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 administered AZA twice at 300-450 mug/kg doses and observed for recovery processes from severe injuries. Slow recoveries from injuries were revealed: erosion and shortened villi persisted in the stomach and small intestine for more than 3 months: edema, bleeding, and infiltration of cells in the alveolar 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 up 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 sacrificed before completion of 40 injections. All these mice showed interstitial pneumonia and shortened small intestinal villi. Most importantly, lung tumor were observed in four mice, one out of ten (10%) at 50 mug/kg and three out 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.