Salicylamide

DEA NFLIS-Drug Category -> Analgesics

Pharmaceuticals -> Listed in ZINC15

Pharmaceutical

Log Kow = 1.28

1.280

1.175 at 284 °F (NTP, 1992) - Denser than water; will sink

1.175 @ 140 °C/4 °C

WHITE OR SLIGHTLY PINK CRYSTALLINE POWDER

YELLOW LEAFLETS FROM DILUTE ALCOHOL

less than 1 mg/mL at 68 °F (NTP, 1992)

SOLUBILITY IN WATER: 0.2% @ 30 °C; 0.8% @ 47 °C; IN GLYCEROL: 2.0% @ 5 °C; 5.0% @ 39 °C; 10.0% @ 60 °C; IN PROPYLENE GLYCOL: 10.0% @ 5 °C

SLIGHTLY SOL IN NAPHTHA, CARBON TETRACHLORIDE

FREELY SOL IN SOLN OF ALKALIES

SOL IN CHLOROFORM, ALC, ETHER

518 °F at 760 mmHg (decomposes) (NTP, 1992)

181.5 °C @ 14 MM HG

181.50 °C. @ 760.00 mm Hg

Warning

H302 (99.3%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 851 reports by companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

Chemical: Benzamide, 2-hydroxy-

Status: Active Update: 21-03-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/2210

Salicylamide: Does not have an individual approval but may be used under an appropriate group standard

SYMPTOMS: Symptoms of exposure to this compound include dizziness, drowsiness, nausea, vomiting, epigastric distress, allergic reactions and blood dyscrasias. It can cause central nervous depression, hypotension and respiratory arrest. This compound may greatly potentiate the hepatic toxicity of acetaminophen. It may also cause hyperpnea, renal failure, prolonged bleeding time, a mild burning pain in the mouth, throat and abdomen, lethargy, tinnitus hearing loss, excitability, delirium, fever, sweating, dehydration, incoordination, restlessness, ecchymoses, coma, convulsions, cyanosis, oliguria, uremia, pulmonary edema, gastric ulcer, weight loss and mental deterioration. Other symptoms may include skin eruptions, headache, difficulty in hearing, dimness of vision, lassitude and hyperventilation.

2-HYDROXYBENZAMIDE is an amide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx). This chemical may be sensitive to prolonged exposure to light. (NTP, 1992)

Acute Tox. 4 (99.3%)

Acute toxicity (Oral) - Category 4

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

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.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

...MUTUAL COMPETITIVE INHIBITION IN THE FORMATION OF SULFATES, AND PROBABLY GLUCURONIDES, OF ACETAMINOPHEN AND SALICYLAMIDE IN MAN /HAS BEEN DEMONSTRATED/.

BIOLOGICAL HALF-LIFE OF SALICYLAMIDE...INCR SOMEWHAT BY IV ASCORBIC ACID & MORE BY ORAL ASCORBIC ACID; PLASMA LEVELS OF SALICYLAMIDE & GLUCURONIDE METABOLITE INCR WHILE LEVELS OF SULFATE METABOLITE DECR. ...MAX INHIBITION OF SULFATE CONJUGATION OR SALICYLAMIDE BY ASCORBIC ACID WHEN BOTH...IN HIGH CONCN IN INTESTINAL WALL & LIVER.

SALICYLAMIDE ADMIN DECR RADIOSULFATE UPTAKE BY MATERNAL SERUM & LIVER, FETUS, & PLACENTA; EFFECTS BEING DOSE-DEPENDENT.

IN THE PRESENCE OF SALICYLAMIDE, 7,12-DIMETHYLBENZ(A)ANTHRACENE LOST ITS ABILITY TO INDUCE DNA-REPAIR SYNTHESIS IN RAT HEPATOCYTES. THIS FAILURE TO INDUCE DNA REPAIR IS DUE TO INHIBITION OF A SULFATE ESTER INTERMEDIATE.

