Baseline Toxic Mixtures of Non-Toxic Chemicals: “Solubility Addition” Increases Exposure for Solid Hydrophobic Chemicals

Abstract

This study addresses the question whether hydrophobic organic chemicals exerting no toxicity at their solubility limit (saturation) can form a toxic mixture. Spiking methods generally do not allow testing exactly at saturation without introducing microcrystals. Passive dosing was thus applied to test the acute toxicity of several high melting point PAHs and their mixtures at the respective saturation levels to aquatic and terrestrial invertebrates. With the aquatic Daphnia magna, anthracene, chrysene, and benzo(a)pyrene resulted in no or limited acute toxicity (0-20%), whereas binary and tertiary mixtures of these resulted in significant acute toxicity (70-88%). Toxicity of PAHs and their mixtures could be fitted with one (sum) chemical activity-response curve in accordance with a similar mode of toxic action (i.e., concentration addition). The effective chemical activity (Ea-50) of 0.029 and the effective concentration on a lipid basis (EC(lipid, eq.)-50) of 95.7 mM were well within the range for baseline toxicity. Similar mixtures showed less toxicity to the terrestrial Folsomia candida due to steady-state body-burdens being below equilibrium partitioning levels. The results of the present study raise questions about the focus of risk assessment schemes and toxicity testing guidelines on individual substances, since apparently non-toxic chemicals might become toxic in a mixture.

The potentiation effect makes the difference: Non-toxic concentrations of ZnO nanoparticles enhance Cu nanoparticle toxicity in vitro

“…Although potentiation effects are considered when evaluating risk in specific cases, such as in workplace exposure or for pesticide residues in food and feed (Smith et al, 2013), most regulatory frameworks for chemicals continue to focus on the testing of single substances. However, here we demonstrate that the combined toxicity of several substances-a realistic scenario-can differ greatly from that produced by each individual substance alone.…”

“…Here we found that the combination of two distinct NPs at concentrations causing no or very limited cytotoxic effects when present alone led to a strong enhancement of toxicity. Potentiation phenomena have been described for a variety of chemicals in a number of systems (for instance studies of Smith et al (2013) in D. magna and Torre- Roche et al (2013) in C. pepo and G. max). However, few data are available on such effects after exposure to a mixture of NPs (Chen et al, 2008;Tang et al, 2013).…”

Endocrine activity of persistent organic pollutants accumulated in human silicone implants — Dosing assays by partitioning from silicone

“…Importantly, the toxicity of single chemicals can be modified when present in a mixture through toxicokinetic interactions with cosolutes, solubility addition (Smith et al, 2013b) or a joint action at the target site, which can enhance or inhibit the effect of endogenous hormones (Carpenter et al, 2002;Silva et al, 2002). It has also been shown that minor changes in mixture composition can cause larger shifts of endocrine responses (Kortenkamp, 2007).…”

QSARs for aquatic toxicity: celebrating, extending and displaying the pioneering contributions of Ferguson, Konemann and Veith

“…The median value of chemical activity associated with acute baseline narcosis in fish is quite similar to previously reported values using other datasets. Median lethal activity values of 0.037 for fish and 0.19 for rodents have been calculated [8,9] and 0.02 to 0.05 for aquatic invertebrates have been measured [16].…”