pyrethroids are modified versions of a natural chemical, pyrethrin,
isolated from chrysanthemums. The modifications make them lipophilic
and persistent, increasing the likelihood of accumulation in animal
(including human) tissue. Synthetic pyrethroids are used widely
as pesticides against "against ticks, mites, mosquitoes (found
in bednetting as a control against malaria), and as treatment for
human head lice and scabies."
et al. test a series of synthetic pyrethroids to determine
their ability to disrupt estrogen signalling in experiments using
a cell-culture line of human breast cancer cells (MCF-7), using
two assays: expression of pS2 and MCF-7 cell proliferation.
compounds they tested were sumithrin, fenvalerate, d-trans
allethrin and permethrin, at concentrations "similar to the
amounts necessary to observe the estrogenic properties of various
chemicals including o,p´-DDT, pesticides, and some polychlorinated
biphenyls (PCBs) in various estrogen responsive bioassays."
of the compounds caused effects at the levels tested, although the
details of the responses varied among the compounds. Higher pyrethrin
levels were required to induce effects than for the other three
compounds and the effects induced were modest by comparison. In
contrast, the other three compounds tested had striking impacts
at low levels.
behaved like a classic estrogen mimic. It provoked pS2 induction
and cell proliferation at very low levels, but its impact was eliminated
when it was combined with an anti-estrogen. This indicates that
the mechanism of action of sumithrin is via interaction with the
behaved somewhat differently. It provoked pS2 induction at very
low levels, but somewhat higher exposures were required to cause
cell proliferation. Its effects on pS2 induction were not eliminated
by an anti-androgen. This suggests that at least some of fenvalerate's
action may be through a signalling pathway other than the estrogen
allethrin (see figure below) at very low levels (1 µM) was a moderate
estrogen blocker but at higher levels it provoked estrogen-like
responses. At even higher levels it was toxic to the cell-line.
The resulting dose-response curve had the classic "inverted-U"
form of a non-monotonic
induction by d-trans allethrin (DTA). This
graph compares the level of pS2 induction by DTA compared to
a positive control (estradiol).
points connected by the dotted line labeled "Inhibition"
shows the inhibitory effect of increasing amounts of DTA when
it is added to a treatment of estradiol. The higher the concentration,
the lower the pS2 induction.
Adapted from Go et al. 1999.
points connected by the solid line labeled "Induction"
shows the effect on pS2 induction of DTA by itself. Induction is
modest at low levels. It increases in the middle ranges. But at
high concentrations induction disappears.