Regulatory Toxicology and Pharmacology最新文献

{"title":"Comparison of permitted daily exposure (PDE) values for active pharmaceutical ingredients (APIs) - Evidence of a robust approach","authors":"Claudia Sehner ,&nbsp;Tanja Bernier ,&nbsp;Kamila Blum ,&nbsp;Nicole Clemann ,&nbsp;Milica Glogovac ,&nbsp;William A. Hawkins ,&nbsp;Martin Kohan ,&nbsp;Fenneke Linker ,&nbsp;Ester Lovsin-Barle ,&nbsp;Osahon Osadolor ,&nbsp;Thomas Pfister ,&nbsp;Elisa Schulze ,&nbsp;Markus Schwind ,&nbsp;Gregor Tuschl ,&nbsp;Lisa Wiesner","doi":"10.1016/j.yrtph.2024.105649","DOIUrl":"10.1016/j.yrtph.2024.105649","url":null,"abstract":"<div><p>Permitted Daily Exposure Limits (PDEs) are set for Active Pharmaceutical Ingredients (APIs) to control cross-contamination when manufacturing medicinal products in shared facilities. With the lack of official PDE lists for pharmaceuticals, PDEs have to be set by each company separately. Although general rules and guidelines for the setting of PDEs exist, inter-company variations in the setting of PDEs occur and are considered acceptable within a certain range. To evaluate the robustness of the PDE approach between different pharmaceutical companies, data on PDE setting of five marketed APIs (amlodipine, hydrochlorothiazide, metformin, morphine, and omeprazole) were collected and compared. Findings show that the variability between PDE values is within acceptable ranges (below 10-fold) for all compounds, with the highest difference for morphine due to different Point of Departures (PODs) and Adjustment Factors (AFs). Factors of PDE variability identified and further discussed are: (1) availability of data, (2) selection of POD, (3) assignment of AFs, (4) route-to-route extrapolation, and (5) expert judgement and differences in company policies. We conclude that the investigated PDE methods and calculations are robust and scientifically defensible. Additionally, we provide further recommendations to harmonize PDE calculation approaches across the pharmaceutical industry.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"150 ","pages":"Article 105649"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining recommended acceptable intake limits for N-nitrosamine impurities in pharmaceuticals: Development and application of the Carcinogenic Potency Categorization Approach (CPCA)","authors":"Naomi L. Kruhlak ,&nbsp;Marianne Schmidt ,&nbsp;Roland Froetschl ,&nbsp;Stefan Graber ,&nbsp;Bodo Haas ,&nbsp;Irene Horne ,&nbsp;Stephen Horne ,&nbsp;Sruthi T. King ,&nbsp;Iryna A. Koval ,&nbsp;Govindaraj Kumaran ,&nbsp;Anja Langenkamp ,&nbsp;Timothy J. McGovern ,&nbsp;Tyler Peryea ,&nbsp;Alan Sanh ,&nbsp;Aline Siqueira Ferreira ,&nbsp;Leon van Aerts ,&nbsp;Alisa Vespa ,&nbsp;Rhys Whomsley","doi":"10.1016/j.yrtph.2024.105640","DOIUrl":"10.1016/j.yrtph.2024.105640","url":null,"abstract":"<div><p><em>N</em>-Nitrosamine impurities, including nitrosamine drug substance-related impurities (NDSRIs), have challenged pharmaceutical industry and regulators alike and affected the global drug supply over the past 5 years. Nitrosamines are a class of known carcinogens, but NDSRIs have posed additional challenges as many lack empirical data to establish acceptable intake (AI) limits. Read-across analysis from surrogates has been used to identify AI limits in some cases; however, this approach is limited by the availability of robustly-tested surrogates matching the structural features of NDSRIs, which usually contain a diverse array of functional groups. Furthermore, the absence of a surrogate has resulted in conservative AI limits in some cases, posing practical challenges for impurity control. Therefore, a new framework for determining recommended AI limits was urgently needed. Here, the Carcinogenic Potency Categorization Approach (CPCA) and its supporting scientific rationale are presented. The CPCA is a rapidly-applied structure-activity relationship-based method that assigns a nitrosamine to 1 of 5 categories, each with a corresponding AI limit, reflecting predicted carcinogenic potency. The CPCA considers the number and distribution of α-hydrogens at the <em>N</em>-nitroso center and other activating and deactivating structural features of a nitrosamine that affect the α-hydroxylation metabolic activation pathway of carcinogenesis. The CPCA has been adopted internationally by several drug regulatory authorities as a simplified approach and a starting point to determine recommended AI limits for nitrosamines without the need for compound-specific empirical data.