ii)acetylcholine esterase (ACH-E), which ensures the signal transmission is stopped

once the receptor site receives the signal.

Imidacloprid attaches to specific ACH binding sites known as nicotinergic receptors on
the receiving nerve cells.
Imidacloprid prevents ACH, from binding and transmitting electrical impulses.
Once bound to the ACH receptor, Imidacloprid is not degraded by ACH-E, leading to a
lasting impairment of the nervous system and death of the insect.

Development History of Premise:

Imidacloprid belongs to a new class of chemistry, the chloronicotinyls, which were never
used before 1985 in insect control.
The Bayer developmental program for Premise was the most comprehensive research
program ever conducted for soil-applied termiticides
Conventional soil-applied termiticides used before 1985 were all members of three
chemical classes: chlorinated hydrocarbons, organophosphates and pyrethroids.
With the removal of chlorinated hydrocarbons from structural pest control in 1987, only
Organophosphates (OP), Pyrethroids (Py) and Boric Acid products remained.
Having this limited number of chemical tools restricted the ability to provide successful
termite protection. New termite control chemistry was urgently needed. Resulting new
chemistries should be effective at lower use rates and have lower toxicity in order to
reduce the risk to people, pets, wildlife and environment.
Bayer Corporation recognized the need for new technical active ingredients with
increased performance but with significantly reduced environmental, ecological and
mammalian risks.
With these objectives and goals, efforts to incorporate the characteristics resulted in the
development of Imidacloprid Insecticide. Although several compounds in the class of
chloronicotinyls were found to be effective insecticides, none was stable enough to be
commercially developed until 1985, when chemists at Bayer synthesized Imidacloprid.
This molecule proved to be very stable with excellent insecticidal properties.
Because of the high priority placed on the development of Imidacloprid by Bayer,
numerous registrations for a variety of uses already have been granted worldwide.
The first termiticide registration of Imidacloprid was granted in Japan in 1993, and in
United States in February 1995, for control of all economically damaging subterranean
termite species affecting structures prior to and after construction.
Premise® was first introduced in Japan in 1993 and then in US in 1996. The active
ingredient Imidacloprid, is a Neonicotinoid insecticide which is a synthetic derivative of
nicotine, an alkaloid compound found in the leaves of many plants in addition to tobacco.
Nicotine is naturally found in many plants, including tobacco and is toxic to insects.
Premise Present Status:
Premise® is an anti-termite treatment solution in structural pest control and contains the
active ingredient Imidacloprid in the proportion of 30.5% w/w. In India, Premise is
registered with Central Insecticide Board and Registration Committee (CIB & RC) and is
recommended for the control of termites in buildings through pre-construction and post-
construction anti-termite treatment. In India, Premise is being used over last 16 years and
has been successfully protecting the houses, buildings and structures from the termites
menace. Similarly, Bayer brand Premise containing Imidacloprid is manufactured and
marketed over last 26 years in more than 20 countries.
Salient features of Imidacloprid
The unique chemistry of Imidacloprid enables to have low environmental impact and low
mammalian toxicity
Imidacloprid is used to control termites through contact, ingestion and by transfer via the
Domino Effect®. Termites cannot detect Premise, they tunnel through treated soil, acquire
a dose, and unknowingly pass the same throughout the colony, thus impacting the entire
colony.
Anti-termite treatment of buildings through pre-construction and post-construction can
also be done by using repellent insecticides. However, small gaps in repellent termiticide
treatments are detected by termites and are exploited as an entry point into the home.
However, because termites cannot detect Premise, any small gaps caused by a physical
disturbance of the treated zone are unimportant and do not affect the efficacy of the
product.
Mammalian Toxicity:
Toxicity values established for submission to CIB & RC
Toxicology data
Test animal LD50 mg/kg body weight
a) Acute oral Technical Rat Male & Female: ~ 450
toxicity Male: 768
Formulation Rat Female: 1042
Test animal mg/kg body weight
b) Acute LD50 Dermal:
Technical Rat Male & Female: > 5000
percutaneous
Toxicity LD50 Dermal:
Formulation Rabbit Male & Female: > 5000
Test animal 4 h LC50
c) Acute
inhalation Technical Rat (aerosol) 69 mg active ingredient/m3 air
toxicity Formulation Rat(aerosol) Male & Female: > 1752 mg/m3 air
Test animal Findings
d) Skin irritation Technical Rabbit Non-irritant to the skin of rabbit
Formulation Rabbit Non-irritant to skin
Test animal Findings
e) Eye irritation Technical Rabbit Non-irritant to the eyes of rabbit
Formulation Rabbit Non-irritant to eyes

