Screening for frequently detected quaternary ammonium mixture systems in waters based on frequent itemset mining and prediction of their toxicity.

Screening and prioritizing research on frequently detected mixture systems in the environment is of great significance, as conducting toxicity testing on all mixtures is impractical. Therefore, the frequent itemset mining (FIM) was introduced and applied in this paper to identify variables that commonly co-occur in a dataset. Based on the dataset of the quaternary ammonium compounds (QACs) in the water environment, the four frequent QAC mixture systems with detection rate ≥ 35 % were found, including [BDMM]+Cl--[BTMM]+Cl- (M1), [BDMM]+Cl--[BHMM]+Cl- (M2), [BTMM]+Cl- -[BHMM]+Cl- (M3), and [BDMM]+Cl--[BTMM]+Cl--[BHMM]+Cl- (M4). [BDMM]+Cl-, [BTMM]+Cl-, and [BHMM]+Cl- are benzyl dodecyl dimethyl ammonium chloride, benzyl tetradecyl dimethyl ammonium chloride, and benzyl hexadecyl dimethyl ammonium chloride, respectively. Then, the toxicity of the representative mixture rays and components for the four frequently detected mixture systems was tested using Vibrio qinghaiensis sp.-Q67 (Q67) as a luminescent indicator organism at 0.25 and 12 h. The toxicity of the mixtures was predicted using concentration addition (CA) and independent action (IA) models. It was shown that both the components and the representative mixture rays for the four frequently detected mixture systems exhibited obvious acute and chronic toxicity to Q67, and their median effective concentrations (EC50) were below 7 mg/L. Both CA and IA models predicted the toxicity of the four mixture systems well. However, the CA model had a better predictive ability for the toxicity of the M3 and M4 mixtures than IA at 12 h.

Time-dependent nonmonotonic concentration-response and synergism of alkyl glycosides with different alkyl side chain to Vibrio qinghaiensis sp. -Q67.

Alkyl glycosides (AGs), commonly used nonionic surfactants, may have toxic effects on the environmental organisms. However, the complex concentration-response patterns of AGs with varying alkyl side chains and their mixtures have not been thoroughly studied. Therefore, the luminescence inhibition toxicities of six AGs with different alkyl side chains, namely, ethyl (AG02), butyl (AG04), hexyl (AG06), octyl (AG08), decyl (AG10), and dodecyl (AG12) glucosides, were determined in Vibrio qinghaiensis sp. -Q67 (Q67) at 0.25, 3, 6, 9, and 12 h. The six AGs exhibited time- and side-chain-dependent nonmonotonic concentration- responses toward Q67. AG02, with a short side chain, presented a concentration-response curve (CRC) with two peaks after 6 h and stimulated the luminescence of Q67 at both 6 and 9 h. AG04, AG06, and AG08 showed S-shaped CRCs at five exposure time points, and their toxicities increased with the side-chain length. AG10 and AG12, with long side chains, exhibited hormesis at 9 and 12 h. Molecular docking was performed to explore the mechanism governing the possible influence of AGs on the luminescence response. The effects of AGs on Q67 could be attributed to multiple luminescence-regulatory proteins, including LuxA, LuxC, LuxD, LuxG, LuxI, and LuxR. Notably, LuxR was identified as the primary binding protein among the six AGs. Given that they may co-exist, binary mixtures of AG10 and AG12 were designed to explore their concentration-response patterns and interactions. The results revealed that all AG10-AG12 binary mixture rays showed time-dependent hormesis on Q67, similar to that shown by their individual components. The interactions of these binary mixtures were mainly characterized by low-concentration additive action and high-concentration synergism at different times.

Beneficial or harmful: Time-dependent hormesis induced by typical disinfectants and their mixtures with toxicological interaction.

