Regulatory Toxicology and Pharmacology最新文献

{"title":"Interpretable machine learning unveils key predictors and default values in an expanded database of human in vitro dermal absorption studies with pesticides","authors":"D. Sarti ,&nbsp;J. Wagner ,&nbsp;F. Palma ,&nbsp;H. Kalvan ,&nbsp;M. Giachini ,&nbsp;D. Lautenschalaeger ,&nbsp;V. Lupianhez ,&nbsp;J. Pires ,&nbsp;M. Sales ,&nbsp;P. Faria ,&nbsp;L. Bertomeu ,&nbsp;M. Le Bras","doi":"10.1016/j.yrtph.2025.105801","DOIUrl":"10.1016/j.yrtph.2025.105801","url":null,"abstract":"<div><div>The skin is the main route of exposure to plant protection products for operators, workers, residents, and bystanders. Assessing dermal absorption is key for evaluating pesticide exposure. The initial approach to risk assessment involves using default dermal absorption values or applying read-across data from experimental results from different formulations. In this way, to support non-dietary pesticide risk assessment focused but not limited to Brazil, this project evaluated 759 GLP-compliant <em>in vitro</em> human skin dermal absorption studies covering 25 formulation types and 248 active substances at multiple concentrations using interpretable machine learning techniques. Bayesian Additive Regression Trees – BART method indicated that Log Pow and molecular weight have the highest importance when predicting dermal absorption; both parameters exhibit moderate interaction uncertainty within each other and with formulation groups water-based and organic-solvent based and with tested form (concentrates or dilutions). The default values for each formulation group were determined using the upper bound of a non-parametric confidence interval for a specified quantile, with calculations conducted via bootstrapping methods; the proposed values correspond to the upper limit of the 95% confidence interval for the 95th percentile: for concentrates, 10% for organic-solvent based, 4% for water-based and 3% for solid formulations. For dilutions, 42% for organic-solvent based, 37% for water-based and 39% for solid formulations. Organic-solvent based dermal absorption values from experimental data can be used as conservative surrogates for solid and water-based formulations. When no experimental data is available for higher spray dilutions of a given formulation type, a pro-rated correction is proposed to a 2 to 5-fold concentration difference, limited to the respective formulation group default value.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"159 ","pages":"Article 105801"},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573704","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":"Isolation and investigation of anti-tubercular ilicic acid from Sphaeranthus indicus against Mycobacterium tuberculosis H37Rv and MDR strains","authors":"Alex Yagoo ,&nbsp;M.C. John Milton ,&nbsp;Jelin Vilvest ,&nbsp;A. Arokia Ahino Jessie ,&nbsp;Kedike Balakrishna","doi":"10.1016/j.yrtph.2025.105800","DOIUrl":"10.1016/j.yrtph.2025.105800","url":null,"abstract":"<div><div>The global burden of tuberculosis, particularly multidrug-resistant (MDR) strains of <em>Mycobacterium tuberculosis</em>, necessitates the urgent development of novel and effective therapeutic agents. Natural products derived from plants have long served as an essential resource for drug discovery, offering structurally diverse bioactive compounds. <em>Sphaeranthus indicus</em>, a plant traditionally valued for its medicinal properties, has shown promise as a source of antimicrobial agents. This study evaluated the antimycobacterial potential of S. indicus extracts and the isolated compound ilicic acid against <em>M. tuberculosis</em> H₃₇Rv and MDR isolates. Hexane, chloroform, and methanol extracts were screened using the microbroth dilution assay, with the hexane extract demonstrating superior activity (MIC: 125 μg/mL) against the H₃₇Rv strain. Purification of the hexane extract led to the isolation of ilicic acid, which exhibited significant antimycobacterial activity, inhibiting H₃₇Rv at 125 μg/mL. Against MDR isolates, ilicic acid displayed MIC values of 500 μg/mL for isolate 1, 125 μg/mL for isolate 2, and 250 μg/mL for isolate 3. These findings underscore the therapeutic potential of ilicic acid as a lead compound for developing anti-TB drugs, especially against drug-resistant strains. The study highlights <em>S. indicus</em> as a valuable source for discovering novel antimycobacterial agents, contributing to global efforts to combat TB resistance.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"158 ","pages":"Article 105800"},"PeriodicalIF":3.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547989","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":"No toxic effects or interactions between aflatoxin B1 and zearalenone in broiler chickens fed diets at China's regulatory limits","authors":"Wanjun Zhang,&nbsp;Yongpeng Jin,&nbsp;Ying Liu,&nbsp;Ruiqi Tan,&nbsp;Gaoyi Liu,&nbsp;Wenjun He,&nbsp;Sunlin Luo,&nbsp;Yutong Tang,&nbsp;Qiao Chen,&nbsp;Yiqiang Chen","doi":"10.1016/j.yrtph.2025.105799","DOIUrl":"10.1016/j.yrtph.2025.105799","url":null,"abstract":"<div><div>Currently, several countries such as China have established regulatory limits for six major mycotoxins in animal feed. However, these limits are primarily designed for single mycotoxin exposure. Co-contamination with multiple mycotoxins is increasingly common, and simultaneous exposure may lead to additive toxic effects. This study aimed to investigate the effects of individual and combined contamination of aflatoxin B₁ (AFB₁) and zearalenone (ZEA) at China's regulatory limits on the growth performance, oxidative stress, serum biochemistry, immunity indicators, intestinal morphology, liver and kidney histopathology of broilers by incorporating mycotoxin standards into the feed. A total of 432 one-day-old male AA broilers were randomly assigned to four treatment groups, each consisting of six replicates of 18 birds. The control group received a basic diet, while the experimental groups were supplemented with 10 μg/kg AFB₁, 500 μg/kg ZEA, or a combination of both in the basic diet. The experimental period lasted for 35 days. The results revealed no significant differences among the groups in terms of growth performance, oxidative damage markers, serum biochemistry, cytokine levels, intestinal health, or histopathological assessments of the liver and kidneys. Furthermore, no toxic interactions between the two mycotoxins were observed. Taken together, these results suggest that future assessments should take into account the combined toxicological effects of a wider range of mycotoxins to inform the revision and formulation of feed safety standards.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"159 ","pages":"Article 105799"},"PeriodicalIF":3.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567976","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":"Subchronic safety assessment of CIGB-500 in beagle dog after repeated daily dose administration over 28 days","authors":"Jorge Castro ,&nbsp;Imran Shaikh ,&nbsp;Sherwin Silo ,&nbsp;Carolyn Hum ,&nbsp;Michel Carrier ,&nbsp;Rocky DiFruscia ,&nbsp;Fred Thouin ,&nbsp;Jeremy Chan ,&nbsp;Lizet Aldana ,&nbsp;Ariana Garcia ,&nbsp;Jorge Berlanga ,&nbsp;Leigh Berryman","doi":"10.1016/j.yrtph.2025.105798","DOIUrl":"10.1016/j.yrtph.2025.105798","url":null,"abstract":"<div><div>CIGB-500 is a product whose active pharmaceutical ingredient is GHRP-6, (Growth Hormone Releasing Peptide-6), a synthetic peptide that allows the rescue of cardiac mass affected during Acute Myocardial Infarction. The objective of the study was to determine the toxicity profile of CIGB-500 in dogs. As general methodology, CIGB-500 was administered daily to dogs by intravenous route for 28 consecutive days. All animals were allocated to four groups: Control, Low-Dose (300 μg/kg/day), Mid dose (1000 μg/kg/day) and High-Dose (2000 μg/μg/day). Hypersalivation, hypoactivity, reduced heart rate, changes in respiration, pale gums and erythema of the head region were observed in some animals administered at 1000 and 2000 μg/kg/day. These clinical signs were transient, and were therefore considered non-adverse. Treatment with CIGB-500 did not result in any adverse macroscopic or microscopic changes. A decrease in heart rate value was noted following CIGB-500 treatment at all dose levels an at the end of recovery period, the heart rate effects at 2000 μg/kg/day were comparable to controls. In conclusion, the daily administration of CIGB-500 at doses up to 2000 μg/kg/day was well-tolerated, findings noted were transient, minor, non-adverse and reversible, and the no observable adverse effect level (NOAEL) was considered to be 2000 μg/kg/day.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"158 ","pages":"Article 105798"},"PeriodicalIF":3.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535226","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":"Report on the European Partnership for Alternative Approaches to Animal Testing (EPAA) “New Approach Methodologies (NAMs) User Forum Kick-Off Workshop”","authors":"Mark T.D. Cronin ,&nbsp;Maria T. Baltazar ,&nbsp;Tara S. Barton-Maclaren ,&nbsp;Ofelia Bercaru ,&nbsp;K. Nadira De Abrew ,&nbsp;Christian Desaintes ,&nbsp;Sylvia E. Escher ,&nbsp;Petra Kern ,&nbsp;Gavin Maxwell ,&nbsp;Vera Rogiers ,&nbsp;Katrin Schutte ,&nbsp;Tomasz Sobanski","doi":"10.1016/j.yrtph.2025.105796","DOIUrl":"10.1016/j.yrtph.2025.105796","url":null,"abstract":"<div><div>The European Partnership for Alternative Approaches to Animal Testing (EPAA) held the “New Approach Methodologies (NAMs) User Forum Kick-Off Workshop”, at the European Chemicals Agency (ECHA), Helsinki, Finland on 7–8 December 2023. The aim of the User Forum was to gain insight into the regulatory use of NAMs, with a particular reference to Next Generation Risk Assessment (NGRA), for chemical safety assessment. To achieve this, presentations summarised the learnings and experiences of previous EPAA Skin Sensitisation User Forums as well as that of the European Commission's Scientific Committee on Consumer Safety (SCCS). The findings of five case studies were summarised that illustrated the use of NAMs. The presentations and subsequent discussions allowed for learnings and insights to be compiled from all stakeholders with regard to the use of NAMs. Recommendations for the regulatory use of NAMs in NGRA were made, namely for exposure assessment; hazard identification; using tiered and targeted testing strategies; performing risk assessment using NAM data; the practical implementation of NAMs; the use of -omics technologies; and the needs for capacity building and training. The EPAA User Forum provided an open platform for safety assessors to share learnings and experiences. Recommendations for the format and topics of future EPAA User Forums were also made.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"159 ","pages":"Article 105796"},"PeriodicalIF":3.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537737","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":"A review of the genotoxic effects of antiparasitic drugs on parasites and their hosts","authors":"Nikolajs Sjakste ,&nbsp;Domagoj Dinter ,&nbsp;Goran Gajski","doi":"10.1016/j.yrtph.2025.105797","DOIUrl":"10.1016/j.yrtph.2025.105797","url":null,"abstract":"<div><div>Antiparasitic medications are drugs used to treat infections caused by parasites like protozoa, helminths, and ectoparasites by either killing the parasite or inhibiting its growth and reproduction. These medications are crucial for treating parasitic diseases and can vary in dosage and administration depending on the type of infection with proper diagnosis being essential for effective treatment. Nevertheless, such drugs can also cause a range of side effects including genotoxicity, depending on the type of medication and the individual's response. Therefore, here we will summarize data on the genotoxic effects of some antiparasitic drugs since many parasites provoke DNA damage <em>per se</em>, and therapy can enhance such genotoxic effects. The DNA-damaging effects of antiparasitic drugs enable the use of some of them for cancer treatment. Since a parasitic disease comes with severe consequences, the cost-benefit should be considered when taking drugs against such a disease even in terms of their potential genotoxicity. While some antiparasitic drugs have shown genotoxic potential in laboratory studies, most are considered safe for human use at therapeutic doses. Long-term or high-dose exposure may carry more risk; moreover, the genotoxic effects of the drugs can interfere with the genotoxicity of the parasitic infection. More research is needed to fully understand the implications for human health. Nevertheless, the present study has confirmed the need for further cytogenetic research and regular patient monitoring to minimize the risk of an adverse event, especially among frequent travellers visiting parasite-affected areas.