Assessing joint toxicity of chemicals in Enchytraeus albidus (Enchytraeidae) and Porcellionides pruinosus (Isopoda) using avoidance behaviour as an endpoint

Contamination problems are often characterized by complex mixtures of chemicals. There are two conceptual models usually used to evaluate patterns of mixture toxicity: Concentration Addition (CA) and Independent Action (IA). Deviations from these models as synergism, antagonism and dose dependency also occur. In the present study, single and mixture toxicity of atrazine, dimethoate, lindane, zinc and cadmium were tested in Porcellionides pruinosus and Enchytraeus albidus, using avoidance as test parameter. For both species patterns of antagonism were found when exposed to dimethoate and atrazine, synergism for lindane and dimethoate exposures (with the exception of lower doses in the isopod case study) and concentration addition for cadmium and zinc occurred, while the exposure to cadmium and dimethoate showed dissimilar patterns.This study highlights the importance of dose dependencies when testing chemical mixtures and that avoidance tests can also be used to asses the effects of mixture toxicity.     

The interaction effects of binary mixtures of benzene and toluene on the developing heart of medaka (Oryzias latipes)

The United States Environmental Protection Agency (USEPA) has pursued the estimation of risk of adverse health effects from exposure to chemical mixtures since the early 1980s. Methods used to calculate risk estimates of mixtures were often based on single chemical information that required assumptions of dose-addition or response-addition and did not consider possible changes in response due to interaction effects among chemicals. Full factorial designs for laboratory studies can produce interactions information, but these are expensive to perform and may not provide the information needed to evaluate specific environmentally relevant mixtures. In this research, groups of Japanese medaka (Oryzias latipes) embryos were exposed to binary mixtures of benzene and toluene as well as to each of these chemicals alone. Endpoint specific dose-response models were built for the hydrocarbon mixture under an assumption of dose-additivity, using the single chemical dose-response information on benzene and toluene. The endpoints included heart rate, heart rate progression, and lethality. Results included a synergistic response for heart rate at 72 h of development, and either additivity or antagonism for all other endpoints at 96 h of development. This work uses an established statistical method to evaluate the toxicity of an environmentally relevant mixture to ascertain whether interaction effects are occurring, thus providing additional information on toxicity.     

A comparison of mixture toxicity assessment: examining the chronic toxicity of atrazine, permethrin and chlorothalonil in mixtures to Ceriodaphnia cf. dubia

Pesticides predominantly occur in aquatic ecosystems as mixtures of varying complexity, yet relatively few studies have examined the toxicity of pesticide mixtures. Atrazine, chlorothalonil and permethrin are widely used pesticides that have different modes of action. This study examined the chronic toxicities (7-d reproductive impairment) of these pesticides in binary and ternary mixtures to the freshwater cladoceran Ceriodaphnia cf. dubia. The toxicity of the mixtures was compared to that predicted by the independent action (IA) model for mixtures, as this is the most appropriate model for chemicals with different modes of action. Following this they were compared to the toxicity predicted by the concentration addition (CA) model for mixtures. According to the IA model, the toxicity of the chlorothalonil plus atrazine mixture conformed to antagonism, while that of chlorothalonil and permethrin conformed to synergism. The toxicity of the atrazine and permethrin mixture as well as the ternary mixture conformed to IA implying there was either no interaction between the components of these mixtures and/or in the case of the ternary mixture the interactions cancelled each other out to result in IA. The synergistic and antagonistic mixtures deviated from IA by factors greater than 3 and less than 2.5, respectively. When the toxicity of the mixtures was compared to the predictions of the CA model, the binary mixture of chlorothalonil plus atrazine, permethrin plus atrazine and the ternary mixture all conformed to antagonism, while the binary mixture of chlorothalonil plus permethrin conformed to CA. Using the CA model provided estimates of mixture toxicity that did not markedly underestimate the measured toxicity, unlike the IA model, and therefore the CA model is the most suitable to use in ecological risk assessments of these pesticides.     

