DOCSLIB.ORG

Provisional Peer Reviewed Toxicity Values for 2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Provisional Peer Reviewed Toxicity Values for 2 EPA/690/R-19/003F | September 2019 | FINAL Provisional Peer-Reviewed Toxicity Values for 2-Nitropropane (CASRN 79-46-9) U.S. EPA Office of Research and Development Center for Public Health and Environmental Assessment EPA/690/R-19/003F FINAL September 2019 Provisional Peer-Reviewed Toxicity Values for 2-Nitropropane (CASRN 79-46-9) Center for Public Health and Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268 ii 2-Nitropropane AUTHORS, CONTRIBUTORS, AND REVIEWERS CHEMICAL MANAGERS Jon Reid, PhD, DABT Center for Public Health and Environmental Assessment, Cincinnati, OH J. Phillip Kaiser, PhD, DABT Center for Public Health and Environmental Assessment, Cincinnati, OH CONTRIBUTOR Scott C. Wesselkamper, PhD Center for Public Health and Environmental Assessment, Cincinnati, OH DRAFT DOCUMENT PREPARED BY SRC, Inc. 7502 Round Pond Road North Syracuse, NY 13212 PRIMARY INTERNAL REVIEWERS J. Allen Davis, MSPH Center for Public Health and Environmental Assessment, Cincinnati, OH Dan D. Petersen, PhD, DABT Center for Public Health and Environmental Assessment, Cincinnati, OH This document was externally peer reviewed under contract to: Eastern Research Group, Inc. 110 Hartwell Avenue Lexington, MA 02421-3136 Questions regarding the contents of this document may be directed to the U.S. EPA Office of Research and Development’s Center for Public Health and Environmental Assessment. To the memory of Dr. Jon Brice Reid (1937−2019) iii 2-Nitropropane TABLE OF CONTENTS COMMONLY USED ABBREVIATIONS AND ACRONYMS...................................................... v BACKGROUND .................................................................................................................................. 1 DISCLAIMERS .................................................................................................................................... 1 QUESTIONS REGARDING PPRTVs ............................................................................................... 1 INTRODUCTION ................................................................................................................................ 2 REVIEW OF POTENTIALLY RELEVANT DATA (NONCANCER AND CANCER) .............. 6 HUMAN STUDIES ....................................................................................................................... 14 ANIMAL STUDIES ...................................................................................................................... 16 Oral Exposures............................................................................................................................ 16 Inhalation Exposures .................................................................................................................. 19 OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS) .................................. 29 Genotoxicity Studies .................................................................................................................. 29 Supporting Human Toxicity Studies ......................................................................................... 48 Supporting Animal Toxicity Studies ......................................................................................... 49 Absorption, Distribution, Metabolism, and Elimination Studies ............................................ 60 Mode-of-Action/Mechanistic Studies ....................................................................................... 61 DERIVATION OF PROVISIONAL VALUES ............................................................................... 63 DERIVATION OF ORAL REFERENCE DOSES ...................................................................... 