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groups 1) Sham control early term(CO-E), 2) Sham control late term (CO-L), 3) BPA early term (BPA-E) and 4) BPA late term (BPA-L). BPA exposed animals received subcutaneous BPA in two doses 4 weeks apart and lungs were sampled at 100 days gestational age (DGA) or 150DGA. The distribution and abundance of secretory proteins was defined using immunohistochemistry for Clara cell secretory protein (CCSP) and pro-surfactant protein C (SP-C). Histologic staining with Alcian Blue-Periodic Acid Schiff (AB-PAS) identified mucous containing cells. Further we quantified gene expression of SPC and CCSP in microdissected lung subcompartments from the same animals. CCSP protein was increased in proximal airways in the BPA-L group; more cells contained CCSP and the cells that contained it had more CCSP per cell. There was a 3 fold increase in CCSP gene expression in the proximal airways of the BPA-L treated animals compared to age CO-L. Mucous cells in the large conducting airways were increased in the BPA-L group. In the alveoli, BPA exposure increased the expression of pro-SP-C in both the BPA-E and BPA-L groups compared to CO. BPA exposure induced a dichotomous response in the alveoli depending on the timing of the exposure. In the BPA- E group there was an approximately 2.5 fold increase in SPC expression. The trend in the BPA-L group was a slight decrease in SPC compared to CO-L. We conclude 1) that conducting airway secretory cell maturation is accelerated by BPA exposure when it occurs late in gestation but not early, 2) that alveolar type II cell secretory product maturation is also affected by BPA exposure both early and late in gestation and 3) the timing of exposure also influences the nature and extent of the response. Support: ES016770, ES016249 and ES000628 1636 ESTIMATED DIETARY EXPOSURE AND PREDICTORS OF SERUM CONCENTRATIONS OF PERFLUORINATED COMPOUNDS IN 119 PREGNANT NORWEGIAN WOMEN. A. Brantsaeter, M. Haugen, L. S. Haug, H. K. Knutsen, H. E. Kvalem, C. Thomsen, G. Becher, J. Alexander and H. Meltzer. Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway. Sponsor: M. Løvik. Diet, and seafood in particular, has been shown to be an important source of perfluorinated compounds (PFCs) in humans. The aim of the present study was to identify predictors of serum perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations in 119 pregnant women participating in a validation study within the Norwegian Mother and Child Cohort Study (MoBa). Blood mercury and serum concentrations of 19 PFCs were analysed, and information about habitual dietary intake, demographic and sociodemographic factors were given by self-report around gestational week 20. The mean estimated dietary exposure to PFOS and PFOA was 55.1 and 36.6 ng/kg bw/day, and mean serum concentrations were 16.6 ng/ml and 2.9 ng/ml respectively. Predictors of PFOS and PFOA concentrations were evaluated using multiple linear regression analysis, adjusting for dietary intake. The following predictors were identified; for each month of previous breastfeeding the concentration of PFOS was lowered by 1.85% [β=-0.30 (95% CI: -0.40, -0.19)] and of PFOA by 1.75% [β=-0.07 (95% CI: - 0.09, -0.05)]. Blood Hg (a marker of seafood consumption) was associated with an increase in the concentration of PFOS with 7.3% and of PFOA with 5.3%. Current smoking was associated with reduced PFOS, but not PFOA concentration. Age and body mass index influenced these PFCs but did not reach statistical significance. MoBa, which in the years 1999 to 2008 has included more than 108 000 pregnant women, offers a unique opportunity for investigating potential health effects of pre- and postnatal exposure to these compounds. The children are followed up through questionnaires, clinical sub-studies and national registries. In future studies we plan to use predicative models to identify infants having high exposure to PFCs in utero and during early life and to relate the exposures to physical and neurodevelopmental outcomes. 