Aspirin

1.18

log Kow = 1.19

1.19

1.19

Odorless, but in moist air it is gradually hydrolyzed and acquires odor of acetic acid

Odorless [Note: Develops the vinegar-like odor of acetic acid on contact with moisture].

1.4 (NTP, 1992) - Denser than water; will sink

1.40

1.4 g/cm³

1.35

1.35

Monoclinic tablets or needle-like crystals

Colorless to white, crystalline powder.

less than 1 mg/mL at 73 °F (NTP, 1992)

10

1 g sol in: 300 mL water at 25 °C, 100 mL water at 37 °C, 5 mL alcohol, 17 mL chloroform, 10-15 mL ether; less sol in anhydrous ether

In water, 4,600 mg/L at 25 °C

Solubility in water, g/100ml at 15 °C: 0.25 (poor)

(77 °F): 0.3%

482 °F (NTP, 1992)

284 °F at 760 mmHg (decomposes) (NTP, 1992)

140

284 °F (decomposes)

284 °F (Decomposes)

When heated to decomposition it emits acrid smoke and fumes.

140 °C

275 °F (NTP, 1992)

138-140

135 °C (rapid heating)

135 °C

135 °C

275 °F

0 mmHg (approx) (NIOSH, 2024)

2.52X10-5 mm Hg at 25 °C (calc)

Vapor pressure, Pa at 25 °C: ~ 0.004

0 mmHg (approx)

0 mmHg (approx)

Acetylsalicylic acid appears as odorless white crystals or crystalline powder with a slightly bitter taste. (NTP, 1992)

Odorless, colorless to white, crystal-line powder. [aspirin] [Note: Develops the vinegar-like odor of acetic acid on contact with moisture.]

Solid

COLOURLESS-TO-WHITE CRYSTALS OR WHITE CRYSTALLINE POWDER WITH CHARACTERISTIC ODOUR.

Odorless, colorless to white, crystal-line powder.

Odorless, colorless to white, crystal-line powder. [aspirin] [Note: Develops the vinegar-like odor of acetic acid on contact with moisture.]

STABLE IN DRY AIR; IN MOIST AIR IT IS GRADUALLY HYDROLYZED INTO SALICYLIC AND ACETIC ACIDS

In aqueous solutions, aspirin is most stable at a pH of 2-3, less stable at a pH of 4-8, and least stable at a pH less than 2 or greater than 8. In a saturated aqueous solution at a pH of 5-7, aspirin is almost completely hydrolyzed within 1 week at 25 °C.

This chemical does not meet GHS hazard criteria for 0.3% (1 of 315) of reports.

Warning

H302 (95.6%): Harmful if swallowed [Warning Acute toxicity, oral]；H315 (20.6%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (22.2%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H335 (20%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, 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 315 reports by companies from 23 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 1 of 315 reports by companies.；There are 22 notifications provided by 314 of 315 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Chemical: Benzoic acid, 2-(acetyloxy)-

Hazard Traits - Developmental Toxicity; Reproductive Toxicity；Authoritative List - Prop 65；Report - regardless of intended function of ingredient in the product

Status: Active Update: 02-04-2013 https://echa.europa.eu/registration-dossier/-/registered-dossier/10841；Status: Active Update: 27-03-2015 https://echa.europa.eu/registration-dossier/-/registered-dossier/7490

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

IMAP assessments - Benzoic acid, 2-(acetyloxy)-: Environment tier I assessment；IMAP assessments - Benzoic acid, 2-(acetyloxy)-: Human health tier I assessment

Poison

This chemical is combustible. (NTP, 1992)

Combustible. Finely dispersed particles form explosive mixtures in air.

SLIGHT WHEN EXPOSED TO HEAT OR FLAME

Excerpt from NIOSH Pocket Guide for Acetylsalicylic acid:；Exposure Routes: Inhalation, ingestion, skin and/or eye contact；Symptoms: Irritation eyes, skin, upper respiratory system; increased blood clotting time; nausea, vomiting; liver, kidney injury；Target Organs: Eyes, skin, respiratory system, blood, liver, kidneys (NIOSH, 2024)

Aspirin poisoning was one of the leading causes of accidental death in children until child-proof bottles were developed; After ingestion, causes stimulation of respiratory center in brain and metabolic acidosis; Prolongs prothrombin time and complicated by cerebral and pulmonary edema; 1 aspirin tablet = 325-650 mg acetylsalicylic acid; 1 teaspoon concentrated oil of wintergreen = 5 g of methyl salicylate (equivalent to 7.5 g of acetylsalicylic acid); Acute ingestion of 150-200 mg/kg aspirin = mild intoxication; Acute ingestion of 300-500 mg/kg aspirin = severe intoxication; [Olson, p. 410-11] TLV Basis = Bleeding and respiratory sensitization. An oral dose of 30mg/person of ASA (0.45 mg/kg per day) given daily for 3 weeks resulted in a significant prolongation of bleeding time (1.6 times control values) . . . ASA is a known respiratory and systemic allergen in humans, which may result in an anaphylactic phenomenon known as aspirin-exacerbated respiratory disease (AERD). It can occur at oral doses as low as 81 mg daily. [ACGIH TLVs and BEIs]

