Fatal Salicylate Poisoning after Topical Application

[cjm]

Full text and link below. Further down, some comments.

"TWO CASES OF FATAL SALICYLATE POISONING AFTER TOPICAL APPLICATION OF AN ANTIFUNGAL SOLUTION

C. PAUL LINDSEY, M.B., B.S. (District Medical Officer)
Bougainville, T.P.N.G.

Two cases of fatal salicylate poisoning are reported. Whilst aspirin has become an increasingly unfashionable poison amongst adults [edit: lol], and the clinical effects of salicylism are less commonly seen than in the past, fatal salicylate poisoning still occurs, as these unusual iatrogenic cases illustrate.

CLINICAL RECORD

On April 29, 1967, two brothers, K. and W., Sepik labourers working on a coastal plantation in Bougainville, were painted over 50% of their total body areas respectively with a proprietary "grilli" lotion. This was done twice that day. Grilli, or tinea imbricata, is an extremely common cutaneous fungous infection (caused by Trichophyton concentricum) within the Territory of Papua and New Guinea. The lotion with which they were painted was found by Dr. R. A. Cooke to be an alcoholic solution of salicylic acid (20.7%), iodine (3.2%) and potassium iodide (2.8%). Within six hours, both brothers became unwell, and were given the day off. Both were slightly mentally confused, W. more so than his brother.

That evening, W. vomited and became unconscious and febrile, and was noted to be breathing very rapidly. His brother, K., also developed rapid respiration, and became extremely restless, walking with incoordinate gait and talking and behaving wildly. Eventually he had to be restrained. The next morning he was found unconscious. Both were placed on a boat at 11 a.m., and arrived at Kieta Hospital at 4 p.m. W. was dead on arrival.

On examination, K. was deeply comatose, with a temperature of 42° C. The skin was blistered over both shoulders. His blood pressure was 90/40 mm. Hg, and his pulse rate was 160 per minute. His muscle tone was flaccid and no response to stimuli could be elicited. His respirations numbered 35 per minute, his breathing being shallow but regular. Examination of a blood film for malaria parasites showed none present. Cooling measures were immediately initiated, and vigorous resuscitation was commenced. Despite this, the patient's temperature remained elevated, his respirations became gasping and irregular, and he died at 4.45 p.m. on April 30.

A post-mortem examination performed on both patients revealed nothing abnormal that would account for their deaths, and the findings on microscopic examination were normal also. The solution with which the brothers were painted was analysed.

Since the clinical signs and symptoms were consistent with salicylate poisoning, and since the proprietary "grilli" lotion contained a concentration of salicylic acid twice that recommended by the Public Health Department in the Territory, the cause of the deaths was diagnosed as salicylate poisoning, which diagnosis was accepted by the coroner's court.

DISCUSSION

Salicylates are absorbed readily through the skin, and toxic effects will be seen when the blood level reaches 30 mg. per 100 ml. The salicylate acts directly on the respiratory centres, producing hyperpnoea and then respiratory alkalosis. Subsequent vomiting with loss of base, disturbed renal function and derangement of carbohydrate metabolism eventually lead to a decompensated acidosis.

Clinical signs of acute salicylic toxicity include hyperpnoea, vomiting, sweating, hyperpyrexia, dehydration, irritability, delirium, incoordination, restlessness, coma and respiratory failure. All these signs were seen here. Also, signs of acute salicylism are tinnitus, abdominal pain, cyanosis, ecchymoses and ureemla (Dreisbach, 1963).

The recommended formula of the treatment of tinea imbricata is as follows: salicylic acid, 10%; malachite green, 0,1%; and alcohol, 70%; to make 100 parts of sipoma paint (Public Health Department Handbook, 1962). "The Extra Pharmacopreia (Martindale)" (Council of the Pharmaceutical Society of Great Britain, 1958) suggests a strength of salicylic acid from 2% to 10%. Never more than one-fifth of the total body area should be painted at one time or within 24 hours; nor is it wise to prolong a course of treatment for more than, say, five days. Symptoms of acute salicylate poisoning have been reported ("Martindale", 1958) in children after prolonged application of salicylic acid ointment to large areas of the body surface. Evidently rapid absorption occurs when alcoholic solutions are applied.

The indiscriminate and untutored application of grilli lotions of uncertain ingredients effects very little good, since the patient usually returns to don his dirty clothes, and even after a supervised treatment in hospital, recurrence of the fungous infection is the rule. The dangers of treatment are commonly forgotten, until the public's attention is drawn to them by fatalities such as these.

SUMMARY

Two cases of death from salicylate poisoning due to topical application of 20.7% salicylic acid in alcohol are described."

~~

~~

This is what the two brothers were trying to treat:

Tinea Imbricata as a Clue to Occult Immunodeficiency (Jimenez et al., 2014)

Grilli lotion is similar to an old formulation called Whitfield's Ointment that was first developed in 1907. It can be used to treat grilli, or tinea imbricata.

