Regulatory Toxicology and Pharmacology最新文献_第7页

Biomonitoring of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide: A global view 2,4-二氯苯氧乙酸（2,4-D）除草剂的生物监测：全球视野。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-08-19 DOI: 10.1016/j.yrtph.2024.105687

Denali Boon , Carol J. Burns

{"title":"Biomonitoring of 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide: A global view","authors":"Denali Boon , Carol J. Burns","doi":"10.1016/j.yrtph.2024.105687","DOIUrl":"10.1016/j.yrtph.2024.105687","url":null,"abstract":"<div><p>We conducted a literature review of urinary 2,4-D in populations not associated with a herbicide application. Of the 33 studies identified, the median/mean concentrations were similar for children, adults, and pregnant women regardless of geography. Individuals with highest concentrations may have had opportunities to directly contact 2,4-D outside of an application. Most studies were conducted in populations in North America and did not examine potential sources of 2,4-D, or what factors might influence higher or lower urinary 2,4-D concentrations. In the future, prioritizing the examination of 2,4-D biomonitoring in other regions and collecting information on sources and factors influencing exposures would better our understanding of 2,4-D exposures globally. In all the studies reviewed the concentrations of urinary 2,4-D observed were orders of magnitude below the US regulatory endpoints, suggesting that people are not being exposed to 2,4-D at levels high enough to result in adverse health effects.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105687"},"PeriodicalIF":3.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001284/pdfft?md5=d176f9b39800327fd586b648c6567b0a&pid=1-s2.0-S0273230024001284-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018434","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}

引用次数: 0

Prenatal developmental toxicity studies of allyl alcohol in rats and rabbits 工作标题：烯丙醇对大鼠和兔子的产前发育毒性研究。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-08-14 DOI: 10.1016/j.yrtph.2024.105684

Wade Barranco , Jefferson Fowles , Erik K. Rushton

{"title":"Prenatal developmental toxicity studies of allyl alcohol in rats and rabbits","authors":"Wade Barranco , Jefferson Fowles , Erik K. Rushton","doi":"10.1016/j.yrtph.2024.105684","DOIUrl":"10.1016/j.yrtph.2024.105684","url":null,"abstract":"<div><p>Allyl alcohol (C3H6O; prop-2-en-1-ol; CAS RN 107-18-6; EINECS 203-470-7) is used as an intermediate/monomer in polymerization reactions producing chemicals/optical resins or as a coupling/cross-linking agent for unsaturated polyester and alkyd resins. Human exposure to allyl alcohol (AA) is restricted to workplace manufacturing facilities where it is used in enclosed systems, which limits release and impact on environmental receptors. To address regulatory questions about possible developmental toxicity, two OECD Guideline studies were conducted. A rat developmental toxicity study found fetal and maternal toxicity, in the form of resorptions and decreased body weight and food consumption, but no teratogenic effects. A rabbit developmental toxicity study was subsequently conducted upon request by the European Chemical Agency in 2011 under the REACH program and likewise reported maternal toxicity in the form of reductions in body weight gain and food consumption, but neither fetal toxicity or teratogenic effects. The results of both studies are presented and compared in this paper. Based on our review of the collective results of these studies, AA is considered non-teratogenic, yet does elicit increased post-implantation loss and reduced fetal body weight, possibly resulting from concomitant maternal toxicity. Based on the results of these studies, a maternal and developmental toxicity No Observed Adverse Effect Level of 10 mg/kg/day was apparent for both species.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105684"},"PeriodicalIF":3.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996340","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

Toxicity reference values for force health protection: Provisional occupational exposure guidelines 部队健康保护毒性参考值：暂定职业接触准则》。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-08-14 DOI: 10.1016/j.yrtph.2024.105686

