METHYL SALICYLATE
CASRN: 119-36-8
For other data, click on the Table of Contents

Human Health Effects:

Human Toxicity Excerpts:

THE LETHAL DOSE OF METHYL SALICYLATE IS CONSIDERABLY LESS THAN THAT OF SODIUM SALICYLATE. AS LITTLE AS 4 ML (4.7 G) OF METHYL SALICYLATE MAY BE FATAL IN CHILDREN. /METHYL SALICYLATE/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 651]**PEER REVIEWED**

Symptoms of poisoning by methyl salicylate differ little from those described for aspirin. Central excitation, intense hyperpnea, and hyperpyrexia are prominent features. The odor of the drug can easily be detected on the breath and in the urine and vomitus. /Methyl salicylate/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 651]**PEER REVIEWED**

In reviews of methyl salicylate poisoning, dimness of vision is mentioned as occurring in about 15% of all cases, but the nature of the impairment has been poorly characterized, and the impression is given that it is a manifestation of disturbance of the CNS. /Methyl salicylate/
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 627]**PEER REVIEWED**

MILD CHRONIC SALICYLATE INTOXICATION IS TERMED SALICYLISM /&/...SYNDROME INCLUDES HEADACHE, DIZZINESS, RINGING IN EARS, DIFFICULTY IN HEARING, DIMNESS OF VISION, MENTAL CONFUSION, LASSITUDE, DROWSINESS, SWEATING, THIRST, HYPERVENTILATION, NAUSEA, VOMITING, & OCCASIONALLY DIARRHEA. /SALICYLATES/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 651]**PEER REVIEWED**

TOXIC EFFECTS SIMILAR TO OTHER SALICYLATES. HYPERPNEA, FOR WHICH PATIENT SHOULD BE CLOSELY OBSERVED, IS FIRST SIGN. THIS INITIAL HYPERVENTILATION MAY LEAD TO RESPIRATORY ALKALOSIS AND, IN SEVERE CASES FOLLOWED BY A METABOLIC ACIDOSIS.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

Salicylates cross the placental barrier. A 33 week old fetus died in utero 20 hours after 3 g salicylate was ingested by the mother. The salicylate level of the mother was 568 mg/l at admission and 212 mg/l at the time fetal heart tones stopped. Autopsy blood from the fetus, which aborted 8 days later, was 243 mg/l. /Salicylates/
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 564]**PEER REVIEWED**

Generally, ingestion /of salicylates at/ doses larger than 150 mg/kg (or 70 mg/lb) can produce toxic symptoms such as tinnitus, nausea, and vomiting. Serious toxicity can be seen with ingestions greater than 400 mg/kg (approximately 180 mg/lb), with severe vomiting, hyperventilation, hyperthermia, confusion, coma, convulsions, hyper- or hypoglycemia, and acid-base disturbances such as respiratory alkalosis or metabolic acidosis. In severe cases, the clinical course may progress to pulmonary edema, hemorrhage, acute renal failure, or death. It is important to note that the salicylate-overdose patient can progress to a more serious condition over time as additional drug is absorbed from the gastrointestinal tract. Chronic salicylism presents clinically in a similar fashion to the acute situation, although it is often associated with a higher morbidity and mortality as well as more pronounced hyperventilation, dehydration, coma seizures, and acidosis. /Salicylates/
[Amdur, M.O., J. Doull, C.D. Klaasen (eds). Casarett and Doull's Toxicology. 4th ed. New York, NY: Pergamon Press, 1991. 940]**PEER REVIEWED**

Methyl salicylate (Oil of Wintergreen, Ben Gay) is one infrequent cause of salicylate poisoning but is the most dangerous salicylate formulation by strength. One teaspoon contains 7,000 mg of salicylate, equivalent to 21 aspirin tablets, and childhood fatalities may occur after ingestion of as little as 4 ml of Oil of Wintergreen. A 1 oz tube of external liniment (20% methyl salicylate) is equivalent to the above fatal dose of Oil of Wintergreen. When applied to large areas of skin, topical salicylic acid may cause sufficient dermal absorption to produce toxic serum salicylate levels.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 562]**PEER REVIEWED**

The ingestion of salicylate may result in epigastric distress, nausea, and vomiting. ... Salicylate may also cause gastric ulceration; exacerbation of peptic ulcer symptoms (heartburn, dyspepsia), gastrointestinal hemorrhage, and erosive gastritis have all been reported in patients on high dose therapy, but may occur rarely with low doses as a hypersensitivity response. Salicylate induced gastric bleeding is painless and may lead to an iron deficiency anemia. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 646]**PEER REVIEWED**

... Salicylates can cause retention of salt and water as well as acute reduction of renal function in patients with congestive heart failure or hypovolemia. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 647]**PEER REVIEWED**

There is no evidence that moderate therapeutic doses of salicylates cause fetal damage in human beings; however, babies born to women who ingest salicylates for long periods may have significantly reduced weights at birth. In addition, there is an increase in perinatal mortality, anemia, antepartum and postpartum hemorrhage, prolonged gestation, and complicated deliveries ... . /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 649]**PEER REVIEWED**

The average lethal dose /SRP: 95-98% methyl salicylate/ for children is 10 ml, and for adults, 30 ml or 0.5 g/kg.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2309]**PEER REVIEWED**

... One patient complained of dimness of vision and difficulty in hearing on first regaining consciousness after ingestion of 30 ml of methyl salicylate, after going through severe acidosis, coma, and convulsions, which were treated with iv amytal, sodium lactate, and calcium gluconate. Vision and hearing were said to have returned to normal within two weeks, but no actual measurements of visual acuity, visual fields or examination of the fundi were reported.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 627]**PEER REVIEWED**

... /A/ patient, who took 24 ml of methyl salicylate in the course of 48 hr, complained of xanthopsia and inability to read. This patient was reported to have recovered in about five days after the drug was discontinued, but the reason for the inability to read was not explained.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 627]**PEER REVIEWED**

A topically applied rubifacient delivered by aerosol (Deep-Heat) was studied. After spray application to the forearms of volunteers, without massage, the erythema produced was measured by thermography and correlated with the concentration of 2 salicylate components of the mixture found in local and systemic venous blood. Maximum erythema occurred at about 30 minutes, while blood salicylate levels were maximal between 20 and 30 minutes after application. Methyl salicylate was absorbed before ethyl salicylate. Over the time period of the erythematous response oxygen levels in local venous blood were raised. Finally, platelets collected from venous blood draining from the sprayed site, when induced to clump by the addition of arachidonic acid in an aggregometer, showed increased resistance to clumping when compared with control cells.
[Collins AJ et al; Ann Rheum Dis 43 (3): 411-5 (1984)]**PEER REVIEWED**

 

Human Toxicity Values:

LDLO Child oral 0.17 g/kg; LD50 Adult oral 0.5 g/kg
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2310]**PEER REVIEWED**

 

Drug Warnings:

OINTMENTS OR LINIMENTS ... . SHOULD NOT BE APPLIED TO BURNED AREAS OR TO OTHERWISE DAMAGED SKIN...USUALLY IN CONCN FROM 10-25% ... .
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

ABSORPTION OF METHYL SALICYLATE CAN OCCUR THROUGH THE SKIN, & DEATH HAS RESULTED FROM SYSTEMIC POISONING FROM THE LOCAL MISAPPLICATION OF THE DRUG. IT IS A COMMON PEDIATRIC POISON, & ITS USE SHOULD BE STRONGLY DISCOURAGED.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 653]**PEER REVIEWED**

Children with fever and dehydration are particularly prone to intoxication from relatively small doses of salicylate. ... The use of aspirin is contraindicated in children and adolescents with febrile viral illnesses because of the risk of Reye's syndrome. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 651]**PEER REVIEWED**

 

Probable Routes of Human Exposure:

The primary route of human exposure is the consumption of consumer products which contain methyl salicylate as a flavoring agent. Methyl salicylate is used in chewing gum, baked goods, syrups, candy, non-alcoholic beverages and ice cream. Other potential routes of exposure include dermal contact resulting from its use in perfumes. (SRC)
**PEER REVIEWED**

NIOSH (NOES Survey 1981-1983) has statistically estimated that 284,093 workers are exposed to methyl salicylate in the USA(1). Ninety five percent of exposures are with trade name products containing methyl salicylate(1).
[(1) NIOSH; National Occupational Exposure Survey (1989)]**PEER REVIEWED**

 

Minimum Fatal Dose Level:

4= VERY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 50-500 MG/KG, BETWEEN 1 TEASPOON &1 OZ FOR 70 KG PERSON (150 LB).
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-205]**PEER REVIEWED**

 

Emergency Medical Treatment:

 

 

Emergency Medical Treatment:

 

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The following Overview, *** SALICYLATES ***, is relevant for this HSDB record chemical.