1637 EFFECTS OF PCBS ON EMBRYONIC CARDIAC DEVELOPMENT IN GALLUS (GALLUS DOMESTICUS). T. Carro and M. Ottinger. Animal and Avian Sciences, University of Maryland, College Park, MD. Sponsor: R. Schuh. Polychlorinated biphenyls (PCBs) are a class of synthetically made compounds that have been linked to a variety of adverse health conditions. Previous studies have suggested a link between exposure to PCBs in mammalian and avian species and adverse cardiovascular effects, especially in high-risk populations, such as organisms in the developmental stages of life. The purpose of this study was to determine the effects of exposure to an environmentally relevant mixture of PCBs on embryonic hatch success, embryonic heart function, and embryonic heart development in a model species, Gallus gallus domesticus (domestic chicken). Chicken eggs were prepared by drilling a small hole into the side of the shell; treatments were administered via micropipette injection directly into the albumen and then sealed with paraffin wax. Twenty eggs per treatment group were randomly assigned as follows: 352 SOT 2011 ANNUAL MEETING untreated control, sham injection, 0.0 μg/g egg wt, 0.03 μg/g egg wt, 0.08 μg/g egg wt, 0.3 μg/g egg wt, 0.5 μg/g egg wt, 0.7 μg/g egg wt, and 2.06 μg/g egg wt (total volume administered was less than 1.5 μl/egg). Embryo viability was monitored by candling at four day intervals throughout development; heart rate was measured by external detection of heart beat during the last week of incubation. Chicks were necropsied at hatch; hearts were immediately collected, weighed, and uniformly fixed in 10% buffered formalin. Hearts were embedded in paraplast wax, transversely sectioned, and stained with hematoxylin and eosin. Heart morphology was analyzed at four layers, using heart structures to establish uniformity across sections. Results showed dose-related effects between the concentrations of PCBs, heart rates, and hatch success. No significant differences were detected in organ indices or body weight. Heart morphology showed gross cardiomyopathies in PCB treated hatchling hearts. These results provide supporting evidence to deleterious effects of embryonic exposure to PCBs. 1638 POLYCYCLIC AROMATIC HYDROCARBONS EXERT STRUCTURE-DEPENDENT DIFFERENTIAL MECHANISMS OF TOXICITY IN DEVELOPING ZEBRAFISH. B. C. Goodale 1 , J. K. La Du 1 , S. C. Tilton 2 , K. M. Waters 2 and R. L. Tanguay 1 . 1 Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR and 2 Pacific Northwest National Laboratory, Richland, WA. While polycyclic aromatic hydrocarbons (PAHs) are well-known for their carcinogenic properties, recent studies have drawn attention to other PAH-induced human health effects including cardiac and developmental toxicity. These alternate toxicological mechanisms are of particular concern as fossil fuel combustion and accidental spills increase levels of PAHs in the environment. Studies in aquatic organisms indicate that PAHs induce differential structure-dependent effects during development. Many 4-5 ring PAHs activate the aryl hydrocarbon receptor (AHR), which regulates expression of a number of responsive genes including CYP1A, and induce AHR- and CYP1A-dependent developmental effects. Other PAHs induce toxicity, such as cardiac malformations, via AHR-independent mechanisms. Understanding the mechanisms by which structurally-similar groups of PAHs induce toxicity is essential for evaluating potential health risks associated with environmental exposure to these compounds. In this study, zebrafish were exposed to the model PAHs pyrene, benz(a)anthracene and dibenzothiophene at 6 hours post fertilization (hpf) and assessments were conducted to establish concentrations that induce morphological effects but not mortality at 120 hpf. These 3-4 ring PAHs induce distinct biological responses in zebrafish that are AHR2 and CYP1A dependent, AHR2 dependent, and AHR2 independent, respectively. Whole animal mRNA microarray analysis was conducted at 24 and 48 hpf to compare mRNA expression levels in PAH and vehicle control-exposed zebrafish embryos. Comparative analysis identified differential mRNA expression between exposure groups, which was further analyzed to uncover regulatory networks of PAH-induced toxicity. These data will inform future studies aimed at elucidating the multiple mechanisms by which PAH structures disrupt developmental processes. This research is supported by NIEHS grants P30ES00210, P42ES016465 and T32ES07060. 1639 GENE EXPRESSION EVALUATION OF THE RELATIVE SAFETY OF PRENATAL STRESS AND/OR ANTIDEPRESSANT EXPOSURE. C. H. Bourke, C. F. Capello and M. J. Owens. Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA. Pregnancy expands a woman’s health considerations beyond herself to include her unborn child. In the case of a woman diagnosed with major depressive disorder, drug intervention may be the only effective treatment. While most clinical studies show that intervention with an SSRI is generally safe during pregnancy, long-term effects on the infant are unknown. The purpose of this study is to evaluate the effects of these prenatal treatments on the offspring’s gene expression in adulthood. Female rats were implanted with osmotic minipumps that delivered clinically relevant concentrations of the SSRI escitalopram throughout the entire course of pregnancy. After mating, females were exposed to a chronic unpredictable mild stress model that putatively recapitulates aspects of clinical depression. The offspring were divided into four groups based on their in utero environment: control, stress, escitalopram, and stress+escitalopram. The offspring were analyzed at adulthood to determine the long-term effects of prenatal stress and/or escitalopram exposure. Evaluation at baseline showed statistically significant changes in several endocrine measurements, but these were not believed to be physiologically relevant. Microarray analysis of the amygdala, hippocampus, and hypothalamus comparing all treatment groups revealed no significantly regulated genes. RT-PCR was used to determine more subtle gene expression differences that would not be detected with a microarray analysis (i.e.,
egulated targets were selected for analysis in the hippocampus. Several genes related to vascular density (VegfC, vWF) and hypothalamic-pituitary-adrenal axis function (Gr, Pomc) were altered by prenatal treatments. No changes were observed in several serotonin receptor subtypes or TrkB. These results show that alterations in the in utero environment modeled on maternal depression and its treatment may result in long-term effects on the gene expression in adult offspring. Studies are underway to investigate the importance of these observations. 1640 FACIAL ANOMALIES IN A RAT MODEL WITH ETHANOL: ANIMAL FRIENDLY MARKERS FOR FETAL ALCOHOL SYNDROME (FAS). R. Slieker, L. vd Horst, R. Nederlof, M. Otto and D. De Groot. TNO Quality of Life, Zeist, Netherlands. Sponsor: R. Woutersen. Background. Fetal alcohol syndrome (FAS) is the teratogenic consequence of excessive maternal consumption of alcohol during pregnancy. In addition to neurocognitive and behavioural disabilities children with FAS show facial anomalies including short palpebral fissures, a hypoplastic philtrum and a thin upper lip. These anomalies are used for the diagnosis of FAS in children. Goal. Three questions were raised: 1. Are similar facial anomalies present in a rat model of prenatal exposure to ethanol? 2. Can facial anomalies be derived and quantified from photographs, taken straightforward from the rat’s snout? 3. Can facial anomalies thus serve as animal friendly markers for normal development and development of FAS in a rat model thereby reducing or even replacing conventional daily testing of senses and reflexes of rat pups during the preweaning period, or testing of cognition and motor performance during adolescence and adulthood? Strategy. A recently developed protocol for an Extended One Generation Reproduction Toxicology Study (OECD EOGRTS) was performed in rats, exposing them daily to ethanol via drinking water (0, 1.5, 4.0, 6.5, 9.0, 11.5, 14%) from 2 weeks pre-mating to postnatal day (PND) 70 of the offspring. For the purpose of this research, the offspring was photographed with a high resolution camera on PND8, PND37, PND61 and PND70. A number of parameters was selected analogues to analysis in man, i.e. height of the philtrum, width and height of the nose and the width of the lower lips. Parameters were measured digitally with correction for the magnification used. Conventional daily testing of senses and reflexes of the rat pups, testing of cognition and motor performance at later test age was performed as well. Results / Conclusions. Facial anomalies, similar to children with FAS, were observed in ethanol exposed rats showing ethanol induced retardation in conventional guideline testing, i.e. significant reduction in height of the philtrum and changes in width / height of the nose, thus offering early and animal friendly markers for FAS in a rat model with ethanol. 