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Species/Study Design
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Results and Conclusions
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Acute toxicity studies, gavage or oral administration
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Toxicity Data
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Species
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LD50
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Route
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Rat
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5.5 g/kg
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Gavage (Lehman et al., 1951)
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Mouse
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4 g/kg
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Gavage (Lehman et al., 1951)
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Mouse
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0.1–0.8 g/kg
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i.p. (Fujii et al., 1970; Kozubik et al., 1993; Madrigal-Bujaidar et al., 1998)
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Guinea pig 0.8 g/kg
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Gavage (Lehman et al., 1951)
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Rats (male, S/D), NDGA (single dose at 25 or 50 mg/kg body weight, gavage), ± indomethacin mucosa (20 mg/kg body weight, gavage), animals were sacrificed 4 hr later
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NDGA enhanced indomethacin-induced mast cell degranulation in gastric
NDGA increased prostanoid activity in gastric glandular mucosa
With NDGA pretreatment, indomethacin-induced lesions in the gastric mucosa were more severe; this is a possible cytotoxic effect (Cho and Ogle, 1987)
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Acute toxicity studies, other routes of administration
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Rats (Wistar Albino), NDGA (1 dose at 10 μg/kg body weight, i.v.)
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In a model of ischemia reperfusion injury to the liver, rats were given NDGA 5 min before reperfusion (± iloprost, 25 μg/kg i.v., given just before warm ischemia)
By histopathologic examination, liver damage was more extensive in the rats treated with NDGA compared with the control (saline-injected) animals (Okboy et al., 1992)
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Mice (female, CD1), NDGA (50 mg/kg body weight, i.v.)
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Pharmacokinetic analysis (using M4NDGA as a standard):
Peak plasma concentration = 14 μg/mL
Exposure (AUC) = 248 μg/mL/min
Clearance = 202 mL/(min/kg)
Volume of distribution = 3.4 L/kg
Half-life in 1st compartment = 30 min
Half-life in 2nd compartment = 135 min
NDGA appears to follow a 2-compartment pharmacokinetic model (Lambert et al., 2001)
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Mice (male, CBA), NDGA (2 doses, 2-h apart, 50 mg/kg body weight, i.p.)
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At 2 wk after treatments (NDGA, galactosamine, and endotoxin), histological examination of liver showed small foci of necrosis adjacent to areas of infiltration of inflammatory cells; some of this hepatic damage was due to endotoxin administration (Parry, 1993)
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