Journal of Toxicology and Environmental Health-Part B-Critical Reviews最新文献

{"title":"Systematic review of adverse human health effects following oral exposure to inorganic nitrate and nitrite.","authors":"Krista Y Christensen, Paige A Bommarito, Rachel M Shaffer, Benjamin Davis, Alexandra L Lee","doi":"10.1080/10937404.2025.2559344","DOIUrl":"10.1080/10937404.2025.2559344","url":null,"abstract":"<p><p>Inorganic nitrate and nitrite are naturally occurring anions that play an essential role in Earth's nitrogen cycle. The general population is exposed to nitrate and nitrite from both food and drinking water sources. However, there is evidence that under certain exposure conditions, nitrate and nitrite may be associated with adverse health effects across multiple organ systems. Therefore, a systematic review was undertaken to identify, evaluate, and synthesize the available human evidence for adverse health effects following oral exposure to inorganic nitrate and nitrite. This review includes a literature search that builds upon health assessments by federal, state, and international health agencies, supplemented by a comprehensive search for recently published literature (January 2016-August 2024). Studies underwent screening in two stages (title and abstract, full-text) using a Populations, Exposures, Comparators, Outcomes (PECO) criteria. PECO-relevant studies were evaluated for risk of bias and sensitivity, then synthesized by health effect type. Overall, 267 PECO-relevant human studies were identified examining cancer and non-cancer health outcomes. Database characteristics varied widely across health effects, as did the characterization of nitrate and nitrite exposure. Overall, there were more consistent patterns of increased risk for certain cancer sites (urinary tract, bladder, and kidney; prostate; thyroid), type 2 diabetes, and birth defects. For other endpoints, there was less consistency across studies, and in some cases, evidence was too sparse to identify patterns of association. This review serves not only to identify potential hazards of nitrate and nitrite exposure but also data gaps that would benefit from further research.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"169-235"},"PeriodicalIF":8.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human biomonitoring and environmental health: a critical review of global exposure patterns, methodological challenges and research gaps.","authors":"Eduardo de Paula Nunes, Badr Abou Dehn Pestana, Boscolli Barbosa Pereira","doi":"10.1080/10937404.2025.2529845","DOIUrl":"10.1080/10937404.2025.2529845","url":null,"abstract":"<p><p>Human biomonitoring (HBM) is an essential approach for assessing exposure to environmental toxicants and for informing risk assessment frameworks. However, the global expansion of HBM has (1) outpaced efforts to harmonize methodologies, (2) addressed contextual inequalities, and (3) translated findings into public health interventions. This review examined literature regarding HBM across different contaminant categories including atmospheric pollutants, heavy metals, mycotoxins, persistent organic pollutants (POPs) and per- and polyfluoroalkyl substances (PFAS). Drawing on recent studies, key trends, methodological inconsistencies, and systemic biases in research design and population coverage were identified. This review noted an overrepresentation of studies in high-income countries, limited data from vulnerable populations, and a persistent reliance on cross-sectional designs. There is significant heterogeneity in biomarker selection, analytical protocols, and interpretation of exposure-health relationships. Further, many investigations failed to control for confounding variables or explore toxicokinetic and toxicodynamic mechanisms, limiting causal inference. Further, exposure to complex chemical mixtures was routinely underexplored, despite evidence of potential interactive effects. The review presents critical gaps in current knowledge, particularly regarding long-term health effects and translation of biomonitoring data into risk management policies. This review emphasizes the need for standardized methodologies, expanded research in low- and middle-income settings, and integration of biomonitoring with community-based surveillance and environmental justice frameworks. Future research needs to prioritize longitudinal designs, interdisciplinary approaches, and greater inclusion of socially and geographically marginalized groups. By reconceptualizing HBM as both a scientific and socio-political endeavor, the field might more effectively contribute to global environmental health protection.