A Study of the Prospect of Abamectin: Taking EFSA Latest Risk Assessment Analysis Report as an Example

By Chasel Huang; Yuga Huang（REACH24H Consulting Group）

On August 28, 2020, the Ministry of Commerce and the Ministry of Science and Technology adjusted and issued the Catalogue of Technologies Prohibited or Restricted from Export, banning for the first time the export of strains and production technologies of Abamectin and other biopesticide strains. Recently, the EFSA risk assessment report of Abamectin has also been officially released, which is of "wind vane" significance to the global registration of Abamectin. By analyzing the EFSA risk assessment results of Abamectin, this paper reviews the development process of Abamectin at home and abroad, and discusses the future prospect of Abamectin.

Abamectin

Abamectin was first screened out of more than 40,000 soil samples in 1975 by Satoshi Omura of Japan's Kitasato University and William Campbell of Merck. It was developed as a pesticide and put on the market in 1985. As a macrolide antibiotic, Abamectin has a unique mechanism of action. It can simultaneously target multiple targets inside bodies of pests such as nematodes and arthropods which damage the agriculture, paralyze and kill such pests by blocking nerve signal transmission. It features in broad spectrum, high efficiency and low toxicity insecticidal activity (IRAC MoA Classification: 6). Therefore, after more than 30 years of continuous development since its successful commercialization, Abamectin has become the biopesticide with the largest production and application globally and occupies a pivotal position in pesticide categories in various countries and regions.  

Figure 1: Structure of Abamectin

On August 20, 2020, the European Food Safety Authority (EFSA) officially updated the risk assessment report for Abamectin reevaluation based on the assessment contents and public comments of member countries. Since the Europe is the region with the strictest pesticide regulation in the world, the EFSA assessment results undoubtedly have the significance of "wind vane". They not only systematically review the existing registration data of Abamectin's health toxicology, ecotoxicology, environmental fate, residue and efficacy; At the same time, complying with the requirements of EU pesticide residue regulations and the latest endocrine disruption assessment guidelines, supplementary data have been submitted to further improve the Abamectin risk assessment conclusion.  

Figure 2: Latest EFSA risk assessment report of Abamectin (Source: EFSA)

What impact will this EFSA risk assessment report have on the global registration and market prospects of Abamectin? As the world's largest producer of Abamectin and its derivatives, how can the corresponding Abamectin manufacturers improve their competitiveness in the current situation where the threat of global trade protectionism is increasing? This article comprehensively analyzes and discusses relevant issues.

The re-evaluation process of Abamectin in the EU

The EFSArecently released Abamectin risk assessment report is a staged work in the EU renewal assessment of Abamectin. Prior to this, starting in 2019, the approval periods of the active substance Abamectin has been extend for 2 years in order to allow more time for review in the EU. In addition, before the expanded use of Syngenta Abamectin (nematicide) was approved by the EU in 2017, EFSA has also fully evaluated this part of the data. Therefore, the successive release of the two risk assessment reports of EFSA marked the completion of the re-evaluation of Abamectin. The final EU-level renew or ban on Abamectin may also be issued in the near future.

In accordance with Article 1 of Regulation (EU) No 844/2012, the rapporteur Member State (RMS), Austria, and co-rapporteur Member State (co-RMS), Malta, received an application from the Abamectin Task Force comprising Industrias Afrasa, S.A., Lainco, S.A., Probelte S.A.U., Rotam Agrochem International Co Ltd and SAPEC Agro, S.A. for the renewal of approval of the active substance Abamectin. 

Analysis of EFSA Abamectin risk assessment report

The representative assessment scenario in this risk assessment is the extended use of Abamectin preparations. The use places are permanent greenhouses and greenhouses. The content of Abamectin EC is 18g/L, and tomatoes and strawberries are controlled by knapsack spray. For insect pests, the single application rate is 2.7-18 kg/ha, the maximum number of applications is 3 times, and the safety interval is set to 3 days.

