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Toxicological Studies on Ferastral®, an Iron‐poly‐(sorbitol‐gluconic acid) complex
Author(s) -
FLODH H.,
MAGNUSSON G.,
MALMFORS T.
Publication year - 1977
Publication title -
scandinavian journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0036-553X
DOI - 10.1111/j.1600-0609.1977.tb01217.x
Subject(s) - spleen , lymph , chemistry , intramuscular injection , pharmacology , injection site , endocrinology , medicine , pathology
This paper presents a review of the toxicological studies in animals on Ferastral®, an iron‐poly (sorbitol‐gluconic acid) complex. Studies after single administration were performed in mice, rats and dogs, and LD 50 ‐values were calculated in mice and rats. Studies after repeated administration were performed in rats and dogs. The test compound was given intramuscularly twice a week for five weeks to rats in doses varying from 50 to 400 mg Fe 3+ /kg, and to dogs from 5 to 200 mg Fe 3+ /kg. In a special study Ferastral was given intravenously to dogs every day for 12 days at the dose levels 5 and 20 mg Fe 3+ /kg. Imferon®, iron‐dextran, was used as a reference compound in some of the studies. Ferastral induced very little inflammatory reaction at the injection site. Depositions of iron‐containing pigments were found in all examined organs, being most pronounced at the intramuscular injection site, in the liver, spleen, and lymph nodes. Hyperplasia and hypertrophy as a reaction to the iron‐containing pigments resulted in increased weights of the liver and the spleen. Iron deposits in the liver occurred in both hepatocytes and Kupffer cells. With low doses the distribution was diffuse and with higher doses also focally accentuated. In both rats and dogs the focally accentuated distribution of iron in the liver was accompanied by granulomatous changes. There was a dose difference between rats and dogs. In rats iron was stored at the intramuscular injection site to a much greater extent than in dogs, and severe proliferation of iron‐loaded macrophages at the intramuscular injection site was seen in rats at much lower dose levels than in dogs. Imferon caused liver changes of similar appearance as those with Ferastral.