Herbicide Dose: What Is a Low Dose? - ACS Publications - American

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Herbicide Dose: What Is a Low Dose? Per Kudsk*,1 and Stephen Moss2 1Department

of Agroecology, Aarhus University, Forsoegsvej 1, DK-4200 Slagelse, Denmark 2Stephen Moss Consulting, Harpenden, Herts AL5 5SZ, United Kingdom *E-mail: [email protected].

In the wake of the steadily increasing number of cases of non-target site resistance (NTSR) in recent years, the discussion of low versus high herbicide doses (‘the dose discussion’) has attracted renewed attention. Several studies have concluded that low doses can select for NTSR phenotypes and this has led to a general recommendation to farmers not to apply doses lower than the recommended dose. The objective of this paper is to discuss whether this simple, and easy to convey, recommendation is justified. It is concluded that the term ‘low dose’ is misleadingly over-simplistic as it makes no reference to herbicide efficacy. Lower doses often provide the same, or very similar, level of control as the recommended dose and therefore can be applied without jeopardizing the sustainability of cropping systems. Some herbicides (e.g. ACCase and ALS inhibitors), some weeds (e.g. Lolium spp.) and some agronomic practices (e.g. repeated application of herbicides with the same site of action) pose a much greater resistance risk than others. Compared to these risk factors, herbicide dose is relatively insignificant. It is recommended 1) that more focus is devoted to generating information on herbicide dose response relationships, 2) that terms like ‘low’ or ‘reduced’ doses are omitted and there is more focus on efficacy levels and 3) that diversity in management and avoidance of ‘high risk’ practices becomes the key points in the advice to farmers, rather than herbicide dose.

© 2017 American Chemical Society Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Introduction Herbicide resistance is one of the major threats to effective weed management in the future. Currently 472 unique cases of herbicide resistance have been reported globally, and weeds have developed resistance to 23 of the 26 known herbicide site of actions (1). In most cases resistance is due to a major gene mutation causing resistance to a specific site of action referred to as target site resistance (TSR) but, in recent years, an increasing number of cases of non-target site resistance (NTSR) conferring resistance to several herbicide sites of action have been found (2). In most cases the cause of NTSR is the enhanced ability of the weed to metabolise the herbicide. In contrast to TSR, NTSR is believed to be a polygenic trait. NTSR is widespread in grass species like Alopecurus myosuroides and Lolium rigidum. Evolution of herbicide resistance is primarily determined by the intensity of herbicide selection. Frequent use of herbicides with the same mode of action has proven to be the single most important cause of selection for herbicide resistance, but herbicide dose is also important. It has long been acknowledged that the use of high herbicide doses will promote the evolution of TSR. The reason is that most TSR phenotypes exhibit a very high level of resistance and only resistant plants are likely to survive an application with a high herbicide dose. The resistance level observed in NTSR phenotypes is often much lower than in TSR phenotypes, and the role of herbicide dose on the evolution of NTSR was for a long time unknown and resulted in the so-called ‘dose rate debate’ (3). Recent years have seen a number of publications concluding that the use of low herbicide doses can lead to the rapid development of NTSR in out-crossing species (e.g. (4–7)), whereas the role of dose is less evident in a self-crossing species like Avena fatua (8). The underlying assumption is that recombination between surviving plants will lead to an accumulation of genes conferring NTSR. The fact that both high and low doses select for herbicide resistance, albeit different types, has been described as a ‘Catch 22’ situation (9). As NTSR is considered a bigger threat to weed management than TSR, at least in grass weeds, recommendations on herbicide dose have changed markedly in recent years, promoting the use of high doses and discouraging the use of low doses. In the discussion of the role of herbicide dose on the evolution of herbicide resistance it is often assumed that a ‘high dose’ is a dose equal to, or higher than, the recommended dose while a ‘low dose’ is anything less than the recommended dose. We find this to be a grossly and misleading simplification, not taking into account some important aspects of chemical weed control. Herbicides vary in their efficacy against individual weed species, so a reduced rate (‘low dose’) of a highly active herbicide may be more effective than the full rate, or even double rate (‘high dose’), of a less active herbicide. This is the reality in many practical situations worldwide making the generalized concept of greater selection for resistance at low doses meaningless. Sometimes, there is a naïve assumption that the full rate of a herbicide will kill all weeds, whereas a reduced rate (‘low dose’) will allow survivors. This is rarely the case in real field situations - if it were, many weed species would be eliminated once the residual seed bank in the soil had been exhausted. Ag-chem companies are keen to promote the idea that 16 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


reduced rates encourage resistance for obvious and understandable commercial reasons. However, we are not aware that any commercial company has generated its own data to support this position in relation to herbicides. Higher herbicide doses are associated with an increased cost to the farmers but, besides the link to the costs of weed management, the choice of herbicide dose also has practical significance in parts of the world, like Europe, where pesticide legislation attempts to reduce pesticide use and farmers are encouraged to minimize doses. The purpose of this paper is to clarify and broaden the discussion on herbicide dose and to call in question the assumption that the recommended dose is an appropriate reference when assessing the risk of NTSR to herbicides.

