The presence of pesticides in honey bees, honey, pollen, and wax has been reported as a worldwide issue (Chauzat et al., 2011; Mitchell et al., 2017), as well as in specific regions and countries, e.g. North America (Mullin et al., 2010), Belgium (Ravoet et al., 2015; Agrebi et al., 2020), Kenya (Irungu et al. 2016), Argentina (Medici et al., 2019), Uganda (Amulen et al., 2017), Mexico (Valdovinos-Flores et al., 2017) and in the Seychelles Islands (Muli et al., 2018).

The presence of pesticides in hives is closely related to the surrounding environment (García-Chao et al., 2010; Mullin et al., 2010; Chauzat et al., 2011; Panseri et al., 2014; Malhat et al., 2015), particularly when this environment is used for agriculture (Kremen et al., 2002; Biesmeijer et al., 2006; Potts et al., 2010a; Gleiciani Bürger & Campos, 2014).

Assessing the impact of pesticides and agricultural intensification on managed hives of A. mellifera is a difficult task, given that it develops almost all over the world, with a wide range of climates, landscapes, vegetation, etc. and fundamentally with different types of beekeepers who own from a few to thousands of colonies, and manage hives both as a business or as a hobby (Vandame & Palacio, 2010). Thus, bringing together the most recent published scientific evidence, which addresses the risk of agricultural pesticides to honey bees and their products for human consumption from different approaches, is especially relevant because it contributes to informed decision-making. In this regard, reports of a decrease or disappearance in the number of hives around the world (often labelled as Colony Collapse Disorder or CCD) are widely known and referred widely in the scientific literature (Van Engelsdorp et al., 2017). However, the real causes of this event do not have the same level of agreement in the scientific community, although the consensus in characterizing this phenomenon is to attribute it to multiple causes (Van Engelsdorp et al., 2009), among which are agricultural pesticides (Watson & Stallins, 2016).

Currently, US beekeepers lose approximately 40% of their colonies each year, although with important variations between the different states (Kulhanek et al., 2017), while annual losses of approximately 30% are reported for Europe and South Africa (Pirk et al., 2014) and 3–13% in China, both for A. mellifera and Apis cercana (Chen et al., 2017). Argentina estimates an average loss of 30% of colonies per year (Maggi et al., 2016), which means the annual death of about 840,000 hives compared to the country’s 2.8 million registered hives (Gallacher & Justo, 2016). These percentages merit some considerations due to their magnitudes: the death of managed hives, particularly during the winter season, is a completely normal phenomenon, contemplated by beekeepers and implicit in the activity. Obviously, 30 or 40 % is a very high number, yet every year beekeepers, with different agronomic practices, replenish these losses in good proportion (Genersch et al., 2010). In fact, the number of managed honey bee colonies has increased over the last decade (Aizen et al., 2009; Steinhauer et al., 2018). This simple clarification (the winter mortality of managed honey bees is a normal phenomenon and that beekeepers compensate with different hive multiplication techniques) is not always present in published studies and leads, in many cases, hasty conclusions and incorrect sizing of the problem.

As previously stated, the causes of these high losses are very diverse, and although it is not only a result of agricultural intensification and pesticide use, but these are also two powerful factors surely involved in the high reported mortality rates. Recent research suggests that some consequences of agricultural intensification observed in bees, especially nutritional limitation for reduction of floral supply (Foley et al., 2012), and exposure to sub-lethal doses of pesticides (Wu et al., 2012), induce immune suppression in A. mellifera, which in time makes it difficult for bees to defend against the increasing levels of viruses associated with varroa or other pathologies of relevance to beekeeping production.

This point is interesting because different conclusions could be reached depending on the level of analysis: if only a few hives are evaluated in small areas the cause of death might be assigned to diseases or poor nutrition (derived from poor management by the beekeeper or deficiencies of the apiary site), but a higher level of analysis could possibly position agricultural intensification as the leading cause of decline in the floral offer and thus inadequate nutrition for the bees. In time, this would result in more severe immune suppression, which can be aggravated by different stressors, among which pesticides might play an important role (Nazzi & Pennacchio, 2014). This could turn out a negative spiral of harmful interactions, and the way out of it probably requires, at the very least, a territorial-level approach.

Since 2014, glyphosate has been used in more than 140 countries (Benbrook, 2016) and can be found in more than 750 formulated products (Guyton et al., 2015). Currently, it is the most widely used herbicide worldwide, as well as the most “politicized” agrochemical (Ledoux et al., 2020).

