- Email: [email protected]
Prenatal exposure to tetrachloroethylene(PCE)-contaminated drinking water and the risk of learning and attention disabilities
406
Abstracts / Neurotoxicology and Teratology 29 (2007) 395–414
Meo-DIPT caused a decrease in weight gain with 5-Meo-DIPT producing the greatest reduction. Both 5-Meo-DIPT and MDMA-treated animals exhibited increased latencies and path lengths in the Morris water maze during acquisition and reversal learning, but only MDMA affected performance in a shiftedreduced platform phase of learning. MDMA also produced deficits in path integration learning in the Cincinnati water maze compared to saline and Meo-DIPT treated animals. In addition, MDMA-treated animals exhibited increased anxiety in a marble burying task, although these animals displayed no differences in the elevated zero maze or locomotor behavior. The data suggest that while users may take the drugs for similar reasons, they affect development of the CNS differently. Supported by grants: ES07051, DA006733, DA014269, DA021394. doi:10.1016/j.ntt.2007.03.036
NBTS 33 Prenatal exposure to tetrachloroethylene(PCE)contaminated drinking water and the risk of learning and attention disabilities P.A. Janulewicz a, R.F. Whitea, M. Winterd, J. Weinbergc, L. Gallaghera, V. Vieiraa, T. Webstera , A. Aschengraub a Department of Environmental Health, Boston University School of Public Health, Boston, MA, United States b Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States c Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States d Department of Data Coordinating Center, Boston University School of Public Health, Boston, MA, United States We report on a population-based retrospective cohort study that examined the association between developmental disorders of learning and attention following prenatal drinking water exposure to PCE on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using information from town water departments, EPAnet water flow modeling software, and Geographical Information Systems (GIS). Mothers completed a questionnaire on disorders of attention and learning in their children and on confounding variables. The final cohort consisted of 2086 subjects. Results of crude and multivariate Generalized Estimating Equation (GEE) analyses showed no association between prenatal exposure and receiving tutoring for reading or math, being placed on an Individual Education Plan, or repeating a school grade (Adjusted Odds Ratios = 1.0–1.2) when compared to unexposed. There was also no consistent pattern of increased risk for receiving a diagnosis of Attention Deficit Disorder (ADD) or Hyperactive Disorder, special class placement for academic or behavioral problems, or lower educational attainment. Modest associations were observed only in the low exposure group (e.g., adjusted ORs for ADD = 1.4 and 1.0 for low and high exposure, respectively. Reference
group = unexposed). We conclude that prenatal PCE exposure is not associated with disorders of attention and learning using these outcome measures and at the exposure levels in our study population. Postnatal exposure results will be presented later. Supported by the National Institute of Environmental Health Sciences Superfund Basic Research Program. doi:10.1016/j.ntt.2007.03.037
NBTS 34 Complementary zebrafish and rat models of developmental neurobehavioral toxicity: the case of organophosphate pesticide exposure E.D. Levina , E. Linneyb, T.A. Slotkinb a Department of Psychiatry, Duke University, United States b Duke University Medical Center, Durham, NC, United States Zebrafish and rats provide excellent complementary models for determining the relationships between cellular and molecular impacts of toxicants and persisting cognitive impairment. Zebrafish have advantages of continuous visual accessibility during development and molecular tools to uncover bases of neurodevelopment. Rats have the advantage of greater similarity to human neurotransmitter systems and anatomic regions involved in cognition. Decades of research concerning the neural bases of cognition in rats have demonstrated its usefulness for understanding mechanisms for toxicant effects. We developed comparable approaches for learning and memory in zebrafish and found that developmental chlorpyrifos exposure causes persisting impairment in a three chamber tank test. Similarly, we found that developmental chlorpyrifos exposure in rats causes persisting impairment in radial-arm maze learning and memory. Parallel studies will determine if changes in serotonin, dopamine and acetylcholine systems seen after chlorpyrifos exposure in the rat are also paralleled in zebrafish. Comparative zebrafish and rat studies using a “gold standard” toxicant such as chlorpyrifos, for which mechanisms and outcomes are well-established, will help determine the opportunities and limits of zebrafish as a complementary model for developmental neurobehavioral toxicology. Supported by Superfund Basic Research Center (ES010356). doi:10.1016/j.ntt.2007.03.038
NBTS 35 If nicotine is a developmental neurotoxicant in animal studies, dare we recommend nicotine replacement therapy in pregnant women and adolescents? T.A. Slotkin Duke University Medical Center, Durham, NC, United States Tobacco use in pregnancy is a leading cause of perinatal morbidity/mortality and SIDS, and contributes in major ways to
