Toxicological safety assessment of the human ‐identical milk oligosaccharide 3′‐sialyllactose sodium salt
AbstractHuman breastmilk is a mixture of nutrients, hormones and bioactive molecules that are vital for infant growth and development. Infant formula (IF) lacks many of these compounds, most notably human milk oligosaccharides (HMOs), which are abundant in breastmilk but scarce in IF. Sialyllactoses, such as 3 ′‐sialyllactose, constitute a large portion of the HMO fraction. To produce IF that matches breastmilk more closely, biosynthesized human‐identical milk oligosaccharides (structurally identical to HMOs) such as 3′‐sialyllactose sodium salt (3′‐SL) are proposed for use in IF and foods f or th...
Source: Journal of Applied Toxicology - August 16, 2019 Category: Toxicology Authors: Kirt R. Phipps, Nigel J. Baldwin, Barry Lynch, Diane R. Stannard, Alica Šoltésová, Ben Gilby, Marta H. Mikš, Christoph H. Röhrig Tags: RESEARCH ARTICLE Source Type: research

Food ‐grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood‐testis barrier disruption in mice
This study highlights the attention on matrix food containing E171 and possible adverse effects on testis when E171 is consumed in a liquid matrix. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - August 15, 2019 Category: Toxicology Authors: Juan Carlos Rodr íguez‐Escamilla, Estefany I. Medina‐Reyes, Carolina Rodríguez‐Ibarra, Alejandro Déciga‐Alcaraz, José O. Flores‐Flores, Adriana Ganem‐Rondero, Miriam Rodríguez‐Sosa, Luis I. Terrazas, Norma L. Delgado‐Buenrostr Tags: RESEARCH ARTICLE Source Type: research

Early ‐life exposure to low levels of permethrin exerts impairments in learning and memory with the effects on neuronal and glial population in adult male mice
In this study, we investigated the effects of low‐level, chronic permethrin exposure in early life on the brain functions of adult mice, using environmentally relevant concentrations. We exposed mice to the acceptable dail y intake level of permethrin (0.3 ppm) in drinking water during the prenatal and postnatal periods. We then examined the effects on the central nervous system in adult male offspring. In the permethrin group, we detected behavior that displayed incomplete adaptation to a novel environment, as well as an impairment in learning and memory. In addition, immunohistochemical analysis revealed an increa...
Source: Journal of Applied Toxicology - August 15, 2019 Category: Toxicology Authors: Hirokatsu Saito, Kenshiro Hara, Takashi Tominaga, Kinichi Nakashima, Kentaro Tanemura Tags: RESEARCH ARTICLE Source Type: research

Toxicological safety evaluation of the human ‐identical milk oligosaccharide 6′‐sialyllactose sodium salt
AbstractHuman milk oligosaccharides (HMOs) are abundant in breastmilk, but their presence in infant formula is negligible. Sialylated HMOs, such as 6 ′‐sialyllactose, constitute a significant portion of the HMO fraction of human milk and are linked to important biological functions. To produce infant formula that is more comparable with human milk, biosynthesized sialyllactoses known as human‐identical milk oligosaccharides (structurally id entical counterparts to their respective naturally occurring HMOs in breastmilk) are proposed for use in infant formula and other functional foods for the general population. ...
Source: Journal of Applied Toxicology - August 7, 2019 Category: Toxicology Authors: Kirt R. Phipps, Nigel J. Baldwin, Barry Lynch, Diane R. Stannard, Alica Šoltésová, Ben Gilby, Marta H. Mikš, Christoph H. Röhrig Tags: RESEARCH ARTICLE Source Type: research

Acetaminophen ‐induced hepatocyte injury: C2‐ceramide and oltipraz intervention, hepatocyte nuclear factor 1 and glutathione S‐transferase A1 changes
In this study, we investigated the effects of C2‐ceramide and oltipraz on APAP‐induced hepatocyte injury and the changes of HNF‐1 and GSTA 1. Results showed that C2‐ceramide (6 μmol/L) exacerbated APAP‐induced hepatocyte injury and caused a significant decrease (P 
Source: Journal of Applied Toxicology - August 6, 2019 Category: Toxicology Authors: Yicong Chang, Feng Wang, Yang Yang, Yuanyuan Zhang, Ishfaq Muhammad, Rui Li, Changwen Li, Ying Li, Chenxi Shi, Xin Ma, Beili Hao, Fangping Liu Tags: RESEARCH ARTICLE Source Type: research

Neuro ‐ and hepatic toxicological profile of (S)‐2,4‐diaminobutanoic acid in embryonic, adolescent and adult zebrafish
This study further highlights the low cost and ease of using zebrafish as an early ‐stage toxicological screening tool. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - August 6, 2019 Category: Toxicology Authors: Rosa ‐Maria Ferraiuolo, Daniel Meister, Dominique Leckie, Mohadeseh Dashti, Jonathan Franke, Lisa A. Porter, John F. Trant Tags: RESEARCH ARTICLE Source Type: research