63 DERIVATION OF INHALATION REFERENCE CONCENTRATIONS ............................... 64 Derivation of Subchronic Provisional Reference Concentration ............................................ 64 Derivation of Chronic Provisional Reference Concentration .................................................. 68 CANCER WEIGHT-OF-EVIDENCE DESCRIPTOR................................................................ 68 MODE-OF-ACTION DISCUSSION ............................................................................................ 69 DERIVATION OF PROVISIONAL CANCER POTENCY VALUES ..................................... 71 Derivation of Provisional Oral Slope Factor ............................................................................ 71 Derivation of Provisional Inhalation Unit Risk ........................................................................ 71 APPENDIX A. SCREENING PROVISIONAL VALUES ............................................................. 72 APPENDIX B. DATA TABLES ....................................................................................................... 78 APPENDIX C. BENCHMARK DOSE MODELING RESULTS ................................................ 117 APPENDIX D. REFERENCES ....................................................................................................... 139 iv 2-Nitropropane COMMONLY USED ABBREVIATIONS AND ACRONYMS1 α2u-g alpha 2u-globulin MN micronuclei ACGIH American Conference of Governmental MNPCE micronucleated polychromatic Industrial Hygienists erythrocyte AIC Akaike’s information criterion MOA mode of action ALD approximate lethal dosage MTD maximum tolerated dose ALT alanine aminotransferase NAG N-acetyl-β-D-glucosaminidase AR androgen receptor NCI National Cancer Institute AST aspartate aminotransferase NOAEL no-observed-adverse-effect level atm atmosphere NTP National Toxicology Program ATSDR Agency for Toxic Substances and NZW New Zealand White (rabbit breed) Disease Registry OCT ornithine carbamoyl transferase BMD benchmark dose ORD Office of Research and Development BMDL benchmark dose lower confidence limit PBPK physiologically based pharmacokinetic BMDS Benchmark Dose Software PCNA proliferating cell nuclear antigen BMR benchmark response PND postnatal day BUN blood urea nitrogen POD point of departure BW body weight PODADJ duration-adjusted POD CA chromosomal aberration QSAR quantitative structure-activity CAS Chemical Abstracts Service relationship CASRN Chemical Abstracts Service registry RBC red blood cell number RDS replicative DNA synthesis CBI covalent binding index RfC inhalation reference concentration CHO Chinese hamster ovary (cell line cells) RfD oral reference dose CL confidence limit RGDR regional gas dose ratio CNS central nervous system RNA ribonucleic acid CPHEA Center for Public Health and SAR structure activity relationship Environmental Assessment SCE sister chromatid exchange CPN chronic progressive nephropathy SD standard deviation CYP450 cytochrome P450 SDH sorbitol dehydrogenase DAF dosimetric adjustment factor SE standard error DEN diethylnitrosamine SGOT serum glutamic oxaloacetic DMSO dimethylsulfoxide transaminase, also known as AST DNA deoxyribonucleic acid SGPT serum glutamic pyruvic transaminase, EPA Environmental Protection Agency also known as ALT ER estrogen receptor SSD systemic scleroderma FDA Food and Drug Administration TCA trichloroacetic acid FEV1 forced expiratory volume of 1 second TCE trichloroethylene GD gestation day TWA time-weighted average GDH glutamate dehydrogenase UF uncertainty factor GGT γ-glutamyl transferase UF A interspecies uncertainty factor GSH glutathione UFC composite uncertainty factor GST glutathione-S-transferase UFD database uncertainty factor Hb/g-A animal blood-gas partition coefficient UFH intraspecies uncertainty factor Hb/g-H human blood-gas partition coefficient UFL LOAEL-to-NOAEL uncertainty factor HEC human equivalent concentration