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"158 ","pages":"Article 105797"},"PeriodicalIF":3.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535227","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":"Next generation risk assessment of hair dye HC yellow no. 13: Ensuring protection from liver steatogenic effects","authors":"Sara Sepehri,&nbsp;Dinja De Win,&nbsp;Anja Heymans,&nbsp;Freddy Van Goethem,&nbsp;Robim M. Rodrigues,&nbsp;Vera Rogiers,&nbsp;Tamara Vanhaecke","doi":"10.1016/j.yrtph.2025.105794","DOIUrl":"10.1016/j.yrtph.2025.105794","url":null,"abstract":"<div><div>This study employs animal-free Next Generation Risk Assessment (NGRA) principles to evaluate the safety of repeated dermal exposure to 2.5% (w/w) HC Yellow No. 13 (HCY13) hair dye. As multiple <em>in silico</em> tools consistently flagged hepatotoxic potential, likely due to HCY13's trifluoromethyl group, which is known to interfere with hepatic lipid metabolism, liver steatosis was chosen as the primary mode of action for evaluation. AOP-guided <em>in vitro</em> tests were conducted, exposing human stem cell-derived hepatic cells to varying HCY13 concentrations over 72 h. The expression of 11 lipid metabolism-related marker genes (<em>AHR</em>, <em>PPARA</em>, <em>LXRA</em>, <em>APOB</em>, <em>ACOX1</em>, <em>CPT1A</em>, <em>FASN</em>, <em>SCD1</em>, <em>DGAT2</em>, <em>CD36</em>, and <em>PPARG</em>) and triglyceride accumulation, a phenotypic hallmark of steatosis, were measured. PROAST software was used to calculate <em>in vitro</em> Points of Departure (PoD_NAM) for each biomarker. Using GastroPlus 9.9, physiologically-based pharmacokinetic (PBPK) models estimated internal liver concentrations (C_{max liver}) of HCY13, ranging from 4 to 20 pM. All PoD_NAM values significantly exceeded the predicted C_{max liver}, indicating that HCY13 at 2.5% (w/w) is unlikely to induce liver steatosis under the assumed conditions. This research demonstrates the utility of NGRA, integrating AOP-based <em>in vitro</em> assays and computational models to protect human health and support regulatory decision-making without animal testing.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"159 ","pages":"Article 105794"},"PeriodicalIF":3.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537684","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":"Nonclinical teratogenicity safety assessment of CRBN-engaging targeted protein degraders: Points to consider","authors":"Lise I. Loberg ,&nbsp;William R. Proctor ,&nbsp;Andrew D. Burdick ,&nbsp;Annick Cauvin ,&nbsp;Anthony M. DeLise ,&nbsp;Michelle Hemkens ,&nbsp;Andreas M. Hohlbaum ,&nbsp;Renee Hukkanen ,&nbsp;Alanna E. Sedgwick ,&nbsp;Dana Shuey ,&nbsp;Doris T. Zane ,&nbsp;Katie Stamp","doi":"10.1016/j.yrtph.2025.105793","DOIUrl":"10.1016/j.yrtph.2025.105793","url":null,"abstract":"<div><div>Targeted protein degraders (or degraders) are an emerging small molecule drug modality with transformative therapeutic potential. Currently, most degraders are developed for severe life-threatening disorders and engage the E3 ligase cereblon. One barrier to the broader use of degraders is the potential risk of embryofetal toxicity with cereblon-engaging degraders, exemplified by thalidomide. Thalidomide (and analogs, known as immunomodulatory drugs) binds cereblon and modifies its substrate repertoire, leading to degradation of intended and multiple unintended neosubstrates. Some cereblon-engaging degraders have been engineered to avoid the degradation of unintended neosubstrates implicated in teratogenicity, specifically SALL4. Mechanistic links between SALL4 degradation by thalidomide and human teratogenicity have been established; further, SALL4 degradation by thalidomide (and its analogs) has been linked to teratogenicity in susceptible nonclinical species. It is generally accepted that SALL4 degradation is unlikely to be the only mechanism of teratogenicity associated with thalidomide and its analogs. Currently, best practices to evaluate the teratogenicity risk of cereblon-engaging degraders have not been established. Here, we present points to consider in the teratogenicity safety assessment of cereblon-engaging degraders from the perspective of an IQ consortium working group.