“The Whitfield’s ointment (10 % benzoic acid and 10 % salicylic acid in vaseline and lanoline) is helpful to remove squamous and hyperkeratotic lesions.” Tinea Imbricata in an Italian Child and Review of the Literature (Veraldi et al., 2015)

Product link: Bunny's Jamaican Whitfield's Ointment 28g, Double Strength, Treatment for Fungus Infection of The Skin

Fungal infection can lead to organ failure:

"Fungi usually enter the human body through the respiratory tract and are then disseminated to the central nervous system (CNS) via the blood. However, fungi (including Exophiala dermatitidis and E. rostratum) can directly infect the CNS or bone marrow of even immunocompetent individuals in cases of surgery, trauma, intravenous drug use, or exposure to contaminated medical supplies. Fungi can also be spread from adjacent tissues (sinus structures, mastoids, or eyelids) to the CNS." Multiple organ dysfunction caused by severe fungal infection: report of one case and a literature review (Xiao et al., 2019)

Benzoic acid, as in Whitfield's Ointment, is a natural defense against fungal infection (and a growth/yield (read: health) promoter):

“Tomato early blight, caused by Alternaria solani, is a destructive foliar fungal disease. Herein, the potential defensive roles of benzoic acid (BA) and two of its hydroxylated derivatives, ρ-hydroxybenzoic acid (HBA), and protocatechuic acid (PCA) against A. solani were investigated. All tested compounds showed strong dose-dependent fungistatic activity against A. solani and significantly reduced the disease development. Benzoic acid, and its hydroxylated derivatives, enhanced vegetative growth and yield traits. Moreover, BA and its derivatives induce the activation of enzymatic (POX, PPO, CAT, SlAPXs, and SlSODs) and non-enzymatic (phenolics, flavonoids, and carotenoids) antioxidant defense machinery to maintain reactive oxygen species (ROS) homeostasis within infected leaves.” Benzoic Acid and Its Hydroxylated Derivatives Suppress Early Blight of Tomato (Alternaria solani) via the Induction of Salicylic Acid Biosynthesis and Enzymatic and Nonenzymatic Antioxidant Defense Machinery (Nehela et al., 2021).

“Whitfield ointment (WO) is an antiseptic ointment that was widely used in the past to treat topical fungal infections but seldom used currently because of the availability of new therapies. The reasons for the underutilization of the Whitfield ointment could be its tendency to irritate the skin (especially in flexures and face) and being less targeted to dermatophytes than the newer therapies. Its efficacy has been shown to be equal to other topical antifungal in several studies....It combines the fungistatic action of benzoic acid with the keratolytic action of salicylic acid. The original formula contains 6% benzoic acid and 3% salicylic acid and World Health Organization (WHO) suggested a modified Whitfield ointment (MWO) with 5% benzoic acid and 5% salicylic acid for tropical countries.... It is economical and can be manufactured locally.” Treatment of difficult-to-treat-dermatophytosis: results of a randomized, double-blind, placebo-controlled study (Fonseka et al, 2021)

~

~

My next post may or may not be about the often forgotten primary action of salicylic acid, keratolysis, or peeling, as well as the vast benefits of its metabolite, benzoic acid.

 

[tasfarelel]

I would say if they really died because of the tincture - then it must have been some kind of contamination. I would classify the study as another attempt to vilify aspirin.

 

[haidut]

Full text and link below. Further down, some comments.

"TWO CASES OF FATAL SALICYLATE POISONING AFTER TOPICAL APPLICATION OF AN ANTIFUNGAL SOLUTION

C. PAUL LINDSEY, M.B., B.S. (District Medical Officer)
Bougainville, T.P.N.G.

Two cases of fatal salicylate poisoning are reported. Whilst aspirin has become an increasingly unfashionable poison amongst adults [edit: lol], and the clinical effects of salicylism are less commonly seen than in the past, fatal salicylate poisoning still occurs, as these unusual iatrogenic cases illustrate.

CLINICAL RECORD

On April 29, 1967, two brothers, K. and W., Sepik labourers working on a coastal plantation in Bougainville, were painted over 50% of their total body areas respectively with a proprietary "grilli" lotion. This was done twice that day. Grilli, or tinea imbricata, is an extremely common cutaneous fungous infection (caused by Trichophyton concentricum) within the Territory of Papua and New Guinea. The lotion with which they were painted was found by Dr. R. A. Cooke to be an alcoholic solution of salicylic acid (20.7%), iodine (3.2%) and potassium iodide (2.8%). Within six hours, both brothers became unwell, and were given the day off. Both were slightly mentally confused, W. more so than his brother.

That evening, W. vomited and became unconscious and febrile, and was noted to be breathing very rapidly. His brother, K., also developed rapid respiration, and became extremely restless, walking with incoordinate gait and talking and behaving wildly. Eventually he had to be restrained. The next morning he was found unconscious. Both were placed on a boat at 11 a.m., and arrived at Kieta Hospital at 4 p.m. W. was dead on arrival.

