Assignment On:

Chemistry, Application & Toxicity Of

Commonly Used Pesticides in Veterinary

Course Title: Veterinary & Agro Pharmaceuticals

Course Code: PHAR 3111

Submitted To Mohammad Sarowar Uddin

Lecturer
Department of Pharmacy
NSTU

Name Roll
Md. Murad ASH1803019M
Submitted By Shahadul Islam ASH1803020M
Subrina Chowdhury BKH1803022F
Morsheda Khanam Sinthia MUH180323F
A.S.M Asif Khan ASH1803024M

Deadline: 15th September, 2020

1|Page
 Content

Name Page No

Defination of Pesticides ………………………………………………………………...…..…….01

Classification of Pesticides………………………….……………………………….……….. 01-04

Different Types of Pesticides For Veterinary Use ……………………………………....…..04-07

Chemistry, Application & Toxicity Of Commonly Used Pesticides in Veterinary………..07-37

2|Page
Defination of Pesticides:
A pesticide is any substance used to kill, repel, or control certain forms of plant or animal life that are considered to
be pests. Pesticides include herbicides for destroying weeds and other unwanted vegetation, insecticides for
controlling a wide variety of insects, fungicides used to prevent the growth of molds and mildew, disinfectants for
preventing the spread of bacteria, and compounds used to control mice and rats. Because of the widespread use of
agricultural chemicals in food production, people are exposed to low levels of pesticide residues through their diets.
Scientists do not yet have a clear understanding of the health effects of these pesticide residues.

The Food and Agriculture Organization (FAO) has defined pesticide as:

Any substance or mixture of substances intended for preventing, destroying, or controlling any pest, including
vectors of human or animal disease, unwanted species of plants or animals, causing harm during or otherwise
interfering with the production, processing, storage, transport, or marketing of food, agricultural commodities, wood
and wood products or animal feedstuffs, or substances that may be administered to animals for the control of
insects, arachnids, or other pests in or on their bodies. The term includes substances intended for use as a plant
growth regulator, defoliant, desiccant, or agent for thinning fruit or preventing the premature fall of fruit. Also used
as substances applied to crops either before or after harvest to protect the commodity from deterioration during
storage and transport.

According to the Environmental Protection Agency (EPA)- the government body that regulates pesticides in the
U.S., a pesticide is any substance or mixture of substances intended for preventing, destroying, repelling or
mitigating any pest. Though often misunderstood to refer only to insecticides, the term pesticide also applies to
herbicides, fungicides, and various other substances used to control pests. Pesticides also include plant regulators,
defoliants and desiccants.

Classification of Pesticides:
There are many different types of pesticides, each is meant to be effective against specific pests. The term "-cide"
comes from the Latin word "to kill."

Algaecides: Algaecides are used for killing and/or slowing the growth of algae.

Antimicrobials: Antimicrobials control germs and microbes such as bacteria and viruses.

Biopesticides: Biopesticides are made of living things, come from living things, or they are found in nature.

Desiccants: Desiccants are used to dry up living plant tissues.

Defoliants: Defoliants cause plants to drop their leaves.

Disinfectants: Disinfectants control germs and microbes such as bacteria and viruses.

Foggers: Foggers (total release foggers) are used to kill insects that are in the open and touch the pesticides.

Fungicides: Fungicides are used to control fungal problems like molds, mildew, and rust.

Herbicides: Herbicides kill or inhibit the growth of unwanted plants, aka weeds.

Illegal and Counterfeit Pesticides: Illegal and Counterfeit Pesticides are imported or sold illegally.

Insecticides: Insecticides are used to control insects.

Insect Growth Regulators: Insect Growth Regulators disrupt the growth and reproduction of insects.

3|Page
Minimum Risk Pesticides: Minimum Risk Pesticides are exempt from EPA registration, but many states require them
to be registered.

Miticides: Miticides control mites that feed on plants and animals. Mites are not insects, exactly.

Molluscicides: Molluscicides are designed to control slugs, snails and other molluscs.

Mothballs: Mothballs are insecticides used to kill fabric pests by fumigation in sealed containers.

Natural and Biological Pesticides: Natural and Biological Pesticides control pests using things found in nature, or
man-made versions of things found in nature.

Ovicides: Ovicides are used to control eggs of insects and mites.

Pheromones: Pheromones are biologically active chemicals used to attract insects or disrupt their mating behavior.
The ratio of chemicals in the mixture is often species-specific.

Plant Growth Regulators: Plant Growth Regulators are used to alter the growth of plants. For example, they may
induce or delay flowering

Repellents: Repellents are designed to repel unwanted pests, often by taste or smell.

Rodenticides: Rodenticides are used to kills rodents like mice, rats, and gophers

Synergists: Synergists make certain pesticides more effective, but they are not effective when used alone.

Treated Seeds: Treated Seeds are coated with a pesticide to limit crop damage from fungus and insects.

Wood Preservatives: Wood Preservatives are used to make wood resistant to insects, fungus and other pests.

Different Types of Pesticides For Veterinary Use in DOGS, CATS, HORSES and LIVESTOCK - cattle,
sheep, goat, pigs, poultry:
Natural Pesticides for Veterinary Use:

Natural organic compounds produced by plants:

Azadirachtin: insecticide & acaricide; very scarce use in domestic animals

Carvacrol: insecticide; not used directly in veterinary products

Citronellal (& citronellol): repellent; scarce use in domestic animals

D-limonene: insecticide, acaricide & repellent; scarce use in domestic animals

Eucalyptol: repellent; very scarce use in domestic animals

Eugenol: insecticide, acaricide & repellent; very scarce use in domestic animals

Geraniol: repellent; very scarce use in domestic animals

Linalool: insecticide, acaricide & repellent: very scarce use in domestic animals

Pyrethrins: insecticides, acaricides & repellents: abundant use in domestic animals

Rotenone: insecticide; scarce use in domestic animals

Thymol: insecticide; very scarce use in domestic animals

4|Page
These compounds are sometimes used as active ingredients in veterinary antiparasitics, but often also in the form
of essential oils of various plant extracts that contain a more or less variable mixture of some of these and other
natural compounds. These natural compounds or the corresponding plant extracts are often used in OTC (over-
the-counter) "soft" antiparasitics such as shampoos, soaps, sprays, powders, lotions and the like for petsor horses,
typically to protect them against fleas, mosquitoes, flies, etc. The use of such natural compounds on livestock is
irrelevant.

Natural organic compounds produced by microorganisms:

Abamectin: insecticide, acaricide & anthelmintic; abundant use in livestock

Spinosad: insecticide & acaricide, abundant use in domestic animals

Natural inorganic compounds of mineral origin:

Sulfur: insecticide; very scarce use in domestic animals

Borax: insecticide; very scarce use in domestic animals

Silica, diatomaceous earth: insecticide, acaricide; scarce use in domestic animals

Copper: anthelmintic, very scarce use in livestock.

Derris elliptica: its roots contain rotenone.

It must be remembered that the natural origin does not guarantee at all that such compounds are less toxic than
the synthetic parasiticides. They are as "chemical" as the synthetic ones. Toxicity is a matter of dose! But as a general
rule, natural compounds are less persistent in the treated animals and in the environment than most classic synthetic
parasiticides. The reason is that they are often sensitive to sunlight and/or are relatively quickly excreted,
metabolized or otherwise broken down in the environment.

Regarding their antiparasitic efficacy, a common feature of most natural compounds is that they are less potent, not
as fast-acting and almost always less persistent than modern synthetic parasiticides. The only exception are
abamectin, which is similar to ivermectin, a semi-synthetic compound, and spinosad. But what may be a
disadvantage from the efficacy point of view can be a benefit from the safety point of view, e.g. in ecological
productionwhere the absence of residues (in meat, milk, eggs, etc.) is a key benefit.

As a rule, products with such natural compounds are often submitted to a much looser authorizationprocess than
veterinary medicines regarding quality (e.g., specifications), proof of efficacy and safety. This is why there are so
many brands: it is quite cheap to develop them.

Many home remedies against veterinary parasites are based on recipes using medicinal plants that contain such
natural compounds.

CHEMICAL CLASSES of VETERINARY PESTICIDES(PARASITICIDES) for use in LIVESTOCK, HORSES, DOGS and CATS:

From a purely chemical point of view almost all active ingredients with parasiticidal activity (either internal or
internal parasiticides) discovered so far are synthetic organic molecules, i.e. they do not occur in nature but have
been synthesized in the laboratory. Very few such active ingredients occur naturally in plants or other organisms.
And even fewer are of mineral (i.e. inorganic) origin.

Most active ingredients can be grouped into chemical classes or families with similar functional groups, i.e. they
share a specific molecular structure. E.g. organophosphates are all derivatives of phosphoric acid.

5|Page
Active ingredients of the same chemical groups have usually the same mechanism of action at the molecular level.
What differs considerably for active ingredients of the same chemical class is often the spectrum of activity, the
toxicity to both parasitesand non-target organisms, the behavior in the environment, etc.

The most relevant chemical classes of parasiticidesdiscovered so far are the following ones, ordered by spectrum of
activity and by the decade the first compounds were introduced, regardless of whether they are still marketed today
or not:

Endectocides

Active against both external and internal parasites

Macrocyclic Lactones (1980s) or endectocides: broad-spectrum systemic ecto and endoparasiticides,

Ectoparasiticides

Active against external parasites (mainly insects, ticks and mites)

Organochlorines (1940s): broad-spectrum insecticides and acaricides, nowadays prohibited in most countries.

Organophosphates (1950s): broad-spectrum insecticides and acaricides. Are being phased out in some countries.

Carbamates (1950s): broad-spectrum insecticides and acaricides. Are being phased out in some countries.

Amidines (1960s): mainly acaricides and tickicides.

Synthetic Pyrethroids (1970s): broad-spectrum insecticides and acaricides.

Benzoylureas (1970s): development inhibitors (= growth regulators).

Juvenile Hormone Analogues (1970s): development inhibitors (= growth regulators).

Neonicotinoids (1990s): broad-spectrum insecticides and acaricides.

Phenylpyrazoles (1990s): broad-spectrum insecticides and acaricides.

Spinosyns (1990s): broad-spectrum insecticides and acaricides, partly systemic.

Isoxazolines (2010s): broad spectrum, systemic insecticides and acaricides.

A few relevant ectoparasiticides do not belong to these chemical classes, e.g. cyromazine, dicyclanil.

Other chemicals frequently used on livestock and pets against external parasites are not properly ectoparasiticides,
nor build an own chemical class, but they share a common funtionality regarding their use against external parasites:

Repellents: do not kill the parasites, but keep them away from the treated animals. They are not properly a chemical
class, but a functional class.

