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data provided insight into how the feedback control mechanisms embedded in the HPG axis mediate these changes. As this work progresses we will obtain a refined understanding of how adaptive responses within the HPG axis of fathead minnows affect DRTC behaviors for fadrozole. This work was reviewed by the U.S. EPA and approved for publication but does not necessarily reflect Agency policy. 731 APPLICATION OF A HUMAN PHYSIOLOGICALLY- BASED PHARMACOKINETIC MODEL TO EVALUATE BENZENE BLOOD LEVELS FOR PUBLIC HEALTH CONCERN. D. A. Fowler 1 , R. R. Worley 1 ,J. S. Wheeler 1 , C. Welsh 1 ,D. Moffett 1 and J. Fisher 2 . 1 Agency for Toxic Substances and Disease Registry, CDC/ATSDR/NCEH, Atlanta, GA and 2 National Center for Toxicological Research, U.S. FDA, Jefferson, AR. ATSDR recently evaluated exposure to benzene and related petroleum VOCs in two neighborhoods located near petroleum refineries and a major interstate. Each resident provided a blood sample that was analyzed for benzene levels and smoking biomarkers. We used a human physiologically-based pharmacokinetic (PBPK) model for benzene (multi-route, multi-compartment, developed in Berkeley Madonna simulation software) to model possible exposure scenarios resulting in measured benzene blood levels and evaluate the public health significance of those benzene blood levels. Measured benzene blood concentrations were an order of magnitude higher in smokers relative to non-smokers. Because benzene is rapidly metabolized, benzene blood concentrations predominantly reflect recent exposures preceding blood collection. We modeled peak and steady state inhalation of benzene resulting in the observed benzene blood levels. By doing so, we were able to evaluate PBPK predicted inhalation exposures that could result in the measured benzene blood concentrations with respect to health guidelines. Our comparative analyses included ATSDR’s chronic inhalation minimal risk level (MRL) and the Benchmark Concentration lower bound estimate (BMCL). Measured benzene blood levels in non-smokers correspond to modeled exposures that were below ATSDR’s chronic inhalation MRL and do not suggest a public health hazard. Blood from smokers had higher levels of benzene that correlated with smoking biomarkers, suggesting an elevated benzene blood level association with smoking. These elevated benzene levels correspond to modeled exposures above the MRL and near the BMCL, suggesting a health concern for smokers. This model application demonstrates the combined use of a human PBPK model and biomonitoring data in enhancing exposure analysis and public health decision-making. 732 CHARACTERIZATION OF STRAIN- & DOSE- DEPENDENT ROUTES OF ELIMINATION FOR BENZENE & ITS METABOLITES IN 4 MOUSE STRAINS. G. A. Knudsen 1 , R. K. Kuester 1 , M. L. Cunningham 2 , J. E. French 2 and I. G. Sipes 1 . 1 Medical Pharmacology, University of Arizona, Tucson, AZ and 2 National Toxicology Program, National Institutes of Environmental Health Sciences, Research Triangle Park, NC. Benzene & its metabolites are eliminated in the urine, feces or expired-air, in a dose-dependent manner. To characterize the strain- & dose-dependent routes of elimination for benzene, four strains were selected based on data from previously reported PK studies in 18 isogenic strains: C57BL/6J (reference), NZW/LacJ (high blood, marrow AUC), PWK/PhJ (highest marrow AUC) & FVB/NJ (lowest blood, marrow AUC). In C57BL/6J, elimination patterns were similar for doses 0.1-10 mg/kg (3-5% expired, 4-7% feces, 70-88% urine); at 100 mg/kg, 30% was expired while 66% micturated. At 1,000 mg/kg, 70% of the dose was expired with the remainder recovered in urine. In all doses tested (0.1-100 mg/kg), elimination in NZW/LacJ, PWK/PhJ, & FVB/NJ mice was similar to C57BL/6J mice, with few exceptions. All strains of mice eliminated the majority of administered [14C] radioactivity in the urine (NZW/LacJ: 80-88%; FVB/NJ: 75-85%; PWK/PhJ: 70- 77%). Fecal recovery for NZW/LacJ was similar to C57BL/6J (3-7%), while FVB/NJ mice eliminated more on average (7-11%). Doses recovered in feces were highest in PWK/PhJ (9-13%); however, at the highest dose, recovery was 4%. In C57BL/6J, NZW/LacJ, & FVB/NJ, expired [14C] benzene did not change significantly over the low doses (3-7%). In PWK/PhJ, a 10 mg/kg dose resulted in significantly more expiration of the dose when compared to the same dose in FVB/NJ & NZW/LacJ (p
global parameter sensitivity analysis (GSA) on various model parameters and studied their impact on several key metabolites such as ATP, mitochondrial membrane potential, GSH, NADH, Acetyl CoA, Malonyl-CoA, Cholesterol, DG and TG. Model parameters are varied by 10%, and the changes in metabolite profiles are quantified. This analysis allows parameters to be ranked in order of their impact on liver metabolism. We mimicked drug-induced perturbations on the rat liver by changing the kinetic parameters of sensitive enzymatic reactions either singly or in combination and obtained metabolite profiles. An optimization problem was formulated to estimate the values of parameters that were potentially responsible for this metabolite profile. An objective function was defined to minimize the error between predicted and observed metabolite profiles of key metabolites described above. The estimated values of the parameters were then compared with the values used in the simulations and found to match well. This provides a mechanistic basis for relating metabolite changes to specific pathways being deranged by a drug. This approach works well for both steady state and time-varying metabolite profiles. 