Journal of Applied Toxicology

Sat, 12/19/2020 - 22:05
Lung cancer is the most common neoplasm and the primary cause‐related mortality in developed and in most of nondeveloped countries. Epidemiological studies have demonstrated that even at low arsenic doses, the lungs are one of the main target organs and that chronic arsenic exposure has been associated with an increase in lung cancer development. Among the risk factors for cancer, arsenic...
Fri, 12/18/2020 - 22:05
To improve our understanding of underlying toxic mechanisms, it is important to evaluate differences in effects that a variety of metals exert at concentrations representing the same toxic level to the organism. Therefore, the main goal of the present study was to compare the effects of waterborne copper (Cu(II)), zinc (Zn(II)) and cadmium (Cd (II)) on a freshwater fish, the common carp (Cyprinus...
Fri, 12/18/2020 - 22:05
The G protein‐coupled estrogen receptor 1 (Gper1) is a membrane‐bound estrogen receptor that mediates non‐genomic action of estrogens. A Gper1‐mediating pathway has been implicated in reproductive activities in fish, including oocyte growth, but Gper1 has been characterized in only a very limited number of fish species. In this study, we cloned and characterized two genes encoding medaka (Oryzias...
Mon, 12/14/2020 - 22:05
Worldwide demand for petroleum products has resulted in increased oil and gas activities in many countries. Conventional and unconventional oil and gas extraction, production, and transport lead to increased levels of petroleum‐derived polycyclic aromatic hydrocarbons (PAHs) in the environment. PAH exposure has profound effects on reproduction by affecting pathways involved in placental...
Tue, 12/08/2020 - 22:05
Itai‐itai (Japanese, “It hurts! It hurts!”) disease (IID), a form of osteomalacia, can be induced in ovariectomized rats by long‐term administration of cadmium (Cd). This IID rat model shows severe anemia, severe nephropathy, and osteomalacia accompanied by iron (Fe) deposition at the mineralization front. We characterized the pathogenesis of Cd‐induced bone lesions by investigating the...
Thu, 11/26/2020 - 22:06
This study aimed to observe the effects of Selenium (Se) on aflatoxin B1 (AFB1)‐induced uterine injury in female mice and necrosis of human endometrial microvascular endothelial cells (HEMECs). Fifty female mice were randomly divided into control group; AFB1 group; Se group (0.2 mg/kg each day); AFB1 + Se group; and positive control group. After continuous treatment for 30 days, uterine tissues...
Thu, 11/26/2020 - 22:06
Asarone isomers are naturally occurring in Acorus calamus Linné, Guatteria gaumeri Greenman, and Aniba hostmanniana Nees. These secondary plant metabolites belong to the class of phenylpropenes (phenylpropanoids or alkenylbenzenes). They are further chemically classified into the propenylic trans‐ and cis‐isomers α‐asarone and β‐asarone and the allylic γ‐asarone. Flavoring, as well as potentially...
Wed, 11/18/2020 - 22:06
Cadmium (Cd) is an occupational and environmental heavy metal pollutant derived from many sources that is linked to endothelial homeostasis. The endothelium is an important site of Cd deposition, while increasing evidence has revealed there is a close relationship between endothelial dysfunction and abnormal lipid metabolism. However, the effects of the alterations in lipid metabolism on...
Wed, 11/04/2020 - 22:07
Cetylated fatty acids (CFAs) are a group of fats that contain a single ester group within a hydrocarbon chain, which are reported to have beneficial biological effects. A novel mixture of CFAs produced by combining fatty acids derived from refined olive oil with cetyl esters (Lipocet®) is proposed for use as a food ingredient and was therefore subjected to a nonclinical safety assessment. The...
Tue, 11/03/2020 - 22:08
Contamination of animal feed with Fusarium spp results in accumulation of mycotoxins including deoxynivalenol. In animals, deoxynivalenol is metabolized to de‐epoxy deoxynivalenol (DOM‐1), which is generally considered to be a non‐toxic metabolite; however, recent studies demonstrated that DOM‐1 can reduce steroid production and induce apoptosis in the bovine ovary. The objectives of this study...
