A critical review of the acetaminophen preclinical carcinogenicity and tumor promotion data and their implications for its carcinogenic hazard potential
| Autor: | Edwin Kuffner, Samuel M. Cohen, Milind Deore, Andrew D. Monnot, Evren Atillasoy, Gary Eichenbaum, Cathy K. Gelotte, Anne Hermanowski-Vosatka, Suren B. Bandara, Michael Kovochich, Jerry F. Hardisty, Brett A. Howell, Suresh Kumar Pitchaiyan, F. Jay Murray, Kyunghee Yang, John C.K. Lai, Yeshitila Gebremichael, Kenneth M. Unice, David Jacobson-Kram |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Male medicine.medical_specialty Carcinogenicity Tests Tumor initiation 010501 environmental sciences Hazard analysis Toxicology 030226 pharmacology & pharmacy 01 natural sciences Risk Assessment 03 medical and health sciences Mice 0302 clinical medicine Qualitative analysis Species Specificity Internal medicine Neoplasms Medicine Animals Humans Carcinogen Biotransformation 0105 earth and related environmental sciences Acetaminophen Dose-Response Relationship Drug business.industry Hazard potential General Medicine Analgesics Non-Narcotic Hazard Rats Toxicokinetics Cell Transformation Neoplastic Tumor promotion Female business medicine.drug |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 118 |
| ISSN: | 1096-0295 |
| Popis: | In 2019 the California Office of Environmental Health Hazard Assessment (OEHHA) initiated a review of the carcinogenic hazard potential of acetaminophen, including an assessment of the long-term rodent carcinogenicity and tumor initiation/promotion studies. The objective of the analysis herein was to inform this review process with a weight-of-evidence assessment of these studies and an assessment of the relevance of these models to humans. In most of the 14 studies, there were no increases in the incidences of tumors in any organ system. In the few studies in which an increase in tumor incidence was observed, there were factors such as absence of a dose response and a rodent-specific tumor supporting that these findings are not relevant to human hazard identification. In addition, we performed qualitative analysis and quantitative simulations of the exposures to acetaminophen and its metabolites and its toxicity profile; the data support that the rodent models are toxicologically relevant to humans. The preclinical carcinogenicity results are consistent with the broader weight of evidence assessment and evaluations of multiple international health authorities supporting that acetaminophen is not a carcinogenic hazard. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect