Journal of Toxicological Sciences最新文献

Evaluation of rewarding effects of nitazene analogs: results from conditioned place preference tests and in vivo microdialysis experiments in mice. 评价nitazene类似物的奖励作用：条件位置偏好试验和小鼠体内微透析实验的结果。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.33

Kyoko Hataoka, Motoki Hojo, Sakiko Nomura, Yoshio Nakagawa, Ayaka Kawai, Mari Nakamura, Kiyomi Ikushima, David B Alexander, Jin Suzuki, Toshinari Suzuki, Akiko Inomata

{"title":"Evaluation of rewarding effects of nitazene analogs: results from conditioned place preference tests and in vivo microdialysis experiments in mice.","authors":"Kyoko Hataoka, Motoki Hojo, Sakiko Nomura, Yoshio Nakagawa, Ayaka Kawai, Mari Nakamura, Kiyomi Ikushima, David B Alexander, Jin Suzuki, Toshinari Suzuki, Akiko Inomata","doi":"10.2131/jts.50.33","DOIUrl":"https://doi.org/10.2131/jts.50.33","url":null,"abstract":"In illicit drug markets, the most recently expanding new synthetic opioid subclass is benzimidazoles, also known as nitazenes, which were originally developed as analgesics in the 1950s. The emergence of this classical, potent drug family has attracted extensive research interest in the field of forensic toxicology; however, information on their psychological and physical dependence is very limited. Herein, we evaluated the rewarding effects of four nitazene analogs using a battery of in vivo experiments, with a positive control drug (isotonitazene). The four test materials, metonitazene, etodesnitazene, metodesnitazene, and flunitazene, were administered to male C57BL/6J mice by i.p. administration at 0.5, 2, 20, and 20 mg/kg, respectively. In comprehensive behavioral observation tests, representative opioid-related physiological and behavioral states, including analgesia, stereotypic circling behavior, hyperlocomotion, and Straub tail response, were observed. A set of conditioned place preference tests revealed that all the four analogs induced palatability in mice. Furthermore, measurements of dopamine levels in the nucleus accumbens shell by in vivo microdialysis resulted in significant elevations in all test material-treated groups, suggesting that the nitazenes elicit the rewarding effect through a neural circuit originating from the μ-opioid receptor activation at the ventral tegmental area. Our findings add important data regarding the psychological dependence of nitazenes and highlight the abuse potential of these four materials and other prevailing nitazene analogs.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"33-43"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxicity of nickel, copper, and selenium in medaka embryos (oryzias latipes): a comparative study. 镍、铜和硒对稻尾草胚毒性的比较研究。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.23

Sylvester Addai-Arhin, Seiya Shino, Masaya Uchida, Hiroshi Ishibashi, Koji Arizono, Nobuaki Tominaga

{"title":"Toxicity of nickel, copper, and selenium in medaka embryos (oryzias latipes): a comparative study.","authors":"Sylvester Addai-Arhin, Seiya Shino, Masaya Uchida, Hiroshi Ishibashi, Koji Arizono, Nobuaki Tominaga","doi":"10.2131/jts.50.23","DOIUrl":"https://doi.org/10.2131/jts.50.23","url":null,"abstract":"The indispensability of biometals nickel, copper, and selenium in pharmaceutical, agricultural, and other industrial applications, coupled with their release from mining processes, has made them potent environmental contaminants, especially when present in aquatic ecosystems at levels above the essential range. The toxicity of these biometals in fish embryogenesis, including their toxicity levels, was studied using medaka embryos. Test solutions (0.001-10 ppm) of the biometals, along with an isotonic solution as a control, were introduced into the embryos using a nanosecond pulsed electric field application. The exposed embryos were cultured at 25 ± 1°C and microscopically observed daily for 14 days in an isotonic solution. Developmental abnormalities and toxicity were observed during the 14-day observation period. All biometals caused some abnormalities in developing embryos at all concentrations. Major abnormalities included delayed development; deformities such as curvature of bones or spines; abnormal formation of the hearts, eyes, and circulatory systems; and mortality. The toxicity of the biometals was significantly different (p < 0.05) from that of the control. Gene expression analysis revealed that 4747, 1961, and 1952 genes were affected by copper, nickel, and selenium, respectively. Copper affected the highest number of genes and caused the highest toxicity. These results indicate that nickel, copper, and selenium can cause toxicity in developing fish embryos at concentrations ranging from 0.01 ppb to 10 ppm. Therefore, there is a need to constantly monitor the levels of these biometals, particularly in aquatic ecosystems, to preserve aquatic life.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"23-32"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Per- and polyfluoroalkyl substances: toxicokinetics, exposure and health risks.

