Transcript Pesticides - Professor Monzir Abdel

Pesticides
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
The term ‘pesticide’ encompasses a wide variety of
substances used to destroy unwanted life forms.
Pesticides are applied in agriculture for crop
protection and pest control, and in human and animal
hygiene. They are classified as insecticides,
herbicides, rodenticides, fungicides, nematocides,
molluscicides and acaricides on the basis of their field
of use. Commercial formulations can be mixtures of
pesticides from different classes.
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insecticides
substance that destroys insects
herbicides
rodenticides
substance that kills weeds (wild
unwanted plant )
substance which kills rodents
fungicides
substance that destroys fungi
nematocides
substance which kills nematodes
(class of cylindrical worms)
invertebrate animal with a soft body
and a hard shell
material or substance for killing mites
(parasitic on animals or plants )
molluscicides
acaricides
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
Most pesticides have common names agreed by the
International Standardisation Organisation (ISO)
through its Technical Committee. These common
names are used throughout this chapter for
convenience and brevity, but their equivalent
systematic chemical names can be ascertained easily
according to the rules of the International Union of
Pure and Applied Chemistry (IUPAC) and the
Chemical Abstracts Service Registry Number .
Pesticides are also divided into different chemical
subclasses. Often the type of chemical is also
indicated by a stem in the common name (e.g. ‘uron’
for ureas, and ‘carb’ for carbamates).
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Insecticides
Insecticides may be classified into eight
chemical groups, of which the following five
are the most important:
Organophosphorus (OP) compounds, which have
the general structure 1.
Carbamates (structure 2 , where R1 = methyl,
R2 = H or methyl, and R3 = aryl, heterocyclic
or oxime groups) (e.g. aldicarb, structure 3)
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Chlorinated hydrocarbons, which include
dichlorodiphenyltrichlorethane (DDT) and its analogues (e.g.
methoxychlor), hexachlorocyclohexane isomers (e.g. lindane)
and bridged polycyclic chlorinated compounds (e.g.
endosulfan, structure 4).
Pyrethroids, both natural (e.g. pyrethrin II, structure 5) and
synthetic (e.g. deltamethrin, structure 6 )
Substituted ureas (e.g. diflubenzuron, structure 7) .
Other insecticide groups are organotin (e.g. cyhexatin, structure
8 ), and heterocyclic compounds (e.g. dazomet, structure 9 ).
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Herbicides
Herbicides may be classified into at least 12
groups, but the seven most important are:
Chlorinated phenoxy acids (e.g. 2,4–
dichlorophenoxyacetic acid (2,4-D), structure
10).
Substituted ureas (e.g. metobromuron, structure
11).
Triazines (e.g. atrazine, structure 12).
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Uracils (e.g. lenacil, structure 13).
Quaternary ammonium compounds (e.g. paraquat,
structure 14, and diquat).
Carbamates, which include not only the carbamates
(e.g. propham), but also thiocarbamates (e.g. tri–
allate, structure 15).
Carboxylic acids and esters (e.g. dicamba).
Other herbicides include amides chloroacetanilide,
OP and organoarsenic compounds
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Fungicides

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Chemicals from many groups belong to this class:
benzimidazoles (e.g. carbendazim), dithiocarbamates
(e.g. thiram, structure 16, acylalanines (e.g.
metalaxyl) and OP compounds (e.g. pyrazophos). The
most important are:
Dithiocarbamate complexes with manganese, nickel
and zinc.
Organic and inorganic compounds of copper and
mercury
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Rodenticides
Three types of compounds are notable in this
category
Phosphines (derived by the reaction of moisture
with magnesium, aluminium and zinc
phosphides).
Thallium salts, usually sulfates.
Coumarin anticoagulants (e.g. brodifacoum,
bromadiolone, coumatetralyl, difenacoum
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Acaricides, molluscicides and
nematicides
These include organotin (acaricide), niclosamide
(molluscicide) and phorate (nematicide). Some
of these compounds that have more than one
application can be found among those
mentioned above
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Toxicity

The large variety of chemical compounds that show
pesticide properties means that there is a very wide
range of toxicity in humans. It is believed that an oral
dose of only several drops (100 mg) of terbufos is
fatal to most adults, whereas another pesticide
(amitrole) is non–toxic in humans even when several
hundred grams are ingested.
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
Within a particular class of pesticide the lethal
dose may vary considerably. Moreover, the
metabolites of many pesticides (e.g. oxygen
analogues of phosphorothionates) are much
more toxic than the parent compounds
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
The commercially available preparations usually
contain an active substance mixed with filler (solids)
or dissolved in an organic solvent (liquids). Although
certain pesticides are unlikely to cause acute toxicity,
the vehicle in which they are formulated (toluene,
xylenes, butan-1-ol, cyclohexanone, and solvent
naphtha may itself be toxic and, in some cases, can be
the main causative agent for the symptoms observed.
