UNIT 6 PESTICIDE RESIDUES IN FOODS THEIR

TOXICOLOGY AND SAFETY

Structure
6.0 Objectives
6.1 Introduction
6.2 Terms and definitions
6.3 Classification of pesticides
6.3.1 Classification based on target pests
6.3.2 Classification based on mode of action
6.3.3 Categorization of pesticide based on toxicity level
6.3.4 Classification based on chemical structure
6.4 Mode of action, pharmacokinetics, and toxic dose of chemical pesticides
6.4.1 Organochlorine compounds
6.4.2 Organo Phosphorous compounds
6.4.3 Carbamates
6.4.4 Pyrethroids
6.5 Safety evaluation of pesticide residues
6.5.1 Maximum residue limits
6.6 Management of chemical pesticides and its regulation
6.6.1 Role of WHO
6.6.2 Role of Codex Alimentarius Commission
6.6.3 Pesticide regulation in India
6.7 Reduction of pesticide residues in food
6.8 Let Us Sum Up
6.9 Key Words
6.10 References/Suggested Readings
6.11 Answers to Check Your Progress Exercises

6.0 OBJECTIVES
After studying this unit, you shall be able to
 Identify the sources and occurrence of pesticides in food commodities
 Classification of pesticides based on differentcriteria
 Explain mode of action and toxicokineticsof pesticides
 Describe safety evaluation measures with the help of maximum residue limits; and
  Outline the measures for pesticide residue controlin food commodities

6.1 INTRODUCTION
In the previous units, you have studied about the basics of food toxicology,natural toxins
that could be present in food chain. You have also learned various detection methods to identify
the presence of toxicants in foods and their toxicological assessment by undertaking in vitro and
in vivostudies. You are also familiarwith the factors that makes food unfit for consumption
especially presence of contaminants, toxic substances,and adulterants. Pesticides are one such
potential contaminants that posegreat risk to humans and ecosystems, if not used wisely. Instead
of occurring naturally, pesticides are man-made contaminant. We all know that chemical
pesticides play a significant role in agriculture. There are more than 1000 pesticides used around
the world to protect crops against insects, weeds, fungi and other pests. Each oneexhibits
different properties and toxicological effects.Depending on the quantity, duration, and mode of
exposure, pesticides can cause acute and chronic health effects in humans. In India, most
abundantly used pesticides includes insecticides and fungicides followed by herbicides and
rodenticides. In FY2020, the pesticide consumption in India was 192 thousand metric tons which
was raised to 255 thousand metric tons in 2021. India is also one of the largest manufacturers of
pesticides globally.The highest pesticide consumption can be seen in the states of Maharashtra,
followed by UP, Punjab, and Haryana. Still, per hectare consumption of pesticides is
considerably lower in India ascompared toother countries..
According to World Health Organization (WHO), pesticides shall be tested for all
possible health risks andthe outcomes shall be analysedby experts before they are authorized for
use. It is also important to note that just because a pesticide residue is detected on a food
commodity, that doesn’t mean it is unfit for consumption. Very small amounts of pesticide
residuesremain on the harvested fruits, vegetables, grains, and other food commoditiesand their
concentration decreases considerably during further handling and transportation due to exposure
to sunlight, washing, and preparation of food. General sources of exposure of pesticides in
humans may be accidental, intentional, or occupational. Accidentally, pesticides may enter
water, air, or anywhere when it is sprayed or applied to crops. Residues occur when these
pesticides are sprayed on crop products in excess of recommended levels/not following
withdrawal period. There are three ways by which a pesticide can enter the human body: by
direct contact through the skin, oral ingestion, and by inhalation. Keeping this in view, the
present unit deals with the occurrence, classification, sources, mode of toxic action, toxicity, and
related regulations of various pesticides. The unit also discusses importance of corrective actions
to reduce usage of pesticides in safeguarding public health.

6.2 TERMS AND DEFINITIONS

Pest:According to Food and Agricultural Organization (FAO,2014),pest means “any species,
strain or biotype of plant, animal or pathogenicagent injurious to plantsand plantproducts,
materials or environmentand includes vectors of parasites orpathogens of human and animal
disease and animals causing public healthnuisance.”
Pesticide:Pesticides are defined as broad spectrum of chemical or organic substances which
include insecticides, fungicides, herbicides, plant growth regulators, etc. Pesticides are defined
by the pesticide management bill, 2020 as “any substance or mixture of substances, including a
formulation of chemical or biological origin intended for preventing, destroying, attracting,
repelling, mitigating or controlling any pest in agriculture, industry, pest control operations,
public health, storage or for ordinary use, and includes any substance intended for use as a plant
growth regulator, defoliant, desiccant, fruit thinning agent, or sprouting inhibitor and any
substance applied to crops either before or after harvest to protect them from deterioration during
storage and transport”.
Residue: A residue is defined by the European Union (EU) and the Center for Veterinary
Medicine (FDA/CVM), an agency working under the Food and Drug Administration (FDA) of
the USA as follows: “pharmacologically active substances (either active principles, recipients or
degradation products of these) and their metabolites remaining in foodstuffs or any place at any
point of time”.
Maximum Residue Limit (MRL): According to FAO,“the maximum concentration of aresidue
that is legally permitted or recognized as acceptable in or on a food oragricultural commodity or
animal feedstuff (FAO, 2014).”
Life cycle: According to FAO, life cycle of a pesticide referes to “all the stages a pesticide might
pass through from productionto its degradation in the environment after use, or its destruction as
an unusedproduct. The life cycle includes manufacture, formulation, packaging, distribution,
storage, transport, use and finaldisposal of a pesticide product and/or itscontainer (FAO, 2014).”
Good agricultural practice (GAP): According to FAO,“GAP in theuse of pesticides includes
the officiallyrecommended or nationally authorizeduses of pesticides under actual
conditionsnecessary for effective and reliable pestcontrol.
It encompasses a range of levelsof pesticide applications up to the highestauthorized use, applied
in a manner whichleaves a residue which is the smallestamount practicable (FAO, 2014).”
Withdrawal period: The wait time between the pesticide application and harvesting of a crop.
During withdrawal period, pesticide is either completely broken down in the plant/soil or present
in a very miniscule quantity well below the MRL.

