Toxic Metabolite: Mechanisms of APAP-mediated injury are plausible. The body converts a fraction of acetaminophen into a toxic metabolite called NAPQI.

Oxidative Stress: Genetic, epigenetic, and environmental factors associated with an increased risk of ASD are also associated with oxidative stress, which has an adverse effect on the body’s ability to safely metabolize APAP.

One enzyme (CyP450 2E1) which produces the toxic metabolite of APAP (NAPQI) is expressed in the human brain from before birth, is a target of epigenetic alterations in mothers who have children with ASD and in mothers who took APAP during labor and delivery.

Phase II metabolism is the way the body processes APAP without producing the toxic metabolite. The first study showing that children with ASD are deficient in a phase II metabolic pathway necessary to safely detoxify APAP in babies (sulfation) is now more than a quarter of a century old, and was subsequently corroborated.

Toxicity in cats: APAP is not used in domestic cats because they lack of a robust glucuronidation-dependent capacity for metabolism, making them susceptible to APAP-mediated injury. Human neonates also lack a robust glucuronidation-dependent pathway.

Increasing evidence suggests that the gut/brain axis may play a role in many cases of ASD, and APAP is known to adversely affect gut function in laboratory animal models and possibly in humans.

APAP binds directly to arachidonic acid and affects arachidonic acid metabolism. Alterations of arachidonic acid and enzymes involved in arachidonic acid metabolism are associated with ASD.

Decreased phase II metabolism at birth: Human neonates lack a robust glucuronidation-dependent pathway, one of the two main metabolic pathways that avoids the production of NAPQI, the toxic metabolite of APAP.

Mitochondrial function may be impaired in individuals with ASD, and aberrant metabolism of APAP can impair mitochondrial function. Calcium signaling is known to be important in ASD, and APAP adversely affects calcium signaling.

Hormesis is the toxicological principle in which exposure to a relatively low dose of toxin can result in protection from exposure to the same or even other toxins later in life. Evidence indicates that low levels of exposure to ethanol and perhaps APAP during pregnancy can protect an individual from ASD, suggesting that exposure to toxin later in life (after pregnancy) may be critical in the etiology of ASD.