Imidacloprid SC 350 is moderately toxic after acute oral administration to rats and
non-toxic after acute dermal and inhalative administration to rats. It is not irritating to
the skin and eyes of rabbits and shows no sensitizing potential.
Human Safety:
Research conducted at the University of California-Berkeley, indicates that certain
insects have a larger proportion of nicotinergic ACH receptors to which Imidacloprid
binds making them very susceptible to Premise.
Other organisms, including mammals and other vertebrates, have a larger
proportion of muscarinergic receptors, which do not bind Premise.
According to Dr. Liu and Casida8 (Pesticide Biochemistry and Physiology 46, 40-46
1993), this explains why Imidacloprid is so toxic to certain insects but has such low
mammalian toxicity.
Carcinogenicity: The long-term studies on Imidacloprid in rats and mice produced no
evidence of carcinogenic properties.
Effects on reproduction: In a feeding study in rats over two generations, Imidacloprid
in a concentration of 250 mg/kg feed was tolerated without any adverse effect on
reproductive performance, any damage to the offspring or any influence on the male
rats. Dams tolerated a concentration of 100 mg/kg feed without adverse effect.
Embryotoxic and teratogenic effects: The offspring of rabbits and rats, given
imidacloprid orally during the sensitive phase of gestation, did not exhibit any primary
embryotoxic or teratogenic effects.
Mutagenic effects: The results of various in-vitro and in vivo tests performed with
imidacloprid do not indicate any genotoxic hazard to man.
Neurotoxic effects: Tests with repeated administration of imidacloprid to different
species of animals did not produce any clinical or histopathological evidence of
neurotoxic effects.
Volatile Organic Compounds
Imidacloprid has a very low volatility.
Volatility is expressed as vapor pressure in the physical and chemical properties in
the table above (Refer Table below).
Premise has a vapor pressure of 1.5 x 10-9 mm Hg @ 20 ºC. The average indoor
air concentration of Premise at different types of construction was approximately
8000 times lower than the concentration measured for the surrogate compound.
Comparing the Premise exposure estimates to the inhalation No-Observable-Effect-
Level of 2.4 mg/kg/day (2.4 million ng/kg/day) for Premise results in Margins of
Safety of approximately 240 million for adults and approximately 80 million for
children.
This low volatility means there is little concern for presence of Premise in the air
after a treatment.
Mixer, loader and application exposure estimates demonstrate that Premise can be
used without significant risk to workers.
 Sampling Interval Concrete Slab Basement Crawl Space
During treatment <0.010 <0.009 <0.016
Immediately after treatment <0.008 <0.004 <0.008
24 hours after treatment <0.004 <0.003 <0.004
7 days after treatment <0.004 <0.003 <0.003
30 days after treatment <0.003 <0.003 <0.003
90 days after treatment <0.003 <0.006 <0.003
1 year after treatment <0.003 <0.003 <0.003
Note: < means that average air concentrations were less than the indicated value based on a quantitation limit of 0.003
ng/ m3

Environmental Fate:
Half Life:
Hydrolysis half-life >30 days (25°C at pH 7)
Aqueous photolysis half-life <1 hour (24°C at pH 7)
Anaerobic half-life 27.1 days
Aerobic half-life 997 days
Soil photolysis half-life 38.9 days
Field dissipation half-life 26.5 229 days

Leaching Effect
Environmental Protection Agency (EPA) of USA for addressing factors that might affect
Premise after application.
Compounds degrade in two ways in the soil: chemical degradation, which occurs
when naturally occurring chemicals in the soil interact with the compound, and
microbial degradation, which occurs when soil microorganisms use the chemical as
a food source.
Premise binds very effectively to soil particles which limits the amount of active
ingredient available for microbial degradation.
A vertical and lateral movement within soil is dependent upon the
solubility in water and how it interacts with soil particles.
Studies conducted for Premise indicate that rod holes along the outer foundation
wall should be spaced 6 inches apart for thorough coverage. Slabs can be drilled at
12-inch spacing.
Leaching studies conducted for premise indicate little likelihood that Premise will
leach under application conditions.
-
life, or how long the compound will persist in the soil.
Field residual studies conducted for Premise indicate a half-life of 6 to 12 months
under termticidal-use conditions.
Characteristics of Repellent Termiticides:
Fast Acting Termiticides
Means - termites that have acquired lethal doses die within a short period of time (usually
within 24 h);
However, those surviving the first 24 h of exposure generally do not die.
Repellency and toxicity are both dose dependent; thus, a concentration showing no
repellency will have little or no toxicity.
E.g. Pyrethroid-based termiticides work as repellents and are fast acting. However, they
degrade rapidly after exposure to sunlight or other atmospheric elements.
Control Concept of Repellent Termiticides:
When repellent termiticides are applied to the soil at the recommended label rates, they
will provide quick kill of termites that come in contact with the treated substrate, or
They will cause a directional change in tunneling, away from the treated area (Su and
Scheffrahn, 19909, Gahlhoff and Koehler, 199910).
To provide a long-term protection to the structure, a thorough application of a repellent
termiticide is needed to create a chemical barrier without gaps.

