The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Octyldodecyl Stearoyl Stearate. Octyldodecyl Stearoyl Stearate is reported to function in cosmetics as a skin conditioning and viscosity increasing agent. The Panel reviewed the relevant new data concerning the safety of this ingredient in cosmetic formulations, as well as data from previously published safety assessments, and concluded that Octyldodecyl Stearoyl Stearate is safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of red algae-derived ingredients. Sixty red algae-derived ingredients were found in the International Cosmetic Ingredient Dictionary (Dictionary); however, several of these ingredients may be equivalent according to accepted scientific names. These ingredients are mostly reported to function in cosmetics as skin-conditioning agents. Impurities, particularly arsenic, heavy metals, and pesticides, may be present in these ingredients; industry should continue to use good manufacturing practices to monitor and limit these possible impurities. The Panel considered the available data and concluded that 16 red algae-derived ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment. The Panel also concluded that the data are insufficient to make a determination of safety that the remaining 44 ingredients are safe under the intended conditions of use in cosmetic formulations.

Drug-induced seizures are among the most frequent safety concerns for neuroactive drug candidates. Currently, no guidelines are defined for interrogating and mitigating seizure liability. Because of the risks to patient safety during clinical trials, improved nonclinical characterization of seizure liability is an area of intense interest among drug developers and regulators. During the 2022 annual meeting of the American College of Toxicology (ACT), a continuing education course titled "Identifying and Understanding Seizure Liability in Drug Development" addressed challenges in this field. The course (and now this paper) used a series of detailed nonclinical case studies based on the authors' experiences to illustrate core principles and a flexible menu of methods to evaluate potential seizure liability. Key points to consider include lists of (1) procedures for detecting seizures and defining their mechanisms when performing pivotal and/or investigational toxicity studies; (2) constellations of common neurological findings (functional and structural) that indicate potential seizure liability, and in particular (3) event patterns that warrant an electroencephalographic (EEG) study; and (4) major principles for mitigating seizure liability during clinical trials. Taken together, this approach provides a logical workflow by which nonclinical testing of drug-related seizures may be used to best protect patient safety.

The Expert Panel for Cosmetic Ingredient Safety (Panel) considered whether the safety of l-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as used in cosmetics should be reassessed. The Panel reviewed newly available safety data related to these ingredients. The Panel concluded, based on the available data contained in the report, that these 6 ingredients are safe as cosmetic ingredients in the present practices of use and concentration as described in the report.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reassessed the safety of benzophenones in cosmetic products; these ingredients are reported to function mainly as light stabilizers in cosmetics. The Panel reviewed the relevant data relating to the safety of these ingredients in cosmetic formulations provided in this safety assessment, and data from the previously published safety assessments, and concluded that Benzophenone-1, -2, -3, -4, -5, -6, -8, -9, -10, -11, and -12 are safe in cosmetics in the present practices of use and concentration described in this safety assessment.

Given that alpinetin possesses hypoglycemic and cardioprotective properties, it holds potential for co-administration with the antidiabetic agent glimepiride. The aim was to evaluate the impact of alpinetin on the pharmacokinetics and hypoglycemic efficacy of glimepiride, thereby providing a foundation for the development of alpinetin and informing its potential clinical translation. Pharmacokinetic studies were performed in rats following oral administration of glimepiride (1 mg/kg) alone or combined with alpinetin (30 mg/kg). The effect of the combination of glimepiride and alpinetin on blood glucose levels was investigated in a rat model of type 2 diabetes mellitus (T2DM). In vitro experiments were conducted to evaluate the effect of alpinetin on glimepiride metabolic stability and to assess its role on cytochrome P450 2C9 (CYP2C9) activity. Co-administration of glimepiride with alpinetin resulted in significant changes in the pharmacokinetics of glimepiride, as evidenced by an increase in area under the concentration-time curve (AUC), elimination half-life (t1/2), maximum concentration (Cmax), and a decrease in clearance. Glimepiride in combination with alpinetin enhanced the hypoglycemic effect in T2DM rats. Mechanistic studies in liver microsomes revealed that alpinetin improved glimepiride metabolic stability and inhibited CYP2C9 activity. The combination of glimepiride with alpinetin may increase the systemic exposure of glimepiride through inhibition of CYP2C9 activity. This likely contributes to the enhanced hypoglycemic effect observed, but also underscores the need for caution regarding the potential risk of hypoglycemia.

