Regulatory Toxicology and Pharmacology最新文献_第2页

The association between cadmium exposure and the risk of early liver disease: A systematic review and meta-analysis 镉暴露与早期肝病风险之间的关系：一项系统综述和荟萃分析。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-15 DOI: 10.1016/j.yrtph.2025.105942

Hualing Zhang , Yue Jing , Lan Guan , Jianlan Luo , Ming Zeng

{"title":"The association between cadmium exposure and the risk of early liver disease: A systematic review and meta-analysis","authors":"Hualing Zhang , Yue Jing , Lan Guan , Jianlan Luo , Ming Zeng","doi":"10.1016/j.yrtph.2025.105942","DOIUrl":"10.1016/j.yrtph.2025.105942","url":null,"abstract":"<div><div>Currently, liver diseases are considered to be one of the most prevalent diseases that jeopardize people's health. Existing studies have found that heavy metal cadmium (Cadmium, Cd) exposure is associated with liver disease, but the results of studies on the risk of cadmium on liver disease are inconsistent. In order to further investigate the relationship between cadmium exposure and the risk of early liver disease in the population, this study was conducted by searching PubMed, Cochrane Library, Web of Science, CNKI and Wanfang databases and performing meta-analysis of the relevant literature, so as to systematically evaluate the effect of cadmium exposure on the risk of liver disease. A total of 5201 relevant articles were retrieved. Based on inclusion and exclusion criteria, 25 articles were included in the meta-analysis. Review Manager 5.4 was used for quality assessment, with most studies rated as low risk of bias. Heterogeneity testing showed significant results (<em>P</em> < 0.05). Meta-analysis showed that cadmium exposure increased the risk of elevated liver enzymes (OR = 1.38, 95 % CI: 1.27–1.50), MAFLD (OR = 1.14, 95 % CI: 1.07–1.22) and liver fibrosis (OR = 1.39, 95 % CI: 1.14–1.70). Sensitivity analysis and publication bias detection indicated that the results were reliable. Therefore, the conclusion of this study is that environmental cadmium exposure increases the risk of liver disease, and the extent and dose of cadmium exposure in the population should be further controlled.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105942"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081476","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}

引用次数: 0

Dose level selection for developmental and reproductive toxicology (DART) studies: Insights from the EUROTOX 2024 satellite workshop 发育和生殖毒理学（DART）研究的剂量水平选择：来自EUROTOX 2024卫星研讨会的见解。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-15 DOI: 10.1016/j.yrtph.2025.105945

Fiona Sewell , Mark Blee , Daphne Peperkamp-van den Oetelaar , Manon Beekhuijzen

{"title":"Dose level selection for developmental and reproductive toxicology (DART) studies: Insights from the EUROTOX 2024 satellite workshop","authors":"Fiona Sewell , Mark Blee , Daphne Peperkamp-van den Oetelaar , Manon Beekhuijzen","doi":"10.1016/j.yrtph.2025.105945","DOIUrl":"10.1016/j.yrtph.2025.105945","url":null,"abstract":"<div><div>In 2022, the European Chemicals Agency (ECHA) issued updated advice on high-dose selection for developmental and reproductive toxicity (DART) studies, aiming to ensure reproductive hazards are identified without causing excessive toxicity or severe suffering in test animals. However, the advice faced much criticism from the scientific community with concerns around animal welfare and use of unnecessarily high doses. To better understand the background to the advice and explore the implications of this guidance, a satellite workshop was held at EUROTOX 2024 in Copenhagen, in collaboration with ECHA, that brought together over 120 global stakeholders from industry, regulatory bodies, academia, and contract research organisations. Discussions focused on the interpretation and application of the advice across OECD test guidelines (TGs 414, 421/422, and 443), highlighting areas of uncertainty, such as dose spacing, sex-specific sensitivity, and balancing fertility versus developmental endpoints. Interactive sessions revealed differing interpretations and underscored the need for clearer guidance. The workshop fostered mutual understanding and identified opportunities to refine the advice to better align scientific, regulatory, and animal welfare objectives. This report summarises key discussions and outlines the need for continued collaboration to support harmonised, scientifically justified dose selection practices that support both human health protection and 3Rs principles</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105945"},"PeriodicalIF":3.5,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081555","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}