The efficacy experiment showed that, in this application scenario, the Abamectin formulation can effectively control the damage to tomatoes including Tetranychus urticase, Liriomyza trifolii, and Tuta absoluta. The uses of abamectin according to the representative uses as an insecticide and acaricide on tomato and strawberry in permanent greenhouses and walk-in tunnels, as proposed at European union (EU) level result in a sufficient insecticidal and acaricidal efficacy against the target organisms. 

Figure 3: Efficacy Evaluation Results of EU Abamectin Expanded Use (Sourse: EFSA)

In the area of mammalian toxicology, Abamectin has not been identified with a new significant hazard effect, and the results of its hazard classification are basically the same as the previous ones, and except for dietary risks, other related health risks are acceptable. However, the MRL proposed in Article 12 of Regulation (EC) No 396/2005 will need to be revised as for change of toxicological reference values (ADI and acute reference dose (ARfD)), since it is envisaged that acute risk may be identified for some of the crops. The more sensitive rat neurodevelopmental toxicity endpoint NOAEL = 0.12 mg/kg bw/day should be selected to set ADI, ARfD, AOEL and AAOEL. Therefore, the important parameters ADI and AOEL in the risk assessment of Abamectin are reduced by half compared with the previous setting values. In addition, the Abamectin Working Group submitted new data in accordance with the requirements of the EU Endocrine Disruption Assessment Guidelines in 2018. Based on the existing data, the assessment experts have clarified that Abamectin does not have endocrine effects on humans and other non-target organisms.

The data available on environmental fate and behaviour are sufficient to carry out the required environmental exposure assessments at EU level, with the notable exception that a data gap was identified for information on the effect of water treatment processes on the nature of residues of both the active substance and its identified metabolites potentially present in surface water, when surface water is abstracted for the production of drinking water. This gap leads to the consumer risk assessment from the consumption of drinking water being not finalised for all the representative uses. 

In the area of ecotoxicology, a critical area of concern has been identified regarding the chronic risk to aquatic invertebrates from Abamectin for all the uses in permanent greenhouses and in walk-in tunnels. In addition, a high risk was identified for walk-in tunnels uses for birds and mammals, aquatic invertebrates (for the metabolite 8-carboxy-6-hydroxy avermectin B1a in permanent greenhouses as well), honeybees non-target arthropods, earthworms and other soil macro-organisms.

 When it comes to dietary risk assessment, there are basically no data gaps in the southern European representative assessment scenario, and dietary risks are acceptable. However, as mentioned above, the drinking water risk assessment is still to be the data gap. Due to the lack of field residue test data, dietary risk assessment under the representative assessment scenario in NEU cannot be carried out yet. It should be noted that because the toxicological endpoints set for ADI, ARfD, AOEL and AAOEL are more sensitive, based on the existing MRL of Abamectin in certain crops, acute dietary risks cannot be guaranteed Acceptable, so the MRL of Abamectin needs to be revised urgently.

The results of the latest EFSA assessment report show that Abamectin has no new significant harmful effects and has been identified in health toxicology and ecotoxicology, and the critical endocrine disrupting assessment also determined that Abamectin is non-endocrine disrupting properties. Comprehensive considerations After the benefit analysis, it can be considered that Abamectin is likely to renew in the EU. Abamectin still has broad market prospects, and the future is still promising.

In this risk assessment for the expansion of the use of Abamectin formulation, it is shown that there is uncertainty in its use in NEU. Only the use in SEU basically meets the registration requirements. This result may influence the registration of related preparations in NEU. At the same time, because the preparation has a greater ecological risk, its use process must fully consider the application environment and effective risk mitigation.

It is important to point out that in this renewal assessment, it was determined that a more sensitive toxicological endpoint was used to set the ADI and other indexes of Abamectin, so the EU may have different levels of MRL for Abamectin in some crops The reduction of the relevant residue supervision will inevitably be stricter, and may gradually affect the import and export trade of agricultural products in China.

