Toxicity-distribution relationships among 3-alkylfurans in mouse liver and kidney.

The present study was designed to extend previous observations regarding toxicity of furans and related compounds to liver and kidney. It was desired to test a series of homologous 3- alkylfurans , where changes in lipophilic character might be related to changes in toxicity. Additionally, it was desired to measure distribution of toxins to the target organs to ascertain whether organ selectivity might be determined by the concentrations attained in the target organs by the toxins. A synthesis for 3- ethylfuran and 3- pentylfuran was devised, and the toxicity of these, in addition to 3- methylfuran and furan itself, to mouse liver and kidney at 2.6 mmol/kg was determined. 2- Furamide and 2- ethylfuran were used as examples of substances known to be toxic to liver and kidney, respectively. 3- Methylthiophene was also included to determine whether results with furans extend to the closely related thiophenes . Histopathological examination of both organs was done, and quantitative estimates of liver toxicity were obtained from plasma levels of glutamate-pyruvate transaminase. Renal urine concentrating ability and plasma urea nitrogen levels were useful as quantitative indices of nephrotoxicity. It was found that both 3-ethyl and 3- pentylfuran exhibited pronounced toxicity to the kidney, and that both also caused moderate liver damage. Furan caused serious damage to the liver and produced somewhat lesser effects on the kidney. Equimolar doses of 3- methylfuran did not significantly damage either organ. Among the 3-alkyl furans, there is an impression that the more volatile compounds damage lung (3- methylfuran is reported to be a potent lung toxin), with liver and kidney toxicity increasing with molecular weight, and that compounds found in higher concentration produce greater damage in liver and kidney. However, among compounds other than alkyl furans, there is no obvious correlation between toxicity and organ concentration of toxin.