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Reproductive Toxicology (Elmsford, N.Y.) Aug 2018Known endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. Its structural analogs: bisphenol S (BPS), bisphenol F (BPF),... (Review)
Review
Known endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. Its structural analogs: bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) are increasingly being used in consumer products. However, these analogs may exert similar adverse effects on the reproductive system, and their toxicological data are still limited. This mini-review examined studies on both BPA and BPA analog exposure and reproductive toxicity. It outlines the current state of knowledge on human exposure, toxicokinetics, endocrine activities, and reproductive toxicities of BPA and its analogs. BPA analogs showed similar endocrine potencies when compared to BPA, and emerging data suggest they may pose threats as reproductive hazards in animal models. While evidence based on epidemiological studies is still weak, we have utilized current studies to highlight knowledge gaps and research needs for future risk assessments.
Topics: Animals; Benzhydryl Compounds; Endocrine Disruptors; Female; Humans; Male; Phenols; Reproductive Health
PubMed: 29925041
DOI: 10.1016/j.reprotox.2018.06.005 -
Toxics Nov 2023Plastics, including microplastics, have generally been regarded as harmful to organisms because of their physical characteristics. There has recently been a call to... (Review)
Review
Plastics, including microplastics, have generally been regarded as harmful to organisms because of their physical characteristics. There has recently been a call to understand and regard them as persistent, bioaccumulative, and toxic. This review elaborates on the reasons that microplastics in particular should be considered as "toxic pollutants". This view is supported by research demonstrating that they contain toxic chemicals within their structure and also adsorb additional chemicals, including polychlorinated biphenyls (PCBs), pesticides, metals, and polycyclic aromatic hydrocarbons (PAHs), from the environment. Furthermore, these chemicals can be released into tissues of animals that consume microplastics and can be responsible for the harmful effects observed on biological processes such as development, physiology, gene expression, and behavior. Leachates, weathering, and biofilm play important roles in the interactions between microplastics and biota. Global policy efforts by the United Nations Environmental Assembly via the international legally binding treaty to address global plastic pollution should consider the designation of harmful plastics (e.g., microplastics) with associated hazardous chemicals as toxic pollutants.
PubMed: 37999586
DOI: 10.3390/toxics11110935 -
Toxics Oct 2022Large amounts of enriched cadmium (Cd) in the environment seriously threatens the healthy and sustainable development of the aquaculture industry and greatly restricts... (Review)
Review
Large amounts of enriched cadmium (Cd) in the environment seriously threatens the healthy and sustainable development of the aquaculture industry and greatly restricts the development of the food processing industry. Studying the distribution and toxic effects of Cd in fish, as well as the possible toxic effects of Cd on the human body, is very significant. A large number of studies have shown that the accumulation and distribution of Cd in fish are biologically specific, cause tissue differences, and seriously damage the integrity of tissue structure and function, the antioxidant defense system, the reproductive regulation system, and the immune system. The physiological, biochemical, enzyme, molecular, and gene expression levels change with different concentrations and times of Cd exposure, and these changes are closely related to the target sites of Cd action and tissues in fish. Therefore, the toxic effects of Cd on fish occur with multiple tissues, systems, and levels.
PubMed: 36287901
DOI: 10.3390/toxics10100622 -
Toxics Sep 2021Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of... (Review)
Review
Introduction to a collection. This article is intended to introduce a collection of papers on toxic neuropathies. Toxic neuropathies can be caused by a variety of substances and by different mechanisms. Toxic agents are numerous and can be distinguished between drugs, recreational agents, heavy metals, industrial agents, pesticides, warfare agents, biologic substances and venoms. Toxic agents reach the nervous system by ingestion, transcutaneously, via the mucous membranes, parenterally and by aerosols. The most frequent types are cumulative toxicities. Other types are acute or delayed toxicities. Pathogenetic mechanisms range from a specific toxic substance profile causing axonal or demyelinating lesions, towards ion channel interferences, immune-mediated mechanisms and a number of different molecular pathways. In addition, demyelination, focal lesions and small fiber damage may occur. Clinically, neurotoxicity presents most frequently as axonal symmetric neuropathies. In this work, we present a panoramic view of toxic neuropathy, in terms of symptoms, causes, mechanisms and classification.