Check Your Progress Exercise 1

Note a) Use the space below for your answer
b) Compare your answers with those given at the end of the unit.

1. Substance that is used to eradicate plants that grow along with food crops are ……. Tick
mark (√ ) the right choice.

i) Pests
ii) Weeds
iii) Weedicides
iv) Insect

2. Expand the following terms

a) GAP
b) FAO
c) MRL

3. Define the following terms:

a) Pesticide

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b) Life cycle of pesticide

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4. What is a residue? What is its significance?

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6.3 CLASSIFICATION OF PESTICIDES

You are now familiar with the terms pests and pesticides. In this section, you can learn how
pesticides are classified.Pesticides can be classified based on their use/ target pests, mode of
action, toxicity, and molecular structure.

6.3.1 Classification based on target pests

S. Term Definition Examples

No.

1 Acaricides Used to kill mites and ticks, DDT, Fenpyroximate, dicofol

or for disrupting their
growth and development

2 Antifeedants To preventinsects or other Chlordimeforn, Azadirachtin,

pests from feeding Fentin

3 Bactericides To destroy or inhibit Copper hydroxide, Kasugamycin,

bacteria in soil/plants Streptomycin, Tetracycline

4 Fungicides To prevent or cure the Thiabendazole, thiophanate-

fungal infection methyl, carbendazim

5 Chemosterillants Prevents reproducing Aziridinyl, Diflubenzuron

capacity of insects

6 Herbicides Pesticides used to destroy Paraquat, Glyphosate, 2,4-D

plants
7 Insecticides Pesticides used to destroy Imp. groups Organophosphates,
insects organochlorines, carbamates,
phenylpyarazole, neonicotenoids,
etc
Source: WHO (2009)

Pesticidesare use in India for the following purposes:

1. To control insects (80%)
2. To destroy weeds (15%)
3. To control fungal diseases (1.46%)
4. For other reasons (3%)
On the other hand, global pesticide consumption is as follows:
1. Herbicides - 47.5%
2. Insecticides - 29.5%
3. Fungicides are 17.5%
4. Others - 5.5%

6.3.2 Classification based on mode of action

The following table gives the classification of pesticides based on their mode of action.

S.No Type Defintion Examples

1 Contact Acts on the pesticides and enters the pest Endosulfan,

insecticides through dermal contact Malathion,
fenvalerate

2 Stomach Act inside the gut, enter through ingestion toxins produced by
insecticides bacterium Bacillus
thuringiensis, zinc
phosphide
(rodenticide)

3 Fumigant Gaseous pesticides Aluminium

Phosphide, methyl
to control pests in storage houses or other sites
bromide,chloropicrin
and iodoform

4 Systemic The active ingredient in such pesticides are Monocrotophos,

pesticides taken up by the plant and transported to carbofuran
 various location throughout the plant where it
prevent plant eating pests

Source: JECFA (2000)

6.3.3 Categorization ofpesticides based on toxicity level

The following table gives the classification of pesticides based on toxicity level

Dermal LD50
Oral LD50mg/kg body Label colour
Level of toxicity mg/kg body wt. of Indication
wt. of test animals to be used
test animals

Extremely toxic 1-50 1-200 Brightred

Highlytoxic 50-500 200-2000 Brightyellow

Moderately toxic 500-5000 2000-20000 Brightblue

Slightly toxic Above5000 Above 20000 Brightgreen

Source: Draft manual for certificate course on plant protection &pesticide management, ICAR

6.3.4 Classification based on chemical structure

Classification based on chemical structure is given in the table below:

S.No Criteria Types

1 Based on molecular 1. Organic

structure 2. Inorganic

Source: WHO (2009)

6.3.4.1 Organic pesticides

Most of the currently used pesticides are organic in nature. They can be further classified into
the following sub types.
 Natural organics, and
 Synthetic organics
Natural Organics in Pesticides:
Natural organics in pesticides are compounds derived from natural sources that are used to
control pests. These substances are often extracted from plants or microorganisms. Here are a
few examples:
Pyrethrin: derived from chrysanthemum flowers - commonly used in household insect sprays and
pet shampoos.
Rotenone: extracted from the roots of certain plants, such as the jicama vine - broad-spectrum
insecticide - interferes with the cellular respiration of pests
Neem oil: derived from the seeds of the neem tree - contains several active compounds - has
insecticidal, fungicidal, and miticidal properties - widely used in organic farming.
Synthetic Organics in Pesticides:
Synthetic organics in pesticides are chemical compounds that are artificially synthesized and
used for pest control purposes. These compounds are typically designed to be more potent and
persistent than their natural counterparts.
It's important to note that the distinction between natural and synthetic pesticides can be
complex, as some synthetic pesticides may be based on natural compounds or derived from
natural sources but are chemically modified to enhance their effectiveness or stability.
Synthetic organics pesticides are further classified into different sub classes as following
 Organochlorines
 Organophosphates
 Carbamates
 Pyrethroids
Different categories of synthetic pesticides are illustrated in the following table
Class Example Area of action
Organochlorine DDT, aldrin, dieldrin, Reproductive system, nervous system,
pesticides toxaphene endocrine glands, and immune system
Organophosphate Diazinon, malathion, Nervous system
compounds glyphosate
Carbamate pesticides Carbofuran, carbaryl, Nervous system
aldicarb
Pyrethroid compounds Fenpropanthrin, Nervous system
cypermethrin, deltamethrin,

Source: WHO (2009)

6.3.4.2 Inorganic pesticides

Inorganic pesticides are chemical compounds that are derived from non-living matter, typically
minerals, and are used for pest control purposes. They differ from organic pesticides in that they
do not contain carbon-based compounds.
Example: Copper sulfate is a commonly used inorganic pesticide. It is a compound composed of
copper, sulfur, and oxygen. It is available in various forms, such as copper sulfate pentahydrate,
and is used to control fungi, bacteria, and some insect pests.
Inorganic pesticides are still used today, but their usage is often limited to specific situations and
crops. use of inorganic pesticides has decreased over time due to increasing concerns about their
potential toxicity and environmental impact. Many countries have implemented regulations and
restrictions on their use to ensure safer and more sustainable pest control practices.

