Navigating hurdles to bring pheromone pesticides to market

In the days before environmental regulation was a reality, pesticides were referred to as “economic poisons.” The term was fitting, because many of the early pesticides used were, in fact, dangerous poisons, but they could also serve important economic goals. Chemistry, and, perhaps more importantly, toxicology and regulation have come a long way in the years since pesticides came into common use. Laws and regulations governing their production and use are designed to ensure that pesticides are safe when used according to label instructions. However, in the last few years creative and environmentally conscious scientists have learned to use the biology of insect mating behavior to control pests and protect crops without harming pest insects, desirable insects or the environment. The products they are designing do not poison anything, and they have the promise of providing great economic benefit to the agricultural community. They break the mold of being economic poisons and rather function as economic chaperones: They keep harmful insects from mating in the wrong place at the wrong time. 
 

Pheromones are a class of semiochemicals that insects (and other organisms) release to communicate with individuals of the same species. Insects typically release pheromones into the air and they are detected through the antennae of other individual insects. These substances can have several uses in the insect world, but the function that is important to this discussion, is the use of pheromones by insects to locate mates.

 

Insect pheromones were first identified in the late 1950’s, but the development of their use in pest management systems has been slow. This has been due primarily to the complexity of isolating species-specific pheromone blends and the cost of producing pheromone products that can be used successfully in the field. In the past, pheromones have been used primarily to monitor pest populations and in mass trapping applications designed to capture and destroy target pests. However, in recent years scientists have developed new and cost effective methods of producing species-specific pheromones that can be used to disrupt mating of insects. This has been used most effectively in certain species of harmful moths whose larvae infest and consume important agricultural crops. Dispensers are used to disperse clouds of pheromones across acreage of commercial crops. As a result of this wide dispersion of pheromones, male moths are confused and cannot locate females who are available to mate. When mating is disrupted, the destructive larvae are not produced, and the crops are protected without the use of pesticides that can have toxicological effects, including, but not limited to, the destruction of beneficial insects.

 

As was the case with early economic poisons, the law has adapted to this new technology.

 

Congress’ first attempt to regulate pesticides came in the Insecticide Act of 1910. As was common with regulatory legislation of the period, it functioned more to address consumer fraud than to protect human health or the environment. Although the act made it illegal to sell adulterated or misbranded pesticides, it did not require testing or agency approval of products. As more and more chemicals were developed to control pests, more regulation was needed to keep up with the fast-developing science and in 1947 Congress passed the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). 7 U.S.C. §136, et. seq. FIFRA has been amended many times over the years. Each amendment imposed new and more stringent requirements for evaluating the safe use of pesticides in the environment and on foods. Registering a pesticide — once a relatively simple undertaking — became an enormous undertaking that required years of research to produce the data necessary to satisfy the health and environmental requirements of the U.S. Environmental Protection Agency.

 

In its modern form, registration requirements under FIFRA are relatively clear, but the data required for registration can be onerous. A draft label, governing the legal uses of a product, must be presented to the EPA and the data package that accompanies it must demonstrate that the product will cause no unreasonable adverse effects to the environment. If the product is intended for use on food crops the data must demonstrate a reasonable certainty of no harm. See 40 CFR Part 158. Depending on the product, the applicant must present data on:

 

• Residue chemistry,

 

• Environmental fate,

 

• Toxicology,

 

• Reentry protection,

 

• Spray drift,

 

• Wildlife and aquatic organisms,

 

• Plant protection,

 

• Nontarget insects,

 

• Product performance, and

 

• Product chemistry.

 

For a given pesticide this can involve a vast amount of data and many years of testing and product development. However, it should be obvious that many of these precautions should not apply to pheromones used for pest management. The EPA has recognized that and adjusted its review of pheromone-based products to recognize their benign environmental footprint.

 

 

Certain uses of pheromones do not require registration under FIFRA at all. Whether FIFRA regulates a particular pheromone use depends on whether the EPA deems such usage as having a pesticide purpose. See, EPA Pesticide Registration and Classification Procedures 40 C.F.R. §152.10 (2017). Toxicant-free attractants intended only for surveying or detection purposes are not required to be registered under FIFRA. Pheromones used in a pheromone trap, by which arthropod pheromones are used to attract and trap or kill target pests in a confined portion of the treated area, are also exempt from FIFRA registration. Id at 40 C.F.R. §152.25. The regulations go on to provide that pheromones need not be registered under FIFRA if labeled for a use the EPA determines poses no greater environmental risk than pheromone traps. The final outright exemption from FIFRA registration is to allow experimental use on up to 250 acres before requiring an experimental use permit (EUP) (as opposed to 10 acres for conventional products). Lepidopteran Pheromones; Experimental Use Permits, 60 Fed. Reg. 45,156 (Aug. 30, 1995).