Influence factors of multicomponent mixtures containing reactive chemicals and their joint effects

Organic chemicals usually coexist as a mixture in the environment, and the mixture toxicity of organic chemicals has received increased attention. However, research regarding the joint effects of reactive chemicals is lacking. In this study, we examined two kinds of reactive chemicals, cyanogenic toxicants and aldehydes and determined their joint effects on Photobacterium phosphoreum. Three factors were found to influence the joint effects of multicomponent mixtures containing reactive chemicals, including the number of components, the dominating components and the toxic ratios. With an increased number of components, the synergistic or antagonistic effects (interactions) will weaken to the additive effects (non-interactions) if the added component cannot yield a much stronger joint effect with an existing component. Contrarily, the joint effect of the mixture may become stronger instead of weaker if the added components can yield a much stronger joint effect than the existing joint effect of the multicomponent mixture. The components that yield the strongest interactions in their binary mixture can be considered the dominating components. These components contribute more to the interactions of multicomponent mixtures than other components. Moreover, the toxic ratios also influence the joint effects of the mixtures. This study provides an insight into what are the main factors and how they influence the joint effects of multicomponent mixtures containing reactive chemicals, and thus, the findings are beneficial to the study of mixture toxicology.     

Assessment of combined antiandrogenic effects of binary parabens mixtures in a yeast-based reporter assay

To date, toxicological studies of endocrine disrupting chemicals (EDCs) have typically focused on single chemical exposures and associated effects. However, exposure to EDCs mixtures in the environment is common. Antiandrogens represent a group of EDCs, which draw increasing attention due to their resultant demasculinization and sexual disruption of aquatic organisms. Although there are a number of in vivo and in vitro studies investigating the combined effects of antiandrogen mixtures, these studies are mainly on selected model compounds such as flutamide, procymidone, and vinclozolin. The aim of the present study is to investigate the combined antiandrogenic effects of parabens, which are widely used antiandrogens in industrial and domestic commodities. A yeast-based human androgen receptor (hAR) assay (YAS) was applied to assess the antiandrogenic activities of n-propylparaben (nPrP), iso-propylparaben (iPrP), methylparaben (MeP), and 4-n-pentylphenol (PeP), as well as the binary mixtures of nPrP with each of the other three antiandrogens. All of the four compounds could exhibit antiandrogenic activity via the hAR. A linear interaction model was applied to quantitatively analyze the interaction between nPrP and each of the other three antiandrogens. The isoboles method was modified to show the variation of combined effects as the concentrations of mixed antiandrogens were changed. Graphs were constructed to show isoeffective curves of three binary mixtures based on the fitted linear interaction model and to evaluate the interaction of the mixed antiandrogens (synergism or antagonism). The combined effect of equimolar combinations of the three mixtures was also considered with the nonlinear isoboles method. The main effect parameters and interaction effect parameters in the linear interaction models of the three mixtures were different from zero. The results showed that any two antiandrogens in their binary mixtures tended to exert equal antiandrogenic activity in the linear concentration ranges. The antiandrogenicity of the binary mixture and the concentration of nPrP were fitted to a sigmoidal model if the concentrations of the other antiandrogens (iPrP, MeP, and PeP) in the mixture were lower than the AR saturation concentrations. Some concave isoboles above the additivity line appeared in all the three mixtures. There were some synergistic effects of the binary mixture of nPrP and MeP at low concentrations in the linear concentration ranges. Interesting, when the antiandrogens concentrations approached the saturation, the interaction between chemicals were antagonistic for all the three mixtures tested. When the toxicity of the three mixtures was assessed using nonlinear isoboles, only antagonism was observed for equimolar combinations of nPrP and iPrP as the concentrations were increased from the no-observed-effect-concentration (NOEC) to effective concentration of 80 %. In addition, the interactions were changed from synergistic to antagonistic as effective concentrations were increased in the equimolar combinations of nPrP and MeP, as well as nPrP and PeP. The combined effects of three binary antiandrogens mixtures in the linear ranges were successfully evaluated by curve fitting and isoboles. The combined effects of specific binary mixtures varied depending on the concentrations of the chemicals in the mixtures. At low concentrations in the linear concentration ranges, there was synergistic interaction existing in the binary mixture of nPrP and MeP. The interaction tended to be antagonistic as the antiandrogens approached saturation concentrations in mixtures of nPrP with each of the other three antiandrogens. The synergistic interaction was also found in the equimolar combinations of nPrP and MeP, as well as nPrP and PeP, at low concentrations with another method of nonlinear isoboles. The mixture activities of binary antiandrogens had a tendency towards antagonism at high concentrations and synergism at low concentrations.     