Tue, 11/03/2020 - 22:08
Neurotoxicity studies are important in the preclinical stages of drug development process, because exposure to certain compounds that may enter the brain across a permeable blood brain barrier damages neurons and other supporting cells such as astrocytes. This could, in turn, lead to various neurological disorders such as Parkinson's or Huntington's disease as well as various dementias. Toxicity...
Sat, 10/31/2020 - 22:09
The regulatory community is transitioning to the use of nonanimal methods for dermal sensitization assessments; however, some in vitro assays have limitations in their domain of applicability depending on the properties of chemicals being tested. This study explored the utility of epidermal sensitization assay (EpiSensA) to evaluate the sensitization potential of complex and/or “difficult to test...
Sat, 10/31/2020 - 22:09
Arsenic is a contaminant found in many foods and drinking water. Exposure to arsenic during development can cause improper neuronal progenitor cell development, differentiation, and function, while in vitro studies have determined that acute arsenic exposure to stem and progenitor cells reduced their ability to differentiate. In the current study, P19 mouse embryonal stem cells were exposed...
Thu, 10/29/2020 - 22:07
Environmental epigenetic findings shed new light on the roles of epigenetic regulations in environmental exposure‐induced toxicities or disease susceptibilities. Currently, environmental emerging contaminants (ECs) are in focus for further investigation due to the evidence of human exposure in addition to their environmental occurrences. However, the adverse effects of these environmental ECs on...
Fri, 10/09/2020 - 22:09
Quantum dots (QDs), as one of the emerging nanomaterials, have been widely studied by scientists due to their advantages and potential in bioimaging, especially cell imaging. Cadmium (Cd)‐based QDs, which have the best photoluminescence property, have received widespread attention. However, due to the obvious toxicity problem of these QDs, their cell imaging application is hindered. Recently, the...
Thu, 10/08/2020 - 22:07
Chemical warfare (CW) exposure could be fatal to military and civilians through skin contamination. Our work and others focus on investigating stratum corneum reservoir with less regards to skin appendageal routes including hair follicles. Here, C‐14 CW simulants (CWS) with specific activity of 0.1 mCi/ml were tested on abdominal and scalp human cadaver skin using flow‐through diffusion system....
Mon, 10/05/2020 - 22:07
Polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UV) represent genotoxic factors that commonly occur in the living and working environment. The dermal form of exposure represents a significant part of the total load of dangerous chemical and physical environmental factors to which an organism is subjected. However, simultaneous dermal exposures to PAHs (pharmaceutical crude coal...
Mon, 10/05/2020 - 22:07
We compared the toxicokinetics of methylmercury (MeHg) in KK‐Ay type 2 diabetic mice and C57BL/6J mice to evaluate how metabolic changes associated with diabetes affect MeHg toxicokinetics. A single dose of MeHg (0.2, 1, or 5 mg mercury/kg) was administered orally to 12‐week‐old KK‐Ay and C57BL/6J male mice. Total mercury concentrations in plasma, blood cells, whole blood, and tissues (brain,...
Thu, 10/01/2020 - 22:07
Human milk oligosaccharides (HMOs) are a complex group of bioactive molecules largely observed in human breast milk but also occurring in limited amounts in other mammalian milks. Advances in biotechnology have enabled production of human‐identical milk oligosaccharides (HiMOs), structurally identical molecules to HMOs found naturally in human milk, intended for addition to infant formula to more...
Mon, 09/28/2020 - 22:07
Percutaneous penetration of chemicals from clothing can result in both acute and chronic toxicities. Although personal protective equipment composed of nonwoven material can provide thorough protection, it is often uncomfortable under normal occupational conditions. Certain everyday textiles are often utilized as protective clothing due to their cost, comfort, and convenience. Although common...
