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2605 CO-EXPOSURE TO RADIATION AND ENVIRONMENTAL TOXICANTS (PBDE 99 AND MEHG) DURING A DEFINED CRITICAL PHASE OF NEONATAL BRAIN DEVELOPMENT ENHANCES COGNITIVE DEFECTS IN ADULT MICE. P. Eriksson1 , B. Stenerlöw2 , A. Fredriksson1 and S. Sundell-Bergman3 . 1Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden, 2Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden and 3Department of Soil and Environment, Swedish University of Agricultural Sciences, Uppsala, Sweden. Organisms, including man, are continuously exposed to low doses of ionizing radiation (IR) as well as to environmental toxicants. Hence, in the process of developing numerical limits for environmental protection, there is a strong need to consider interactive effects between radiation and other environmental stressors. It is known that exposure to IR during gestation can cause developmental neurotoxic effects in mammals. Animal studies have shown that flame retardants, polybrominated diphenyl ethers (e.g. PBDE 99), and methyl mercury (MeHg) can cause developmental neurotoxic effects. Today there is a lack of knowledge concerning effects and consequences from low-dose exposure to IR during neonatal brain development and its interaction with environmental chemicals. Epidemiological studies have indicated that IR exposure to the brain during infancy might deteriorate cognitive ability in adulthood. Ten-day old neonatal NMRI male mice were exposed to a single oral dose of PBDE 99 (2,2’,4,4’,5-pentabromodiphenyl ether) (0.8 mg/kg bw) or MeHg (0.40 or 4.0 mg/kg bw). Four hours after this exposure the mice were irradiated with 60Co gamma radiation at doses of 0,2 and 0,5 Gy. The animals were observed for spontaneous behaviour at the ages of 2- and 4months, and swim maze performance at the age of 5 months. Neither the single dose of PBDE 99 (0.8 mg/kg bw), MeHg (0.4 mg/kg bw) nor the radiation dose of 0.2 Gy affected the spontaneous behaviour, but co-exposure to IR and PBDE 99 or MeHg caused developmental neurobehavioural defects. The study shows that coexposure to IR and environmental toxicants like PBDE 99 and MeHg, during a critical period of neonatal brain development, significantly enhance developmental neurobehavioural defects and with consequence for adult cognitive functions. 2606 PERINATAL EXPOSURE OF MICE TO DIOXIN INDUCES DEPRESSION-LIKE BEHAVIOR IN A LOW- DOSE SPECIFIC MANNER. A. Haijima, Y. Zhang, T. Endo, M. Kakeyama and C. Tohyama. Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. The goal of our study is to characterize and clarify the mechanism of developmental neurotoxicity of dioxins. In our recent studies, deficits in fear memory were observed in mice exposed to dioxins in a dose-dependent manner (e.g., Haijima et al., 2010), and that the impaired learning and enhanced perseverative behavior were induced in a low-dose-specific manner (Endo et al., 2010). Here, we studied the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on depression-like behaviors as well as its dose-response relationship in mice. Pregnant C57BL/6 mice were administered TCDD by gavage at a dose of 0, 0.6 or 3.0 μg/kg b.w. on gestational day 12.5. The TCDD dose is approximately 1/300 or 1/60 of the LD50 value. After the mice reached adulthood, they were subjected to a forced swim test (FST) to examine emotional stress responses. The plasma corticosterone level was measured by ELISA at 0, 30 and 120 min after the FST. In the FST, mice perinatally exposed to 0.6 μg TCDD/kg b.w. showed a significantly shorter latency to become immobile and a significantly longer duration of immobility than the control mice, particularly in the first 2 min of the FST, while mice exposed to 3.0 μg TCDD/kg b.w. showed profiles almost indistinguishable from those of the control mice. In addition, mice exposed to 0.6 but not 3.0 μg TCDD/kg b.w. showed high plasma corticosterone level just after the FST. These results suggest that perinatal exposure of mice to TCDD induces depression-like behavior in mice in a low-dose-specific manner. 2607 ASSESSING LATER-LIFE BEHAVIORAL PHENOTYPES IN RESPONSE TO PRENATAL EXPOSURE TO BENZOPYRENE. M. M. McCallister1 , M. Maguire2 , A. Ramesh3 and D. B. Hood4 . 1Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 2Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 3Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN and 4Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN. Benzo(a)pyrene is an environmental contaminant that is a member of the polycyclic aromatic hydrocarbon (PAH) family. It was reported that environmental levels encountered in the air of New York City can affect child IQ scores adversely. 