trans-permethrin in vitro assay was approximately 62-fold higher than with cispermethrin exposure.
In a study that assessed adverse effects on physiology, histopathology and gene
expression levels (T synthesis), cis-permethrin induced the greatest endocrine
disruption effects, resulting in reproductive toxicity in male mice during puberty
age [70]. In female mammals, adverse effects on reproductive function have
been reported after exposure to beta-cypermethrin, permethrin, fenvalerate and
deltamethrin, which include decreased fertility and inhibition of hormones affecting
the endocrine system [71, 72]. However, considering a chiral approach, studies on
potential adverse effects on the reproductive function of female mammals (e.g. mice)
are still scarce. This fact has relevance, since studies note possible adverse effects,
such as endocrine disruption, through the mother-foetus system (Table 2) [41, 74].
At the enantiomeric level, C-1 in the S-configuration of bifenthrin resulted in
greater effects as endocrine disruptors in assays performed in vivo and in vitro with
mammals [41, 74, 75]. For example, 1S-cis-bifenthrin induced 2.2-fold oestrogenic
activity compared to 1R-cis-enantiomers measured through the expression of biomarker genes in a breast cancer cell line (MCF-7) [12]. The authors also observed
enantioselective cytotoxicity in macrophage cells by 1S-cis-bifenthrin, indicating
possible adverse effects on the immunological system (Table 2). In another study
with bifenthrin, 1S-cis enantiomers also induced adverse effects with significant
accumulation of cellular triglycerides in human hepatoma cells (HepG2) compared
to their epimers [76]. Other in vitro studies reported that permethrin modifies lipid
metabolism, affecting the intracellular functions of adipocytes and glucose homeostasis through the reduction of glucose uptake in myotubes [77, 78]. In addition,
epidemiological and in vivo studies contribute to evidence between exposure to
insecticides and the development of obesity and type 2 diabetes [79].
Pyrethroids undergo selective diastereomeric metabolization in mammals, being
more persistent cis-diastereomers [31, 73]. This fact deserves attention regarding the
possible impacts on human health, since cis-permethrin induced the greatest adverse
effects on the reproductive system, as well as endocrine disruption, as shown in
previous assays with mammals [70, 73].
In addition, endocrine disruption in mammalian assays by the 1S-configuration of
bifenthrin [41, 74, 75] was also observed in aquatic organisms by the same configuration of bifenthrin and permethrin [10, 39], suggesting a broad potential to affect
organisms from different environmental compartments, including humans.
3.4 Abiotic and Laboratory-Based Epimerization
In addition to the selectivity in biological systems, epimerization can occur by
photolytic isomerization in sunlight, during sample preparation and analysis with
polar solvents, and by heat [27, 51, 80]. Stereoisomer epimerization can decrease the
insecticidal activity of commercial formulations. This effect may lead to erroneous
analytical interpretation and may influence the results of bioassays, since polar
Stereoselectivity and Environmental Behaviour of Pyrethroids
163
In a study that assessed adverse effects on physiology, histopathology and gene
expression levels (T synthesis), cis-permethrin induced the greatest endocrine
disruption effects, resulting in reproductive toxicity in male mice during puberty
age [70]. In female mammals, adverse effects on reproductive function have
been reported after exposure to beta-cypermethrin, permethrin, fenvalerate and
deltamethrin, which include decreased fertility and inhibition of hormones affecting
the endocrine system [71, 72]. However, considering a chiral approach, studies on
potential adverse effects on the reproductive function of female mammals (e.g. mice)
are still scarce. This fact has relevance, since studies note possible adverse effects,
such as endocrine disruption, through the mother-foetus system (Table 2) [41, 74].
At the enantiomeric level, C-1 in the S-configuration of bifenthrin resulted in
greater effects as endocrine disruptors in assays performed in vivo and in vitro with
mammals [41, 74, 75]. For example, 1S-cis-bifenthrin induced 2.2-fold oestrogenic
activity compared to 1R-cis-enantiomers measured through the expression of biomarker genes in a breast cancer cell line (MCF-7) [12]. The authors also observed
enantioselective cytotoxicity in macrophage cells by 1S-cis-bifenthrin, indicating
possible adverse effects on the immunological system (Table 2). In another study
with bifenthrin, 1S-cis enantiomers also induced adverse effects with significant
accumulation of cellular triglycerides in human hepatoma cells (HepG2) compared
to their epimers [76]. Other in vitro studies reported that permethrin modifies lipid
metabolism, affecting the intracellular functions of adipocytes and glucose homeostasis through the reduction of glucose uptake in myotubes [77, 78]. In addition,
epidemiological and in vivo studies contribute to evidence between exposure to
insecticides and the development of obesity and type 2 diabetes [79].
Pyrethroids undergo selective diastereomeric metabolization in mammals, being
more persistent cis-diastereomers [31, 73]. This fact deserves attention regarding the
possible impacts on human health, since cis-permethrin induced the greatest adverse
effects on the reproductive system, as well as endocrine disruption, as shown in
previous assays with mammals [70, 73].
In addition, endocrine disruption in mammalian assays by the 1S-configuration of
bifenthrin [41, 74, 75] was also observed in aquatic organisms by the same configuration of bifenthrin and permethrin [10, 39], suggesting a broad potential to affect
organisms from different environmental compartments, including humans.
3.4 Abiotic and Laboratory-Based Epimerization
In addition to the selectivity in biological systems, epimerization can occur by
photolytic isomerization in sunlight, during sample preparation and analysis with
polar solvents, and by heat [27, 51, 80]. Stereoisomer epimerization can decrease the
insecticidal activity of commercial formulations. This effect may lead to erroneous
analytical interpretation and may influence the results of bioassays, since polar
Stereoselectivity and Environmental Behaviour of Pyrethroids
163