On examination, K. was deeply comatose, with a temperature of 42° C. The skin was blistered over both shoulders. His blood pressure was 90/40 mm. Hg, and his pulse rate was 160 per minute. His muscle tone was flaccid and no response to stimuli could be elicited. His respirations numbered 35 per minute, his breathing being shallow but regular. Examination of a blood film for malaria parasites showed none present. Cooling measures were immediately initiated, and vigorous resuscitation was commenced. Despite this, the patient's temperature remained elevated, his respirations became gasping and irregular, and he died at 4.45 p.m. on April 30.

A post-mortem examination performed on both patients revealed nothing abnormal that would account for their deaths, and the findings on microscopic examination were normal also. The solution with which the brothers were painted was analysed.

Since the clinical signs and symptoms were consistent with salicylate poisoning, and since the proprietary "grilli" lotion contained a concentration of salicylic acid twice that recommended by the Public Health Department in the Territory, the cause of the deaths was diagnosed as salicylate poisoning, which diagnosis was accepted by the coroner's court.

DISCUSSION

Salicylates are absorbed readily through the skin, and toxic effects will be seen when the blood level reaches 30 mg. per 100 ml. The salicylate acts directly on the respiratory centres, producing hyperpnoea and then respiratory alkalosis. Subsequent vomiting with loss of base, disturbed renal function and derangement of carbohydrate metabolism eventually lead to a decompensated acidosis.

Clinical signs of acute salicylic toxicity include hyperpnoea, vomiting, sweating, hyperpyrexia, dehydration, irritability, delirium, incoordination, restlessness, coma and respiratory failure. All these signs were seen here. Also, signs of acute salicylism are tinnitus, abdominal pain, cyanosis, ecchymoses and ureemla (Dreisbach, 1963).

The recommended formula of the treatment of tinea imbricata is as follows: salicylic acid, 10%; malachite green, 0,1%; and alcohol, 70%; to make 100 parts of sipoma paint (Public Health Department Handbook, 1962). "The Extra Pharmacopreia (Martindale)" (Council of the Pharmaceutical Society of Great Britain, 1958) suggests a strength of salicylic acid from 2% to 10%. Never more than one-fifth of the total body area should be painted at one time or within 24 hours; nor is it wise to prolong a course of treatment for more than, say, five days. Symptoms of acute salicylate poisoning have been reported ("Martindale", 1958) in children after prolonged application of salicylic acid ointment to large areas of the body surface. Evidently rapid absorption occurs when alcoholic solutions are applied.

The indiscriminate and untutored application of grilli lotions of uncertain ingredients effects very little good, since the patient usually returns to don his dirty clothes, and even after a supervised treatment in hospital, recurrence of the fungous infection is the rule. The dangers of treatment are commonly forgotten, until the public's attention is drawn to them by fatalities such as these.

SUMMARY

Two cases of death from salicylate poisoning due to topical application of 20.7% salicylic acid in alcohol are described."

~~

~~

This is what the two brothers were trying to treat:

Tinea Imbricata as a Clue to Occult Immunodeficiency (Jimenez et al., 2014)

Grilli lotion is similar to an old formulation called Whitfield's Ointment that was first developed in 1907. It can be used to treat grilli, or tinea imbricata.

“The Whitfield’s ointment (10 % benzoic acid and 10 % salicylic acid in vaseline and lanoline) is helpful to remove squamous and hyperkeratotic lesions.” Tinea Imbricata in an Italian Child and Review of the Literature (Veraldi et al., 2015)

Product link: Bunny's Jamaican Whitfield's Ointment 28g, Double Strength, Treatment for Fungus Infection of The Skin

Fungal infection can lead to organ failure:

"Fungi usually enter the human body through the respiratory tract and are then disseminated to the central nervous system (CNS) via the blood. However, fungi (including Exophiala dermatitidis and E. rostratum) can directly infect the CNS or bone marrow of even immunocompetent individuals in cases of surgery, trauma, intravenous drug use, or exposure to contaminated medical supplies. Fungi can also be spread from adjacent tissues (sinus structures, mastoids, or eyelids) to the CNS." Multiple organ dysfunction caused by severe fungal infection: report of one case and a literature review (Xiao et al., 2019)

Benzoic acid, as in Whitfield's Ointment, is a natural defense against fungal infection (and a growth/yield (read: health) promoter):

“Tomato early blight, caused by Alternaria solani, is a destructive foliar fungal disease. Herein, the potential defensive roles of benzoic acid (BA) and two of its hydroxylated derivatives, ρ-hydroxybenzoic acid (HBA), and protocatechuic acid (PCA) against A. solani were investigated. All tested compounds showed strong dose-dependent fungistatic activity against A. solani and significantly reduced the disease development. Benzoic acid, and its hydroxylated derivatives, enhanced vegetative growth and yield traits. Moreover, BA and its derivatives induce the activation of enzymatic (POX, PPO, CAT, SlAPXs, and SlSODs) and non-enzymatic (phenolics, flavonoids, and carotenoids) antioxidant defense machinery to maintain reactive oxygen species (ROS) homeostasis within infected leaves.” Benzoic Acid and Its Hydroxylated Derivatives Suppress Early Blight of Tomato (Alternaria solani) via the Induction of Salicylic Acid Biosynthesis and Enzymatic and Nonenzymatic Antioxidant Defense Machinery (Nehela et al., 2021).

