Comment from Americans for Scientific Integrity

Supplemental Comment to FDA Docket FDA-2025-P-4153-0001 Americans for Scientific Integrity submits this supplemental comment to bring FDA’s attention to a recently accepted peer-reviewed study that further strengthens the biological plausibility underlying ICAN’s pending citizen petition regarding acetaminophen use during pregnancy. The attached study, Sex-dependent effects of early-life paracetamol exposure on behavior and monoamines in the rat central nervous system (Górawski et al., Chemico-Biological Interactions, accepted January 2026), evaluates prenatal and early postnatal acetaminophen exposure in rodents and reports sex-dependent behavioral and neurochemical effects, with male and female offspring exhibiting different patterns of impact across behavioral domains and brain regions Importantly, the findings do not reflect nonspecific or random neurotoxicity. Rather, the presence of systematic, sex-dependent differences suggests a biologically mediated effect consistent with known differences in neurodevelopment, hormone signaling, metabolism, and neurotransmitter systems between males and females. This pattern strengthens biological plausibility by arguing against chance injury and in favor of a drug-related developmental mechanism. These sex-dependent findings align with observations in humans, where neurodevelopmental conditions such as autism spectrum disorder and ADHD are known to differ by sex in prevalence, presentation, and developmental trajectory. As such, this study adds relevant and timely preclinical evidence supporting ICAN’s request that FDA evaluate the need for precautionary labeling regarding acetaminophen use during pregnancy. ASFI respectfully requests that FDA include this newly published study in its review and analysis of ICAN’s petition.