Pub Date : 2022-10-03DOI: 10.1080/10937404.2022.2124563
Felix Effah, Benjamin Taiwo, Deborah Baines, Alexis Bailey, Tim Marczylo
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.
{"title":"Pulmonary effects of e-liquid flavors: a systematic review.","authors":"Felix Effah, Benjamin Taiwo, Deborah Baines, Alexis Bailey, Tim Marczylo","doi":"10.1080/10937404.2022.2124563","DOIUrl":"https://doi.org/10.1080/10937404.2022.2124563","url":null,"abstract":"<p><p>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 <i>in vitro</i> and <i>in vivo</i> studies published between 2006 and 2021. Data collected demonstrated greater detrimental effects <i>in vitro</i> 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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"25 7","pages":"343-371"},"PeriodicalIF":7.2,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10491846","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}
Pub Date : 2022-10-03DOI: 10.1080/10937404.2022.2131663
A Pauchet, A Chaussavoine, J C Pairon, C Gabillon, A Didier, I Baldi, Y Esquirol
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.
{"title":"Idiopathic Pulmonary Fibrosis: What do we Know about the Role of Occupational and Environmental Determinants? A Systematic Literature Review and Meta-Analysis.","authors":"A Pauchet, A Chaussavoine, J C Pairon, C Gabillon, A Didier, I Baldi, Y Esquirol","doi":"10.1080/10937404.2022.2131663","DOIUrl":"https://doi.org/10.1080/10937404.2022.2131663","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"25 7","pages":"372-392"},"PeriodicalIF":7.2,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10434041","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}
Pub Date : 2022-08-18DOI: 10.1080/10937404.2022.2104981
Ka Roach, Jr Roberts
Allergic disease represents one of the most prominent global public health crises of the 21st 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.
{"title":"A comprehensive summary of disease variants implicated in metal allergy.","authors":"Ka Roach, Jr Roberts","doi":"10.1080/10937404.2022.2104981","DOIUrl":"https://doi.org/10.1080/10937404.2022.2104981","url":null,"abstract":"<p><p>Allergic disease represents one of the most prominent global public health crises of the 21<sup>st</sup> 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.<b>Abbreviations:</b> 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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"25 6","pages":"279-341"},"PeriodicalIF":7.2,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9968405/pdf/nihms-1862327.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9532502","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}
Pub Date : 2022-07-04DOI: 10.1080/10937404.2022.2092569
Johan du Plessis, Sonette du Preez, Aleksandr B Stefaniak
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.
增材制造(AM)是指从计算机辅助设计文件中,将材料一层一层地连接起来以构建物体的几种类型的工艺。许多增材制造过程在打印和相关任务中释放潜在的有害颗粒和气体。人们对包括消除、替代、行政和个人防护技术在内的控制措施在减少或消除排放方面的效力了解有限,这阻碍了风险缓解战略的实施。使用Medline、Embase、Environmental Science Collection、CINAHL、Scopus和Web of Science数据库和其他资源确定了42篇符合本综述纳入标准的文章。主要调查结果如下:1)与单独隔离相比,包含局部排气通风的材料挤出型熔丝制造(FFF) 3d打印机和材料喷射打印机的工程控制通常在降低颗粒和气体水平方面表现出更高的效果;2)与细颗粒相比,FFF 3d打印机的颗粒排放工程控制在超细颗粒和测试室中表现出更高的效果。确定的关键知识差距包括对数据的需求:1)对所有增材制造工艺类型的控制效果,2)更好地理解控制不同尺寸颗粒和气相排放的方法,3)使用标准化收集方法获得,以促进研究结果的相互比较,4)超越吸入暴露途径的方法,包括控制以最大限度地减少皮肤暴露,5)不仅评估工程层,还有通过设计进行预防和其他层次的控制。
{"title":"Identification of effective control technologies for additive manufacturing.","authors":"Johan du Plessis, Sonette du Preez, Aleksandr B Stefaniak","doi":"10.1080/10937404.2022.2092569","DOIUrl":"https://doi.org/10.1080/10937404.2022.2092569","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"25 5","pages":"211-249"},"PeriodicalIF":7.2,"publicationDate":"2022-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420827/pdf/nihms-1827034.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9748633","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}
Pub Date : 2022-04-03Epub Date: 2022-01-30DOI: 10.1080/10937404.2022.2032517
Aileen M Feschuk, Nadia Kashetsky, Chavy Chiang, Anuk Burli, Halie Burdick, Howard I Maibach
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.