Life Support:
  o   This overview assumes that basic life support measures
      have been instituted.                           
Clinical Effects:
  SUMMARY OF EXPOSURE
   0.2.1.1 ACUTE EXPOSURE
     o   MILD/MODERATE INTOXICATION - Patients with mild to
         moderate intoxication may develop fever, tachypnea,
         tinnitus, respiratory alkalosis, metabolic acidosis,
         lethargy, mild dehydration, nausea and vomiting.
     o   SEVERE INTOXICATION - Encephalopathy, coma,
         hypotension, pulmonary edema, seizures, acidemia,
         coagulopathy, cerebral edema and dysrhythmias may
         develop in severe toxicity.
     o   RISK FACTORS - Toxicity is generally more severe in
         patients with chronic overdose, the elderly, those with
         underlying medical problems, and infants.
     o   ROUTE - Toxicity may result from ingestion or dermal
         absorption.
  VITAL SIGNS
   0.2.3.1 ACUTE EXPOSURE
     o   Hyperventilation, mild tachycardia and hyperthermia are
         common; hypotension may develop in severe overdose.
  HEENT
   0.2.4.1 ACUTE EXPOSURE
     o   Ototoxicity has been reported with both therapeutic use
         and overdose.   Effects include tinnitus, hearing loss,
         and electrocochleographic changes.
     o   Salicylic acid in topical wart removers can cause
         mucosal burns.
  CARDIOVASCULAR
   0.2.5.1 ACUTE EXPOSURE
     o   Tachycardia is common.  Hypotension and dysrhythmias
         may develop with severe intoxication.
  RESPIRATORY
   0.2.6.1 ACUTE EXPOSURE
     o   Tachypnea and hyperpnea are common.  Noncardiogenic
         pulmonary edema may develop  in patients with severe
         intoxication.
  NEUROLOGIC
   0.2.7.1 ACUTE EXPOSURE
     o   Lethargy, agitation and confusion may be early findings
         in patients with severe toxicity.  Coma and seizures
         may develop subsequently.  Cerebral edema is a common
         autopsy finding.
  GASTROINTESTINAL
   0.2.8.1 ACUTE EXPOSURE
     o   Nausea and vomiting are common.  Gastrointestinal
         bleeding, perforation and pancreatitis are rare
         complications.
  HEPATIC
   0.2.9.1 ACUTE EXPOSURE
     o   Hepatic injury has been reported with chronic toxicity
         and chronic therapeutic use.  Salicylates have been
         linked with Reye's syndrome in children.
  GENITOURINARY
   0.2.10.1 ACUTE EXPOSURE
     o   Renal insufficiency is an uncommon complication that
         may develop secondary to rhabdomyolysis or hypotension.
  ACID-BASE
   0.2.11.1 ACUTE EXPOSURE
     o   Respiratory alkalosis develops early in the course of
         intoxication and may be the only acid base disturbance
         with mild salicylism.
     o   Respiratory alkalosis with compensatory metabolic
         acidosis develops in most adults with moderate
         intoxication.
     o   Metabolic acidosis with acidemia and compensatory
         respiratory alkalosis develops in severe overdose and
         is associated with a higher rate of complications and
         death.  In infants respiratory alkalosis may be short
         lived or not occur at all; metabolic acidosis with
         acidemia predominates.
  FLUID-ELECTROLYTE
   0.2.12.1 ACUTE EXPOSURE
     o   Dehydration and hypokalemia are common.
  HEMATOLOGIC
   0.2.13.1 ACUTE EXPOSURE
     o   PT prolongation is fairly common; DIC and
         thrombocytopenia occur rarely.
  MUSCULOSKELETAL
   0.2.15.1 ACUTE EXPOSURE
     o   Rhabdomyolysis is an unusual complication of salicylate
         overdose.
  METABOLISM
   0.2.17.1 ACUTE EXPOSURE
     o   Hypoglycemia may develop, especially in children.
  REPRODUCTIVE HAZARDS
    o   Chronic maternal ingestion is associated with an
        increased incidence of stillbirths,
        antepartum/postpartum bleeding, prolonged
        pregnancy/labor, and lower birth weight.
Laboratory:
  o   Monitor serum salicylate level, glucose and electrolytes
      every 2 hours  until the salicylate level is consistently
      falling and acid base abnormalities are improving.  Peak
      salicylate levels develop rapidly after methyl salicylate
      ingestion, but may be delayed 6 hours or more following
      ingestion of tablets and more than 12 hours after
      ingestion of  enteric coated or sustained release
      products.
  o   Obtain an arterial blood gas in symptomatic patients and
      follow until acid base abnormalities are improving.
  o   Obtain a CBC, renal and hepatic function tests and INR or
      PT and PTT in patients with clinical evidence of moderate
      to severe toxicity.                                     
Treatment Overview:
  ORAL EXPOSURE
    o   ACTIVATED CHARCOAL:  Administer charcoal as slurry (240
        mL water/30 g charcoal).  Usual dose:  25 to 100 g in
        adults/adolescents, 25 to 50 g in children (1 to 12
        years), and 1 g/kg in infants less than 1 year old.
    o   GASTRIC LAVAGE:  Consider after ingestion of a
        potentially life-threatening amount of poison if it can
        be performed soon after ingestion (generally within 1
        hour).  Protect airway by placement in Trendelenburg and
        left lateral decubitus position or by endotracheal
        intubation.  Control any seizures first.
     1.  CONTRAINDICATIONS:  Loss of airway protective reflexes
         or decreased level of consciousness in unintubated
         patients; following ingestion of corrosives;
         hydrocarbons (high aspiration potential); patients at
         risk of hemorrhage or gastrointestinal perforation; and
         trivial or non-toxic ingestion.
    o   Correct dehydration with 0.9% NaCl at a rate of 10 to 20
        mL/kg/hr over 1 to 2 hours until a good urine flow is
        obtained.  Do not overhydrate and follow pulmonary
        status carefully.  Potassium should be added to
        subsequent fluid.  Monitor urine output, urine pH, and
        serum potassium.
    o   Alkalinize the urine in patients with clinical or
        laboratory evidence of toxicity.  Infuse a solution of
        132 mEq/L sodium bicarbonate (3 amps) in 1  liter D5W at
        1.5 to 2 times maintenance fluid requirements to achieve
        a urine  pH greater than 7.5.  Additional KCl (20 to 40
        mEq/L) may be required.
    o   ACIDOSOS - Administer IV NaHCO3.  Correct pH to 7.40;
        even mild acidemia can facilitate movement of salicylate
        into the brain.  Monitor ABGs.
    o   HYPERTHERMIA - should be treated with external cooling.
    o   HEMODIALYSIS INDICATIONS - Patients with high blood
        salicylate levels (> 100 mg/dL), or refractory acidosis,
        persistent CNS symptoms, progressive clinical
        deterioration despite appropriate therapy, pulmonary
        edema, or renal failure are candidates for hemodialysis.
  EYE EXPOSURE
    o   DECONTAMINATION:  Irrigate exposed eyes with copious
        amounts of tepid water for at least 15 minutes.  If
        irritation, pain, swelling, lacrimation, or photophobia
        persist, the patient should be seen in a health care
        facility.                              
Range of Toxicity:
  o   Accidental ingestions of <150 mg/kg can usually be treated
      at home with fluids and telephone follow-up.
  o   Accidental ingestion of 150 to 300 mg/kg; if less than 2
      to 3 hours after ingestion, induction of emesis and
      follow-up for 24 hours is suggested.
  o   Accidental ingestion of >300 mg/kg; refer to health care
      facility.
  o   CHRONIC INGESTION > 100 mg/kg/day over 2 days may produce
      toxicity.


