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Pulmonary Toxicity of Ethiodized Oil in the Venous Circulation in Mice: Radiological Findings and Pathological
Shimpei Kato1, Haruto Sugawara2, Naomasa Okimoto1
1Department of Radiology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Purpose:
To evaluate the acute and chronic pulmonary toxicity and determine the median lethal dose (lethal dose 50% [LD50]) of intravenously administered ethiodized oil given the limited data on its systemic toxicity despite its known risk of inadvertent venous entry during lymphangiography.
Materials And Methods:
Twenty female BALB/c mice received tail vein injections of saline (n = 4) or ethiodized oil (Lipiodol; Guerbet, Villepinte, France) at 10 μL (n = 4), 30 μL (n = 8), or 50 μL (n = 4). Survival outcomes, computed tomography (CT) imaging findings, and histopathological features including hemosiderin deposition were evaluated. Chronic effects were assessed at 10 weeks through histopathology and hemosiderin deposition quantification. Human equivalent doses (HEDs) were calculated using body weight ratio conversion.
Results:
The LD50 was determined to be 30 μL in mice, corresponding to an HED of 94.7 mL for a 60-kg human. All mice receiving 50 μL died immediately, whereas the 30-μL group showed 50% survival. CT imaging revealed dose-dependent ethiodized oil accumulation predominantly in pulmonary vasculature, with regional heterogeneity in distribution patterns. Surviving mice from the 30-μL group exhibited significantly higher hemosiderin deposition compared with the 10-μL group (P = .0054), indicating chronic microvascular damage.
Conclusions:
Intravenous ethiodized oil induces dose-dependent pulmonary embolism with an LD50 of 30 μL in mice, and even sublethal doses cause chronic pulmonary injury, highlighting the need for clinical monitoring in cases of suspected venous exposure.
