A biology-based approach for mixture toxicity of multiple endpoints over the life cycle
Jager, T., Vandenbrouck, T., Baas, J., Coen, W. M. De and Kooijman, S. A. L. M.
2010.
A biology-based approach for mixture toxicity of multiple endpoints over the life cycle.
Ecotoxicology, 19: 351 - 361
Abstract
Typical approaches for analyzing mixture ecotoxicity data only provide
a description of the data; they cannot explain observed interactions,
nor explain why mixture effects can change in time and differ between
endpoints. To improve our understanding of mixture toxicity we need to
explore biology-based models. In this paper, we present an integrated
approach to deal with the toxic effects of mixtures on growth,
reproduction and survival, over the life cycle. Toxicokinetics is
addressed with a one-compartment model, accounting for effects of
growth. Each component of the mixture has its own toxicokinetics
model, but all compounds share the effect of body size on uptake
kinetics. The toxicodynamic component of the method is formed by an
implementation of dynamic energy budget theory; a set of simple rules
for metabolic organization that ensures conservation of mass and
energy. Toxicant effects are treated as a disruption of regular
metabolic processes such as an increase in maintenance costs. The
various metabolic processes interact, which means that mixtures of
compounds with certain mechanisms of action have to produce a response
surface that deviates from standard models (such as concentration
addition ). Only by separating these physiological interactions from
the chemical interactions between mixture components can we hope to
achieve generality and a better understanding of mixture effects. For
example, a biology-based approach allows for educated extrapolations to
other mixtures, other species, and other exposure situations. We
illustrate our method with the interpretation of partial lifecycle
data for two polycyclic aromatic hydrocarbons in Daphnia magna.