Journal Article

Sexually Dimorphic Behavioral Responses to Prenatal Dioxin Exposure

Cox, Christopher, Kost, James T., Hojo, Rieko, Weiss, Bernard, Zareba, Grazyna, Markowski, Vincent P., Stern, Sander

2002

Overview

Pregnant Sprague-Dawley rats received a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetra-chlorodibenzo-p-dioxin on day 8 of gestation. Each litter contributed a single male-female pair trained to press a lever to obtain food pellets under two operant behavior procedures. Initially, each lever press was reinforced. The fixed-ratio (FR) requirement was then increased every four sessions from the initial setting of 1 to values between 6 and 71. We then studied responses for 30 days under a multiple schedule combining FR 11 and another schedule requiring a pause of at least 10 sec between responses (DRL 10-sec). TCDD evoked a sexually dimorphic response pattern. Generally, TCDD-exposed males responded at lower rates than control males. In contrast, exposed females responded at higher rates than controls. Each response measure from the mult-FR DRL schedule yielded a male-female difference score. We used the differences in response rate to calculate benchmark doses based on the relative displacement from modeled zero-dose performance of the effective dose at 1% ( ED01) and 10% ( ED10), as determined by a second-order polynomial fit to the dose-effect function. For the male-female difference in FR rate of responding, the mean ED10was 2.77 ng/kg with a 95% lower bound of 1.81 ng/kg. The corresponding ED01was 0.27 ng/kg with a 95% lower bound of 0.18 ng/kg. For the male-female difference in DRL rate, the mean ED10was 2.97 ng/kg with a 95% lower bound of 2.02 ng/kg. The corresponding ED01was 0.30 ng/kg with a 95% lower bound of 0.20 ng/kg. These values fall close to, but below, current estimates of human body burdens of 13 ng/kg, based on TCDD toxic equivalents.

• Publisher: National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare,National Institute of Environmental Health Sciences
• Subject: Administration, Oral / Animals / Body Burden / Chemical hazards / Conditioning, Operant / Dioxins - adverse effects / Dosage / Dose response relationship / Dose-Response Relationship, Drug / Environmental health / Environmental Pollutants - adverse effects / Female / Learning / Male / Pregnancy / Prenatal Exposure Delayed Effects / Rats / Rats, Sprague-Dawley / Reproduction / Response rates / Sex Characteristics / Sex linked differences