UFS subchronic-to-chronic uncertainty factor HED human equivalent dose U.S. United States of America i.p. intraperitoneal WBC white blood cell IRIS Integrated Risk Information System IVF in vitro fertilization LC50 median lethal concentration LD50 median lethal dose LOAEL lowest-observed-adverse-effect level 1Abbreviations and acronyms not listed on this page are defined upon first use in the PPRTV document. v 2-Nitropropane FINAL September 2019 PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR 2-NITROPROPANE (CASRN 79-46-9) BACKGROUND A Provisional Peer-Reviewed Toxicity Value (PPRTV) is defined as a toxicity value derived for use in the Superfund Program. PPRTVs are derived after a review of the relevant scientific literature using established Agency guidance on human health toxicity value derivations. All PPRTV assessments receive internal review by at least two Center for Public Health and Environmental Assessment (CPHEA) scientists and an independent external peer review by at least three scientific experts. The purpose of this document is to provide support for the hazard and dose-response assessment pertaining to chronic and subchronic exposures to substances of concern, to present the major conclusions reached in the hazard identification and derivation of the PPRTVs, and to characterize the overall confidence in these conclusions and toxicity values. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of this substance. Currently available PPRTV assessments can be accessed on the U.S. EPA’s PPRTV website at https://www.epa.gov/pprtv. PPRTV assessments are eligible to be updated on a 5-year cycle to incorporate new data or methodologies that might impact the toxicity values or characterization of potential for adverse human-health effects and are revised as appropriate. Questions regarding nomination of chemicals
Load more

Recommended publications
  • Cell Proliferation Or Cell Labeling
    ALZET® Bibliography References on the Cell Proliferation Studies Using ALZET Osmotic Pumps 1. BrdU Q8564: K. Kawamoto, et al. Cell proliferation analysis is a reliable predictor of lack of carcinogenicity: Case study using the pyrethroid imiprothrin on lung tumorigenesis in mice. Regul Toxicol Pharmacol 2020;113(104646 Agents: uridine, bromodeoxy-; Vehicle: DMSO; Route: SC; Species: Mice; Pump: 2001; Duration: 7 days; ALZET Comments: Dose (40 mg BrdU/mL); 10% DMSO used; animal info (Male mice aged 9 weeks); bromodeoxyuridine aka BrdU; cancer (carcinogenicity); R0384: A. A. Pieper, et al. Benefits of Enhancing Nicotinamide Adenine Dinucleotide Levels in Damaged or Diseased Nerve Cells. Cold Spring Harbor Symposia on Quantitative Biology 2019; Agents: Uridine, bromodeoxy-; aminopropylcarbazole Vehicle: Not stated; Route: CSF/CNS; Species: Mice; Pump: Not stated; Duration: 1 week; ALZET Comments: neurodegenerative (missing NPAS3 impaired hippocampal neurogenesis ); Therapeutic indication (Missing NPAS1 inhanced hippocampal neurogenesis); Q6967: M. Kondo, et al. Involvement of peroxisome proliferator-activated receptor-alpha in liver tumor production by permethrin in the female mouse. Toxicol Sci 2019; Agents: Uridine, Bromodeoxy Vehicle: DMSO; Route: SC; Species: Mice; Rat; Pump: 2001; 2ML2; Duration: 7 days; 14 days; ALZET Comments: Dose (8.4 mgBrdU/mouse.; 33.6 mg BrdU/rat); 10% DMSO used; cancer (liver); stress/adverse reaction: One animal was dead due to anesthesia at implantation of osmotic pump; Q8139: H. Mziaut, et al. miR-132 controls pancreatic beta cell proliferation and survival in mouse model through the Pten/Akt/Foxo3 signaling. bioRxiv 2018; Agents: Uridine, Bromodeoxy- Vehicle: DMSO; Route: IP; Species: Mice; Pump: 1007D; Duration: 7 days; ALZET Comments: Dose (0.5 ul/hr/day); 50% DMSO used; animal info (C57Bl/6N mice with an age of 13-19 weeks and a body weight of 28-34 g); Bromodeoxyuridine aka BrdU ; cardiovascular; Q8107: E.
