This report contains the collective views of an inter- national group of experts and does not necessarily represent the decisions or the stated policy of either the World Health Organization or the United Nations Environment Programme. Environmental Health Criteria 10 CARBON DISULFIDE Published under the joint sponsorship of the United Nations Environment Programme and the World Health Organization I - - V b: IQ\_- - Vkl l World Health Organization Geneva, 1979 ISBN 924 1540702 © World Health Organization 1979 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. For rights of reproduction or translation of WHO publications, in part or in toto, application should be made to the Office of Publications, World Health Organization, Geneva, Switzerland. The World Health Organization welcomes such applications. The designations employed and the presentation of the material in this publication do rrot 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. S The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization 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 THE UNITED KINGDOM CONTENTS Page ENVIRONMENTAL HEALTH CRITERIA FOR CARBON DISULFIDE - . 9 I. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH . Ii 1.1 Summary .......................... It 1.1.1 Uses and sources of exposure ................ II 1.1.2 Populations at risk .................... II 1.1.3 Estimation of exposure .................. II 1.1.4 Metabolism ...................... [ 2 1.1.5 Mechanisms of toxic action ................ 13 1.1.6 Carbon disulfide poisoning; evaluation of the health risk to man . 13 1.1.7 Diagnosis of carbon disutfide poisoning ............ 15 1.1.8 Surveillance of exposed workers ............... 15 1.2 Recommendations for further research ............... 16 1.2.1 Analytical aspects .................... 16 1.2.2 Studies on health effects .................. 16 1.2.3 Mechanisms of toxic action ................ 16 2. PROPERTIES AND ANALYTICAL METHODS ............17 2.1 Chemical and physical properties .................17 2.2 Analytical procedures ..................... 17 2.2.1 Measurement of carbon disulfide in air ............ 17 2.2.2 Sampling methods .................... IS 2.2.2.1 The activated charcoal tube method .......... 18 2.2.2.2 The liquid absorption method ............ 18 2.23 Methods for the determination of carbon disulfide ........ 19 2.2.3.1 Direct measurement using gas detector tubes ...... 19 2.2.3.2 Photometric determination ............. 19 2.2.3.3 Gas—liquid chromatographic determination ....... 19 2.2.3.4 Continuous measurement using gas analysers ...... 20 2.2.3.5 Determination of metabolites in urine ......... 20 3. EXPOSURE TO CARBON DISULFIDE ............... 22 3.1 Occupational exposure ..................... 22 3.2 Community exposure ..................... 22 4. METABOLISM .........................24 4.1 Absorption .........................24 4.1.1 Inhalation .......................24 4.1.2 Skin absorption .....................25 4.2 Distribution and biotransformation ................25 4.2.1 Balance of absorbed carbon disulfide .............25 4.2.2 Transport by the bloodstream ...............26 4.2.3 Determination of carbon disulfide in blood ...........26 4.2.4 Distribution in the organism ................26 4.2.5 Binding in blood and tissues ................28 4.3 Elimination of carbon disulfide and metabolites ............28 4.3.1 Elimination by breath, saliva, sweat, and faeces .........28 4.3.2 Excretion of carbon disulfide and metabolites in urine .......29 3 5. BIOCHEMICAL EFFECTS OF CARBON DISULFIDE 32 5.1 Chelating effects of carbon disulfide metaholitcs ............ 33 5.2 Effects on enzyme systems .................... 5.3 Effects on vitamin metabolism .................. 36 5.3.1 Vitamin B........................16 5.3.2 Nicotinic acid ..................... 38 5.4 Effects on catecholaminc metabolism ................ 38 S 5.5 Effects on lipid metabolism ................... 38 5.6 Interaction with microsomal drug metabolism ............ 39 6. CARBON DISULFtDE POISONING ................. 41 6. t Historical review ....................... 41 6.2 Clinical picture of carbon disulfide poisoning ............. 42 6.3 Effects on organ systems .................... 43 6.3.1 Dermatological effects .................. 43 6.3.2 Ophthalmological effects ................. 43 6.3.3 Otnlogical effects .................... 45 6.3.4 Respiratory effects .................... 46 6.3.5 Gastrointestinal effects .................. 