引用次数: 0

An extended Reference Chemical Potency List (RCPL) for characterising the performance of New Approach Methodologies (NAMs) in measuring the skin sensitisation potency of fragrance chemicals 一种扩展的参考化学效价表（RCPL），用于表征新方法方法（NAMs）在测量芳香化学品的皮肤致敏效价方面的性能。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-13 DOI: 10.1016/j.yrtph.2025.105944

Amaia Irizar , Hans Bender , James W. Bridges , Peter Griem , Andreas Natsch , Matthias Vey , Ian Kimber

{"title":"An extended Reference Chemical Potency List (RCPL) for characterising the performance of New Approach Methodologies (NAMs) in measuring the skin sensitisation potency of fragrance chemicals","authors":"Amaia Irizar , Hans Bender , James W. Bridges , Peter Griem , Andreas Natsch , Matthias Vey , Ian Kimber","doi":"10.1016/j.yrtph.2025.105944","DOIUrl":"10.1016/j.yrtph.2025.105944","url":null,"abstract":"<div><div>The development of a Reference Chemical Potency List (RCPL), and its purpose, has been described previously. That original RCPL comprised 33 chemicals, of varying skin sensitising activity, for each of which a discrete Potency Value (PV) was derived, based upon the best available human and/or animal (local lymph node assay) data. The purpose of the RCPL was to provide a reliable tool that would facilitate evaluation of the ability of New Approach Methodologies (NAMs) to measure skin sensitising potency. We here report the construction of an extended RCPL with 77 additional chemicals by applying the weight of evidence framework used previously. This extended RCPL adheres to the salient features of the original database. These comprise a focus largely on fragrance chemicals, provision of a wide range of chemical structures and of skin sensitising potency, the inclusion of both direct and indirect (pre- and pro-) haptens, the exclusion of NAMs data for the derivation of PVs, and avoidance of the use of potency categories for the classification of chemicals. It is anticipated that this extended RCPL will provide a more powerful database with which to assess the strengths and weakness of recently developed NAMs in the measurement of skin sensitising potency.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105944"},"PeriodicalIF":3.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070352","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}

引用次数: 0

The skin sensitization prediction model: an algorithm for real-world prediction of skin sensitization risk and minimization of human sensitization testing. 皮肤致敏预测模型：一种用于真实世界皮肤致敏风险预测和人类致敏试验最小化的算法。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-13 DOI: 10.1016/j.yrtph.2025.105941

Ladan Fakhrzadeh, Otto Mills, Jim Bowman, Michael J Cork, Alain Khaiat, James A McGuire, Teginder Singh, Evren Atillasoy

{"title":"The skin sensitization prediction model: an algorithm for real-world prediction of skin sensitization risk and minimization of human sensitization testing.","authors":"Ladan Fakhrzadeh, Otto Mills, Jim Bowman, Michael J Cork, Alain Khaiat, James A McGuire, Teginder Singh, Evren Atillasoy","doi":"10.1016/j.yrtph.2025.105941","DOIUrl":"https://doi.org/10.1016/j.yrtph.2025.105941","url":null,"abstract":"<p><p>Skin sensitization testing to ensure the safety of skincare products for public consumption has largely relied on human repeat insult patch test (HRIPT). The desire to minimize reliance on HRIPT has prompted a search for alternative methods to assess the sensitization risk of consumer products to inform decision-making about their suitability before being brought to market. The novel Skin Sensitization Prediction Model (SSPM) is a methodology that draws upon a database consisting of more than 20 years of historical HRIPT data pertaining to 1,274 unique product formulations, comprising 1,226 common ingredients, for which HRIPT testing has been performed on 203,640 human subjects. The SSPM sets modifiable thresholds for each individual ingredient of a proposed formulation and for the formulation as a whole, applying risk calculations based on dosage density, potential for skin occlusion, potential for skin barrier impairment, and potential effects on immune-primed skin. Tabulations of a formulation's risk characteristics allow for a numerical risk calculation that is compared to the preset thresholds to determine whether the product may continue its development or should be reformulated or discontinued. This methodology points to a new model for sensitization testing for a wide array of products without recourse to in vivo testing.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"105941"},"PeriodicalIF":3.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070369","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}