    [Show full text]
  • Bromodeoxyuridine-Induced Mutations in Synchronous Chinese Hamster Cells: Temporal Induction of 6-Thioguanine and Ouabain Resistance During Dna Replication
    BROMODEOXYURIDINE-INDUCED MUTATIONS IN SYNCHRONOUS CHINESE HAMSTER CELLS: TEMPORAL INDUCTION OF 6-THIOGUANINE AND OUABAIN RESISTANCE DURING DNA REPLICATION H. JOHN BURKP AND PAUL M. AEBERSOLD2 Group in Structural Biophysics, Biomedical Diuision, Lawrence Berkeley Laboratory', and Dept. of Molecular Biology2, Uniuersity of California, Berkeley, California 94720 Manuscript received November 14, 1977 Revised copy received April 25, 1978 ABSTRACT Mutations were induced in synchronous Chinese hamster cells by bromo- deoxyuridine (BUdR) incorporated into cells for one-hour periods in the cell cycle. There was a very pronounced temporal dependence during the first half of the DNA synthesis period for th:! induction of damage leading to 6-thio- guanine (6TG) and ouabain resistance. No mutants above background were induced by exposure to BUdR in GI and G2 cells, and very few mutants were induced in the latter part of the DNA synthesis period. The peak for the induction of 6TG resistance occurs at about two hr in the DNA synthesis period; one hour later there is a peak for the induction of ouabain resistance. Both peaks occur before the time of maximum incorporation of BUdR into DNA. These results suggest that the mutagenesis by BUdR is associated with at least two nuclear genes, which replicate at two hr and three hr in the DNA synthesis period. AMMALIAN cells replicate their several meters of DNA under culture Mconditions in about six to eight hr. Replicating units of the DNA replicate in two directions at a rate of about 1 micron per minute (HUBERMANand RIGGS 1968). The number of replicating units replicating during any one minute of the DNA synthesis period is on the average about lo4 (PAINTERand SCHAFER1969; PAINTER,JERMANY and RASMUSSEN1966).
    [Show full text]
  • Multiplex Cell Fate Tracking by Flow Cytometry
    Protocol Multiplex Cell Fate Tracking by Flow Cytometry Marta Rodríguez-Martínez 1,*, Stephanie A. Hills 2, John F. X. Diffley 2 and Jesper Q. Svejstrup 1,* 1 Mechanisms of Transcription Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK 2 Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK * Correspondence: [email protected] (M.R.-M.); [email protected] (J.Q.S.) Received: 18 June 2020; Accepted: 15 July 2020; Published: 17 July 2020 Abstract: Measuring differences in cell cycle progression is often essential to understand cell behavior under different conditions, treatments and environmental changes. Cell synchronization is widely used for this purpose, but unfortunately, there are many cases where synchronization is not an option. Many cell lines, patient samples or primary cells cannot be synchronized, and most synchronization methods involve exposing the cells to stress, which makes the method incompatible with the study of stress responses such as DNA damage. The use of dual-pulse labelling using EdU and BrdU can potentially overcome these problems, but the need for individual sample processing may introduce a great variability in the results and their interpretation. Here, we describe a method to analyze cell proliferation and cell cycle progression by double staining with thymidine analogues in combination with fluorescent cell barcoding, which allows one to multiplex the study and reduces the variability due to individual sample staining, reducing also the cost of the experiment. Keywords: BrdU; EdU; fluorescent cell barcoding 1. Introduction Assessing cell proliferation and cell cycle distribution is often at the basis of cell behavior studies.
    [Show full text]
  • 5-Bromodeoxyuridine Followed by Hoechst 33258 Flow Cytometry (Cell Cycle Idnetics/Growth Control/Human Diploid Cells/Life-Span in Vitro) PETER S
    Proc. NatL Acad. Sci. USA Vol. 80, pp. 2951-2955, May 1983 Cell Biology Regulation of human fibroblast growth rate by both noncycling cell fraction and transition probability is shown by growth in 5-bromodeoxyuridine followed by Hoechst 33258 flow cytometry (cell cycle Idnetics/growth control/human diploid cells/life-span in vitro) PETER S. RABINOVITCH Department of Pathology, SM-30, University of Washington, Seattle, Washington 98195 Communicated by Earl P. benditt, February 18, 1983 ABSTRACT Growth of human diploid fibroblasts in the pres- toradiographic analysis of HDFC cultures has yielded results ence of 5-bromodeoxyuridine, followed by flow cytometric anal- that have been interpreted as showing no noncycling popula- ysis of DNA-specific fluorescence with Hoechst 33258 dye, allows tion (14), noncycling cells arising only in the last 10 population quantitation of the proportion of cells that have not cycled, as well doubling levels (15), or proportions of noncycling cells pro- as those in G1 and G2 of two subsequent cell cycles. This technique gressively increasing with age (16). The inconsistencies are pre- allows rapid and accurate quantitation of the growth fraction and sumably related to problems with method (13) and may be ex- G1/S transition rate of these cells. The cell cycle kinetics of hu- plained in part by the use of [3H]thymine pulse periods that are man diploid fibroblasts at all population doubling levels reveal two too short to label slowly dividing cells, or the proliferation of components: cycling cells showing a probabilistic rate of G1/S labeled cells the interval. More this transition, and a variable proportion of noncycling cells.
