Chronic effects in mice caused by oral administration of sublethal doses of azaspiracid, a new marine toxin isolated from mussels

Toxicological effects of orally administered azaspiracid (AZA), a new toxin isolated from mussels, were investigated. First, a total of 25 mice were a dministered AZA twice at 300-450 mug/kg doses and observed for recovery pro cesses from severe injuries. Slow recoveries from injuries were revealed: e rosion and shortened villi persisted in the stomach and small intestine for more than 3 months: edema, bleeding, and infiltration of cells in the alve olar wall of the lung for 56 days; fatty changes in the liver for 20 days; and necrosis of lymphocytes in the thymus and spleen for 10 days. Secondly, low doses of AZA (50, 20, 5 and 1 mug/kg) were administered twice a week u p to 40 times to four groups of mice. Many mice, nine out of ten at 50 mug/ kg and three out of ten at 20 mug/kg, became so weak that they were sacrifi ced before completion of 40 injections. All these mice showed interstitial pneumonia and shortened small intestinal villi. Most importantly, lung tumo r were observed in four mice, one out of ten (10%) at 50 mug/kg and three o ut of ten (30%) at 20 mug/kg. Tumors were not observed in I 1 mice treated at lower doses and in 19 control mice. Hyperplasia of epithelial cells was also observed in the stomach of six mice out of ten administered at 20 mug/ kg. (C) 2001 Elsevier Science Ltd. All rights reserved.