“Whitfield ointment (WO) is an antiseptic ointment that was widely used in the past to treat topical fungal infections but seldom used currently because of the availability of new therapies. The reasons for the underutilization of the Whitfield ointment could be its tendency to irritate the skin (especially in flexures and face) and being less targeted to dermatophytes than the newer therapies. Its efficacy has been shown to be equal to other topical antifungal in several studies....It combines the fungistatic action of benzoic acid with the keratolytic action of salicylic acid. The original formula contains 6% benzoic acid and 3% salicylic acid and World Health Organization (WHO) suggested a modified Whitfield ointment (MWO) with 5% benzoic acid and 5% salicylic acid for tropical countries.... It is economical and can be manufactured locally.” Treatment of difficult-to-treat-dermatophytosis: results of a randomized, double-blind, placebo-controlled study (Fonseka et al, 2021)

~

~

My next post may or may not be about the often forgotten primary action of salicylic acid, keratolysis, or peeling, as well as the vast benefits of its metabolite, benzoic acid.

The study says more than 50% of the body surface area was covered in a 20%+ salicylate solution. That would probably amount to putting 100g+ salicylate on their skin. So, it basically shows that some people are plainly idiotic. However, how is this applicable to people using aspirin or other salicylates orally, in doses of <1g in most cases?
Oh, btw, the salicylate solution was in alcohol and if anybody covers half their body surface area in, say, vodka or rubbing alcohol, that would also reliably kill most people on its own. So, it is not even clear here, which substance was the primary culprit. Yes, salicylates can kill in very high doses, but so can caffeine, ibuprofen, and especially acetaminophen and all those in doses much lower than the LD50 of salicylates. That's why it is those latter substances that are much more often used in suicide attempts than salicylate/aspirin.

 

[cjm]

how is this applicable to people using aspirin or other salicylates orally, in doses of <1g in most cases?

This is an extreme example demonstrating absorption from a transdermal. My question will be what the appropriate dose is for systemic absorption.

 

[Nokoni]

This is an extreme example demonstrating absorption from a transdermal. My question will be what the appropriate dose is for systemic absorption.

In a much more recent event, a young female athlete died from using too much BenGay or equivalent: Muscle-rub blamed for athlete's death

I have significant experience using methyl salicylate topically, and in significant doses, for joint issues. I bought a bottle of pure methyl salicylate from Amazon. To avoid adverse effects I titrated up from a little bit to a little more and on to quite a bit, on knees, etc. In that fashion I eventually and regularly got into mitochondrial uncoupling but never had any adverse effects. Some months ago I stopped taking it because it is actually quite a hassle, and I wanted to try DeFibron for anti-inflammatory effect. It seemed to work well, but topical DeFibron eventually gives rise to irritating little bumps on the skin when taken regularly in significant doses, so I stopped that, though I still take it orally. I was thinking I might restart the MS where I could still use some spot anti-inflammatory effect. Anyhow, if you don't bathe in it then it's pretty unlikely that you're going to hurt yourself, especially if you use the titrate up approach. But I have come to believe that the acetylated form (aspirin) has additional benefits that the MS doesn't. So if you want systemic effects, and if your gut can handle it, aspirin may be better. Taking a pill or two is certainly easier.

 

[cjm]

In that fashion I eventually and regularly got into mitochondrial uncoupling but never had any adverse effects.

Very cool you noticed that.

Some months ago I stopped taking it because it is actually quite a hassle

So if you want systemic effects, and if your gut can handle it, aspirin may be better. Taking a pill or two is certainly easier.

I fully agree. One challenge with topicals is the skin can be variably permeable depending on the medium of the transdermal and more significantly the pre-existing condition of the skin, i.e., if it is healthy or if there is any dermatitis present:

“Comparing the SA penetration in barrier-perturbed skin with the penetration in unmodified skin in the same subject, the mean SA penetration increase was 2·2-fold in acetone-treated skin (P ¼ 0·012), 46-fold in mild dermatitis and 146- and 157-fold in severe dermatitis and tape stripped skin, respectively (P < 0·001).”
Effect of barrier perturbation on cutaneous salicylic acid penetration in human skin: in vivo pharmacokinetics using microdialysis and non-invasive quantification of barrier function. (Benfeldt et al., 1999)

Also thank you for sharing about the more recent case. It escaped my attention in the 1967 case report that the alcohol solution itself was a confounder for cause of the eventual deaths, but water should be the primary ingredient in muscle rub type creams, though rubbing alcohol is usually second or third, just not 70+% as with the homemade grilli "lotion."