Synergists: enhance the parasiticidal activity of certain active ingredients or help to overcome resistance.

Endoparasiticides = anthelmintics

active against internal parasites mostly parasitic worms (roundworms, tapeworms, flukes)

Benzimidazoles (1960s): broad-spectrum anthelmintics: nematicides, taenicides, flukicides

Imidazothiazoles (1960s): broad-spectrum nematicides (only against roundworms)

Tetrahydropyrimidines (1960s): narrow-spectrum nematicides

6|Page
Isoquinolines (1970s): taenicides

Salicylanilides (1970s): narrow-spectrum nematicides, taenicides, flukicides

A few relevant endoparasiticides do not belong to these chemical classes, e.g. clorsulon, monepantel, nitroscanate,
nitroxinil, piperazine derivatives.

Other parasiticides

A few parasiticides are of mineral (i.e. non-synthetic) origin, or are directly obtained from plants: Mineral insecticides

Natural plant insecticides

Copper: used mainly as an anthelmintic against a few parasitic roundworms in the stomach of ruminants.

Chemistry, Application & Toxicity Of Commonly Used Pesticides in Veterinary:

FENVALERATE

Introduction:

FENVALERATE is an antiparasitic active ingredient used in veterinary medicine mainly in livestock against external
parasites (lice,mites,fleas,flies,ticks etc).

Chemical Structure:

Other Names: ESFENVALERATE

Type: Pesticide.

Chemical Class: synthetic pyrethroid

Application & Use:

• Fenvalerate is a synthetic pyrethroid particularly effective against insects (flies, lice, mosquitoes, etc.) but
only mediocre against ticks and mites. As most synthetic pyrethroids, fenvalerate is a mediocre larvicide,
i.e. it is not indicated for the large-scale prevention of cutaneous myiases (e.g. screwworms, blowfly strike,
etc.) with sprays, pour-ons, etc.
• Fenvalerate is a mixture of various optic isomers with different insecticidal efficacy. Commercial products
may contain different isomer mixtures. For most users, it often doesn't make any difference regarding
efficacy, because if one product uses a mixture with more of the most effective isomers, it will be used at a
lower concentration than a product using a mixture with less effective isomers
• Fenvalerate has applications against a wide range of pests including some of the more destructive such as
the Helicoverpa assulta.
• Use in livestock: yes,very scarce
• Use in horses: yes,very scarce
• Use in dogs and cats: No
• Use in agriculture: yes

7|Page
 • Use in human medicine: No

Toxic effect:

01.Fenvalerate is an insecticide of moderate mammalian toxicity. In laboratory animals, central nervous

system toxicity is observed following acute or short-term exposure.

02.Fenvalerate is most toxic to bees and fish. It is found in some emulsifiable concentrates, ULV, wettable
powders, slow release formulations, insecticidal fogs, and granules.

O3.Fenvalerate does not affect plants, but is active for an extended period of time.

04.Fenvalerate may irritate the skin and eyes on contact, and is also harmful if swallowed.

TRICHLORFON

Introduction:

Trichlorfon is an antiparasitic active ingredient used in veterinary medicine in dogs and livestock mainly against
external parasites (lice, mites, fleas, flies, ticks, etc.). It is also used against agricultural and household pests. It
belongs to the chemical class of the organophosphates .

Chemical Structure:

Use:

It is used as an insecticide.

It can be used to treat schistosomiasis caused by Schistoma haematobium,but is no longer commercially available.

It has been proposed for use in treatment of Alzheimer's disease, but use for that purpose is not currently
recommended.

Application :

• Trichlorfon is a classical, veteran parasiticide belonging to the organophosphates.

• Trichlorfon was the first ectoparasiticide that could be administered as a spot-on to both livestock and pets,
but not in single-dose vials or pipettes as most modern spot-ons for pets, but as simple drops.
• In livestock it is still used in some countries in cattle, sheep and pig in concentrates for dipping and spraying,
in ready-to-use pour-ons and dressings and in drenches against several gastrointestinal roundworms.
• Trichlorfon is one of the very few organophosphates still used in some countries against gastrointestinal
roundworms of sheep and goats that have become resistant to modern anthelmintics (benzimidazoles,
macrocyclic lactones, imidazothiazoles). For this puropose it is administered orally. It has to be done very
accurately because the safety margin is extremely low and slight overdosing can easily cause toxic side
effects.
• In dogs and cats it is still used in shampoos, soaps, baths, sprays, powders and the like, but its usage has
strongly declined after the introduction of more modern and safer flea and tick control spot-ons (= pipettes)
and tablets. It is often used in mixtures, mainly with synthetic pyrethroids (e.g. cypermethrin, permethrin).

8|Page
Efficacy of Trichlorfon:

As most organophosphates trichlorphon is a broad-spectrum insecticide, acaricide and larvicide. Trichlorfon is

particularly effective against various livestock myiases such as maggots from warble flies (Hypoderma spp), human
bot flies (e.g. Dermatobia hominis) and screwworm flies.

However, resistance of important veterinary parasites to all organophosphates, including trichlorfon is widespread,
especially in cattle ticks (Boophilus spp), horn flies (Haematobia irritans), sheep lice (Damalinia ovis), poultry mites
(Dermanyssus gallinae), mosquitoes, dog and cat fleas (Ctenocephalides spp) and houseflies (Musca domestica). As
a consequence, products with this active ingredient may not achieve the expected efficacy in many places. The same
applies to all other organophosphates. This is also a reason for their progressive replacement with newer active
active ingredients with a different mode of action.

Toxicity:

Acute Toxicity and Tolerance of Trichlorphon

1.LD50 acute, rats, p.o. 430 to 630 mg/kg (depending on the studies)

2.LD50 acute, mice, p.o. 660 mg/kg

3.LD50 acute, rats, dermal 2000 to 5000 mg/kg (depending on the studies)

4.LD50 acute, rabbits, p.o. 160 mg/kg (depending on the studies)

5.LD50 acute, dogs, p.o. 420 mg/kg

6.LD50 acute, cats, p.o. 94 mg/kg

7.LD50 acute, sheep, p.o. 300 mg/kg

8.Toxic dose, calves: p.o. 20 mg/kg

9.Toxic dose, cattle, p.o. 75 mg/kg

10.Toxic dose, sheep, p.o. 200 mg/kg

11.Toxic dose, horses, p.o. 100 mg/kg

12.Toxic dose, pigs, 100 mg/kg

13.Topical administration of trichlorfon is usually well tolerated by pets and livestock.

15.Weak animals, certain dog breeds (e.g. greyhounds), cats and certain birds (e.g. geese) and are also more
susceptible to dichlorvos.

Toxic Symptoms caused by Trichlorfon

• Toxic symptoms caused by organophosphate intoxications are the same as those of carbamates
intoxication, but are usually more severe and recovery is slower because organophosphates bind
irreversibly to acetylcholinesterase, whereas carbamate binding is reversible.

9|Page
 • Acute intoxication. Is caused by inhibition of the acetylcholinesterase: as a consequence acetylcholine
accumulates in the neuromuscular synapses (including those in skeletal, smooth and cardiac muscles),
in the neuroglandular connections, and in the CNS (Central Nervous System). This causes
hyperexcitation in all the muscarinic and nicotinic cholinergic receptors, which disturbs the normal
functioning of the affected organs.

• After accidental ingestion or massive dermal overdose, intoxication follows an acute development.
Ingested trichlorfon is vastly and quickly absorbed into blood. The symptoms appear within a few
minutes to 2 hours after ingestion, often dramatically. If the patient survives the first 24-48 hours,
prognosis is favorable.

• Usually muscarinic symptoms are the first to manifest, followed by hyperexcitation of the nicotinic
receptors of vegetative ganglions and motor end plates. If the intoxication crosses the blood-brain
barrier the CNS becomes hyperexcited as well.

• Main muscarinic symptoms:

• Exocrine glands: salivation (drooling), lacrimation (excessive secretion of tears), sudoration

(excessive sweating).
• Eyes: miosis (constriction of the pupil), in swine nystagmus (uncontrolled eye movements).
• Digestive system: nausea, vomit (particularly in dogs), diarrhea, tenesmus (need for
imperative defecation), fecal incontinence.
• Cardiovascular system: bradycardia (low heart rate), low blood pressure.
• Respiratory system: bronchoconstriction, bronchospasms, cough, tachypnea (low breathing
rate), dispnea (shortness of breath).
• Urinary system: frequent urination.

• Main CNS symptoms:

Lethargy, fatigue, trembling, spasms and coma with respiratory paralysis. Death is mostly a
consequence of paralysis of the respiratory muscles, of the inhibition of the respiratory center
and of excessive bronchial constriction and secretion. In swine death can follow within 15 to
30 minutes after exposure to the lethal dose.

• Chronic intoxication:

In addition to the acute intoxication, some organophosphates can have a delayed neurotoxic
effect (so called OPIDN = organophosphorous ester-induced delayed neuropathy), which
develops 7 to 21 days after exposure to the toxic dose and appears as weakness, ataxia
(uncoordinated movements), proprioceptive dysfunctions (disturbed awareness of posture
and movements), particularly of the hind legs, and paralysis. It is due to degeneration of the
axons (nerve fibers) of central and peripheral nerve cells, which is species-specific. Depending
on which particular organophosphate caused the intoxication, OPIDN is irreversible or allows
a slow recovery after several weeks.

• Organophosphate induced Intermediate Syndrome (IMS) is another possible clinical development

observed mainly in dogs and cats (and humans) after massive overdosing with certain
organophosphates, including e.g. diazinon, chlorpyrifos, fenthion, malathion, phosmet and trichlorfon.
Clinical symptoms include acute paralysis and weakness in several muscles (e.g. neck flexors, proximal
limbs, etc)

10 | P a g e
 Other symptoms include weakness, depression, ptosis (drooping or falling of the lower of upper
eyelids), double vision (diplopia), disturbed deep tendon reflexes. These symptoms may last for a few
days or several weeks, depending on the compound involved and the dose.