经皮吸收在局部药物、透皮药物系统和皮肤毒理学中发挥重要作用。许多因素影响经皮穿透,包括解剖区域,尽管目前对这一参数知之甚少。因此,本研究的目的是总结体外人体模型中经皮渗透的区域差异的现有数据。检索PubMed、Embase、Web of Science和美国专利文献,收集相关数据。8篇符合条件的文章被确定,它们一起探索了15个解剖位置。四项调查比较了头皮和腹部皮肤的经皮穿透性,均得出结论,头皮的渗透性更强。在这四项研究中,对10种不同物理/化学性质的渗透剂进行了测试,表明在这些特定的研究条件下,解剖位置对渗透剂的经皮吸收的影响大于渗透剂的物理/化学性质。此外,在两项研究中,躯干区域比阴囊吸收更少。总之,与腹部等其他部位相比,阴囊和头皮似乎对经皮吸收非常敏感。据推测,这主要是由于这些区域的毛囊密度高,能够通过附属物途径进行更大的渗透。然而,关于其他解剖位置的穿透性,缺乏结论性数据。考虑到(1)经皮给药和去污方案的重要性,(2)了解这些差异的潜在机制和程度可能有助于我们的药理学/毒理学判断,对不同解剖区域的易感性进行调查、测试和排序至关重要。
{"title":"Regional variation in percutaneous absorption in <i>in vitro</i> human models: a systematic review.","authors":"Aileen M Feschuk, Nadia Kashetsky, Chavy Chiang, Anuk Burli, Halie Burdick, Howard I Maibach","doi":"10.1080/10937404.2022.2032517","DOIUrl":"https://doi.org/10.1080/10937404.2022.2032517","url":null,"abstract":"<p><p>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 <i>in vitro</i> 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.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"25 3","pages":"97-112"},"PeriodicalIF":7.2,"publicationDate":"2022-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39870852","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}
Pub Date : 2022-03-15DOI: 10.1080/10937404.2022.2041516
J. Bus, B. Gollapudi, G. Hard
ABSTRACT Methyl-tert-butyl ether (MTBE) is a fuel oxygenate used in non-United States geographies. Multiple health reviews conclude that MTBE is not a human-relevant carcinogen, and this review provides updated mode of action (MOA), exposure, dosimetry and risk perspectives supporting those conclusions. MTBE is non-genotoxic and has large margins of exposure between blood concentrations at the overall rat 400 ppm inhalation NOAEL and blood concentrations in typical workplace or general population exposures. Non-cancer and threshold cancer hazard quotients range from a high of 0.046 for fuel-pump gasoline station attendants and are 100–1,000-fold lower for general population exposures. Cancer risks conservatively assuming genotoxicity for these same scenarios are all less than 1 × 10−6. The onset of MTBE nonlinear toxicokinetics (TK) in rats at inhalation exposures less than 3,000 ppm, a dose that is also not practically achievable in fuel-use scenarios, indicates that high-dose specific male rat kidney and testes (3,000 and 8,000 ppm) and female mouse liver tumors (8000 ppm) are not quantitatively relevant to humans. Mode of action analyses also indicate MTBE male rat kidney tumors, and lesser so female mouse liver tumors, are not qualitatively relevant to humans. Thus, an integrated analysis of the toxicology, exposure/dosimetry, TK, and MOA data indicates that MTBE presents minimal human cancer and non-cancer risks.