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"150 ","pages":"Article 105640"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024000813/pdfft?md5=a41cbb76ac67c29706ef30352a080f5e&pid=1-s2.0-S0273230024000813-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of non-mutagenic substances in the context of drug impurity assessment - Few are potent toxicants.","authors":"Catrin Hasselgren, Michelle Kenyon, Lennart T Anger, Paul Cornwell, Eric Watt, Joel Bercu","doi":"10.1016/j.yrtph.2024.105645","DOIUrl":"10.1016/j.yrtph.2024.105645","url":null,"abstract":"<p><p>ICH Q3A/B guidelines provide qualification thresholds for impurities or degradation products in new drug substances and products. However, the guidelines note that certain impurities/degradation products may warrant further safety evaluation for being unusually potent or toxic. The purpose of this study was to confirm that especially toxic non-mutagenic compounds are rare and to identify classes of compounds that could warrant lower qualification thresholds. A total of 2815 compounds were evaluated, of which 2213 were assessed as non-mutagenic. For the purpose of this analysis, compounds were considered potent when the point of departure was ≤0.2 mg/kg/day based on the qualification threshold (1 mg/day or 0.02 mg/kg/day for a 50 kg human) in a new drug substance, with an additional 10-fold margin. Only 54 of the entire set (2.4%) would be considered potent based on this conservative potency analysis, confirming that the existing ICH Q3A/B qualification thresholds are appropriate for the majority of impurities. If the Q3A/B threshold, without the additional 10-fold margin is used, 14 compounds (0.6%) are considered \"highly potent\". Very few non-mutagenic structural classes were identified, including organothiophosphates and derivatives, polychlorinated benzenes and polychlorinated polycyclic aliphatics, that correlate with potential high potency, consistent with prior publications.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"105645"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deriving acceptable limits for non-mutagenic impurities in medicinal products - Durational adjustments.","authors":"Michelle O Kenyon, Matthew Martin, Elizabeth A Martin, Susanne Brandstetter, Teresa Wegesser, Nigel Greene, James Harvey","doi":"10.1016/j.yrtph.2024.105644","DOIUrl":"10.1016/j.yrtph.2024.105644","url":null,"abstract":"<p><p>ICH Q3A/B guidelines are not intended for application during the clinical research phase of development and durationally adjusted qualification thresholds are not included. A central tenet of ICH Q3A is that lifetime exposure to 1 mg/day of an unqualified non-mutagenic impurity (NMI) is not a safety concern. An analysis of in vivo toxicology data from 4878 unique chemicals with established NO(A)ELs was conducted to determine whether durationally adjusted qualification limits can be supported. Although not recommended in ICH Q3A/B, a conservative approach was taken by using allometric scaling in the analysis. Following allometric scaling of the 5th percentile of the distribution of NO(A)ELs from available chronic toxicology studies, it was reconfirmed that there is a safety basis for the 1 mg/day qualification threshold in ICH Q3A. Additionally, allometric scaling of the 5th percentile of the distribution of NO(A)ELs from sub-acute and sub-chronic toxicology studies could support acceptable limits of 20 and 5 mg/day for an unqualified NMI for dosing durations of less than or greater than one month, respectively. This analysis supports durationally adjusted NMI qualification thresholds for pharmaceuticals that protect patient safety and contribute to 3Rs efforts for qualifying impurities using new approach methods.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"105644"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of non-mutagenic substances in the context of drug impurity assessment – Few are potent toxicants","authors":"Catrin Hasselgren ,&nbsp;Michelle Kenyon ,&nbsp;Lennart T. Anger ,&nbsp;Paul Cornwell ,&nbsp;Eric Watt ,&nbsp;Joel Bercu","doi":"10.1016/j.yrtph.2024.105645","DOIUrl":"10.1016/j.yrtph.2024.105645","url":null,"abstract":"<div><p>ICH Q3A/B guidelines provide qualification thresholds for impurities or degradation products in new drug substances and products. However, the guidelines note that certain impurities/degradation products may warrant further safety evaluation for being unusually potent or toxic. The purpose of this study was to confirm that especially toxic non-mutagenic compounds are rare and to identify classes of compounds that could warrant lower qualification thresholds. A total of 2815 compounds were evaluated, of which 2213 were assessed as non-mutagenic. For the purpose of this analysis, compounds were considered potent when the point of departure was ≤0.2 mg/kg/day based on the qualification threshold (1 mg/day or 0.02 mg/kg/day for a 50 kg human) in a new drug substance, with an additional 10-fold margin. Only 54 of the entire set (2.4%) would be considered potent based on this conservative potency analysis, confirming that the existing ICH Q3A/B qualification thresholds are appropriate for the majority of impurities. If the Q3A/B threshold, without the additional 10-fold margin is used, 14 compounds (0.6%) are considered “highly potent”. Very few non-mutagenic structural classes were identified, including organothiophosphates and derivatives, polychlorinated benzenes and polychlorinated polycyclic aliphatics, that correlate with potential high potency, consistent with prior publications.