PFASs-restriction proposal commentary on ECHA's Annex XV restriction report, proposal for a restriction, March 2023
Arch Toxicol. 2023 Oct 6. doi: 10.1007/s00204-023-03597-y. Online ahead of print.ABSTRACTPFASs are defined as substances that contain at least one fully fluorinated methyl (CF3-) or methylene (-CF2-) carbon atom. The excellent technical properties of members of the PFAS group have led to their use in a wide range of applications. The substance group comprises more than 10,000 individual compounds. A variety of adverse effects has been described for single substances. For the majority of the PFASs, neither toxicokinetic data nor effect data is available. Hence, because of the small number of PFASs for which a full toxicolog...
Source: Archives of Toxicology - October 6, 2023 Category: Toxicology Authors: Klaus-Michael Wollin Monika Batke Georg Damm Alexius Freyberger Ursula Gundert-Remy Aswin Mangerich Jan G Hengstler Falko Partosch Thomas Schupp Anna Sonnenburg Heidi Foth Source Type: research
PFASs-restriction proposal commentary on ECHA's Annex XV restriction report, proposal for a restriction, March 2023
Arch Toxicol. 2023 Oct 6. doi: 10.1007/s00204-023-03597-y. Online ahead of print.ABSTRACTPFASs are defined as substances that contain at least one fully fluorinated methyl (CF3-) or methylene (-CF2-) carbon atom. The excellent technical properties of members of the PFAS group have led to their use in a wide range of applications. The substance group comprises more than 10,000 individual compounds. A variety of adverse effects has been described for single substances. For the majority of the PFASs, neither toxicokinetic data nor effect data is available. Hence, because of the small number of PFASs for which a full toxicolog...
Source: Archives of Toxicology - October 6, 2023 Category: Toxicology Authors: Klaus-Michael Wollin Monika Batke Georg Damm Alexius Freyberger Ursula Gundert-Remy Aswin Mangerich Jan G Hengstler Falko Partosch Thomas Schupp Anna Sonnenburg Heidi Foth Source Type: research
PFASs-restriction proposal commentary on ECHA's Annex XV restriction report, proposal for a restriction, March 2023
Arch Toxicol. 2023 Oct 6. doi: 10.1007/s00204-023-03597-y. Online ahead of print.ABSTRACTPFASs are defined as substances that contain at least one fully fluorinated methyl (CF3-) or methylene (-CF2-) carbon atom. The excellent technical properties of members of the PFAS group have led to their use in a wide range of applications. The substance group comprises more than 10,000 individual compounds. A variety of adverse effects has been described for single substances. For the majority of the PFASs, neither toxicokinetic data nor effect data is available. Hence, because of the small number of PFASs for which a full toxicolog...
Source: Archives of Toxicology - October 6, 2023 Category: Toxicology Authors: Klaus-Michael Wollin Monika Batke Georg Damm Alexius Freyberger Ursula Gundert-Remy Aswin Mangerich Jan G Hengstler Falko Partosch Thomas Schupp Anna Sonnenburg Heidi Foth Source Type: research
SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice
In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing h...
Source: Archives of Toxicology - October 5, 2023 Category: Toxicology Authors: Jia-Wen Chen Tian-Kai Shan Tian-Wen Wei Qi-Qi Jiang Chong Du Ling-Feng Gu Tong-Tong Yang Liu-Hua Zhou Si-Bo Wang Yu-Lin Bao Hao Wang Yong Ji Li-Ping Xie Ai-Hua Gu Chong-Qi Sun Qi-Ming Wang Lian-Sheng Wang Source Type: research
Reduced lysosomal activity and increased amyloid beta accumulation in silica-coated magnetic nanoparticles-treated microglia
Arch Toxicol. 2023 Oct 6. doi: 10.1007/s00204-023-03612-2. Online ahead of print.ABSTRACTNanoparticles have been used in neurological research in recent years because of their blood-brain barrier penetration activity. However, their potential neuronanotoxicity remains a concern. In particular, microglia, which are resident phagocytic cells, are mainly exposed to nanoparticles in the brain. We investigated the changes in lysosomal function in silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]-treated BV2 murine microglial cells. In addition, we analyzed amyloid beta (Aβ) accumu...
Source: Archives of Toxicology - October 5, 2023 Category: Toxicology Authors: Tae Hwan Shin Gwang Lee Source Type: research
SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice
In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing h...
