We would like to express our gratitude for your contributions to our official scientific journals, The Journal of Toxicological Sciences and Fundamental Toxicological Sciences.

We have decided to make both journals open access in order to internationalize them and expand their reach to a broader audience. Articles will be published under the Creative Commons license with the highest degree of freedom, CC BY (4.0). As a result of this change, article copyright will belong to the authors, and secondary use, including copying, distribution, display, storage, modification, and commercial use, can be carried out without the relevant society’s permission.

The new Instructions for Authors will be published on the journal websites in advance. These new submission guidelines 
will apply to papers submitted on or after June 1, 2025 (Japan time). Please note that the previous Instructions for Authors will apply to papers submitted until May 31, 2025 (Japan time).

We hope that this change will encourage you to submit more of your excellent papers to The Journal of Toxicological Sciences and Fundamental Toxicological Sciences.

Toshiyuki Kaji, Ph.D.

Editor-in-Chief

The Journal of Toxicological Sciences

Akira Naganuma, Ph.D.

Editor-in-Chief

Fundamental Toxicological Sciences

Pharmacokinetic data are not generally available for evaluating the toxicological potential of food chemicals. A simplified physiologically based pharmacokinetic (PBPK) model has been established to evaluate internal exposures to chemicals in rats or humans with no reference to in vitro or in vivo experimental data. In this study, reported liver toxicity levels in rats were extrapolated to humans using virtual hepatic concentration–time curves (AUC) as the interspecies factor. Virtual liver exposures to 27 lipophilic food chemicals (octanol–water partition coefficient logP >1) with reported rat hepatic lowest-observed-effect levels (LOELs) of ≤1000 mg/kg/day were generated using PBPK models with input parameters obtained entirely in silico via machine learning algorithms. The resulting virtual rat and human liver AUCs were correlated (n = 27, r = 0.52, p < 0.01). However, AUCs for the phenolic compounds emodin, isoeugenol, and tert-butylhydroquinone, which have reported rat LOEL values of ≤300 mg/kg/day, were located outside the relatively wide 95% confidence interval, indicating more extensive hepatic elimination in rats than in humans. In vitro depletion of tert-butylhydroquinone in rat liver fractions via sulfation was confirmed to be faster than that in humans. For emodin, isoeugenol, and tert-butylhydroquinone, human-to-rat AUC ratios ranged from 10- to 13-fold; consequently, their extrapolated human hepatic LOEL values were estimated as ≤30 mg/kg/day, i.e., one order of magnitude smaller than the rat LOELs. Despite the small number of lipophilic food chemicals considered here, the PBPK modeling approach using in silico-generated input parameters for rats and humans has the potential to facilitate toxicological studies.

Welding fumes are metal particles of 1 µm or less generated during welding. Welding fumes generated in welding factories spread throughout the workplace. However, the effects of exposure have been measured primarily in welding workers, and no research has been conducted on the effects of fumes on workplace office workers. In this study, we recruited welding and office workers who worked in the same factories at ten workplaces in Japan, mainly in the Kyushu and Kanto regions, and separated their serum after blood sampling. We also obtained serum from the general subjects of Minami-Kagoshima City, which is located far from the welding factory. Cytokines and chemokines were quantified in the serum samples, and the concentration of interleukin (IL)-1β was significantly increased in office workers and welders compared with general subjects. Importantly, the serum concentrations of IL-12p70, IL-17A, IL-33, tumor necrosis factor α, and C-C motif chemokine ligand 3 in office workers were significantly higher than those in the general subjects, and there was no significant difference in the levels of these inflammatory molecules between welders and general subjects. This study suggests that office workers exposed to high fume concentrations exhibit increased systemic inflammation. Exposure assessments should be conducted not only for welders but also for office workers to reduce exposure risks.

Perinatal perfluorooctane sulfonate (PFOS) exposure of the next generation through placenta and breast milk has been of high concern. Epidemiological and animal studies have reported that perinatal PFOS exposure is associated with neurodevelopmental disorders such as learning and autism spectrum disorders in children. However, the sensitive time window of perinatal PFOS exposure for neurodevelopment has yet to be elucidated. Here we examined differential effects of different time windows of postnatal PFOS exposure (postnatal day (PD) 1-7 or 8-14) on cognitive development and gene expression profiles in the hippocampus. Pups were exposed to PFOS from PD 1 to 7 (PD 1-7 group) or from PD 8-14 (PD 8-14 group) through breastfeeding by dams who received a daily gavage of 1 mg/kg body weight PFOS per day during each period. An object location test and an object recognition test revealed the impairment in spatial memory in PD 1-7 group at PD 70. Learning ability was also retarded in a visual discrimination test. According to RNA-seq analysis and real-time PCR, Serpina3g and Tmem91 were significantly downregulated in the hippocampus of PD 1-7 group at PD 21. These results suggest that the first 7 days after birth are critically vulnerable to PFOS exposure and consequent neurodevelopmental deficits rather than the late phase of postpartum. Our work puts a strong emphasis on the importance of monitoring PFOS concentration in pregnant women and potential impact on retardation of neurodevelopment in children.

With a fourth-place death rate among all malignancies, gastric cancer (GC) is one of the most prevalent tumors globally. As a primary malignant characteristic of GC, metastasis contributes substantially to a high death rate and unfavorable prognosis. miRNA-214-3p can influence cell apoptosis since it is an autophagy-regulating molecule. Its significance in GC malignant development has not, however, been investigated in terms of mechanism. qRT-PCR was utilized to confirm expression of miRNA-214-3p in GC tissues and cells. Bioinformatics analysis was then implemented to examine BNIP3 expression in GC as well as binding interaction between BNIP3 and miRNA-214-3p. The targeting capability of miRNA-214-3p on BNIP3 was confirmed using the dual-luciferase assay. Capacities of cells to proliferate, migrate, and invade were assayed using Transwell assays and colony formation. In order to determine if GC cells were capable of autophagy, immunofluorescence and western blot were employed. In GC, miRNA-214-3p was substantially expressed in GC tissues and cells, but BNIP3 was downregulated, as shown by bioinformatics analysis and verified by cell tests. MiRNA-214-3p targeted BNIP3, as shown by further bioinformatics analysis, and dual-luciferase experiment verified this binding connection. MicroRNA-214-3p facilitated cell invasion, migration, and proliferation, as shown by Transwell tests and colony formation. MiRNA-214-3p accelerated malignant development of GC by targeting BNIP3 to impact autophagy, as demonstrated by immunofluorescence and western blot analyses. By targeting BNIP3 to affect autophagy, miRNA-214-3p aided in the malignant growth of GC. This suggested that miRNA-214-3p may function as a likely therapeutic target or biomarker for the disease, with significant implications for early diagnosis and treatment of patients.