引用次数: 0

Challenges and opportunities of read-across for the tumor promotion effects of microcystins 微囊藻毒素促肿瘤作用的解读挑战与机遇。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-11 DOI: 10.1016/j.yrtph.2025.105938

Cynthia B. Pestana , Daniela Morais Leme , Enzo Zini Moreira Silva , Sahra Kiessig , James W. Firman , Carsten Kneuer , Philip Marx-Stoelting , Mark T.D. Cronin

{"title":"Challenges and opportunities of read-across for the tumor promotion effects of microcystins","authors":"Cynthia B. Pestana , Daniela Morais Leme , Enzo Zini Moreira Silva , Sahra Kiessig , James W. Firman , Carsten Kneuer , Philip Marx-Stoelting , Mark T.D. Cronin","doi":"10.1016/j.yrtph.2025.105938","DOIUrl":"10.1016/j.yrtph.2025.105938","url":null,"abstract":"<div><div>The microcystins (MCs) are a family of cyclic oligopeptides toxins expressed in at least 30 cyanobacterial species and are liable to pose significant hazard to human health due to hepatotoxicity. Microcystin-leucine arginine (MC-LR) is the most extensively studied and toxic congener and classified as possibly carcinogenic to humans based on tumor promotion activity in the liver. Given the substantial toxicity data gaps for the MCs, read-across was assessed to evaluate the tumor promotion effects of a series of data-poor MC congeners based on <em>in vivo</em> information for MC-LR as the source molecule. Lines of evidence from <em>in silico</em> estimates of structural similarity, physico-chemical properties, hepatotoxicity, genotoxic and carcinogenicity were compiled to support the filling of data gaps. Uncertainties were evaluated according to scenario 4 of the European Chemicals Agency's (ECHA's) Read-Across Assessment Framework (RAAF). The read-across process followed a previously proposed harmonized framework to apply the common principles together with information from new approach methodologies (NAMs). Lines of evidence were consistent across the MC congeners and the uncertainties were found to be acceptable for data gap filling. Read-across strategies, with known caveats and restrictions, were shown to be applicable for large, complex molecules such as the MCs.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105938"},"PeriodicalIF":3.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058456","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}

引用次数: 0

Comparative assessment of 24 pigment dusts reveals analogue inhalation effects 24种颜料粉尘的比较评估揭示了类似的吸入效应。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-11 DOI: 10.1016/j.yrtph.2025.105934

Anne Herrmann , Laura Puente , Lan Ma-Hock , Heidi Stratmann

{"title":"Comparative assessment of 24 pigment dusts reveals analogue inhalation effects","authors":"Anne Herrmann , Laura Puente , Lan Ma-Hock , Heidi Stratmann","doi":"10.1016/j.yrtph.2025.105934","DOIUrl":"10.1016/j.yrtph.2025.105934","url":null,"abstract":"<div><div>A comparative analysis of 24 short-term inhalation studies with pigments revealed that while all pigments were well-tolerated without signs of systemic toxicity, most caused pulmonary inflammation and a slight to moderate increase in lung weight and neutrophil infiltration. The pathological and histopathological effects and changes observed were reversible at low and mid-level concentrations and declined within the 21 days recovery at the maximum concentration of 60 mg/m<sup>3</sup>. The slight to moderate epithelial hypertrophy and hyperplasia of the airways is considered being non-specific and adaptive. Benchmark calculations showed a 10 % lung weight increase and neutrophil infiltration at 5–20 mg/m<sup>3</sup>. Exposure levels above 30 mg/m<sup>3</sup> ended up in lung overload and impaired alveolar macrophage mediated lung clearance. Pigment particles showed a consistent effect pattern of particle-related pulmonary inflammation after short-term exposure, which was transient in nature below lung overload causing concentrations. Sub-chronic inhalation studies for three of the pigments tested confirmed the identified effect-pattern and the absence of substance-specific or chemical class-related effects. Consequently, classification and labelling according to the regulatory guidance values and criteria in place is not considered meaningful. The establishment of clear definitions, criteria and human exposure limits for poorly soluble particles is considered a pragmatic approach.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105934"},"PeriodicalIF":3.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058519","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}