1641 DEVELOPMENTAL ARSENIC EXPOSURE INCREASES PERINATAL MORTALITY AND CAUSES LIVER INFLAMMATION IN FEMALE MICE. M. W. Carmody, A. R. King, A. E. Hill and R. J. Sommer. Biology Department, Bates College, Lewiston, ME. Recently, more attention is being paid to the risks of early life exposure to arsenic. In our laboratory, developmental exposure of C57BL/6 mice to 50 or 500 ppb sodium arsenite (given in maternal drinking water 1 week prior to mating until PND 21) decreased the average number of live pups per litter on PND 2 (7.1 ± 0.4 to 4.7 ± 0.9 and 4.7 ± 1.1 neonates/litter, mean ± SEM, for the 0, 50, 500 ppb groups, respectively, N=9-10). Small decreases in uterine implantation sites (8.7 ± 0.4, 7.9 ± 0.3, 7.7 ± 0.4, N=14-16) may have contributed to the smaller litter size on PND 2. However, no difference in maternal body weight gain during pregnancy, combined with no change in the percentage of the number of live fetuses per uterine implantation sites on gestation day (gd) 18, indicates that more pup lost occurred late in gestation or soon after birth. No additional pup mortality occurred after PND 2. On PND 21, all offspring were weaned to cages with “clean” water (no arsenic). Thus, arsenic exposure in our study occurred only from the time of conception until PND 21. At 4 months of age, females exposed to arsenic early in life had livers with many perivascular and lobular collections of leukocytes. Small collections of inflammatory cells were observed in control female livers but the number and size of inflammatory collections increased in females developmentally exposed to arsenic. Control females averaged 5.2 ± 1.8 small lesions/mm 2 (N=5), whereas 50 and 500 ppb females averaged 13.1 ± 3.7 (N=7) and 13.5 ± 5.6 (N=4) small to large lesions per mm 2 of liver. At 4 months of age, liver organ weight was decreased (1.12 ± 0.04, 1.19 ± 0.06, 0.93 ± 0.03 g, N=6-8) and the percentage of hepatocytes with multiple nuclei were increased (46 ± 4, 47 ± 4, 64 ± 6 %, N=6-8) in female offspring exposed to 500 ppb arsenic from conception to PND 21. In summary, developmental arsenic exposure caused a modest increase in perinatal mortality and caused liver toxicity in female mice in adulthood. Supported by NIH R15 ES019108 and Bates College. 1642 MICRORNA EXPRESSION PROFILES AFTER DEVELOPMENTAL EXPOSURE OF ZEBRAFISH (DANIO RERIO) EMBRYOS TO TCDD. N. Aluru 1 , M. J. Jenny 1, 2 and M. E. Hahn 1 . 1 Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA and 2 Department of Biological Sciences, University of Alabama, Tuscaloosa, AL. MicroRNAs are an important group of small non-coding RNAs that regulate mRNA expression. MicroRNA roles in early embryonic development are well established, and their disruption during development can cause abnormalities. However, little is known about the effect of developmental toxicants on microRNA expression. We hypothesized that the developmental exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters microRNA expression patterns in embryos. In an initial experiment, zebrafish embryos were exposed to 5 nM TCDD or DMSO at 30 hr post-fertilization (hpf) for 1 hr and sampled at 36 and 60 hpf, prior to and at the onset of TCDD-induced phenotypic abnormalities, respectively. MicroRNA expression profiles were determined using microarrays (Agilent and Exiqon) and qRT-PCR. Microarray results revealed modest changes in microRNA expression. Exiqon microarray revealed altered expression of 8 and 14 microRNAs at 36 and 60 hpf, respectively; Agilent microarray revealed no changes at 36 hpf and 8 microRNAs altered at 60 hpf. Both Exiqon and Agilent platforms showed similar patterns for miR-451, 23a, 23b, 24 and 27e. These microRNAs are known to target genes involved in erythrocyte maturation (miR-451) and cardiac development (miRs-23a, 23b and 24). To characterize the temporal profiles of TCDD-induced changes in microRNA expression, we exposed embryos to 5 nM TCDD or DMSO for 1 hr at 4 hpf and sampled at 24, 48, 60, 72, and 96 hpf. The greatest changes occurred later in development (72 hpf). These results suggest that TCDD exposure causes modest changes in expression of microRNAs, including some that are critical for hematopoiesis and cardiac development. Ongoing studies are evaluating effects of other teratogens on microRNA expression and are comparing deep sequencing (Illumina, SOLiD) and microarray approaches for measuring microRNA profiles. [Supported by R21ES017304] 1643 MIRNAS ARE ESSENTIAL FOR BILE ACID HOMEOSTASIS DURING LIVER DEVELOPMENT. Y. J. Cui, J. Liu, Z. Fu, Y. Guo and C. D. Klaassen. Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS. One critical pathway that is often compromised in many pediatric liver diseases is bile acid (BA) homeostasis, leading to cholestasis and malnutrition in children. Growing evidence suggests that miRNAs are implicated in a wide range of pathological processes in liver by regulating the mRNA stability and protein formation of genes, but very little is known about miRNAs in normal liver development. The purpose of the present study was to determine the roles of mRNAs in BA homeostasis during liver development. Mice with hepatocyte-specific depletion of Dicer, an essential enzyme in producing all mature miRNAs were engineered. Dicer depletion markedly increased BA concentrations from 20 to 45-days of age (UPLC- MS/MS), corresponding to profound progressive hepatocyte degeneration and compensatory cell proliferation (H&E). Surprisingly, although BA concentrations were high, the mRNA of the rate-limiting BA-synthesizing enzyme, Cyp7a1, generally did not change in livers of Dicer-null mice (RT-PCR). Conversely, there was a marked decrease in the mRNAs of Sult1b1 and Ugt2b1 (enzymes for BA-detoxification), as well as Ugt1a1 (an enzyme for bilirubin-conjugation). For BA-transporters, there was a decrease in both the mRNAs and proteins of the BA-uptake transporters Ntcp and Oatp1b2, as well as an increase in the BA-efflux transporter Mrp4 in Dicer-null livers. However, the mRNA of the rate-limiting BA-efflux transporter Bsep did not change in Dicer-null livers during development, and in fact, the Bsep protein even decreased at 20-days of age (western blot), which correlated with a decrease in both mRNAs and proteins of the major BA-sensor, FXR. In conclusion, depletion of mature miRNAs produced cholestasis in developing livers corresponding to impaired compensatory regulation of many essential BA-processing genes, highlighting the importance of miRNAs in maintaining normal BA homeostasis during liver development. (Supported by NIH grants ES-07078, ES- 09649, ES-09716, ES-013714, and ES-021940.) 1644 AN INHALATION DEVELOPMENTAL TOXICITY STUDY OF N-ETHYL ACETAMIDE IN RATS. J. Domoradzki 1 , T. Edwards 2 and D. Kirkpatrick 2 . 1 Dow Corning Corporation, Auburn, MI and 2 WIL Research Laboratories, LLC, Ashland, OH. Developmental effects of alkylated acetamides have been reported in laboratory animals by various routes of administration. Since inhalation of N-ethyl acetamide (NEA) is a potential route of worker exposure, data from whole-body inhalation exposures of rats to NEA were relevant to health risk assessment. The objective was to SOT 2011 ANNUAL MEETING 353
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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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Page 363 and 364: showed similar levels of apoptosis
Page 365 and 366: 1676 TWO BIOMARKERS FOR EVALUATION
Page 367 and 368: motifs selected. This system was ap
Page 369 and 370: 1693 VOC SERUM LEVELS IN THE GENERA
Page 371 and 372: 1702 DOES THE CLOCK MAKE THE POISON
Page 373 and 374: those with high nickel content are
Page 375 and 376: isk assessment. However, unique cha
Page 377 and 378: model of APAP metabolism and glutat
Page 379 and 380: logically & morphologically similar
Page 381 and 382: posure, blood chemistry was analyze
Page 383 and 384: elated to oxidative stress by measu
Page 385 and 386: ostasis), but work is needed to tra
Page 387 and 388: tokine products during carcinogenes
Page 389 and 390: ways as chemical stressors and, the
Page 391 and 392: toxicity of nanomaterials relates s
Page 393 and 394: 1815 MEASURING COMPOUND SELECTIVITY
Page 395 and 396: 1825 EFFECTS OF METABOLISM BY INTES
Page 397 and 398: cyanoacetic acid increased 2-3 fold
Page 399 and 400: 1845 IS THE PROMISCUITY OF THE ARYL
Page 401 and 402: crorarray analysis. RT-PCR results
Page 403 and 404: are a family of phase-II biotransfo
Page 405 and 406: ous labs. As a result of positive s
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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