Effect of gestational exposure to perfluorononanoic acid on neonatal mice testes
In conclusion, the results suggest that the gestational exposure to PFNA decreased testo sterone biosynthesis and altered the expression of critical factors involved in the development of the testis, thereby advocating a potential risk of PFNA to male reproductive health. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - August 6, 2019 Category: Toxicology Authors: Shilpi Singh, Shio Kumar Singh Tags: RESEARCH ARTICLE Source Type: research

Free radicals, antioxidants, nuclear factor ‐E2‐related factor‐2 and liver damage
AbstractOxidative/nitrosative stress is proposed to be a critical factor in various diseases, including liver pathologies. Antioxidants derived from medicinal plants have been studied extensively and are relevant to many illnesses, including liver diseases. Several hepatic disorders, such as viral hepatitis and alcoholic or nonalcoholic steatohepatitis, involve free radicals/oxidative stress as agents that cause or at least exacerbate liver injury, which can result in chronic liver diseases, such as liver fibrosis, cirrhosis and end ‐stage hepatocellular carcinoma. In this scenario, nuclear factor‐E2‐related factor...
Source: Journal of Applied Toxicology - August 6, 2019 Category: Toxicology Authors: Erika Ramos ‐Tovar, Pablo Muriel Tags: REVIEW ARTICLE Source Type: research

N ‐acetylcysteine alleviated paraquat‐induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells
In this study, primary murine neural progenitor cells (mNPCs) from the subventricular zone were used as a research model. In add ition, paraquat (PQ) was used to elicit oxidative stress andN‐acetylcysteine (NAC) was used as a powerful antioxidant. mNPCs were treated with 80 μm PQ for 24  hours with or without 4 hours of NAC pretreatment. Our results showed that PQ treatment increased intracellular reactive oxygen species production, decreased cell viability and DNA synthesis, and promoted cell apoptosis. Meanwhile, pretreatment with NAC alleviated PQ‐induced cytotoxicity in mNP Cs. To elucidate the me...
Source: Journal of Applied Toxicology - August 1, 2019 Category: Toxicology Authors: Guiya Xiong, Lina Zhao, Mengling Yan, Xinjin Wang, Zhijun Zhou, Xiuli Chang Tags: RESEARCH ARTICLE Source Type: research

Nanoscale zerovalent iron particles induce differential cytotoxicity, genotoxicity, oxidative stress and hemolytic responses in human lymphocytes and erythrocytes in vitro
AbstractThe growing usage of nanoscale zerovalent iron particles (nZVI) in the remediation of soil, ground/surface water has elicited large ‐scale environmental release triggering human exposure. The size of nanomaterials is a key regulator of toxicity. However, the effect of a variable size of nZVI on genotoxicity is unexplored in human cells. To the best of our knowledge, in this study, the cytotoxic, genotoxic and hemolytic potenti al of nZVI‐1 (15 nm) and nZVI‐2 (50 nm) at concentrations of 5, 10 and 20 μg/mL was evaluated for the first time in human lymphocytes and erythrocytes treated for 3&nb...
Source: Journal of Applied Toxicology - July 29, 2019 Category: Toxicology Authors: Ilika Ghosh, Amitava Mukherjee, Anita Mukherjee Tags: RESEARCH ARTICLE Source Type: research

Developmental programming: Sex ‐specific programming of growth upon prenatal bisphenol A exposure
AbstractIn both human and animals, in utero exposure to bisphenol A (BPA), an endocrine ‐disrupting chemical used in the production of plastics and epoxy resins, has been shown to affect offspring reproductive and metabolic health during adult life. We hypothesized that the effect of prenatal exposure to environmentally relevant doses of BPA will be evident during fetal organogenesis and fetal/postnatal growth trajectory. Pregnant ewes were administered BPA subcutaneously from 30 to 90 days of gestation (term 147 days). Fetal organ weight, anthropometric measures, maternal/fetal hormones and postnatal growth tr...
Source: Journal of Applied Toxicology - July 23, 2019 Category: Toxicology Authors: Arpita Kalla Vyas, Almudena Veiga ‐Lopez, Wen Ye, Bachir Abi Salloum, David H. Abbott, Shengping Yang, Chunyang Liao, Kurunthachalam Kannan, Vasantha Padmanabhan Tags: RESEARCH ARTICLE Source Type: research

Triptolide ‐induced hepatotoxicity via apoptosis and autophagy in zebrafish
This study successfully established a TP ‐induced zebrafish hepatotoxicity model and applied the HCIS technique in a zebrafish hepatotoxicity study. The result indicatedFas might be the main target of TP ‐induced hepatotoxicity. Autophagy played a more important role than apoptosis and was characterized by the overexpression ofBeclin1 andAtg5. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - July 19, 2019 Category: Toxicology Authors: Jingting Huo, Qinwei Yu, Yun Zhang, Kechun Liu, Chung ‐der Hsiao, Zhenzhou Jiang, Luyong Zhang Tags: RESEARCH ARTICLE Source Type: research

