Hepatic changes in rats following subchronic administration of FYROL 6, an organophosphorus ester flame retardant

This study conducted to evaluate the subchronic toxicity of FYROL 6 [diethyl N,N-bis-(2-hydroxyethyl)aminomethylphosphonate] in rats demonstrated an hepatic effect not commonly reported for related compounds. Sprague-Dawley rats of both sexes were gavaged daily with 0, 10, 100, or 500 mg/kg FYROL 6 in corn oil for 13 wk. No treatment-related mortality and few signs of toxicity were noted during the study. Fyrol 6 did not inhibit plasma, erythrocyte, or brain cholinesterase activities. Treatment-related necropsy and microscopic alterations were restricted to the liver. Increased liver weights, hepatocellular hypertrophy, and eosinophilia of centrilobular hepatocytes were evident in 100-mg/kg females and in both sexes at 500 mg/kg. Morphometric analysis revealed a 40% increase in cross-sectional area of individual hepatocytes in 500-mg/kg males, compared to controls. There was no morphologic evidence of hepatic necrosis or clinical evidence of liver dysfunction. This study demonstrated low toxicity for FYROL 6 and treatment-related changes restricted to the liver suggestive of an adaptive response to FYROL 6.