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Four-Week GLP Immunotoxicity Assessment of Lactoferrin Alpha Produced by Komagataella phaffii in Sprague-Dawley Rats.

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-

[Interactions between alcohol and work exposure to chemical substances].

BACKGROUND AND OBJECTIVES: The quite diffused habit of a significant assumption of alcohol drinks, can interfere with the professional exposure to chemical substances. The interaction may result in increasing their toxicity and/or modifying the parameters of the biological monitoring. It may also act as a confounding factor, not only in epidemiologic researches but also at individual level when the assessment of the occupational exposure and/or the diagnosis of an occupational diseases, is under consideration. We review available references in the literature summarizing major scientific eviden

Integrating variability in half-lives and dietary intakes to predict mercury concentration in hair.

Methylmercury (MeHg) is a bioaccumulative environmental toxin that exerts its effect on fetal and infant neurodevelopment. Mercury concentration in hair is a good biomarker of MeHg accumulation in the body, with seafood being the main source of MeHg in humans. Therefore, modeling the link between food intake and mercury concentration in hair is a key step in assessing the risk of MeHg exposure. Using repeated measurements of diet and mercury concentration in hair, we studied 125 French pregnant women who consumed seafood (e.g., fish, mollusks and crustaceans) and compared their individual esti

When nanoplastics (NPs) meet algae: Heteroaggregates exacerbate bioaccumulation, immunotoxicity, and microbial dysbiosis in the green mussel (Perna viridis).

Heteroaggregates (HAs) formed by nanoplastics (NPs) and microalgae occur ubiquitously in natural aquatic systems. However, their influence on the toxicokinetics and biological effects of NPs in marine mussels remains largely unknown. Here, the green mussels (Perna viridis) were exposed to NPs and HAs at their environmentally relevant concentrations for 21 d, followed by a 7-d depuration phase. The effects on toxicokinetics, immunological responses, and microbiota of digestive gland were evaluated. The results showed that HAs increased the uptake rate constant in digestive gland by 5.5-fold and…

Extending standard testing period in honeybees to predict lifespan impacts of pesticides and heavy metals using dynamic energy budget modelling.

Concern over reported honeybee (Apis mellifera spp.) losses has highlighted chemical exposure as a risk. Current laboratory oral toxicity te … 0 hours (summer worker lifespan) for cadmium, as the most time-dependent chemical as driven by slow toxicokinetics. Clothianidin and dimethoate exhibited more rapid toxicokinetics with 48 to 720 hour LC50s changes of <4 fold. As effects from long-term exposure may exceed those measured in short-term tests, future regulatory tests should extend to 96 hours as sta …

Is the tapeworm able to affect tissue Pb-concentrations in white rat?

The effect of gastrointestinal helminths on Pb accumulation in the host body is ambiguous. A laboratory experiment with Rattus norvegicus/Hymenolepis diminuta model was conducted to determine Pb toxicokinetics in a terrestrial host-parasite system. The ET-AAS or ICP-OES techniques were used to determine Pb concentrations (CPb) in both tapeworms and host tissues (kidney, liver, bone, testes, muscle and intestinal wall). Concerning the entire host-parasite system, the highest CPb were detected in H. diminuta. Rat kidneys and bone were the only two tissues whose mean Pb levels were lower in paras…

Incorporation of the glutathione conjugation pathway in an updated physiologically-based pharmacokinetic model for perchloroethylene in mice.

BACKGROUND: Perchloroethylene (perc) induced target organ toxicity has been associated with tissue-specific metabolic pathways. Previous physiologically-based pharmacokinetic (PBPK) modeling of perc accurately predicted oxidative metabolites but suggested the need to better characterize glutathione (GSH) conjugation as well as toxicokinetic uncertainty and variability. OBJECTIVES: We updated the previously published "harmonized" perc PBPK model in mice to better characterize GSH conjugation metabolism as well as the uncertainty and variability of perc toxicokinetics. METHODS: The updated PBP…

Evidence on Invasion of Blood, Adipose Tissues, Nervous System and Reproductive System of Mice After a Single Oral Exposure: Nanoplastics versus Microplastics.

OBJECTIVE: This study was designed to provide the evidences on the toxicokinetics of microplastics (MPs) and nanoplastics (NPs) in the bodies of mammals. METHODS: 100 nm, 3 μm, and 10 μm fluorescent polystyrene (PS) beads were administered to mice once by gavage at a dose of 200 mg/kg body weight. The levels and change of fluorescence intensity in samples of blood, subcutaneous fat, perirenal fat, peritesticular fat, cerebrum, cerebellum, testis, and epididymis were measured at 0.5, 1, 2, and 4 h after administration using an IVIS Spectrum small-animal imaging system. Histological examination…

Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human health.

Enniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic dat

Evaluation of antivenom therapy in children severely envenomed by Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus (Bot) scorpions.

One hundred and forty-seven cases of envenomed children under 15 years old presenting local and general symptoms without failure in vital functions (clinical grade II) or presenting serious general symptoms with failure in vital functions (clinical grade III) were collected during the summer seasons of 1993-1997. They were classified in six groups according to the use or not of antivenom, the route and the frequency of antivenom administration. The determination, by a sensitive ELISA, of blood venom concentration before and until 6 h after antivenom therapy, allowed the establishment of the ve

Absence of irreversible effects of aliskiren in standard juvenile rat toxicity studies.

BACKGROUND: Aliskiren is the first orally bioavailable direct renin inhibitor approved for the treatment of hypertension in adults. Juvenile toxicity studies in rats were initiated to support treatment in the pediatric population. METHODS: In Study 1, aliskiren oral administration was initiated on postpartum day (PPD) 14, after nephrogenesis was completed, and continued through PPD 70 at doses of 0, 30, 100, and 300 mg/kg/day. In-life, clinical pathology, anatomic pathology, developmental, behavioral, reproductive, and toxicokinetics evaluations were performed. In Study 2, oral administration…

The effect of environmental factors on the pharmacokinetic behaviour of organic solvent vapours.