Synergistic effects caused by atrazine and terbuthylazine on chlorpyrifos toxicity to early-life stages of the zebrafish Danio rerio

This study examined the effects of three widely used pesticides that have been previously detected in aquatic systems neighbouring agricultural fields on the early-life stages of the zebrafish Danio rerio. Tests involving single exposures and binary combinations of the s-triazine herbicides (atrazine and terbuthylazine) and the organophosphate insecticide chlorpyrifos were performed. Several endpoints, such as swimming behaviour, morphological abnormalities and mortality, were studied. In addition, the inhibition of acetylcholinesterase (AChE) activity was investigated in order to evaluate the mode of action and toxicity of chlorpyrifos in the presence of these herbicides. Results indicate that both binary mixtures elicited synergistic responses on the swimming behaviour of zebrafish larvae. Moreover, although the herbicides were not effective inhibitors of the AChE on their own, a synergistic inhibition of the enzyme activity was obtained by exposure to mixtures with chlorpyrifos. We observed a correlation between impairment of swimming behaviour of the larvae and inhibition of AChE activity. This study supports previous studies concerning the risk assessment of mixtures since the toxicity may be underestimated when looking only at the single toxicants and not their mixtures.     

The joint effects of sulfonamides and their potentiator on Photobacterium phosphoreum: differences between the acute and chronic mixture toxicity mechanisms

Organisms are typically exposed to mixtures of chemicals over long periods of time; thus, chronic mixture toxicity analysis is the best way to perform risk assessment in regards to organisms. However, most studies focus on the acute mixture toxicity. To investigate the difference between chronic mixture toxicity and acute mixture toxicity, Photobacterium phosphoreum were exposed to chronic (24 h exposure) and acute (15 min exposure) toxicity of single sulfonamide (SA) and their potentiator (trimethoprim, TMP), both individually and mixtures (SA with TMP). A comparison of chronic vs. acute mixture toxicity revealed the presence of an interesting phenomenon, that is, that the joint effects vary with the duration of exposure; the acute mixture toxicity was antagonistic, whereas the chronic mixture toxicity was synergistic. Based on the approach of Quantitative Structure Activity Relationships (QSARs) and molecular docking, this phenomenon was proved to be caused by the presence of two points of dissimilarity between the acute and chronic mixture toxicity mechanism: (1) the receptor protein of SAs in acute toxicity was Luc, while in chronic toxicity it was Dhps, and (2) there is a difference between actual concentration of binding-Luc in acute toxicity and individual binding-Dhps in chronic toxicity. This deep insight into the difference between chronic and acute mixture toxicity will benefit environmental science, medical science, and other disciplines. The existence of these differences poses a challenge for the assessment of routine combinations in medicine, risk assessment, and mixture pollutant control, in which, previously, only a synergistic effect has been observed between SA and their potentiator.     

An overall risk probability-based method for quantification of synergistic and antagonistic effects in health risk assessment for mixtures: theoretical concepts

Purpose

In the assessment of health risks of environmental pollutants, the method of dose addition and the method of independent action are used to assess mixture effects when no synergistic and/or antagonistic effects are present. Currently, no method exists to quantify synergistic and/or antagonistic effects for mixtures. The purpose of this paper is to develop the theoretical concepts of an overall risk probability (ORP)-based method to quantify the synergistic and antagonistic effects in health risk assessment for mixtures.

