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International Journal of
Environmental Research
and Public Health
Review
Methanol as an Unlisted Ingredient in Supposedly
Alcohol-Based Hand Rub Can Pose Serious
Health Risk
Alan P. L. Chan 1and Thomas Y. K. Chan 1,2,3,*
1
Division of Clinical Pharmacology and Drug and Poisons Information Bureau, Department of Medicine and
Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;
alanchanpl@hotmail.com
2Prince of Wales Hospital Poison Treatment Centre, Shatin, New Territories, Hong Kong, China
3Asia Pacific Network of Clinical Toxicology Centres, Drug and Poisons Information Bureau,
Hong Kong, China
*Correspondence: tykchan@cuhk.edu.hk; Tel.: +852-3505-3907
Received: 11 June 2018; Accepted: 5 July 2018; Published: 9 July 2018
Abstract:
Alcohol-based hand rub (hand sanitizer) is heavily used in the community and the
healthcare setting to maintain hand hygiene. Methanol must never be used in such a product
because oral, pulmonary and/or skin exposures can result in severe systemic toxicity and even
deaths. However, sporadic cases of acute poisoning indicate that alcohol-based hand rub with
undeclared methanol may be found in the market from time to time. The unexpected presence of
methanol poses a serious threat to public health. Unintentional ingestion by young children and
inadvertent consumption by older subjects as alcohol (ethanol) substitute can occur. Methanol is
more lethal and poisoning often requires antidotal therapy, in addition to supporting therapy and
critical care. However, specific therapy may be delayed because the exposure to methanol is initially
not suspected. When repeatedly used as a hand rub, skin absorption resulting in chronic toxicity
(e.g., visual disturbances) occurs, particularly if methanol induced desquamation and dermatitis
are present. Nationwide surveillance systems, regional/international toxicovigilance networks
and situational awareness among the healthcare professionals should facilitate the early detection,
management and prevention of such poisoning incidents of public health significance.
Keywords: methanol; poisoning; hand sanitizers; product substitution; risk assessment
1. Introduction
Hand hygiene products are heavily used in everyday life. In the healthcare setting, most of the
cross-infections occur by direct contact via the hands of health workers, and their strict adherence
to good hand hygiene is the most effective strategy to stop infections spreading [
1
]. By reducing
cross-transmission, the use of alcohol-based hand rub (hand sanitizer) helps decrease the risk of
healthcare associated infections, and hence selection pressure of antibiotics and the emergence of
antibiotic resistance [
2
]. In the community, the combination of hand hygiene and face mask is effective
in reducing influenza transmission [
3
]. In the educational setting, hand hygiene may decrease the risk
of respiratory tract infection among children [
4
]. There are national and WHO guidelines on hand
hygiene [
5
,
6
]. In general, hands should be washed with soap and water if they are visibly dirty. If hands
look clean, alcohol-based hand rub is an effective alternative and, in the healthcare setting, the preferred
method for routine hand antisepsis. Hand hygiene products contain an antiseptic to inactivate
microorganisms and/or temporarily suppress their growth on the skin [
6
]. Many preparations are
Int. J. Environ. Res. Public Health 2018,15, 1440; doi:10.3390/ijerph15071440 www.mdpi.com/journal/ijerph
Int. J. Environ. Res. Public Health 2018,15, 1440 2 of 6
available [
6
], but alcohol-based hand rub is always preferred because of its greater effectiveness and
better compliance rate, while causing less skin irritation and requiring less time for application [1,6].
Alcohol-based hand rub mostly contains ethanol, isopropyl alcohol, n-propyl alcohol, or their
combinations [
2
]. When misused, these preparations can become toxic to humans. For example,
after accidental or deliberate ingestion, isopropyl alcohol causes more severe central nervous system
and respiratory depression than ethanol [
7
]. Methanol is even more toxic after inhalation, oral or skin
exposures [
8
] and must never be used in hand hygiene products. However, sporadic cases of human
poisoning [
9
] indicate that such hazardous products may be found in the market from time to time.
