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- INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY Environmental Health Criteria 136 1,1 ,1-Trichloroethane 0 nder the joint sponsorship of the United Nations Environment Programme, iternational Labour Organisation, and the World Health Organization. THE ENVIRONMENTAL HEALTH CRITERIA SERIES Acrolein (No. 127, 1991) DDT and its derivatives (No. 9, 1979) Acrylamide (No. 49, 1985) DDT and its derivatives - environmental Acrylonitrile (No. 28, 1983) aspects (No. 83, 1989) Aldicarb(No. 121, 1991) Deltamethrin (No. 97, 1990) Aldrin and dieldrin (No. 91, 1989) Diaminotoluenes (No. 74, 1987) Allethrins (No. 87, 1989) Dichlorvos (No. 79, 1988) Ammonia (No. 54, 1986) Diethylhexyl phthalate (No. 131, 1992) Arsenic (No. 18, 1981) Dimethoate (No. 90, 1989) Asbestos and other natural mineral fibres Dimethylformamide (No. 114, 1991) (No. 53, 1986) Dimethyl sulfate (No. 48, 1985) Barium (No. 107, 1990) Diseases of suspected chemical etiology and Beryllium (No. 106, 1990) their prevention, principles of studies on Biotoxins, aquatic (marine and freshwater) (No. 72, 1987) (No. 37, 1984) Dithiocarbamate pesticides, ethylenethio- Butanols - four isomers (No. 65, 1987) urea, and propylenethiourea: a general Cadmium (No. 134, 1992) introduction (No. 78, 1988) Cadmium - environmental aspects (No. 135, Endosulfan (No. 40, 1984) 1992) Endrin (No. 130, 1992) Camphechlor (No. 45, 1984) Environmental epidemiology, guidelines on Carbamate pesticides: a general introduction studies in (No. 27, 1983) (No. 64, 1986) Epichlorohydrin (No. 33, 1984) Carbon disulfide (No. 10, 1979) Ethylene oxide (No. 55, 1985) Carbon monoxide (No. 13, 1979) Extremely low frequency (ELF) fields Carcinogens, summary report on the evalu- (No. 35, 1984) ation of short-term in vitro tests (No. 47, Fenitrothion (No. 133, 1992) 1985) Fenvalerate (No. 95, 1990) Carcinogens, summary report on the evalu- Fluorine and fluorides (No. 36, 1984) atioo of short-term in vivo tests (No. 109, Food additives and contaminants in food, 1990) principles for the safety assessment of Chlordane (No. 34, 1984) (No. 70, 1987) Chlordecone (No. 43, 1984) Formaldehyde (No. 89, 1989) Chlorine and hydrogen chloride (No. 21, Genetic effects in human populations, 1982) guidelines for the study of (No. 46, 1985) Chlorobenzenes other than hexachloro- Heptachlor (No. 38, 1984) benzene (No. 128, 1991) Alpha- and beta-hexachlorocyclohexanes Chlorofluorocarbons, fully halogenated (No. 123, 1991) (No. 113, 1990) Hexachlorocyclopentadiene (No. 120, 1991 Chlorofluorocarbons, partially halogenated n-Hexane (No. 122, 1991) (methane derivatives) (No. 126, 1991) Hydrazine (No. 68, 1987) Chlorophenols (No. 93, 1989) Hydrogen sulfide (No. 19, 1981) Chromium (No. 61, 1988) Infancy and early childhood, principles for Cyhalothrin (No. 99, 1990) evaluating health risks from chemicals Cypermethrin (No. 82, 1989) during (No. 59, 1986) 1,2-Dichloroethane (No. 62, 1987) Isobenzan (No. 129, 1991) 2,4-Dichlorophenoxyacetic acid (2,4-D) Kelevan (No. 66, 1986) (No. 29, 1984) Lasers and optical radiation (No. 23, 1982) 2,4-Dichlorophenoxyacetic acid - Lead (No. 3, 1977)' environmental aspects (No. 84, 1989) Out of print continued inside back cover This repoi-r contains the collective views of an in- ternational group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the Interna- tional Labour Organisation, or the World Health Organization. Environmental Health Criteria 136 to) 4i ANO 1,1 ,1-TRICHLOROETHANE First draft prepared by Dr S. Dobson, (Institute of 'terrestrial Ecology, United Kingdom) and Dr AA. Jensen (Danish Technological institute) World Health Organization Geneva, 1992 The Internalional