The cyanobacterial toxin, cylindrospermopsin, induces fetal toxicity in the mouse after exposure late in gestation.
Cylindrospermopsin (cyn) is a cyanobacterial toxin implicated in human and wildlife poisonings. We have completed studies investigating the potential of purified cyn to induce developmental toxicity in mammals. The teratology study involved intraperitoneal injections (8.0-128 microg kg(-1)) on gestational days (GD) 8-12 with subsequent examination of term fetuses for viability, weight and morphological anomalies. Cyn was lethal to a significant portion of the dams receiving > or = 32 microg kg(-1). Surviving pregnant females were killed and fetuses removed for examination. Analysis indicates no adverse effects on litter size, fetal weight, or incidence of anomalies. Subsequently, 50 microg kg(-1) cyn was administered on GD 8-12 or 13-17. Animals were allowed to give birth and litters monitored for growth and viability. A reduction in litter size occurred in treated groups. Avg. pup wt. was only affected in the GD 13-17 group. GD 13-17 dams did not exhibit the toxicity noted in the GD 8-12 group but gave birth significantly earlier than controls. There was a significant number of dead GD 13-17 pups and incidences of blood in the gastrointestinal tract and hematomas in the tips of the tails in survivors. Pups were cross-fostered to control mothers in litters of 10. On postnatal days (PND) 5-6 there were no significant differences in weight gain or viability in GD 8-12 litters, while GD 13-17 litters had significantly reduced weight gain and viability. GD 13-17 exposed male pups still weighed significantly less than the controls after 15 months.
Rogers
E H
EH
US EPA, ORD, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, USA.
Zehr
R D
RD
Gage
M I
MI
Humpage
A R
AR
Falconer
I R
IR
Marr
M
M
Chernoff
N
N
D000470:Alkaloids; D000818:Animals; D000831:Animals, Newborn; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000633:toxicity*; D000458:Cyanobacteria; D000087522:Cyanobacteria Toxins; D004622:Embryo, Mammalian / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D007274:Injections, Intraperitoneal; D008297:Male; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D052998:Microcystins / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
D000470:Alkaloids; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; C089595:cylindrospermopsin; D014498:Uracil