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Elin M. Ulrich,¹ Andrea Caperell-Grant,² Sin-Ho Jung,³ Ronald A. Hites,¹ Robert M. Bigsby²

¹School of Public and Environmental Affairs and Department of Chemistry, Indiana University, Bloomington, Indiana, USA
²Department of Obstetrics-Gynecology and ³Division of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA

Abstract

The effects of xenoestrogens have been extensively studied in rodents, generally under single, high-dose conditions. Using a continuous-release, low-dose system in ovariectomized mice, we correlated the estrogenic end points of uterine epithelial height (UEH) and vaginal epithelial thickness (VET) with concentrations of two organochlorine pesticide isomers in fat and blood. Silastic capsules containing a range of doses of either ß-hexachlorocyclohexane (ß-HCH) or o,p´-dichlorodiphenyltrichloroethane (o,p´-DDT) were 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 ß-HCH. Fat concentrations of o,p´-DDT and ß-HCH correlated linearly to blood levels (o,p´-DDT, r² = 0.94 ; ß-HCH, r² = 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 ß-HCH, respectively. The VET ranged from 12 ± 0.9 µm in controls to 114 ± 8 µm in treated animals, and was correlated to blood levels of either treatment compound. The UEH ranged from an average of 7.7 ± 0.3 µm in controls to 26 ± 2 µm in high-dose o,p´-DDT-treated animals. The UEH was also correlated with ß-HCH concentration, but it plateaued at approximately 11 µm at the highest doses. 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 ß-HCH. These values are within the same order of magnitude of blood concentrations found in some human subjects from the general population, suggesting that human blood concentrations of these organochlorines may reach estrogenic levels. Key words: ß-HCH, dose response, histology, mouse, o, p´-DDT, uterine epithelium, vaginal epithelium, xenoestrogen. Environ Health Perspect 108:973-977 (2000) . [Online 7 September 2000]

http://ehpnet1.niehs.nih.gov/docs/2000/108p973-977ulrich/ abstract.html

Address correspondence to R.M. Bigsby, Department of Obstetrics-Gynecology, Indiana University School of Medicine, 975 W. Walnut St., IB 360, Indianapolis, Indiana, 46202 USA. Telephone: (317) 274-8970. Fax: (317) 278-2884. Email: rbigsby@iupui.edu

We thank K. Willett for the preliminary efforts necessary for this study. This work was supported in part by the U.S. Department of Defense, grant DAMD17-98-1-8011, to R.M.B.

Received 13 January 2000 ; accepted 2 June 2000.