Comparison of modes of action among different trophic levels of aquatic organisms for pesticides and medications based on interspecies correlations and excess toxicity: Theoretical consideration.

Pesticides and medications have adverse effects in non-target organisms that can lead to different modes of action (MOAs). However, no study has been performed to compare the MOAs between different levels of aquatic species. In this study, theoretical equations of interspecies relationship and excess toxicity have been developed and used to investigate the MOAs among fish, Daphnia magna, Tetrahymena pyriformis and Vibrio fischeri for pesticides and medications. The analysis on the interspecies correlation and excess toxicity suggested that fungicides, herbicides and medications share the similar MOAs among the four species. On the other hand, insecticides share different MOAs among the four species. Exclusion of insecticides from the interspecies correlation can significantly improve regression coefficient. Interspecies relationship is dependent not only on the difference in interaction of chemicals with the target receptor(s), but also on the difference in bio-uptake between two species. The difference in physiological structures will result in the difference in bioconcentration potential between two different trophic levels of organisms. Increasing of molecular size or hydrophobicity will increase the toxicity to higher level of aquatic organisms; on the other hand, chemical ionization will decrease the toxicity to higher level organisms. Hydrophilic compounds can more easily pass through cell membrane than skin or gill, leading to greater excess toxicity to Vibrio fischeri, but not to fish and Daphnia magna.

Theoretical consideration on the prediction of in vivo toxicity from in vitro toxicity: Effect of bio-uptake equilibrium, kinetics and mode of action.

Although in vitro assay is an ideal alternative method for the in vivo toxicity prediction, different in vivo-in vitro correlations have been observed for the toxicity endpoints obtained from different levels of species. In this paper, theoretical in vivo-in vitro toxicity correlations have been developed for cytotoxicity versus human, mammalian and fish toxicity, respectively. These theoretical models were then used to investigate the correlations and the influencing factors between in vivo and in vitro toxicity. Bio-uptake equilibrium theory can well explain why there is a significant correlation between fish and cell toxicity (R2 = 0.70); why human toxicity is very close to fish toxicity; and why hydrophobic compounds exhibit relatively greater toxicity than reactive or specifically-acting compounds to human and fish as compared to cells. The kinetic theory can well explain why there is a very poor relationship between mammal and cell toxicity (R2 = 0.44). This paper reveals that polar and ionized compounds can more easily pass through cell membrane and have greater bioconcentration potential. Increasing of hydrophobicity and ionization can increase the cytotoxicity. Inclusion of descriptors representing hydrophobicity, ionization, acidity and absorption into the correlation equations can significantly improve the correlations of cytotoxicity with human and fish toxicity (R2 > 0.8), but not with mammal toxicity (R2 = 0.49). These descriptors reflect the differences of the toxicodynamics and toxicokinetics between cells and organisms.