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"109-127"},"PeriodicalIF":8.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From histological and molecular pathology to the inclusion of antibody-drug conjugates in clinical practice against ovarian cancers: Mechanisms of action and pharmacological safety.","authors":"Silvia Leticia Maciel Barbosa, Jhonatas Cley Santos Porto, Joedna Cavalcante Pereira, José Ivo Araújo Beserra Filho, Felipe Carneiro Cavalcanti da Silva, João Marcelo de Castro E Sousa, José Roberto de Oliveira Ferreira, Gardenia Carmen Gadelha Militão, Paulo Michel Pinheiro Ferreira","doi":"10.1080/10937404.2026.2664722","DOIUrl":"10.1080/10937404.2026.2664722","url":null,"abstract":"<p><p>Approximately 75% of the ovarian cancer (OC) patients are diagnosed in advanced stages and platinum-based chemotherapy presents severe side effects and high recurrence rates. This narrative review consolidates current knowledge and describes the pathophysiological characteristics of OC and how molecular aspects influence clinical outcomes of traditional and antibody-drug chemotherapies. Subsequently, a comprehensive picture regarding the current benefits identifies gaps and potential adverse risks of ADCs to treat OC. High-grade serous carcinomas, the most frequently diagnosed OCs, present <i>TP53</i> and <i>BRCA</i>1/2 mutations, hypermethylation, and deregulation of retinoblastoma 1 and phosphatidylinositol 3-kinase (PI3K)/Akt/Ras pathways. After conventional treatment (surgery with or without systemic chemotherapy) and follow-up by CA125 levels, poly(ADP-ribose) polymerase inhibitors and hormone therapies were included. Unfortunately, approximately half of advanced patients who achieved a complete response following chemotherapy exhibit residual tumor(s). In this context, ADCs displayed marked cytotoxicity and incorporated a hypothesis-driven target identification strategy to recognize specific/tumor overexpressing-proteins. Independent clinical studies bibliographic searches in the PubMed database conducted between January 2020 and May 2025 revealed some ADCs have expanded progression-free survival and displayed partial/complete remission in OC patients at small doses if compared to traditional chemotherapies, suggesting acceptable safety profiles and potential synergism among cisplatin/carboplatin/paclitaxel/doxorubicin and ADC-based immunotherapies. A total of 18 clinical trials selected indicate (i) mild-to-moderate severity of side/adverse effects up to grade 2, (ii) low intervention or drug discontinuation, (iii) few drug-related deaths, and/or (iv) reversible toxicity. Thus, therapeutic performance of ADCs demonstrated that personalized treatment maximizes clinical benefits and improves efficacy for heterogeneous populations and polyclonal tumors.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"483-514"},"PeriodicalIF":11.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147823105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights derived from testing a library of per- and polyfluoroalkyl substances (PFAS) in a battery of new approach methods (NAMs).","authors":"Grace Patlewicz, Richard Judson, Katie Paul Friedman, Barbara A Wetmore, Michael J DeVito, Joshua A Harrill, Kelly E Carstens, Keith A Houck, John F Wambaugh, Stephanie Padilla, Katy N Britton, Timothy J Shafer, Sigmund Degitz, Jo Nyffeler, Anna Kreutz, Ann M Richard, Antony J Williams, Katherine Coutros, Michael W Hornung, John Cowden, Logan J Everett, Clinton M Willis, Marci G Smeltz, M Scott Clifton, Madison Feshuk, Jonathan T Wall, Risa R Sayre, Jason Brown, Russell S Thomas","doi":"10.1080/10937404.2025.2521615","DOIUrl":"10.1080/10937404.2025.2521615","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) comprise a large class of human-made chemicals that are in widespread use and present concerns for persistence, bioaccumulation and toxicity. Whilst a handful of PFAS have been characterized for their hazard profiles, the vast majority of PFAS have not been extensively studied. A comprehensive evaluation to characterize the hazard profiles of the thousands of available PFAS would require extensive resources in terms of cost, number of animals and time. An alternative and more efficient approach is to develop a structural chemical categorization approach to prioritize which PFAS or categories of PFAS should be subject to additional study. To that end, the U.S. Environmental Protection Agency (EPA), in collaboration with the National Institute of Environmental Health Sciences (NIEHS) Division of Translational Toxicology (DTT), initiated a research project in 2018 to screen approximately 150 PFAS through a battery of alternative model organisms, <i>in vitro</i> cell and biochemical assays, and <i>in vitro</i> toxico kinetic (TK) assays in order to inform chemical category and read-across approaches. The aim of this review summarizes the experimental testing undertaken, how data were processed, what insights were derived from a category perspective and how these might potentially inform subsequent tiered testing.