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group of 222 genes altered 2-fold or more at 2, 4 and 8 h. Few “new” genes were altered after 24 h. Functional Gene Ontology analysis of the 222 member geneset revealed clusters of genes in pathways involved in cell death regulation (9 genes), inflammatory responses (9 genes), transition metal ion binding (19 genes), DNA binding (15 genes) and response to external stimuli (12 genes). These findings help clarify the mechanisms underlying pulmonary injury and inflammation in the acrolein-intoxicated lung. 568 GAS-PHASE AND PARTICULATE COMPONENTS OF DIESEL EXHAUST PRODUCE DIFFERENTIAL CARDIOPHYSIOLOGICAL IMPAIRMENTS IN HEALTHY RATS. C. Gordon 1 , Q. Krantz 2 , P. J. Rowsey 3 , M. C. Schladweiler 2 , A. D. Ledbetter 2 and U. P. Kodavanti 2 . 1 Toxicity Asessment Division, U.S. EPA, Research Triangle Park, NC, 2 Environmental Public Health Divsion, U.S. EPA, Research Triangle Park, NC and 3 University of North Carolina, Chapel Hill, NC. We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicited changes in cardiac gene expression pattern that broadly mimicked gene expression in non-exposed spontaneously hypertensive rats. We hypothesized that healthy WKY rats would develop hypertension when exposed to whole DE but not gas-phase components which includes carbon monoxide, a known inhibitor of blood pressure. Male WKY rats (12-14 wk old) were implanted with radiotelemetry units (Data Sciences) to monitor blood pressure (BP), heart rate (HR), core temperature (CT), QA interval, and motor activity (MA). Rats were placed unrestrained in chambers and exposed for 5 h/d, 5d/wk for 4 wks to filtered air (CON), gas-phase components of filtered DE (FDE), or whole DE consisting of 1.81 mg/m3 of ultrafine particles plus gas-phase components (N=4 per exposure condition). Telemetry parameters were monitored continuously at 10 min intervals during exposure and between exposures while rats were housed in their home cages. DE and FDE led to mild reductions in BP and HR during the first week of exposure. CT and MA were unaffected. QA interval was elevated in DE but not FDE during all four wks of exposure. Telemetry parameters recovered during the recovery phase each night. However, QA interval showed a tendency to remain elevated during recovery from DE. An increase in QA interval is an indication of reduction in cardiac contractility. The data suggest that particulate but not gas-phase components of DE selectively impairs cardiac contractility in a persistent manner in healthy normotensive rats, while causing acute and transient reduction in blood pressure, possibly mediated by gas phase components (Abstract does not represent U.S. EPA policy). 569 A POSSIBLE MECHANISM ASSOCIATED WITH AMIODARONE-INDUCED PULMONARY TOXICITY. B. M. ALShammari 1 , S. AlBakheet 2 and M. Khalifa 2 . 1 National Food and Drug Authority, Saudi Food and Drug Authority, Riyadh, Saudi Arabia and 2 Pharmacology, King Saud University, Riyadh, Saudi Arabia. Pulmonary toxicity is one of the most serious adverse effects associated with the antiarrhythmic drug amiodarone (AM). This study is an extension of our previous work to resolve the controversy regarding the AM-induced pulmonary toxicity (AIPT). To accomplish this goal, Male Wistar rats (n=10/group) were weighed and given AM in a dose level of 80mg/kg/day/i.p for 7, 14, 21 and 28 in consecutive days. Rats were weighed and sacrificed in day 7, 14, 21 and 28 following AM injection. Bronchoalveolar lavage (BAL) was collected to assess total leukocytic count. Lung samples collected from each group were weighed. Homogenization was done freshly and used for determination of ATP content and hydroxyproline levels. Histopathological changes were also evaluated. The AM-treated animals show a significant decrease in body weight, indicated that the animals have reacted adversely to the AM treatment and the indicators of general lung cell injury, including lung weights and lung/ body weight coefficient, were all increased early after AM dosing and remained elevated at every time examined. In rats treated with AM for two weeks, an increased total leukocytic count is observed in BALF and histopathological examination. Such increase is an informative measure of inflammation in the lung. Treatment for two and three weeks produced a significant depletion in ATP level and the lung hydroxyproline of AM-treated groups was significantly increased by approximately 50%, 61%, 71% and 70.6% respectively. Histopathological diagnosis was mostly granulamatous inflammation and thickened alveolar walls in rats treated for three and four weeks respectively. Collectively, these data suggest that the increased hydroxyproline level may correlate as result with edema early after AM administration followed by the inflammation as a consequence days after and Loss of cellular ATP can be considered as subsequent event in AIPT ending ultimately in sever lung toxicity. 