Source: Archives of Toxicology - October 5, 2023 Category: Toxicology Authors: Jia-Wen Chen Tian-Kai Shan Tian-Wen Wei Qi-Qi Jiang Chong Du Ling-Feng Gu Tong-Tong Yang Liu-Hua Zhou Si-Bo Wang Yu-Lin Bao Hao Wang Yong Ji Li-Ping Xie Ai-Hua Gu Chong-Qi Sun Qi-Ming Wang Lian-Sheng Wang Source Type: research
Reduced lysosomal activity and increased amyloid beta accumulation in silica-coated magnetic nanoparticles-treated microglia
Arch Toxicol. 2023 Oct 6. doi: 10.1007/s00204-023-03612-2. Online ahead of print.ABSTRACTNanoparticles have been used in neurological research in recent years because of their blood-brain barrier penetration activity. However, their potential neuronanotoxicity remains a concern. In particular, microglia, which are resident phagocytic cells, are mainly exposed to nanoparticles in the brain. We investigated the changes in lysosomal function in silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]-treated BV2 murine microglial cells. In addition, we analyzed amyloid beta (Aβ) accumu...
Source: Archives of Toxicology - October 5, 2023 Category: Toxicology Authors: Tae Hwan Shin Gwang Lee Source Type: research
Species-differences in the in vitro biotransformation of trifluoroethene (HFO-1123)
Arch Toxicol. 2023 Oct 4. doi: 10.1007/s00204-023-03603-3. Online ahead of print.ABSTRACT1,1,2-Trifluoroethene (HFO-1123) is anticipated for use as a refrigerant with low global warming potential. Inhalation studies on HFO-1123 in rats indicated a low potential for toxicity (NOAELs ≥ 20,000 ppm). In contrast, single inhalation exposure of Goettingen® minipigs (≥ 500 ppm) and New Zealand white rabbits (≥ 1250 ppm) resulted in severe toxicity. It has been suggested that these pronounced species-differences in toxicity may be attributable to species-differences in biotransformation of HFO-1123 via the mercapturic acid ...
Source: Archives of Toxicology - October 4, 2023 Category: Toxicology Authors: R Dekant R Bertermann J Serban S Sharma M Shinohara Y Morizawa H Okamoto W Brock W Dekant A Mally Source Type: research
Induction of apoptosis by cannabidiol and its main metabolites in human Leydig cells
In this study, we examined the effects of CBD and its main metabolites, 7-carboxy-CBD and 7-hydroxy-CBD, on primary human Leydig cells, which play a crucial role in male reproductive health. Our results showed that CBD, at concentrations below the Bayesian benchmark dose (BMD)50, inhibited the growth of human Leydig cells by arresting the cell cycle at G1/S transition, disrupting cell cycle regulators, and decreasing DNA synthesis. Concentration-response transcriptomic profiling identified that apoptosis was one of the top biological processes significantly affected by treatment with CBD for 24 h. The occurrence of apoptos...
Source: Archives of Toxicology - October 4, 2023 Category: Toxicology Authors: Yuxi Li Xilin Li Patrick Cournoyer Supratim Choudhuri Lei Guo Si Chen Source Type: research
Comparative metabolism of aflatoxin B < sub > 1 < /sub > in mouse, rat and human primary hepatocytes using HPLC-MS/MS
Arch Toxicol. 2023 Oct 5. doi: 10.1007/s00204-023-03607-z. Online ahead of print.ABSTRACTAflatoxin B1 (AFB1) is a highly hepatotoxic and carcinogenic mycotoxin produced by Aspergillus species. The compound is mainly metabolized in the liver and its metabolism varies between species. The present study quantified relevant AFB1- metabolites formed by mouse, rat, and human primary hepatocytes after treatment with 1 µM and 10 µM AFB1. The use of liquid chromatographic separation coupled with tandem mass spectrometric detection enabled the selective and sensitive determination of phase I and phase II metabolites of AFB1 over i...
Source: Archives of Toxicology - October 4, 2023 Category: Toxicology Authors: Andrea Gerdemann Benedikt Cramer Gisela H Degen Jannik Veerkamp Georgia G ünther Wiebke Albrecht Matthias Behrens Melanie Esselen Ahmed Ghallab Jan G Hengstler Hans-Ulrich Humpf Source Type: research
Site-specific genotoxicity of rubiadin: localization and histopathological changes in the kidneys of rats
Arch Toxicol. 2023 Oct 5. doi: 10.1007/s00204-023-03610-4. Online ahead of print.ABSTRACTRubiadin (Rub) is a genotoxic component of madder color (MC) that is extracted from the root of Rubia tinctorum L. MC induces renal tumors and preneoplastic lesions that are found in the proximal tubule of the outer stripe of the outer medulla (OSOM), suggesting that the renal carcinogenicity of MC is site specific. To clarify the involvement of Rub in renal carcinogenesis of MC, we examined the distribution of Rub in the kidney of male gpt delta rats that were treated with Rub for 28 days. We used desorption electrospray ionization qu...
