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NADPH), for potent reversible inhibitors varied by the assay dilution factor, e.g. for mibefradil (irreversible and potent reversible inhibitor), shifted IC50 with 10x dilution is 0.33μM, shifted IC50 with no dilution is 0.033μM. Consequently the fold shift (ratio of IC50 30 minute pre-incubation minus NADPH/IC50 30 minute pre-incubation plus NADPH) does not change. As a result the difference between different assay conditions and the way they should be interpreted is dependent upon how the direct inhibition is accounted for. A dilution step between pre-incubation and incubation helps to reduce direct inhibition although this can skew data. By assessing the single point and IC50 shift screens we propose a reversible inhibition and TDI screening platform to cover early phase compounds, which should enable early accurate decisions to be made regarding development of those compounds which could potentially cause DDIs and associated toxicity. 2281 REACTIVITY OF BRO3- EXPLAINS POOR APPARENT ABSORPTION OF LOW ORAL DOSES F344 RATS. R. J. Bull 1 , N. Kolisetty 2 , Z. Guo 3 , J. W. Fisher 4 , J. A. Cotruvo 5 and B. S. Cummings 2 . 1 Washington State University, Richland, WA, 2 University of Georgia, Athens, GA, 3 Center for Water Technology, Public Utility Board, Singapore, Singapore, 4 U.S. FDA, Jefferson, AR and 5 Joseph Cotruvo & Associates, LLC, Washington, DC. BrO3- is a by-product of ozone use to disinfect drinking water. At high doses, BrO3- has been shown to be carciongenic in F344 rats. The experiments reported here are part of an effort to characterize the pharmacokinetics of BrO3-. A first pass effect (75%) is seen at oral doses of BrO3- in the range that produce cancer. However, it has been very difficult to estimate plasma conc. of BrO3- with of doses 2 fold difference in several PK parameters among mouse strains in the total [14C] radioactivity for blood and bone marrow following [14C] benzene administration to a series of genetically diverse murine strains selected from the NTP-Perlegen Mouse Genome Project. Current studies investigated the disposition over time of total [14C] radioactivity in liver and kidneys of male and female mice of selected strains following a single oral dose of [14C] benzene. Mice (5 per time point) were administered [14C] benzene (0.1 mg/kg, 75 μCi/kg) and euthanized at time points between 5 min and 2 h. Kidneys and livers were excised and solubilized. Total [14C] content was quantified using liquid scintillation counting. Pharmacokinetic parameters were estimated using a one-compartment model assuming first order elimination kinetics. The AUC, CL_F and Cmax of [14C] equivalents in livers ranged from 82 to 1224 min*μmol/mg protein, 0.003-176 nmol/min* /mg protein, 0.7- 2.5 nmol/mg protein, respectively. In general, the AUC values for liver were 2-3 fold greater than those of the kidneys while CL_F from the kidney exceeded that of the liver across the strains. In a few outlier strains, liver (MOLF/EiJ, KK/HiJ, A/J, C3H/HeJ, WSB/EiJ and Balb/cByJ, females and MOLF/EiJ, NOD/ShiLtJ and WSB/Ei,J males) and kidneys (A/J, females and DBA/2K males) the data could not 490 SOT 2011 ANNUAL MEETING be fit to the model either due to a failure to ‘capture’ the elimination phase (Cmax >120 min) or a flat elimination phase (t1/2β Ç ∞). These data suggest that the disposition of benzene to the liver and kidneys is dependent upon the genetic background of a mouse. This research was supported in part by the NIEHS NTP Grant No. N01-ES-45529 and NIEHS-sponsored Southwest Environmental Science Center Grant Number P3-ES-06694. 2283 PYRIDAZINE REDUCES TRICHLOROACETIC ACID (TCA) BIOAVAILABILITY BY ENHANCING ITS URINARY ELIMINATION. J. Bruckner, S. Lee, C. A. White, S. Muralidhara and R. Govindaarajan. Pharmacology and Biomedical Sciences, University of Georgia, Athens, GA. TCA, a proximate mouse hepatocarcinogen, is a major metabolite of halocarbons, as well as a by-product of chlorination of water. Lee et al. (2010) found pretreatment of male Sprague-Dawley (S-D) rats with pyridazine (PZ), a potent cytochrome P4502E1 inducer, resulted in a marked decrease rather than increase in TCA bioavailability. The objective of the current study was to explore mechanisms for this unanticipated change in dosimetry. Male S-D rats received 200 mg PZ/kg ip for 3 days. Controls received saline. PZ-pretreated rats given 10 or 50 mg TCA/kg iv