Tue, 09/22/2020 - 22:08
The objective of this study was to assess the effect of environmental cadmium exposure according to urinary cadmium concentration (U‐Cd) on noncancer mortality in a general Japanese population. We conducted a longitudinal study for 19 years in 2804 inhabitants (1107 men and 1697 women) in some cadmium nonpolluted regions in Japan. The participants were classified into quartiles based on U‐Cd (μg/...
Thu, 09/03/2020 - 22:08
Cadmium (Cd) is a toxic heavy metal with no known biological functions in the human body. Due to a considerably long biological half‐life and very low rate of excretion, accumulation of Cd in different body organs (eg, liver, kidney, and testes) over time is associated with perturbed functioning of these organs. Recent studies have shown the extreme sensitivity of the testes to Cd toxicity. In...
Thu, 08/27/2020 - 22:08
The branched isomer mixture 4‐nonylphenol (4‐NP) has been used worldwide as a surfactant, and can have endocrine‐disrupting effects on aquatic organisms. For instance, 4‐NP induces the formation of testis‐ova (i.e., testicular and ovarian tissue in the same gonad) or male to female sex reversal of various teleost fishes. Recently, our group revealed that altered gsdf gene expression is associated...
Tue, 08/25/2020 - 22:07
Drug development includes imaging agents, contrast agents and radiopharmaceuticals; these materials differ from therapeutic drugs in that they are largely used to diagnose and/or monitor diseases and not treat them. Consequently, nonclinical safety testing needs are different. An examination of testing packages supporting clinical entry and/or marketing of these materials has shown a common...
Sat, 08/08/2020 - 22:08
Parabens (PBs) are compounds widely used in industry for food and personal care products as antimicrobials and preservatives. Their indiscriminate use has resulted in their detection in different ecosystems so that humans and other organisms are highly exposed. Methylparaben (MePB), compared with other PBs, is mostly detected in food, personal care and baby care products. PBs could be linked to...
Wed, 07/29/2020 - 22:07
Gut microorganisms are vital for many aspects of human health, and the commensal bacterium Akkermansia muciniphila has repeatedly been identified as a key component of intestinal microbiota. Reductions in A. muciniphila abundance are associated with increased prevalence of metabolic disorders such as obesity and type 2 diabetes. It was recently discovered that administration of A. muciniphila has...
Thu, 07/16/2020 - 22:07
Microplastics (MPs) have become a global environmental pollutant because of their unique properties. The extensive MP toxicity reports have focused on the aquatic environment, while the pervasive MP contamination in the soil and air has largely been overlooked. This review summarizes the abundance, sources and transport of MPs in different environments. It analyzes the toxicity of MPs based on...
Wed, 07/15/2020 - 22:08
The relationship between urinary β2‐microglobulin (β2‐MG) and the risk of all‐cause mortality and cause‐specific mortality in a cadmium (Cd)‐polluted area was investigated in 3139 inhabitants (1404 men and 1735 women) of the Kakehashi River basin in Japan at 35‐year follow‐up. The subjects had been participants in the 1981–1982 health impact survey that assessed Cd‐induced renal dysfunction, as...
Wed, 07/15/2020 - 22:08
Accidental intoxications from environmental pollutants, as well as intentional self‐ and chemical warfare‐related poisonings affect millions of people worldwide each year. While many toxic agents can readily enter the central nervous system (CNS), the blood‐brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. Consequently, poisoning antidotes usually cannot reach their site of...
Wed, 07/15/2020 - 22:08
Fumonisins are a family of potentially carcinogenic mycotoxins produced by Fusarium verticillioides. Several fumonisins have been identified with fumonisin B1 (FB1) being the most toxic. The canonical mechanism of FB1 toxicity is centered on its structural resemblance with sphinganine and consequent competitive inhibition of ceramide synthase and disruption of lipidomic profiles. Recent and...
