C57BL/6N mice used to model induction of
cleft palate and kidney malformations in offspring following maternal treatment with
TCDD, were dosed on gestation day (gd) 9 with
2,2',4,4',5,5'-hexachlorobiphenyl (
HCB) (62.5, 125, 250, 500, 1000 mg/kg) and/or gd 10 with
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD) (15 or 18 micrograms/kg) to investigate the potential protective effects of
HCB against
TCDD-induced teratogenicity. Maternal
body weight gain was increased by combinations of 15 micrograms
TCDD/kg and 125-500 mg
HCB/kg and decreased at doses of 15 micrograms
TCDD/kg + 1000
HCB mg/kg. At the doses used in this study, there was no effect of either compound on number of live or dead offspring.
Fetal body weight was slightly decreased in all groups dosed with greater than or equal to 250 mg
HCB/kg.
HCB did not induce
cleft palate at a dose of 1000 mg/kg, but did induce increases in
hydronephrosis and hydroureter at 500 and 1000 mg/kg. Combinations of
HCB and
TCDD decreased the incidence of
cleft palate induced by
TCDD alone, but only at doses of 15 micrograms
TCDD/kg combined with 125-500 mg
HCB/kg. The antagonism of
hydronephrosis (incidence and severity) appeared over a narrower dose range (15 micrograms
TCDD/kg + 500 mg
HCB/kg).
HCB induced increases (3-fold) in
ethoxyresorufin-O-deethylase (
EROD) activity at doses of 500 and 1000 mg/kg, suggesting that the limited antagonism of
TCDD teratogenicity by
HCB could be under the control of the
Ah-receptor.