Strictly speaking, glyphosate is not directly applied to hives, but can be found around places where bees live, visit and forage (Berg et al., 2018). Since beekeeping and agricultural activities usually occur simultaneously and in the same territory, glyphosate can be easily transported to hives and pollute the supply of honey (Karise et al., 2017). There are numerous scientific studies reporting that bees can be exposed to glyphosate through pollen, nectar, and water during the search for food (Herbert et al., 2014; Karise et al., 2017; Goñalons & Farina, 2018). This pesticide can even enter the hives attached to the body of bees (Rortais et al., 2017) and consequently transfer this pollutant into the hive and its products (Dai et al., 2018). When glyphosate eventually enters the hive, it negatively affects learning behavior, an essential mechanism used during food gathering flights, in adult bees exposed to this herbicide (Herbert et al., 2014; Balbuena et al., 2015). However, clearly documented cases do not abound in the scientific literature due to the difficulties of collecting samples of stray bees and identifying the specific chemicals that cause the losses and at the same time ruling out other possible causes of the phenomenon.

A number of researchers have suggested offering economic incentives to farmers to restore pollinator-friendly habitats, including the supply of flowers in or around fields and the elimination of insecticide use by adopting agroecological production methods (Nicholls et al., 2013; Prado et al., 2018). Some of these proposals were put into practice with encouraging results, albeit in reduced areas (Schulte et al., 2017; Kordbacheh et al., 2020). Nevertheless, for these strategies to have an effect and without forgetting the multi-causal nature of the problem, it is necessary that the proposed habitat restoration be, at least, on a regional scale.

The phenomenon of chemical contamination of bees and their products is supra-national in nature and therefore the palliative possibilities of the same scale should be considered, since there is little value in the efforts of individual beekeepers or farmers or grouped into small consortia in the face of the real size of the problem.

As previously mentioned, the possibility of chemical contamination of bees in agricultural landscapes is high. In fact, agricultural activities are decidedly the most common cause of loss of pollinators and/or contamination of their products for some authors (Potts et al., 2010b). Thus, it is appropriate to focus the analysis on the emerging environmental impact of soybean, one of the main crops, at least in terms of occupied area (particularly in the Americas) and its superlative economic relevance worldwide.

Extensive agriculture, widely represented in American continent by maize (Zea mays) and soybean (Glycine max), has grown to unprecedented levels in recent years (Hartman et al., 2011). This expansion of the sown area has been even proportionally larger for soybean in countries such as Argentina (Reboratti, 2010), Brazil and the USA (Pagano & Miransari, 2016). This has led to a loss of biodiversity at the landscape-level (Aizen, 2009) and habitat fragmentation (Pacheco, 2012) in large regions of the world. The soybeans crop is strongly linked to bio-technological developments that facilitate its production and allow to increasingly expand, the edaphoclimatic borders that make it possible to sow it.

The flight radius of A. mellifera is considerably extensive. Hagler et al. (2011) determined that honey bees have flight distances of up to 6 km; consequently, the foraging area of a hive or apiary is very significant (more than 11,000 ha). This area would cover numerous private farms anywhere in the world, even in countries with large areas of countryside such as Argentina, in which agricultural establishments in the Pampean region average between 200 and 500 ha (CNA, 2018). This fact, together with the need for approaches at the landscape-level mentioned above, highlights the need to promote large-scale actions, not action limited to a few farmers or in small areas. It is clear then that economic incentive strategies require very large sums of money and active policies historically delegated to the private sector.

Regardless of the multiple economic benefits this crop generates to farmers, it is clear that the continuous increase in area allocated to soybean and other crops (under the technique of hegemonic production, strongly dependent on agricultural inputs) affects the survival of bee colonies (both Apis and non-Apis), in two main ways:

1) By the loss of the local flora available: a multiplicity of fanerogamous species available for the foraging by honey bees provide diversity in the source of nectar and pollen, which is relevant for a successful immune response (Negri et al., 2015). Consequently, its deficiency (monocultures) is the cause of immune problems of various kinds in bees, especially in A. mellifera (Alaux et al., 2010; Castelli et al., 2020).