    [Show full text]
  • Prioritizing Chemical Constituents in Tobacco Products and Smoke to Predict Developmental Osteotoxicity in Human Embryonic Stem Cells
    California State University, San Bernardino CSUSB ScholarWorks Electronic Theses, Projects, and Dissertations Office of aduateGr Studies 12-2018 PRIORITIZING CHEMICAL CONSTITUENTS IN TOBACCO PRODUCTS AND SMOKE TO PREDICT DEVELOPMENTAL OSTEOTOXICITY IN HUMAN EMBRYONIC STEM CELLS Joseph Madrid Follow this and additional works at: https://scholarworks.lib.csusb.edu/etd Part of the Cell Biology Commons, and the Developmental Biology Commons Recommended Citation Madrid, Joseph, "PRIORITIZING CHEMICAL CONSTITUENTS IN TOBACCO PRODUCTS AND SMOKE TO PREDICT DEVELOPMENTAL OSTEOTOXICITY IN HUMAN EMBRYONIC STEM CELLS" (2018). Electronic Theses, Projects, and Dissertations. 767. https://scholarworks.lib.csusb.edu/etd/767 This Thesis is brought to you for free and open access by the Office of aduateGr Studies at CSUSB ScholarWorks. It has been accepted for inclusion in Electronic Theses, Projects, and Dissertations by an authorized administrator of CSUSB ScholarWorks. For more information, please contact [email protected]. PRIORITIZING CHEMICAL CONSTITUENTS IN TOBACCO PRODUCTS AND SMOKE TO PREDICT DEVELOPMENTAL OSTEOTOXICITY IN HUMAN EMBRYONIC STEM CELLS A Thesis Presented to the Faculty of California State University, San Bernardino In Partial Fulfillment of the Requirements for the Degree Master of Science in Biology by Joseph Valenzuela Madrid December 2018 PRIORITIZING CHEMICAL CONSTITUENTS IN TOBACCO PRODUCTS AND SMOKE TO PREDICT DEVELOPMENTAL OSTEOTOXICITY IN HUMAN EMBRYONIC STEM CELLS A Thesis Presented to the Faculty of California State University, San Bernardino by Joseph Valenzuela Madrid December 2018 Approved by: Dr. Nicole Bournias, Committee Chair, Biology Dr. Nicole zur Nieden, Committee Member, UCR, Biology Dr. Jeffrey Thompson, Committee Member © 2018 Joseph Valenzuela Madrid ABSTRACT Though it is well known that tobacco related products can cause prenatal maldevelopment, very little is known on how tobacco products affect bone tissue as it develops in the embryo.
