Journal of Environmental Protection, 2010, 1, 231-241
doi:10.4236/jep.2010.13028 Published Online September 2010 (http://www.SciRP.org/journal/jep)
231
Hazard Assessment of Alternatives to Dicofol
Ana I. Sánchez1*, M. Dolores Hernando1, Juan J. Vaquero2, Eloy García3,4, José M. Navas5
1Parque Científico Tecnológico, University of Alcala, Alcalá de Henares, Madrid, Spain; 2Department of Organic Chemistry, Faculty
of Pharmacy, University of Alcala, Alcalá de Henares, Madrid, Spain; 3Department of Analytical Chemistry and Engineering Chem-
istry, Faculty of Chemistry, University of Alcala, Alcalá de Henares, Madrid, Spain; 4IMDEA Water Foundation, Alcalá de Henares,
Madrid, Spain; 5Department of Environment, Spanish National Institute for Agricultural and Food Research and Technology (INIA),
Madrid, Spain.
Received April 21st, 2010; revised May 12th, 2010; accepted May 22nd, 2010.
ABSTRACT
Dicofol was listed by International POPs Elimination Network (IPEN) as requiring immediate and urgent considera-
tion and thus was considered as a new candidate by Persistent Organic Pollutant Review Committee (POPRC) as a
possible persistent organic pollutant (POP). Dicofol is structurally similar to DDT. It is persistent in food and water,
highly toxic to aquatic life and causes egg-shell thinning in some bird species. High concern, due to the lack of dicofol
measurements in the Arctic, proving long range transport and bioaccumulation in wild life species, supports further
impact assessment of this product. Under Stockholm Convention, substances identified as POPs are regulated with the
objective to protect the environment and the human health. According to this objective, the search of environmental and
healthy alternatives is helpful. This paper discusses the use of three groups of chemicals currently applied as alterna-
tives to dicofol. An exhaustive review of the synthesis of dicofol, starting from DDT, and compared to possible substi-
tutes is presented: 1) active principle with fluoralkenyl are proposed as an environmental and healthy alternative to
dicofol, 2) inhibitor agents of mitochondrial electron transport as chlorfenapyr, hydramethylnon and pyridaben and 3)
pesticides commonly applied in agricultural practices as oxythioquinox, fenbutatin-oxide and formetanate hydrochlo-
ride.
Keywords: Dicofol, POPs, Chemical Structure, Effects, Alternatives
1. Introduction
Dicofol (1,1´-bis( p-chlorophenyl)-2,2,2-trichloro-ethanol)
is an organochlorine compound, miticide and acaricide. It
is applied in a wide variety of crops, fruits, vegetables,
ornamental and field crops. The use of this product is
extended on more than 30 countries, and on more than 60
different crops (aprox. 0.4 to 3.0 Kg a.i./ha) [1].
The worldwide consumption of dicofol is 2750 tons/
year as the following: 290 tons/year in Western Europe,
180 tons/year in Africa and Western Asia, 1820 tons/year
in Asia, 170 tons/year in South America and 290 tons/
year in North America. In Spain the use is 100-150 tons/
year [2].
Dicofol production was temporarily banned by U.S.
EPA in 1986. Afterwards it was reinstated as conse-
quence of a new manufacturing process which produced
technical-grade dicofol (< 0.1% DDTr, DDT and related
substances). DDTr level in dicofol can´t exceed 0.1% in
Canada.
The use of dicofol is allowed in several countries of
the EU (451/2000) [3]. Council Directive 79/117/EEC
prohibits the use and marketing of products containing
less than 78% p,p’-dicofol or more than 1 g/kg (= 0.1%)
of DDTr.
Persistent, bioaccumulative and toxic substances
(PBTs) and Persistent Organic Pollutants (POPs) are
identified or addressed through various national, regional
and global initiatives [4]. In the Stockholm Convention
framework, the assessment of POPs is described as an
evaluation of whether the chemical is likely, to lead to
significant adverse human health and/or environmental
effects, as a result of its long range environmental trans-
port, so that global action is warranted.
Dicofol is currently under a review process for its de-
signation as POP under the Stockholm Convention. Di-
cofol meets POP criteria but further assessment is needed
regarding ecotoxicity of metabolites, monitoring in re-
mote areas of dicofol and its metabolites [5].

