scholarly journals UJI TOKSISITAS ORAL REPEATED DOSE FILTRAT BUAH LUWINGAN (Ficus hispida L.f.) MENGGUNAKAN MODEL TIKUS (Rattus norvegicus Berkenhout, 1769) GALUR WISTAR

2020 ◽  
Vol 19 (3A) ◽  
Author(s):  
Laksmindra Fitria ◽  
Rosita Dwi Putri Suranto ◽  
Indira Diah Utami ◽  
Septy Azizah Puspitasari
Keyword(s):  
Adverse Effect ◽  
Toxicity Test ◽  
Sublethal Effects ◽  
Complete Blood Count ◽  
Repeated Dose ◽  
Toxicity Tests ◽  
Oral Toxicity ◽  
Food Ingredient ◽  
Adverse Effect Level ◽  
Effect Level

Hairy fig is a tropical medium-sized tree that produces abundant fruits throughout the year. In some Asian countries, the fruits are consumed as traditional medicine and food ingredient. Meanwhile in Indonesia there has not been much use. A series of oral toxicity tests must be conducted to study the possibility of toxic effects and the safety before further exploration. Oral single dose toxicity study of young and ripe hairy fig fruit filtrate has been carried out. Results demonstrated no observed adverse effect level (NOAEL) at a concentration of 100%. This study was aimed to continue the oral toxicity test with repeated dose following standard toxicity procedure by OECD Test Guideline No. 407 with some modifications. Parameters observed were mortality, sublethal effects consisted of physical conditions and behavior, body weight, core temperature, complete blood count, as well as liver, heart, and renal functions by measuring ALT, AST, and creatinine, respectively. Sampling points on day 0, 7, 14, 21, and 28. Results showed no observed adverse effect level (NOAEL) in both young and ripe fruits filtrate at a concentration of 100% however with a tendency to cause anemia and associate with renal dysfunction. Therefore, it is necessary to perform similar method of toxicity test but with lower concentration, also continue with further toxicity tests (subchronic and chronic periods).  

scholarly journals UJI TOKSISITAS ORAL AKUT SINGLE DOSE FILTRAT BUAH LUWINGAN (Ficus hispida L.f.) PADA TIKUS (Rattus norvegicus Berkenhout, 1769) GALUR WISTAR

Mangifera Edu ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 1-18
Author(s):  
Laksmindra Fitria
Keyword(s):  
Single Dose ◽  
Sublethal Effects ◽  
Complete Blood Count ◽  
Toxicity Tests ◽  
Acute Oral Toxicity ◽  
Asian Countries ◽  
Oral Toxicity ◽  
Tropical Regions ◽  
Ficus Hispida ◽  
Oecd Guideline

Genus Ficus is important plant for health benefits. Hairy fig (F. hispida) trees grow abundantly in tropical regions and fruiting throughout the year. In West Asian countries, the fruit is commonly used as food and medicinal materials. However, in Indonesia, the fruit has not been utilized. First step in exploring the potential of natural resources for consumption is toxicity test to provide information about safety and adverse effects. This research was aimed to study acute oral toxicity of young and ripe hairy fig fruits using Wistar rats as model. Procedure followed OECD Guideline Test No.420 with modification. Pure filtrate (100 %) of young or ripe fruits were administered orally at volume 1 mL/individual on day-0 in fasting animals. Control received distilled water in the same way. Parameters observed including mortality, sublethal effects, behavior/activities, body weight, complete blood count, as well as evaluation of liver, heart, and renal functions. Results showed that values for all variables fluctuated during the experiment but eventually back into normal range. However, the number of lymphocytes elevated until the end of experiment (day-14) thus increased the total leukocytes count. Accordingly, we are preparing to conduct further toxicity tests to investigate this finding. Key words : acute oral toxicity, Ficus hispida, fruit filtrate, hairy fig, single dose toxicity

A No-Observed-Adverse-Effect Level of 1000 Mg/Kg in A 28-Day Repeated-Dose Study as a Limit Value for Acute Toxicity Testing

1998 ◽  
Vol 17 (1) ◽  
pp. 23-33 ◽  
Author(s):  
Moniek N. Pieters ◽  
Hester J. Kramer ◽  
Wout Slob
Keyword(s):  
Adverse Effect ◽  
Acute Toxicity ◽  
Toxicity Testing ◽  
Repeated Dose ◽  
Limit Value ◽  
Adverse Effect Level ◽  
Dose Study ◽  
Effect Level ◽  
Animal Use ◽  
Acute Toxicity Testing