Here's an article about the 2007 case without a paywall:

Better labeling urged after teen's sports cream overdose

The 17-year-old died from an accidental overdose of methyl salicylate, the...

www.seattlepi.com

"one teaspoon of orally ingested methyl salicylate is equal to a dose of 21 to 22 aspirin tablets."

Seems like a low dose to be fatal if applied topically. That's about how many I added to a bath, though the absorption would be much lower.

 

[cjm]

I have come to believe that the acetylated form (aspirin) has additional benefits that the MS doesn't.

Yes, vast, unexplored benefits:

"Aspirin acetylates human serum albumin and fibrinogen in vitro and in vivo (Hawkins et al, 1968; Bjornsson et al, 1989). It can also acetylate several other proteins and biomolecules, such as haemoglobin, DNA, RNA, histones, transglutaminase as well as other plasma constituents including hormones and enzymes (Pinckard et al, 1968; Lai et al, 2010). In a remarkable study, it was found that in vivo administration of radiolabelled 3H or 14C aspirin to rats, led to the binding of the acetyl group of aspirin to several proteins, glycoproteins and lipids of the stomach, kidney, liver and bone marrow (Rainsford et al, 1983), demonstrating that the acetyl group is able to reach distant organs." Molecular targets of aspirin and cancer prevention (Alfonso et al., 2014)

 

[cjm]

I have significant experience using methyl salicylate topically, and in significant doses, for joint issues.

Dd you notice benefits from oral for these issues at any point?

At risk of stating the obvious, some issues, like pain or joint immobility, seem to be resolved only through local contact at the site:

"This trial has demonstrated that topical aspirin in moisturizer is clearly superior to oral aspirin in relieving the pain of acute herpetic neuralgia.” Concerning the management of pain associated with herpes zoster and of postherpetic neuralgia (King & Robert, 1988)

 

[Nokoni]

"one teaspoon of orally ingested methyl salicylate is equal to a dose of 21 to 22 aspirin tablets."

Seems like a low dose to be fatal if applied topically. That's about how many I added to a bath, though the absorption would be much lower.

If that is true (a little math would tell us, but I'm too lazy) then maybe only a smallish fraction is getting absorbed. I used about 1/2 of a liter of the stuff over a period of some months. Was I using a teaspoon per day? Could have been, but again the math problem, plus the input parameters are also pretty vague. And I was applying it at full strength directly on the skin. And it's definitely effective.

Dd you notice benefits from oral for these issues at any point?

Yes, but only in the form of aspirin, which is very helpful for joint inflammation. I never took the MC orally. But oral is less effective than topical MC right where you need it.

 

[cjm]

I used about 1/2 of a liter of the stuff over a period of some months. Was I using a teaspoon per day?

I'm more of a philosopher so math is not my strong suit (and I'm lazy too!) but if half a liter is approx. 2 cups and there are 48 teaspoons in a cup, you applied around 100 teaspoons. A teaspoon per session every other day would last you roughly 6 months. The young athlete had to have been using much, much more. We can start to make an educated guess about her usage with a revelation from the toxicology report:

""She told me her legs felt like cement," her mother said. "She was working so hard to turn her season around."

Even with repeated use, however, it is unclear how the extremely high levels of the substance remained in her body. Dr. Kristen Roman of the ME's office told Mrs. Newman the toxicology report revealed more six times the safe amount of methyl salicylate in Arielle's blood.

Her mother said she took Arielle to several doctors after she complained of a fatigue and shortness of breath in February and March [she died in April]. An asthma specialist prescribed an inhaler, and a dermatologist prescribed for her some creme for a skin condition.

Neither doctor could pinpoint any other medical problems, her mother said. And none of the other medication Arielle was taking contributed to her death, according to the medical examiner.

The night before her death, Arielle returned from a party and spoke with her mother for hours before going to bed. After she was found the next morning, her parents discovered vomit on two pairs of pants she had apparently worn the night before."

EXCLUSIVE: Medical Examiner's report: NDA track star died from rare toxic dose of sports cream

A 17-year-old Notre Dame Academy track star died in April from rare toxic dose of sports cream, the city Medical Examiner said today. Toxicology tests revealed Arielle Newman's blood contained lethal amounts of methyl salicylate, the active ingredient in...

www.silive.com

The simple treatment for salicylate poisoning, for our edification: "The dextrose will treat the central nervous system (CNS) hypoglycemia. The sodium bicarb will help correct the metabolic acidosis. Potassium may be supplemented if hypokalemia is present." Salicylates Toxicity - StatPearls - NCBI Bookshelf (Runde & Nappe, 2022)

 

[Nokoni]

I'm more of a philosopher so math is not my strong suit (and I'm lazy too!) but if half a liter is approx. 2 cups and there are 48 teaspoons in a cup, you applied around 100 teaspoons. A teaspoon per session every other day would last you roughly 6 months.