Hazardous Assessment of Alternatives to Dicofol 232
Dicofol is degraded in water, sediments and soil. In
water, p,p’-dicofol meets the persistence criteria with a
half life of two months at pH = 5; o,p’-isomer has a half
life of 47, 0.3 and < 0.1 days at pH 5, 7 and 9 respec-
tively; p,p’-isomer has a half life of 85, 4 and < 0.1 days
at pH 5, 7 and 9 respectively. In sediments, isomers o,p’-
and p,p’-(pH of aqueous phase between 7.6 and 7.8) fail
the persistence criteria, as the half life is lower than one
day. The half life of dicofol metabolites in sediments is
between 7 and 429 days. In soils, half life of the o,p’- and
p,p’-isomer is between 8 and 35 days, and between 21
and 60 days, respectively [5].
The mechanism of bioaccumulation of dicofol is simi-
lar to other POPs. Dicofol has a log Kow of 4.08-5.02
and a bioconcentration factor in fish of 8050-13000.
Due to its vapour pressure (1 Pa) and estimated half
life in atmosphere (3.1 days), dicofol is expected to vola-
tilise significantly and it is assumed to be transported in
the atmosphere. Up to now, it is worthy of note that no
monitoring data are available in remote areas. It has been
hypothesized that dicofol may be globally distributed and
should meet criterion for potential long-range atmos-
pheric transport.
Dicofol is fairly toxic to mammals but isn´t carcino-
genic. It is reported to be repro-toxic in wildlife, and it
may reduce eggshell quality as well. Dicofol is very toxic
for aquatic organisms with lethal/effective concentration,
L(E)C50 values of 15-120 μg/l obtained by acute toxicity
tests and, no observed effect concentration, NOEC values
of 4.4-125 μg/l for chronic effects. Evidence of induction
hepatic microsomal metabolism is available for rats [6].
Metabolites show similar toxic effects for aquatic organ-
ism based on range-finding studies and quantity struc-
ture-activity relationship (QSAR) model estimations. In
Scheme 1, degradation (biotic and abiotic) pathways of
dicofol and metabolites are shown [7].
This work shows a review of possible substitution al-
ternatives to dicofol from the chemical perspective, ana-
lyzing the product synthesis, its chemical structure and
its effects on the environment and human health. Target
chemical groups in this article are: 1) active principles
such as fluoralkenyl derivatives introduced as an envi-
ronmental and healthy solution to dicofol, 2) second
group based on the mode of action, mitochondrial elec-
tron transport inhibitors as chlorfenapyr, hydramethylnon
and pyridaben; and 3) alternative pesticides commonly
used in agricultural practices as oxythioquinox, fenbu-
tatin-oxide and formetanate hydrochloride.
2. Chemistry Facts
2.1. DDT and Dicofol Synthetic Processes
DDT is produced as an intermediate in dicofol synthesis.
OH
Cl Cl
H
Cl Cl
OH
Cl Cl
Cl
Cl
Cl
OH
Cl Cl
Cl
Cl Cl Cl
O
Cl
p,p'-dicofol
p,p'-diclorodicofol
p,p'-dicloroben zofeno na
p,p'-diclorob enzidrol
Scheme 1. Metabolite pathway in dicofol transformation.
Reaction pathways shown are from Brown & Casida (1987).
Arrow thickness is added to roughly indicate relative rates
of conversion.
The active ingredient dicofol is a mixture of approxi-
mately 80% of p,p’-dicofol and 20% of o,p’-dicofol [8].
It is produced by hydroxylation reaction of DDT, which
is an emulsionable concentrate and can be commercial-
ized as wettable tablets or water-soluble.
DDT was first synthesized in 1874 by Zeidler and its
insecticidal properties were discovered by J.R. Geigy.
The formation of technical DDT was optimized by
Mosher, improving the original synthesis by Zeidler and
the variation of Baeyer [9], Scheme 2.
The reaction rate at low temperatures is slow, and at
high temperatures results on the degradation of the prod-
uct, although this can be avoided by using major acid
concentration and lower temperature, or by using diluted
acid and higher temperatures. A secondary reaction it is
always raised, that supposes the chlorobenzene sulfona-
tion. At last, the higher DDT yield is obtained at 90℃,
with a 98% sulphuric acid concentration, and a 1:4 chlo-
robenzene excess, stirring for 8 h at 5-10℃, DDT yield is
97%.
Technical DDT contains approximately 77% of p,p’-
DDT, 15% of o,p’-DDT and 1.5% of an oily compound
that is 2-trichloro-1-p-chloro-phenylethanol.
DDT synthesis was optimized using fluorhydric acid
as condensing agent [10], Scheme 3.
Latterly, DDT analogues synthesis has been prepared
to examine its insecticidal properties [11].
Dicofol is produced from chloral (trichloroacetic alde-
hyde), monochlorobenzene and oleum (fuming sulphuric
acid: sulphur VI containing excess of sulphur trioxide),
Scheme 4.
