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.
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.
