Not so soft soap

As the novel coronavirus grips the world in fear, demand for soaps, sanitisers and disinfectants has soared. But could over-washing lead to other problems of skin sensitisation and increased microbial resistance? XiaoZhi Lim reports

Although we still have much to learn about the transmissibility and lethality of the novel SARS-CoV-2 coronavirus, what scientists do know of the virus is enough to kill it. ‘It’s useful to stop and think about its structure,’ says James Malley, a civil engineer at the University of New Hampshire. The SARS-CoV-2 is an enveloped virus, with a lipid membrane enclosing an RNA nucleus – ‘a little globule of fat,’ explains John Newsam of skin formulation development firm Tioga Research based in San Diego, US.

The World Health Organization (WHO), governments and public health officials around the world have thus recommended frequent handwashing with soap for at least 20s as a first line of defence against the coronavirus. ‘Soap and water can do a great deal of damage to the encapsulated surface of this virus,’ Malley says. Amphiphilic molecules found in soap can not only dislodge the virus from skin but also tear its lipid envelope apart, killing the virus.

When soap and running water are not available, hand sanitiser is a good second option, Newsam says. Most sanitisers use alcohol as the active ingredient. While some evidence suggests alcohol acts by denaturing the surface proteins of the virus, it is also possible the lipid membrane dissolves in the alcohol because of the high alcohol content typically required, Newsam explains.

Hand sanitisers that are alcohol-free often use cationic quaternary ammonium surfactants like benzalkonium chloride, also known as quats, which are also commonly used in surface disinfectants. These cationic compounds bind well to the surfaces of negatively charged virus membranes and dissolve them (J. Surfact. Deterg., doi: 10.1002/jsde.12293).

Supply chain shifts

Between December 2019 and February 2020, demand for hand sanitisers surged 1400%, according to Adobe Analytics, while market research firm IBISWorld revised its forecast for 2020’s revenue growth in disinfectant manufacturing up from 2.3% to 6.7%.
Chemical companies have moved quickly to step up production. Governments relaxed regulations to allow more manufacturers to help produce key chemicals needed in high volumes, like ethanol.

The European Chemicals Agency, for example, has fast-tracked the evaluation of applications for chemical companies to become approved suppliers of disinfectant substances. Dow Chemical, which does not normally produce hand sanitiser, received permission to do so at its facilities in Germany in late March 2020. The company has also expanded sanitiser production at its facilities in the US, Belgium and Brazil.

WHO published two formulations for hand sanitiser to guide producers ranging from chemical companies to university chemistry laboratories. The formulations comprise either 80% ethanol or 75% isopropyl alcohol, and small quantities of glycerol and hydrogen peroxide. Following these recipes, chemistry laboratories worldwide, from the University of Warwick in the UK to the Indian Institute of Technology to Louisiana State University in the US, have begun supplying local healthcare facilities and communities with hand sanitiser.

Manufacturers of ethanol from corn or sugar crops normally for transportation fuels have also joined sanitiser production. In India, for example, the government has permitted sugar mills to supply ethanol, and distilleries to convert surplus rice to ethanol for hand sanitiser. Distilleries and sugar mills in the state of Uttar Pradesh reportedly have a combined manufacturing capacity of 200,000l/day.
In the US, gasoline contains 10% ethanol, usually from corn crops, but demand for transportation fuels has dried up. Of some 200 ethanol plants in the US, only around 60 are operating at normal rates, says Geoff Cooper who leads the US Renewable Fuels Association. The association projected the US corn ethanol industry could lose $10m due to the pandemic.

The US Food and Drug Administration (FDA) relaxed regulations to allow corn ethanol producers and spirit distilleries to help provide ethanol for hand sanitiser production. Since then, at least two dozen producers of corn-based ethanol have done so, Cooper said. ‘I don’t think most producers are going to offset their losses by ramping up hand sanitiser production, but it certainly does give our industry a way to contribute.’

Sensitisation issues

While handwashing helps to protect against viruses, frequent washing with soap and water could damage our skin.

‘Soaps have a high pH and are quite alkaline,’ wrote Celestine Wong, a dermatologist at Monash Health for The Conversation (theconversation.com/my-skins-dry-with-all-this-hand-washing-what-can-i-do-134146). ‘Milder soaps or soap-free washes with pH closer to that of the skin’s – 5.4 to 5.9 – are less likely to be irritating,’ she noted.

