Table I.

Proposed extra-hepatic adverse effects of APAP

Toxicity	Evidence	Proposed mechanisms	Comments
Renal	Clinical and rodent studies	Protein binding, ɤ-glutamyl cycling	Strong human and rodent data
Pulmonary	Epidemiology, limited preclinical studies	GSH depletion, oxidative stress, neurogenic inflammation	Better study designs needed
Endocrine	Epidemiology, limited preclinical studies	Altered sex steroid metabolism, inhibition of prostaglandin synthesis	Conflicting human and experimental data
Ototoxicity	Case reports, limited preclinical studies	Oxidative stress, ER stress	Strong human data, conflicting experimental data
Neurobehavioral	Epidemiology, limited preclinical studies	Endocrine disruption, endocannabinoid signaling, direct neurotoxicity	Better study designs needed