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"1-69"},"PeriodicalIF":8.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of mode-of-action and human relevance of cumene-induced mouse liver tumors.","authors":"Lynn H Pottenger, B Bhaskar Gollapudi, James S Bus","doi":"10.1080/10937404.2026.2637147","DOIUrl":"10.1080/10937404.2026.2637147","url":null,"abstract":"<p><p>Chronic inhalation exposure of mice to high concentrations of cumene resulted in liver tumors. The aim of this review was to investigate the mode of action (MOA) for these tumors and their relevance to humans. A pilot study demonstrated the activation of constitutive-androstane receptor (CAR) and induction of hepatocyte proliferation following 7-day oral gavage of 1000 mg/kg/day cumene to female C57BL/6 mice. The induction of hepatic enzyme activities in the pilot study was consistent with CAR activation. In a 5-day inhalation study, activation of the CAR nuclear receptor, as indicated by induction of hepatic <i>Cyp2b10</i> transcripts, was observed in C57BL/6 and B6C3F1, but not in CAR/Pregnane-X-Receptor knock-out (CAR/PXR-KO) female mice. Hepatocyte proliferation was identified only in cumene-exposed wild-type, but not in CAR/PXR-KO, mice. The MOA data were integrated with other existing findings for alignment with CAR-mediated MOA to determine whether alternative mechanisms may be excluded. The weight-of-evidence was evaluated using the evolved Bradford Hill criteria for causality. In addition, a human relevance framework analysis of cumene-induced liver tumors was conducted. This evaluation concluded that the CAR-mediated MOA is responsible for cumene-induced mouse liver tumors, and these tumors are not relevant to humans based upon qualitative and quantitative differences between species.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"407-436"},"PeriodicalIF":11.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Underexplored terrain: effects of high priority environmental toxicants on skeletal muscle.","authors":"Zachary Clemens, Lauren Weaver, Abraham Brown, Jagruti Kosaraju, Aaron Barchowsky, Iva Miljkovic, Amrita Sahu","doi":"10.1080/10937404.2025.2593824","DOIUrl":"10.1080/10937404.2025.2593824","url":null,"abstract":"<p><p>In recent decades, evidence has continuously mounted regarding the myriad adverse health effects that environmental exposures exert on human health, yet little attention has been given to skeletal muscle-related outcomes. With its important metabolic, hormonal, and functional properties, skeletal muscle exerts a critical effect on human health and quality of life. The aim of this review was to survey the literature regarding potential impacts of environmental exposures on skeletal muscle health. The focus was on 10 substances atop the Agency for Toxic Substances and Disease Registry's Substance Priority List including arsenic, lead, mercury, vinyl chloride, polychlorinated biphenyls, benzene, cadmium, benzo(a)pyrene, polycyclic aromatic hydrocarbons, and benzo(b)fluoranthene. In addition, per- and poly-fluoroalkyl compounds were included due to an increasing interest in the field of toxicology. Cell, animal, human, and population studies were all examined to determine toxicant effects on skeletal muscle, though the literature is scarce for many individual agents. Some commonalities, such as effects on mitochondrial function and sexually dimorphic consequences, were observed across compounds. Evidence indicates the need for further investigation of this important topic, with an emphasis on longitudinal large-scale population studies, and investigations which synthesize population and mechanistic research to interrogate causality.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"304-328"},"PeriodicalIF":11.