Andrey Massarsky, Ernest S Fung, Veneese Jb Evans, Andrew Maier
{"title":"<i>In silico</i> occupational exposure banding framework for data poor compounds in biotechnology.","authors":"Andrey Massarsky, Ernest S Fung, Veneese Jb Evans, Andrew Maier","doi":"10.1177/07482337241289184","DOIUrl":"10.1177/07482337241289184","url":null,"abstract":"<p><p>Occupational exposure limits (OELs) and occupational exposure bands (OEBs) provide quantitative benchmarks for worker health protection. If empirical toxicology data are insufficient to derive an OEL, an OEB is often assigned using partial toxicology data along with other relevant hazard information. There is no consensus methodology to assign OEBs for chemicals lacking any empirical toxicology data. Thus, this study developed an <i>in</i> <i>silico</i> framework for OEB assignment of data poor compounds. It relies upon computational tools to evaluate standard toxicological end points and to assign reliability ratings, which are then used to assign Global Harmonization System (GHS) hazard categories. Subsequently, the hazard categories are entered into the National Institute for Occupational Safety and Health (NIOSH) occupational exposure banding tool to assign bands for individual end points as well as an overall OEB. As a proof-of-concept, five compounds with established OELs (i.e., \"knowns\") were evaluated. The knowns were assigned to overall OEBs C, D, or E, four of which were equal to or lower than the OEBs based on actual harmonized GHS categories as well as established OELs, indicating that the OEBs assigned using this framework are likely to be protective. Subsequently, five compounds with little to no experimental data and no established OELs from any U.S. agency or consensus OEL-setting organizations were evaluated (i.e., \"unknowns\"). The unknowns were assigned to overall OEBs D or E. It was concluded that the proposed framework can be used to assign protective OEBs to compounds with little to no toxicology testing data. As additional data become available, the compound may be de-risked, and a precautionary OEB (or an OEL) can be assigned. The proposed framework provides an example of a practical methodology to evaluate data poor compounds and shows that the output of this framework is expected to be protective of worker health.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"20-31"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cole M Higley, Katelyn D Waligora, Jessica R Clore, Shannon C Timmons, Aleksandra Kuzmanov
{"title":"Effects of bisphenol A, bisphenol S, and tetramethyl bisphenol F on male fertility in <i>Caenorhabditis elegans</i>.","authors":"Cole M Higley, Katelyn D Waligora, Jessica R Clore, Shannon C Timmons, Aleksandra Kuzmanov","doi":"10.1177/07482337241287967","DOIUrl":"10.1177/07482337241287967","url":null,"abstract":"<p><p>Research has shown that exposure to bisphenol A (BPA), a widely used plasticizer, can lead to meiotic errors, resulting in poor reproductive cell quality and infertility. Health-related concerns have prompted the search for BPA alternatives; however, evidence suggests that currently used BPA analogs, such as bisphenol S (BPS), may pose similar risks to human health. While the effects of BPA on female fertility are well documented, the impact of BPA exposure on sperm quality is poorly understood. To better understand the effects of bisphenol analogs on spermatogenesis, we synthesized a less investigated BPA analog, tetramethyl bisphenol F (TMBPF), and compared its reprotoxic potential to that of widely used BPA and BPS using <i>C. elegans</i>-based assays. We evaluated germ cell count, spermatid size, morphology, and activation in males treated with 0.5 mM ethanol-dissolved bisphenol analogs for 48 h as well as their cross-progeny number and viability. Our results indicated that all of the evaluated bisphenol analogs-BPA, BPS, and TMBPF-adversely affect male fertility to varying degrees. Whereas all three bisphenols reduced spermatid size, only BPA exposure resulted in impaired spermatid activation and significantly reduced brood size. In addition, a decrease in embryonic viability, suggestive of an increased incidence of sperm chromosomal aberrations, was observed following exposure to all of the tested bisphenols. Further investigation is necessary to fully elucidate the underlying mechanisms and implications of BPA, BPS, and TMBPF on spermatogenesis.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"11-19"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael E Stevens, Brett P Tuttle, David W Brew, Dennis J Paustenbach
