Toxicological Sciences最新文献

{"title":"Transcriptomic analysis in liver spheroids identifies a dog-specific mechanism of hepatotoxicity for amcenestrant.","authors":"Piyush Bajaj, Richard J Brennan, Sébastien Laurent, Sylvie Sauzeat, Michael Dufault, Brenda Richards, Karissa Adkins","doi":"10.1093/toxsci/kfaf012","DOIUrl":"10.1093/toxsci/kfaf012","url":null,"abstract":"<p><p>Therapeutic drugs can sometimes cause adverse effects in a nonclinical species that do not translate to other species, including human. Species-specific (rat, dog, and human) in vitro liver spheroids were employed to understand the human relevance of cholestatic liver injury observed with a selective estrogen receptor degrader (amcenestrant) in dog, but not in rat, during preclinical development. Amcenestrant showed comparable cytotoxicity in liver spheroids from all 3 species; however, its M5 metabolite (RA15400562) showed dog preferential cytotoxicity after 7 days of treatment. Whole genome transcript profiles generated from liver spheroids revealed downregulation of genes related to bile acid synthesis and transport indicative of strong farnesoid X receptor (FXR) antagonism following treatment with both amcenestrant and its M5 metabolite in the dog but not in rat or human. In human spheroids, upregulation of genes for detoxification enzymes indicative of pregnane X receptor (PXR) agonism was observed following amcenestrant treatment, whereas in the dog these genes were downregulated. The M5 metabolite showed gene dysregulation indicating PXR agonism in both rat and human, and antagonism in dog. Analysis of liver samples from a 3-mo dog toxicity study conducted with amcenestrant showed downregulation of several genes associated with PXR and FXR, corroborating the in vitro results. These results support the hypothesis that dogs are uniquely susceptible to cholestatic hepatotoxicity following administration of amcenestrant due to species-specific antagonism of FXR and highlight the value of in vitro liver spheroids to investigating mechanisms of toxicity and possible species differences.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"228-241"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A perspective review on factors that influence mutagenicity in medicinal plants and their health implications.","authors":"Victoria Fasiku, Doreen Kyagaba, Atlehang Hlalele, Ayodeji Adegoke, Ochuko L Erukainure, Mamello Sekhoacha","doi":"10.1093/toxsci/kfaf004","DOIUrl":"10.1093/toxsci/kfaf004","url":null,"abstract":"<p><p>Medicinal plants are products from natural sources that have found relevance in medicine for several decades. They are rich in bioactive compounds; thus, they are widely used to treat different ailments globally. Medicinal plants have provided hope for the healthcare industry as most are used to synthesize modern medicines currently used in the treatment of various diseases. However, there are still concerns with respect to the mutagenic properties of medicinal plants. Over the years, researchers have embarked on various studies aimed at investigating the mutagenicity of several medicinal plants found in different regions of the world. In this review, we discussed factors that may influence plant mutagenicity and the findings of in vitro and in vivo mutagenicity studies of several medicinal plants from across the globe. In addition, this review considers the potential health implications of mutagenic medicinal plants and safety measures that can be used to mitigate mutagenesis in medicinal plants. To achieve this, we searched for articles reporting on medicinal plants and mutagenesis on the PubMed, Scopus, and Web of Science databases. Several journal articles reported on the mutagenicity of some medicinal plants; however, it was observed that the majority of the articles reported the nonmutagenicity of medicinal plants. The findings from these studies imply that medicinal plants have good prospects in treating diseases and that they are clinically relevant. However, these reports will require further validation to determine their safety for human use as limited in vivo studies were conducted and there are no clinical safety reports for any of the plants discussed in this review.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"121-142"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays.","authors":"Mark D Jankowski, Amy F Carpenter, Joshua A Harrill, Felix R Harris, Bridgett Hill, Rochelle Labiosa, Sergei S Makarov, Dalma Martinović-Weigelt, Jo Nyffeler, Stephanie Padilla, Timothy J Shafer, Marci G Smeltz, Daniel L Villeneuve","doi":"10.1093/toxsci/kfaf008","DOIUrl":"10.1093/toxsci/kfaf008","url":null,"abstract":"<p><p>6PPD-quinone (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone), a transformation product of the antiozonant 6PPD (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine) is a likely causative agent of coho salmon (Oncorhynchus kisutch) pre-spawn mortality. Stormwater runoff transports 6PPD-quinone into freshwater streams, rapidly leading to neurobehavioral, respiratory distress, and rapid mortality in laboratory-exposed coho salmon, but causing no mortality in many laboratory-tested species. Given this identified hazard, and potential for environmental exposure, we evaluated a set of U.S. Environmental Protection Agency's high-throughput assays for their capability to detect the large potency difference between 6PPD and 6PPD-quinone observed in coho salmon and screen for bioactivities of concern. Assays included transcriptomics in larval fathead minnow (FHM), developmental and behavioral toxicity in larval zebrafish, phenotypic profiling in a rainbow trout gill cell line, acute and developmental neurotoxicity in mammalian cells, and reporter transcription factor activity in HepG2 cells. 