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.97

Yukiko Fujii, Kouji H Harada

{"title":"Per- and polyfluoroalkyl substances: toxicokinetics, exposure and health risks.","authors":"Yukiko Fujii, Kouji H Harada","doi":"10.2131/jts.50.97","DOIUrl":"https://doi.org/10.2131/jts.50.97","url":null,"abstract":"Per- and polyfluoroalkyl substances (PFAS) are a group of chemicals containing stable per- or polyfluoroalkyl groups. Recent epidemiological studies have shown that PFAS cause health risks even at low concentrations. This review outlines the toxicokinetics, exposure and health risks of PFAS, with a focus on perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and long-chain perfluoroalkyl carboxylic acids (LC-PFCAs). These compounds are known to interact with various proteins in vivo, including the peroxisomal proliferator-activated receptor-α (PPARα). PFOA and PFOS have been identified as carcinogenic. It is known that PFOA and PFOS are transported by transporters such as organic anion transporter. Significant species differences in the behavior of these compounds exist, with much longer half-lives in humans than in mice and rats. One of the reasons that the half-lives of PFOA and PFOS are long in humans is that their renal clearance is low in humans. For animal toxicity experiments, it is essential that the doses in animal experiments are converted to equivalent doses in humans using pharmacokinetic models. Compared with PFOA, some LC-PFCAs have longer half-lives and accumulate more in the liver. Although tap water is a source of exposure to PFAS, the most common exposure source is food, with seafood being an important source for exposure to PFAS in Japan. PFOS and PFOA concentrations in human blood in Japan have been decreasing in recent years. However, according to clinical guidance published in 2022 by the United States National Academies, most Japanese residents are still in the medium risk group (PFAS concentration in plasma or serum is greater than 2 ng/mL and less than 20 ng/mL) or above. Further research is needed to help reduce exposure, and further risk assessments are required.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"97-104"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Male rat-specific fatty change in liver by DS-1971a: Elevation in phospholipids and adenosine as early responses to the fatty change in male rat-derived primary hepatocytes. DS-1971a 对雄性大鼠肝脏特异性脂肪变化的影响：磷脂和腺苷的升高是雄性大鼠原代肝细胞对脂肪变化的早期反应。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.125

Kazunori Fujimoto, Hiroyuki Kishino, Jun Hirao, Takanori Maejima, Kazuhiko Mori, Yoshimi Tsuchiya

{"title":"Male rat-specific fatty change in liver by DS-1971a: Elevation in phospholipids and adenosine as early responses to the fatty change in male rat-derived primary hepatocytes.","authors":"Kazunori Fujimoto, Hiroyuki Kishino, Jun Hirao, Takanori Maejima, Kazuhiko Mori, Yoshimi Tsuchiya","doi":"10.2131/jts.50.125","DOIUrl":"https://doi.org/10.2131/jts.50.125","url":null,"abstract":"In a 3-month repeated oral dose toxicity study of DS-1971a, a selective inhibitor of the Nav1.7 voltage-gated sodium channel, fatty change of hepatocytes was observed only in male rats at doses of 100 mg/kg and above. However, this change was not observed in female rats even at the highest dose of 1500 mg/kg. Furthermore, fatty change was not observed in mice and monkeys administered the highest dose of 1000 mg/kg for 6 and 9 months, respectively. To further investigate species differences of this fatty change, lipid accumulation was evaluated by staining with the LipidTOX dye in primary cultured hepatocytes derived from male and female rats, male monkeys, and male and female humans. After exposure to DS-1971a for 72 hr, the staining showed an increase in intensity specifically in male rat-derived hepatocytes in a concentration-dependent manner. Metabolomic analysis using rat-derived primary cultured hepatocytes exposed to DS-1971a for 24 and 72 hr revealed that phospholipids, not neutral lipids like triacylglycerols, and adenosine were elevated in the male-derived hepatocytes. These results suggest that the elevation of phospholipids and adenosine in the hepatocytes may contribute to the specific fatty change observed in male rats.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"125-134"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induction of VEGF-A expression by methylmercury is mediated by the EGFR-p38 MAPK-COX-2-PKA pathway in cultured human brain microvascular pericytes.

