Toxicokinetics and time-dependent PAH toxicity in the amphipod Hyalella azteca

The relationship between toxicokinetics and time-dependent PAH toxicity to Hyalella azteca was examined to test the constant critical body residue (CBR) model. A constant CBR model is based on the assumption that the body residue for 50% mortality is constant for each PAH across exposure times. With a constant CBR, kinetic parameters determined through kinetic experiments would be similar to those estimated from time series toxicity data. Time-dependent toxicity was investigated using three types of data: time series LCW data, LT50(c), and CBR values measured at multiple exposure times for live and dead animals. Kinetic parameters were measured independently. The constant CBR model did not predict the PAH toxicity time course for H. azteca. Since a first-order kinetic model predicted the bioaccumulation of the parent PAH except for naphthalene, this result is not due to a failure to predict the internal dose (body residue). The influence of metabolites on toxicity was negligible except for naphthalene. The LC50 values at multiple exposure times decreased to an incipient lethal concentration after H. azteca reached steady state. Measured CBR values also decreased with increasing exposure time. Thus, the time course of PAH toxicity is determined not only by the bioconcentration kinetics but also by the cumulative toxicity with increasing exposure time. Therefore, time-to-death or hazard models must be developed as a complement to toxicokinetic models to describe and predict the toxicity time course.     

Application of multi-component Damage Assessment Model (MDAM) for the toxicity of metabolized PAH in Hyalella azteca

Biotransformation and time-dependent toxicity of pyrene and fluorene, in the presence and absence of the biotransformation inhibitor 6-propylpiperonyl butyl diethylene glycol ether known as piperonyl butoxide (PBO), were investigated in Hyalella azteca. Toxicokinetics and biotransformation were determined in both short- and longterm experiments. For pyrene, the uptake rate coefficient (ku = 99 +/- 9 L kg(-1) h(-1)), elimination rate constant for parent compound (kep = 0.050 +/- 0.008 h(-1)), biotransformation rate constant (km = 0.016 +/- 0.003 h(-1)), and elimination rate constant for metabolites (kem = 0.021 +/- 0.007 h(-1)) were determined from a short-term study. For fluorene, ku (130 +/- 30 L kg(-1) h(-1)) and kep (1.7 +/- 0.2 h(-1)) were estimated based on km (0.015 +/- 0.002 h(-1)) and kem (0.011 +/- 0.002 h(-1)) determined from a long-term study. At steady state, the percent metabolites for pyrene and fluorene were 43% and 58%, respectively, determined from km/(km +/- kem). Time-dependent toxicity was determined as both lethal water concentration and lethal body residue in the presence and absence of PBO. Co-exposure to PBO decreased the median lethal residue (LBR50) for parent pyrene and shortened the median lethal time (LT50). Pyrene toxicity was explained by the body residues of parent pyrene and PBO, where the metabolites' contribution was negligible. Forfluorene, co-exposure to PBO increased the LBR50 for parent fluorene and shortened the LT50. Thus, fluorene metabolites contributed significantly to the toxicity. Using a multicomponent damage assessment model, the toxicodynamic parameters, damage accrual rate coefficient, and damage recovery rate constant for parent pyrene and parent fluorene were very similar and estimated to be from 0.009 to 0.020 micromol(-1) g h(-1) and from 0.003 to 0.013 h(-1), respectively, and the incipient LBR50 at the infinite time (LBR50(t = infinity)) was from 0.24 to 0.46 micromol g(-1), respectively. These values are similar to the reported LBR50(t = infinity) for other nonpolar narcotics such as pentachlorobenzene (PCBz, 0.38 +/- 0.13 micromol g(-1)) and dichlorophenylchloroethylene (DDE, 0.41 +/- 0.19 micromol g(-1)). For fluorene metabolites, these values were 0.10 +/- 0.03 micromol(-1) g h(-1), 0.034 +/- 0.021 h(-1), and 0.33 +/- 0.23 micromol g(-1), respectively. However, for pyrene metabolites, since toxicity of pyrene metabolites was negligible, the parameters could not be estimated.     

