A quantitative weight-of-evidence review of preclinical studies examining the potential developmental neurotoxicity of acetaminophen
Notice bibliographique
Résumé
Acetaminophen [paracetamol; N-acetyl-para-aminophenol (APAP)] is an antipyretic/analgesic commonly used in the treatment of fever and mild to moderate pain, headache, myalgia, and dysmenorrhea. Recent literature has questioned the safety of acetaminophen use during pregnancy, with an emphasis on whether exposure to the developing nervous system results in behavioral changes consistent with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and/or other cognitive deficits in the offspring. No previous review has used a fully detailed, quantitative weight-of-evidence (QWoE) approach to critically examine the preclinical acetaminophen data with regards to potential developmental neurotoxicity (DNT). Following regulatory guidance, a QWoE framework using prespecified scoring criteria was developed consistent with previous approaches to characterize potential adverse DNT outcomes with considerations for biological relevance of the response to adverse outcomes (outcome score) and the strength of methods and study design (methods score). Considerations for the methods score included (1) experimental design, (2) details/reliability of measurement(s), (3) data transparency, and (4) translational/methodological relevance. Considerations for the outcome score included response-related (1) statistical significance, (2) dose-response, (3) relevance/reliability/magnitude, (4) plausibility, and (5) translational relevance, including consideration of systemic toxicity/hepatotoxicity and therapeutic and/or non-systemically toxic doses and durations of use. Application of this QWoE framework to the 34 in vivo studies identified that assess the potential DNT of acetaminophen resulted in 188 QWoE entries documented across 11 DNT endpoints: social behavior, stereotypic behavior, behavioral rigidity, attention/impulsivity, hyperactivity, anxiety-like behavior, sensorimotor function, spatial learning/memory, nonspatial learning/memory, neuroanatomy, and neurotransmission. For each endpoint, the mean outcome score and methods score were calculated for total entries and for entries segregated by sex to assist in determining data quality and potential adversity. Informed by all 188 entries, the QWoE analysis demonstrated data of moderate quality showing no consistent evidence of DNT in male and female rodents following exposure to acetaminophen at therapeutic and/or nonsystemically toxic doses. Although some of the DNT endpoints (behavioral rigidity, attention/impulsivity, spatial learning/memory, neuroanatomy, and neurotransmission) generally displayed a more limited dataset and/or relatively lower data quality, similar conclusions were drawn based on results indicating a lack of biological relevance and reliability of reported adverse effects. Overall, this QWoE analysis on the preclinical in vivo data demonstrates no consistent evidence of adverse effects following developmental exposure to acetaminophen at therapeutic and/or non-systemically toxic doses on the structure and function of the nervous system, including neuroanatomical, neurotransmission, and behavioral endpoints.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,005 | 0,185 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,007 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,002 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».