[Rumack BH: POISINDEX(R) Information System. Micromedex, Inc., Englewood, CO, 2001; CCIS Volume 110, edition exp November, 2001. Hall AH & Rumack BH (Eds):TOMES(R) Information System. Micromedex, Inc., Englewood, CO, 2001; CCIS Volume 110, edition exp November, 2001.] **PEER REVIEWED**

 

Animal Toxicity Studies:

 

 

Non-Human Toxicity Excerpts:

METHYL SALICYLATE, GIVEN ORALLY BY CAPSULE TO DOGS AT RATE OF 1200 MG/KG/DAY, WAS FATAL IN 3-4 DAYS; 500-800 MG/KG/DAY WAS FATAL IN A MONTH; 350 MG/KG/DAY COULD BE FED FOR 2 YEARS CAUSING ONLY LOSS IN WEIGHT AND SOME ENLARGEMENT OF THE LIVER.
[Humphreys, D.J. Veterinary Toxicology. 3rd ed. London, England: Bailliere Tindell, 1988. 93]**PEER REVIEWED**

UNLIKE SALICYLATE SALTS, METHYL SALICYLATE DID NOT AFFECT FERTILITY & FECUNDITY OF DAMS OR GROWTH & VIABILITY OF PUPS IN 3-GENERATION FEEDING STUDY IN OSBORNE-MENDEL RATS. NO GROSSLY ABNORMAL PUPS WERE FOUND.
[The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975. 649]**PEER REVIEWED**

DRUG-INDUCED RENAL ABNORMALITY IS APPARENT HYDRONEPHROSIS IN OFFSPRING OF RATS EXPOSED TO METHYL SALICYLATE ON DAYS 10 & 11 OF GESTATION. IT ALSO CAUSED RETARDED RENAL DEVELOPMENT, PARTICULARLY GROWTH OF RENAL PAPILLA, & INCR NUMBER OF RENAL ABNORMALITIES IN FETUSES.
[GIBSON E; ENVIRON HEALTH PERSPECTIVES 15: 121 (1976)]**PEER REVIEWED**

Methyl salicylate was found to be negative when tested for mutagenicity using the Salmonella/microsome preincubation assay, using the standard protocol approved by the National Toxicology Program (NTP). Methyl salicylate was tested in as many as 5 Salmonella typhimurium strains (TA1535, TA1537, TA97, TA98, and TA100) in the presence and absence of rat and hamster liver S-9, at doses of 1,000, 3,300,10,000, 33,300, 100,000, and 333,300 ug/plate. The highest ineffective dose tested in any Salmonella typhimurium strain was 333,000 ug/plate.
[Mortelmans K et al; Environ Mutagen 8: 1-119 (1986)]**PEER REVIEWED**

Methyl salicylate (MS) is teratogenic in animals and can be absorbed in toxic quantities by the dermal route. Consequently the dermal absorption and teratogenic potential of a petroleum-based grease (PBG) manufactured using methyl salicylate (3%) was assessed. The test material (petroleum based grease/methyl salicylate) was dermally applied at doses of either 0, 1, 3, or 6 g/kg/day to groups (N greater than or equal to 12) of pregnant rats on gestational days 6-15. Undiluted methyl salicylate was applied to the positive control group at a dose of 2 g/kg/day and was reduced to 1 g/kg/day on gestational days 10-15 due to maternal toxicity (ie, 25% mortality and severe dermal irritation). Positive control animals evidenced a 100% incidence of total resorptions. Urinalysis revealed very high concentrations of salicylic acid in the positive controls and that a significant proportion of the available methyl salicylate was absorbed from the petroleum based grease/methyl salicylate test material. However, the urinary concentrations of salicylic acid in petroleum based grease/methyl salicylate treated animals were far below the toxic levels observed in methyl salicylate treated animals. Despite the high doses of petroleum based grease/methyl salicylate, there were no signs of maternal toxicity (as measured by food consumption and body weight parameters or clinical signs) and no alterations in reproductive parameters. Fetal external and visceral examinations revealed no malformations or variations that were related to petroleum based grease/methyl salicylate treatment. These findings confirm the developmental toxicity of methyl salicylate and indicate that petroleum based grease/methyl salicylate was not a teratogenic hazard under these test conditions. The maternal and developmental No-Observable-Adverse-Effect-Level for petroleum based grease/methyl salicylate was greater than 6 g/kg/day.
[Infurna R et al; Teratology 41 (5): 566 (1990)]**PEER REVIEWED**

Prenatal exposure to methyl salicylate on kidney function in rats were studied. Pregnant female Sprague Dawley rats were treated with methyl salicylate by intraperitoneal injections between gestational days 10 and 14. Functional assessments of renal toxicity included baseline urinary parameters, urine concentrating ability and in-vitro determination of the transport function of the renal cortex. Methyl salicylate exposure was teratogenic and embryotoxic. Prenatal exposure decreased fetal weight and increased the number of resorptions, fetal mortality, and the incidence of fetal malformations including ectopic kidneys. The primary postnatal renal defect associated with prenatal methyl salicylate treatment was a decreased urine concentrating ability in weanlings.
[Daston GP et al; Fundam and Appl Toxicol 11 (3): 381-400 (1988)]**PEER REVIEWED**

Methyl salicylate was administered topically to pregnant hamsters at 7 day 9 hr and the teratogenic results were compared with those obtained following oral treatment with the same compound. Both treatments produced the same defect in embryos recovered at day 9: failure of fusion of the neural tube, especially in the area of the developing brain. Analysis of serum salicylate levels following both treatments produced similar curves and indicated that teratogenic levels of salicylate can reach the maternal circulation after topical exposure.
[Overman DO, White JA; Teratology 28 (3): 421-6 (1983)]**PEER REVIEWED**

 

Non-Human Toxicity Values:

LD50 Rat oral 0.887 g/kg
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2310]**PEER REVIEWED**

LD50 Rabbit oral 2.8 g/kg
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2310]**PEER REVIEWED**

LD50 Guinea pig oral 1.060 g/kg
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2310]**PEER REVIEWED**

LD50 Dog oral 2.1 g/kg
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2310]**PEER REVIEWED**

LD50 Guinea pig dermal 0.70 ml/kg
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2310]**PEER REVIEWED**

 

Metabolism/Pharmacokinetics:

 

 

Metabolism/Metabolites:

...EVIDENCE THAT CONSIDERABLE HYDROLYSIS OF ESTER OCCURS IN INTESTINAL TRACT... IN SOME SPECIES, SUCH AS RABBIT, MAY BE PARTLY EXCRETED AS SULFATE OR GLUCURONIC ACID CONJUGATE ON THE FREE HYDROXYL GROUP. CONJUGATION APPEARS TO TAKE PLACE BEFORE HYDROLYSIS OF THE METHYL ESTER.
[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963. 1899]**PEER REVIEWED**

For small doses 80% of the hepatic metabolism results from conjugation with glycine to form salicyluric acid and with glucuronic acid to form salicyl acyl and phenolic glucuronide. The two parallel pathways (glycine, glucuronide conjugation) have limited capacity and saturate easily above therapeutic doses. /Salicylates/
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 563]**PEER REVIEWED**