Acids, Carboxylic；Esters, Sulfate Esters, Phosphate Esters, Thiophosphate Esters, and Borate Esters

International Programme on Chemical Safety; Poisons Information Monograph: Acetylsalicylic Acid (PIM 006) (1991) Available from http://www.inchem.org/pages/pims.html as of March 10, 2008

Vacated 1989 OSHA PEL TWA 5 mg/cu m is still enforced in some states.

The active ingredient in common aspirin. Incompatible with oxidizers and strong acids. Also incompatible with strong bases. May react with water or nucleophiles (e.g. amines and hydroxy groups). May also react with acetanilide, amidopyrine, phenazone, hexamine, iron salts, phenobarbitone sodium, quinine salts, potassium and sodium iodides, alkali hydroxides, carbonates, stearates and paracetanol. (NTP, 1992)

The solution in water is a weak acid.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Use water spray, powder, foam, carbon dioxide.

Fresh air, rest. Refer for medical attention.

Rinse skin with plenty of water or shower. Refer for medical attention .

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Refer for medical attention .

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.；SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.；INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.；INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

(General first aid procedures)；Eye: Irrigate immediately - If this chemical contacts the eyes, immediately wash (irrigate) the eyes with large amounts of water, occasionally lifting the lower and upper lids. Get medical attention immediately.；Skin: Soap wash - If this chemical contacts the skin, wash the contaminated skin with soap and water.；Breathing: Respiratory support；Swallow: Medical attention immediately - If this chemical has been swallowed, get medical attention immediately.

Well closed.

Chewable aspirin tablets containing 81 mg of the drug should be stored in child-resistant containers holding not more than 36 tablets each in order to limit the potential toxicity associated with accidental ingestion in children. Aspirin suppositories should be stored at 2-15 °C.

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.；STORAGE PRECAUTIONS: You should store this material under ambient temperatures and protect it from moisture. (NTP, 1992)

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.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

Contact lenses should not be worn when working with this chemical.

The worker should immediately wash the skin when it becomes contaminated.

Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premises.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]:；IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.；SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.；FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

Wear safety goggles.

NO open flames. Closed system, dust explosion-proof electrical equipment and lighting. Prevent deposition of dust.

Acetylsalicylic acid and the acetylsalicylate ion were detected in the breast milk of nursing mothers within 1 hour of aspirin (acetylsalicylic acid) ingestion(1).

Prolonged concurrent use of acetaminophen with a salicylate is not recommended because chronic, high-dose administration of the combined analgesics (1.35 g daily, or cumulative ingestion of 1 kg annually, for 3 years or longer) significantly increases the risk of analgesic nephropathy, renal papillary necrosis, end-stage renal disease, and cancer of the kidney or urinary bladder; also, recommended that for short-term use the combined dose of acetaminophen plus a salicylate not exceed that recommended for acetaminophen or a salicylate given individually. /Salicylates/

The possibility should be considered that additive or multiple effects leading to impaired blood clotting and/or increased risk of bleeding may occur if a salicylate, especially aspirin, is used concurrently with any medication having a significant potential for causing hypoprothrombinemia, thrombocytopenia, or gastrointestinal ulceration or hemorrhage.

Aspirin may decrease the bioavailability of many nonsteroidal anti-inflammatory drugs (NSAIDs), including diflunisal, fenoprofen, indomethacin, meclofenamate, piroxicam (up to 80% of the usual plasma concentration), and the active sulfide metabolite of sulindac; aspirin has also been shown to decrease the protein binding and increase the plasma clearance of ketoprofen, and to decrease the formation and excretion of ketoprofen conjugates. Concurrent use of other NSAIDs with aspirin may also increase the risk of bleeding at sites other than the gastrointestinal tract because of additive inhibition of platelet aggregation.

Concurrent use of these medications /alcohol or other nonsteroidal anti-inflammatory drugs (NSAIDs)/ with a salicylate may increase the risk of gastrointestinal side effects, including ulceration and gastrointestinal blood loss; also, concurrent use of a salicylate with an NSAID may increase the risk of severe gastrointestinal side effects without providing additional symptomatic relief and is therefore not recommended. /Salicylate/

For more Interactions (Complete) data for ACETYLSALICYLIC ACID (21 total), please visit the HSDB record page.

