Model-based experimental design for assessing effects of mixtures of chemicals.
We exposed flour beetles (Tribolium castaneum) to a mixture of four poly aromatic hydrocarbons (PAHs). The experimental setup was chosen such that the emphasis was on assessing partial effects. We interpreted the effects of the mixture by a process-based model, with a threshold concentration for effects on survival. The behavior of the threshold concentration was one of the key features of this research. We showed that the threshold concentration is shared by toxicants with the same mode of action, which gives a mechanistic explanation for the observation that toxic effects in mixtures may occur in concentration ranges where the individual components do not show effects. Our approach gives reliable predictions of partial effects on survival and allows for a reduction of experimental effort in assessing effects of mixtures, extrapolations to other mixtures, other points in time, or in a wider perspective to other organisms.
Baas
Jan
J
Vrije Universiteit of Amsterdam, Dept of Theoretical Biology, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands. jan.baas@falw.vu.nl
Stefanowicz
Anna M
AM
Klimek
Beata
B
Laskowski
Ryszard
R
Kooijman
Sebastiaan A L M
SA
D000818:Animals; D005449:Fluorenes / Q000633:toxicity; D008962:Models, Theoretical; D010616:Phenanthrenes / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011721:Pyrenes / Q000633:toxicity; D014231:Tribolium / Q000187:drug effects*
D005449:Fluorenes; D010616:Phenanthrenes; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C007738:fluoranthene; C041509:fluorene; C031181:phenanthrene; C030984:pyrene