Trichlorfon Side Effects, Adverse Drug Reactions (ADRs) and Warnings:

• After slight overdose the following effects have been reported: vomit, soft feces, tenesmus (frequent
urination and defecation). In horses mainly diarrhea, colic and tenesmus (frequent urination and
defecation) In cattle salivation (drooling), tremor, miosis (contraction of the pupils), diarrhea and
frequent urination. Usually these symptoms peak 1 to 2 hours after administration and resolve in about
4 hours.
• In dairy cows orally administered trichlorfon leaves residues in milk that can affect its color and taste.
• Certain solvents in the formulation can enhance the toxicity of trichlorfon because they accelerate its
cutaneous or mucosal absorption.
• Young and weak animals must be treated with utmost care. Cats younger than 1 year should not be
treated with trichlorfon.
• Colts and fillies younger than 4 months as well as calves younger than 3 months should not be treated
with trichlorfon.
• Trichlorfon should not be administered orally to pregnant dams during the last third of gestation.
• Trichlorfon should not be administered orally to pregnant mares or sows.
• Trichlorfon should not be administered to animals suffering diarrhea, chronic constipation, colic,
convulsions, respiratory, renal and/or cardiac disturbances.
• In case of large skin injuries topical treatment with trichlorfon can lead to excessive cutaneous
absorption with development of paraysmpathetic symptoms.
• Organophosphates must not be administered together with other acetylcholinesterase inhibitors such
as carbamates, levamisole, morantel, pyrantel and neostigmine.
• Depolarising muscle relaxants must not be administered within 10 days following organophosphate
administration because they enhance the side effects.
• Trichlorfon must not be administered together with neuroleptic drugs such as phenotiazines.

Environmental Toxicity of Trichlorfon:

1.Trichlorfon is moderately to highly toxic to birds, and highly toxic to fish and aquatic invertebrates.
Toxicity varies considerably depending on temperature, pH and water hardness. As a general rule, toxicity
increases with temperature and pH.

2.Trichlorfon breaks down quickly in soils under aerobic conditions with a half-life between 3 and 30 days.

3.Trichlorfon does not bind to soil particles and is quite soluble in water. Consequently it can easily
contaminate groundwater.

4.In alkaline aqueous environment trichlorfon breaks down in a few hours; it takes longer at acid pH.

5.The major break down molecule is dichlorvos, another organophosphate pesticide.

6.Correctly used on livestock and pets trichlorfon is unlikely to be detrimental for the environment,
provided that disposal of old dip wash, product waste and used containers is done according to the label
recommendations

11 | P a g e
CYPERMETHRIN:

Cypermethrin is an antiparasitic active ingredient used in veterinary medicine in livestock and pets against external
parasites (lice, mites, fleas, flies, ticks, etc.). It is also used against agricultural and household pests. It belongs to the
chemical class of the synthetic pyrethroids.

Chemical Structure:

Application & Use:

• Cypermethrin is the ectoparasiticide most used in livestock worldwide. It is the generic ectoparasiticide par
excellence. There are thousands of products, mainly dips, sprays and pour-ons. It is much less used in dogs:
permethrin is often preferred in dogs.
• There are also many mixtures: with amitraz, organophosphates, carbamates, insect development inhibitors,
etc. Many products contain also synergists.
• Cypermethrin used in veterinary products can be of different "qualities" regarding the content of various
optic isomers (cis or trans) that show different efficacy against parasites. You can learn more about such
mixtures of various optic isomers in the article on synthetic pyrethroids. Some brands praise a high content
of such active isomers: high-cis cypermethrin, alpha-cypermethrin, beta-cypermethrin, etc. For most users,
it often doesn't make any difference regarding efficacy, because if one product uses a mixture with more
of the most effective isomers, it will be used at a lower concentration than a product using a mixture with
less effective isomers. However, some isomers are significantly more toxic than other ones, and this can
negatively influence the tolerance of livestock or pets to a particular product.
• Efficacy of Cypermethrin:
✓ Cypermethrin is an ectoparasiticide, i.e. active only against external parasites such as flies,
ticks, mites, lice, fleas, mosquitoes, etc. It can be considered as a broad-spectrum
generalist, i.e. quite good against almost all insects, ticks and mites, but not outstanding
against a particular parasite. It is certainly less efficient against multi-host ticks (e.g.
Amblyomma, Rhipicephalus, Ixodes, Dermacentor, etc.) than several other tickicides (e.g.
amitraz, chlorfenvinphos, coumaphos, flumethrin, etc.).
✓ As most synthetic pyrethroids, cypermethrin is a mediocre larvicide, i.e. it is often not a
good option for the large-scale prevention of cutaneous myiases (e.g. screwworms,
blowfly strike, etc.) with sprays, pour-ons, etc. However cypermethrin is often included in
dressings for the therapeutic treatment on animal injuries already infected with fly
maggots.
✓ Cypermethrin, as well as many other synthetic pyrethroids has a significant repellent
effect on certain insects and ticks, which strongly depends on the delivery form and the
dose administered.
✓ However, resistance to cypermethrin is widespread and can be very high in cattle ticks
(Boophilus spp), horn flies (Haematobia irritans), red poultry mites (Dermanyssus
gallinae), sheep lice (Damalinia ovis), houseflies (Musca domestica), dog and cat fleas
(Ctenocephalides spp) and mosquitoes.

12 | P a g e
Toxicity:

• Toxicity of cypermethrin depends strongly on the cis:trans isomer ratios (usually 80:20; 40:60; 25:75),
whereby the cis isomers are biologically more active but also more toxic than the trans isomers.
• LD50 acute, rats, p.o. 250 (oily vehicle) to 5150 mg/kg (aqueous vehicle). The vehicle-dependent and
isomer-dependent differences in the acute oral toxicity are typical for synthetic pyrethroids and some other
active ingredients.
• LD50 acute, rats, dermal >4920 mg/kg
• As a general rule, dogs, livestock (cattle, sheep, goats, swine), horses, and poultry tolerate cypermethrin
and most synthetic pyrethroids very well, since toxicity is about 1000x higher to insects and other
arthropods than to mammals. But in case of sustained skin or inhalation exposure, or after direct contact
with open wounds toxicity to mammals can be higher.
• Besides neurotoxic effects, cypermethrin has also hepatotoxic effects and induces microsomal enzymes in
the liver.
• WARNING: cypermethrin is toxic to cats! Cats do not tolerate therapeutic doses for dogs. This is associated
with glucuronidase deficiency in cats, the enzyme responsible for breaking down cypermethrin and other
synthetic pyrethroids in the organism in a process called glucuronidation. As a consequence, cypermethrin
remains much longer in the cat's organism than in dogs or other mammals.
• Toxic Symptoms caused by Cypermethrin Poisoning
• The primary symptoms of intoxication with cypermethrin and other synthetic pyrethroids affect mainly the
nervous and muscular systems.
• Most frequent symptoms are:
• Ataxia (uncoordinated movements)
• Hyperreactivity (exaggerated reaction to stimuli)
• Tremor (uncoordinated trembling or shaking movements)
• Paresthesia (skin sensation of tingling, tickling, prickling)
• Exhaustion (lethargy, fatigue)
• Hypersalivation (drooling)
• Vomit
• Diarrhea
• Urinary incontinence
• Other symptoms after severe poisoning include: hyperthermia (fever) or hypothermia (too low body
temperature), dyspnea (difficult breathing), disorientation, cramps or spasms (sudden, involuntary
contractions of muscles or hollow organs).
• Symptoms appear a few hours after exposure, but depend strongly on the formulation, the dose and the
kind of contact (skin, inhalation, ingestion etc).
• Sustained skin exposure can cause local dermatitis (skin irritation) with pruritus (itching) and erythema (red
skin).
• Mucous membranes are particularly sensitive to synthetic pyrethroids, e.g. in the nose and the respiratory
system (coughing), in the eyes (conjunctivitis), genital organs, etc.
• After excessive inhalation of synthetic pyrethroids patients can develop allergic sensitization with asthmatic
symptoms. In extreme cases, sustained inhalation of high doses can cause respiratory paralysis and death.
• As a general rule, young animals are more sensitive to overdosing and react stronger.

13 | P a g e
Propoxur:

Introduction:

Propoxur is an antiparasitic active ingredient used in veterinary medicine. It is used in dogs and cats against external
parasites (lice, fleas, etc.). It is also used against agricultural and household pests. It belongs to the chemical class of
the carbamates.

Chemical Structure:

Uses and Application:

• Propoxur is a broad-spectrum carbamate insecticide abundantly used in dogs and cats in the 1970's to
1990's before the introduction of modern highly effective flea and tick spot-ons.
• In livestock it is used only in a few dressings against fly maggots and off-animal for premise and
environmental treatment on livestock operations.
• It is still used a lot in public and domestic hygiene products.
• It is quite effective against all kinds of insects. However, resistance of dog and cat fleas (Ctenocephalides
spp) and mosquitoes to carbamates is already quite frequent and products with propoxur may not achieve
the expected efficacy.

Toxicity:

• Acute Toxicity and Tolerance of Propoxur

• LD50 acute, rats, p.o. 50 mg/kg
• LD50 acute, mice, p.o. ~100 mg/kg
• LD50 acute, rats, dermal 4000 mg/kg
• LD50 acute, rabbits, dermal 4000 mg/kg
• Dogs tolerated daily oral doses of 20 mg/kg/day during months without toxic symptoms.
• In chickens delayed neurotoxic effects with degeneration of the spinal cord has been reported.
• As a general rule, dogs, cats and livestock tolerate topically applied propoxur very well (shampoos, soaps,
baths, aerosols, lotions, creams, dusts, collars, etc.).
• Toxic Symptoms caused by Propoxur Poisoning
• Toxic symptoms caused by carbamate intoxications are the same as those of organophosphate intoxication,
but are usually less severe and recovery is faster because carbamates bind reversibly to
acetylcholinesterase, whereas organophosphate binding is irreversible. This means that the organism can
hydrolyze carbamates, which allows the enzyme to retake its normal function in a few hours. However, in
case of massive overdose the organism cannot break down the poisonous substance fast enough.
• Ingested propoxur affects mainly the nervous system and the liver.
• Acute intoxication. Is caused by inhibition of the acetylcholinesterase: as a consequence acetylcholine
accumulates in the neuromuscular synapses (including those in skeletal, smooth and cardiac muscles), in
the neuroglandular connections, and in the CNS (Central Nervous System). This causes hyperexcitation in
all the muscarinic and nicotinic cholinergic receptors, which disturbs the normal functioning of the affected
organs.

14 | P a g e
 • After accidental ingestion The symptoms appear a few minutes to 2 hours after ingestion, often
dramatically. If the patient survives the first 24-48 hours, prognosis is favorable.