Characteristics of Non-Repellent Termiticides:

Slow Acting Termiticides
Use of non-repellent termiticides is a relatively modern approach to termite management.
These termiticides include some of the new chemical classes (e.g. neonicotinoids, phenyl
pyrazoles, etc.) and have a proven high control efficiency against termites.
Non-repellent termiticides kills termites faster than bait products but slower than
repellents.
When used at the recommended label rates, they are non-repellent, slow acting, and
transmissible from contaminated termites to unexposed colony members, and hence
cause secondary mortality.
They usually have a low odour, low volatility and low mammalian toxicity, but high efficacy
and long soil persistence.
Control Concept of Non-Repellent Termiticides:
Non-repellent termiticides include some of the new chemical classes. They will not cause
quick kill even after coming in contact with termites
They have unique modes of action and have proven to have high control efficacy against
termites.
They do not cause a directional change in tunneling, away from the treated area
To provide a long-term protection to the structure, a thorough application of a non-
repellent termiticide may not be necessary to create an effective chemical barrier.
Disadvantages of Repellent Termiticides:
Termites that encounter repellent termiticide treated soil often change directions in
search of untreated soil or for a gap to cross the barrier (Forschler, 1994)11.
They may also seal off tunnels to avoid contact with the treatment site (Su et. al., 1982)12.
Termites foraging above ground or within the structure at the time of treatment may be

1999)13.
The trapped groups may trigger and produce secondary reproductives and start new
colonies, as in Reticulitermes species.
 Post-application activities like burrowing vertebrates, soil erosion and other physical soil
disturbances.
Repellents require rigorous application to all the possible entry points around and
beneath the structure, and to all interior active infestations, in order to have an immediate
control effect.
Lower control efficacy due to use of low dose rates to make a cost-effective application
may cause breach in the chemical barriers (Mampe, 1994)14.
Termites coming into contact with the treated zone die quickly, they are not able to retreat
back to affect the rest of the colony.
This prevents lethal transfer of the insecticide
2005)15.
For effective chemical barrier, termite control professionals need in-depth understanding
of the construction type, methods and architectural materials, and the features of the
building.
Any untreated or poorly treated area or gap can be used by termites to invade and infest.
How Non-Repellent Termiticides Work?
When termites encounter soil treated with non-repellent termiticide, they do not detect
the compound and may actually enter the treated zone.
They would not killed immediately, nor are they repelled.
Once in the treated zone, they encounter an intoxicating dose of non-repellent termiticide
and symptoms begin.
In the next step, termites do not tunnel far because dysfunction quickly set in.
Initial symptoms include inability to function and cessation of feeding, which immediately
protects the structure from additional damage.
Exposed termites return to the colony but stay in the vicinity of the treatment.
They may even begin to wander aimlessly away from the colony into open air and
sunlight, exposing themselves to harsh environmental conditions.
Once the termite become dysfunctional, it no longer functions as a contributing member
of the colony.
It stops foraging, grooming and caring for other members of the colony.
If enough termites are exposed, the efficiency of the colony can decrease dramatically,
placing stress on the colony.
Because there is no repellency to non-repellent termiticide and foragers may leave the
treated area before dying, other foraging termites are not it.
When termites meet in a darkened gallery of their subterranean world, they instinctively
each other a series of antennae touching and mutual grooming.
The unexposed, normal behaving termites continue to interact with the other termites,
including termites that have been exposed to non-repellant termiticide.
It is here that active ingredient transmission between termites known as the Domino
Effect occurs.
Termites contaminated by non-repellant termiticide first become restive, moving less and,
over time, their movements become severely uncoordinated (known as ataxia).
Throughout this progressive intoxication, the termite has not yet died, at low doses, death
may not occur for days.
Termites become dysfunctional and eventually die, but the rest of the colony does not try
to breach the they are unaware one exists.
The result is that structural protection is accomplished immediately because the termites
stop feeding.
How rapidly an exposed termite dies depends on the amount of non-repellent termiticide
it encountered.
 Termites contacting higher concentrations will die much more rapidly, generally within a
few days.
However, the effective soil concentration range of non-repellent termiticide is broad and
can be defined not only by the presence or absence of dead termites, but also by the
length of time to achieve death of termites.
For example, termites contacting even very low concentrations of non-repellent
termiticide will stop feeding and become dysfunctional, but do not die immediately.
Regardless of the concentration of non-repellent termiticide in properly treated soils,
exposed termites eventually die.
The effectiveness of non-repellent termiticide over a broad concentration range ensures
efficacy across various soil types, application techniques and species differences.
This attribute is significantly different from repellent termiticides, that cause rapid contact
mortality within a narrow effective dose range.
A narrow efficacy range might not cover all soil types and use patterns, not to mention
inadequate application.
This effectiveness of non-repellent termiticide observed in laboratory studies has been
confirmed in Europe and other field trials.
Non-repellent termiticide also work hand-in-hand with nature to control termites by
interfering with the ability to groom and prevent diseases from spreading.

