Toxicity Evaluation, HET-CAM Irritation, and Anti-Irritant Potential of Rice Bran Wax Policosanol Nanoemulsion

2017 ◽  
Vol 49 ◽  
pp. 44-55 ◽  
Author(s):  
Aminu Ishaka ◽  
Maznah Ismail ◽  
Mustapha Umar Imam ◽  
Rozi Mahmud ◽  
Ismaila Muhammad Sani ◽  
...  

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects. However, it has a bioavailability of less than 10%. One of the ways of improving bioavailability is by nanoemulsion formulation. We developed rice bran wax policosanol nanoemulsion (npol) using high-pressure homogenization. Even though earlier toxicological studies did not show policosanol-related toxicity, it is an essential part of the development of the therapeutic formulation to evaluate its toxicity status. In this study, in vitro, in vivo toxicity, and irritation and anti-irritation potential of the npol were evaluated. 3T3-L1 cells and Sprague Dawley rats were treated with npol in the in vitro and acute oral toxicity tests; while the Hen’s Egg Test Chorio-Allantoic membrane (HET-CAM) was used to test for its irritation and anti-irritation potential. npol at 2mg/mL showed lower toxicity to 3T3-L1 cells by MTT assay compared to the same concentration of policosanol after 24 (60 and 50% viabilities), 48 (62 and 58% viabilities), and 72 (110 and 89% viabilities) hours, respectively. npol was non-irritant and has slightly anti-irritant potential based on the HET-CAM test. There was also no significant toxicity to a limit test dose of 40 ml/Kg body weight of npol (containing 2000 mg/Kg body weight of policosanol) in acute oral toxicity test on Sprague-Dawly rats. The results suggest that policosanol nanoemulsion is a safe formulation devoid of toxicity and irritation potential.

2020 ◽  
Vol 99 (11) ◽  
pp. 1276-1279
Author(s):  
Valery N. Rakitskii ◽  
Tatiana M. Epishina ◽  
Elena G. Chkhvirkiya

Introduction. Historically, pesticides are evaluated more strictly from a medical point of view than other chemicals. Since their features, such as deliberate introduction into the environment, the possibility of contact with them by large masses of the population, and the high biological activity determine their potential danger to humans. Purpose of research - study of the biological effect of a technical product derived from triazoles when it is repeatedly ingested orally in mammals (rats), establishment of inactive and active doses, justification of the permissible daily dose (DSD) for humans. Material and methods. In acute experiments, white rats were used, including 6 animals in the group. Tested dose: 500-4000 mg/kg of body weight. A chronic (12 months) experiment was performed on 80 male rats with a bodyweight of 180-190 g at the beginning of the study. Tested doses: 5.0; 16.0 and 55.0 mg/kg of body weight (1 control and 3 experimental animals, 20 individuals each). In the dynamics of the experiment, we observed the condition and behavior of animals, water, and food consumption, recorded the timing of death, changes in body weight, physiological, biochemical, and hematological indices. Results. Indices of the acute oral toxicity on the studied product LD50 male rats were 2250 ± 483 mg/kg body weight. The dose of 5.0 mg / kg of body weight was not found to cause significant changes in all studied indices. The doses of 16.0 and 55.0 mg/kg of body weight had a polytropic effect on the body in experimental animals. Discussion. The studied product for the acute oral toxicity refers to low-hazard compounds, the doses of 16.0 and 55.0 mg/kg of body weight has a polytropic effect on the mammalian body, causing changes in carbohydrate, lipid, and lipoprotein metabolism in the body of rats - was accepted as acting. The dose of 5.0 mg / kg of body weight, when administered in rats, there are no changes in all the studied parameters throughout the experiment, is accepted as invalid. Based on the inactive dose-5.0 mg/kg of body weight and taking into account the reserve factor of 100, we have scientifically justified DSD for a person at the level of 0.05 mg/kg. Summary. The conducted sanitary and Toxicological studies indicate the need to assess the toxicity of new technical products to the mammalian body, to increase the reliability of the developed hygiene standards in environmental objects and food products.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chandrasekaran Chinampudur Velusami ◽  
Srinivasa Rao Boddapati ◽  
Srikanth Hongasandra Srinivasa ◽  
Edwin Jothie Richard ◽  
Joshua Allan Joseph ◽  
...  

Curcuma longaLinn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery ofin vitrogenotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract ofC. longawas found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight.