Although soybean flowering is relatively attractive to bees (Fagúndez et al., 2016b) and floral input is massive (millions of flowers/ha), this offering is only available in synchronous periods lasting for only a few weeks a year. This is also true for all extensive agricultural monocultures, which provide limited value forage resources for bees due to rapid growth with short periods of rotation and low floral diversity (Allsopp & Cherry, 2004; De Lange et al., 2013). Therefore, it has been proposed that chemical fallows (highly efficient in weed control) could be dispensed with and make use of old agricultural practices (use of plow), of massive use prior to the adoption of the direct sowinmethod (Altieri & Whitcomb, 1979), for soil preparation in agricultural areas, that improve the abundance and diversity of beneficial insects, including pollinators.

This simple proposal seemingly delivers promising, low-cost results. However, these practices are currently marginal, given the many agronomic disadvantages they entail (soil erosion, volatilization and carbon loss, subsurface soil compaction, etc), which have converged on the mass adoption of the direct seeding method with chemical fallows by most farmers (García et al., 2000). In fact, it is possible to ensure that there is a great dependence on chemical weed control of major extensive crops, even though mechanical weed control practices remain (Scursoni et al., 2019). In fact, the excellent control of weeds that pesticides allow explain much of the formidable agricultural success that reports yields that were unthinkable only a few decades ago. Thus, reverting to old agricultural practices would only be possible by increasing the area allocated to crops to support of current agricultural production, which in turn would entail even more environmental deterioration.

In line with this, the maintenance and restoration of hedges and other vegetation at the edges of the agricultural fields have been proposed to house pollinators (Garibaldi et al., 2013). Unfortunately, further work has determined that weeds and other plants on the edges of the fields are suppliers of pollen and nectar (often contaminated) to bees, by behaving as depositors of pesticides applied to adjacent crops and also other pesticides (frequently used to control nuisance pests such as mosquitoes) that were not applied to the crops (Long & Krupke, 2016). Fortunately, under certain conditions, pesticides on surrounding plants are observed in low concentrations (Hall et al., 2022).

2) By the use of pesticides (associated with crop safekeeping), which involves the weakening or death of bees (Malaspina et al., 2008).

The massive use of agricultural pesticides leads to the contamination of bees and their products (Pareja et al., 2011; Benuszak, 2017; Tosi et al., 2018). In an interesting review, Maggi et al. (2016) refer to numerous authors who blame pesticides for the loss of bees in agricultural areas of South America. For example, fipronil and imidacloprid have been detected in high doses in colonies of depopulated honey bees in Uruguay (Pareja et al., 2011). Additionally, pesticides can also affect non-Apis bee populations, as the harmful impact of insecticides on stingless bees has been documented (Barbosa et al., 2015).

At this point, most actions traditionally proposed to reduce pesticide damage to bees are aimed at counteracting the effect of nearby disturbances in time and space, for example, the proposal of transient closure of bottom boards in the face of imminent agricultural spraying near hives, the use of surfactants that reduce product drift or the restriction of sprays when the wind direction is towards the hive, among others (May et al., 2015).

It is tempting then to suggest mitigation strategies focused on to avoid pesticide drift and that spray at times when the bees do not exhibit foraging activity (Blettler et al., 2016). Unfortunately, this proposal might be too simplistic as well, if it is not accompanied by other strategies that converge on the same objective. It has recently been reported that bees make use of the floral resource of agricultural crops even if it has recently been sprayed with pesticides (Fagúndez et al., 2016a), which means that the most commonly used pesticide products for the control of agricultural pests do not present repellence, immediate or delayed, towards bees. This fact was proven in research conducted precisely on soybean crops, which indicates that the problem takes on another dimension and exposes the limitations of the previously proposed strategy since, according to these results (Fagúndez et al., 2016a), the problem would not be solved by keeping the bees away during sprays. On the contrary, it seems clear that it is the bees themselves that go voluntarily towards sprayed cultivation.

The behavior of foraging on recently pulverized soybean flowers acquires greater dimension considering that a positive effect of entomophilous pollination (promoted by A. mellifera) on the granary yields of soybeans has been proven (first in Brazil by Chiari et al., 2005 and later in Argentina by Blettler et al., 2018 and Garibaldi et al., 2021). Taking these findings into consideration, the incentive to provide pollination services to this crop to maximize the yields of this crop should be clear. Nevertheless, this has limited chances of effective application since the production technology of this crop currently demands huge amounts of pesticides for its protection of phytophagous insects (considering the width of the occupied area: soybeans cover 129 million hectares globally http://www.fao.org/faostat/en/#home), which limits the possibilities of a joint strategy involving managed and non-Apis bees pollinating insects.