• Usually muscarinic symptoms are the first to manifest, followed by hyperexcitation of the nicotinic
receptors of vegetative ganglions and motor end plates. If the intoxication crosses the blood-brain barrier
the CNS becomes hyperexcited as well.
• Main muscarinic symptoms:
✓ Exocrine glands: salivation (drooling), lacrimation (excessive secretion of tears), sudoration
(excessive sweating).
✓ Eyes: miosis (constriction of the pupil), in swine nystagmus (uncontrolled eye movements).
✓ Digestive system: nausea, vomit (particularly in dogs), diarrhea, tenesmus (need for imperative
defecation), fecal incontinence.
✓ Cardiovascular system: bradycardia (low heart rate), low blood pressure.
✓ Respiratory system: bronchoconstriction, bronchospasms, cough, tachypnea (low breathing rate),
dispnea (shortness of breath).
✓ Urinary system: frequent urination.
• Main CNS symptoms:
✓ Lethargy, fatigue, trembling, spasms and coma with respiratory paralysis. Death is mostly a
consequence of paralysis of the respiratory muscles, of the inhibition of the respiratory center and
of excessive bronchial constriction and secretion. In swine death can follow within 15 to 30 minutes
after exposure to the lethal dose.
• DIAGNOSIS. An important diagnostic parameter is the global acetylcholinesterase (AchE) activity in blood.
A drop below 25% of the normal value indicates intoxication with an AchE inhibitor (not necessarily an
organophosphate or carbamate pesticide).

Propoxur Side Effects, Adverse Drug Reactions (ADRs) and Warnings

• After slight overdose the following effects have been reported: reduced heart rate and vascular dilatation,
increase of bronchial secretion and contraction, salivation (drooling), sphincter relaxation (gastrointestinal
and urinary), miosis.
• In case of large skin injuries topical treatment with propoxur can lead to excessive cutaneous absorption
with development of paraysmpathetic symptoms.
• Propoxur-impregnated collars for dogs and cats can cause local skin irritation. During the first 3 days after
getting the collar, a reduction in the number of red blood cells and of the plasmatic cholinesterase levels
has been reported.
• Propoxur should not be administered to animals suffering digestive (particularly mechanical intestinal or
urinary obstruction), respiratory (mainly bronchial asthma) and cardiovascular disturbances.
• Propoxur should not be administered to pregnant dams during the last third of gestation.
• Certain solvents in the formulation can enhance the toxicity of Propoxur because they accelerate its
cutaneous or mucosal absorption.
• Environmental Toxicity of Propoxur:
✓ Propoxur is highly to moderately toxic to birds, depending on the species.
✓ Propoxur is only slightly toxic to fish and many aquatic invertebrates, but is highly toxic to
numerous insects.
✓ Propoxur is moderately persistent in the soil. Half-life in soil is 14 to 50 days. It hardly binds to soil
particles. For these reasons and because it is quite soluble in water it has potential for
contaminating groundwater.

15 | P a g e
Spinosad:

Introduction:

Spinosad is a natural active ingredient of microbial origin used in veterinary medicine in dogs and livestock against
some external parasites (lice, fleas, flies, etc.). It is also used against agricultural and household pests. It belongs to
the chemical class of the spinosyns.

Chemical Structure:

Uses and Application:

• Spinosad is a natural insecticide and acaricide with topical and systemic effect (after oral administration). It
is highly effective against fleas in pets (mainly in tablets), against a lice and blowfly strike (e.g. Lucilia spp)
in sheep, and against poultry mites ( e.g. Dermanyssus gallinae, Ornithonyssus spp). It is not effective
against internal parasites.
• Spinosad, a mixture of spinosyn A and spinosyn D (ratio about 17:3), is a natural insecticide extracted from
cultures of Saccharopolyspora spinosa, a soil bacterium.
• Use in livestock is still scarce. It is available in a few countries for use in sprays, dips and pour-ons in sheep
against lice and blowfly strike, and in sprays for off-animal use in poultry facilities against the fowl mites
(e.g. Dermanyssus gallinae). It is also available as bait against houseflies (Musca domestica) and other
nuisance flies.
• It is also used in tablets and pills for oral administration to dogs against fleas.
• It is also used in human medicines against lice (pediculosis).

Toxicity:

• LD50 acute, rats, p.o. >3600 mg/kg

• LD50 acute, mice, p.o. >5000 mg/kg
• LD50 acute, geese, p.o. >2000 mg/kg
• LD50 acute, rabbit, dermal >5000 mg/kg
• LD50 acute, rabbits, dermal 354 mg/kg
• As a general rule, dogs and livestock (sheep, goats) tolerate spinosad very well.
• In a study on dogs treated orally at 2.5x the therapeutic dose (=30-60 mg/kg), close to 85% of the animals
vomited 20 to 120 minutes after administration, most of them more than once. In a study on puppies (6
months old) treated once at 90 mg/kg (~3x the therapeutic dose), 45% of the animals vomited within 60
minutes after administration.
• Reproductive studies in pregnant and nursing bitches and lactating puppies did not completely confirm the
harmlessness of spinosad during pregnancy and lactation. Use should be decided after a risk/benefit
analysis.

Toxic Symptoms caused by Spinosad Poisoning:

• The most frequent symptom of intoxication in dogs is vomit, which also happens as adverse side effect after
correct treatment at the therapeutic dose.

16 | P a g e
 • In rodents exposed to high overdosing exhaustion and cachexia (wasting: loss of weight, muscle atrophy,
etc.) were reported.
• In toxicity studies on rats, deaths were recorded at the highest doses tested. Pathological analysis showed
vacuolization (phospholipidosis) of epithelial cells in numerous organs (liver, lymphatic nodes, kidneys,
stomach, lungs, etc.).
• As a general rule, young animals are more sensitive to overdosing and react stronger.
• A frequent administration error in dogs that can lead to overdosing and subsequent poisoning is partial
administration to small dogs of tablets approved for larger animals.

Spinosad Side Effects, Adverse Drug Reactions (ADRs) and Warnings

• The most frequently reported side effect is vomiting (~12.5% of dogs). At a dose of 30 to 90% mg/kg there
is a linear increase in the vomiting frequency. Between 70 and 90 mg/kg about 17% of the dogs showed
vomiting.
• Other relatively frequent side effects of spinosad are loss of appetite (~9%), lethargy (~7.5%), diarrhea
(~7%), cough (~4%) and excessive thirst (~2.5). Less frequent side effects reported are redness of the skin,
drooling, itching and trembling.
• In epileptic dogs treatment at a dose higher than the therapeutic one can cause seizure.
• Spinosad can enhance the toxicity of ivermectin when used at a high dose (e.g. 0.6 mg/kg, against
demodicosis): they should not be administered concomitantly.
• Spinosad can be problematic when used in dogs with the MDR-1 mutation (e.g. Collies), as all macrocyclic
lactones. Nevertheless, tolerance studies have shown that dogs sensitive to ivermectin treated with
spinosad at 300 mg/kg (~4.5x the therapeutic dose) or with spinosad and milbemycin oxime at 5x the
therapeutic dose showed no neurotoxic symptoms.
• Never use tablets for large dogs in small dogs. It happens that some users want to save money buying large
tablets or spot-ons for treating smaller dogs (or even cats!) twice or more times. The risk of overdosing is
considerable, either due to erroneous calculations or to unskilled manipulation. In addition, dog medicines
may sometimes contain other ingredients that are toxic to cats.
• Spinosad is approved for use on dips and pour-ons for sheep and goats in some countries (e.g. Australia,
New Zealand). It is well tolerated by these animals.
• Unless prescribed by a veterinary doctor, never use in dogs or cats products for livestock that are not
explicitly approved for such use. There is a high risk of overdosing or of adverse drug reactions due to
ingredients that are not tolerated by pets or are even toxic to them.

Environmental Toxicity of Spinosad:

• Toxicity of spinosad to fish, birds and wildlife in general is quite low.

• Spinosad breaks down in the soil. Half-life in well-oxygenated silt loam soil is ~2 weeks. Half-life in soil
without oxygen is 5 to 8 months.
• Spinosad solved in water is broken down by sunlight rather quickly (half-life ~20 hours).
• Microorganisms in the soil are able to break down spinosad.
• Spinosad does not bioaccumulate.
• Correct use on dogs is unlikely to cause environmental pollution.
• There is a certain environmental risk of water pollution from run-off after pour-on administration to large
sheep flocks, or after undue disposal of old dip wash

17 | P a g e
Flumethrin:

Introduction

Flumethrin is an antiparasitic active ingredient used in veterinary medicine in livestock and pets against external
parasites (lice, mites, fleas, flies, ticks, etc.). It is not used against agricultural or household pests. It belongs to the
chemical class of the synthetic pyrethroids.

Chemical Structure:

Application & Uses:

• As all synthetic pyrethroids, flumethrin products are always used for topical administration and act by
contact without any systemic efficacy. Flumethrin is used moderately in livestock in the form of
concentrates for dipping or spraying, or in ready-to-use pour-ons. Use in dogs is rather scarce mainly in the
form of a few insecticide-impregnated collars, spot-ons or low-cost topicals such as shampoos, soaps,
sprays, etc.
• Flumethrin (and many other synthetic pyrethroids) is effective against most external livestock and dog
parasites (flies, ticks, mites, lice, fleas, mosquitoes, etc.) but is completely ineffective against internal
parasites. It is one of the best synthetic pyrethroids against ticks and mites, but rather mediocre against
insects (flies, mosquitoes, lice, etc.).
• Flumethrin is a synthetic pyrethroid particularly effective against ticks and mites, but only mediocre against
insects. It has been vastly used on livestock, but very seldom on pets.
• Flumethrin is a mixture of various optic isomers, but all commercial products contain the same mixture, i.e.
this makes no difference in the product quality or efficacy.
• Although patent has expired long ago, there are only a few generic veterinary products available.
• Flumethrin is an ectoparasiticide, i.e. active only against external parasites such as flies, ticks, mites, lice,
fleas, mosquitoes, etc. However it is certainly more effective against livestock ticks and mites than other
pyrethroid generalists such as cypermethrin, deltamethrin and permethrin. It is one of the best active
ingredients against both single-host ticks (e.g Boophilus spp) and multi-host ticks (e.g. Amblyomma,
Rhipicephalus, Ixodes, Dermacentor, etc,). It is also excellent against several scab and mange mites (e.g.
Psoroptes spp., Sarcoptes spp, etc.). However, it is only a mediocre insecticide less effective against flies,
lice, fleas and mosquitoes than other synthetic pyrethroids.
• As most synthetic pyrethroids, flumethrin is a mediocre larvicide, i.e. it is not a good option for the large-
scale prevention of cutaneous myiases (e.g. screwworms, blowfly strike, etc.) with sprays, pour-ons, etc.
• Flumethrin, as well as many other synthetic pyrethroids has a significant repellent effect on certain ticks,
which strongly depends on the delivery form and the dose administered
• Synthetic pyrethroids, including flumethrin, have a similar mode of action as organochlorines. They act on
the membrane of nerve cells blocking the closure of the ion gates of the sodium channel during re-
polarization.At low concentrations insects and other arthropods suffer from hyperactivity. At high
concentrations they are paralyzed and die. Sensory and nervous cells are particularly sensitive.