Check Your Progress Exercise 2

Note a) Use the space below for your answer

b) Compare your answers with those given at the end of the unit.

1. You have read about the categorization of pesticides based on different criteria. How do you
think these pesticides affect human systems?
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2.List the different criteria for pesticide classification.
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6.4 MODE OF ACTION, PHARMACOKINETICS, AND TOXIC DOSE

OF CHEMICAL PESTICIDES IN HUMANS
Before understanding pharmacokinetics and toxicity, we need to understand that the routes of
exposure to pesticides, could be oral (through swallowing by mouth), dermal (ingestion through
the skin), or the parenteral route (administration by injection). WHO (World Health
Organization) has providedspecific limits for different routes of exposure of pesticides. The
below table gives you an idea of different dosages expected to cause toxicity or risk through any
chemical.

Oral route of exposure

LD 50 (mg/kg
Category No. Hazard level statement
body weight)

1
<5 Fatal on swallowing

2 5–50 Fatal on swallowing

3 50–300 Toxic on swallowing

4 300–2000 Harmful on swallowing

5 2000–5000 It may be harmful when swallowed

Source: JECFA (2000)

6.4.1 Organochlorine compounds

Organochlorine compounds are a class of chemicals that contain carbon atoms bonded to
chlorine atoms. These pesticides compounds attached with five or more chlorine atoms. DDT
[dichloro-diphenyl-trichloroethane] is an example, which has bee now banned to be used as a
pesticide. Some other examples include BHC, lindane, methoxychlor, chlorobenzilate, and
cyclodienes including aldrin, dieldrin, chlordane, heptachlor, and endrin.

6.4.1.1. Mode of action: These are known to be neurotoxins that disturb the nerve impulses
transmission to the brain. It may lead to behavioral changes, restriction of respiratory spots,
involuntary muscle movements, etc. These are also hepatotoxic that may lead to liver or renal
injury, which is mainly due to the production of toxic metabolites. Various compounds of this
category are also found to be carcinogenic.

6.4.1.2 Mechanism of Toxic Action

While some organochlorine compounds have been widely used in the past, their usage has been
significantly restricted due to concerns about their persistence in the environment and potential
toxicity. Here are examples of organochlorine compounds and their mechanism of toxicity:
Dichlorodiphenyltrichloroethane (DDT): DDT is a well-known organochlorine insecticide that
was widely used for pest control in agriculture and disease vector control. Its mechanism of
toxicity involves disrupting the nervous system of insects. DDT targets the sodium channels in
insect nerve cells, leading to their prolonged activation and disruption of normal nerve signal
transmission. This causes overstimulation, paralysis, and ultimately death in susceptible insects.

Polychlorinated Biphenyls (PCBs): PCBs are a group of organochlorine compounds that were
commonly used as coolants and lubricants in electrical equipment, as well as in various industrial
applications. PCBs are persistent organic pollutants that can accumulate in the environment and
organisms. The exact mechanism of their toxicity is not fully understood, but it is believed that
they can disrupt endocrine function, interfere with the immune system, and have carcinogenic
effects.

Chlorinated Pesticides (e.g., chlordane, lindane): Various chlorinated pesticides have been used
in the past, but many of them are now banned or restricted due to their potential toxicity and
environmental persistence. These pesticides can have different mechanisms of toxicity
depending on their specific chemical structure. For example, chlordane and lindane are
insecticides that affect the nervous system by interacting with GABA receptors, which are
involved in inhibitory neurotransmission. This interference with GABA receptors can lead to
hyperexcitability of nerve cells, resulting in insect death.

The toxicity of organochlorine compounds can vary depending on their specific chemical
properties and the organism being exposed. While some organochlorines have been phased out
or restricted due to their adverse effects on human health and the environment, their persistence
in the environment means they can still be detected in certain areas even today. Use of
organochlorine compounds has been largely replaced by alternative chemicals and more
environmentally friendly approaches to pest control to mitigate the risks associated with their
toxicity and persistence.

These compounds are seen to be absorbed well in the gastrointestinal tract, into the skin, and by
air inhalation. These compounds getrapidly accumulated in fatty tissues owing to the lipophilic
nature. The elimination of such compounds will not happen any sooner since these reactions do
not follow first-order kinetics. Slow release of these into circulation over months or years will
take place.

6.4.1.3 Toxic dose

Toxic doses have been fixed based on various in vivostudies. The toxic dose is measured with
LD50, which is the dosage of a substance required to kill 50% of the population of test animals. It
is usually carried out in vivo in the laboratory animals like rats, mice, rabbits, etc.
The table below gives the LD50 of chemicals belonging to this category.
S.No Chemical Toxic Dose Level of toxicity
(LD50 mg/kg)
1 Ethylan(Perthane) >1 LowToxicity
2 Hexachlorobenzene >1 LowToxicity
3 Methoxychlor >1 LowToxicity
4 Chlordane >50 ModeratelyToxic
5 DDT >50 ModeratelyToxic
6 Heptachlor >50 ModeratelyToxic
7 Kepone >50 ModeratelyToxic
8 Lindane >50 ModeratelyToxic
9 Mirex >50 ModeratelyToxic
10 Toxaphene >50 ModeratelyToxic
11 Aldrin <50 HighlyToxic
12 Dieldrin <50 HighlyToxic
13 Endrin <50 HighlyToxic
14 Endosulfan <50 HighlyToxic
Source: Jayarajet al., (2017), Organochlorine pesticides, their toxic effects on living organisms
and their fate in the environment