Acute toxicity of intratracheal arsenic trioxide instillation in rat lungs
This study investigated the acute toxicity of different concentrations of arsenic trioxide (As2O3; ATO) on rat lungs. In total, 160 Wistar rats were randomly divided into the control, low ‐, medium‐ and high‐dose groups, which were exposed to 0, 0.16, 1.60 and 16 μg/kg of ATO by intratracheal instillation, respectively. Samples were collected at 6, 12, 24, 48 and 72 hours after exposure and the dynamic changes indicative of acute lung toxicity were monitored. Compared with t he control group, the exposure groups exhibited significant changes such as increased lung water content ratio and protein concentr...
Source: Journal of Applied Toxicology - July 18, 2019 Category: Toxicology Authors: Su Mingxing, Wang Haiying, Sun Congsong, Yuan Chunyu, Chao Liu, Qiang Wang Tags: RESEARCH ARTICLE Source Type: research

Lunar soil simulants alter macrophage survival and function
AbstractLunar regolith samples collected during previous Apollo missions were found to contain components that were established to be toxic to humans; however, the health effects due to inhalation of lunar soil as a whole are still unknown. Macrophages residing in the alveolar sacs of the lungs constitute one of the last lines of defense against inhaled particulates before entry into the bloodstream. Here, we examine the macrophage response to lunar simulants that are similar in chemical composition to the lunar regolith. We assess cytotoxicity, cellular morphology, phagocytosis of simulants and expression of inflammatory ...
Source: Journal of Applied Toxicology - July 18, 2019 Category: Toxicology Authors: Melvin Li, Kaitlyn K. Thompson, Jillian C. Nissen, Donald Hendrix, Joel A. Hurowitz, Stella E. Tsirka Tags: RESEARCH ARTICLE Source Type: research

Acute toxicity of intratracheal arsenic trioxide instillation in rat lungs
This study investigated the acute toxicity of different concentrations of arsenic trioxide (As2O3; ATO) on rat lungs. In total, 160 Wistar rats were randomly divided into the control, low ‐, medium‐ and high‐dose groups, which were exposed to 0, 0.16, 1.60 and 16 μg/kg of ATO by intratracheal instillation, respectively. Samples were collected at 6, 12, 24, 48 and 72 hours after exposure and the dynamic changes indicative of acute lung toxicity were monitored. Compared with t he control group, the exposure groups exhibited significant changes such as increased lung water content ratio and protein concentr...
Source: Journal of Applied Toxicology - July 18, 2019 Category: Toxicology Authors: Su Mingxing, Wang Haiying, Sun Congsong, Yuan Chunyu, Chao Liu, Qiang Wang Tags: RESEARCH ARTICLE Source Type: research

Lunar soil simulants alter macrophage survival and function
AbstractLunar regolith samples collected during previous Apollo missions were found to contain components that were established to be toxic to humans; however, the health effects due to inhalation of lunar soil as a whole are still unknown. Macrophages residing in the alveolar sacs of the lungs constitute one of the last lines of defense against inhaled particulates before entry into the bloodstream. Here, we examine the macrophage response to lunar simulants that are similar in chemical composition to the lunar regolith. We assess cytotoxicity, cellular morphology, phagocytosis of simulants and expression of inflammatory ...
Source: Journal of Applied Toxicology - July 18, 2019 Category: Toxicology Authors: Melvin Li, Kaitlyn K. Thompson, Jillian C. Nissen, Donald Hendrix, Joel A. Hurowitz, Stella E. Tsirka Tags: RESEARCH ARTICLE Source Type: research

Benchmark dose estimation of urinary and blood cadmium as biomarkers of renal dysfunction among 40 ‐75‐year‐old non‐smoking women in rural areas of southwest China
This study evaluated the association between urinary cadmium (U ‐Cd) and blood Cd (B‐Cd) and several biomarkers of renal dysfunction (α1‐microglobulin [α1‐MG], β2‐microglobulin [β2‐MG],N‐acetyl‐β‐d‐glucosaminidase, metallothionein, retinol‐binding protein and microalbumin [mALB]) and identified the biomarker(s) that was most closely correlated with U‐Cd and B‐Cd among female residents in rural areas of southwest China. U‐Cd, creatinine (Cr), B‐Cd and the above‐mentioned six biom arkers in morning spot urine samples were measured from 288 randomly selected 40‐75...
Source: Journal of Applied Toxicology - July 17, 2019 Category: Toxicology Authors: Jiuming Yan, Jiao Huo, Renjia Li, Zhenchao Jia, Yang Song, Jinyao Chen, Lishi Zhang Tags: RESEARCH ARTICLE Source Type: research

