Basic Substances, a Sustainable Tool to Complement and Eventually Replace Synthetic Pesticides in the Management of Pre and Postharvest Diseases: Reviewed Instructions for Users

Synthetic pesticides are widely used to protect crops from pathogens and pests, especially for fruits and vegetables, and this may lead to the presence of residues on fresh produce. Improving the sustainability of agriculture and, at the same time, reducing the adverse effects of synthetic pesticides on human health requires effective alternatives that improve the productivity while maintaining the food quality and safety. Moreover, retailers increasingly request fresh produce with the amounts of pesticides largely below the official maximum residue levels. Basic substances are relatively novel compounds that can be used in plant protection without neurotoxic or immune-toxic effects and are still poorly known by phytosanitary consultants (plant doctors), researchers, growers, consumers, and decision makers. The focus of this review is to provide updated information about 24 basic substances currently approved in the EU and to summarize in a single document their properties and instructions for users. Most of these substances have a fungicidal activity (calcium hydroxide, chitosan, chitosan hydrochloride, Equisetum arvense L., hydrogen peroxide, lecithins, cow milk, mustard seed powder, Salix spp., sunflower oil, sodium chloride, sodium hydrogen carbonate, Urtica spp., vinegar, and whey). Considering the increasing requests from consumers of fruits and vegetables for high quality with no or a reduced amount of pesticide residues, basic substances can complement and, at times, replace the application of synthetic pesticides with benefits for users and for consumers. Large-scale trials are important to design the best dosage and strategies for the application of basic substances against pathogens and pests in different growing environments and contexts.


Introduction
The world population continues to grow and will reach 9.7 billion by 2050 [1]. For this, increasing food production is the primary objective of all countries. According to the latest estimates of the Food and Agriculture Organization of the United Nations [2], up to 40% of food crops worldwide are lost every year due to pests and plant diseases. Crop losses caused by plant disease alone cost the global economy $220 billion annually [3]. Crop protection is essential to reduce yield losses, improve food quality, and increase grower profitability. The application of plant protection products (PPPs) is the main way to protect crops against pathogens, pests, and weeds [4]. However, human, animal, and environmental risks associated with the use of chemical PPPs are a growing concern. All these concerns have encouraged the onset of research to develop alternative approaches to control plant diseases [5]. Reducing the use of pesticides being a major challenge in   2 The product cannot be applied in case of hot temperature. It is used in case of rainy period; 3 Indirect actions, no direct insecticide and fungicide properties; 4 maximum of rate per application; 5 maximum total rate per crop/season; 6 The aqueous solutions in this application are applied with few or without dilution. Here the case without dilution is calculated. Usually, not all trees are treated with brush application but only injured trees. In the calculation of maximum rate, it was assumed that 3000 trees per ha are treated with 0.15 L product per tree. This means that all trees of an orchard would be treated with several big wounds, which would be really the maximum rate and in reality, is very improbable; 7 Expressed as acetic acid. 1/1 dilution of vinegar/water L/L; 8 Considering 0.9 to 2 qt of seeds per ha; 9 Expressed as acetic acid. 50 mL/1 L dilution of vinegar/water for vinegar at 8% acetic acid; 10 Of main active substance acetic acid for vinegar at 10% acetic acid; 11 Expressed as acetic acid in a preparation with 60% vinegar (diluted in water), for vinegar at 10% acetic acid; 12 Treatments must be delayed 24-48 h or more after rain; 13 Spray when there is sun (preferably morning); 14 Do not apply when any plant is at a later growth stage than BBCH 49; 15 With a maximum of 10% concentration (30 L in 300 L); 16 Do not apply on treating fingertips right before or during harvest of edible commodities; 17 Depending upon environmental factors such as climate and topography; 18 The quantities of fresh nettle (or dry matter) written represents the quantities of nettle used in the recipe, but not the quantities that are effectively put in field-there is a filtration before; 19 Treatment, just before sowing; 20 Assuming plant density of between 0.1/m 2 to 1/m 2 ; 21 300 g of granules per nest multiplied by 120 nest/ha = 36 kg product/ha. Considering a maximum of 8% L-cysteine in the product, the maximum application rate per treatment of L-cysteine is 2.88 kg/ha; 22 Do not apply when any plant is at a later growth stage than BBCH 57; 23 Do not apply when any plant in the greenhouse is at a later growth stage than BBCH 06 and in presence of fruits; 24 Do not apply when any plant in the greenhouse is at a later growth stage than BBCH 49.     The scientific literature dealing with basic substances is relatively limited but increasing in recent years (Figure 2), and there is poor information about the effectiveness in field trials of basic substances toward pests and pathogens. The scientific literature dealing with basic substances is relatively limited but increasing in recent years (Figure 2), and there is poor information about the effectiveness in field trials of basic substances toward pests and pathogens. In the last decade, MRLs for pesticides with agricultural trade are becoming important. In the EU, there are increasing requirements from retailers to their suppliers to provide fruits and vegetables with an amount of pesticide residue below the MRLs (Table  5).  In the last decade, MRLs for pesticides with agricultural trade are becoming important. In the EU, there are increasing requirements from retailers to their suppliers to provide fruits and vegetables with an amount of pesticide residue below the MRLs (Table 5). In the last decade, MRLs for pesticides with agricultural trade are becoming important. In the EU, there are increasing requirements from retailers to their suppliers to provide fruits and vegetables with an amount of pesticide residue below the MRLs (Table  5). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network).  The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network).  The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network).  The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network).  The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network).  The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS

70%
150% 70% 100% - The substances tested during Casdar programs '4P', 'Carie', 'Sweet', 'HE, Ecophyto 'Usage' and some from projects have already been described (Marchand, 2016) (Table 6). New projects are ongoing to develop extensions of use, describe better efficacy through better positioning during the season or to investigate compatibility/incompatibility with other biocontrol agents (i.e., reduce copper and macro-organisms). This is the ongoing work for Coperreplace, ABAPIC (ITAB), Vitinnova (UNIVPM), and Euphresco BasicS (Euphresco Network). Each use of plant extracts and natural products, such as decoctions, herbal teas, or aqueous solutions, have been defined and tested in the field or identified from the literature then controlled or cross-referenced with producer surveys. Whenever water is mentioned in these tests, it is either natural spring water or rainwater. Each basic substance preparation is described in Section 2.5 of Basic substances applications in EU 2012. The evaluation process of the basic substance application is getting longer, and legal delays fixed by EC are not consistently respected. The evaluation process lasts an average of 19 months (Supplementary Table S1 and Figure S1), while the legal maximum delay is fixed at 18 months until basic substance application admissibility. Even not considering admissibility evaluation delays that are considered outside of the evaluation process, this process becomes longer from year to year, resulting in a delay in availability of additional basic substances.