18 | P a g e
Toxicity:

• Acute Toxicity and Tolerance of FlumethrinLD50 acute, rats, p.o. 41 (oil vehicle) to 3859 (aqueous vehicle).
The vehicle-dependant differences in the acute oral toxicity are typical for synthetic pyrethroids.
• LD50 acute, rats, dermal, >2000 mg/kg
• In toxicity studies, dogs (Beagles) were fed flumethrin mixed with food at 25, 50, 100 and 200 mg/kg feed
during 13 weeks. At the end of the study all dogs showed skin lesions (thickened skin covered with
hyperkeratotic material) at doses >50 mg/kg feed. The NOEL (No Observable Effect Level) was 25 mg/kg
feed, equivalent to 0.88 mg/kg bw per day.
• In cattle treated topically at 2x the therapeutic dose a few animals showed erythema (skin redness) at the
application site and transient diarrhea.
• In cattle, the pour-on formulation has a safety margin of 50. At doses of up to 10 mg/kg no adverse effects
were recorded on skin, hair coat or hides. Five consecutive treatments at a dose 4 mg/kg in intervals of 3
to 4 days did not cause adverse effects.
• As a general rule, dogs and livestock (cattle, sheep, goats) tolerate flumethrin and most synthetic
pyrethroids very well, since toxicity is about 1000x higher to insects and other arthropods than to mammals.
But toxicity to mammals can be higher in case of sustained skin or inhalation exposure, or after direct
contact with open wounds.
• WARNING: cats are more susceptible to synthetic pyrethroids than dogs. Cats may not tolerate doses of
flumethrin that are harmless for dogs. This is associated with glucuronidase deficiency in cats, the enzyme
responsible for breaking down most synthetic pyrethroids in the organism in a process called
glucuronidation. As a consequence, synthetic pyrethroids remain much longer in the cat's organism than in
dogs or other mammals.
• Toxic Symptoms caused by Flumethrin Poisoning
✓ The primary symptoms of intoxication with flumethrin and other synthetic pyrethroids affect mainly
the nervous and muscular systems.
✓ Most frequent symptoms are:
▪ Ataxia (uncoordinated movements)
▪ Hyperreactivity (exaggerated reaction to stimuli)
▪ Tremor (uncoordinated trembling or shaking movements)
▪ Paresthesia (skin sensation of tingling, tickling, prickling)
▪ Exhaustion (lethargy, fatigue)
▪ Hypersalivation (drooling)
▪ Vomit
▪ Diarrhea
▪ Urinary incontinence
• Other symptoms after severe poisoning include: hyperthermia (fever) or hypothermia (too low body
temperature), dyspnea (difficult breathing), disorientation, cramps or spasms (sudden, involuntary
contractions of muscles or hollow organs).
• Symptoms appear a few hours after exposure, but depend strongly on the formulation, the dose and the
kind of contact (skin, inhalation, ingestion etc).
• Sustained skin exposure can cause local dermatitis (skin irritation) with pruritus (itching) and erythema (red
skin).
• Mucous membranes are particularly sensitive to synthetic pyrethroids, e.g. in the nose and the respiratory
system (coughing), in the eyes (conjunctivitis), genital organs, etc.

19 | P a g e
 • After excessive inhalation of synthetic pyrethroids patients can develop allergic sensitization with asthmatic
symptoms. In extreme cases, sustained inhalation of high doses can cause respiratory paralysis and death.
• As a general rule, young animals are more sensitive to overdosing and react stronger.
• A frequent administration error in dogs is partial administration to small dogs of spot-ons approved for
large dogs.

Flumethrin Side Effects, Adverse Drug Reactions (ADRs) and Warnings:

• Do not administer flumethrin topically (spot-on, shampoos, soaps, sprays, etc.) in case of extended skin
lesions: this can lead to an excessive absorption through the damaged skin.
• Pour-ons containing flumethrin and other synthetic pyrethroids can be irritant for cattle. This can be
particularly annoying when handling dairy cows for milking.
• In small dogs paresthesia (skin sensation of tingling, tickling, prickling) can happen at the therapeutic dose,
which usually disappears in 12 to 24 hours.

Toxic effects can be potentiated after simultaneous exposure to organophosphates or other synthetic pyrethroids:

• Never use spot-ons or other products on cats that are approved only for dogs: synthetic pyrethroids can be
toxic to cats.
• Never use spot-ons for large dogs on small dogs. It happens that some users want to save money buying
large spot-ons for treating smaller dogs twice or more times. The risk of overdosing is considerable, either
due to erroneous calculations or to unskilled manipulation. Remaining product in opened spot-on vials can
deteriorate.
• Unless prescribed by a veterinary doctor, never use on dogs or cats products for livestock that are not
explicitly approved for such use. There is a high risk of overdosing or of adverse drug reactions due to
ingredients that are not tolerated by pets or are even toxic to them.

Environmental Toxicity of Flumethrin

• Flumethrin, as all synthetic pyrethroids is extremely toxic to fish and aquatic invertebrates (more in cold
than in warm water). For this reason disposal of flumethrin residues (e.g. in empty containers) in
watercourses must be absolutely avoided. Disposal of old dip wash charged with flumethrin (or other
synthetic pyrethroids) into watercourses is strictly forbidden worldwide because it would have catastrophic
consequences for fish and other aquatic animals. There are countries where products for livestock dipping
containing synthetic pyrethroids have been withdrawn by the regulatory authorities for this reason.
• In contrast with organophosphates flumethrin (as most synthetic pyrethroid) is not toxic to birds.
• There is a certain environmental risk of water pollution from run-off after pour-on administration to large
cattle herds. However this risk is substantially lower than the one associated with the use of synthetic
pyrethroids in crop pesticides.
• Correct use on livestock and pets is unlikely to result in any significant environmental pollution.
• Flumethrin is quite resistant to photodegradation, i.e. exposed to sunlight it breaks down rather slowly.
• Flumethrin is almost insoluble in water and tends to bind to soil particles.
• Soil bacteria contribute to the biodegradation of flumethrin.
• Flumethrin does not bioaccumulate

Dichlorvos:

Introduction: Dichlorvos is one of a class of insecticides referred to as organophosphates. These chemicals act by
interfering with the activities of cholinesterase, an enzyme that is essential for the proper working of the nervous

20 | P a g e
systems of both humans and insects. Please refer to the Toxicology Information Brief on cholinesterase-inhibition
for a more detailed description of this topic.

In 1955, it was discovered that crystalline trichlorfon, another organophosphate pesticide, gave off a vapor which
was capable of killing insects. That vapor was dichlorvos, which has since been developed for insect control in
enclosed spaces .

Chemical Structure:

Application & Use:

Dichlorvos is effective against mushroom flies, aphids, spider mites, caterpillars ,thrips , and whiteflies in
greenhouses and in outdoor crops. It is also used in the milling and grain handling industries and to treat a variety
of parasitic worm infections in animals and humans. It is fed to livestock to control bot fly larvae in manure. It acts
against insects as both a contact and a stomach poison. It is available as an aerosol and soluble concentrate. It is
also used in pet collars and “no pest strips" in the form of a pesticide-impregnated plastic; this material has been
available to households since 1964 and has been the source of some concern, partly due to its misuse.

Toxicity:

• Dichlorvos exerts its toxic effect by irreversibly inhibiting neural acetylcholinesterase.The inhibition
provokes the accumulation of acetylcholine in synapses with disruption of nerve function. The
consequences of the altered cholinergic neurotransmission in the parasympathetic autonomic nervous
system includes perspiration, nausea, lacrimation, vomiting, diarrhea, excessive bronchial secretion or even
death. Effects on motor nerve fibers in skeletal muscles can include muscle cramps, muscle fasciculation,
muscle weakness and flaccidity. The cholinergic effect in the central nervous system results in drowsiness,
fatigue, mental confusion, headache, convulsions, coma and even death.

Amitraz:

Introduction: is a non-systemic acaricide and insecticide and has also been described as a scabicide. It was first
synthesized by the Boots Co. in England in 1969. Amitraz has been found to have an insect repellent effect, works as
an insecticide and also as a pesticide synergist.

Chemical Structure:

Application & Use:

• It is used topically to control ticks, mites, and lice on cattle, pigs and dogs as well as to treat demodectic
mange in dogs
• Amitraz is also used as an animal ectoparaciticide on cattle, goats, sheep, pigs and dogs.

21 | P a g e
 • Applied to treat demodicosis of cats or dogs, an exceeding infestation of mites of the family Demodicidae
• The most common use of amitraz is in tick collars, which contain 9% amitraz as an active ingredient

Toxicity:

• LD50 acute, rats, p.o. 800 mg/kg

• LD50 acute, mice, p.o. >1600 mg/kg
• LD50 acute, dogs, p.o. 100 mg/kg
• LD50 acute, rats, dermal >1600 mg/kg
• LD50 acute, rabbits, dermal >200 mg/kg
• As a general rule, dogs and livestock tolerate amitraz very well.

Clorsulon:

Introduction:

Clorsulon is a compound belonging to the benzenesulphonamide family which is recommended for the treatment
and control of adult liver flukes (Fasciola hepatica and Fasciola gigantica) in cattle as suspensions for oral use or
injectable formulations for subcutaneous administrations.

Chemical structure:

Application & Uses:

It is used in veterinary medicine for the treatment of liver fluke (monotherapy), gasrtointestinal and lung worms,
lice, grubs and mites (in combination with ivermectin) in cattles. Clorsulon inhibits the enzymes involved in the
glycolytic pathways of the common liver fluke (Fasciola hepatica or Fasciola gigantica), namely phosphoglycerate
kinase and phosphoglyceromutase.

Toxicity:

• LD50 acute, rats, p.o. 930 to >10000 mg/kg (depending on the studies)
• LD50 acute, rats ands mice, i.p. 678 to 938 mg/kg (depending on the studies)
• Cattle, sheep and goats tolerate clorsulon very well, both after oral and subcutaneous administration.
• Sheep tolerated single closulon doses of up 200 mg/kg without toxic symptoms (usual therapeutic dose: 4
to 21 mg/kg).
• Cattle tolerated single closulon doses of up 400 mg/kg without toxic symptoms (usual therapeutic dose: 4
to 21 mg/kg).

Chlorpyrifos :

Introduction:

Chlorpyrifos is a broad spectrum insecticide, a chemical used to kill a wide variety of insects. It was introduced in
1965 . These chemicals act by interfering with the activities of cholinesterase, an enzyme that is essential for the
proper working of the nervous systems of both humans and insects.

