Toxicological Profile for Radon
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Exposure to Carcinogens and Work-Related Cancer: a Review of Assessment Methods
European Agency for Safety and Health at Work ISSN: 1831-9343 Exposure to carcinogens and work-related cancer: A review of assessment methods European Risk Observatory Report Exposure to carcinogens and work-related cancer: A review of assessment measures Authors: Dr Lothar Lißner, Kooperationsstelle Hamburg IFE GmbH Mr Klaus Kuhl (task leader), Kooperationsstelle Hamburg IFE GmbH Dr Timo Kauppinen, Finnish Institute of Occupational Health Ms Sanni Uuksulainen, Finnish Institute of Occupational Health Cross-checker: Professor Ulla B. Vogel from the National Working Environment Research Centre in Denmark Project management: Dr Elke Schneider - European Agency for Safety and Health at Work (EU-OSHA) Europe Direct is a service to help you find answers to your questions about the European Union Freephone number (*): 00 800 6 7 8 9 10 11 (*) Certain mobile telephone operators do not allow access to 00 800 numbers, or these calls may be billed. More information on the European Union is available on the Internet ( 48TU http://europa.euU48T). Cataloguing data can be found on the cover of this publication. Luxembourg: Publications Office of the European Union, 2014 ISBN: 978-92-9240-500-7 doi: 10.2802/33336 Cover pictures: (clockwise): Anthony Jay Villalon (Fotolia); ©Roman Milert (Fotolia); ©Simona Palijanskaite; ©Kari Rissa © European Agency for Safety and Health at Work, 2014 Reproduction is authorised provided the source is acknowledged. European Agency for Safety and Health at Work – EU-OSHA 1 Exposure to carcinogens and work-related cancer: -
Carcinogens Are Mutagens
-Proc. Nat. Acad. Sci. USA Vol. 70, No. 8, pp. 2281-2285, August 1973 Carcinogens are Mutagens: A Simple Test System Combining Liver Homogenates for Activation and Bacteria for Detection (frameshift mutagens/aflatoxin/benzo(a)pyrene/acetylaminofluorene) BRUCE N. AMES, WILLIAM E. DURSTON, EDITH YAMASAKI, AND FRANK D. LEE Biochemistry Department, University of California, Berkeley, Calif. 94720 Contributed by Bruce N. Ames, May 14, 1973 ABSTRACT 18 Carcinogens, including aflatoxin Bi, methylsulfoxide (Me2SO), spectrophotometric grade, was ob- benzo(a)pyrene, acetylaminofluorene, benzidine, and di- tained from Schwarz/Mann, sodium phenobarbital from methylamino-trans-stilbene, are shown to be activated by liver homogenates to form potent frameshift mutagens. Mallinckrodt, aflatoxin B1 from Calbiochem, and 3-methyl- We believe that these carcinogens have in common a ring cholanthrene from Eastman; 7,12-dimethylbenz(a)anthracene system sufficiently planar for a stacking interaction with was a gift of P. L. Grover. Schuchardt (Munich) was the DNA base pairs and a part of the molecule capable of being source for the other carcinogens. metabolized to a reactive group: these structural features are discussed in terms of the theory of frameshift muta- Bacterial Strains used are mutants of S. typhimurium LT-2 genesis. We propose that these carcinogens, and many have been discussed in detail others that are mutagens, cause cancer by somatic muta- and (2). tion. A simple, inexpensive, and extremely sensitive test for Source Liver. Male rats (Sprague-Dawley/Bio-1 strain, detection of carcinogens as mutagens is described. It con- of sists of the use of a rat or human liver homogenate for Horton Animal Laboratories) were maintained on Purina carcinogen activation (thus supplying mammalian metab- laboratory chow. -
Virulence and Transcriptome Profile of Multidrug-Resistant Escherichia Coli from Chicken Received: 3 April 2017 Hafiz I.Hussain 1, Zahid Iqbal1,4, Mohamed N