Discussion
The use of pesticides, if not appropriate, may lead to problems like contamination of the water, potential damage to sensitive species (e.g., bees), contamination of final food products and water, with up to 90% of applied pesticides not reaching the target species, and, also, because of the development of resistant pathogens and pests [39]. A high number of PPPs were not reauthorized (or companies did not provide the dossier for the reregistration of products out of patent, due to high costs and uncertain benefits) and leaves a gap for several uses. It is important that authorities provide a good number of options to growers to protect their crops, since farmers cannot stand without PPPs for certain crops and uses, and there is an increasing need, because a lot of substance prohibition dates are fixed without substitution mean. Just as an example, this occurred with the fungicide mancozeb in January 2022 and a risk to occur in 2025 with copper, that is fundamental for plant protection in organic agriculture and a good support to prevent the appearing of resistant isolates in IPM. In France, the use of neonicotinoids, known as dangerous insecticides, is extended when there is no other way to preserve crops and productivity. With Farm to Fork Strategy of the European Green Deal, the European Commission is committed to reduce the use of the most dangerous synthetic pesticides of 50% and achieve at least 25% of the EU agricultural land under organic farming by 2030, although the decrease of synthetic pesticides is already ongoing. These trends, together with the implementation of sustainable development goals-SDGs by the United Nations-are demanding for new alternatives, such as basic substances, to tackle some of these issues. To achieve these goals, more research is needed to advance the design of better farming systems and the development of alternatives to synthetic pesticides and to copper formulations.
Three decades ago, the concept of MRLs was poorly known, while, in recent years, MRLs for pesticides arguably have become the first action growers should consider in their pest management decisions [40]. Trying to interpret consumer demands, retailers are increasingly required to reduce pesticide residues even more than the allowed thresholds (MRLs), which are defined considering a wide security factor (e.g., ×100) using the presence of pesticide residues as a factor of competition among companies. Requests from the retailers and consumer to reduce synthetic pesticide residues from fresh produce even more than the allowed threshold, such that the rules defined by the public administration have become more limiting for farmers in terms of the active ingredients allowed and MRLs [40,41]. The reduction of the presence of fungicide residues well beyond MRL may allow the pathogen to develop after harvest, resulting food loss and waste along the value chain. These developments have driven the search for alternative management strategies that are effective and not reliant just on conventional fungicide applications [5,42,43]. European regulation followed and carried this development with the introduction of new classes of phytosanitary products, in particular basic substances, but also new laws and simplification accompanied by the reduction of registration processes of low-risk substances, theoretically. Basic substances are approved for use in the EU and are products that are already sold for certain purposes, e.g., as a foodstuff or a cosmetic. Basic substances may be of major importance in biocontrol and several advantages can explain it. Basic substance regulatory application is simplified [44] and particularly reduced compared to other substances, therefore representing a lower cost to applicant (around 35-40 kEuro for approval of a basic substance and overall around 45 kEuro including approval for organic agriculture), thanks to the fact that these substances are already on the market for another purpose than plant protection, and safety is not an issue to be demonstrated. These substances are good alternatives available today and wide targets. Basic substances can be used in the crop protection as fungicide, bactericide, insecticide, etc., and most of them are allowed in organic production [18,[45][46][47]. The basic substances are in order from 2014, when was the first approved application of Equisetum arvense L., chitosan hydrochloride, and sucrose until 2022, when a second chitosan formulation was approved. In some conditions basic substances were already at farm level, with a level of pest management not different than the standard. Just as example, chitosan hydrochloride was also applied in commercial conditions, in the field, and postharvest treatments, and several studies proved that it could have an effectiveness comparable to some commercial PPPs [42,48]. Basic substances, probably less efficient and practical to use than other active substances authorized as PPPs, are known and used by producers since decades as substitution means and have already demonstrated their effectiveness. Basic substances were the perfect tool to provide to producers as known, easy-to-use, less dangerous, and environmentally more respectful. Today, there is a consensus among a wide range of stakeholders that synthetic pesticide used need to be gradually reduced to a level that is effectively required to ensure crop production and that risks of pesticide application should be reduced as far as possible. Basic substances are good alternatives available today in our hands. The use of these substances needs to be integrated in vocational education, training, and technical advice to farmers. Further research around the world on the efficacy of basic substances may prove in the future that these substances can replace pesticides without reducing yields or increasing production costs. To develop the uses and the field trials we listed here the main usages of basic substances. However, rates included in the approval schedule may not produce a significant containment of diseases and pests in specific pathosystems. Just as example, the advised application rate of chitosan hydrochloride is between 100 and 800 g/ha, equal to a concentration ranging among 0.05 and 0.2% with 200-400 L/ha, while trials in commercial vineyards found a good effectiveness delivering the chitosan hydrochloride, with a concentration of at least 0.5% and with a volume of at least 500 L/ha [34,49]. For this reasons, large-scale trials are very important to demonstrate the effectiveness toward pathogens and pests in different environments and growing contexts, and a flexibility could be required in suggested dosages to avoid that applying basic substances at suggested rated can lead to a lack of or poor effectiveness and then the disaffection of users toward these innovative compounds, and this is in contrast with the requirements of finding solutions alternatives to the application of synthetic pesticides keeping the standard quality and quantity of the production, which is one of the drivers of the Farm-to=Fork Strategy of European Green Deal. Moreover, the diluent allowed for basic substance, up to now concretely restricted to water, may be another substance. In this case, vinegar has just been authorized for chitosan. Finally, increasing the demand from growers and competition among companies can lead to the reduction of costs of the treatments that, nowadays, are often higher than standard treatments.