The effects of cannabidiol on male reproductive system: A literature review
AbstractCannabidiol (CBD) is one of the most abundant phytocannabinoids present in the plantCannabis sativa (marijuana). There have been several studies of CBD in the last few decades, mainly focused on its neuroprotective properties, particularly after the identification of the endocannabinoid system and its participation in the central nervous system. On the other hand, the peripheral effects of CBD, particularly on reproductive physiology, were also evidenced. A narrative review was conducted using the PubMed database to identify studies that analyzed the pharmacological effects of CBD on the male reproductive system of...
Source: Journal of Applied Toxicology - July 17, 2019 Category: Toxicology Authors: Renata K. Carvalho, Monica L. Andersen, Renata Mazaro ‐Costa Tags: REVIEW ARTICLE Source Type: research

The within ‐ and between‐laboratory reproducibility and predictive capacity of the in chemico amino acid derivative reactivity assay: Results of validation study implemented in four participating laboratories
AbstractThe amino acid derivative reactivity assay (ADRA) is an in chemico alternative method that focuses on protein binding as the molecular initiating event for skin sensitization. It is a simple and versatile method that has successfully solved some of the problems of the direct peptide reactivity assay (DPRA). The transferability and within ‐ and between‐laboratory reproducibility of ADRA were evaluated and confirmed as part of a validation study conducted at four participating laboratories. The transfer of ADRA technology from the lead laboratory to the four participating laboratories was completed successfully d...
Source: Journal of Applied Toxicology - July 17, 2019 Category: Toxicology Authors: Masaharu Fujita, Yusuke Yamamoto, Shinichi Watanabe, Tsunetsugu Sugawara, Koji Wakabayashi, Yu Tahara, Nobuyuki Horie, Keiichi Fujimoto, Kei Kusakari, Yoshihiko Kurokawa, Tsuyoshi Kawakami, Kohichi Kojima, Takashi Sozu, Takuto Nakayama, Take Tags: RESEARCH ARTICLE Source Type: research

Benchmark dose estimation of urinary and blood cadmium as biomarkers of renal dysfunction among 40 ‐75‐year‐old non‐smoking women in rural areas of southwest China
This study evaluated the association between urinary cadmium (U ‐Cd) and blood Cd (B‐Cd) and several biomarkers of renal dysfunction (α1‐microglobulin [α1‐MG], β2‐microglobulin [β2‐MG],N‐acetyl‐β‐d‐glucosaminidase, metallothionein, retinol‐binding protein and microalbumin [mALB]) and identified the biomarker(s) that was most closely correlated with U‐Cd and B‐Cd among female residents in rural areas of southwest China. U‐Cd, creatinine (Cr), B‐Cd and the above‐mentioned six biom arkers in morning spot urine samples were measured from 288 randomly selected 40‐75...
Source: Journal of Applied Toxicology - July 17, 2019 Category: Toxicology Authors: Jiuming Yan, Jiao Huo, Renjia Li, Zhenchao Jia, Yang Song, Jinyao Chen, Lishi Zhang Tags: RESEARCH ARTICLE Source Type: research

The effects of cannabidiol on male reproductive system: A literature review
AbstractCannabidiol (CBD) is one of the most abundant phytocannabinoids present in the plantCannabis sativa (marijuana). There have been several studies of CBD in the last few decades, mainly focused on its neuroprotective properties, particularly after the identification of the endocannabinoid system and its participation in the central nervous system. On the other hand, the peripheral effects of CBD, particularly on reproductive physiology, were also evidenced. A narrative review was conducted using the PubMed database to identify studies that analyzed the pharmacological effects of CBD on the male reproductive system of...
Source: Journal of Applied Toxicology - July 17, 2019 Category: Toxicology Authors: Renata K. Carvalho, Monica L. Andersen, Renata Mazaro ‐Costa Tags: REVIEW ARTICLE Source Type: research

The within ‐ and between‐laboratory reproducibility and predictive capacity of the in chemico amino acid derivative reactivity assay: Results of validation study implemented in four participating laboratories
AbstractThe amino acid derivative reactivity assay (ADRA) is an in chemico alternative method that focuses on protein binding as the molecular initiating event for skin sensitization. It is a simple and versatile method that has successfully solved some of the problems of the direct peptide reactivity assay (DPRA). The transferability and within ‐ and between‐laboratory reproducibility of ADRA were evaluated and confirmed as part of a validation study conducted at four participating laboratories. The transfer of ADRA technology from the lead laboratory to the four participating laboratories was completed successfully d...
Source: Journal of Applied Toxicology - July 17, 2019 Category: Toxicology Authors: Masaharu Fujita, Yusuke Yamamoto, Shinichi Watanabe, Tsunetsugu Sugawara, Koji Wakabayashi, Yu Tahara, Nobuyuki Horie, Keiichi Fujimoto, Kei Kusakari, Yoshihiko Kurokawa, Tsuyoshi Kawakami, Kohichi Kojima, Takashi Sozu, Takuto Nakayama, Take Tags: RESEARCH ARTICLE Source Type: research