www.nature.com/scientificreports OPEN Virulence and transcriptome profile of multidrug-resistant Escherichia coli from chicken Received: 3 April 2017 Hafiz I.Hussain 1, Zahid Iqbal1,4, Mohamed N. Seleem3, Deyu Huang2, Adeel Sattar2, Haihong Accepted: 3 July 2017 Hao1 & Zonghui Yuan1,2 Published: xx xx xxxx Numerous studies have examined the prevalence of pathogenic Escherichia coli in poultry and poultry products; however, limited data are available regarding their resistance- and virulence-associated gene expression profiles. This study was designed to examine the resistance and virulence of poultryE. coli strains in vitro and in vivo via antibiotic susceptibility, biofilm formation and adhesion, and invasion and intracellular survivability assays in Caco-2 and Raw 264.7 cell lines as well as the determination of the median lethal dose in two-day old chickens. A clinical pathogenic multidrug-resistant isolate, E. coli 381, isolated from broilers, was found to be highly virulent in cell culture and 1000-fold more virulent in a chicken model than other strains; accordingly, the isolate was subsequently selected for transcriptome analysis. The comparative gene expression profile of MDRE. coli 381 and the reference human strain E. coli ATCC 25922 was completed with Illumina HiSeq. 2500 transcriptome analysis. Differential gene expression analysis indicates that there are multiple pathways involved in the resistance and virulence of this highly virulent strain. The results garnered from this study provide critical information about the highly virulent MDR E. coli strain of poultry origin and warrant further investigation due to its significant threat to public health. Escherichia coli is a Gram-negative bacterium that displays a wide range of genomic diversity. -
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development Gerlie Gieser, Ph.D. Office of Clinical Pharmacology, Div. IV Objectives • Outline the Phase 1 studies conducted to characterize the Clinical Pharmacology of a drug; describe important design elements of and the information gained from these studies. • List the Clinical Pharmacology characteristics of an Ideal Drug • Describe how the Clinical Pharmacology information from Phase 1 can help design Phase 2/3 trials • Discuss the timing of Clinical Pharmacology studies during drug development, and provide examples of how the information generated could impact the overall clinical development plan and product labeling. Phase 1 of Drug Development CLINICAL DEVELOPMENT RESEARCH PRE POST AND CLINICAL APPROVAL 1 DISCOVERY DEVELOPMENT 2 3 PHASE e e e s s s a a a h h h P P P Clinical Pharmacology Studies Initial IND (first in human) NDA/BLA SUBMISSION Phase 1 – studies designed mainly to investigate the safety/tolerability (if possible, identify MTD), pharmacokinetics and pharmacodynamics of an investigational drug in humans Clinical Pharmacology • Study of the Pharmacokinetics (PK) and Pharmacodynamics (PD) of the drug in humans – PK: what the body does to the drug (Absorption, Distribution, Metabolism, Excretion) – PD: what the drug does to the body • PK and PD profiles of the drug are influenced by physicochemical properties of the drug, product/formulation, administration route, patient’s intrinsic and extrinsic factors (e.g., organ dysfunction, diseases, concomitant medications, -
Microrna Pharmacoepigenetics: Posttranscriptional Regulation Mechanisms Behind Variable Drug Disposition and Strategy to Develop More Effective Therapy
1521-009X/44/3/308–319$25.00 http://dx.doi.org/10.1124/dmd.115.067470 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 44:308–319, March 2016 Copyright ª 2016 by The American Society for Pharmacology and Experimental Therapeutics Minireview MicroRNA Pharmacoepigenetics: Posttranscriptional Regulation Mechanisms behind Variable Drug Disposition and Strategy to Develop More Effective Therapy Ai-Ming Yu, Ye Tian, Mei-Juan Tu, Pui Yan Ho, and Joseph L. Jilek Department of Biochemistry & Molecular Medicine, University of California Davis School of Medicine, Sacramento, California Received September 30, 2015; accepted November 12, 2015 Downloaded from ABSTRACT Knowledge of drug absorption, distribution, metabolism, and excre- we review the advances in miRNA pharmacoepigenetics including tion (ADME) or pharmacokinetics properties is essential for drug the mechanistic actions of miRNAs in the modulation of Phase I and development and safe use of medicine. Varied or altered ADME may II drug-metabolizing enzymes, efflux and uptake transporters, and lead to a loss of efficacy or adverse drug effects. Understanding the xenobiotic receptors or transcription factors after briefly introducing causes of variations in drug disposition and response has proven the characteristics of miRNA-mediated posttranscriptional gene dmd.aspetjournals.org critical for the practice of personalized or precision medicine. The regulation. Consequently, miRNAs may have significant influence rise of noncoding microRNA (miRNA) pharmacoepigenetics and on drug disposition and response. Therefore, research on miRNA pharmacoepigenomics has come with accumulating evidence sup- pharmacoepigenetics shall not only improve mechanistic under- porting the role of miRNAs in the modulation of ADME gene standing of variations in pharmacotherapy but also provide novel expression and then drug disposition and response. -