PubMed: 34564369
DOI: 10.3390/toxics9090218 -
Integrative Medicine (Encinitas, Calif.) Feb 2020The worldwide prevalence of obesity has near tripled between 1975 and 2016. Diabetes was the direct cause of an estimated 1.6 million deaths in 2015. Diabetogens,... (Review)
Review
The worldwide prevalence of obesity has near tripled between 1975 and 2016. Diabetes was the direct cause of an estimated 1.6 million deaths in 2015. Diabetogens, otherwise known as toxicants that cause insulin resistance in animal models and humans as a result of pancreatic β-cell damage include the persistent organochlorine pesticides -nonachlor, oxychlordane, and DDE -the main metabolite of DDT, as well as another class of persistent organic pollutants, polychlorinated biphenyls (PCBs). Other toxicants that are now considered diabetogens: BPA, arsenic, phthalates, perfluorinates (PFOS), diethyl hexyl phthalate (DEHP), and dioxin (TCDD) are commonly found in the blood and urine in the CDC NHANES populations and presumed to also be commonly found in the U.S. population as a whole. A review of the literature on the risk for diabetes in epidemiologic studies considering these toxicants, challenges for clinicians using lab testing for these diabetogens, and the necessary interventions for lowering body burden of persistent toxicants are discussed.
PubMed: 32549860
DOI: No ID Found -
Archives of Pharmacal Research Mar 2020Liver plays essential roles in the metabolism of many endogenous chemicals and exogenous toxicants. Mechanistic studies in liver have been at the forefront of efforts to... (Review)
Review
Liver plays essential roles in the metabolism of many endogenous chemicals and exogenous toxicants. Mechanistic studies in liver have been at the forefront of efforts to probe the roles of bioactivation and detoxication of environmental toxins and toxicants in hepatotoxicity. Moreover, idiosyncratic hepatoxicity remains a key barrier in the clinical development of drugs. The now vast Nrf2 field emerged in part from biochemical and molecular studies on chemical inducers of hepatic detoxication enzymes and subsequent characterization of the modulation of drug/toxicant induced hepatotoxicities in mice through disruption of either Nrf2 or Keap1 genes. In general, loss of Nrf2 increases the sensitivity to such toxic chemicals, highlighting a central role of this transcription factor and its downstream target genes as a modifier to chemical stress. In this review, we summarize the impact of Nrf2 on the toxicology of multiple hepatotoxicants, and discuss efforts to utilize the Nrf2 response in predictive toxicology.
Topics: Animals; Chemical and Drug Induced Liver Injury; Humans; Liver; NF-E2-Related Factor 2
PubMed: 31782059
DOI: 10.1007/s12272-019-01192-3 -
The Journal of Endocrinology Jul 2023Based on biological sex, the consequential health outcomes from exposures to environmental chemicals or toxicants can differ in disease pathophysiology, progression, and... (Review)
Review
Based on biological sex, the consequential health outcomes from exposures to environmental chemicals or toxicants can differ in disease pathophysiology, progression, and severity. Due to basal differences in cellular and molecular processes resulting from sexual dimorphism of organs including the liver and additional factors influencing 'gene-environment' interactions, males and females can exhibit different responses to toxicant exposures. Associations between environmental/occupational chemical exposures and fatty liver disease (FLD) have been well-acknowledged in human epidemiologic studies and their causal relationships demonstrated in experimental models. However, studies related to sex differences in liver toxicology are still limited to draw any inferences on sex-dependent chemical toxicity. The purpose of this review is to highlight the present state of knowledge on the existence of sex differences in toxicant-associated FLD (TAFLD), discuss potential underlying mechanisms driving these differences, implications of said differences on disease susceptibility, and emerging concepts. Chemicals of interest include various categories of pollutants that have been investigated in TAFLD, namely persistent organic pollutants, volatile organic compounds, and metals. Insight into research areas requiring further development is also discussed, with the objective of narrowing the knowledge gap on sex differences in environmental liver diseases. Major conclusions from this review exercise are that biological sex influences TAFLD risks, in part due to (i) toxicant disruption of growth hormone and estrogen receptor signaling, (ii) basal sex differences in energy mobilization and storage, and (iii) differences in chemical metabolism and subsequent body burden. Finally, further sex-dependent toxicological assessments are warranted for the development of sex-specific intervention strategies.