The unexpected presence of methanol poses a serious threat to public health since hand rub is widely
used both in the healthcare and community settings.
In this review, the main objective is to describe the serious health risk caused by methanol as
an unlisted ingredient in supposedly alcohol-based hand rub. Reports of acute methanol poisoning
and chronic toxicity are reviewed.
2. Literature Search to Identify Relevant Reports of Methanol Toxicity
To identify published papers in indexed/non-indexed journals, news and other reports, a search
of Medicine/Embase (1989 to 29 June 2018), WanFang Data (1989 to June 2018), Google and Google
Scholar was performed, using methanol, hand sanitizers, hand hygiene products and alcohol-based
hand rub as the keywords. Additional cases, if any, were retrieved from the annual reports of poison
control centers [
10
] and international [
11
] or national [
12
–
15
] studies of methanol poisoning from the
USA [10,12], Europe [11,13,14], Africa [11,15] and Asia [11].
Only reports of acute poisoning (Section 3), following ingestion, inhalation and skin exposure to
undeclared methanol in alcohol-based hand rub, were reviewed. Acute methanol poisoning caused by
methylated spirits (denatured alcohol) [16] and adulterated alcohol [17] was not included.
Reports of chronic toxicity (Section 4) were also reviewed to characterize the risk and severity of
impaired vision and other organ damages, if methanol containing products were inadvertently used
as hand rub. Reports of toxic effects when the preparations were used for medicinal purposes [
18
,
19
]
were excluded because the doses, exposure time and intensity of use were quite different.
3. Acute Poisoning Caused by Methanol as an Unlisted Ingredient in Alcohol-Based Hand Rub
The search of biomedical literature databases, Google and Google Scholar altogether identified 3
relevant reports of acute methanol poisoning [
9
,
10
,
20
]. Details about the poisoning incidents and their
year of occurrence are summarized in Table 1.
Table 1. Reports of acute poisoning caused by methanol in alcohol-based hand rub.
Country (Year) Details
Canada (2013) [9]2 deaths after ingesting a hand sanitizer containing methanol (an undeclared
ingredient), but ethyl alcohol was the active ingredient actually listed
USA (2014) [10] M/42 died after ingesting a hand sanitizer containing methanol and ethanol
Hong Kong (2016) [20]M/29 required hemodialysis and IV ethanol infusion after ingesting a hand sanitizer
containing methanol (undeclared) 22%, isopropyl alcohol 36% and ethanol 3.5%
In Canada [
9
], two Ontario residents had died after ingesting a hand sanitizer. Both bottles were
found to contain methanol, an undeclared ingredient, rather than ethyl alcohol, the active ingredient
listed on the label. Health Canada issued a warning to consumers and worked with its manufacturer
to implement a recall of these products.
In USA [
10
], a 42-year-old man died after ingesting a hand sanitizer. According to the Annual
Report of the American Association of Poison Control Centers, the product contained methanol and
ethanol. Methanol was detected in serum (0.31 mmol/L), but the blood sampling time was not stated.
No further information was provided.
Int. J. Environ. Res. Public Health 2018,15, 1440 3 of 6
In Hong Kong [
20
], a 29-year-old man required intensive care unit care for severe methanol
and isopropyl alcohol poisoning after drinking 500 mL of an alcohol-based hand rub. He presented
with deep coma (GCS 3/15) and metabolic acidosis (arterial pH 7.28) with an increased osmolar gap
(131.5 mOsm/kg). His serum methanol and isopropyl alcohol levels at 4 h post ingestion were 72.0 and
55.9 mmol/L, respectively. Hemodialysis, folinic acid and intravenous ethanol infusion were started.
He regained consciousness and was extubated 2 days later. His vision was intact. He was transferred
to a psychiatric unit after 9 days of medical treatment. The hand rub was listed to contain isopropyl
alcohol, glycerine and triethanolamine, but was found to contain isopropyl alcohol 36%, methanol
22%, and ethanol 3.5%.