{"title":"Methyl-tert-butyl ether (MTBE): integration of rat and mouse carcinogenicity data with mode of action and human and rodent bioassay dosimetry and toxicokinetics indicates MTBE is not a plausible human carcinogen","authors":"J. Bus, B. Gollapudi, G. Hard","doi":"10.1080/10937404.2022.2041516","DOIUrl":"https://doi.org/10.1080/10937404.2022.2041516","url":null,"abstract":"ABSTRACT Methyl-tert-butyl ether (MTBE) is a fuel oxygenate used in non-United States geographies. Multiple health reviews conclude that MTBE is not a human-relevant carcinogen, and this review provides updated mode of action (MOA), exposure, dosimetry and risk perspectives supporting those conclusions. MTBE is non-genotoxic and has large margins of exposure between blood concentrations at the overall rat 400 ppm inhalation NOAEL and blood concentrations in typical workplace or general population exposures. Non-cancer and threshold cancer hazard quotients range from a high of 0.046 for fuel-pump gasoline station attendants and are 100–1,000-fold lower for general population exposures. Cancer risks conservatively assuming genotoxicity for these same scenarios are all less than 1 × 10−6. The onset of MTBE nonlinear toxicokinetics (TK) in rats at inhalation exposures less than 3,000 ppm, a dose that is also not practically achievable in fuel-use scenarios, indicates that high-dose specific male rat kidney and testes (3,000 and 8,000 ppm) and female mouse liver tumors (8000 ppm) are not quantitatively relevant to humans. Mode of action analyses also indicate MTBE male rat kidney tumors, and lesser so female mouse liver tumors, are not qualitatively relevant to humans. Thus, an integrated analysis of the toxicology, exposure/dosimetry, TK, and MOA data indicates that MTBE presents minimal human cancer and non-cancer risks.","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"19 1","pages":"135 - 161"},"PeriodicalIF":7.2,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82186339","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}
Pub Date : 2022-02-27DOI: 10.1080/10937404.2022.2042443
Thomas James, Lydia Izon-Cooper, S. Collins, Haydn Cole, T. Marczylo
ABSTRACT Decontamination of skin by washing may increase dermal absorption, a phenomenon known as the wash-in effect. The wash-in effect is frequently discussed in studies investigating casualty decontamination where potentially life-saving interventions may enhance the dermal penetration of toxic chemicals, leading to an increase in incidence of morbidity and rates of mortality. However, the wash-in effect is seldom investigated within the context of mass casualty decontamination and real-life consequences are therefore poorly understood. This paper reviews the existing literature on the wash-in effect to highlight the proposed mechanisms for enhanced absorption and evaluate the wash-in effect within the context of mass casualty chemical decontamination.
{"title":"The wash-in effect and its significance for mass casualty decontamination","authors":"Thomas James, Lydia Izon-Cooper, S. Collins, Haydn Cole, T. Marczylo","doi":"10.1080/10937404.2022.2042443","DOIUrl":"https://doi.org/10.1080/10937404.2022.2042443","url":null,"abstract":"ABSTRACT Decontamination of skin by washing may increase dermal absorption, a phenomenon known as the wash-in effect. The wash-in effect is frequently discussed in studies investigating casualty decontamination where potentially life-saving interventions may enhance the dermal penetration of toxic chemicals, leading to an increase in incidence of morbidity and rates of mortality. However, the wash-in effect is seldom investigated within the context of mass casualty decontamination and real-life consequences are therefore poorly understood. This paper reviews the existing literature on the wash-in effect to highlight the proposed mechanisms for enhanced absorption and evaluate the wash-in effect within the context of mass casualty chemical decontamination.","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"25 1","pages":"113 - 134"},"PeriodicalIF":7.2,"publicationDate":"2022-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41793861","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}
Pub Date : 2022-02-17Epub Date: 2022-01-03DOI: 10.1080/10937404.2021.2013372
Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme
The skin is an immune-competent organ and this function may be impaired by exposure to chemicals, which may ultimately result in immune-mediated dermal disorders. Interindividual variability to chemical-induced skin immune reactions is associated with intrinsic individual characteristics and their genomes. In the last 30-40 years, several genes influencing susceptibility to skin immune reactions were identified. The aim of this review is to provide information regarding common genetic variations affecting skin immunotoxicity. The polymorphisms selected for this review are related to xenobiotic-metabolizing enzymes (CYPA1 and CYPB1 genes), antioxidant defense (GSTM1, GSTT1, and GSTP1 genes), aryl hydrocarbon receptor signaling pathway (AHR and ARNT genes), skin barrier function transepidermal water loss (FLG, CASP14, and SPINK5 genes), inflammation (TNF, IL10, IL6, IL18, IL31, and TSLP genes), major histocompatibility complex (MHC) and neuroendocrine system peptides (CALCA, TRPV1, ACE genes). These genes present variants associated with skin immune responses and diseases, as well as variants associated with protecting skin immune homeostasis following chemical exposure. The molecular and association studies focusing on these genetic variants may elucidate their functional consequences and contribution in the susceptibility to skin immunotoxicity. Providing information on how genetic variations affect the skin immune system may reduce uncertainties in estimating chemical hazards/risks for human health in the future.