Effects of sediment characteristics on the toxicity of chromium(III) and chromium(VI) to the amphipod, Hyalella azteca

We evaluated the influence of sediment characteristics, acid-volatile sulfide (AVS) and organic matter (OM), on the toxicity of chromium (Cr) in freshwater sediments. We conducted chronic (28-42-d) toxicitytests with the amphipod Hyalella azteca exposed to Cr(VI) and Cr(III) in water and in spiked sediments. Waterborne Cr(VI) caused reduced survival of amphipods with a median lethal concentration (LC50) of 40 microg/L. Cr(VI) spiked into test sediments with differing levels of AVS resulted in graded decreases in AVS and sediment OM. Only Cr(VI)-spiked sediments with low AVS concentrations (< 1micromol/g) caused significant amphipod mortality. Waterborne Cr(III) concentrations near solubility limits caused decreased survival of amphipods at pH 7 and pH 8 but not at pH 6. Sediments spiked with high levels of Cr(III) did not affect amphipod survival but had minor effects on growth and inconsistent effects on reproduction. Pore waters of some Cr(III)-spiked sediments contained measurable concentrations of Cr(VI), but observed toxic effects did not correspond closely to Cr concentrations in sediment or pore waters. Our results indicate that risks of Cr toxicity are low in freshwater sediments containing substantial concentrations of AVS.     

Predicting bioavailability of sediment polycyclic aromatic hydrocarbons to Hyalella azteca using equilibrium partitioning, supercritical fluid extraction, and pore water concentrations

Polycyclic aromatic hydrocarbon (PAH) bioavailability to Hyalella azteca was determined in 97 sediments from six former manufactured-gas plants and two aluminum smelter sites. Measurements of Soxhlet extractable, rapidly released based on mild supercritical fluid extraction, and pore water dissolved concentrations of 18 parent and 16 groups of alkyl PAHs (PAH34) were used to predict 28 daysurvival based on equilibrium partitioning and hydrocarbon narcosis models. Total PAH concentrations had little relationship to toxicity. Amphipods survived in sediments with PAH34 concentrations as high as 2990 microg/g, while sediments as low as 2.4 microg/g of PAH34 resulted in significant mortality. Equilibrium partitioning using either total extractable or rapidly released concentrations significantly improved predictions. However, pore water PAH34 concentrations were best for predicting amphipod survival and correctly classified toxic and nontoxic sediment samples with an overall model efficiency of 90%. Alkyl PAHs accounted for 80% of the toxicity, demonstrating that careful measurement of the 16 alkyl clusters in pore water is required. Regression analysis of the pore water PAH34 data from 97 field sediments against amphipod survival resulted in a mean 50% lethal residue value of 33 micromol/g of lipid, consistent with 32 micromol/g of lipid for fluoranthene determined by others in controlled laboratory conditions, thus demonstrating the applicability of EPA's hydrocarbon narcosis model when using pore water PAH34 concentrations.     

Human exposure assessment: a case study of 8 PAH contaminated soils using in vitro digestors and the juvenile swine model

In vitro digestors can be used to provide bioaccessibility values to help assess the risk from incidental human ingestion of contaminated soils. It has been suggested that these digestors may need to include a lipid sink to mimic human uptake processes. We compare the correspondence between in vivo polycyclic aromatic hydrocarbon (PAH) uptake for eight different PAH contaminated soils with PAH release in in vitro digestors in the presence and absence of a lipid sink. Lipid sinks were essential to the success of the in vitro digestors in predicting juvenile swine PAH uptake. In the presence of the lipid sink, results of the In Vitro Digestion model (IVD) closely corresponded with a slope of 0.85 (r(2) = 0.45, P < 0.07) to the in vivo results. The Relative Bioaccessibility Leaching Procedure (RBALP) results did not correspond to the in vivo study but did tightly reflect total soil PAH concentration. We conclude that the basis of this difference between digestors is that the RBALP used an aggressive extraction technique that maximized PAH release from soil. Systemic uptake in juvenile swine was not linked to soil PAH concentration but rather to the thermodynamic properties of the soil.     

Predicting pore water EPA-34 PAH concentrations and toxicity in pyrogenic-impacted sediments using pyrene content