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.199

Eiko Yoshida, Kenta Sakurai, Akishige Hirata, Tomoko Sasaoka, Takashi Hirooka, Tomoya Fujie, Takato Hara, Chika Yamamoto, Yasuyuki Fujiwara, Yo Shinoda, Komyo Eto, Toshiyuki Kaji

{"title":"Induction of VEGF-A expression by methylmercury is mediated by the EGFR-p38 MAPK-COX-2-PKA pathway in cultured human brain microvascular pericytes.","authors":"Eiko Yoshida, Kenta Sakurai, Akishige Hirata, Tomoko Sasaoka, Takashi Hirooka, Tomoya Fujie, Takato Hara, Chika Yamamoto, Yasuyuki Fujiwara, Yo Shinoda, Komyo Eto, Toshiyuki Kaji","doi":"10.2131/jts.50.199","DOIUrl":"10.2131/jts.50.199","url":null,"abstract":"Methylmercury is the causative organometallic compound of Minamata disease. Pathological changes in the cerebrum of patients are localized along the deep sulci and fissures of the cerebral cortex such as the calcarine fissure. It has been suggested that the occurrence of brain edema is important for the cerebral damage caused by methylmercury. Previously, we found that methylmercury induces vascular endothelial growth factor-A in cultured human brain microvascular pericytes, which may increase permeability of the brain microvasculature. In the present study, our findings suggest that this induction is mediated via the epidermal growth factor receptor-p38 mitogen-activated protein kinase-cyclooxygenase-2-protein kinase A pathway in cultured human brain microvascular pericytes. These results partly support our hypothesis that methylmercury causes neurotoxicity by activation of intracellular signaling pathways in various cell types, including neurons, macrophages, vascular endothelial cells, and pericytes.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 4","pages":"199-204"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Benzalkonium chloride initiates proinflammatory responses via NLRP3 inflammasome activation. 苯扎氯铵通过NLRP3炎性体激活引发促炎反应。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.11

Tomohiro Kagi, Maoko Tan, Wakana Suzuki, Kohei Otani, Sara Suzuki, Yusuke Hirata, Takuya Noguchi, Atsushi Matsuzawa

{"title":"Benzalkonium chloride initiates proinflammatory responses via NLRP3 inflammasome activation.","authors":"Tomohiro Kagi, Maoko Tan, Wakana Suzuki, Kohei Otani, Sara Suzuki, Yusuke Hirata, Takuya Noguchi, Atsushi Matsuzawa","doi":"10.2131/jts.50.11","DOIUrl":"https://doi.org/10.2131/jts.50.11","url":null,"abstract":"A representative surfactant, benzalkonium chloride (BAC) is used as a disinfectant, but sometimes causes serious side effects, including lung disorders such as interstitial pneumonia. However, its pathogenic mechanisms remain unexplained. In this study, we identified a novel mechanism by which BAC initiates inflammatory responses that may be responsible for its side effects. We firstly investigated whether BAC initiates inflammation, and found that BAC promotes the secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β) but not tumor necrosis factor-α (TNF-α) in macrophages. Interestingly, the IL-1β secretion triggered by the surfactants was completely blocked by the K-ATP channel blocker glibenclamide or the calcium chelating agent 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM. Moreover, genetic experiments revealed that BAC-dependent IL-1β secretion is mediated by the NLRP3 inflammasome. These results suggest that derangement of ion fluxes associated with the interfacial effects of BAC triggers NLRP3 inflammasome activation and subsequent inflammation. Thus, the NLRP3-dependent mechanisms triggered by BAC may explain the pathogenesis of surfactant-caused adverse effects.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"11-21"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prolonged QRS duration in patients with acute poisoning occurs both xenobiotics and with low level of potassium: a single-center retrospective case control study.

