Objectives:
In utero and
lactational exposure to 2,3,7,8-tetrachlorodibenzo-
p-dioxin (TCDD) results in a wide variety of developmental effects in pups at doses much lower than those causing overt toxicity in adult animals. We investigated the relationship between tissue concentrations of TCDD in dams
and
fetuses
and
developmental effects on pups.
Materials
and
Methods: Pregnant Long-Evans rats were given TCDD at a single oral dose of 12.5, 50, 200, or 800 ng of TCDD or [
3H]-TCDD/kg bw on gestation day (GD) 15. Dams were sacrificed on GD16
and
GD21,
and
the tissue concentrations of TCDD were measured in dams
and
fetuses. Pups were sacrificed on postnatal day (PND) 49
and
PND63 for males
and
PND70 for females,
and
the reproductive effects
and
tissue concentrations of TCDD were determined.
Results: The sex ratio (male/female) on GD21 was significantly reduced at 50 ng TCDD/kg
and
at 12.5
and
50 ng TCDD/kg at birth, but not at other doses. Delayed puberty was observed in males at 200 ng TCDD/kg
and
in males
and
females at 800 ng TCDD/kg. Anogenital distance, testis weight, epididymal sperm count, sperm motility,
and
ejaculated sperm count were not affected. Estrous cyclicity was not different
from
that of the control in any treatment group. A dose-dependent decrease in weight of seminal vesicle
and
prostate on PND49 was observed. Prostate weight was significantly decreased at 800 ng TCDD/kg. At this dose, maternal body burden
and
TCDD concentration in fetuses were 290 pg TCDD/g
and
52 pg TCDD/g on GD16, respectively.
Reduced prostate weight is a sensitive
and
commonly observed endpoint so that the body burdens of dams
and
fetuses at the LOAEL of this endpoint could be served as the basis for establishing TDI for dioxins.
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