Towards Greener Agrochemicals: Overview of Biopesticides Registration & Mammalian Toxicology Data Requirement

Posted on 2019-03-26
Bio-pesticides include naturally occurring substances that control pests (biochemical pesticides), micro-organisms that control pests (microbial pesticides), and pesticidal substances produced by plants containing added genetic material (plant-incorporated protectants) or PIPs. 
The microbial pesticide (Bacillus popilliae, a naturally occurring bacterium) was registered in 1948. Since the late 1960s and early 1970s, interest in the application of live microbes and viruses for control of pests and diseases has been slowly gathering speed. There was a time, when these products were expected to largely replace chemical agents. The realization that they wouldn’t replace the chemical cousins, surfaced after a few years of their trials, and the current thought process is driven IPM (Integrated Pest Management). The Microbial products are registered for use in agriculture, forestry, mosquito control, lawns and home-gardens. Both EPA and EFSA have considered risk from such products to health and safety as low, especially for Bacullus subtilis and B. amyloliquefaciens (EFSA DAR 2012). 
Synthetic chemical agents have been traditionally used for crop protection as well as healthy, rich, and bountiful process. However, a strong movement has gathered momentum over the last decade to enter into “IPM” using natural, biological as well as chemical agents for control of pests and diseases. 
Generally the Microbial Products consist of preparations of living microorganisms. They provide several distinct benefits, in that, being natural life forms, they are expected to be inherently safe as compared to their chemical cousins, since they generally only impact the target organism. This eliminates unwanted adverse effects on the ecosystem as products and their degradants are natural, non-accumulative, and non-toxic. Bio-pesticides fall into 3 Major Classes: 
1. Microbial Pesticides: Microbial pesticides are microorganisms that produce a pesticidal effect. They have pesticidal modes of action that often include competition or inhibition, toxicity and even use of the target pest as a growth substrate. 
2. Biochemical Pesticides: Biochemical pesticides are naturally occurring substances or are synthetically derived equivalents that have a non-toxic mode of action to the target pest(s), and have a history of exposure to humans and the environment demonstrating minimal toxicity. Synthetically derived biochemical pesticides are equivalent to a naturally occurring chemical with such a history.
3. Plant-Incorporated Protectants (PIPs): PIPs are pesticidal substances that plants produce from the genetic material that has been added to the plant.
What are the Benefits of Biopesticides?
There are several benefits to using biopesticides, including: 
Decreased risk without affecting yield. Bio-pesticides—when used as a component of an IPM program—can greatly decrease the use of conventional pesticides, without affecting crop yield.
Often less toxic. Generally, biopesticides are inherently less toxic than conventional pesticides and are safer to those using them.
Often effective in very small quantities and decompose quickly. This can result in lower exposures and avoid pesticide pollution problems.
Targeting of specific pests. Biopesticides generally affect only the target pest and closely related organisms, in contrast to broad spectrum, conventional pesticides that may affect non-target organisms such birds, insects, and mammals.
●  When used in rotation with conventional products, bio-pesticides can help prevent development of pest resistance problems.

Improved residue management. Buyers and consumers are becoming increasingly selective in their purchasing habits. Illegal pesticide residues, left on produce, can result not only in the loss of markets and related fines, but also other consumer avoidance. Bio-pesticides often contain natural products that are normally consumed and do not have residue concerns.
Registration requirements:
Generally, the global registration authorities tend to follow the lead established by the US EPA in determination of the relevant 2 guidelines (OCSPP guidelines series 885). These are designed to ensure no potential pathogenicity implications in mammals, when these enter via alimentary canal or respiratory route for the safety of the farm operator. 
There may be different requirements for technical grade material and the marketed product, but it is clear from processes and procedures adopted in various jurisdictions that identity a pesticide, determined by its composition: 
●  Details and concentration of active ingredients/active agents 
●  Details and concentration of formulants 
●  Details and concentration of impurities 
In addition, in case of certain types of microbial active agents it may be necessary to complete the identity check of a microbial bio-pesticide by providing: 
●  Details and concentration of microbiologically-derived contaminants such as specific metabolites 
General data requirements across various regulators are mainly focussed on: 
●  Product Characterization and Analysis 
●  Human Health and Safety Testing
●  Exposure Assessment 
●  Food and Feed Residues Requirements 
●  Environmental Fate 
●  Environmental Toxicology 
JRF has developed deep expertise in handling MPCAs. JRF is capable of performing different types of in vivo studies: 
1. Acute Oral Toxicity / Infectivity 
2. Acute Pulmonary Toxicity / Infectivity 
3. Acute Injection Toxicity / Pathogenicity 
The purpose of reviewing mammalian toxicology data for microbial pesticides is to ensure that the use of these products causes no unreasonable adverse effects to human health or non-target mammals. In order to do this, Regulators must verify that the microbial product is correctly identified, presents little possibility of pathogenicity or toxicity to humans or other mammals, and is manufactured in a manner to prevent contamination with human pathogens. 
To assure the safety of microbial pest control agents toward mammalian species, EPA has adopted a tiered testing scheme similar to the tiered scheme used for biochemical pesticides. Tier I is designed to expose the test animal, mice or rats, to a single acute, maximum hazard or limit dose of the live microbial pesticide. Tests involving mammalian tissue cultures are required for viral pest control agents to insure there is no possibility of mammalian infection given optimal conditions for expression of viral pathogenesis. 
The basic principle of testing is to evaluate toxic effects of the preparation, after potential oral ingestion or respiratory exposure. The product is tested for development of significant clinical signs, morbidity, and mortality as well as survival in organs of the test system (generally wistar/SD rats). The testing also evaluates potential effects of the microbial secondary metabolites, as well as possible invasion/ colonization inter and intra organs exposed to the product. 
If any adverse effect is noted in the Tier I of the toxicity/pathogenicity tests, further testing is indicated using a tier progression to verify observed effects and clarify the source of effects. These Tier II tests could involve a sub-chronic toxicity/ pathogenicity test or, if the adverse effect was believed to be due to a toxic reaction rather than pathogenicity, an acute toxicity test to establish an LD50 value for the toxin. Residue data are required, if significant human health concerns arise from the toxicology testing. The majority of bio-pesticide products screened to date have not indicated any adverse effects to warrant testing further than Tier I. Genotoxicity testing hasn't been mandated by EPA. However, some of the EU DAR’s do show that genotoxicity testing has been undertaken voluntarily by some of the manufacturers.


Source: AgroNews