Regulatory Toxicology and Pharmacology最新文献

A physiologically based pharmacokinetic (PBPK) model to align dosimetry of the isobutyl metabolic series in rats and humans. 基于生理的药代动力学（PBPK）模型来校准大鼠和人异丁基代谢系列的剂量测定。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-12-01 Epub Date: 2025-07-26 DOI: 10.1016/j.yrtph.2025.105914

Jordan N Smith, Kimberly J Tyrrell, Karl K Weitz, Willem Faber

{"title":"A physiologically based pharmacokinetic (PBPK) model to align dosimetry of the isobutyl metabolic series in rats and humans.","authors":"Jordan N Smith, Kimberly J Tyrrell, Karl K Weitz, Willem Faber","doi":"10.1016/j.yrtph.2025.105914","DOIUrl":"10.1016/j.yrtph.2025.105914","url":null,"abstract":"<p><p>We developed a physiologically based pharmacokinetic (PBPK) model in rats and humans for the isobutyl metabolic series, which includes isobutyl acetate, isobutanol, isobutyraldehyde, and isobutyric acid. Given chemical similarities, we used a previously developed PBPK model for the propyl metabolic series as a framework to create the isobutyl PBPK model. To support model development, we measured in vitro metabolism of isobutyl acetate in rat and human blood and liver S9 fractions. Our findings indicated that humans exhibited faster isobutyl acetate hydrolysis in liver S9 fractions compared to rats, while hydrolysis rates in blood were similar between the two species. Experiments involving closed chamber exposures of rats to isobutyl acetate or isobutanol revealed higher isobutanol concentrations in blood compared to other isobutyl compounds. Using these data to parameterize the model, the PBPK model accurately simulated available time-course concentrations of isobutyl compounds in blood of rats and humans. The isobutyl PBPK model enables comparisons of internal dose metrics across various isobutyl compound exposures and species and allows for calculation of equivalent external exposures that result in the same dose metric. Regulators can employ this PBPK model to predict and align internal dose metrics of isobutyl compounds for risk assessment purposes.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"105914"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732945","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

Comprehensive study of radon levels, health risks, and physiochemical properties in tap water consumed in Iraqi Kurdistan using solid-state nuclear track detectors. 使用固态核径迹探测器对伊拉克库尔德斯坦饮用自来水中的氡水平、健康风险和理化性质进行全面研究。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-10-10 DOI: 10.1016/j.yrtph.2025.105960

Hiwa Mohammad Qadr, Najeba Farhad Salih, Alla Ahmed Muhamad Amin

{"title":"Comprehensive study of radon levels, health risks, and physiochemical properties in tap water consumed in Iraqi Kurdistan using solid-state nuclear track detectors.","authors":"Hiwa Mohammad Qadr, Najeba Farhad Salih, Alla Ahmed Muhamad Amin","doi":"10.1016/j.yrtph.2025.105960","DOIUrl":"https://doi.org/10.1016/j.yrtph.2025.105960","url":null,"abstract":"<p><p>Water quality assessment represents a fundamental component of public health surveillance programs. Radon concentrations in potable water constitute a significant contributor to environmental contamination and radiological exposure pathways. Consequently, this investigation quantified radon concentrations in tap water samples collected from the Ranya region of Iraqi Kurdistan, utilizing passive detection methodology employing CR-39 solid-state nuclear track detectors. Radiological safety and physicochemical properties of the tap water were evaluated. Measured radon concentrations exhibited a range of 0.068 to 0.194 Bq L<sup>-1</sup>, with a mean of 0.107 Bq L<sup>-1</sup>. All concentrations remained substantially below established regulatory thresholds of 11.1 Bq L<sup>-1</sup> for USEPA and 100 Bq L<sup>-1</sup> for WHO guidelines. In addition, the maximum annual effective doses from <sup>222</sup>Rn ingestion were 4.143, 4.888, and 8.167 μSv y<sup>-1</sup> for adults, children, and infants, respectively. Children and adults received lower annual effective doses than infants, though all age groups remained well below the WHO safety threshold of 100 μSv y<sup>-1</sup>. Cancer risk estimates for all age groups also remained below global reference levels. A strong positive correlation was not found between <sup>222</sup>Rn levels and tap water parameters. It appears that the results dispel local fears of significant radioactive risks by showing that radon concentrations are within the limits set by international organizations.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"105960"},"PeriodicalIF":3.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280764","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