The biotransformation of salicylates takes place in many tissues, but particularly in the hepatic endoplasmic reticulum and mitochondria. The three chief metabolic products are salicyluric acid (the glycine conjugate), the ether or phenolic glucuronide, and the ester or acyl glucuronide. In addition, a small fraction is oxidized to gentisic acid (2,5-dihydroxybenzoic acid) and to 2,3-dihydroxybenzoic and 2,3,5-trihydroxybenzoic acids; gentisuric acid, the glycine conjugate of gentisic acid, is also formed. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 649]**PEER REVIEWED**

 

Absorption, Distribution & Excretion:

MAY BE ABSORBED RAPIDLY THROUGH INTACT SKIN. BOWEL ABSORPTION IS SOMEWHAT ERRATIC ... ABSORBED AT LEAST IN PART AS THE INTACT ESTER AND SMALL AMT ARE EVEN EXCRETED AS SUCH BY THE KIDNEYS ... .
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-205]**PEER REVIEWED**

HUMAN SUBJECTS WERE GIVEN 7 MG/KG OF METHYL SALICYLATE BY MOUTH. AFTER 0.25 HOURS THE BLOOD CONCN WAS 1.28 MG%. AFTER 1.5 HOURS THE BLOOD CONCN WAS 1.33 MG%. /FROM TABLE/
[Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969. 362]**PEER REVIEWED**

At therapeutic doses, conjugation accounts for most salicylic elimination, whereas renal elimination becomes more important with large or multiple doses. A substantial first-pass effect occurs at therapeutic doses. /Salicylates/
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 563]**PEER REVIEWED**

Orally ingested salicylates are absorbed rapidly, partly from the stomach but mostly from the upper small intestine. Appreciable conc are found in plasma in less than 30 min; after a single dose, a peak value is reached in about 2 hr and then gradually declines. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 649]**PEER REVIEWED**

After absorption, salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes. Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus. The drug readily crosses the placental barrier. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 649]**PEER REVIEWED**

Salicylates are excreted in the urine as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl (5%) glucuronides, and gentisic acid (less than 1%). However, excretion of free salicylate is extremely variable and depends upon both the dose and the urinary pH. In alkaline urine, more than 30% of the ingested drug may be eliminated as free salicylate, whereas in acidic urine this may be as low as 2%. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 650]**PEER REVIEWED**

 

Biological Half-Life:

The plasma half-life for ... salicylate is 2 to 3 hr in low doses and about 12 hr at usual antiinflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 650]**PEER REVIEWED**

 

Interactions:

... The prolonged and excessive ingestion of analgesic mixtures containing salicylates in combination with acetaminophen or salicylamide can produce papillary necrosis and interstitial nephritis. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 647]**PEER REVIEWED**

 

Pharmacology:

 

 

Therapeutic Uses:

OINTMENTS OR LINIMENTS CONTAINING METHYL SALICYLATE ARE APPLIED TOPICALLY AS COUNTERIRRITANTS FOR RELIEF OF PAIN ASSOCIATED WITH LUMBAGO, SCIATICA, AND RHEUMATIC CONDITIONS. FORMERLY USED INTERNALLY IN SMALL DOSES AS A CARMINATIVE.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

MEDICATION (VET): ORALLY, PRIMARILY AS FLAVORING AGENT OR AS CARMINATIVE; TOPICALLY, AS IRRITANT OR COUNTERIRRITANT AIDED BY MASSAGE OR RUBBING AS IN UDDER OINTMENTS (1-3% CONCN), POULTICES & COUNTERIRRITANT MIXT (@ LEAST 5-10%) OVER SORE JOINT, MUSCLE, & BONE AREAS.
[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974. 360]**PEER REVIEWED**

LOCAL ANALGESIC FOR HUMAN AND VETERINARY MEDICINE
[SRI]**PEER REVIEWED**

 

Drug Warnings:

OINTMENTS OR LINIMENTS ... . SHOULD NOT BE APPLIED TO BURNED AREAS OR TO OTHERWISE DAMAGED SKIN...USUALLY IN CONCN FROM 10-25% ... .
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

ABSORPTION OF METHYL SALICYLATE CAN OCCUR THROUGH THE SKIN, & DEATH HAS RESULTED FROM SYSTEMIC POISONING FROM THE LOCAL MISAPPLICATION OF THE DRUG. IT IS A COMMON PEDIATRIC POISON, & ITS USE SHOULD BE STRONGLY DISCOURAGED.
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 653]**PEER REVIEWED**

Children with fever and dehydration are particularly prone to intoxication from relatively small doses of salicylate. ... The use of aspirin is contraindicated in children and adolescents with febrile viral illnesses because of the risk of Reye's syndrome. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 651]**PEER REVIEWED**

 

Interactions:

... The prolonged and excessive ingestion of analgesic mixtures containing salicylates in combination with acetaminophen or salicylamide can produce papillary necrosis and interstitial nephritis. /Salicylates/
[Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990. 647]**PEER REVIEWED**

 

Minimum Fatal Dose Level:

4= VERY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 50-500 MG/KG, BETWEEN 1 TEASPOON &1 OZ FOR 70 KG PERSON (150 LB).
[Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984.,p. II-205]**PEER REVIEWED**

 

Environmental Fate & Exposure:

 

 

Environmental Fate/Exposure Summary:

Methyl salicylate is produced in significant quantities and may be released to the environment during its production, transport, disposal, and use in perfumes and sunburn lotions and in foods, beverages and pharmaceuticals. It is also a plant volatile and will be released by some plants. In soil, methyl salicylate is likely to biodegrade. In alkaline soil, chemical hydrolysis may contribute to its disappearance. It may also undergo direct photolysis on the soil surface. Methyl salicylate is expected to be fairly mobile in soil. It should partially volatilize from dry soil. If released in water, methyl salicylate should slowly volatilize (half-life 49 days in a model river), biodegrade, and be lost as a result of direct photolysis and photooxidation in surface waters. In alkaline water, hydrolysis may also be a significant fate process (estimated half-life 14 days at pH 7.5). Methyl salicylate is not likely to bioconcentrate in aquatic organisms. Methyl salicylate will react with photochemically-produced hydroxyl radicals in the atmosphere resulting in as estimated half-life of 1.4 days. It is fairly soluble in water and may be washed out by rain. Exposure to methyl salicylate will be via ingestion of foods and dermal contact with various consumer products. Occupational exposure will probably be via dermal contact and inhalation. (SRC)
**PEER REVIEWED**

 

Probable Routes of Human Exposure:

The primary route of human exposure is the consumption of consumer products which contain methyl salicylate as a flavoring agent. Methyl salicylate is used in chewing gum, baked goods, syrups, candy, non-alcoholic beverages and ice cream. Other potential routes of exposure include dermal contact resulting from its use in perfumes. (SRC)
**PEER REVIEWED**

NIOSH (NOES Survey 1981-1983) has statistically estimated that 284,093 workers are exposed to methyl salicylate in the USA(1). Ninety five percent of exposures are with trade name products containing methyl salicylate(1).
[(1) NIOSH; National Occupational Exposure Survey (1989)]**PEER REVIEWED**

 

Natural Pollution Sources:

Methyl salicylate occurs in the leaves of Gaulteria procumbens L. Ericacae, in the bark of Betula lenta L. Betulaceae(1) and in the leaves of Burnum dilitatum(2). It was tentatively identified in emissions from agricultural and natural plant species in the San Joaquin and Sacramento Valley in California(3).
[(1) Windholz M et al; Merck Index 9th ed Merck & Co Inc; Rahway NJ pp.798 (1976) (2) Clayton GD, Clayton FE; Patty's Industrial Hygiene and Toxicology 3r ed; Wiley and Sons Inc NY Vol 2a (1981) (3) Winer AM; Atmos Environ 26A; 2647-5 (1992)]**PEER REVIEWED**

