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THE CYANOBACTERIAL TOXIN, CYLINDROSPERMOPSIN, INDUCES FETAL TOXICITY IN THE MOUSE AFTER EXPOSURE LATE IN GESTATION
Citation:
ROGERS, E. H., R. D. ZEHR, M. I. GAGE, A. R. HUMPAGE, I. R. FALCONER, M. MARR, AND N. CHERNOFF. THE CYANOBACTERIAL TOXIN, CYLINDROSPERMOPSIN, INDUCES FETAL TOXICITY IN THE MOUSE AFTER EXPOSURE LATE IN GESTATION. TOXICON. Elsevier Science Ltd, New York, NY, 49(6):855-864, (2007).
Impact/Purpose:
In 1979, an algal bloom in an Australian reservoir supplying water to the community of Palm Island resulted in severe sickness requiring the hospitalization of over 100 people, most of whom were children. The affected people exhibited anorexia, and abnormal levels of protein, glucose and ketones, as well as blood in the urine. The disease progressed to acidotic shock and bloody diarrhea (Byth, 1980). Investigation of the reservoir revealed the presence of a cyanobacterial species, C. raciborskii. The algicide copper sulfate had been used to kill the bloom and despite standard chlorination procedures, enough of the toxin (subsequently named cylindrospermopsin (cyn) of this species remained to cause the resulting illness. Studies in Australian laboratories have shown that administration of cyn in the mice produces a spectrum of symptoms that are similar to those seen in humans. C raciborskii has become one of the primary algal species responsible for blooms in north central Florida, although the species has been found in most States. In Florida, the use of surface water for drinking supplies is predicted due to the depletion of the aquifer making the possibility of a toxic bloom in that part of the U.S. a distinct possibility. To date this is the first study on the potential developmental toxicity of this toxin and the results indicate that at dose levels producing equivalent symptoms as those seen in affected humans, cyn is a potent developmental toxicant. The impact of this paper, therefore, is to alert regulatory officials to the possibility of an episode of adverse birth defects in any community experiencing exposure to cylindrospermopsin.
Description:
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¿128ug/kg) 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 ¿32ug/kg. 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, 50ug/kg cyn was administered on GD8-12 or GD13-17. 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 GD13-17 group. GD13-17 dams did not exhibit the toxicity noted in the GD8-12 group but gave birth significantly earlier than controls. There was a significant number of dead GD13-17 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 PND5-6 there were no significant differences in weight gain or viability in GD8-12 litters, while GD13-17 litters had significantly reduced weight gain and viability. GD13-17 exposed male pups still weighed significantly less than the controls after 15 months.