Studies on the fate of vegetable oit after intramuscular injection into experimental animals.

Abstract

Abstract The fate of sesame oil and Viscoleo was studied in dogs after single intramuscular injection into the thigh of 14C‐labelled oil (0.5 ml/kg). Parts of Viscoleo was absorbed as liquid oil to the regional lymph nodes occasionally to such an extent that small oil droplets were drained from the iliac lymph nodes into the lymph of the thoracic duct causing pulmonary oil microembolisation. Sesame oil was also absorbed to the regional lymph nodes after single injection but in no case to such an extent that pulmonary oil microembolism occurred. In dogs which received unlabelled sesame oil (0.45 and 1.0 ml/kg) or Viscoleo (0.45 ml/kg) intramuscularly once a week for six months and finally an injection of 14C‐labelled oil, pulmonary oil microembolism was seen in all three groups and most markedly after the higher sesame oil dose. The iliac lymph nodes in both sesame oil dose groups were highly enlarged and appeared cystic due to presence of oil. The lungs from the dogs receiving Viscoleo were seat of small mononuclear interstitial cell infiltrations sometimes present in the vicinity of oil microemboli. In the sesame oil groups oil was additionally found extravascularly in the lung interstities together with accumulation of macrophages and leucocytes and focal hemosiderosis in the lungs occurred on the highest dose level. In the sesame oil groups of dogs pulmonary oil microembolism was found microscopically in a higher number than that seen on autoradiograms. The embolisation obtained at one injection may thus not disappear before the next injection. Except for presence of very few oil microemboli and small focal areas with interstitial oil deposits the lungs were normal in dogs examined three months after six month chronic weekly injection of sesame oil. Small oil deposits were still present at the injection site and in the iliac lymph nodes of these dogs, but the lymphoid tissue of the nodes had partly recovered. Pulmonary oil microembolism was also seen microscopically in rabbits after intramuscular injection of sesame oil or Viscoleo three times a week for two weeks, and also in rats after injection of sesame oil three times a week for five weeks. The content of radioactivity in the heart, kidneys, liver and lungs were generally low and the liver had the highest content (up to 1.32% of dose). The content in the lungs was not increased by presence of Viscoleo microemboli whereas sesame oil microembolisation significantly raised the amount of radioactivity in the lungs. The amounts of radioactivity at the injection site of dogs were reduced to half of the injected dose two days after injection of 14C‐Viscoleo and five weeks after injection of 14C‐sesame oil. In rats receiving an intramuscular injection (0.5 ml) into the thigh of 14C‐Viscoleo or 14C‐sesame oil the amounts of radioactivity at the injection site disappeared exponentially with time, and half of the dose had disappeared one week after injection of 14C‐Viscoleo and 9 weeks after injection of 14C‐sesame oil. The acute intravenous toxicity of sesame oil and Viscoleo was estimated in rabbits by determination of the LD50 dose which for sesame oil was 0.74 ml/kg and for Viscoleo 0.84 ml/kg. In the lungs of rabbits receiving 0.5 ml/kg of sesame oil or Viscoleo intravenously, numerous focal haemorrhages were present in the sesame oil group. Four weeks after the injection oil microembolisation was still pronounced in lungs from the sesame oil group while only few emboli were found in lungs from the Viscoleo group two weeks after the injection, In addition sesame oil was found extravascularly in the lung interstities with cellular infiltrate. Thus the pulmonary Viscoleo microemboli disappeared considerably faster than the sesame oil microemboli. In conclusion the present studies have revealed that chronic intramuscular injection of large volumes of two different oily drug vehicles may cause pulmonary oil microembolisation after lymphatic absorption as liquid oil. This occurred in spite of markedly different absorption rates of oil from the injection site. Toxicological implications of the present experiments with intramuscular injections of oil were related to the injection site, the regional lymph nodes and the lungs. Consequently the present finding demonstrate that the regional lymph nodes and the lungs may be the organs of interest in future studies on the relations to the human clinic. If pulmonary oil microembolisation should occur in patients receiving large volumes of oil the pathological sequelae may according to the present findings in animals be without importance.