 

Artificial Pollution Sources:

Methyl salicylate may be released to the environment in effluent and emission as a result of its production, transport, disposal and use as a flavoring in foods, beverages, pharmaceuticals(1) and dentrifices(2), fragrance agent in cosmetics and perfumes(2), UV-absorber in sunburn lotions(1) counterirritant in some ointments and linaments(3), carrier for fabric dyes and UV stabilizer in acrylic resins(2).
[(1) Hawley GG; Condensed chemical dictionary 10th ed; Van Nostrand Reinhold Co NY (1981) (2) Kirk-Othmer Encycl Chem Tech 3rd ed; John Wiley & Sons Inc NY 20:200-524 (1982) (3) Clayton GD, Clayton FE; Patty's Industrial Hygiene & Toxicology 3rd ed; Wiley & Sons Inc NY Vol 2a (1981)]**PEER REVIEWED**

 

Environmental Fate:

TERRESTRIAL FATE: If released on soil, methyl salicylate would readily leach. It would also be expected to partially volatilize from dry soil and photolyze on the soil surface. Based on the results of sceening tests, it would be expected to readily biodregrade. Chemical hydrolysis may be important in alkaline soil. (SRC)
**PEER REVIEWED**

AQUATIC FATE: Methyl salicylate is readily biodegradable in screening tests and may be expected to biodegrade in surface waters. Methyl salicylate is expected to hydrolyze in water, the hydrolysis rate increasing with pH. At pH 7.5, its hydrolysis half-life is estimated to be 14.1 days(1,2,SRC). Methyl salicylate will react with singlet oxygen in natural surface waters resulting in a half-life of about 52 hr(3). Methyl salicylate absorbs UV radiation >290 nm and therefore may undergo direct photolysis under environmental conditions. Based on an estimated Henry's Law constant of 9.3X10-7 atm-cu-m/mol(4,5,SRC), a volatilization half-life of 49 days would be expected in a model river(SRC).
[(1) Magid LJ, Larsen JW; J Org Chem 39: 3142-4 (1974) (2) Senent S et al; An Quim; 69:13-23 (1973) (3) Scully FE Jr, Hoigne J; Chemosphere 16: 681-94 (1987) (4) Daubert TE, Danner RP; Data Compilation Tables of Properties of Pure Compounds NY, NY: Amer Inst for Phys Prop Data (1989) (5) Riddick JA et al; Organic Solvents 4th ed; NY, NY: Wiley (1986) ]**PEER REVIEWED**

ATMOSPHERIC FATE: Methyl salicylate reacts with photochemically-produced hydroxyl radicals in the atmosphere resulting in an estimated half-life of 1.4 days(1,SRC). It is fairly soluble in water, 7400 mg/L(2) and may be washed out by rain.
[(1) Meylan WM, Howard PH; Chemosphere 26: 2293-9 (1993) (2) Riddick JA et al; Organic Solvents 4th ed; NY, NY: Wiley (1986)]**PEER REVIEWED**

 

Environmental Biodegradation:

Methyl salicylate in a five day BOD test exhibited a value of 55-57% of the theoretical BOD(1,2). Another 5-day BOD determination yielded 65% of the theoretical BOD(3). Methyl salicylate was completely degraded by a microbial mixture when incubated for 7 days at 30 deg C(4). Significant biodegradation of methyl salicylate in the environment would be expected from this result; however no data concerning biodegradation in natural waters or soil could be located.
[(1) Maggio P et al; Ind Carta 14:105-11 (1976) (2) Maggio P et al; Tinctoria 73:15-20 (1976) (3) Crespi-Rosell M, Cegarra-Sanchez J; Bol Inst Invest Text Coop Ind 77: 41-57 (1980) (4) Goulding C et al; J Appl Bact 65: 1-5 (1988)]**PEER REVIEWED**

 

Environmental Abiotic Degradation:

Methyl salicylate hydrolyzes in water by acid and base-catalyzed reaction(3). The base-catalyzed rate constant can be estimated to be 4.0X10-2 L/mole-sec if the ortho consituents to the phenyl ring are ignored(4). The half-life of methyl salicylate calculated from this rate constant is 201 days at pH 8(SRC). A rate constant of 1.59X10(-5) sec(-1) was determined for the hydrolysis of methyl salicylate at pH 9.2 and a temperature of 25 deg C(1). A half-life of 12.1 hours was calculated from this rate constant(SRC). At pH 11.26 the hydrolysis rate constant was 3.62X10(-3) min(-1) at 24 C(2). A half-life value of 3.2 hours was calculated from this rate constant. Another investigator measured a hydrolysis half-life of 57 min at a pH of 9.48 and temperature of 44 deg C(5). Data from these studies indicate a general increase in rate constant with increasing pH as would be expected from abase-catalyzed reaction. Although the two first order rate constants do not lead to identical second order rate constants, an approximate half-life at pH 7.5 of 22 days can be estimated(SRC).
[(1) Magid LJ, Larsen JW; J Org Chem 39: 3142-4 (1974) (2) Senent S et al; An Quim; 69: 13-23 (1973) (3) Mill T; Environ Toxicol Chem 1: 135-141 (1982) (4) USEPA; PCGEMS (Graphical Exposure Modeling System) PCHYDRO (1988) (5) Mata F, Mucientes A; Z Phys Chem Leipzig 259: 881-8 (1978)]**PEER REVIEWED**

The UV absorption maximum of a methanol solution of methyl salicylate is 305 nm(1) which indicates that methyl salicylate can undergo direct photolysis. One photolysis study was performed which yielded a half-life of methyl salicylate in solution of about 48 min(2). The exact medium was not identified, but the authors stated that compounds with low water solubilities were dissolved in a 10% ethanol-water mixture. Based on the concentration of methyl salicylate which was used (3.5 g/L), and the water solubility of the ester of 7.4 g/L(3), it is likely that the result above was obtained using an ethanol-water mixture or absolute ethanol. The UV dose used in the study was 0.0077 erg/sq cm/min, and the UV wavelengths ranged from 300 nm to 400 nm with a maximum at 350 nm. Direct photolysis may, therefore, be an important degradative process in the environment; no available data, however, were collected under environmental conditions.
[(1) Sadtler S; UV Spectrum Sadtler Res Lab Inc Philadelphia PA Utk6751 (1969) (2) Kondo M; Simulation studies of degradation of chemicals in the water and soil; Office of Health Studies Environment Agency Japan (1978) (3) Riddick JA et al; Organic Solvents 4th ed; NY, NY: Wiley (1986)]**PEER REVIEWED**

Methyl salicylate, which has a pKa of 9.8, reacts with singlet oxygen in water which is produced by sunlight absorbed by humic substances in natural surface waters(1). The rate of the ionized phenol is much greater than that of the neutral molecule and therefore the rate increases with pH. Assuming a steady state concentration of singlet oxygen of 4X10-14 moles/L (47 deg N latitude with noon summer sunlight), the half life of methyl salicylate is 52 hr(1). In the atmosphere, methyl salicylate reacts with photochemically-produced hydroxyl radicals with an estimated rate constant of 11.6X10-12 cu cm/molecule-s(2). Assuming a hydroxyl radical concn of 5X10+5 radicals/cu cm, the half-life of methyl salicylate in the atmosphere would be 1.4 days(SRC).
[(1) Scully FE Jr, Hoigne J; Chemosphere 16: 681-94 (1987) (2) Meylan WM, Howard PH; Chemosphere 26: 2293-9 (1993)]**PEER REVIEWED**

 

Environmental Bioconcentration:

