Breast milk-mediated exposure to dioxins and antigen in infancy enhances antigen-specific antibody production capacity in adulthood in mice
J Toxicol Sci. 2024;49(5):209-218. doi: 10.2131/jts.49.209.ABSTRACTThe immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Hideki Kakutani Tomohiro Yuzuriha Teruyuki Nakao Source Type: research
Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions
J Toxicol Sci. 2024;49(5):219-230. doi: 10.2131/jts.49.219.ABSTRACTQuantitative structure permeation relationship (QSPR) models have gained prominence in recent years owing to their capacity to elucidate the influence of physicochemical properties on the dermal absorption of chemicals. These models facilitate the prediction of permeation coefficient (Kp) values, indicating the skin permeability of a chemical under infinite dose conditions. Conversely, obtaining dermal absorption rates (DAs) under finite dose conditions, which are crucial for skin product safety evaluation, remains a challenge when relying solely on Kp pred...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Ryoki Kunita Takafumi Nishijima Hiroaki Todo Masaaki Miyazawa Source Type: research
Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis
J Toxicol Sci. 2024;49(5):231-240. doi: 10.2131/jts.49.231.ABSTRACTDrug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were ad...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Kazuhiro Kuga Motohiro Shiotani Kentaro Hori Hiroshi Mizuno Yusaku Matsushita Harushige Ozaki Kohei Hayashi Takatomi Kubo Manabu Kano Source Type: research
Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons
In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 low...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Eiko Yoshida Kazuhiro Aoki Yu Sasaki Hinako Izuhara Tsutomu Takahashi Yasuyuki Fujiwara Tomoya Fujie Ke Du Komyo Eto Yo Shinoda Toshiyuki Kaji Source Type: research
Breast milk-mediated exposure to dioxins and antigen in infancy enhances antigen-specific antibody production capacity in adulthood in mice
J Toxicol Sci. 2024;49(5):209-218. doi: 10.2131/jts.49.209.ABSTRACTThe immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Hideki Kakutani Tomohiro Yuzuriha Teruyuki Nakao Source Type: research
Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions
J Toxicol Sci. 2024;49(5):219-230. doi: 10.2131/jts.49.219.ABSTRACTQuantitative structure permeation relationship (QSPR) models have gained prominence in recent years owing to their capacity to elucidate the influence of physicochemical properties on the dermal absorption of chemicals. These models facilitate the prediction of permeation coefficient (Kp) values, indicating the skin permeability of a chemical under infinite dose conditions. Conversely, obtaining dermal absorption rates (DAs) under finite dose conditions, which are crucial for skin product safety evaluation, remains a challenge when relying solely on Kp pred...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Ryoki Kunita Takafumi Nishijima Hiroaki Todo Masaaki Miyazawa Source Type: research
Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis
J Toxicol Sci. 2024;49(5):231-240. doi: 10.2131/jts.49.231.ABSTRACTDrug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were ad...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Kazuhiro Kuga Motohiro Shiotani Kentaro Hori Hiroshi Mizuno Yusaku Matsushita Harushige Ozaki Kohei Hayashi Takatomi Kubo Manabu Kano Source Type: research
Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons
In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 low...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Eiko Yoshida Kazuhiro Aoki Yu Sasaki Hinako Izuhara Tsutomu Takahashi Yasuyuki Fujiwara Tomoya Fujie Ke Du Komyo Eto Yo Shinoda Toshiyuki Kaji Source Type: research
Breast milk-mediated exposure to dioxins and antigen in infancy enhances antigen-specific antibody production capacity in adulthood in mice
J Toxicol Sci. 2024;49(5):209-218. doi: 10.2131/jts.49.209.ABSTRACTThe immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Hideki Kakutani Tomohiro Yuzuriha Teruyuki Nakao Source Type: research
Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions
J Toxicol Sci. 2024;49(5):219-230. doi: 10.2131/jts.49.219.ABSTRACTQuantitative structure permeation relationship (QSPR) models have gained prominence in recent years owing to their capacity to elucidate the influence of physicochemical properties on the dermal absorption of chemicals. These models facilitate the prediction of permeation coefficient (Kp) values, indicating the skin permeability of a chemical under infinite dose conditions. Conversely, obtaining dermal absorption rates (DAs) under finite dose conditions, which are crucial for skin product safety evaluation, remains a challenge when relying solely on Kp pred...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Ryoki Kunita Takafumi Nishijima Hiroaki Todo Masaaki Miyazawa Source Type: research
Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis
J Toxicol Sci. 2024;49(5):231-240. doi: 10.2131/jts.49.231.ABSTRACTDrug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were ad...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Kazuhiro Kuga Motohiro Shiotani Kentaro Hori Hiroshi Mizuno Yusaku Matsushita Harushige Ozaki Kohei Hayashi Takatomi Kubo Manabu Kano Source Type: research
Comparative study of susceptibility to methylmercury cytotoxicity in cell types composing rat peripheral nerves: a higher susceptibility of dorsal root ganglion neurons
In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 low...