Eyes, skin, respiratory system, blood, liver, kidneys

Might increase the risk of gastrointestinal bleeding; large doses of salicylate, a metabolite of aspirin, have been proposed to cause tinnitus; Reye's syndrome, a severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illnesses or infections. [Wikipedia]

Patients on long term, moderate-to-high dose aspirin therapy frequently have elevations in serum ALT levels. With high doses, ALT elevations are common and can be marked and associated with mild increases in alkaline phosphatase and bilirubin. The more dramatic examples of aspirin hepatotoxicity usually occur with doses of 1,800 to 3,200 mg daily (>100 mg/kg) and with salicylate levels of greater than 25 mg/dL, but mild-to-moderate ALT elevations occur with even lower doses and lower serum levels. These abnormalities resolve rapidly with discontinuation of aspirin, but instances of resolution despite continuation of aspirin in the same or lower doses (adaptation) have also been described. The hepatotoxicity of aspirin is usually mild and asymptomatic, although with higher doses symptoms of nausea, anorexia and abdominal pain and even encephalopathy with signs of hepatic dysfunction (hyperammonemia and coagulopathy) can occur. Bilirubin elevations are usually mild or absent. Mild eosinophilia may accompany the enzyme elevations, but rash, fever and other allergic manifestations are rare. Liver biopsy histology generally shows minimal injury despite the height of the enzyme elevations; electron microscopy may reveal fat and mitochondrial abnormalities. Aspirin can often be continued in lower doses safely.；Likelihood score: A[HD] (well known cause of clinically apparent liver injury when given in high doses).

LC50; Species: Daphnia magna (Water flea, <24 hr neonate); Conditions: freshwater, static, 21 °C, pH 7.6; Concentration: 8.15 mM for 24 hr

LC50; Species: Daphnia pulex (Water flea, <24 hr); Conditions: freshwater, static, 20 °C, pH 7.6; Concentration: 2.00 mM for 24 hr

LC50; Species: Artemia salina (Brine shrimp, age 2-3 instar larva); Conditions: saltwater, static, salinity 35 ppt; Concentration: 2120 umol/L for 24 hr

LC50; Species: Streptocephalus proboscideus (Fairy shrimp, age 2-3 instar larva); Conditions: saltwater, static, 25 °C, salinity 15 ppt; Concentration: 988 umol/L for 24 hr

For more Ecotoxicity Values (Complete) data for ACETYLSALICYLIC ACID (6 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 100(SRC), determined from a log Kow of 1.19(2) and a regression-derived equation(3), indicates that acetylsalicylic acid is expected to have high mobility in soil(SRC). The pKa of acetylsalicylic acid is 3.49(4), indicating that this compound will almost entirely exist in anion form in the environment and anions generally do not adsorb as strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of acetylsalicylic acid from moist soil surfaces will not be an important fate process(SRC) since anions do not volatilize. Acetylsalicylic acid is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 2.5X10-5 mm Hg(6). No biodegradation studies were located for acetylsalicylic acid in soil(SRC, 2008); however, acetylsalicylic acid was classified as readily biodegradable in screening tests(7,8). An aqueous hydrolysis half-life of 6.3 days at pH 7.4 and 17 °C(9), suggests hydrolysis may occur in moist soils(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 100(SRC), determined from a log Kow of 1.19(2) and a regression-derived equation(3), indicates that acetylsalicylic acid is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 3.49(4) indicates acetylsalicylic acid will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A hydrolysis half-life of 6.3 days at pH 7.4 and 17 °C was calculated for acetylsalicylic acid(7). No biodegradation studies were located for acetylsalicylic acid in water(SRC, 2008); however, acetylsalicylic acid was classified as readily biodegradable in screening tests(8,9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), acetylsalicylic acid, which has a vapor pressure of 2.5X10-5 mm Hg at 25 °C(2) is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase acetylsalicylic acid 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 12 days(SRC), calculated from its rate constant of 1.3X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase acetylsalicylic acid may be removed from the air by wet or dry deposition(SRC). Acetylsalicylic acid contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).

Asthma - Reversible bronchoconstriction (narrowing of bronchioles) initiated by the inhalation of irritating or allergenic agents.；ACGIH Carcinogen - Not Classifiable.

The substance can be absorbed into the body by inhalation and by ingestion.

inhalation, ingestion, skin and/or eye contact

Absorption is generally rapid and complete following oral administration but may vary according to specific salicylate used, dosage form, and other factors such as tablet dissolution rate and gastric or intraluminal pH.

EXPERIMENTAL: Acetylsalicylic acid and the acetylsalicylate ion were detected in the breast milk of nursing mothers within 1 hour of aspirin (acetylsalicylic acid) ingestion(1).

Peak salicylate concentrations of 173 to 483 ug/mL have been measured in /breast milk/ 5 to 8 hours after maternal ingestion of a single 650 mg dose /of aspirin/.