The log octanol/water partition coefficient for methyl salicylate is 2.55(1). The BCF estimated from this log Kow using a regression equation is 4 which indicates that the ester will not bioconcentrate in fish(SRC).
[(1) Hansch C, Leo AJ; Medchem Project Issue No 26 Claremont, CA: Pomona College (1985) (2) Lyman WJ et al (eds); Handbook of Chemical Property Estimation Methods, NY: McGraw-Hill Chapt 5 (1982)]**PEER REVIEWED**

 

Soil Adsorption/Mobility:

The Koc for methyl salicylate estimated from molecular structure is 128(1) and is 33(3,SRC) estimated from its water solubility, 7400 mg/L(2), using a regression equation. According to a suggested classification scheme(4), these low Koc values suggest that methyl salicylate would be highly or very highly mobile in soil(SRC).
[(1) Meylan WM et al; Environ Sci Technol 26: 1560-7 (1992) (2) Riddick JA et al; Organic Solvents 4th ed; NY, NY: Wiley (1986) (3) Lyman WJ et al ; Handbook of Chemical Property Estimation Methods, NY: McGraw-Hill Chapt 4 (1982) (4) Swann RL et al; Res Rev 85: 17-28 (1983)]**PEER REVIEWED**

 

Volatilization from Water/Soil:

The Henry's Law constant for methyl salicylate is 9.3X10-7 atm-cu-m/mol(SRC) calculated from its vapor pressure, 0.0343 mm Hg(1), and water solubility, 7400 mg/L(2). Using this value for the Henry's Law constant, one can estimate a volatilization half-life of 49 days in a model river 1 m deep flowing at 1 m/s with a wind speed of 3 m/s(3). Similarly, the volatilization half-life of methyl salicylate from a model lake 1 m deep, with a 0.05 m/s current and a 0.5 m/s wind is estimated to be 359 days. Methyl salicylate sprayed onto air-dried soil volatilizes rapidly(4). The amount of chemical that is adsorbed to the soil, evaporates more slowly by a diffusion-controlled mechanism(4).
[(1) Daubert TE, Danner RP; Data Compilation Tables of Properties of Pure Compounds NY, NY: Amer Inst for Phys Prop Data (1989) (2) Riddick JA et al; Organic Solvents 4th ed; NY, NY: Wiley (1986) (3) Lyman WJ et al (eds); Handbook of Chemical Property Estimation Methods, NY: McGraw-Hill Chapt 15 (1982) (4) Reichman R et al; Soil Sci 148: 191-8 (1989)]**PEER REVIEWED**

 

Environmental Water Concentrations:

SURFACE WATER: Methyl salicylate was identified in 2 surface water within the blast zone of Mount St Helens, WA, 3 months after the volcano erupted(1). In another surface water it was identified 2 months after the volcano erupted but not after 3 months(1).
[(1) McKnight DM et al; Org Geochem 4: 85-92 (1982)]**PEER REVIEWED**

 

Effluent Concentrations:

In a comprehensive survey of wastewater from 4000 industrial and publicly owned treatment works (POTWs) sponsored by the Effluent Guidelines Division of the U.S. EPA, methyl salicylate was identified in discharges of the following industrial category (positive occurrences, median concn in ppb): organics and plastics (2; 419), aluminum (3; 127), electronics (1; 29) and organic chemicals (2; 6.2)(1). The highest effluent concn was 1881 ppb in the organics and plastics industry(1).
[(1) Shackelford WM et al; Analyt Chim Acta 146: 15-27 (supplemental data) (1983)]**PEER REVIEWED**

 

Food Survey Values:

Methyl salicylate concentrations of 54 ppm in bakery goods, 840 ppm in candy, 59 ppm in non-alcoholic beverages, 8400 ppm in chewing gum, 27 ppm in ice cream and 200 ppm in syrups. Methyl salicylate has been identified as a volatile component of meat(2).
[(1) Furia TE, Bellanca N; Fenaroli's Handbook of Flavor Ingredients. CRC Press Cleveland OH (1975) (2) Shahidi F et al; CRC Crit Rev Food Sci Nature 24: 141-243 (1986)]**PEER REVIEWED**

FLAVOR INGREDIENT, METHYL SALICYLATE...NON-ALCOHOLIC BEVERAGES 59 PPM; ICE CREAM, ICES, ETC 27 PPM; CANDY 840 PPM; BAKED GOODS 54 PPM; CHEWING GUM 8400 PPM; SYRUPS 200 PPM.
[Fenaroli's Handbook of Flavor Ingredients. Volume 2. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975. 406]**PEER REVIEWED**

 

Environmental Standards & Regulations:

 

 

FIFRA Requirements:

Residues of wintergreen oil are exempted from the requirement of a tolerance when used as a attractant in accordance with good agricultural practices as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest.
[40 CFR 180.1001(c) (7/1/92)]**PEER REVIEWED**

 

Allowable Tolerances:

Residues of wintergreen oil are exempted from the requirement of a tolerance when used as a attractant in accordance with good agricultural practices as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest.
[40 CFR 180.1001(c) (7/1/92)]**PEER REVIEWED**

 

Chemical/Physical Properties:

 

 

Molecular Formula:

C8-H8-O3
**PEER REVIEWED**

 

Molecular Weight:

152.14
**PEER REVIEWED**

 

Color/Form:

COLORLESS, YELLOWISH OR REDDISH, OILY LIQ
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 961]**PEER REVIEWED**

 

Odor:

LIQUID HAVING THE CHARACTERISTIC ODOR OF WINTERGREEN
[Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975. 335]**PEER REVIEWED**

 

Taste:

LIQUID HAVING THE CHARACTERISTIC TASTE OF WINTERGREEN
[Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975. 335]**PEER REVIEWED**

 

Boiling Point:

220-224 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 961]**PEER REVIEWED**

 

Melting Point:

-8.6 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 961]**PEER REVIEWED**

 

Density/Specific Gravity:

1.184 @ 25 DEG C/25 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 961]**PEER REVIEWED**

 

Dissociation Constants:

pKa = 9.8
[Scully FE Jr, Hoigne J; Chemosphere 16: 681-94 (1987)]**PEER REVIEWED**

 

Heat of Combustion:

-902.2 kcal/mole @ 25 deg C
[Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985. 715]**PEER REVIEWED**

 

Heat of Vaporization:

11.155 kcal/mol @ the boiling point
[Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985. 715]**PEER REVIEWED**

 

Octanol/Water Partition Coefficient:

Log Kow = 2.55
[Hansch, C. and A. Leo. The Log P Database. Claremont, CA: Pomona College, 1987.]**PEER REVIEWED**

 

Solubilities:

SOL IN CHLOROFORM, ETHER; MISCIBLE WITH ALC, GLACIAL ACETIC ACID
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 961]**PEER REVIEWED**

SOL IN DIETHYL ETHER
[Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969. 76]**PEER REVIEWED**

SOLUBLE IN MOST COMMON ORGANIC SOLVENTS
[Fenaroli's Handbook of Flavor Ingredients. Volume 2. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975. 406]**PEER REVIEWED**

Sol in water: 0.74%w @ 30 deg C
[Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985. 715]**PEER REVIEWED**

 

Spectral Properties:

INDEX OF REFRACTION: 1.5369 AT 20 DEG C/D; MAX ABSORPTION: 306 NM (LOG E= 3.64); SADTLER REFERENCE NUMBER: 2238 (IR, PRISM); MAX ABSORPTION (ALC): 238 NM (LOG E= 3.97)
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979.,p. C-192]**PEER REVIEWED**

Intense mass spectral peaks: 65 m/z, 92 m/z, 120 m/z, 152 m/z
[Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, FederalRepublic of Germany. 1985. 210]**PEER REVIEWED**

 

Surface Tension:

44.2 dynes/cm @ -19.8 deg C; 19.8 dynes/cm @ 212.2 deg C
[Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985. 715]**PEER REVIEWED**

 

Vapor Density:

5.2
[Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963. 1896]**PEER REVIEWED**