122 SOT 2011 ANNUAL MEETING 570 VARIABILITY IN ONSET OF ECG CHANGES INDICATIVE OF ISCHEMIA AFTER EXPOSURE TO WHOLE VS. FILTERED DIESEL EXHAUST IN HYPERTENSIVE RATS. INSIGHT ON MECHANISM? C. M. Lamb 1 , N. Haykal-Coates 2 , A. P. Carll 3 , M. S. Hazari 2 , D. W. Winsett 2 , D. L. Costa 4 and A. K. Farraj 2 . 1 Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC, 2 EPHD, U.S. EPA, Research Triangle Park, NC, 3 EHE, UNC School of Public Health, Chapel Hill, NC and 4 ORD, U.S. EPA, Research Triangle Park, NC . Diesel exhaust (DE) is a complex mixture of gases including CO 2 , O 2 , NO 2 , CO, aldehydes, benzene, and polycyclic aromatic hydrocarbons (PAHs) as well as highly respirable particulate matter. DE is a significant component of fine particulate matter (PM 2.5 ) air pollution, which itself has been positively associated with hospital admissions and cardiovascular morbidity and mortality, especially in individuals with pre-existing cardiovascular diseases including hypertension. We hypothesized that diesel exhaust exposure will result in concentration dependent cardiac dysfunction in hypertensive but not normal rats. Spontaneously hypertensive (SH) and Wistar Kyoto (WKY; rats with normal blood pressure) rats, were implanted with biopotential radiotelemetry transmitters to monitor electrocardiogram (ECG) and heart rate (HR), and exposed once for 4 hours to 150ug/m 3 or 500ug/m 3 of whole (WDE; gases + PM) or filtered (FDE; gases alone) diesel exhaust, or filtered air (control) in whole body exposure chambers. Only the FDE, but not the WDE, caused decreases in HR during exposure at both concentrations in SH rats. In addition, only the low concentration of FDE caused ST depression (a change in the ECG often associated with myocardial ischemia) during exposure in SH rats, and this change persisted 18 hours after exposure. DE exposure also caused a decrease in HR in normal rats but did not affect ST amplitude. Taken together, the data suggest that hypertension may predispose to the potential ischemic effects of DE and that the components of DE may have divergent effects with some eliciting immediate irritant effects (e.g., gases) while others (e.g., PM) triggering persistent effects potentially via separate mechanisms. (This abstract does not reflect EPA policy). 571 THE ROLE OF RELMα (RESISTIN LIKE MOLECULE α) IN THE RESPONSES OF THE LUNG’S VASCULATURE TO ANTIGEN AND URBAN PARTICULATE MATTER. G. Grunig, M. Sisco, T. Gordon and C. Hoffman. Environmental Medicine, New York University, Tuxedo, NY. Mouse RELMα is a member of the resistin family of adipokines and is expressed by many cell types including intestinal and airway epithelial cells, macrophages activated in the course of Th2 responses (alternatively activated) and white adipose tissue. This molecule is also known as Found in Inflammatory Zone (FIZZ) and Hypoxia Induced Mitogenic Factor (HIMF). The human homologue, RELMβ, is expressed at increased levels in the pulmonary artery in pulmonary arterial hypertension and is a mitogen for human vascular smooth muscle cells. Our studies focused on the role of RELMα in severe pulmonary arterial remodeling induced by a T helper 2 (Th2) response to antigen. We have shown that the number of cells that stain positively for RELMα by immunohistochemistry was significantly correlated with the severity of pulmonary arterial remodeling. Furthermore, our studies showed a significant exacerbation of pulmonary arterial remodeling in wild type mice exposed to a combination of antigen and urban particulate matter. RELMα deficient mice, in contrast, failed to show the exacerbation and developed pulmonary arterial thickening to exposure with antigen and respirable urban particulate matter to a significantly smaller degree relative to wild type. The severity of inflammation and the type of the immune response in the antigen challenged RELMα deficient mice was comparable to wild type. Because RELMα is known to have a critical role in hypoxia induced pulmonary arterial remodeling, and hypoxiamimetic metals have been identified in respirable urban particulate matter, our data suggest that cellular signals induced by the Th2 response synergize with hypoxia- (mimetic) induced signaling via the shared mediator, RELMα. This knowledge is significant for the understanding of the maintenance of the pulmonary arterial bed in the lungs. 