Lisa M. Sweeney , Teresa R. Sterner

{"title":"Toxicity reference values for force health protection: Provisional occupational exposure guidelines","authors":"Lisa M. Sweeney , Teresa R. Sterner","doi":"10.1016/j.yrtph.2024.105686","DOIUrl":"10.1016/j.yrtph.2024.105686","url":null,"abstract":"<div><p>Force Health Protection programs in the U.S. Air Force endeavor to sustain the operational readiness of the warfighters. We have previously identified hundreds of chemical substances of interest and toxicity reference value (TRV) knowledge gaps that constrain risk based-decision-making for potential exposures. Multiple approaches to occupational TRV estimation were used to generate possible guideline values for 84 compounds (18% of the substances of interest). These candidate TRVs included values from international databases, chemical similarity (nearest neighbor) approaches, empirical adjustments to account for duration differences, quantitative activity relationships, and thresholds of toxicological concern. This present work describes derivation of provisional TRVs from these candidate values. Rodent bioassay-derived long-term worker Derived No-Effect Levels (DNELs) were deemed presumptively the most reliable, but only 19 such DNELs were available for the 84 substances with TRV gaps. In the absence of DNELs, the quality of the approaches and consistency among candidate values were key elements of the weight of evidence used to select the most suitable guideline values. The use of novel nearest-neighbor approaches, empirical adjustment of short term TRVs, and occupational exposure bands were found to be options that would allow occupational TRV estimation with reasonable confidence for nearly all substances evaluated.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105686"},"PeriodicalIF":3.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996339","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

Toxicity reference values (TRVs) for force health protection: Gap identification and TRV prediction 保护部队健康的毒性参考值 (TRV)：差距识别和 TRV 预测。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-08-13 DOI: 10.1016/j.yrtph.2024.105685

Lisa M. Sweeney , Teresa R. Sterner

{"title":"Toxicity reference values (TRVs) for force health protection: Gap identification and TRV prediction","authors":"Lisa M. Sweeney , Teresa R. Sterner","doi":"10.1016/j.yrtph.2024.105685","DOIUrl":"10.1016/j.yrtph.2024.105685","url":null,"abstract":"<div><p>The mission of the Force Health Protection (FHP) program of the U.S. Air Force (USAF), sustaining the readiness of warfighters, relies on determinations of acceptable levels of exposure to a wide array of substances that USAF personnel may encounter. In many cases, exposure details are limited or authoritative toxicity reference values (TRVs) are unavailable. To address some of the TRV gaps, we are integrating several approaches to generate health protective exposure guidelines. Descriptions are provided for identification of chemicals of interest for USAF FHP (467 to date), synthesis of multiple TRVs to derive Operational Exposure Limits (OpELs), and strategies for identifying and developing candidate values for provisional OpELs when authoritative TRVs are lacking. Rodent bioassay-derived long-term Derived No Effect Levels (DNELs) for workers were available only for a minority of the substances with occupational TRV gaps (19 of 84). Additional occupational TRV estimation approaches were found to be straightforward to implement: Tier 1 Occupational Exposure Bands, cheminformatics approaches (multiple linear regression and novel nearest-neighbor approaches), and empirical adjustment of short term TRVs. Risk assessors working in similar contexts may benefit from application of the resources referenced and developed in this work.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105685"},"PeriodicalIF":3.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988741","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

Endeavours made by trade associations, pharmaceutical companies and regulators in the replacement, reduction and refinement of animal experimentation in safety testing of pharmaceuticals 行业协会、制药公司和监管机构在替代、减少和改进药品安全测试中的动物实验方面所做的努力。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-08-06 DOI: 10.1016/j.yrtph.2024.105683

Andrew W. Harrell , Kirsty Reid , John Vahle , Frederic Brouta , Mario Beilmann , Graeme Young , Kylie A. Beattie , Jean Pierre Valentin , Shajahan Shaid , Peter Brinck

