In ecotoxicology, the state of the art for effect assessment of chemical mixtures is through multiple dose-response analysis of single compounds and their combinations. Investigating whether such data deviate from the reference models of concentration addition and/or independent action to identify overall synergism or antagonism is becoming routine. However, recent data show that more complex deviation patterns, such as dose ratio-dependent deviation and dose level-dependent deviation, need to be addressed. For concentration addition, methods to detect such deviation patterns exist, but they are stand-alone methods developed separately in literature, and conclusions derived from these analyses are therefore difficult to compare. For independent action, hardly any methods to detect such deviations from this reference model exist. This paper describes how these well-established mixture toxicity principles have been incorporated in a coherent data analysis procedure enabling detection and quantification of dose level-and dose ratio-specific synergism or antagonism from both the concentration addition and the independent action models. Significance testing of which deviation pattern describes the data best is carried out through maximum likelihood analysis. This analysis procedure is demonstrated through various data sets, and its applicability and limitations in mixture research are discussed.

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Time‐dependent toxicity in bioassays is usually explained in terms of uptake and elimination kinetics of the toxicant By comparing different species with essentially different accumulation kinetics, a firm test of this concept may be made This article compares the sensitivity of six soil arthropods, the collembolans Orchesella cincta and Tomocerus minor, the oribatid mite Platynothrus peltifer, the isopods Porcellio scaber and Oniscus asellus, and the diplopod Cylindroiulus britannicus, when exposed to cadmium in the food Survival was determined at various time intervals, accumulation of cadmium in the animals was measured at one time interval Kinetic based toxicity models were fitted to the data, and estimates were obtained for lethal body concentration, uptake rate constant, elimination rate constant, and ultimate LC50 Two different accumulation patterns could be discerned, these were correlated with time‐survival relationships One, species that have the possibility to eliminate cadmium will reach an equilibrium for the internal concentration and also an ultimate LC50 Two, species that are unable to eliminate cadmium but store it in the body will have an ultimate LC50 equal to zero For these species the time in which the lethal body concentration is reached is more important Taxonomically related species appeared to have comparable accumulation patterns, but lethal body concentrations differed It is concluded that knowledge of the accumulation pattern is indispensable for the evaluation of species' sensitivities to toxicants

In this work we demonstrate how the reduction state of the Q-pool determines the distribution of electron flow over the two quinol-oxidising branches in Paracoccus denitrificans: one to quinol oxidase, the other via the cytochrome bc 1 complex to the cytochrome c oxidases. The dependence of the electron-flow rate to oxygen on the fraction of quinol in the Q-pool was determined in membrane fractions and in intact cells of the wild-type strain, a bc 1 -negative mutant and a quinol oxidase-negative mutant. Membrane fractions of the bc 1 -negative mutant consumed oxygen at significant rates only at much higher extents of Q reduction than did the wild-type strain or the quinol oxidase-negative mutant. In the membrane fractions, dependence on the Q redox state was exceptionally strong corresponding to elasticity coefficients close to 2 or higher. In intact cells, the dependence was weaker. In uncoupled cells the dependence of the oxygen-consumption rates on the fractions of quinol in the Q-pool in the wildtype strain and in the two mutants came closer to that found for the membrane fractions. We also determined the dependence for membrane fractions of the wild-type in the absence and presence of antimycin A, an inhibitor of the bc 1 complex. The dependence in the presence of antimycin A resembled that of the bc 1 -negative mutant. These results indicate that electron-flow distribution between the two quinol-oxidising branches in P. denitrificans is not only determined by regulated gene expression but also, and to a larger extent, by the reduction state of the Q-pool.