IDENTIFICATION: Acetylsalicylic acid is colorless or white crystals or white crystalline powder or granules; odorless or almost odorless with a slight acid taste. It is soluble in water. Indications: It is used as an analgesic for the treatment of mild to moderate pain, as an anti-inflammatory agent for the treatment of soft tissue and joint inflammation, and as an antipyretic drug. In low doses salicylate is used for the prevention of thrombosis. HUMAN EXPOSURE: The toxic effects of salicylate are complex. The following appear to be the principal primary effects of salicylate in overdose: Stimulation of the respiratory center; inhibition of citric acid cycle (carbohydrate metabolism); stimulation of lipid metabolism; inhibition of amino acid metabolism; and uncoupling of oxidative phosphorylation. Respiratory alkalosis, metabolic acidosis, water and electrolyte loss occur as the principal secondary consequences of salicylate intoxication. Central nervous system toxicity (including tinnitus, hearing-loss, convulsions and coma), hypoprothrombinemia and non-cardiogenic pulmonary edema may also occur, though for some the mechanism remains uncertain. Target organs: The target organs are: all tissues (whose cellular metabolism is affected), but in particular the liver, kidneys, lungs and the VIIIth cranial nerve. Summary of clinical effects: the following are symptoms of intoxication: Nausea, vomiting, epigastric discomfort, gastrointestinal bleeding (typically with chronic and rarely with acute intoxication); tachypnea and hyperpnea; tinnitus, deafness, sweating, vasodilatation, hyperpyrexia (rare), dehydration; irritability, tremor, blurring of vision, subconjunctival haemorrhages. The following are the effects on blood glucose: hyper- or hypoglycemia; effects on blood: hypoprothrombinemia; effects on liver: increased serum aminotransferase activities (SGOT and SGPT). Non-cardiogenic pulmonary edema; confusion, delirium, stupor, asterixis, coma, cerebral ede

The analgesic, antipyretic, and anti-inflammatory effects of acetylsalicylic acid are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Acetylsalicylic acid directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes acetylsalicylic acid different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Acetylsalicylic acid's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms; the therapeutic effects are not due to pituitary-adrenal stimulation. The platelet aggregation-inhibiting effect of acetylsalicylic acid specifically involves the compound's ability to act as an acetyl donor to cyclooxygenase; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Irreversible acetylation renders cyclooxygenase inactive, thereby preventing the formation of the aggregating agent thromboxane A2 in platelets. Since platelets lack the ability to synthesize new proteins, the effects persist for the life of the exposed platelets (7-10 days). Acetylsalicylic acid may also inhibit production of the platelet aggregation inhibitor, prostacyclin (prostaglandin I2), by blood vessel endothelial cells; however, inhibition prostacyclin production is not permanent as endothelial cells can produce more cyclooxygenase to replace the non-functional enzyme.

/BIRDS and MAMMALS/ The impact of acetyl salicylic add (ASA) on reproductive performance during periods of heat stress was studied in Japanese quail (Coturnix coturnix japonica). During a season when daily high temperatures averaged between 34 and 40 degrees C, four treatments each containing four replicates of five males and five females were given 0, 0.5, 1.0, or 1.5 g/L ASA in drinking water from 34 to 45 wk of age. At 39 wk of age control quail were lighter than quail fed ASA. Quail receiving 1.5 g/L ASA exhibited increased fertility, hatchability, and egg production and decreased late dead and total embryonic mortality. Early dead embryos, pips, chick weight, and egg weight were not different among treatments. The lumen of uterovaginal junction sperm host glands (UVJSHG) from control quail was apparently devoid of spermatozoa, whereas quail receiving 1.5 g/L ASA had the greatest apparent accumulation of spermatozoa. Control caudal infundibulum host glands (CPOI) were devoid of spermatozoa in contrast with CPOI from quail receiving ASA. Results show that UVJSHG lumens from quail receiving 1.5 g/L ASA had larger inside diameters than other treatment groups. However, the CPOI inside diameter and the outside diameters of both UVJSHG and CPOI were not affected by ASA. Adding 1.5 g/L ASA to the drinking water of quail under heat stress improved body weight, fertility, hatchability, embryonic mortality, egg production, egg specific gravity, and sperm storage capacity.

/AQUATIC SPECIES/ Metabolic products are often more toxic than their pharmacological parent compounds. Therefore, the acute and chronic effects of the main metabolites--salicylic acid (SAL), gentisic acid (GEN), and o-hydroxyhippuric acid (HDP)--of acetylsalicylic acid (ASA), the active ingredient in Aspirin and many other pharmaceuticals, were assessed using standard (Daphnia magna) and autochthonous (Daphnia longispina) cladocerans. The sequence of decreasing levels of acute and chronic toxicity of ASA metabolites to daphnids was GEN > SAL > HDP. HDP did not present acute toxicity, but chronic exposures enabled the production of abnormal neonates and, in particular, egg abortion. Thus, reproduction was the end point most susceptible to HDP. On the other hand, SAL and GEN induced changes in the normal patterns of reproduction and growth of both species. In general, D. longispina was more sensitive than was D. magna, although the population growth of the autochthonous species was superior under SAL exposures than that of the standard test species. Although the concentrations that were determined to have a toxic effect were above the levels detected in aquatic environmental samples, exposure to low levels of pharmacologically active substances for a duration longer than the test period may induce changes in nontarget organisms.

