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

The complex, variable mixtures present in fine particulate matter (PM_2.5) have been well established, and associations between chemical constituents and human health are expanding. In the past decade, there has been an increase in PM_2.5 toxicology studies that include chemical analysis of samples. This investigation is a crucial component for identifying the causal constituents for observed adverse health effects following exposure to PM_2.5. In this review, investigations of PM_2.5 that used both in vivo models were explored and chemical analysis with a focus on respiratory, cardiovascular, central nervous system, reproductive, and developmental toxicity was examined to determine if chemical constituents were considered in the interpretation of the toxicity findings. Comparisons between model systems, PM_2.5 characteristics, endpoints, and results were made. A vast majority of studies observed adverse effects in vivo following exposure to PM_2.5. While limited, investigations that explored connections between chemical components and measured endpoints noted significant associations between biological measurements and a variety of PM_2.5 constituents including elements, ions, and organic/elemental carbon, indicating the need for such analysis. Current limitations in available data, including relatively scarce statistical comparisons between collected toxicity and chemical datasets, are provided. Future progress in this field in combination with epidemiologic research examining chemical composition may support regulatory standards of PM_2.5 to protect human health.

Microplastics (MPs) are contaminants widely distributed in the environment and biota. Previously, most studies focused on identifying and characterizing microplastics in the marine environment, while their impact on freshwater ecosystems remains to be determined. This review summarizes recent findings regarding MPs physiological, immunological, and genetic effects on amphibians based upon the biological relevance of this species as indicators of freshwater pollution. Data demonstrated that MPs contamination may potentially alter various physiological processes in aquatic animals, mainly in the embryonic stages. It is worthwhile noting that adverse effects might be enhanced in synergy with other pollutants. However, amphibians might counteract the effect of MPs and other pollutants through microbiota present both in the intestine and on the skin. In addition, amphibian microbial composition might also be altered by MPs themselves in a manner that leads to unpredicted health consequences in amphibians.

Read-across, an alternative approach for hazard assessment, has been widely adopted when in vivo data are unavailable for chemicals of interest. Read-across is enabled via in silico tools such as quantitative structure activity relationship (QSAR) modeling. In this study, the current status of structure activity relationship (SAR)-based read-across applications in the Republic of Korea (ROK) was examined considering both chemical risk assessments and chemical registrations from different sectors, including regulatory agencies, industry, and academia. From the regulatory perspective, the Ministry of Environment (MOE) established the Act on Registration and Evaluation of Chemicals (AREC) in 2019 to enable registrants to submit alternative data such as information from read-across instead of in vivo data to support hazard assessment and determine chemical-specific risks. Further, the Ministry of Food and Drug Safety (MFDS) began to consider read-across approaches for establishing acceptable intake (AI) limits of impurities occurring during pharmaceutical manufacturing processes under the ICH M7 guideline. Although read-across has its advantages, this approach also has limitations including (1) lack of standardized criteria for regulatory acceptance, (2) inconsistencies in the robustness of scientific evidence, and (3) deficiencies in the objective reliability of read-across data. The application and acceptance rate of read-across may vary among regulatory agencies. Therefore, sufficient data need to be prepared to verify the hypothesis that structural similarities might lead to similarities in properties of substances (between source and target chemicals) prior to adopting a read-across approach. In some cases, additional tests may be required during the registration process to clarify long-term effects on human health or the environment for certain substances that are data deficient. To improve the quality of read-across data for regulatory acceptance, cooperative efforts from regulatory agencies, academia, and industry are needed to minimize limitations of read-across applications.

Electronic cigarettes (ECs) are purported to be tobacco harm-reduction products whose degree of harm has been highly debated. EC use is considered less hazardous than smoking but is not expected to be harmless. Following the banning of e-liquid flavors in countries such as the US, Finland, Ukraine, and Hungary, there are growing concerns regarding the safety profile of e-liquid flavors used in ECs. While these are employed extensively in the food industry and are generally regarded as safe (GRAS) when ingested, GRAS status after inhalation is unclear. The aim of this review was to assess evidence from 38 reports on the adverse effects of flavored e-liquids on the respiratory system in both in vitro and in vivo studies published between 2006 and 2021. Data collected demonstrated greater detrimental effects in vitro with cinnamon (9 articles), strawberry (5 articles), and menthol (10 articles), flavors than other flavors. The most reported effects among these investigations were perturbations of pro-inflammatory biomarkers and enhanced cytotoxicity. There is sufficient evidence to support the toxicological impacts of diacetyl- and cinnamaldehyde-containing e-liquids following human inhalation; however, safety profiles on other flavors are elusive. The latter may result from inconsistencies between experimental approaches and uncertainties due to the contributions from other e-liquid constituents. Further, the relevance of the concentration ranges to human exposure levels is uncertain. Evidence indicates that an adequately controlled and consistent, systematic toxicological investigation of a broad spectrum of e-liquid flavors may be required at biologically relevant concentrations to better inform public health authorities on the risk assessment following exposure to EC flavor ingredients.