Programme on Chemical Safety (JPCS) is a joint venture of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization. The main objective of the IPCS is to carry out and disseminate evaluations of the effects of chemicals on human health and the quality of the environment. Supporting activities include thedevelopment ofepidemiological, experimental laboratory, and risk-assessment methods that could produce internationally comparable results, and the develop- ment of manpower in the field of toxicology. Other activities carried out by the IPCS include the development of know-how for coping with chemical accidents, coordination of laboratory testing and epidemiological studies, and promotion of research on the mechanisms of the biological action of chemicals. WHO Library Cataloguing in Publication Data l,l,l-Trichloroethane. (Environmental health criteria 136) I .Trichloroethanes - adverse effects 2.Trichloroethanes - toxicity 3.Environmental exposure 4.Environmental pollutants l.Series ISBN 92 4 157136 5 (NLM Classification: QV 633) ISSN 0250-863X The World Health Organization welcomes requests for permission to repro- duce or translate its publications, in part or in full. Applications and enquiries should be addressed to the Office of Publications, World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on any change.c made to the text, plans for new editions, and reprints and translations already available. ©Wo rld Health Organization 1992 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Conven- tion. All rights reserved. The designations employed and the presentation of the material in this publi- cation do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, City or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organiz- ation in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. Printed in Finland 92/9011 Rev I Vammala - 5500 CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR 1,1,1 -TRICJ-ILOROETHANE SUMMARY 13 IDENTITY, PHYSiCAL AND CHEMICAL PROPERTIES, AND ANALYTICAL METHODS 15 2.1 Identity 15 2.2 Physical and chemical properties 16 12.1 Physical characteristics 16 16 2.2.2 Chemical reactivity 16 2.23 Commercial products 18 2.3 Conversion factors 2.4 Analytical methods 18 SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE 20 20 3.1 Production processes 20 3.2 Production levels 3.3 Uses 22 ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION 23 23 4.1 Distribution and transport between media 24 4.1.1 Atmospheric transport 4.1.2 Transport in water 25 4.1.3 Transport in soil 25 4.2 Degradation and transformation 26 4.2.1 Abiotic degradation 26 4.2.1.1 In the atmosphere 26 4.2.1.2 In water 27 4.12 Biodegradation 27 4.2.2.1 Anaerobic 27 4.2.2.2 Aerobic 29 4.3 Bioaccumulation 30 ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 31 Environmental levels 31 5.1 5.1.1 Air 31 3 EHC 136: 1,1, 1-Trichloroethane 5.1.2 Water 35 5.1.3 Sediment and soil 35 5.1.4 Biota 38 5.2 General population exposure 39 5.2.1 Food 39 5.2.2 Drinking-water 40 5.2.3 Air 42 5.2.4 Consumer products and cosmetics 43 5.3 Occupational exposure 43 KINETICS AND METABOLISM IN LABORATORY ANIMALS AND HUMANS 45 6.1 Absorption 45 6.1.1 Animal studies 45 6.1.1.1 Inhalation 45 6.1.1.2 Oral absorption 46 6.1.1.3 Skin absorption 46 6.1.2 Human studies 46 6.1.2.1 Inhalation 46 6.1.2.2 Skin contact 47 6.2 Distribution and retention 47 6.2.1 Animal studies 47 6.2.2 Human studies 48 6.3 Metabolic transformation 49 6.3.1 Animal studies 49 6.3.2 Human studies 51 6.3.3 Metabolic interactions 51 6.4 Elimination 51 6.4.1 Animal studies 51 6.4.2 Human studies 52 6.5 Biological monitoring 52 6.6 Bioaccumulation 54 EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS 55 7.1 Acute toxicity 56 7.1.1 Irritation 59 7.1 .2 Short-term exposure 59 7.1.2.1 Inhalation 59 7.1.2.2 Oral administration 61 7.2 Long-term exposure 62 7.3 Reproductive toxicity, embryotoxicity, and teratogenicity 63 4 64 7.4 Mutagenicity 7.5 Carcinogenicity 68 Oral administration 68 7.5.1 Inhalation 69 7.5.2 7.6 Immunotoxicity and sensitization 69 7.7 Interactions 70 7.8 Mechanisms of action 70 8 EFFECTS ON HUMANS 8.1 Controlled human studies 72 Single exposure period 75 8.1.1 76 8.1.2 Repeated exposure 77 8.2 Accidental exposure 8.2.1 Confined spaces at workplaces 77 78 8.2.2 Solvent abuse 8.2.3 Medical use 79 79 8.2.4 Ingestion Drinking-water Contamination 80 8.2.5 80 8.3 Effects on the skin and eyes 8.4 Long-term occupational exposure 80 8.5 Interactions 81 EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD 83 9.1 Microorganisms 83 9.2 Aquatic organisms 83 9.3 Terrestrial organisms 86 EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT 88 10.1 Evaluation of human health risks 88 10.2 Evaluation of effects on the environment 89 RECOMMENDATIONS FOR PROTECTION OF HUMAN HEALTH AND THE ENVIRONMENT 90 FURTHER RESEARCH 91 PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES 92 REFERENCES 93 5 EHC 136: 1,1, 1-Trichloroetbane RESUME 113 RESUMEN 116 WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR 1,1,1 -TRICHLOROETHANE Members Dr L.A. Albert, Consultores Ambientales Asociados, Xalapa, Veracruz, Mexico (Vice-Chairman) Dr A.H. El-Sebae, Faculty of Agriculture, Alexandria University, Alexandria, Egypt Dr S. Fairhurst, Medical Division, Health and Safety Executive, Bootle, Merseyside, United Kingdom (Chairman) Dr B. Gilbert, Technology Development Company (CODETEC), Cidade Universitaria, Campinas, Brazil Dr A.A. Jensen, Danish Technological Institute, Taastrup, Den ma rI< Dr T.
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  • Calcium Current Block by (-)-Pentobarbital, Phenobarbital

    Calcium Current Block by (-)-Pentobarbital, Phenobarbital

    The Journal of Neuroscience, August 1993, 13(E): 321 l-3221 Calcium Current Block by (-)-Pentobarbital, Phenobarbital, and CHEB but not (+)-Pentobarbital in Acutely Isolated Hippocampal CA1 Neurons: Comparison with Effects on GABA-activated Cl- Current Jarlath M. H. ffrench-Mullen,’ Jeffery L. Barker,* and Michael A. Rogawski3 ‘Department of Pharmacology, Zeneca Pharmaceuticals Group, Zeneca Inc., Wilmington, Delaware 19897 and *Laboratory of Neurophysiology, and 3Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 Block of a voltage-activated Ca*+ channel current by pheno- Ca*+ current, whereas the sedative effects that occur at high- barbital (PHB), 5-(2-cyclohexylideneethyl)-5-ethyl barbituric er concentrations could reflect stronger Ca2+ current block- acid (CHEB), and the optical R(-)- and S(+)-enantiomers of ade. The powerful sedative-hypnotic action of (-)-PB may pentobarbital (PB) was examined in freshly dissociated adult reflect greater maximal enhancement of GABA responses guinea pig hippocampal CA1 neurons; the effects of the in conjunction with strong inhibition of Ca2+ current. The barbiturates on GABA-activated Cl- current were also char- convulsant action of CHEB is unlikely to be related to its acterized in the same preparation. (-)-PB, PHB, and CHEB effects on the Ca*+ current. produced a reversible, concentration-dependent block of the [Key words: calcium channel, GABA receptor, (-)-pen- peak Ca*+ channel current (3 mM Ba2+ as the charge carrier) tobarbital, (+)-pentobarbital, phenobarbital, CHEB [S-(2-cy- evoked by depolarization from -80 to - 10 mV (I&,, values, clohexylideneethyl)-S-ethyl barbituric acid], CA 1 hippocam- 3.5, 72, and 118 PM, respectively).