ROBUST ESTIMATION OF THE MEDIAN LETHAL DOSE

2002 ◽  
Vol 12 (2) ◽  
pp. 137-147 ◽  
Author(s):  
G. E. Kelly ◽  
J. K. Lindsey
2021 ◽  
Author(s):  
Paul Story ◽  
Lyn A Hinds ◽  
Steve Henry ◽  
Andrew C. Warden ◽  
Greg Dojchinov

Abstract A lack of toxicity data quantifying responses of Australian native mammals to agricultural pesticides prompted an investigation into the sensitivity of the stripe-faced dunnart, Sminthopsis macroura (Gould 1845) to the insecticide, fipronil (5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinyl pyrazole, CAS No. 120068-37-3). Using the Up-And-Down method for determining acute oral toxicity in mammals, derived by the Organisation for Economic Cooperation and Development (OECD), median lethal dose estimates of 990 mg kg− 1 (95% confidence interval (CI) = 580.7–4770.0 mg kg− 1) and 270.4 mg kg− 1 (95% CI = 0.0 - >20000.0 mg kg− 1) were resolved for male and female S. macroura respectively. The difference between median lethal dose estimates for males and females may have been influenced by the increased age of two female dunnarts. Further modelling of female responses to fipronil doses used the following assumptions: (a) death at 2000 mg kg− 1, (b) survival at 500 mg kg− 1 and (c) a differential response (both survival and death) at 990 mg kg− 1. This modelling revealed median lethal dose estimates for female S. macroura of 669.1 mg kg− 1 (95% CI = 550–990 mg kg− 1; assuming death at 990 mg kg− 1) and 990 mg kg− 1 (95% CI = 544.7–1470 mg kg− 1; assuming survival at 990 mg kg− 1). These median lethal dose estimates are 3–10-fold higher than the only available LD50 value for a similarly sized eutherian mammal, Mus musculus (L. 1758; 94 mg kg− 1) and that available for Rattus norvegicus (Birkenhout 1769; 97 mg kg− 1). Implications for pesticide risk assessments in Australia are discussed.


2018 ◽  
Vol 30 (4-5) ◽  
pp. 195-202 ◽  
Author(s):  
Jillian M. Staugler ◽  
Michael C. Babin ◽  
M. Claire Matthews ◽  
Matthew K. Brittain ◽  
Mark R. Perry

2010 ◽  
Vol 29 (6) ◽  
pp. 507-512 ◽  
Author(s):  
Yng-Tay Chen ◽  
Jiunn-Wang Liao ◽  
Dong-Zong Hung

2-Chloroethanol (2-CE) is a widely used industrial solvent. In Taiwan, Taiwanese farmers apply 2-CE on grape-vines to accelerate grape growth, a practice that in some cases have caused poisoning in humans. Thus, there is strong interest in identifying antidotes to 2-CE. This study examines the protective role in 2-CE intoxicated rats. Alcohol dehydrogenase and glutathione were hypothesized to be important in the metabolism of 2-CE. This study used fomepizole, an alcohol dehydrogenase inhibitor, and chemicals that affected glutathione metabolism to study 2-CE toxicity. Notably, fomepizole 5 mg/kg significantly increased median lethal dose (LD50) of 2-CE from 65.1 to 180 mg/kg and reduced the production of a potential toxic metabolite chloroacetaldehyde (CAA) in animal plasma. In contrast, disulfiram (DSF), an aldehyde dehydrogenase inhibitor, increased the toxicity of 2-CE on the lethality in rats. Additional or pretreatment with N-acetylcysteine (NAC) and fomepizole significantly reduced plasma CAA concentrations. Fomepizole also significantly reduced 2-CEinhibited glutathione activity. Otherwise, pretreatment with NAC for 4 days followed by co-treatment with fomepizole significantly decreased formation of the metabolic CAA. These results indicated that its catalytic enzyme might play a vital role during 2-CE intoxication, and the combination of fomepizole and NAC could be a protective role in cases of acute 2-CE intoxication.


ILAR Journal ◽  
2002 ◽  
Vol 43 (4) ◽  
pp. 233-243 ◽  
Author(s):  
A. Rispin ◽  
D. Farrar ◽  
E. Margosches ◽  
K. Gupta ◽  
K. Stitzel ◽  
...  

Author(s):  
Siva Kumar T ◽  
Shobha Rani A ◽  
Sujatha K ◽  
Purushotham B ◽  
Neeraja P

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.


2010 ◽  
Vol 9 (2) ◽  
pp. 53
Author(s):  
E. M. Rashid, Sh. Jamal, and Sh. M. Al-khazraji

The study was intended to investigate the in vitro activity of alcoholic extract of Garlic on the inhibition of growth of Staph. aureus which was isolated from skin infections , and determine the median lethal dose ( LD 50 ) of the extract in lab. mice. The Garlic was extracted by ethyl alcohol 95% , the ratio of ethanolic extraction amounted 44% of the weight of dry substance. Graduated concentration were prepared from alcoholic extract of Garlic from 10-100 mg/ml. Their activities were checked up against Staph.aureus by agar diffusion method using ethylene glycol as control. The results showed that the sensitivity of the test bacteria was gradually increased with increasing the extract concentration , the concentration 10-30 mg/ml were rather low active in preventing the growing of Staph. aureus in culturing media , the concentrations 40-70 mg/ml were moderately active ,meanwhile the concentrations 80-100 mg/ml were highly active against the growing of Staph.aureus . The results also showed that the LD50 of the ethanolic extract of Garlic when it is orally administered to the lab mice by gradual concentrations was about 8000 mg/kg body weight . The toxic signs during 24 hrs after initial feeding with the extract were rapid breathing followed by dullness , then death


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