Environmental Health Criteria 122 n-Hexane Please note that the layout and pagination of this web version are not identical with the printed version. Hexane, n- (EHC 122, 1991) INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 122 n-HEXANE This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organisation, or the World Health Organization. Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization First draft prepared by Dr. K. Chipman, University of Birmingham, United Kingdom World Health Orgnization Geneva, 1991 The International Programme on Chemical Safety (IPCS) 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 the development of epidemiological, experimental laboratory, and risk-assessment methods that could produce internationally comparable results, and the development 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 n-Hexane. (Environmental health criteria ; 122) Page 1 of 107 Hexane, n- (EHC 122, 1991) 1.Hexanes - adverse effects 2.Hexanes - toxicity I.Series ISBN 92 4 157122 5 (NLM Classification: QV 633) ISSN 0250-863X The World Health Organization welcomes requests for permission to reproduce 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 changes made to the text, plans for new editions, and reprints and translations already available. (c) World Health Organization 1991 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved. The designations employed and the presentation of the material in this publication 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 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. CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR n-HEXANE 1. SUMMARY 2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS 2.1. Identity 2.2. Physical and chemical properties 2.3. Conversion factors 2.4. Analytical methods 3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE 3.1. Natural occurrence 3.2. Production and uses 3.2.1. Production levels and processes 3.2.1.1 Production figures 3.2.1.2 Manufacturing processes 3.2.2. Uses 4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION 4.1. Transport and distribution between media 4.2. Biotransformation and photochemical reactivity 5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE 5.1. Environmental levels Page 2 of 107 Hexane, n- (EHC 122, 1991) 5.1.1. Air 5.1.2. Water 5.1.3. Food 5.2. Occupational exposure during manufacture, formulation, or use 6. KINETICS AND METABOLISM 6.1. Experimental animals 6.1.1. Absorption, distribution, metabolism, and excretion 6.1.2. Kinetics of 2,5-hexanedione 6.1.3. In vitro studies 6.1.4. Effects of other chemicals on n-hexane metabolism 6.2. Human beings 7. EFFECTS ON ORGANISMS IN THE ENVIRONMENT 8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS 8.1. Single exposures 8.1.1. Inhalation exposure 8.1.2. Oral administration 8.1.3. Dermal exposure 8.1.4. Parenteral administration 8.1.5. In vitro exposure 8.2. Short- and long-term exposures 8.2.1. Inhalation studies 8.2.1.1 Combined-exposure effects 8.2.1.2 Effects on the respiratory tract 8.2.1.3 Effects on the testes 8.2.1.4 Other effects 8.2.2. Oral studies 8.2.3. Dermal studies 8.2.4. In vitro studies 8.2.5. Parenteral studies 8.3. Reproduction, embryotoxicity, and teratogenicity 8.3.1. Teratogenicity studies 8.3.1.1 Inhalation studies 8.3.1.2 Oral 8.3.2. Fertility studies 8.4. Mutagenicity and related end-points 8.5. Carcinogenicity 8.5.1. Inhalation studies 8.5.2. Skin-painting studies 8.6. Neurotoxicity 8.6.1. Central nervous system effects 8.6.2. Peripheral nervous system effects 8.6.2.1 Clinical and morphological findings 8.6.2.2 Electrophysiological effects 8.6.2.3 Grip strength 8.7. Toxicity of n-hexane metabolites 9. EFFECTS ON MAN 9.1. Single exposures 9.2. Skin and eye irritation; sensitization 9.2.1. Skin irritation 9.2.2. Eye irritation 9.2.3. Skin sensitization 9.3. Short- and long-term exposures 9.3.1. Effects on the nervous system 9.3.1.1 Peripheral neuropathy Page 3 of 107 Hexane, n- (EHC 122, 1991) 9.3.1.2 Effects on vision and optic nerves 9.3.2. Effects on the kidney 9.3.3. Effects on other organs 10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT 10.1. Animal studies 10.1.1. Short- and long-term exposure 10.1.2. Genotoxicity 10.1.3. Carcinogenicity 