Sediment and freely dissolved pore water concentrations of the U.S. Environmental Protection Agency's list of 34 alkyl and parent PAHs (EPA-34) were measured in 335 sediment samples from 19 different sites impacted by manufactured gas plants, aluminum smelters and other pyrogenic sources. The total EPA-34 freely dissolved pore water concentration, C(pw,EPA-34), expressed as toxic units (TU) is currently considered one of the most accurate measures to assess risk at such sites; however, it is very seldom measured. With this data set, we address how accurately C(pw,EPA-34) can be estimated using limited 16 parent PAH data (EPA-16) commonly available for such sites. An exhaustive statistical analysis of the obtained data validated earlier observations that PAHs with more than 3 rings are present in similar relative abundances and their partitioning behavior typically follows Raoult's law and models developed for coal tar. As a result, sediment and freely dissolved pore water concentrations of pyrene and other 3- and 4-ring PAHs exhibit good log-log correlations (r2 > 0.8) to most individual EPA-34 PAHs and also to C(pw,EPA-34). Correlations improve further by including the ratio of high to low molecular weight PAHs, as 2-ring PAHs exhibit the most variability in terms of their relative abundance. The most practical result of the current work is that log C(pw,EPA-34) estimated by the recommended pyrene-based estimation techniques was similarly well correlated to % survival of the benthic amphipods Hyalella azteca and Leptocheirus plumulosus as directly measured log C(pw,EPA-34) values (n = 211). Incorporation of the presented C(pw,EPA-34) estimation techniques could substantially improve risk assessments and guidelines for sediments impacted by pyrogenic residues, especially when limited data are available, without requiring any extra data or measurement costs.     

应用Caco-2细胞模型评价真菌毒素毒性研究进展

真菌毒素是一些病原真菌在侵染作物过程中产生的次级代谢产物, 许多食品和饲料在生产、加工、贮存和流通过程中都有可能受到真菌毒素的污染。人和动物摄入真菌毒素后, 体内能够引发多种生理毒性反应, 如肝肾毒性、致癌性、肠道损伤及炎症、中枢神经系统异常、生殖紊乱等。肠上皮细胞是分隔机体内部环境与外界的屏障, 在真菌毒素的毒性评价中, 对真菌毒素引起肠上皮细胞损伤的评价是一个重要方面。人结肠癌Caco-2细胞系常用于建立体外肠道屏障模型, 该模型可应用于体外评价药物或毒素在小肠粘膜或上皮的吸收转运效率, 以及对肠道屏障功能的影响。本文综述了Caco-2细胞单层模型的建立和评价指标, 应用该模型评价几种常见真菌毒素对肠上皮细胞的运输、屏障功能的影响, 以及肠上皮细胞毒性等研究进展, 为进一步研究多种真菌毒素对肠上皮损伤的机制提供支持。     

Diffusion of PAH in potato and carrot slices and application for a potato model

A method for quantifying the effect of medium composition on the diffusive mass transfer of hydrophobic organic chemicals through thin layers was applied to plant tissue. The method employs two silicone disks, one serving as source and one as sink for a series of PAHs diffusing through thin layers of water, potato tissue, and carrot tissue. Naphthalene, phenanthrene, anthracene, and fluoranthene served as model substances. Their transfer from source to sink disk was measured by HPLC to determine a velocity rate constant proportional to the diffusive conductivity. The diffusive flux through the plant tissue was modeled using Fick's first law of diffusion. Both the experimental results and the model suggest that mass transfer through plant tissue occurs predominantly through pore water and that, therefore, the mass transfer ratio between plant tissue and water is independent of the hydrophobicity of the chemical. The findings of this study provide a convenient method to estimate the diffusion of nonvolatile organic chemicals through various plant materials. The application to a radial diffusion model suggests that "growth dilution" rendersthe concentration of highly hydrophobic chemicals in potatoes below their equilibrium partitioning level. This is in agreement with field results for the bioconcentration of PAHs in potatoes.     

Prediction of fabric handle value using ordinal regression model

Bed sheet fabric as a kind of home textile has been used since many years ago. Bed sheet is very significant because of being in direct contact with body consecutively for a long period of time. Bed sheet surplus qualitative parameters such as fiber substance, method of printing, finishing, etc., have a significant parameter called handle. In this paper, we proceeded to consider the relationship between fabric handle as a qualitative parameter and physical parameters which influenced the fabric handle using statistical modeling. The statistical model used was ordinal regression model. The modeling was done by SPSS V.19 software. We used 15 bed sheet fabrics. For subjective evaluation of 15 bed sheet fabrics, we selected 55 persons randomly as sample members according to Cochran’s formula. Population was selected from senior BS students and MS students at Isfahan University of Technology (IUT). We asked persons to classify bed sheet fabrics based on their preference of fabric handle from 1 (lowest) to 5 (highest). Physical parameters values were obtained through standard experiments. Finally, we analyzed obtained data through SPSS V.19 using ordinal regression model. Results showed a satisfying match between extracted data from the software and the real data from person’s evaluation.     