/PLANTS/ PHYTOTOXICITY: CHROMOSOMAL ABERRATIONS & ALTERATIONS IN ROOT CELLS OF BROAD BEAN PLANTS TREATED WITH ACETYLSALICYLIC ACID (1.0 GRAIN).

Chemical: Benzoic acid, 2-(acetyloxy)-

Hazard Traits - Developmental Toxicity; Reproductive Toxicity；Authoritative List - Prop 65；Report - regardless of intended function of ingredient in the product

Status: Active Update: 02-04-2013 https://echa.europa.eu/registration-dossier/-/registered-dossier/10841；Status: Active Update: 27-03-2015 https://echa.europa.eu/registration-dossier/-/registered-dossier/7490

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

N02BA01

N - Nervous system；N02 - Analgesics；N02B - Other analgesics and antipyretics；N02BA - Salicylic acid and derivatives；N02BA01 - Acetylsalicylic acid

A - Alimentary tract and metabolism；A01 - Stomatological preparations；A01A - Stomatological preparations；A01AD - Other agents for local oral treatment；A01AD05 - Acetylsalicylic acid

B - Blood and blood forming organs；B01 - Antithrombotic agents；B01A - Antithrombotic agents；B01AC - Platelet aggregation inhibitors excl. heparin；B01AC06 - Acetylsalicylic acid

QB - Blood and blood forming organs；QB01 - Antithrombotic agents；QB01A - Antithrombotic agents；QB01AC - Platelet aggregation inhibitors, excl. heparin；QB01AC06 - Acetylsalicylic acid

QA - Alimentary tract and metabolism；QA01 - Stomatological preparations；QA01A - Stomatological preparations；QA01AD - Other agents for local oral treatment；QA01AD05 - Acetylsalicylic acid

50% to 90% of a normal therapeutic concentration salicylate (a main metabolite of acetylsalicylic acid) binds plasma proteins, particularly albumin, while acetylsalicylic acid itself binds negligibly. Acetylsalicylic acid has the ability to bind to and acetylate many proteins, hormones, DNA, platelets, and hemoglobin.

**Effects on pain and fever** Acetylsalicylic acid disrupts the production of prostaglandins throughout the body by targeting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Prostaglandins are potent, irritating substances that have been shown to cause headaches and pain upon injection into humans. Prostaglandins increase the sensitivity of pain receptors and substances such as histamine and bradykinin. Through the disruption of the production and prevention of release of prostaglandins in inflammation, this drug may stop their action at pain receptors, preventing symptoms of pain. Acetylsalicylic acid is considered an antipyretic agent because of its ability to interfere with the production of brain prostaglandin E1. Prostaglandin E1 is known to be an extremely powerful fever-inducing agent. **Effects on platelet aggregation** The inhibition of platelet aggregation by ASA occurs because of its interference with thromboxane A2 in platelets, caused by COX-1 inhibition. Thromboxane A2 is an important lipid responsible for platelet aggregation, which can lead to clot formation and future risk of heart attack or stroke. **A note on cancer prevention** ASA has been studied in recent years to determine its effect on the prevention of various malignancies. In general, acetylsalicylic acid is involved in the interference of various cancer signaling pathways, sometimes inducing or upregulating tumor suppressor genes. Results of various studies suggest that there are beneficial effects of long-term ASA use in the prevention of several types of cancer, including stomach, colorectal, pancreatic, and liver cancers. Research is ongoing.

Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-selective for COX-1 and COX-2 enzymes. Inhibition of COX-1 results in the inhibition of platelet aggregation for about 7-10 days (average platelet lifespan). The acetyl group of acetylsalicylic acid binds with a serine residue of the cyclooxygenase-1 (COX-1) enzyme, leading to irreversible inhibition. This prevents the production of pain-causing prostaglandins. This process also stops the conversion of arachidonic acid to thromboxane A2 (TXA2), which is a potent inducer of platelet aggregation. Platelet aggregation can result in clots and harmful venous and arterial thromboembolism, leading to conditions such as pulmonary embolism and stroke. It is important to note that there is 60% homology between the protein structures of COX-1 and COX-2. ASA binds to serine 516 residue on the active site of COX-2 in the same fashion as its binding to the serine 530 residue located on the active site of COX-1. The active site of COX-2 is, however, slightly larger than the active site of COX-1, so that arachidonic acid (which later becomes prostaglandins) manages to bypass the aspirin molecule inactivating COX-2. ASA, therefore, exerts more action on the COX-1 receptor rather than on the COX-2 receptor. A higher dose of acetylsalicylic acid is required for COX-2 inhibition.