{"title":"An evaluation of trends for mesothelioma mortality in American women: Addressing the content of a recent Morbidity and Mortality Weekly Report (MMWR).","authors":"Michael E Stevens, Brett P Tuttle, David W Brew, Dennis J Paustenbach","doi":"10.1177/07482337241293201","DOIUrl":"10.1177/07482337241293201","url":null,"abstract":"<p><p>Mesothelioma is a fatal disease that has historically been associated with exposure to airborne asbestos. Because occupational asbestos exposures dropped dramatically in the late 1960s and early 1970s, far fewer cases of mesothelioma today are due to these fibers but, instead, are usually a result of the aging process or genetic predisposition. In May of 2022, a Morbidity and Mortality Weekly Report (MMWR) was issued by the Centers for Disease Control and Prevention (CDC) regarding malignant mesothelioma incidence in women from 1999 to 2020. While this MMWR alerted citizens to the continued presence of the disease, after reading this article one might have thought that the CDC was suggesting that the disease was increasing in women due to asbestos exposures (which it is not). In the present analysis, we investigate several factors related to the interpretation of epidemiological data for mesothelioma, including the role of asbestos as a risk factor over time. The authors conducted a review of the scientific community's understanding of mesothelioma incidence and asbestos exposures amongst women, as well as an investigation of the methods and references in the MMWR article. Although various articles have recently discussed the incidence of both peritoneal and pleural mesothelioma in women, it is fortunate that the age-adjusted rates for mesothelioma have remained flat (neither increased nor decreased significantly) in women for the past 50 years. Incredibly few women in the U. S. have had appreciable cumulative exposures to any type of asbestos (chrysotile, amosite, or crocidolite) in the workplace or from the ambient environment, especially since about 1965-1970. In this paper, we highlight six factors that should be considered when evaluating the incidence of mesothelioma amongst American women in the current era. Without sufficient consideration of these factors, improper conclusions have been drawn over the past several years.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"40-60"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sayed Vahid Esmaeili, Ali Alboghobeish, Vafa Feyzi, Fatemeh Ravannakhjavani, Rezvan Zendehdel
{"title":"Virtual screening study for biological activity assessment and metabolism pathway of a fuel dye in airborne exposure scenario.","authors":"Sayed Vahid Esmaeili, Ali Alboghobeish, Vafa Feyzi, Fatemeh Ravannakhjavani, Rezvan Zendehdel","doi":"10.1177/07482337241286187","DOIUrl":"10.1177/07482337241286187","url":null,"abstract":"<p><p>The utilization of synthetic dyes increases the risk to human health. Despite the progress of information on azo dyes, very little attention has been reported on toxicity assessment of anthraquinone dyes. Solvent Blue 35 (SB35) is one of the anthraquinone dyes likely to be encountered because of its increasing use in various industries. Whereas the design of laboratory tests is very expensive, in silico screening was used to predict the metabolic profile and toxicity effect of SB35. MetaTox software was used to predict the metabolites of phase I and II in two layers. Since airborne exposure has been considered, the pathways of inhalation and dermal absorption of SB35 were investigated through the SwissADME model based on the modified Lipinski's rule of five. To predict the biological effect and toxicity of SB35 and each of the metabolites, PASS online software was used. Chemical activity was considered according to the probability of activation values (Pa) higher than the probability of inactivation values (Pi). N- dealkylation of SB35 was predicted in the first layer, while seven active compounds were obtained in the second layer from phases I and II reactions. Investigating the physicochemical properties of SB35 confirmed inhalation absorption for occupational exposure scenarios. All metabolites are absorbed from intestinal routes based on the RO5 rules. SB35 and their metabolites have an effective substrate role for the sub-type of CYP 450 enzymes. The toxicity effect of carcinogenicity for SB35 and mutagenicity for metabolites are predicted while confirmed with some biological effects. However, reproductive disorders are pointed with SB35 by probability higher than 70%. Virtual screening methods are efficient tools for creating cost-effective predictions in the hazard's evaluation of SB35. However, a perspective view is suggested before decision-making for laboratory designing tests.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"1-10"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noor Asyikin Suaidi, Mohammed Abdullah Alshawsh, See-Ziau Hoe, Mohd Helmy Mokhtar, Siti Rosmani Md Zin