Source: Journal of Toxicological Sciences - May 1, 2024 Category: Toxicology Authors: Eiko Yoshida Kazuhiro Aoki Yu Sasaki Hinako Izuhara Tsutomu Takahashi Yasuyuki Fujiwara Tomoya Fujie Ke Du Komyo Eto Yo Shinoda Toshiyuki Kaji Source Type: research
Octanol/water partition coefficients estimated using retention times in reverse-phase liquid chromatography and calculated in silico as one of the determinant factors for pharmacokinetic parameter estimations of general chemical substances
J Toxicol Sci. 2024;49(4):127-137. doi: 10.2131/jts.49.127.ABSTRACTThe octanol/water partition coefficient P (logP) is a hydrophobicity index and is one of the determining factors for the pharmacokinetics of orally administered substances because it influences membrane permeability. To illustrate the wide-ranging variety of compounds in the chemical space, a two-dimensional data plot consisting of 25 blocks was previously proposed based on a substance's in silico chemical descriptors. The logP values of approximately 200 diverse chemicals (test plus reference compounds covering all 25 blocks of the chemical space) were est...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Koichiro Adachi Makiko Shimizu Fumiaki Shono Kimito Funatsu Hiroshi Yamazaki Source Type: research
Histological differences between the central and peripheral areas of the testes of busulfan-administered mice
In this study, busulfan was intraperitoneally injected at 40 mg/kg body weight into C57BL/6J male mice. After 28 days, in busulfan-treated mice, the diameters of seminiferous tubules were significantly higher in the central than in the peripheral area of the testes. The seminiferous tubular areas also significantly decreased in the peripheral areas compared with the central areas. The number of germ cells per seminiferous tubule was significantly higher in the central than in the peripheral area. Sertoli cell nuclei were detached into the lumen in the peripheral area. The number of Leydig cells was significantly lower in t...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hidenobu Miyaso Satoshi Yokota Kousuke Suga Yui Hashimoto C éline Kouno Kenta Nagahori Masahiro Itoh Satoshi Kitajima Source Type: research
Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin
The objective of this study was to evaluate the effect of AGIQ on the gut microbiota of animals in different dose groups. Male rats and mice received different doses of AGIQ (1.5%, 3%, or 5% w/v) in diet for carcinogenic or chronic toxicity studies (rasH2 mice: 6 months; Sprague-Dawley rats: 12 months). Male minipigs received 100, 300, or 1000 mg/kg/day for 28 days. Fecal samples were collected from the different animal species and analyzed using 16S-rRNA gene sequencing. No significant changes were observed in alpha and beta diversity of the gut microbiota. Characteristic bacteria that responded to AGIQ were identified in...
Source: Journal of Toxicological Sciences - March 31, 2024 Category: Toxicology Authors: Hong Liu Ryo Inoue Mihoko Koyanagi Shim-Mo Hayashi Gen Watanabe Kentaro Nagaoka Source Type: research