572 TOXIC LOAD METHOD FOR CALCULATING INHALATION DOSES FOLLOWING TOXIC VAPOR EXPOSURES. S. Chesler 1 , H. Salem 1 and J. Moser 2 . 1 Edgewood Chemical Biological Center, Gunpowder, MD and 2 Chemical Security Analysis Center, Aberdeen Proving Ground, MD. The U.S. Army’s Edgewood Chemical Biological Center (ECBC), has established procedures and practices for characterizing human exposures to chemical warfare agents and other toxic compounds. In order to effectively calculate dose, morbidity
and lethality associated with these types of exposures, the use of mathematical tools not ordinarily utilized in conventional toxicology are necessary. These tools are based, not on the simplistic Haber’s Rule of dose calculation, but on the more rigorous Toxic Load concept of exposure. Haber’s Rule: Dose = C x t; Toxic Load: Dose = Cn x t; where C is the concentration of the toxic gas or aerosol, n is the experimentally determined toxic load exponent, and t is the exposure time. Using Haber’s Rule, median lethal dose (LCt50) is defined as the product of C and t at which 50% of the exposed population suffers death. This definition assumes that LCt50 is constant as exposures times decrease and concentration increases, but this assumption is usually found to be fallacious for most volatile compound and it is experimentally observed that as concentration increases LCt50 tend to decrease, i.e. as the concentration increases the toxicity appears to increase. This is illustrated in the Table below: Data in the last column assumes that n is equal to 1.5, and since the resulting values in this data set are essentially identical validates that assumption. Actual reported data will be used to illustrate how to calculate the Toxic Load constants. Modeling will be used to calculate the overestimation of casualties that will occur if Haber’s Rule is applied when n is not equal to one. Models for both outdoor and indoor chemical releases will be shown and compared. Actual reported accidental releases will be used as examples. The thermodynamics of large releases will be discussed to show that simple assumption of flash evaporation leads to very significant errors in dispersion calculations. The effect of experimental errors, both random and systematic, will be determined. 573 PRELIMINARY ASSESSMENT OF PULMONARY TOXICITY OF MIDDLE EASTERN SOIL EXTRACT IN A RAT MODEL. M. L. Foster 1 , K. H. Taylor 1 , M. G. Stockelman 2 , J. A. Centeno 3 and D. C. Dorman 1 . 1 College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 2 Naval Medical Research Unit, Dayton, Wright-Patterson AFB, OH and 3 Armed Forces Institute of Pathology, Washington, DC. Soldiers deployed to the Middle East are exposed to potentially high concentrations of airborne particulate matter (PM) from local soils. In this study, we characterized the respiratory toxicity of the soluble components of Middle Eastern Dust [MED]. MED was irradiated, mixed with PBS, and incubated overnight. The soluble extracts were screened for cytotoxicity using the MTT metabolism assay in a rat lung epithelial cell culture [RLE-6TN]. The in vivo study examined the effects of MED extract after a single intra-tracheal dose. Adult male CD rats were randomly assigned to PBS Control [CN], Camp Victory [CV], Afghanistan [AF], and Taji [TJ] groups. Rats were anesthetized and dosed with 500 μl of MED extract intratracheally. Rats were killed at 8, 24, 72 h, 2 or 4 wk after dosing. Broncho-alveolar lavage fluid [BALF] was collected from the left lung and total cell count, differential cell count, lactate dehydrogenase [LDH] activity, and total protein concentration were determined. TJ and AF were significantly more cytotoxic in vitro than CV or CN. In the in vivo study, a subset of TJ rats demonstrated acute respiratory distress and 3/40 animals from the TJ group and 1/40 CV died within 30 min of dosing. Body weight gain changes in treated rats compared with CN were not significant. Total BALF cell counts showed significant increases in the AF/8h and TJ/4wk group. BALF LDH activity was significantly increased compared to CN for TJ/72h. BALF protein values were unaffected by MED extract exposure. Metal analysis of the extracts demonstrated different metal profiles that likely contributed to these observed differences in response. Our data indicate that the inflammatory response seen in rats exposed to MED extracts was complex, depending on geographic region of the MED and sampling time. Cytokine, histopathology and tissue metal analyses are underway and may prove helpful in further characterizing the effects of MED extract. 