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The pesticides have been classified into five groups
according to the World Health Organisation (WHO)
toxicity classification for estimating the oral acute
toxicity of pesticides. Toxicity was determined on the
basis of LD50 for the rat and the estimated lethal
doses related to a 70 kg person. However, realistic
human lethal doses of pesticides can be estimated
only on the basis of well–documented cases of
poisoning
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WHO Pesticide Classification
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WHO PESTICIDE LIST
1.
Active ingredients believed to be obsolete or discontinued for
use as pesticides
2.
Extremely hazardous (Class 1a) technical grade active
ingredients of pesticide
3.
Highly hazardous (Class 1b) technical grade active ingredients
of pesticides
4.
Moderately hazardous (Class II) technical grade active
ingredients of pesticides
5.
Slightly hazardous (Class III) technical grade ingredients of
pesticides
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Colour tests
Some colour tests can be very useful preliminary
indicators of the class of compound and can confirm
the constituents of a proprietary formulation. Simple
quantification of compounds that belong to specific
groups is also possible. To reduce false positives from
artefactual sources, a blank solution should be
subjected to the same procedure as the sample. It is
also essential to check the viability of the reagents by
analysing a reference compound
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Sample preparation
The major metabolites of many pesticides (e.g.
carbamates and organophosphates) are sulfate and
glucuronide conjugates. Cleavage of conjugates by
enzymatic or acid hydrolysis is necessary before
extraction. However, deconjugation of pesticides by
acid hydrolysis drastically increases the formation of
artefacts and can destroy analytes completely.
Therefore, the gentle enzymatic method is
recommended. The extraction of body fluids is
further complicated because certain pesticides are
decomposed readily by acids or alkalis
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Enzyme hydrolysis (urine)
To 5 mL of urine specimen are added 1 mL of 1 M
acetate buffer (pH 5) and 40 μL of beta-glucuronidase
plus arylsulfatase (30 U/mL plus 60 U/mL) and the
mixture incubated overnight at 37° in a closed test
tube. Incubation for 45 min at 56° is less time–
consuming, but the quantitative results are more
variable – this shorter process can be used in
emergency cases
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Derivatisation procedures

methyl (ME, trifluoroacetyl (TFA) and acetyl
derivatives (AC) derivatives of pesticides are
usually obtained. Trifluoroacetylation and
acetylation processes can be carried out for
5 min under microwave irradiation at about
400 W
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Thin–layer chromatography

Four TLC systems are used; each consists of an independent
mobile phase and a sequence of different spray reagents,
widely used for pesticide visualisation. General systems TZ
and TAA( are used to reveal any pesticide in an examined
sample and to enable presumptive chemical classification. Two
more systems, TX and TY, are used to identify the type of
pesticide. The TX and TY systems give good reproducibility.
The Rf values of the reference compounds chosen for the four
screening systems are derived using 5 to 10 μg of each
substance. Each extract is spotted onto a TLC plate in an
amount corresponding to 2 g of the biological material being
analysed. For additional information, two other solvent
systems (TAB and TAC) can be applied
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The chromatographic process uses silica–gel plates of
0.25 mm layer thickness, without fluorescent
indicator, and four mobile phases in saturated
chambers in ascending mode. Seven spray reagents
are suggested, which produce a variety of colours to
facilitate differentiation. A large number of pesticides
react with more than one reagent. The reagent
sequences chosen allow the plates to be oversprayed
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The LOD for most pesticides is 10 μg after reagent
overspraying and 2 to 5 μg after single–reagent spray
detection. After drying, all the chromatograms are
first examined under ultraviolet (UV) light (366 nm
and 254 nm) and then sprayed successively with the
location reagents appropriate for each system. The
plate is sprayed with a location reagent, dried and a
note is taken of any colours. The plate is then
oversprayed with another reagent and again any
changes are noted.
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Spray reagents
Silver nitrate (AgNO3)
 The plates are sprayed with a 0.1 M aqueous solution of
AgNO3. After spraying, the dry plates are exposed to UV
radiation (254 nm) for 10 min. Many pesticides give white,
grey and brown spots on a bright brown background
Rhodamine B and sodium hydroxide
 (RHB–NaOH) A 0.02% (w/v) solution of rhodamine B (RHB)
in ethanol and a saturated solution of NaOH in ethanol are
used as the spray. After both the RHB and NaOH solutions
have been sprayed, compounds are located as navy–blue spots
by examination under UV .
