Paracetamol

Endpoint summary

Description of key information

In healthy humans, paracetamol (synonym = acetaminophen) is expected to have low bio-accumulation potential since approximately 85% of a dose of acetaminophen is excreted in urine as free and conjugated acetaminophen within 24 hours after ingestion. However, administration of acetaminophen to patients with moderate to severe renal impairment may result in accumulation of acetaminophen conjugates.

Thus, the bio-accumulation potential of paracetamol is expected to be related to the health status and age of the humans that are administered oral doses of the chemical

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - dermal (%):

0.017

Additional information

Absorption:Acetaminophen is rapidly and almost completely absorbed from the GI tract following oral administration.Food may delay slightly absorption of extended-release tablets of acetaminophen

Distribution:Acetaminophen is rapidly and uniformly distributed into most body tissues About 25% of acetaminophen in blood is bound to plasma proteins Following oral administration of immediate- or extended-release acetaminophen preparations, peak plasma concentrations are attained within 10-60 or 60-120 minutes, respectively. Following oral administration of a single 500-mg conventional tablet or a single 650-mg extended-release tablet, average plasma acetaminophen concentrations of 2.1 or 1.8 ug/mL, respectively, occur at 6 or 8 hours, respectively.

Metabolism:About 80-85% of the acetaminophen in the body undergoes conjugation principally with glucuronic acid and to a lesser extent with sulfuric acid. Acetaminophen also is metabolized by microsomal enzyme systems in the liver.

In vitro and animal data indicate that small quantities of acetaminophen are metabolized by a cytochrome P-450 microsomal enzyme to a reactive intermediate metabolite (N-acetyl-p-benzoquinoneimine, N-acetylimidoquinone, NAPQI) which is further metabolized via conjugation with glutathione and ultimately excreted in urine as a mercapturic acid. It has been suggested that this intermediate metabolite is responsible for acetaminophen-induced liver necrosis and that high doses of acetaminophen may deplete glutathione so that inactivation of this toxic metabolite is decreased. At high doses, the capacity of metabolic pathways for conjugation with glucuronic acid and sulfuric acid may be exceeded, resulting in increased metabolism of acetaminophen by alternative pathways. In addition, it also has been suggested that in fasting individuals conjugation of high doses of acetaminophen with glucuronic acid may be reduced, secondary to decreased hepatic carbohydrate reserves and microsomal oxidation may be increased, resulting in increased risk of hepatotoxicity.

Excretion:Acetaminophen is excreted in urine principally as acetaminophen glucuronide with small amounts of acetaminophen sulfate and mercaptate and unchanged drug. Approximately 85% of a dose of acetaminophen is excreted in urine as free and conjugated acetaminophen within 24 hours after ingestion.Administration of acetaminophen to patients with moderate to severe renal impairment may result in accumulation of acetaminophen conjugates.