A modified arithmetical method of Reed and Muench for determination of a relatively ideal median lethal dose (LD50)

Saganuwan, Saganuwan Alhaji

doi:10.5897/ajpp11.393

Cited by 51 publications

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“…The range of LD 50 estimated by Saganuwan (38,39) Human-animal equivalent therapeutic dose translation showed that 1 mg/kg body weight of adult human translated to 1.1 mg/kg in mini-pig and 9.1 mg/kg body weight in hamster respectively. But, 1.9 mg/kg body weight in human translated to 2.02 mg/kg in mini-pig and 18.1 mg/kg in hamster respectively.…”

Section: Resultsmentioning

confidence: 99%

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The Paradox of Human Equivalent Dose Formula: A Canonical Case Study of Abrus Precatorius Aqueous Leaf Extract in Monogastric Animals

Saganuwan¹,

Onyeyili²

2016

Macedonian Veterinary Review

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There is abundant literature on the toxicity of A. precatorius seeds. However there is a need to define the toxicity limit of the Abrus precatorius leaf in monogastric animals. Human Equivalent Dose (HED) which is equal to animal dose multiplied by animal km (metabolism constant) divided by human km was used to project the LD 50 of fifteen monogastric animals , where human km factor is body weight (kg) divided by body surface area (m 2 ). Human Equivalent No-observable Adverse Effect Doses were determined by multiplying the animal no-observable adverse effect dose by animal weight (Wa) divided by human weight (Wh). The LD 50 of the aqueous leaf extract of Abrus precatorius in mice was estimated to be between 2559.5 and 3123.3 mg/kg body weight. The LD 50 extrapolated from mouse to rat (1349.3-1646.6 mg/kg), hamster (1855.3-2264.1 mg/kg), guinea pig (1279.5-1561.4 mg/kg), rabbit (618.4-754.7 mg/kg), monkey (593.7-724.5 mg/kg), cat (392.7-479.2 mg/kg), dog and baboon (371.1-452.8 mg/kg), child (297-362 mg/kg) and adult human (197.8-241.5 mg/kg) body weight respectively could be a reality. The therapeutic safe dose range for the animals was 1-12.5 mg/kg body weight for a period of 7 days, but at a dose (≤ 200 mg/kg body weight) the leaf extract showed haematinic effect. However, at a higher dose (> 200 mg/kg), the extract showed haemolytic activity in rats, whereas at a dose (≥25.0 mg/kg), the leaf extract might be organotoxic in hamster, guinea pig, rabbit, monkey, cat, dog, baboon, child and adult human if administered orally for a period of 7 days.

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Section: Resultsmentioning

confidence: 99%

“…Fresh leaves may be pressed on the gum for the treatment of stomatitis, skin cancer and nervousness (8), suppuration, acne, boils, abscesses, tetanus, rabies (58), colic, convulsion (27), cough, sore throat and insomnia (33). Aqueous extract of the plant has haematinic and plasma expander effects in mice (38).…”

Section: Introductionmentioning

confidence: 99%

The Paradox of Human Equivalent Dose Formula: A Canonical Case Study of Abrus Precatorius Aqueous Leaf Extract in Monogastric Animals

Saganuwan¹,

Onyeyili²

2016

Macedonian Veterinary Review

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“…Jumlah kematian ikan dihitung untuk mendapat nilai LD50. Penghitungan nilai LD50 dilakukan menggunakan metode Reed dan Muench (Saganuwan, 2011).…”

Section: Uji Patogenisitas E Ictaluriunclassified

Kajian patogenisitas bakteri Edwardsiella ictaluri pada ikan patin Pangasionodon hypophthalmus

Indrawati

Pasaribu

2016

Jurnal Akuakultur Indonesia

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One of major problem of striped catfish Pangasionodon hypophthalmus culture is enteric septicemia of catfish (ESC), bacterial disease of Edwardsiella ictaluri, caused of more than 50% of mortalities. This reaserch was aimed to determine pathogenicity of local isolate E. ictaluri. Thirty individu of five group fishes, 6-10 g in body weight, injected intraperitoneally with 0,1 mL of bacteria suspension of 10 2 cfu/mL; 10 4 cfu/mL; 10 6 cfu/mL; 10 8 cfu/mL; 10 10 cfu/mL; and PBS as control, were culture in 18 of 60×40×45 cm 3 aquarium for seven days. External organs of fish (skin and abdomen) and internal organs (liver, kidney, and brain) were examined macroscopicly and microscopicly. Internal organ sample were taken on the 5 th day for histopatologic test while blood sample was on the 1 st , 3 rd , and 5 th day after infection. Mortality rate was count to reach LD50. Clinical signs and pathology anatomy of co-infection fish showed vertical swim, petechial hemorrhage in the skin, dropsy, ascites in the abdominal cavity, pale liver and the kidney was dark red. Histopathology showed hydropic degeneration, fatty degeneration, hemorrhage and necrosis in the liver, melano macrophage center (MMC) and necrosis in the kidneys, hemorrhage, and inflammatory cell infiltrates were also found in the kidneys and brain. Decreased of hematocrit and hemoglobin values of all tread group were statistically significant different (P<0,05) compared to controls. LD50 dose was 2,8×10 4 cfu/mL. The result indicated that E. ictaluri was very pathogenic on striped catfish P. hypophthalmus.Keywords: Edwardsiella ictaluri, enteric septicemia of catfish (ESC), pathogenicity, striped catfish ABSTRAKSalah satu kendala yang dijumpai pada budidaya ikan patin Pangasionodon hypophthalmus yaitu serangan penyakit bakterial. Enteric septicemia of catfish (ESC) adalah penyakit infeksi bakteri Edwardsiella ictaluri yang dapat menyebabkan kematian ikan patin sampai >50%. Penelitian ini dilakukan untuk mengetahui patogenisitas E. ictaluri isolat lokal pada ikan patin. Masing-masing 30 ekor ikan patin ukuran 6-10 g/ekor diinjeksi secara intraperitoneal dengan 0,1 mL larutan bakteri kepadatan 10 2 cfu/mL; 10 4 cfu/mL; 10 6 cfu/mL; 10 8 cfu/mL; 10 10 cfu/mL; dan PBS sebagai kontrol. Ikan dipelihara selama tujuh hari pada akuarium berukuran 60×40×45 cm 3 . Pemeriksaan makroskopis dan mikroskopis dilakukan terhadap organ eksternal (kulit dan abdomen) dan internal (hati, ginjal, dan otak). Pengambilan sampel organ internal untuk uji histopatologi pada hari kelima dan sampel darah untuk uji gambaran darah pada hari pertama, ketiga, dan kelima pascainfeksi. Jumlah kematian ikan dihitung untuk mendapat nilai LD50. Pengamatan gejala klinis dan patologi anatomi ditemukan ikan berenang vertikal, adanya bercak merah pada kulit, pembengkakan abdomen, asites, hati pucat, dan ginjal berwarna merah kehitaman. Hasil histopatologi terlihat terjadinya degenerasi hidropik, degenerasi lemak, melano macrophage center (MMC), nekrosa, hemoragi, dan infiltrasi sel radang pad...

