weight-of-the-evidence assessment in neurodevelopmental epidemiology: a plea for consistency

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estimation of toxicant effects; uncertainties in the degree of measurement equivalence when tests are transported into different languages and cultures; and the influence of normal developmental brain changes on the domain of functioning and the stability and predictive validity of test scores. Conclusion: The field of environ- mental epidemiology is nearing a stage where a formal set of meth- odological and reporting guidelines could be developed to help in the design of future studies, as has been done with clinical trials, studies of diagnostic assessment tools, and medical epidemiological studies. Supported by Cefic-LRI. doi:10.1016/j.ntt.2010.04.037 NBTS37 Weight-of-the-evidence assessment in neurodevelopmental epidemiology: A plea for consistency Michael Goodman Emory University, Atlanta, GA, United States doi:10.1016/j.ntt.2010.04.038 NBTS38 Effects of domoic acid on early visual memory in infants from the Coastal Cohort Kimberly Grant a , Tom Burbacher a , Sparkle Roberts b , Lynn Grattan b a University of Washington, Seattle, WA, United States b University of Maryland, Baltimore, Maryland, United States The effect of domoic acid on infant growth and development is an emerging public health issue but largely unexplored in the scientific arena. The Coastal Cohort study is an on-going prospective investiga- tion focused on the cognitive effects of domoic acid (DA) exposure in Native Americans living on the coast of Washington State. As part of this larger epidemiological study, 35 infants were tested on the Fagan Test of Infant Intelligence© (FTII). Fetal exposure to DA was estimated through maternal dietary reports and environmental monitoring data from local beaches. The Fagan Test of Infant Intelligence is a cognitive test that measures attention and visual recognition memory and has been successfully used in field and laboratory studies to examine the neurobehavioral consequences of prenatal exposure to environmen- tal contaminants. In this study, infants in the Coastal Cohort, ranging in age from nine to twelve months, completed all ten problems on the FTII. The preliminary results from this study show that infants in this cohort are, as a group, performing well within the normal range on this test (mean infant novelty preference across all study sites= 62.9%, sd=6.4). The range of novelty scores from 51.4% to 78.2% demonstrates there were strong individual differences in perfor- mance. Preliminary results suggest a moderate trend for lower memory scores in infants with putative DA exposures of 2 ppm to 4 ppm compared with exposures of .5 ppm (65.0% vs 61.3%, p < .09). Maternal estimates of exposure are still being calculated as we move forward with the analyses. doi:10.1016/j.ntt.2010.04.039 NBTS39 Acute postnatal exposure to the pentaBDE commercial mixture DE-71 at low doses (5 or 15 mg/kg/day) does not produce learning or attention deficits in rats Lori Driscoll Colorado College, Colorado Springs, CO, United States Polybrominated diphenyl ethers (PBDEs) are additive flame retardants used in the manufacturing of furniture, household ap- pliances and many textiles. Human PBDE exposure occurs primarily through inhalation and ingestion; in infants, high doses are ingested in breast milk. Previously in our laboratory, learning deficits were observed in rats exposed to DE-71, a commercial PBDE mixture, at a dose of 30 mg/kg/day during the second postnatal week. The purpose of the current study was to determine if this effect is observed at lower doses of DE-71. Rats received one of three daily oral treatment doses of DE-71 (0 mg/kg, 5 mg/kg, or 15 mg/kg) from postnatal days 612 and were tested as adults on variations of a 5-choice serial reaction time task. Learning was measured by acquisition rate of the initial visual discrimination task, in which the rats were trained to make a nosepoke to the randomly selected port in which a visual cue appeared. Attention was assessed by measuring the rats' response accuracy and error types when the visual cues were made brief and unpredictable. No significant effect of DE-71 treatment group was found on any of the dependent variables, suggesting that the in- vestigated doses were below threshold to induce impairment in these tasks. Therefore, future research should investigate doses between 15 mg/kg and 30 mg/kg in order to determine the critical levels required to generate learning impairments. doi:10.1016/j.ntt.2010.04.040 NBTS40 Gene-toxicant interactions: Developmental PBDE effects on the behavioral phenotype of the Mecp2-308 Rett syndrome mouse model Mari Golub, Roxanne Vallero, Joanne Suarez, Ta Tram Anh, Pessah Isaac, Berman Robert, LaSalle Janine University of California Davis, Davis, CA, United States Gene-environment interactions may play a role in childhood neurobehavioral disease. Chronic low dose developmental exposure to the flame retardant PBDE-47 (0.03 mg/kg d, oral administration to the dam from 30 day prior to mating to weaning of the litter) was studied for interaction with the behavioral phenotype of the Mecp2- 308 mouse, a transgenic model for Rett syndrome. Infant, juvenile and adult tests were included in the offspring behavioral test battery. During the dosing period, PBDE-47 influenced sensory maturation and separation-induced vocalizations but later tests were not affected. Interactions between genotype and PBDE occurred on some tests important to the intellectual and social phenotype associated with reduced MECP2 expression in humans, namely infant vocalization during social isolation, juvenile social preference, and adult learning and memory. The interactions occurred primarily for the heterozygous Mecp2 308/+ female rather than in the hemizygous Mecp2 308/y males suggesting a greater sensitivity of the phenotype to environmental toxicants in females. Supported by NIH ES015171. doi:10.1016/j.ntt.2010.04.041 NBTS 2010 Abstract 507

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estimation of toxicant effects; uncertainties in the degree ofmeasurement equivalence when tests are transported into differentlanguages and cultures; and the influence of normal developmentalbrain changes on the domain of functioning and the stability andpredictive validity of test scores. Conclusion: The field of environ-mental epidemiology is nearing a stage where a formal set of meth-odological and reporting guidelines could be developed to help in thedesign of future studies, as has been done with clinical trials, studiesof diagnostic assessment tools, and medical epidemiological studies.Supported by Cefic-LRI.

doi:10.1016/j.ntt.2010.04.037

NBTS37Weight-of-the-evidence assessment in neurodevelopmentalepidemiology: A plea for consistency

Michael GoodmanEmory University, Atlanta, GA, United States

doi:10.1016/j.ntt.2010.04.038

NBTS38Effects of domoic acid on early visual memory in infants from theCoastal Cohort

Kimberly Granta, Tom Burbachera, Sparkle Robertsb, Lynn Grattanb

aUniversity of Washington, Seattle, WA, United StatesbUniversity of Maryland, Baltimore, Maryland, United States

The effect of domoic acid on infant growth and development is anemerging public health issue but largely unexplored in the scientificarena. The Coastal Cohort study is an on-going prospective investiga-tion focused on the cognitive effects of domoic acid (DA) exposure inNative Americans living on the coast of Washington State. As part ofthis larger epidemiological study, 35 infants were tested on the FaganTest of Infant Intelligence© (FTII). Fetal exposure to DAwas estimatedthrough maternal dietary reports and environmental monitoring datafrom local beaches. The Fagan Test of Infant Intelligence is a cognitivetest that measures attention and visual recognition memory and hasbeen successfully used in field and laboratory studies to examine theneurobehavioral consequences of prenatal exposure to environmen-tal contaminants. In this study, infants in the Coastal Cohort, rangingin age from nine to twelve months, completed all ten problems on theFTII. The preliminary results from this study show that infants in thiscohort are, as a group, performing well within the normal range onthis test (mean infant novelty preference across all study sites=62.9%, sd=6.4). The range of novelty scores from 51.4% to 78.2%demonstrates there were strong individual differences in perfor-mance. Preliminary results suggest a moderate trend for lowermemory scores in infants with putative DA exposures of 2 ppm to4 ppm compared with exposures of .5 ppm (65.0% vs 61.3%, p<.09).Maternal estimates of exposure are still being calculated as we moveforward with the analyses.

doi:10.1016/j.ntt.2010.04.039

NBTS39Acute postnatal exposure to the pentaBDE commercial mixtureDE-71 at low doses (5 or 15 mg/kg/day) does not produce learningor attention deficits in rats

Lori DriscollColorado College, Colorado Springs, CO, United States

Polybrominated diphenyl ethers (PBDEs) are additive flameretardants used in the manufacturing of furniture, household ap-pliances and many textiles. Human PBDE exposure occurs primarilythrough inhalation and ingestion; in infants, high doses are ingestedin breast milk. Previously in our laboratory, learning deficits wereobserved in rats exposed to DE-71, a commercial PBDE mixture, at adose of 30 mg/kg/day during the second postnatal week. The purposeof the current study was to determine if this effect is observed atlower doses of DE-71. Rats received one of three daily oral treatmentdoses of DE-71 (0 mg/kg, 5 mg/kg, or 15 mg/kg) from postnatal days6–12 and were tested as adults on variations of a 5-choice serialreaction time task. Learning was measured by acquisition rate of theinitial visual discrimination task, in which the rats were trained tomake a nosepoke to the randomly selected port in which a visual cueappeared. Attention was assessed by measuring the rats' responseaccuracy and error types when the visual cues were made brief andunpredictable. No significant effect of DE-71 treatment group wasfound on any of the dependent variables, suggesting that the in-vestigated doses were below threshold to induce impairment in thesetasks. Therefore, future research should investigate doses between15 mg/kg and 30 mg/kg in order to determine the critical levelsrequired to generate learning impairments.

doi:10.1016/j.ntt.2010.04.040

NBTS40Gene-toxicant interactions: Developmental PBDE effects on thebehavioral phenotype of the Mecp2-308 Rett syndromemouse model

Mari Golub, Roxanne Vallero, Joanne Suarez, Ta Tram Anh,Pessah Isaac, Berman Robert, LaSalle JanineUniversity of California Davis, Davis, CA, United States

Gene-environment interactions may play a role in childhoodneurobehavioral disease. Chronic low dose developmental exposureto the flame retardant PBDE-47 (0.03 mg/kg d, oral administration tothe dam from 30 day prior to mating to weaning of the litter) wasstudied for interaction with the behavioral phenotype of the Mecp2-308mouse, a transgenic model for Rett syndrome. Infant, juvenile andadult tests were included in the offspring behavioral test battery.During the dosing period, PBDE-47 influenced sensorymaturation andseparation-induced vocalizations but later tests were not affected.Interactions between genotype and PBDE occurred on some testsimportant to the intellectual and social phenotype associated withreduced MECP2 expression in humans, namely infant vocalizationduring social isolation, juvenile social preference, and adult learningandmemory. The interactions occurred primarily for the heterozygousMecp2308/+ female rather than in the hemizygous Mecp2308/y malessuggesting a greater sensitivity of the phenotype to environmentaltoxicants in females. Supported by NIH ES015171.

doi:10.1016/j.ntt.2010.04.041

NBTS 2010 Abstract 507