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determine the potential of NEA, to induce developmental toxicity after maternal exposure via whole-body vapor inhalation (6 h per day) from implantation to 1 day prior to parturition, to characterize maternal toxicity, and to determine a NOAEL for maternal and developmental toxicity. Groups of bred female Crl:CD(SD) rats (25/group), ~ 14 weeks of age, were exposed to either filtered air or vapor atmospheres of NEA during gestation days (GD) 6-19. Target concentrations were 4, 10, and 40 (highest achievable) ppm. On GD 20, a laparohysterectomy was performed. The uteri, placentae, and ovaries were examined, and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. Gravid uterine weights were recorded, and net body weights and net body weight changes were calculated. The fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations and developmental variations. All animals survived to the scheduled necropsy on GD 20. There were no test substance-related clinical findings noted at the daily examinations, mid-point of exposure, or 1 hour following completion of exposure. Mean body weights, body weight changes, net body weights, net body weight changes, gravid uterine weights, and food consumption in the 4, 10, and 40 ppm groups were similar to that of the control group throughout the entire exposure period. Intrauterine growth and survival and external, visceral, and skeletal fetal morphology were unaffected by test substance administration at all exposure levels. No signs of maternal or developmental toxicity were observed at any exposure level evaluated. A NOAEL of 40 ppm was assigned for maternal and prenatal developmental toxicity. 1645 EFFECTS OF THALIDOMIDE ON NORMAL FETAL GROWTH AND HEART RATE IN CYNOMOLGUS MONKEYS. C. Diabo, M. Kob, C. Cohle, K. Griffin, B. Lewis, A. Kuzmin, S. Magness and A. S. Faqi. Drug Safety Evaluation, MPI Research, Mattawan, MI. Due to increasing numbers of biologics, developmental toxicity testing in nonhuman primates (NHPs) has become more common as NHPs are often the only species that express pharmacologic responses similar to humans. One of the technical challenges in the developmental toxicity studies of NHPs is the establishment of pregnancy and ensuring the normal development of the fetus during the study. In nonhuman primates ultrasound is used as in humans to determine pregnancy, the embryo/fetal size, weight and to measure growth thus making sure the fetus is developing according to plan. The objective of this study was to determine whether administration of thalidomide during the window of sensitivity in pregnant NHPs will adversely impact fetal growth and heart rate. Sexually mature Vietnamese female cynomolgus monkeys were bred in-house for the study. Prior to mating menstrual cycle of each female was monitored for at least 3 months. Pregnancy was confirmed on Gestation Days (GDs) 18-20 using ultrasound. Pregnant cynomolgus monkeys received either vehicle (n=10) or 7.5 mg/kg/day of thalidomide (n=10) on GDs 26, 27 and 29. C-section was performed on 50% of the animals on GD 100. The remaining 50% of the animals (n= 5/group) were allowed to deliver naturally. During pregnancy ultrasound measurements including fetal crown-rump length (GD 48-52), cranial, and femoral measurements and heart rate were performed. Typical thalidomide-related malformations were noted in the fetuses of the thalidomide group. No statistical differences in fetal growth as determined by fetal crown-rump length, cranial and femur length measurements were observed between control animals and the thalidomide group. Likewise, analysis of fetal heart rates didn’t indicate significant difference among the groups (control: 372.2 ± 15.0 vs. thalidomide: 379.5 ± 13.0 BPM). Based on the results of this study, there seems to be no indication that thalidomide induces effects on fetal growth and heart rate in pregnant monkeys when exposed during the window of sensitivity. 1646 COMPARATIVE EVALUATION OF LEARNING AND MEMORY IN RATS USING MORRIS MAZE VIDEO TRACKING SYSTEM AND PASSIVE AVOIDANCE. C. Lanphear, A. Terpstra, A. Rohr and A. S. Faqi. Drug Safety Evaluation, MPI Research, Mattawan, MI. The objective of the study was to determine the difference in sensitivity between Morris Maze and Gemini systems of detecting effects on learning and memory impairment when rats were exposed to Scopolamine. Four groups of 25 rats/sex/group were administered subcutaneously either the vehicle (0.9% Sodium Chloride for Injection) [Groups 1 and 3] or Scopolamine (Groups 2 and 4) on Days 1-5, at a dose volume of 1 mL/kg. Daily (Days 1-5), each rat was administered either the vehicle or Scopolamine 20 minutes prior to the beginning of the testing with the Morris maze. The procedure consisted of placing each rat in a large circular pool of water and the rat was expected to escape from water onto a hidden platform whose location can be identified only using spatial memory. A total of 5 trials was performed with the fifth trial (Day 5) described as probe trial conducted with the plat- 354 SOT 2011 ANNUAL MEETING form removed. The time to reach the platform, path length, cumulative path length, and swim speed were measured for each interval. For passive avoidance, trials to criterion with stop were performed. This involves 5 sessions where the animal received foot shock until they reached a criterion, defined as remaining passive for 2 consecutive 180 s trials. Significant increase in the time to reach the platform (latency), path length, cumulative path length and a decrease in swim speed for males and females treated with Scopolamine were observed. Review of the pictograms on Day 5 showed that Scopolamine treated animals have not learned the location of the hidden platform after five consecutive testing days. In passive avoidance, the number of Scopolamine treated males that did not pass increased significant (32% vs. 4% of controls). Scopolamine treated females were comparable with the vehicle controls. Based on the results of this study Morris water-maze is a more sensitive test than the step-through passive avoidance procedure when evaluating spatial learning and memory. 