6PPD was more consistently bioactive across assays, with distinct activity in the developmental neurotoxicity assay (mean 50th centile activity concentration = 0.91 µM). Although 6PPD-quinone was less potent in FHM and zebrafish, and displayed minimal neurotoxic activity in mammalian cells, it was highly potent in altering organelle morphology in RTgill-W1 cells (phenotype-altering concentration = 0.024 µM compared with 0.96 µM for 6PPD). Although in vitro sensitivity of RTgill-W1 cells may not be as sensitive as intact Coho salmon, the assay may be a promising approach to test chemicals for 6PPD-quinone-like activities. The other assays each identified unique bioactivities of 6PPD, with neurobehavioral and developmental neurotoxicity being most affected, indicating a need for further assessment of this chemical. Our results demonstrate that the common tire additive, 6PPD, is bioactive in a broader set of assays than the environmental transformation product 6PPD-quinone and that it may be a developmental neurotoxicant in mammals, whereas 6PPD-quinone was much more potent than 6PPD in altering the intracellular phenotype of rainbow trout gill cells. Application of the set of high-throughput and high-content bioassays to test the bioactivity of this emerging pollutant has provided data to inform both ecological and human health assessments.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"198-217"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of Caco-2 cells and human jejunal and duodenal enteroid-derived cells in gel- and membrane-based barrier models of intestinal permeability.","authors":"Haley L Moyer, Leoncio Vergara, Clifford Stephan, Courtney Sakolish, Lucie C Ford, Han-Hsuan D Tsai, Hsing-Chieh Lin, Weihsueh A Chiu, Remi Villenave, Philip Hewitt, Stephen S Ferguson, Ivan Rusyn","doi":"10.1093/toxsci/kfaf011","DOIUrl":"10.1093/toxsci/kfaf011","url":null,"abstract":"<p><p>Intestinal absorption is a key toxicokinetics parameter. Although the colon carcinoma cell line Caco-2 is the most used in vitro model to estimate human drug absorption, models representing other intestinal segments are available. We characterized the morphology, tissue-specific markers, and functionality of 3 human intestinal cell types: Caco-2, primary human enteroid-derived cells from jejunum (J2), and duodenum (D109) when cultured in the OrganoPlate 3-lane 40 microphysiological system (MPS) or static 24-well Transwells. In both conditions, J2 and D109 formed dome-like structures; Caco-2 formed uniform monolayers. In MPS, only Caco-2 formed tubules. Cells grown on Transwells formed a thicker monolayer. All cells and conditions exhibited expression of ZO-1 (tight junctions). Polarization markers Ezrin and Villin were highest in J2 and D109 in MPS, highest expression of Mucin was observed with J2. However, J2 and D109 exhibited poor barrier (70 kDa TRITC-dextran) in MPS, whereas robust barrier was recorded in Transwells. Barrier function and drug transport were evaluated using caffeine, indomethacin, and propranolol. The gel lane in MPS acted as a blockade; only a small fraction crossed, even without cells. The permeability ratios were used to parameterize the probabilistic compartmental absorption model to determine whether in vitro data could reduce uncertainty. The most accurate prediction of the fraction absorbed was achieved with Transwell-derived data from Caco-2, combined with the experimentally derived segment-specific absorption ratios. The impact of this study includes demonstration that enteroid-derived cells cultured in MPS show most physiological morphology, but that studies of drug permeability in this MPS are challenging.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"181-197"},"PeriodicalIF":3.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent exposure to Δ9-tetrahydrocannabinol (THC) impairs testicular function in young adult male mice.","authors":"Jinhwan Lim, Caitlin Quach, Julie Nguyen, Andrew Rizk, Samantha Getze, Kwang-Mook Jung, Stephen V Mahler, Daniele Piomelli, Ulrike Luderer","doi":"10.1093/toxsci/kfaf035","DOIUrl":"https://doi.org/10.1093/toxsci/kfaf035","url":null,"abstract":"<p><p>Cannabis use typically starts in early to mid-adolescence. Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, targets cannabinoid receptors (CBRs) to exert its pharmacological effects. Expression of CBRs has been observed in human and rodent testes, but their potential role in the control of reproductive function remains unclear. We aimed to elucidate how THC exposure during adolescence or young adulthood affects the reproductive health of males. C57BL/6N male mice were given THC (5 mg/kg) or vehicle, once daily by intraperitoneal (ip) injection from postnatal day (PND) 30 to PND 43 (adolescent exposure) or PND 70 to PND 83 (adult exposure), and testes were harvested at PND 70 and PND 110, respectively. Results showed that CBRs (CB1R and CB2R) and enzymes that biosynthesize or inactivate the endocannabinoid anandamide (AEA) -N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) or fatty acid amide hydrolase (FAAH), respectively-are expressed in the mouse testis. THC exposure in adolescence decreased sperm numbers and increased seminiferous tubule degeneration in young adult testes, while adult exposure did not affect spermatogenesis and seminiferous tubule morphology. Both adolescent and adult THC exposure resulted in decreased plasma testosterone levels; however, only mice with adolescent THC exposure showed impaired steroidogenesis with dysregulated expression of steroidogenic acute regulatory protein (StAR) and steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1). Our results support that adolescent THC exposure may cause testicular toxicity through direct and aberrant activation of CBRs in the testis. These studies show that the adolescent testis is more sensitive than the adult testis to THC-induced disruption of spermatogenesis.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of polybrominated diphenyl ethers (PBDEs) in placental tissues of maternal and fetal origin in exposed Wistar rats and associations with thyroid hormone levels.","authors":"Shaza Gaballah, Brian Hormon, Genavieve St Armour Mason Nelson, Jinyan Cao, Kate Hoffman, Heather B Patisaul, Heather M Stapleton","doi":"10.1093/toxsci/kfae151","DOIUrl":"10.1093/toxsci/kfae151","url":null,"abstract":"<p><p>In utero exposure to polybrominated diphenyl ethers (PBDEs) is linked to adverse pregnancy and fetal health outcomes, including altered thyroid hormone (TH) levels. Despite their phase-out, PBDEs are still commonly detected in newborn cord blood. While PBDEs can cross the placenta, few studies have separately assessed PBDEs or THs in the maternal and fetal placental tissues. Additionally, no studies have separately assessed THs in these tissues across mid- and late gestation, during the onset of fetal TH synthesis. To address these gaps, we conducted a study with Wistar rats and examined PBDE accumulation in the maternal and fetal placenta. Pregnant dams were exposed daily to sesame oil vehicle, a low dose, or high dose PBDE mixture. At GD15 and 20, dams were sacrificed and placental tissues were collected. Tissues were analyzed for PBDEs, T3, rT3, and T4 using mass spectrometry. BDE-47, -99, -100, and -209 were frequently detected in both the fetal and maternal placenta. At GD15, higher concentrations of BDE-99, -100, and -209 were measured in the fetal placenta; however, this trend reversed by GD20, with higher maternal placental concentrations. Placental T3 and T4 were significantly impacted by exposure, tissue, and exposure × tissue at GD15, with significant reductions in both THs following low-dose exposure in the maternal placenta. By GD20, maternal placental T3 was only significantly reduced in the high exposure groups and there was no effect on placental T4. Overall, these results highlight the rapid developmental changes that occur throughout gestation between the maternal and fetal placenta, and the differential impacts of gestational PBDE exposure on placental T3 and T4 across mid- and late gestation.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"20-30"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Haloacetamides exacerbate non-alcoholic fatty liver disease induced by a high-fat diet in C57BL/6J mice.","authors":"Zhiqiang Jiang, Lili Yang, Qinxin Liu, Meiyue Qiu, Yu Chen, Mengying Teng, Yubin Zhang, Xing Liu, Zhonghua Zhao, Yuxin Zheng, Melvin Andersen, Weidong Qu","doi":"10.1093/toxsci/kfae160","DOIUrl":"10.1093/toxsci/kfae160","url":null,"abstract":"<p><p>Obesity, a significant global health issue, heightens the risk of non-alcoholic fatty liver disease (NAFLD). Its interaction with environmental pollutants might exacerbate NAFLD's severity. Haloacetamides (HAcAms), a group of emerging nitrogenous disinfection byproducts (DBPs) and potent oxidative stressors, are found in chlorinated drinking water. Since oxidative stress is associated with HAcAms-DBP cytotoxicity and a key factor in NAFLD pathogenesis, we hypothesize that HAcAms-DBPs could exacerbate liver injury and NAFLD, particularly with high-fat diets. This study examined HAcAms-DBPs' impact on liver lipid metabolism in mice treated with 1 to 100 times the background drinking water level (13.05 µg/L) for up to 16 weeks of oral administration. Compared to a high-fat-only group, mice co-exposed to a high-fat diet and HAcAms-DBPs for 16 weeks had elevated serum alanine transaminase, aspartate transaminase, triglyceride, hepatic lipid aggregation, and inflammation response. Under high-fat conditions, background drinking water levels of HAcAms significantly upregulated liver Acetyl-CoA carboxylase 1, fatty acid synthase, peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator-1α, glucose transporter 1 and 4 protein expression in C57BL/6J mice; 10 times background significantly increased expression of inflammatory marker tumor necrosis factor and liver fibrosis marker protein alpha-smooth muscle actin; 100 times further increased both liver damage and markers of early non-alcoholic steatohepatitis phenotypes like steatosis and lobular inflammation. HAcAms-DBPs plus high-fat conditions worsened liver damage. The possible health risks of NAFLD induced by HAcAms in obese individuals deserve further study.