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

This review systematically gathers and provides an analysis of pollutants levels emitted from wildfire (WF) and their impact on short-term health effects of affected populations. The available literature was searched according to Population, Exposure, Comparator, Outcome, and Study design (PECOS) database defined by the World Health Organization (WHO) and a meta-analysis was conducted whenever possible. Data obtained through PECOS characterized information from the USA, Europe, Australia, and some Asian countries; South American countries were seldom characterized, and no data were available for Africa and Russia. Extremely high levels of pollutants, mostly of fine fraction of particulate matter (PM) and ozone, were associated with intense WF emissions in North America, Oceania, and Asia and reported to exceed several-fold the WHO guidelines. Adverse health outcomes include emergency department visits and hospital admissions for cardiorespiratory diseases as well as mortality. Despite the heterogeneity among exposure and health assessment methods, all-cause mortality, and specific-cause mortality were significantly associated with WF emissions in most of the reports. Globally, a significant association was found for all-cause respiratory outcomes including asthma, but mixed results were noted for cardiovascular-related effects. For the latter, estimates were only significant several days after WF emissions, suggesting a more delayed impact on the heart. Different research gaps are presented, including the need for the application of standardized protocols for assessment of both exposure and adverse health risks. Mitigation actions also need to be strengthened, including dedicated efforts to communicate with the affected populations, to engage them for adoption of protective behaviors and measures.

Carbon tetrachloride (CCl₄) has been extensively used and reported to produce toxicity, most notably involving the liver. Carbon tetrachloride metabolism involves CYP450-mediated bioactivation to trichloromethyl and trichloromethyl peroxy radicals, which are capable of macromolecular interaction with cell components including lipids and proteins. Radical interaction with lipids produces lipid peroxidation which can mediate cellular damage leading to cell death. Chronic exposure with CCl₄ a rodent hepatic carcinogen with a mode of action (MOA) exhibits the following key events: 1) metabolic activation; 2) hepatocellular toxicity and cell death; 3) consequent regenerative increased cell proliferation; and 4) hepatocellular proliferative lesions (foci, adenomas, carcinomas). The induction of rodent hepatic tumors is dependent upon the dose (concentration and exposure duration) of CCl₄, with tumors only occurring at cytotoxic exposure levels. Adrenal benign pheochromocytomas were also increased in mice at high CCl₄ exposures; however, these tumors are not of relevant importance to human cancer risk. Few epidemiology studies that have been performed on CCl₄, do not provide credible evidence of enhanced risk of occurrence of liver or adrenal cancers, but these studies have serious flaws limiting their usefulness for risk assessment. This manuscript summarizes the toxicity and carcinogenicity attributed to CCl₄, specifically addressing MOA, dose-response, and human relevance.

The purpose of this study was to determine the toxicological and pharmacokinetic properties of sucralose-6-acetate, a structural analog of the artificial sweetener sucralose. Sucralose-6-acetate is an intermediate and impurity in the manufacture of sucralose, and recent commercial sucralose samples were found to contain up to 0.67% sucralose-6-acetate. Studies in a rodent model found that sucralose-6-acetate is also present in fecal samples with levels up to 10% relative to sucralose which suggest that sucralose is also acetylated in the intestines. A MultiFlow® assay, a high-throughput genotoxicity screening tool, and a micronucleus (MN) test that detects cytogenetic damage both indicated that sucralose-6-acetate is genotoxic. The mechanism of action was classified as clastogenic (produces DNA strand breaks) using the MultiFlow® assay. The amount of sucralose-6-acetate in a single daily sucralose-sweetened drink might far exceed the threshold of toxicological concern for genotoxicity (TTC_genotox) of 0.15 µg/person/day. The RepliGut® System was employed to expose human intestinal epithelium to sucralose-6-acetate and sucralose, and an RNA-seq analysis was performed to determine gene expression induced by these exposures. Sucralose-6-acetate significantly increased the expression of genes associated with inflammation, oxidative stress, and cancer with greatest expression for the metallothionein 1 G gene (MT1G). Measurements of transepithelial electrical resistance (TEER) and permeability in human transverse colon epithelium indicated that sucralose-6-acetate and sucralose both impaired intestinal barrier integrity. Sucralose-6-acetate also inhibited two members of the cytochrome P450 family (CYP1A2 and CYP2C19). Overall, the toxicological and pharmacokinetic findings for sucralose-6-acetate raise significant health concerns regarding the safety and regulatory status of sucralose itself.