引用次数: 0

Strengthening next generation risk decision-making: A contemporary review 加强下一代风险决策：当代回顾

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-10 DOI: 10.1016/j.yrtph.2025.105939

Yadvinder Bhuller , Raywat Deonandan , Daniel Krewski

{"title":"Strengthening next generation risk decision-making: A contemporary review","authors":"Yadvinder Bhuller , Raywat Deonandan , Daniel Krewski","doi":"10.1016/j.yrtph.2025.105939","DOIUrl":"10.1016/j.yrtph.2025.105939","url":null,"abstract":"<div><div>Risk decision-making inherently requires consideration of fundamental principles and other factors pertinent for addressing important health and environmental risks of concern. The risk decision-making process has evolved from linear frameworks to more integrated and dynamic strategies. A recent scoping review mapped this evolution and demonstrated a transition to more holistic and complex approaches. The term next generation risk decision-making captures these contemporary strategies by incorporating all aspects of risk assessment, management, and communication involved in risk decision-making, thereby going beyond recently articulated next generation risk assessment frameworks. While this scoping review included best practices and ten attributes of risk decision-making, it did not address how to consider these factors when developing strategies for next generation risk decision-making. This contemporary review addresses this limitation by discussing the role of decision theories prior to presenting a model for characterizing, categorizing, and visualizing these ten considerations: foresight and planning, research and development, regulatory, risk, upstream and downstream attributes, risk culture, ONE Health lens, broad regulatory factors, risk management, and risk communication. The realist paradigm-based model and corresponding considerations are then analyzed using a strengths, weaknesses, opportunities, and threats analysis of top-down, bottom-up, and fully integrated risk science strategies to next generation risk decision-making.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105939"},"PeriodicalIF":3.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044766","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}

引用次数: 0

Assessment of phototoxicity potential of botanicals as cosmetic ingredients using the in vitro 3T3 neutral red uptake phototoxicity test 用体外3T3中性红吸收光毒性试验评价植物化妆品成分的光毒性潜力。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-09 DOI: 10.1016/j.yrtph.2025.105940

Allison Hilberer , Lisa Hoffman , Megan Madrid , Ramez Labib , Gertrude-Emilia Costin

{"title":"Assessment of phototoxicity potential of botanicals as cosmetic ingredients using the in vitro 3T3 neutral red uptake phototoxicity test","authors":"Allison Hilberer , Lisa Hoffman , Megan Madrid , Ramez Labib , Gertrude-Emilia Costin","doi":"10.1016/j.yrtph.2025.105940","DOIUrl":"10.1016/j.yrtph.2025.105940","url":null,"abstract":"<div><div>Cosmetics and personal care products are frequently formulated with botanical ingredients due to their beneficial properties, the nature of their composition, and consumers’ interest for products with more natural or organic profiles. Compounds that absorb light significantly and are in contact with the skin have potential to become phototoxic upon exposure to sunlight. Here we demonstrate that an <em>in vitro</em> test methodology, the 3T3 Neutral Red Uptake Phototoxicity Test (3T3 NRU PT), is an effective screening tool in evaluation of botanical ingredients that absorb light in the Ultraviolet/Visible (UV/Vis) range. Thirty-eight prospective botanical ingredients were evaluated in the 3T3 NRU PT assay. Five botanicals were identified to have phototoxicity potential, and were eliminated from consideration for use. Thirty three botanicals were identified to have no phototoxicity potential in the 3T3 NRU PT; and a subset of six were further evaluated in a clinical confirmatory test that corroborated the data obtained using the <em>in vitro</em> test. Our results support this <em>in vitro</em> test method as a reliable, high throughput model in evaluating a large subset of compounds to efficiently identify those that pose a potential risk and to ensure that marketed cosmetic products do not contain ingredients with phototoxicity potential.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105940"},"PeriodicalIF":3.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041187","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}

