Biomedical subjects

Nina Cedergreen

Publications and source records attributed to Nina Cedergreen.

7 recordsLinked to original sources

PubMed2006

Is prochloraz a potent synergist across aquatic species? A study on bacteria, daphnia, algae and higher plants.

Fungicides inhibiting the biosynthesis of ergostrol, such as the triazoles and imidazoles, have been shown to enhance the effect of insecticides on birds, mammals and invertebrates in the terrestrial environment. The synergy is proposed to be due to an effect on P450 monooxygenase enzymes active in pesticide metabolism in these organisms. Fungicides often enter the aquatic environment jointly with other pesticides. It is therefore possible that they could act as synergists also in the aquatic environment. In this study we tested the joint effect of the imidazole fungicide prochloraz together with the herbicides acifluorfen, diquat and terbuthylazine, the fungicide azoxystrobin and the insecticides chlorfenvinphos, dimethoate, and pirimicarb on the bacteria Vibrio fischeri (six binary mixtures), the crustacean Daphnia magna (four binary mixtures), the algae Pseudokirchneriella subcapitata (four binary mixtures) and the floating plant Lemna minor (three binary mixtures). All the binary mixtures were evaluated both in relation to the model of concentration addition (CA) and independent action (IA) using isobolograms. The study showed strong synergy in relation to CA between prochloraz and azoxystrobin, diquat and esfenvalerat on D. magna with sums of toxic units for the 50:50% effect mixture ( summation TU(50:50)) as low as 0.25. The mixture with dimethoate was however antagonistic with summation TU(50:50) of 2.04. Four out of the six mixtures testes on V. fisheri showed synergy in relation to CA, but for three of the mixtures the response could be explained by IA. Only the mixture with diquat showed synergy in relation to both IA and CA with summation TU(50:50) around 0.50. There was no significant synergy for any of the combinations tested on the plant and the algae species in relation to CA and only for diquat in the algae-test in relation to IA. Hence, prochloraz does synergise the effect of some pesticides in the aquatic environment, but not consistently across species. The organism most susceptible to synergy by prochloraz in this study was D. magna. Especially the combination with insecticides such as esfenvalerate, where the concentration needed to immobilize 50% of the daphnia was reduced from >3microgL(-1) to less than 0.5microgL(-1) when prochloraz was added, could be problematic as these concentrations are environmentally realistic. Furthermore, insecticides and ergostrol-biosynthesis-inhibitors (EBI-fungicides) are often applied together, and are therefore likely to co-exist in surface waters, enhancing the problem of the already very potent insecticides.

Animals↗

PubMed2006

Activities of mixtures of soil-applied herbicides with different molecular targets.

The joint action of soil-applied herbicide mixtures with similar or different modes of action has been assessed by using the additive dose model (ADM). The herbicides chlorsulfuron, metsulfuron-methyl, pendimethalin and pretilachlor, applied either singly or in binary mixtures, were used on rice (Oryza sativa L.). The growth (shoot) response curves were described by a logistic dose-response model. The ED50 values and their corresponding standard errors obtained from the response curves were used to test statistically if the shape of the isoboles differed from the reference model (ADM). Results showed that mixtures of herbicides with similar molecular targets, i.e. chlorsulfuron and metsulfuron (acetolactate synthase (ALS) inhibitors), and with different molecular targets, i.e. pendimethalin (microtubule assembly inhibitor) and pretilachlor (very long chain fatty acids (VLCFAs) inhibitor), followed the ADM. Mixing herbicides with different molecular targets gave different results depending on whether pretilachlor or pendimethalin was involved. In general, mixtures of pretilachlor and sulfonylureas showed synergistic interactions, whereas mixtures of pendimethalin and sulfonylureas exhibited either antagonistic or additive activities. Hence, there is a large potential for both increasing the specificity of herbicides by using mixtures and lowering the total dose for weed control, while at the same time delaying the development of herbicide resistance by using mixtures with different molecular targets.