Safe Usage Levels of Aqueous Hippophae rhamnoides Fruit Extract in Cosmetics Estimated by Threshold of Toxicological Concern, Point of Departure, and History of Safe Consumption. 根据毒理学关注阈值、起始点和安全消费历史估计化妆品中沙棘果提取物的安全使用水平。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-10-10 DOI: 10.1016/j.yrtph.2025.105961

Hyejeon Cho, Ye Ji Koo, Seung Ha Lee, Seungjin Bae, Jaeyun Choi, Kyung-Min Lim

{"title":"Safe Usage Levels of Aqueous Hippophae rhamnoides Fruit Extract in Cosmetics Estimated by Threshold of Toxicological Concern, Point of Departure, and History of Safe Consumption.","authors":"Hyejeon Cho, Ye Ji Koo, Seung Ha Lee, Seungjin Bae, Jaeyun Choi, Kyung-Min Lim","doi":"10.1016/j.yrtph.2025.105961","DOIUrl":"https://doi.org/10.1016/j.yrtph.2025.105961","url":null,"abstract":"<p><p>Botanical ingredients pose challenges to cosmetic safety assessors due to complex and variable composition. We estimated the safe usage levels of aqueous Hippophae rhamnoides fruit extract (HRFE) in cosmetics using Threshold of Toxicological Concern (TTC), Point of Departure (PoD) estimation, and history of safe consumption approaches. Skin and eye irritation and genotoxicity of HRFE were excluded through in vitro tests, first. The safe usage level of HRFE was estimated using TTC approach through identifying 85 constituents accounting for 98.46% of HRFE on mass basis, and calculating systemic exposure dosage levels. PoD from the rodent 90-day oral repeated-dose toxicity study and history of safe food consumption of Hippophae rhamnoides fruit were also utilized to derive safe usage levels of HRFE in cosmetics. Maximum safe usage levels of HRFE were estimated to be 0.125 mg/kg bw/day (extract powder), 0.5 mg/kg bw/day, and 166 mg/kg bw/day with TTC, PoD and history of safe consumption approach respectively, showing that TTC is the most conservative and history of safe consumption, the least. However, questions of material equivalence and route-difference remained for PoD and history of safe consumption. Collectively, this study may help to understand the pros and cons of current safety assessment methodologies for botanical ingredients.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"105961"},"PeriodicalIF":3.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280988","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

Mode of action analysis for induction of mouse lung tumors by permethrin: Involvement of CYP2F2 enzyme and human relevancy 氯菊酯诱导小鼠肺肿瘤的作用模式分析：CYP2F2酶的参与与人的相关性。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-10-04 DOI: 10.1016/j.yrtph.2025.105958

Dai Hasegawa , Kensuke Kawamoto , Keiko Ogata , Satoki Fukunaga , Samuel M. Cohen , Hiroyuki Asano

