title: Lack of teratogenicity of microcystin-LR in the mouse and toad.
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 160 microg kg (-1) 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 2 to 128 microg kg(-1). 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 32-128 microg kg(-1) on gestation days 7-8, 9-10 or 11-12 were allowed to give birth and the growth and development of their pups were followed postnatally. There were no significant effects noted in the offspring of the treated dams. Neurulation-staged CD-1 mouse conceptuses were exposed to 50-1000 nM MC-LR in whole embryo culture for 24 h. 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 of 1-20 mg l(-1). No effect on morphological development or survival was noted in any exposed groups. These data indicate that microcystin does not appear to affect development adversely in the mouse (in vivo or in vitro) or the toad at the doses and exposure parameters used.
authors.affiliation: US EPA, ORD, National Health and Ecological Effects Research Laboratory, Research Triangle Park, NC 27711, USA.
authors.forename: N
authors.initials: N
authors.lastname: Chernoff
authors.forename: E S
authors.initials: ES
authors.lastname: Hunter
authors.forename: L L
authors.initials: LL
authors.lastname: Hall
authors.forename: M B
authors.initials: MB
authors.lastname: Rosen
authors.forename: C F
authors.initials: CF
authors.lastname: Brownie
authors.forename: D
authors.initials: D
authors.lastname: Malarkey
authors.forename: M
authors.initials: M
authors.lastname: Marr
authors.forename: J
authors.initials: J
authors.lastname: Herkovits
mesh_terms: D000818:Animals; D002022:Bufo arenarum / Q000002:abnormalities*; D000458:Cyanobacteria / Q000472:pathogenicity; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008387:Marine Toxins; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D052998:Microcystins; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000633:toxicity*; D015996:Survival Rate; D023382:Toxicity Tests, Acute
chemical_list: D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C057862:cyanoginosin LR