引用次数: 0

Toxicology of bromoform, a natural constituent of the seaweed Asparagopsis spp. used to inhibit methanogenesis in cattle, suggests negligible risks to humans 溴仿是海藻天冬酰胺属的一种天然成分，用于抑制牛体内的甲烷生成，其毒理学表明对人类的风险可以忽略不计。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-08 DOI: 10.1016/j.yrtph.2025.105937

P.J. Cressey , A. Gautam , A.J. Pearson , J. Fowles , P. Tyagi , C.T. Eason

{"title":"Toxicology of bromoform, a natural constituent of the seaweed Asparagopsis spp. used to inhibit methanogenesis in cattle, suggests negligible risks to humans","authors":"P.J. Cressey , A. Gautam , A.J. Pearson , J. Fowles , P. Tyagi , C.T. Eason","doi":"10.1016/j.yrtph.2025.105937","DOIUrl":"10.1016/j.yrtph.2025.105937","url":null,"abstract":"<div><div>The red seaweeds, <em>Asparagopsis taxiformis and A. armata</em> inhibit methane production in ruminants, considered to be mediated by bromoform. This review examines the toxicology, metabolism, epidemiology and pharmacology of bromoform. IARC concludes bromoform is not classifiable as a carcinogen to humans, whereas the US EPA classifies it as a probable human carcinogen based on a low incidence of intestinal tumours in female rats given high gavage doses chronically. Under the same conditions, mice exhibited no tumours, suggesting that tumour formation is secondary to localised cytotoxicity. While there is some <em>in vitro</em> evidence of mutagenic potential for bromoform, likely via a metabolic pathway involving GSTT11-1, this pathway is unlikely to be relevant at low doses. The human evidence, from drinking water disinfection by-product studies, is inconclusive. While some residue studies find bromoform in milk, the concentrations approach background levels and pose no significant cancer risk. The collective implication of these findings is that bromoform, as an environmental inhibitor, does not pose a significant risk. A precautionary approach would ensure that bromoform intake does not exceed the capacity for rumen degradation such that concentrations of residues in tissues and milk and consequent dietary exposure are minimised and below relevant health-based guidance values.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105937"},"PeriodicalIF":3.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034043","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}

引用次数: 0

Evaluation of an anti-thyroid mode of action for thyroid follicular cell adenomas in female mice exposed to tertiary butyl alcohol 叔丁醇对雌性小鼠甲状腺滤泡细胞腺瘤抗甲状腺作用模式的评价。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-04 DOI: 10.1016/j.yrtph.2025.105936

Susan J. Borghoff , Melissa M. Heintz , Brianna N. Rivera , Laurie Haws , Chad Thompson

{"title":"Evaluation of an anti-thyroid mode of action for thyroid follicular cell adenomas in female mice exposed to tertiary butyl alcohol","authors":"Susan J. Borghoff , Melissa M. Heintz , Brianna N. Rivera , Laurie Haws , Chad Thompson","doi":"10.1016/j.yrtph.2025.105936","DOIUrl":"10.1016/j.yrtph.2025.105936","url":null,"abstract":"<div><div>Chronic exposure to tertiary butyl alcohol (TBA) in drinking water (DW) is associated with low but increased incidence (15 % vs 3 % in controls) of thyroid follicular cell adenomas in female mice. The U.S. Environmental Protection Agency evaluated this data in the context of an anti-thyroid mode of action (MOA) and identified data gaps while noting evidence for thyroid adenomas as “suggestive”. A study was designed to address data gaps in the MOA for TBA thyroid tumors. Female mice were exposed for 5 days to TBA by oral gavage (500 or 1000 mg/kg) or via DW (5–40 mg/mL) for up to 28 days. TBA activated upstream key events (KEs) within the anti-thyroid MOA framework including CAR/PXR signaling and upregulation of UGT and SULT transcripts. However, increased UGT and SULT activity was not observed. Downstream events (decreased serum TSH and thyroid histopathology prior to 2-years) were not demonstrated. The inability to demonstrate downstream KEs is likely a consequence of a weak tumor response with chronic exposure to TBA. With previously published data, an anti-thyroid MOA is a plausible explanation for a weak TBA tumor response, with analysis highlighting important consequences of conducting risk assessments on weak, suggestive tumor data.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105936"},"PeriodicalIF":3.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008486","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}

引用次数: 0