The aim of this review was to (i) acknowledge structural advantages of natural products (NPs) for designing therapeutic drugs; (ii) emphasize how wildlife conservation is socially and economically necessary for scientific and commercial progress in Brazilian regions; and (iii) show how decisions by governmental regulations exert damaging effects on safeguarding of biodiversity. Natural products (NPs) from animals (e.g.: bufadienolides as marinobufagin), plants (diterpenes: casearin X and paclitaxel; triterpenes: betulinic acid) and microorganisms (depsipeptides: geodiamolides; antraciclines: doxorubicin) are the main source of oral drugs and have innate advantages for enteral and parenteral drug design, synthesis and combinational chemistry using novel techniques, including green chemistry. NPs possess high chemical diversity, binding flexibility to biological targets, chiral centers, aliphatic systems, hydrogen-bond acceptors and donors, and/or heteroatoms, and broad-spectrum pharmacological properties, including against malign disorders. Nonetheless, all Brazilian biomes and connected ecosystems have been systemically threatened since 2019 by the following fire, deforestation, monocultures, cattle raising, mining and/or oil spills mainly as consequence of financial cuts in key institutions which oversee environmental stability for terrestrial and marine Brazilian fauna and flora. Nevertheless, natural chemical entities, broad traditional knowledge on agrobiodiversity, fishing, fire management, and pioneering processes of economic interest play a vital role for "Science of Biodiversity," which arises as business bioeconomy opportunities to convert Brazil into a self-sufficient country for production of pharmaceutical supplies, cosmeticsand foods. Hence, Brazil needs sustainable development projects supported by government and scientific input if one wishes to use the chemical and biological biodiversity to treat individuals and improve the quality of life.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, and its global health burden is increasing. COPD is characterized by emphysema, mucus hypersecretion, and persistent lung inflammation, and clinically by chronic airflow obstruction and symptoms of dyspnea, cough, and fatigue in patients. A cluster of pathologies including chronic bronchitis, emphysema, asthma, and cardiovascular disease in the form of hypertension and atherosclerosis variably coexist in COPD patients. Underlying causes for COPD include primarily tobacco use but may also be driven by exposure to air pollutants, biomass burning, and workplace related fumes and chemicals. While no single animal model might mimic all features of human COPD, a wide variety of published models have collectively helped to improve our understanding of disease processes involved in the genesis and persistence of COPD. In this review, the pathogenesis and associated risk factors of COPD are examined in different mammalian models of the disease. Each animal model included in this review is exclusively created by tobacco smoke (TS) exposure. As animal models continue to aid in defining the pathobiological mechanisms of and possible novel therapeutic interventions for COPD, the advantages and disadvantages of each animal model are discussed.

Firefighters are the principal line of defense against fires, being at elevated risk of exposure to health-relevant pollutants released during fires and burning processes. Although many biomonitoring studies exist, only a limited number of human in vitro investigations in fire risk assessment are currently available. In vitro studies stand out as valuable tools to assess the toxicity mechanisms involved following exposure to fire pollutants at a cellular level. The aim of the present review was to contextualize existing in vitro studies using human cell models exposed to chemicals emitted from fire emissions and wood smoke and discuss the implications of the observed toxic outcomes on adverse health effects detected in firefighters. Most of the reported in vitro investigations focused on monocultures respiratory models and exposure to particulate matter (PM) extracts collected from fire effluents. Overall, (1) a decrease in cellular viability, (2) enhanced oxidative stress, (3) increased pro-inflammatory cytokines levels and (4) elevated cell death frequencies were noted. However, limited information remains regarding the toxicity mechanisms initiated by firefighting activities. Hence, more studies employing advanced in vitro models and exposure systems using human cell lines are urgently needed taking into consideration different routes of exposure and health-related pollutants released from fires. Data are needed to establish and define firefighters' occupational exposure limits and to propose mitigation strategies to promote beneficial human health.

This review examined the mutagenicity and genotoxicity associated with exposure to outdoor air pollutants in Brazil. A search was performed on the Web of Science database using a combination of keywords that resulted in 134 articles. After applying exclusion criteria, a total of 75 articles were obtained. The articles were classified into three categories: (1) studies with plants and animals, (2) in vitro studies, and (3) human biomonitoring. The investigations were conducted in 11 of 27 Brazilian states with the highest prevalence in the southeast and south regions. Only 5 investigations focused on the effects of burning biomass on the quality of outdoor air. Plants, especially Tradescantia pallida, were the main air pollution biomonitoring tool. When available, a significant association between levels of air pollutants and genetic damage was described. Among the in vitro studies, Salmonella/microsome is the most used test to evaluate mutagenesis of outdoor air in Brazil (n = 26). Human biomonitoring studies were the least frequent category (n = 18). Most of the investigations utilized micronucleus bioassay, in oral mucosa cells (n = 15) and lymphocytes (n = 5), and the comet assay (n = 6). The analysis in this study points to the existence of gaps in genotoxicity studies and our findings indicate that future studies need to address the variety of potential sources of pollution existing in Brazil. In addition to extent of the impacts, consideration should be given to the enormous Brazilian biodiversity, as well as the determination of the role of socioeconomic inequality of the population in the observed outcomes.

Occupational exposure as a firefighter has recently been classified as a carcinogen to humans by International Agency for Research on Cancer (IARC). Biomonitoring has been increasingly used to characterize exposure of firefighting forces to contaminants. However, available data are dispersed and information on the most relevant and promising biomarkers in this context of firefighting is missing. This review presents a comprehensive summary and critical appraisal of existing biomarkers of exposure including volatile organic compounds such as polycyclic aromatic hydrocarbons, several other persistent other organic pollutants as well as heavy metals and metalloids detected in biological fluids of firefighters attending different fire scenarios. Urine was the most characterized matrix, followed by blood. Firefighters exhaled breath and saliva were poorly evaluated. Overall, biological levels of compounds were predominantly increased in firefighters after participation in firefighting activities. Biomonitoring studies combining different biomarkers of exposure and of effect are currently limited but exploratory findings are of high interest. However, biomonitoring still has some unresolved major limitations since reference or recommended values are not yet established for most biomarkers. In addition, half-lives values for most of the biomarkers have thus far not been defined, which significantly hampers the design of studies. These limitations need to be tackled urgently to improve risk assessment and support implementation of better more effective preventive strategies.

Several studies have been conducted to address the potential adverse health risks attributed to exposure to nanoscale materials. While in vivo studies are fundamental for identifying the relationship between dose and occurrence of adverse effects, in vitro model systems provide important information regarding the mechanism(s) of action at the molecular level. With a special focus on exposure to inhaled (nano)particulate material toxicity assessment, this review provides an overview of the available human respiratory models and exposure systems for in vitro testing, advantages, limitations, and existing investigations using models of different complexity. A brief overview of the human respiratory system, pathway and fate of inhaled (nano)particles is also presented.