Drug Antagonism↗

PubMed2005

The toxicity of herbicides to non-target aquatic plants and algae: assessment of predictive factors and hazard.

Widely used herbicides sometimes inadvertently contaminate surface waters. In this study we evaluate the toxicity of herbicides to aquatic plants and algae and relate it to environmental herbicide concentrations and exposure scenarios, herbicide formulation and mode of action. This was done experimentally for ten herbicides, using the aquatic macrophyte Lemna minor L. and the green alga Pseudokirchneriella subcapitata (Korshikov) Hindak, supplemented with a database study comprising algae toxicity data for 146 herbicides. The laboratory study showed that herbicide formulations in general did not enhance herbicide efficacy in the aquatic environment. The Roundup formulation of glyphosate proved to be the only exception, decreasing the EC(50) of the technical product for both L. minor and P. subcapitata approximately fourfold. Comparison of the sensitivity of L. minor and P. subcapitata revealed up to 1000-fold higher sensitivity of L. minor for the herbicides categorized as weak acids (pK(a) < 5), emphasizing the importance of higher plants in hazard assessment. Database analyses showed that no herbicide group, categorized by site of action, was significantly more toxic than another. Synthetic auxins were the exception as they are virtually non-toxic to unicellular algae. There was no strong correlation between toxicity to algae and K(ow) of the herbicides, not even within groups having the same site of action. Evaluating all data, few herbicides were toxic at concentrations below 1 microg l(-1), which is the 99.9th percentile of the herbicide concentrations measured in the Danish surveillance programme. Joint action of several herbicides cannot however be excluded.

Agriculture↗

PubMed2005

Can the choice of endpoint lead to contradictory results of mixture-toxicity experiments?

Theoretically, the effect of two independently acting compounds in a mixture will depend on the slope of the dose-response curves of the individual compounds if evaluated in relation to the model of concentration addition (CA). In the present study, we explored development of the shape of the dose-response relationship for four different recommended endpoints (surface area, frond number, fresh weight-specific, and dry weight-specific relative growth rates [RGRA, RGRF, RGRFW, and RGRDW, respectively]) and for two differently acting herbicides (metsulfuron-methyl and terbuthylazine) over time (3-15 d) on the standard test plant Lemna minor to identify endpoints and experiment times for which predictions of independent action (IA) would depart the most from those of CA. After a test time of 6 d, predictions of IA based on RGRA and RGRFW showed antagonism in relation to CA. Based on RGRDW, synergy was predicted, whereas IA based on RGRF was indistinguishable from CA. To test the prediction of choice of endpoint giving different results in mixture-toxicity experiments, three endpoints and six combinations of independently acting herbicides were evaluated using isobolograms. The experiments showed that in four of six herbicide combinations, different conclusions were reached depending on endpoint. The contradictory isoboles did not follow the theory of IA and, therefore, are more likely to be related to differences in susceptibility of the physiological processes affecting each endpoint than to the shape of the dose-response curve.

Araceae↗

PubMed2005

Improved empirical models describing hormesis.

During the past two decades, the phenomenon of hormesis has gained increased recognition. To promote research in hormesis, a sound statistical quantification of important parameters, such as the level and significance of the increase in response and the range of concentration where it occurs, is strongly needed. Here, we present an improved statistical model to describe hormetic dose-response curves and test for the presence of hormesis. Using the delta method and freely available software, any percentage effect dose or concentration can be derived with its associated standard errors. Likewise, the maximal response can be extracted and the growth stimulation calculated. The new model was tested on macrophyte data from multiple-species experiments and on laboratory data of Lemna minor. For the 51 curves tested, significant hormesis was detected in 18 curves, and for another 17 curves, the hormesis model described that data better than the logistic model did. The increase in response ranged from 5 to 109%. The growth stimulation occurred at an average dose somewhere between zero and concentrations corresponding to approximately 20 to 25% of the median effective concentration (EC50). Testing the same data with the hormesis model proposed by Brain and Cousens in 1989, we found no significant hormesis. Consequently, the new model is shown to be far more robust than previous models, both in terms of variation in data and in terms of describing hormetic effects ranging from small effects of a 10% increase in response up to effects of an almost 100% increase in response.