The preclinical safety of human-equivalent lactoferrin alpha (heqLFα; effera[®]), produced by Komagataella phaffii, was evaluated to support its use as a food ingredient in infant formula and products for young children. Genotoxicity was assessed using a bacterial reverse mutation (Ames) assay in five strains of Salmonella typhimurium and Escherichia coli, and an in vitro micronucleus assay in TK6 cells. Both studies followed OECD guidelines and were conducted up to the recommended limit concentrations (5000 µg/plate and 2000 µg/mL, respectively). A 14-day non-GLP juvenile dose range-finding study and a 13-week GLP juvenile rat toxicity study with a 4-week recovery phase were conducted under ICH S11 guidance. Neonatal Sprague-Dawley rats received heqLFα at 0, 1500, 3000, or 5000 mg/kg body weight/day by twice-daily oral gavage from postnatal day 7 to 98. Bovine lactoferrin (bLF) and whey protein at 5000 mg/kg body weight/day served as reference controls. heqLFα was non-mutagenic and non-clastogenic in both genotoxicity assays. In the 13-week juvenile rat study, no heqLFα-related mortality, clinical signs, developmental, neurobehavioral, or immune toxicity effects were observed. Minor, non-adverse renal findings consistent with high protein intake were observed and largely reversed during recovery. Clinical pathology parameters fully resolved during recovery. Toxicokinetic evaluation showed no systemic accumulation. Based on the absence of toxicologically relevant adverse findings, heqLFα is well tolerated at doses up to 5000 mg/kg body weight/day, establishing a no observed adverse effect level (NOAEL) of 5000 mg/kg/day, the highest dose tested, and supporting its safety across intended populations from birth to adulthood.

The Cosmetic Ingredient Review (CIR) program marks its 50th anniversary as an enduring model of independent, transparent, and science-forward evaluation of cosmetic ingredient safety. Established in 1976 by the Personal Care Products Council (PCPC), with the support of the US Food and Drug Administration (FDA) and the Consumer Federation of America (CFA), CIR has completed evidence-based safety assessments for more than 6000 ingredients, with comprehensive findings published in International Journal of Toxicology. Through a defined governance framework, Expert Panel review, and fully public deliberations, CIR conducts safety evaluations via a structured and transparent process that incorporates broad stakeholder engagement. The program has continued to evolve in parallel with global regulatory and methodological advances. CIR remains an independent scientific resource that complements regulatory oversight and supports robust safety substantiation of cosmetic products. In addition, it has increasingly adopted an exposure-driven evaluation paradigm aligned with Next-Generation Risk Assessment (NGRA) principles, integrating validated New Approach Methodologies (NAMs) to inform hazard identification and refine risk characterization while complementing traditional toxicology. Collectively, these efforts promote scientific harmonization and the continued modernization of cosmetic ingredient safety assessment. At 50 years, CIR stands as a globally recognized, science-based, and publicly accountable program, exemplifying independence and advancing integrated, exposure-led, and human-relevant risk assessment consistent with modern regulatory science.

The Expert Panel for Cosmetic Ingredient Safety (Panel) considered whether the safety of Glyceryl Collagenate, Glyceryl Sesquioleate, Glyceryl/Sorbitol Oleate/Hydroxystearate, Glyceryl Stearate/Maleate, and Glyceryl Thiopropionate as used in cosmetics should be reassessed. The Panel considered that there were no newly available safety data related to these ingredients and no reported uses in cosmetics. The Panel concluded, based on the lack of sufficient data and the lack of reported uses, that the use of these ingredients in cosmetics is not supported.

This review examines the historical development of biological warfare from premodern contamination practices to twentieth-century state programs, post-9/11 bioterrorism, and the renewed prominence of biological risk in the COVID-19 era. Drawing on historical, policy, and public-health scholarship, it shows how disease came to be understood not only as a natural threat but also as a strategic instrument shaped by scientific knowledge, military organization, and administrative secrecy. The review traces the transition from empirical uses of contamination in siege warfare and colonial settings to laboratory-based weaponization in the 20th century, including German sabotage during the First World War, Imperial Japan's Unit 731, British anthrax trials on Gruinard Island, and the expansion of United States and Soviet biological warfare programs during the Cold War. It also evaluates the limits of international restraint through the 1925 Geneva Protocol and the 1972 Biological Weapons Convention, emphasizing the persistent problem of verification illustrated by the 1979 Sverdlovsk anthrax outbreak. The analysis then follows the shift from state arsenals to public fear through Aum Shinrikyo and the 2001 anthrax letters before situating epidemic and pandemic disease within the broader politics of biological vulnerability. COVID-19 and gain-of-function research are treated as cases of intensified scrutiny of biosafety, uncertainty, and public mistrust, rather than evidence for any single-origin hypothesis. The review concludes that biological warfare is best understood not solely as the deliberate use of pathogens but as a broader political and institutional phenomenon emerging where scientific capacity, strategic fear, concealment, and social vulnerability converge.