Collection of Data
A systematic literature search from 2009 to 2021 was performed using the database of Scopus with the keywords 'basic substance' and 'basic substances'. In the EU, several retailers request an amount of pesticide residue on fruit and vegetables below the legal limit (MRL), and data on some protocols were collected through companies and plant doctors.

Legislation
Basic substance criteria are defined by article 23 of Regulation (EC) No. 1107/2009, cited in introduction. By way of derogation from Article 4 of this regulation, a basic substance is approved when all relevant evaluations conducted in accordance with other Community legislation, governing other uses of this substance, showing that it has neither an immediate or delayed harmful effect on human or animal health nor any unacceptable influence on the environment. Active substances that could be defined as 'foodstuff' are intrinsically considered as basic substances, following Article 2 of Regulation (EC) No. 178/2002. Basic substances shall be approved in accordance with paragraphs 2-6 of regulation (EC) No. 1107/2009 and by way of derogation from Article 5, the approval shall be for an unlimited period. By way of derogation from Article 7 of Regulation (EC) No. 1107/2009, an application for approval of a basic substance can be made by a Member State or any interested party. At the end of the evaluation process, basic substances shall be listed separately in the Regulation referred to in Article 13 (4). The Commission may review the approval of an active substance at any time. It may take into account the request of a Member State to review the approval. Article 28 of Regulation (EC) No. 1107/2009 set the absence of marketing authorizations and usages allowance for basic substances. However, no formal authorization is required as long as the product contains exclusively basic substances (see corresponding Review Report) [49,50].

Approval Process
The approval process of a basic substance starts with a request for approval ( Figure 3). The applicant estimates if the substance concerned fulfil all criteria of basic substances category and then complete the BSAT, in English, to obtain a Basic Substance Application. Several guidance documents, such as the official SANCO guide or the teaching guide from the ITAB, have been published to help applicants to build basic substance application correctly [50]. For the transmission of the basic substance application, once completed, the file should be sent to the DGSanté, representing the European Commission (EC). The Basic Substance Application can firstly be sent to national competent authorities for a preassessment and possibly a support. For example, in France, the Basic Substance Application can be sent to the Ministry of Agriculture (DGAl in France), who can ask for the National Authority' opinion and then transfer the file to the EC. Upon receipt of the Basic Substance Application, EC implements the approval procedure detailed in Article 23 of Regulation (EC) No. 1107/2009. Admissibility may be pronounced at any time, directly or after questions from DGSanté. It constitutes the real start of the application (black line in Figure 3). The first stage is based on the Basic Substance Application evaluation by Member States and EFSA as scientific assistance leading to a request for corrections and questions. The request is sent to the applicant, and his answers shall be sent back within one month to the EFSA. For decision and approval, at the end of the basic substance application evaluation, EFSA will deliver its opinion, append a comment, and send the basic substance application to the DG Health within 3 months for the final vote of Member States in the PAFF committee ( Figure 3). Approval, if accorded, is effective at the date of the publication of an implementing Regulation modifying Regulation (EU) No. 540/2011 [8]. the National Authority' opinion and then transfer the file to the EC. Upon receipt of the Basic Substance Application, EC implements the approval procedure detailed in Article 23 of Regulation (EC) No. 1107/2009. Admissibility may be pronounced at any time, directly or after questions from DGSanté. It constitutes the real start of the application (black line in Figure 3). The first stage is based on the Basic Substance Application evaluation by Member States and EFSA as scientific assistance leading to a request for corrections and questions. The request is sent to the applicant, and his answers shall be sent back within one month to the EFSA. For decision and approval, at the end of the basic substance application evaluation, EFSA will deliver its opinion, append a comment, and send the basic substance application to the DG Health within 3 months for the final vote of Member States in the PAFF committee ( Figure 3). Approval, if accorded, is effective at the date of the publication of an implementing Regulation modifying Regulation (EU) No. 540/2011 [8].
The period of examination of the basic substance application is established in paragraph 1 of article 37 of Regulation (EC) No. 1107/2009. It is said: 'The Member State examining the application shall decide within 12 months of receiving it whether the requirements for authorization are met. Where the Member State needs additional information, it shall set a period for the applicant to supply it. In that case, the 12-month period shall be extended by the additional period granted by the Member State. That additional period shall be a maximum of 6 months and shall cease at the moment when the additional information is received by the Member State. Where at the end of that period the applicant has not submitted the missing elements, the Member State shall inform the applicant that the application is inadmissible.' [10]. The maximum delay is therefore set at 18 months. However, although clearly defined, these steps are not so straightforward in many cases [51].