Method

The ORP for health effects of environmental chemicals was determined from the cumulative probabilities of exposure and effects. This method was used to calculate the ORP for independent mixtures and for mixtures with synergistic and antagonistic effects.

Results

For the independent mixtures, a mixture ORP can be calculated from the product of the ORPs of individual components. For systems of interacting mixtures, a synergistic coefficient and an antagonistic coefficient were defined respectively to quantify the ORPs of each individual component in the mixture. The component ORPs with synergistic and/or antagonistic effects were then used to calculate the total ORP for the mixture.

Conclusions

An ORP-based method was developed to quantify synergistic and antagonistic effects in health risk assessment for mixtures. This represents a first method to generally quantify mixture effects of interacting toxicants.     

Individual and mixture toxicity of three pesticides; atrazine,chlorpyrifos, and chlorothalonil to the marine phytoplankton species Dunaliella tertiolecta

This study analyzed the toxicity of three pesticides (the herbicide atrazine, the insecticide chlorpyrifos and the fungicide chlorothalonil) individually, and in two mixtures (atrazine and chlorpyrifos; atrazine and chlorothalonil) to the marine phytoplankton species Dunaliella tertiolecta (Chlorophyta). A standard 96 h static algal bioassay was used to determine pesticide effects on the population growth rate of D. tertiolecta. Mixture toxicity was assessed using the additive index approach. Atrazine and chlorothalonil concentrations > or = 25 microg/L and 33.3 microg/L, respectively, caused significant decreases in D. tertiolecta population growth rate. At much higher concentrations (> or = 400 microg/L) chlorpyrifos also elicited a significant effect on D. tertiolecta population growth rate, but toxicity would not be expected at typical environmental concentrations. The population growth rate EC50 values determined for D. tertiolecta were 64 microg/L for chlorothalonil, 69 microg/L for atrazine, and 769 microg/L for chlorpyrifos. Atrazine and chlorpyrifos in mixture displayed additive toxicity, whereas atrazine and chlorothalonil in mixture had a synergistic effect. The toxicity of atrazine and chlorothalonil combined was approximately 2 times greater than that of the individual chemicals. Therefore, decreases in phytoplankton populations resulting from pesticide exposure could occur at lower than expected concentrations in aquatic systems where atrazine and chlorothalonil are present in mixture. Detrimental effects on phytoplankton population growth rate could impact nutrient cycling rates and food availability to higher trophic levels. Characterizing the toxicity of chemical mixtures likely to be encountered in the environment may benefit the pesticide registration and regulation process.     

Does lipophilicity of toxic compounds determine effects on drought tolerance of the soil collembolan Folsomia candida?

The ability of Collembola to survive drought stress is crucial for their distribution in the terrestrial environment. Previous studies have suggested that several toxic compounds affect the drought tolerance of Folsomia candida in a synergistic manner and that these compounds have the feature in common that they elicit their toxicity by causing membrane damage. We hypothesised that the detrimental effect of toxic chemicals on drought tolerance in F. candida depends on the lipophilicity (log K(ow)) of the compound because a higher log K(ow) would mean a closer interaction with membranes. In this study the three chemicals 4-nonylphenol, pyrene and p,p'-DDE were tested. Surprisingly, 4-nonylphenol, with the lowest log K(ow), was the most potent with respect to reducing drought tolerance followed by pyrene, suggesting that interactions between drought tolerance and chemical stress do not depend on lipophilicity alone.     

