International Journal of Toxicology最新文献

The Crl:CD(SD) Sprague Dawley rat and the Crl:WI(Han) Wistar Hannover (Wistar Han) rat are two outbred rat models commonly used in 2-year carcinogenicity testing. In this presentation, the spontaneous incidences of common, rare, and fatal neoplasms in the two models in 2-year carcinogenicity studies were compared from 51 Sprague Dawley rat studies and 31 Wistar Han rat studies that were completed from 2016 to 2023. All Wistar Han rat studies completed the intended 104 weeks of dosing, whereas 47 of the 51 Sprague Dawley rat studies were terminated early in both sexes or terminated early in one sex. The incidence of total spontaneous neoplasms was greater in Sprague Dawley rats when compared to Wistar Han rats of either sex, with the greatest incidence found in female Sprague Dawley rats (95.93%). Of palpable masses that corresponded to neoplasms, approximately 85-90% of masses were mammary tumors in females of either strain, while a similar percentage of masses corresponded to skin tumors in male rats of either strain. Common fatal tumors included pituitary adenoma of the pars distalis, carcinoma of the pars distalis, mammary adenocarcinoma, and mammary fibroadenoma, and were found at a lower incidence in Wistar Han rats; where calculable, the onset of these neoplasms was earlier in Sprague Dawley rats.

Orodispersible films (ODFs) are advanced drug delivery systems that consist of thin, mechanically robust polymeric films designed to dissolve or disintegrate quickly in the oral cavity, facilitating local and systemic drug administration. Orphyllo™ is a novel ODF vehicle developed to enhance the stability and delivery efficiency of active pharmaceutical ingredients. This study aimed to assess the safety profile of Orphyllo™ through a comprehensive evaluation of its cytotoxicity and genotoxicity on human oral mucosa cell lines. The cytotoxicity was evaluated using (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) MTT, Neutral Red Uptake (NR), and Lactate Dehydrogenase (LDH) assays, which tested the impact of Orphyllo™ at concentrations of 5.0% and 10.0% over 24, 48, and 72 hours. Results indicated no significant reduction in cell viability (P > 0.05), demonstrating the formulation's biocompatibility. To evaluate genotoxicity, the micronucleus test was performed, showing no significant increase in the frequency of micronuclei compared to the control group, thus indicating no DNA damage. Additionally, the Annexin/7-AAD assay was employed to assess apoptosis and necrosis, revealing no significant induction of cell death at the tested concentrations (P > 0.05). These findings highlight that Orphyllo™ presents, even at an early stage, the potential to become a promising vehicle for oral drug administration applications, with potential benefits in several therapeutic areas, especially for populations that require ease of administration.

Physiologically based pharmacokinetic (PBPK) modeling is increasingly used to anticipate, quantify, and strategically manage drug-drug (DDI) and herb-drug (HDI) interactions that can alter the exposure of chemotherapy agents together with co-administered phytochemicals or nutraceuticals. To evaluate current knowledge, we performed a comprehensive Google Scholar search (2003-2024) and selected studies that employed PBPK platforms, reported quantitative validation, and focused on chemotherapy-related interactions. From these reports, key modeling parameters, validation metrics, and clinically relevant outcomes were extracted, and then the information was synthesized to identify common trends. Collectively, the evidence indicates that unintended changes in drug exposure-most often mediated by CYP3A4 inhibition or induction-may modify efficacy, toxicity, and overall anticancer response; nevertheless, PBPK models reproduce these effects with high accuracy, and emerging AI-enhanced approaches promise even finer precision. Accordingly, our synthesis underscores how PBPK modeling can help clinicians forecast interaction risk, individualize dosing, and avert therapeutic failure, especially in polypharmacy settings. Integrating these models into routine oncology practice therefore offers a proactive path toward safer, more personalized chemotherapy and, ultimately, better patient outcomes within an increasingly complex therapeutic landscape.