Source: Archives of Toxicology - October 4, 2023 Category: Toxicology Authors: Tatsuya Mitsumoto Yuji Ishii Norifumi Takimoto Shinji Takasu Moeka Namiki Takehiko Nohmi Takashi Umemura Kumiko Ogawa Source Type: research
Species-differences in the in vitro biotransformation of trifluoroethene (HFO-1123)
Arch Toxicol. 2023 Oct 4. doi: 10.1007/s00204-023-03603-3. Online ahead of print.ABSTRACT1,1,2-Trifluoroethene (HFO-1123) is anticipated for use as a refrigerant with low global warming potential. Inhalation studies on HFO-1123 in rats indicated a low potential for toxicity (NOAELs ≥ 20,000 ppm). In contrast, single inhalation exposure of Goettingen® minipigs (≥ 500 ppm) and New Zealand white rabbits (≥ 1250 ppm) resulted in severe toxicity. It has been suggested that these pronounced species-differences in toxicity may be attributable to species-differences in biotransformation of HFO-1123 via the mercapturic acid ...
Source: Archives of Toxicology - October 4, 2023 Category: Toxicology Authors: R Dekant R Bertermann J Serban S Sharma M Shinohara Y Morizawa H Okamoto W Brock W Dekant A Mally Source Type: research
Induction of apoptosis by cannabidiol and its main metabolites in human Leydig cells
In this study, we examined the effects of CBD and its main metabolites, 7-carboxy-CBD and 7-hydroxy-CBD, on primary human Leydig cells, which play a crucial role in male reproductive health. Our results showed that CBD, at concentrations below the Bayesian benchmark dose (BMD)50, inhibited the growth of human Leydig cells by arresting the cell cycle at G1/S transition, disrupting cell cycle regulators, and decreasing DNA synthesis. Concentration-response transcriptomic profiling identified that apoptosis was one of the top biological processes significantly affected by treatment with CBD for 24 h. The occurrence of apoptos...
Source: Archives of Toxicology - October 4, 2023 Category: Toxicology Authors: Yuxi Li Xilin Li Patrick Cournoyer Supratim Choudhuri Lei Guo Si Chen Source Type: research
Comparative metabolism of aflatoxin B < sub > 1 < /sub > in mouse, rat and human primary hepatocytes using HPLC-MS/MS
Arch Toxicol. 2023 Oct 5. doi: 10.1007/s00204-023-03607-z. Online ahead of print.ABSTRACTAflatoxin B1 (AFB1) is a highly hepatotoxic and carcinogenic mycotoxin produced by Aspergillus species. The compound is mainly metabolized in the liver and its metabolism varies between species. The present study quantified relevant AFB1- metabolites formed by mouse, rat, and human primary hepatocytes after treatment with 1 µM and 10 µM AFB1. The use of liquid chromatographic separation coupled with tandem mass spectrometric detection enabled the selective and sensitive determination of phase I and phase II metabolites of AFB1 over i...
Source: Archives of Toxicology - October 4, 2023 Category: Toxicology Authors: Andrea Gerdemann Benedikt Cramer Gisela H Degen Jannik Veerkamp Georgia G ünther Wiebke Albrecht Matthias Behrens Melanie Esselen Ahmed Ghallab Jan G Hengstler Hans-Ulrich Humpf Source Type: research
Site-specific genotoxicity of rubiadin: localization and histopathological changes in the kidneys of rats
Arch Toxicol. 2023 Oct 5. doi: 10.1007/s00204-023-03610-4. Online ahead of print.ABSTRACTRubiadin (Rub) is a genotoxic component of madder color (MC) that is extracted from the root of Rubia tinctorum L. MC induces renal tumors and preneoplastic lesions that are found in the proximal tubule of the outer stripe of the outer medulla (OSOM), suggesting that the renal carcinogenicity of MC is site specific. To clarify the involvement of Rub in renal carcinogenesis of MC, we examined the distribution of Rub in the kidney of male gpt delta rats that were treated with Rub for 28 days. We used desorption electrospray ionization qu...
Source: Archives of Toxicology - October 4, 2023 Category: Toxicology Authors: Tatsuya Mitsumoto Yuji Ishii Norifumi Takimoto Shinji Takasu Moeka Namiki Takehiko Nohmi Takashi Umemura Kumiko Ogawa Source Type: research
