Endocrine disruptors are a class of environmentally prevalent compounds that include the dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the polychlorinated biphenyls, and some isoflavonoid phytoestrogens. Their potential health hazards, until recently, were dominated by concerns over carcinogenicity following exposure of adults to high doses. Developmental toxicity now seems to be achieving a leading role and may even displace cancer as the basis for assessing the human risks posed by these compounds. One source of this shifting concern is data describing impaired sexual development in rats exposed prenatally to surprisingly low doses of TCDD. TCDD and related endocrine disrupters appear to alter the perinatal gonadal hormone milieu. Such activity triggers a cascade of disturbances in brain development and neuroendocrine function. Although such disturbances might be seen most readily in reproductive studies, a constellation of much more subtle consequences is conceivable. These outcomes might include altered gender-specific cognition. For example, female rats tend to emit different patterns of responding than male rats on schedule-controlled operant behavior assays. The current proposal is guided by the hypothesis that prenatal TCDD modifies the usual pattern of differences between male and female rats. Tests of the hypothesis will be based on three situations in which gender-specific learning, memory, and spatial cognition are assessed. One assessment situation will examine a sexually-motivated behavior in exposed females, a second situation will examine sexual motivation in exposed males, and the third situation will examine nonsexual cognitive function in both males and females. In order to determine sensitive critical periods of prenatal development, the behavioral endpoints will be examined across groups of offspring that have been exposed under one of three different prenatal schedules. All of these measures will be examined in subjects exposed to a new, low dose range of TCDD that approaches background levels in the environment. The coupling of several functional measures is adduced as a model of risk assessment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES008958-02
Application #
6017013
Study Section
Special Emphasis Panel (ZRG4-ALTX-3 (01))
Project Start
1998-06-01
Project End
2001-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Rochester
Department
Public Health & Prev Medicine
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Hojo, Rieko; Zareba, Grazyna; Kai, Joshua W et al. (2006) Sex-specific alterations of cerebral cortical cell size in rats exposed prenatally to dioxin. J Appl Toxicol 26:25-34
Markowski, Vincent P; Cox, Christopher; Preston, Raymond et al. (2002) Impaired cued delayed alternation behavior in adult rat offspring following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on gestation day 15. Neurotoxicol Teratol 24:209-18
Zareba, Grazyna; Hojo, Rieko; Zareba, Karolina M et al. (2002) Sexually dimorphic alterations of brain cortical dominance in rats prenatally exposed to TCDD. J Appl Toxicol 22:129-37
Weiss, Bernard; Clarkson, Thomas W; Simon, William (2002) Silent latency periods in methylmercury poisoning and in neurodegenerative disease. Environ Health Perspect 110 Suppl 5:851-4
Weiss, B (2000) Vulnerability to pesticide neurotoxicity is a lifetime issue. Neurotoxicology 21:67-73
Davidson, P W; Weiss, B; Myers, G J et al. (2000) Evaluation of techniques for assessing neurobehavioral development in children. Neurotoxicology 21:957-72
Weiss, B (2000) Vulnerability of children and the developing brain to neurotoxic hazards. Environ Health Perspect 108 Suppl 3:375-81