A comparison of the acute pathology induced by 3-phenylamino-1,2-propanediol (PAP) and its mono-oleoyl ester in rodents with the toxic oil syndrome in man

Phenylamino-1,2 propanediol (PAP) and its mono-oleoyl ester have been identified in samples of the cooking oil thought to be responsible for the Toxic Oil Syndrome (TOS) which occurred in Spain in 1981. The acute toxicity of PAP and its mono-oleoyl ester have been examined in rats and mice, after daily administration for periods of up to 14 days to determine whether these compounds could produce any of the pathologies of TOS. Even at the highest dose, the 1-mono-oleoyl ester of 3-phenylamino-1,2 propanediol did not cause any toxicity in rats or mice when given intraperitoneally. 3-Phenylamino-1,2 propanediol, however, was toxic when administered to rats by this route. After 6-10 consecutive daily doses of PAP, at the highest dose administered (350 mg kg-1), all of the rats became unwell. Postmortem examination showed that the major pathology present was massive pulmonary thromboembolism. Further investigations of the toxicity of PAP after intravenous administration showed that it was not directly vasotoxic. The pulmonary thromboembolism seen with intraperitoneally administered PAP was due to the toxic effect of PAP on the mesenteric tissue and blood vessels, causing thrombosis which subsequently embolised the blood vessels in the lung. Intra-gastric administration of PAP caused no toxicity in rats. Comparatively, the pathology seen after intraperitoneal administration of PAP was not thought to be representative of the pathology of the toxic oil syndrome in man.