6.4.2 Organophosphate compounds

Organophosphorus compounds are a class of chemicals that contain phosphorus atoms bonded to
organic groups. They are widely used as insecticides, herbicides, and nerve agents. While their
insecticidal properties make them effective for pest control, they can also pose a significant risk
to human health and the environment. These are class of compounds widely used owing to their
broad spectrum of activity against pests. Malathion and parathion are two compounds of this
group that are widely utilized . Methyl parathion, diazinon, naled, dichlorvos, and others are
some notable compounds of this class. The effect is majorly on the sucking pests like mites,
aphids, etc. which damage the plant by sucking plant juices. These compounds are usually
absorbed into plants by spraying over the leaves or by spraying into the soil to get ingested
through the root system. The residual action of organophosphate compounds are limited. Yet,
residue tolerance levels has to be considered when choosing a chemical for use. Some of the
newer generation of organophosphates are biodegradable and does not persist in the
environment, indicating minimum environmental pollution.
6.4.2.1 Mode of action
Organophosphate compounds (OP)inhibit two enzymes acetylcholinesterase (AChE) and
butyrylcholinesterase or plasma cholinesterase (PChE). These enzymes are known to breakdown
acetylcholine.
1. Blockage of AChE leads to excessive accumulation of acetylcholine majorly in the
central nervous system (CNS).
2. Aging may be occurred due to total inhibition of AChE when these compounds bind
covalently to the enzymes. The rate of aging varies highly dependent upon the type of
active ingredient, level of exposure, and the route of exposure. Dimethylated OP
compounds such as dimethoate cause aging faster than the diethyl agents such as
chlorpyrifos; while, lipophilic OP compounds could be seen to get released through the
blood circulation over days to weeks after exposure thereby prolonging the aging.

6.4.2.2 Mechanism of toxic action

OP molecules are known to be absorbed via skin, inhalation, or through gastrointestinal (GI)
tract. As soon as the molecule gets absorbed and binds to acetylcholinesterase receptor, it starts
its inactivating action. Inhibiting the activity of the enzyme acetylcholinesterase, which is
responsible for breaking down the neurotransmitter acetylcholine.
Malathion: By inhibiting this enzyme, malathion leads to an accumulation of acetylcholine in the
nervous system, disrupting normal nerve signaling. This disruption affects both insects and
mammals. Excessive accumulation of acetylcholine leads to flaccid paralysis. Extreme cases
may lead to hypertension, sweating, leukocytosis, tachycardia, etc.
Parathion: Parathion functions similarly to malathion by inhibiting acetylcholinesterase. Its toxic
effects are overstimulation of the nervous system. Parathion is highly toxic and has been phased
out or restricted in many countries due to its potential health hazards.

Sarin: Sarin is an extremely toxic organophosphorus nerve agent developed for chemical warfare
as it is a potent acetylcholinesterase inhibitor. Sarin rapidly penetrates the body through
inhalation, ingestion, or skin contact. It affects the nervous system by blocking the breakdown of
acetylcholine, resulting in overstimulation of nerve receptors. Exposure to even small amounts of
sarin can lead to severe symptoms, including convulsions, respiratory distress, and ultimately,
death.
The overstimulation of cholinergic receptors leads to a wide range of symptoms, such as muscle
tremors, respiratory distress, paralysis, convulsions, and ultimately, if untreated, can result in
death. While organophosphorus compounds can be highly toxic, they are also used for beneficial
purposes such as agricultural pest control and public health measures against disease-carrying
insects. However, their use should always be strictly regulated, and appropriate safety measures
should be in place to minimize the risks associated with their toxicity.

6.4.2.3 Toxic dose

The table below gives the toxic dose of some of the OP compounds

S.No Chemical Toxic Dose Level of toxicity

(LD50 mg/kg body
weight)

1 Malathion <50 HighlyToxic

2 Chlorpyrifos <50 HighlyToxic

3 Bendiocarb <50 HighlyToxic

 5 Parathion 10–12 HighlyToxic

6 Methylparathion 30 HighlyToxic

7 Methylparaoxon 1.4 HighlyToxic

8 Paraoxon 0.6–0.8 HighlyToxic

Source: NCBI Gov books, NBK470430

6.4.3 Carbamates

Chemically, carbamates are similar to the organophosphates. They are derived from carbamic
acid; whereas,OP compounds are derivatives of phosphoric acid.Carbamates get volatilized
easily from the soil. Hence the risk of long-term residues with carbamates is minimal.
Carbamates are usually applied directly to the plants and then tend to reach the soil.
Bioaccumulation happens to a small extent. But if they reach water bodies, they occur in
drinking water. Various sources of carbamates are following:
Natural sources: Methyl carbamate physostigmine (or eserine) is a naturally occurring compound
that is isolated earlier from calabar beans.

Man-made sources: Benomyl and carbendazim, which belong to the benzimidazole class of
fungicides are those used in farming practices. These synthetic and organic pesticides are largely
produced and widely used.
6.4.3.1 Mode of action
Carbamates like OP compounds inactivate AChE, thereby affectingthe nervous system. The
reaction is known as carbamylation in which carbamates bind to AChE. Regeneration of AChE
tends to be faster than with phosphorylated compounds. It is observed that the proportion
required to cause death is relatively larger than that needed to elicit symptoms for carbamates in
comparison to that of OP compounds. Due to their highly volatile nature,they can be easily
degraded with minimum environmental pollution.

6.4.3.2 Mechanism of toxic action

Carbamate compounds are a class of chemicals that contain the carbamate functional group (a
carbonyl group attached to an amino group). They have been widely used as insecticides and
pesticides due to their effectiveness against a range of pests. Here are examples of carbamate
compounds and their mechanism of toxicity:

Carbaryl: Carbaryl is a commonly used carbamate insecticide. It acts as an acetylcholinesterase

inhibitor, similar to organophosphorus compounds. Carbaryl binds reversibly to the active site of
acetylcholinesterase, inhibiting its function. This leads to the accumulation of acetylcholine, a
neurotransmitter, in the synaptic cleft, resulting in overstimulation of cholinergic receptors and
disruption of nerve signaling. Carbaryl toxicity affects both insects and mammals.