Produce analgesia through a peripheral action by blocking pain impulse generation and via a central action, possibly in the hypothalamus. The peripheral action may predominate and probably involves inhibition of the synthesis or prostaglandins, and possibly inhibition of the synthesis and/or actions of other substances, which sensitize pain receptors to mechanical or chemical stimulation. /Salicylates/

May produce antipyresis by acting centrally on the hypothalamic heat-regulating center to produce peripheral vasodilation resulting in increased cutaneous blood flow, sweating, and heat loss. The central action may involve inhibition of prostaglandin synthesis in the hypothalamus; however, there is some evidence that fevers caused by endogenous pyrogens that do not act via a prostaglandin mechanism may also respond to salicylate therapy. /Salicylates/

CNS ... ESP NUCLEI LOCATED IN HYPOTHALAMUS PLAYS MAJOR ROLE IN REGULATION OF PERIPHERAL MECHANISMS CONCERNED WITH BODY HEAT PRODN & LOSS. WITH SALICYLATES, HEAT PRODN IS NOT INHIBITED, BUT HEAT LOSS IS INCR BY INCR PERIPHERAL BLOOD FLOW & PERSPIRATION. /SALICYLATES/

Aspirin acetylates prostaglandin endoperoxide synthase (prostaglandin G/H-synthase) and irreversibly inhibits its cyclooxygenase (COX) activity. The enzyme catalyzes the conversion of arachidonic acid to PGH2, the first committed step in prostanoid biosynthesis. Two isoforms of prostaglandin endoperoxide synthase exist, PGHS-1 and PGHS-2 (also referred to as COX-1 and COX-2, respectively). PGHS-1 (COX-1) is expressed constitutively in most cell types, including platelets. PGHS-2 (COX-2) is undetectable in most mammalian cells, but its expression can be induced rapidly in response to mitogenic and inflammatory stimuli. Aspirin is a relatively selective inhibitor of platelet PGHS-1 (cyclooxygenase-1, COX-1). The existence of 2 isoenzymes with different aspirin sensitivities, coupled with extremely different recovery rates of their cyclooxygenase (COX) activity following inactivation by aspirin, at least partially explains the different dosage requirements and durations of aspirin effects on platelet function versus the drug's analgesic and anti-inflammatory effects. Human platelets and vascular endothelial cells process PGH2 to produce thromboxane A2 and prostacyclin (epoprostenol, PGI2), respectively. Thromboxane A2 induces platelet aggregation and vasoconstriction, while prostacyclin inhibits platelet aggregation and induces vasodilation. Aspirin is antithrombotic in a wide range of doses inhibiting thromboxane A2 and prostacyclin.

For more Mechanism of Action (Complete) data for ACETYLSALICYLIC ACID (12 total), please visit the HSDB record page.

The half-life of ASA in the circulation ranges from 13 - 19 minutes. Blood concentrations drop rapidly after complete absorption. The half-life of the salicylate ranges between 3.5 and 4.5 hours.

15 to 20 minutes (for intact molecule); rapidly hydrolyzed to salicylate. In breast milk (as salicylate): 3.8 to 12.5 hours (average 7.1 hours) following a single 650 mg dose of aspirin.

Cats are deficient in glucuronyl transferase and have a prolonged excretion of aspirin (the half-life in cats is 37.5 hr).

Acetylsalicylic acid is hydrolyzed in the plasma to salicylic acid. Plasma concentrations of aspirin following after administration of the extended-release form are mostly undetectable 4-8 hours after ingestion of a single dose. Salicylic acid was measured at 24 hours following a single dose of extended-release acetylsalicylic acid. Salicylate is mainly metabolized in the liver, although other tissues may also be involved in this process. The major metabolites of acetylsalicylic acid are salicylic acid, salicyluric acid, the ether or phenolic glucuronide and the ester or acyl glucuronide. A small portion is converted to gentisic acid and other hydroxybenzoic acids.

Acetylsalicylic acid is hydrolyzed in the stomach and in blood to salicylic acid and acetic acid; ... .

MAJOR URINARY METABOLITES OF ASPIRIN INCL SALICYLURONIC ACID ... SALICYL-O-GLUCURONIDE ... & SALICYL ESTER GLUCURONIDE ... & FREE SALICYLIC ACID ... .

A 52 year-old woman ingested approximately 300 tablets (325 mg) of aspirin in a suicide attempt. /Investigators/ analyzed the concentrations of salicylic acid (SA) and salicyluric acid (SUA) in body fluids and organs using a modified previous high-performance liquid chromatographic method. The concentrations of SA in heart and femoral blood were 1.1 mg/mL and 1.3 mg/mL, respectively; the results were far higher than the lethal level. The concentration of SA was 0.3-0.4 mg/g in brain, 0.9-1.4 mg/g in lung, 0.6-0.8 mg/g in liver and 0.9 mg/mL in kidney.