 

The newest iteration of pheromone products does not fit neatly within any of these registration exemptions. Moreover, the EPA has consistently considered pheromone products used to disrupt mating to be pesticides within the scope of FIFRA. See EPA, Pesticide Registration Manual: Chapter 3 – Additional Considerations for Biopesticide Products. As noted above, the EPA could determine pheromones used as mating disruptors pose no greater environmental risk than pheromone traps and thereby exempt all such products from FIFRA registration. At the time of writing, however, the EPA has shown no inclination to carve out such a broad exemption.

 

Although mating disrupting pheromones are still required to be registered under FIFRA, the EPA has reduced and removed several requirements to complete the process. The EPA has also reduced fees and wait times in the application process.

 

Pheromones used in pest management are a subset of a class of pesticide products known as biochemical pesticides, or biopesticides. The EPA’s Office of Pesticide Programs (OPP) has three divisions, each responsible for registering certain categories of pesticides. The Biopesticide & Pollution Prevention Division (BPPD) processes registration applications for all biopesticides, and its requirements for approval are considerably less onerous than for conventional pesticides. Specifically, several data requirements have been removed altogether, and others have been made less stringent. The biopesticide-specific registration guidelines are divided into three types of required tests: product analysis, toxicology and nontarget organisms, and environmental testing.

 

The BPPD’s product analysis requirements depart most obviously from those of conventional pesticide registration by referencing completely different Office of Prevention, Pesticides and Toxic Substances (OPPTS) guidelines for determining the adequacy of an application’s product identity and composition, description of materials and processes, and discussion of impurities. However, the biopesticide-specific guidelines routinely reference and often appear to incorporate conventional pesticide registration guidelines, so the difference in stringency between the two is not immediately apparent. For instance, conventional pesticide registration uses OPPTS guideline 830.1670 to assess a product’s impurities; however, the guideline BPPD uses to assess impurities refers to the conventional guideline when listing the various ways impurities may form. Office of Prevention, Pesticides and Toxic Substances, OPPTS 880.1400, Biochemicals Test Guidelines: Discussion of Formation of Impurities (1996) (“As described under OPPTS 830.1670, such unintentional ingredients may be introduced during the following manufacturing process ...”).

 

This cross-referencing ultimately reveals that, to the degree biopesticides include nonbiochemical ingredients, the registration process with regard to those conventional ingredients will be similar to a conventional pesticide registration. That is, just because a particular pesticide is considered a biopesticide for registration purposes does not necessarily guarantee an expedited registration process. The BPPD’s guidelines for assessing the identity and composition of a biopesticide product require certain information for each biochemical but different and more detailed information about ingredients “other than biochemical.” The biopesticide registration guidelines pertaining to materials, production and formulation similarly differentiate between biochemical ingredients and “other ingredients, active and inert,” for which BPPD follows conventional OPPTS guidelines. This distinction makes sense, as biochemical ingredients typically pose less of an environmental risk than the active ingredients in conventional pesticides. The distinction is also largely irrelevant for pheromone pesticides used as mating disruptors, because the active ingredients in these products are biochemical.

 

Under EPA rules biochemical ingredients require less stringent information regarding materials, production and formulation processes. Compared to the process required for conventional pesticides, which requires three separate guideline sections and five pages to articulate fully, the process for registering materials, production and formulation processes for biochemical ingredients is remarkably concise. Manufacturers of biopesticides must:

 

1. List starting materials;

 

2. Provide steps taken to ensure integrity and limit contamination of starting materials;

 

3. Verify identity and purity of the seed stock; and

 

4. Report quality control methods and the techniques used to ensure product uniformity.

 

Product analysis for pheromone pesticide registration is also less cumbersome than it is for conventional pesticides. These differences recognize that pheromone pesticides, as a subset of biochemical pesticides, do not pose the same environmental risk as more traditional pesticides. However, the loosened restrictions are often ingredient-specific, such that biopesticides with nonbiochemical ingredients will still need to go through the more stringent requirement with regard to registering those particular ingredients.

 

The BPPD does provide biopesticide-specific test guidelines to analyze potential effects on nontarget organisms and potential to pollute water. The first guideline, aimed at testing a pesticide’s effect on nontarget organisms, requires Tier 1 testing on a case-by-case basis, but it is not entirely clear what kinds of biopesticides would require such analysis. See Office of Prevention, Pesticides and Toxic Substances, OPPTS 880.4350(b), Biochmeicals Test Guidelines: Nontarget Insect Testing (1996).

 

The differences in registration procedures detailed above apply generally to biopesticides, not just pheromones. However, the EPA provides some additional regulatory relief specifically for pheromones. For example, pheromones are exempt from many food tolerance procedures typically applied to conventional pesticides. In addition, the EPA frequently grants data requirement waivers for biochemical pesticides.

 

EPA Has Generally Been Supportive, Helping Foster New Era of Pest Control

 

To its credit, the EPA has recognized the enormous potential environmental benefits of using pheromones to manage pests. The ease, relatively speaking, of registration of these products should encourage their more widespread use in the near future. Products that kill nothing, and still protect vital crops, could become a vital part of our agricultural economy.