Papers by Nina Cedergreen
Weed Research, Sep 22, 2010
... Chlorophyll a fluorescence was measured on the youngest fully developed leaf 24, 48 and 72 h ... more ... Chlorophyll a fluorescence was measured on the youngest fully developed leaf 24, 48 and 72 h after spraying, using a chlorophyll fluorometer (Handy-PEA, Hansatech Instruments, Kings Lynn, Norfolk, UK) measuring at 650 nm with a light intensity 3000 μmol photons m −2 s ...

Ecotoxicology and Environmental Safety, Feb 1, 2004
The sensitivity of 12 aquatic plant species to the herbicide metsulfuron-methyl was tested in mic... more The sensitivity of 12 aquatic plant species to the herbicide metsulfuron-methyl was tested in microcosm experiments under two growth conditions. As reference species, barley (Hordeum vulgare) and oil-seed rape (Brassica napus) were grown with their roots submerged in the microcosms. Two response variables were chosen: relative growth rate and specific leaf area (SLA). SLA was the most sensitive response variable, with 11 of the 12 aquatic species responding to the herbicide. EC(50) values varied 56-fold between species, with the commonly used aquatic test species Lemna minor being one of the most sensitive. Fast-growing species with a small exposed leaf area proved to be more sensitive to the herbicide than slow growing species with a large exposed leaf area, which was believed to be primarily due to variations in growth rates rather than to variations in exposed leaf area. The aquatic plants displayed high tolerance in growth to metsulfuron compared with the sensitive crop oil-seed rape. Hence, possible spray-drift events and leaching of the herbicide applied at agricultural rates are not considered to have a large impact on the growth of the aquatic flora tested.

Ecotoxicology and Environmental Safety, Jul 1, 2004
The s-triazine herbicide terbutylazine, an inhibitor of photosystem II, is often found in surface... more 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.

Aquatic Toxicology, Jun 1, 2006
Fungicides inhibiting the biosynthesis of ergostrol, such as the triazoles and imidazoles, have b... more 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 ( TU 50:50 ) as low as 0.25. The mixture with dimethoate was however antagonistic with 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 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 >3 g L -1 to less than 0.5 g L -1 when prochloraz was added, could be problematic as these concentrations are environmentally realistic. Furthermore, insecticides and ergostrol-biosynthesis-inhibitors (EBIfungicides) are often applied together, and are therefore likely to co-exist in surface waters, enhancing the problem of the already very potent insecticides.

Environmental Toxicology and Chemistry, 2005
Theoretically, the effect of two independently acting compounds in a mixture will depend on the s... more Theoretically, the effect of two independently acting compounds in a mixture will depend on the slope of the doseresponse 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 [RGR A , RGR F , RGR FW , and RGR DW , 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 RGR A and RGR FW showed antagonism in relation to CA. Based on RGR DW , synergy was predicted, whereas IA based on RGR F 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.

Environmental Toxicology and Chemistry, 2005
During the past two decades, the phenomenon of hormesis has gained increased recognition. To prom... more 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.

Pest Management Science, 2005
Widely used herbicides sometimes inadvertently contaminate surface waters. In this study we evalu... more 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 EC50 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 (pKa < 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 Kow of the herbicides, not even within groups having the same site of action. Evaluating all data, few herbicides were toxic at concentrations below 1 µg litre−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. Copyright © 2005 Society of Chemical Industry
Hortscience, Dec 1, 2010
Various plant extracts are being marketed claiming to enhance both crop yield
Journal of Agricultural Biological and Environmental Statistics, Dec 1, 2010

Science of The Total Environment, Jun 1, 2012
The joint effect of the majority of chemical mixtures can be predicted using the reference model ... more The joint effect of the majority of chemical mixtures can be predicted using the reference model of Concentration Addition (CA). It becomes a challenge, however, when the mixtures include chemicals that synergise or antagonise the effect of each other. In this study we examine if the deviation from CA of seven ternary mixtures of interacting chemicals can be predicted from knowledge of the binary mixture responses involved. We hypothesise that the strongest interactions will take place in the binary mixtures and that the size of the ternary mixture response can be predicted from knowledge of the binary interactions. The hypotheses were tested using a stepwise modelling approach of incorporating the information held in binary mixtures into a ternary mixture model, and comparing the model predictions with observed ternary mixture toxicity data derived from studies of interacting chemical mixtures on the floating plant Lemna minor and the bacteria Vibrio fischeri. The results showed that for both the antagonistic and the synergistic ternary mixtures the ternary model predictions were superior to the conventional CA reference model and provided robust estimations of the size of the experimentally derived ternary mixture toxicity effects.