exhibited more rapid systemic elimination of TCA, due largely to enhanced urinary excretion. A less pronounced effect at the higher dose is suggestive of a saturable renal reabsorption process. Other PZ-pretreated and conrol rats received saline or 200 mg probenecid (PB)/kg ip 10 min before 50 mg TCA/kg iv. PB, an organic anion transporter (OAT) inhibitor, produced a modest decrease in systemic TCA clearance (CL) in controls and partially offset the marked PZ-induced increase in CL. Pilot in vitro experiments indicate P2 also inhibits H- and Na-dependent monocarboxylate transporters (MCT). These data suggest PB modestly inhibits OAT transport of TCA into urine; and PZ substantially inhibits TCA reabsorption from urine. MCT-mediated reabsorption may be a significant contributor to TCA’s long half-life. Suppoted by U.S. DOE DE-FC09-02CH11109. 2284 DETERMINATION OF TACROLIMUS IN RAT WHOLE BLOOD USING DRIED BLOOD SPOT ANALYSES BY LC-MS/MS. M. Kim 1 , G. Ray 1 , Y. Liu 1 , R. Losson 2 and G. Bricker 2 . 1 KCAS, Shawnee, KS and 2 Xenometrics, Stilwell, KS. Sponsor: D. Dandekar. Tacrolimus (FK-506) is an immunosuppressive agent that is used to lower organ rejection following transplantation and to treat various autoimmune diseases of the skin. However, tacrolimus has significant toxicity, in particular cardiotoxicity to dogs. In the development of a novel dosage form of tacrolimus, a dried blood spot (DBS) method was desirable for toxicokinetic assessment from serial sampling from rats. DBS is an appropriate approach, since tacrolimus is highly sequestered in to red blood cells. Serial blood samples (40 μL) were removed from cannulated rats following oral gavage administration, placed onto DBS cards (Ahlstrom), and allowed to dry at ambient conditions. DBS punches where then placed into methanolic extraction solvent containing internal standard (ascomycin) and extensively vortexed using a multitube vortexor. The resulting extraction solvent was evaporated to dryness and reconstituted in mobile phase for LC-MS/MS. The samples were chromatographed using a Betasil cyano column (100x2.1 mm, 5 μ) and methanol-based mobile phase solutions. A valve switching system with a trap column (Betasil cyano, 10x2.1 mm) was used for eliminating background noise built up with injections of extracted samples. The analytes were detected by Turboion Spray API 4000 LC-MS/MS system under positive MRM mode. The quantitation ranges were 5 - 250 ng/mL. The method was suitable for PK and TK analyses with accuracy, precision and stability of the data within FDA guidelines. 2285 A SENSITIVE LC-MS/MS ASSAY FOR DETERMINATION OF BENAZEPRIL AND BENAZEPRILAT IN DOG PLASMA. C. Chung, M. Luna, Y. Liu, G. Ray and D. Dadgar. KCAS, Shawnee, KS. Sponsor: D. Dandekar. Benazepril, an angiotensin-converting enzyme inhibitor, is widely used for the treatment of cardiovascular diseases. Benazepril is converted by hepatic cleavage of the ester group to the active metabolite, benazeprilat, which have both renal and hepatic elimination. In order to support an appropriate dosing form for the treat-
ment of hypertension in companion animals, a sensitive and selective LC-MS/MS method has been developed and validated for determination of benazepril and benazeprilat in dog plasma. In this method, following a solid phase extraction procedure using Oasis WCX SPE cartridges (3cc, 60 mg) for sample cleanup, the extract was chromatographed using a Betasil phenyl column (10 X 2.1 mm, 3μ) and methanol-based mobile phase solutions. A valve switching system is used for eliminating background noise built up with injections of extracted samples. The analytes were detected by TurboIonSpray API 4000 LC-MS/MS system under positive MRM mode. The quantitation ranges were 0.1 to 20 ng/mL and 0.5 to 100 ng/mL for benazepril and benazeprilat, respectively. Overall intra-assay accuracy [% bias] and precision [%CV] observed during validation for four levels of QC samples (six replicates each level, including the LLOQ level) in three runs were -1.5 to 0.1% and 1.8 to 10.4%, respectively, for benazepril compared to -0.5 to 0.6% and 1.7 to 10.3% for benazeprilat. Matrix effect was evaluated for benazepril and benazeprilat in six different lots of blank dog plasma at concentrations of 0.3 and 1.5 ng/mL, respectively, with variation of response [CV%] of 0.1% for both analytes. The extraction recovery, potential conversion effect from benazepril to benazeprilat, stability results, and results for incurred sample reanalysis will be presented. The validated method can be demonstrated to be reliable in drug development and GLP studies. 