In the Requirements for Pesticide Registration Data (hereinafter referred to as Requirements) implemented on November 1, 2017, although there is no clear definition of Biogenic Pesticides or biopesticides, pesticides are classified into chemical pesticides, biochemical pesticides, microbial pesticides and botanical pesticides according to their sources, and the latter three categories are biogenic pesticides.
Agricultural antibiotics are produced by microbial fermentation, although they are also biogenic pesticides, but in terms of registration data requirements, except for some test items which can not be provided due to the special nature of products (can be applied for exemption), other basic equivalent to chemical pesticides, which are hardly treated as biopesticides in other countries in the world at present. Because many kinds of agricultural antibiotics such as abamectin and jingangmycin A are used in agricultural production, there are many new varieties such as Ningnan mycin and pyrimidine nucleoside antibiotics in China, which are also used as biopesticides in some occasions. Therefore, biochemical pesticides, microbial pesticides, botanical pesticides and agricultural antibiotics are temporarily classified as biogenic pesticides.
Registration of Biogenic Pesticides
As of December 31, 2017, there were 102 active ingredients and 1,379 products of biogenic pesticides, accounting for 15% and 3.6% of the total active ingredients and total products of pesticides, except agricultural antibiotics. For example, 115 active ingredients of agricultural antibiotics and 3,764 products accounted for 17% and 9.8% respectively. Among them, microbial pesticides have the most active ingredients and agricultural antibiotic products.
In 2017, 17 new pesticides were registered, of which biological pesticides accounted for 59%, and the number of new biological pesticides exceeded the number of new chemical pesticides for the first time, indicating that biological pesticides are developing rapidly, increasing at a rate of about 4% per year. Trichoderma harzianum, d-limonene, pyrethrins from Australia, oriental fruit mothsex pheromone, Muscalure from the Netherlands, ethyl acetylaminopropionate (IR3535) from Germany and azadirachtin from India were also registered as biopesticides in China. Products of overseas companies such as azadirachtin.
Registration data requirements.
The new Requirements are classified according to the registration data of biochemical pesticides, microbial pesticides, botanical pesticides (general information, product chemistry, toxicology, environmental impact, etc.) and pharmaceuticals (general information, product chemistry, toxicology, pharmacodynamics, residual environmental impact, etc.), and summarize the basic requirements and concerns of biopesticide registration data. Specific documents and related supporting policies can be found in the China Pesticide Information Network (http://www.chinapesticide.org.cn/).
The newly revised Regulations on Pesticide Management encourage and support the development, production, use of safe, efficient and economical pesticides, promote pesticide risk assessment, promote the upgrading of pesticide industry, raise the threshold of pesticide registration and production licensing, give relatively relaxed policies for the registration of biopesticides, and create good opportunities for the development of biopesticides.
Standardization of Biopesticides
Up to now, China has formulated more than 120 standards for biological pesticides, including more than 60 standards for product quality and method; nearly 30 standards for evaluation of pharmacodynamics and technical regulations for use; 6 criteria for toxicology test of microorganisms (NY/T 2186.1-6-2012); and 9 new criteria for environmental risk assessment of microbial pesticides (avian, bee, silkworm, silkworm, etc.). Fish, daphnia, algae, NY/T 3152.1-6-2017, microbial pesticides, soil, water, plant leaf surface (NY/T 3278.1-3-2018), and 14 residual standards. Abmectin, kasugamycin, polyoxin B, spinosad, jingangmycin A, Ningnan mycin, pyrethrins, matrine and rotenone are stipulated in GB 2763-2016. Daily maximum allowable intake (ADI) and maximum allowable residue limit (MRL) of biological pesticides such as rotenone and sodium nitrophenolate.
In a word, great progress has been made in the standards of biopesticides, which cover many fields. It is of great significance to improve the overall quality of biopesticide products and to standardize the policies and requirements of registration management of biopesticides scientifically. However, there is a lack of systematization and general standards for standardizing inspection technology, quality management standards, evaluation criteria, safe use and storage and transportation.