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Diphenylamine and zinc chloride
 (DPA–ZnCl2) The spray comprises 0.7% (w/v)
diphenylamine (DPA) and 0.7% (w/v) ZnCl2
solution in acetone. After spraying, the plates
are exposed to UV radiation for 10 min and
then heated at 100° until no further colour
change is observed. Light blue, blue, green and
pink spots are observed on a white background
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2,6-Dibromoquinone–4–chlorimide and sodium
hydroxide
 (DBQ–NaOH) A 0.2% (w/v) solution of 2,6–
dibromoquinone–4–chlorimide (DBQ) in acetone and
a saturated solution of NaOH in ethanol are used to
spray the plates. After spraying, the plates are heated
at 100° for 10 min. Navy blue, pink, violet spots on a
light blue background are observed
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
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Palladium chloride
To make the spray, dissolve 0.5 g PdCl2 in
2.5 mL of 35% (v/v) HCl and carefully dilute
with water to 100 mL. After spraying, yellow
and brown spots are observed
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4-(4-Nitrobenzyl)pyridine and
tetraethylenepentamine
(NBP–Tetren) To make the spray, dissolve 5 g of 4-(4–
nitrobenzyl)pyridine (NBP) in 100 mL of acetone and dilute
1:5 (v/v) of Tetren with acetone . Spray the plate with the NBP
solution and dry at 110° for 10 min. After cooling, spray the
plate with the dilute Tetren solution and observe the blue–to–
violet spots on a white background. The colours are not stable.
The stability of the colours can be enhanced by spraying the
plate with a 20% (v/v) solution of acetic acid and drying at
room temperature and at 110° before using Tetren . The
reagents should be freshly prepared
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Dragendorff spray, ferric chloride, iodine and
hydrochloric acid
 The reagents are Dragendorff spray, a 5%
(w/v) solution of FeCl3, 1 g of iodine and 4 g
of KI dissolved in 100 mL of ethanol, and
finally a 25% (v/v) solution of concentrated
HCl made up in ethanol. Spray the reagents
consecutively and examine any spots and
colour changes
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Chromatography systems
System TX
Mobile phase is hexane:acetone (4:1).
Reference compounds are trichlorfon (Rf 7),
carbofuran (Rf 17), methoxychlor (Rf 43),
dieldrin (Rf 65) and quintozene (Rf 84).
Location systems are DPA–ZnCl2, NBP–Tetren
and DBQ–NaOH
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System TY
Mobile phase is toluene:acetone (95:5).
Reference compounds are thiophanate (Rf 8),
2,4-D (Rf 10), desmedipham (Rf 22), captan
(Rf 42), tetramethrin (Rf 52) and fenitrothion
(Rf 76).
Location systems are AgNO3 and PdCl2
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System TZ
Mobile phase is chloroform:acetone (9:1).
Reference compounds are trichlorfon (Rf 15),
dimethoate (Rf 37), propoxur (Rf 66) and DDT
(Rf 90).
Location systems are AgNO3, RHB–NaOH,
DBQ–NaOH and PdCl2
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System TAA
Mobile phase is chloroform.
Reference compounds are methomyl (Rf 9),
dichlorvos (Rf 36), chlorfenvinphos (Rf 42),
methoxychlor (Rf 65) and fenvalerate (Rf 75).
Location system is Dragendorff–FeCl3–I3- in
KI–HCl
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System TAB
Mobile phase is dichloromethane.
Reference compounds are any compounds examined in
the TAB system
System TAC
Mobile phase is ethyl acetate:isooctane (15:85).
Reference compounds are any compounds examined in
the TAC system.
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Location reagents for TAB and TAC
Compounds are located with the DPA–ZnCl2 reagent. A second
spray system is as follows:
Reagent A (fluorescein in dimethylformamide): dilute 1 mL of a
0.25% (w/v) solution of fluorescein in dimethyl formamide to
50 mL with ethanol.
Reagent B (silver nitrate and phenyl cellosolve): dissolve 1.7 g of
silver nitrate in 5 mL of water and mix with 10 mL of phenyl
cellosolve and 185 mL of acetone.
To develop the colours, expose the developed plates to an
atmosphere of bromine vapour for 1 min and then spray
sequentially with reagents A and B. Yellow spots on a pink
background appear which, after exposure to UV radiation,
produce yellow spots on a black background
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Other Spray Reagents
Chlorine and o-toluidine
Dissolve 1 g of o-toluidine in 10 mL of anhydrous acetic acid and
4 g of potassium iodide in 10 mL of distilled water. Mix the
two solutions and dilute with distilled water to 1 L. To develop
the colours, put the plate in a closed tank with chlorine gas
(prepared by adding 2 mL of concentrated HCl to 1 g of
potassium permanganate) for 1 min. Remove excess chlorine
from the plate under a stream of air in a fume cupboard. Dip
the plate in the reagent for about 3 s. Yellow–orange spots
appear against a white–to–blue background.
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Specific pesticides
Organophosphorus compounds
Organophosphorus compounds are by far the most important
class of pesticides, both in terms of worldwide usage and their
toxicity to humans. They act by the irreversible inhibition of
cholinesterases, which are responsible for hydrolysing, and
thereby deactivating, the neurotransmitter acetylcholine
(AcCh). Build–up of AcCh at the neural junction leaves the
muscles, glands and nerves in a constant state of stimulation,
which produces a wide range of acute symptoms. These
include dizziness, confusion and blurred vision, excessive
salivation and sweating, nausea and vomiting, and muscular
weakness.