Development of a multi-component Damage Assessment Model (MDAM) for time-dependent mixture toxicity with toxicokinetic interactions

A new mixture toxicity model was developed to predict the time-dependent toxicity of a mixture with toxicokinetic interactions directed specifically toward addressing biotransformation. The Damage Assessment Model (DAM), a toxicokinetic-toxicodynamic model that describes and predicts the time-dependent toxicity of a single compound, was extended to a multicomponent model for mixture toxicity. The model assumes that cumulative damage from the parent compound, metabolites, and/or a biotransformation inhibitor are additive, and the sum of the cumulative damage determines mixture toxicity. Since incorporation of the damage addition hypothesis into the DAM was equivalent to an independent action model for mixture toxicity, it was applied to describe the combined effect of mixture components with potentially dissimilar modes of action. From the multicomponent DAM, a time-dependent toxic unit model was derived and applied to determine the toxic units of mixture components. This model suggests a series of experimental designs required to assess the role of biotransformation in the toxicity of metabolized organic compounds and a data analysis method to separately estimate toxicodynamic parameters forthe parent compound and metabolites.     

Safety assessment of food-contact paper and board using a battery of short-term toxicity tests: European union BIOSAFEPAPER project

An European Union (EU)-funded project QLK1-CT-2001-00930 (BIOSAFEPAPER) involves the development, validation and intercalibration of a short-term battery of toxicological tests for the safety assessment of food-contact paper and board. Dissemination of the results to industry, legislators (e.g. DG Consumer Protection, DG Enterprises, DG Research), standardization bodies such as CEN, and consumers will create an agreed risk evaluation procedure. The project involves pre-normative research in order to establish a set of in-vitro cytotoxicity and genotoxicity tests that will be easily adaptable to food-contact fibre-based materials and have endpoints relevant to consumer safety, including sub-lethal cellular events. These tests will be performed on samples representing actual migration conditions from food-contact paper and board with respect to different foodstuffs, and should form an experimental basis for scientifically sound recommendations for a harmonized system of risk evaluation and product testing.     

Modeling trade-off between PAH toxicity reduction and negative effects of sorbent amendments to contaminated sediments

Adding activated carbon (AC) to contaminated sediment has been suggested as an effective method for sediment remediation. AC binds chemicals such as polycyclic aromatic hydrocarbons (PAHs), thus reducing the toxicity of the sediment. Negative effects of AC on benthic organisms have also been reported. Here, we present a conceptual model to quantify the trade-off, in terms of biomass changes, between the advantageous PAH toxicity reduction and the negative effects of AC on populations of benthic species. The model describes population growth, incorporates concentration-effect relationships for PAHs in the pore water and for AC, and uses an equilibrium sorption model to estimate PAH pore water concentrations as a function of AC dosage. We calibrated the model using bioassay data and analyzed it by calculating isoclines of zero population growth for two species. For the sediment evaluated here, the results show that AC may safely protect the benthic habitat against considerable sediment PAH concentrations as long as the AC dosage remains below 4%.     

Predicting PAH bioaccumulation and toxicity in earthworms exposed to manufactured gas plant soils with solid-phase microextraction

Soils from former manufactured gas plant (MGP) sites are often heavily contaminated with polycyclic aromatic hydrocarbons (PAHs). Current risk assessment methods that rely on total PAH concentrations likely overstate adverse effects of such soils since bioavailability is ignored. In this study, solid-phase microextraction (SPME) was applied to estimate bioavailable PAH concentrations and toxicity in earthworms exposed to 15 MGP soils. In addition, PAH sorption to all soils (K0o values) was determined. The results showed a several orders of magnitude variation in Koc values, demonstrating that generic organic carbon-normalized sorption coefficients will typically be overconservative at MGP sites. SPME-predicted bioaccumulation generally was within a factor of 10 of measured bioaccumulation (in earthworm bioassays), in contrast to current risk assessment model estimates that overpredicted bioaccumulation 10-10 000 times. Furthermore, on the basis of estimated total body residues of narcotic PAHs, SPME correctly predicted worm mortality observed during bioassays in the majority of cases. For MGP sites where current risk assessment procedures indicate concerns, SPME thus provides a useful tool for performing a refined, site-specific assessment.     

