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of chemical/dietary induced changes in serum thyroxine (T 4 ) concentrations in either euthyroid or sensitive populations, such as the developing fetus. Collaborative researchers are examining the effects of iodide deficiency on CNS development in the rat pup at the USEPA using propylthiouracil as a positive control. Electrophysiological, biochemical and molecular studies of the pup brain combined with behavioral studies are used for evaluating HPT mediated developmental neurotoxicity. A Biologically Based Dose Response (BBDR) HPT axis model for the lactating rat and nursing pups predicts the relationship between brain concentration of T 3 and serum concentration of T 4 as a function of iodide intake. The BBDR HPT axis model describes two negative feedback loops: 1) TSH production controlled by the brain concentration of T 3 , and 2) TSH stimulation of thyroid iodide uptake and T 3 and T 4 synthesis and secretion. The model is calibrated to predict dietary iodine deficiency-induced perturbations in serum and brain thyroid hormones. The model successfully described published data sets in the dam and pup for both euthyroid and iodide deficient conditions. After successful validation for iodide deficiency, the model will be expanded to include thyroid active chemicals. The model will allow for simulation of complex dose response and exposure conditions and serve as a template for the future development of human gestation and lactation BBDR HPT axis models for use in risk assessment. 703 AGE-DEPENDENT METABOLISM OF CHLOPYRIFOS AND CHLORPYRIFOS-OXON IN HUMAN PLASMA AND HEPATIC MICROSOMES. T. S. Poet 1 , C. Timchalk 1 , M. J. Bartels 2 and J. N. Smith 1 . 1 Biological Monitoring & Modeling, Battelle, Pacific Northwest Division, Richland, WA and 2 The Dow Chemical Company, Midland, MI. Young animals and, potentially, children may have increased sensitivity to chlorpyrifos (CPF) exposure compared to adults at higher exposure levels, which could be in part due to age differential metabolism of CPF and CPF-oxon (ultimate toxicant). In humans, there have not been studies characterizing CPF or CPF-oxon metabolism over various ages. Thus, age-dependent enzymatic metabolism of CPF and CPF-oxon were quantified in vitro using human donor hepatic microsomes (n = 30, ages 13 d-75 y) and plasma (n = 20, ages 3 d-43 y) by measuring product formation of 3,5,6-trichloro-2-pyridinol (TCPy) and CPF-oxon using gas chromatography/mass spectrometry (GC/MS). Mean hepatic CPF desulfation and dearylation Vmax values across ages were 0.35 and 0.73 nmol/min/mg microsomal protein, respectively. The mean hepatic CPF-oxon hydrolysis Vmax value was 78 nmol/min/mg microsomal protein. All hepatic measures of metabolism were consistent across ages on a per microsomal protein basis using a linear regression model (p = 0.90, 0.60, and 0.17, respectively). Ratios of desulfation to dearylation also did not show any age dependent relationships (p = 0.87). Pearson product-moment correlation coefficients of pseudo first order rate estimates and Vmax values with substrate marker activities provided by the vendor implicated CYP2B6, 3A4/5, 2C8, and 2D6 with CPF desulfation and CYP2C19 and 3A4/5 with CPF dearylation. CPF-oxon metabolism in plasma showed age-dependent increases over two factors: (1) metabolism on a per protein basis (p = 0.03) and (2) total plasma protein levels (p = 0.005). The mean overall CPF-oxon metabolism Vmax value for children < 6 mo of age was 1901 nmol/min/mL vs. 6829 nmol/min/mL for adults, > 3.5 times higher. These results are useful when evaluating potential response of different age individuals to CPF and will be integrated into a lifestage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF. 704 DEVELOPMENT OF A LIFESTAGE PHYSIOLOGICALLY BASED PHARMACOKINETIC AND PHARMACODYNAMIC (PBPK/PD) MODEL FOR CHLORPYRIFOS IN RATS AND HUMANS. J. N. Smith 1 , P. M. Hinderliter 1 , C. Timchalk 1 , M. J. Bartels 2 and T. S. Poet 1 . 1 Biological Monitoring & Modeling, Battelle, Pacific Northwest Division, Richland, WA and 2 The Dow Chemical Company, Midland, MI. Young animals and, potentially, children may have increased sensitivity to chlorpyrifos (CPF) exposure compared to adults at higher exposure levels. Thus, an agedependent, lifestage PBPK/PD model was developed to computationally predict disposition of CPF and its metabolites chlorpyrifos-oxon (CPF-oxon) and 3,5,6trichloro-2-pyridinol (TCPy) as well as corresponding cholinesterase (ChE) inhibition in rats and humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Blood flows among compartments were calculated as a constant flow per compartment volume. Carboxylesterase activity, hepatic microsomal protein, and CPF-oxon metabolism in plasma have all demonstrated age-dependency and were scaled as such. PK of TCPy was handled as a one compartment model. Consistent with literature results, simulations of rats 152 SOT 2011 ANNUAL MEETING dosed with a single dose of 10 mg/kg CPF orally at 5, 12, and 45 days of age demonstrate increased peak CPF concentrations in blood (0.72, 0.49, and 0.40 μM) and greater maximal inhibition of plasma ChE activity (97, 93, and 77%), red blood cell ChE activity (82, 67, and 34%), and brain ChE activity (80, 56, and 25%), respectively. In humans, PBPK/PD model simulations predict similar agedependent outcomes. For humans 6 mo, 3 y, and 30 y of age, peak CPF concentration in blood were (0.20, 0.18, and 0.17 μM), maximal inhibition of plasma ChE activity were (98, 91, and 85%), and red blood cell ChE activity were (19, 11, and 9%), respectively, after receiving a single oral dose of 0.5 mg/kg CPF. This model provides a computational framework for age comparative simulations that can be utilized to evaluate age-related responses resulting from CPF exposure. 