Intra- and Inter-Specific Variation In the ongoing discussion on high- and low-dose selection, focus has been solely on the intra-specific variation in herbicide susceptibility, i.e. the variation within a population of one weed species. This is illustrated in Figure 1 (3). The intra-specific variation in the dose required to kill an individual is represented by the normal distribution of resistance phenotypes. The broken arrow illustrates the applied dose. Applying a high dose will kill all individuals in the population. Only TSR phenotypes exhibiting a very high level of resistance (located far to the right of the broken arrow) will survive. Where a lower dose is applied, the least susceptible individuals in the population will survive (grey shading area) and, in outcrossing species, it is envisaged that recombination can result in the accumulation of genes conferring NTSR in the offspring. This can, over time, reduce the overall susceptibility of the population (an increasing proportion of the population will survive the low dose, i.e. the normal distribution curve will gradually shift to the right).

Figure 1. A conceptual model illustrating (a) high-dose and (b) low-dose herbicide resistance selection. The variation in susceptibility within a population is represented by the normal distribution curve. The mean resistance phenotype is equivalent to the LD50 value for the population. (Reproduced with permission from reference Neve et al. (2014).Copyright John Wiley and Sons Inc.) 17 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


In contrast to pest and disease control, where often only one pest species is targeted at a time, with weeds the farmer will normally be applying herbicides to a weed flora consisting of several weed species with some being more abundant or important than others. Major differences are observed in the susceptibility of different weed species ranging from no to full effect at a given dose, as illustrated in Figure 2 for two herbicides and five weed species. Little information is available on the magnitude of the intra-specific variation but it is definitely significantly lower than the inter-specific variation.

Determining the ‘Recommended Dose’ In the EU, as in most countries, an applicant seeking authorization of a herbicide will have to provide a ‘Biological Assessment Dossier’ (BAD) which includes information on the efficacy and selectivity of the herbicide, effects on succeeding and adjacent crops and risk of herbicide resistance. The information is used by the applicant to justify the label claims and support the proposed recommendations of correct use. One part of the biological assessment dossier is a justification of the so-called ‘minimum effective dose’. Typically the minimum effective dose is justified by providing data on the effect of two to four doses on a limited range of weed species with varying susceptibilities. The ‘minimum effective dose’, that will later become the label or recommended dose, is determined largely by the response of the least susceptible weed species.

Figure 2. Efficacy of chlorsulfuron and ioxynil+bromoxynil applied to five weed species in spring barley at the recommended dose (1 N) and 50, 25, 12.5 and 6.25% of the recommended dose (1 N = 4 g a.i./ha chlorsulfuron and 200+200 g/ha ioxynil +bromoxynil). Data from two field trials conducted by Aarhus University. 18 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


By increasing the dose beyond the ‘minimum effective dose’ the applicant may be able to target more weed species but crop tolerance could be lost or it may no longer be possible to meet the human health and/or environmental criteria that pesticides have to fulfill to be authorized. Hence, from a legislative point of view, it is more correct to talk about a maximum registered dose. Having justified the ‘minimum effective dose’ the remaining part of the BAD only includes data from experiments where the recommended dose was applied, i.e. very little dose response information can be deduced from the BAD. Anyway, the data contained in the BAD is confidential and can only be shared with consultants and farmers with the consent of the applicant. In practice, this means that dose response information is typically generated post-authorization as part of the trials conducted by public institutes, advisory services etc. In many countries no, or little, information is available in the public domain for farmers to make decisions on the appropriate dose. In Denmark herbicides have, for many years, been examined at lower, as well as the recommended dose in the efficacy trials conducted by Aarhus University. Hence, we have access to a unique database on dose response of commercial herbicides. The database forms the backbone of the Danish web-based decision support system ‘Crop Protection Online – Weeds’ (CPO-Weeds). The data have been used to generate the doseresponse curves simulating more than 50,000 combinations of herbicides, weed species, crops and seasons (10, 11). We believe that the data available to farmers in Denmark can serve to illustrate that the term ‘the recommended dose’ makes good sense when considering the spectrum of weed species that can be controlled, but makes little sense when it comes to determining what is a ‘low’ and a ‘high’ dose.

Classification of Dose Depends on the Inherent Activity of the Herbicide Figure 3 shows the dose response curves included in CPO-Weeds for the herbicide mesotrione applied in maize to weeds at the 3 to 4-leaf stage. Of the 45 weed species included (plus three sulfonylurea resistant phenotypes of Alopecurus myosuroides, Papaver rhoeas and Tripleurospermum inodorum), 21 weed species are listed on the label as being effectively controlled by the recommended product dose of 1.5 L/ha (1 N in Figure 3). It is obvious, however, that several of these weed species can be controlled effectively by lower doses. Several weed species would be controlled satisfactorily at e.g. 50% of the recommended dose (1/2 N in Figure 2), whereas doses lower than 50% of the recommended dose will only control a few species. Applying the recommended dose without considering the composition of the weed flora could result in overdosing that, besides being an additional cost to the farmer, is not in compliance with either good agricultural practice or IPM.