558 SOT 2011 ANNUAL MEETING These results are comparable to that reported for low-level lead exposure. The hallmark of lead exposure in studies involving children and animals is behavioral deficits. Since in animal studies the most common way to study adverse effects of lead on behavior is operant conditioning, we have used this same behavioral technique in the present study. Animal model studies have shown that prenatal exposure to PAH’s causes behavioral deficits accompanied by a downregulation of glutamate receptor subunits. This reduction is postulated to be correlated with impairments in neuronal activity in later life. In this study, we hypothesize that prenatal exposure to benzo(a)pyrene results in deficits in behavioral learning. Timedpregnant Long Evans Hooded rats were orally exposed to 0, 150, 300, 600 or 1200μg/kg of B(a)P by oral gavage. The disposition of B(a)P to fetal brain was quantified as a function of exposure (E14-E17) during peak periods of neurogenesis for cerebral cortex and hippocampus. Beginning on P90, offspring pups were habituated and tested in a discrimination reversal-operant behavioral paradigm. The results demonstrate a dose-dependent decrease in the ability to learn the reversal task with associated decreases in correct responses and an enhancement in incorrect responses in the exposure cohort. Taken together, these studies provide mechanistic insights into how in utero polycyclic aromatic hydrocarbon exposure contributes to adverse neurobiological outcomes. Supported in part by U54NS041071, S11ES014156, T32MH065782, and RRO3032. 2608 DEVELOPMENTAL IODIDE DEFICIENCY: REDUCTIONS IN THYROID HORMONES AND IMPAIRED HIPPOCAMPAL TRANSMISSION. M. Gilbert 1 , J. Hedge 1 , R. Zoeller 2 , K. Kannan 3 , K. Crofton 1 , L. Valentin- Blasini 4 , B. Blount 4 and J. Fisher 5 . 1 U.S. EPA, Research Triangle Park, NC, 2 University of Massachusetts, Amherst, MA, 3 New York Department of Health, Albany, NY, 4 CDC, Atlanta, GA and 5 U.S. FDA, Little Rock, AR. Iodine (I) is essential for thyroid hormone (TH) synthesis, and severe iodine deficiency (ID) during development produces neurological impairments. ID may exacerbate the effects of environmental chemicals on the thyroid axis. This study examined graded levels of ID during pregnancy on the thyroid axis, neurobehavior, and hippocampal electrophysiology in exposed offspring. Female LE rats were placed on diets with varying degrees of ID for 6 wks prior to breeding. I was added to a casein-based diet to produce 5 levels from adequate (>200 ng/gm) to deficient (
grouped into 9 observation periods (PNDs 25-85, 102-120, 137-155, 193-267, 284-302, 319-337, 375-449, 466-484, 501-519) and accuracy, percent task completed and response rates were analyzed using separate repeated measures analyses. We previously reported learning impairments in the high ACR dose group (5 mg/kg/day) on the IRA task through the first 52 test sessions. However, across further testing, statistically significant impairments in learning became apparent down to the lowest ACR dose tested (0.1 mg/kg/day). ACR exposed groups completed less of the IRA task than control animals beginning on PND 102 and continuing through the remainder of testing. These results show that daily exposure to ACR from implantation through adulthood impairs performance on a learning task in rats as shown here at dose levels approximately 40 times the estimated daily intake for humans. Performance of the IRA learning task has been identified as the most sensitive endpoint in this study. Supported by Interagency Agreement #224-07- 0007 between FDA and NIEHS/NTP (JG and CR participated as ORISE fellows). 2610 BIOFUELS HEALTH RESEARCH AT THE EPA: INITIAL STUDIES WITH INHALED ETHANOL IN RATS. P. J. Bushnell 1 , T. E. Beasley 1 , W. K. Boyes 1 , H. El-Masri 1 , P. A. Evansky 1 , J. Ford 1 , M. E. Gilbert 1 , D. W. Herr 1 , W. R. LeFew 1 , S. A. Martin 1 , K. L. McDaniel 1 , E. D. McLanahan 2 , V. C. Moser 1 , D. K. MacMillan 1 and W. M. Oshiro 1 . 1 NHEERL, U.S. EPA, Research Triangle Park, NC and 2 NCEA, U.S. EPA, Research Triangle Park, NC . The Energy Independence and Security Act of 2007 mandates increased use of alternative fuels in the US automobile fleet. Currently, the primary alternative to petroleum fuels is ethanol, and the public health risk associated with adding ethanol to gasoline at concentrations above 10% is uncertain. Potential neurological and immunological effects from developmental exposure to evaporative emissions from ethanol-gasoline blends are particular concerns. We have therefore begun a research effort involving computational modeling and animal experimentation, with the goal of estimating the toxicity of inhaled vapors from gasoline blended with any concentration of ethanol. Modeling approaches include PBPK models parameterized in pregnant rats for inhaled ethanol (SA Martin abstract) and complex mixtures (WR LeFew abstract). The experimental model system involves exposing pregnant female rats to vapors of ethanol and gasoline-ethanol blends from gestational day 9 through 20, quantifying target-tissue doses by analysis of ethanol concentrations, and determining internal dose-effect relationships in their offspring, using behavioral, neurophysiological, and immunological assessments. Initial studies demonstrated that pregnant female Long-Evans rats (N = 8/group) tolerated a high concentration of inhaled ethanol (20,000 ppm, 6 hr/day for 12 days) without apparent distress and delivered viable litters. No significant differences in maternal weight gain, litter size, or offspring brain weight were observed, nor was fear conditioning affected in the pups at post-natal day (PND) 60. However, compared to controls, exposed pups grew more slowly, and motor activity was increased in females at PND 13 and decreased in males at PND 21. These effects remain to be replicated in a larger study with additional exposure concentrations. Future studies will compare dose-effect relationships across a range of gasoline-ethanol blend ratios. This abstract does not reflect EPA policy. 