Tue, 07/14/2020 - 22:08
Bisphenol A (BPA), as a common industrial component, is generally consumed in the synthesis of polymeric materials. To gain a deeper understanding of the detrimental effects of BPA, BPA‐induced microRNA (miRNA) alterations were investigated. A systematic search was performed in the PubMed, SCOPUS and Web of Science databases to evoke relevant published data up to August 10, 2019. We identified...
Mon, 07/13/2020 - 22:07
Polychlorinated dibenzo‐p‐dioxins (PCDDs) are hypothesized to exert their toxic effects in wildlife and humans via endocrine disruption. However, very scanty information is available on the underlying molecular interactions that trigger this disruption. In this study, molecular docking simulation was used to predict the susceptibility of 12 nuclear receptors to disruption via PCDD bindings....
Sat, 07/11/2020 - 22:07
An understanding of polychlorinated biphenyl (PCB) congener‐specific effects on cell membrane and intercellular communication is important within the studies of PCB absorption, organ‐related PCB accumulation and exertion of toxic responses. Toxic potential of PCBs is linked to various deleterious effects on human health, including neurotoxicity, immunotoxicity, reproductive toxicity and...
Mon, 07/06/2020 - 22:07
Di‐n‐butyl phthalate (DBP) is known to have adverse effects on reproduction in mammals and is pervasive in the aquatic environment. The objective of the present study was to investigate whether long‐term exposure to low concentrations of DBP can affect fish reproduction. In this study, zebrafish (Danio rerio) embryos (F0) were exposed to low concentrations (4.9, 13.6 and 43.8 μg/L) of DBP from 2...
Tue, 05/19/2020 - 03:24
Polychlorinated biphenyls (PCBs) are a class of persistent organic environmental pollutants with a total of 209 homologs. The homolog 2,3′,4,4′,5‐pentachlorobiphenyl (PCB118) is one of the most important dioxin‐like PCBs and is highly toxic. PCB118 can accumulate in human tissues, serum and breast milk, which leads to direct exposure of the fetus during development. In the present study, pregnant...
Wed, 05/06/2020 - 03:25
We previously demonstrated that particulate matter ≤2.5 μm (PM2.5) suppresses the immune response in the spleen in vivo. Although PM2.5 includes the polycyclic aromatic hydrocarbon (PAH) such as dibenzo[a,h]anthracene (DBA), it is unclear whether PAH has a direct effect on the responses of splenocytes. In our study, the concentration of DBA used was approximately 0.8 μm, which is much lower than...
Thu, 04/30/2020 - 03:24
Pantoea agglomerans is a Gram‐negative bacterium that is ubiquitous in the environment, colonizing animals, humans, and numerous plants, including cotton and wheat. A lipopolysaccharide‐containing fermented wheat flour extract from P. agglomerans (Somacy‐FP100) is proposed for use as a food ingredient for individuals seeking foods for healthy aging. Previously published genotoxicity studies with...
Thu, 04/30/2020 - 03:24
Globally, more than a billion people smoke tobacco making it one of the biggest public health problems and a leading risk factor for global deaths. Nicotine, the main alkaloid in tobacco, has been shown to be associated with fertility problems in men and women. The adverse effects of tobacco/nicotine on reproduction have been attributed to deleterious effects on gametes, steroidogenic imbalance,...
Sun, 04/26/2020 - 03:21
Deoxynivalenol (DON) is a common mycotoxin, which often induces oxidative stress and cytotoxicity in humans and animals. Astilbin (AST), as a natural antioxidant, exhibits multiple pharmacological functions. The aim of this study was to investigate the effects of AST on alleviating DON‐induced cytotoxicity in intestinal porcine epithelial cells (IPEC‐J2). The results demonstrated that 0.5 μg/mL...