19 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Figure 3. Simulated dose response curves for the herbicide mesotrione (Callisto, 100 g/L mesotrione) applied in maize to weeds at the 3-4 leaf-stage. Dose response curves were generated based on data from field trials conducted by Aarhus University and data supplied by Syngenta Crop Protection. The signatures are predicted and not observed values

Another example is shown in Figure 4 for the herbicide prosulfocarb. Prosulfocarb is primarily used for grass weed control in winter cereals and is recommended for use in rotation with ALS and ACCase herbicides to reduce the risk of evolution of resistance to these resistance-prone herbicide groups (Heap, 2016). Clearly, the most common grass weed species in Denmark respond very differently to prosulfocarb and applying the maximum recommended product dose of 5 L/ha (1 N in Figure 4) to all grass species would not be sustainable either from an economic or agronomic point of view. Used against Lolium multiflorum the recommended dose should be applied to ensure satisfactory control but against Apera spica-venti dose reductions are possible due to the very flat dose response around the recommended dose. This should not increase the risk of selection of NTSR phenotypes and thus jeopardizing the long-term sustainability of the cropping system.



Figure 4. Simulated dose response curves for the herbicide prosulfocarb (Boxer EC, 800 g/L prosulfocarb) applied in winter wheat in the autumn to weeds at the 0-2 leaf-stage. Dose response were generated based on data from field trials conducted by Aarhus University and data supplied by Syngenta Crop Protection, the company holding the authorization of this prosulfocarb product.

Returning to the conceptual model for ‘high’ and ‘low’ dose herbicide selection (Figure 1), the results in Figures 2, 3 and 4 reveal that, in the field, three scenarios are possible depending on the weed species and herbicide. Firstly, a dose reduction has no impact because reduced doses, as well as the recommended dose, provide full control of the whole population (Figure 5A). Secondly, where full doses give full control, a reduced dose will select for the least susceptible phenotypes in the population which may result in a build up of NTSR (Figure 5B = Figure 1). Thirdly, a herbicide will select for the least susceptible phenotypes, irrespective of dose applied, in situations where even the recommended dose does not provide full control (Figure 5C). Knowing which scenario applies is pertinent in a political environment where farmers not only have to address agronomic issues like herbicide resistance, but also have to meet a public demand to reduce the adverse impact of pesticide use on the environment and human health. 21 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Figure 5. A modified conceptual model illustrating three possible scenarios of high-dose and low-dose herbicide resistance selection. (The original figure was reproduced with permission from reference Neve et al. (2014).Copyright John Wiley and Sons Inc.)

Conclusions and Recommendations The examples provided here clearly illustrate that no unequivocal relationship exists between reductions in herbicide dose and reductions in herbicide efficacy -maximum control can often be achieved with less than the full recommended dose. This is by no means novel information but, nonetheless, it seems not to be widely reflected either on herbicide labels or in the ongoing discussion on ‘high’ versus ‘low’ doses. We conclude that the term ‘low dose’ is misleadingly over22 Duke et al.; Pesticide Dose: Effects on the Environment and Target and Non-Target Organisms ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


simplistic, as it makes no reference to herbicide efficacy. The dose rate debate would benefit from omitting the terms ‘low’ or ‘reduced’ doses and should focus instead on efficacy levels. We acknowledge that detailed information on dose response relationships is not available in all countries but, as highlighted in this paper, such information is important for decision making, not only in relation to the risk of evolution of herbicide resistance, but also to integrated weed management (IWM). Adjusting doses to the conditions in the field is an important component of IWM. It is clear that some herbicides (e.g. ACCase and ALS inhibitors), some weeds (e.g. Alopecurus myosuroides, Lolium spp.) and some agronomic practices (e.g. repeated application of herbicides with the same mode of action) pose a much greater resistance risk than others. Compared to these risk factors, herbicide dose appears relatively insignificant. It is recommended: 1) that more focus is devoted to generating information on herbicide dose response relationships, 2) that terms like ‘low’ or ‘reduced’ doses are omitted and there is more focus on efficacy levels and 3) that encouraging diversity in management and avoidance of ‘high risk’ practices become the key points in the advice to farmers, rather than herbicide dose. Although anecdotal, it is interesting that in the Scandinavian countries, where the use of lower than recommended doses has been promoted more than in any other country in Europe due to long-standing political pressure to reduce pesticide use, herbicide resistance is causing less problems than in most other European countries. In addition, we know of no evidence to support the view that reduced rates of herbicides have been a significant factor in the widespread evolution of herbicide resistance in Europe. We therefore view the dose rate debate as an unfortunate distraction from more important aspects of herbicide resistance evolution.

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Herbicide Dose: What Is a Low Dose? - ACS Publications - American

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