Lab to Label, Phase 3

LAB TO LABEL Phase III: Registration

Phase III of ag-chemical research & development is the last stage before a chemical becomes a product and this phase is the preparation for product registration.

Registration Data

Only one compound in every one to three years makes it to Phase III. Field testing for efficacy is completed on the intended crop and pests. If new chemistry is involved, the patent has already been submitted and revisions are in progress.

During Phase III (Preparation for Registration), active compounds are tested in 10 categories such as Toxicology, Wildlife and Aquatic Protection, Botannical Protection, Environmental Fate, and Residue. Some 142 studies dealing with potential dangers are conducted on every potential product.

Acute toxicology are 90-day studies looking for potential poisoning such as

  • inhalation
  • feeding and excretion
  • nervous system reaction
  • dermal exposure.

Then, chronic or repeated, and long-term feeding exposure studies are conducted on mammals. Meanwhile, studies continue on determining any dangers to wildlife and aquatic animals, both acute and chronic exposure studies. There are even test to find out if there is in bad effect on pollinating insects such as bees.

Many and intensive, long-term (years) studies on any cancerous potential are conducted and safe levels are determined. Food residue and 'bread-basket' studies are now intensely surveyed. Residue tolerances are determined and set by the Environmental Protection Agency (EPA).

Metabolic studies are conducted on the compounds and their breakdown products. The breakdown products are each tested for their health safety and their fate in the environmental. Environmental fate studies include leaching and run-off, drift, and microbial breakdown of the materials in soil. What happens to any residue on the plants and in the soil are identified.

Large scale farm trials are conducted by growers under an 'emergency use permit' (EUP). The company begins large scale manufacturing research in anticipation that the product will be registered and in preparation for building a manufacturing facility.

After all studies are completed, the registration package containing many thousands of pages of test data is submitted to the EPA's Office of Pesticide Programs (OPP) for evaluation and comments.

Risk Assessment

A major determination done by the EPA, not the company, is to determine the potential risk of a new active ingredient. Risk equals the hazard times the exposure. This is the most important part and the key to registration.

Hazard is evaluated from the toxicology studies. From laboratory animal feeding studies a "No Observable Effect Level" (NOEL) in the diet is determined. The NOEL is divided by a safety factor of at least one-hundred (100). This hazard level is the "Reference Dose" (RfD) also called the "Acceptable Daily Intake" (ADI). This (ADI = RfD) is the amount of the compound or material or active ingredient which may be ingested by the average person every day for a lifetime without causing any ill effects. This level is will below anything that showing an effect on even the most sensitive animal.

The exposure part of the above equation is determined by all the residue studies. Residue levels are determined by combining the levels for all treated crops. Then, the tolerance is set by the EPA at a level falling well below (usually a tenth) the ADI.

Phase IV and Beyond

During and after EPA's analysis for product approval, the manufacturing company looks for additional uses of the potential product, the "me too" phases. "Minor crop" uses usually fruits and vegetables are explored. Each added use must go through additional research including efficacy, residue and metabolism. Each must be scrutinized by the EPA and approval given. Residue level are calculated into the risk assessment equation above.

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