Wong recommended using alcohol-based sanitiser instead of washing with soap, to keep hands dry. Water can act as a skin irritant by causing the outer layer of skin to swell and shrink repeatedly. A 2014 review identified links between occupational hand dermatitis and wet work – when workers have to immerse their hands in water for more than two hours/shift, or wash their hands over 20 times/shift (Saf. Health Work, doi: 10.1016/j.shaw.2014.08.001).

Another study recommended healthcare workers, who need to wash their hands very frequently, use alcohol-based sanitisers rather than wash their hands with soap and water to reduce skin dermatitis (Ind. Health, doi: 10.2486/indhealth.45.645).

"Given the indiscriminate production and use of these ingredients, I would be surprised if we do not see some major problems either to the environment or human health directly or indirectly"
Winston Morgan, reader in toxicology and clinical biochemistry, University of East London, UK

Repeated application of sanitisers, particularly with high alcohol concentrations, can also compromise the barrier function of our skin, Newsam says. ‘Ethanol is actually a known permeation enhancer of skin,’ he says, which is usually used to help deliver drugs through the skin by temporarily making it more penetrable. To repair the skin’s barrier function, Newsam recommends applying a moisturiser that can restore the lipids on its outer layer.

While soaps and sanitisers can remove virus particles from our hands, they do so transiently. ‘It doesn’t provide anything in the way of sustained benefit,’ Newsam says. Another potential issue with frequent handwashing or sanitising is the indiscriminate elimination of normal bacterial flora on our hands, he says.

An antibody-based hand lotion developed by San Diego firm Pagoda Genomics, which Newsam consults for, could address both issues, he says. Antibodies act specifically against their target pathogens and, when formulated into a lotion designed to stay on between hand washings, can provide selective and long-lasting protection. The firm has developed a lotion that acts against the norovirus and is now working on a formulation for the SARS-CoV-2 virus, Newsam says.

Environmental concerns

With the surge in use of soaps and sanitisers, some ingredients may become a cause for concern further down the road, particularly as they are washed down drains and discharged into wastewater treatment plants. ‘Our attempts to protect ourselves from Covid-19 may also be creating an environment where even more antimicrobial resistant microorganisms can emerge,’ wrote Winston Morgan, a toxicologist at the University of East London, UK, for the Conversation (theconversation.com/coronavirus-heavy-use-of-hand-sanitisers-could-boost-antimicrobial-resistance-136541).

Antimicrobial resistance is a big problem in hospitals and drug-resistant diseases kill at least 700,000 people every year, according to an April 2019 report from WHO. While the problem is typically associated with overuse and misuse of antibiotics, any chemical with antimicrobial activity could promote resistance acquisition if used at concentrations lower than those that kill cells but sufficiently high to change cellular processes, Morgan explained. This is now a major concern with consumers sanitising and disinfecting frequently to protect against Covid-19 but also perhaps with home-made sanitisers or failing to follow directions for proper use, leaving surviving cells, he says.

Even alcohol can encourage resistance development. A 2018 study found isolates of a multidrug-resistant bacterium Enterococcus faecium obtained after 2010 were ten times more tolerant to alcohol than earlier isolates from 1997 to 2009 (Sci. Transl. Med., doi: 10.1126/scitranslmed.aar6115). In a mouse model, the alcohol-tolerant bacterium withstood surface disinfection with 70% isopropanol.

Some antimicrobial chemicals are worrying because they are persistent in the environment and can transform into toxic compounds (Environ. Health Perspect., doi: 10.1289/EHP1788). Triclosan and triclocarban, for example, are common antimicrobial ingredients added to over 2000 consumer products including hand soaps and detergents. ‘It took us 14 years to produce data showing that these chemicals are not only ineffective but also contaminating the water cycle, dust, air and people,’ said Rolf Halden, an environmental health engineer at Arizona State University, US. Triclosan converts to dioxins when exposed to sunlight and when sewage sludge containing it is incinerated. Triclocarban also biodegrades into carcinogenic chloroanilines.

In September 2016, the US FDA banned the two ingredients, along with 17 others, in over-the-counter consumer products. But triclosan can still be found in cleaning products like disinfectants, Halden says. It also remains in personal care products in some countries, including China, Canada and the Association of Southeast Asian Nations, often with a maximum permitted concentration of 0.3%. And replacements for triclosan could be equally or more harmful. In one study, benzalkonium chloride was found to be more toxic to zebrafish embryos than triclosan (Environ. Pollut., doi: 10.1016/j.envpol.2017.12.108).

‘Given the indiscriminate production and use of these ingredients, I would be surprised if we do not see some major problems either to the environment or human health directly or indirectly,’ Morgan said.