Oecd Guideline for the Testing of Chemicals
Draft November 2009 OECD GUIDELINE FOR THE TESTING OF CHEMICALS PROPOSAL FOR A NEW TEST GUIDELINE 223 Avian Acute Oral Toxicity Test INTRODUCTION 1. This test guideline describes procedures designed to estimate the acute oral toxicity of substances to birds, and it provides three testing options: (1) limit dose test, (2) LD50-slope test, and (3) LD50-only test. The LD50-slope and LD50-only options are sequential testing procedures. The test method selected will depend on whether or not a definitive median dose (LD50) and slope of the dose-response curve are both needed. Sequential testing procedures target the placement of doses and match the precision of the endpoint with the precision required. These sequential procedures were designed to minimise the numbers of birds used. A computer programme is available to aid the placement of doses and estimate the LD50, slope and confidence limits. 2. Development of this test guideline began at the SETAC/OECD Workgroup on avian toxicity testing following a workshop held in Pensacola, Florida, United States, in 1994 (1) with subsequent open SETAC and closed OECD Expert Group meetings in Europe and the United States to develop and optimise the sequential testing design. The sequential testing design has been developed with extensive statistical validation (2). INITIAL CONSIDERATIONS 3. The information required by different hazard assessment schemes may vary considerably. To satisfy these various needs, the following three tests are described: Limit dose test – This is the preferred test when toxicity is expected to be low and lethality is unlikely at the limit dose. The limit dose must be adequate for assessment purposes, and it is usually 2000 mg/kg-bwt. -
Toxicological Profile for Hydrazines. US Department Of
TOXICOLOGICAL PROFILE FOR HYDRAZINES U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry September 1997 HYDRAZINES ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. HYDRAZINES iii UPDATE STATEMENT Toxicological profiles are revised and republished as necessary, but no less than once every three years. For information regarding the update status of previously released profiles, contact ATSDR at: Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch 1600 Clifton Road NE, E-29 Atlanta, Georgia 30333 HYDRAZINES vii CONTRIBUTORS CHEMICAL MANAGER(S)/AUTHOR(S): Gangadhar Choudhary, Ph.D. ATSDR, Division of Toxicology, Atlanta, GA Hugh IIansen, Ph.D. ATSDR, Division of Toxicology, Atlanta, GA Steve Donkin, Ph.D. Sciences International, Inc., Alexandria, VA Mr. Christopher Kirman Life Systems, Inc., Cleveland, OH THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 1 . Green Border Review. Green Border review assures the consistency with ATSDR policy. 2 . Health Effects Review. The Health Effects Review Committee examines the health effects chapter of each profile for consistency and accuracy in interpreting health effects and classifying end points. 3. Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to substance-specific minimal risk levels (MRLs), reviews the health effects database of each profile, and makes recommendations for derivation of MRLs. HYDRAZINES ix PEER REVIEW A peer review panel was assembled for hydrazines. The panel consisted of the following members: 1. Dr. -
Method of Rough Estimation of Median Lethal Dose (Ld50)