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Severe poisoning leads to coma, flaccid paralysis, breathing
difficulties, cyanosis (blueness of skin) and irregular heartbeat.
Atropine and pralidoxime are effective antidotes in severe
cases. In acute clinical poisoning, diagnostic tests for
depressed cholinesterase activity are the most crucial.
Detecting, identifying and quantifying the particular agent
responsible has less bearing on immediate treatment, although
some of the lipophilic diethyl phosphothiolates can be
sequestered in the tissues for several days and patients who
appear to have recovered may suffer a recurrence of toxic
effects. Identification of the agent involved can alert clinicians
to this possibility
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Determination of plasma or serum
cholinesterase activity

Adjust the temperature of 3 mL 0.02% (w/v)
dithiobisnitrobenzoic acid in 0.1 M sodium
dihydrogen phosphate buffer solution (pH 7.4) to 25°,
add 20 μL of sample serum and 0.1 mL of 5% (w/v)
acetylthiocholine iodide solution, mix well, and
record the absorbance of a 1 cm layer at 405 nm at
0.5 min intervals for 2 min. If the change in
absorbance exceeds 0.2 to 30 seconds, dilute the
sample (one in ten) with normal saline and repeat the
measurements (the readings must then be multiplied
by 10). The cholinesterase activity is calculated
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Cholinesterase (mUnits/ml, at 25°) = change in
absorbance in 30 seconds × 23 400.
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Normal values of ChE activity in serum range from
1900 to 4000 mU/ml. Commercial kits for the
determination of ChE activity in plasma and serum
are available (Sigma Chemical Co., St. Louis, MO;
Biotron Diagnostics, Inc., Hemet, CA; Lovibond,
Tintometer GmbH, Dortmund).
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Determination of whole–blood
acetylcholinesterase activity
The reagents for this are:

Phosphate buffer (0.134 M, pH 7.2).
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AcCh (0.04 M), prepared by dissolving 0.7266 g of
acetylcholine chloride in 100 mL of 0.001 M acetate buffer
(pH 4.5); stable indefinitely in the cold.
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AcCh (0.004 M), prepared by diluting Solution 2 with nine
volumes of phosphate buffer (Solution 1); made daily in the
quantity required for the analyses.
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4.
5.
6.
7.
8.
Hydroxylamine hydrochloride (2 M), made by dissolving
27.8 g in water to 200 mL.
NaOH (3.5 M), made by dissolving 28 g in water to
200 mL.
Alkaline hydroxylamine prepared from equal volumes of
Solutions 4 and 5, mixed shortly before use in a quantity
required for the samples being analysed, and made up
freshly for each set of samples analysed.
HCl (concentrated acid, specific gravity 1.18), diluted with
two volumes of water.
Ferric chloride (FeCl3, 0.37 M), made with 10 g of
FeCl3.6H2O dissolved in 100 mL of 0.1 M HCl
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Prepare three test tubes. To the first tube (E), add 0.95 mL of
0.01% saponin solution, 50 μL of heparinised blood sample
and then 1 mL of 0.004 M AcCh, mix well and incubate at 25°
for 10 min. For the control, 1 mL of 0.004 M AcCh solution is
incubated in a second tube (C) alongside the experimental
sample. After exactly 10 min the reaction is stopped by the
addition of 4 mL of alkaline hydroxylamine reagent (with
vigorous shaking) to both experimental and control samples.
After a wait of at least 1 min, 0.95 mL of saponin and 50 μL of
blood sample are added to the control solution of AcCh. Then
2 mL of HCl reagent is added to each sample, followed by
2 mL of FeCl3 reagent, with mixing after each addition
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The solutions are filtered through Whatman filter paper,
and the absorbance of a 1 cm layer at 520 nm is
recorded 10 min after the addition of the FeCl3. The
absorbance (AE, in mmol/L) is measured against a
reagent mixture that consists of 4 mL of alkaline
hydroxylamine, 2 mL of HCl and 2 mL of FeCl3
reagent. The measured value of absorbance of the
control sample (AC) should be in the range of 0.3 to
0.4. The activity of AChE in blood is calculated as
follows:
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4 – (4AE/AC) × 2000 = IU/ml (International
Units per millilitre)
The precision of the method is 210 IU/ml.
