Latest News on Acute Toxicity: Jan 2020

Latest News on Acute Toxicity: Jan 2020

Measurement of pollutant toxicity to fish I. Bioassay methods for acute toxicity

The review describes profitable methods for measuring lethal levels of pollutants for aquatic organisms. Methods for research in the laboratory are emphasized but the same principles could be applied in field work. Greater use of standard toxicological methods and terminology is urged.

For 211 out of 375 toxicity tests reviewed, acute lethal action apparently ceased within 4 days, although this tabulation may have been biased towards short times by a large number of static tests.

The incipient LC50 (lethal concentration for 50 per cent of individuals on long exposure) is recommended as the most useful single criterion of toxicity. If this cannot be estimated, the 4-day LC50 is a useful substitute, and often its equivalent.

A desirable first step in toxicity tests is to estimate median lethal time for each of a series of concentrations. A toxicity curve should be drawn by plotting median survival times against concentrations on logarithmic paper. The curve helps to reveal any unusual features of toxicity. Whenever possible, tests should be prolonged until the toxicity curve becomes parallel to the time axis, indicating a lethal threshold concentration. The incipient LC50 is then estimated by selecting an exposure time from the asymptotic part of the toxicity curve; for this exposure time, observed mortality is plotted against concentration on log-probit paper, and the LC50 is read from an eye-fitted line.
Confidence limits of the LC50 may also be estimated by simplified methods. These should be given in published work along with a value for slope of the probit line. [1]

Acute toxicity of pesticides

LD50 values have been determined for 98 pesticides and 2 metabolites of DDT administered in a single dose by the oral or dermal route to Sherman strain adult rats. Most compounds tested by the oral route were more toxic to female than to male rats, but 9 of 85 compounds (aldrin, chlordane, heptachlor, Abate, Imidan, methyl parathion, ronnel, schradan, and metepa) tested in both sexes were markedly more toxic in male rats. Although the pesticides were generally more toxic by the oral than by the dermal route, 5 compounds (fenitrothion, Merphos, mevinphos, Isolan, and Omite) were more toxic by the dermal route. LD50 values for rats treated by the dermal route with parathion or dichlorvos and restrained so as to prevent the possibility of oral or respiratory exposure were not significantly different from those values in rats treated according to the procedure used routinely in this laboratory.

In screening tests for the production of paralytic effect in chicken hens 3 of 9 carbamate and 22 of 30 organic phosphorus pesticides tested caused paralysis. The onset of paralysis was delayed at least 3 days in chickens treated with Dursban and Merphos and at least 14 days in chickens treated with DEF. Chickens treated with the other 22 pesticides that produced paralysis showed this effect within 24 hours. [2]

Acute toxicity of ropivacaine compared with that of bupivacaine.

The acute central nervous and cardiovascular effects of the local anesthetics ropivacaine and bupivacaine were compared in 12 volunteers in a randomized double-blind manner with use of intravenous infusions at a rate of 10 mg/min up to a maximal dose of 150 mg. The volunteers were all healthy men. They were familiarized with the central nervous system (CNS) toxic effects of local anesthetics by receiving a preliminary intravenous injection of lidocaine. The infusions of ropivacaine and bupivacaine were given not less than 7 days apart. CNS toxicity was identified by the CNS symptoms and the volunteers were told to request that the infusion be stopped when they felt definite but not severe symptoms of toxicity such as numbness of the mouth, lightheadedness, and tinnitus. In the absence of definite symptoms, the infusion was stopped after 150 mg had been given. Cardiovascular system (CVS) changes in conductivity and myocardial contractility were monitored using an interpretive electrocardiograph (which measured PR interval, QRS duration, and QT interval corrected for heart rate) and echocardiography (which measured left ventricular dimensions from which stroke volume and ejection fraction were calculated). Ropivacaine caused less CNS symptoms and was at least 25% less toxic than bupivacaine in regard to the dose tolerated. Both drugs increased heart rate and arterial pressure. Stroke volume and ejection fraction were reduced. There was no change in cardiac output. Although both drugs caused evidence of depression of conductivity and contractility, these appeared at lower dosage and lower plasma concentrations with bupivacaine than with ropivacaine. [3]


In vitro Antisickling and Radical Scavenging Activities of a Poly-herbal Formula (Drepanoalpha®) in Sickle Cell Erythrocyteand Acute Toxicity Study in Wistar Albino Rats

Aims: To evaluate the antisickling and radical scavenging activities and acute toxicity of indigenous nutritive formula Drepanoalpha®, produced through a bio-guided based plant selection.

Study Design: Drepanoalpha® extracts, Antisickling activity by Emmel test, Antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl bleaching methods; acute toxicity on rats, determination of biological and haematological parameters.

Place and Duration of Study: Science Faculty University of Kinshasa, between January 2013 and February 2014.