2611 ACETAMINOPHEN METABOLITES MAY MODULATE HIPPOCAMPAL SENSITIVITY TO SEROTONIN AND SOCIAL INTERACTION BEHAVIOR THROUGH CB1 RECEPTORS. G. G. Gould 1 , L. Nguyen 2 , T. F. Burke 2 , J. G. Hensler 2 , K. Treat 1 , L. C. Daws 1 and T. Gu 3 . 1 Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, 2 Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX and 3 Restorative Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX. Concordant with replacement of aspirin by acetaminophen (paracetamol) to manage pediatric fever, the rate of autism incidence has increased. A parental survey indicates that acetaminophen use after vaccines in infants may increase the risk for autism in some children. Exposure mediated autism susceptibility could stem from gene polymorphisms in key metabolic enzymes and/or neurotransmitter receptor proteins. Abnormalities in serotonin (5-HT) systems are common among autistic individuals. Acetaminophen’s analgesic activity occurs through the action of its metabolites at endocanabinoid CB1 receptors, which are unlikely to bind to 5- HT 1A receptors. CB1 and 5-HT receptor modulatory interactions have been reported, but details of their nature in the hippocampus and impact on behavior remains unclear. We have examined this interaction in BTBR and 129Sv mice that exhibit social behavior impairments similar to those seen in autism. Through [ 35 S]GTPgS, [ 3 H] 8-OH-DPAT and [ 3 H] CP 55,940 autoradiography, we found that 129Sv mice have 20% higher 5-HT 1A receptor density and BTBR mice have 40-80% increases in 5-HT 1A and CB1 receptor function (measured by agonist-induced G-protein coupling) in the hippocampal CA1 (N=4). BTBR mice also exhibited increased social behavior with acute administration of the 5-HT 1A partial agonist buspirone (2 mg/kg), acetaminophen (100-500 mg/kg) or the cannabinoid receptor agoninst WIN 55,212 (0.1 mg/kg) in three-chamber sociability tests. These data support modulation of 5-HT systems via CB1 receptors and potential for 5-HT system disruption by acetaminophen overdose. 2612 PERSISTENT CNS EFFECTS OF POSTNATAL EXPOSURE TO CONCENTRATED AMBIENT PARTICLES. J. L. Allen, J. N. Finkelstein, C. J. Johnston, G. Oberdörster and D. A. Cory- Slechta. Environmental Medicine & Pediatrics, University of Rochester Medical Center, Rochester, NY. Increasing evidence suggests that ultrafine particulate matter (UFP) may adversely influence the brain, particularly early in development, a period of brain vulnerability. If so, air pollutants may represent a largely underappreciated contribution to CNS diseases and disorders. That hypothesis was tested in male and female C57BL6 mice exposed to concentrated ultrafine ambient particles (CAPS) at postnatal days (PN) 4-13, with a subset also re-exposed as adults (AD) at 56-60 days of age (PN + AD). Blood corticosterone levels were decreased in PN males 24 hr after the final CAPS exposure, but increased in both PN and PN+AD females, consistent with hypothalamic-pituitary-adrenal (HPA) axis dysfunction. In males, PN alone persistently suppressed overall response rates during acquisition of prototypical fixed interval (FI) operant schedule-controlled behavior; locomotor activity levels measured 2 wks after final CAPS exposure were comparably reduced in PN and PN+AD groups. In AD females, FI overall response rates were increased, whereas locomotor activity levels were reduced in PN+AD, but not PN alone groups, consistent with enhanced effects. Preliminary assessment of learning using novel object recognition suggests impairment in PN females. Glial fibrillary acidic protein immunoreactivity, a marker of astrogliosis measured in mice sacrificed at 62 days of age, was still increased in midbrain, corpus callosum and hippocampus/dentate gyrus of mice (n=2-3/treatment) after PN only CAPS. Collectively, these findings indicate that CAPS can produce, differentially by gender, persistent behavioral, CNS and HPA dysfunction even following PN only exposure. Given that such exposures are essentially life-long, these results also support the potential for air pollution to serve as a risk factor for neurodevelopmental and/or neurodegenerative disorders. Supported by ES001247 and ES019105. 2613 LIFE SPAN ALCOHOL EXPOSURE MONITORED BY FDG BRAIN PET IMAGING. MORE INFORMATION FROM FEWER ANIMALS. D. De Groot 1 , M. Boogaard 1 , R. Nederlof 1 , M. Berk 1 , E. Uitvlugt 2 , L. vd Horst 1 , M. Otto 1 , A. Wolterbeek 1 and E. De Vries 2 . 