{"title":"Impact of xylene exposure during organogenesis on foeto-placental efficiency and foetal viability: Exploring its association with oxidative stress-induced inflammation and apoptosis <i>in utero</i>.","authors":"Noor Asyikin Suaidi, Mohammed Abdullah Alshawsh, See-Ziau Hoe, Mohd Helmy Mokhtar, Siti Rosmani Md Zin","doi":"10.1177/07482337241286569","DOIUrl":"10.1177/07482337241286569","url":null,"abstract":"<p><p>The potential maternal and foetal toxicity resulting from exposure to xylene at or below the allowable limit of 100 ppm during gestation is not thoroughly studied. The aim of this study was to investigate maternal and foetal outcomes following prenatal exposure to xylene during organogenesis. Pregnant Sprague Dawley (SD) rats were administered intraperitoneal (IP) corn oil (vehicle), 100, 500, and 1000 parts per million (ppm) of xylene from gestational day (GD) 6 until GD17. Clinical signs, maternal weight gain, and food consumption were recorded daily. A caesarean hysterectomy was performed on GD21 to assess the reproductive and foetal outcomes. Exposure to 1000 ppm of xylene caused a significant decrease in the maternal body weight and food consumption, and an increase in intrauterine foetal deaths. Foetal assessment revealed a significant decrease in foetal weight in both male and female foetuses of female rats treated with 500 and 1000 ppm. Male placental weight was significantly decreased in all xylene-treated groups, while 1000 ppm xylene significantly decreased female placental weight. Histologically, marked uterine inflammatory lesions, fibrosis of the liver and renal tissues, as well as increased placental glycogen content were observed. Immunohistochemistry revealed a significant increase in lipid peroxidation and apoptotic markers. Thus, the foeto-maternal toxicities of xylene have been shown to be mediated by a systemic inflammatory response that exacerbates intrauterine oxidative stress and impairs foeto-placental transfer, leading to an increase in foetal mortality.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"692-710"},"PeriodicalIF":1.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katarzyna Olszak-Wąsik, Andrzej Tukiendorf, Aleksandra Kasperczyk, Anita Olejek, Mateusz Zamłyński, Stanisław Horák
{"title":"Environmental exposure to lead and cadmium only minimally affects the redox system of the follicular fluid and the outcome of intracytoplasmic sperm injection.","authors":"Katarzyna Olszak-Wąsik, Andrzej Tukiendorf, Aleksandra Kasperczyk, Anita Olejek, Mateusz Zamłyński, Stanisław Horák","doi":"10.1177/07482337241285103","DOIUrl":"10.1177/07482337241285103","url":null,"abstract":"<p><p>The purpose of our study was to determine the influence of lead and cadmium in concentrations commonly found in the environment on the redox system of the follicular fluid (FF) and on the results of assisted reproduction. A prospective study of 113 patients with unexplained infertility who qualified for intracytoplasmic sperm injection (ICSI). Patients with moderate or severe endometriosis or poor ovarian reserve were excluded from the study. Biochemical analyses and heavy metal assays of follicular fluid and serum (blood) were followed by statistical analyses of dependencies between lead and cadmium and the components of redox system and results of assisted reproduction. A highly significant linear correlation of lead (Pb) and cadmium (Cd) concentrations in serum and in FF was stated. The number of retrieved oocytes and MII (metaphase II stage) oocytes depended on the malondialdehyde (MDA), catalase (CAT), catalase/g of protein (CAT/g of protein), and glutathione reductase (GR) concentrations. Among biochemical factors, MDA was the only factor that correlated negatively with cadmium concentration in serum and FF and simultaneously influenced the number of retrieved oocytes and MII oocytes. The fertilization rate of MII oocytes was influenced by thiol groups-SH, SH/g of protein, CAT, CAT/g of protein, and glutathione peroxidase/g of protein (GPx/g of protein). The Pb and Cd concentrations in FF did not significantly influence the fertilization rates. Lead as well as cadmium at concentrations commonly found in women of reproductive age despite some adaptive changes in the redox system in follicular fluid do not cause large changes in the ovarian follicular environment as a whole and do not significantly worsen the final results of assisted reproduction.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"679-691"},"PeriodicalIF":1.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thiago Guedes Pinto, Ana Claudia Muniz Renno, Patricia Ramos Cury, Daniel Araki Ribeiro