{"title":"Endeavours made by trade associations, pharmaceutical companies and regulators in the replacement, reduction and refinement of animal experimentation in safety testing of pharmaceuticals","authors":"Andrew W. Harrell , Kirsty Reid , John Vahle , Frederic Brouta , Mario Beilmann , Graeme Young , Kylie A. Beattie , Jean Pierre Valentin , Shajahan Shaid , Peter Brinck","doi":"10.1016/j.yrtph.2024.105683","DOIUrl":"10.1016/j.yrtph.2024.105683","url":null,"abstract":"<div><p>Following the European Commission decision to develop a roadmap to phase out animal testing and the signing of the US Modernisation Act, there is additional pressure on regulators and the pharmaceutical industry to abandon animal experimentation in safety testing. Often, endeavours already made by governments, regulators, trade associations, and industry to replace, reduce and refine animal experimentation (3Rs) are unnoticed. Herein, we review such endeavours to promote wider application and acceptance of 3Rs. ICH guidelines have stated 3Rs objectives and have enjoyed many successes driven by global consensus. Initiatives driven by US and European regulators such as the removal of the Abnormal Toxicity Test are neutralised by reticent regional regulators. Stream-lined testing requirements have been proposed for new modalities, oncology, impurity management and animal pharmacokinetics/metabolism. Use of virtual controls, value of the second toxicity species, information sharing and expectations for life-threatening diseases, human specific or well-characterised targets are currently being scrutinised. Despite much effort, progress falls short of the ambitious intent of decisionmakers. From a clinical safety and litigation perspective pharmaceutical companies and regulators are reluctant to step away from current paradigms unless replacement approaches are validated and globally accepted. Such consensus has historically been best achieved through ICH initiatives.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105683"},"PeriodicalIF":3.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001247/pdfft?md5=a065c7247cca8766e1977adf59e6dda1&pid=1-s2.0-S0273230024001247-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907581","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}

引用次数: 0

The use of weight-of-evidence approaches to characterize developmental toxicity risk for therapeutic monoclonal antibodies in humans without in vivo studies 在没有进行体内研究的情况下，使用证据权重法确定治疗性单克隆抗体对人类发育的毒性风险。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-07-31 DOI: 10.1016/j.yrtph.2024.105682

Hsiao-Tzu Chien , Puck Roos , Frans G.M. Russel , Peter T. Theunissen , Peter J.K. van Meer

{"title":"The use of weight-of-evidence approaches to characterize developmental toxicity risk for therapeutic monoclonal antibodies in humans without in vivo studies","authors":"Hsiao-Tzu Chien , Puck Roos , Frans G.M. Russel , Peter T. Theunissen , Peter J.K. van Meer","doi":"10.1016/j.yrtph.2024.105682","DOIUrl":"10.1016/j.yrtph.2024.105682","url":null,"abstract":"<div><p>Regulatory guidance for global drug development relies on animal studies to evaluate safety risks for humans, including risk of reproductive toxicity. Weight-of-evidence approaches (WoE) are increasingly becoming acceptable to evaluate risk. A WoE for developmental risk of monoclonal antibodies (mAbs) was evaluated for its ability to retrospectively characterize risk and to determine the need for further <em>in vivo</em> testing based on the remaining uncertainty. Reproductive toxicity studies of 65 mAbs were reviewed and compared to the WoE. Developmental toxicities were absent in 52/65 (80%) mAbs. Lack of toxicity was correctly predicted in 29/52 (56%) cases. False positive and equivocal predictions were made in 9/52 (17%) and 14/52 (27%) cases. For 3/65 (5%) mAbs, the findings were equivocal. Of mAbs with developmental toxicity findings (10/65, 15%), the WoE correctly anticipated pharmacology based reproductive toxicity without any false negative predictions in 9/10 (90%) cases, and in the remaining case (1/10, 10%) an <em>in vivo</em> study was recommended due to equivocal WoE outcome. Therefore, this WoE approach could characterize presence and absence of developmental risk without animal studies. The current WoE could have reduced the need for developmental toxicity studies by 42% without loss of important patient information in the label.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105682"},"PeriodicalIF":3.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001235/pdfft?md5=92ae6c775b152d6be4806e19a44bdb32&pid=1-s2.0-S0273230024001235-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879320","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}

引用次数: 0

N-nitrosamine impurity risk assessment in pharmaceuticals: Utilizing In vivo mutation relative potency comparison to establish an acceptable intake for NTTP 药品中的 N-亚硝胺杂质风险评估：利用体内突变相对效力比较法确定NTTP的可接受摄入量。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-07-26 DOI: 10.1016/j.yrtph.2024.105681