22 | P a g e
Chemical structure:

Application & Uses:

CPY is a widely used organophosphate pesticide with broad spectrum insecticidal activity. It is used against a broad
array of insects and mites, primarily as a contact insecticide, although it does have some efficacy through ingestion.
It provides control for many adult and larval forms of insects. Foliar pests for which CPY provides control include:
aphids, beetles, caterpillars, leafhoppers, mites, and scale. CPY is also effective against many soil insects, including
rootworms, cutworms, wireworms, and other grubs. Although it does not translocate readily, CPY can effectively
control boring insects in corn, fruit, and other crops through contact exposure. It can also provide contact control of
such insects as case-bearers, orange-worms, and other flies that damage fruits and nuts. The diversity of arthropod
pests subject to control with CPY has made it one of most widely used insecticides.

Toxicity:

Chlorpyrifos is considered moderately hazardous to humans by the World Health Organization based on its acute
toxicity. Exposure surpassing recommended levels has been linked to neurological effects, persistent developmental
disorders, and autoimmune disorders.

Phorate:

Introduction:

Phorate, an organophosphorus compound, is an insecticide and acaricide that controls pests by systemic,
contact, and fumigant action. It is used against sucking and chewing insects, leafhoppers, leafminers,
mites, some nematodes and rootworms.

Phorate is a Restricted Use Pesticide (RUP) and is among the most poisonous chemicals commonly used
for pest control.

Chemical Structure:

Application & Use:

• Restricted Use Pesticides may be purchased and used only by certified applicators.
• Phorate is an organophosphorus insecticide and acaricide used to control a wide variety of sucking
and chewing insects, leafhoppers, leafminers, mites, some nematodes, and rootworms.
• It is used on many crops, including root and field crops such as corn, cotton, coffee, potatoes.

23 | P a g e
 • Phorate has been shown to be responsible for a large number of bird kills and it is extremely toxic
to mammals.

Toxicity:

Phorate is closely related to demeton (see Demeton). It is a systemic insecticide and miticide. The oral
LD50 in rats is 1.6 mg/kg, and the dermal LD50 in rabbits is 2.5 mg/kg. The minimum toxic dose PO is 0.25
mg/kg in calves, 0.75 mg/kg in sheep, and 1 mg/kg in cattle.

BHC(Lindane):

Introduction:

Lindane, also known as gamma-hexachlorocyclohexane (γ-HCH), gammaxene, Gammallin and sometimes

incorrectly called benzene hexachloride (BHC), is an organochlorine chemical and an isomer of
hexachlorocyclohexane that has been used both as an agricultural insecticide and as a pharmaceutical
treatment for lice and scabies.

Lindane is a neurotoxin that interferes with GABA neurotransmitter function by interacting with the
GABAA receptor-chloride channel complex at the picrotoxin binding site. In humans, lindane affects the
nervous system, liver, and kidneys, and may well be a carcinogen.Whether lindane is an endocrine
disruptor is unclear.

Chemical Structure:

Application & Use:

This medication is used to treat scabies only after safer medications (such as permethrin or crotamiton)
have failed or caused side effects. It works by killing the tiny insects (mites) and their eggs, which cause
scabies. An infection with scabies is also called an infestation. This drug should not be used to prevent
scabies infestation or re-infestation.

This medication is used to treat scabies only after safer medications (such as permethrin or crotamiton)
have failed or caused side effects. It works by killing the tiny insects (mites) and their eggs, which cause
scabies. An infection with scabies is also called an infestation. This drug should not be used to prevent
scabies infestation or re-infestation.

Toxicity:

This medication may cause stinging, burning, or redness of the skin. If any of these effects persist or
worsen, notify your doctor or pharmacist promptly.Remember that your doctor has prescribed this
medication because the benefit to you is greater than the risk of side effects. Many people using this
medication do not have serious side effects.Tell your doctor immediately if these rare but very serious
side effects occur: vomiting, dizziness, drowsiness, seizures.A very serious allergic reaction to this drug is

24 | P a g e
unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may
include: rash, itching/swelling (especially of the face/tongue/throat).

Imidacloprid:

Introduction:

Imidacloprid is a systemic, chloro-nicotinyl insecticide with soil, seed and foliar uses for the control of
sucking insects including rice hoppers, aphids, thrips, whiteflies, termites, turf insects, soil insects and
some beetles.The chemical works by interfering with the transmission of stimuli in the insect nervous
system. Specifically, it causes a blockage in a type of neuronal pathway (nicotinergic) that is more
abundant in insects than in warm-blooded animals (making the chemical selectively more toxic to insects
than warm-blooded animals). This blockage leads to the accumulation of acetylcholine, an important
neurotransmitter, resulting in the insect's paralysis, and eventually death. It is effective on contact and
via stomach action.

Chemical Structure:

Application and use:

• Imidacloprid is a contact insecticide without systemic effect that belongs to the chemical class of
the neonicotinoids. It is highly effective against fleas and certain lice species, but not against ticks
or mites, or any internal parasites. It is often used in combination with a tickicide/acaricide (e.g.
cypermethrin, permethrin).
• Imidacloprid is abundantly used in dogs and cats, mainly in spot-ons and in a few collars and low-
cost sprays, shampoos, soaps, etc. Use in livestock is marginal, with a few pour-ons for cattle
(against horn flies) or sheep (against lice).
• Imidacloprid is a modern "classic" insecticide, introduced in the 1990's. It belongs to the
neonicotinoids and is BAYER's own flea active ingredient in the ADVANTAGE product range. It is
extensively used in agriculture.
• Imidacloprid has a broad spectrum of activity against insects (e.g. fleas and lice), but no efficacy
whatsoever against ticks or mites.
• In dogs and cats it is used a lot in spot-ons (= pipettes), alone against fleas and certain lice species,
or in mixtures with other active ingredients that broaden the spectrum of efficacy to control ticks
or other parasites. As most flea spot-ons it controls existing flea infestations in about 1 to 2 days,
and provides about 4 weeks protection against re-infestations.
• Use of imidacloprid on livestock is very scarce. It is approved for use as a louisicide on sheep in a
few countries (e.g. Australia), and there are also a few pour-ons for cattle, mainly against horn
flies (in Latin America).

25 | P a g e
 • Interestingly, BAYER introduced imidacloprid for pets in the 1990's but not for livestock. Only
recently it has introduced an off-shears sheep lousicide in Australia and New Zealand. So far
BAYER has not introduced it for use in cattle

Toxicity:

ACUTE TOXICITY

Imidacloprid is moderately toxic. The oral dose of technical grade imidacloprid that resulted in mortality
to half of the test animals (LD50) is 450 mg/kg body weight in rats, and 131 mg/kg in mice. The 24-hour
dermal LD50 in rats is >5,000 mg/kg. It is considered non-irritating to eyes and skin (rabbits), and non-
sensitizing to skin (guinea pigs). Some granular formulations may contain clays as inert ingredients that
may act as eye irritants. In acute inhalation toxicity tests with rats, the airborne concentration of
imidacloprid that resulted in mortality to half of the test organisms (LC50) is > 69 mg/meters cubed air in
the form of an aerosol, and >5323 mg/meters cubed air in the form of dust. These values represent the
maximum attainable airborne concentrations.

CHRONIC TOXICITY

A 2-year feeding study in rats fed up to 1,800 ppm resulted in a No Observable Effect Level (NOEL) of 100
ppm (5.7 mg/kg body weight in males and 7.6 mg/kg in females). Adverse effects included decreased body
weight gain in females at 300 ppm, and increased thyroid lesions in males at 300 ppm and females at 900
ppm. A 1-year feeding study in dogs fed up to 2,500 ppm resulted in a NOEL of 1,250 ppm (41 mg/kg).
Adverse effects included increased cholesterol levels in the blood, and some stress to the liver.

Teratogenic Effects

A developmental toxicity study in rats given doses up to 100 mg/kg/day by gavage on days 6 to 16 of
gestation resulted in a NOEL of 30 mg/kg/day (based on skeletal abnormalities observed at the next
highest dose tested of 100 mg/kg/day). In a developmental toxicity study with rabbits given doses of
imidacloprid by gavage during days 6 through 19 of gestation, resulted in a NOEL of 24 mg/kg/day based
on decreased body weight and skeletal abnormalities observed at 72 mg/kg/day.

Mutagenic Effects

Imidacloprid may be weakly mutagenic. In a battery of 23 laboratory mutagenicity assays, imidacloprid

tested negative for mutagenic effects in all but two of the assays.

Organ Toxicity

In short-term feeding studies in rats, there were thyroid lesions associated with very high doses of
imidacloprid.

Fate in Humans and Animals

Imidacloprid is quickly and almost completely absorbed from the gastrointestinal tract, and eliminated via
urine and feces (70-80% and 20-30%, respectively, of the 96% of the parent compound administered

26 | P a g e
within 48 hours). The most important metabolic steps include the degradation to 6-chloronicotinic acid,
a compound that acts on the nervous system as described above. This compound may be conjugated with
glycine and eliminated, or reduced to guanidine.

Carbaryl

Introduction:

Carbaryl is an antiparasitic active ingredient used in veterinary and human medicine. It is used in dogs and
livestock against external parasites (lice, mites, fleas, flies, ticks, etc.). It is also used against agricultural
and household pests. It belongs to the chemical class of the carbamates.

Chemical structure:

Application and Use:

• Carbaryl is a contact insecticide and acaricide without systemic effect that belongs to the chemical
class of the carbamates. It is effective against several external parasites of pets (e.g. fleas, ticks,
lice, mites) and livestock. It is not effective against internal parasites. Carbaryl is still used
moderately in dogs and cats, mainly in low-cost sprays, shampoos, soaps, etc. or in insecticide-
impregnated collars. It is still moderately used in swine and poultry, often as a powder, and in
larvicidal dressings and a few pour-ons for cattle in some countries (mainly Latin America) against
horn flies, cattle ticks.
• Carbaryl is a veteran pesticide, one of the first carbamates introduced in the 1950's.
• Use of carbaryl in livestock has always been scarce, because organophosphates and synthetic
pyrethroids were more effective. Today carbaryl is only used in a few dusts for pig & poultry, some
cattle pour-ons against flies, and a few dressing against fly maggots (myiases).
• In pets carbaryl was used a lot in the 1970's to 1990's before the introduction of modern highly
effective flea and tick spot-ons. Today it is still used in insecticide-impregnated collars, Shampoos,
soaps, powders, etc.
• In an evaluation from 2009 the US EPA (Environmental Protection Agency) classified carbaryl as a
potential carcinogen and prohibited all carbaryl products for pets.
• Carbaryl is quite effective against all kinds of insects, ticks and mites. However, resistance of dog
and cat fleas (Ctenocephalides spp), mosquitoes and poultry mites (Dermanyssus gallinae) to
carbamates is already quite frequent and products with carbaryl may not achieve the expected
efficacy
• The carbamates do not have the persistence of chlorinated pesticides. Although toxic to insects,
carbaryl is detoxified and eliminated rapidly in vertebrates. It is neither concentrated in fat nor
secreted in milk, so is favored for food crops, at least in the US.It is the active ingredient in
Carylderm shampoo.

