Age-dependent changes in toxicity of N-nitroso compounds to Japanese medaka (Oryzias latipes) embryos

Three different developmental stages of embryonated eggs of Oryzias latipes were exposed to 2-h pulses of a number of different concentrations of MNU, MNNG, and DENA. Lethality and teratogenic endpoints were assessed through 24 h posthatch. MNU (≥2.5 mM) and MNNG (≥0.75 mM) exposure at the multicell stage was lethal, but the same exposure during early organogenesis was largely teratogenic. Four days before hatching, embryos were very resistant to MNU and proceeded to hatch normally; 7.5 mM MNU was required to significantly reduce the percent normal hatch. Effects of DENA were equivocal and only seen at the multicell stage. In order to differentiate between potential changes in chorion permeability, and toxicity per cell, the same three stages were exposed to a series of radiolabeled compounds of varying hydrophobicity, and apparent uptake measured. There were no differences in uptake rate or equilibrium concentration between any of the compounds at the different stages. These results suggest that, as in mammals, certain stages of development are more susceptible than others, and that these differences are a result of embryo sensitivity rather than chemical bioavailability. The most sensitive indicator of exposure was posthatch inflation of the swimbladder. Other terata included pericardial edema, anisophthalmia, and partial rupture of the chorion. © 1990.

Duke Scholars

Author David E. Hinton Environmental Sciences and Policy