Environmentally relevant xenoestrogen tissue concentrations correlated to biological responses in mice

The effects of xenoestrogens have been extensively studied in rodents, gene rally under single, high-dose conditions. Using a continuous-release, low-d ose system in ovariectomized mice, we correlated the estrogenic end points of uterine epithelial height (UEH) and vaginal epithelial thickness (VET) w ith concentrations of two organochlorine pesticide isomers in fat and blood . Silastic capsules containing a range of doses of either beta -hexachloroc yclohexane (beta -HCH) or o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT) w ere implanted subcutaneously, and animals were killed after 1 week. Average blood levels achieved by the various doses were 4.2-620 ng/mL for o,p'-DDT and 5.0-300 ng/mL for beta -HCH. Fat concentrations of o,p'-DDT and beta - HCH correlated linearly to blood levels (o,p'-DDT, r(2) = 0.34; beta -HCH, r(2) = 0.83). Fat concentrations (nanograms per gram of tissue) were higher than blood concentrations (nanograms per milliliter) by 90 +/- 5- and 120 +/- 9-fold (mean +/- SE) for o,p'-DDT and beta -HCH, respectively. The VET ranged from 12 +/- 0.3 mum in controls to 114 +/- 8 mum in treated animals, and was correlated to blood levels of either treatment compound. The UEH r anged from an average of 7.7 +/- 0.3 mum in controls to 26 +/- 2 mum in hig h-dose o,p'-DDT-treated animals. The UEH was also correlated with beta -HCH concentration, but it plateaued at approximately 11 pm at the highest dose s. The lowest blood concentrations that produced statistically significant increases in VET or UEH were 18 +/- 2 ng/mL o,p'-DDT and 42 +/- 4 ng/mL bet a -HCH. These values are within the same order of magnitude of blood concen trations found in some human subjects from the general population, suggesti ng that human blood concentrations of these organochlorines may reach estro genic levels.