Acetylsalicylic acid is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine (forming salicyluric acid) and glucuronic acid and excreted largely in the urine. Half Life: The plasma half-life is approximately 15 minutes; that for salicylate lengthens as the dose increases: doses of 300 to 650 mg have a half-life of 3.1 to 3.2 hours; with doses of 1 gram, the half-life is increased to 5 hours and with 2 grams it is increased to about 9 hours.

R16CO5Y76E

ASPIRIN

Mechanisms of Action [MoA] - Cyclooxygenase Inhibitors

Physiologic Effects [PE] - Decreased Prostaglandin Production

Chemical Structure [CS] - Anti-Inflammatory Agents, Non-Steroidal

Established Pharmacologic Class [EPC] - Nonsteroidal Anti-inflammatory Drug

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.

Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN.

Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.

Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.

Drugs that are used to reduce body temperature in fever.

Absorption is generally rapid and complete following oral administration but absorption may be variable depending on the route, dosage form, and other factors including but not limited to the rate of tablet dissolution, gastric contents, gastric emptying time, and gastric pH. **Detailed absorption information** When ingested orally, acetylsalicylic acid is rapidly absorbed in both the stomach and proximal small intestine. The non-ionized acetylsalicylic acid passes through the stomach lining by passive diffusion. Ideal absorption of salicylate in the stomach occurs in the pH range of 2.15 - 4.10. Intestinal absorption of acetylsalicylic acid occurs at a much faster rate. At least half of the ingested dose is hydrolyzed to salicylic acid in the first-hour post-ingestion by esterases found in the gastrointestinal tract. Peak plasma salicylate concentrations occur between 1-2 hours post-administration.

Excretion of salicylates occurs mainly through the kidney, by the processes of glomerular filtration and tubular excretion, in the form of free salicylic acid, salicyluric acid, and, additionally, phenolic and acyl glucuronides. Salicylate can be found in the urine soon after administration, however, the entire dose takes about 48 hours to be completely eliminated. The rate of salicylate is often variable, ranging from 10% to 85% in the urine, and heavily depends on urinary pH. Acidic urine generally aids in reabsorption of salicylate by the renal tubules, while alkaline urine increases excretion. After the administration of a typical 325mg dose, the elimination of ASA is found to follow first order kinetics in a linear fashion. At high concentrations, the elimination half-life increases.

This drug is distributed to body tissues shortly after administration. It is known to cross the placenta. The plasma contains high levels of salicylate, as well as tissues such as spinal, peritoneal and synovial fluids, saliva and milk. The kidney, liver, heart, and lungs are also found to be rich in salicylate concentration after dosing. Low concentrations of salicylate are usually low, and minimal concentrations are found in feces, bile, and sweat.

The clearance rate of acetylsalicylic acid is extremely variable, depending on several factors. Dosage adjustments may be required in patients with renal impairment. The extended-release tablet should not be administered to patients with eGFR of less than 10 mL/min.

The materno-fetal transfer of salicylic acid and its distribution in the fetal organism was investigated in women of early pregnancy. Acetylsalicylic acid was administered orally in a single dose or in repeated doses at different times before legal interruption. The mean passage rates were about 6-15%. They were independent of the maternal serum concentrations of salicylic acid. The distribution of salicylic acid on the fetal liver, intestine, kidneys, lungs and brain was different. All fetal organs (9th to 15th week of gestation) studied exhibit an acetylsalicylic acid-splitting esterase activity. The esterase activity of the fetal liver was about 30% of the hydrolytic activity of the adult liver. The esterase activity was mainly located in the 105 000 X g-supernatant of cell homogenates.

Approximately 80-100% of an oral dose of aspirin is absorbed from the GI tract. However, the actual bioavailability of the drug as unhydrolyzed aspirin is lower since aspirin is partially hydrolyzed to salicylate in the GI mucosa during absorption and on first pass through the liver. There are relatively few studies of the bioavailability of unhydrolyzed aspirin. In one study in which aspirin was administered IV and as an oral aqueous solution, it was shown that the solution was completely absorbed but only about 70% reached the systemic circulation as unhydrolyzed aspirin. In another study in which aspirin was administered IV and orally as capsules, only about 50% of the oral dose reached the systemic circulation as unhydrolyzed aspirin. There is some evidence that the bioavailability of unhydrolyzed aspirin from slowly absorbed dosage forms (e.g., enteric-coated tablets) may be substantially decreased. Food does not appear to decrease the bioavailability of unhydrolyzed aspirin or salicylate; however, absorption is delayed and peak serum aspirin or salicylate concentration may be decreased. There is some evidence that absorption of salicylate following oral administration may be substantially impaired or is highly variable during the febrile phase of Kawasaki disease.