574 THE CIGARETTE ADDITIVE MENTHOL BLOCKS THE RESPIRATORY TRACT IRRITATION RESPONSE TO ACROLEIN, A PRIMARY IRRITANT IN CIGARETTE SMOKE. D. N. Willis 1 , B. Liu 2 , J. B. Morris 1 and S. Jordt 2 . 1 Toxicology Program, University of Connecticut, Storrs, CT and 2 Pharmacology, Yale University Medical School, New Haven, CT. Menthol, a compound derived from peppermint, produces a cooling sensation which is thought to be mediated via neuronal TRPM8 channels. Menthol is widely used in preparations for the treatment of cough, pain and itch and is a common additive to cigarettes. The current study was performed to characterize the effects on menthol on the respiratory tract irritation response induced by two irritants in cigarette smoke: acrolein and acetic acid. Acrolein is an electrophilic irritant which acts through the TRPA1 receptor. Acetic acid is an acidic irritant that likely acts through the ASIC receptor. Towards these ends female C57Bl/6J mice were exposed to menthol, irritant, or the combination of the two for 15 minutes during which time respiratory parameters were measured. The primary response to irritant vapors in the mouse is sensory irritation. The response, mediated by the trigeminal nerve, is characterized by reduced breathing frequency due to braking at the onset of each expiration. The average duration of braking (DB) during exposure was used to quantify this response. At a concentration of 16 ppm menthol exerted a minimal transient sensory irritation response (50 msec DB). Acrolein (2 ppm) exerted a strong irritation response (200 msec DB). The response to acrolein was blocked by concurrent exposure to 16 ppm menthol. This level of menthol is significantly lower than that present in smoke from mentholated cigarettes. Menthol partially diminished the irritation response to acetic acid, another irritant present in cigarette smoke. It is not known if the counter-irritating effects of menthol are mediated via interactions of menthol with the TRPA1 and/or ASIC receptor and/or via TRM8-mediated pathways. The inhibition of the irritation response to two irritants present in cigarette smoke suggests that mentholated cigarette smoke may contain pharmacologically active concentrations of menthol vapor. 575 THE USE OF E-CADHERIN IMMUNOFLUORESCENCE IN PULMONARY TOXICOLOGIC PATHOLOGY STUDIES. L. A. Battelli, V. Castranova, D. W. Porter, S. Friend, D. Schwegler-Berry, P. Willard and A. F. Hubbs. HELD, NIOSH, Morgantown, WV. E-cadherin is a calcium dependent adhesion molecule with important roles in epithelial intercellular adhesion and cellular structure. Immunofluorescent staining can localize and quantify protein expression in cells or tissues. Co-localization of 2 or more different proteins used in combination with fluorochromes of different colors can reveal the location of each protein. We investigated the use of e-cadherin immunofluorescence in different species (rat and mouse), with different fixatives (10% neutral buffered formalin, 4% paraformaldehyde, and 2.5% glutaraldehyde), with and without antigen retrieval, and as a dual label with immunofluorescence for other proteins. Mouse monoclonal anti-e-cadherin antibodies (BD Biosciences, San Jose, CA) in conjunction with fluorochrome-conjugated donkey anti-mouse antibodies clearly delineated sites of e-cadherin expression in lungs of rats or mice. EDTA heat-induced epitope retrieval was required to restore antigenicity to fixed tissues. E-cadherin could be demonstrated in formalin or paraformaldehyde fixed tissues but not in glutaraldehyde fixed tissue. Immunofluorescent double-labeling with e-cadherin can be used with immunofluorescent detection of podoplanin, a lymphatic endothelial cell marker that is also expressed by alveolar type I cells in the lung. Low levels of e-cadherin expression in type I cells allowed the double labeled type I cells to be distinguished from lymphatic endothelium and facilitated diagnosis of lymphangiectasia. E-cadherin immunofluorescent double labeling can also be used with activated caspase 3 or β-catenin immunofluorescence to localize the expression of these proteins in damaged airways. Thus, in the lung, e-cadherin immunofluorescence can demonstrate abnormal and normal epithelial cell junctions, facilitate demonstration of airway epithelial changes, and distinguish podoplaninexpressing alveolar type I cells from lymphatic endothelium. 