PFPC Daily - November 16, 2004

Rogers E, Black M - "Effects of fluoxetine on development and
metamophosis in Xenopus laevis" Fourth SETAC World Congress November
14-18, 2004, Portland, Oregon, USA; The Society of Environmental
Toxicology and Chemistry (SETAC) (2004)

ABSTRACT - Pharmaceuticals detected at low concentrations in surface
water may have the potential to affect aquatic organisms, including
developing amphibians. Our research focuses on fluoxetine, a
selective serotonin reuptake inhibitor and widely prescribed
antidepressant.

Mammalian research indicates that fluoxetine may inhibit the thyroid
axis. In larval frogs, increasing levels of thyroid hormones are
necessary for metamorphosis to occur, and the presence of fluoxetine
in aquatic habitats has the potential to decrease thyroid hormone
levels in tadpoles, thus delaying the completion of metamorphosis. To
test this hypothesis, we exposed Xenopus laevis tadpoles individually
in small aquaria to fluoxetine from early development until the
completion of metamorphosis. We used the following measured
concentrations of fluoxetine: 0.059, 0.295, 2.95, and 29.5 ppb, which
overlap concentrations detected in effluent dominated streams.
Ammonium perchlorate, a known inhibitor of the thyroid axis and
anuran metamorphosis was used as a positive control at 10 ppb, and
FETAX solution served as the negative control. Dates of completion of
forelimb emergence and tail resorbtion and were recorded for each
individual, and tadpoles were measured and staged at 10-day
intervals. Severe malformations were observed at all concentrations of
fluoxetine tested. Malformations appeared during metamorphic climax
and included stunted forelimbs and primary rotation of the hind
limbs.

Tadpoles exposed to 50 ppb fluoxetine exhibited impaired balance and
swimming behavior. These tadpoles floated upside down at the surface
of the tank and swam in circles when prodded. As this research is
on-going, final times to metamorphosis are not available, but our
preliminary results indicate that fluoxetine impairs normal
development in X. laevis tadpoles at concentrations that may occur in
the environment.