Disinfectants and their mixtures can induce hormesis. However, how the mixture hormesis is related to those of components and the interactions in disinfectant mixtures remain unclear. In this paper, the luminescence inhibition toxicities of chlorinated sodium phosphate (CSP), dodecyl dimethyl benzyl ammonium bromide (DOB), dodecyl dimethyl benzyl ammonium chloride (DOC), ethanol (EtOH), glutaraldehyde (GLA), hydrogen peroxide (H2O2), isopropyl alcohol (IPA), n-propanol (NPA), and 20 mixture rays in four mixture systems (EtOH-H2O2, DOB-H2O2, DOC-EtOH, and EtOH-IPA-NPA) containing at least one component showing hormesis to Vibrio qinghaiensis sp.-Q67 (Q67) were determined at 0.25, 3, 6, 9, and 12 h. The synergism-antagonism heatmap based on independent action model (noted as SAHmapIA) was developed to systematically evaluate the interactions in various mixtures. It was shown that five disinfectants (CSP, EtOH, H2O2, NPA, and IPA) and 17 mixture rays exhibited time-dependent hormesis. The hormetic component was responsible for the hormesis of the mixture rays. Most mixture rays showed low- concentration/dose additive action and high-concentration/dose synergism at different time. This study further exemplified the interrelationship between the hormesis in the mixtures and their components and implied the need to pay attention to the time-dependent hormesis and interactions induced by the disinfectants.

Transfer pattern of hormesis into personal care product mixtures from typical hormesis-inducing compounds.

Some personal care products (PCPs) and their chemical components showed a hormetic effect in the freshwater photobacterium Vibrio qinghaiensis sp. -Q67 (Q67) after long-term exposure. However, how hormesis transfers between chemical components and PCP mixture, and which chemical component plays a major role remain unknown. To this end, according to the seven compounds detected in one skin lotion (SK5) and their concentration ratios, many mixture rays were constructed to simulate the SK5. Of these seven compounds, three presented monotonic concentration-response curves (CRC) to Q67 at 0.25 and 12 h (called a S-shaped compound). The other four compounds showed hormetic CRCs after 12 h and monotonic CRCs at 0.25 h (called a J-shaped compound). Based on their mixture ratios, we designed one ternary mixture ray of all S-shaped compounds, one quaternary mixture ray of all J-shaped compounds, and four quaternary mixture rays of one J-shaped and three S-shaped compounds. It was shown that SK5 could be approximately simulated by the mixture ray of the seven compounds detected in SK5 and only the mixture rays containing at least one hormesis-inducing compound produced hormesis to Q67 at 12 h. Based on the concentration ratios of various compounds and comparison of four hormetic characteristic parameters to those of various mixture rays, it was found that the compound betaine (BET) is a key compound affecting the hormesis of mixtures. Additionally, we studied the hormesis mechanism of BET on Q67 via quorum sensing (QS). This preliminarily indicated that the autoinducer-2 triggered the QS pathway. This study elucidated the transfer pattern of hormesis into mixtures, which would be an efficient method to identifying the potential components that affect hormesis transfer in mixtures. We expect that this study will provide new insights into hormesis and its mixtures.

Application of the combination index integrated with confidence intervals to study the toxicological interactions of antibiotics and pesticides in Vibrio qinghaiensis sp.-Q67.

It is necessary to explore the effect of confidence intervals on the combination index (CI) so that rationally evaluate the toxicological interaction (synergism or antagonism) which is dependent on the concentration ratio, the mixture concentration and the exposure time. To effectively detect the toxicological interaction taking place in mixtures, we combined the CI with the observation-based confidence intervals (OCI) which can characterize the uncertainty in toxicity test and in data fitting. In time scale, the short-term (15min) and long-term (12h) toxicities of three chemicals (imidacloprid (IMI), pirimicarb (PIR) and streptomycin sulfate (STR)) and their binary mixtures on Vibrio qinghaiensis sp.-Q67 were determined by the microplate toxicity analysis (MTA). The mixtures of IMI, PIR and STR have additive actions all but four IMI-PIR rays (R2-R5) at the effect levels above about 30-40% whose long-term toxicological interaction are synergism.