10.1.4. Reproductive effects 10.2. Human studies 10.2.1. Effects on the nervous system 10.2.2. Other effects 10.3. Environmental effects 11. RECOMMENDATIONS 11.1. Human health protection 11.2. Environmental protection 12. FURTHER RESEARCH REFERENCES RESUME EVALUATION DES RISQUES POUR LA SANTE HUMAINE ET DES EFFETS SUR L'ENVIRONNEMENT RECOMMANDATIONS RECHERCHES A EFFECTUER RESUMEN EVALUACION DE LOS RIESGOS PARA LA SALUD HUMANA Y DE LOS EFECTOS EN EL MEDIO AMBIENTE RECOMENDACIONES NUEVAS INVESTIGACIONES WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR n-HEXANE Members Professor E.A. Bababunmi, Department of Tropical Paediatrics, Liverpool School of Tropical Medicine, Liverpool, United Kingdom (Rapporteur) Dr M. Cikrt, Centre of Industrial Hygiene and Occupational Diseases, Institute of Hygiene and Epidemiology, Prague, Czechoslovakia (Vice-Chairman) Dr S. Dobson, Pollution and Ecotoxicology Section, Institute of Terrestrial Ecology, Monks Wood Experimental Station, Huntingdon, United Kingdom Professor C.L. Galli, Toxicology Laboratory, Institute of Pharmacological Sciences, University of Milan, Milan, Italy (Chairman) Page 4 of 107 Hexane, n- (EHC 122, 1991) Dr S.D. Gangolli, British Industrial Biological Research Association, Carshalton, Surrey, United Kingdom Dr C. Konantakieti, Technical Division, Food and Drug Administration, Ministry of Public Health, Bangkok, Thailand Dr O. Ladefoged, Laboratory of Pathology, Institute of Toxicology, National Food Agency of Denmark, Ministry of Health, Soborg, Denmark Professor A. Massoud, Department of Community Environmental and Occupational Medicine, Ainshams Faculty of Medicine, Cairo, Egypt Dr V. Riihimäki, Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland Observer Dr H.P.A. Illing, Health and Safety Executive, Bootle, Merseyside, United Kingdom Secretariat Dr P.G. Jenkins, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland Ms B. Labarthe, International Register of Potentially Toxic Chemicals, United Nations Environment Programme, Geneva, Switzerland Dr E. Smith, International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland (Secretary) NOTE TO READERS OF THE CRITERIA DOCUMENTS Every effort has been made to present information in the criteria monographs as accurately as possible without unduly delaying their publication. In the interest of all users of the environmental health criteria monographs, readers are kindly requested to communicate any errors that may have occurred to the Manager of the International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland, in order that they may be included in corrigenda, which will appear in subsequent volumes. * * * A detailed data profile and a legal file can be obtained from the International Register of Potentially Toxic Chemicals, Palais des Nations, 1211 Geneva 10, Switzerland (Telephone No. 7988400 or 7985850). ENVIRONMENTAL HEALTH CRITERIA FOR n-HEXANE A WHO Task Group on Environmental Health Criteria for n-Hexane met in Carshalton, United Kingdom, from 12 to 16 March 1990. Dr E.M. Smith opened the meeting and welcomed the participants on behalf of the heads of the three IPCS cooperating organizations (UNEP/ILO/WHO). The Task Group reviewed and revised the draft criteria document and made an evaluation of the health risks of Page 5 of 107 Hexane, n- (EHC 122, 1991) exposure to n-hexane. The first draft of this document was prepared by Dr K. Chipman, University of Birmingham, United Kingdom. The second draft was also prepared by Dr Chipman, incorporating comments received following circulation of the first draft to IPCS contact points for Environmental Health Criteria monographs. Particularly valuable comments on the draft were made by the National Food Agency, Denmark, the National Institute of Public Health and Environmental Protection, The Netherlands, the European Chemical Industry Ecology and Toxicology Centre (ECETOC), and the US Environmental Protection Agency, National Institute of Environmental Health Sciences, Food and Drug Administration, and Centers for Disease Control. Dr E.M. Smith and Dr P.G. Jenkins, both members of the IPCS Central Unit, were responsible for the overall scientific content and technical editing, respectively, of this monograph.