On the dynamic model of yarn with time-dependent tension

In order to control yarn vibration and improve carpet quality, it is essential to research the fluctuation of yarn tension and its influences during tufting process. Assuming the polypropylene yarn has linear elasticity with a circular cross-section, we take the dynamic tension as the output and the friction acted on yarn by Jacquard roller as the input. At the moment of clutch operation and release, the tension fluctuation of polypropylene yarn during transmission from pulling roller to Jacquard roller was theoretically analyzed. A mathematical model describing yarn tension fluctuation was derived based on the moment of momentum theorem and mass conservation. The dynamic tension was obtained by applying Laplace’s transformation, providing the input-breaking moment as a step response. The result shows that tension fluctuation has an important influence on the carpet quality; therefore, it is necessary to carefully design the Jacquard roller and the control friction plate of clutch. Moreover, the effects of the yarn length between Jacquard rollers and pulling rollers on natural frequency and damping coefficient of yarn tension fluctuation were analyzed.     

Field comparison of particulate PAH measurements using a low-flow denuder device and conventional sampling systems

Polyaromatic hydrocarbons (PAHs) are complex carbonaceous compounds emitted to the atmosphere by various combustion processes. Because the toxicity of many of them is now well recognized and documented, the determination of their atmospheric concentrations is of great interest to better understand and develop future atmospheric pollution control strategies. Hence, a common sampling protocol has to be defined to homogenize the results. With this goal in mind, field studies were carried out under different environmental conditions (74 samples) by simultaneously operating both a conventional sampler and a sampler equipped with a denuder tube upstream from the filter. The experimental results presented in this work show that the atmospheric particulate PAH concentrations are underestimated at least by a factor of 2 using a conventional sampler. The discrepancy between the two kinds of samplers used varied a lot from one compound to another and from one field campaign to another. This discrepancy may be explained by a simple degradation of particulate PAH in the natural atmosphere and on the filter. This is particularly worrisome because, based on the results presented in this work, the atmospheric PAH concentrations measured using conventional samplers not equipped with an ozone trap can underestimate the PAH concentration by more than 200%. This is especially true when the samples are collected in the vicinity of the point source of particulate PAHs and for highly reactive compounds such as benzo[a]pyrene.     

Prediction of the herd somatic cell count of the following month using a linear mixed effect model

An accurate prediction of the average somatic cell count (SCC) for the next month would be a valuable tool to support udder health management decisions. A linear mixed effect (LME) model was used to predict the average herd SCC (HSCC) for the following month. The LME model included data on SCC, herd characteristics, season, and management practices determined in a previous study that quantified the contribution of each factor for the HSCC. The LME model was tested on a new data set of 101 farms and included data from 3 consecutive years. The farms were split randomly in 2 groups of 50 and 51 farms. The first group of 50 farms was used to check for systematic errors in predicting monthly HSCC. An initial model was based on older data from a different part of the Netherlands and systematically overestimated HSCC in most months. Therefore, the model was adjusted for the difference in average HSCC between the 2 sets of farms (from the previous and current study) using the data from the first group of 50 farms. Subsequently, the data from the second group of 51 farms were used to independently assess this final model. A null model (no explanatory variables included) predicted 48 and 59% of the HSCC within the predetermined range of 20,000 and 30,000 cells/mL, respectively. The final LME model predicted 72 and 81% of the HSCC of the next month correctly within these 2 ranges. These outcomes indicate that the final LME model was a valid additional tool for farmers that could be useful in their short-term decisions regarding udder health management and could be included in dairy herd health programs.     

Noninvasive assessment of autonomic activity for evaluation of pain in calves, using surgical castration as a model