576 TELEMETERED THORACIC IMPEDANCE PNEUMOGRAPHY: COMPARISON WITH AMBULATORY RESPIRATION MEASUREMENT STANDARDS IN THE ANESTHETIZED BEAGLE DOG AND PHARMACOLOGICAL VALIDATION. S. Milano 1 , C. Bory 1 , S. Baudet 1 and B. Moon 2 . 1 Ricerca Biosciences SAS, Lyon, France and 2 Data Sciences International, St. Paul, MN. Recent developments in thoracic-impedance-pneumography (TIP) as a telemetry based approach to measure respiratory activity seems very suitable for assessment of pharmacological effects of drugs in non-restrained conditions, and for combination with ambulatory telemetered cardiovascular investigations in toxicology studies. As a first validation step, we have implemented TIP in the anaesthetized beagle dog and compared the respiratory parameters with existing, non-restrained respiratory assessment methods. Four dogs were implanted with DSI D70-PCTR transmitters whose pressure catheters were placed intrathoracically for pleural pressure (PP) measurement. Four weeks later, the animals were isoflurane-anesthetized and instrumented with a tracheal pneumotachometer (PNT) used as the reference method, and a JET® RIP (Respiratory Inductive Plethysmography, DSI) system. One hour after induction, baseline data was collected for 15 min, followed by experimental modifications of the respiratory function: three hypercapnia levels (5.3, 5.8 and 6.1 % ETCO2, 15 min recovery/level) followed by a subcutaneous bolus of Morphine (M) at 2 mg/kg. Three days later the same procedures were repeated replacing Morphine with Buspirone intramuscularly administered at 3 mg/kg. Regression analysis was conducted for the PNT, RIP, TIP and PP based tidal volume (TV), respiratory rate (RR), and minute ventilation (MV) values. When comparing values between RIP, TIP or PP versus PNT, correlation coefficients (R2) SOT 2011 ANNUAL MEETING 123
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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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Page 77 and 78: events and carcinogenesis. Here we
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Page 81 and 82: 358 CHARACTERIZATION OF GENOME-WIDE
Page 83 and 84: RNAi were also performed to identif
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Page 87 and 88: UGT1A gene induction, while this re
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Page 93 and 94: histone deacetylase that is necessa
Page 95 and 96: ment. Paradoxically, buthionine sul
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Page 99 and 100: 442 GENE EXPRESSION AND MORPHOLOGIC
Page 101 and 102: 451 INHIBITION OF THE MITOCHONDRIAL
Page 103 and 104: 460 SULFORAPHANE PREVENTS ACETAMINO
Page 105 and 106: drophilic/lipophilic balance. Other
Page 107 and 108: pharmacokinetic and toxicological p
Page 109 and 110: 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
Page 117 and 118: sorption in the gastrointestinal (G
Page 119 and 120: (ABC) transporters actively transpo
Page 121 and 122: 545 BEHAVIORAL EFFECTS OF REPIN IN
Page 123 and 124: a blood pressure phenotype that res
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Page 131 and 132: therefore more accurate and reprodu
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Page 135 and 136: elative to their controls. ST-depre
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Page 141 and 142: corneum thickness, cellular epiderm
Page 143 and 144: 645 EVALUATION OF THE IN VITRO EPIS
Page 145 and 146: 654 TCDD ADSORBED ONTO NATURAL AND
Page 147 and 148: tion revealed no test article-relat
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
Page 155 and 156: NAC + LPS yielded different levels
Page 157 and 158: 707 LIFE-STAGE PBPK MODELS FOR MULT
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Page 163 and 164: global parameter sensitivity analys
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Page 167 and 168: 754 PLASMA, URINE, AND TISSUE CONCE