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"150 ","pages":"Article 105645"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024000862/pdfft?md5=bfcf487302a79c6e98f8b6973a7f34d4&pid=1-s2.0-S0273230024000862-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141042130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the EMA log kow trigger for fish BCF testing based on data for several human pharmaceuticals","authors":"Lisa A. Constantine ,&nbsp;Natalie Burden ,&nbsp;Todd Davidson ,&nbsp;David G. Dolan ,&nbsp;Gemma Janer ,&nbsp;Andreas Häner ,&nbsp;Michael R. Lee ,&nbsp;Samuel K. Maynard ,&nbsp;Erick Nfon ,&nbsp;Alison Nimrod Perkins ,&nbsp;James J. Ryan ,&nbsp;Joan Tell","doi":"10.1016/j.yrtph.2024.105651","DOIUrl":"10.1016/j.yrtph.2024.105651","url":null,"abstract":"<div><p>In the European Medicines Agency (EMA) “Guideline for Environmental Risk Assessment of Medicinal Products for Human Use,” a fish bioconcentration factor (BCF) study is triggered in Phase I for pharmaceuticals having log Kow &gt;4.5, to support Persistence, Bioaccumulation and Toxicity (PBT) screening, and in Phase II to assess secondary poisoning and bioaccumulation (‘B’) potential when log Kow ≥3. The standard sampling schedule outlined in OECD Test Guideline 305 (TG305) may require assessment of approximately 200 fish following exposure to low- and high-test concentrations and a negative control. We report experimental log Kow and BCF values for 64 human pharmaceuticals that were used to evaluate the current BCF testing trigger of log Kow ≥3, and whether a single BCF exposure concentration allows accurate classification of bioaccumulation potential. Our data support raising the BCF testing trigger to log Kow ≥4, and use of a single test concentration. The resulting reduction in the use of fish is consistent with the 3 R s principle and did not adversely affect classification accuracy. An assessment of potential risk of secondary poisoning was also conducted for three drugs classified as either B or vB, and no risks were identified.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"151 ","pages":"Article 105651"},"PeriodicalIF":3.4,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatotoxicity of silver nanoparticles: Benchmark concentration modeling of an in vitro transcriptomics study in human iPSC-derived hepatocytes","authors":"Xiugong Gao ,&nbsp;W. Evan Johnson ,&nbsp;Miranda R. Yourick ,&nbsp;Kayla Campasino ,&nbsp;Robert L. Sprando ,&nbsp;Jeffrey J. Yourick","doi":"10.1016/j.yrtph.2024.105653","DOIUrl":"10.1016/j.yrtph.2024.105653","url":null,"abstract":"<div><p>Despite two decades of research on silver nanoparticle (AgNP) toxicity, a safe threshold for exposure has not yet been established, albeit being critically needed for risk assessment and regulatory decision-making. Traditionally, a point-of-departure (PoD) value is derived from dose response of apical endpoints in animal studies using either the no-observed-adverse-effect level (NOAEL) approach, or benchmark dose (BMD) modeling. To develop new approach methodologies (NAMs) to inform human risk assessment of AgNPs, we conducted a concentration response modeling of the transcriptomic changes in hepatocytes derived from human induced pluripotent stem cells (iPSCs) after being exposed to a wide range concentration (0.01–25 μg/ml) of AgNPs for 24 h. A plausible transcriptomic PoD of 0.21 μg/ml was derived for a pathway related to the mode-of-action (MOA) of AgNPs, and a more conservative PoD of 0.10 μg/ml for a gene ontology (GO) term not apparently associated with the MOA of AgNPs. A reference dose (RfD) could be calculated from either of the PoDs as a safe threshold for AgNP exposure. The current study illustrates the usefulness of <em>in vitro</em> transcriptomic concentration response study using human cells as a NAM for toxicity study of chemicals that lack adequate toxicity data to inform human risk assessment.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"151 ","pages":"Article 105653"},"PeriodicalIF":3.4,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024000941/pdfft?md5=39ad87697b3b09ed1c1f2ce559b35a54&pid=1-s2.0-S0273230024000941-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testing of acute and sub-acute toxicity profile of novel naproxen sodium nanoformulation in male and female mice","authors":"Irfan Zia Qureshi ,&nbsp;Ayesha Razzaq ,&nbsp;Syeda Sohaila Naz","doi":"10.1016/j.yrtph.2024.105650","DOIUrl":"10.1016/j.yrtph.2024.105650","url":null,"abstract":"<div><p>Nanodrugs offer promising alternatives to conventionally used over the counter drugs. Compared to its free form, therapeutic benefits, and gastric tissue safety of naproxen sodium nanoformulation (NpNF) were recently demonstrated. Essential regulatory safety data for this formulation are, however, not available. To address this, male