27 | P a g e
 • Use in HORSES: NO
• Use in DOGS and CATS: Yes, quite frequent
• Use in human medicine: Yes, against lice
• Use in public/domestic hygiene: Yes
• Use in agriculture: Yes
• Generics available: Yes, a lot

Toxicity:

CHRONIC TOXICITY

Athough it may cause minor skin and eye irritation, carbaryl does not appear to be a significant chronic
health risk at or below occupational levels. Male volunteers who consumed low doses of carbaryl for six
weeks did not show symptoms, but tests indicated slight changes in their body chemistry.

Reproductive and Teratogenic Effects

No reproductive or fetal effects were observed during a long-term study of rats which were fed high doses
of carbaryl. The evidence for teratogenic effects due to chronic exposure are minimal in test amimals.
Birth defects in rabbit and guinea pig offspring occurred only at dosage levels which were highly toxic to
the mother. A 1980 New Jersey epidemiological study found no evidence of excess birth defects in a town
sprayed with carbaryl for gypsy moth control. There is only limited evidence that carbaryl causes birth
defects in humans. The EPA has concluded that carbaryl does not pose a teratogenic risk to humans if
used properly .

Carcinogenic Effects

Carbaryl has not caused tumors in ten longterm and lifetime studies of mice and rats. Rats were
administered high daily doses of the pesticide for two years, and mice for eighteen months, with no signs
of carcinogenicity. However, N-nitrosocarbaryl, formed by the reaction of carbaryl and nitrite, has been
shown to be carcinogenic in rats at high doses. Also, mice exposed to carbaryl in the product, tricaprylin,
for four weeks each, developed lung tumors.

Organ Toxicity

Ingestion of carbaryl affects the lungs, kidneys and liver. Inhalation will also affect the lungs. Nerve
damage can occur after administration of high doses for 50 days in rats and pigs. Several studies indicate
that carbaryl can affect the immune system in animals and insects. These effects however have not been
documented in humans.

ECOLOGICAL EFFECTS

Carbaryl is lethal to many nontarget insects. The pesticide is more active in insects than in mammals. The
destruction of honeybee populations in sprayed areas is sometimes a problem. Carbaryl is moderately
toxic to aquatic organisms, such as rainbow and lake trout, bluegill, and cutthroat. It is also moderately
toxic to wild bird species, with low toxicity to Canada geese.

Accumulation of carbaryl can occur in catfish, crawfish, and snails, as well as in algae and duckweed.
Residue levels in fish were 140 fold greater than the concentration of carbaryl in water. In general, due to

28 | P a g e
its rapid metabolism and rapid degradation, carbaryl should not pose a significant bioaccumulation risk in
alkaline waters. However, under conditions below neutrality it may be significant.

Fipronil:

Introduction :

Fipronil is an antiparasitic active ingredient used in veterinary medicine in dogs, cats and livestock against
external parasites (fleas, flies, ticks, lice, mites, etc.). It is also used against agricultural and household
pests. It belongs to the chemical class of the phenylpyrazoles.

Chemical Structure:

Uses:

• Under the trade name Regent, it is used against major lepidopteran (moth, butterfly, etc.) and
orthopteran (grasshopper, locust, etc.) pests on a wide range of field and horticultural crops and
against coleopteran (beetle) larvae in soils. In 1999, 400,000 hectares were treated with Regent.
It became the leading imported product in the area of rice insecticides, the second-biggest crop
protection market after cotton in China.
• Under the trade names Goliath and Nexa, it is employed for cockroach and ant control, including
in the United States. It is also used against pests of field corn, golf courses, and commercial lawn
care under the trade name Chipco Choice.
• It has been used under the trade name Adonis for locust control in Madagascar and Kazakhstan.
• Marketed under the names Termidor, Ultrathor, and Taurus in Africa and Australia, fipronil
effectively controls termite pests, and was shown to be effective in field trials in these countries.
• Termidor has been approved for use against the Rasberry crazy ant in the Houston, Texas, area,
under a special "crisis exemption" from the Texas Department of Agriculture and the
Environmental Protection Agency. The chemical is only approved for use in Texas counties
experiencing "confirmed infestations" of the newly discovered ant species.Use of Termidor is
restricted to certified pest control operators in the following states: Alaska, Connecticut,
Nebraska, South Carolina, Massachusetts, Indiana, New York, and Washington.[citation needed]
• In Australia, it is marketed under numerous trade names, including Combat Ant-Rid, Clear-out,
Fipforce, Radiate and Termidor, and as generic fipronil.
• In the UK, provisional approval for five years has been granted for fipronil use as a public hygiene
insecticide.
• Fipronil is the main active ingredient of Frontline TopSpot, Fiproguard, Flevox, and PetArmor
(used along with S-methoprene in the 'Plus' versions of these products); these treatments are
used in fighting tick and flea infestations in dogs and cats.
• In New Zealand, fipronil was used in trials to control wasps (Vespula spp.), which are a threat to
indigenous biodiversity. It is now being used by the Department of Conservation to attempt local
eradication of wasps, and is being recommended for control of the invasive Argentine ant.

29 | P a g e
Toxicity

• Fipronil is classed as a WHO Class II moderately hazardous pesticide, and has a rat acute oral LD50
of 97 mg/kg.
• It has moderate acute toxicity by the oral and inhalation routes in rats. Dermal absorption in rats
is less than 1% after 24 h and toxicity is considered to be low. It has been found to be very toxic
to rabbits.
• The photodegradate MB46513 or desulfinylfipronil, appears to have a higher acute toxicity to
mammals than fipronil itself by a factor of about 10.
• Symptoms of acute toxicity via ingestion includes sweating, nausea, vomiting, headache,
abdominal pain, dizziness, agitation, weakness, and tonic-clonic seizures. Clinical signs of
exposure to fipronil are generally reversible and resolve spontaneously. As of 2011, no data were
available regarding the chronic effects of fipronil on humans. The United States Environmental
Protection Agency has classified fipronil as a group C (possible human) carcinogen based on an
increase in thyroid follicular cell tumors in both sexes of the rat. However, as of 2011, no human
data are available regarding the carcinogenic effects of fipronil.
• Two Frontline TopSpot products were determined by the New York State Department of
Environmental Conservation to pose no significant exposure risks to workers applying the
product. However, concerns were raised about human exposure to Frontline spray treatment in
1996, leading to a denial of registration for the spray product. Commercial pet groomers and
veterinary physicians were considered to be at risk from chronic exposure via inhalation and
dermal absorption during the application of the spray, assuming they may have to treat up to 20
large dogs per day.Fipronil is not volatile, so the likelihood of humans being exposed to this
compound in the air is low.
• In contrast to neonicotinoids such as acetamiprid, clothianidin, imidacloprid, and thiamethoxam,
which are absorbed through the skin to some extent, fipronil is not absorbed substantially through
the skin.
• Detection in body fluids
• Fipronil may be quantitated in plasma by gas chromatography-mass spectrometry or liquid
chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalised patients
or to provide evidence in a medicolegal death investigation.
• Ecological toxicity
✓ Fipronil is highly toxic for crustaceans, insects and zooplankton, as well as bees, termites,
rabbits, the fringe-toed lizard, and certain groups of gallinaceous birds. It appears to reduce
the longevity and fecundity of female braconid parasitoids. It is also highly toxic to many fish,
though its toxicity varies with species. Conversely, the substance is relatively innocuous to
passerines, wildfowl, and earthworms.
✓ Its half-life in soil is four months to one year, but much less on soil surface because it is more
sensitive to light (photolysis) than water (hydrolysis).
✓ Few studies of effects on wildlife have been conducted, but studies of the nontarget impact
from emergency applications of fipronil as barrier sprays for locust control in Madagascar
showed adverse impacts of fipronil on termites, which appear to be very severe and long-
lived.

30 | P a g e
 ✓ Nontarget effects on some insects (predatory and detritivorous beetles, some parasitic wasps
and bees) were also found in field trials of fipronil for desert locust control in Mauritania, and
very low doses (0.6-2.0 g a.i./ha) used against grasshoppers in Niger caused impacts on
nontarget insects comparable to those found with other insecticides used in grasshopper
control. The implications of this for other wildlife and ecology of the habitat remain unknown,
but appear unlikely to be severe. Unfortunately, this lack of severity was not observed in bee
species in South America. Fipronil is also used in Brazil and studies on the stingless bee
Scaptotrigona postica have shown adverse reactions to the pesticide, including seizures,
paralysis, and death with a lethal dose of .54 ng a.i./bee and a lethal concentration of .24 ng
a.i./μl diet. These values are highly toxic in Scaptotrigona postica and bees in general. Toxic
baiting with fipronil has been shown to be effective in locally eliminating German wasps. All
colonies within foraging range were completely eliminated within one week.
✓ In May 2003, the French Directorate-General of Food at the Ministry of Agriculture
determined that a case of mass bee mortality observed in southern France was related to
acute fipronil toxicity. Toxicity was linked to defective seed treatment, which generated dust.
In February 2003, the ministry decided to temporarily suspend the sale of BASF crop
protection products containing fipronil in France. The seed treatment involved has since been
banned.
✓ Notable results from wildlife studies include:
✓ Fipronil is highly toxic to fish and aquatic invertebrates. Its tendency to bind to sediments and
its low water solubility may reduce the potential hazard to aquatic wildlife.
✓ Fipronil is toxic to bees and should not be applied to vegetation when bees are foraging.
✓ Based on ecological effects, fipronil is highly toxic to upland game birds on an acute oral basis
and very highly toxic on a subacute dietary basis, but is practically nontoxic to waterfowl on
both acute and subacute bases.
✓ Chronic (avian reproduction) studies show no effects at the highest levels tested in mallards
(NOEC) = 1000 ppm) or quail (NOEC = 10 ppm). The metabolite MB 46136 is more toxic than
the parent to avian species tested (very highly toxic to upland game birds and moderately
toxic to waterfowl on an acute oral basis).
✓ Fipronil is very highly toxic to bluegill sunfish and highly toxic to rainbow trout on an acute
basis.
✓ An early-lifestage toxicity study in rainbow trout found that fipronil affects larval growth with
a NOEC of 0.0066 ppm and an LOEC of 0.015 ppm. The metabolite MB 46136 is more toxic
than the parent to freshwater fish 6.3 times more toxic to rainbow trout and 3.3 times more
toxic to bluegill sunfish). Based on an acute daphnia study using fipronil and three
supplemental studies using its metabolites, fipronil is characterized as highly toxic to aquatic
invertebrates.
✓ An invertebrate lifecycle daphnia study showed that fipronil affects length in daphnids at
concentrations greater than 9.8 ppb.