{"title":"Mode of action analysis for induction of mouse lung tumors by permethrin: Involvement of CYP2F2 enzyme and human relevancy","authors":"Dai Hasegawa , Kensuke Kawamoto , Keiko Ogata , Satoki Fukunaga , Samuel M. Cohen , Hiroyuki Asano","doi":"10.1016/j.yrtph.2025.105958","DOIUrl":"10.1016/j.yrtph.2025.105958","url":null,"abstract":"<div><div>Permethrin increases the incidence of bronchiolo-alveolar adenomas in female mice. The proposed mode of action (MOA) for permethrin-induced lung tumorigenesis involves increased mitogenesis in Club cells. Additionally, CYP2F2, which is particularly expressed in mouse lung Club cells and different from human CYP2F1, is considered to be a key factor in mouse-specific lung tumorigenesis. In this study, we investigated the relationship between permethrin-induced mouse lung tumorigenesis and CYP2F2 in CYP2f2 knockout (KO) mice. Fluensulfone and isoniazid were selected as positive controls. We showed that the increased proliferation of Club cells and increased proliferation of smooth endoplasmic reticulum (SER) within them were abolished in permethrin-treated CYP2f2 KO mice, while these changes were clearly observed in permethrin- and positive control-treated wild type mice. Additionally, the disappearance of the Club cell reaction was also observed in positive control-treated CYP2f2 KO mice. Based on these results, it was concluded that CYP2F2 is essential in the MOA of mouse lung tumorigenesis by permethrin, also suggesting that permethrin metabolism by CYP2F2 corresponds to a chain of early key events, including the molecular initiating event (MIE). Furthermore, the data suggested that CYP2F2 played a crucial role in mouse lung tumorigenesis induced by isoniazid, which is known to cause lung tumors in mice but not in humans. The collective data on permethrin-treated mouse lung tumorigenesis, including findings from this study, would lead to the conclusion that the lung tumors induced by permethrin treatment are mouse-specific and not relevant to human lung cancer risk.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105958"},"PeriodicalIF":3.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239524","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

Chemical characterization and toxicological evaluation of acrylic-based dental implant devices used for different purposes within the scope of ISO 10993 ISO 10993范围内用于不同用途的丙烯酸基牙科植入装置的化学特性和毒理学评价。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-27 DOI: 10.1016/j.yrtph.2025.105949

Tuğçe Kuruca , Deniz Demir , Esin Akarsu , Murat Akarsu

{"title":"Chemical characterization and toxicological evaluation of acrylic-based dental implant devices used for different purposes within the scope of ISO 10993","authors":"Tuğçe Kuruca , Deniz Demir , Esin Akarsu , Murat Akarsu","doi":"10.1016/j.yrtph.2025.105949","DOIUrl":"10.1016/j.yrtph.2025.105949","url":null,"abstract":"<div><div>Medical devices have the potential to release chemical constituents, either as residual manufacturing additives or as leachable under clinical conditions, which may pose potential toxicological risks. Therefore, comprehensive chemical characterization is crucial to identify and quantify extractable compounds that could migrate from the device during clinical use, in accordance with ISO 10993 standards.</div><div>This study provides a comprehensive chemical characterization and toxicological risk assessment of acrylic-based dental devices intended for various clinical applications. By adhering to ISO 10993–12:2021 for extraction protocols and employing both polar (water) and apolar (50:50 ethanol-water) solvents, leachable were analyzed after 72-h incubations at 50 °C. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the use of polymethyl methacrylate (PMMA) in device matrices, while thermogravimetric analysis (TGA) revealed the presence of inorganic pigments.</div><div>Extractable compounds were identified by using a broad range of analytical techniques-including Gas Chromatography-Mass Spectrometry (GC-MS), High Performance Liquid Chromatography (HPLC), UV–VIS–NIR Spectrophotometry because of extractable studies, Liquid Chromatography – Tandem Mass Spectrometry (LC-MS/MS) and Inductively Coupled Plasma–Optical Emission Spectrometry (ICP-OES) techniques, detecting compounds such as phenyl benzoate, N,N-dimethyl-p-toluidine, benzoyl peroxide, ethylene glycol dimethacrylate, and benzoic acid. Toxicological risk assessments were subsequently conducted in accordance with ISO 10993–17:2023, demonstrating that all tested devices were biocompatible and posed no toxicological hazard under intended clinical conditions.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105949"},"PeriodicalIF":3.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192701","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

Expert panel evaluation of the tumor modes of action for 1,4-dioxane and their implications for human risk assessment 专家小组对1,4-二恶烷的肿瘤作用方式及其对人类风险评估的影响的评估。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-25 DOI: 10.1016/j.yrtph.2025.105950