    [Show full text]
  • Mutagenesis Is Independent of the Amount of Bromouracil in DNA (Syrian Hamster/Ouabain/Thioguanine/Aminopterin/Fluorodeoxyuridine) ELLIOT R
    Proc. Natl. Acad. Sci. USA Vol. 75, No. 10, pp. 4982-4986, October 1978 Cell Biology Bromodeoxyuridine mutagenesis in mammalian cells: Mutagenesis is independent of the amount of bromouracil in DNA (Syrian hamster/ouabain/thioguanine/aminopterin/fluorodeoxyuridine) ELLIOT R. KAUFMAN AND RICHARD L. DAVIDSON Division of Human Genetics, Children's Hospital Medical Center, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115 Communicated by Arthur B. Pardee, July 10, 1978 ABSTRACT Studies were undertaken to determine how a MATERIALS AND METHODS line of mutant Syrian hamster melanoma cells (HAB-2E) that displays unlimited growth potential when all of the thymine Cell Lines. The characteristics of the cell lines in this study residues in nuclear DNA are replaced by bromouracil (BrUra) have been described. RPMI 3460 is a pigmented Syrian hamster could avoid the deleterious effects of bromodeoxyuridine melanoma line (13). HAB-2 is a line derived from RPMI 3460 (BrdUrd) mutagenicity. It was found that BrdUrd could be by selection for viability with all the Thy residues in nuclear mutagenic to these cells. However, there was a nonlinear rela- DNA replaced by BrUra (8). To avoid detection of preexisting tionship between mutagenicity and the amount of BrUra in the drug resistant mutants, HAB-2 cells were cloned in the absence DNA of the HAB-2E cells. With these cells, mutagenicity ap- of BrdUrd, and a clone called HAB-2E was isolated and used parently is determined by the concentration of BrdUrd to which in all the mutagenesis experiments. the cells are exposed rather than the amount of BrUra in DNA.
    [Show full text]
  • Draft TR-601: Di(2-Ethylhexyl) Phthalate (CASRN 117-81-7)
    1 NTP Technical Report on the 2 Toxicology and Carcinogenesis Studies of 3 Di(2-ethylhexyl) Phthalate (CASRN 117-81-7) 4 Administered in Feed to Sprague Dawley ® ® 5 (Hsd:Sprague Dawley SD ) Rats 6 Technical Report 601 7 February 2021 8 National Toxicology Program 9 Public Health Service 10 U.S. Department of Health and Human Services 11 ISSN: 2378-8925 12 Research Triangle Park, North Carolina, USA NOTICE This DRAFT Technical Report is distributed solely for the purpose of predissemination peer review under the applicable information quality guidelines. It has not been formally disseminated by NTP. It does not represent and should not be construed to represent NTP determination or policy. Peer Review Draft NOT FOR ATTRIBUTION 1 Foreword 2 The National Toxicology Program (NTP), established in 1978, is an interagency program within 3 the Public Health Service of the U.S. Department of Health and Human Services. Its activities 4 are executed through a partnership of the National Institute for Occupational Safety and Health 5 (part of the Centers for Disease Control and Prevention), the Food and Drug Administration 6 (primarily at the National Center for Toxicological Research), and the National Institute of 7 Environmental Health Sciences (part of the National Institutes of Health), where the program is 8 administratively located. NTP offers a unique venue for the testing, research, and analysis of 9 agents of concern to identify toxic and biological effects, provide information that strengthens 10 the science base, and inform decisions by health regulatory and research agencies to safeguard 11 public health. NTP also works to develop and apply new and improved methods and approaches 12 that advance toxicology and better assess health effects from environmental exposures.
    [Show full text]
  • Flow Cytometric Analysis by Bromodeoxyuridine/DNA Assay of Cell Cycle Perturbation of Methotrexate-Treated Mouse LI 210 Leukemia Cells1
    [CANCER RESEARCH 48, 4288-4293, August I, 1988] Flow Cytometric Analysis by Bromodeoxyuridine/DNA Assay of Cell Cycle Perturbation of Methotrexate-treated Mouse LI 210 Leukemia Cells1 Masahito Tsurusawa,2 Makoto Niwa, Naoyuki Katano, and Takeo Fujimoto Department of Pediatrics, Aichi Medical University, Nagakute-cho, Aichi-gun, Aichi-ken, 480-11, Japan ABSTRACT on cultured LI210 leukemia cells. In this study, we show that the self-limiting action with MTX is different from that which The in vitro effects of methotrexate (MTX) on cell cycle progression has been commonly believed. and DNA synthesis of LI 210 leukemia cells were studied by the bro- modeoxyuridine (BrdUrd)/DNA analysis technique. Low dose (10~8 M) MTX which slightly inhibits clonal replication of the cells, delays MATERIALS AND METHODS progress across the S phase, and treatment for 24 h results in a slight increase of the S-phase population. Much higher doses (IO"7 M and Cells. 1,1210 leukemia cells were supplied by the Cancer Chemo 10 ''M) of MTX, which strongly reduce the clonogenicity, prevented the therapy Center, Japan Foundation, Tokyo. The cells were grown in progression of cells at the Gi-S boundary and across the S phase, but not RPMI 1640 medium supplemented with L-glutamine and 5% PCS at in the other phases. The cells arrested at the d-S boundary were able 37°Cin a humidified atmosphere of 95% air and 5% CO2. Cultures to incorporate BrdUrd in the medium for 6-12 h after the start of initiated at a density of 5 x IO4cells/ml grew exponentially to about 1 treatment and then lost the ability to incorporate BrdUrd.
