Metabolism matters: Interspecies variability and ecological traits of biotransformation kinetics

Biotransformation critically influences the bioaccumulation / biomagnification and the toxicity of chemicals, and is therefore key to understanding cross-species difference in various ecotoxicological traits. This study attempted to characterize and compare interspecies difference and dependence of in vivo biotransformation rate constant, k_M, using pyrene as an exemplary parent compound. A total of 241 k_M (4.9 × 10^-5 - 6.7 × 10^-1 h^-1), were derived from experimental data using the early-time method across 61 unique species under 24 classes and 13 phyla/divisions. Cross-species k_M's were visualized using a species-sensitivity distribution (SSD). Intraspecies uncertainty in k_M was typically within ±0.5 log unit with additional variability explained by k_M's dependence on exposure conditions and environmental parameters. k_M generally declined with higher exposure concentration regardless of exposure medium. The effect of temperature, inhibitor, and bioavailability modifiers on k_M were generally more ambiguous and secondary when compared to exposure level or intraspecies variation, and tissue-specific biotransformation can be significant (e.g., Carcinus maenas). Significant cross-species k_M differences were also observed among species within fish, bivalves, worms, and algae (e.g., oyster > mussel or clam; polychaete > oligochaete). Analysis showed that omnivores had the highest k_M than the other feeding guilds. This dependence on feeding ecology broadly agreed with the hypothesis that generalists with broad dietary choices may have evolved more mechanisms and diverse gut microflora to neutralize/detoxify/excrete toxic moieties. The approach, data, and findings presented here can support the linking of toxicokinetics with ecotoxicological traits, further validation of in vitro-in vivo extrapolation, and the development of next generation biology-specific ecological risk assessment. The need for species-specific metabolites profile, intermediates selectivity, and pathway-specific kinetics is also advocated.