Topics: Female; Humans; Male; Sex Characteristics; Non-alcoholic Fatty Liver Disease; Environmental Pollutants; Models, Theoretical
PubMed: 37074385
DOI: 10.1530/JOE-22-0247 -
ALTEX 2015Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after...
Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks.
Topics: Adaptation, Physiological; Animal Testing Alternatives; Animals; Cell Death; Cell Physiological Phenomena; Humans; Stress, Physiological
PubMed: 26536287
DOI: 10.14573/altex.1509271 -
Toxicology Apr 2019Electron-deficient chemicals (electrophiles) react with compounds that have one or more unshared valence electron pairs (nucleophiles). The resulting covalent reactions... (Review)
Review
Electron-deficient chemicals (electrophiles) react with compounds that have one or more unshared valence electron pairs (nucleophiles). The resulting covalent reactions between electrophiles and nucleophiles (e.g., Michael addition, S2 reactions) are important, not only to Organic Chemistry, but also to the fields of Molecular Biology and Toxicology. Specifically, covalent bond formation is the operational basis of many critically important cellular processes; e.g., enzyme function, neurotransmitter release, and membrane-vesicle fusion. Given this context it is understandable that these reactions are also relevant to Toxicology, since a significant number of xenobiotic chemicals are toxic electrophiles that can react with endogenous nucleophilic residues. Therefore, the purpose of this Review is to discuss electrophile-nucleophile chemistry as it pertains to cell injury and resulting organ toxicity. Our discussion will involve an introduction to the Hard and Soft, Acids and Bases (HSAB) theory of Pearson. The HSAB concept provides a framework for calculation of quantum chemical parameters that classify the electrophile and nucleophile covalent components according to their respective electronic nature (softness/hardness) and reactivity (electrophilicity/nucleophilicity). The calculated quantum indices in conjunction with corroborative in vivo, in chemico (cell free) and in vitro research can offer an illuminating approach to mechanistic discovery. Accordingly, we will provide examples that demonstrate how this approach has been used to discern mechanisms and sites of electrophile action.
Topics: Animals; Cell Death; Environmental Exposure; Environmental Pollutants; Hardness; Humans; Models, Biological; Models, Molecular; Molecular Conformation; Risk Assessment; Structure-Activity Relationship; Xenobiotics
PubMed: 30826385
DOI: 10.1016/j.tox.2019.02.005 -
Current Opinion in Biotechnology Jun 2017Man-made xenobiotics, whose potential toxicological effects are not fully understood, are oversaturating the already-contaminated environment. Due to the rate of... (Review)
Review
Man-made xenobiotics, whose potential toxicological effects are not fully understood, are oversaturating the already-contaminated environment. Due to the rate of toxicant accumulation, unmanaged disposal, and unknown adverse effects to the environment and the human population, there is a crucial need to screen for environmental toxicants. Animal models and in vitro models are ineffective models in predicting in vivo responses due to inter-species difference and/or lack of physiologically-relevant 3D tissue environment. Such conventional screening assays possess limitations that prevent dynamic understanding of toxicants and their metabolites produced in the human body. Organ-on-a-chip systems can recapitulate in vivo like environment and subsequently in vivo like responses generating a realistic mock-up of human organs of interest, which can potentially provide human physiology-relevant models for studying environmental toxicology. Feasibility, tunability, and low-maintenance features of organ-on-chips can also make possible to construct an interconnected network of multiple-organs-on-chip toward a realistic human-on-a-chip system. Such interconnected organ-on-a-chip network can be efficiently utilized for toxicological studies by enabling the study of metabolism, collective response, and fate of toxicants through its journey in the human body. Further advancements can address the challenges of this technology, which potentiates high predictive power for environmental toxicology studies.
Topics: Animals; Ecotoxicology; Environmental Pollutants; Humans; Manufactured Materials; Microfluidics; Models, Animal; Models, Biological; Xenobiotics
PubMed: 28088094
DOI: 10.1016/j.copbio.2016.11.019