International Journal of Toxicology最新文献

Probiotics are living microorganisms that, when given in sufficient quantities, boost the host's health. Probiotics have been used more often in recent years as dietary supplement to prevent illnesses, including diarrhea, obesity, and constipation. The probiotic strain Bacillus subtilis BSP110 is being developed as a dietary supplement. In this work, we assessed the in vivo safety of the probiotic strain Bacillus subtilis BSP110 in rats as per OECD-423 and 407 guidelines. Female rats were given a single oral (gavage) dosage of 2000 mg/kg (4 × 10¹¹ CFU/g) to assess the maximum tolerated dose (MTD). This was followed by a 28-day sub-acute toxicity study in which Bacillus subtilis BSP110 was given orally (gavage) once daily to male and female rats at dose levels of 250, 500, and 1000 mg/kg/day. No effects of Bacillus subtilis BSP110 were noted at any of the dosage levels given over the course of 28 days. Between the control and test groups, there was no discernible difference in body weight, clinical symptoms, urinalysis, hematological tests, clinical biochemistry, gross pathology, or histopathological evaluation. Additionally, in vitro cytotoxicity was evaluated using the MTT assay with the VERO cell line, and Bacillus subtilis BSP110 was found to be non-cytotoxic at 4 × 10¹¹ CFU/kg. The single dose MTD was ≥2000 mg/kg, and the NOAEL was 1000 mg/kg/day.

The international cosmeceutical sector has experienced unprecedented expansion, compelling regulatory bodies to enhance and update systems to tackle consumer protection, product effectiveness, and ethical issues. This review critically evaluates and contrasts regulatory settings in key markets, such as the European Union, United States, Canada, Japan, China, India, and Brazil. The examination is concentrated on key features including product definitions, pre-market approval procedures, and ingredient regulation, labeling requirements, post-market surveillance, and integrating ethical and environmental considerations. The outcome shows significant advances in regulatory harmonization, especially in the area of ingredient safety and adverse event reporting; however, there are still considerable challenges. Pioneering among these are the lack of a standard definition for "cosmeceuticals," highly variable ingredient limitations, and uneven application practice across jurisdictions. The speedy growth of e-commerce and cross-border sales additionally complicates regulatory control, adding to the possibility of non-compliant or counterfeited products reaching consumers. The review also identifies a shortage of empirical evidence to document the actual impact of recent regulatory reforms in the real world, as well as on innovation and market access. The present study recommends the promotion of international harmonization of standards, enhancement of post-market surveillance, convergence of ethical and sustainability dimensions, and targeted support for small- and medium-sized enterprises. Henceforth, while important progress has been achieved, the future of the industry rests on creating nimble, science-informed, and internationally harmonized regulatory systems that can keep pace with changing technologies and consumers' and public health priorities, ensuring both consumer safety and industry innovation.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 24 silicate ingredients that are solid inorganic oxides, comprising, in part, silicon dioxide, which can be derived from naturally occurring minerals or can be produced synthetically. Reported functions in cosmetics include abrasives, absorbents, bulking agents, and deodorant agents. The Panel reviewed all relevant data and concluded that the silicate ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating, with the exception that the available data are insufficient to make a determination of safety for the use of naturally sourced (i.e., mined) silicate ingredients in products that may be incidentally inhaled.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Salicylic Acid and 17 salicylates; 15 of these ingredients were previously reviewed by the Panel, and 3 are reviewed herein for the first time. Some of the reported functions in cosmetics for ingredients in this group are hair and skin conditioning agents, and, less frequently, preservatives and fragrance ingredients. Upon review of relevant new data, including frequency and concentration of use, and consideration of data from the previous CIR report, the Panel concluded that these ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be non-irritating and non-sensitizing, which may be based on a quantitative risk assessment (QRA).

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Tetrasodium Glutamate Diacetate and Beta-Alanine Diacetic Acid, which are reported to function as chelating agents in cosmetic products. The Panel reviewed the available data to determine the safety of these ingredients. The Panel concluded that Tetrasodium Glutamate Diacetate is safe in cosmetics in the practices of use and concentration described in this safety assessment, and that the available data are insufficient to make a determination that Beta-Alanine Diacetic Acid is safe under the intended conditions of use in cosmetic formulations.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 7 saccharides/saccharide derivatives as used in cosmetic products; all of these ingredients are reported to function as skin-conditioning agents-humectant in cosmetics. The Panel reviewed data relevant to the safety of these ingredients in cosmetic formulations and concluded that Anhydrogalactose, Anhydroglucitol, Anhydroxylitol, Arabinose, Psicose, Saccharide Hydrolysate, and Saccharide Isomerate are safe in cosmetics in the present practices of use and concentration described in this safety assessment.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 4 Saccharum officinarum (sugarcane)-derived ingredients. These ingredients are mostly reported to function in cosmetics as skin-conditioning agents. Industry should use good manufacturing practices to minimize impurities that could be present in botanical ingredients. The Panel considered the available data and concluded that Saccharum Officinarum (Sugarcane) Bagasse Powder, Saccharum Officinarum (Sugarcane) Extract, Saccharum Officinarum (Sugarcane) Juice Extract, Saccharum Officinarum (Sugarcane) Wax are safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Bisphenol A (BPA) is a prevalent environmental endocrine disruptor with potential impacts to the neurological system in humans. This study used an integrated method combining network toxicology, molecular docking, and molecular dynamics simulations to explore the molecular mechanisms underlying BPA-induced neurotoxicity. We identified 255 potential neurotoxicity-related targets through the integration and comprehensive analysis of multiple data sources, including the Comparative Toxicogenomics Database (CTD), ChEMBL, STITCH, GeneCards, and the Online Mendelian Inheritance in Man (OMIM) database. Analysis of the protein-protein interaction (PPI) network unveiled 52 core targets, among which TNF, TP53, INS, ESR1, and PTGS2 emerged as pivotal hubs in the toxicity network. Functional enrichment analysis indicated that the core targets of BPA's influence on neurotoxicity are predominantly enriched in vital signaling cascades, including inflammatory responses, pathways of neurodegeneration, MAPK signaling pathway, serotonergic synapse pathway, and pathways in cancer. Molecular docking results demonstrated that BPA exhibited stable binding interactions with core targets. Furthermore, molecular dynamics simulations provided insights into the interactions between BPA and key targets (ESR1, TNF, and TP53), supporting the potential conformational stability of these complexes. Collectively, these computational findings contribute to understanding the potential molecular mechanisms of BPA-induced neurotoxicity and are informative for generating hypotheses related to its pathogenesis.

The device development process encompasses an intersection of biological, physical, and engineering sciences principles culminating in translation of data from nonclinical animal studies to predict potential tissue responses in human patients. Evaluation of tissue reactions to the implanted device relies heavily on the core discipline of toxicologic pathology. Historically and currently, a disconnect between physical and biological scientists is highlighted by the frequent miscommunications due to differences in scientific language and divergent approaches to animal study design and/or data generation and interpretation. To facilitate communication among biologists, engineers, and materials scientists in the medical device community, this article provides fundamental principles and key resources necessary for rational pathology evaluation of tissue responses to implanted devices from the expert perspective of experienced toxicologic pathologists. The unique contributions of toxicologic pathologists to developing and marketing medical devices will be discussed, emphasizing the role of expert pathologists in balancing scientific issues with respect to evaluating biological responses and regulatory considerations. Additionally, discrepancies will be addressed that may arise if regulatory guidance is applied rigidly rather than adjusted as warranted by the context-specific evidence to best answer particular safety-related questions.