b Meta olis g m & ru D T o f x o i Journal of Drug Metabolism and l c a o n l o r Saganuwan, J Drug Metab Toxicol 2015, 6:3 g u y o J Toxicology DOI: 10.4172/2157-7609.1000180 ISSN: 2157-7609 Research Article Open Access Arithmetic-Geometric-Harmonic (AGH) Method of Rough Estimation of Median Lethal Dose (Ld50) Using Up – and – Down Procedure *Saganuwan Alhaji Saganuwan Department of Veterinary Physiology, Pharmacology and Biochemistry, College Of Veterinary Medicine, University Of Agriculture, P.M.B. 2373, Makurdi, Benue State, Nigeria *Corresponding author: Saganuwan Alhaji Saganuwan, Department of Veterinary Physiology, Pharmacology and Biochemistry, College Of Veterinary Medicine, University Of Agriculture, P.M.B. 2373, Makurdi, Benue State, Nigeria, Tel: +2348027444269; E-mail: [email protected] Received date: April 6,2015; Accepted date: April 29,2015; Published date: May 6,2015 Copyright: © 2015 Saganuwan SA . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Earlier methods adopted for the estimation of median lethal dose (LD50) used many animals (40 – 100). But for the up – and – down procedure, 5 – 15 animals can be used, the number I still consider high. So this paper seeks to adopt arithmetic, geometric and harmonic (AGH) mean for rough estimation of median lethal dose (LD50) using up – and – down procedure by using 2 – 6 animals that may likely give 1 – 3 reversals. The administrated doses should be summed up and the mean, standard deviation (STD) and standard error of mean (SEM) should be determined. -
Cancer Cause: Biological, Chemical and Physical Carcinogens
Merit Research Journal of Medicine and Medical Sciences (ISSN: 2354-323X) Vol. 6(9) pp. 303-306, September, 2018 Available online http://www.meritresearchjournals.org/mms/index.htm Copyright © 2018 Merit Research Journals Review Cancer Cause: Biological, Chemical and Physical Carcinogens Asst. Prof. Dr. Chateen I. Ali Pambuk* and Fatma Mustafa Muhammad Abstract College of Dentistry / University of Cancer arises from abnormal changes of cells that divide without control Tikrit and are able to spread to the rest of the body. These changes are the result of the interaction between the individual genetic factors and three *Corresponding Author Email: categories of external factors: a chemical carcinogens, radiation, hormonal [email protected]. imbalance, genetic mutations and genetic factors. Genetic deviation leads to Mobile phone No. 009647701808805 the initiation of the cancer process, while the carcinogen may be a key component in the development and progression of cancer in the future. Although the factors that make someone belong to a group with a higher risk of cancer, the majority of cancers actually occur in people who do not have known factors. The aim of this descriptive mini-review, generally, is to shed light on the main cause of cancer and vital factors in cellular system and extracellular system that may be involved with different types of tumors. Keywords: Cancer, Cancer cause, physical Carcinogens, Chemical carcinogens, biological carcinogens INTRODUCTION Carcinogen is any substance (radioactive or radiation) .Furthermore, the chemicals mostly involve as the that is directly involved in the cause of cancer. This may primary cause of cancer, from which dioxins, such as be due to the ability to damage the genome or to disrupt benzene, kibon, ethylene bipromide and asbestos, are cellular metabolism or both rendering the cell to be classified as carcinogens (IUPAC Recommendations, sensitive for cancer development. -
Detection of Carcinogens As Mutagens in the Salmonella/Microsome Test
Proc. Nat. Acad. Sci. USA Vol. 73, No. 3, pp. 950-954, March 1976 Medical Sciences Detection of carcinogens as mutagens in the Salmonella/microsome test: Assay of 300 chemicals: Discussion* (prevention of cancer and genetic defects/somatic mutation/environmental insult to DNA) JOYCE MCCANN AND BRUCE N. AMES Department of Biochemistry, University of California, Berkeley, Calif. 