2286 EVALUATION OF ADVERSE EFFECTS ON HUMAN LUNG FUNCTION CAUSED BY OZONE. R. L. Prueitt 1 and J. E. Goodman 2 . 1 Gradient, Seattle, WA and 2 Gradient, Cambridge, MA. Biological changes in response to an environmental exposure occur along a continuum that may eventually, depending on exposure dose and duration, lead to adverse effects. Recently, a framework was described that evaluates biomarkers of exposure and effect that are found on this continuum to determine whether an exposure is likely to be causal and an effect is likely to be adverse (Goodman et al., 2010). We applied this framework to estimate the ozone concentration at which short-term exposures cause respiratory effects and to characterize the degree of adversity of these effects. We evaluated human clinical studies and observational epidemiology studies that examined associations between ambient ozone levels and effects on lung function. Using the framework, we assessed causality by determining whether effects observed in these studies are statistically significantly different between exposed and non-exposed subjects, isolated or independent, secondary, observed because of study limitations, or exposure related but unrelated to the apical effect. We assessed the degree of adversity of the observed effects by determining whether they are adaptive or compensatory, transient, reversible, early precursors of an apical effect, of low severity, or do not result in functional impairment. Our analysis indicates that the available evidence supports a short-term exposure threshold of 70 ppb for effects on lung function, although these effects do not meet the criteria for adversity as specified in the framework. Below this dose, effects are isolated or independent and not statistically different in exposed subjects in clinical studies, and study limitations affect interpretation of results from observational studies. The available evidence indicates that adverse effects are observed at ozone exposures of at least 87 ppb, and these effects are reversible and of low severity. We conclude that the available evidence supports a short-term exposure threshold of 70 ppb ozone for effects on lung function, with adverse effects occurring at ozone concentrations of at least 87 ppb. 2287 MODELING NF-κB REDOX SENSITIVITY: APPLICATIONS TO OZONE-INDUCED LUNG INFLAMMATION. D. J. Miller and P. D. White. U.S. EPA, Washington, DC. Sponsor: S. Vulimiri. The NF-κB intracellular signal transduction pathway plays a well-established role in inflammatory signaling, including transcriptional control of a variety of cytokines that are critical to inflammatory response to ozone within lung airway epithelial cells. Less understood are the mechanisms involved in NF-κB pathway activation in the presence of oxidative stress, despite the absence of canonical pathway receptor stimuli. We have constructed a redox-sensitive pathway model that is based upon multiple biological components described in recent literature. This includes a central role for oxidative inhibition of phosphatases, leading to a buildup of upstream kinase activity and subsequent downstream signaling of NF-κB. Computational modeling of this pathway elucidates these testable mechanisms of activation, and systematic perturbation of the model informs our understanding of sensitive subpopulations by identifying pathway components that are most critical to regulation of pathway response. As part of a larger multidisciplinary effort to apply such next-generation approaches to risk assessment, we describe this model of the NF-κB signaling pathway, and demonstrate both (1) a potential mechanism for pathway activation via intracellular reactive oxygen intermediates generated by ozone and (2) applications of the model to informing human risk. 2288 COMBINED CFD/PBPK MODELS FOR DETERMINING SITE-SPECIFIC UPTAKE AND TISSUE CONCENTRATIONS OF REACTIVE GASES IN THE RESPIRATORY TRACT OF RATS AND HUMANS. R. A. Corley 1 , S. Kabilan 1 , J. E. Carson 1 , R. Jacob 1 , K. R. Minard 1 , R. W. Glenny 2 , S. Pipavath 2 , M. Fanucchi 3 and D. R. Einstein 1 . 