31 | P a g e
 ✓ A lifecycle study in mysids shows fipronil affects reproduction, survival, and growth of mysids
at concentrations less than 5 ppt.
✓ Acute studies of estuarine animals using oysters, mysids, and sheepshead minnows show that
fipronil is highly acutely toxic to oysters and sheepshead minnows, and very highly toxic to
mysids. Metabolites MB 46136 and MB 45950 are more toxic than the parent to freshwater
invertebrates (MB 46136 is 6.6 times more toxic and MB 45950 is 1.9 times more toxic to
freshwater invertebrates).
✓ Colony collapse disorder
✓ Fipronil is one of the main chemical causes blamed for the spread of colony collapse disorder
among bees. It has been found by the Minutes-Association for Technical Coordination Fund
in France that even at very low nonlethal doses for bees, the pesticide still impairs their ability
to locate their hive, resulting in large numbers of forager bees lost with every pollen-finding
expedition. A synergistic toxic effect of fipronil with the fungal pathogen Nosema ceranae was
recently reported. The functional basis for this toxic effect is now understood: the synergy
between fipronil and the pathogenic fungus induces changes in male physiology leading to
infertility

Flumethrin:

Introduction

Flumethrin is an antiparasitic active ingredient used in veterinary medicine in livestock and pets against
external parasites (lice, mites, fleas, flies, ticks, etc.). It is not used against agricultural or household pests.
It belongs to the chemical class of the synthetic pyrethroids.

Chemical Structure:

Application & Use:

• As all synthetic pyrethroids, flumethrin products are always used for topical administration and
act by contact without any systemic efficacy. Flumethrin is used moderately in livestock in the
form of concentrates for dipping or spraying, or in ready-to-use pour-ons. Use in dogs is rather
scarce mainly in the form of a few insecticide-impregnated collars, spot-ons or low-cost topicals
such as shampoos, soaps, sprays, etc.
• Flumethrin (and many other synthetic pyrethroids) is effective against most external livestock and
dog parasites (flies, ticks, mites, lice, fleas, mosquitoes, etc.) but is completely ineffective against
internal parasites. It is one of the best synthetic pyrethroids against ticks and mites, but rather
mediocre against insects (flies, mosquitoes, lice, etc.).

32 | P a g e
 • However, resistance to all synthetic pyrethroids is already very frequent worldwide and can be
extremely high, particularly in cattle ticks, horn & buffalo flies, houseflies, red fowl mites,
mosquitoes, fleas, etc.
• Flumethrin is a synthetic pyrethroid particularly effective against ticks and mites, but only
mediocre against insects. It has been vastly used on livestock, but very seldom on pets.
• Flumethrin is a mixture of various optic isomers, but all commercial products contain the same
mixture, i.e. this makes no difference in the product quality or efficacy.
• Although patent has expired long ago, there are only a few generic veterinary products available.
• Flumethrin is an ectoparasiticide, i.e. active only against external parasites such as flies, ticks,
mites, lice, fleas, mosquitoes, etc. However it is certainly more effective against livestock ticks and
mites than other pyrethroid generalists such as cypermethrin, deltamethrin and permethrin. It is
one of the best active ingredients against both single-host ticks (e.g Boophilus spp) and multi-host
ticks (e.g. Amblyomma, Rhipicephalus, Ixodes, Dermacentor, etc,). It is also excellent against
several scab and mange mites (e.g. Psoroptes spp., Sarcoptes spp, etc.). However, it is only a
mediocre insecticide less effective against flies, lice, fleas and mosquitoes than other synthetic
pyrethroids.
• As most synthetic pyrethroids, flumethrin is a mediocre larvicide, i.e. it is not a good option for
the large-scale prevention of cutaneous myiases (e.g. screwworms, blowfly strike, etc.) with
sprays, pour-ons, etc.
• Flumethrin, as well as many other synthetic pyrethroids has a significant repellent effect on
certain ticks, which strongly depends on the delivery form and the dose administered
• Synthetic pyrethroids, including flumethrin, have a similar mode of action as organochlorines.
They act on the membrane of nerve cells blocking the closure of the ion gates of the sodium
channel during re-polarization. This strongly disrupts the transmission of nervous impulses,
causing spontaneous depolarization of the membranes or repetitive discharges. At low
concentrations insects and other arthropods suffer from hyperactivity. At high concentrations
they are paralyzed and die. Sensory and nervous cells are particularly sensitive.

Toxicity:

Acute Toxicity and Tolerance:

• LD50 acute, rats, p.o. 41 (oil vehicle) to 3859 (aqueous vehicle). The vehicle-dependant
differences in the acute oral toxicity are typical for synthetic pyrethroids.
• LD50 acute, rats, dermal, >2000 mg/kg
• In toxicity studies, dogs (Beagles) were fed flumethrin mixed with food at 25, 50, 100 and 200
mg/kg feed during 13 weeks. At the end of the study all dogs showed skin lesions (thickened skin
covered with hyperkeratotic material) at doses >50 mg/kg feed. The NOEL (No Observable Effect
Level) was 25 mg/kg feed, equivalent to 0.88 mg/kg bw per day.
• In cattle treated topically at 2x the therapeutic dose a few animals showed erythema (skin
redness) at the application site and transient diarrhea.
• In cattle, the pour-on formulation has a safety margin of 50. At doses of up to 10 mg/kg no adverse
effects were recorded on skin, hair coat or hides. Five consecutive treatments at a dose 4 mg/kg
in intervals of 3 to 4 days did not cause adverse effects.

33 | P a g e
 • Sheep and goats treated at 10x the therapeutic dose didn't show signs of intoxication. At 20x the
therapeutic dose 50% of the sheep died, but it could not be excluded that this was due to the
vehicle.
• As a general rule, dogs and livestock (cattle, sheep, goats) tolerate flumethrin and most synthetic
pyrethroids very well, since toxicity is about 1000x higher to insects and other arthropods than to
mammals. But toxicity to mammals can be higher in case of sustained skin or inhalation exposure,
or after direct contact with open wounds.
• WARNING: cats are more susceptible to synthetic pyrethroids than dogs. Cats may not tolerate
doses of flumethrin that are harmless for dogs. This is associated with glucuronidase deficiency in
cats, the enzyme responsible for breaking down most synthetic pyrethroids in the organism in a
process called glucuronidation. As a consequence, synthetic pyrethroids remain much longer in
the cat's organism than in dogs or other mammals.
• Toxic Symptoms caused by Flumethrin Poisoning
• The primary symptoms of intoxication with flumethrin and other synthetic pyrethroids affect
mainly the nervous and muscular systems.
• Most frequent symptoms are:
• Ataxia (uncoordinated movements)
• Hyperreactivity (exaggerated reaction to stimuli)
• Tremor (uncoordinated trembling or shaking movements)
• Paresthesia (skin sensation of tingling, tickling, prickling)
• Exhaustion (lethargy, fatigue)
• Hypersalivation (drooling)
• Vomit
• Diarrhea
• Urinary incontinence
• Other symptoms after severe poisoning include: hyperthermia (fever) or hypothermia (too low
body temperature), dyspnea (difficult breathing), disorientation, cramps or spasms (sudden,
involuntary contractions of muscles or hollow organs).
• Symptoms appear a few hours after exposure, but depend strongly on the formulation, the dose
and the kind of contact (skin, inhalation, ingestion etc).
• Sustained skin exposure can cause local dermatitis (skin irritation) with pruritus (itching) and
erythema (red skin).
• Mucous membranes are particularly sensitive to synthetic pyrethroids, e.g. in the nose and the
respiratory system (coughing), in the eyes (conjunctivitis), genital organs, etc.
• After excessive inhalation of synthetic pyrethroids patients can develop allergic sensitization with
asthmatic symptoms. In extreme cases, sustained inhalation of high doses can cause respiratory
paralysis and death.
• As a general rule, young animals are more sensitive to overdosing and react stronger.
• A frequent administration error in dogs is partial administration to small dogs of spot-ons
approved for large dogs.
• Flumethrin Side Effects, Adverse Drug Reactions (ADRs) and Warnings
• Do not administer flumethrin topically (spot-on, shampoos, soaps, sprays, etc.) in case of
extended skin lesions: this can lead to an excessive absorption through the damaged skin.

34 | P a g e
 • Pour-ons containing flumethrin and other synthetic pyrethroids can be irritant for cattle. This can
be particularly annoying when handling dairy cows for milking.
• In small dogs paresthesia (skin sensation of tingling, tickling, prickling) can happen at the
therapeutic dose, which usually disappears in 12 to 24 hours.
• Toxic effects can be potentiated after simultaneous exposure to organophosphates or other
synthetic pyrethroids.
• Never use spot-ons or other products on cats that are approved only for dogs: synthetic
pyrethroids can be toxic to cats.
• Never use spot-ons for large dogs on small dogs. It happens that some users want to save money
buying large spot-ons for treating smaller dogs twice or more times. The risk of overdosing is
considerable, either due to erroneous calculations or to unskilled manipulation. Remaining
product in opened spot-on vials can deteriorate.
• Unless prescribed by a veterinary doctor, never use on dogs or cats products for livestock that are
not explicitly approved for such use. There is a high risk of overdosing or of adverse drug reactions
due to ingredients that are not tolerated by pets or are even toxic to them.

Environmental Toxicity of Flumethrin

• Flumethrin, as all synthetic pyrethroids is extremely toxic to fish and aquatic invertebrates (more
in cold than in warm water). For this reason disposal of flumethrin residues (e.g. in empty
containers) in watercourses must be absolutely avoided. Disposal of old dip wash charged with
flumethrin (or other synthetic pyrethroids) into watercourses is strictly forbidden worldwide
because it would have catastrophic consequences for fish and other aquatic animals. There are
countries where products for livestock dipping containing synthetic pyrethroids have been
withdrawn by the regulatory authorities for this reason.
• In contrast with organophosphates flumethrin (as most synthetic pyrethroid) is not toxic to birds.
• There is a certain environmental risk of water pollution from run-off after pour-on administration
to large cattle herds. However this risk is substantially lower than the one associated with the use
of synthetic pyrethroids in crop pesticides.
• Correct use on livestock and pets is unlikely to result in any significant environmental pollution.
• Flumethrin is quite resistant to photodegradation, i.e. exposed to sunlight it breaks down rather
slowly.
• Flumethrin is almost insoluble in water and tends to bind to soil particles. Therefore groundwater
contamination is unlikely to occur. Persistence in water depends on pH and temperature.
• Soil bacteria contribute to the biodegradation of flumethrin.
• Flumethrin does not bioaccumulate

35 | P a g e