705 EFFECT OF PARAMETER VARIABILITY AND UNCERTAINTY IN A LIFESTAGE PBPK MODEL FOR CHLORPYRIFOS. P. M. Hinderliter 1 , J. N. Smith 1 , M. J. Bartels 2 , P. S. Price 2 and T. S. Poet 1 . 1 Biological Monitoring & Modeling, Battelle, Pacific Northwest Division, Richland, WA and 2 The Dow Chemical Company, Midland, MI. Physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models are important tools in risk assessment, allowing for the evaluation of predicted effects of chemical exposures on humans that occur as the result of real world exposures. Human populations are unique in their differences and more specifically are sexually dimorphic and exhibit a wide range in heights and weights and body composition. A lifestage model has been constructed to include growth from birth to adulthood and inter-individual variability in organ sizes and metabolic parameters. The model incorporates measured body weights (from NHANES or other published datasets) and calculates the necessary model body compartments (i.e., liver, brain, fat, blood, rapid, and slow) which are scaled based on body weight from polynomial functions on a fractional body weight basis. Variability in enzymatic parameters is included, based on measured chlorpyrifos bioactivation and detoxification in humans of different ages. To validate the model, human exposure data were simulated and matched from two controlled human oral studies. Variability was determined by calculating confidence intervals around in vitro-derived metabolic rate constants for age-dependent plasma PON1 activity. The activities measured in vitro were bootstrapped into the PBPK/PD model to account for variability and uncertainty in these parameters. As an example, RBC AChE was examined as a function of metabolic and physiological parameters using daily oral exposures from diet (CARES). The results indicate that there are no trends between RBC AChE inhibition with BMI, cardiac output, liver PON1, blood PON1, liver P450, or brain P450 in adults. Simulation of higher doses does show a trend between PON1 activities and AChE inhibition. This suggests that human variability will not substantially impact predictions of inhibition at real-world low exposures. At higher doses reduced levels of PON1 may be associated with increased inhibition. 706 DEVELOPMENT OF HUMAN GESTATION AND LACTATION PBPK MODELS FOR PERFLUOROOCTANOATE (PFOA) AND PERFLUOROOCTANESULFONATE (PFOS). A. E. Loccisano 1 , M. E. Andersen 1 , J. Butenhoff 2 and H. J. Clewell 1 . 1 The Hamner Institutes for Health Sciences, Research Triangle Park, NC and 2 3M Corporation, St. Paul, MN. Conflicting results have been reported for associations between maternal serum/plasma concentrations of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) and human birth outcomes. Physiological changes during pregnancy such as plasma volume expansion can affect pharmacokinetics and can also be associated with birth outcomes. We have developed PBPK models for PFOA and PFOS for the gestation and lactation life stages in humans to understand more fully how the physiological changes associated with development affect tissue distributions of these compounds in the mother, fetus, and neonate. These models were derived from PBPK models for PFOA and PFOS that we previously developed for adult humans and for rats during gestation and lactation. The same model structure and parameters used in the adult human model could be used to simulate plasma concentrations in pregnant and lactating women, indicating that pharmacokinetics is not appreciably affected. Transfer of both chemicals to the human fetus was described by simple diffusion, while transfer of chemical from plasma to milk was assumed to be flow-limited. The models simulated PFOA and PFOS concentrations in maternal and fetal plasma and milk and were compared to available epidemiologic data and also used to estimate maternal exposure in the populations studied. Another application was to estimate maternal and fetal PFOA plasma concentrations in communities with contaminated drinking water. The model development identified several research needs, including the identification of transporters involved in renal resorption to explain the multi-year half-lives of these compounds in humans, factors affecting the clearance of PFOA and PFOS during gestation, and data to estimate clearance of PFOA and PFOS in the human neonate.