Tue, 03/31/2020 - 03:17
Broad application of reduced graphene oxide (rGO) and ubiquitous lead (Pb) pollution may increase the possibility of combined exposure of humans. Information on the combined effects of rGO and Pb in human cells is scarce. This work was designed to explore the potential effects of rGO on Pb‐induced toxicity in human alveolar epithelial (A549) cells. Prepared rGO was polycrystalline in nature. The...
Thu, 03/26/2020 - 03:16
We previously reported that immunostaining for γ‐H2AX, a biomarker of DNA damage, in the rat urinary bladder is useful for early detection of bladder carcinogens in 28‐day toxicity studies. Here, we aimed to examine the dose dependency of γ‐H2AX formation in the urinary bladder of rats. Male F344 rats (aged 6 weeks) were orally administered N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (BBN; 0%, 0.0001...
Thu, 03/26/2020 - 03:16
Assessment of reproductive toxicity is one of the important safety considerations in drug development. Thus, in the present research, the naïve Bayes (NB)‐classifier method was applied to develop binary classification models. Six important molecular descriptors for reproductive toxicity were selected by the genetic algorithm. Then, 110 classification models were developed using six molecular...
Sun, 03/15/2020 - 03:27
The potential toxicity of cadmium‐containing quantum dots (QDs) has received much attention because of increasing biomedical applications. However, little has been known about how cadmium telluride (CdTe) QDs influence the gut microbiota and lipid metabolism. In this study, mice were exposed orally to CdTe QDs (200 μL of 0.2, 2, 20 or 200 μm; twice per week) for 4 weeks. The oral experiments...
Sat, 03/14/2020 - 03:16
Metal exposure has recently been related to the risk of hypertension. However, the association remains unclear and relevant epidemiologic studies are limited. The present study aimed to assess the associations between exposure to metals and the odds of hypertension, as well as blood pressure (BP) levels. A total of 816 participants were enrolled in southwestern China. Hypertension was defined as...
Sat, 03/14/2020 - 03:16
Benzo[a]pyrene (B[a]P), a typical carcinogenic polycyclic aromatic hydrocarbon, exists worldwide in vehicle exhaust, cigarette smoke and other polluted environments. Recent studies have demonstrated a strong association between B[a]P and lung cancer. However, whether B[a]P at human blood equivalent level can promote epithelial‐mesenchymal transition (EMT), a crucial molecular event during cell...
Fri, 02/28/2020 - 03:17
In recent years, many new opioids, particularly fentanyl analogues, have appeared on the drug market. The extreme potency of even low doses of these compounds leads to numerous fatal poisonings. This also results in the fact that only sophisticated techniques are capable of detecting fentanyl analogues at concentrations that can be expected in blood. In this context, the purpose of this study was...
Thu, 02/20/2020 - 03:17
Many obese patients are exposed to hypolipidemic and serotonin‐norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse...
Wed, 02/05/2020 - 03:17
Bisphenol A (BPA), a very important raw material in the plastics industry, is an endocrine‐disrupting chemical in teleost fish. Although BPA induces testis‐ova and sex reversal in teleost fish species, the molecular mechanism remains unclear. We evaluated the effects of BPA (measured concentrations: 45, 92, 326, 1030 and 3406 μg/L) on Japanese medaka (Oryzias latipes) using OECD TG234 (2011, Fish...
Sat, 02/01/2020 - 03:27
Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant owing to its efficient fire‐breaking property. However, leaching of TBBPA into the environment has been a global health concern due to the endocrine‐disrupting activity (EDA) associated with TBBPA exposure. Limited studies are available on the hazardous effects of TBBPA on reproductive function. The aim of the present study...
Sat, 01/25/2020 - 03:15
Exposure to air pollution is associated with increased morbidity and mortality. Once the fine atmospheric particulate matter (FP) is inhaled, some of its compounds can pass through the lungs and reach the bloodstream where they can come into contact with immune cells. Exposure to FP particularly affects sensitive populations such as the elderly. Aging affects the immune system, making the elderly...

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