and female BALB/c mice were subjected to acute and 14-day repeated-oral dose assessments. Our data indicate that NpNF was well tolerated up to 2000 mg/kg b.w. A 14-day subacute toxicity testing revealed that the oral administration of low dose (30 mg/kg) NpNF did not produce any adverse effects on blood profile and serum biochemical parameters. Levels of oxidative stress markers and antioxidant enzymes neared normal. Histology of selected tissues also showed no evidence of toxicity. In contrast, a ten-fold increase in NpNF dosage (300 mg/kg), demonstrated, irrespective of gender, mild to moderate toxicity (p &lt; 0.05) in the brain, stomach, and heart tissues, while ROS, LPO, CAT, SOD, POD, and GSH levels remained unaffected in the liver, kidney, spleen, testis, and seminal vesicles. No effect on serum biochemical parameters, overall indicated a no-observed-adverse-effect level (NOAEL) is 300 mg/kg. Further increase in dosage (1000 mg/kg) significantly altered all parameters demonstrating that high dose is toxic.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"150 ","pages":"Article 105650"},"PeriodicalIF":3.4,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in the anatomy and physiology of the human and rat respiratory tracts and impact on toxicological assessments","authors":"Andreas O. Stucki ,&nbsp;Ursula G. Sauer ,&nbsp;David G. Allen ,&nbsp;Nicole C. Kleinstreuer ,&nbsp;Monique M. Perron ,&nbsp;Krystle L. Yozzo ,&nbsp;Anna B. Lowit ,&nbsp;Amy J. Clippinger","doi":"10.1016/j.yrtph.2024.105648","DOIUrl":"10.1016/j.yrtph.2024.105648","url":null,"abstract":"<div><p>Inhalation is a critical route through which substances can exert adverse effects in humans; therefore, it is important to characterize the potential effects that inhaled substances may have on the human respiratory tract by using fit for purpose, reliable, and human relevant testing tools. In regulatory toxicology testing, rats have primarily been used to assess the effects of inhaled substances as they—being mammals—share similarities in structure and function of the respiratory tract with humans. However, questions about inter-species differences impacting the predictability of human effects have surfaced. Disparities in macroscopic anatomy, microscopic anatomy, or physiology, such as breathing mode (<em>e.g.</em>, nose-only versus oronasal breathing), airway structure (<em>e.g.</em>, complexity of the nasal turbinates), cell types and location within the respiratory tract, and local metabolism may impact inhalation toxicity testing results. This review shows that these key differences describe uncertainty in the use of rat data to predict human effects and supports an opportunity to harness modern toxicology tools and a detailed understanding of the human respiratory tract to develop testing approaches grounded in human biology. Ultimately, as the regulatory purpose is protecting human health, there is a need for testing approaches based on human biology and mechanisms of toxicity.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"150 ","pages":"Article 105648"},"PeriodicalIF":3.4,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024000898/pdfft?md5=7be3c9fb7e5bc88bed83dc22a805d5d4&pid=1-s2.0-S0273230024000898-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prioritizing of potential environmental exposure carcinogens beyond IARC group 1–2B based on weight of evidence (WoE) approach","authors":"Lu Zhang ,&nbsp;Min Li ,&nbsp;Dalong Zhang ,&nbsp;Wenbo Yue ,&nbsp;Zhiyong Qian","doi":"10.1016/j.yrtph.2024.105646","DOIUrl":"10.1016/j.yrtph.2024.105646","url":null,"abstract":"<div><p>Environmental exposures are the main cause of cancer, and their carcinogenicity has not been fully evaluated, identifying potential carcinogens that have not been evaluated is critical for safety. This study is the first to propose a weight of evidence (WoE) approach based on computational methods to prioritize potential carcinogens. Computational methods such as read across, structural alert, (Quantitative) structure-activity relationship and chemical-disease association were evaluated and integrated. Four different WoE approach was evaluated, compared to the best single method, the WoE-1 approach gained 0.21 and 0.39 improvement in the area under the receiver operating characteristic curve (AUC) and Matthew's correlation coefficient (MCC) value, respectively. The evaluation of 681 environmental exposures beyond IARC list 1–2B prioritized 52 chemicals of high carcinogenic concern, of which 21 compounds were known carcinogens or suspected carcinogens, and eight compounds were identified as potential carcinogens for the first time. This study illustrated that the WoE approach can effectively complement different computational methods, and can be used to prioritize chemicals of carcinogenic concern.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"150 ","pages":"Article 105646"},"PeriodicalIF":3.4,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}