Another synthetic process used to obtain technical di-
cofol was developed by Tang [12], it starts from DDT

Hazardous Assessment of Alternatives to Dicofol 233
Scheme 2. Preparation of technical DDT.
Scheme 3. Improved preparation of technical DDT.
and after chlorination and hydrolysis the desired product
is obtained, Scheme 5. Impurities generated throughout
the synthetic process are DDT and Cl-DDT.
2.2. Alternative Products
The pesticidal natural action of a compound is predomi-
nantly associated with its structure [13]. Also, the differ-
ent moieties attached to parent compound, their spatial
arrangements within the molecule, nature of substituents,
polarity, symmetry and asymmetry of molecules, the
solubility, sorption values, etc., have a direct or indirect
bearing on the toxicity of the parent pesticidal compound.
So, having an insight into the structure and toxicity rela-
tionship within each class of pesticides provides a better
understanding of this correlation. The understanding of
this relationship is vital in order to generate a molecule
with a tailored fragment powered to act on the pests.
2.2.1. Fluoralkenyl Derivatives
Fluoroalkenyls [14], including all the geometric and
stereoisomers, N-oxides, and salts thereof, can be an op-
tion to dicofol. These are compounds of Figure 1
wherein X is H, F, C1-C4 haloalkyl, A is O, S or NR1; B
is C1-C4 alkylene; Y is a 5- or 6-membered heteroaro-
matic ring or an aromatic 8-, 9- or 19-membered fused
heterobicyclic ring system, each ring or ring system op-
tionally substituted with 1 to 6 substituents independently
selected from R2, or Y is O(CH2CH2O)mR3; and R1, R2
and R3, n and m are as defined in the figure. These prod-
ucts have showed extremely effective for controlling
invertebrate pest comprising contacting the invertebrate
pest or its environment, thus an amount of a fluoroal-
kenyl compound is conjugated with an amount of at least
one additional biologically active compound or agent.
Scheme 4. Synthesis of dicofol starting from DDT.
Scheme 5. Alternative synthesis of dicofol starting from DDT.
F
F
X
O
AB
Y
(CH2CH2)n
Figure 1. Fluoroalkenyl derivatives.
These additional biologically active compounds are
showed on Table 1.
The mode of action of the pesticide in target organism
is closely associated with the structure of the pesticidal
compound. The structure of the parent molecule of
structure is not only responsible for the activity but also
the nature of substituents, or also the presence of an ep-
oxide ring, double–triple bond, conjugation, aromaticity
and stereochemistry determine the toxicity of the pesti-
cidal compound. So, understanding of the structure of

Hazardous Assessment of Alternatives to Dicofol 234
Table 1. Control agents for invertebrate pest based on its
mode of action.
Mode of Action Control Active Principle
Sodium channel
modulators
Bifenthrin, cypermethrin, cyhalothrin,
lambda-cyhalothrin, cyfluthrin, beta-
cyfluthrin, deltamethrin, dimefluthrin,
esfenvalerate, fenvalerate, indoxacarb,
metofluthrin, profluthrin, pyrethrin and
tralomethrin.
Acetyl cholinesterase
inhibitors
Chlorpyrifos, methomyl, oxamyl, thio-
dicarb, formetanate hydrochloride and
triazamate.
Neocotinic receptor
modulator
Acetamiprid, clothianidin, dinotefuran,
imidacloprid, nitenpyram, nithiazine,
thiacloprid and thiamethosam.
Insecticidal
macrocycles lactones
Spinetoram, spinosad, abamectin, aver-
mectin and emamectin.
(Gamma-aminobutyric
acid)-regulated chloride
channel modulators
[GABA]
Endosulfan, dicofol, ethiprole and
fipronil.
Chitin synthesis
inhibitor
Buprofezin, cyrimazine, flufenosuron,
hexaflumuron, lufenuron, novaluron,
noviflumuron and triflumuron.
Juvenile hormone
mimics
Diofenolan, fenoxycarb, methoprene
and pyriproxyfen.
Inhibitors of oxidative
phosphorylation, dis-
rupters of ATP forma-
tion (inhibitors of ATP
synthase)
Fenbutatin-oxide.
Octapamine receptor
modulators Amitraz.
Ecdysone receptor
agonists
Azadirachtin, methosyfenozide and te-
bufenozide.
Ryanodine receptor
ligands
Ryanodine, anthranilic diamides such us
chloroantraniliprole and flubendiamide.
Nereistoxin analogs Cartap.
Mitochondrial electron
transport inhibitors
Chlorfenapyr, hydramethylnon and pyri-
daben.
Lipid biosynthesis
inhibitors Spirodiclofen and spiromesifen.
Disrupting protein
function Oxythioquinox.