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.117

Hironori Katsuki, Tetsuhisa Yamada, Katsuhiko Ayukawa

{"title":"Prolonged QRS duration in patients with acute poisoning occurs both xenobiotics and with low level of potassium: a single-center retrospective case control study.","authors":"Hironori Katsuki, Tetsuhisa Yamada, Katsuhiko Ayukawa","doi":"10.2131/jts.50.117","DOIUrl":"https://doi.org/10.2131/jts.50.117","url":null,"abstract":"Prolongation of QRS duration (prolonged QRS) is associated with severe outcomes in non-tricyclic antidepressant poisoning. However, factors other than xenobiotics affecting QRS duration have not yet been investigated. Hence, this study aimed to identify factors contributing to prolonged QRS. This study was a single-center retrospective case control study. Patients who had overdosed on drugs or orally ingested xenobiotics that they would not normally ingest orally were included in the study. Patients were divided into two groups: prolonged QRS and normal QRS. Subsequently, these groups were compared. We performed a logistic regression analysis with the factors extracted by comparison as explanatory variables and prolonged QRS as the objective variable. In total, 108 patients were analyzed; 19 belonged to the prolonged QRS group. In the prolonged QRS group, factors such as male sex, low level of potassium, and xenobiotic ingestion resulted in prolonged QRS. In a logistic regression analysis, significant differences were observed in terms of male sex (odds ratio [OR], 27.00; 95% confidence interval [CI], 5.93-123.00; p<0.001), xenobiotics ingested that resulted in prolonged QRS (OR, 8.55; 95% CI, 1.84-39.70; p<0.001), and potassium levels (OR, 0.15; 95% CI, 0.03-0.88; p=0.035). Ingestion of sodium channel blockers, male sex, and low level of potassium may contribute to prolonged QRS.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"117-123"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glasgow coma scale may be a predictive factor for delayed neurological sequelae after carbon monoxide poisoning: a retrospective analysis of a nationwide multicenter observational registry in Japan.

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.69

Tadashi Kaneko, Motoki Fujita, Ryosuke Tsuruta

{"title":"Glasgow coma scale may be a predictive factor for delayed neurological sequelae after carbon monoxide poisoning: a retrospective analysis of a nationwide multicenter observational registry in Japan.","authors":"Tadashi Kaneko, Motoki Fujita, Ryosuke Tsuruta","doi":"10.2131/jts.50.69","DOIUrl":"https://doi.org/10.2131/jts.50.69","url":null,"abstract":"Acute carbon monoxide poisoning (ACOP) is a cause of accidental or deliberate deaths worldwide. Subsequent complications, particularly delayed neurological sequelae (DNS), are preventable and treatable based on their pathophysiology. Hyperbaric oxygenation therapy (HBO) is a potential procedure for preventing and treating DNS; however, the effects of HBO on DNS are unclear and debated. In the present study, we investigated which factors are associated with the development of DNS and the effects of HBO in patients with ACOP. We performed retrospective subanalyses of the COP-J registry, focusing on adults who underwent HBO, regardless of whether they developed DNS. The multivariable analysis showed that the Glasgow coma scale (GCS) on admission was significantly associated with DNS (odds ratio 0.736; 95% confidence interval 0.608-0.892; P = 0.002). The receiver operating characteristic curve analysis of GCS for DNS revealed a cutoff value of 12.5 according to Youden's index (sensitivity 80.8%, specificity 76.9%). This retrospective analysis of a nationwide Japanese registry of ACOP showed that low GCS scores on admission could be a predictive factor for DNS, with a possible cutoff value of ≤12, in patients who undergo HBO.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"69-73"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of anemia on the timing of pubertal onset in female rats.