Good job! Since I was using it daily, and 6 months is a good guess for duration of treatment, it was just half a teaspoon daily. I honestly didn't know. I would decant it from the liter bottle into a little glass jar and use the jar to dip my fingers in and then apply. That way I didn't contaminate my big bottle. So if one dip was the measure, I could titrate up step by step safely without even knowing how much I was using.

the toxicology report revealed more six times the safe amount of methyl salicylate in Arielle's blood.

Safe amount. I wonder about that. It seems like maybe she had more going on than just methyl salicylate and maybe they couldn't find anything else. I assisted on autopsies in the pathology lab at the hospital 50 years ago. Worked with 2 pathologists. One was good. The other never found anything. Everything was "coronary thrombosis". You can always find a blood clot in a cadaver :)

The simple treatment for salicylate poisoning, for our edification: "The dextrose will treat the central nervous system (CNS) hypoglycemia. The sodium bicarb will help correct the metabolic acidosis. Potassium may be supplemented if hypokalemia is present." Salicylates Toxicity - StatPearls - NCBI Bookshelf (Runde & Nappe, 2022)

Very good info. Thanks.

 

[cjm]

Safe amount. I wonder about that. It seems like maybe she had more going on than just methyl salicylate and maybe they couldn't find anything else. I assisted on autopsies in the pathology lab at the hospital 50 years ago. Worked with 2 pathologists. One was good. The other never found anything. Everything was "coronary thrombosis". You can always find a blood clot in a cadaver :)

That's a pretty cool experience under your belt.

I wonder, too, so let's check it out:

"salicylate level – rough benchmarks​

• 15-30 mg/dL (1-2.2 mM): Therapeutic.
• >40-50 mg/dL (>2.9-3.6 mM): Intoxication in most patients.
• >80-100 mg/dL (>5.7-7.2): Scary high, dialysis* may be indicated."

Salicylate intoxication

CONTENTS Rapid Reference 🚀 Diagnosis Epidemiology Signs & symptoms General laboratory abnormalities Salicylate level Treatment Airway management & decontamination Delirium & dysglycemia Alkalinization Volume resuscitation Hemodialysis Lab monitoring When to stop Podcast Questions & discussion...

emcrit.org

Upper level of therapeutic is 30 mg. So, 180 mg/dl is 6 times the highest "safe" level. Dang.

*A 3 year old ingested half a teaspoon of oil of wintergreen, blood levels persisted for 2.5 hours @ 70 mg/dl before they decided to do a blood transfusion.

Oil of Wintergreen (Methyl Salicylate) Poisoning Treated by Exchange Transfusion

www.ncbi.nlm.nih.gov

(Miller & Bowman, 1961)

 

[Nokoni]

That's a pretty cool experience under your belt.

I wonder, too, so let's check it out:

"salicylate level – rough benchmarks​

• 15-30 mg/dL (1-2.2 mM): Therapeutic.
• >40-50 mg/dL (>2.9-3.6 mM): Intoxication in most patients.
• >80-100 mg/dL (>5.7-7.2): Scary high, dialysis* may be indicated."

Salicylate intoxication

CONTENTS Rapid Reference 🚀 Diagnosis Epidemiology Signs & symptoms General laboratory abnormalities Salicylate level Treatment Airway management & decontamination Delirium & dysglycemia Alkalinization Volume resuscitation Hemodialysis Lab monitoring When to stop Podcast Questions & discussion...

emcrit.org

Upper level of therapeutic is 30 mg. So, 180 mg/dl is 6 times the highest "safe" level. Dang.

*A 3 year old ingested half a teaspoon of oil of wintergreen, blood levels persisted for 2.5 hours @ 70 mg/dl before they decided to do a blood transfusion.

Oil of Wintergreen (Methyl Salicylate) Poisoning Treated by Exchange Transfusion

www.ncbi.nlm.nih.gov

(Miller & Bowman, 1961)

Man, you are full of useful information. So first off, I'm going to treat MS with a little more respect than maybe I did previously. But secondly, is there a large population of people like you in Baltimore? I haven't been there in 30 years since I went to see an Orioles game (at which Ripken homered). Would love to go to the aquarium, and I am a fan of Mencken, but I have the distinct impression that it has changed considerably since his day. Hope you are well :)

 

[cjm]

Man, you are full of useful information. So first off, I'm going to treat MS with a little more respect than maybe I did previously. But secondly, is there a large population of people like you in Baltimore? I haven't been there in 30 years since I went to see an Orioles game (at which Ripken homered). Would love to go to the aquarium, and I am a fan of Mencken, but I have the distinct impression that it has changed considerably since his day. Hope you are well :)

I moved to Carroll County (Westminster-ish, 45 minutes from downtown Baltimore) last November after I parted ways with the brawling woman with whom I shared a rather narrow house.