1992 ◽  
Vol 20 (3) ◽  
pp. 396-405 ◽  
Author(s):  
Mabel C. Calleja ◽  
Guido Persoone

In the framework of the multicentre evaluation of in vitro cytotoxicity (MEIC) programme, the first ten chemicals of the prescribed list were tested for acute toxicity in four standardised cyst-based aquatic invertebrate tests, consisting of two rotifer species (the estuarine Brachionus plicatilis and the freshwater Brachionus calyciflorus) and two crustacean species (the halophilic anostracan Artemia salina and the freshwater anostracan Streptocephalus proboscideus). Mortality was the test criterion and toxic effects, expressed as 24-hour LC50 values, were correlated with rodent and human acute oral toxicity data. Generally, a good correlation was obtained between any of the invertebrate tests and the rodent data. Likewise, the predictive screening potential of the aquatic invertebrate tests for acute oral toxicity in man was slightly better than the rat test for eight (excluding diazepam and digoxin) and nine (including diazepam, excluding digoxin) of the ten substances. The aquatic test systems, however, appear to be more suitable for compounds soluble in water.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
T. Somarathna ◽  
M. G. Thammitiyagodage ◽  
K. K. D. S. Ranaweera ◽  
G. A. S. Premakumara ◽  
M. A. Akbarsha ◽  
...  

The objective of the study was to evaluate the potential toxicity of crude n-hexane extract of Alpinia malaccensis rhizome. The in vivo acute oral toxicity was evaluated by administering a single oral dose of the extract at 0, 300, or 2000 mg/kg body weight to female Wistar rats according to modified OECD Test Guideline 423. For the in vitro cytotoxicity study, A549, HepG2, 3T3, and COS-7 cell lines were exposed to different doses of A. malaccensis extract and cell viability was assessed adopting MTT assay followed by AO/EB staining, Hoechst staining, and comet assay with a view to compare the cellular and molecular mechanisms underlying the toxicity, if any. It was found that administration of 2000 mg/kg bw dose in in vivo oral acute toxicity study did not produce significant toxicity or mortality. No significant ( p < 0.05 ) differences were observed for body weight and hematological and biochemical parameters compared to control after 14 days of treatment. No changes in behavior, body weight, hematological and biochemical parameters, and aspects of histopathology were observed when compared to the control. Thus, the possible oral lethal dose for A. malaccensis extract is above 2000 mg/kg body weight. The in vitro cytotoxicity analysis showed nontoxicity concentrations of the extract to be 2, 1.4, 30, and 1.4 µg/mL for A549, HepG2, 3T3, and COS-7 cells, respectively, where no apoptotic/necrotic cell death and DNA damage were observed. In conclusion, the extract of rhizome of A. malaccensis did not produce apparent cytotoxicity or acute oral toxicity, confirming the scope to use A. malaccensis as a safe food preservative and a natural therapeutic product after further subacute and chronic toxicity studies.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 684-684
Author(s):  
Maria Amelita Estacio ◽  
Liezl Atienza ◽  
Roxanne Gapasin ◽  
Jonna Rose Maniwang ◽  
James Ryan Aranzado ◽  
...  

Abstract Objectives “Bignay” (Antidesma bunius), “lipote” (Syzygium polycephaloides) and “duhat” (Syzgium cumini) are indigenous berries in the Philippines that are known to contain high antioxidant properties and other health-promoting and disease-preventing compounds. However, oral toxicity studies on these berries are not yet explored. Hence, this study evaluated the acute oral toxicity of these berries in freeze-dried forms using 6-week old ICR mice following the OECD guidelines 425 (up and down method). Methods Treatment groups were administered with freeze-dried powders of “bignay”, “lipote” and “duhat” reconstituted in distilled water at various doses: 55 mg/kg body weight (BW), 175 mg/kg BW, 550 mg/kg BW, 2000 mg/kg BW and 5000 mg/kg BW while control group was administered with distilled water. Body weight, feed and water intake were obtained daily. Biochemical profiles were measured prior to administration of reconstituted berries at day 1 and prior to euthanasia. Toxicity, morbidity and mortality cases were observed daily. Euthanasia and necropsy were performed to check for gross organ abnormalities. Results Mice that received the different concentrations of “bignay”, “lipote” and “duhat” had normal feed and water consumption and gained weight during the test period. No clinical and behavioral signs of toxicity were observed and there was zero morbidity and mortality. Post-mortem evaluation showed no lesions on various organs examined. Blood ALT, BUN and creatinine levels were within normal published values. Conclusions These results show that different concentrations of freeze-dried “bignay”, “lipote” and “duhat” are non-toxic using ICR mice and therefore have high potential to be developed into food supplements and nutraceuticals. Funding Sources Philippine Council for Health Research and Development - Department of Food Science and Technology Enhanced Creative Work and Research Grant - Office of Vice Chancellor for Academic Affairs, University of the Philippines.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jyoti Kaushik ◽  
Simran Tandon ◽  
Rishi Bhardwaj ◽  
Tanzeer Kaur ◽  
Surinder Kumar Singla ◽  
...  