For more Interactions (Complete) data for SALICYLAMIDE (12 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a recommended classification scheme(1), an estimated Koc value of 118(SRC), determined from an experimental log Kow(2) and a recommended regression-derived equation(3), indicates that salicylamide will have high mobility in soil(SRC). Volatilization of salicylamide will not be important from moist soil surfaces(SRC) given an estimated Henry's Law constant of 2.9X10-10 atm-cu m/mole(4,SRC), or from dry soil surfaces(SRC) based on an estimated vapor pressure of 6.9X10-6 mm Hg(5,SRC). Insufficient data are available to determine the rate or importance of biodegradation of salicylamide in soil(SRC), but its structure would suggest rapid biodegradation(6,SRC).

AQUATIC FATE: Based on a recommended classification scheme(1), an estimated Koc value of 118(SRC), determined from an experimental log Kow(2) and a recommended regression-derived equation(3), indicates that salicylamide may not adsorb to suspended solids and sediment(SRC) in the water. Salicylamide will be essentially nonvolatile from water surfaces based on an estimated Henry's Law constant of 2.9X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). An estimated BCF value of 5.5(3,SRC), from an experimental log Kow(2), suggests that salicylamide will not bioconcentrate in aquatic organisms(SRC) according to a recommended classification scheme(5). Insufficient data are available to determine the rate or importance of biodegradation of salicylamide in water(SRC), but its structure would suggest rapid biodegradation(6,SRC).

ATMOSPHERIC FATE: According to a suggested classification scheme(1), an estimated vapor pressure of 6.9X10-6 mm Hg at 25 °C(2,SRC) indicates that salicylamide will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase salicylamide is degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be about 12 hours(3,SRC). Particulate-phase salicylamide may be physically removed from the air by wet and dry deposition(SRC). The reaction of phenols with nitrate radicals may also be important(4).

The Koc of salicylamide is estimated as approximately 118(SRC), using an experimental log Kow of 1.28(1) and a regression-derived equation(2,SRC). According to a recommended classification scheme(3), this estimated Koc value suggests that salicylamide has high mobility in soil(SRC).

GASTROINTESTINAL IRRITATION OCCURS IN ABOUT 10% OF PATIENTS, AND DROWSINESS AND DIZZINESS ARE OBSERVED IN APPROXIMATELY 10 AND 20%, RESPECTIVELY.

In contrast to salicylates, salicylamide overdosage produces CNS depression, hypotension, and eventually respiratory arrest, but does not produce excitement, seizures, metabolic acidosis, or hypoprothrombinemia.

Little information is available on the acute toxicity of salicylamide. Salicylamide is generally considered to be less toxic than salicylates in overdosage but unequivocal evidence in humans is lacking ... .

Toxic epidermal necrolysis (Lyell's syndrome) with erythematous skin lesions and bulla formation developed in a 4 yr old girl. An accurate diagnosis using the cryostat technique on top of a bulla was available within 1 hr of hospital admission. The course was unusually mild, probably because of early treatment with corticosteroids. Skin prick tests revealed salicylamide was the agent responsible for inducing the /condition/. The patient was advised to avoid this substance for the rest of her life.

Salicylamide's production and use as an analgesic(1), antipyretic(1), antirheumatic(2), sedative(2), and for protection against mildew and fungus in a variety of soaps, salves, lotions, and oils(3) may result in its release to the environment through various waste streams(SRC).

An estimated BCF value of 5.5 was calculated for salicylamide(SRC), using an experimental log Kow of 1.28(1) and a recommended regression-derived equation(2). According to a recommended classification scheme(3), this BCF value suggests that bioconcentration in aquatic organisms will not be an important fate process(SRC).

The Henry's Law constant for salicylamide is estimated as 2.9X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This value indicates that salicylamide will be essentially nonvolatile from water surfaces(2,SRC). Salicylamide's low vapor pressure, 6.9X10-6 mm Hg(3,SRC) and low Henry's Law constant(1,SRC) indicate that volatilization from dry and moist soil will not occur(SRC).