1 Pacific Northwest National Laboratory, Richland, WA, 2 University of Washington, Seattle, WA and 3 University of Alabama at Birmingham, Birmingham, AL. 3D computational fluid dynamic (CFD) airflow models have been developed for the full respiratory system of rats and humans. The CFD models include the external nares and mouth to provide more realistic airway inlets for nasal vs. oral breathing. Site-specific airflow patterns are heavily influenced by species-specific 3D anatomy and breathing patterns. Since potentially significant human exposures to reactive gases occurs via cigarette smoking, we incorporated a two-compartment PBPK model for acetaldehyde as airway boundary conditions for the CFD model to demonstrate the impact of using full respiratory airflow models in comparative target tissue dosimetry. The airway PBPK models were compartmentalized according to species-specific cell type (nose) or anatomic region (rest of respiratory tract). Physiological constants for the two compartments representing mucus and surface epithelium (compartment 1) and submucosa with blood perfusion (compartment 2) were taken from the literature or measured directly. Chemical-specific constants were taken from the PBPK model of Teeguarden et al. Inhal. Toxicol. 20 (2008) 375-390. Site-specific flux rates, Cmax’s, AUC’s and Lifetime average Daily Dose (LADD) levels for each compartment and region were determined at the NOAEL for subchronic nasal olfactory degeneration in the rat (50 ppm) and at an average yield of acetaldehyde in cigarette smoke for humans. Although the concentrations of acetaldehyde can achieve very high initial concentrations (>1000 ppm) in the mouth, the transient nature of a bolus, puff inhalation results in 13- to 50-fold lower LADD’s in human tissues than the rat olfactory region depending upon the number of cigarettes smoked/day, with the larynx in humans being the region of greatest tissue concentration following oral inhalation. Funded by NHLBI R01 HL073598 and RJR Project 56296. 2289 MODELING VAPOR UPTAKE AND TISSUE DISPOSITION IN HUMAN LUNGS. M. Singal 1 , B. Asgharian 2 , O. T. Price 2 , J. S. Schroeter 3 and J. S. Kimbell 4 . 1 Research Institute for Fragrance Materials, Inc., Woodcliff Lake, NJ, 2 Health Effects & Medical Response, Applied Research Associates, Raleigh, NC, 3 Division of Computational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, NC and 4 Department of Otolaryngology/Head and Neck Surgery, University of North Carolina, Chapel Hill, NC. Estimates of the uptake of inhaled vapors in the lung and transport to other tissues and organs of the body are needed to assess body burden and biological response. Vapor transport through the lung is usually modeled as a steady flow process through a representative cylindrical tube or simply an input parameter to a pharmacokinetic (PK) model. When the target site in toxicology studies is the lung and improved PK predictions are desired, a mechanistic model is needed that can predict regional lung vapor uptake and tissue concentration using a realistic lung geometry and ventilation pattern. A vapor uptake model in the airways and adjacent tissues was developed based on the momentum and mass conservation of air and inhaled material through the airways. Mass transfer coefficients for unsteady breathing during inhalation, pause, and exhalation were developed to uncouple transport equations in the air and tissue phases. Vapor transport in the tissue occurred by diffusion while the absorbed vapor was eliminated by linear and saturable pathways. The model was used to study the fate of vapors of different solubilities and reactivities in the tissue. Highly soluble vapors such as formaldehyde were found to reach only the first few airway generations of the lung while less soluble vapors such as acetaldehyde penetrated deep into the lung with a significant accumulation in the lung tissue at the end of a breathing cycle. A lung-tissue vapor uptake model coupled with a PK model alleviates, or reduces the need for parameter optimization and enables capturing physical and biological mechanisms of action to study potential health effects of exposure to vapors. SOT 2011 ANNUAL MEETING 491
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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
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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
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: 2276 METABOLISM AND DISPOSITION OF
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 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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