More detailed information of bioaccumulation of pyrethroids in wildlife and
humans is presented in Chapter “Bioavailability and Bioaccumulation of Pyrethroid
Insecticides in Wildlife and Humans”.
The Water Framework Directive (Directive 2000/60/EC) named a group of pesticides that could be toxic, persistent and bioaccumulate. Among them, cypermethrin
was listed. Due to their production volume and extensive application, pesticides such
as pyrethroids are always present in the environment despite not being persistent and
are therefore considered pseudo-persistent organic contaminants [26].
4 Metabolisation
The capacity of mammals of metabolising pyrethroids has been regarded as one of
the best qualities of these pesticides. The metabolisation route differs with the
organism. However, the routes are equivalent for many mammals, and the mechanism in humans will serve as an example.
The liver is the main organ responsible for disintoxication in humans, although
other organs and tissues possess the required enzymes to treat xenobiotics. This
disintoxication usually proceeds in two steps [27]. The first step consists in increasing the polarity of the xenobiotic molecular through processes like hydroxylation,
deamination or the N-oxidation. In the second step, the metabolite – which is more
polar than the original molecule – is combined with endogen products of the cell,
such as methyl or acetyl groups, monosaccharides or amino acids. This increases the
metabolite solubility making it easier for it to be excreted in urine. This is the reason
why exposition of humans to pyrethroids is studied through the analysis of their
metabolites in urine [28].
The first step of the metabolisation of pyrethroids in humans can occur through
two pathways. One is the breakdown of the ester to produce carboxylic acid and the
corresponding alcohol by the action of carboxylesterases [29]. Then, alcohol can be
oxidised to a benzoic acid (Fig. 4).
The carboxylesterases required for this metabolisation are found in the plasma of
mammals at higher concentrations than in fish or birds [30]. This could be a factor in
explaining the lower toxicity of pyrethroids in mammals.
On the other hand, carboxylesterases present isoenzymes that can be found in
different proportions in each individual depending on factors such as species, age or
gender [30]. Each isoenzyme can have a different activity on different isomers of
pyrethroids, thus making the capacity of metabolising these compounds change not
only among species, but also among individuals of different age and gender [31].
The second pathway for the first step of the metabolisation of pyrethroids in
humans is hydroxylation by monooxygenases. The process usually undergoes transformation via both pathways producing secondary products such as 4-hydroxy-3phenoxybenzoyl and 4-hydroxy-3-phenoxylbenzaldehyde for permethrin. These
compounds can be stronger endocrine disruptors than their non-hydroxylated
analogues [32].
8
Ò. Aznar-Alemany and E. Eljarrat
humans is presented in Chapter “Bioavailability and Bioaccumulation of Pyrethroid
Insecticides in Wildlife and Humans”.
The Water Framework Directive (Directive 2000/60/EC) named a group of pesticides that could be toxic, persistent and bioaccumulate. Among them, cypermethrin
was listed. Due to their production volume and extensive application, pesticides such
as pyrethroids are always present in the environment despite not being persistent and
are therefore considered pseudo-persistent organic contaminants [26].
4 Metabolisation
The capacity of mammals of metabolising pyrethroids has been regarded as one of
the best qualities of these pesticides. The metabolisation route differs with the
organism. However, the routes are equivalent for many mammals, and the mechanism in humans will serve as an example.
The liver is the main organ responsible for disintoxication in humans, although
other organs and tissues possess the required enzymes to treat xenobiotics. This
disintoxication usually proceeds in two steps [27]. The first step consists in increasing the polarity of the xenobiotic molecular through processes like hydroxylation,
deamination or the N-oxidation. In the second step, the metabolite – which is more
polar than the original molecule – is combined with endogen products of the cell,
such as methyl or acetyl groups, monosaccharides or amino acids. This increases the
metabolite solubility making it easier for it to be excreted in urine. This is the reason
why exposition of humans to pyrethroids is studied through the analysis of their
metabolites in urine [28].
The first step of the metabolisation of pyrethroids in humans can occur through
two pathways. One is the breakdown of the ester to produce carboxylic acid and the
corresponding alcohol by the action of carboxylesterases [29]. Then, alcohol can be
oxidised to a benzoic acid (Fig. 4).
The carboxylesterases required for this metabolisation are found in the plasma of
mammals at higher concentrations than in fish or birds [30]. This could be a factor in
explaining the lower toxicity of pyrethroids in mammals.
On the other hand, carboxylesterases present isoenzymes that can be found in
different proportions in each individual depending on factors such as species, age or
gender [30]. Each isoenzyme can have a different activity on different isomers of
pyrethroids, thus making the capacity of metabolising these compounds change not
only among species, but also among individuals of different age and gender [31].
The second pathway for the first step of the metabolisation of pyrethroids in
humans is hydroxylation by monooxygenases. The process usually undergoes transformation via both pathways producing secondary products such as 4-hydroxy-3phenoxybenzoyl and 4-hydroxy-3-phenoxylbenzaldehyde for permethrin. These
compounds can be stronger endocrine disruptors than their non-hydroxylated
analogues [32].
8
Ò. Aznar-Alemany and E. Eljarrat