EXPERIMENTS IN RATS SHOW...A MUCH MORE RAPID AND GREATER CENTRAL NERVOUS SYSTEM DEPRESSANT EFFECT THAN ASPIRIN... THIS DRUG IS REPORTED TO BE LESS IRRITATING TO THE GASTRIC MUCOSA OF THE RAT THAN IS ASPIRIN.

.../IT/ IS TEN TIMES AS TOXIC TO THE CAT AS IT IS TO THE RAT, RABBIT, DOG...CAUSING ACUTE OLIGURIC NEPHROSIS.

.../SALICYLAMIDE/ PRODUCES /SRP: CNS DEPRESSION/, DEPRESSION, PARALYSIS, & DEATH IN HIGH DOSAGE WHEREAS COMPARABLE USE OF ORDINARY SALICYLATES PRODUCES STIMULATIONS & CONVULSIONS...FOLLOWED BY DEATH.

ABSENCE OF A GLUCURONIDATION PATHWAY IN CAT COULD EXPLAIN THE VERY MUCH GREATER TOXICITY OF SALICYLAMIDE IN THIS SPECIES COMPARED WITH MAN & MOST ANIMALS.

For more Non-Human Toxicity Excerpts (Complete) data for SALICYLAMIDE (7 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of salicylamide with photochemically produced hydroxyl radicals has been estimated as 3.25X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1,SRC). This corresponds to an atmospheric half-life of about 12 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1,SRC). The reaction of phenols with nitrate radicals may also be important(2).

Based on its use as an analgesic(1), antipyretic(1), antirheumatic(2), sedative(2), and for protection against mildew and fungus in a variety of soaps, salves, lotions, and oils(3), the general population may be exposed to salicylamide through ingestion of salicylamide containing pharmaceuticals and through dermal contact from the use of certain soaps and lotions(SRC).

Salicylamide's production and use as an analgesic, antipyretic, antirheumatic, sedative, and for protection against mildew and fungus in a variety of soaps, salves, lotions, and oils may result in its release to the environment through various waste streams. If released to soil, salicylamide will have high mobility. Volatilization of salicylamide will not be important from moist or dry soil surfaces. Insufficient data are available to determine the rate or importance of biodegradation of salicylamide in soil or water but its structure would suggest rapid biodegradation. If released to water, salicylamide may not adsorb to suspended solids and sediment. Salicylamide will be essentially nonvolatile from water surfaces. An estimated BCF value of 5.5(3,SRC) suggests that salicylamide will not bioconcentrate in aquatic organisms. If released to the atmosphere, salicylamide will exist in both the vapor and particulate phases. Although salicylamide has not been detected in the atmosphere, vapor-phase salicylamide is degraded in the atmosphere by reaction with photochemically produced hydroxyl radicals with an estimated half-life of about 12 hours. Particulate-phase salicylamide may be physically removed from the air by wet and dry deposition. The reaction of phenols with nitrate radicals may also be important. The general population may be exposed to salicylamide through ingestion of salicylamide containing pharmaceuticals and use of certain soaps and lotions. (SRC)

N - Nervous system

QN - Nervous system

SALICYLAMIDE IS CONJUGATED BY INTESTINAL MUCOSA AFTER ORAL ADMINISTRATION...

AFTER ADMIN OF SALICYLAMIDE TO CATS NO GLUCURONIDE CONJUGATE COULD BE DETECTED IN URINE. INCR AMT OF SULFURIC ACID ESTER CONJUGATE & SUBSTANTIALLY GREATER AMT OF 2,3-DIHYDROXYBENZAMIDE WERE PRODUCED BY CAT COMPARED WITH RABBIT.

