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

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.

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, in vitro cell and biochemical assays, and in vitro 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.

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 in vivo 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.

Manganese (Mn) is an essential trace element that, in excess, may initiate adverse health effects. Recent evidence suggested that environmental exposure to Mn may produce thyroid hormone imbalances leading to adverse neurodevelopmental outcomes. The aim of this review was to summarize available evidence regarding Mn exposure and consequent adverse thyroid effects, including potential implications for neurodevelopmental impairment in children. Medline, EMBASE, and Scopus were systematically searched using two concepts: Mn exposure and thyroid function. A total of 31 studies (17 human studies, 14 toxicological studies) fulfilled eligibility criteria. Evidence for effects attributed to Mn on the thyroid from human studies is inconclusive. No apparent studies were identified to directly characterize Mn thyroid-mediated effects on neurodevelopmental outcomes. Although limited evidence from animal studies provides some support for the effects of Mn on thyroid-related hormones, it is unclear whether such hormonal imbalance is a result of a direct or indirect biological mechanism of action. Toxicokinetic data demonstrated that Mn accumulates in thyroid tissue and might interfere with thyroid function. Currently, there are limited data on biological mechanisms of action for the effects of Mn on the thyroid. Although evidence to date is suggestive of Mn thyroid-related activity, the lack of adequate studies precludes a causal interpretation.

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.

Methicillin-resistant Staphylococcus aureus (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.

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.

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.

The increasing detection of emerging mycotoxins in food and feed emphasizes the need to assess their potential adverse health risks. Unlike regulated compounds, many mycotoxins lack toxicological data, especially regarding genotoxicity or carcinogenic potential. This systematic review aimed to identify and prioritize emerging mycotoxins for future research and risk assessment. From an initial list of 102 compounds, 32 were excluded for having already been assessed by EFSA, with 15 also regulated in Europe. The remaining 70 were classified as "emerging" and examined through a PubMed and a Web of Science search. A total of 63 articles were included, encompassing in vitro, in vivo, or both types of studies, in conjunction with contextual data from reviews and human studies. Data were extracted from validated or widely used assays and clustered following international genotoxicity testing guidelines (OECD, EFSA, ICH). In the few studies available, genotoxicity was observed for kojic acid, apicidin, tryptophol and, to a lesser extent, with equivocal or conflicting results, for 3-nitropropionic acid, aurofusarin, averufin, fusaric acid, secalonic acids D and F, and mycophenolic acid. Butenolide was also positive but was only tested in one experiment. Bikaverin, culmorin, and skyrin showed no marked genotoxic effects but were only tested once or twice or in protocols not following OECD standards, yielding limited or conflicting results. Overall, the limited number of assays, significant data gaps and methodological limitations hinder conclusive human health risk assessment, emphasizing the need for standardized and comprehensive genotoxicological testing of the emerging mycotoxins.

The global spread of Aedes aegypti poses increasing challenges for vector control programs, especially in the context of insecticide resistance and growing environmental concerns. Innovative control strategies include integrated vector management and use of biopesticides as sustainable alternatives to conventional insecticides. However, despite recent advances, critical knowledge gaps remain regarding the efficacy, safety, and sustainability of integrated biopesticide-based strategies for environmentally friendly Aedes aegypti management. The aim of this review was to critically examine the ecotoxicological risks associated with isolated use of conventional pesticides and highlight the benefits and limitations of integrated vector management approaches. Publications from the last 10 years were searched in PubMed, Scopus, Web of Science, and Google Scholar, with inclusion criteria focusing on studies addressing ecotoxicological effects and sustainability of integrated biopesticide-based strategies. Recent evidence demonstrated that integrated strategies provide enhanced efficacy and reduced environmental impact compared to chemical-only interventions. However, knowledge gaps remain regarding long-term ecological safety, operational feasibility, and resistance development. Comprehensive toxicological assessments and further studies are crucial to ensure the safe, effective, and sustainable use of integrated vector control approaches, with a focus on minimizing adverse environmental impacts and delaying insecticidal resistance development.