Toxic masking and synergistic modulation of the estrogenic activity of chemical mixtures in a yeast estrogen screen (YES)

Background, aim and scope

Estrogenic and non-estrogenic chemicals typically co-occur in the environment. Interference by non-estrogenic chemicals may confound the assessment of the actual estrogenic activity of complex environmental samples. The aim of the present study was to investigate whether, in which way and how seriously the estrogenic activity of single estrogens and the observed and predicted joint action of estrogenic mixtures is influenced by toxic masking and synergistic modulation caused by non-estrogenic chemical confounders.

Materials and methods

The yeast estrogen screen (YES) was adapted so that toxicity and estrogenicity could be quantified simultaneously in one experimental run. Mercury, two organic solvents (dimethyl sulfoxide (DMSO) and 2,4-dinitroaniline), a surfactant (LAS-12) and the antibiotic cycloheximide were selected as toxic but non-estrogenic test chemicals. The confounding impact of selected concentrations of these toxicants on the estrogenic activity of the hormone 17ß-estradiol was determined by co-incubation experiments. In a second step, the impact of toxic masking and synergistic modulation on the predictability of the joint action of 17ß-estradiol, estrone and estriol mixtures by concentration addition was analysed.

Results

Each of the non-estrogenic chemicals reduced the apparent estrogenicity of both single estrogens and their mixtures if applied at high, toxic concentrations. Besides this common pattern, a highly substance- and concentration-dependent impact of the non-estrogenic toxicants was observable. The activity of 17ß-estradiol was still reduced in the presence of only low or non-toxic concentrations of 2,4-dinitroaniline and cycloheximide, which was not the case for mercury and DMSO. A clear synergistic modulation, i.e. an enhanced estrogenic activity, was induced by the presence of slightly toxic concentrations of LAS-12. The joint estrogenic activity of the mixture of estrogens was affected by toxic masking and synergistic modulation in direct proportion to the single estrogens, which allowed for an adequate adaptation of concentration addition and thus unaffected predictability of the joint estrogenicity in the presence of non-estrogenic confounders.

Discussion

The modified YES proved to be a reliable system for the simultaneous quantification of yeast toxicity and estrogen receptor activation. Experimental results substantiate the available evidence for toxic masking as a relevant phenomenon in estrogenicity assessment of complex environmental samples. Synergistic modulation of estrogenic activity by non-estrogenic confounders might be of lower importance. The concept of concentration addition is discussed as a valuable tool for estrogenicity assessment of complex mixtures, with deviations of the measured joint estrogenicity from predictions indicating the need for refined analyses.

Conclusions

Two major challenges are to be considered simultaneously for a reliable analysis of the estrogenic activity of complex mixtures: the identification of known and suspected estrogenic compounds in the sample as well as the substance- and effect-level-dependent confounding impact of non-estrogenic toxicants.

Recommendations and perspectives

The application of screening assays such as the YES to complex mixtures should be accompanied by measures that safeguard against false negative results which may be caused by non-estrogenic but toxic confounders. Simultaneous assessments of estrogenicity and toxicity are generally advisable.     

化学物质对发光菌的联合毒性评价方法

毒性单位法(TU)的理论基础来源于剂量加和模型(DA),目前仅在二元联合毒性评价中广泛应用。为了确定TU模型适合评价的混合物类型,实验选取5种剂量效应曲线类型不同的物质,采用微板光度计测试了一元、二元混合物对发光菌青海弧菌-Q67(Vibrio-qinghaiensis sp.-Q67)的急性毒性。根据物质的剂量效应曲线形状将物质分为A、B、C 3类,利用毒性单位法(TU)和联合作用定义法分别对AA类、AB类、AC类、BC类混合物进行分析。结果表明,TU法仅适合于由剂量效应曲线接近直线的物质组成的混合物进行联合毒性的评价。以效应为基准、TU模型为框架建立了TU’模型,该模型可以满足对任何类型已知成分的混合物或者未知成分的实际水样之间的多元联合作用的评价。     

A novel method dependent only on the mixture information (MIM) for evaluating the toxicity of mixture

