Quantifying synergy:a systematic review of mixture toxicity studies within environmental toxicology

Cocktail effects and synergistic interactions of chemicals in mixtures are an area of great concern to both the public and regulatory authorities. The main concern is whether some chemicals can enhance the effect of other chemicals, so that they jointly exert a larger effect than predicted. This phenomenon is called synergy. Here we present a review of the scientific literature on three main groups of environmentally relevant chemical toxicants: pesticides, metal ions and antifouling compounds. The aim of the review is to determine 1) the frequency of synergy, 2) the extent of synergy, 3) whether any particular groups or classes of chemicals tend to induce synergy, and 4) which physiological mechanisms might be responsible for this synergy. Synergy is here defined as mixtures with minimum two-fold difference between observed and predicted effect concentrations using Concentration Addition (CA) as a reference model and including both lethal and sub-lethal endpoints. The results showed that synergy occurred in 7%, 3% and 26% of the 194, 21 and 136 binary pesticide, metal and antifoulants mixtures included in the data compilation on frequency. The difference between observed and predicted effect concentrations was rarely more than 10-fold. For pesticides, synergistic mixtures included cholinesterase inhibitors or azole fungicides in 95% of 69 described cases. Both groups of pesticides are known to interfere with metabolic degradation of other xenobiotics. For the four synergistic metal and 47 synergistic antifoulant mixtures the pattern in terms of chemical groups inducing synergy was less clear. Hypotheses in terms of mechanisms governing these interactions are discussed. It was concluded that true synergistic interactions between chemicals are rare and often occur at high concentrations. Addressing the cumulative rather than synergistic effect of co-occurring chemicals, using standard models as CA, is therefore regarded as the most important step in the risk assessment of chemical cocktails

Assessment of risks related to agricultural use of sewage sludge, pig and cattle slurry

In April 2017, the Organic Business Development Team released a report with 25 recommendations for the Minister of Environment and Food (Det økologiske erhvervsteam 2017). Among these was a recommendation that organic farmers should have opportunities for utilizing nutrients from treated domestic wastewater for nutrient recycling. A prerequisite for future use of nutrients from treated wastewater is, that quality requirements are met and that application can be explained to (and accepted by) consumers. In partial fulfilment of this, the business team identified a need for a scientific overview of the risks of using nutrients from treated municipal wastewater in relation to other authorized fertilizer sources – e.g. conventional animal manures. Thus, it was assumed that a comparative approach to assess potential risk of using sewage sludge and conventional manures, could usefully inform decision makers in the future regulation of organic farming systems. Dependent on the result of the scientific investigation, the Organic Business Development Team foresaw that Denmark could chose to work to expand Annex 1 of the EU Ecology Regulation, to allow the organic farmers to use nutrients from municipal wastewater or other acceptable derived sludge products. Mobilization of support for this should be done by the Ministry of Environment and Food in collaboration with the Organic Farming Industry. Thus, based on available literature, this report aims at creating an overview of the environmental and human risks associated with application of pig and cattle slurry as well as sewage sludge to agricultural soils. The risk evaluation was performed for the following compound groups: Metals, Chlorophenyls, Dioxins, Furans, Halogenated aliphatic and aromatic hydrocarbons (HAH), Linear alkylbenzenesulfonates (LAS), Polyaromatic hydrocarbons (PAH), Polybrominated diphenyl ethers (PBDE), Polychlorinated biphenyls (PCB), Poly- and perfluorinated alkylated substances (PFAS), Phenols, Phosphate-triesters VII, Phthalates, Polychlorinated naphtalenes (PCN), Polychlorinated alkanes (PCA), Triclosan, Triclocarban, Medicines, Estrogens, Antibiotic resistance genes. Additionally the fertilizer potential of the two nutrient sources was characterized and compared

Variable temperature stress in the nematode Caenorhabditis elegans (Maupas) and its implications for sensitivity to an additional chemical stressor

A wealth of studies has investigated how chemical sensitivity is affected by temperature, however, almost always under different constant rather than more realistic fluctuating regimes. Here we compared how the nematode Caenorhabditis elegans responds to copper at constant temperatures (8–24°C) and under fluctuation conditions of low (±4°C) and high (±8°C) amplitude (averages of 12, 16, 20°C and 16°C respectively). The DEBkiss model was used to interpret effects on energy budgets. Increasing constant temperature from 12–24°C reduced time to first egg, life-span and population growth rates consistent with temperature driven metabolic rate change. Responses at 8°C did not, however, accord with this pattern (including a deviation from the Temperature Size Rule), identifying a cold stress effect. High amplitude variation and low amplitude variation around a mean temperature of 12°C impacted reproduction and body size compared to nematodes kept at the matching average constant temperatures. Copper exposure affected reproduction, body size and life-span and consequently population growth. Sensitivity to copper (EC50 values), was similar at intermediate temperatures (12, 16, 20°C) and higher at 24°C and especially the innately stressful 8°C condition. Temperature variation did not increase copper sensitivity. Indeed under variable conditions including time at the stressful 8°C condition, sensitivity was reduced. DEBkiss identified increased maintenance costs and increased assimilation as possible mechanisms for cold and higher copper concentration effects. Model analysis of combined variable temperature effects, however, demonstrated no additional joint stressor response. Hence, concerns that exposure to temperature fluctuations may sensitise species to co-stressor effects seem unfounded in this case

Soil pH effects on the comparative toxicity of dissolved zinc, non-nano and nano ZnO to the earthworm Eisenia fetida

To determine how soil properties influence nanoparticle (NP) fate, bioavailability and toxicity, this study compared the toxicity of nano zinc oxide (ZnO NPs), non-nano ZnO and ionic ZnCl2 to the earthworm Eisenia fetida in a natural soil at three pH levels. NP characterisation indicated that reaction with the soil media greatly controls ZnO properties. Three main conclusions were drawn. First that Zn toxicity, especially for reproduction, was influenced by pH for all Zn forms. This can be linked to the influence of pH on Zn dissolution. Secondly, that ZnO fate, toxicity and bioaccumulation were similar (including relationships with pH) for both ZnO forms, indicating the absence of NP-specific effects. Finally, earthworm Zn concentrations were higher in worms exposed to ZnO compared to ZnCl2, despite the greater toxicity of the ionic form. This observation suggests the importance of considering the relationship between uptake and toxicity in nanotoxicology studies