    [Show full text]
  • 5-Bromodeoxyuridine-Induced Differentiation of a Neuroblastoma
    Proceedings of the National Academy of Sciences Vol. 67, No. 1, pp. 247-254, September 1970 5-Bromodeoxyuridine-Induced Differentiation of a Neuroblastoma David Schubert and Francois Jacob SERVICE DE GENETIQUE CELLULAIRE DE L INSTITUT PASTEUR ET DU COLLEGE DE FRANCE, INSTITUT PASTEUR, PARIS, FRANCE Communicated June 8, 1970 Abstract. 5-Bromodeoxyuridine induces the differentiation of mouse neuro- blastoma C1300 to cells that morphologically resemble mature neurons. The induced differentiation can take place in the absence of DNA synthesis. This suggests that the halogenated pyrimidine need not be incorporated into DNA to alter the phenotype of the cell. It has been demonstrated that a cloned tissue-culture line of mouse neuro- blastoma C1300 can be induced to "differentiate" in vitro.' When the cells are grown in suspension in Petri dishes, they have an anaplastic round-cell morphol- ogy. If, however, cells are transferred to tissue-culture dishes, they attach to the surface and differentiate to cells which are morphologically and physiologi- cally similar to mature sympathetic neurons. The round neuroblastoma cell and its differentiated derivative differ in staining characteristics, presence of microtubules, chromosome number, and spectrum of proteins synthesized.1'2 In addition, the development of acetylcholine sensitivity is analogous to that observed with parasympathetic neurons in vivo.' Since the previously described differentiation of these cells was an asynchronous process requiring several days, it was desirable to define conditions that lead to a rapid and synchronous differentiation. The following experiments describe the induced differentiation of the neuroblastoma by 5-bromodeoxyuridine (BrdU). Materials and Methods. The culture conditions, cloning procedures, and mor- phological and physiological characteristics of mouse neuroblastoma C1300 have been previously described.'-' The cells were maintained in Eagle's modified medium containing 10% fetal calf serum at 370C.