At present, there are 12 standards for biopesticides in international organizations, including 5 FAO/WHO standard manuals - TK/WP/WG/WT/SC specification for microbial larvicidal bacteria (which is being revised to Section 9 of FAO/WHO Standard Guidelines for Microbial Pesticides, and its trial version is scheduled to be released by the end of 2018). There are 5 WHO and 2 FAOs in product standards. Although FAO/WHO of Bacillus subtilis QST 713 TK/WP/SC did not pass at the joint FAO/WHO meeting of FAO/WHO pesticide standards in 2018, it will continue to discuss this standard in 2019 and the FAO standard of Spodoptera exigua nucleopolyhedrovirus TK/SC put forward by China. This shows the development of international biopesticide standards in China. Biopesticide standards are also accelerating into the international arena.
Biopesticides for Health
Active ingredients and products
China's health pesticides have registered 95 active ingredients (up to 2018.9.11), more than 2,600 products (up to 2018.6.20), of which 7.1% are original drugs/maternal drugs, and more than 700 manufacturers. According to Agricultural Letter No. 17, 2018, the sale and use of pesticide products containing fipronil have been prohibited since March 26, 2019.
According to the structure of sanitary pesticides, they can be classified into seven categories: pyrethroids, organic phosphorus, carbamate, microorganism, organic chlorine, benzene and others, accounting for 42% of the pesticide varieties (73% of the total products), 11% of the products, 6% of the inorganic pesticides, 4% of the products, 4% of the products, 1% of the products, 1% of the products and 1% of the other pesticides (including benzene). The proportion of pyrazole, nicotine and benzoyl urea was 27% (product 16%).
The active ingredients of health bio-pesticides accounted for 11.6% (up to 2018.9.24), and their products accounted for 3.4% of health products.
S-methoprene, a new health biological pesticide, has been registered for the first time in recent years. It is similar to sesquiterpenes of insect growth regulators. It belongs to insect regulators of biochemical pesticides. 95% of the original pesticides (WP20180181) and 20% of the microcapsule suspension agents (WP20180179) have been registered. This product embodies the characteristics of biological pesticides "from nature, higher than nature, returning to nature" and has been used in the United States for 50 years. There are also S-kinoprene, S-hydroprene, triprene and other "family" products.
New dosage forms were registered as follows: 5.6% Eucalyptus oil/eucalyptol belonged to botanical pesticides (WP20180149).
Main characteristics of registered products
Decline in the number of registrations
In the past five years, the annual cumulative and annual incremental ratio of the registered amount of sanitary pesticides to the total registered amount of pesticides in that year decreased from 7.5% to 6.6%, 8.7% to 4.2%, respectively. This shows that the registered amount of sanitary pesticide products is declining significantly.
This trend meets the requirement of zero growth of pesticide use, and may also be restricted by policies such as environmental protection and the issuance of production licenses for pesticide production enterprises, which will lead to the transformation, merger and reorganization of enterprises.
Less anti-mosquito larvae products
The products of mosquito control larvae are few, the varieties are limited and the development is slow. Our country is similar to the international situation. Its products only account for 1.7% of the total amount of sanitary pesticides, and the biological pesticides of mosquito control larvae account for 25% of the total amount of sanitary biological pesticides. But these products will play an important pioneering role in promoting the "trilogy" of integrated vector biological control (i.e. cleaning, killing young and mosquito control).
At present, the registered insecticides against mosquito larvae have eight active ingredients: Bacillus thuringiensis subsp. Israel accounts for 36% of the products against mosquito larvae, Bacillus globosa accounts for 9%, pyridyl ether accounts for 16%, pyrethroid accounts for 2%, imidacloprid accounts for 2%, S-enoxate accounts for 5%, fenthiphos accounts for 16%, disulfide accounts for 14% (the United States has stopped using two organophosphorus pesticides in 2015).
Six formulations: granule GR (39% of mosquito control larvae), suspension SC (26%), wettable powder WP (19%), microcapsule suspension CS, water emulsion EW and powder DP.
Development of Biogenic Pesticides
Biogenic pesticides have a long history in China. China is one of the earliest countries to use botanical pesticides to control crop diseases and insect pests. As early as the 10th century B.C., shield grass (fennel narrowleaf, awn grass), Veratrum and other plants were used to control diseases and insect pests. In 1935, a small amount of pyrethrum was planted in China. At the beginning of the 21st century, its main producing areas are Kenya, Tanzania, Africa, Japan, Australia, Jiangsu, Yunnan, Taiwan and so on. With China's reform and opening up, the introduction of new pesticides and the rapid development of industrialization, coupled with the characteristics of biological pesticides (low efficacy), its pace seems to be somewhat slow, but it is the main force in the development of green agriculture. As academician Shen Yinchu said, "Biogenic compounds are the treasure house of preconditions for pesticide activity", in fact, pyrethroids are the leading compounds of pyrethroid pesticides.