Normal values for AChE activity in whole blood
range from 3500 to 8000 IU/ml. Commercial
kits for the determination of AChE activity in
red blood cells, whole blood and plasma are
available
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Determination of organophosphates in
urine
Most compounds of this chemical class are hydrolysed rapidly by
plasma and tissue enzymes with the production of many
metabolites. Metabolites and their conjugates are excreted in
urine and are known to be unstable in stored specimens. To
derive data that accurately represent the true degree of
exposure, as indicated by the concentration of OP compounds,
it is essential to obtain and analyse samples as soon as possible
after an incident. Urine samples should be analysed within a
week of obtaining the sample and kept at –20° prior to
analysis
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Colorimetric procedure
In the colorimetric procedure , to 1 mL of urine (pH 5 to 8)
add 0.1 mL of 45% (w/v) of 4-(4-nitrobenzyl)pyridine
(NBP) solution in acetone, vortex mix for 30 s and heat at
100° in a heating block for 20 min. After cooling to room
temperature, add 0.1 mL of tetraethylenepentamine
(Tetren) and 1 mL of diethyl ether, then close the tube and
vortex mix for 3 min. Measure the absorbance of the
ethereal layer at 520 nm against a reagent mixture.
Construct a calibration graph for the analysis of the
standard OP compound solutions and calculate the
concentration in the sample. The limits of detection range
from 0.1 to 3.0 mg/L for 24 OP compounds .
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, DDTClofenotane
Pesticide
 Chlorophenothane; Chlorphenothanum; Dicophane;
DDT; Dichlorodiphenyltrichloroethane;
Dichophanum; Parachlorocidum; Penticidum.
 Clofenotane contains about 70% of 1,1,1–trichloro–
2,2–bis(4–chlorophenyl)ethane (pp′-DDT) together
with varying quantities of an isomer, 1,1,1–trichloro–
2-(2–chlorophenyl)-2-(4-chlorophenyl)ethane (op′DDT) and other related compounds
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

White or nearly white crystals, small granules,
flakes, or powder. M.p. about 109°. The
technical product is a waxy solid of indefinite
melting point.
Practically insoluble in water; soluble 1 in 50
of ethanol, 1 in 6 of boiling ethanol, 1 in 2.5 of
acetone, 1 in 3.5 of chloroform, and 1 in 4 of
ether
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Colour Tests
Liebermann's Test—brown; Nitric–Sulfuric
Acid—red→orange→green.
Heat a small quantity with a 0.5% solution of
hydroquinone in sulfuric acid—red.
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Disposition in the Body
Clofenotane dry powder is poorly absorbed from the gastro–
intestinal tract and is not absorbed through the skin. Solutions
of clofenotane in oils are rapidly absorbed through intact skin
and are also readily absorbed from the gastro–intestinal tract.
Clofenotane is metabolised to a small extent by
dehydrochlorination to dichlorodiphenyldichloroethylene
(DDE) which is less toxic; DDE does not appear to be
metabolised further and is stored indefinitely in adipose
tissues. Most of the DDE present in human fat is thought to
result from preformed DDE taken in the diet rather than being
due to ingestion of clofenotane. The major metabolic route for
clofenotane is dechlorination to
dichlorodiphenyldichloroethane (DDD) followed by
degradation to dichlorodiphenylacetic acid (DDA) which is the
major urinary excretion product. Urinary concentrations of
DDA are indicative of storage of DDT in adipose tissue
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Blood concentration
The following tissue concentrations of total DDT plus
metabolites were reported in 35 industrially exposed
subjects: blood 0.11 to 2.2 μg/mL (mean 0.6), fat 38
to 647 μg/g (mean 204), urine 0.05 to 3.4 μg/mL
(mean 1.3); DDE accounted for about 40% of the
material stored in fat and 6% of the urinary material.
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Toxicity
The estimated minimum lethal dose is 30 g but a
single oral dose of 10 mg/kg may produce
toxic symptoms; the maximum permissible
atmospheric concentration is 1 mg/m3 and the
maximum acceptable daily intake is 5 μg/kg.
The toxicity of some of the organic solvents,
such as kerosene, used in the application of
clofenotane has probably contributed to
clofenotane fatalities
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Lindane
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Pesticide
Synonyms. 666; Benhexachlor; Gamma
Benzene Hexachloride; Gamma-BHC;
Gamma-HCH; HCH; Hexicide
A white crystalline powder. M.p. 112.5°.
Practically insoluble in water; soluble 1 in 19
of dehydrated alcohol, 1 in 2 of acetone, 1 in
3.5 of chloroform, and 1 in 5.5 of ether
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Disposition in the Body
Readily absorbed after ingestion, inhalation, or through
the skin. It is stored in the body fat and adrenal
glands. Metabolised by oxidation and
dehydrohalogenation to a series of chlorinated
phenols which are excreted mainly in the urine in free
and conjugated form.
After intravenous administration, about 25% of the dose
is excreted in the urine; after topical administration
about 10% of the dose is recovered in the urine
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Blood concentration
Blood–lindane concentrations in subjects with low occupational
exposure ranged from 1 to 9 μg/L (mean 4), and
concentrations in subjects with high dermal occupational
exposure ranged from 6 to 93 μg/L (mean 31). [
Average serum concentrations of 0.07, 0.19, and 0.04 mg/L of αbenzene hexachloride (α-BHC), β-BHC, and γ-BHC,
respectively, were reported in 57 subjects who worked in a
factory manufacturing lindane; β-BHC was the only isomer
observed to accumulate on chronic exposure. A mean fat
concentration of 45.6 μg/g of β-BHC was reported in 8
subjects.