Establishment of a mouse model of troglitazone ‐induced liver injury and analysis of its hepatotoxic mechanism
In conclusion, a single intraperitoneal dose of TGZ exposure could induce liver injury in BALB/c female mice and, by a hepatic transcriptomic analysis, we found that the activation of JAK/STAT pathway might be related to TGZ‐induced hepatotoxicity. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - July 11, 2019 Category: Toxicology Authors: Ru Jia, Shingo Oda, Koichi Tsuneyama, Yuya Urano, Tsuyoshi Yokoi Tags: RESEARCH ARTICLE Source Type: research

Toxic effects and involved molecular pathways of nanoparticles on cells and subcellular organelles
AbstractOwing to the increasing application of engineered nanoparticles (NPs), besides the workplace, human beings are also exposed to NPs from nanoproducts through the skin, respiratory tract, digestive tract and vein injection. This review states pathways of cellular uptake, subcellular distribution and excretion of NPs. The uptake pathways commonly include phagocytosis, micropinocytosis, clathrin ‐ and caveolae‐mediated endocytosis, scavenger receptor‐related pathway, clathrin‐ or caveolae‐independent pathway, and direct penetration or insertion. Then the ability of NPs to decrease cell viability and metabolic...
Source: Journal of Applied Toxicology - July 11, 2019 Category: Toxicology Authors: Na Liu, Meng Tang Tags: REVIEW ARTICLE Source Type: research

Establishment of a mouse model of troglitazone ‐induced liver injury and analysis of its hepatotoxic mechanism
In conclusion, a single intraperitoneal dose of TGZ exposure could induce liver injury in BALB/c female mice and, by a hepatic transcriptomic analysis, we found that the activation of JAK/STAT pathway might be related to TGZ‐induced hepatotoxicity. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - July 11, 2019 Category: Toxicology Authors: Ru Jia, Shingo Oda, Koichi Tsuneyama, Yuya Urano, Tsuyoshi Yokoi Tags: RESEARCH ARTICLE Source Type: research

Toxic effects and involved molecular pathways of nanoparticles on cells and subcellular organelles
AbstractOwing to the increasing application of engineered nanoparticles (NPs), besides the workplace, human beings are also exposed to NPs from nanoproducts through the skin, respiratory tract, digestive tract and vein injection. This review states pathways of cellular uptake, subcellular distribution and excretion of NPs. The uptake pathways commonly include phagocytosis, micropinocytosis, clathrin ‐ and caveolae‐mediated endocytosis, scavenger receptor‐related pathway, clathrin‐ or caveolae‐independent pathway, and direct penetration or insertion. Then the ability of NPs to decrease cell viability and metabolic...
Source: Journal of Applied Toxicology - July 11, 2019 Category: Toxicology Authors: Na Liu, Meng Tang Tags: REVIEW ARTICLE Source Type: research

Benzo fury: A new trend in the drug misuse scene
AbstractBenzofurans, also known by users asbenzo fury orbenzofury, are synthetic phenethylamines and constitute the third most prominent group of new psychoactive substances (NPS). As the use of these substances has been spread as an alternative to the classic illicit psychostimulants, such as amphetamines, their legal status was reviewed, resulting in an utter prohibition of these NPS in many countries worldwide. Herein, the prevalence of abuse, chemistry, biological effects, metabolism, and the potential harms and risky behaviors associated with the abuse of benzofurans are reviewed. The congeners of this group are mainl...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Rita Roque Bravo, Helena Carmo, F élix Carvalho, Maria de Lourdes Bastos, Diana Dias da Silva Tags: REVIEW ARTICLE Source Type: research

Issue Information
No abstract is available for this article. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Tags: ISSUE INFORMATION Source Type: research

Protective effects of S ‐carvedilol on doxorubicin‐induced damages to human umbilical vein endothelial cells and rats
AbstractDoxorubicin (DOX) is a highly active anticancer drug with severe cytotoxicity, which is strongly associated with oxidative stress. Carvedilol (CAR), used as its racemate withS‐CAR andR‐CAR (1:1), has been previously reported to ameliorate the DOX‐induced cytotoxicity. However, the main contributor from CAR of its protective effects has not been clear. Therefore, in this study, we aimed to investigate further the different effects of CAR enantiomers on DOX‐induced cytotoxici ty in human umbilical vein endothelial cells and rats, respectively. Results indicated thatS‐CAR could significantly attenuate DOX‐...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Ting Wu, Haixin Li, Qunsheng Lan, Ze ‐an Zhao, Ying Cao, Pingzheng Zhou, Shanhe Wan, Jiajie Zhang, Hong Jiang, Qun Zhang, Jianxin Pang Tags: RESEARCH ARTICLE Source Type: research

