Academic journal article Environmental Health Perspectives

Environmentally Relevant Xenoestrogen Tissue Concentrations Correlated to Biological Responses in Mice

Academic journal article Environmental Health Perspectives

Environmentally Relevant Xenoestrogen Tissue Concentrations Correlated to Biological Responses in Mice

Article excerpt

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 [Beta]-hexachlorocyclohexane ([Beta]-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 [Beta]-HCH. Fat concentrations of o,p'-DDT and [Beta]-HCH correlated linearly to blood levels (o,p'-DDT, [r.sup.2] = 0.94; [Beta]-HCH, [r.sup.2] = 0.83). Fat concentrations (nanograms per gram of tissue) were higher than blood concentrations (nanograms per milliliter) by 90 [+ or -] 5- and 120 [+ or -] 9-fold (mean [+ or -] SE) for o,p'-DDT and [Beta]-HCH, respectively. The VET ranged from 12 [+ or -] 0.9 [micro]m in controls to 114 [+ or -] 8 [micro]m in treated animals, and was correlated to blood levels of either treatment compound. The UEH ranged from an average of 7.7 [+ or -] 0.3 [micro]m in controls to 26 [+ or -] 2 [micro]m in high-dose o,p'-DDT-treated animals. The UEH was also correlated with [Beta]-HCH concentration, but it plateaued at approximately 11 [micro]m at the highest doses. The lowest blood concentrations that produced statistically significant increases in VET or UEH were 18 [+ or -] 2 ng/mL o,p'-DDT and 42 [+ or -] 4 ng/mL [Beta]-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: [Beta]-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

Although banned in most industrialized nations, organochlorine (OC) pesticides are still used in Third World countries and are ubiquitous and persistent pollutants (1). Dichlorodiphenyltrichloroethane (DDT) is infamous as an endocrine disruptor in birds (2), and the o,p'- isomer of DDT, which constitutes approximately 15% of the technical mixture, is estrogenic in vitro and in vivo (3). Another estrogenic pesticide residue is the [Beta]-isomer of hexachlorocyclohexane (HCH), which constitutes 7-12% of technical HCH (4). [Beta]-HCH has several toxicologic effects in addition to estrogenic activity; also, it preferentially accumulates in the fat of biota and biomagnifies as it moves through the food web (4). Because virtually all humans have been exposed to these compounds, the concern over their potential health effects continues to grow. Recent epidemiologic studies have been controversial regarding the relationship of OC blood levels and human disease (5-16). The debate is likely to continue because there are no "unexposed" cohorts for comparison, and exposure information is difficult to obtain. For these reasons, we must rely on experimental animal studies as a guide to determine rational safety levels for humans.

Many studies, both in vivo and in vitro, probe a variety of effects caused by these OC pesticides. Although [Beta]-HCH does not competitively bind to the estrogen receptor (17,18), it does produce a number of estrogen-like responses: it stimulates proliferation and increases synthesis of progesterone receptors in cultures of human breast cancer cells (17,18), and it produces moderate uterotrophic effects in the rodent uterus (18,19). In contrast, o,p'-DDT does competitively bind to the estrogen receptor (18,20,21), and it produces a range of estrogenic responses (18-23). …

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