Considering that 35% of the world’s production comes from crops that depend on animal pollination (Gallai et al., 2009) and that honey bees are the main pollinating insect of these crops (Klein et al., 2007), it is crucial to understand that this problem no longer belongs to farmers or beekeepers alone, but to the society as a whole. Furthermore, in this work we challenge the widespread idea that the sum of partial solutions over a considerable period will lead to a substantive improvement in the problem since it is essential to fully assess the consequences of interventions from a holistic perspective.

A number of studies have identified negative effects of pesticides on bees even at very low concentrations (i.e., sublethalif considered individually) these adverse effects are magnified when certain combinations of pesticides are involved (Spurgeon et al., 2016), which is clear evidence of synergies between different products, even if the detected concentrations of these products are well below the concentrations of environmental relevance granted for each product individually (EFSA-PPR, 2012; Johnson, 2015; Rortais et al., 2017).

Unfortunately, even these relatively low concentrations cause synergistic or subletal effects on bee colonies such as decreased ability to survive the winter and decreased work of worker bees, alterations in foraging capacity, decreased pollen and honey reserves, irregularities in honeycomb construction, reduction in olfactory capacities, increase in the number of empty breeding cells, decrease in the production of queen bees, decrease in learning capacity and disorientation in the return flight to the hive (Liu et al., 2014). This becomes especially concerning if we consider that many of the commercial pesticides have a similar mode of action; consequently, the effects of additive toxicity on bees are very likely when bees and their larvae are exposed to a mixture of contaminants from the surrounding environment and/or from various treatments intended to preserve the health of the hives (Zhu et al., 2014).

Rortais et al. (2017) described examples of agonisms by similar action principles:

• – Fungicides that inhibit ergosterol biosynthesis, in combination with neonicotinoids, pyrethroids and organophosphates.
• – Acaricides such as coumaphos and fluvalinate in combination with antibiotics in the hive (oxytetracycline).
• – Neonicotinoid insecticides in combination with antibiotics in the hive (oxytetracycline).

Additionally, other factors, such as poor bee nutrition, can exacerbate such mixing effects (Johnson et al., 2012). Taken together, all these factors result in a pressing need for more research on the underlying mechanisms of the synergistic effects of pesticides on the health of honey bees (Pettis et al., 2013).

So far, the problem of agricultural intensification and chemical contamination of hives has been addressed in relation to the impact on the survival and behaviour of bees and the negative effect on pollination of agricultural crops involved in the loss of pollinating services. However, an even more significant risk than those described above is faced by humans themselves, who are exposed to these chemical agents of known toxicity by consuming potentially contaminated bee products in their diet (Bommuraj et al., 2019). Importantly, the chemicals have the ability to bioaccumulate and biomagnify in the body over time (Al-Waili et al., 2012).

In each agronomic practice involving pesticides, it should be considered that honey bees that visited crop flowers or approached to sip water of guttation should be expected to come mostly from hives managed for food production, and they will be transporting contaminants that end up, sooner rather than later, as part of food products (Simon-Delso et al., 2017) and can cause commercialization problems for these products (Virgen, 2008). Although recent scientific literature suggests that exposure to pesticides through guttation water is unlikely to adversely affect honey bee colonies (Schmolke et al., 2018) this route cannot be particularly ruled out in places with little availability of clean water sources for bees (Böhme et al., 2017).

The two main products obtained from the hives are honey and pollen, and both are food for direct human consumption. Furthermore, they are subjected to very little treatment (pre-consumption) which is mostly reduced to minimum conditioning for commercial purposes and therefore the contaminants are not removed. In the face of this, the European Union establishes maximum permitted concentrations for certain products, which are called Maximum Residue Levels (MRLs). The MRL is the highest level of pesticide residue that is legally tolerated in or on food or feed when pesticides are applied correctly, to protect the general population and particularly vulnerable groups such as children and the unborn.

MRLs for honey are set in Regulation (EC) No. 396/2005 (OJ, 2005), and are calculated from data obtained from supervised field tests, performed under the critical use pattern detailed on labels of plant protection products. It is important to note that MRLs are not toxicological limits, but are toxicologically acceptable limits, under the assumption of an application that follows Good Agricultural Practices protocols, thus representing the maximum amount of waste that can be found in a plant-based food product because of the legal and rational use of phytosanitary products. In addition, it should be noted that standardized values have not been established globally, and unfortunately MRLs remain variable (Yamada, 2017). Additionally, developed countries likely have stricter regulations than developing countries, which often lack the resources and willingness to enforce pesticide residue legislation (Handford et al., 2015).