Subchronic toxicity evaluation of anthraquinone in Fischer 344 rats

Female F344 rats were exposed to anthraquinone (AQ) by dietary feed at concentrations of 0, 50, 150, 469, 938, 1875, or 3750 ppm for 2 or 13 weeks. End points evaluated included clinical observations, body weights, serum chemistry, blood AQ, gross pathology, organ weights, and select tissue histopathology. Mean body weight and food consumption were 5% to 10% lower than control values in rats of the ≥938 ppm group during study weeks 2 through 13. Occasional decreases in body weight means were also observed in rats of the 150 and 469 ppm groups. Increases in liver, kidney, and spleen weights were observed in rats exposed to AQ diet concentrations ≥150 ppm for 13 weeks. Urinary bladder weights were increased at ≥469 ppm. Liver and spleen weights were also increased following 2 weeks of exposure. Liver weight increases were clearly dependent on AQ concentration. At 2 weeks, decreases in serum aspartate aminotransferase (AST), blood urea nitrogen, and creatinine concentrations were observed in higher AQ exposure groups, and AST was decreased at 13 weeks (≥1875 ppm). Microscopic alterations were observed in the liver (mild centrilobular hypertrophy), spleen (mild hematopoietic cell proliferation and pigmentation), and kidneys (minimal hyaline droplets) of rats exposed to AQ for 13 weeks. Blood AQ concentrations ranged from 0.75 to 14.8 µg/mL in rats of the 150 to 3750 ppm groups, respectively, and were similar in value following either 2 weeks or 13 weeks of exposure. A no observed adverse effect level of 469 ppm AQ (31.3 mg/kg/d) was selected based on the absence of liver histopathology.