Page 169 and 170: cently characterized transporter OA
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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
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
Page 407 and 408:
down the doses may produce more tox
Page 409 and 410:
spectively. Below 100 mg/l of gemfi
Page 411 and 412:
1900 GENERATION OF PRECISION CUT LI
Page 413 and 414:
iomarkers or observation of lesions
Page 415 and 416:
creased reticulocytes and lymphocyt
Page 417 and 418:
statistically significant interacti
Page 419 and 420:
monize sample preparation and analy
Page 421 and 422:
NPC and sinonasal cancer in neighbo
Page 423 and 424:
showed incidences of lung and nasal
Page 425 and 426:
utylbenzenes, exhibited most simila
Page 427 and 428:
1975 DIFFERENTIAL MODULATION OF CYP
Page 429 and 430:
organic As to MMA(V) and a lower ca
Page 431 and 432:
ole in invasion and metastasis of c
Page 433 and 434:
3T3-L1 cells to low-levels of arsen
Page 435 and 436:
2011 IDENTIFICATION OF A NOVEL VX M
Page 437 and 438:
This work was supported by Cooperat
Page 439 and 440:
2029 EFFICACY OF ENDOTRACHEAL ADMIN
Page 441 and 442:
Diazepam injections and its combina
Page 443 and 444:
2047 ESTERASE ACTIVITIES AND HEMOST
Page 445 and 446:
nanoparticle-induced toxicity progr
Page 447 and 448:
house, were iv infused into rats ov
Page 449 and 450:
een explored. This study investigat
Page 451 and 452:
croscopic analysis revealed that on
Page 453 and 454:
egg yolk collected from turtles inh
Page 455 and 456:
consistency of results in both expe
Page 457 and 458:
2111 CYTOCHROME P450 3A5 GENOTYPE I
Page 459 and 460:
esidues of organophosphates or thei
Page 461 and 462:
manganism. Recent work from our lab
Page 463 and 464:
Aβ1-40 in CSF and hippocampus in P
Page 465 and 466:
2147 CATALASE MANIPULATIONS MODIFY
Page 467 and 468:
ation based on real-world exposure
Page 469 and 470:
NPs. Aggregation of citrate-stabili
Page 471 and 472:
2175 THE ROLE OF SURFACE CHEMISTRY
Page 473 and 474:
seen rapid uptake in biological ima
Page 475 and 476:
effect on uterine weight or vaginal
Page 477 and 478:
dicating widespread exposure. While
Page 479 and 480:
components into the liver parenchym
Page 481 and 482:
2223 ISOLATION AND DETECTION OF RIC
Page 483 and 484:
stored (-20 celsius degree). The co
Page 485 and 486:
2241 DDA, A BIOMARKER FOR ENVIRONME
Page 487 and 488:
2249 INTERACTION BETWEEN DIETARY SE
Page 489 and 490:
2258 PHARMACOKINETICS, EXCRETION BA
Page 491 and 492:
2267 SENSITIVE AND SPECIFIC FLUORES
Page 493 and 494:
2276 METABOLISM AND DISPOSITION OF
Page 495 and 496:
ment of hypertension in companion a
Page 497 and 498:
for the propyl series can be used f
Page 499 and 500:
2304 IN VITRO EXPOSURE AND EVALUATI
Page 501 and 502:
2313 THE SYNERGISTIC EFFECT OF SODI
Page 503 and 504:
genes that play a crucial role in M
Page 505 and 506:
2330 THE ROLE OF TRANSFORMING GROWT
Page 507 and 508:
ined following up to 96 h continuou
Page 509 and 510:
effect doses obtained with the rat
Page 511 and 512:
diated transcriptional response of
Page 513 and 514:
docrine disruptor activities of EDC
Page 515 and 516:
individuals. Week 6 results were qu
Page 517 and 518:
functionality of photosystem II and
Page 519 and 520:
wild mice (Mus musculus) from areas
Page 521 and 522:
2406 TOXICITY AND BIOACCUMULATION O
Page 523 and 524:
Isocitric acid is the acid in the h
Page 525 and 526:
2425 EFFECTS OF FUMONISINS IN ETHAN
Page 527 and 528:
centration(μg/g) were: 5.1-95.3; 2
Page 529 and 530:
2445 AUTOPHAGY IN DEVELOPMENT: A LI
Page 531 and 532:
sures to inhaled Mn in dust. Nevert
Page 533 and 534:
2466 CRITICAL EVALUATION OF ANIMAL
Page 535 and 536:
elationships predict that resting r
Page 537 and 538:
2489 COMPARATIVE TOXICITY OF BIODIE
Page 539 and 540:
2497 TRANSCRIPTIONAL REGULATION OF
Page 541 and 542:
2506 TOXICOLOGICAL CONSIDERATIONS O
Page 543 and 544:
launched with the aim of developing
Page 545 and 546:
forms mRNA expression levels were a
Page 547 and 548:
2534 CUTANEOUS WOUND HEALING IN THE
Page 549 and 550:
wells (0, 1, 5, 10, 25, 50, 100, an
Page 551 and 552:
2553 AN ORGANOTYPIC MICROLIVER PLAT
Page 553 and 554:
serum-free media. At 24 hrs, the gr
Page 555 and 556:
2572 INCREASED ARSENIC BIOACCESSIBI
Page 557 and 558:
nology to develop improved methods.
Page 559 and 560:
tuna, swordfish, or mako shark (3.5
Page 561 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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