707 LIFE-STAGE PBPK MODELS FOR MULTIPLE ROUTES OF ETHANOL EXPOSURE IN THE RAT. S. A. Martin 1, 7 , J. L. Campbell 2 , K. Choi 2 , H. J. Clewell 2 , H. El-Masri 3, 7 , W. R. LeFew 3, 7 , T. E. Beasley 1, 7 , W. M. Oshiro 1, 7 , L. L. Degn 1, 7 , P. A. Evansky 4, 7 , A. Ledbetter 4, 7 , J. Ford 5, 7 , D. W. Herr 1, 7 , W. K. Boyes 1, 7 , P. J. Bushnell 1, 7 and E. D. McLanahan 6, 7 . 1 NB/TAD/NHEERL/ORD, Research Triangle Park, NC, 2 The Hamner Institutes for Health Sciences, Research Triangle Park, NC, 3 SBB/ISTD/NHEERL/ORD, Research Triangle Park, NC, 4 ITFB/EPHD/NHEERL/ORD, Research Triangle Park, NC, 5 ACRC/RCU/NHEERL/ORD, Research Triangle Park, NC, 6 NCEA/ORD, Research Triangle Park, NC and 7 U.S. EPA, Research Triangle Park, NC. Ethanol is commonly blended with gasoline (10% ethanol) in the US, and higher ethanol concentrations are being considered. While the pharmacokinetics and toxicity of orally-ingested ethanol are widely reported, comparable work is limited for inhalation exposure (IE), particularly at concentrations producing blood (BEC) and brain (BrEC) ethanol concentrations associated with developmental neurotoxicity (DNT). Multi-route, life-stage PBPK models for adult, pregnant, and neonatal rats were developed and used to predict inhalation exposure concentrations yielding BEC and BrEC associated with DNT. Based on model predictions, Long- Evans rats received multiple 6-hr IE at 5,000 to 20,000ppm to assess the pharmacokinetics of ethanol. Tissues (blood, brain, eyes, liver) were collected for analysis via headspace gas chromatography to provide quantitative data and support model calibration. Kinetic time points were specific to each IE and designed to capture loading, peak, and clearance phases across low and high IE and tissue concentrations, while remaining comparable to literature data at lower concentrations. Simulations using the calibrated ethanol model were in good agreement with peak and post-exposure BEC and BrEC for most datasets, though additional work is needed to refine estimates of metabolism. This work covers a range of ethanol tissue concentrations associated with DNT in rodents, and thus may be useful for risk assessments. These models will be coupled with a gasoline model to describe biofuel blends. This abstract does not reflect EPA policy. 708 ANALYSIS OF BISPHENOL A KINETICS AND METABOLISM IN NEONATAL AND ADULT MONKEYS AND RATS USING A PBPK MODEL. J. Fisher, N. C. Twaddle, M. Vanlandingham and D. R. Doerge. Biochemical Toxicology Division, U.S. FDA/NCTR, Jefferson, AR. Bisphenol A (BPA) is a widespread contaminant found in urine of over 90% of samples from NHANES. The pharmacokinetics of aglycone BPA and its primary phase II metabolite, BPA-glucuronide (BPAG) were recently reported by our laboratory in immature and mature non-human primates and rats (Doerge et al., 2010). PBPK models are under development to include this new kinetic data for aglycone BPA in the developing rat and non-human primate. First pass presystemic metabolism of orally ingested BPA (GI tract and hepatic) and enterhepatic recirculation are included in a six compartment model for BPA. BPA is metabolized by intestinal and hepatic UDPGT to BPAG. BPAG is metabolized to BPA by bacterial glucuronidase in the colon. The kinetics of BPAG are described as a two compartment sub-model. Physiological model parameters for the maturing rat were retrieved from the literature and allometric scaling was used for the monkey. These PBPK models will provide computational tools to compare the internal dosimetry of administered BPA in immature rats, which are commonly used for toxicity studies, with immature nonhuman primates, a species more similar to humans than rodents. 709 PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING (PBPK) AS A TOOL TO PREDICT 2, 3, 7, 8- TETRACHLORODIBENZO-P-DIOXIN (TCDD) PHARMACOKINETICS (PK) DURING GESTATION AND LACTATION. C. Emond 1, 2 , M. J. Devito 3 , M. Warner 4 , B. Eskenazi 4 , P. Mocarelli 5 and L. S. Birnbaum 6 . 