{"title":"The impact of genetic polymorphism for detecting genotoxicity in workers occupationally exposed to formaldehyde: A systematic review.","authors":"Thiago Guedes Pinto, Ana Claudia Muniz Renno, Patricia Ramos Cury, Daniel Araki Ribeiro","doi":"10.1177/07482337241279894","DOIUrl":"10.1177/07482337241279894","url":null,"abstract":"<p><p>Formaldehyde is a chemical compound capable of preserving cells and tissue morphology, being extensively used worldwide in industrial and medical processes. However, due to the many biological effects that take place after an individual is chronically exposed to formaldehyde, this compound poses a greater cancer risk for workers under its occupational exposure, even at lower concentrations. Thus, the present systematic review aimed to understand whether there may be a positive relation between polymorphism (in terms of individual susceptibility) and genotoxicity in individuals occupationally exposed to formaldehyde. For this purpose, a total of eight selected studies were carefully analyzed by two reviewers, who attributed scores to each study according to the used analysis parameters. First, all studies investigated either pathologists under formaldehyde exposure or anatomical laboratory pathology workers. In addition, the majority of studies were categorized as moderate or strong in the quality assessment. The results revealed a positive association between some polymorphism and genotoxicity in individuals exposed to formaldehyde, since more than half of the studies observed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing genes. We understand such parameters influence individuals' susceptibility to genomic damage induced by formaldehyde in peripheral blood. In conclusion, individuals with certain genotypes may show higher or lower DNA damage and/or lower or higher DNA repair potential.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"643-652"},"PeriodicalIF":1.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142155001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nadielle Silva Bidu, Diogo Sousa Lemos, Bruno José Dumêt Fernandes
{"title":"Occupational exposure to arsenic and leukopenia risk: Toxicological alert.","authors":"Nadielle Silva Bidu, Diogo Sousa Lemos, Bruno José Dumêt Fernandes","doi":"10.1177/07482337241277261","DOIUrl":"10.1177/07482337241277261","url":null,"abstract":"<p><p>Arsenic and its inorganic compounds affect numerous organs and systemic functions, such as the nervous and hematopoietic systems, liver, kidneys, and skin. Despite a large number of studies on arsenic toxicity, rare reports have investigated the leukopenia incidence in workers exposed to arsenic. In workplaces, the main source of workers' exposure is the contaminated air by the inorganic arsenic in mines, arsenic or copper smelter industries, and chemical factories. Erythropoiesis inhibition is one of the arsenic effects and it is related to regulatory factor GATA-1. This factor is necessary for the normal differentiation of early erythroid progenitors. JAK-STAT is an important intracellular signal transduction pathway responsible for the mediating normal functions of several cytokines related to cell proliferation and hematopoietic systems development and regulation. Arsenic inactivates JAK-STAT by inhibiting JAK tyrosine kinase and using the IFNγ pathway. The intravascular hemolysis starts after the absorption phase when arsenic binds to the globin of hemoglobin in erythrocytes and is transported into the body, which increases the oxidation of sulfhydryl groups in hemoglobin. So, this article intends to highlight the potential leukopenia risk via inhalation for workers exposed to arsenic and suggests a possible mechanism for this leukopenia through the JAK-signal transducer and activator of transcription (STAT) pathway inhibition.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"637-642"},"PeriodicalIF":1.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cui Jiajing, Yan Shuqi, Ma Haoyan, Wang Pingwei, Liu Dongge, Liu Yanping, Chen Qianqian, Fajrin Saleh, Ren Shuping