Platelet

Cytoplasm

Acetylsalicylic Acid Action Pathway

Used in manufacturing and health care; [ACGIH TLVs and BEIs]

Therapeutic Category: Analgesic; antipyretic; anti-inflammatory; antithrombotic.

Therapeutic Category (Vet): Analgesic; antipyretic; anti-inflammatory; antithrombotic.

MEDICATION

CHEMICAL PROFILE: Virtually all aspirin is used in pharmaceutical products in aspirin tablets or in concert with other ingredients (1981)

For more Uses (Complete) data for ACETYLSALICYLIC ACID (7 total), please visit the HSDB record page.

4-hydroxybenzoic acid; 4-hydroxybenzene-1,3-dicarboxylic acid (4-hydroxyisophthalic acid); salicylic acid; 2-[[2-(acetyloxy)benzoyl]oxy]benzoic acid (acetylsalicylsalicylic acid); 2-[(2-hydroxybenzoyl)oxy]benzoic acid (salicylsalicylic acid); 2-(acetyloxy)benzoic anhydride (acetylsalicylic anhydride)

(1972) 8.74X10+8 GRAMS (BULK)

(1975) 1.06X10+8 GRAMS

(1984) 1.26X10+9 g (bulk)

CHEMICAL PROFILE: Aspirin exports were 1.3 million lb /in 1989/.

For more U.S. Exports (Complete) data for ACETYLSALICYLIC ACID (7 total), please visit the HSDB record page.

(1972) 2.04X10+8 GRAMS

(1975) 1.42X10+8 GRAMS

(1984) 1.65x10+9 g

CHEMICAL PROFILE: Aspirin imports were 2.6 million lb last year /1989/.

For more U.S. Imports (Complete) data for ACETYLSALICYLIC ACID (6 total), please visit the HSDB record page.

(1972) 1.59X10+10 GRAMS

(1975) 1.16X10+10 GRAMS

(1984) 1.54X10+10 g

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#1911]

For more U.S. Production (Complete) data for ACETYLSALICYLIC ACID (7 total), please visit the HSDB record page.

54% AS AN ANALGESIC IN COMBINATION WITH OTHER ACTIVE OR INERT INGREDIENTS; 46% AS AN ANALGESIC IN SINGLE INGREDIENT ASPIRIN TABLETS (1973)

CHEMICAL PROFILE: Aspirin. Almost all aspirin manufactured in the US is used in aspirin tablets, pharmaceutical products or in conjunction with other ingredients for its analgesic and antipyretic properties. Approx 10% of US production is exported in bulk.

CHEMICAL PROFILE: Aspirin. Demand: 1986: 29.5 million lb; 1987: 30.0 million lb; 1991 /projected/: 31.8 million lb.

CHEMICAL PROFILE: Aspirin. Almost all aspirin manufactured in the US is used in aspirin tablets, pharmaceutical products or in conjunction with other ingredients for its analgesic and antipyretic properties. Approximately 5% of US production is exported in bulk.

For more Consumption Patterns (Complete) data for ACETYLSALICYLIC ACID (8 total), please visit the HSDB record page.

Acetylsalicylic acid is prepared by reacting acetic anhydride with salicylic acid at a temperature of <90 °C either in a solvent (e.g., acetic acid or aromatic, acyclic, or chlorinated hydrocarbons) or by the addition of catalysts such as acids or tertiary amines.

Manufacture from salicylic acid and acetic anhydride. ... Crystallization from acetone..

Aspirin Formulations:；Table: Aspirin Formulations: [Table#1910]

Cosmetics product ingredient: Aspirin (Acetylsalicylic acid)；Source: Aspirin is a non-steroidal anti-inflammatory over-the-counter drug. Aspirin relieves pain and reduces fever. Aspirin prevents blood from clotting quickly. Aspirin is added to cosmetics in order to reduce irritation and inflammation.；Potential health impacts: The major routes of exposure to aspirin in cosmetics are through the skin or by ingestion. Some people are sensitive to aspirin and can have severe reactions to small amounts. In high doses, aspirin can affect the liver. Aspirin is not recommended for children because of a link to Reye Syndrome, a serious liver disease. Aspirin is generally not recommended for use as a pain reliever during pregnancy, because it can cause changes in the heart of the unborn child and may delay or prolong labor. It also increases the risk of bleeding.；The U.S. Food and Drug Administration (FDA) classifies aspirin as FDA Pregnancy Category D; there is a known risk to the fetus when the drug is used during pregnancy, but potential benefits may sometimes outweigh the risk. California Proposition 65 lists aspirin as a chemical known to cause developmental effects and reproductive harm.；Product count: 11

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Benzoic acid, 2-(acetyloxy)-: ACTIVE

Acetylsalicylic acid otherwise known as aspirin, has been the most widely used over the counter drug.