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.83

Mariko Shimada, Yoshinori Hosokawa, Ryo Ihara, Keiko Ogata, Katsumasa Iwashita, Ryoko Matsuyama, Hiroyuki Asano

{"title":"The effects of anemia on the timing of pubertal onset in female rats.","authors":"Mariko Shimada, Yoshinori Hosokawa, Ryo Ihara, Keiko Ogata, Katsumasa Iwashita, Ryoko Matsuyama, Hiroyuki Asano","doi":"10.2131/jts.50.83","DOIUrl":"https://doi.org/10.2131/jts.50.83","url":null,"abstract":"Attainment of vaginal patency is an endpoint for the onset of puberty in female animals in toxicity studies. It is widely acknowledged that certain substances with endocrine-modulating effects can influence the timing of puberty in female rats and that factors unrelated to endocrine mechanisms, such as malnutrition and stress, can also affect pubertal onset. Some epidemiological studies have also suggested a link between anemia and delay in pubertal onset in women, however, little is known regarding the relation between hematological changes and female pubertal onset in experimental animals. The purpose of this study was to examine the effects of anemia during the prepubertal period on pubertal onset and reproductive organs in female rats. In this study, anemia was induced by drawing a certain amount of blood from the jugular vein or by intraperitoneal administration of phenylhydrazine, a well-known inducer of hemolytic anemia. As a result, both treatment groups showed a transient anemia characterized by an approximately 20-35% decrease in hemoglobin levels compared to the control group. Anemia in these female rats produced no obvious changes in body weight on each postnatal day and had no effect on the weights and histopathology of reproductive organs after sexual differentiation, but the age at vaginal opening (VO) was delayed and the body weight at VO was higher than the same parameters in the control group. These results suggest that anemia in prepubertal females could cause a delay in pubertal onset.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"83-95"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of additional suitable positive controls in the human Cell Line Activation Test. 人类细胞系激活试验中其他合适阳性对照的研究。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.1

Kanako Nakayama, Shiho Oeda, Hideyuki Mizumachi, Morihiko Hirota, Akiko Tamura, Masaaki Miyazawa

{"title":"Investigation of additional suitable positive controls in the human Cell Line Activation Test.","authors":"Kanako Nakayama, Shiho Oeda, Hideyuki Mizumachi, Morihiko Hirota, Akiko Tamura, Masaaki Miyazawa","doi":"10.2131/jts.50.1","DOIUrl":"https://doi.org/10.2131/jts.50.1","url":null,"abstract":"The human Cell Line Activation Test (h-CLAT) is an in vitro skin sensitization assay adopted by the OECD as Test Guideline 442E. In the h-CLAT, 2,4-dinitrochlorobenzene (DNCB) is used as a positive control; however, DNCB is considered a poisonous substance under the Poisonous and Deleterious Substances Control Act in Japan since 2014 because of its high acute toxicity. Strict control, handling, and storage are required when using DNCB, which is a burden to the users. Although the use of other suitable positive controls with historical data is accepted by the guideline, to our knowledge, there have been no reports of such substances. Therefore, in this study, we investigated suitable positive controls that can be used in addition to DNCB for the h-CLAT. Three candidates that are not considered poisonous substances, imidazolidinyl urea, hydroxycitronellal, and 2,4-dinitrofluorobenzene, were selected. To determine their suitability as positive controls, the h-CLAT was performed repeatedly for each chemical in two laboratories. For imidazolidinyl urea, the results that failed the positive control criteria were observed in both laboratories, indicating that it was inconclusive for the suitability as a positive control at the tested concentration. In contrast, all experiments with hydroxycitronellal and 2,4-dinitrofluorobenzene met the criteria and resulted in relative fluorescence intensity values of CD86/CD54, which were comparable to those for DNCB. Based on these results, hydroxycitronellal and 2,4-dinitrofluorobenzene may be used as positive controls. This study would provide valuable information for users examining other suitable positive controls in the h-CLAT.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0