Aldicarb: Aldicarb is another carbamate insecticide. It is highly toxic and has a rapid onset of
action. Aldicarb also inhibits acetylcholinesterase, leading to the buildup of acetylcholine in the
nervous system. It affects both central and peripheral nervous systems, causing symptoms such
as excessive salivation, muscle tremors, convulsions, and respiratory paralysis.

Methomyl: Methomyl is a carbamate insecticide used for controlling a wide range of pests. Its
mechanism of toxicity is similar to other carbamates. Methomyl inhibits acetylcholinesterase,
resulting in the accumulation of acetylcholine and disruption of nerve signaling. It affects both
the central and peripheral nervous systems, leading to symptoms such as muscle twitching,
respiratory distress, and neurological abnormalities.

The mechanism of toxicity of carbamate compounds involves the reversible inhibition of

acetylcholinesterase, leading to the accumulation of acetylcholine and disruption of normal nerve
function. Unlike organophosphorus compounds, carbamates generally have a shorter duration of
action because their inhibition of acetylcholinesterase is reversible. However, carbamates can
still pose risks to human health and the environment.

These compounds are said to be synthetic analogs of toxic alkaloid compound physostigmine
that occur in calar beans. These are highly poisonous when orally administered to mammals;
aldicarb is an exception that causes skin irritation. The breakdown of carbamates occurs in two
steps. In the first step, hydrolysis of carbamates to carbamic acid happens and in the second
stage, carbamic acid decomposes to carbon dioxide and the respective amine group. Carbamates
produce moderate eye and skin irritation, dependent upon the method of usage, time of exposure,
and whether the chemical comes in contact with the skin directly or not. The carbamate
compounds apart from AchE inhibition activity are also known to cause liver damage and kidney
injuries. It might also lead to degeneration of the testes. The effect is also seen in the nervous
system. All these dysfunctionalities and effects are mostly related to the type and structure of the
carbamates and the species to a smaller extent. Ethyl carbamate is also known as urethane and is
a known carcinogen. Carbamates can be converted into N-Nitroso compounds, which are potent
mutagens and carcinogens. This conversion to N-Nitroso compounds is evident from in-vivo
trials.

Due to concerns about their potential toxicity and environmental impact carbamates use is
decreased over years. Integrated Pest Management (IPM) strategies, including the use of
biological control agents and less toxic alternatives, are often recommended to minimize reliance
on carbamate insecticides and promote safer pest management practices.

6.4.4 Pyrethroids

Pyrethroids are organic compounds like pyrethrin that occur naturally in flowers of pyrethrums
(Chrysanthemum cinerariafolium and Chrysanthemum coccineum). Pyrethroids are used as
common insecticides in households. These compounds are usually harmless to people.

6.4.4.1 Mode of action

These are known to be potent inhibitors of cytochrome 450 enzymes thereby disturbing the
respiratory system of pests. They can cause paralysis of the organisms by disrupting the activities
of ion channel gateways. they are also capadle of disrupting neuroendocrine activity leading to
serious misfunctioning of CNS.

6.4.4.2 Mechanism of Toxic Action

Pyrethroids are a class of synthetic insecticides that are derived from natural pyrethrins, which
are extracted from chrysanthemum flowers. Pyrethroids are widely used in agriculture, public
health, and household insecticides due to their effectiveness against a range of pests. Here are
examples of pyrethroid compounds and their mechanism of toxicity:

Permethrin: Permethrin is one of the most commonly used pyrethroids. It is used in agricultural
settings, as well as in household insecticides and mosquito control programs. Permethrin acts by
disrupting the nervous system of insects. It affects the voltage-gated sodium channels in the
nerve cells, leading to prolonged sodium channel opening and delayed repolarization. This
results in repetitive nerve firing and eventually paralysis and death of the insects.

Cypermethrin: Cypermethrin is another widely used pyrethroid insecticide. It shares a similar

mechanism of action with permethrin. Cypermethrin also affects voltage-gated sodium channels,
causing prolonged opening and inhibition of normal repolarization. This disrupts nerve signal
transmission, leading to paralysis and death of the target pests.

Deltamethrin: Deltamethrin is a pyrethroid insecticide known for its strong insecticidal activity
and long-lasting effectiveness. Like other pyrethroids, deltamethrin acts on sodium channels in
the nerve cells, leading to their prolonged opening and inhibition of repolarization. This results in
overstimulation of the nervous system, paralysis, and eventual death of the targeted insects.

The mechanism of toxicity of pyrethroids involves their interaction with voltage-gated sodium
channels in the nerve cells of insects. By prolonging the opening of these channels, pyrethroids
disrupt the normal electrical signaling process, leading to hyperexcitability, paralysis, and
ultimately death of the pests. It's important to note that pyrethroids generally have low toxicity to
mammals and humans due to their rapid breakdown and elimination from the body.

However, it's crucial to use pyrethroids according to the recommended dosage and safety
guidelines to minimize any potential risks to human health and the environment. Additionally,
some individuals may be more sensitive to pyrethroids, so proper precautions should be taken,
such as avoiding direct exposure and using protective measures when handling or applying
pyrethroid-based products.

Check Your Progress Exercise 3

Note a) Use the space below for your answer
b) Compare your answers with those given at the end of the unit.

1) Tick mark ( ) in front of correct and mark (X) in front of wrong sentences.

1. Organochlorinated compounds are known to be neurotoxins that disturb the nerve

impulses transmission to the brain.
2. Organo-phosphorous compounds are usually much more than that chlorine compounds.
3. Bioaccumulation of carbamates is a serious concern, and they are banned worldwide.
4. Pyrethroids are known to be potent inhibitors of cytochrome 650 enzymes there
disturbing respiratory systems.