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"57-69"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diet-induced obesity alters the ovarian chemical biotransformation and oxidative stress response proteins both basally and in response to 7,12-dimethylbenz[a]anthracene exposure.","authors":"Kelsey Timme, Imaobong Inyang, Hunter E White, Aileen F Keating","doi":"10.1093/toxsci/kfae150","DOIUrl":"10.1093/toxsci/kfae150","url":null,"abstract":"<p><p>7,12-Dimethylbenz[a]anthracene (DMBA) is a polycyclic aromatic hydrocarbon that causes female infertility via DNA damage, and the ovary has the capacity to mitigate DMBA exposure via the action of proteins including the glutathione S-transferase (GST) family. Due to previous findings of DNA damage and a reduced ovarian chemical biotransformation response to DMBA exposure in hyperphagia-induced obese mice, this study investigated the hypothesis that diet-induced obesity would hamper the ovarian biotransformative response to DMBA exposure. Six-week-old C57BL6/J mice were fed either a normal rodent diet (L) or a high fat high sucrose diet (O) until the O group was ∼30% heavier than the L. Both L and O mice were exposed to either corn oil (C) or DMBA (1 mg/kg) for 7 d. Liver weight was increased (P < 0.05) in obese mice exposed to DMBA but no effect on spleen weight, uterine weight, ovary weight, estrous cyclicity, or circulating 17β-estradiol and progesterone were observed. Primordial and preantral follicle numbers were higher (P < 0.05) in the obese mice and there was a tendency (P = 0.055) for higher antral follicles in DMBA-exposed obese mice. The ovarian proteome was identified by LC-MS/MS analysis to be altered both by diet-induced obesity and by DMBA exposure with changes observed in levels of proteins involved in oocyte development and chemical biotransformation, including GST isoform pi. Fewer proteins were affected by the combined exposure of diet and DMBA than by a single treatment, indicating that physiological status impacts the response to DMBA exposure.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"9-19"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing systemic toxicity risk assessment: Evaluation of a NAM-based toolbox approach.","authors":"Sophie Cable, Maria Teresa Baltazar, Fazila Bunglawala, Paul L Carmichael, Leonardo Contreas, Matthew Philip Dent, Jade Houghton, Predrag Kukic, Sophie Malcomber, Beate Nicol, Katarzyna R Przybylak, Ans Punt, Georgia Reynolds, Joe Reynolds, Sharon Scott, Dawei Tang, Alistair M Middleton","doi":"10.1093/toxsci/kfae159","DOIUrl":"10.1093/toxsci/kfae159","url":null,"abstract":"<p><p>For many years, a method that allowed systemic toxicity safety assessments to be conducted without generating new animal test data, seemed out of reach. However, several different research groups and regulatory authorities are beginning to use a variety of in silico, in chemico, and in vitro techniques to inform safety decisions. To manage this transition to animal-free safety assessments responsibly, it is important to ensure that the level of protection offered by a safety assessment based on new approach methodologies (NAMs), is at least as high as that provided by a safety assessment based on traditional animal studies. To this end, we have developed an evaluation strategy to assess both the level of protection and the utility offered by a NAM-based systemic safety \"toolbox.\" The toolbox comprises physiologically based kinetic models to predict internal exposures, and bioactivity NAMs designed to give broad coverage across many different toxicity modes of action. The output of the toolbox is the calculation of a bioactivity:exposure ratio (analogous to a margin of internal exposure), which can be used to inform decision-making. In this work, we have expanded upon an initial pilot study of 10 chemicals with an additional 38 chemicals and 70 consumer exposure scenarios. We found that, for the majority of these (>90%), the NAM-based workflow is protective of human health, enabling us to make animal-free safety decisions for systemic toxicity and preventing unnecessary animal use. We have also identified critical areas for improvement to further increase our confidence in the robustness of the approach.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"79-95"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reader comment on: \"Comprehensive genotoxicity and carcinogenicity assessment of molnupiravir\".","authors":"Clay B Frederick, Raymond F Schinazi, Ronald Swanstrom","doi":"10.1093/toxsci/kfae156","DOIUrl":"10.1093/toxsci/kfae156","url":null,"abstract":"","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":"116-117"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}