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"158 ","pages":"Article 105793"},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524287","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":"Comparison of carbonyls and tobacco-specific nitrosamines in aerosols of heated tobacco products and conventional cigarette smoke using both targeted and untargeted analytical methods","authors":"Hsiang-Tsui Wang ,&nbsp;Ping-Huai Wang ,&nbsp;Chun-Yu Chen ,&nbsp;Tsung-Yun Liu ,&nbsp;Han-Hsing Tsou","doi":"10.1016/j.yrtph.2025.105786","DOIUrl":"10.1016/j.yrtph.2025.105786","url":null,"abstract":"<div><div>Cigarette smoke (CS) exposes users to harmful substances, contributing to chronic lung diseases. Heated tobacco products (HTPs) are marketed as safer alternatives due to their lower toxicant emissions from heating rather than burning tobacco. However, HTPs may produce unique toxicants that are not found in CS. The emissions of carbonyls and tobacco-specific nitrosamines (TSNAs) were compared using targeted analysis using liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UPLC-MS/MS) and untargeted analysis with UPLC-QToF and Progenesis® QI software. Targeted analysis revealed that HTP aerosol emissions contain significantly lower levels of harmful compounds compared to CS, with reductions of 8.7%–91.6% in 11 carbonyls and 85.7%–95.4% in four TSNAs) Untargeted analysis identified 25 carbonyls and seven nitrosamines in both HTPs and conventional cigarettes, with acetoin, dimethylbenzaldehyde, furfural, and diisopropanolnitrosamine (DIPN) found at relatively high levels in HTPs. While untargeted methods introduce some uncertainty, these findings underscore distinct chemical differences between HTPs and conventional cigarettes. Long-term studies are essential to fully understand the health implications of HTP use.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"157 ","pages":"Article 105786"},"PeriodicalIF":3.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422315","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":"Accurate regulatory classification of chemical respiratory allergens: The case for robust characterisation of causation","authors":"Mark A. Pemberton ,&nbsp;Ian Kimber","doi":"10.1016/j.yrtph.2025.105785","DOIUrl":"10.1016/j.yrtph.2025.105785","url":null,"abstract":"<div><div>Occupational health standards, worker safety and effective regulatory classification relies upon characterisation of occupational asthma and discrimination between allergic asthma, irritant-induced asthma, and work-exacerbated asthma, and the accurate identification of chemical allergens of the respiratory tract.</div><div>No <em>in silico, in vitro or in vivo</em> experimental method can, either alone or in combination, accurately identify chemical respiratory allergens and provide a sound basis for regulatory classification. Measurement of IgE antibody and skin prick testing can characterise allergy to proteins, but not to chemical respiratory allergens.</div><div>Therefore, characterisation of causation and accurate regulatory classification of work-related asthma relies upon characterisation of clinical and workplace histories and specific inhalation challenge tests conforming to current guidelines and best practice.</div><div>This manuscript reviews the important of accurate characterisation of causation in cases of work-related asthma to ensure accurate classification and robust regulation, and to promote a sound basis for clinical and experimental research. Commentaries on selected clinical case studies are provided that highlight key issues that confound attribution of causation. Specific recommendations are made regarding the design, conduct and interpretation of clinical investigations of work-related asthma that could provide a basis of more robust regulatory practice, and the more reliable identification of chemical respiratory allergens.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"157 ","pages":"Article 105785"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422316","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}