2) Highlight the mode of action of Organo-phosphorous compounds

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3) Explain the pharmacokinetics of chlorinated pesticides.

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4) Discuss carbamate pesticides.

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6.5 SAFETY EVALUATION OF PESTICIDE RESIDUES

You have now learned the importance of pesticides in food production. The use of pesticides are
especially important indeveloping and under developed countries that face food shortages.
However, long term as well asindiscriminate use of pesticides has resulted in serioushealth
effects, especially to highly vulnerable population includinginfants. Pesticides can cause both
acute and chronic health effects if not used properly. To protect people from the adverse effects
of pesticides, WHO hadeveloped internationallyaccepted maximum residue limits(MRL) for
each class of pesticides/individually used pesticides. Risk assessment of pesticide residues in
food commodities are carried out based on the data submitted for national registrations of
pesticides globallyas well as from reported research in peer reviewed journals. After assessing
the risk level, safe limits of pesticide residue were established considering the fact that life time
exposure shall not result in adverse health effects.FSSAI has also set MRL/maximum limits of
pesticide redidues in different food commodities (you can find it in the FSS (Contaminants,
toxins and residues) regulation, 2011 and its further amendments.Codex standards are considered
as a reference for international trade in food, and currently there are Codex standards for more
than 100 different pesticides.

6.5.1 Maximum residue limits (i.e. MRL)

MRL can be defined as a maximum concentration of a residue that may result from the
registered use of a particular veterinary or agricultural chemical, which is legally recommended,
permitted, or recognized as acceptable to use in or on a food animal, agricultural commodity,
and/or animal feed. The concentration will be expressed as milligrams per kilogram of that
commodity (or in milligrams per liter in the case of liquid commodities).

6.6 MANAGEMENT OF CHEMICAL PESTICIDES AND ITS

REGULATION
6.6.1 Role of WHO
As we have discussed earlier, it is the responsibility of WHO and FAO[Joint FAO/WHO
Meeting on Pesticide Residues (JMPR)]for assessing potential health risks associated with
pesticides on humans considering all possible routes of exposure. After assessing the level of risk
from the collected data, JMPR establishes safe limits of intake ensuring that the life time
exposure of pesticide residue food consumption will not cause adverse health effects.WHO and
FAO have jointly developed the International Code of Conduct on Pesticide Management,
available from WHO and FAO have jointly developed the International Code of Conduct on
Pesticide Management, available from https://www.fao.org/3/I3604E/i3604e.pdf. The JMPR is
also responsible for providing recommendations on adequate protection measures to avoid
toxicity related to exposure of pesticides.

6.6.2 Role of Codex Alimentarius Commission

The acceptable daily intakedata provided by JMPR is used by the Codex Committee on Pesticide
Residues (CCPR) of Codex Alimentarius Commission (the intergovernmental body that sets
food standards), to establish maximum residue limits (MRLs) for pesticides in food.
Followingthe codex standards for pesticide residues help in international trading of food and feed
commoditieswhich otherwise couldbe problematic when limits differ between countries.

6.6.3 Pesticide regulation in India

The Insecticides act, 1968: the legislation was formed with a view to prevent health risks to
humans and animals in connection with the use of insecticides. A registration committee was
established by the central government by which it become mandatory to register the insecticides.
The committeeverifyes the claims made by the manufacturer or importer regarding the efficacy
and safety of the insecticide.
As per food safety and standards act, 2006, a scientific panel was constituted by the FSSAI to
recommend MRL on the basis of data provided by Central Insecticides Boardand Registration
Committee. These MRLs are notified under FSS (Contaminants, Toxins and
Residues)Regulations, 2011 and its amendments.
MRL (ppm) of Insecticide as per FSSAI for eggs, fishes, and dry fruits

S. No. Pesticide residue Eggs Fish Dry fruits

1 2,4-Dichlorophenoxy Acetic Acid 0.05

2 Benomyl 0.1 0.1

3 Carbaryl 0.2

4 Carbendazim 0.1 0.1

5 Edifenphos 0.01

6 Ethion (Residues to be determined as ethion and its 0.2 0.1

oxygen analog and expressed as ethion)
7 Malathion (Malathion to be determined and expressed as 8
combined residues of malathion and malaoxon)

8 Monocrotophos 0.02

9 Phenthoate 0.05

10 Phorate (sum of Phorate, its oxygen analog, and their 0.05

sulphoxides and sulphones, expressed as phorate)

11 Pirimiphos-methyl 0.05

12 Quinalphos 0.01
Source: FSSAI (Contaminants, Toxins and Residue regulations), 2011

MRL (ppm) of Insecticide as per FSSAI for Food grains

S.no. Pesticide residue Food grains

1 2,4-Dichlorophenoxy Acetic 0.01

Acid

2 Benomyl 0.5

3 Carbaryl 1.5

4 Carbendazim 0.1

5 Chlorpyriphos 0.05

6 Deltamethrin (Decamethrin) 0.3

7 Dichlorvos (DDVP) 1
Source: FSSAI (Contaminants, Toxins and Residue regulations), 2011

6.7 REDUCTION OF PESTICIDE RESIDUES IN FOOD

A code of conduct for the management of pesticides was developed by the WHO and FAO in
2014, which provides guidance for regulating bodies, private bodies, and various stakeholders on
acceptable practices for use of pesticides. To implement a residue avoidance program effectively
in the food production practices, people need to be aware of all the pharmacological principles of
pesticides. The half-life (t1/2) of a pesticide is the time required by the pesticide to get 50%
removed from the soil. A pesticide with large volumes of distribution (Vd) generally has
reported possessing good tissue distribution characteristics as compared to a pesticide of
restricted distribution.
People are facing an increased change in their attitude and behavior concerning pesticide
residues. The most likely reason for the occurrence of pesticide residues in food commodities is
aresult ofmis-management and unsafe practices, such as improper usage, including extra-label
usage or illegal applications. Moreover, the most likely reason for the unacceptable residues
might be attributed to the inordinate use of pestidices (in the pretext of more yield by the
farmers), monitoring and survelliancefailure, weak enforcement, etcVarious practices to be
followed for the reduction of pesticide residues in food products are following.
 Pesticide industry should adhere to the relevant national/international regulatory
guidelines
 While importing or exporting, government shouldensure that good trading practices are
followed
 Adhering to good agricultural practiceswhile application of pesticides in the farm level
 It is advised to always read labels on containers to make necessary calculations on dosage
before application of pesticides on crops
 While processing of food commodities, adhering to good manufacturing practices can
help reducing pesticide residues in the final commodity
 At the household level, washing with water or soaking in solutions of salt and some
chemicals, e.g., chlorine, chlorine dioxide, hydrogen peroxide, ozone, acetic acid,
hydroxy peracetic acid, iprodione and detergents can reduce the level of pesticide
residues.

