Environmentally relevant xenoestrogen tissue concentrations correlated to biological responses in mice

Elin M. Ulrich, Andrea Caperell-Grant, Sin Ho Jung, Ronald A. Hites, Robert M. Bigsby

Research output: Contribution to journalArticle

33 Scopus citations

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 β-hexachlorocyclohexane (β-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 β-HCH. Fat concentrations of o,p'-DDT and β-HCH correlated linearly to blood levels (o,p'-DDT, r2 = 0.94; β-HCH, r2 = 0.83). Fat concentrations (nanograms per gram of tissue) were higher than blood concentrations (nanograms per mililiter) by 90 ± 5- and 120 ± 9-fold (mean ± SE) for o,p'-DDT and β-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 β-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 β-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.

Original languageEnglish (US)
Pages (from-to)973-977
Number of pages5
JournalEnvironmental Health Perspectives
Volume108
Issue number10
DOIs
StatePublished - Jan 1 2000

Keywords

  • β-HCH
  • Dose response
  • Histology
  • Mouse
  • o,p'-DDT
  • Uterine epithelium
  • Vaginal epithelium
  • Xenoestrogen

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

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