Modelling the joint effects of a metal and a pesticide on reproduction and toxicokinetics in Lumbricid earthworms.

It is important to understand the aetiology of interactive mixtures effects (i.e. synergism and antagonism) if results from known cases are to be extrapolated to untested combinations. The key role of toxicokinetics in determining internal concentrations at target sites means that understanding chemical uptake in mixtures is an essential requirement for mechanistic understanding of interactions. In this paper, a combined approach using mixture toxicity testing, toxicokinetic studies and modelling has been used to address the link between joint toxicity and internal concentration. The study is conducted in Lumbricid earthworms with a binary mixture of a metal (nickel) and an organophosphate insecticide (chlorpyrifos) not a priori expected to show interactive toxicity. As expected from their dissimilar modes of action and detoxification, exposure to combinations of nickel and chlorpyrifos resulted in additive toxicity. Measurement of internal concentrations indicated that both chemicals were rapidly accumulated (within 3 days) to equilibrium. When exposed as a mixture, Ni uptake followed the same pattern as found for the single chemical. This was not the case for chlorpyrifos which showed a faster rate of uptake and elimination and a slightly higher equilibrium concentration in a mixture. That the difference in chlorpyrifos kinetics in the mixture did not result in interactive toxicity highlights the need to assess chemical toxicodynamics as well as toxicokinetics. Measurement of chlorpyrifos-oxon identified the presence of this toxic form but implementation of more complex approaches encompassing toxicogenomics and epigenetics are ultimately needed to resolve the toxicokinetic to toxicodynamic link for these chemicals.

Comparative transcriptomic responses to chronic cadmium, fluoranthene, and atrazine exposure in Lumbricus rubellus.

Transcriptional responses of a soil-dwelling organism (the earthworm Lumbricus rubellus) to three chemicals, cadmium (Cd), fluoranthene (FA), and atrazine (AZ), were measured following chronic exposure, with the aim of identifying the nature of any shared transcriptional response. Principal component analysis indicated full or partial separation of control and exposed samples for each compound but not for the composite set of all control and exposed samples. Partial least-squares discriminant analysis allowed separation of the control and exposed samples for each chemical and also for the composite data set, suggesting a common transcriptional response to exposure. Genes identified as changing in expression level (by the least stringent test for significance) following exposure to two chemicals indicated a substantial number of common genes (> 127). The three compound overlapping gene set, however, comprised only 25 genes. We suggest that the low commonality in transcriptional response may be linked to the chronic concentrations (approximately 10% EC50) and chronic duration (28 days) used. Annotations of the three compound overlapping gene set indicated that genes from pathways most often associated with responses to environmental stress, such as heat shock, phase I and II metabolism, antioxidant defense, and cation balance, were not represented. The strongest annotation signature was for genes important in mitochondrial function and energy metabolism.