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Toxicity
Lindane is not highly toxic when applied externally in the
concentrations usually employed (0.1 to 1%), but when
ingested it may cause convulsions; dusts may irritate the nose
and throat when used in a confined space. Blood
concentrations greater than 0.02 mg/L have been associated
with toxic effects. The estimated minimum oral lethal dose is
200 mg/kg and the maximum permissible atmospheric
concentration is 0.5 mg/m3. Toxic doses or long-term exposure
may cause liver necrosis. The maximum acceptable daily
intake is 10 μg/kg
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A young girl who ingested about 1.6 g of lindane was
found to have a serum concentration of 0.84 mg/L
after 2 h, following convulsions; the concentration
decreased to 0.49 mg/L after 4 h; urinary
concentrations of individual free phenolic metabolites
determined 5.5 h after ingestion ranged from 0.04 to
0.74 mg/L
A fat concentration of 343 μg/g was reported in a
fatality caused by lindane
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Dieldrin
Insecticide
Proprietary name. Dilstan EC-15
Dieldrin contains about 85% of HEOD,
(1aα,2β,2aα,3β,6β,6aα,7β,7aα)-3,4,5,6,9,9–
hexachloro–1a,2,2a,3,6,6a,7,7a–octahydro–2,7:3,6–
dimethanonaphth[2,3-b]oxirene, the remaining 15%
being mainly chlorinated organic compounds related
to HEOD
A light–tan, flaky, crystalline solid. M.p. 176° to 177°.
Practically insoluble in water; soluble 1 in 4 of ethanol,
1 in 40 of carbon tetrachloride, and 1 in 1 of
methanol; moderately soluble in chloroform
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

Colour Tests
Nitric–Sulfuric Acid—pink; Sulfuric Acid–
Fuming Sulfuric Acid—red
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Disposition in the Body
Both dieldrin powder and solutions are readily absorbed
after oral administration, through the lungs, and
through intact skin. Dieldrin is selectively stored in
body fat and persists for several weeks after cessation
of exposure. It is eliminated in the faeces mainly as
unknown hydrophilic metabolites; a small amount is
excreted in the urine as metabolites but very little as
unchanged dieldrin.
Dieldrin is a metabolite of aldrin
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Blood concentration
Blood concentrations averaging 0.001 mg/L have
been reported in subjects with no occupational
exposure to dieldrin
Serum concentrations ranging from 0.001 to
0.137 mg/L (mean 0.02) were reported in 71
industrially exposed workers, and fat
concentrations of 0.6 to 32 μg/g (mean 6) were
reported in 28 of these subjects
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Steady–state blood concentrations of about 0.007
and 0.02 mg/L were reported in 2 groups of 3
subjects who received doses of 0.05 mg and
0.21 mg daily for 2 years; maximum fat
concentrations of 1.3 to 1.6 μg/g and 2.2 to
4.9 μg/g were reported in the same subjects
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Toxicity
The estimated minimum lethal dose is 5 g;
ingestion of 10 mg/kg may produce toxic
effects. The maximum permissible
atmospheric concentration is 0.25 mg/m3 and
the maximum acceptable daily intake is
0.1 μg/kg. Blood concentrations greater than
0.15 μg/mL are usually toxic. Several fatalities
due to accidental or deliberate ingestion of
dieldrin have been reported.
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
A serum concentration of 0.27 mg/L and a fat
concentration of 47 μg/g were reported 3 days
after ingestion of dieldrin by a 4–year–old boy
who survived

In a fatality due to the ingestion of dieldrin,
postmortem blood and liver concentrations of
0.5 mg/L and 29 μg/g, respectively, were
reported
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Half–life.
Blood half–life, 50 to 170 days (mean 97).
Distribution in blood.
Plasma:whole blood ratio, about 1.5.
Protein binding.
In plasma, more than 99%.
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Chlordane


Pesticide
Synonym .Chlordan
Technical chlordane is a mixture of chlorinated
methano-indenes, the major components being the
two stereoisomers cis-chlordane and trans-chlordane
The technical grade is an amber viscous liquid which is
decomposed by alkalis
Insoluble in water; miscible with ethanol, chloroform,
and ether
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Disposition in the Body
Readily absorbed from the gastro–intestinal tract, lungs,
and the skin. It is stored in adipose tissue.
