Predicting the occurrence of antagonism within ternary guanidine mixture pollutants based on the concentration ratio of components.

The widespread prevalence and coexistence of diverse guanidine compounds pose substantial risks of potential toxicity interactions, synergism or antagonism, to environmental organisms. This complexity presents a formidable challenge in assessing the risks associated with various pollutants. Hence, a method that is both accurate and universally applicable for predicting toxicity interactions within mixtures is crucial, given the unimaginable diversity of potential combinations. A toxicity interaction prediction method (TIPM) developed in our past research was employed to predict the toxicity interaction, within guanidine compound mixtures. Here, antagonism were found in the mixtures of three guanidine compounds including chlorhexidine (CHL), metformin (MET), and chlorhexidine digluconate (CDE) by selecting Escherichia coli (E. coli) as the test organism. The antagonism in the mixture was probably due to the competitive binding of all three guanidine compounds to the anionic phosphates of E. coli cell membranes, which eventually lead to cell membrane rupture. Then, a good correlation between toxicity interactions (antagonisms) and components' concentration ratios (pis) within binary mixtures (CHL-MET, CHL-CDE, MET-CDE) was established. Based on the correlation, the TIPM was constructed and accurately predicted the antagonism in the CHL-MET-CDE ternary mixture, which once again proved the accuracy and applicability of the TIPM method. Therefore, TIPM can be suggested to identify or screen rapidly the toxicity interaction within ternary mixtures exerting potentially adverse effects on the environment.

Quantitative characterization of toxicity interaction within antibiotic-heavy metal mixtures on Chlorella pyrenoidosa by a novel area-concentration ratio method.

Toxicity interaction, synergism and antagonism, may occur when multiple pollutants are exposed to the environment simultaneously, which limits the utility of some standard models to assess toxicity hazards and risks. The development and application of models which can provide an insight into the combined toxicity of pollutants becomes necessary. Therefore, a novel model, area-concentration ratio (ACR) method, was developed to characterize the toxicity interaction within mixtures of three aminoglycoside antibiotics (AGs), kanamycin sulfate (KAN), paromomycin sulfate (PAR), tobramycin (TOB) and one heavy metal copper (Cu) in this study. The inhibition toxicity of single contaminants and mixtures designed by direct equilibration ray method and uniform design ray method to Chlorella pyrenoidosa (C. pyrenoidosa) was determined by the microplate toxicity analysis (MTA). The results showed that the novel method ACR could be used for quantitative characterization of combined toxicity. According to the ACR, all the binary AG antibiotic mixture systems display obvious synergism and weak antagonism. The addition of the heavy metal Cu into binary AG antibiotic mixtures can obviously change toxicity interaction, but toxicity interaction changing trend varies greatly in different ternary mixture systems. Toxicity interaction in the six mixture systems has component concentration-ratio dependence. ACR can be suggested as an effective novel method to quantitatively characterize toxicity interaction when assessing the hazards and risks of the combined pollution.

Comprehensive Study of Isocarbophos to Various Terrestrial Organisms: Enantioselective Bioactivity, Acute Toxicity, and Environmental Behaviors.

The enantioselective bioactivity, toxicity, and environmental behaviors of isocarbophos (ICP) were investigated. The order of the bioactivity and toxicity was S-(+) ≥ rac > R-(-), and the difference of R-(-) and S-(+) was up to 232 times. The usage of S-(+)-ICP may efficiently reduce the usage amount of rac-ICP by 35% under the same effect, and the toxicity was not increased. Based on the toxic unit analysis, the additive effect and synergistic effect of ICP enantiomers were found in the four nontarget organisms, and R-(-)-ICP might cooperate the side-effects of S-(+)-ICP. The accumulation of rac-ICP in earthworms was enantioselective with an enantioenrichment of R-(-)-ICP, so the usage of racemic ICP might increase the exposure risk of R-(-)-ICP to earthworms. From the comprehensive results, the production of enantiomer enriched S-(+)-ICP might increase bioactivity and reduce environmental pollution, while the toxicity of S-(+)-ICP to other nontarget organisms needs to be further assessed.

Toxicity interactions between manganese (Mn) and lead (Pb) or cadmium (Cd) in a model organism the nematode C. elegans.

Manganese (Mn) is considered as an emerging metal contaminant in the environment. However, its potential interactions with companying toxic metals and the associated mixture effects are largely unknown. Here, we investigated the toxicity interactions between Mn and two commonly seen co-occurring toxic metals, Pb and Cd, in a model organism the nematode Caenorhabditis elegans. The acute lethal toxicity of mixtures of Mn+Pb and Mn+Cd were first assessed using a toxic unit model. Multiple toxicity endpoints including reproduction, lifespan, stress response, and neurotoxicity were then examined to evaluate the mixture effects at sublethal concentrations. Stress response was assessed using a daf-16::GFP transgenic strain that expresses GFP under the control of DAF-16 promotor. Neurotoxicity was assessed using a dat-1::GFP transgenic strain that expresses GFP in dopaminergic neurons. The mixture of Mn+Pb induced a more-than-additive (synergistic) lethal toxicity in the worm whereas the mixture of Mn+Cd induced a less-than-additive (antagonistic) toxicity. Mixture effects on sublethal toxicity showed more complex patterns and were dependent on the toxicity endpoints as well as the modes of toxic action of the metals. The mixture of Mn+Pb induced additive effects on both reproduction and lifespan, whereas the mixture of Mn+Cd induced additive effects on lifespan but not reproduction. Both mixtures seemed to induce additive effects on stress response and neurotoxicity, although a quantitative assessment was not possible due to the single concentrations used in mixture tests. Our findings demonstrate the complexity of metal interactions and the associated mixture effects. Assessment of metal mixture toxicity should take into consideration the unique property of individual metals, their potential toxicity mechanisms, and the toxicity endpoints examined.