4. Chronic Toxicity Caused by Methanol Containing Hand Rub
The search of literature databases, Google and Google Scholar had not identified any reports of
subacute or chronic toxicity caused by methanol as an unlisted ingredient in alcohol-based hand rub.
However, the case series [
21
] summarized here clearly indicates transdermal absorption of methanol
and a very high risk of systemic toxicity among users of alcohol rub containing methanol.
In China [
21
], a hospital mistakenly purchased industrial (denatured) alcohol for surgeons to
disinfect the hands and forearms before surgery. It was used 3–5 sessions per week. There were soon
skin dryness and desquamation of the areas exposed to the hand rub. Six months later, 6 surgeons
in the same unit developed erythema and rash in the affected areas, with intense itching, especially
the fingers and finger web. Four surgeons stopped using this product and recovered spontaneously.
The fifth surgeon had further exposures until the skin condition worsened. About 1 month after
stopping using the product, he developed mild visual impairment which gradually improved after
treatment. The sixth surgeon continued to use the hand rub until blurred vision occurred. Methanol
poisoning was suspected. Chemical analysis of the product revealed that its methanol concentration
was 3000–5000 times the legal limit. Neither the actual methanol concentration nor its legal limit was
stated. There was initial improvement in vision after cessation of use. However, a month later, visual
acuity deteriorated to 0.3 and 0.7. Neurological symptoms included lower limb weakness, paroxysmal
electric shock sensation in 4 limbs and peripheral neuropathy. Subsequently, further assessments
revealed a diagnosis of retrobulbar neuritis and retinitis. Three months later, the visual impairment
markedly improved and neurological symptoms gradually improved. Eighteen months later, there was
still numbness of left hand fingers.
5. Discussion
Alcohol-based hand rub should not contain methanol [
6
], for obvious reasons. Methanol is
very toxic, following oral, pulmonary and/or skin exposures [
8
]. Severe systemic toxicity and even
deaths can occur after occupational or non-occupational exposures [
12
–
15
,
17
,
22
,
23
]. In acute poisoning,
the main toxicity of methanol does not manifest until its metabolite formic acid has accumulated
to toxic levels, typically 12–24 h after exposure [
24
]. Apart from severe metabolic acidosis, nausea,
vomiting, headache, semi-coma, and ocular toxicity may be seen [
8
]. Unless timely antidotal therapy
is given [
25
], substantial exposure can result in coma, seizures, death, permanent blindness, and
permanent damage to the central nervous system [
8
,
23
]. Subacute poisoning has also been reported
in workers with inhalation and skin exposures [
25
]. There are little data on chronic toxicity due to
continuous or repeated exposures over a period of time. Chronic inhalation exposure to methanol can
result in eye irritation and headache in workers [
8
]. Rarely, repeated exposures to methanol have been
reported to cause visual disturbances and clinical symptoms of multiple sclerosis [21,26].
Albeit very rarely reported, alcohol-based hand rub with methanol as an undeclared ingredient
could be found in the market from time to time [
9
,
10
,
20
]. The reasons for its use as the substitute
for isopropyl alcohol or ethyl alcohol are not known. The present review highlights the serious
threat to public health if such preparations are available to the public (Section 3) and healthcare
professionals (Section 4).
Int. J. Environ. Res. Public Health 2018,15, 1440 4 of 6
Health authorities and the manufacturers repeatedly remind the consumers that alcohol-based
hand rub is for external use only. As clearly stated on its product labelling, hand rub should never be
swallowed. However, unintentional ingestion by young children is common [
27
]. In older children,
adolescents and adults, hand rub is increasingly used as alcohol (ethanol) substitute rather than for
self-harm. [
27
–
29
]. In fact, consumption of surrogate alcohols (non-beverage alcohols and illegally
produced alcohols) is a major public health problem in many parts of the world [
30
,
31
]. When taken
by mouth, methanol, if ever used as a substitute for isopropyl alcohol or ethanol, in the hand rub
will cause a much greater mortality and morbidity. Methanol has a lower lethal dose (~1.2 versus
1–4 and 3.6–6 mL/kg) and poisoning often requires antidotal therapy (fomepizole or ethanol) [
24
,
32
],
in addition to supporting therapy and critical care [
13
]. Methanol also causes severe metabolic acidosis
and more target organ toxicity (e.g., ocular toxicity) [
8
]. Specific therapy [
24
,
32
] may be inadvertently
delayed because the exposure to methanol is initially not suspected.