736 DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODEL FOR RDX (HEXAHYDRO-1, 3, 5-TRINITRO-1, 3, 5-TRIAZINE) IN FEMALE B6C3F1 MICE. M. L. Gargas 1 , C. P. Gut 1 , M. R. Okolica 1 , A. Ntamack 1 , L. M. Sweeney 1 , L. R. Williams 2 , G. Reddy 2 and M. S. Johnson 2 . 1 Naval Medical Research Unit - Dayton, Wright-Patterson AFB, OH and 2 U.S. Army Public Health Command, Aberdeen Proving Ground, MD. RDX is an explosive used in military applications and has been detected in ground water surrounding US military installations and at manufacturing facilities. The current cancer slope factor was estimated from the incidence of liver neoplasms in female mice (no cancers were found in either sex of rats chronically exposed to RDX) and is based on outdated animal to human scaling techniques and mouse tumor data that has subsequently been revised using more current pathological criteria. In addition, dose-response was not evaluated using Benchmark Dose (BMD) approaches. There is a need to derive an updated cancer potency factor for RDX using more current data and techniques, including the use of internal dose and BMD modeling. The purpose of the work reported here was to finalize the development of a PBPK model for RDX kinetics in the female mouse. An initial PBPK model structure for female mice was constructed using an existing model for rats and existing data on tissue partition coefficients. The rate of RDX metabolism for female mice was determined experimentally in our laboratory using hepatic microsomal preparations and the resulting rate constant was incorporated as a PBPK model parameter. Model verification was performed by comparing model predictions to blood and liver concentration time-course data collected in our laboratory from female mice orally dosed with RDX at target doses of 1.5, 7, or 35 mg/kg. The cancer potency of RDX in humans will be determined in future evaluations using the female mouse PBPK model developed in this current work together with a PBPK model for RDX kinetics in humans. 737 BIOMARKERS OF EXPOSURE VERSUS PBPK MODEL ESTIMATES OF INTERNAL DOSE: A CASE STUDY WITH ACRYLAMIDE. R. S. DeWoskin. U.S. EPA, Research Triangle Park, NC . Estimates of internal dose greatly improve the confidence in risk assessments for systemic toxicants when extrapolating dose-response relationships across species, routes of exposure, subpopulations, or study conditions (e.g., in vitro to in vivo). Two leading methods to estimate internal dose are: 1) biomarker of exposure models, and 2) physiologically based pharmacokinetic (PBPK) models. Hemoglobin (Hb) adducts are good biomarkers of exposure to acrylamide (AA) and its mutagenic metabolite, glycidamide (GA). The U.S. EPA posted an IRIS assessment for acrylamide that estimated internal blood levels in rats and humans with an AA-Hb and GA-Hb adduct model. Concurrent with the posting of the IRIS assessment, an updated AA PBPK model was published providing an opportunity to compare results, and to evaluate the advantages each method has for specific applications. The Hb-adduct model and the PBPK model gave similar results for the ratio of the rat external dose (mg/kg/day) to the equivalent human external dose of AA (i.e., the dose that would produce comparable internal levels of AA and GA in blood). External dose ratios were in the 4.5-6.5 range for comparable levels of AA in blood, and in the 0.75-1.0 range for GA in blood. The ratio for AA in blood is similar to the value from a body weight scaling (BW 2/3 or 3/4), while the lower ratio for comparable GA internal levels reflects the considerably different production and clearance of GA in humans compared with rats (i.e., BW scaling would grossly overestimate this ratio). The Hb-adduct model only estimates internal dose of AA or GA in blood. Thus, when blood levels suffice as a surrogate dose metric for an adverse effect, the simpler seven parameter Hb-adduct model is preferred (i.e., based on AIC) to the nine compartment, 68 parameter PBPK model. The PBPK model, however, estimates a variety of dose metrics (e.g., unbound AA or GA in blood and tissues), and provides more functionality for extrapolating risks and hypothesis testing. [The views expressed are those of the authors and do not necessarily reflect the views or policies of the U.S. EPA] 738 IN VITRO 3, 5-DICHLOROANILINE NEPHROTOXICITY IN FRESHLY ISOLATED RAT RENAL CORTICAL CELLS. C. Smurthwaite, S. Baksi, T. Ferguson, C. Schuetz, D. Anestis and G. O. Rankin. Pharmacology, Physiology, and Toxicology, Marshall University, Huntington, WV. Chloroanilines are widely used in manufacturing dyes, drugs, agricultural chemicals and industrial intermediates. Previously, we demonstrated that 3,5-dichloroaniline (3,5-DCA) induced nephrotoxicity in vivo in rats and in vitro in a rat renal cortical slice model. In this study, freshly isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats were used to