46 6.3.6 Hepatic effects ..................... 46 6.3.7 Renal effects ...................... 48 6.3.8 Haematological effects .................. 48 6.3.9 The endncrine system .................. 49 6.3.10 Effects on the nervous system ................ SI 6.3.10.1 Central nervous system ............. SI 6.3,10,2 Peripheral nervous system ............ 56 6.3.11 Cardiovasctslareffects .................. 59 ' 6.3.12 Carcinogenicity and mutagenicit .............. 62 6.3.13 Teratogenic effects ................... 62 6.3.14 Other effects ...................... 62 6.3.15 Interactions with other chemical compounds .......... 63 6.4 Diagnosis .......................... 64 6.5 Surveillance of the health of exposed workers ............. 66 6.6 Contraindications for exposure to carbon disulfide ........... 68 7. EXPOSURE-EFFECT AND EXPOSURE-RESPONSE RELATIONSHIPS . . 69 7.1 Validity of exposure data .................... 69 7.2 Experimental data ....................... 69 7.2.1 Acute animal exposure .................. 69 7.2.2 Long-term animal exposure ................ 69 7.3 Epidemiological data ...................... 70 7.3.1 Neurological and behavioural effects ............. 70 7.3.2 Cardiovascular effects .................. 71 7.3.3 Ophthalmological effects ................. 72 7.3.4 Gonadal effects ..................... 73 - 8. CONTROL OF EXPOSURE IN THE VISCOSE INDUSTRY ........ 74 REFERENCES ........................... 77 ANNEX t Production of viscose and its end-products ............ 95 ANNEX II Maximum permissible concentrations for carbon disulfide in different countries ........................ 99 4 NOTE TO READERS OF THE CRITERIA DOCUMENTS While every effort has been made to present information in the criteria documents as accurately as possible without unduly delaying their publication, mistakes might have occurred and are likely to occur in the - future. In the interest of all users of the environmental health criteria documents, readers are kindly requested to communicate any errors found to the Division of Environmental Health, World Health Organization, Geneva, Switzerland, in order that they may be included in corrigenda which will appear in subsequent volumes. In addition, experts in any particular field dealt with in the criteria documents are kindly requested to make available to the WHO Secretariat any important published information that may have inadvertently been omitted and which may change the evaluation of health risks from exposure to the environmental agent under examination, so that the infor- mation may be considered in the event of updating and re-evaluation of the conclusions contained in the criteria documents. WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR CARBON DISULFIDE Participants - Members Or G. Avilova, Institute of Hygiene and Preventive Medicine, Academy of Medical Sciences. Moscow, USSR Dr A. Cavalleri. Institute of Occupational Medicine. University of Pavia. Pavia, Italy Or D. Djuriê, Institute of Occupational and Radiological Health. Belgrade, Yugoslavia Professor K. J. Freundt. Institute of Pharmacology and Toxicology. Faculty of Clinical Medicine, Mannheim, Federal Republic of Germany Dr S. Hernberg, tnstitute of Occupational Health, Helsinki, Finland Dr F. Luki, Institute of Hygiene and Epidemiology, Centre of Industrial Hygiene and Occupational Diseases, Prague, Czechoslovakia Professor A. A. F. Massoud, Department of Preventive and Industrial Medicine. Fin Shams University, Cairo, Egypt Professor W. 0. Phoon. Department of Social Medicine and Public Health. Faculty of Medicine, University of Singapore. Singapore Mr V. Rose, National Institute for Occupational Safety and Health. Rockville, MD, USA Or S. Tarkowski. Department of Biochemistry. Institute of Occupational Medicine, Lodz, Poland Professor J. Teisinger. Institute of Hygiene and Epidemiology, Prague, Czechoslovakia (Chairman) .. Dr H. Thiele, Central Institute for Occupational Medicine, Berlin, German Democratic Republic Professor S. Yamaguchi, Department of Public Health. Isukuba University, School of Medicine, Niihari-Gun, Ibaraki ken, Japan Professor S. H. Zaidi, Industrial Toxicology Research Centre. Lucknnw. tndia Secretariat Dr. A. David. tnstitute of Hygiene and Epidemiology. Centre of tndustrial Hygiene and Occupational Diseases. Prague, Czechoslovakia (Notional Coordinotor and Co-Chairman) Dr M. A. El Batawi, Chief Medical Officer, Office of Occupational Health, World Health Organization, Geneva, Switzerland (Secretor;) ENVIRONMENTAL HEALTH CRITERIA