Sub-acute versus sub-chronic oral toxicity study in rats: comparative study of 82 compounds.

Evaluation of the acute and sub-acute toxicity of the ethanolic extract of Pericampylus glaucus (Lam.) Merr. in BALB/c mice

A sub-chronic (13 weeks) oral toxicity study in rats and an in vitro genotoxicity study with Korean pine nut oil (PinnoThin TG™)

Comparative subchronic studies on 2,4-dichlorophenoxyacetic acid, amine, and ester in rats.

Ocimum gratissimum is a medicinal plant that is widely used in the world, and has multiple uses in traditional medicine, including the treatment of epilepsy in children. The objective of this study was to evaluate the acute and subacute toxicity of decoction of Ocimum gratissimum leaves in Mus musculus mice. For the acute toxicity test, a single dose of 50, 300 and 2000 mg/kg of extract was administered orally to randomly selected to mice; then they were observed for 14 days. In the subacute study, the extract was administered orally daily to mice of both sexes at doses of 250, 500 and 1000 mg/kg body weight during the 28 days of the experiment. finally, Body weight was measured weekly, haematological, biochemical and histological analysis were performed. The aqueous extract of Ocimum gratissimum did not cause any mortality or significant changes in relative animal and organ weights during the acute and subacute tests at all doses. Few significant changes in food and water intake were observed at the dose of 1000 mg/kg. The highest dose of aqueous extract (2000 mg/kg) administered orally in the acute toxicity did not induce mortality. There were no significant changes in haematological parameters in the different batches treated. Therefore, the oral aqueous extract of Ocimum gratissimum did not produce any adverse side effects compared to the control group (distiller water) in the acute and subacute study. We can therefore conclude that Ocimum gratissimum can be considered safe in oral administration at the dose tested since it did not cause lethality or undesirable effects in general behaviour in white mice.

Prediction of carcinogenic potential of chemicals using repeated-dose (13-week) toxicity data

HC Red No. 7 functions as a semipermanent (direct) hair colorant in one cosmetic product at 1%. Analytical studies found the relative purity of HC Red No. 7 to be > 98.5%. Impurities may include 2-nitro-benzene-1,4-diamine; 3-(4-amino-3-nitro-phenyl)-oxazolin-2-one; 2-chloroethyl 4-amino-3-nitrophenylcarbamate; residual solvents ethanol, DMF, or isopropyl acetate; chloride ions; and heavy metals. Around 0.10% of the applied HC Red No. 7 was absorbed in human dermatomed skin samples. In an acute oral toxicity study in rats, the maximum nonlethal dose was 300 mg/kg. The no observed effect level (NOEL) in a subchronic oral toxicity study in rats was 50 mg/kg day(- 1). HC Red No. 7 was not a dermal or ocular irritant in rabbits, but lymphoproliferative responses in mice indicated that HC Red No. 7 should be considered a moderate sensitizer. The NOEL for maternal toxicity was 50 mg/kg/day and the no observed adverse effect level (NOAEL) for embryonic development was 200 mg/kg/day in a prenatal toxicity study of HC Red No. 7 using rats. HC Red No. 7 was nonmutagenic at the hprt locus but mutagenic at the TK locus in mouse lymphoma cells, was mutagenic in several Salmonella typhimurium strains, was not active in an unscheduled DNA synthesis assay, and was unclear in a micronucleus assay in human lymphocyte cultures. No carcinogenicity studies were available, nor were any clinical tests reported. Available hair dye epidemiology studies are insufficient to conclude a causal relationship between hair dye use and cancer or other diseases, but more relevant is that direct hair dyes, although not the focus in all investigations, appear to have little evidence of an association with adverse events as reported in epidemiology studies. As reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, HC Red No. 7 appears to be a moderate sensitizer in animals. No human sensitivity data concerning this ingredient have been reported. However, hair dyes containing HC Red No. 7, as coal tar hair dye products, are exempt from the principal adulteration provision and from the color additive provisions in sections 601 and 706 of the Federal Food, Drug, and Cosmetic Act, when the label bears a caution statement and patch test instructions for determining whether the product causes contact dermatitis. The Expert Panel expects that following this procedure will identify prospective individuals who would have an irritation/sensitization reaction and allow them to avoid significant exposures. The CIR Expert Panel also noted that mutagenicity studies available for HC Red No. 7 gave both positive and negative results. Based on the available data, it was concluded that, at most, this ingredient is a weak mutagen. Due to its low dermal absorption potential and its use as a semipermanent hair dye, the CIR Expert Panel believes there is low risk of genotoxicity and that HC Red No. 7 is safe as a hair dye ingredient in the practices of use and concentrations as described in this safety assessment.

Autoimmune diseases exhibit active and remission phases. Tissues may retain an 'inflammatory memory', increasing relapse risk after stopping treatment, necessitating ongoing therapy following remission induction. Understanding inflammatory memory and remission-to-recurrence transitions could guide strategies for achieving lasting remission while minimising long-term medication use and costs. Integrative approaches may address autoimmune conditions' multifaceted pathophysiology. Literature suggests utilising modern medicine in ultra-diluted form, with chemotherapy drugs like methotrexate undergoing ultra-dilution. However, extreme dilutions may increase toxicity due to nanoparticles' larger surface area. This study evaluated methotrexate's toxicity at 12c and 30c dilutions. An acute toxicity study evaluated single-dose effects of methotrexate 12c and 30c (2000 μL/kg) in female mice over 14days, per OECD 423 guidelines. A repeated dose study investigated the impacts of methotrexate 12c and 30c (200 μL/kg) on male and female mice, following OECD 407 protocol. Mortality, clinical signs, body weight, haematology, biochemistry, and histopathology were comprehensively assessed. The acute toxicity study showed no animal fatalities with methotrexate, indicating the median lethal dose exceeded 2000 μL/kg. In the subacute study, methotrexate at 12c and 30c caused no mortality, adverse effects, or abnormal weight changes. Evaluations of haematological parameters, biochemical markers, and histopathological analyses of vital organs revealed no abnormalities. The research study indicates that the oral administration of methotrexate at 12c and 30c to mice over an extended duration, with a dosage of 200 μL/kg, did not exhibit any signs of toxicity or adverse reactions, thus suggesting a safe profile for these potencies.

BackgroundAzadirachta indica, Khaya senegalensis, Anogeissus leiocarpus and Tamarindus indica are important ethnomedicinal plants used for health mitigation since the history of mankind. They are used discretionarily in folkloric medicine on the premise that they are natural products devoid of synthetic preservatives. However, nature endows plants with metabolites for warding off potential attacks from animals and the environment. Some of these metabolites are responsible for toxicity of some plants. Furthermore, drug-induced liver injuries and nephrotoxicity are the leading causes of pharmaceutical attrition of promising drug candidates in clinical trials. Thus, we aimed to evaluate the safety of four ethnomedicinal plants in short-, medium- and long-term usage.MethodsRats dosed once with 5000 mg/kg extracts of each of these plants served as acute study (AS) while rats dosed daily with 2000 mg/kg for 2, 12 and 14 weeks served as sub-acute (SAS), sub-chronic (SCS) and chronic (CS) studies, respectively. Rats administered distilled water served as the negative control (NC).ResultsA. leiocarpus and T. indica significantly reduced percentage weight gain in the SCS compared to the NC. A. leiocarpus significantly (P< 0.05) increased transaminases and alkaline phosphatase in the AS only; and total protein (TP) in the AS, SAS, SCS and CS compared to the NC. K. senegalensis significantly (P< 0.05) increased alanine aminotransferase but significantly (P< 0.05) decreased TP in the AS only compared to the NC. However, A. indica and T. indica significantly (P< 0.05) increased globulin and aspartate transaminase in the CS only. Whereas A. leiocarpus and K. senegalensis significantly (P< 0.05) increased urea and creatinine in the AS than SAS, SCS and CS; Na+ and K+ were significantly higher in the SCS and CS studies compared to the NC. The histological lesions seen ranged from cellular degeneration, congestion, fibrosis to necrosis.ConclusionThus, nonlethal, reversible toxic insults occur in short-term usage (AS); while, insidious lethal toxic effects occur in medium-term (SAS) and long-term usage (SCS and CS). The ability of these plant to maintain adequate hematological parameters, bodyweight and absence of mortality may explain free usage of preparations made from these plants in folkloric medicine.

Introduction: Antibiotics are compounds used to treat inflammation; fluoroquinolones are antibiotics used in resistant cases. Objective: The purpose of this study was to investigate acute and subacute toxicity for a new modified flouroquinolone compound (MFC 6C) – a broad spectrum antibiotic which was invented at Faculty of Pharmacy in University of Jordan – using BALB/c mice. Materials and methods: In the pilot study (8 groups; 1 Male:1 Female/group), MFC 6C was administered to these mice at dose levels of 500, 600, 700, 1000, 1200, 1600, 3000 and 5000 mg/kg/d. In the subacute study (5 groups; 5 Males:5 Females/group), MFC 6C was administered for two groups at dose levels of 500, 250 mg/kg/d for 20 d by oral gavage; other groups were control groups. Results: Before the acute study, a pilot study was conducted (on 8 separate days) and no mortality was found even at 5000 mg/kg; therefore, LD50 was found to be >5000 mg/kg and no further acute effects need to be investigated; so MFC 6C is slightly toxic. The biochemical study revealed that, in subacute toxicity study (20 consecutive days), MFC 6C 500 mg/kg caused a decrease in male and female mice blood serum SGOT [p = 0.0189 (for males), 0.0309 (for females)] and a decrease in male mice blood serum CPK level (p = 0.023). MFC 6C (250 mg/kg) caused a significant decrease of male mice blood serum sugar (p = 0.04278) and CPK level (p = 0.005). The histopathological study revealed that, in subacute toxicity study (20 consecutive days), MFC 6C (500 mg/kg) caused; periportal lymphocytic inflammation (male, 60%; female 40%), lymphoid follicle (female, 60%), neutrophilic aggregation and mitotic activity (female, 40%) in the liver. Moreover, it caused interstitial lymphocytic inflammation (male 60%; female 20%) in the kidney. Other changes like follicular hyperplasia (male 40%) were observed in the spleen. It also caused neutrophilic aggregation (male 40%) in the heart. Also, congestion and macrophages were observed. Changes like lymphocytic infiltration (male 20%; female 20%), congestion (male, 20%) and pleural mesothelial hyperplasia (female, 20%) were found in the lungs. MFC 6C (250 mg/kg), in subacute study, caused; lobular lymphocytic infiltration (male 100%; female 100%), portal lymphocytic inflammation (male 40%; female 40%), granuloma and extramedullary hematopoeisis (male 20%; female 20%), apoptotic bodies and plasma collection in the liver. On the other hand, it caused; reactive lymphoid hyperplasia (male 20%; female 20%) in the spleen. Fibrinous pericarditis (male 40%; female 40%), pericardial mesothelial hyperplasia and degenerated myofibers (male 20%; female 20%) were observed in the heart. Parenchymal lymphocytic infiltration was observed in the lungs (male 40%; female 40%). While no changes occurred in testis at the dose (250 mg/kg). No observed effect level (NOEL) was 125 mg/kg/d for 20-d subacute toxicity study. Conclusion: MFC 6C may suppress the function and\\or morphology of the body organs.

Purpose: The aim of the investigation was to find out the degree of toxicity of the herbal composite for humans, animals, or the environment. Acute and 28 days repeated sub-acute oral toxicity study of herbal composite (Herbodil®) carried out as per the current OECD guidelines.Materials and Methods: 2000mg/kg of the herbal composite was orally administered to the animals to find out the acute toxicity. The treated animals were observed for toxic signs at thirty min, one, two and four hours and thereafter once a day for the next 14 days. In sub-acute study i.e.,28 days repeated dose oral study, the mice were segregated into four groups (two set for each sex) of six mice each. Group-1 mice served as a control (untreated). Group II mice consumed lower dose of herbal composite i.e., 100 mg/kg, Group III mice consumed middle/moderate dose i.e., 200 mg/kg and Group IV mice received high dose of 400 mg/kg (orally) once daily for 28 days respectively.Results: This experimental in vivo study confirm that neither the acute toxicity study of herbal composite at the dose level of 2000mg/kg nor the sub-acute 28 days oral toxicity study developed any toxic signs, behavioural changes, or mortality during the whole study. Haematological and biochemical parameters dose not changes during the sub-acute study. Relative body weight of the mice also not change after the study.Conclusion: Experimental results obtained from the current investigation suggest that LD50 of developed herbal composite was &gt;2000 mg /kg and the herbal composite is completely safe and non-toxic for therapy.

Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study

Subchronic toxicity and genotoxicity studies of Antrodia mushroom β-glucan preparation

Toxicological assessment of a particulate yeast (1,3/1,6)-β- d-glucan in rats

Safety evaluation of arachidonic acid rich Mortierella alpina biomass in albino rats—A subchronic study

Acute and subchronic toxicity studies with detirelix, a luteinizing hormone-releasing hormone antagonist, in the rat and monkey