 

Vapor Pressure:

Vapor pressure = 0.0343 mm Hg @ 25 deg C
[Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.]**PEER REVIEWED**

 

Other Chemical/Physical Properties:

DENSITY OF NATURAL ESTER IS ABOUT 1.180
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 961]**PEER REVIEWED**

WINTERGREEN ESSENTIAL OIL: ESTER VALUE: 354-356; OPTICAL ROTATION: -0 DEG 25' TO -1 DEG 30'
[Fenaroli's Handbook of Flavor Ingredients. Volume 1. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975. 490]**PEER REVIEWED**

1 MM HG @ 54.0 DEG C
[Sax, N.I. Dangerous Properties of Industrial Materials. 5th ed. New York: Van Nostrand Rheinhold, 1979. 832]**PEER REVIEWED**

Heat capacity = 59.46 cal/deg K-mol @ 15-30 deg C
[Riddick, J.A., W.B. Bunger, Sakano T.K. Techniques of Chemistry 4th ed., Volume II. Organic Solvents. New York, NY: John Wiley and Sons., 1985. 715]**PEER REVIEWED**

 

Chemical Safety & Handling:

 

 

Fire Potential:

SLIGHT, WHEN EXPOSED TO HEAT OR FLAME; CAN REACT WITH OXIDIZING MATERIALS.
[Sax, N.I. Dangerous Properties of Industrial Materials. 5th ed. New York: Van Nostrand Rheinhold, 1979. 832]**PEER REVIEWED**

 

NFPA Hazard Classification:

Health: 1. 1= Materials that, on exposure, would cause irritation, but only minor residual injury, including those requiring the use of an approved air-purifying respirator. These materials are only slightly hazardous to health and breathing protection is needed.
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-72]**PEER REVIEWED**

Flammability: 1. 1= Materials that must be preheated before ignition will occur, such as class IIIB combustible liquids and solids and semi-solids whose flash point exceeds 200 deg F (93.4 deg C), as well as most ordinary combustible materials. Water may cause frothing if it sinks below the surface of the burning liquid and turns to steam. However, a water fog that is gently applied to the surface of the liquid will cause a frothing which will extinguish the fire.
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-72]**PEER REVIEWED**

Reactivity: 0. 0= Includes materials that are normally stable, even under fire exposure conditions, and that do not react with water. Normal fire fighting procedures may be used.
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-72]**PEER REVIEWED**

 

Flash Point:

205 Deg F (96 deg C) (Closed cup)
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-72]**PEER REVIEWED**

 

Autoignition Temperature:

850 DEG F
[National Fire Protection Guide. Fire Protection Guide on Hazardous Materials. 10 th ed. Quincy, MA: National Fire Protection Association, 1991.,p. 325M-72]**PEER REVIEWED**

 

Fire Fighting Procedures:

WATER, FOAM, CARBON DIOXIDE, DRY CHEMICAL.
[Sax, N.I. Dangerous Properties of Industrial Materials. 5th ed. New York: Van Nostrand Rheinhold, 1979. 832]**PEER REVIEWED**

 

Hazardous Reactivities & Incompatibilities:

INCOMPATIBILITIES: DECOMP BY ALKALIES TO FORM METHYL ALC & SALICYLATE.
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975. 1232]**PEER REVIEWED**

 

Stability/Shelf Life:

SENSITIVE TO LIGHT AND HEAT
[Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969. 77]**PEER REVIEWED**

 

Storage Conditions:

METHYL SALICYLATE SHOULD BE STORED AND DISPENSED IN TIGHT CONTAINERS.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

 

Disposal Methods:

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
**PEER REVIEWED**

 

Occupational Exposure Standards:

Manufacturing/Use Information:

Major Uses:

OIL: IN FERN AND CYPRESS TYPE PERFUMES & IN TOOTHPASTE
[Fenaroli's Handbook of Flavor Ingredients. Volume 1. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975. 490]**PEER REVIEWED**

MEDICATION (VET)
**PEER REVIEWED**

MEDICATION
**PEER REVIEWED**

UV-absorber in sunburn lotions; flavor in foods, beverages, pharmaceuticals; odorant
[Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987. 781]**PEER REVIEWED**

CHEWING GUM; FRAGRANCE IN DETERGENTS; SOLVENT FOR INSECTICIDES, POLISHES, AND INKS
[SRI]**PEER REVIEWED**

REPORTED USES: ... NON-ALCOHOLIC BEVERAGES 10 PPM; CANDY 900-5000 PPM.
[Fenaroli's Handbook of Flavor Ingredients. Volume 1. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975. 490]**PEER REVIEWED**

In perfumery as a modifier in blossom fragrances and as a mild antiseptic in oral hygiene products
[Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present.,p. VA11 202]**PEER REVIEWED**

/Medication:/ As a pharmaceutical, it is used in liniments & ointments for the relief of pain in the lumbar & sciatic regions, and for rheumatic conditions ... other misc applications for methyl salicylate are as a dye carrier, UV light stabilizer in acrylic resins, & chem intermed
[Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984.,p. V20 513]**PEER REVIEWED**

AS PHARMACEUTICAL NECESSITY, IT IS USED TO FLAVOR OFFICIAL AROMATIC CASCARA SAGRADA FLUID EXTRACT ... .
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975. 1232]**PEER REVIEWED**

 

Manufacturers:

Dow Chemical USA, 2020 Dow Center, Midland, MI 48674, (517) 636-1000
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 644]**PEER REVIEWED**

Kalama Chemical Inc, Hq, The Bank of California Center, Suite 1110, Seattle, WA 98164, (206) 682-7890; Production site: Garfield, NJ 07026
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 644]**PEER REVIEWED**

Penta Manufacturing Co, PO Box 1448, Fairfield, NJ 07007, (201) 740-2300
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 644]**PEER REVIEWED**

Rhone-Poulenc Inc, Hq, CN 5266, Princeton, NJ 08543-5266, (908) 297-0100; Rhone-Poulenc Specialty Chemicals Div, Fine Organics Business Group, Prospect Palins Rd, CN-7500, Cranbury, NJ 08512, (609) 860-4000; Production site: St Louis, MO 63104
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 644]**PEER REVIEWED**

 

Methods of Manufacturing:

...OIL IS WATER-STEAM DISTILLED FROM LEAVES CHARGED INTO THE STILL AND ALLOWED TO MACERATE FOR SEVERAL HR TO HYDROLYZE GAULTHERIN GLUCOSIDE (METHYL SALICYLATE + GLUCOSE). DISTILLATION FROM 5-6 HR YIELDS APPROXIMATELY 0.7% ESSENTIAL OIL. OFTEN ADULTERATED BY CO-DISTILLING SWEET BIRCH BARK.
[Fenaroli's Handbook of Flavor Ingredients. Volume 1. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975. 490]**PEER REVIEWED**

MOSTLY PREPD BY ESTERIFICATION OF SALICYLIC ACID WITH METHANOL. PRODUCT OF COMMERCE IS ABOUT 99% PURE.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 961]**PEER REVIEWED**

 

General Manufacturing Information:

WINTERGREEN: DESCRIPTION OF BOTANICAL SOURCE: EVERGREEN SHRUB WITH SLENDER, CREEPING STEMS, ASSURGENT, FLOWERING BRANCHES WITH LEAVES CLUSTERED AT TOP, WHITE, BELL-SHAPED FLOWERS BLOSSOMING IN JULY-AUGUST, FOLLOWED BY RED BERRIES (CHECKERBERRY). ...IN WOODS OF CANADA AND US.
[Fenaroli's Handbook of Flavor Ingredients. Volume 1. Edited, translated, and revised by T.E. Furia and N. Bellanca. 2nd ed. Cleveland: The Chemical Rubber Co., 1975. 489]**PEER REVIEWED**