Check Your Progress Exercise 4

Note a) Use the space below for your answer

b) Compare your answers with those given at the end of the unit.

1) Define ADI. How is it calculated?

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…
6.8 LET US SUM UP
 Pesticides are defined as a broad spectrum of chemical or organic substances which
include insecticides, fungicides, herbicides, plant growth regulators, etc
 Pesticides are defined by the pesticide management bill, 2020 as “any substance or
mixture of substances, including a formulation of chemical or biological origin intended
for preventing, destroying, attracting, repelling, mitigating or controlling any pest in
agriculture, industry, pest control operations, public health, storage or for ordinary use,
and includes any substance intended for use as a plant growth regulator, defoliant,
desiccant, fruit thinning agent, or sprouting inhibitor and any substance applied to crops
either before or after harvest to protect them from deterioration during storage and
transport”.
 Residue is defined by the European Union (EU) and the Center for Veterinary Medicine
(FDA/CVM), which is an agency working under the Food and Drug Administration of
the USA as follows: “pharmacologically active substances (either active principles,
recipients or degradation products of these) and their metabolites remaining in foodstuffs
or any place at any point of time”.
 Pesticides may be categorized in the following ways:
o Target pests
o Mode of Action
o Toxic potential
o Structure and Chemical nature
 WHO (World Health Organization has classified specific limits for different routes of
exposure. Since the dermal route would be having a slow rate of action compared to oral
or parenteral routes (as the case may be).
 Organochlorine compoundsare the earlier discovered pesticides. DDT [dichloro-
diphenyl-trichloroethane] is an example, which is now banned to be used as a pesticide.
Some other examples include BHC, lindane, methoxychlor, Chlorobenzilate, and
cyclodienes including aldrin, dieldrin, chlordane, heptachlor, and endrin.
 Organo Phosphorous compounds are a class of compounds widely used in recent times.
Malathion and parathion are the two compounds of this group that widely find
applicability. Methyl parathion, diazinon, Naled, dichlorvos, and others are some notable
 compounds of this class. The effect is majorly on the sucking pests like mites, aphids, etc.
which damage the plant by sucking plant juices
 Carbamates get volatilized easily from the soil. Hence the risk of long-term residues with
carbamates is minimal. Carbamates are usually applied directly to the plants and then
tend to reach the soil.
 ADI is defined as the amount of a substance ingested daily over a lifetime without any
appreciable health risk. ADI is calculated based on a series of toxicological safety
evaluations which takes acute, long-term exposure to a chemical and its potential
impacts. If a chemical is no carcinogen, then the No Observed Effect Level (NOEL) is
one of the most sensitive in the most sensitive species which is again divided by a safety
factor and used to determine ADI for that chemical residue.
 FDA will calculate the safe concentration for each edible tissue using the ADI, the weight
in kg of an average adult (60 kg), and the amount of the product eaten per day in grams as
follows.
 Safe concentration limit = [ADI (as µg/kg/day) x 60 as kg] /[Grams consumed / day].
 MRL can be defined as a maximum concentration of a residue that may result from the
registered use of a particular veterinary or agricultural chemical, which is legally
recommended, permitted, or recognized as acceptable to use in or on a food animal,
agricultural commodity, and/or animal feed. The concentration will be expressed as
milligrams per kilogram of that commodity (or in milligrams per liter in the case of liquid
commodities).

6.9 KEY WORDS

Pesticides Pesticides are defined by the pesticide management bill, 2020 as
“any substance or mixture of substances, including a formulation
of chemical or biological origin intended for preventing,
destroying, attracting, repelling, mitigating or controlling any pest
in agriculture, industry, pest control operations, public health,
storage or for ordinary use, and includes any substance intended
for use as a plant growth regulator, defoliant, desiccant, fruit
 thinning agent, or sprouting inhibitor and any substance applied to
crops either before or after harvest to protect them from
deterioration during storage and transport”.