Abstract Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.


Author(s):  
Savin Chanthala Ganapathi ◽  
Rajendra Holla ◽  
Shivaraja Shankara Ym ◽  
Ravi Mundugaru

Objective: To study the acute oral toxicity of ethanolic extract of Actinoscirpus grossus (L.f.) Goetgh. and D.A. Simpson in Wistar albino rats.Methods: Ethanolic extract of the plant was assessed for single dose acute toxicity by employing Organisation for Economic Co-Operation and Development(OECD) guidelines 425 using Acute Oral Toxicity(AOT) software. The dosed (up or down as per the requirement) rats were observed for 14 days for general appearance, behavior, mortality, and necropsy. A total of 5 healthy female rats of body weight 225±25 g were used.Results: The test substance did not produce any mortality up to the dose of 2000 mg/kg per oral.Conclusion: Test substance is without any toxic potential even at the dose of 2000 mg/kg in animals and the Lethal Dose (LD50) value of A. grossus (L.f.) Goetgh. and D.A. Simpson was found to be more than 2000 mg/kg body weight.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Sundararaju Dodda ◽  
Venkata Krishnaraju Alluri ◽  
Trimurtulu Golakoti ◽  
Krishanu Sengupta

The present communication describes a battery of toxicity studies that include an acute oral toxicity, a subacute twenty-eight-day repeated oral dose toxicity, and genotoxicity studies on a herbal formulation CinDura® (GMCT). This proprietary herbal composition contains the extracts of the Garcinia mangostana fruit rind (GM) and the Cinnamomum tamala leaf (CT). The toxicological evaluations were performed following the Organization for Economic Cooperation and Development (OECD) guidelines. The acute oral toxicity study in Wistar rats suggests that the median lethal dose of CinDura® is at least 2000 mg/kg body weight. Acute dermal and eye irritation tests in New Zealand white rabbits indicate that the test item is nonirritant to the skin and eyes. A twenty-eight-day repeated dose oral toxicity study was conducted in male and female Wistar rats using daily doses of 250, 500, and 1000 mg/kg body weight, followed by a fourteen-day reversal period for two satellite groups. The CinDura®-supplemented animals did not show any sign of toxicity on their body weights, organ weights, and on the hematobiochemical parameters. The gross pathology and histopathological examinations indicated no treatment-related changes in the experimental animals. Overall, the no-observed-adverse-effect level (NOAEL) of the herbal blend is 1000 mg/kg body weight, the highest tested dose. Also, the results of the bacterial reverse mutation test and the erythrocyte micronucleus assay in mouse bone marrow suggest that CinDura® (GMCT) is neither mutagenic nor clastogenic.


1946 ◽  
Vol 84 (3) ◽  
pp. 247-261 ◽  
Author(s):  
Leo G. Nutini ◽  
Sister Eva Maria Lynch

1. The ability of alcoholic-precipitated extracts of beef tissue—brain, spleen, heart, and kidney—to stimulate the growth of Staphylococcus aureus, in vitro, and to convert the yellow S form to a white R variant with altered biochemical characteristics conforming to those of an avirulent organism, has been confirmed. 2. The avirulence of the white R variant has been established by tests in vivo on mice. 3. Staphylococcus aureus infections induced subcutaneously, intraperitoneally, and intravenously in mice responded favorably to brain extract following subcutaneous or oral administration. The mortality was 2 per cent in 444 experimental animals and 81 per cent in 448 control animals. 4. The extracts appeared equally efficient when used therapeutically (mortality 2 per cent of 162 experimental animals and 90 per cent in the control series) or prophylactically (mortality 2 per cent of 282 experimental animals and 76 per cent in 286 control mice). Extracts of brain and spleen were more effective than those of either heart or kidney. 5. Studies concerning the mechanism of action of the tissue extracts indicate that they prevented the formation of toxin by Staphylococcus aureus, and had but little effect on toxin actions. 6. Toxicity tests revealed that the brain and spleen extracts were relatively non-toxic, dosages equivalent to 2 per cent of the body weight being well tolerated. Kidney and heart extracts were much more toxic, producing mortality in dosages as low as 0.3 per cent of the body weight.


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