Mark W. Powley , Zhanna Sobol , George E. Johnson , Robert W. Clark , Stephen M. Dalby , Bridget A. Ykoruk , Alema Galijatovic-Idrizbegovic , Mark D. Mowery , Patricia A. Escobar

{"title":"N-nitrosamine impurity risk assessment in pharmaceuticals: Utilizing In vivo mutation relative potency comparison to establish an acceptable intake for NTTP","authors":"Mark W. Powley , Zhanna Sobol , George E. Johnson , Robert W. Clark , Stephen M. Dalby , Bridget A. Ykoruk , Alema Galijatovic-Idrizbegovic , Mark D. Mowery , Patricia A. Escobar","doi":"10.1016/j.yrtph.2024.105681","DOIUrl":"10.1016/j.yrtph.2024.105681","url":null,"abstract":"<div><p>The finding of <em>N</em>-nitrosodiethylamine (NDEA) and <em>N</em>-nitrosodimethylamine (NDMA) in marketed drugs has led to implementation of risk assessment processes intended to limit exposures to the entire class of <em>N</em>-nitrosamines. A critical component of the risk assessment process is establishing exposure limits that are protective of human health. One approach to establishing exposure limits for novel <em>N</em>-nitrosamines is to conduct an in vivo transgenic rodent (TGR) mutation study. Existing regulatory guidance on <em>N</em>-nitrosamines provides decision making criteria based on interpreting in vivo TGR mutation studies as an overall positive or negative. However, point of departure metrics, such as benchmark dose (BMD), can be used to define potency and provide an opportunity to establish relevant exposure limits. This can be achieved through relative potency comparison of novel <em>N</em>-nitrosamines with model <em>N</em>-nitrosamines possessing robust in vivo mutagenicity and carcinogenicity data. The current work adds to the dataset of model <em>N</em>-nitrosamines by providing in vivo TGR mutation data for <em>N</em>-nitrosopiperidine (NPIP). In vivo TGR mutation data was also generated for a novel <em>N</em>-nitrosamine impurity identified in sitagliptin-containing products, 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo-[4,3-a]pyrazine (NTTP). Using the relative potency comparison approach, we have demonstrated the safety of NTTP exposures at or above levels of 1500 ng/day.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105681"},"PeriodicalIF":3.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788940","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

Estimation of acceptable daily intake values based on modeling and in vivo mutagenicity of NDSRIs of fluoxetine, duloxetine and atomoxetine 根据氟西汀、度洛西汀和阿托莫西汀的 NDSRIs 的模型和体内突变性估算每日可接受摄入量。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-07-04 DOI: 10.1016/j.yrtph.2024.105672

{"title":"Estimation of acceptable daily intake values based on modeling and in vivo mutagenicity of NDSRIs of fluoxetine, duloxetine and atomoxetine","authors":"","doi":"10.1016/j.yrtph.2024.105672","DOIUrl":"10.1016/j.yrtph.2024.105672","url":null,"abstract":"<div><p>Nitrosamine drug substance related impurities or NDSRIs can be formed if an active pharmaceutical ingredient (API) has an intrinsic secondary amine that can undergo nitrosation. This is a concern as 1) nitrosamines are potentially highly potent carcinogens, 2) secondary amines in API are common, and 3) NDSRIs that might form from such secondary amines will be of unknown carcinogenic potency. Approaches for evaluating NDSRIs include read across, quantum mechanical modeling of reactivity, <em>in vitro</em> mutation data, and transgenic <em>in vivo</em> mutation data. These approaches were used here to assess NDSRIs that could potentially form from the drugs fluoxetine, duloxetine and atomoxetine. Based on a read across informed by modeling of physicochemical properties and mechanistic activation from quantum mechanical modeling, NDSRIs of fluoxetine, duloxetine, and atomoxetine were 10-100-fold less potent compared with highly potent nitrosamines such as NDMA or NDEA. While the NDSRIs were all confirmed to be mutagenic <em>in vitro</em> (Ames assay) and <em>in vivo</em> (TGR) studies, the latter data indicated that the potency of the mutation response was ≥4400 ng/day for all compounds-an order of magnitude higher than published regulatory limits for these NDSRIs. The approaches described herein can be used qualitatively to better categorize NDSRIs with respect to potency and inform whether they are in the ICH M7 (R2) designated Cohort of Concern.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"152 ","pages":"Article 105672"},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538572","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