Extension of Uses Process
The request for an extension is somehow similar, except the need of support from corresponding agricultural sectors at the deposit step. Some extensions were voted after The period of examination of the basic substance application is established in paragraph 1 of article 37 of Regulation (EC) No. 1107/2009. It is said: 'The Member State examining the application shall decide within 12 months of receiving it whether the requirements for authorization are met. Where the Member State needs additional information, it shall set a period for the applicant to supply it. In that case, the 12-month period shall be extended by the additional period granted by the Member State. That additional period shall be a maximum of 6 months and shall cease at the moment when the additional information is received by the Member State. Where at the end of that period the applicant has not submitted the missing elements, the Member State shall inform the applicant that the application is inadmissible.' [10]. The maximum delay is therefore set at 18 months. However, although clearly defined, these steps are not so straightforward in many cases [51].

Extension of Uses Process
The request for an extension is somehow similar, except the need of support from corresponding agricultural sectors at the deposit step. Some extensions were voted after submission, some others were granted with admissibility and voted rapidly after; some later were following the full approval pathway, including admissibility, evaluation, outcome, full vote at PAFF Committee (appearance in Part A (lecture, discussion), C (proposal) and B (effective vote)). This latter process sometimes takes the same amount of time compared to a new approval, which is considered very excessive by the applicants, having an approved substance at the beginning of their request and only asking for one line sometimes in the Good Agricultural Practices (GAP) table.

Regulation Analysis
The EU Pesticides Database [52] was used to detect basic substances and their status (approved, nonapproved, pending, and modifications of Review Reports). Corresponding linked Implementing Regulations [20] attached to each active substance were found using the same method and cross-verified with Implementing Regulation (EU) 540/2011. The EU law database for Eur-Lex was also used to track each Implementing Regulation publication. Furthermore, EFSA documents were also compiled to extract decisions supportive analyses.

Conclusions
Searching for alternative products for crop protection is an important strategy for promoting more sustainable food systems. The use of basic substances is in line with the restriction on the application of chemical PPPs and the principles of the European Green Deal and SDGs, mostly renewables and with no MRL. There is relatively poor information about the effectiveness of basic substances as compared to synthetic pesticides and biological PPPs. A higher testing and validation of the use of basic substances as a phytosanitary measure can lead to further reduction of application of synthetic pesticides. In addition, searching for the most effective dosage of the basic substance is critical and an important question for phytosanitary consultants (the plant doctors that are opinion leaders in application of innovations in pest management), growers, stakeholder, and companies to avoid that their application at the recommended dose can lead to a lack of or poor effectiveness of these substances. For this reason, a flexibility might be required in the suggested dosage of basic substances approved to ensure good maintenance of the quality and quantity of production, which is one of the keys of the Farm to Fork Strategy of the European Green Deal. Moreover, a defined timeline for approval is basilar to have the chance to increase the number of basic substances available for growers, the scientific community, and the whole agricultural sector, with final benefits for the consumers.

Patents
All Implementing Regulations may be considered as patents but with free exploitation, since no Marketing Authorizations are needed for basic substances.
Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/molecules27113484/s1, Figure S1: Time needed for Basic Substance Application admissibility evaluation over time (bars) and tendency line (dotted line); Table S1: Total time of basic substance application process within admissibility to Implementing Regulation publication in months.