An up-and-down procedure for acute toxicity testing

Bruce, Robert D.

doi:10.1016/0272-0590(85)90059-4

Cited by 301 publications

(123 citation statements)

References 7 publications

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“…Birds were monitored for clinical signs of toxicosis, onset of signs, and time to death. Results of the initial exposure were used to select the subsequent dose, using the up-anddown method to estimate the lethal dose (Bruce, 1985). Dosages used were 2,000, 2,500, 3,000, 3,500, 4,000, 4,500, and 5,500 mg/kg.…”

Section: Lethal Dose Estimationmentioning

confidence: 99%

Toxicity of Sodium Chloride to House Sparrows (Passer Domesticus)

Bollinger

Mineau

Wickstrom

2005

Journal of Wildlife Diseases

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Sodium chloride (NaCl) is widely used as a deicing agent on roadways. There are numerous anecdotal reports of poisoning of passerine birds by road salt in the United States and Canada, but little is known about the toxicity of NaCl to songbirds. The objectives of this study were to determine the lethal dose range for NaCl in a representative passerine species (house sparrow [Passer domesticus]); to determine the clinical, physiologic, and pathologic effects of sublethal and lethal oral NaCl exposure; and to assess the potential for recovery after exposure to granular salt or highly concentrated salt solutions. The up-and-down method was used in a pilot study to estimate the lethal oral dose of granular NaCl in wild caught house sparrows. The toxicity of highly concentrated NaCl solution also was investigated. This was followed by an acute dose response study in which house sparrows were dosed orally with granular NaCl at 0, 500, 1,500, 2,500, or 3,500 mg/kg. Sparrows were deprived of water for 6 hr postexposure (PE) in an attempt to mimic specific winter conditions. Groups of three birds at each dose were euthanized at 1, 3, 6, and 12 hr PE, and samples were collected for histopathology and brain and plasma electrolyte analyses. Results indicated an approximate mean lethal dose (LD 50 ) of 3,000-3,500 mg/kg in water-deprived birds, which is similar to mammalian values. House sparrows dosed with a concentrated solution of NaCl generally died at doses of 8,000 mg/kg. Clinical signs observed at Ն1,500 mg/kg included rapid onset (Ͻ30 min) of depression (indicated by reduced activity and reduced response to visual and auditory stimuli), ataxia, inability to fly or perch, and death in as little as 45 min. Birds that survived for 6 hr usually recovered. Plasma Na concentrations Ͼ200 mmol/l were consistently associated with clinical signs. Pathologic lesions consisted of edema and distension of the caudoventral thin muscled region of the gizzard and were observed 1 hr PE in most birds dosed with Ն500 mg/kg. Brain Na concentrations in clinically ill sparrows and those that died of NaCl toxicity ranged from 1,297 to 1,615 (meanϭ1,450; SDϭ115) ppm wet weight or 5,603 to 6,958 (meanϭ6,367; SDϭ454) ppm dry weight, which differed significantly from control birds. No histologic lesions were observed in brain sections of exposed birds, likely reflecting the acute nature of the exposure. However, fluid accumulation beneath the koilin layer of the gizzard was observed in the majority of birds at high dosage levels. These results indicate that passerines ingesting relatively small numbers of road salt granules or small quantities of highly concentrated NaCl solutions are at risk of sodium poisoning.

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Section: Lethal Dose Estimationmentioning

confidence: 99%

Toxicity of Sodium Chloride to House Sparrows (Passer Domesticus)

Bollinger

Mineau

Wickstrom

2005

Journal of Wildlife Diseases

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“…The UDP testing method is the toxicological testing approach most recommended by various regulatory agencies because this method reduces the number of vertebrate animals in research. This method involves dosing single animals sequentially at 48 h intervals [22]. Female rodents are preferable for UDP testing.…”

Section: Discussionmentioning

confidence: 99%

“…Swiss albino mice, weighing (18)(19)(20)(21)(22), were obtained from the Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Kingdom of Saudi Arabia. All the animals were housed in groups of (n=3/cage) in standard plastic cages with wood chips as bedding material.…”

Section: Experimental Animalsmentioning

confidence: 99%

Acute Toxicity Testing of Newly Discovered Potential Antihepatitis B Virus Agents of Plant Origin

Aljofan

et al. 2017

Asian J Pharm Clin Res

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Objective: Our previous studies indicate that alkaloids could be developed as potential antihepatitis B agents. In the present study, we investigated the in vitro antihepatitis B virus (HBV) activity and in vivo acute oral toxicity of three isoquinoline alkaloids [-(-) Canadine, Corydadine, and Berberine] obtained from Fumaria and Corydalis species. The compounds were selected based on their therapeutic indexes calculated previously in vitro. Methods:The antiviral activity and cytotoxicity of selected isoquinoline alkaloids were evaluated in vitro in HepG2 cells. In vivo, acute oral toxicity was performed in female mice following the Organization for Economic Cooperation and Development test guideline-423 (acute toxicity class method). Results:The selected agents have shown high antiviral activity against HBV and low cytotoxicity in vitro. The results obtained from an acute oral toxicity study revealed that the LD 50 of all the test compounds was >2000 mg/kg when administered orally to mice. All the tested compounds fall under the category 5 (unclassified) according to the Globally Harmonized System, with a LD 50 value >2000 mg/kg when orally administered to mice. Conclusion:The results of the study revealed that OR-13 and MNAD can be studied further and can be developed as antihepatitis B drugs.

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“…The exposure dosage was determined according to previous studies (Bruce, 1985;Lu and Tomchik, 2002) with some modifications. Briefly, a single fish was injected (i.p.)…”

Section: Toxin Exposure Dosagementioning

confidence: 99%

Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins

Zhang

et al. 2014

Aquatic Toxicology

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An up-and-down procedure for acute toxicity testing

Cited by 301 publications

References 7 publications

Toxicity of Sodium Chloride to House Sparrows (Passer Domesticus)

Toxicity of Sodium Chloride to House Sparrows (Passer Domesticus)

Acute Toxicity Testing of Newly Discovered Potential Antihepatitis B Virus Agents of Plant Origin

Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins

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