Can next generation ecological risk assessment decisions be made today?―A case study of regulatory risk assessment in the United States 下一代生态风险评估决策能否在今天做出？--美国监管风险评估案例研究。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-07-04 DOI: 10.1016/j.yrtph.2024.105674

Paul C. DeLeo

{"title":"Can next generation ecological risk assessment decisions be made today?―A case study of regulatory risk assessment in the United States","authors":"Paul C. DeLeo","doi":"10.1016/j.yrtph.2024.105674","DOIUrl":"10.1016/j.yrtph.2024.105674","url":null,"abstract":"<div><p>We examined the need for new <em>in vivo</em> avian toxicity testing for three common industrial chemicals (1,2 dichloropropane, 1,1,2-trichloroethane and triphenyl phosphate) based on estimated avian exposures using fugacity and multimedia fate models for current conditions of use compared to hazard information including existing <em>in vivo</em> test data for the chemicals and analogs, interspecies correlation estimates and results from hundreds of acute avian dietary toxicity studies. The data indicated that acute avian toxicity is not likely to be observed below 10 ppm in the diet for any chemical with the exception of those with a specific mode of toxic action. Modeling indicated low exposure potential for terrestrial birds to any of the three chemicals, with estimated dietary concentration of less than 0.001 ppm. Despite uncertainty associated with the underlying data sources, the four order of magnitude gap between potential exposure and a <em>minimum</em> hazard threshold suggests that additional avian <em>in vivo</em> testing would not generate valuable data. However, a weight of evidence approach for integrating data is necessary to engender greater confidence among government decision-makers in cases where data from a particular <em>in vivo</em> study is not expected to improve risk decision-making and an existing data gap can remain unfilled.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"151 ","pages":"Article 105674"},"PeriodicalIF":3.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001156/pdfft?md5=2feab968c085abb432bccab03d61b0c1&pid=1-s2.0-S0273230024001156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538571","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}

引用次数: 0

Resource and animal use implications of the proposed REACH information requirements for endocrine disruptor assessment 拟议的 REACH 内分泌干扰物评估信息要求对资源和动物使用的影响。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-07-03 DOI: 10.1016/j.yrtph.2024.105671

{"title":"Resource and animal use implications of the proposed REACH information requirements for endocrine disruptor assessment","authors":"","doi":"10.1016/j.yrtph.2024.105671","DOIUrl":"10.1016/j.yrtph.2024.105671","url":null,"abstract":"<div><p>Revised information requirements for endocrine disruptor (ED) assessment of chemicals under the European Union's Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation have been proposed. Implementation will substantially increase demands for new data to inform ED assessment. This article evaluates the potential animal use and financial resource associated with two proposed ED policy options, and highlights areas where further clarification is warranted. This evaluation demonstrates that studies potentially conducted to meet the proposed requirements could use tens of millions of animals, and that the approach is unlikely to be feasible in practice. Given the challenges with implementing either policy option and the need to minimise the reliance on animal testing, further consideration and clarification is needed on several aspects prior to implementation of the requirements. This includes how testing will be prioritised in a proportionate approach; how to harness new approach methodologies to waive higher-tier animal testing; and need for provision of clear guidance particularly in applying weight-of-evidence approaches. There is now a clear opportunity for the European Commission to lead the way in developing a robust and transparent ED assessment process for industrial chemicals which fully implements replacement, refinement, and reduction of the use of animals (the 3Rs).</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"151 ","pages":"Article 105671"},"PeriodicalIF":3.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001120/pdfft?md5=7dc6e42412be95085dcba39db0925dbf&pid=1-s2.0-S0273230024001120-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538573","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}

引用次数: 0