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 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

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 In VitroandIn VivoToxicity ofGarciniaor Hydroxycitric Acid: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Li Oon Chuah ◽  
Swee Keong Yeap ◽  
Wan Yong Ho ◽  
Boon Kee Beh ◽  
Noorjahan Banu Alitheen
Keyword(s):  
Adverse Effect ◽  
Weight Control ◽  
Scientific Evidence ◽  
Potential Toxicity ◽  
Hydroxycitric Acid ◽  
Diet Supplements ◽  
Adverse Effect Level ◽  
History Of ◽  
Effect Level

Obesity is one of the pandemic chronic diseases commonly associated with health disorders such as heart attack, high blood pressure, diabetes or even cancer. Among the current natural products for obesity and weight control,Garciniaor more specifically hydroxycitric acid (HCA) extracted fromGarciniahas been widely used. The evaluation of the potential toxicity of weight control supplement is of the utmost importance as it requires long term continuous consumption in order to maintain its effects. Majority of reports demonstrated the efficacy ofGarcinia/HCA without any toxicity found. However, a few clinical toxicity reports on weight-loss diet supplements of which some were combinations that includedGarcinia/HCA as an active ingredient showed potential toxicity towards spermatogenesis. Nonetheless, it cannot be concluded thatGarcinia/HCA is unsafe. Those products which have been reported to possess adverse effects are either polyherbal or multi-component in nature. To date, there is no case study or report showing the direct adverse effect of HCA. The structure, mechanism of action, long history of the use ofGarcinia/HCA and comprehensive scientific evidence had shown “no observed adverse effect level (NOAEL)” at levels up to 2800 mg/day, suggesting its safety for use.

scholarly journals Looking for the LOAEL or NOAEL Concentration of Nickel-Oxide Nanoparticles in a Long-Term Inhalation Exposure of Rats

2021 ◽  
Vol 22 (1) ◽  
pp. 416
Author(s):  
Boris A. Katsnelson ◽  
Ivan N. Chernyshov ◽  
Svetlana N. Solovyeva ◽  
Ilzira A. Minigalieva ◽  
Vladimir B. Gurvich ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Nickel Oxide ◽  
Inhalation Exposure ◽  
Oxide Nanoparticles ◽  
Nickel Oxide Nanoparticles ◽  
Adverse Effect Level ◽  
Effect Level

Rats were exposed to nickel oxide nano-aerosol at a concentration of 2.4 ± 0.4 µg/m3 in a “nose only” inhalation setup for 4 h at a time, 5 times a week, during an overall period of 2 weeks to 6 months. Based on the majority of the effects assessed, this kind of exposure may be considered as close to LOAEL (lowest observed adverse effect level), or even to NOAEL (no observed adverse effect level). At the same time, the experiment revealed genotoxic and allergic effects as early as in the first weeks of exposure, suggesting that these effects may have no threshold at all.

scholarly journals Toxicological evaluation of alpha-galacto-oligosaccharides shows no adverse effects over a 90-day study in rats

2017 ◽  
Vol 1 ◽  
pp. 239784731771640
Author(s):  
Claire Kruger ◽  
Nicole Beauchamp ◽  
Virginie Modeste ◽  
Fanny Morel-Despeisse ◽  
Eric Chappuis
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Toxicological Evaluation ◽  
Organ Weights ◽  
Naturally Occurring ◽  
Adverse Effect Level ◽  
Effect Level

AlphaGOS®, an alpha-galacto-oligosaccharides product, is a mixture of bi-, tri- and tetrasaccharides derived from oligosaccharides in the raffinose family of oligosaccharides (RFOs), naturally occurring plant-derived sugars. RFOs are alpha α-1,6-linked chains of D-galactose attached to the 6-position of D-glucose and differ from the currently commercially available beta-galacto-oligosaccharides products in the chirality and glyosidic bonds. In order to determine the safety of AlphaGOS, rats were given 2000 mg AlphaGOS/kg/day daily via gavage over 90 days. Daily assessments of the animals showed no adverse clinical signs. No adverse treatment-related changes in feed consumption, body weight, clinical chemistry or hematology were noted. There were no adverse treatment-related changes in organ weights, gross or histopathology. Given these findings, it can be concluded that the no observed adverse effect level for AlphaGOS is greater than 2000 mg/kg/day.

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 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

Selective Vulnerability of Dopaminergic Systems To Industrial Chemicals: Risk Assessment of Related Neuroendocrine Changes

1998 ◽  
Vol 14 (1-2) ◽  
pp. 311-323 ◽  
Author(s):  
Antonio Mutti ◽  
Audrey Smargiassi
Keyword(s):  
Adverse Effect ◽  
Selective Vulnerability ◽  
Common Finding ◽  
Serum Prolactin ◽  
Industrial Chemicals ◽  
Limit Values ◽  
Reference Limit ◽  
Individual Level ◽  
Adverse Effect Level ◽  
Effect Level

Increased serum prolactin (PRL) is a common finding among subjects exposed to styrene, perchloroethylene, lead (Pb), and manganese (Mn) at levels below the current threshold limit values. On a group basis, abnormally high basal PRL shows a dose-related distribution among workers exposed to styrene, Pb, and Mn. On the basis of dose-response relationships, the benchmark doses (BMD) for styrene metabolites in urine, lead in blood (Pb-B), and Mn in urine (Mn-U), are 4 mg/g creatinine, 112 μg/L, and 0.3 μg/L, respectively. Noteworthy, the BMD for Mn-U and Pb-B is well below the upper reference limit. A shift in the distribution but not in the prevalence of abnormally high values of serum PRL was observed among perchloroethylene-exposed dry cleaners, which makes interpretation in terms of risk difficult. The measurement of PRL thus provides opportunities for early identification of excess exposure to neurotoxic chemicals affecting dopaminergic control of pituitary secretion. For styrene, Pb, and Mn the BMD provides an objective and statistically determined threshold, which seems to be in good agreement with the estimated no-observed-adverse-effect-level (NOAEL). The NOAEL, however, is based on traditional approaches that require the application of uncertainty factors, e.g., a default factor of 10 when extrapolating the NOAEL from the lowest-observed- adverse-effect-level (LOAEL). Due to its sensitivity to a number of potential confounders, caution must be exercised when using PRL as a screening test at the individual level. Also, age and sex dependent variations in susceptibility may hamper extrapolations from the occupational settings to the general population.

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