C.R. Kirman , J.S. Bus , S. Gupta , J.E. Klaunig , M.E. Meek , S.M. Hays

{"title":"Expert panel evaluation of the tumor modes of action for 1,4-dioxane and their implications for human risk assessment","authors":"C.R. Kirman , J.S. Bus , S. Gupta , J.E. Klaunig , M.E. Meek , S.M. Hays","doi":"10.1016/j.yrtph.2025.105950","DOIUrl":"10.1016/j.yrtph.2025.105950","url":null,"abstract":"<div><div>Mode of action (MOA) plays an important role in key decisions made in risk assessments, including that for low-dose extrapolation. To support MOA-dependent decisions for 1,4-dioxane (1,4-DX), an independent panel of topic experts evaluated the available evidence on the MOA and human relevance of 1,4-DX tumors reported in rodent studies. The panel considered MOA data on liver tumors in rodents, as well as for other tissue sites (nasal cavity, peritoneal mesothelioma). For liver tumors, the panelists found strongest support for an indirect genotoxic MOA involving metabolic saturation of the enzyme that metabolizes 1,4-DX (CYP2E1), followed by induction of CYP2E1, oxidative stress, cytotoxicity, and regenerative proliferation. Metabolic saturation was identified as an early key event. Although available evidence for nasal and peritoneal tumors was limited, similar non-genotoxic MOAs were considered plausible. For all three tumor types, confidence ratings (scale of −5 to +5) from the panel for the best supported MOAs (+2.5 to +3.3) were significantly higher than the confidence rating for a direct genotoxic MOA (−3.8 to −4.5). The conclusions from this independent panel, which included careful consideration of recently published studies, provide support for use of non-linear extrapolation methods in human health risk assessment for 1,4-DX rodent tumors.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105950"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182211","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

Suitability of the use of the intraperitoneal route in the in vivo micronucleus test to evaluate the genotoxicity of hair dyes 用腹膜内途径进行体内微核试验评价染发剂遗传毒性的适宜性

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-24 DOI: 10.1016/j.yrtph.2025.105948

Nicola J. Hewitt , Hind Assaf Vandecasteele , Paul Benndorf , Rolf Fautz , Anne Fuchs , Karma Fussell , Carsten Goebel , Torben König , Fabrice Nesslany , Juliane Werner , Paul Fowler

{"title":"Suitability of the use of the intraperitoneal route in the in vivo micronucleus test to evaluate the genotoxicity of hair dyes","authors":"Nicola J. Hewitt , Hind Assaf Vandecasteele , Paul Benndorf , Rolf Fautz , Anne Fuchs , Karma Fussell , Carsten Goebel , Torben König , Fabrice Nesslany , Juliane Werner , Paul Fowler","doi":"10.1016/j.yrtph.2025.105948","DOIUrl":"10.1016/j.yrtph.2025.105948","url":null,"abstract":"<div><div>New <em>in vivo</em> data cannot be generated for cosmetics. New safety assessments for genotoxicity must rely on <em>in vivo</em> data from the <em>in vivo</em> Mammalian Erythrocyte Micronucleus (MN) Test generated before the ban. Many used intraperitoneal (i.p.) administration, which is no longer recommended without scientific justification. Therefore, we investigated whether these studies are still valid for evaluating genotoxicity of hair dyes. Small to medium size molecules, including hair dyes, are preferentially absorbed via the portal vein and undergo first-pass metabolism, whereas large molecules are taken up by the lymphatics directly into the systemic circulation. Plasma concentrations of small molecules are generally similar, if not higher, after i.p. than after p.o. administration. Importantly, outcomes from <em>in vivo</em> MN Test using the i.p. and p.o. routes were equivalent. Most genotoxic carcinogens with positive outcomes in the <em>in vivo</em> MN Test were administered by i.p. injection. Differences between <em>in vivo</em> genotoxicity assay results using administration routes are attributed to the Mode of Action and/or tissue-specific effects. In conclusion, the i.p. route achieves sufficiently high internal exposure i.e., in the plasma and bone marrow. Therefore, legacy OECD test guideline compliant studies using the i.p. route are valid for current safety assessments of hair dyes.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105948"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160017","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

Beyond molecular structure: Comparing Australian and European regulatory approaches to nano-identification and classification 超越分子结构：比较澳大利亚和欧洲的纳米鉴定和分类管理方法

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-24 DOI: 10.1016/j.yrtph.2025.105947