SALICYLAMIDE GIVES SALICYLAMIDE-2-BETA-D-GLUCURONIDE & SALICYLAMIDE-2-SULFATE IN MAN. /FROM TABLE/

AFTER ADMIN OF 5 MG/KG SALICYLAMIDE IN 5 MG/KG TYLENOL SUSPENSION, CHILDREN EXCRETED 78% OF DOSE AS SALICYLAMIDE SULFATE; ADULTS 36%. IN ADULTS, GLUCURONIDE WAS MAJOR PRODUCT. GLUCURONIDE CONJUGATION DEFICIENCY IN CHILDREN IS ACCOMPANIED BY A HIGHER RATE OF SULFATE FORMATION.

For more Metabolism/Metabolites (Complete) data for SALICYLAMIDE (10 total), please visit the HSDB record page.

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.

WHEN...GIVEN ORALLY...IT IS ABSORBED AND EXCRETED SO RAPIDLY THAT HIGH PLASMA LEVELS ARE NOT OBTAINED. IT DIFFUSES QUICKLY INTO THE VARIOUS BODY TISSUES AND INTO A MUCH GREATER APPARENT VOLUME OF BODY WATER... ANIMAL STUDIES SHOW...DIFFUSION RAPIDLY INTO THE BRAIN.

/IN THE RABBIT/ RATE OF TRANSPORT OF FREE DRUG ACROSS BASAL BARRIER WAS BLOOD-FLOW-LIMITED, WHILE TRANSPORT OF THE GLUCURONIDE WAS LIMITED BY TRANSPORT STEP OUT OF EPITHELIAL CELL RATHER THAN BY RATE OF SYNTHESIS.

...WHEN DOSE OF SALICYLAMIDE EXCEEDS ABOUT 1 G...SIGNIFICANT LEVELS OF UNCHANGED DRUG APPEAR IN PLASMA.

BIOAVAILABILITY STUDIES IN HUMAN/S/...INDICATED THAT SODIUM SALICYLAMIDE IN SOLN IS ABSORBED FASTER AFTER ORAL DOSES THAN SALICYLAMIDE IN TABLETS. SEDATIVE EFFECT OCCURRED EARLIER WITH NA SALT THAN WITH SALICYLAMIDE & EXTENT OF SEDATION INCR WITH INCR DOSES OF BOTH COMPD.

For more Absorption, Distribution and Excretion (Complete) data for SALICYLAMIDE (9 total), please visit the HSDB record page.

MEDICATION

MEDICATION (VET):

(1972) 1.6X10+8 GRAMS (PRINCPL CUSTMS DISTS)

(1975) 1.38X10+8 GRAMS (PRINCPLE CUSTMS DISTS)

(1983) 7.54X10+7 g

SALICYLAMIDE, NF CAPSULES, 200 MG, WITH METHAPYRILENE HYDROCHLORIDE 50 MG & SCOPOLAMINE AMINOXIDE HYDROBROMIDE 500 UG (SOMINEX); CAPSULES, 324 MG, WITH METHAPYRILENE HYDROCHLORIDE 12 MG & SCOPOLAMINE AMINOXIDE HYDROBROMIDE 150 MG (DEVAREX).

TABLETS, NF, 230 MG (AMID-SAL) & 600 MG (SALRIN); TABLETS, 200 MG WITH METHAPYRILENE HYDROCHLORIDE 25 MG (NYTOL); WITH SCOPOLAMINE AMINOXIDE HYDROBROMIDE 250 UG (SOMINEX); TABLETS, 250 MG WITH METHAPYRILENE HYDROCHLORIDE 25 MG & SCOPOLAMINE HYDROBROMIDE 200 UG (SURE-SLEEP).

LIQUIPRIN...ORAL: SOLN 60 MG/ML; SALAMIDE...SALICIM...ORAL: TABLETS 300 MG; SALRIN...ORAL: TABLETS 300 & 600 MG.

GRADES: TECHNICAL; NF.

Cosmetics -> Keratolytic

Pharmaceuticals