduce Soil and Microbial Contamination on Farmworker Hands during Harvest, but Produce Type Matters.

Hand hygiene interventions are critical for reducing farmworker hand contamination and preventing the spread of produce-associated illness. Hand hygiene effectiveness may be produce-commodity specific, which could influence implementation strategies. This study's goal was to determine if produce commodity influences the ability of handwashing with soap and water or two-step alcohol-based hand sanitizer (ABHS) interventions to reduce soil and bacteria on farmworker hands. Farmworkers (n = 326) harvested produce (cantaloupe, jalapeño, and tomato) for 30 to 90 minutes before engaging in handwashing, two-step ABHS (jalapeño and cantaloupe), or no hand hygiene. Hands were rinsed to measure amounts of soil (absorbance at 600 nm) and indicator bacteria (coliforms, Enterococcus sp., generic Escherichia coli, and Bacteroidales universal [AllBac] and human-specific [BFD] 16S rRNA gene markers). Without hand hygiene, bacterial concentrations (0.88 to 5.1 log10 CFU/hand) on hands significantly differed by the produce commodity harvested. Moderate significant correlations (ρ = -0.41 to 0.56) between soil load and bacterial concentrations were observed. There were significant produce-commodity-specific differences in the ability of handwashing and two-step ABHS interventions to reduce soil (P < 0.0001), coliforms (P = 0.002), and Enterococcus sp. (P = 0.003), but not the Bacteroidales markers AllBac (P = 0.4) or BFD (P = 0.3). Contamination on hands of farmworkers who harvested cantaloupe was more difficult to remove. Overall, we found that a two-step ABHS intervention was similar to handwashing with soap and water at reducing bacteria on farmworker hands. In summary, produce commodity type should be considered when developing hand hygiene interventions on farms.IMPORTANCE This study demonstrated that the type of produce commodity handled influences the ability of handwashing with soap and water or a two-step alcohol-based hand sanitizer (ABHS) intervention to reduce soil and bacterial hand contamination. Handwashing with soap and water, as recommended by the FDA's Produce Safety Rule, when tested in three agricultural environments, does not always reduce bacterial loads. Consistent with past results, we found that the two-step ABHS method performed similarly to handwashing with soap and water but also does not always reduce bacterial loads in these contexts. Given the ease of use of the two-step ABHS method, which may increase compliance, the two-step ABHS method should be further evaluated and possibly considered for implementation in the agricultural environment. Taken together, these results provide important information on hand hygiene effectiveness in three agricultural contexts.

Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.

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.

Is Alcohol in Hand Sanitizers Absorbed Through the Skin or Lungs? Implications for Disulfiram Treatment.

AIM: In view of the increase in the use of ethanol-containing hand sanitizers throughout the world due to the current COVID-19 pandemic, we wished to review the possible risks to patients treated with disulfiram, following a case report in which an apparent DER (disulfiram-ethanol reaction) was attributed to the cutaneous absorption of alcohol from hand sanitizers as well as by inhalation of vapour. METHOD: Simple experiments to assess the levels of absorption by each route separately. RESULTS: Our results strongly suggest that while amounts of alcohol sufficient to cause a DER may be inhaled when hand sanitizers are used in confined spaces, absorption can be avoided by dispersal of the fumes, and absorption from the skin alone does not occur in pharmacologically significant quantities. CONCLUSION: Warnings about absorption of alcohol through the skin from hand sanitizers and products such as perfumes, deodorants and after-shave (whose use is often warned against when disulfiram is prescribed) should be modified accordingly.

Thoughts on What Chemists Can Contribute to Fighting SARS-CoV-2 - A Short Note on Hand Sanitizers, Drug Candidates and Outreach.

The SARS-CoV-2 outbreak causing the respiratory disease COVID-19 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three-pronged approach is proposed.

Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid.

BACKGROUND: Hand disinfectants are important for the prevention of virus transmission in the health care system and environment. The development of broad antiviral spectrum hand disinfectants with activity against enveloped and non-enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses. METHODS: A new hand disinfectant was developed based upon 69.39 % w/w ethanol and 3.69 % w/w 2-propanol. Different amounts of citric acid and urea were added in order to create a virucidal claim against poliovirus (PV), adenovirus type 5 (AdV) and polyomavirus SV40 (SV40) as non-enveloped test viruses in the presence of fetal calf serum (FCS) as soil load. The exposure time was fixed to 60 s. RESULTS: With the addition of 2.0 % citric acid and 2.0 % urea an activity against the three test viruses was achieved demonstrating a four log10 reduction of viral titers. Furthermore, this formulation was able to inactivate PV, AdV, SV40 and murine norovirus (MNV) in quantitative suspension assays according to German and European Guidelines within 60 s creating a virucidal claim. For inactivation of vaccinia virus and bovine viral diarrhea virus 15 s exposure time were needed to demonstrate a 4 log10 reduction resulting in a claim against enveloped viruses. Additionally, it is the first hand disinfectant passing a carrier test with AdV and MNV. CONCLUSIONS: In conclusion, this new formulation with a low alcohol content, citric acid and urea is capable of inactivating all enveloped and non-enveloped viruses as indicated in current guidelines and thereby contributing as valuable addition to the hand disinfection portfolio.

Commercial Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) Testing is Not Vulnerable to Incidental Alcohol Exposure in Pregnant Women.

BACKGROUND: Ethyl Glucoronide (EtG) and Ethyl Sulfate (EtS) have shown promise as biomarkers for alcohol and may be sensitive enough for use with pregnant women in whom even low-level alcohol use is important. However, there have been reports of over-sensitivity of EtG and EtS to incidental exposure to sources such as alcohol-based hand sanitizer. Further, few studies have evaluated these biomarkers among pregnant women, in whom the dynamics of these metabolites may differ. OBJECTIVES: This study evaluated whether commercial EtG-EtS testing was vulnerable to high levels of environmental exposure to alcohol in pregnant women. METHODS: Two separate samples of five nurses-one pregnant and the other postpartum, all of whom reported high levels of alcohol-based hand sanitizer use-provided urine samples before and 4-8 hours after rinsing with alcohol-based mouthwash and using hand sanitizer. The five pregnant nurses provided urine samples before, during, and after an 8-hour nursing shift, during which they repeatedly cleansed with alcohol-based hand sanitizer (mean 33.8 uses). The five postpartum nurses used hand sanitizer repeatedly between baseline and follow-up urine samples. RESULTS: No urine samples were positive for EtG-EtS at baseline or follow-up, despite use of mouthwash and-in the pregnant sample-heavy use of hand sanitizer (mean of 33.8 uses) throughout the 8-hour shift. CONCLUSIONS/IMPORTANCE: Current, commercially available EtG-EtS testing does not appear vulnerable to even heavy exposure to incidental sources of alcohol among pregnant and postpartum women.

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.

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.

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.