Ecotoxicology and Environmental Safety, Mar 1, 2008
Mixture toxicity of similar-and dissimilar-acting toxicants can be predicted by the models concen... more Mixture toxicity of similar-and dissimilar-acting toxicants can be predicted by the models concentration addition (CA) and independent action (IA) using single substance toxicity data. Knowledge of the toxicants mode of action is thus required in order to use the models. In order to test the predictive capability of the models, we conducted Daphnia magna 48 h immobilization experiments with three toxicants with known modes of action (dimethoate, pirimicarb and linear alkyl benzene sulfonate) singly, and in binary and ternary mixtures. Our results indicate that CA and IA predict binary mixtures of similar-and dissimilar-acting toxicants equally well. CA and IA also equally predicted the ternary mixture consisting of both similar-and dissimilar-acting chemicals. The paper discusses the concept of mode of action and the implications the definition of mode of action has on the choice of reference model for mixture toxicity studies.
Ecotoxicology, Oct 15, 2013

Food and Chemical Toxicology, 2018
Relatively few studies are available on realistic cumulative risk assessments for dietary pestici... more Relatively few studies are available on realistic cumulative risk assessments for dietary pesticide exposure. Despite available studies showing low risk, public concern remains. Recent estimates of realistic exposure levels have a high level of uncertainty, and more accurate estimates are needed. A method to estimate realistic residue levels based on information from spraying journals and supervised residue trials was described in a previous publication. This method was applied to estimate residues in domestically produced food commodities. The present article proposes a new method to estimate average residue levels in imported food commodities based on residue monitoring data and knowledge about agronomic practices in the main exporting countries. The two methods were used in combination to estimate average pesticide residue levels in 47 commodities on the Danish market in the years 2013 and 2014. The chronic consumer exposure was estimated in six typical diets in the Danish population. The Hazard Index (HI) method, which is based on the dose addition model, was used to assess the consumer risk. Despite the conservative (cautious) risk assessment approach, low HI values where obtained. The HI was 16 % for adults and 44 % for children, combining the risk of all pesticides in the diet. In conclusion, the present study adds to the body of evidence showing that adverse health effects of pesticide residues in the Danish population are very unlikely.

Analytical and Bioanalytical Chemistry, Dec 16, 2015
Pyrethroids are highly toxic towards aquatic macroinvertebrates such as Daphnia magna and can be ... more Pyrethroids are highly toxic towards aquatic macroinvertebrates such as Daphnia magna and can be synergized when co-occurring with azole fungicides. A sensitive analytical method for the measurement of azole-pyrethroid mixtures in aquatic macroinvertebrates is not available at present. We developed and validated an extraction, cleanup, and quantification procedure for four pyrethroid insecticides and four azole fungicides at the picograms per milligram wet weight level in D. magna using a QuEChERS approach and GC-ECD analysis. Short-and long-term matrix effects were analyzed by injection of a series of extracts from D. magna, and the best surrogate standards were identified through correlation analysis of analyte responses. The presence of matrix clearly stabilized the analyte responses (≤6 % relative standard deviation of peak area compared to up to 22 % when injected without matrix). The sensitivity was high with detection limits and limits of quantification between 58-168 and 119-571 pg mg(wet weight) -1 for the azoles and 5.8-27 and 12-84 pg mg(wet weight) -1 for the pyrethroids, respectively. Accuracy (% recovery) was between 95 and 111 % and the precision (repeatability) below 10 % relative standard deviation for all analytes. In the case of prochloraz, α-cypermethrin, and deltamethrin, normalization to surrogate standards led to a clear improvement of accuracy and precision by up to 8 and 4 %, respectively. The method was successfully applied to the measurement of internal α-cypermethrin concentrations in D. magna under environmentally relevant exposure conditions (exposure to a pulse in the micrograms per liter range) with and without co-exposure to propiconazole.
Reviews of Environmental Contamination and Toxicology, Oct 24, 2008

Aquatic Toxicology, 2016
One of the ultimate goals of green chemistry is to produce greener and more environmentally frien... more One of the ultimate goals of green chemistry is to produce greener and more environmentally friendly chemicals to replace the existing toxic chemicals. In this study, Japanese medaka were exposed to 1.5mg/L of bisphenol A or lignin-derived bisphenol for 60 days, and the expressions of various biochemical markers, effects on reproduction, and histopathology were evaluated. The results showed that concentrations of liver vitellogenin of LD-BP exposed males were approximately 125% higher compared to the control males. Total number of eggs from the BPA and LD-BP exposed fish was approximately 47% (p<0.001) and 25% (p<0.05) less than the control fish, respectively. Total number of brood was lower from the BPA (46%, p<0.05) and LD-BP (17%, p<0.05) exposed fish than that of the control fish. Relative to the control fish, catalase and glutathione-S-transferase were significantly affected by the two chemicals in all tested tissues. BPA and LD-BP caused lipid peroxidation in all the tested tissues. Furthermore, acetylcholinesterase and α-glucosidase activity were significantly inhibited. Histopathological analysis showed that both the testis and ovary were mildly damaged by both chemicals. LD-BP affected medaka slightly more severe than BPA except on the reproduction, which was most likely due to different uptake, translocation, binding to targets and metabolism. Our results demonstrated that chronic exposure to both chemicals caused several adverse effects to medaka. Further research on the toxicity of LD-BP to other aquatic organisms is needed before substitution of traditional BPA with LD-BP can be recommended.
Human and Ecological Risk Assessment, Nov 19, 2009
Journal of Environmental Management, Aug 1, 2017
Environmental Pollution, Dec 1, 2008
Uploads
Papers by Nina Cedergreen