Oxychlordane has been detected in adipose tissue and
breast milk
Toxicity
Severe toxicity may result after ingestion or skin
contamination with greater than 1 g, and fatalities
have occurred after the ingestion of more than 2 g
and after excessive skin contamination. The
maximum permissible atmospheric concentration is
0.5 mg/m3
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In a non–fatal poisoning case, a 4–year–old child who
ingested an unknown amount of chlordane and
developed intermittent convulsions had an initial
serum concentration of 3.4 mg/L which decreased to
0.14 mg/L after 72 h; the rate of decline of the serum
concentration was non–linear with a terminal half–
life of 88 days. Urine samples obtained during the
first 3 days after ingestion showed a decrease from
1.9 mg/L to 0.05 mg/L, but increased to 0.13 mg/L on
the 35th day
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The following postmortem concentrations were reported
in a fatality due to the ingestion of chlordane: blood
4.4 mg/L, urine 0.24 mg/L.
A 66–year–old man who ingested about 400 mL of a
70% commercial solution and died after 40 h had the
following postmortem tissue concentrations: blood
1.7 mg/L, fat 378 μg/g, kidney 14 μg/g, liver 43 μg/g,
urine 0.6 mg/L.
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Heptachlor
Insecticide
Proprietary names. Drinox; Heptamul; Velsicol 104
The pure substance is a white crystalline solid and the
technical grade is a soft, waxy solid which contains
about 72% of heptachlor and 28% of related
compounds. Heptachlor may be found as an impurity
in chlordane. M.p. 95° to 96° (pure substance), 46° to
74° (technical grade).
Practically insoluble in water; soluble 1 in 22 of ethanol
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Carbamates: Aldicarb
Acaricide, Insecticide, Nematicide
Synonyms . Aldicarbe; carbanolate
A white crystalline powder. M.p. 90° to 100°.
It is soluble in water (0.1 to 1.0 mg/mL at 22°), DMSO
(>100 mg/mL at 21°), 95% ethanol (>100 mg/mL at
21°), acetone (>100 mg/mL at 21°), chloroform,
isopropane, toluene, and most organic solvents;
insoluble in heptane and mineral oils
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Disposition in the Body
Aldicarb is efficiently absorbed from the gastrointestinal
tract and at a lesser extent through the skin. It is
distributed to all tissues, but it does not significantly
cross the blood–brain barrier, and is metabolised to
aldicarb sulfoxide and aldicarb sulfone metabolites
which are both toxic. Both metabolites can be
detoxified by hydrolysis to oximes and nitriles. The
drug and metabolites are excreted primarily in urine.
Aldicarb does not accumulate in the body during
long-term exposure
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Toxicity
Aldicarb exposure may be fatal and may occur
by ingestion, inhalation, or when absorbed
through the skin. Very high doses may result in
paralysis of the respiratory system and the
nervous system. Toxicity can occur between
15 min and 3 h post–exposure but effects can
disappear quite quickly within 4 to 12 h. The
allowed daily intake is 5 μg/kg bodyweight
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Atrazine
Colourless crystals.
M.p. 171° to 174°
Practically insoluble
in water; soluble 1
in 20 of chloroform,
1 in 80 of ether, and
1 in 55 of methanol
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Organophosphorus Compounds:
Dichlorvos
Insecticide
Synonyms .DDVP; Dichlorfos; Dichlorovos;
Dichlorphos
It is soluble in water (8000 mg/L at 20°) and glycerol
(0.5 g/100 mL); very soluble in dichloromethane, 2–
propanol, and toluene; soluble in ethanol, chloroform,
acetone, and kerosene; miscible with many organic
solvents and aerosol propellents; moderately soluble
in diesel oil, kerosene, isoparaffinic hydrocarbons,
and mineral oils
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A colourless to
amber, oily liquid .
M.p. <25°. B.p.
140° at 20 mmHg
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Disposition in the Body
Dichlorvos is easily absorbed through the skin. It is
absorbed after ingestion and rapidly moved to the
liver where it is quickly detoxified by degrading
enzymes, found in tissues and blood plasma. It is
distributed in tissues especially kidneys, liver,
stomach, and intestines. It is rapidly metabolised and
eliminated from the body via expired air and urine.
One metabolite is dimethylphosphate (DMP) which is
common for some of the organophosphate
compounds and another is dichloroacetaldehyde. It
does not accumulate in tissues
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Toxicity
Dichlorvos is highly toxic by inhalation, dermal absorption, and
ingestion. Severe poisoning will affect the CNS. A lethal oral
dose of 400 mg/kg body weight has been reported and a toxic
dose of 300 mg/kg. The allowed daily intake is 0.04 mg/kg
A 72–year–old woman was found dead after ingesting
dichlorvos. A 500 mL bottle of dichlorvos was found beside
the body (concentration 75%). 250 mL of a volatile fluid was
found in the stomach which was equivalent to 300 g
dichlorvos. Dichlorvos was detected in the spleen (3.34 mg/g),
heart (815 μg/g), urine (4.5 mg/L), blood (29 mg/L), brain
(9.7 μg/g), lung (81 μg/g), kidney (80 μg/g), and liver
(20 μg/g).
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Malathion




Pesticide
Synonyms .Carbofos
A colourless to light amber liquid which
decomposes in strong acid or high humidity.