Following the guidelines of the European Community (EC), chemicals are not classified according to acute toxicity if the estimated LD50 exceeds 2000 mg kg-1. Instead of an LD50 test, a limit test is often performed for relatively nontoxic chemicals. Since a short-term repeated-dose study is required in addition to an acute toxicity test, our investigation was aimed at finding out if acute toxicity testing could be omitted under certain circumstances. The latter would contribute to the reduction of (unnecessary) animal use. Data on LD50 and the no-observed-adverse-effect level values of 28-day repeated-dose studies (NO AEL 28-d) were retrieved from EC notifications for new substances. We statistically evaluated the LD50 and the NOAEL28-d values of 766 compounds (rat data only). At a NO AEL28-d of 1000 mg kg-1 there was a 4% probability of the associated LD50 being lower than 2000 mg kg-1. The probability of the LD50 being lower than 200 mg kg-1 was estimated at 0.04%. If such small probabilities of misclassification are considered acceptable, acute toxicity testing could be omitted at a NOAEL28-d of 1000 mg kg-1 or higher. A NOAEL28-d of 1000 mg kg-1 could thus function as a limit value for the acute toxicity testing requirement. Application of this limit value would have made acute toxicity testing redundant for 286 out of 766 compounds reviewed. The use of the limit value may thus form an important contribution to the reduction of animal use.

scholarly journals In Vivo Toxicity and the Antioxidant Activity of the Hot Water Extract of Glechoma Hederacea

2020 ◽  
Author(s):  
Yun-Chin Chung ◽  
Jiunn-Wang Liao ◽  
Kuo-Yuan Li ◽  
Jyun-Kai Jhan ◽  
Su-Tze Chou
Keyword(s):  
Adverse Effect ◽  
Water Extract ◽  
Hot Water ◽  
Oral Toxicity ◽  
Subacute Toxicity ◽  
Hot Water Extract ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Glechoma Hederacea

Abstract Background Glechoma hederacea belongs to the Labiatae family and has many biological effects. Our previously in vitro studies, hot water extract of G. hederacea (HWG) possessed antioxidant and anti-inflammatory activities. Also, the Ames test indicated that HWG had no mutagenicity. However, the in vivo toxicity and antioxidant capacity have not been clearly demonstrated. Thus, this study was aimed to evaluate the antioxidant properties and the safety level of HWG by using animal models. Methods The genotoxicity were performed by micronucleus assays in mice. Acute oral toxicity and 28-day repeated feeding toxicity tests were performed via the oral gavage method for Sprague-Dawley (SD) rats. Furthermore, the effect of HWG on the oxidation–antioxidation equilibrium of male rats was also evaluated. Results HWG did not induce an increase in micronucleus ratios in vivo, no acute lethal effect at a maximum tested dose of 5.0 g HWG /kg bw was observed in rats. The 28-day oral toxicity study revealed the no observed adverse effect level (NOAEL) of HWG in rats was 1.0 g/kg bw. The HWG-treatment significantly elevated the vitamin C level and the SOD activity in heart, and increased the vitamin E concentrations in brain. The HWG-treatment maintained the balance of the glutathione level and the activities of catalase and glutathione peroxidase. Besides, the level of lipid peroxidation and plasma of total antioxidant status (TAS) showed that HWG-treated rats were not significantly changed compared with the control group. Conclusions HWG had no genotoxicity, and did not induce acute or subacute toxicity in SD rat. The level of no observed adverse effect level (NOAEL) of HWG rats was 1.0 g/kg bw for subacute toxicity study. HWG possessed antioxidant potential and reduced oxidative stress by improving the antioxidant system in animal.

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 Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril

2020 ◽  
Author(s):  
Keyu Zhang ◽  
Xiaoyang Wang ◽  
Shuya Wei ◽  
Chunmei Wang ◽  
Mi Wang ◽  
...  
Keyword(s):  
Clinical Pathology ◽  
Dosage Level ◽  
Oral Toxicity ◽  
Safety Database ◽  
Clinical Observations ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Anticoccidial Activity ◽  
Anticoccidial Agent ◽  
Histologic Changes

Abstract Background: Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. To support the safety assessment of the new potent anticoccidial agent, the subchronic toxicity of ethanamizuril was studied in beagle dogs administered ethanamizuril by diet at doses of 12, 60 or 300 mg/kg/day for 90 days.Results: Ethanamizuril was well tolerated at low and middle dosages and there were no ethanamizuril related effects on survival, clinical observations, clinical pathology parameters, organs weight, macroscopic or microscopic evaluations. The ethanamizuril related changes were limited to effects on food consumption and histologic changes of kidneys in the 300 mg/kg/day group in both sexes. However, the characteristic toxicities of ethanamizuril in kidneys are recoverable in convalescence dogs of 300 mg/kg/day group. Conclusions: Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 60 mg/kg/day, the middle dosage level tested. These results add to the safety database for ethanamizuril with potential for use as a novel coccidiostat.

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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