Cyclodiene
insecticides
Dieldrin, cyflumetofen, fenothiocarb,
flonicamid, metaflumizone, pyrafluprole,
pyridalyl, pyripole, spirotetramat and
thiosultap-sodium.
Nucleopolyhedrovirus
mixture
HzNPV and AfNPV. Bacillus thur-
ingiensis and encapsulated delta-endo-
toxins or Bacillus thuringiensis such us
Celicap, MPV and MPVII, as well as
naturally occurring and genetically mo-
dified viral insecticides including mem-
bers of the family Baculoviridae as well
as entomophagous fungi.
compounds and their correlation with toxicity to target
organism is a very important parameter for developing
better designed pesticidal compounds with tailored tox-
icidal properties on different pests.
These invertebrate pests can be arthropods (e.g. insects,
mites, spiders, scorpions, centipedes, millipedes, pill bugs
and symphylans, etc.), gastropods (e.g. snail, slugs, etc.)
and nematodes (e.g. warms, etc.).
These compounds can generally be used as a formula-
tion or a composition with a carrier suitable for agro-
nomic or nonagronomic uses comprising at least one of a
liquid diluent, a solid diluent or a surfactant. The formu-
lation or composition ingredients are selected to be con-
sistent with the physical properties of the active ingredi-
ent, mode of application and environmental factors such
as soil type, moisture and temperature. Useful formula-
tions include liquids such as solutions (including emulsi-
fiable concentrates), suspensions, emulsions (including
microemulsions and/or suspoemulsions) and the like
which optionally can be thickened into gel; others in-
clude solids such as dusts, powders, granules, pellets,
tablets, films (including seed coatings), and the like
which can be water-dispersible (“wettable”) or water-
soluble. Encapsulation can control or delay release of the
active ingredient. Sprayable formulations can be ex-
tended in suitable media and used at spray volumes from
about one to several hundred liters per hectare.
2.2.2. Inhibition Agents Acting as Mitochondrial
Electron Transport
Pardini et al. [15] have determined that dicofol acts as a
mitochondrial electron transport inhibitor, studies sug-
gest that some organochlorine pesticides and the hy-
droxylated breakdown products of carbaryl are inhibitory
towards mitochondrial electron transport systems in vitro.
Further investigations should be conducted to determine
if the inhibition of mitochondrial electron transport sys-
tems is of toxicological importance in the intact organism.
Consequently, dicofol ought to be compared with prod-
ucts that have the same mode of action, such as chlor-
fenapyr, hydramethylnon and pyridaben.
Chlorfenapyr synthesis was developed by Xu [16]
starting from α-p-chlorophenyl) glycine, Scheme 6. Gly-
cine reacts with trifluoroacetic anhydride, and latterly
with 2-chloroacrilonitrile, giving an intermediate that is
2-(p-chlorophenyl)-5-(trifluoromethyl)pyrrol-3-carbonitri
le. This intermediate reacts through a bromination reac-
tion at pyrrol ring in the presence of a weak base, and the
resulting bromide performs an ethoxymethylation with
methyl dibromide and sodium ethoxide, total yield is
65%. Chlorfenapyr purity is 95%, and the bromination
process has been improved significantly.
Hydramethylnon synthesis was achieved through the
coupling in alcoholic media refluxing the compound
1,5-bis[p-(trifluoromethoxy)phenyl]-1,4-pentadien-3-one
afforded the desired product in 50% yield [17], Scheme
7.

Hazardous Assessment of Alternatives to Dicofol 235
O
O
O
F3C
F3C
Cl
NH2
CO2H
O
N
O
F3C
Cl
Cl
CN N
H
Cl
F3C
CN
N
H
Cl
F3C
CN
Br
N
Cl
F3C
CN
Br
OEt
+
r.t. reflux
2 h. reflux
93 %
Et3N
r.t. reflux
90 %
NaHCO3
Br2
r.t. 4 h.
r.t.
92 %
i) NaH, THF, 30 min. r.t.
ii) CH2Br2, NaOEt, 2 h. reflux. 12 - 16 h. r.t.
90 %
reflux
Scheme 6. Synthesis of chlorfenapyr.
O
F3C
F3C
NH
N
H
NN
F3C
F3C
NH
N
H NNH2
+
EtOH
3 h. reflux
50 %
Scheme 7. Synthesis of hydramethylnon.
Pyridaben synthesis was developed by Xu [18] starting
from 2-tert-butyl-4,4-dichloropyridazin-3(2H)-one, and
4-tert-(butylphenyl)methanothiol, in sodium methoxide
media, stirring for one hour at controlled temperature,
obtaining the final product in 96% yield, Scheme 8.