Compound contamination and toxicity interaction necessitate the development of models that have an insight into the combined toxicity of chemicals. In this paper, a novel and simple model dependent only on the mixture information (MIM), was developed. Firstly, the concentration-response data of seven groups of binary and multi-component (pseudo-binary) mixtures with different mixture ratios to Vibrio qinghaiensis sp.-Q67 were determined using the microplate toxicity analysis. Then, a desirable non-linear function was selected to fit the data. It was found that there are good linear correlations between the location parameter (α) and mixture ratio (p) of a component and between the steepness (β) and p. Based on the correlations, a mixture toxicity model independent of pure component toxicity profiles was built. The model can be used to accurately estimate the toxicities of the seven groups of mixtures, which greatly simplified the predictive procedure of the combined toxicity.     

Synergism of MGK-264 and piperonyl butoxide on the toxicity of plant derive molluscicides

The binary mixture of ethanolic extract of powder, hecogenin, tigogenin, seed powder and thymol with synergiats MGK-264 and piperony butoxide in a 1:5 ratio were used against the . It was observed that the toxic effect of these mixtures were time and dose dependent. The binary mixtures of plant molluscicides with synergist were more toxic with respect to the independent toxicity of these plant molluscicides. Maximum synergistic action (10 fold) of MGK-264 and piperonyl butoxide was observed with hecogenin.     

Tumor promoting effects of cyanobacterial extracts are potentiated by anthropogenic contaminants--evidence from in vitro study

Inhibition of gap junctional intercellular communication (GJIC) is affiliated with tumor promotion process and it has been employed as an in vitro biomarker for evaluation of tumor promoting effects of chemicals. In the present study we investigated combined effects of anthropogenic environmental contaminants 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153) and fluoranthene, cyanotoxins microcystin-LR and cylindrospermopsin, and extracts of laboratory cultures of cyanobacteria Aphanizomenon gracile and Cylindrospermopsis raciborskii, on GJIC in the rat liver epithelial cell line WB-F344. Binary mixtures of PCB 153 with fluoranthene and the mixtures of the two cyanobacterial strains elicited simple additive effects on GJIC after 30 min exposure, whereas microcystin-LR and cylindrospermopsin neither inhibited GJIC nor altered effects of PCB 153 or fluoranthene. However, synergistic effects were observed in the cells exposed to binary mixtures of anthropogenic contaminants (PCB 153 or fluoranthene) and cyanobacterial extracts. The synergistic effects were especially pronounced after prolonged (6-24 h) co-exposure to fluoranthene and A. gracile extract, when mixture caused nearly complete GJIC inhibition, while none of the individual components caused any downregulation of GJIC at the same concentration and exposure time. The effects of cyanobacterial extracts were independent of microcystin-LR or cylindrospermopsin, which were not detected in cyanobacterial biomass. It provides further evidence on the presence of unknown tumor promoting metabolites in cyanobacteria. Clear potentiation of the GJIC inhibition observed in the mixtures of two anthropogenic contaminants and cyanobacteria highlight the importance of combined toxic effects of chemicals in complex environmental mixtures.     

Prediction of mixture toxicity with its total hydrophobicity

Based on the C18 Empore disk/water partition coefficient of a mixture, quantitative structure-activity relationships (QSARs) are presented, which are used to predict the toxicity of mixed halogenated benzenes to P. phosphoreum. The predicted toxicity of 10 other related mixtures based on the QSAR model, agree well with the observed data with r2 = 0.973, SE = 0.113 and F = 287.785 at a level of significance P < 0.0001. The joint effect of these chemicals is simple similar action and the toxicity of the mixtures can be predicted from total hydrophobicity and is independent of hydrophobicity of the components or the ratio of the individual chemicals.     