In silico prediction of drug ‐induced rhabdomyolysis with machine‐learning models and structural alerts
AbstractDrug ‐induced rhabdomyolysis (DIR) is a serious adverse reaction and can be fatal. In the present study, we focused on the modeling and understanding of the molecular basis of DIR of small molecule drugs. A series of machine‐learning models were developed using an Online Chemical Modeling Environment platform with a diverse dataset. A total of 80 machine‐learning models were generated. Based on the top‐performing individual models, a consensus model was also developed. The consensus model was available athttps://ochem.eu/model/32214665, and the individual models can be accessed with the corresponding model ...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Xueyan Cui, Juan Liu, Jinfeng Zhang, Qiuyun Wu, Xiao Li Tags: RESEARCH ARTICLE Source Type: research

Sex ‐specific endocrine‐disrupting effects of three halogenated chemicals in Japanese medaka
The objective of this study was to assess sex differences on thyroid and estrogenic effects after exposure of Japanese medaka (Oryzias latipes, SK2MC) to halogenated compounds. This strain is an excellent model for these studies as sex can be determined non ‐destructively a few hours postfertilization. Medaka embryos were exposed to sublethal concentrations of Tris(1,3‐dichloro‐2‐propyl) phosphate (TDCPP, 0.019 mg/L), perfluorooctanoic acid (PFOA, 4.7 mg/L) and its next generation alternative, perfluorobutyric acid (PFBA, 137 mg/L). Methimaz ole (inhibits thyroid hormone synthesis) and the thyroid ho...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Amy Godfrey, Blair Hooser, Ahmed Abdelmoneim, Maria S. Sep úlveda Tags: RESEARCH ARTICLE Source Type: research

Liver safety evaluation of endothelin receptor antagonists using HepatoPac ®: A single model impact assessment on hepatocellular health, function and bile acid disposition
AbstractMarketed (bosentan, ambrisentan) and discontinued (sitaxsentan, CI ‐1034) endothelin receptor antagonists were examined in the human micropatterned hepatocyte co‐culture (MPCC) model HepatoPac®. Differences across hepatocellular health (cellular adenosine triphosphate/glutathione content), function (urea production/albumin secretion) and taurocholic acid transport (biliary clearance/excretion index) were compared using amiodarone and ciclosporin A as positive controls. Ambrisentan had the weakest potency in all six endpoints, while sitaxsentan, bosentan and CI ‐1034 had more potent effects on hepatobiliar...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Michael D. Aleo, Okechukwu Ukairo, Amanda Moore, Onyi Irrechukwu, David M. Potter, Richard P. Schneider Tags: RESEARCH ARTICLE Source Type: research

The toxic potential of a fourth ‐generation E‐cigarette on human lung cell lines and tissue explants
AbstractThe use of electronic cigarettes (E ‐cigs) is rapidly increasing. The latest generation of E‐cigs is highly customizable, allowing for high heating coil temperatures. The aim of this study was to assess the toxic potential of a fourth‐generation E‐cig. Aerosols generated from E‐liquid with (24 mg/mL) and without nicotine, u sing a fourth‐generation E‐cig, were chemically analysed and compared with cigarette smoke (K3R4F). Human lung epithelial cell lines and distal lung tissue explants were exposed to E‐cig vapour extract (EVE) and cigarette smoke extract for 24 hours and assessed for viab...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Gregory D. Rankin, H åkan Wingfors, Oskari Uski, Linnéa Hedman, Barbro Ekstrand‐Hammarström, Jenny Bosson, Magnus Lundbäck Tags: RESEARCH ARTICLE Source Type: research

Rebaudioside A administration prevents experimental liver fibrosis: an in vivo and in vitro study of the mechanisms of action involved
AbstractRebaudioside A (Reb A) is a diterpenoid isolated from the leaves ofStevia rebaudiana (Bertoni) that has been shown to possess pharmacological activity, including anti ‐inflammatory and antioxidant properties. However, the ability of Reb A to prevent liver injury has not been evaluated. Therefore, we aimed to study the potential of Reb A (20 mg/kg; two times daily intraperitoneally) to prevent liver injury induced by thioacetamide (TAA) administration (200 mg/ kg; three times per week intraperitoneally). In addition, cocultures were incubated with either lipopolysaccharide or ethanol. Antifibrotic, antio...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Sael Casas ‐Grajales, Karina Reyes‐Gordillo, Carlos M. Cerda‐García‐Rojas, Víctor Tsutsumi, M. Raj Lakshman, Pablo Muriel Tags: RESEARCH ARTICLE Source Type: research