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13249150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mode of action (MOA) for nasal tumors induced by methyl isothiocyanate (MITC) in Sprague Dawley rats.","authors":"Melissa Badding, B Bhaskar Gollapudi, Richard Reiss, Jack R Harkema, Samuel M Cohen","doi":"10.1080/10937404.2026.2640072","DOIUrl":"10.1080/10937404.2026.2640072","url":null,"abstract":"<p><p>Methyl isothiocyanate (MITC), a soil fumigant, induced nasal tumors in Sprague Dawley rats exposed by inhalation to a high concentration (20 ppm), but not at 0.5 or 5 ppm. In an inhalation study (1 day, 5 days, or 4 weeks) with MITC, nasal lesions were observed at the tumorigenic concentration, including acute/subacute inflammation, epithelial cell degeneration/necrosis, epithelial cell proliferation (epithelial hyperplasia, increased DNA synthesis, and regeneration), olfactory sensory neuron apoptosis and loss resulting in atrophy/loss of olfactory epithelium, and/or respiratory cell metaplasia. The available toxicity data were examined using the International Programme on Chemical Safety framework and a mode of action (MOA) was proposed that included key events: 1) direct cytotoxicity in nasal mucosa because of irritation; 2) consequent regenerative cell proliferation; 3) onset and persistence of squamous cell metaplasia as an adaptive response; and 4) development of tumors. Data in support of the key events are discussed, along with possible alternative MOAs as well as human relevance of the proposed MOA. Findings are consistent with the proposed MOA and indicated that tumorigenicity of MITC exhibits exposure thresholds but is not likely to pose a carcinogenic risk to humans under normal use patterns and corresponding exposure levels.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"437-461"},"PeriodicalIF":11.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of environmentally persistent free radical (EPFR) formation, characteristics, and health effects: are there sufficient data for risk assessment?","authors":"Avinash Kumar, Divine Nde, Chuqi Guo, Rashmi Pathak, Fox Foley, Syed Ahmad, Prakash Dangal, Farhana Hasan, Myron Lard, Ankit Aryal, Martine E Mathieu-Campbell, Jennifer Irving, Oluwafeyikemi Ogunmusi, Jennifer Richmond-Bryant, Slawomir Lomnicki, Lavrent Khachatryan, Stephania A Cormier, Tammy R Dugas","doi":"10.1080/10937404.2025.2602154","DOIUrl":"10.1080/10937404.2025.2602154","url":null,"abstract":"<p><p>Environmentally persistent free radicals (EPFRs) are stable free radicals formed on particulate matter (PM) through processes such as combustion and pyrolysis. These free radicals are generated on transition metal oxide surfaces in the presence of aromatic precursors. Exposure to EPFRs occurs primarily via inhalation of PM deriving from combustion, traffic, industrial activities, and both indoor and outdoor burning. Other environmental factors that might generate EPFRs are radon, electronic and tobacco cigarettes. EPFRs exhibit unexpectedly long half-lives, ranging from several weeks to, in some cases, several years. EPFRs may be carbon-centered, oxygen-centered or mixed, identified by g-values exhibited in electron paramagnetic resonance analysis. The radicals undergo redox cycling within aqueous solutions and in biological tissues/fluids triggering production of reactive oxygen species (ROS), comprised primarily of hydroxyl, superoxide, and peroxyl radicals. The stability of EPFRs, their association with PM_2.5, and their ability to generate ROS may pose significant concerns for human health. To determine whether there are sufficient data for risk assessment, recent advances were examined in the following important aspects of EPFR research: (1) atmospheric chemistry, (2) human exposures, (3) animal toxicity, and (4) epidemiology. Our review found insufficient epidemiological and exposure studies; however, toxicological data in animals suggested that EPFR inhalation contributes to cardiovascular, respiratory, and metabolic diseases. Although EPFRs are not currently surveyed by a regulatory monitoring system, data indicate their widespread presence in the environment and their potential to initiate/exacerbate diseases.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"358-378"},"PeriodicalIF":11.