2.2.3 Pesticide Alternatives to Dicofol of Common Use
Other pesticides analyzed due to its major use in different
crops are oxythioquinox, fenbutatin-oxide and formetan-
ate hydrochloride [19]. These alternatives are more poi-
sonous than dicofol to beneficial insects, but many trials
suggest that the efficacy is superior even though the
production lost is about three percent. Oxythioquinox is a
sulphur containing chemical, this quinoxaline-2,3-dithio-
carbonate is obtained reacting a quinoxaline-2,3-dithiol
substituted with an alkyl group with a carbonylating agent
selected from triphosgene, and diphosgene. It is prefer-
able that the quantity of the carbonylating agent is 0.34-5
molar times, for triphosgen, or 0.5-5 molar times, for
diphosgene. The above reaction is better conducted under
basic conditions to scavenge hydrochloric acid produced
as by-product. The reaction temperature has to be main-
tained from –78 to 50℃ [20], Scheme 9.
An alternative synthesis to obtain this product starts
from 2,6-dimercapto-6-methylquinoxaline that reacts with
an hydroxide or the alike of an alkali metal in water or an
alcohol solvent, and an organic solvent such as aromatic
hydrocarbons, for example, toluene or xylene is added to
the reaction mixture. The reaction mixture with the or-
ganic solvent is subjected to an azeotropic dehydration
and a solvent replacement to form an alkali salt, and the
alkali salt is reacted with the intermediated, where R is a
methyl group preferably in an amount of 1.0-4.0 molar
times in the presence of a phase transfer catalyst (e.g. a
quaternary ammonium salt or a pyridinium salt) in an
amount of 1-5% mol% at 0-150℃ for 0.5-10 h. to pro-
vide the objective compound S,S-(6-methylquinoxaline-
2,3-diyl)dithiocarbonate [21], Scheme 10.
Fenbutatin-oxide is an organotin compound, the syn-
thesis of this compound is achieved starting from neo-
phyl chloride, it occurs through a magnesium intermedi-
ate that reacts with tin tetrachloride, hydrolysis adding
Scheme 8. Synthesis of pyridaben.
N
H
N
H
CH3S
SN
N
CH3
S
S
O
Cl3CO
O
OCl3C
96 %
KOH aq.
DIOXANE
+
Scheme 9. Synthesis of oxythioquinox.

Hazardous Assessment of Alternatives to Dicofol 236
sodium hydroxide provides the final product [22], Scheme
11.
Formetanate hydrochloride is a bifuntional pesticide,
so the two reactive groups of this molecule are forma-
midine and carbamate, and this remarks the water solu-
bility, and also the toxicity and potential mobility in
aqueous environments. The formetanate is obtained from
meta-aminophenol and dimethylformamide in phospho-
rous oxychloride, after purification of the intermediate
and reaction with methyl isocianate and acid treatment
produce the formetanate [23], Scheme 12. The final step
in the synthesis may be accomplished by treating the
formetanate with the appropriate acid chloride or anhy-
dride in an inert solvent as diethyl ether [24].
N
H
N
H
CH3S
S
N
N CH3
S
S
O
O
O
Cl
N+Br Bu4
+
92 %
i) NaOH,/ MeOH
ii) TOLUENE
Scheme 10. Alternative synthesis of oxythioquinox.
CH3CH3
Cl
CH3CH3
Mg Cl
CH3
CH3
CH3
CH3
CH3CH3
CH3
CH3
Sn OSn
CH3CH3
CH3
CH3
CH3
CH3
Sn CH3
CH3
CH3CH3
+Mg
SnCl4
+ H2O
NaOH
Scheme 11. Synthesis of fenbutatin-oxide.
OH
NH2
N
CH3
CH3
O
H
OH
N C
HN
CH3
CH3
N OCH3
O
N C
HN
CH3
CH3
N
H
O
CH3
+
POCl3
+
Scheme 12. Synthesis of formetanate.
These anthropogenic compounds have some structural
similarities, due to the relation structure-toxicity; most of
them are organochlorines pesticides.
Dicofol is a chlorinated compound as well as chlor-
fenapyr and pyridaben, similarly dicofol shows a tri-
chloromethyl group, and chlorfenapyr and hydramethyl-
non have a trifluoromethyl group, in most cases fluor
enlarge the activity of a biologically active compound.
Sulphur is contained in pyridaben and oxythioquinox, as
historically use of pure sulphur to control insect pests.
