Further Exploring Linear Concentration Addition and Independent Action for Predicting Non-interactive Mixture Toxicity

Since it is unrealistic to do an experimental mixture assessment on every possible combination, mathematical model plays an important role in predicting the mixture toxicity. The present study is devoted to the further application of linear concentration addition（CA）-based model（LCA） and independent action（IA）-based model（LIA） to predict the non-interactive mixture toxicity. The 26 mixtures including 312 data points were used to evaluate the predictive powers of LCA and LIA models. The models were internally validated using the leave-one-out cross-validation and y-randomization test, and the external validations were evaluated by the test tests. Both LCA and LIA models agree well with the experimental values for all mixture toxicity, and present high internally（R2 and Q2 〉 0.98） and externally（Q2F1, Q2F2, and Q2F3 〉 0.99） predictive power. The use of LCA and LIA led to improved predictions compared to the estimates based on the CA and IA models. Both LCA and LIA were found to be appropriate methods for modeling toxicity of non-interactive chemical mixtures.

Single and Repeat Dose Toxicity Study of 7-Hydroxycoumarin, Ethanol, and Their Mixture in Rats

Acute and repeat-dose toxic effects ofHOC （7-hydroxycoumarin）, ethanol and their mixture were studied in rats. Single oral administration of HOC （5,000 mg/kg） caused transitional glycosuria associated with lowered serum glucose levels, decreased urea clearance. HOC given orally during 28 days （200 mg/kg） decreased serum glucose, and increased serum triglyceride concentrations. No enhancement of acute toxic effect of HOC （5,000 mg/kg） and ethanol （6,000 mg/kg） mixture was found in the acute toxicity study phase. Effect of HOC （200 mg/kg） and ethanol （750 mg/kg） during 28 days of exposure was less pronounced in comparison with HOC effect only, as far as neither decrease of glucose, nor increase oftriglyceride serum concentrations were found.

Mixture Toxicities of Three Pesticides Having Different Time-Toxicity Profiles

In the environment,chemical pollutants always exist as mixtures.To evaluate mixture toxicity,we should ex-amine the concentration ratios and the concentration levels of mixture components as well as the interactive time between the components and testing organism.Selecting three pesticides,metribuzin(MET),dodine(DOD)and ri-domil(RID),as mixture components,Vibrio qinghaiensis sp.-Q67 as testing organism,and 96-well microplate as exposure experiment carrier,the luminescence inhibition toxicities of the pesticides and their binary mixtures at six exposure time points(0.25,2,4,8,12,and 16 h)were determined.The results showed that the three pesticides have different time-toxicity profiles.The toxicity of MET increases over time,and those of DOD and RID show a slight decrease or increase in the first 4 h,respectively,and then remain unchanged to 16 h.The toxicities of the binary mixtures consisting of the three pesticides depend on not only the mixture composition but also the exposure time.The time-toxicity profiles of all rays in MET-DOD mixture system are U-shaped curves,those in MET-RID system are basically monotonically increased and those in DOD-RID system are basically monotonically decreased.How-ever,our findings indicate that for the test substances,mixture toxicity can be predicted by the extended concentra-tion addition model.

Comparative cytotoxicity of nanoparticles and ions to Escherichia coli in binary mixtures

The objective of this study was to understand toxicity of mixture of nanoparticles （NPs） （ZnO and TiO2） and their ions to Escherichia coll. Results indicated the decrease in percentage growth of E. coli with the increase in concentration of NPs both in single and mixture setups. Even a small concentration of I mg/L was observed to be significantly toxic to E. coli in binary mixture setup （exposure concentration： 1 mg/L ZnO and 1 mg/L TiO2; 21.15% decrease in plate count concentration with respect to control）. Exposure ofE. coli to mixture of NPs at 1000 mg/L （i.e., 1000 mg/L ZnO and 1000 mg/L TiO2） resulted in 99.63% decrease in plate count concentration with respect to control. Toxic effects of ions to E. coli were found to be lesser than their corresponding NPs. The percentage growth reduction was found to be 36% for binary mixture of zinc and titanium ions at the highest concentration （i.e., 803.0 mg/L Zn and 593.3 mg/L Ti where ion concentrations are equal to the Zn ions present in 1000 mg/L ZnO NP solution and Ti＋4 ions present in 1000 mg/L TiO2 NP solution）. Nature of mixture toxicity of the two NPs to E. coli was found to be antagonistic. The alkaline phosphatase （Alp） assay indicated that the maximum damage was observed when E. coli was exposed to 1000 mg/L of mixture of NPs. This study tries to fill the knowledge gap on information of toxicity of mixture of NPs to bacteria which has not been reported earlier.

Joint effects of Penta-BDE and heavy metals on Daphnia magna survival,its antioxidant enzyme activities and lipid peroxidation

The joint toxicity of Penta-BDE(Pe-BDE)and heavy metals including cadmium and copper on Daphnia magna(D.magna)was evaluated on the basis of determining the 48 h survival,antioxidative enzyme responses,and lipid peroxidation.The response was classified as additive,greater than additive,or less than additive by comparing the measured“toxic units,TU”with one.Based on the survival of D.magna,less-than-additive interactions were found in most of mixtures treatments.This may be attributed to the different toxicity mechanism between Pe-BDE and metals.Cu and Cd played a greater role in toxicity than what Pe-BDE did.As for the superoxide dismutase(SOD)and catalase(CAT)activity,most response was less than additive.For the glutathione S-transferases(GST)activity,most of the greater-thanadditive responses were found in the Cu plus Pe-BDE treatments,but the additive responses occurred in Cd plus Pe-BDE treatments and binary metal treatments.For lipid peroxide levels,which were measured as malondialdehyde(MDA)levels,less-than-additive response occurred in the 50%Cd plus 50%Cu and ternary mixture treatments.Results suggested that Pe-BDE,Cd,and Cu could induce different patterns of antioxidant enzyme responses,such as antioxidant/prooxidant responses,depending on their capability to produce reactive oxygen species and antioxidant enzymes to detoxify them.

Effects of multiple but low pesticide loads on aquatic fungal communities colonizing leaf litter

In the first tier risk assessment（RA） of pesticides, risk for aquatic communities is estimated by using results from standard laboratory tests with algae, daphnids and fish for single pesticides such as herbicides, fungicides, and insecticides. However, fungi as key organisms for nutrient cycling in ecosystems as well as multiple pesticide applications are not considered in the RA. In this study, the effects of multiple low pesticide pulses using regulatory acceptable concentrations（RACs） on the dynamics of non-target aquatic fungi were investigated in a study using pond mesocosm. For that, fungi colonizing black alder（Alnus glutinosa） leaves were exposed to multiple, low pulses of 11 different pesticides over a period of 60 days using a real farmer＇s pesticide application protocol for apple cropping.Four pond mesocosms served as treatments and 4 as controls. The composition of fungal communities colonizing the litter material was analyzed using a molecular fingerprinting approach based on the terminal Restriction Fragment Length Polymorphism（t-RFLP） of the fungal Internal Transcribed Spacer（ITS） region of the ribonucleic acid（RNA） gene（s）. Our data indicated a clear fluctuation of fungal communities based on the degree of leaf litter degradation. However significant effects of the applied spraying sequence were not observed. Consequently also degradation rates of the litter material were not affected by the treatments. Our results indicate that the nutrient rich environment of the leaf litter material gave fungal communities the possibility to express genes that induce tolerance against the applied pesticides. Thus our data may not be transferred to other fresh water habitats with lower nutrient availability.