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Vincent P. Markowski,¹ Grazyna Zareba,² Sander Stern,² Christopher Cox,³ and Bernard Weiss²

¹Department of Psychology, University of Southern Maine, Portland, Maine, USA; ²Department of Environmental Medicine, and ³Department of Biostatistics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA

Abstract

Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation. Their adult female offspring were trained to respond on a lever for brief opportunities to run in specially designed running wheels. Once they had begun responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio requirement for lever pressing was increased at five-session intervals to values of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each behavior session to track estrous cyclicity. Under each of the FR values, perinatal TCDD exposure produced a significant dose-related reduction in the number of earned opportunities to run, the lever response rate, and the total number of revolutions in the wheel. Estrous cyclicity was not affected. Because of the consistent dose-response relationship at all FR values, we used the behavioral data to calculate benchmark doses based on displacements from modeled zero-dose performance of 1% (ED₀₁) and 10% (ED₁₀) , as determined by a quadratic fit to the dose-response function. The mean ED₁₀ benchmark dose for earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg. The corresponding ED₀₁ was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The mean ED₁₀ for total wheel revolutions was calculated as 7.32 ng/kg with a 95% lower bound of 5.41 ng/kg. The corresponding ED₀₁ was 0.71 ng/kg with a 95% lower bound of 0.60. These values should be viewed from the perspective of current human body burdens, whose average value, based on TCDD toxic equivalents, has been calculated as 13 ng/kg. Key words: benchmark dose, estrous cycle, operant behavior, prenatal exposure, TCDD, wheel running. Environ Health Perspect 109:621-627 (2001) . [Online 11 June 2001]

http://ehpnet1.niehs.nih.gov/docs/2001/109p621-627markowski/ abstract.html

Address correspondence to B. Weiss, Department of Environmental Medicine, Room G6820, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 USA. Telephone: (716) 275-1736. Fax: (716) 256-2591. E-mail: bernard_weiss@urmc.rochester.edu

TCDD was administered in the University of Rochester Environmental Health Sciences Center's Supertox facility, directed by T. Gasiewicz.

This research was supported by National Institute of Environmental Health Sciences (NIEHS) Center grant ES01247 and by grant ES089858 to B. Weiss from the NIEHS.

Received 16 November 2000 ; accepted 19 March 2001.