Investigating combined toxicity of binary mixtures in bees: Meta-analysis of laboratory tests, modelling, mechanistic basis and implications for risk assessment.

Bees are exposed to a wide range of multiple chemicals "chemical mixtures" from anthropogenic (e.g. plant protection products or veterinary products) or natural origin (e.g. mycotoxins, plant toxins). Quantifying the relative impact of multiple chemicals on bee health compared with other environmental stressors (e.g. varroa, viruses, and nutrition) has been identified as a priority to support the development of holistic risk assessment methods. Here, extensive literature searches and data collection of available laboratory studies on combined toxicity data for binary mixtures of pesticides and non-chemical stressors has been performed for honey bees (Apis mellifera), wild bees (Bombus spp.) and solitary bee species (Osmia spp.). From 957 screened publications, 14 publications provided 218 binary mixture toxicity data mostly for acute mortality (lethal dose: LD50) after contact exposure (61%), with fewer studies reporting chronic oral toxicity (20%) and acute oral LC50 values (19%). From the data collection, available dose response data for 92 binary mixtures were modelled using a Toxic Unit (TU) approach and the MIXTOX modelling tool to test assumptions of combined toxicity i.e. concentration addition (CA), and interactions (i.e. synergism, antagonism). The magnitude of interactions was quantified as the Model Deviation Ratio (MDR). The CA model applied to 17% of cases while synergism and antagonism were observed for 72% (MDR > 1.25) and 11% (MDR < 0.83) respectively. Most synergistic effects (55%) were observed as interactions between sterol-biosynthesis-inhibiting (SBI) fungicides and insecticide/acaricide. The mechanisms behind such synergistic effects of binary mixtures in bees are known to involve direct cytochrome P450 (CYP) inhibition, resulting in an increase in internal dose and toxicity of the binary mixture. Moreover, bees are known to have the lowest number of CYP copies and other detoxification enzymes in the insect kingdom. In the light of these findings, occurrence of these binary mixtures in relevant crops (frequency and concentrations) would need to be investigated. Addressing this exposure dimension remains critical to characterise the likelihood and plausibility of such interactions to occur under field realistic conditions. Finally, data gaps and further work for the development of risk assessment methods to assess multiple stressors in bees including chemicals and non-chemical stressors in bees are discussed.

Nested interactions in the combined toxicity of uranium and cadmium to the nematode Caenorhabditis elegans.

Uranium is a natural, ubiquitous radioactive element for which elevated concentrations can be found in the vicinity of some nuclear fuel cycle facilities or intensive farming areas, and most often in mixtures with other contaminants such as cadmium, due to co-occurrence in geological ores (e.g. U- or P-ore). The study of their combined effects on ecosystems is of interest to better characterize such multi-metallic polluted sites. In the present study, the toxicity of binary mixture of U and Cd on physiological parameters of the soil nematode Caenorhabditis elegans was assessed over time. Descriptive modeling using concentration and response addition reference models was applied to compare observed and expected combined effects and identify possible synergistic or antagonistic interactions. A strong antagonism between U and Cd was identified for length increase and brood size endpoints. The study revealed that the combined effects might be explained by two nested antagonistic interactions. We demonstrate that the first interaction occurred in the exposure medium. We also identified a significant second antagonistic interaction which occurred either during the toxicokinetic or toxicodynamic steps. These findings underline the complexity of interactions that may take place between chemicals and thus, highlight the importance of studying mixtures at various levels to fully understand underlying mechanisms.

Metal-based nanoparticles in soil: fate, behavior, and effects on soil invertebrates.

Metal-based nanoparticles (NPs) (e.g., silver, zinc oxide, titanium dioxide, iron oxide) are being widely used in the nanotechnology industry. Because of the release of particles from NP-containing products, it is likely that NPs will enter the soil compartment, especially through land application of sewage sludge derived from wastewater treatment. This review presents an overview of the literature dealing with the fate and effects of metal-based NPs in soil. In the environment, the characteristics of NPs (e.g., size, shape, surface charge) and soil (e.g., pH, ionic strength, organic matter, and clay content) will affect physical and chemical processes, resulting in NP dissolution, agglomeration, and aggregation. The behavior of NPs in soil will control their mobility and their bioavailability to soil organisms. Consequently, exposure characterization in ecotoxicological studies should obtain as much information as possible about dissolution, agglomeration, and aggregation processes. Comparing existing studies is a challenging task, because no standards exist for toxicity tests with NPs. In many cases, the reporting of associated characterization data is sparse, or missing, making it impossible to interpret and explain observed differences in results among studies.