The acute intravenous toxicity of biological stains, dyes, and other fluorescent substances
Lutty, G.A.
Toxicology and Applied Pharmacology 44(2): 225-249
1978
ISSN/ISBN: 0041-008X PMID: 79242 Document Number: 132344
Sodium fluorescein and indocyanine green are currently used as indicators for angiography of the retinal and choroidal vasculatures. This study was conducted to suggest additional indicator substances for this technique. Fifty-three dyes and biological stains were evaluated by the following criteria: i.v. LD50, histopathological damage from i.v. administration, binding properties in blood, in vivo metabolism of the substances, fluorescent and absorption spectra, and impurities detected with TLC. Male Swiss-Webster mice were used for the i.v. toxicity studies and for the metabolism and LD50 determinations. Several cyanines were modified by recrystallization with sodium iodide and an oxazine was sulfonated to improve their solubility and biocompatibility. Both techniques were successful in improving the i.v. toxicity and the solubility of the dyes in water. Iodination was not successful on the merocyanines. Patent blue VF and 8-hydroxy-1,3,6-pyrene trisulfonic acid trisodium salt were promising since both had impurities yet their LD50 exceeded 1000 mg/kg. Fluorones with 2 salt sites (NaO- and -COONa) were soluble at 10% or more in water. Nonhalogenated fluorones were excreted totally in the urine, while those with 8 halogen atoms were removed via the biliary system. Those fluorones with 6 or less halogen atoms were excreted by both systems. Twenty-three of the 53 dyes were tolerated well enough for use in angiography of the ocular fundus. The majority of the substances had at least 1 impurity. In general, the cationic dyes were poorly tolerated; only 2 of the 23 acceptable substances were cationic. Those dyes that were anionic or dipolar were the best tolerated, with the dipolar molecules being cleared, at least partially, by the liver.