A novel screening method for transition metal ‐based anticancer compounds using zebrafish embryo‐larval assay and inductively coupled plasma‐mass spectrometry analysis
In this study, we used ICPMS quantitation with the zebrafish embryo assays to detect metal equivalents at multiple response endpoints for two compounds, the chemotherapeutic agent cisplatin and ruthenium (Ru)‐based prospective metallodrug, PMC79. We hypothesized that cisplatin and PMC79 have different mechanisms for inducing apoptosis and result in similar lesions but different potencies following water‐borne exposure. An ICPMS me thod was developed to detect the metal in waterborne solution and tissue (detection limit: 5 parts per trillion for Ru or platinum [Pt]). The Ru‐based compound was more potent (LC50: 7.8 &n...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Brittany F. Karas, Leonor C ôrte‐Real, Cathleen L. Doherty, Andreia Valente, Keith R. Cooper, Brian T. Buckley Tags: RESEARCH ARTICLE Source Type: research

Activation of the N ‐methyl‐d‐aspartate receptor is involved in glyphosate‐induced renal proximal tubule cell apoptosis
In this study, we treated a human renal proximal tubule cell line (HK‐2) with glyphosate for 24 hours at concentrations of 0, 20, 40 and 60 μm. Glyphosate was found to reduce cell viability and induce apoptosis and oxidative stress in a dose ‐dependent manner. Because the chemical structures of glyphosate and those of its metabolite AMPA are similar to glycine and glutamate, which are agonists of theN‐methyl‐d‐aspartate receptor (NMDAR), we investigated the potential role of the NMDAR pathway in mediating the proapoptotic effect of glyphosate on proximal tubule cells. We found that NMDAR1 expression,...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Hui Gao, Jing Chen, Fan Ding, Xin Chou, Xiaoyan Zhang, Yi Wan, Jianying Hu, Qing Wu Tags: RESEARCH ARTICLE Source Type: research

Baicalin attenuates gentamicin ‐induced cochlear hair cell ototoxicity
AbstractGentamicin can lead to cochlear hair cells associated ototoxicity by inducing apoptosis and oxidative stress, which can be alleviated by baicalin, one flavonoid extracted from the root ofScutellaria baicalensis. The role of baicalin in protecting gentamicin ‐induced hearing loss is unclear. Interference with oxidative stress was investigated in this study using House Ear Institute‐Organ of Corti1 (HEI‐OC1) cells, which were simultaneously treated with baicalin (0‐400 μm) and gentamicin (0.2 or 1  mm). MTT was used to assay cell viability and apoptosis was detected with Annexin V ‐fluorescein ...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Xianfen Zhang, Jun Yu Tags: RESEARCH ARTICLE Source Type: research

Growth ‐promoting effects of low‐level butyl benzyl phthalate exposure on human neuroblastoma SH‐SY5Y cells
AbstractThe purpose of present study was to investigate the impact of butyl benzyl phthalate (BBP) on SH ‐SY5Y neuroblastoma cells in vitro. The cell counting kit‐8 was used to measure cell proliferation and flow cytometry was utilized to study cell cycle phases and apoptosis. Western blotting and quantitative real‐time polymerase chain reaction were used to detect levels of aromatase, estrogen r eceptors (ERs) and some apoptosis and cell cycle‐related genes. Results showed BBP‐stimulated SH‐SY5Y cells in a dose‐dependent manner and produced a reverted U‐shaped dose‐response curve. BBP at lower concentrat...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Fan Zhang, Juan Zhang, Nian Shi, Tao Li Tags: RESEARCH ARTICLE Source Type: research

Is normalized hindlimb length measurement in assessment of thyroid disruption in the amphibian metamorphosis assay relevant?
AbstractThe amphibian metamorphosis assay represents an OECD Level 3 and EDSP Tier 1 ecotoxicity test assessing thyroid activity of chemicals in African clawed frog (Xenopus laevis). To evaluate the effectiveness of snout ‐vent length (SVL) normalization of hindlimb length (HLL), correlation between the HLL and SVL or body weight was evaluated in the control groups of 10 individual studies from three laboratories. Two studies required separate analysis of the Nieuwkoop‐Faber (NF) stage ≤60 and>60 animals creating a total of 12 data sets. On study day 7, significant positive correlation between HLL and SVL or body...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Sascha Pawlowski, Martina Dammann, Lennart Weltje, Samantha Champ, Michael Mathis, Douglas J. Fort Tags: RESEARCH ARTICLE Source Type: research

Cytotoxic and proinflammatory responses induced by ZnO nanoparticles in in vitro intestinal barrier
AbstractZnO nanoparticles (NPs) are widely used nowadays, thus the gastrointestinal exposure to ZnO NPs is likely to be relevant and the effects on the intestinal barrier should be investigated. Polarized Caco ‐2 cells were exposed from the apical (Ap) and basolateral (Bl) compartments to increasing concentrations (0, 10, 50 and 100 μg/mL) of sonochemical (sono) and commercial ZnO NPs. The transepithelial electrical resistance (TEER), cell viability, proinflammatory cytokine release and presence of pr otein oxidative damage were evaluated after exposure. TEER was not significantly affected by Ap exposure to eithe...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Graziano Colombo, Cristina Cortinovis, Elisa Moschini, Nicholas Bellitto, Maria Chiara Perego, Marco Albonico, Emanuela Astori, Isabella Dalle ‐Donne, Alessia Bertero, Aharon Gedanken, Ilana Perelsthein, Paride Mantecca, Francesca Caloni Tags: RESEARCH ARTICLE Source Type: research