A review of the literature concerning environmental factors affecting toxicokinetic behaviour of organic solvents revealed that alcohol consumption and exposure to other organic solvents are of great importance among such factors. An insight into how environmental factors affect the toxicokinetic behaviour of organic solvents is discussed by modelling (a) the effect of alcohol consumption on the toxicokinetics of trichloroethylene (TRI), and (b) the effect of the metabolic interaction between benzene and toluene. In general, hepatic metabolism of an organic solvent (substrate) is assumed to fo…

Biotransformation of the fungal neurotoxin Thomitrem A by primary rat hepatocytes.

The tremorgenic mycotoxin Thomitrem A is a secondary metabolite produced mainly by the fungus Penicillium crustosum that is frequently found on spoiled stored food and feed. Typical signs of intoxication observed in dogs after the consumption of food waste are emesis, tremors, seizures progressing to ataxia and lack of coordinated movements. How uptake of Thomitrem A relates to exposure is unknown so far since data on biotransformation and toxicokinetics are missing. In this study the toxin was therefore metabolised in an exploratory in vitro experiment by rat hepatocytes, and substrate deplet…

Токсичность тяжелых металлов в клиническом и экологическом здравоохранении: источники, механизмы, диагностика и научно обоснованное управление ртутью, свинцом, кадмием и арсеником.

Тяжелые металлы, включая ртуть (Hg), свинец (Pb), кадмий (Cd) и мышьяк (As), по-прежнему остаются значительными глобальными токсинами в силу их экологической стойкости, широкомасштабного антропогенного высвобождения и серьезного биологического воздействия. Этот обзор укрепляет нынешнее понимание их природных и промышленных источников, круговорота окружающей среды, маршрутов воздействия на человека и факторов уязвимости на уровне населения. Она охватывает их токсикокинетику и токсикодинамику, делая акцент на специфических для каждого вида механизмах поглощения, распределения и травмирования, вк

Совпадение в аннотации оригинала
Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental p … environmental cycling, human exposure routes, and population-level vulnerabilities. It covers their toxicokinetics and toxicodynamics, emphasizing species-specific absorption, distribution, and injury mechanisms, including oxidative stress, thiol binding, mitochondrial dysfunction, endocrine disruption, and cancer risk. Clinical signs range from subtle neurocogn …

Toxicity studies for the use of prodrug of voriconazole in rats.

It has been reported that voriconazole is used to treat infections caused by invasive aspergillosis, fluconazole-resistant Candida, Actinopl … ion treatment. Liver-related toxic response could be reversed after recovery period. The results of toxicokinetics showed that POV can rapidly converts to voriconazole in SD rats after administration. The exposure of voriconazole in each group was significantly different between male and female rats. The results showed that the target organ for the toxic effect …

[Metal poisoning].

Metals are amongst the oldest toxic substances known to man. In today's industrialized world the sources of exposure to metals are ubiquitous both in the field of work and from polluted water, foodstuffs and the environment. Their toxicity is characterized by the metallic element in question, but this is modified by the type of compound, whether organic or inorganic, and its characteristics of hydrosolubility and liposolubility, which determines its toxicokinetics and thus the possibilities of it reaching its targets. The biomolecules most affected by metals are the proteins with enzymatic act…

Firm evidence for the detoxification of senecionine-induced hepatotoxicity via N-glucuronidation in UGT1A4-humanized transgenic mice.

Uridine diphosphate glucuronosyltransferase (UGT)1A4 is responsible for N-glucuronidation of tertiary amines but is a pseudogene in commonly used rodent models in toxicity and safety assessment. As a continuation of our investigation into the toxicity and safety assessment of pyrrolizidine alkaloid (PA)-containing herbs, we generated a UGT1A4-humanized (hUGT1A4) transgenic mouse model to systematically study the toxicity, metabolism network, and toxicokinetic characteristics of senecionine (a representative toxic PA) and compared with that in the wide-type controls in parallel. As results, sen

[Delirium as a late onset manifestation of quetiapine intoxication].

In this article we describe the developments of two patients who were hospitalized after a quetiapine overdose, subsequently developing deli … redict further clinical outcome. The changes in pharmacokinetics due to the intoxication, so-called toxicokinetics, are the underlying cause.

Developmental Toxicity Study for the Antimalarial Drug Combination Cabamiquine-Pyronaridine Using a Translational Approach.

BACKGROUND: The safety of pharmacological treatments during pregnancy is a significant concern, as many medications lack comprehensive repro … ses in the ZEDTA revealed no toxicity effects at ongoing clinical study doses. Pharmacokinetics and toxicokinetics modeling do not suggest the potential of cabamiquine and pyronaridine to cause toxicity at the forecast clinical study doses and anticipated exposures. DISCUSSION: The combined findings from the rat EFD study, ZEDTA, and model-based pharmacokinetic …

Temephos, an organophosphate larvicide for residential use: a review of its toxicity.

Temephos (O,O,O',O'-tetramethyl O,O'-thiodi-p-phenylene bis(phosphorothioate)) is a larvicide belonging to the family of organophosphate pesticides used for the control of different vectors of diseases, such as dengue, Zika, chikungunya, and dracunculiasis. The aim of this review was to discuss the available published information about temephos toxicokinetics and toxicity in mammals. Temephos is quickly absorbed in the gastrointestinal tract, distributed to all organs, and then it accumulates mainly in adipose tissue. It is metabolized by S-oxidation, oxidative desulfuration, and hydrolysis re…