Although stable in light, it decomposes at high
temperatures
Slightly soluble in water; miscible with many
organic solvents
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Colour Tests.
Palladium Chloride—brown; Phosphorus Test—yellow;
Half–life.
Derived from urinary excretion data, about 3 h.
Use.
Topically in concentrations of 0.5 or 1% in the treatment
of pediculosis
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Disposition in the Body.

Absorbed after oral ingestion but absorbed only slowly and to
a small extent through intact skin. It is metabolised by
conversion to malaoxon, the toxic keto analogue, and by
hydrolysis to malathion α-mono- and dicarboxylic acids which
are the major metabolites. Other hydrolysis products include
dimethylthiophosphoric acid (DMTP) and
dimethyldithiophosphoric acid (DMDTP) which have been
detected in the urine of subjects exposed to malathion. After
ingestion, up to 25% is excreted in the 24 h urine as ether–
extractable phosphates, mostly in the first 8 h.
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Toxicity
Malathion is less toxic than most other organophosphorus
pesticides; the estimated minimum lethal dose is 25 g; the
maximum permissible atmospheric concentration is 10 mg/m3
and the maximum acceptable daily intake is 20 μg/kg.
In 6 cases of suspected poisoning caused by malathion,
postmortem tissue concentrations were as follows: blood, 175
to 517 mg/L, lungs 77 to 330 μg/g, liver 198 to 383 μg/g,
kidneys 280 to 616 μg/g, spleen 175 to 475 μg/g, brain 84 to
387 μg/g, heart 160 to 315 μg/g, muscles 8 to 40 μg/g, urine
33 to 189 mg/L, gastric contents 452 to 989 mg/L
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An 80–year–old woman who committed suicide by
ingesting malathion mixed with a fruit drink had an
antemortem blood concentration of 23.9 mg/L
In a fatality involving a 40–year–old woman who
ingested a malathion-based pesticide (up to 350 to
400 mL), postmortem tissue concentrations were as
follows: blood 1.7 to 1.9 mg/L, gastric contents 975
to 981 mg/L, liver not detected
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Parathion
Pesticide
Proprietary names. Alkron; Aphamite; Folidol; Fostex
E; Fosferno 20; Niran; Nitrostigmine; Paraphos;
Rhodiatox; Thiophos
A pale yellow liquid which is decomposed by heat and
darkens on exposure to light. M.p. 6°. B.p. 375°.
Practically insoluble in water; miscible with most
organic solvents. It is rapidly hydrolysed in alkaline
solution
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Half–life.
Derived from urinary excretion data, about 8 h
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Disposition in the Body.
Parathion is activated in the liver by metabolism to paraoxon.
Parathion and paraoxon are further metabolised to
diethylthiophosphoric acid (DETP), diethylphosphoric acid
(DEP), and 4–nitrophenol which are the major urinary
excretion products although DETP and DEP are unstable in
stored urine. Urinary 4–nitrophenol concentrations may be
indicative of the extent of exposure to parathion. 4Nitrophenol is rapidly excreted in the urine and is not
detectable 48 h after exposure by inhalation or ingestion, but
excretion is more prolonged after exposure of intact skin due
to the much slower absorption of parathion by this route.
Aminoparathion has been detected in postmortem blood and
tissues
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Toxicity
The estimated minimum lethal dose by
inhalation or ingestion is 20 mg and the
maximum permissible atmospheric
concentration is 0.1 mg/m3. Urinary
concentrations of about 2 mg/L or more of 4–
nitrophenol may be associated with severe
toxicity. Numerous fatalities have occurred due
to contamination of food by parathion and also
from suicidal ingestion
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The following postmortem tissue concentrations
were reported in 19 fatalities due to parathion
poisoning (determined by a bioassay based on
cholinesterase inhibition): blood 0.5 to
34 mg/L (mean 9.0, 11 cases); brain 0.9 to
12.5 μg/g (mean 4.9, 4 cases); kidney 0.2 to
11.9 μg/g (mean 3.3, 9 cases); liver 0.08 to
120 μg/g (mean 11, 13 cases); urine 0.4 to
78 mg/L (mean 10, 10 cases)
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Azinphos–ethyl
Acaricide, Insecticide
Synonyms. Bayer 16259; ENT-22014; Ethyl
Guthion; Gusathion A
Colourless crystals. M.p. 53°. B.p. 111° at
0.001 mmHg
It is soluble in water (4 to 5 mg/L at 20°); readily
soluble in most organic solvents except
aliphatic hydrocarbons
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Disposition in the Body.
Azinphos is rapidly absorbed from the gastro–intestinal
tract after ingestion. It is excreted in urine.
Toxicity
In a series of azinphos–ethyl poisoning cases, fatal
cases were found to have blood levels of 1.112 mg/L
and above, serious cases of intoxication with levels of
494 μg/L and above, and less serious cases with
levels above 57 μg/L. Serious intoxication was
always observed with concentrations above 370 μg/L
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