People in developed countries are exposed
to multiple endocrine disruptors, including bisphenol A (BPA), the monomer of
polycarbonate plastics, and triclosan, an antimicrobial agent. Few studies have
investigated their distribution and interactions at doses that might
represent human exposure. We examined single and repeated low dietary doses of BPA
in mice and rats, and determined the influences of concurrent triclosan
exposure upon the presence and metabolism of BPA. In females receiving 50 µg/kg
14C-BPA, radioactivity was found throughout the body, but much less
in brain than reproductive tissues. Pre-treatment with estradiol or the
estrogen antagonist ICI 182,780 significantly reduced radioactivity in the
uterus. GC-MS indicated that the
majority of BPA in the uterus was aglycone (receptor-active). Mice given 0.5,
5, or 50 µg/kg 14C-BPA also showed more radioactivity in the uterus
than in other non-metabolic tissues. Females given 7 or 28 daily doses of 14C-BPA
showed significantly more radioactivity in reproductive tissues than did those
given just one dose, in measures taken 24 hours after the last dose. We then examined
whether triclosan exposure affects the distribution of ingested 14C-BPA
in select tissues. Mice were each injected sc with triclosan, in doses ranging
from 0.2 to 18 mg, followed by oral administration of either 5 or 50 µg/kg 14C‑BPA.
In females, radioactivity was elevated in the heart, lungs, muscle, uterus,
ovaries, and blood serum in those receiving triclosan compared to those given 14C-BPA
alone. This effect was also observed in the epididymides and serum of males. The
effective dose of triclosan depended upon the tissue. These data show that BPA
preferentially localizes to reproductive tissues following single and repeated
low oral doses. They also indicate that triclosan exacerbates BPA presence in vivo, consistent with in vitro evidence that triclosan
utilizes enzymes responsible for the metabolism and excretion of BPA.