1 TNO Quality of Life, Zeist, Netherlands and 2 Groningen University Medical Center, Groningen, Netherlands. Sponsor: R. Woutersen. Objective. To investigate whether in vivo FDG PET imaging can detect adverse effects of alcohol consumption on brain development and compare the results with conventional indicators of behaviour; all this within the scope of animal reduction and refinement (animal 2Rs) in (regulatory) animal experimentation. Strategy. A recently developed protocol for an Extended One Generation Reproduction Toxicity Study [OECD EOGRTS] designed to reduce animal experimentation in reproduction toxicity testing without giving in on safety testing for man was applied. Rats were exposed daily via the drinking water (0, 1.5, 4.0, 6.5, 9.0, 11.5, 14%) from 2 weeks pre-mating to postnatal day (PND) 70 of F1-offspring. F1 offspring of all groups (n=10) was tested for motor, neuromuscular and cognitive functioning. Littermates of ethanol dose groups 0, 4 and 9% (n=3-5) were subjected to [18F]FDG microPET imaging on PND 18, 21, 35, 62 to study brain glucose metabolism. Results/discussion. Behavioral testing demonstrated impairment of neuromuscular functioning in higher dose groups (9, 11.5 and 14%), but no loss of cognition. However, FDG brain uptake showed a dose-dependent (4 and 9%) global decrease over time indicative of mental impairment. In addition, 1) decreased relative uptake was observed in striatum (PND 18) and 2) frontal cortex (PND62), and 3) increased uptake in cerebellum (PN 62), pointing at reduced dopamine function and basal ganglia volume (1), loss of reason and inhibition (2) SOT 2011 ANNUAL MEETING 559
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIODEGRADABLE MATERIALS FOR TISSU
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that genetic toxicology data are ge
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well-orchestrated lung inflammation
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scribed in the literature. We have
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years ago). We will illustrate how
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involved in the biodegradation proc
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stem cells but rather a treatment i
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additional compound showed agreemen
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82 COMPARISON OF 3H-THYMIDINE INCOR
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irritants. While in practice these
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alleles are especially vulnerable t
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109 CD4+ T CELL INTRINSIC TNF RECEP
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118 TO STUDY THE SIGNAL TRANSDUCTIO
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PAHs, such as dioxins, are prevalen
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containing substituents and/or hydr
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146 COMPUTATIONAL MODELING FOR QT P
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suggest that the combination of too
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164 TRANSLOCATOR PROTEIN (18 KDA) (
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function as a metal binding protein
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laboratory has demonstrated that NR
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known. The aim of this study was to
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from 5 to 28 days in duration) in e
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positive cells, caspase-3 activatio
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creased level in the 46 kDa preproe
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invasiveness at concentrations repr
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thracene (DMBA,50 μg in acetone, a
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247 CO-CARCINOGENESIS OF N, N- DIET
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sponds to the endosomal dsRNA that
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ODD in both WT (maximum 177% of con
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Lastly, using p53siRNA cells, p53 w
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its receptor Mpl to exert its funct
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294 LOW LEVEL OF LEAD CAN INDUCE PH
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lunar surface presented potential h
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lar about cellular export mechanism
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DNA in the kidney medulla, grandula
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5.00 and 7.50 mg/kg/day by oral gav
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events and carcinogenesis. Here we