Efficacy and Residuality:

Several important questions are often asked about what certain chemical properties mean to
the everyday use of a product.
Bayer Corporation has performed numerous studies according to the guidelines of the
Environmental Protection Agency (EPA) addressing factors that might Premise after
application. These studies are designed to evaluate persistence of active ingredient at the
site of application under field conditions. The results of these studies give us a good
understanding of how several components of both the soil and the termiticide can combine
to influence the residual and efficacy of Premise.
References:

1. Plumlee, K. H., Ed.; Mosby: St. Louis, MO, 2004. Wismer, T. Novel Insecticides. Clinical Veterinary
Toxicology; pp 184-185.
2. Tomlin, C. D. S. 2006. The Pesticide Manual, A World Compendium, 14th ed.; British Crop Protection
Council: Surry, England, pp 598-599.
3. Costa, L. G. 2008. Toxic Effects of Pesticides. Casarett and Toxicology: The Basic Science of
Poisons, 7th ed.; Klaassen, C. D., Ed.; McGraw Hill: New York, NY, pp 907, 922-930.
4. Copping, L. G. 2001. The Biopesticide Manual, 2nd ed.; British Crop Protection Council: Surrey, England,
pp 202-203.
5. Ware, G. W.; Whitacre, D. M. 2004. The Pesticide Book; MeisterPro Information Resources: Willoughby,
OH, pp 70-71.
6. Hovda, L. R.; Hooser, S. B. 2002. Toxicology of newer pesticides for use in dogs and cats. Vet. Clin. Small
Anim. 32, 455-467.
7. Fossen, M. 2006. Environmental Fate of Imidiacloprid; Department of Pesticide Regulation, Environmental
Monitoring: Sacramento, CA,.
8. Liu and Casida 1993. (Pesticide Biochemistry and Physiology) 46, 40-46
9. Su, N. Y., and R. H. Scheffrahn. 1990. Comparison of eleven soil termiticides against the Formosan
subterranean termite and eastern subterranean termite (Isoptera: Rhinotermitidae). J. Econ. Entomol. 83:
1918-1924.
10. Gahlhoff, J. and Koehler, P. (1999). To kill or not to kill? Pest Control Technology 27, 22-28.
11. Forschler B.T., 1994. Survivorship and tunneling activity of Reticulitermes flavipes (Kollar) (Isoptera:
Rhinotermitidae) in response to termiticides soil barriers with and without untreated soil. - J. Entomol. Sci.
29: 43-54.
12. Su, N.Y., M. Tamashiro, J.R. Yates and M.I. Harvey (1982). Effect of behavior on the evaluation of
insecticides for prevention of or remedial control of Formosan subterranean termite. J. Econ. Entomol. 75,
188-193.
13. Potter, M.F. (1999). The changing face of termite control. II. Pest Control Technology 27, 33 23, 36, 38 39,
42, 90.
14. Mampe, C.D. (1994). Reducing termite treatment. Pest Control 62, 4.
15. Shelton, T.G., Bell, C.D. and Wagner, T.L. (2005). Lack of transfer of permethrin among nestmates of
Reticulitermes avipes in laboratory trials (Isoptera: Rhinotermitidae) Sociobiology 45, 69 75.