Diazacompounds exhibit also activity as pyrimidine in
hydramethylnon, pyridazine in pyridaben and a pipera-
zine moiety in oxythioquinox. Another hit that increase
the toxicity can be explained by the para-substitution, as
in dicofol, hydramethylnon, pyridaben and oxythioqui-
nox. Toxicity in fenbutatin-oxide can be explained by the
metal element, since organo tin substances are known to
disturb growth, reproduction, enzymatic systems and
feeding patterns of aquatic organism.
Triethyltin is the most dangerous organo tin substance
for humans. It has relatively short hydrogen bonds. When
hydrogen bonds grow longer a tin substance will be less
dangerous to human health. So that is why fenbutatin-
oxide increases volume with a phenyl group. The dimmer
explains double amount of toxic substance. The molecule
geometry is important, as DDT and dicofol have a Z
group of sufficient steric size, e.g. trichloromethyl, to
inhibit the free rotation of the planar phenyl rings so that
they are constrained to positions of minimum steric
grouping, termed a trihedral configuration. Other sym-
metrical molecules are hydramethylnon and oxythioqui-
nox (except methyl substitution that can be here consid-
ered as a minor group, since this group does not interfere
with the C2 operation).
Formetanate hydrochloride has two possible active moie-
ties, is both arylformamidine and arylcarbamate groups, it
appears to exert its toxicity to rats, houseflies, and mites as
an anticholinesterase agent than a formamide [25], car-
bamates inhibit cholinesterase and prevent the termination

Hazardous Assessment of Alternatives to Dicofol 237
of nerve impulse transmission. The formetanate salt must
be prepared to improved aqueous solubility since the car-
bamates are systemic to roots via soil applications or
through leaves from foliar applications [26].
3. Environmental and Human Effects of
Selected Chemicals Alternatives to Dicofol
Dicofol is a miticidal pesticide and acaricide, its precur-
sor DDT was a revolutionary pesticide in agriculture,
since it eradicated malaria from North America and
Europe [27]. There is evidence that DDT plays a role in
the aetiology such as pancreatic cancer, neuropsy-
chological dysfunction, and reproductive outcomes. Re-
search into these and other conditions would benefit from
the same rigorous approaches used in breast cancer re-
search. Until further high quality evidence is available, it
is still too early, even 60 years after the introduction of
this once ubiquitous chemical, to pass judgement on the
role of DDT in a number of common diseases. This im-
plies dicofol could produce the same injuries to humans
since the structure similarities.
The possible alternatives listed show acaricide func-
tion as a majority function, Table 2, mode of action is for
chlorfenapyr oxidative phosphorylation inhibition, given
that it provokes a disruption of production of adenosine
triphosphate (ATP) [29], this induces the cellular death
and ultimately organism mortality, fenbutatin-oxide also
inhibits oxidative phosphorylation [39], but this com-
pound is non-systemic—a systemic pesticide is when the
chemical is transported from the place of application to
other parts of a plant or animal—so the product must
usually be ingested by the organism [40], this usually
affects beneficial insects. Dicofol has been widely use to
control vine mites, the suggestion of DDTr residues in
dried fruit or wine products is potentially extremely
damaging to viticultural industry. At this moment there
are few chemical alternatives cheap and effective, as long
as the only miticide presented here is oxythioquinox,
Table 2. Summary of environmental and human effects of alternatives to dicofol.
Compound Description/
Way of action Uses Human adverse effects Ref. Associate impact Ref.
N
Cl
Br N
O
F
F
F
CHLORFENAPYR
Activity
Acaricide, Insecticide
Halogenated pyrrol group.
Its biological activity de-
pends on its activation to
another chemical compo-
unds.
Oxidative removal of the
N-ethoxymethyl group of
chlorfenapyr by mixed fu-
nction oxidases forms an
intermediate that uncou-
ples oxidative phosphori-
lation at the mitochon-
dria, resulting in disrup-
tion of production of ATP
(adenosin triphosphate),
cellular death and ulti-
mately organism mortality.
Different crops as
cotton, vegeta-
bles, citrus, top
fruits, vines and
Soya bean, or-
namental crops.
Carcinogenic po-
tential: Cannot be
determined but
suggestive.
Tox Category II
(acute test with the
rat).
Tox Category III
(oral, dermal, and
inhalation study
results).
No evidence of
genotoxicity.
[28,29]
Due to its persistence
and adverse reproduc-
tive effects in birds, it is
banned in outdoor
atmospheres; the green
house use is not ex-
pected to result in out-
door residues, drift or
runoff. So it is expected
no wildlife exposure
and other significant
environmental exposure
or risk since It is toxic
to bees and high toxic
to aquatic livings such
as fish, prawn.
[29,30]
F
F
F
F
F
F
N
N
N
H
NH
HYDRAMETHYLNON
Activity
Insecticide, broad-spectrum
fase effective acaricide.