I'm not going back any time soon, besides for work as an electrician (I started changing careers when I was leaving), but Baltimore is bi-polar now. I don't know what it was like when my dad grew up in the northeast in the 50's and 60's, but there is a youth culture raging while the infrastructure continues to be neglected and the homeless population rises. A lot of energy (and sexual deviancy) around the theater kids and their performing rock opera group. A lot of money and new development around the water, yet Harborplace, pride of the 90's revival, is a failure. Murder rate high, stat lords doing their usual end of year fudging to get the numbers down. Aquarium added a rainforest module but the last time I went 15 years ago, I said I don't need to come back for 20. Camden Yards still the gem of the city and MLB, the Orioles are relevant and fun to watch again. But the lightrail that runs north-south from the stadium up to the county is notorious for theft from commuters' parked cars.

In short, there is some charm to be found but the future is not bright.

Coming back to our victim, she wasn't in bad shape the night before if she was talking to her mother for hours before bed. She must have applied a lethal coat before falling asleep. Presumably she didn't need to saturate to 180mg/dl (our rough estimate) from nothing but who knows how high her blood levels already were. Every ounce of 30% MS cream has 8.5 grams of MS. Let's say she emptied a 4 oz tube onto her skin. That's 34 grams of MS. Let's get us in the ballpark of an actual scenario, assume a quarter is absorbed, giving 8.5 grams again, and then maybe go look for a microdialysis study later to validate my assumption before sealing this death report.

 

[Nokoni]

I moved to Carroll County (Westminster-ish, 45 minutes from downtown Baltimore) last November after I parted ways with the brawling woman with whom I shared a rather narrow house.

I'm not going back any time soon, besides for work as an electrician (I started changing careers when I was leaving), but Baltimore is bi-polar now. I don't know what it was like when my dad grew up in the northeast in the 50's and 60's, but there is a youth culture raging while the infrastructure continues to be neglected and the homeless population rises. A lot of energy (and sexual deviancy) around the theater kids and their performing rock opera group. A lot of money and new development around the water, yet Harborplace, pride of the 90's revival, is a failure. Murder rate high, stat lords doing their usual end of year fudging to get the numbers down. Aquarium added a rainforest module but the last time I went 15 years ago, I said I don't need to come back for 20. Camden Yards still the gem of the city and MLB, the Orioles are relevant and fun to watch again. But the lightrail that runs north-south from the stadium up to the county is notorious for theft from commuters' parked cars.

In short, there is some charm to be found but the future is not bright.

Coming back to our victim, she wasn't in bad shape the night before if she was talking to her mother for hours before bed. She must have applied a lethal coat before falling asleep. Presumably she didn't need to saturate to 180mg/dl (our rough estimate) from nothing but who knows how high her blood levels already were. Every ounce of 30% MS cream has 8.5 grams of MS. Let's say she emptied a 4 oz tube onto her skin. That's 34 grams of MS. Let's get us in the ballpark of an actual scenario, assume a quarter is absorbed, giving 8.5 grams again, and then maybe go look for a microdialysis study later to validate my assumption before sealing this death report.

Lol, I do cherish my corner of the housetop. It's certainly sad about Baltimore, but all of our cities have now become virtual no-go zones. I live in Northern Virginia and once loved riding in on the Metro to the beautiful parks and museums of DC, but now I'm persona non grata. Camden Yards is beautiful and I've been pleased to see that the Orioles are doing well again. I don't follow MLB as closely anymore, but I sure didn't see that coming. Glad to hear you're on a good, new trajectory, with a good new trade.

I wonder if it's possible that the cream penetrates better than the pure MS? Maybe it has penetration enhancers? Maybe it just stays on the skin longer, whereas the pure MS evaporates somewhat? I put a lot of that stuff on me and never felt in any danger. Maybe I was just lucky.

 

[cjm]

Lol, I do cherish my corner of the housetop. It's certainly sad about Baltimore, but all of our cities have now become virtual no-go zones. I live in Northern Virginia and once loved riding in on the Metro to the beautiful parks and museums of DC, but now I'm persona non grata. Camden Yards is beautiful and I've been pleased to see that the Orioles are doing well again. I don't follow MLB as closely anymore, but I sure didn't see that coming. Glad to hear you're on a good, new trajectory, with a good new trade.

I wonder if it's possible that the cream penetrates better than the pure MS? Maybe it has penetration enhancers? Maybe it just stays on the skin longer, whereas the pure MS evaporates somewhat? I put a lot of that stuff on me and never felt in any danger. Maybe I was just lucky.

Thank you, appreciate the little aside.

I think you're right about the penetration enhancer in the cream. It was an oil you used? If I'm right about salicylic acid, methyl salicylate acts as its own penetration enhancer, but the effect would be increased by cosolvents like propylene glycol or even plain old ethanol (which may be in those muscle rubs):

"Ethanol can exert its permeation enhancing activity through various mechanisms. As a solvent, it can increase the solubility of the drug in the vehicle (Pershing et al., 1990). Further, permeation of ethanol into the stratum corneum can improve drug partitioning into the membrane. Additionally, it is also feasible that the rapid permeation of ethanol, or evaporative loss of this volatile solvent from the donor phase modifies the thermodynamic activity of the drug within the formulation. A further potential mechanism of action arising as a consequence of rapid ethanol permeation across the skin has been reported; solvent ‘drag’ may carry permeant into the tissue as ethanol traverses (Morimoto et al., 2002). In addition, ethanol as a volatile solvent may extract some of the lipid fraction within the stratum corneum and improve drug flux through the skin. PG permeates well through stratum corneum and its mechanisms of action are probably similar to those suggested for ethanol (Williams and Barry, 2004). On the other hand, a combination of the two vehicles, PG and alcohol, would also inhibit in vitro deacetylation." Design of a transdermal delivery system for aspirin as an antithrombotic drug (Ammar et al., 2006)

 

[Nokoni]

It was an oil you used?