Development of Abamectin at Home and Abroad

The discovery of Abamectin is both accidental and inevitable. Perhaps thanks to the blessing of Lucky Goddess, Satoshi Omura and Campbell's team accidentally extracted microorganisms that can produce active ingredients among 40,000 soil samples. However, it was precisely the necessary factor of strong basic research capability that enabled researchers finally discover Abamectin several years later. The close integration of production, teaching and research has successfully pushed Abamectin to the market. On the basis of previous research, Merck has further improved the chemical structure of Abamectin and developed veterinary drug Ivermectin with low oral mammalian toxicity and insecticide Emamectin Benzoate with enhanced control effect on lepidopteran pests. The discovery of Abamectin is of great significance to all mankind. This natural antibiotic derived from microorganisms and artemisinin discovered by Tu Youyou won the Nobel Prize together in 2015, which was truly worthy of the reputation.  

Figure 4: Nobel Prize in Physiology or Medicine (Sourse: nobelprize.org)

The research of Abamectin in China, which began in the late 1980s, is also spectacular. Although the research on Abamectin in China started late, many microbiologists, pharmacologists and fermentation experts in China have achieved the industrialization of Abamectin with continuous efforts from the "Seventh Five-Year Plan" to the "Ninth Five-Year Plan". At the same time, with the development and application of genetics, metabolic engineering, synthetic biology and other technical methods, the industrialization competitiveness of Abamectin in China has been continuously enhanced and the production cost has been continuously reduced, eventually breaking the monopoly of foreign companies and gradually changing Abamectin from valuableness to moderate in price At present, China has not only become the only producer of Abamectin, but also achieved the feat of independent innovation and corner overtaking in related strains and production processes. It is also because of the leading technology in this area that on August 28, 2020, the Ministry of Commerce and the Ministry of Science and Technology adjusted and issued the Catalogue of Technologies Prohibited or Restricted from Export, banning for the first time the export of strains and production technologies of Abamectin and other biopesticide varieties.  

Figure 5: Biosynthesis of Abamectin (Source: WEN Ying & ZHANG Lixin, 2018)

Prospects in the Future

As an EU pesticide policy with the significance of "wind vane", the latest EFSA risk assessment report shows that Abamectin- registration data are basically complete, and there is a high probability that the Abamectin would be renewed in the EU. Abamectin still has broad market prospects which can still be expected in the future. Although China has a leading advantage in Abamectin production technology, Chinese enterprises still lack comprehensive chemical risk assessment technology in the high-end pesticide markets in Europe and the United States, and their independent registration capability in these countries and regions still needs to be improved. Moreover, further in-depth research is needed for refining the effective components of Abamectin, developing new pest targets, pollution control in production processes and studies of Abamectin derivatives. Ultimately, new products and new processes with low toxicity, high efficacy and in line with green production will emerge for the purpose of integrating production, teaching and research, thus stabilizing China's technological leadership in the field of Abamectin.

References

[1] European Food Safety Authority (EFSA), Conclusion regarding the peer review of the pesticide risk assessment of the active substance Abamectin. EFSA Scientific Report, 2008, 147: 1-106.

[2] European Food Safety Authority (EFSA) Conclusion on the peer review of the pesticide risk assessment of the active substance Abamectin. EFSA Journal, 2016, 14(5): 4491.

[3] European Food Safety Authority (EFSA), Anastassiadou M, Arena M, et al. Peer review of the pesticide risk assessment of the active substance Abamectin. EFSA Journal, 2020, 18(8): e06227.

[4] The European Union extended the validity period of registration of 34 active ingredients, such as abamectin, clodinafop-propargyl and metconazole. AgroPages. 2020 

[5] Wen Ying, Zhang Lixin. Avermectins, intelligently made in China. Hereditas, 2018, 40 (10): 888-899.

Tel: +86-571-87006630

Email: customer@reach24h.com

Website: www.reach24h.com

This article was initially published in AgroPages '2020 Market Insight' magazine. Download it to read more articles.