1 BioSimulation Consulting Inc., Newark, DE, 2 University of Montreal, Montreal, QC, Canada, 3 NIEHS & NTP, Research Triangle Park, NC, 4 School of Public Health, University of California, Berkeley, CA, 5 Department of Laboratory Medicine, University of Milano-Bicocca, School of Medicine, Hospital of Desio, Desio, Desio-Milano, Italy and 6 NCI & NIEHS, Research Triangle Park, NC. The PK of TCDD is relatively well understood in adult humans. TCDD induces its elimination at high exposures, while at low exposures the PK is highly influenced by the percent body fat. Our understanding of the PK of TCDD in pregnant women is less complete. To better understand the PK of TCDD in women a physiologically-based pharmacokinetic (PBPK) model was modified to include a gestational and lactational compartment and used to evaluate serum concentrations from a cohort of women of reproductive age exposed to dioxin in Seveso, Italy. The model was structured in such a way as to allow for multiple gestational scenarios observed in the general population. The gestational and lactational compartments were activated based on the reproductive profile scenario. This work compared actual serum measures of TCDD from Seveso women or from the general population with the prediction developed using the PBPK model. The initial modeling results indicate for the Seveso women, pregnancy and lactation had a small influence on the PK of TCDD, while pregnancy significantly decreased maternal blood concentrations following birth and lactation. Based on the modeling results, it appears that at high body burden, hepatic elimination is significantly induced, which masks the minor elimination from birth and milk. (The information in this abstract has been subjected to review by the NCEA, USEPA, and the NIH and the contents of the abstract does not reflect the views of these Agencies, This research was supported by funding from the U.S. Environmental Protection Agency and grants from USEPA (R82471), NIEHS (R01 ES07171), Regione Lombardia and Fondazione Lombardia Ambiente, Milan, Italy.) 710 DEVELOPMENT OF PHYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODEL TO PREDICT TULATHROMYCIN DISTRIBUTION IN GOATS. T. L. Leavens1 , L. A. Tell2 , K. A. Clothier2 , R. W. Griffith3 , R. E. Baynes1 and J. E. Riviere1 . 1Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC, 2Department of Medicine and Epidemiology, University of California, Davis, CA and 3Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA. Currently, limited data and models exist to guide extrapolation of withdrawal times for approved drugs from major to minor animal species. Because PBPK models incorporate species-specific and chemical-specific parameters, they could be a useful tool to extrapolate withdrawal times of drugs across species and doses. The objective of this research was to develop a PBPK model for goats to simulate the pharmacokinetics of tulathromycin, a macrolide antibiotic. The model compartments were plasma, lung, liver, muscle, fat, kidney, and remaining poorly and richly perfused tissues. Tulathromycin was assumed to be 50% protein bound in the plasma with first order clearance to represent both fecal and urinary excretion of parent drug. Literature values were compiled for goat physiological parameters, partition coefficients were estimated from AUC ratios, and the remaining parameters were estimated by visual comparison with the experimental data. Three separate model structures were compared with plasma and tissue concentrations of tulathromycin in market age (6 mo) goats administered 2.5 mg/kg tulathromycin subcutaneously. The best simulation was achieved with a diffusion-limited PBPK model and absorption from a two compartment injection site. The model with age-appropriate physiological parameters was able to simulate plasma concentrations in juvenile (
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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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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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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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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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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
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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