The objectives of this systematic review of original articles published up until August 2021 and meta-analyses were to identify the links between occupational and non-occupational environmental exposures, types of occupations and idiopathic pulmonary fibrosis (IPF). Sixteen selected case-control studies were qualified as good level with Newcastle-Ottawa quality assessment scale. Sensitivity analyses highlighted the role of choice of control group, tobacco adjustment and diagnostic tools. Significantly increased risks of IPF were observed (OR (95%CI): for metals (1.42(1.05-1.92)), wood (OR:1.32(1.02-1.71)), and general dust (OR:1.32(1.08-1.63)) exposures. Subgroup analyses found a significantly elevated risk for: hardwood (OR:1.75 (1.13-2.70)), organic dusts (OR:1.72 (1.20-2.46)) and pesticides (OR:2.30 (1.30-4.08)), while no significant change was noted for softwoods and solvents. Smoking adjustments: general dust (1.45 (1.04-2.03)/organic dust (2.5 (1.49-4.22)/metals (1.87 (1.16-3)/wood dust OR: 1.16 (0.86-1.61)/pesticide exposure 2.4 (0.84-6.9) were calculated. Among agricultural workers, the risk was also increased (OR:2.06 (1.02-4.16)). Few environmental data were available and no significant associations detected. Thus, these meta-analyses highlighted the role of some occupational exposures in IPF occurrence. A more accurate and thorough assessment of exposures over the entire working life as well as on the duration and intensity of exposure and complex of multi-pollutant exposure is needed in future research and clinical practice.

Allergic disease represents one of the most prominent global public health crises of the 21^st century. Although many different substances are known to produce hypersensitivity responses, metals constitute one of the major classes of allergens responsible for a disproportionately large segment of the total burden of disease associated with allergy. Some of the most prevalent forms of metal allergy - including allergic contact dermatitis - are well-recognized; however, to our knowledge, a comprehensive review of the many unique disease variants implicated in human cases of metal allergy is not available within the current scientific literature. Consequently, the main goal in composing this review was to (1) generate an up-to-date reference document containing this information to assist in the efforts of lab researchers, clinicians, regulatory toxicologists, industrial hygienists, and other scientists concerned with metal allergy and (2) identify knowledge gaps related to disease. Accordingly, an extensive review of the scientific literature was performed - from which, hundreds of publications describing cases of metal-specific allergic responses in human patients were identified, collected, and analyzed. The information obtained from these articles was then used to compile an exhaustive list of distinctive dermal/ocular, respiratory, gastrointestinal, and systemic hypersensitivity responses associated with metal allergy. Each of these disease variants is discussed briefly within this review, wherein specific metals implicated in each response type are identified, underlying immunological mechanisms are summarized, and major clinical presentations of each reaction are described.Abbreviations: ACD: allergic contact dermatitis, AHR: airway hyperreactivity, ASIA: autoimmune/ autoinflammatory syndrome induced by adjuvants, BAL: bronchoalveolar lavage, CBD: chronic beryllium disease, CTCL: cutaneous T-cell lymphoma, CTL: cytotoxic T-Lymphocyte, DRESS: drug reaction with eosinophilia and systemic symptoms, GERD: gastro-esophageal reflux disease, GI: gastrointestinal, GIP: giant cell interstitial pneumonia, GM-CSF: granulocyte macrophage-colony stimulating factor, HMLD: hard metal lung disease, HMW: high molecular weight, IBS: irritable bowel syndrome, Ig: immunoglobulin, IL: interleukin, LMW: low molecular weight, PAP: pulmonary alveolar proteinosis, PPE: personal protective equipment, PRR: pathogen recognition receptor, SLE: systemic lupus erythematosus, SNAS: systemic nickel allergy syndrome, Th: helper T-cell, UC: ulcerative colitis, UV: ultraviolet.