{"title":"Perfluorooctane sulfonate causes damage to L-02 cells via Wnt/β-catenin signal path and endoplasmic reticulum stress pathway.","authors":"Cui Jiajing, Yan Shuqi, Ma Haoyan, Wang Pingwei, Liu Dongge, Liu Yanping, Chen Qianqian, Fajrin Saleh, Ren Shuping","doi":"10.1177/07482337241277259","DOIUrl":"10.1177/07482337241277259","url":null,"abstract":"<p><p>Perfluorooctane sulfonate (PFOS) is one of the most widely used perfluorinated compounds, and as an environmental endocrine disruptor and environmental persistent pollutant, the threat of PFOS to human health is of increasing concern. Exposure to PFOS has been shown to be closely associated with liver disease, but the intrinsic molecular targets and mechanisms of PFOS-induced liver damage are not well understood. This study was conducted to explore whether the Wnt/β-Catenin signaling pathway and the endoplasmic reticulum stress signaling pathway are involved in damage of PFOS to the liver. In this study, we used the CCK-8 method to detect cell viability, a microscope and DAPI staining to observe cell morphology, flow cytometry to detect cell ROS and apoptosis levels; and Western blot to detect the expressions of proteins in the WNT/β-Catenin, endoplasmic reticulum stress and apoptosis-related pathways. We found that PFOS activated WNT/β-Catenin and endoplasmic reticulum stress-related pathways in L-02 cells and could lead to the development of oxidative stress and apoptosis. Our findings showed that PFOS could cause damage to L-02 cells, and the WNT/β-Catenin signaling and endoplasmic reticulum stress pathways were involved in the changes caused by PFOS to L-02 cells, which provided a new theoretical basis for studying the hepatotoxicity and mechanism of PFOS. PFOS can lead to increased intracellular ROS levels, causing oxidative stress, endoplasmic reticulum stress and activation of the WNT/β-catenin signaling pathway. Our experimental results showed that PFOS can cause damage to L-02 cells, and the WNT/β-Catenin signaling pathway and endoplasmic reticulum stress pathway are involved in the process of damage caused by PFOS to L-02 cells.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"653-666"},"PeriodicalIF":1.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farha Shahabuddin, Samina Naseem, Tauseef Alam, Aijaz Ahmed Khan, Farah Khan
{"title":"Chronic aluminium chloride exposure induces redox imbalance, metabolic distress, DNA damage, and histopathologic alterations in Wistar rat liver.","authors":"Farha Shahabuddin, Samina Naseem, Tauseef Alam, Aijaz Ahmed Khan, Farah Khan","doi":"10.1177/07482337241269784","DOIUrl":"10.1177/07482337241269784","url":null,"abstract":"<p><p>Aluminium, a ubiquitous environmental toxicant, is distinguished for eliciting a broad range of physiological, biochemical, and behavioural alterations in laboratory animals and humans. The present work was conducted to study the functional and structural changes induced by aluminium in rat liver. Twenty five adult male Wistar rats (150-200 g) were randomly divided into five groups; control group and four Al-treated groups viz: Al 1 (25 mg AlCl<sub>3</sub>/kg b.wt), Al 2 (35 mg AlCl<sub>3</sub>/kg b.wt), Al 3 (45 mg AlCl<sub>3</sub>/kg b.wt), and Al 4 (55 mg AlCl<sub>3</sub>/kg b.wt). Rats in the aluminium-treated groups were administered AlCl<sub>3</sub> for 30 days through oral gavage. Aluminium significantly increased the serum levels of liver function markers (ALT, AST, and ALP), phospholipids, and cholesterol. The activities of hepatocyte membrane (ALP, GGT, and LAP) and carbohydrate metabolic (G6P, F16BP, HK, LDH, MDH, ME, and G6PDH) enzymes were significantly altered by AlCl<sub>3</sub> administration. Prolonged Al exposure induced oxidative stress in the liver, as evident by significant hepatocellular DNA damage, increased lipid peroxidation, and decreased non-enzymatic and enzymatic antioxidants. The toxic effects observed in this study were AlCl<sub>3</sub> dose-dependent. Histopathological examination of liver sections revealed enlargement of sinusoidal spaces, derangement of the hepatic chord, loss of discrete hepatic cell boundaries, congestion of hepatic sinusoids, and degeneration of hepatocytes in Al-intoxicated rats. In conclusion, aluminium causes severe hepatotoxicity by inhibiting the hepatocyte membrane enzymes and disrupting the liver's energy metabolism and antioxidant defence.</p>","PeriodicalId":23171,"journal":{"name":"Toxicology and Industrial Health","volume":" ","pages":"581-595"},"PeriodicalIF":1.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}