Trifluroromethylamino
hidrazones group, which
act as a metabolic inhibi-
tor.
Causes death by inhibit-
ing the formation of ATP
(adenosine triphosphate);
ATP provides the energy
neces- sary for completing
most biological processes,
without ATP insects just
die.
Control ants in
grasses and
rangelands and
other non-crop
lands (lawns,
turf, and
non-bearing
nursery stock).
Control of
household ant
species and
cockroaches in
non-food use
areas in and
around domestic
dwellings and
commercial
establishments
Carcinogenic po-
tential Group C:
Possible Human
Carcinogen (U.S.
EPA, 1996).
Tox Category III
(acute test oral and
dermal with the
rat).
Tox Category IV
(acute test inhala-
tion with the rat).
No genotoxic in
microbial test sys-
tems or clastogenic
in cultured mam-
malian cells. Not
induce dominant
lethality in male rat
germinal cells.
[28,
31, 32]
Especially toxic for
fishes. High bioconcen-
tration potential, even
though its bioaccumu-
lation potential is low.
Moderated toxicity for
mammals, birds, fishes
an aquatic inverte-
brates, algae and bene-
ficial organism.
[32,33]

Hazardous Assessment of Alternatives to Dicofol 238
Table 3. Summary of environmental and human effects of alternatives to dicofol.
Compound Description/
Way of action Uses Human adverse effects Ref. Associate impact Ref.
S
N
N
Cl
O
PYRIDABEN
Activity
Non-systemic acaricide and
insecticide which is active
control of mites and whiteflies.
Pyridazone group.
Acts as a mitochondrial
electronic transport in-
hibitor at complex I
mode of action.
Control of mite
and white flies
on ornamental
plants, flowers
and foliage
(non-food) crops
in green houses,
and for the use to
control mites on
apples, pears and
almonds.
Grapes, apricots,
cherries,
nectarines,
peaches,
pistachio, plums,
prunes and the
tree nut group.
Carcinogenic
potential: Group E:
Evidence of
Non-Carcinogenici
ty for humans
based on the lack
of evidence of
carcinogenicity in
male and female
rats as well as in
male and female
mice.
Toxicity to hu-
mans, including
carcinogenicity,
reproductive and
developmental
toxicity, neurotox-
icity, and acute
toxicity. Biocon-
centration and
bioaccumulation
factors are low. It
has been demon-
strated human
toxicity since it is
harmful for neuro-
blastoma cells.
[28,34]
Water quality stan-
dards and physical
properties affecting
water contamination
potential. Aquatic
toxicity, bioconcentra-
tion and environmental
fate of pyridaben are
similar to synthetic
pyrethroids used in
agriculture, the main
distinguishing feature
is that pyridaben is
more photo-labile than
most pyrethroid, pyri-
daben can be photo-
chemically degraded
(Rand et al., 2000)
Acute-to-chronic ratios
for pyridaben are low
for fish and inverte-
brates indicating a low
potential for residual
activity.
[35,36]
N
N
CH3
S
S
O
OXYTHIOQUINOX
Activity
Insecticide, acaricide,
fungicide, ovicide.
Thiocarbamate group.
The binding of oxythio-
quinox to proteins prob-
able evolved a mecha-
nism by which the sulf-
hydryl group of proteins
initially attacked the
carbonyl carbon of the
acaricide, and the acari-
cidal action of oxythio-
quinox is due to the
disruption of the normal
function of significant
proteins by the parent
compound itself.
Only to use on
non-food crops
(landscape or-
namentals) and
places (nurseries
and green-
houses). It is
reported to be
incompatible
with oils (caus-
ing phytotoxic-
ity).
Carcinogenic
potential: Group
B2 (probable hu-
man carcinogen)
based on lung
tumours in males
mice.
Toxicity Category
III or IV. Category
II: Causes ire-
versible eye dam-
age. Some by-
standers may ex-
perience a skin
reaction similar to
sun burn, particu-
larly if wind is
present during
applications.
[28,
37,38]
Moderately toxic to
birds and adversely
affected egg produc-
tion, embryo survival
(and perhaps fertility),
hatch ability, offspring
body weight and sur-
vival of offspring in
avian reproduction
studies.
Highly toxic to fish
and other aquatic or-
ganisms.
[38]
Table 3, and it is no recommended for food crops, since
it is a probable human carcinogen.
Formetanate hydrochloride has been applied predomi-
nantly to nectarines crops, and the way of action is simi-
lar to fenbutatin-oxide [41], Table 4, the toxicology is
determined by its high solubility in water, more than
800.00 mg/l, since it is widespread in contaminated water,
it supposes a great danger for aquatic organism, even
though there is no complete data in the risk assessment
about injuries to freshwater fish or invertebrates [42,43].