Due to the late start of pesticide registration management in China, over the past 30 years, pesticide management is changing from focusing on quality and efficacy to focusing on both quality and safety management. Pesticides in China are still in the developing stage. Generations of Chinese people are striving to improve the level of registration, production, use and management of pesticides.
Differences and Directions
FAO/WHO Guidelines for Registration of Biopesticides
In 2017, FAO/WHO jointly issued the Biopesticide Registration Guidelines for Microorganisms, Botanical Sources and Chemical Pheromones for Plant Protection and Public Health, which replaced the 1988 FAO's Biopesticide Registration Guidelines. This is the international code of conduct for pesticide management, which has important reference value and guiding significance for standardizing the registration data requirements of biopesticides in China.
The technical specifications of microbial pesticides are usually expressed in terms of scope rather than absolute numbers. Microbial content can be expressed in terms of g/kg or g/L (or% w/w) and colony forming unit (CFU) or biological titers tested. Relevant secondary compound (metabolite) is considered to be similar to "focus component". If the new source microorganisms are of the same grade I technology, they do not need grade II evaluation. It should be noted that non-native MPCA species may be at higher risk.
Botanical pesticides are complex mixtures of one or more components in plants. For this reason, "Lead component concept" and "Component of concern" are proposed. Botanical pesticides are obtained by processing natural plant materials and are affected by geographical and climatic conditions, plant cultivation, storage and processing, and plant use sites. In general, plant active substances are not produced in batches, so "samples" are replaced by "batches". The range of plant characteristics is the "chemical fingerprint" of Materia medica, whose composition/specifications and technical equivalence have become the focus of product quality; the toxic plants need to take measures to reduce the risk to avoid or minimize the threat to human health; the residual, environmental and ecological toxicological requirements require exposure to be lower or close to natural exposure; and the pharmacodynamics should play its role as effectively as possible and consistently as possible. 。
Usually chemical pheromone pesticides are synthetic natural equivalents. The product has recyclable and non-recyclable dispensers (in "Pesticide Formula Name and Code" GB/T 19378-2017, "Dispersible Core" Formula has been formulated). When the exposure level of the product is similar to the natural exposure level of chemical pheromones (the same way, the exposure is in an order of magnitude), no other information is needed except for the identification, characteristics and analysis methods of the component. Natural exposure levels can be estimated from experimental data, and then the actual reference values are compared with the amount of the product used.
If the original drug is made up of isomers, it is necessary to specify the proportions of the isomers. However, it is not necessary to design technical parameters exactly the same as natural chemical pheromones, because the latter can be changed. Because the amount of active substances needed in products is very small, only a small number of production batches are usually prepared, sometimes only one of them is available. It is recommended that the applicant provide as much data as possible, including laboratory and pilot production data.
The field efficacy test of chemical pheromone pesticides is complex and difficult to repeat on a large scale. Therefore, it is necessary to provide as much information as possible about the possible mechanisms of target biology and chemical pheromones. Chemical pheromone pesticides used in plant protection products or public health products can completely control, partially control or assist in the control of pests. The criteria for measuring the efficacy of chemical pheromone pesticides are usually not the lethal dose to pests, but the reduction of damage to the harvestable part of crops. Generally, the expected effect of chemical pesticides is more changeable than that of conventional chemical pesticides. Dispersion technology can reduce exposure level and/or improve its effectiveness. It is an important means of slow and effective release and prolong its effect as far as possible.
Biopesticide Management in the United States
The United States is the first country to implement the pesticide registration system in the world. In 1947, the Federal Pesticides, Fungicides and Rodenticides Act was enacted. For the first time, pesticides should be registered and the requirements of pesticide registration and labeling were stipulated. It is one of the countries with strict and scientific pesticide management. Its registration framework and concept are worthy of reference by developing countries and also the documents of FAO/WHO of international organizations. The main reference blueprint of the material.