The role of the autonomic nervous system (ANS) in mediating eye temperature responses during painful procedures was examined in thirty 4-mo-old bull calves randomly assigned to 4 treatments: 1) sham handling control (C; n = 8), 2) surgical castration (SC; n = 6), 3) local anesthesia with sham handling (LAC; n = 8), and 4) local anesthesia with surgical castration (LASC; n = 8). Maximum eye temperature (°C), measured by infrared thermography, heart rate (HR), and heart rate variability (HRV) were recorded continuously from 25 min before to 20 min after castration. The HRV was analyzed by examining segments of 512 interbeat intervals before and after treatments and comparing the root mean square of successive differences (RMSSD), high and low frequency (HF and LF, respectively) power, and the ratio of LF and HF powers (LF:HF). Jugular blood samples were analyzed for norepinephrine and epinephrine in C and SC treatments and for cortisol during all treatments. There was an immediate increase in HR following castration in SC (+15.3 ± 2.8 beats/min) and LASC (+6.3 ± 2.4 beats/min) calves. Eye temperature increased during the 20-min observation period in SC and LASC calves (+0.47 ± 0.05°C and +0.28 ± 0.05°C, respectively), and there was a small increase in C calves (+0.10 ± 0.05°C). Following castration in SC calves, there was an increase in RMSSD (+25.8 ± 6.4) and HF power (+11.0 ± 6.5) and LF:HF decreased (−2.1 ± 0.7). Following castration in LASC, there was an increase in RMSSD (+18.1 ± 4.9) and a decrease in LF power (−10.2 ± 5.0). Cortisol increased above baseline within 15 min following treatment in both castrated groups, but was greater for SC calves (+18.4 ± 2.3 ng/mL) than for LASC calves (+11.1 ± 1.9 ng/mL). After castration, norepinephrine increased 3-fold and epinephrine increased by half in SC calves but not in C calves. There were no changes in HR, HRV, or cortisol responses to C or LAC treatments. Local anesthetic reduced, but did not eliminate, responses to surgical castration. The synchronized increase in catecholamine and HR responses immediately following SC treatment suggests the initial response was mediated by the sympathetic branch of the ANS. The subsequent changes in RMSSD, HF power, and LF:HF ratio indicated this was followed by an increase in parasympathetic activity. The use of HR, HRV, and infrared thermography measurements together provide a noninvasive means to assess ANS responses as indicators of acute pain in cattle.     

Mixture toxicity of reactive chemicals by using two bacterial growth assays as indicators of protein and DNA damage

The mixture toxicity of reactive chemicals was investigated with a set of bioanalytical tests that quantify not only the toxic effects but also allow the identification of the preferred target of reactive chemicals in bacterial cells. Softer electrophiles such as acrylates react preferentially with thiol groups in proteins and peptides, and harder electrophiles such as epoxides preferentially attack DNA. In addition, some compounds, e.g., benzyl chloride, have no preference for a biological target and damage both DNA and proteins. A thiophenol was used as a model compound representing nucleophiles. We explored if the paradigms of mixture toxicity also hold true for reactive chemicals. Compounds with the same targets and the same modes of action should act concentration additive in mixtures, and compounds with different modes of action should act according to the concept of independent action. In addition, we investigated the potential for interaction of compounds of mixtures of electrophiles or electrophiles plus nucleophiles, which might lead to synergistic or antagonistic effects. The toxicity of mixtures of electrophiles with a single preferred target was consistent with the prediction for concentration addition. Unfortunately, the predictions for independent action did not differ much from those for concentration addition; therefore it was not possible to differentiate between these two models. Mixtures of two groups with different preferred target sites clearly showed concentration addition. In contrast, mixtures of compounds with multiple targets, i.e., compounds that show nonspecific reactivity toward any biological nucleophile, exhibited effects that lay distinctly between the predictions for concentration addition and independent action. We observed neither synergism (higher toxicity than predicted by concentration addition) nor antagonism (lower toxicity than predicted by independent action) for mixtures of electrophiles. Binary combinations of different electrophiles with the nucleophile 4-chlorothiophenol yielded smaller effects than those expected from the prediction for independent action. The degree of antagonism was correlated with the reaction rate constant of the electrophile with the thiol group of glutathione, which indicates that the interaction between the mixture components occur in the toxicokinetic phase and is purely a result of chemical reactivity between the mixture components. Overall, we conclude that the concepts of mixture toxicity apply not only for baseline toxicity and receptor-mediated mechanisms, as has been shown in a large number of studies, but also for reactive mechanisms of toxicity, provided that one has checked beforehand that no chemical reactions occur between the mixture components.     

真菌毒素DON和ZEN的体外联合毒性评价

选取BEL7402细胞对脱氧雪腐镰刀菌烯醇（Deoxynivalenol,DON）和玉米赤霉烯酮（Zearalenone,ZEN）的联合毒性进行评价。首先将不同浓度的DON、ZEN以及其混合物染毒对数期的BEL7402细胞,刺激24 h后,对细胞增殖率、ROS活性氧水平、钙离子水平、细胞凋亡率以及凋亡相关靶点基因的表达等指标进行监测分析,并对两种毒素的联合毒性作用进行评价。结果表明,真菌毒素DON、ZEN均可抑制细胞活性,IC₅₀分别为9.3、27.2μg/m L,可导致细胞氧化应激损伤,提高细胞内活性氧水平以及钙离子浓度,显著上调凋亡关键基因p53、Bax,下调Bal-2基因,诱导细胞产生早期凋亡甚至坏死,多种毒性指标验证了这两种毒素对细胞的联合毒性作用表现为加和作用。