A nanoparticle-based immunization strategy offers a promising treatment for opioid use disorder (OUD). This study tested the in vivo safety of subunit keyhole limpet hemocyanin-loaded lipid-PLGA hybrid nanoparticles (sKLH-hNPs) as a nanocarrier for OUD vaccine in adult male BALB/c mice by subcutaneous administration at an effective low dose (60 μg) and a dose 5-fold higher (300 μg), with cohorts of animals (n = 10/group, including controls) observed and evaluated for behavioral changes. At 3, 14, 28, and 56 days after dosing, mice (n = 3/dose) were sacrificed, and serum was collected for evaluation of electrolytes, minerals, proteins, liver function, renal function, and energy metabolism. Histological examination included all critical organs, gastrocnemius muscle, and skin from the site of injection. For behavioral evaluation, home cage, open field, and reflex observations were compared among the groups. Results demonstrated no statistical differences among the groups, with the exception of respirations observed in the home cage (O-RESP) on Day 3 (P = 0.03). There was no evidence of any effect of the test product on energy (glucose, cholesterol, triglycerides) or mineral metabolism (phosphorus, calcium) and hepatic function (urea nitrogen, albumin, total bilirubin), and no indication that the test agent caused liver injury, cholestasis, muscle damage, or acid-base imbalance. Histological analysis in control and treated mice generally revealed no significant findings, although small areas of hemorrhage, lymphocyte infiltration, and thick areas in the subcutis were noted in a subset of samples from both control and treated animals. These experiments suggest that the nanoparticle-based product would be safe for vaccines treating OUD.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Acetyl Hexapeptide-8 Amide (synonymous with Acetyl Hexapeptide-8 (sans "Amide")) in cosmetic products; this ingredient is reported to function as a skin conditioning agent - miscellaneous in cosmetics. The Panel reviewed data relevant to the safety of this ingredient in cosmetic formulations, and concluded that Acetyl Hexapeptide-8 Amide is safe in cosmetics in the present practices of use at concentrations up to 0.005%. The Panel further concluded that the available data are insufficient to make a determination that Acetyl Hexapeptide-8 Amide is safe under the intended conditions of use in cosmetic formulations at concentrations greater than 0.005%.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Caprylhydroxamic Acid as used in cosmetic formulations; this ingredient is reported to function as a chelating agent. Positive sensitization results that occurred with the use of a moisturizer containing Caprylhydroxamic Acid appeared to correlate with use on damaged skin. Therefore, the Panel cautioned against the use of Caprylhydroxamic Acid in a manner that would result in increased penetration. A quantitative risk assessment (QRA) was performed, using a weight-of-evidence no-expected-sensitization-induction-level (WoE NESIL) of 1056 μg/cm². The Panel concluded that Caprylhydroxamic Acid is 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 Hydroxy Tetramethylpiperidine Oxide and Tris(Tetramethylhydroxypiperidinol) Citrate as used in cosmetic formulations. These ingredients are reported to function as an antioxidant and a light stabilizer, respectively. The Panel considered the available data and concluded that Hydroxy Tetramethylpiperidine Oxide and Tris(Tetramethylhydroxypiperidinol) Citrate 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 8 glycerin ethoxylates, as used in cosmetic formulations. All of these ingredients are reported to function in cosmetics as skin-conditioning agents, and most are also reported to function as viscosity-decreasing agents. The Panel reviewed relevant data relating to the safety of these ingredients. The Panel concluded that these ingredients are safe in cosmetics in the present practices of use and concentration as described in this safety assessment when formulated to be non-irritating.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 5 titanium complexes as used in cosmetic products; these ingredients have the following reported functions in cosmetics: surface modifier (Isopropyl Titanium Triisostearate); colorant; humectant (Titanium Citrate); binder (Titanium Ethoxide); film former; opacifying agent (Titanium Isostearates); and preservative (Titanium Salicylate). The Panel reviewed relevant data relating to the safety of these ingredients in cosmetic formulations and issued the following separate conclusions. Isopropyl Titanium Triisostearate is safe in cosmetics in the present practices of use and concentration described in the safety assessment, when used as a surface modifier. The data are insufficient to determine the safety of Titanium Citrate, Titanium Ethoxide, Titanium Isostearates, and Titanium Salicylate.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 7 honey-derived ingredients. All of these ingredients are reported to function in cosmetics as skin-conditioning agents. The Panel considered the available data relating to the safety of these ingredients in cosmetic formulations. Because impurities, particularly pesticides and endotoxins, may be present in these ingredients, formulators should continue to use good manufacturing practices to monitor and limit these possible impurities. The Panel concluded the honey-derived ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment.