scholarly journals Toxicity Studies of Ethyl Maltol and Iron Complexes in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Zhen Li ◽  
Jieli Lu ◽  
Chonghui Wu ◽  
Quanhai Pang ◽  
Zhiwei Zhu ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Iron Complexes ◽  
Oral Exposure ◽  
Alternative Strategies ◽  
Male And Female ◽  
Endocrine Organs ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Preliminary Study ◽  
Haematological Data

Ethyl maltol and iron complexes are products of ethyl maltol and the iron found in the cooking pots used to prepare the Chinese dish, hot-pot. Because their safety is undocumented, the toxicity study of ethyl maltol and iron complexes was conducted in male and female Kunming (KM) mice. The animal study was designed based on the preliminary study conducted to determine the median lethal dose (LD50). The doses used in the study were 0, 1/81, 1/27, 1/9, and 1/3 of the LD50(mg kg body weight (BW)−1day−1) dissolved in the water. The oral LD50of the ethyl maltol and iron complexes was determined to be 743.88 mg kg BW−1in mice. The ethyl maltol and iron complexes targeted the endocrine organs including the liver and kidneys following the 90 D oral exposure. Based on the haematological data, the lowest-observed-adverse-effect level (LOAEL) of the ethyl maltol and iron complexes was determined to be 1/81 LD50(9.18 mg kg BW−1 day−1) in both male and female mice. Therefore, we suggest that alternative strategies for preparing the hot-pot, including the use of non-Fe-based cookware, need to be developed and encouraged to avoid the formation of the potentially toxic complexes.

Toxicologic Characterization of a Novel Explosive, Guanidinium 3,4-Dinitropyrazolate (GDNP), in Female Rats and Ames Mutagenicity Assay

2012 ◽  
Vol 31 (5) ◽  
pp. 441-453 ◽  
Author(s):  
Larry R. Williams ◽  
Valerie H. Adams ◽  
Shannon M. Wallace ◽  
Mark S. Johnson
Keyword(s):  
Adverse Effect ◽  
Tap Water ◽  
Water Solution ◽  
Military Training ◽  
Lethal Dose ◽  
Female Rats ◽  
Oral Exposure ◽  
Bacterial Strains ◽  
Adverse Effect Level ◽  
Effect Level

Sustainable use of military training ranges requires the development of compounds that have a minimal impact to the environment when used in a weapon system. Guanidinium 3,4-dinitropyrazolate (GDNP) is a novel explosive compound of interest for application in some weapon systems. Little is known of its toxicologic properties. To ensure the health of potentially exposed personnel and the environment, initial toxicity investigations were conducted and the results were compared with another widely used energetic (hexahydro-1,3,5-trinitro-1,3,5-triazine [RDX]). In a microplate Ames assay, GDNP was not cytotoxic to bacterial tester strains at concentrations less than 100 μg/mL. However, GDNP was mutagenic to 4 of 5 bacterial strains with and without S9 metabolic incubation at concentrations as low as 0.7 μg/mL. Unlike RDX, GDNP did not have an affinity for the γ-aminobutyric acid(A) receptor convulsant site and was predicted to not induce seizure. After acute oral dosing in female rats, the median lethal dose in female rats of GDNP in tap water solution was determined to be 720 mg/kg. Daily oral exposure to 500 mg/kg per d of GDNP for 14 days caused weight loss, increased liver and spleen weights, and adverse histopathologic events in kidney and spleen. These adverse events were not observed in animals receiving lower doses of GDNP. In this study, the lowest-observed-adverse-effect-level from oral exposure to GDNP for 14 days was 500 mg/kg per d and the no-observable-adverse-effect-level was 152 mg/kg per d.

scholarly journals TOXICITY EVALUATION OF AMMONIUM SULFATE TO ALBINO RAT

2016 ◽  
Vol 10 (1) ◽  
pp. 313
Author(s):  
Siva Kumar T ◽  
Shobha Rani A ◽  
Sujatha K ◽  
Purushotham B ◽  
Neeraja P
Keyword(s):  
Adverse Effect ◽  
Single Dose ◽  
Ammonium Sulfate ◽  
Lethal Dose ◽  
Inorganic Fertilizer ◽  
Albino Rats ◽  
Albino Rat ◽  
Median Lethal Dose ◽  
Adverse Effect Level ◽  
Effect Level

ABSTRACTObjective: The present study was designed to find out the acute median lethal dose (LD50) of ammonium sulfate (inorganic fertilizer) in Wister albino rats.Methods: A single dose of ammonium sulfate dissolved in distilled water (Milli-Q) and administered intraperitoneally at concentrations of 10, 30, 50,70, 90, 110, 130, and 170 mg/kg body weight, respectively, to experimental animals, and then, they were observed every 3 hrs from prior dose giventime, later 6 hrs, 12 hrs, 24 hrs, to 48 hrs of noticing any abnormal behaviors and toxic signs, symptoms. After 48 hrs, counted the number of ratsdeparted in each group and mortality percentage was calculated.Results: The obtained results were evaluated by the Statistical Probit Analysis Method and 48 hrs LD value for albino rats was found tobe 91.5 mg/kg. At a single dose of 10 mg/kg, there is no morality and toxic behaviors were observed. Therefore, this concentration is considered asno observed adverse effect level dose.Conclusion: From the earlier consequences, identification and evaluation of the LD5050 against ammonium sulfate is crucial for understanding thehyperammonemia because ammonium sulfate has been highly utilized as inorganic fertilizer in agriculture and household gardens. Thus, theknowledge about toxic impacts of ammonia useful for clinical or toxicological approaches; however, the toxicity data are unclear. Hence, the in vitroLD50 evaluations of target chemical in Wistar rats is highly associated toward in ammonia-related peculiar disorders perceptive and therapy.Keywords: Ammonium sulfate, Fertilizer, Median lethal dose, Mortality, No observed adverse effect level.

Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD50) and No-observed-adverse-effect level (NOAEL)

Toxicon ◽  
2020 ◽  
Vol 177 ◽  
pp. 16-24 ◽  
Author(s):  
Andrea Boente-Juncal ◽  
Carmen Vale ◽  
Mercedes Camiña ◽  
J. Manuel Cifuentes ◽  
Mercedes R. Vieytes ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Acute Toxicity ◽  
Lethal Dose ◽  
Adverse Effect Level ◽  
Effect Level

A Preliminary 13-Week Oral Toxicity Study of Ginger Oil in Male and Female Wistar Rats

2011 ◽  
Vol 30 (6) ◽  
pp. 662-670 ◽  
Author(s):  
Kottarapat Jeena ◽  
Vijayastelter B. Liju ◽  
Ramadasan Kuttan
Keyword(s):  
Wistar Rats ◽  
Hematological Parameters ◽  
Zingiber Officinale ◽  
Female Rats ◽  
Oral Toxicity ◽  
Male And Female ◽  
Male And Female Rats ◽  
Adverse Effect Level ◽  
Female Wistar Rats ◽  
Effect Level

Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

scholarly journals Acuteβ-N-Methylamino-L-alanine Toxicity in a Mouse Model

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Maitham Ahmed Al-Sammak ◽  
Douglas G. Rogers ◽  
Kyle D. Hoagland
Keyword(s):  
Adverse Effect ◽  
Lethal Dose ◽  
Naturally Occurring ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Outbred Mice ◽  
Nih Swiss ◽  
And Control ◽  
Lateral Sclerosis

The cyanobacterial neurotoxinβ-N-methylamino-L-alanine (BMAA) is considered to be an “excitotoxin,” and its suggested mechanism of action is killing neurons. Long-term exposure to L-BMAA is believed to lead to neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases and amyotrophic lateral sclerosis (Lou Gehrig’s disease). Objectives of this study were to determine the presumptive median lethal dose (LD50), the Lowest-Observed-Adverse-Effect Level (LOAEL), and histopathologic lesions caused by the naturally occurring BMAA isomer, L-BMAA, in mice. Seventy NIH Swiss Outbred mice (35 male and 35 female) were used. Treatment group mice were injected intraperitoneally with 0.03, 0.3, 1, 2, and 3 mg/g body weight L-BMAA, respectively, and control mice were sham-injected. The presumptive LD50of L-BMAA was 3 mg/g BW and the LOAEL was 2 mg/g BW. There were no histopathologic lesions in brain, liver, heart, kidney, lung, or spleen in any of the mice during the 14-day study. L-BMAA was detected in brains and livers in all of treated mice but not in control mice. Males injected with 0.03 mg/g BW, 0.3 mg/g BW, and 3.0 mg/g BW L-BMAA showed consistently higher concentrations (P< 0.01) in brain and liver samples as compared to females in those respective groups.

scholarly journals Acute and Subchronic Oral Toxicity of Oil Palm Puree in Sprague–Dawley Rats

2020 ◽  
Vol 17 (10) ◽  
pp. 3404
Author(s):  
Zaida Zainal ◽  
Augustine Ong ◽  
Choo Yuen May ◽  
Sui Kiat Chang ◽  
Afiqah Abdul Rahim ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Pharmaceutical Formulations ◽  
Toxicity Study ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Subchronic Toxicity ◽  
Organ Weights ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Palm puree is rich in antioxidants and is produced via blending various proportions of mesocarp fibre and crude palm oil. The aim of this study was to assess the acute and subchronic toxicity of palm puree in male and female Sprague–Dawley rats. For the acute toxicity study, animals administered single palm-puree doses (2000 mg kg−1) by gavage were observed daily for 14 d. For the subchronic toxicity study, the rats were administered 500, 1000, or 2000 mg kg−1 palm puree daily for 28 d. We evaluated body and organ weights; performed haematological, biochemical, and histopathological analyses of blood and organ samples during and after treatment; and calculated the oral no-observed-adverse-effect level (NOAEL). The toxicity studies showed no signs of toxicity or mortality. The haematological, biochemical, and histopathological analyses and body and organ weights indicated no evidence of substantial toxicity at any dose of palm puree. The oral lethal dose and NOAEL for the palm puree were greater than 2000 mg kg−1 d−1 over 28 d. To the best of our knowledge, the present study is the first to confirm the safety of palm puree as a novel functional food. These encouraging results warrant further studies to elucidate its potential for pharmaceutical formulations.

Acute toxicity of a single dose DATR, recombinant soluble human TRAIL mutant, in rodents and crab-eating macaques

2010 ◽  
Vol 29 (8) ◽  
pp. 645-652 ◽  
Author(s):  
YX Zou ◽  
XD Zhang ◽  
Y. Mao ◽  
GC Lu ◽  
M. Huang ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Single Dose ◽  
Lethal Dose ◽  
Intraperitoneal Administration ◽  
Inflammatory Cell Infiltrate ◽  
Toxic Dose ◽  
Adverse Effect Level ◽  
Liver And Kidney ◽  
Effect Level ◽  
Rats And Mice

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to possess activity of inducing apoptosis in variety of tumor cells in preclinical models. Several mutational versions of TRAIL have been studied as promising agents for cancer therapy and the recombinant soluble human TRAIL mutant (DATR) is one of them. The objective of the present study was to provide possible toxic target organs and proposal non-toxic dose level of DATR for clinical usage. Rodents and crab-eating macaques were used to estimate potential adverse effects of DATR following a single dose administration. The median lethal dose (LD50 ) of intravenous injection to rats and mice was determined as 262.0 and 1018.0 mg/kg b.w., respectively. The LD50 of intraperitoneal administration to mice was found to be 1432.1 mg/kg b.w. The main changes in macaques were found in the following aspects. Hematology analysis revealed an obvious decrease of red blood cell count (RBC), hemoglobin (HB) and hematocrit (HCT) after injection. Serum biochemical analysis showed an apparent increase of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood urea nitrogen (BUN) and creatinine (Crea). Furthermore, inflammatory cell infiltrate in liver and kidney was found by microscope. All the disorders suggested that liver, renal and hematological systems might be the target effectors of toxic effect induced by DATR. Based on the results of this study, the no observed-adverse-effect level (NOAEL) and the lowest observed-adverse-effect level of DATR in macaques are 90.0 and 135.0 mg/kg b.w., respectively.

scholarly journals Ca2+ Imaging With Two-photon Microscopy to Detect the Disruption of Brain Function in Mice Administered With Neonicotinoid Insecticides

2021 ◽  
Author(s):  
Anri Hirai ◽  
Shouta Sugio ◽  
Collins Nimako ◽  
Shouta Nakayama ◽  
Keisuke Kato ◽  
...  
Keyword(s):  
Lethal Dose ◽  
Neuronal Population ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Highly Sensitive Detection ◽  
Neonicotinoid Pesticides ◽  
The Brain

Abstract Neonicotinoid pesticides are insecticides that are insecticides that reportedly have untargeted effects on bees and dragonflies causing a reduction in numbers. Neonicotinoids act as neuroreceptor modulators, and some studies have reported their association with neurodevelopmental disorders. However, the effect of neonicotinoids on the central nervous system has not yet been identified. Herein, we conducted in vivo Ca2+ imaging using a two-photon microscope to detect abnormal activity of neuronal circuits in the brain using a neonicotinoid. The oral administration of acetamiprid (ACE) (20 mg/kg body weight [bw]) in mature mice with a less than the no-observed-adverse-effect level (NOAEL) and a tenth or half of the median lethal dose (LD50) of nicotine (0.33 or 1.65 mg/kg bw, respectively), as a typical nAChRs agonist, increased anxiety-like behavior associated with altered activities of the neuronal population in the somatosensory cortex. Furthermore, we detected ACE and metabolites in the brain 1 h after ACE administration. The results suggested that in vivo Ca2+ imaging using a two-photon microscope enabled the highly sensitive detection of neurotoxicant-mediated brain disturbance of nerves.

scholarly journals Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

Toxins ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 75 ◽  
Author(s):  
Paula Abal ◽  
M. Louzao ◽  
Alvaro Antelo ◽  
Mercedes Alvarez ◽  
Eva Cagide ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Lethal Dose ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Adverse Effect Level ◽  
Effect Level

scholarly journals Toxicity, transfer and depuration of anatoxin-a (cyanobacterial neurotoxin) in medaka fish exposed by single-dose gavage

2019 ◽  
Author(s):  
Simon Colas ◽  
Charlotte Duval ◽  
Benjamin Marie
Keyword(s):  
Single Dose ◽  
Recovery Period ◽  
Lethal Dose ◽  
Medaka Fish ◽  
Fish Flesh ◽  
Oral Liquid ◽  
Adverse Effect Level ◽  
Effect Level ◽  
The Mean ◽  
Kinetics Of

AbstractThe proliferations of cyanobacteria are increasingly prevalent in warm and nutrient-enriched waters and occur in many rivers and water bodies due especially to eutrophication. The aim of this work is to study in female medaka fish the toxicity, the transfer and the depuration of the anatoxin-a, a neurotoxin produced by benthic cyanobacterial biofilms. This work will provide answers regarding acute toxicity induced by single gavage by anatoxin-a and to the risks of exposure by ingestion of contaminated fish flesh, considering that data on these aspects remain particularly limited.The oral LD50 of a single dose of (±)-anatoxin-a was determined at 11.50 µg.g−1. First of all, lethal dose (100% from 20 µg.g−1) provokes rapid respiratory paralysis (in 1-2 min) of the fish inducing the death by asphyxia. Noticeably, no death nor apparent neurotoxicologic effect occurred during the experimentation period for the 45 fish exposed to a single sub-acute dose of (±)-anatoxin-a corresponding to the no observable adverse effect level (NOAEL = 6.67 µg.g−1). Subsequently, the toxico-kinetics of the (±)-anatoxin-a was observed in the guts, the livers and the muscles of female medaka fish for 10 days.In parallel, a protocol for extraction of anatoxin-a has been optimized beforehand by testing 3 different solvents on several matrices, the extraction with 75% methanol + 0.1% formic acid appearing to be the most efficient. Anatoxin-a was quantified by high-resolution qTOF mass spectrometry coupled upstream to a UHPLC chromatographic chain. The toxin could not be detected in the liver after 12 h, and in the gut and muscle after 3 days. The mean clearance rates of (±)-anatoxin-a calculated after 12 h are above 58%, 100% and 90% for the guts, the livers and the muscles, respectively. Non-targeted metabolomics investigations performed on the fish liver indicates that the single sub-acute exposure by gavage induces noticeable metabolome dysregulations, including important phospholipid decreases, with an organism recovery period of above 12-24h. Overall, the medaka fish do not appear to accumulate (±)-anatoxin-a and to largely recover after 24h following a single sub-acute oral liquid exposure at the NOAEL.

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