Octamethylcyclotetrasiloxane (D4) is a low molecular weight cyclic silicone used in the synthesis of larger silicone polymers and the formulation of a variety of personal care products. Its biological activities are being investigated due to its widespread use. Few studies have examined the estrogenic activity of D4. In our studies, the effects of oral exposure to D4 on serum estradiol levels, uterine wet weight, uterine peroxidase activity in mice and in vitro estrogen receptor binding activity were evaluated. Serum estradiol levels were dose responsively decreased after exposure to 100 mg/kg to 1000 mg/kg D4. The decreased serum estradiol levels were not due to inhibition by elevated serum corticosterone levels as shown by the result from adrenalectomized animals. Uterine wet weights in ovariectomized mice were significantly increased by D4 exposure, but not by exposure to the other silicone compounds tested (D3, 14, phenyl-D4 and D5). The D4-induced increase in the uterine weights showed a dose-dependent response between 250 mg/kg and 1000 mg/kg. Uterine peroxidase activity, a marker for estrogen activity, was significantly increased in D4 exposed mice (1000 mg/kg). In an in vitro estrogen receptor binding assay, D4 at concentrations of 10-6M and 10-4M showed a dose-dependent competition with 3H-estradiol for binding to estrogen receptor-a. The data presented here indicate that D4 has estrogenic activity, and the action may be mediated through estrogen receptors.
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