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tinization of cells of the hair fol
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358 CHARACTERIZATION OF GENOME-WIDE
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RNAi were also performed to identif
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376 A FUNCTIONAL CROSSTALK BETWEEN
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UGT1A gene induction, while this re
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tivity, specifically peroxisome pro
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and cytotoxic effects; however, its
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histone deacetylase that is necessa
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ment. Paradoxically, buthionine sul
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drug leflunomide and its major (A77
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442 GENE EXPRESSION AND MORPHOLOGIC
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451 INHIBITION OF THE MITOCHONDRIAL
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460 SULFORAPHANE PREVENTS ACETAMINO
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drophilic/lipophilic balance. Other
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pharmacokinetic and toxicological p
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489 USE OF ‘OMICS DATA TO IMPROVE
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498 APPLICATION OF AGE-SPECIFIC ADJ
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507 A DOSE VOLUME TOLERABILITY STUD
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involved the use of an acute inflam
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sorption in the gastrointestinal (G
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(ABC) transporters actively transpo
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545 BEHAVIORAL EFFECTS OF REPIN IN
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a blood pressure phenotype that res
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and inhalation exposure system that
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and lethality associated with these
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position, on vascular reactivity an
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therefore more accurate and reprodu
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commercial chrysotile product that
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elative to their controls. ST-depre
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ats. The majority of the studies fo
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in the China Jintan Child Cohort St
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corneum thickness, cellular epiderm
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645 EVALUATION OF THE IN VITRO EPIS
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654 TCDD ADSORBED ONTO NATURAL AND
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tion revealed no test article-relat
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671 INFLAMMATION AND TISSUE DAMAGE
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model, ethanol was found to inhibit
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689 ENHANCED SUPPRESSIVE FUNCTION O
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NAC + LPS yielded different levels
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707 LIFE-STAGE PBPK MODELS FOR MULT
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downstream of the apical endpoint o
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726 UPDATED ALUMINUM PHARMACOKINETI
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global parameter sensitivity analys
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and renal inflammation induced by 2
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754 PLASMA, URINE, AND TISSUE CONCE
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cently characterized transporter OA
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exposure system was developed from
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lood cell mass and decrease in urin
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practical alternatives to MC in non
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imals dosed with 167 mg/kg THU alon
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and organ weights, clinical signs a
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yet is induced in most bladder and
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830 RISK ASSESSMENT OF THE SPILL: C
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knowledgebase creation. Results are
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852 UNDERSTANDING STRUCTURAL AND PH
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for integrating epidemiology and an
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motor activity, including age of th