94720 Contributed by Bruce N. Ames, January 7, 1976 ABSTRACT About 300 carcinogens and non-carcinogens Non-Carcinogens. Classification as to non-carcinogenicity of a wide variety of chemical types have been tested for mu- is usually difficult because of the varying completeness and tagenicity in the simple Salmonella/microsome test. The test uses bacteria as sensitive indicators of DNA damage, and modes of treatment in many studies and the statistical limi- mammalian liver extracts for metabolic conversion of carcin- tations inherent in animal tests (4, 8-10). Recent criteria for ogens to their active mutagenic forms. There is a high corre- adequate carcinogenicity tests are much more stringent (4, lation between carcinogenicity and mutagenicity: 90% 8-10). The test should be of adequate duration (lifetime pre- (157/175) of the carcinogens were mutagenic in the test, in- ferred in rodents) in at least two animal species, at several cluding almost all of the known human carcinogens that dose levels, and positive controls should be of the same gen- were tested. Despite the severe limitations inherent in defin- ing non-carcinogenicity, few "non-carcinogens" showed any eral chemical type as the chemical under test. The applica- degree of mutagenicity [McCann et a]. (1975) Proc. -
Radiation and Your Patient: a Guide for Medical Practitioners
RADIATION AND YOUR PATIENT: A GUIDE FOR MEDICAL PRACTITIONERS A web module produced by Committee 3 of the International Commission on Radiological Protection (ICRP) What is the purpose of this document ? In the past 100 years, diagnostic radiology, nuclear medicine and radiation therapy have evolved from the original crude practices to advanced techniques that form an essential tool for all branches and specialties of medicine. The inherent properties of ionising radiation provide many benefits but also may cause potential harm. In the practice of medicine, there must be a judgement made concerning the benefit/risk ratio. This requires not only knowledge of medicine but also of the radiation risks. This document is designed to provide basic information on radiation mechanisms, the dose from various medical radiation sources, the magnitude and type of risk, as well as answers to commonly asked questions (e.g radiation and pregnancy). As a matter of ease in reading, the text is in a question and answer format. Interventional cardiologists, radiologists, orthopaedic and vascular surgeons and others, who actually operate medical x-ray equipment or use radiation sources, should possess more information on proper technique and dose management than is contained here. However, this text may provide a useful starting point. The most common ionising radiations used in medicine are X, gamma, beta rays and electrons. Ionising radiation is only one part of the electromagnetic spectrum. There are numerous other radiations (e.g. visible light, infrared waves, high frequency and radiofrequency electromagnetic waves) that do not posses the ability to ionize atoms of the absorbing matter. -
Lead, Mercury and Cadmium in Fish and Shellfish from the Indian Ocean and Red
Journal of Marine Science and Engineering Review Lead, Mercury and Cadmium in Fish and Shellfish from the Indian Ocean and Red Sea (African Countries): Public Health Challenges Isidro José Tamele 1,2,3,* and Patricia Vázquez Loureiro 4 1 Department of Chemistry, Faculty of Sciences, Eduardo Mondlane University, Av. Julius Nyerere, n 3453, Campus Principal, Maputo 257, Mozambique 2 Institute of Biomedical Science Abel Salazar, University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal 3 CIIMAR/CIMAR—Interdisciplinary Center of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto, Avenida General Norton de Matos, 4450-238 Matosinhos, Portugal 4 Department of Analytical Chemistry, Nutrition and Food Science, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, 15782 A Coruña, Spain; [email protected] * Correspondence: [email protected] Received: 20 March 2020; Accepted: 8 May 2020; Published: 12 May 2020 Abstract: The main aim of this review was to assess the incidence of Pb, Hg and Cd in seafood from African countries on the Indian and the Red Sea coasts and the level of their monitoring and control, where the direct consumption of seafood without quality control are frequently due to the poverty in many African countries. Some seafood from African Indian and the Red Sea coasts such as mollusks and fishes have presented Cd, Pb and Hg concentrations higher than permitted limit by FAOUN/EU regulations, indicating a possible threat to public health. Thus, the operationalization of the heavy metals (HM) monitoring and control is strongly recommended since these countries have laboratories with minimal conditions for HM analysis.