Residue Residue is defined by the European Union (EU) and the Center for
Veterinary Medicine (FDA/CVM), which is an agency working
under the Food and Drug Administration of the USA as follows:
“pharmacologically active substances (either active principles,
recipients or degradation products of these) and their metabolites
remaining in foodstuffs or any place at any point of time”
LD50 Toxic doses are fixed based on various laboratory studies
conducted at different stages. It’s measured with a unit LD50
which is regarded as the dosage of a substance required to kill
50% of the population when administered. It is usually carried out
in the laboratory using lab animals like rats, mice, rabbits, etc.
which can be replicated in humans.
Acceptable daily ADI is defined as the amount of a substance ingested daily over a
intake (ADI) lifetime without any appreciable health risk. ADI is calculated
based on a series of toxicological safety evaluations which takes
acute, long-term exposure to a chemical and its potential impacts.
If a chemical is no carcinogen, then the No Observed Effect Level
(NOEL) is one of the most sensitive in the most sensitive species
which is again divided by a safety factor and used to determine
ADI for that chemical residue.
Maximum MRL can be defined as a maximum concentration of a residue that
residue limits may result from the registered use of a particular veterinary or
(i.e. MRL) agricultural chemical, which is legally recommended, permitted,
or recognized as acceptable to use in or on a food animal,
agricultural commodity, and/or animal feed. The concentration
will be expressed as milligrams per kilogram of that commodity
(or in milligrams per liter in the case of liquid commodities).
6.10 REFERENCES/SUGGESTED READINGS
1. Kumar, A. D., & Reddy, D. N. (2021). The Pesticide Management Bill 2020. Current
Science, 121(3), 348.
2. Food Safety and Standards (Contaminants, Toxins, and Residues) Regulations, 2011.
3. Helferich, W., & Winter, C. K. (2000). Food toxicology. CRC press.
4. Shibamoto, T., &Bjeldanes, L. F. (2009). Introduction to food toxicology.
5. Borzelleca, J. F. (1990). Principles and Methods for Toxicology—2nd Edition. Journal of
the American College of Toxicology, 9(3), 381-382.
6. The International Code of Conduct on Pesticide Management (FAO, 2014) available from
https://www.fao.org/3/I3604E/i3604e.pdf
7. Draft Manual for Certificate Course on Plant Protection &Pesticide Management, ICAR.
Available from https://kvk.icar.gov.in/API/Content/Uploads/3907c7d6-4610-42f8-894b-
acc69468027d/3907c7d6-4610-42f8-894b-acc69468027dbrochure.pdf
8. Food Safety and Standards (Contaminants, Toxins and Residues)Regulations, 2011,
Version –VI (27.01.2022) available from
https://www.fssai.gov.in/upload/uploadfiles/files/Compendium_Contaminants_Regulations
_28_01_2022.pdf

6.11 ANSWERS TO CHECK YOUR PROGRESS EXERCISES

Check Your Progress Exercise 1

1. iii)
2. a)GAP- Good Agricultural Practices
b) FAO- Food and Agricultural Organization
c) MRL- Maximum Residue Limit
3 a) Pesticides are defined as a broad spectrum of chemical or organic substances which include
insecticides, fungicides, herbicides, plant growth regulators, etc. Pesticides are defined by the
pesticide management bill, 2020 as “any substance or mixture of substances, including a
formulation of chemical or biological origin intended for preventing, destroying, attracting,
repelling, mitigating or controlling any pest in agriculture, industry, pest control operations,
public health, storage or for ordinary use, and includes any substance intended for use as a plant
growth regulator, defoliant, desiccant, fruit thinning agent, or sprouting inhibitor and any
substance applied to crops either before or after harvest to protect them from deterioration during
storage and transport”.
3 b) Life cycle: According to FAO, the life cycle of a pesticide referes to “all the stages a
pesticide might pass through from productionto its degradation in the environment after use, or
its destruction as an unuseproduct. The life cycle includes manufacture, formulation, packaging,
distribution, storage, transport, use and finaldisposal of a pesticide product and/or itscontainer
(FAO, 2014).”
4. Residue is defined by the European Union (EU) and the Center for Veterinary Medicine
(FDA/CVM) as follows: “pharmacologically active substances (either active principles,
recipients, or degradation products of these) and their metabolites remaining in foodstuffs or any
place at any point of time”.

Check your Progress Exercise 2

1) Synthetic pesticides affect different systems as follows:
Class Examples Area of action
Organochlorine DDT, aldrin, dieldrin, Reproductive system, nervous system,
pesticides toxaphene endocrine glands, and immune system
Organophosphate Diazinon, malathion, nervous system
compounds glyphosate
Carbamate pesticides Carbofuran, carbaryl, nervous system
aldicarb
Pyrethroid compounds Fenpropanthrin, Not understood
cypermethrin, deltamethrin,

2. Criteria for pesticide classification are as follows:

o Classification based on target Pests
o Classification based on Mode of action
 o Categorization of pesticides based on toxicity level
o Classification based on Chemistry/Chemical structure

Check your Progress Exercise 3

1). iii

2). Organo phosphorous compounds inhibit two enzymes acetylcholinesterase (AChE) and
butyrylcholinesterase or plasma cholinesterase (PChE). These enzymes are known to
breakdown acetylcholine.

1. Blockage of AChE leads to the excessive accumulation of acetylcholine majorly in the

CNS.

2. Aging may be occurred due to total inhibition of AChE when these compounds bind
covalently to the enzymes. The rate of aging varies highly dependent upon the type of OP
compound, level of exposure, and the route of exposure. Dimethylated OP compounds
such as dimethoate cause aging faster than the diethyl agents such as chlorpyrifos. While
lipophilic OP compounds could be seen to get released through the blood circulation over
days to weeks after exposure thereby prolonging the aging term still longer.

3. Chlorinated compounds are seen to be absorbed well in the Gastrointestinal tract, into the
skin,and by air inhalation. These will rapidly accumulate in the fatty tissues by
continuous exposure since they are lipophilic. The elimination of such compounds will
not happen any sooner since these reactions do not follow first-order kinetics. Slow
release of these into circulation over months or years will take place.
4. Large-scale production of carbamate pesticides was seen during the 1950s. Carbamates get
volatilized easily from the soil. Hence the risk of long-term residues with carbamates is minimal.
Carbamates are usually applied directly to the plants and then tend to reach the soil.
Bioaccumulation happens to a small extent. But if they reach water bodies, they occur in
drinking water.
Check your Progress Exercise 4
1. ADI is defined as the amount of a substance ingested daily over a lifetime without any
appreciable health risk. ADI is calculated based on a series of toxicological safety evaluations
which takes acute, long-term exposure to a chemical and its potential impacts. If a chemical is no
carcinogen, then the No Observed Effect Level (NOEL) is one of the most sensitive in the most
sensitive species which is again divided by a safety factor and used to determine ADI for that
chemical residue.
The safe concentrationcalculated for each edible tissue using the ADI, the weight in kg of an
average adult (60 kg), and the amount of the product eaten per day in grams are as follows.
Safe concentration limit = [ADI (as µg/kg/day) x 60 as kg] / [Grams consumed / day].