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“…In another report, LD 50 is calculated using the data on percent mortality instead of percent survival [11]. Having noted the marked difference between the estimated LD 50 from percent survival and percent mortality using Reed and Muench method, Saganuwan [1] modified and validated the method using the average of median lethal dose (LD 50 ) and median survival dose (MSD 50 ) which gave a relatively ideal LD 50 . The method was also validated by other authors with precision and accuracy.…”

mentioning

confidence: 99%

“…It was on this basis the median lethal dose (LD 50 ) was introduced in 1920. LD 50 is the dose which has proven to cause death to 50% of the test group of animals [1]. It is an initial assessment of toxic manifestations and is one of the initial screening experiments usually performed with carcinogenic, anticarcinogenic, venomous, anti-venomous, toxicogenic, anti-toxicogenic, immunogenic and anti-immunogenic compounds.…”

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confidence: 99%

Toxicology: The Basis for Development of Antidotes

As¹

2015

Toxicol Open Access

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EditorialToxicology is the study of poison. Sources of poisons include animals, microorganisms, plants and chemicals. Although, Paracelsus who was a lecturer at the University of Basel, Switzerland in 1520s had hypothesized that the ability of an agent to cause poisoning is dependent on the dose of that agent. It was on this basis the median lethal dose (LD 50 ) was introduced in 1920. LD 50 is the dose which has proven to cause death to 50% of the test group of animals [1]. It is an initial assessment of toxic manifestations and is one of the initial screening experiments usually performed with carcinogenic, anticarcinogenic, venomous, anti-venomous, toxicogenic, anti-toxicogenic, immunogenic and anti-immunogenic compounds. An antidote is any is any substance that counteracts a poison by, However, for Reed and Muench method, the sum of cumulative dead and cumulative survived of each dose is taken. The percent survival to two doses adjacent to LD 50 is calculated and the LD 50 determined [10]. In another report, LD 50 is calculated using the data on percent mortality instead of percent survival [11]. Having noted the marked difference between the estimated LD 50 from percent survival and percent mortality using Reed and Muench method, Saganuwan [1] modified and validated the method using the average of median lethal dose (LD 50 ) and median survival dose (MSD 50 ) which gave a relatively ideal LD 50 . The method was also validated by other authors with precision and accuracy. Kue et al. [12] used quick chick embryo chorioallantoic membrane (CAM) as an alternative predictive model in acute toxicological studies for cyclophosphamide, cisplatin, vincristine, carmustin, campothecin, aloin, mitomycin-C, actinomycin-D, melphalan and paclitaxel. The authors used the method of Reed and Muench modified by Saganuwan [1], and determined LD 50 of all the anticancer agents and there was significant correlation between the ideal LD 50 for the CAM and LD 50 for mice. Signifying the versatility of the revised Reed and Muench method using CAM model as a replacement for toxicological studies in rodents.World Health Organization (WHO) [13] has patented sodium silicate complex (SSC) which comprises trimeric sodium silicate (Na 2 SiO 3 ) 3 and sodium silicate pentahydrate (Na 2 SiO 3 )5H 2 O. SSC has antivenomous activity against Crotalus atrox, Agkistrodon contortrix contortrix and Agkistrodon piscivorus leucostoma venoms using two enzymatic assays, gelatinase and hide powder azure assays at pH of 14.

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A modified arithmetical method of Reed and Muench for determination of a relatively ideal median lethal dose (LD50)

Cited by 51 publications

References 0 publications

The Paradox of Human Equivalent Dose Formula: A Canonical Case Study of Abrus Precatorius Aqueous Leaf Extract in Monogastric Animals

The Paradox of Human Equivalent Dose Formula: A Canonical Case Study of Abrus Precatorius Aqueous Leaf Extract in Monogastric Animals

Kajian patogenisitas bakteri Edwardsiella ictaluri pada ikan patin Pangasionodon hypophthalmus

Toxicology: The Basis for Development of Antidotes

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