Nature and prevalence of non-additive toxic effects in industrially relevant mixtures of organic chemicals

The concentration addition (CA) and the independent action (IA) models are widely used for predicting mixture toxicity based on its composition and individual component dose–response profiles. However, the prediction based on these models may be inaccurate due to interaction among mixture components. In this work, the nature and prevalence of non-additive effects were explored for binary, ternary and quaternary mixtures composed of hydrophobic organic compounds (HOCs). The toxicity of each individual component and mixture was determined using the Vibrio fischeri bioluminescence inhibition assay. For each combination of chemicals specified by the 2ⁿ factorial design, the percent deviation of the predicted toxic effect from the measured value was used to characterize mixtures as synergistic (positive deviation) and antagonistic (negative deviation). An arbitrary classification scheme was proposed based on the magnitude of deviation (d) as: additive (10%, class-I) and moderately (10 < d  30%, class-II), highly (30 < d  50%, class-III) and very highly (>50%, class-IV) antagonistic/synergistic. Naphthalene, n-butanol, o-xylene, catechol and p-cresol led to synergism in mixtures while 1, 2, 4-trimethylbenzene and 1, 3-dimethylnaphthalene contributed to antagonism. Most of the mixtures depicted additive or antagonistic effect. Synergism was prominent in some of the mixtures, such as, pulp and paper, textile dyes, and a mixture composed of polynuclear aromatic hydrocarbons. The organic chemical industry mixture depicted the highest abundance of antagonism and least synergism. Mixture toxicity was found to depend on partition coefficient, molecular connectivity index and relative concentration of the components.     

Toxicity testing of pesticides in zebrafish—a systematic review on chemicals and associated toxicological endpoints

The use of zebrafish (Danio rerio) has arisen as a promising biological platform for toxicity testing of pesticides such as herbicides, insecticides, and fungicides. Therefore, it is relevant to assess the use of zebrafish in models of exposure to investigate the diversity of pesticide-associated toxicity endpoints which have been reported. Thus, this review aimed to assess the recent literature on the use of zebrafish in pesticide toxicity studies to capture data on the types of pesticide used, classes of pesticides, and zebrafish life stages associated with toxicity endpoints and phenotypic observations. A total of 352 articles published between September 2012 and May 2019 were curated. The results show an increased trend in the use of zebrafish for testing the toxicity of pesticides, with a great diversity of pesticides (203) and chemical classes (58) with different applications (41) being used. Furthermore, experimental outcomes could be clustered in 13 toxicity endpoints, mainly developmental toxicity, oxidative stress, and neurotoxicity. Organophosphorus, pyrethroid, azole, and triazine were the most studied classes of pesticides and associated with various toxicity endpoints. Studies frequently opted for early life stages (embryos and larvae). Although there is an evident lack of standardization of nomenclatures and phenotypic alterations, the information gathered here highlights associations between (classes of) pesticides and endpoints, which can be used to relate mechanisms of action specific to certain classes of chemicals.     

等浓度配比法研究苯酚、硝基苯和问硝基苯胺对发光菌的联合毒性作用

分别测定了苯酚、硝基苯和间硝基苯胺对发光菌的单一毒性，以及等浓度配比和等毒性配比的二元及三元混合体系的联合毒性，采用相加指数法对其联合效应进行了评价。结果表明，等浓度比和等毒性比混合体系的联合作用结果一致：苯酚＋间硝基苯胺二元体系为协同作用，其他各体系为相加作用。为简化联合毒性实验方法，建议在研究相关系列化合物的联合毒性作用机制中，可采用等浓度配比方法。     

等浓度配比法研究苯酚、硝基苯和间硝基苯胺对发光菌的联合毒性作用

分别测定了苯酚、硝基苯和间硝基苯胺对发光菌的单一毒性,以及等浓度配比和等毒性配比的二元及三元混合体系的联合毒性,采用相加指数法对其联合效应进行了评价。结果表明,等浓度比和等毒性比混合体系的联合作用结果一致:苯酚+间硝基苯胺二元体系为协同作用,其他各体系为相加作用。为简化联合毒性实验方法,建议在研究相关系列化合物的联合毒性作用机制中,可采用等浓度配比方法。