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y partial purification of urine (fr
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pacity for self-renewal and may dif
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sue. The depth of our analysis led
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910 IMPLEMENTING CALIFORNIA’S GRE
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concentrations in six tissues and b
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934 THE FDA’S LIVER TOXICITY KNOW
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943 GENOME-WIDE DNA METHYLATION DIF
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membrane localization and subsequen
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trols, respectively. Subtoxic and t
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survival using both smoking regimes
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as non-, weak, moderate, or strong
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988 NNK-INDUCED CYTOKINE ALTERATION
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group (one-way ANOVA, p90 % viabili
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ered as an organ involved in xenobi
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Transport of CPZ across the Caco-2
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estrous cycle and sexual behavior d
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mRNA expression levels. Collectivel
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1043 THE EFFECTS OF ENDOCRINE DISRU
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1052 MONO-2-ETHYLHEXYL PHTHALATE IN
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Results: MC was variable within and
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UtSMCs. Phosphorylation of FoxO1 wa
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nonpregnant and pregnant diabetic m
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1089 PFOA-INDUCED LIVER EFFECTS IN
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events in the liver. AZD9056 was ev
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The peppermint oil caused a concent
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OA did not affect food consumption.
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1126 PERSISTENT DEVELOPMENTAL ARYLH
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1135 BACH2 BINDING TO Prdm1 AS A ME
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The purpose of this project was to
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one marrow. Since Chk1 is an attrac
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1163 THE MRNA AND MIRNA PROFILE OF
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have now compared the IC50 values b
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1181 ELUCIDATION OF FACTORS DETERMI
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enced by pre-exposure to cigarette
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if abnormal PF was associated with
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weight (P=0.016) and small for gest
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portant cause of death, compared to
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posure groups. However, the differe
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Naphthalene is routinely analyzed i
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1245 SEASONAL CHARACTERIZATION OF H
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1255 URINARY T, T MUCONIC ACID LEVE
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modating a reliable data evaluation
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enzoquinone generate ROS and arylat
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teins (e.g. C3, 4, and 5, APOB, VDB
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1293 TRANSFORMING GROWTH FACTOR BET
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mation was decreased to the same le
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1312 EVALUATION OF THE SENSITIVITY
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luted OFR and CRL. Culture media ex
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urinary TCPy levels, blood and brai
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activity. The dose-response curves
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mice, each with 4 dose groups. One
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exposure to both ATR and DACT has a
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third tetratricopeptide repeats (TP
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7d. 28d after TMT injury there was
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subunits. Each cell type was treate
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1394 COMPARATIVE EFFECTS OF METHYLM
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1403 GENOTOXICITY AND PRE-NEOPLASTI