Animals↗

PubMed2004

Does the effect of herbicide pulse exposure on aquatic plants depend on Kow or mode of action?

The highest concentrations of herbicides measured in flowing surface waters are often only present for short periods of time. These herbicide pulses can reach concentrations that would affect aquatic plants if present over a long time. The aim of this study was to assess the effect of a 3-h herbicide pulse relative to the effects of long-term (4 and 7 days) exposure of six herbicides with different sites of action and different K(ow) on the growth of the floating macrophyte Lemna minor. The herbicides were the two photosynthetic inhibitors: diquat and terbuthylazine, the inhibitors of acetolactate syntase (ALS), imazamox and metsulfuron-methyl and the microtubule assembly inhibitors propyzamide and pendimethalin. The log K(ow) ranged from -4.6 to 5.2. For imazamox, metsulfuron-methyl, propyzamide and pendimethalin a 3-h pulse induced the effect on area-specific growth as did a 4-day exposure at an approximate 10-fold higher concentration. For diquat and terbuthylazine a concentration closer to a factor of 100 or more was needed for a 3-h pulse to induce an effect similar to that of a 4-day exposure. For diquat, the low pulse-effect was most likely due to a slow uptake of the hydrophilic ion (log K(ow) = -4.6), as no effect was observed on chlorophyll fluorescence within 8 h after exposure. The chlorophyll fluorescence parameters are expected to respond quickly to a PSI inhibitor as diquat. For terbuthylazine, fluorescence measurements showed an effect on photosynthesis within 1h of exposure, and reached a minimum after 3 h. Recovery was fast, and initial fluorescence was restored within 24 h. Hence, the small pulse effect on area-specific growth was due to rapid recovery of photosynthesis. In contrast to terbuthylazine, the stop in area-specific growth observed for the ALS-and microtubule assembly inhibitors, took up to 4 days to recover from. Such a long recovery time after a pulse of only 3 h indicate that at realistic pulse exposures of up to a day or two, pulse-effects will approach the effects obtained in long-term studies. When investigating the effects of pulse exposures on aquatic plants, we should therefore focus more on non-photosynthetic inhibitors, which might not appear in pulses in as large concentrations as the PSII inhibitors investigated up till now, but whose effect, even in a shorter pulse, can be more damaging.

Aniline Compounds↗

PubMed2004

Species-specific sensitivity of aquatic macrophytes towards two herbicides.

The s-triazine herbicide terbutylazine, an inhibitor of photosystem II, is often found in surface waters in concentrations < 1 microg L(-1), but concentrations up to 13 microg L(-1) have been measured. To study the effect on the aquatic flora, we tested the sensitivity of 10 aquatic macrophyte species and a natural epiphyte community in a 2-week laboratory multispecies test at constant terbutylazine concentrations and two irradiance regimes. The data were described by a log-logistic concentration-response model and species sensitivity distributions (SSDs) were created from the EC50 and EC10 values. The 5% hazard concentration (HC5) of the EC10-based SSD for terbutylazine was 1 and 3 microg L(-1); hence the low chronic terbutylazine concentrations measured in the environment are not likely to affect the macrophyte community. To compare the species sensitivity between different groups of herbicides, SSDs were constructed from a published study on the sulfonylurea metsulfuron-methyl, an inhibitor of acetolactate synthase. There was no correlation between species-specific sensitivity to the two herbicides; hence, the combined exposure of different herbicides might affect the macrophyte community more broadly rather than seriously affecting a few susceptible species. Evaluating the standard procedure of leaving at least a factor of 100 between the EC50 of standard tests on Lemna sp. and the predicted environmental concentration seems to be protective for at least 95% of the macrophyte species for both terbutylazine and metsulfuron-methyl.

Arylsulfonates↗