Methodology: The antisickling and antioxidant activities of Drepanoalpha® were determined using Emmel and the 1,1-diphenyl-2-picrylhydrazyl bleaching methods respectively. Acute oral toxicity test was performed to determine the LD50. Liver and kidney functions, the hematological and histopathological examinations were assessed using standard techniques.

Results: Obtained results revealed that Drepanoalpha® possessesinteresting in vitro antisickling and antioxidant activities as revealed by the observed normal biconcave form of sickle erythrocyte (normalization rate >80%) and the radical scavenging activity (ED50= 0.604 ± 0.028 µg/mL). Acute toxicity assessment revealed that the medium lethal dose (LD50) is higher than 4000 mg/kg. Drepanoalpha® significantly increases the values of WBC, RBC, Hb, HCT, PLT, IDR-CV and PCT. Furthermore, this polyherbal formula significantly decreases the values of IDR-SD, P-RGC, AST and ALT (p<0.05). Both the control and treated groups displayed comparable non altered histological architecture of the liver cells.

Discussion: The mean values of biochemical markers and hematological markers of treated rats revealed that Drépanoalpha® is potentially safe indicating non-toxic effect of the phytomedicine on immune cells and blood clotting factors. Moreover, this poly-herbal formulation increases the hemoglobin rate in the all treated rats (500-4000 mg/kg bodyweight) and preserves the histological architecture of the liver cells.

Conclusion: Drepanoalpha® may increase weight gain, promote erythropoiesis and thrombopoeisis in sicklers patients. This phytomedicine could be used in the treatment of all form of anemia and may also prevent bile duct obstruction or intra-hepatic cholestasis. The results can form the basis for clinical trials in humans. [4]

Acute Toxicity and Hypoglycemic Activity of Aqueous Fruit Pulp Extract of Adansonia digitata L. (Afpead) on Alloxan Induced Diabetic Rats

Oral LD50 and hypoglycemic activity of aqueous fruit pulp extract of Adansonia digitata L. (AFPEAD) were investigated in this research. A total of fourty eight (48) rats were used, twelve (12) of the rats were used for oral LD50 determination, and were grouped into four (4) groups of three rats (3) each. The first three groups were administered with 10 mg/kg, 100 mg/kg and 1000 mg/kg body weight of the extract respectively, while the last group was subdivided into three groups of one rat each and were administered with 1600 mg/kg, 2900 mg/kg and 5000 mg/kg body weight of the extract respectively. Thirty (36) rats were used for the diabetic study and were grouped into six (6) groups of six (6) rats each. Group I served as normal control, group II served as diabetic control while Groups III, IV, V and VI were induced with diabetes and administered with AFPEAD at a dose of 1.00 g/kg, 2.00 g/kg and 3.00 g/kg body weight and standard drug (Chlorpropamide, 100 mg/kg) respectively for two weeks. The research found the oral LD50 of the extract to be greater than 5000mg/kg indicating that the extract was practically non-toxic and administration of the extract to test groups shows a significant (p<0.05) decrease in blood glucose level when compared to diabetic control after two weeks treatment with the extract. Thus indicating a hypoglycemic activity by the extract which might be due to the presence of various phytochemicals. [5]

Reference

[1] Sprague, J.B., 1969. Measurement of pollutant toxicity to fish I. Bioassay methods for acute toxicity. Water research, 3(11), pp.793-821.

[2] Gaines, T.B., 1969. Acute toxicity of pesticides. Toxicology and applied pharmacology, 14(3), pp.515-534.

[3] Scott, D.B., Lee, A., Fagan, D., Bowler, G.M., Bloomfield, P. and Lundh, R., 1989. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesthesia and analgesia, 69(5), pp.563-569.

[4] N. Ngbolua, K., T. Mpiana, P., S. T. Tshibangu, D., P. Mazasa, P., Z. Gbolo, B., K. Atibu, E., N. Kadima, J. and M. Kasali, F. (2014) “In vitro Antisickling and Radical Scavenging Activities of a Poly-herbal Formula (Drepanoalpha®) in Sickle Cell Erythrocyteand Acute Toxicity Study in Wistar Albino Rats”, European Journal of Medicinal Plants, 4(10), pp. 1251-1267. doi: 10.9734/EJMP/2014/11861.

[5] U. Muhammad, I., K. Jarumi, I., J. Alhassan, A., M. Wudil, A. and A. Dangambo, M. (2016) “Acute Toxicity and Hypoglycemic Activity of Aqueous Fruit Pulp Extract of Adansonia digitata L. (Afpead) on Alloxan Induced Diabetic Rats”, Journal of Advances in Medical and Pharmaceutical Sciences, 6(3), pp. 1-6. doi: 10.9734/JAMPS/2016/23862.

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