Sarah Wilson, Stephen Northey, Rachael Wakefield-Rann, Nick Florin

{"title":"Beyond molecular structure: Comparing Australian and European regulatory approaches to nano-identification and classification","authors":"Sarah Wilson, Stephen Northey, Rachael Wakefield-Rann, Nick Florin","doi":"10.1016/j.yrtph.2025.105947","DOIUrl":"10.1016/j.yrtph.2025.105947","url":null,"abstract":"<div><div>Across regulation and toxicology, nanomaterials challenge foundational assumptions about substance identity and risk assessment. Through comparing substance identification requirements across Australian and European industrial chemical regulation – the Australian Industrial Chemicals Introduction Scheme (AICIS) and the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) respectively – this article explores how legal actors have incorporated the evolving science of nanotoxicology into the identification frameworks that establish regulatory approaches. These frameworks are important as they structure how regulators delineate between ‘new’ substances requiring novel risk assessment and regulatory approval, and ‘existing’ substances that have already been assessed.</div><div>The findings reveal REACH and AICIS have created contrasting approaches to nano-identification. REACH employs a comprehensive multifactorial method aligned with emerging nanotoxicological principles, while AICIS relies on broader structure-based CAS identifiers. These frameworks differ in both factors used and the specificity of material identification. Such regulatory data discrepancies could impact nano-risk regulation, creating potential scientific and legal vulnerabilities for managing distinct nanoforms with variable risk identities in Australia's regulatory environment. This analysis shows that the effective regulation of complex materials depends not just on accurate material characterisation, but on the structural design of legal information systems that mediate between scientific knowledge and regulatory action.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105947"},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160016","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

How many mutagens are missed under REACH due to limited low tonnage information requirements? 由于有限的低吨位信息要求，在REACH下遗漏了多少诱变剂？

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-22 DOI: 10.1016/j.yrtph.2025.105946

Rune Hjorth , Joop de Knecht , Eva B. Wedebye , Nikolai G. Nikolov , Damiën van Berlo , Henrik Tyle

{"title":"How many mutagens are missed under REACH due to limited low tonnage information requirements?","authors":"Rune Hjorth , Joop de Knecht , Eva B. Wedebye , Nikolai G. Nikolov , Damiën van Berlo , Henrik Tyle","doi":"10.1016/j.yrtph.2025.105946","DOIUrl":"10.1016/j.yrtph.2025.105946","url":null,"abstract":"<div><div>For industrial substances registered under REACH at 1–10 tonnes per registrant/year, only the Ames test is required to address mutagenicity. When a substance tests positive in the Ames test, further testing is needed, but when the test result is negative, additional mutagenicity testing is only mandatory at a higher tonnage level. It is correspondingly known that some mutagens produced up to 10 tonnes per year/registrant are not identified. Based on battery (Q)SAR modelling, relying on agreement from both <em>in vitro</em> and <em>in vivo</em> models, advisory self-classifications (ASC) for mutagenicity are offered by the Danish EPA. In this present study, substances with ASC for mutagenicity are compared to the identified mutagens in low tonnage REACH registrations. We conclude that for only about a quarter of the low-tonnage substances with an Muta. 2 ASC, a positive experimental Ames result is available, leading to follow-up under REACH. We recommend improving the identification of mutagenic substances at the 1–10 tonnage band by including the <em>in vitro</em> micronucleus test to supplement the Ames test. Concerningly, the few low tonnage REACH dossiers that do provide <em>in vivo</em> data, mostly report negative micronucleus test results that are not conclusive due to missing information on bone marrow exposure.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105946"},"PeriodicalIF":3.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138608","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

WITHDRAWN: Analysis and Comparison of New Psychoactive Substances (NPS) Regulation in Mainland China, Taiwan, Hong Kong, and Macao: Lessons for Global Control 中国大陆、台湾、香港和澳门新精神活性物质（NPS）法规的分析与比较：全球管制的经验教训。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-09-15 DOI: 10.1016/j.yrtph.2025.105943

Zhigang Zhou, Lanjun Zheng

引用次数: 0