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12914811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental and animal reservoirs of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA): a One Health challenge.","authors":"Isabela Náthaly Machado da Silva, Marcelino Bemvindo-Souza, Carlos Filipe Camilo-Cotrim, Igor Romeiro Dos Santos, Luciane Madureira de Almeida, Elisa Flávia Luiz Cardoso Bailão","doi":"10.1080/10937404.2025.2600344","DOIUrl":"10.1080/10937404.2025.2600344","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is among the most prevalent nosocomial pathogens. However, in recent decades, infections were reported in communities, infecting individuals without previous hospitalization, and in livestock. Given this public health concern, this systematic review aimed to analyze studies that isolated MRSA from environmental and animal matrices, with an emphasis on the implications of this pathogen's presence from a One Health perspective. A total of 183 articles were selected between 2005 and 2025. These investigations were conducted in 43 countries, with 44% in Europe and 5% in North America. In South America, only studies from Brazil were identified, indicating a lack of data from other countries in the region. The animal matrix was the most extensively investigated source of MRSA, comprising 153 studies (85%) across a range of wild, domestic, and farm species. In the environmental context, MRSA was primarily identified in water (65.8%), followed by soil (21%), and air (13.2%). The predominance of MRSA isolation in the aquatic environment indicates that water is a critical reservoir for the spread of antimicrobial resistance (AMR). The MRSA isolates exhibited a multidrug resistance profile. Resistance was most frequent to tetracycline (11.51%) and erythromycin (11.51%), followed by clindamycin (9.04%) and penicillin (7.67%). Further, some studies have identified MRSA in foods of animal origin, representing a potential route of transmission to humans. Finally, this study indicates that the MRSA contamination cycle, which involves hospitals, the community, environment, and animals, is a growing One Health problem that necessitates a global multisectoral approach.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"329-357"},"PeriodicalIF":8.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Database-calibrated toxicity values for human health assessment based on existing toxicology data for one thousand chemicals.","authors":"Alison H Harrill, Shintaro Hagiwara, Chelsea A Weitekamp, Paul C Stanish, Jonathan T Wall, Risa R Sayre, Sarah E Davidson-Fritz, Kelsey Vitense, Daniel T Chang, Michael J Devito, Chris J Gonzales, Maxwell Groover, Michael F Hughes, Richard S Judson, Jason C Lambert, Charles N Lowe, Esra Mutlu, Katie Paul Friedman, Andrew M Watkins, Antony J Williams, Daniel Krewski, Greg M Paoli, Russell S Thomas","doi":"10.1080/10937404.2025.2552108","DOIUrl":"10.1080/10937404.2025.2552108","url":null,"abstract":"<p><p>The US Environmental Protection Agency (US EPA) and other regulatory agencies routinely assess whether certain chemical exposures might result in harmful health effects. Traditional human health assessments rely upon expert judgment of dose-effect linkages observed in animal toxicology or human studies. Because both collection of toxicology data and synthesis of information might take multiple years to complete, there are relatively few available assessments for decision-making. Identifying methods that yield significant time and resource efficiencies to the process will have scalable public health benefits. To address the need, US EPA developed the database-calibrated assessment process (DCAP) to generate oral, non-cancer human health toxicity values that builds on previously published approaches and guidance. The approach uses the US EPA Toxicity Values Database (ToxValDB) that contains dose-response summary values (DRSVs) from <i>in vivo</i> toxicity studies. The DRSVs are converted to an oral, chronic, human equivalent dose using a series of standard conversion factors. A point-of-departure (POD) is then calculated across a distribution of studies for a given chemical using a calibration percentile that is benchmarked to critical effect PODs from published human health assessments. Traditional and process-specific uncertainties are incorporated to derive a calibrated toxicity value (CTV), defined as an estimate of a daily oral dose to the human population that is likely to be without appreciable risk of adverse non-cancer health effects over a lifetime. This review presents the rationale and methods for the approach, resulting in reporting of 1001 CTVs for chemicals that currently lack a human health assessment.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":" ","pages":"128-167"},"PeriodicalIF":8.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}