The registration of biopesticides in the United States started early and entered a rapid development stage after 1990. On September 30, 2017, the United States announced 390 registered bioactive ingredients of biopesticides, with a variety of varieties. Biochemical pesticides accounted for 52%, microbial pesticides accounted for 32.6%, and other pesticides accounted for 5.9%. There are also 37 genetically modified pesticides (PIPs).
Biopesticides from other countries
There is no uniform international definition and registration policy for biopesticides. Most of microbial and biochemical pesticides are considered as biological pesticides; there is little consensus on natural enemies and genetically modified pesticides, and there is no registration regulation for natural enemies in China in the new Requirements; agricultural antibiotics are almost unanimous, and the U.S. polyoxin D zinc salt of natamycin and polyoxin D zinc salt belong to biological pesticides. Some countries also have invertebrate nematode and so on.
The recognition of botanical pesticides varies from country to country. Because botanical pesticides are mostly complex compounds, there are great differences in their properties and toxicity. The final definition of biopesticides in the United States is low-risk pesticides. In fact, botanical pesticides are divided into two parts. If the low-risk parts without direct toxicity (such as attractants and repellents, such as volatile essential oils) are included in the biopesticides, they can enter the rapid registration process, which is conducive to promoting the development of biopesticides. It does not emphasize whether they are planted or synthesized, but only requires structure and days. However, similar functions may also save resources and encourage industrialized production. For the rest of the pesticides, the differences can be seen in the classification tables of bio-pesticides of countries and organizations at sink headquarters (see table 6) registered according to conventional pesticides (such as pyrethrin, rotenone, nicotine, etc.).
At present, the United States, Canada and Mexico use the most biopesticides, accounting for 44% of the world's total, as shown in Figure 4. Among them, America accounts for 40%, Europe 20%, Asia 13%, Oceania 11%, Latin America 9%, Africa 3%.
Looking ahead to challenges
By the end of 2015, biopesticide enterprises in China accounted for nearly 20% of pesticide enterprises (excluding antibiotic pesticides). According to statistics, the annual output of biopesticides in China has reached nearly 300,000 tons (including raw drugs and preparations), accounting for about 8% of the total output of pesticides. More than 9,600 tons (excluding antibiotic products) of biopesticides were used in forestry alone in 2017, an increase of 65.6% over 2016, of which 64% were biochemical pesticides. With the need of environmental protection and safety, biopesticide production will also face severe challenges.
Biological control is one of the important measures of comprehensive control, but the coverage rate of biopesticide control is only about 10%, which is far below the level of 20%-60% in developed countries. Therefore, it is necessary to improve the production capacity and use level of biological pesticides, delay the resistance of chemical pesticides, optimize the variety structure, improve the application technology, and promote the rapid development of biological pesticides.
At present, China's biopesticide industry has a certain scale, but the pace of registration, production and use is still slow. Pesticide management in China is still growing, and the level of knowledge and technology should be constantly refined and improved. Communication is the best bridge. Let China's biopesticides enter the world as soon as possible.
Summary
The Ministry of Agriculture and Rural Areas proposed that the use of pesticides should achieve zero growth, and advocated the establishment of resource-saving and environment-friendly ecological civilization and green production. This creates space for the survival and development of bio-pesticides and is conducive to promoting the progress of bio-industry. Biopesticides will play an important role in promoting the trilogy of "Clean, Kill Young and Prevent Mosquitoes" of integrated vector biological control.
In the Requirements for Pesticide Registration Data (hereinafter referred to as Requirements) implemented on November 1, 2017, although there is no clear definition of Biogenic Pesticides or biopesticides, pesticides are classified into chemical pesticides, biochemical pesticides, microbial pesticides and botanical pesticides according to their sources, and the latter three categories are biogenic pesticides.
Agricultural antibiotics are produced by microbial fermentation, although they are also biogenic pesticides, but in terms of registration data requirements, except for some test items which can not be provided due to the special nature of products (can be applied for exemption), other basic equivalent to chemical pesticides, which are hardly treated as biopesticides in other countries in the world at present. Because many kinds of agricultural antibiotics such as abamectin and jingangmycin A are used in agricultural production, there are many new varieties such as Ningnan mycin and pyrimidine nucleoside antibiotics in China, which are also used as biopesticides in some occasions. Therefore, biochemical pesticides, microbial pesticides, botanical pesticides and agricultural antibiotics are temporarily classified as biogenic pesticides.