Exposures to the environmental contaminants pentachlorophenol and dichlorodiphenyltrichloroethane increase production of the proinflammatory cytokine, interleukin ‐1β, in human immune cells
This study shows that the increased secretion of IL‐1β seen with both contaminants is due to compound‐induced increases in the production of this cytokine. Increased production began within 6 hours of exposure to PCP and continued to increase up to 24 hours. DDT‐induced stimulation of IL‐1β appear ed to be maximal after 6 hours of exposure and then diminished by 24 hours. The increases seen in IL‐1β production stimulated by PCP appear to be at least partially due to compound‐induced increases in IL‐1β mRNA. Although DDT caused increased production of IL‐1β, it di...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Tamara J. Martin, JaQuel Maise, Sahra Gabure, Margaret M. Whalen Tags: RESEARCH ARTICLE Source Type: research

Nanosized carbon black exposure induces neural injury: effects on nicotinamide adenine dinucleotide phosphate oxidases and endoplasmic reticulum stress
AbstractCarbon black in ambient air is believed to be the cause of many diseases; however, its potential neural toxicity and the underlying mechanisms remain poorly understood. The present study is to evaluate the toxic effects of carbon black nanoparticles, Printex 90, on the neural cell line PC ‐12. The study revealed that Printex 90 treatment significantly decreased cell viability, accompanied by an enormous increase in reactive oxygen species generation and a decrease in ATP. Additionally, NOX2 and NOX4, 4‐hydroxynonenal, endoplasmic reticulum (ER) stress marker proteins (IRE‐1α, ATF‐6, GRP78, PERK and th...
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Authors: Lei Jiang, Tingwei Wang, Jing Xue, Pengfei Yu, Jinsong Zhang, Jun Wang Tags: RESEARCH ARTICLE Source Type: research

Issue Information
No abstract is available for this article. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - July 10, 2019 Category: Toxicology Tags: ISSUE INFORMATION Source Type: research

High ‐throughput COPAS assay for screening of developmental and reproductive toxicity of nanoparticles using the nematode Caenorhabditis elegans
This study also indicates that the COPAS‐based high‐throughput screening system is highly reliable for the assessment of toxicity and health risks of NMs. (Source: Journal of Applied Toxicology)
Source: Journal of Applied Toxicology - July 9, 2019 Category: Toxicology Authors: MinA Kim, Jaeseong Jeong, Heejin Kim, Jinhee Choi Tags: RESEARCH ARTICLE Source Type: research

Markers of oxidative ‐nitrosative stress induced by artesunate are followed by clastogenic and aneugenic effects and apoptosis in human lymphocytes
AbstractArtesunate (ARS) is a semi ‐synthetic derivative of artemisinin, used as an outstanding antimalarial drug, which also displays antitumor, anti‐inflammatory and immunosuppressive effects. In spite of the numerous reports showing the antitumor activity of ARS, the particular mechanisms associated with its cytotoxicity and g enotoxicity in non‐neoplastic human cells remain unclear. Here we aimed to verify the specific chromosome damages and the changes in markers of oxidative‐nitrosative stress and apoptosis triggered by ARS exposure in human peripheral blood lymphocytes. Cultures were incubated in the presenc...
Source: Journal of Applied Toxicology - July 5, 2019 Category: Toxicology Authors: Tatiane C. Mota, Tarcyane B. Garcia, La ís T. Bonfim, Adrhyann J. S. Portilho, Camila A. Pinto, Rommel M. R. Burbano, Marcelo Bahia Tags: RESEARCH ARTICLE Source Type: research

Health effects inflicted by chronic low ‐level arsenic contamination in groundwater: A global public health challenge
AbstractGroundwater arsenic (As) contamination is a global public health concern. The high level of As exposure (100 ‐1000 μg/L or even higher) through groundwater has been frequently associated with serious public health hazards, e.g., skin disorders, cardiovascular diseases, respiratory problems, complications of gastrointestinal tract, liver and splenic ailments, kidney and bladder disorders, reproductive f ailure, neurotoxicity and cancer. However, reviews on low‐level As exposure and the imperative health effects are far less documented. The World Health Organization (WHO) and the United States Environment...
Source: Journal of Applied Toxicology - July 4, 2019 Category: Toxicology Authors: Dona Sinha, Priyanka Prasad Tags: REVIEW ARTICLE Source Type: research