    [Show full text]
  • Toxicological Review of Tert-Butyl Alcohol (Tert-Butanol)
    EPA/635/R-20/370Fa www.epa.gov/iris Toxicological Review of tert-Butyl Alcohol (tert-Butanol) [CASRN 75-65-0] August 2021 Integrated Risk Information System Center for Public Health and Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Washington, DC Toxicological Review of tert-Butyl Alcohol (tert-Butanol) DISCLAIMER This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. ii Toxicological Review of tert-Butyl Alcohol (tert-Butanol) CONTENTS AUTHORS | CONTRIBUTORS | REVIEWERS ................................................................................................... x PREFACE ...................................................................................................................................................... xiv PREAMBLE TO IRIS TOXICOLOGICAL REVIEWS.......................................................................................... xviii EXECUTIVE SUMMARY .............................................................................................................................. xxvi LITERATURE SEARCH STRATEGY | STUDY SELECTION AND EVALUATION ............................................... xxxii 1. HAZARD IDENTIFICATION .................................................................................................................... 1-1 1.1. OVERVIEW OF CHEMICAL PROPERTIES AND TOXICOKINETICS
    [Show full text]
  • A Multidisciplinary Approach Toward High Throughput Label-Free Cytotoxicity Monitoring of Superparamagnetic Iron Oxide Nanoparticles
    bioengineering Article A Multidisciplinary Approach toward High Throughput Label-Free Cytotoxicity Monitoring of Superparamagnetic Iron Oxide Nanoparticles Sonia Abad Tan 1,2, Georg Zoidl 2,3 and Ebrahim Ghafar-Zadeh 1,2,4,* 1 Biologically Inspired Sensors and Actuators Laboratory, Lassonde School of Engineering, York University, Ontario, Toronto, ON M3J 1P3, Canada; [email protected] 2 Department of Biology, York University, Toronto, ON M3J 1P3, Canada; [email protected] 3 Department of Psychology, York University, Toronto, ON M3J 1P3, Canada 4 Department of Electrical Engineering and Computer Science, York University, Toronto, ON M3J 1P3, Canada * Correspondence: [email protected] Received: 23 April 2019; Accepted: 5 June 2019; Published: 10 June 2019 Abstract: This paper focuses on cytotoxicity examination of superparamagnetic iron oxide nanoparticles (SPIONs) using different methods, including impedance spectroscopy. Recent advances of SPIONs for clinical and research applications have triggered the need to understand their effects in cells. Despite the great advances in adapting various biological and chemical methods to assess in-vitro toxicity of SPIONs, less attention has been paid on the development of a high throughput label-free screening platform to study the interaction between the cells and nanoparticles including SPIONs. In this paper, we have taken the first step toward this goal by proposing a label-free impedimetric method for monitoring living cells treated with SPIONs. We demonstrate the effect of SPIONs on the adhesion, growth, proliferation, and viability of neuroblastoma 2A (N2a) cells using impedance spectroscopy as a label-free method, along with other standard microscopic and cell viability testing methods as control methods.
    [Show full text]
  • Effect of 5-Bromodeoxyuridine on Deoxyribonucleic Acid- Thymine Synthesis and Cell Metabolism of Lymphatic Tissues and Tumors*
    Effect of 5-Bromodeoxyuridine on Deoxyribonucleic Acid- Thymine Synthesis and Cell Metabolism of Lymphatic Tissues and Tumors* SAULKIT, CHARLESBECK,ODETTEL. GRAHAM,ANDARTHURGROSS (Department of Biochemistry, University of Texas M. D. Anderson Hospital and Tumor Institute, Houston 25, Texas) 5-Bromodeoxyuridine (BrUDr) is an effective under the same conditions. Although the incor inhibitor of the growth of E. coli and Lactobacitti, poration of isotopically labeled one-carbon com and this growth inhibition can be reversed by pounds into DNA-thymine was inhibited, neither thymidine (1-3). There is evidence that this thy- the labeling of acid-soluble thymine compounds, midine analog can replace the thymine of both serine, nor proteins was inhibited, nor was cell E. coli and bacteriophage deoxyribonucleic acid glycolysis or respiration significantly reduced. It (DNA) on an equimolar basis (7, 11, 12). In would therefore appear that BrUDr represents E. coli, nearly 50 per cent of the thymine can a relatively specific antagonist of the terminal be replaced. Whereas the physical properties and steps in the utilization of thymidine for DNA appearance of bacteriophage particles containing synthesis. incorporated 5-bromouracil appeared normal, a proportion were found to be nonviable. Litman MATERIALS AND METHODS and Pardee have observed that T2r2 stocks grown Cell suspensions of the following tissues were used in this in the presence of 5-bromouracil and sulfanilamide study: rat thymus, mouse spleen, lymphatic leukemia LL5147 under conditions in which the 5-bromouracil is (Ak mice) and E9514A (C3H mice), and lymphosarcoma 6C3HED. The care and handling of the tumor-bearing animals incorporated into the DNA may contain a high and preparation of the cell suspensions have been previously proportion of mutant types (11).
    [Show full text]