{"title":"Genetic variants affecting chemical mediated skin immunotoxicity.","authors":"Isisdoris Rodrigues de Souza, Patrícia Savio de Araujo-Souza, Daniela Morais Leme","doi":"10.1080/10937404.2021.2013372","DOIUrl":"https://doi.org/10.1080/10937404.2021.2013372","url":null,"abstract":"<p><p>The skin is an immune-competent organ and this function may be impaired by exposure to chemicals, which may ultimately result in immune-mediated dermal disorders. Interindividual variability to chemical-induced skin immune reactions is associated with intrinsic individual characteristics and their genomes. In the last 30-40 years, several genes influencing susceptibility to skin immune reactions were identified. The aim of this review is to provide information regarding common genetic variations affecting skin immunotoxicity. The polymorphisms selected for this review are related to xenobiotic-metabolizing enzymes (<i>CYPA1</i> and <i>CYPB1</i> genes), antioxidant defense (<i>GSTM1, GSTT1</i>, and <i>GSTP1</i> genes), aryl hydrocarbon receptor signaling pathway (<i>AHR</i> and <i>ARNT</i> genes), skin barrier function transepidermal water loss (<i>FLG, CASP14</i>, and <i>SPINK5</i> genes), inflammation (<i>TNF, IL10, IL6, IL18, IL31</i>, and <i>TSLP</i> genes), major histocompatibility complex (MHC) and neuroendocrine system peptides (<i>CALCA, TRPV1, ACE</i> genes). These genes present variants associated with skin immune responses and diseases, as well as variants associated with protecting skin immune homeostasis following chemical exposure. The molecular and association studies focusing on these genetic variants may elucidate their functional consequences and contribution in the susceptibility to skin immunotoxicity. Providing information on how genetic variations affect the skin immune system may reduce uncertainties in estimating chemical hazards/risks for human health in the future.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"25 2","pages":"43-95"},"PeriodicalIF":7.2,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39781849","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}
Pub Date : 2022-01-02Epub Date: 2021-10-27DOI: 10.1080/10937404.2021.1996499
Tyler D Sowers, Clay M Nelson, Matthew D Blackmon, Marissa L Jerden, Alicia M Kirby, Gary L Diamond, Karen D Bradham
Extensive research has examined arsenic (As) bioavailability in contaminated soils and is routinely assessed using in vitro bioaccessibility (IVBA) assays. Analysis of differences in bioaccessibility measurements across IVBA assays and phases is expected to provide valuable insights into geochemical mechanisms controlling soil As bioaccessibility and bioavailability. Soil iron (Fe) content and As speciation are expected to significantly influence IVBA gastric and intestinal phases due to fluctuations in precipitation-dissolution chemistry and sorption reactivity as pH and assay chemical complexity changes. The aim of this review was to examine these relationships by 1) conducting a meta-analysis (n = 47 soils) determining the influence of total Fe on As bioaccessibility measurements and 5 IVBA assays and 2) investigating the effect of As speciation on gastric/intestinal phase IVBA and in vitro-in vivo correlations. Our findings indicate that soil Fe content and As speciation heterogeneity are important in elucidating variability of bioaccessibility measurements across IVBA assays and gastrointestinal phases. Greater focus on coupled As speciation and Fe precipitation chemistry may (1) improve our understanding of soil geochemical factors and assay constituents that influence As in vitro-in vivo correlations and (2) resolve variability in the precision of oral relative bioavailability (RBA) estimated using IVBA assays for soils possessing heterogenous As speciation and Fe composition.