Abstracts / Neurotoxicology and Teratology 29 (2007) 395–414
Meo-DIPT caused a decrease in weight gain with 5-Meo-DIPT producing the greatest reduction. Both 5-Meo-DIPT and MDMA-treated animals exhibited increased latencies and path lengths in the Morris water maze during acquisition and reversal learning, but only MDMA affected performance in a shiftedreduced platform phase of learning. MDMA also produced deficits in path integration learning in the Cincinnati water maze compared to saline and Meo-DIPT treated animals. In addition, MDMA-treated animals exhibited increased anxiety in a marble burying task, although these animals displayed no differences in the elevated zero maze or locomotor behavior. The data suggest that while users may take the drugs for similar reasons, they affect development of the CNS differently. Supported by grants: ES07051, DA006733, DA014269, DA021394. doi:10.1016/j.ntt.2007.03.036
NBTS 33 Prenatal exposure to tetrachloroethylene(PCE)contaminated drinking water and the risk of learning and attention disabilities P.A. Janulewicz a, R.F. Whitea, M. Winterd, J. Weinbergc, L. Gallaghera, V. Vieiraa, T. Webstera , A. Aschengraub a Department of Environmental Health, Boston University School of Public Health, Boston, MA, United States b Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States c Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States d Department of Data Coordinating Center, Boston University School of Public Health, Boston, MA, United States We report on a population-based retrospective cohort study that examined the association between developmental disorders of learning and attention following prenatal drinking water exposure to PCE on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using information from town water departments, EPAnet water flow modeling software, and Geographical Information Systems (GIS). Mothers completed a questionnaire on disorders of attention and learning in their children and on confounding variables. The final cohort consisted of 2086 subjects. Results of crude and multivariate Generalized Estimating Equation (GEE) analyses showed no association between prenatal exposure and receiving tutoring for reading or math, being placed on an Individual Education Plan, or repeating a school grade (Adjusted Odds Ratios = 1.0–1.2) when compared to unexposed. There was also no consistent pattern of increased risk for receiving a diagnosis of Attention Deficit Disorder (ADD) or Hyperactive Disorder, special class placement for academic or behavioral problems, or lower educational attainment. Modest associations were observed only in the low exposure group (e.g., adjusted ORs for ADD = 1.4 and 1.0 for low and high exposure, respectively. Reference
group = unexposed). We conclude that prenatal PCE exposure is not associated with disorders of attention and learning using these outcome measures and at the exposure levels in our study population. Postnatal exposure results will be presented later. Supported by the National Institute of Environmental Health Sciences Superfund Basic Research Program. doi:10.1016/j.ntt.2007.03.037
NBTS 34 Complementary zebrafish and rat models of developmental neurobehavioral toxicity: the case of organophosphate pesticide exposure E.D. Levina , E. Linneyb, T.A. Slotkinb a Department of Psychiatry, Duke University, United States b Duke University Medical Center, Durham, NC, United States Zebrafish and rats provide excellent complementary models for determining the relationships between cellular and molecular impacts of toxicants and persisting cognitive impairment. Zebrafish have advantages of continuous visual accessibility during development and molecular tools to uncover bases of neurodevelopment. Rats have the advantage of greater similarity to human neurotransmitter systems and anatomic regions involved in cognition. Decades of research concerning the neural bases of cognition in rats have demonstrated its usefulness for understanding mechanisms for toxicant effects. We developed comparable approaches for learning and memory in zebrafish and found that developmental chlorpyrifos exposure causes persisting impairment in a three chamber tank test. Similarly, we found that developmental chlorpyrifos exposure in rats causes persisting impairment in radial-arm maze learning and memory. Parallel studies will determine if changes in serotonin, dopamine and acetylcholine systems seen after chlorpyrifos exposure in the rat are also paralleled in zebrafish. Comparative zebrafish and rat studies using a “gold standard” toxicant such as chlorpyrifos, for which mechanisms and outcomes are well-established, will help determine the opportunities and limits of zebrafish as a complementary model for developmental neurobehavioral toxicology. Supported by Superfund Basic Research Center (ES010356). doi:10.1016/j.ntt.2007.03.038
NBTS 35 If nicotine is a developmental neurotoxicant in animal studies, dare we recommend nicotine replacement therapy in pregnant women and adolescents? T.A. Slotkin Duke University Medical Center, Durham, NC, United States Tobacco use in pregnancy is a leading cause of perinatal morbidity/mortality and SIDS, and contributes in major ways to