Its acetyl cholinesterase action can even affect to human,
since it has acute toxicity via oral route. Formetanate
hydrochloride is considered a Group E, carcinogenic
potential since there is evidence of no-carcinogenecity
for humans [28]. Hydramethylnon is used to control ants
and cockroaches in domestic and commercial establish-
ments, but pyridaben is more used to control mites out-
door, in different crops of flowers and ornamental plants,
and in grapes, apricots, etc. [31,32]. Pyridaben can be
photochemically degraded, acute and chronic ratios for
fish and invertebrates are low, as well as its bioconcen-
tration and bioaccumulation potential, in front of dicofol.
Hydramethylnon and pyridaben provoke death by inhib-
iting the formation of ATP [32,34], the difference is that

Hazardous Assessment of Alternatives to Dicofol 239
Table 4. Summary of environmental and human effects of alternatives to dicofol.
Compound Description/
Way of action Uses Human adverse effects Ref. Associate impact Ref.
CH3
CH3
Sn OSn
CH3CH3
CH3
CH3
CH3 CH3
CH3
CH3
CH3CH3
FENBUTATIN-OXIDE
Activity
Acaricide.
Organotin compound.
Selective, non systemic
with contact and stomach
action, acts by inhibiting
oxidative phosphoryla-
tion at the site of dinitro-
phenol uncoupling, pre-
venting the formation of
the high-energy phos-
phate molecule adenosine
triphosphate (ATP). Also
inhibit photophosphory-
lation in chloroplasts, the
chlorophyll-bearing
subcellular units) and
could therefore serve as
algicide.
Citrus, blackber-
ries and raspber-
ries, grapes and
pomes fruit,
strawberries,
cucumbers.
Glasshouse
crops.
Carcinogenic po-
tential: Group E:
Evidence of
Non-Carcinogenici
ty for humans.
Hazards to repro-
ductions and de-
velopment effects,
not carcinogen.
[28,39]
Relative immobile and
persistent in the envi-
ronment, with no appar-
ent major route of dissi-
pation.
Practically non-toxic to
birds on an acute basis
and extremely toxic to
both freshwater and
estuarine aquatic organ-
isms.
[39,40]
O
N C
HN
CH3
CH3
N
H
O
CH3
?HCl
FORMETANATE HY-
DROCHLORIDE
Activity
Insecticide, acaricide.
Formamidine and car-
bamate groups.
The toxic acts by contact
and stomach action, by
inhibiting acetylcholi-
nesterase.
Alfalfa (grown
for seed), apples,
pears, peaches,
nectarines and
assorted citrus
crops. There are
no residential
uses for this
product.
Carcinogenic po-
tential: Group E
Evidence of
Non-carcinogenicit
y for Humans.
Known acetyl
cholinesterase
inhibitor.
[28,41]
No indications of phy-
totoxicity on plants. No
acute effects on threat-
ened and endangered
freshwater fish, inverte-
brates, and estuarine
molluscs.
[42,43]
hydramethylnon inhibits mitochondrial complex III elec-
tron transport (site II) and pyridaben inhibits mitochon-
drial complex I electron transport. It is known that this
causes gradual degeneration of the dopamine neurons
and reproduce many of the features of Parkinsonism.
Pyridaben is a Group E, evidence of no-carcinogenecity
for humans, and hydramethylnon and dicofol are classi-
fied as Group C, carcinogenic potential of possible hu-
man carcinogen [28].
4. Conclusions
On the basis of available scientific data, different alterna-
tives for substitution of dicofol examinated here are di-
rectly related with the chemical structure, and the toxicity
of these compounds is at least as potent as dicofol, af-
fecting environmental and human beings.
Properties that identify substances as substances of
high concern (CMR and PBT profile) are discussed in
order to assess the possible substitution alternatives to
dicofol. The understanding of the structure of compounds
and their correlation to target organism is a very impor-
tant parameter to develop better designed pesticidal
compounds with tailored toxicological properties on dif-
ferent pests. Mode of action of fuoroalkenyl derivatives
is demonstrated to act in “specific manner” depending on
the crop and the pest. Chemical inhibitor agents of mito-
chondrial electron transport are as dangerous as dicofol
to environment and/or humans. The third group is better
for humans but in most cases is worst for the environ-
ment, aquatic life specific. Common sense leads to make
insecticide selection decisions which can ensure the most
effective, least expensive and least environmentally dis-
ruptive methods, considering the mode of action, resis-
tance, phytotoxicity, and the possibility of introduce
other biological species to protect crops against pests.
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