VET: NATURAL & SYNTHETIC GRADES ARE USED INTERCHANGEABLY.
[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974. 360]**PEER REVIEWED**

METHYL SALICYLATE MUST BE LABELED TO INDICATE WHETHER IT WAS MADE SYNTHETICALLY OR DISTILLED FROM...PLANTS...
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975. 1232]**PEER REVIEWED**

IN USP, GAULTHERIA OIL, BETULA OIL, & METHYL SALICYLATE ARE COMBINED UNDER SAME TITLE...IT IS DIFFICULT TO DISTINGUISH BETWEEN THEM CHEMICALLY &...SAME TEST APPLY TO ALL. ...SLIGHT DIFFERENCES IN SPECIFIC GRAVITY & OPTICAL ACTIVITY BUT THESE FACTORS ARE NOT SUFFICIENTLY CHARACTERISTIC TO ENABLE DETECTION OF EITHER IN MIXT.
[Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975. 1232]**PEER REVIEWED**

 

Formulations/Preparations:

USP: LINIMENT, COMPOUND: MENTHOL 4.5 G, CAMPHOR OIL RECTIFIED 25 ML, OLIVE OR PEANUT OIL 30 ML, METHYL SALICYLATE TO MAKE 100 ML. OINTMENT, COMPOUND: METHYL SALICYLATE 10 ML, MENTHOL 10 G, WHITE WAX 5 G, HYDROUS WOOL FAT TO MAKE 100 G.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

USP: SPIRIT, PHENOLATED (PODIATRY): LIQUEFIED PHENOL 1 ML, METHYL SALICYLATE 3 ML, COMPOUND MYRCIA SPIRIT 25 ML, ALCOHOL RUBBING COMPOUND TO MAKE 100 ML.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

GRADES: TECHNICAL; USP; FCC.
[Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977. 578]**PEER REVIEWED**

 

U. S. Production:

(1976) 1.27X10+8 G (MIN CONSUMPTION IN FOODS)
[SRI]**PEER REVIEWED**

(1978) 4.09X10+7 G (CONSUMPTION AS FRAGRANCE)
[SRI]**PEER REVIEWED**

 

U. S. Imports:

(1977) 8.19X10+7 GRAMS (PRINCPL CUSTMS DISTS)
[SRI]**PEER REVIEWED**

(1979) 4.58X10+7 GRAMS
[SRI]**PEER REVIEWED**

(1985) 3.43X10+8 g
[BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1985 p.1-564]**PEER REVIEWED**

Laboratory Methods:

Analytic Laboratory Methods:

QUANTITATIVE FOR METHYL SALICYLATE OFFICIAL FINAL ACTION, GAS CHROMATOGRAPHY.
[Association of Official Analytical Chemists. Official Methods of Analysis. 10th ed. and supplements. Washington, DC: Association of Official Analytical Chemists, 1965. New editions through13th ed. plus supplements, 1982.,p. 13/197-12.046]**PEER REVIEWED**

NMR PROCEDURE IS DESCRIBED FOR QUANTITATIVE DETERMINATION OF METHYL SALICYLATE AS DRUG ENTITY & IN WINTERGREEN OIL.
[EL-OBEID HA, HASSAN MM A; SPECTROSC LETT 12 (7-8): 555 (1979)]**PEER REVIEWED**

CONCN OF SALICYLATES OR OTHER COMPLEXING AGENTS IN 26 SAMPLES OF 20 DIFFERENT FLAVORS WAS DETERMINED. COLORIMETRIC METHOD PROVIDING SENSITIVITY TO APPROX 1 PPM WAS USED.
[CATES LA, BRANDINO TF; CAN J HOSP PHARM 32 (NOV-DEC): 169 (1979)]**PEER REVIEWED**

Special References:

Synonyms and Identifiers:

Synonyms:

ANALGIT
**PEER REVIEWED**

BENZOIC ACID, 2-HYDROXY-, METHYL ESTER
**PEER REVIEWED**

BETULA
**PEER REVIEWED**

BETULA OIL
**PEER REVIEWED**

EXAGIEN
**PEER REVIEWED**

FEMA NUMBER 2745
**PEER REVIEWED**

FLUCARMIT
**PEER REVIEWED**

GAULTHERIA OIL
**PEER REVIEWED**

GAULTHERIA OIL, ARTIFICIAL
**PEER REVIEWED**

O-HYDROXYBENZOIC ACID, METHYL ESTER
**PEER REVIEWED**

2-HYDROXYBENZOIC ACID METHYL ESTER
**PEER REVIEWED**

2-(METHOXYCARBONYL)PHENOL
**PEER REVIEWED**

METHYL O-HYDROXYBENZOATE
**PEER REVIEWED**

METHYL 2-HYDROXYBENZOATE
**PEER REVIEWED**

METYLESTER KYSELINY SALICYLOVE (CZECH)
**PEER REVIEWED**

NATURAL WINTERGREEN OIL
**PEER REVIEWED**

Oil of Wintergreen
**PEER REVIEWED**

SALICYLIC ACID, METHYL ESTER
**PEER REVIEWED**

SWEET BIRCH OIL
**PEER REVIEWED**

SYNTHETIC WINTERGREEN OIL
**PEER REVIEWED**

TEABERRY OIL
**PEER REVIEWED**

WINTERGREEN OIL
**PEER REVIEWED**

WINTERGREEN OIL, SYNTHETIC
**PEER REVIEWED**

 

Formulations/Preparations:

USP: LINIMENT, COMPOUND: MENTHOL 4.5 G, CAMPHOR OIL RECTIFIED 25 ML, OLIVE OR PEANUT OIL 30 ML, METHYL SALICYLATE TO MAKE 100 ML. OINTMENT, COMPOUND: METHYL SALICYLATE 10 ML, MENTHOL 10 G, WHITE WAX 5 G, HYDROUS WOOL FAT TO MAKE 100 G.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

USP: SPIRIT, PHENOLATED (PODIATRY): LIQUEFIED PHENOL 1 ML, METHYL SALICYLATE 3 ML, COMPOUND MYRCIA SPIRIT 25 ML, ALCOHOL RUBBING COMPOUND TO MAKE 100 ML.
[American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984.,p. 84:2404]**PEER REVIEWED**

GRADES: TECHNICAL; USP; FCC.
[Hawley, G.G. The Condensed Chemical Dictionary. 9th ed. New York: Van Nostrand Reinhold Co., 1977. 578]**PEER REVIEWED**

RTECS Number:

NIOSH/VO4725000

Administrative Information:

Hazardous Substances Databank Number: 1935

Last Revision Date: 20010808

Last Review Date: Reviewed by SRP on 9/29/1994

Update History:

Field Update on 08/08/2001, 1 field added/edited/deleted.
Field Update on 05/29/2001, 1 field added/edited/deleted.
Field Update on 09/12/2000, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/26/1999, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 04/07/1998, 3 fields added/edited/deleted.
Field Update on 10/23/1997, 1 field added/edited/deleted.
Complete Update on 01/27/1997, 1 field added/edited/deleted.
Complete Update on 05/10/1996, 1 field added/edited/deleted.
Complete Update on 01/23/1996, 1 field added/edited/deleted.
Complete Update on 11/10/1995, 1 field added/edited/deleted.
Complete Update on 05/26/1995, 1 field added/edited/deleted.
Complete Update on 04/25/1995, 1 field added/edited/deleted.
Complete Update on 01/12/1995, 58 fields added/edited/deleted.
Field Update on 12/28/1994, 1 field added/edited/deleted.
Field Update on 11/03/1994, 1 field added/edited/deleted.
Field Update on 11/02/1994, 1 field added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Field update on 12/22/1992, 1 field added/edited/deleted.
Field update on 11/09/1990, 1 field added/edited/deleted.
Complete Update on 11/01/1990, 3 fields added/edited/deleted.
Complete Update on 09/03/1987

Record Length: 74705