investigate the nephrotoxic potential of 3,5- DCA and to examine if metabolites and/or oxidative stress contributed to 3,5- DCA-induced nephrotoxicity in vitro. Nephrotoxicity was determined by incubating IRCC (~4 million cells/ml; 3 ml total volume) with vehicle (dimethyl sulfoxide, DMSO; 30 microL) or 3,5-DCA (0 - 1.5 mM) for 60, 90, or 120 minutes and calculating lactate dehyrogenase (LDH) release as a percent of total LDH. In some experiments, IRCC were pretreated with antioxidants (2.0 mM ascorbate, 1.0 mM glutathione, 1.0 mM alpha-tocopherol, or 2.0 mM N-acetyl-L-cysteine) to explore the role of oxidative stress or pretreated with a cyclooxygenase inhibitor (1.0 mM indomethacin), CYP inhibitor (1.0 mM metyrapone or 1.0 mM piperonyl butoxide) or FMO inhibitor (1.0 mM methimazole or 2.0 mM n-octylamine) to explore the role of metabolites in 3,5-DCA nephrotoxicity. 3,5-DCA nephrotoxicity was evident at 120 min at 0.5 mM 3,5-DCA and by 60 min with higher 3,5-DCA concentrations. All pretreatments reduced 3,5-DCA toxicity to varying degrees. These results suggest that 3,5-DCA is nephrotoxic to IRCC in a time and concentration dependent manner, metabolites contribute to 3,5-DCA nephrotoxicity, and oxidative stress may be a mechanism for inducing 3,5-DCA nephrotoxicity. This work was supported by NIH grant 3P20RR016477-09S1. 739 IN VITRO ANALYSIS OF CYCLOSPORINE A-INDUCED NEPHROTOXICITY BY GENE EXPRESSION AND 1 H- NMR-METABONOMICS OF CELL LYSATES. K. Herrgen 1 , O. Schmal 1 , C. J. Burek 1 , M. Gruene 2 , P. Jennings 3 and W. Dekant 1 . 1 Department of Toxicology, University of Wuerzburg, Wuerzburg, Germany, 2 Department of Organic Chemistry, University of Wuerzburg, Wuerzburg, Germany and 3 Department of Physiology and Medical Physics, Medical University of Innsbruck, Innsbruck, Austria. Early detection of nephrotoxic side effects of drug candidates combined with reduction of animal testings is still a challenge for preclinical drug development. Since some renal biomarker candidates, like KIM-1 and LCN-2 (NGAL) performed well in vivo, the scope of this study was to test their performance in vitro in human proximal tubular epithelial cell lines. To gain additional information, the intracellular metabolite patterns were tracked by 1 H-NMR-Metabonomics and compared to the gene expression data. In the present study, Cyclosporine A (CsA) was used as a model compound for drug induced nephrotoxicity. Differentiated RPTEC/TERT1 and A498 cells were used as cell models and drug treatment was performed up to 6 days by repeated dosing. A multivariate data analysis of the hydrophilic cell lysates examined by 1 H-NMR revealed a clear discrimination between cytotoxic and non-cytotoxic dose groups. The corresponding metabolites are linked to energy consumption as well as alterations of renal osmolytes. This can be interpreted as cellular dedifferentiation, a known effect of Cyclosporine A. Regarding the analyzed biomarker genes, only LCN-2 and GADD153 showed an upregulation. Other markers, like KIM-1 or Clusterin, did not show consistent alterations in this experimental set up. The increased expression of the mechanistic marker GADD153 confirms decompensated ER stress as an early event in proximal tubular cell damage caused by CsA. Effective CsA concentrations were monitored by LC-MS and revealed a bound part of about 20% of the nominal concentration along with varying intracellular concentrations. This highlights the importance of concentration measurements for in vitro testings. SOT 2011 ANNUAL MEETING 159
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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
Page 111 and 112: 498 APPLICATION OF AGE-SPECIFIC ADJ
Page 113 and 114: 507 A DOSE VOLUME TOLERABILITY STUD
Page 115 and 116: involved the use of an acute inflam
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Page 135 and 136: elative to their controls. ST-depre
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Page 143 and 144: 645 EVALUATION OF THE IN VITRO EPIS
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Page 149 and 150: 671 INFLAMMATION AND TISSUE DAMAGE
Page 151 and 152: model, ethanol was found to inhibit
Page 153 and 154: 689 ENHANCED SUPPRESSIVE FUNCTION O
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Page 157 and 158: 707 LIFE-STAGE PBPK MODELS FOR MULT
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Page 183 and 184: 830 RISK ASSESSMENT OF THE SPILL: C
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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
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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
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 and 562:
nificantly reduce circulating thyro
Page 563 and 564:
grouped into 9 observation periods
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 585 and 586:
Page 587 and 588:
Page 589 and 590:
Page 591 and 592:
Page 593 and 594:
Page 595 and 596:
Page 597 and 598:
Page 599 and 600:
Page 601 and 602:
Page 603 and 604:
Page 605 and 606:
Page 607 and 608:
Page 609 and 610:
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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The Toxicologist - Society of Toxicology

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