Additive manufacturing (AM) refers to several types of processes that join materials to build objects, often layer-by-layer, from a computer-aided design file. Many AM processes release potentially hazardous particles and gases during printing and associated tasks. There is limited understanding of the efficacy of controls including elimination, substitution, administrative, and personal protective technologies to reduce or remove emissions, which is an impediment to implementation of risk mitigation strategies. The Medline, Embase, Environmental Science Collection, CINAHL, Scopus, and Web of Science databases and other resources were used to identify 42 articles that met the inclusion criteria for this review. Key findings were as follows: 1) engineering controls for material extrusion-type fused filament fabrication (FFF) 3-D printers and material jetting printers that included local exhaust ventilation generally exhibited higher efficacy to decrease particle and gas levels compared with isolation alone, and 2) engineering controls for particle emissions from FFF 3-D printers displayed higher efficacy for ultrafine particles compared with fine particles and in test chambers compared with real-world settings. Critical knowledge gaps identified included a need for data: 1) on efficacy of controls for all AM process types, 2) better understanding approaches to control particles over a range of sizes and gas-phase emissions, 3) obtained using a standardized collection approach to facilitate inter-comparison of study results, 4) approaches that go beyond the inhalation exposure pathway to include controls to minimize dermal exposures, and 5) to evaluate not just the engineering tier, but also the prevention-through-design and other tiers of the hierarchy of controls.

Risk management decisions in public health require consideration of a number of complex, often conflicting factors. The aim of this review was to propose a set of 10 fundamental principles to guide risk decision-making. Although each of these principles is sound in its own right, the guidance provided by different principles might lead the decision-maker in different directions. For example, where the precautionary principle advocates for preemptive risk management action under situations of scientific uncertainty and potentially catastrophic consequences, the principle of risk-based decision-making encourages decision-makers to focus on established and modifiable risks, where a return on the investment in risk management is all but guaranteed in the near term. To evaluate the applicability of the 10 principles in practice, one needs to consider 10 diverse risk issues of broad concern and explore which of these principles are most appropriate in different contexts. The 10 principles presented here afford substantive insight into the process of risk management decision-making, although decision-makers will ultimately need to exercise judgment in reaching appropriate risk decisions, accounting for all of the scientific and extra-scientific factors relevant to the risk decision at hand.

Studies of nervous system effects of glyphosate, a widely used herbicide, have not been critically examined. The aim of this paper was to systematically review glyphosate-induced neurotoxicity literature to determine its usefulness in regulatory decision-making. The review was restricted to mammalian studies of behavior, neuropathology, and neuropharmacology; in vitro and other biochemical studies were considered supplementary information. Glyphosate formulation studies were also considered, despite uncertainties regarding toxicities of the formulated products; no studies used a formulation vehicle as the control. Inclusion criteria were developed a priori to ensure consistent evaluation of studies, and in vivo investigations were also ranked using ToxRTool software to determine reliability. There were 27 in vivo studies (open literature and available regulatory reports), but 11 studies were considered unreliable (mostly due to critical methodological deficiencies). There were only seven acceptable investigations on glyphosate alone. Studies differed in terms of dosing scenarios, experimental designs, test species, and commercial product. Limitations included using only one dose and/or one test time, small sample sizes, limited data presentation, and/or overtly toxic doses. While motor activity was the most consistently affected endpoint (10 of 12 studies), there were considerable differences in outcomes. In six investigations, there were no marked neuropathological changes in the central or peripheral nervous system. Other neurological effects were less consistent, and some outcomes were less convincing due to influences including high variability and small effect sizes. Taken together, these studies do not demonstrate a consistent impact of glyphosate on the structure or function of the mammalian nervous system.

Percutaneous absorption is of importance given its role in topical medicaments, transdermal drug systems, and dermatotoxicology. Many factors influence percutaneous penetration, including anatomical region, although little is currently known regarding this parameter. Hence, the aim of this study was to summarize existing data on regional variation in percutaneous penetration in in vitro human models. PubMed, Embase, Web of Science, and US patent literature were explored, and relevant data collected. Eight eligible articles were identified, which together, explored 15 anatomical locations. Four investigations compared percutaneous penetration between scalp and abdominal skin, and all concluded that the former was more permeable. Within those four studies, 10 penetrants of varying physical/chemical properties were tested indicating that in those particular study conditions, anatomical location exerted a greater effect on percutaneous absorption than the physicochemical properties of the penetrants. In addition, torso area was less absorptive than scrotum in both studies in which these sites were compared. In conclusion, the scrotum and scalp appear to be highly susceptible to percutaneous absorption compared to other locations such as the abdomen. This is postulated to be largely due to the high density of hair follicles in these areas, enabling greater penetration via the appendageal pathway. However, there is a paucity of conclusive data regarding the penetrability of other anatomical locations. Investigations testing and ranking the susceptibility of different anatomical regions is of vital importance given the importance of (1) transdermal drug delivery and decontamination protocols and (2) understanding the underlying mechanisms and degree of these variances might aid our pharmacologic/toxicologic judgments.