One
to six compounds per year get into the early development stage.
Compounds are synthesized in larger quantities, several pounds,
and sent to university researchers throughout the country to test
for a specific affect and on a specific crop. These tests are
done at many locations to determine broad efficacy data and to
collect data for potential registration. Efficacy is evaluated
in different climatic conditions and soil characteristics.
"Material
Safety Data Sheets" (MSDS) are prepared and accompany test
samples. MSDSs identify the compound and indicate the proper protective
clothing to be worn by the researcher. Physical data are included
such as volatility, solubility, and melting and freezing points.
Flammable limits and explosiveness data are given. Toxicity data
included are acute oral (rat) and dermal (rabbit) LD50s, acute
inhalation LC50, eye and dermal irritation and sensitivity. Also
included on the sheets are first aid information and disposal
procedures.
Manufacturing
technology for these compounds are studied for less expensive
synthesis pathways and methods that may be used in large scale
production. Preliminary cost of production estimates are made
and a pilot plant may be built.
Environmental
tests on these compounds are conducted to determine their volatility,
breakdown by light and microbes, leaching and adsorption properties,
soil dissipation, and flammability and explodability. Formulations
are tested for compound and storage stability.
Residue
studies on environmental persistence and fate are initiated. As
testing progresses, residue studies are expanded to include to
livestock, fish, drinking water, milk and eggs, other foods, processed
foods and feed, and crops. Data are collected to determine tolerance
limits. Ground water monitoring studies are conducted.
Metabolic
studies continue on plant and animal metabolism of test compounds.
Metabolic breakdown products of test compounds are studied to
determine their safety in animals. Mode of action(s) is determined.
Toxicology
testing continues. Studies gradually move from acute (short-term,
7-day) toxicity to 21-day studies and later to chronic toxicity
(long-term, 90-days to two years). Chronic toxicity studies include
feeding, inhaling and neurological effects. As Phase II progresses
and compounds show commercial efficacy, tests are conducted on
cancer risk potential, oncogenicity and teratogenicity studies.
The potential for chromosome or gene damage is determined.
As
compounds advance, toxicity data are required to determine any
potential effects on wildlife. Toxicity tests are conducted on
birds, usually quails and ducks, fish such as sunfish and trout,
fresh water invertebrates, estuarine and marine animals such as
clams and shrimp, and wild mammals. A key study is determining
any bio-accumulation potential through food chains. A potential
would immediately eliminate a potential product.
Only
about one compound every two to three years gets through Phase
II and advances to Phase
III Registration.
This will be covered in part four of this series.
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