1647 2, 3, 7, 8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) INHIBITS EPICARDIAL DEVELOPMENT IN THE EMBRYONIC ZEBRAFISH HEART. J. S. Plavicki, W. Heideman and R. E. Peterson. School of Pharmacy, University of Wisconsin at Madison, Madison, WI. Exposure to 2, 3, 7,8-tetrachlorodibenzo-p-dioxin (TCDD) during early embryonic development produces numerous cardiac phenotypes in zebrafish, including decreased numbers of cardiomyocytes, heart looping defects, valve defects and reduced cardiac output. The window of TCDD sensitivity during embryogenesis correlates with the formation of the outermost layer of the heart, the epicardium, which plays critical roles in cardiac development. The epicardium originates from the proepicardial organ (PEO) and contains cardiac progenitor cells that contribute to both the myocardium and the coronary vasculature. In addition, the epicardium is necessary for maturation of the cardiac conduction system. We hypothesized that disruption of epicardial development may account for the cardiac toxicity produced by TCCD exposure. To test whether TCDD disrupts embryonic epicardial development, we examined the effects of TCCD exposure (1.0 ng/ml waterborne) on epicardium formation by examining sections stained with hematoxylin and eosin (H&E). We also followed the expression of known epicardial markers across multiple stages of embryonic development with in situ hybridization, fluorescence immunocytochemistry (F-ICC) and an epicardial GFP reporter using confocal microscopy. Strikingly, TCCD exposure during the first 24 hours post fertilization (hpf) caused a complete the loss of the embryonic epicardium. The expression of the epicardial markers including Wilms’ Tumor 1 (wt1) and tcf21/epicardin were decreased in TCDD exposed embryos as compared to vehicle controls at 48, 72, 96 and 120 hpf. The H&E stained sections confirmed that epicardial cells were absent in TCCD exposed embryos. Time course and other studies were used to determine whether TCDD alters PEO formation or acts after the specification of epicardial cell fate. Our results show that brief exposure to TCDD in the parts per trillion to parts per billion levels can prevent the formation of an essential component layer of the developing vertebrate heart. Supported by NIH Grant ES012716 and UW Sea Grant. 1648 MINOCYCLINE AND DOXYCYLINE, BUT NOT TETRACYCLINE, DECREASE LIVER AND KIDNEY INJURY AFTER HEMORRHAGIC SHOCK AND RESUSCITATION IN MICE. A. Kholmukhamedov 1 , C. Czerny 1 , J. Hu 1 , J. Schwartz 1 and J. J. Lemasters 1, 2 . 1 Pharmaceutical & Biomedical Sciences, Medical University of South Carolina, Charleston, SC and 2 Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC. Background: Recent evidence suggests that despite recovery of hemodynamics by fluid resuscitation, liver and kidneys experience progressive injury. Minocycline and doxycycline are tetracycline derivatives that are protective to various organs in models of hypoxic, ischemic and oxidative stress and which may act by preserving mitochondrial function. Our overall Aim was to determine whether minocycline and doxycycline protect liver and kidney in a mouse model of HS/R. Methods: Under pentobarbital anesthesia, C57BL6 mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer’s solution containing tetracycline, minocycline, doxycycline or vehicle. For the pretreatment studies, drugs were administered via intraperitoneal injection and then immediately after the blood resuscitation. Serum alanine aminotransferase (ALT) and creatinine, liver and kidney histology were assessed 6 h after resuscitation. Results: ALT increased to 1988 U/L after resuscitation with vehicle and to 1963
U/L after tetracycline. Minocycline and doxycycline post-treatment decreased ALT to 857 and 789 U/L, respectively (p
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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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Page 315 and 316: 1448 DEVELOPMENT OF A METHOD FOR QU
Page 317 and 318: 1457 GLOBAL GENE PROFILING REVEALS
Page 319 and 320: cluding mouse and human macrophage,
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Page 323 and 324: 1484 NANOTOXICOLOGY AND NANOHEALTH
Page 325 and 326: throughput in vitro approach was us
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Page 329 and 330: (CIA) and the Streptococcal cell wa
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Page 333 and 334: 1530 MINIMAL RISK LEVELS FOR STYREN
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Page 337 and 338: vitro with this potentially insect-
Page 339 and 340: their performance on toxicological
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Page 343 and 344: 1577 AN IN VITRO MODEL SYSTEM FOR A
Page 345 and 346: gene expression post-transcriptiona
Page 347 and 348: 1595 GENE EXPRESSION PROFILE OF RAT
Page 349 and 350: to confirm a hepatotoxic property o
Page 351 and 352: 1613 AN INVESTIGATION OF THE CLEARA
Page 353 and 354: its nuclear translocation was reduc
Page 355 and 356: were collected from TK animals at d
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Page 361 and 362: peri-pubertal FasL-/- mice show a d
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Page 369 and 370: 1693 VOC SERUM LEVELS IN THE GENERA
Page 371 and 372: 1702 DOES THE CLOCK MAKE THE POISON
Page 373 and 374: those with high nickel content are
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Page 377 and 378: model of APAP metabolism and glutat
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Page 381 and 382: posure, blood chemistry was analyze
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Page 389 and 390: ways as chemical stressors and, the
Page 391 and 392: toxicity of nanomaterials relates s
Page 393 and 394: 1815 MEASURING COMPOUND SELECTIVITY
Page 395 and 396: 1825 EFFECTS OF METABOLISM BY INTES
Page 397 and 398: cyanoacetic acid increased 2-3 fold
Page 399 and 400: 1845 IS THE PROMISCUITY OF THE ARYL
Page 401 and 402: crorarray analysis. RT-PCR results
Page 403 and 404: are a family of phase-II biotransfo
Page 405 and 406: ous labs. As a result of positive s
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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
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3T3-L1 cells to low-levels of arsen
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2011 IDENTIFICATION OF A NOVEL VX M
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This work was supported by Cooperat
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2029 EFFICACY OF ENDOTRACHEAL ADMIN
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Diazepam injections and its combina
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2047 ESTERASE ACTIVITIES AND HEMOST
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nanoparticle-induced toxicity progr
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house, were iv infused into rats ov
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een explored. This study investigat
