International Journal of Toxicology最新文献

Oral toxicity and toxicokinetic properties of human lactoferrin (LF) alpha produced in Komagataella phaffii (effera™) were investigated in adult Sprague-Dawley rats over a 28-day period under good laboratory practice conditions. Main study dosing used groups of 10 rats/sex/dose, and a secondary study evaluating toxicokinetic parameters used 6 rats/sex/dose. The vehicle control group received sodium citrate buffer, test groups received daily doses of 200, 600, and 2000 mg of effera™ per kg body weight, and the comparative control group received 2000 mg bovine LF (bLF)/kg body weight per day. T-cell-dependent antibody response against keyhole limpet hemocyanin and immunophenotyping of the spleen were performed as measures of immunotoxicity. Clinical observations, body weight, hematology, coagulation, clinical chemistry, urinalysis, immunotoxicity, gross necropsy, and histopathology were assessed. Toxicokinetic parameters were analyzed as an indication of LF bioavailability, and anti-LF antibody assays were conducted to detect antibodies produced against LF to measure immunogenicity. No treatment related toxicologically significant changes were observed. Based on the absence of toxicologically relevant changes, effera™ is well tolerated in rats at doses up to 2000 mg rhLF/kg/day, an amount ∼400 times that of the estimated daily intake at the 90th percentile proposed for human adult use.

Etomidate, an ultrashort-acting non-barbiturate sedative derived from imidazole, exerts potent inhibitory effects on the central nervous system. It is commonly employed for the induction of intravenous general anaesthesia or assisted anaesthesia. Recently, etomidate has emerged as an alternative to narcotics and novel psychoactive substances, leading to an increasing trend of abuse. Chronic overdose of etomidate can result in irreversible brain damage and various mental disorders. Severe cases may manifest as mental disturbances, behavioural disorders, self-mutilation and even death. The toxicological mechanisms of etomidate remain poorly understood. Additionally, there is limited information on the clinical symptoms and histopathological changes associated with etomidate poisoning and standardized detection methods for etomidate in blood, urine and hair are lacking. Consequently, further research on toxicological pathology and the development of reliable testing methods is crucial. This study reviews the metabolism, distribution, adverse reactions, poisoning manifestations, toxicology mechanisms and testing methods of etomidate.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 10 alkanoyl lactyl lactate salts. These ingredients have the surfactant function in cosmetics in common. The Panel reviewed data relevant to the safety of these ingredients, and concluded that these 10 ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be nonirritating and nonsensitizing, which may be based on a quantitative risk assessment (QRA) or other accepted methodologies.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 10 polyol phosphates. Some of the possible functions in cosmetics that are reported for this ingredient group are chelating agents, oral care agents, and skin conditioning agents. The Panel reviewed relevant data relating to the safety of these ingredients under the intended conditions of use in cosmetic formulations, and concluded that Sodium Phytate, Phytic Acid, Phytin, and Trisodium Inositol Triphosphate are safe in cosmetics in the present practices of use and concentration described in the safety assessment. The Panel also concluded that the data are insufficient to determine the safety of the following 6 ingredients as used in cosmetics: Disodium Glucose Phosphate, Manganese Fructose Diphosphate, Sodium Mannose Phosphate, Trisodium Fructose Diphosphate, Xylityl Phosphate, and Zinc Fructose Diphosphate.

The Expert Panel for Cosmetic Ingredient Safety (Panel) first published a safety assessment of Sodium Dehydroacetate and Dehydroacetic Acid in 1985. The Panel previously concluded that Sodium Dehydroacetate and Dehydroacetic Acid are safe as used in the present practices of use and concentration, as stated in that report. Upon re-review in 2003, the Panel reaffirmed the original conclusion, as published in 2006. The Panel reviewed updated frequency and concentration of use data again in 2023, in addition to any newly available, relevant safety data. Considering this information, as well as the information provided in the original safety assessment and the prior re-review document, the Panel reaffirmed the 1985 conclusion.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of three methylxanthines, Caffeine, Theobromine, and Theophylline, as used in cosmetics. All of these ingredients are reported to function as skin-conditioning agents in cosmetic products. The Panel reviewed the data relevant to the safety of these ingredients and concluded that Caffeine, Theobromine, and Theophylline 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) reviewed the safety of 30 vinylpyrrolidone polymers as used in cosmetic products; most of these ingredients have the reported cosmetic function of film former in common. The Panel reviewed data relevant to the safety of these ingredients, and determined that 27 vinylpyrrolidone polymers are safe in cosmetics in the present practices of use and concentration described in the safety assessment. The Panel also concluded that the available data are insufficient to make a determination that 3 vinylpyrrolidone polymers (all urethanes) are safe under the intended conditions of use in cosmetic formulations.

Nonclinical safety studies are typically conducted to establish a toxicity profile of a new pharmaceutical in clinical development. Such a profile may encompass multiple differing types of animal studies, or not! Some types of animal studies may not be warranted for a specific program or may only require a limited evaluation if scientifically justified. The goal of this course was to provide a practical perspective on regulatory writing of a dossier(s) using the weight of evidence (WOE) approach for carcinogenicity, drug abuse liability and pediatric safety assessments. These assessments are typically done after some clinical data are available and are highly bespoke to the pharmaceutical being developed. This manuscript will discuss key data elements to consider and strategy options with some case studies and examples. Additionally, US FDA experience with dossier(s) including WOE arguments is discussed.