Obviously, methanol is highly toxic and, if ingested, can be fatal [
8
]. When used on the skin,
it is well known that methanol can cause irritation and inflammation [
8
]. Dermal exposure resulting in
acute poisoning and systemic toxicity remains the main concern [
22
,
23
,
25
]. Exposure assessments in
healthy volunteers indicate that the extent and rate of skin absorption of methanol depends on many
factors, including its form (vapors, liquid or solution), contact time, dose, concentration, and size of
exposure area [
33
–
35
]. Skin occlusion will enhance the percutaneous absorption of methanol [
36
],
by preventing its evaporation and increasing the stratum corneum hydration and skin temperature.
In diseased skin, such as methanol induced desquamation and dermatitis [
8
,
21
], both the structure and
barrier function become compromised, thus allowing methanol and other chemicals to be absorbed
even more readily [
37
]. The case series described in Section 4[
21
] clearly documents skin absorption
and a very high risk of systemic toxicity among users of alcohol rub containing methanol.
The poisoning incidents due to undeclared methanol in alcohol-based hand rub are all of major
public health significance because of its high intrinsic toxicity, widespread use and easy availability.
Nationwide surveillance systems based on, for example, spontaneous reporting and early detection of
warning signals by poison control centers [
38
], will play an important role in the risk management
strategies. Toxic threats occurring sporadically in different countries necessitate the establishment
of a regional or international toxicovigilance network to detect early warning signals and initiate
immediate preventive measures. The present review should enhance the situational awareness among
health professionals, who provide timely treatment and sound the alarm.
6. Conclusions
Methanol is highly toxic, and severe systemic toxicity and even deaths can occur after oral,
pulmonary and/or skin exposures. Therefore, methanol must never be used in alcohol-based hand rub,
which mostly contains ethanol, isopropyl alcohol, n-propyl alcohol, or their combinations. However,
sporadic reports of acute poisoning indicate that hand rub with undeclared methanol may be found
in the market from time to time. The unexpected presence of methanol poses a serious threat to
public health since hand rub is heavily used and widely available. Unintentional ingestion by young
children and inadvertent consumption by older subjects as alcohol (ethanol) substitute can occur.
Given the frequent consumption of surrogate alcohols in many parts of the world, methanol, if ever
used as a substitute for isopropyl alcohol or ethanol, in the hand rub will cause an even bigger public
health problem. Methanol is more lethal and poisoning often requires antidotal therapy, in addition to
supporting therapy and critical care. However, specific therapy may be delayed, since the exposure
to methanol is initially not suspected. If repeatedly used as a hand rub, skin absorption resulting
in chronic toxicity (e.g., visual disturbances) occurs, particularly if methanol induced desquamation
and dermatitis are present. Nationwide surveillance systems, regional/international toxicovigilance
networks and situational awareness among the healthcare professionals will facilitate the early
detection, management and prevention of poisoning incidents of public health significance.
Int. J. Environ. Res. Public Health 2018,15, 1440 5 of 6
Author Contributions:
A.P.L.C. was responsible for the comprehensive search of biomedical literature databases,
Google and Google Scholar, inclusion and exclusion criteria, initial evaluation of available reports, data synthesis
and original drafts preparation. T.Y.K.C. initiated and coordinated the project and contributed to the data
evaluation and writing of the final report.
Funding:
This work is supported by research funding from the Drug and Poisons Information Bureau, Faculty of
Medicine, the Chinese University of Hong Kong.
Conflicts of Interest: The authors declare no conflict of interest.
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