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vated only in high-dose-treated ani
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1421 DOSE-RESPONSE OF NAPHTHALENE-I
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cisplatin; 1.2-, 1.9- and 2.9-fold
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Day 11 and started to recover on Da
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1448 DEVELOPMENT OF A METHOD FOR QU
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1457 GLOBAL GENE PROFILING REVEALS
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cluding mouse and human macrophage,
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model of lung inflammation and host
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1484 NANOTOXICOLOGY AND NANOHEALTH
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throughput in vitro approach was us
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1502 IMMUNOLOGICAL ASPECTS OF AN AN
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(CIA) and the Streptococcal cell wa
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sitizers were 100% concordant among
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1530 MINIMAL RISK LEVELS FOR STYREN
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ical groups in the field of regulat
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vitro with this potentially insect-
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their performance on toxicological
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need for a better understanding of
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1577 AN IN VITRO MODEL SYSTEM FOR A
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gene expression post-transcriptiona
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1595 GENE EXPRESSION PROFILE OF RAT
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to confirm a hepatotoxic property o
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1613 AN INVESTIGATION OF THE CLEARA
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its nuclear translocation was reduc
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were collected from TK animals at d
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egulated targets were selected for
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U/L after tetracycline. Minocycline
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peri-pubertal FasL-/- mice show a d
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showed similar levels of apoptosis
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1676 TWO BIOMARKERS FOR EVALUATION
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motifs selected. This system was ap
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1693 VOC SERUM LEVELS IN THE GENERA
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1702 DOES THE CLOCK MAKE THE POISON
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those with high nickel content are
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isk assessment. However, unique cha
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model of APAP metabolism and glutat
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logically & morphologically similar
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posure, blood chemistry was analyze
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elated to oxidative stress by measu
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ostasis), but work is needed to tra
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tokine products during carcinogenes
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ways as chemical stressors and, the
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toxicity of nanomaterials relates s
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1815 MEASURING COMPOUND SELECTIVITY
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1825 EFFECTS OF METABOLISM BY INTES
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cyanoacetic acid increased 2-3 fold
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1845 IS THE PROMISCUITY OF THE ARYL
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crorarray analysis. RT-PCR results
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are a family of phase-II biotransfo
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ous labs. As a result of positive s
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down the doses may produce more tox
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spectively. Below 100 mg/l of gemfi
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1900 GENERATION OF PRECISION CUT LI
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iomarkers or observation of lesions
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creased reticulocytes and lymphocyt
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statistically significant interacti
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monize sample preparation and analy
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NPC and sinonasal cancer in neighbo
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showed incidences of lung and nasal
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utylbenzenes, exhibited most simila
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1975 DIFFERENTIAL MODULATION OF CYP
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organic As to MMA(V) and a lower ca
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ole in invasion and metastasis of c
Page 433 and 434:
3T3-L1 cells to low-levels of arsen
Page 435 and 436:
2011 IDENTIFICATION OF A NOVEL VX M
Page 437 and 438:
This work was supported by Cooperat
Page 439 and 440:
2029 EFFICACY OF ENDOTRACHEAL ADMIN
Page 441 and 442:
Diazepam injections and its combina
Page 443 and 444:
2047 ESTERASE ACTIVITIES AND HEMOST
Page 445 and 446:
nanoparticle-induced toxicity progr
Page 447 and 448:
house, were iv infused into rats ov
Page 449 and 450:
een explored. This study investigat
Page 451 and 452:
croscopic analysis revealed that on
Page 453 and 454:
egg yolk collected from turtles inh
Page 455 and 456:
consistency of results in both expe
Page 457 and 458:
2111 CYTOCHROME P450 3A5 GENOTYPE I
Page 459 and 460:
esidues of organophosphates or thei
Page 461 and 462:
manganism. Recent work from our lab
Page 463 and 464:
Aβ1-40 in CSF and hippocampus in P
Page 465 and 466:
2147 CATALASE MANIPULATIONS MODIFY
Page 467 and 468:
ation based on real-world exposure
Page 469 and 470:
NPs. Aggregation of citrate-stabili
Page 471 and 472:
2175 THE ROLE OF SURFACE CHEMISTRY
Page 473 and 474:
seen rapid uptake in biological ima
Page 475 and 476:
effect on uterine weight or vaginal
Page 477 and 478:
dicating widespread exposure. While
Page 479 and 480:
components into the liver parenchym
Page 481 and 482:
2223 ISOLATION AND DETECTION OF RIC
Page 483 and 484:
stored (-20 celsius degree). The co
Page 485 and 486:
2241 DDA, A BIOMARKER FOR ENVIRONME
Page 487 and 488:
2249 INTERACTION BETWEEN DIETARY SE
Page 489 and 490:
2258 PHARMACOKINETICS, EXCRETION BA
Page 491 and 492:
2267 SENSITIVE AND SPECIFIC FLUORES
Page 493 and 494:
2276 METABOLISM AND DISPOSITION OF
Page 495 and 496:
ment of hypertension in companion a
Page 497 and 498:
for the propyl series can be used f
Page 499 and 500:
2304 IN VITRO EXPOSURE AND EVALUATI
Page 501 and 502:
2313 THE SYNERGISTIC EFFECT OF SODI
Page 503 and 504:
genes that play a crucial role in M
Page 505 and 506:
2330 THE ROLE OF TRANSFORMING GROWT
Page 507 and 508:
ined following up to 96 h continuou
Page 509 and 510:
effect doses obtained with the rat
Page 511 and 512: diated transcriptional response of
Page 513 and 514: docrine disruptor activities of EDC
Page 515 and 516: individuals. Week 6 results were qu
Page 517 and 518: functionality of photosystem II and
Page 519 and 520: wild mice (Mus musculus) from areas
Page 521 and 522: 2406 TOXICITY AND BIOACCUMULATION O
Page 523 and 524: Isocitric acid is the acid in the h
Page 525 and 526: 2425 EFFECTS OF FUMONISINS IN ETHAN
Page 527 and 528: centration(μg/g) were: 5.1-95.3; 2
Page 529 and 530: 2445 AUTOPHAGY IN DEVELOPMENT: A LI
Page 531 and 532: sures to inhaled Mn in dust. Nevert
Page 533 and 534: 2466 CRITICAL EVALUATION OF ANIMAL
Page 535 and 536: elationships predict that resting r
Page 537 and 538: 2489 COMPARATIVE TOXICITY OF BIODIE
Page 539 and 540: 2497 TRANSCRIPTIONAL REGULATION OF
Page 541 and 542: 2506 TOXICOLOGICAL CONSIDERATIONS O
Page 543 and 544: launched with the aim of developing
Page 545 and 546: forms mRNA expression levels were a
Page 547 and 548: 2534 CUTANEOUS WOUND HEALING IN THE
Page 549 and 550: wells (0, 1, 5, 10, 25, 50, 100, an
Page 551 and 552: 2553 AN ORGANOTYPIC MICROLIVER PLAT
Page 553 and 554: serum-free media. At 24 hrs, the gr
Page 555 and 556: 2572 INCREASED ARSENIC BIOACCESSIBI
Page 557 and 558: nology to develop improved methods.
Page 559 and 560: tuna, swordfish, or mako shark (3.5
Page 561: nificantly reduce circulating thyro
Page 565 and 566: histopathological or biochemical ev
Page 567 and 568: exhibited a hyperactive phenotype,
Page 569 and 570: the search of effective drugs for e
Page 571 and 572: 2644 COVALENT BINDING OF 14 C 2-MET
Page 573 and 574: aries targeting all transcription f
Page 575 and 576: (p 9 weeks) and CSC phenotype acqui
Page 577 and 578: 2673 IMMUNE-MEDIATED VASCULAR INJUR
Page 579 and 580: for risk identification and charact
Page 581 and 582: to control toxicant delivery in tob
Page 583 and 584: Author Index (Continued) The numera
Page 611 and 612: Keyword Index (Continued) Arsenite
Page 613 and 614:
Keyword Index (Continued) Covalent
Page 615 and 616:
Keyword Index (Continued) flow cyto
Page 617 and 618:
Keyword Index (Continued) innate im
Page 619 and 620:
Keyword Index (Continued) nanoparti
Page 621 and 622:
Keyword Index (Continued) preservat
Page 623 and 624:
Keyword Index (Continued) Thrombocy
Page 625 and 626:
Toxicological Sciences The Official
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