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LACK OF TERATOGENICITY OF MICROCYSTIN-LR IN THE MOUSE AND TOAD
Citation:
Chernoff, N, E S. Hunter III, L. L. Hall, M B. Rosen, C. F. Brownie, D. Malarkey, M. Marr, AND J. Herkovits. LACK OF TERATOGENICITY OF MICROCYSTIN-LR IN THE MOUSE AND TOAD. JOURNAL OF APPLIED TOXICOLOGY 22(1):13-17, (2002).
Description:
Abstract. Microcystin-LR (MC-LR) is a cyanobacterial toxin generated by the organism, Microcystis aeruginosa. Although the hepatotoxicity of this chemical has been characterized, the potential developmental toxicity in vertebrates has not been well studied. The purpose of this study was to elucidate the effects of this toxin on the in vivo and in vitro development of mammals and the development of an Anuran (toad). Initial acute toxicity experiments with female CD-1 mice were accomplished with MC-LR administered i.p. in saline. Lethality occurred at 128 and 160Fg/kg and histopathology revealed massive hepatic necrosis with diffuse hemorrhage. Developmental toxicity studies were done with MC-LR administered i.p. for 2-day periods, gestation days 7-8, 9-10, or 11-12. Doses used ranged from 2Fg/kg to 128Fg/kg. On gestation day 17, fetuses were weighed and analyzed for gross morphological and skeletal defects. No treatment-related differences were seen in litter size, viability, weight, or the incidence of anomalies. Groups of dams dosed with 32-128Fg/kg on gestation days 7-8, 9-10, or 11-12 were allowed to give birth and the growth and development of their pups followed postnatally. There were no significant effects noted in the offspring of the treated dams. Neurulation-staged mouse CD-1 conceptuses were exposed to 50-1000nM MC-LR in whole embryo culture for 24 hours. No significant increase in abnormalities or developmental delays was observed. Finally, exposure of the developing toad, Bufo arenarum was done from stage 17 (tail bud) for 10 days at concentrations from 1-20 mg/L. No effect on morphological development or survival was noted in any exposed groups. These data indicate that microcystin does not appear to adversely affect development in the mouse (in vivo or in vitro) or the toad at the doses and exposure parameters used.