{"title":"Interconnected soil iron and arsenic speciation effects on arsenic bioaccessibility and bioavailability: a scoping review.","authors":"Tyler D Sowers, Clay M Nelson, Matthew D Blackmon, Marissa L Jerden, Alicia M Kirby, Gary L Diamond, Karen D Bradham","doi":"10.1080/10937404.2021.1996499","DOIUrl":"10.1080/10937404.2021.1996499","url":null,"abstract":"<p><p>Extensive research has examined arsenic (As) bioavailability in contaminated soils and is routinely assessed using <i>in vitro</i> bioaccessibility (IVBA) assays. Analysis of differences in bioaccessibility measurements across IVBA assays and phases is expected to provide valuable insights into geochemical mechanisms controlling soil As bioaccessibility and bioavailability. Soil iron (Fe) content and As speciation are expected to significantly influence IVBA gastric and intestinal phases due to fluctuations in precipitation-dissolution chemistry and sorption reactivity as pH and assay chemical complexity changes. The aim of this review was to examine these relationships by 1) conducting a meta-analysis (n = 47 soils) determining the influence of total Fe on As bioaccessibility measurements and 5 IVBA assays and 2) investigating the effect of As speciation on gastric/intestinal phase IVBA and <i>in vitro-in vivo</i> correlations. Our findings indicate that soil Fe content and As speciation heterogeneity are important in elucidating variability of bioaccessibility measurements across IVBA assays and gastrointestinal phases. Greater focus on coupled As speciation and Fe precipitation chemistry may (1) improve our understanding of soil geochemical factors and assay constituents that influence As <i>in vitro-in vivo</i> correlations and (2) resolve variability in the precision of oral relative bioavailability (RBA) estimated using IVBA assays for soils possessing heterogenous As speciation and Fe composition.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"25 1","pages":"1-22"},"PeriodicalIF":6.4,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850428/pdf/nihms-1776006.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550405","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}
Pub Date : 2021-11-17DOI: 10.1080/10937404.2021.1975182
Ryan Takeshita, Steven J Bursian, Kathleen M Colegrove, Tracy K Collier, Kristina Deak, Karen M Dean, Sylvain De Guise, Lisa M DiPinto, Cornelis J Elferink, Andrew J Esbaugh, Robert J Griffitt, Martin Grosell, Kendal E Harr, John P Incardona, Richard K Kwok, Joshua Lipton, Carys L Mitchelmore, Jeffrey M Morris, Edward S Peters, Aaron P Roberts, Teresa K Rowles, Jennifer A Rusiecki, Lori H Schwacke, Cynthia R Smith, Dana L Wetzel, Michael H Ziccardi, Ailsa J Hall
In the wake of the Deepwater Horizon (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.
{"title":"A review of the toxicology of oil in vertebrates: what we have learned following the <i>Deepwater Horizon</i> oil spill.","authors":"Ryan Takeshita, Steven J Bursian, Kathleen M Colegrove, Tracy K Collier, Kristina Deak, Karen M Dean, Sylvain De Guise, Lisa M DiPinto, Cornelis J Elferink, Andrew J Esbaugh, Robert J Griffitt, Martin Grosell, Kendal E Harr, John P Incardona, Richard K Kwok, Joshua Lipton, Carys L Mitchelmore, Jeffrey M Morris, Edward S Peters, Aaron P Roberts, Teresa K Rowles, Jennifer A Rusiecki, Lori H Schwacke, Cynthia R Smith, Dana L Wetzel, Michael H Ziccardi, Ailsa J Hall","doi":"10.1080/10937404.2021.1975182","DOIUrl":"https://doi.org/10.1080/10937404.2021.1975182","url":null,"abstract":"<p><p>In the wake of the <i>Deepwater Horizon</i> (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":"24 8","pages":"355-394"},"PeriodicalIF":7.2,"publicationDate":"2021-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9813131","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}