No, I'm aware that wintergreen oil is almost all MS but I was using pure MS. It is colorless and has the consistency of water, maybe very slightly less runny. But I am really surprised to learn, as is apparently the case, that alcohol or similar could make that much difference. It may be that I could have gotten myself in trouble if I was using it in that way.

 

[cjm]

No, I'm aware that wintergreen oil is almost all MS but I was using pure MS. It is colorless and has the consistency of water, maybe very slightly less runny. But I am really surprised to learn, as is apparently the case, that alcohol or similar could make that much difference. It may be that I could have gotten myself in trouble if I was using it in that way.

The brothers from '67 were lighting the fuse from both ends. Idiots, I believe @haidut rightly called them.

 

[AlaskaJono]

The study says more than 50% of the body surface area was covered in a 20%+ salicylate solution. That would probably amount to putting 100g+ salicylate on their skin. So, it basically shows that some people are plainly idiotic. However, how is this applicable to people using aspirin or other salicylates orally, in doses of <1g in most cases?
Oh, btw, the salicylate solution was in alcohol and if anybody covers half their body surface area in, say, vodka or rubbing alcohol, that would also reliably kill most people on its own. So, it is not even clear here, which substance was the primary culprit. Yes, salicylates can kill in very high doses, but so can caffeine, ibuprofen, and especially acetaminophen and all those in doses much lower than the LD50 of salicylates. That's why it is those latter substances that are much more often used in suicide attempts than salicylate/aspirin.

As @cjm stated,

This is an extreme example demonstrating absorption from a transdermal. My question will be what the appropriate dose is for systemic absorption.

I wonder that myself. What level of absorption of just salicylates alone will occur? 50%? 85%? 100% Does it depend on the person's skin thickness and affinity for this compound? No question that covering more than 50% of the body with strong chemical solutions, 100%, may cause serious issues, and possibly kill not cure. And 100Grams of aspirin is quite a large amount in my book.

Regarding the 'new' jihad (Last 50 years) against aspirin by the medical establishment, how toxic aspirin is and how it can kill is a widely accepted propaganda. My dad is an MD, and about 7 years ago I said I was taking aspirin regularly, daily, for general anti inflammatory, and specifically for something too. He said he had a friend that died of internal bleeding caused by aspirin. I asked how old his friend was (my pop is in his late 80's now), and what medical condition he had. Apparently this man was also in his 80's and he had a heart condition, some kidney issues (BP), and something else. So I couldn't help it and chuckled at my Pop's 'diagnosis' that this friend died of aspirin causing internal bleeding. He most probably was on at least 5 different meds, none of which were cross checked for interactions between them, AND his friend was taking the aspirin whilst seeing his regular doctor. But Lo and behold, "the aspirin killed the man." Absolute undocumented proclamation.

 

[Nokoni]

As @cjm stated,

I wonder that myself. What level of absorption of just salicylates alone will occur? 50%? 85%? 100% Does it depend on the person's skin thickness and affinity for this compound? No question that covering more than 50% of the body with strong chemical solutions, 100%, may cause serious issues, and possibly kill not cure. And 100Grams of aspirin is quite a large amount in my book.

Regarding the 'new' jihad (Last 50 years) against aspirin by the medical establishment, how toxic aspirin is and how it can kill is a widely accepted propaganda. My dad is an MD, and about 7 years ago I said I was taking aspirin regularly, daily, for general anti inflammatory, and specifically for something too. He said he had a friend that died of internal bleeding caused by aspirin. I asked how old his friend was (my pop is in his late 80's now), and what medical condition he had. Apparently this man was also in his 80's and he had a heart condition, some kidney issues (BP), and something else. So I couldn't help it and chuckled at my Pop's 'diagnosis' that this friend died of aspirin causing internal bleeding. He most probably was on at least 5 different meds, none of which were cross checked for interactions between them, AND his friend was taking the aspirin whilst seeing his regular doctor. But Lo and behold, "the aspirin killed the man." Absolute undocumented proclamation.

When I was an adolescent and still planning to follow in my daddy's footsteps and become a doctor, and still starry-eyed at the heroic prospect, I asked him what he thought was the most important medicine ever discovered. Answer? Aspirin. It struck me as deflatingly pedestrian. That would have been the late 60's, but it shows how thoroughly they have shifted the narrative since then. Simple fact is, for a doctor or pharmaceutical exec, aspirin is bad for business.