public health advocates, and the general public in advancing their efforts toaddress the important individual and social issues raised by learning anddevelopmental disabilities. This consensus statement outlines the currentscientific understanding of the links between environmental factors andlearning and developmental disabilities. Environmental agents that we areconfident cause learning and developmental disabilities in humans include:alcohol, lead, mercury, PCBs, PBDEs, manganese, arsenic, solvents, PAHs,pesticides and nicotine/environmental tobacco smoke. An overview of theevidence regarding these agents is presented, along with emerging evidenceabout other potential contributors: endocrine disruptors, fluoride and foodadditives. The statement also identifies important research areas that holdpromise of further advancing our understanding of these links. The scientificevidence reviewed in this statement, with a glossary and more than 200references, indicates environmental contaminants are an important cause oflearning and developmental disabilities. The proportion of environmentallyinduced LDDs is a question of profound human, scientific and public policysignificance. Despite some uncertainty, there is sufficient knowledge to takepreventive action to reduce fetal and childhood exposures to environmentalcontaminants. Given the serious consequences of LDDs, a precautionaryapproach is warranted to protect the most vulnerable of our society.

doi:10.1016/j.ntt.2009.04.024

NBTS21

A zebrafish model of the persisting neurobehavioral impairment causedby developmental chlorpyrifos exposure

Damiyon Sledge, Jerry Yen, Terrell Morton, Laura Dishaw, Kathleen Shuler,Susan Donerly, Elwood Linney, Edward LevinDuke University Medical Center, Durham, NC, USA

Developmental exposure of rats to the pesticide chlorpyrifos (CPF) has beenfound to cause persistent neurobehavioral impairment. In a parallel series ofstudies with zebrafish, we are also finding persisting behavioral dysfunction afterdevelopmental CPF exposure. We have developed a battery of measures ofzebrafish behavior, which are reliable and sensitive to toxicant-induced induceddamage. This study determined the critical window of developmental CPFexposure for causing persisting neurobehavioral effects. Tests of learning (3-chamber tank spatial discrimination), stress response (novel tankdiving test) andsensorimotor response (tap startle response and habituation) were conductedwith adult zebrafish after early developmental CPF exposure. The CPF exposurelevel was 100 ng/ml with durations of 0–1, 0–2, 0–3, 0–4 and 0–5 days afterfertilization. In the 3-chamber learning test, the 0–5 day CPF exposure group hadsignificantly lower learning rate. Developmental CPF exposure (0.29 µM0–5DPF)had persisting behavioral effects in zebrafish tested as adults. In the novel tankexploration test, exposed fish showed decreased escape diving response andincreased swimming activity. In the 3-chamber spatial learning test, exposed fishshowed nearly significantly poorer overall accuracy and significantly slowerlearning. In the tactile startle test, CPF exposed fish showeddecreased habituationto startle and a trend toward increased overall startle response. This studydemonstrates the selective long-term behavioral alterations caused by exposureto CPF in zebrafish. The zebrafish model can facilitate the determination of themolecular mechanisms critical for long-term neurobehavioral impairment afterdevelopmental toxicant exposure. (Supported by NIH ES10356)

doi:10.1016/j.ntt.2009.04.025

NBTS22

Down-regulation of DNA methyltransferase expression is associatedwith increased dopaminergic gene expression following developmentalpyrethroid exposure

Jason RichardsonRobert Wood Johnson Medical School, University of Medicine and Dentistry ofNew Jersey, Piscataway, NJ, USAEnvironmental and Occupational Health Sciences Institute, Rutgers University,Piscataway, NJ, USA

Previously, we have demonstrated that in utero exposure of mice to thepyrethroid pesticide deltamethrin (DM) causes persistent hyperactivity,impulsivity, and alterations of dopaminergic system. However, the mechanismbywhich deltamethrin exerts its effects on the dopamine system andwhy theseeffects persist remains unknown. In utero exposure of mice to DM (3 mg/kg)resulted in persistent (10–11 months) increased expression of the dopaminetransporter (DAT; 82%). This increasewas accompanied by increased expressionof the nuclear transcription factors Nurr1 (68%) and Pitx3 (34%), which havebeen demonstrated to regulate DAT expression. Because of the persistence ofthese effects, we sought to determine whether epigenetic alterations wereresponsible. Indeed, DNA methyltransferase (DNMT) 1, 3a, and 3b expressionwas reduced by 45, 51, and 74%, respectively. To explore mechanisms by whichDMmayalter DNMTexpression,we exposedMES23.5 dopaminergic cells to DM(10nM) and observed increasedDAT (34%),Nurr1 (71%), and Pitx3 (98%)mRNAexpression. These increases were accompanied by decreased DNMTexpression.Because DM causes delay of closing of sodium channels which can result inpersistent depolarization anddepolarizationhas beendemonstrated to decreaseDNMT expression, we depolarized cells with KCl for 24 h. Depolarizationincreased expression of DAT, Nurr1, and Pitx3 by 50%, 46%, and 46%, respectively.Taken in concert, these data suggest that persistent depolarization anddecreased DNMT expression following developmental DM exposure mayprovide a plausible mechanism for the persistence of DM's effects on thedopaminergic system. Supported by NIEHS R01ES015991.

doi:10.1016/j.ntt.2009.04.026

NBTS23

Late-emerging cognitive impairment in male rats after neonatalparathion exposure

Olga Timofeeva, Liwei Yang, Frederic Seidler, Theodore Slotkin, Edward LevinDuke University Medical Center, Durham, NC, USA

Developmental exposure of rats to the organophosphate (OP) pesticideschlorpyrifos, diazinon and parathion has been found in our studies and others tocause persistent neurobehavioral effects in juvenile and young adults. The currentstudy was conducted to determine the persisting effects of early postnatalexposure on cognitive function in older adult and aged rats. On PND 1–4, weadministered parathion to male and female Sprague–Dawley rat pups at dosesnear the threshold for overt signs of systemic toxicity and spanning the thresholdfor barely-detectable cholinesterase inhibition (0, 0.1 or 0.2 mg/kg/day). The ratsbegan training on the 16-arm radialmaze startingwhen theywere 4 or 14monthsof age. In a series of studies we have found that at doses, which cause minimalcholinesterase inhibition chlorpyrifos, diazinonandparathion causequite differenttypes of persisting effects on cognitive function. Brief postnatal exposure to a lowdoseof parathion, causes a slight improvement in accuracy in the radial-armmaze,when the offspring begin training in young adulthood. However, during the agingprocess neurocognitive impairment becomes apparent in males. When trainingbegins in later adulthood, males exposed to low doses of parathion during earlypostnatal development showasignificant impairment in radial-armmaze learningrelative to age matched male controls. The normal sex-difference in accuracy onthis spatial task is eliminated by brief postnatal low-dose parathion exposure. Thiseffect was seen more than a year after the brief period of low-level postnatalexposure. (Supported by NIH ES10356)

doi:10.1016/j.ntt.2009.04.027

NBTS24

Development of a robotic surrogate for measurement of young children'sexposure to environmental toxins

Stuart Shalata,b, Adam Stamblerc, Marta Hernandezb, Kathleen BlackbaEnvironmental and Occupational Health Sciences Institute, Rutgers University,Piscataway, NJ, USAbRobert Wood Johnson Medical School, University of Medicine and Dentistry ofNew Jersey, Piscataway, NJ, USAcRutgers, The State University of New Jersey, New Brunswick, NJ, USA

NBTS 2009 Abstracts242