The Expert Panel for Cosmetic Ingredient Safety (Panel) considered whether the safety of Glyceryl Isostearates and Glyceryl Stearate/Acetate as used in cosmetics should be reassessed. The Panel reviewed newly available safety data related to these ingredients. The Panel concluded, based on the available data contained in the report, that these two ingredients are safe as cosmetic ingredients in the present practices of use and concentration as described in the report.

The FDA has recently approved a medical device which determines a glomerular filtration rate assessment at the point-of-care by transdermal detection of the fluorescent tracer agent relmapirazin. Previous in vitro and in vivo studies on this agent yielded negligible safety/toxicology concern resulting in advancement to phase I, II, and III human clinical studies. Now that clinical use is occurring, herein we investigated possible interference this agent may induce with typical clinical diagnostic assays given to incoming and hospitalized patients. The testing methodology followed the CLSI EP07-A3 Interference Testing in Clinical Chemistry guideline for determination of interference. No interference from relmapirazin was detected in the suite of metabolic and cardiac assays evaluated.

Artificial intelligence (AI) and machine learning are increasingly used in toxicological risk assessment to predict chemical toxicity, identify hazardous compounds, and support regulatory decision-making. However, the widespread adoption of these models is limited by their "black-box" nature, which reduces interpretability, transparency, and regulatory confidence. Explainable artificial intelligence (XAI) has emerged as a promising approach to address these challenges by revealing how input features, including chemical structures, exposure levels, and biological pathways, contribute to toxicity predictions. Techniques such as SHAP (SHapley Additive exPlanations) and LIME (Local Interpretable Model-agnostic Explanations) provide interpretable insights into model decision-making and enhance trustworthiness, accountability, and mechanistic understanding. Despite these advances, most XAI applications in toxicology remain at the computational or preclinical stage, with limited clinical and regulatory translation. This review summarizes current AI-based approaches for toxicity prediction, examines the interpretability challenges that hinder their practical implementation, and highlights the emerging role of XAI in bridging the gap between computational prediction and clinical application. Greater standardization, integration of human data, and collaboration among academia, industry, and regulatory agencies will be essential for advancing transparent and clinically actionable toxicology models.

Novel Psychoactive Substances (NPSs) and other psychoactive or misuse-relevant compounds present a persistent global public health threat, underscoring the critical need for real-time crawling and monitoring tools to investigate and provide valuable information assisting in the management and preparedness against that dynamic and evolving threat. This study utilized the NPSfinder[®] web crawler to analyze NPS trends during the post-pandemic period, with data collected from selected highly trafficked psychonaut websites continuously monitored between January and September 2023. Following a comprehensive filtering process of screening, assessment, and evaluation, the dataset provided insights into the availability and characteristics of recently reported NPSs. Three hundred and sixty-eight molecules were analyzed, of which 158 were newly captured NPSs, suitable for inclusion in the NPSfinder[®] database. Those substances were classified based on their chemical structure, pharmacological mechanism of action, therapeutic indication, if any, and abuse liability. The main NPS classes identified were natural origin/herbal substances (25; 16%), cannabinoids (23; 15%), prescribed medications (23; 15%), synthetic opioids (20; 13%), phenethylamines (14; 9%), cathinones (11; 7%), and anabolic substances (8; 5%). The findings highlight ongoing diversification in substances identified across selected online sources during the post-pandemic period. The study benefits from a timely focus, a substantial and systematically curated dataset, and the application of a continuous web-crawling methodology enabling near real-time detection of emerging substances. The integration of pharmacological and chemical classification further enhances the interpretability and potential clinical relevance of the findings. However, results should be interpreted cautiously. The reliance on predominantly English-language, open-web sources may introduce selection bias and limit geographic generalizability, and the descriptive design does not allow inference regarding prevalence, user behavior, or causal trends. Within these constraints, web-crawling approaches may serve as valuable complementary tools to established early warning systems, supporting early signal detection and informing future toxicological and public health responses.