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croscopic analysis revealed that on
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egg yolk collected from turtles inh
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consistency of results in both expe
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2111 CYTOCHROME P450 3A5 GENOTYPE I
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esidues of organophosphates or thei
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manganism. Recent work from our lab
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Aβ1-40 in CSF and hippocampus in P
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2147 CATALASE MANIPULATIONS MODIFY
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ation based on real-world exposure
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NPs. Aggregation of citrate-stabili
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2175 THE ROLE OF SURFACE CHEMISTRY
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seen rapid uptake in biological ima
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effect on uterine weight or vaginal
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dicating widespread exposure. While
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components into the liver parenchym
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2223 ISOLATION AND DETECTION OF RIC
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stored (-20 celsius degree). The co
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2241 DDA, A BIOMARKER FOR ENVIRONME
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2249 INTERACTION BETWEEN DIETARY SE
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2258 PHARMACOKINETICS, EXCRETION BA
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2267 SENSITIVE AND SPECIFIC FLUORES
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2276 METABOLISM AND DISPOSITION OF
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ment of hypertension in companion a
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for the propyl series can be used f
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2304 IN VITRO EXPOSURE AND EVALUATI
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2313 THE SYNERGISTIC EFFECT OF SODI
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genes that play a crucial role in M
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2330 THE ROLE OF TRANSFORMING GROWT
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ined following up to 96 h continuou
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effect doses obtained with the rat
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diated transcriptional response of
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docrine disruptor activities of EDC
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individuals. Week 6 results were qu
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functionality of photosystem II and
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wild mice (Mus musculus) from areas
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2406 TOXICITY AND BIOACCUMULATION O
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Isocitric acid is the acid in the h
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2425 EFFECTS OF FUMONISINS IN ETHAN
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centration(μg/g) were: 5.1-95.3; 2
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2445 AUTOPHAGY IN DEVELOPMENT: A LI
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sures to inhaled Mn in dust. Nevert
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2466 CRITICAL EVALUATION OF ANIMAL
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elationships predict that resting r
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2489 COMPARATIVE TOXICITY OF BIODIE
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2497 TRANSCRIPTIONAL REGULATION OF
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2506 TOXICOLOGICAL CONSIDERATIONS O
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launched with the aim of developing
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forms mRNA expression levels were a
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2534 CUTANEOUS WOUND HEALING IN THE
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wells (0, 1, 5, 10, 25, 50, 100, an
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2553 AN ORGANOTYPIC MICROLIVER PLAT
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serum-free media. At 24 hrs, the gr
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2572 INCREASED ARSENIC BIOACCESSIBI
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nology to develop improved methods.
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tuna, swordfish, or mako shark (3.5
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nificantly reduce circulating thyro
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grouped into 9 observation periods
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histopathological or biochemical ev
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exhibited a hyperactive phenotype,
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the search of effective drugs for e
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2644 COVALENT BINDING OF 14 C 2-MET
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aries targeting all transcription f
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(p 9 weeks) and CSC phenotype acqui
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2673 IMMUNE-MEDIATED VASCULAR INJUR
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for risk identification and charact
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to control toxicant delivery in tob
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Author Index (Continued) The numera
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Keyword Index (Continued) Arsenite
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Keyword Index (Continued) Covalent
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Keyword Index (Continued) flow cyto
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Keyword Index (Continued) innate im
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Keyword Index (Continued) nanoparti
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Keyword Index (Continued) preservat
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Keyword Index (Continued) Thrombocy
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Toxicological Sciences The Official
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