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 Pro- gramme, the International Labour Organisa- tion, or the World Health Organization Environmental Health Criteria 36 FLUORINE AND FLUORIDES Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Orgaiization- World Health Organization 77, Geneva, 1984 The International Programme on Chemical Safety (IPCS) is a joint venture of the United Nations Environment Programme, the Interna- tional 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, experi- mental laboratory, and risk-assessment methods that could produce inter- nationally comparable results, and the development of manpower in the field of toxicology. Other activities carried out by IPCS include the devel- opment 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. ISBN 92 4 154096 6 ©World Health Organization 1984 Publications of the World Health Organization enjoy copyright protec- tion in accordance with the provisions of Protocol 2 of the Universal Copy- right Convention. For rights of reproduction or translation of WHO publica- tions, in part or in toto, application should be made to the Office of Publica- tions, 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 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 con- cerning 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 men- tioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. PRINTED IN FINLAND 84/6150 - VAMMALA - 6000 -3- CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR FLUORINE AND FLUORIDES Rage PREFACE ......................... 1. SUJINARY AND RECOMMENDATIONS FOR FURTHER RESEARCH 1.1 Summary .................... 1 1 1.1.1 Analytica1 methods ........... 11 1.1.2 Sources and magnitude of exposure . 11 1.1.3 Chemobiokinetics and metabolism ..... 12 1.1.4 Effect of fluoride on plants and animals ............... 12 1.1.5 Beneficial effects on human beings . 13 1.1.6 Toxic effects on human beings ...... 13 1.2 Recommendations for further research ...... 14 2. PROPERTIES AND ANALYTICAL METHODS .......... 15 2.1 Chemical and physical properties of fluorine and its compounds ............... 15 2.1.1 Fluorine ................ 15 2.1.2 Hydrogen fluoride ............ 16 2.1.3 Sodium fluoride and other alkali fluorides ................ 16 2.1.4 Fluorspar, cryolite, and fluorapatite . 17 2.1.5 Silicon tetrafluoride, fluorosilicic acid, and fluorosilicates ........ 17 2.1.6 Sodium monoflurophosphate ........ 18 2.1.7 Organic fluorides ............ 18 2.2 Determination of fluorine ........... 19 2.2.1 Sampling and sample preparation ..... 19 2.2.1.1 Air ............... 20 2.2.1.2 Soil and rocks .......... 20 2.2.1.3 Water .............. 21 2.2.1.4 Animal tissues .......... 21 2.2.1.5 Plants .............. 22 2.2.2 Separation and determination o.f fluoride 22 2.2.2.1 Colorimetric methods ....... 23 2.2.2.2 The fluoride selective electrode 23 2.2.2.3 Other methods .......... 24 3. FLUORIDE IN THE HUMAN ENVIRONMENT .......... 25 3.1 Fluoride in rocks and soil ........... 25 3.2 Fluoride in water ............... 25 -4-, Page 3.3 Airborne fluoride ...............26 3.4 Fluoride in food and beverages .........27 3.5 Total human intake of fluoride .........31 4. CHEMOBIOKINETICS AND METABOLISM ...........37 4.1 Absorption ................... 37 4.2 Retention and distribution ........... 37 4.2.1 The fluoride balance .......... 37 4.2.2 Blood .................. 38 4.2.3 Bone .................. 40 4.2.4 Teeth .................. 41 4.2.5 Soft tissues .............. 42 4.3 Excretion ................... 42 4.3.1 Urine .................. 42 4.3.2 Faeces ................. 43 4.3.3 Sweat .................. 44 4.3.4 Saliva ................. 44 4.3.5 Milk .................. 44 4.3.6 Transpiacental transfer ......... 44 4.4 Indicator media ................ 44 5. EFFECTS ON PLANTS AND ANIMALS ............ 46 5.1 Plants ..................... 46 5.2 Insects .................... 48 5.3 Aquatic animals ................ 48 5.4 Birds ..................... 49 5.4.1 Acute effects .............. 49 5.4.2 Chronic effects ............. 52 5.5 Mammals .................... 52 5.5.1 Acute effects .............. 52 5.5.1.1 Exposure to sodium fluoride . 52 5.5.1.2 Exposure to fluorine, hydrogen fluoride, or silicon tetrafluoride 54 5.5.2 Chronic effects on small laboratory animals ................. 55 5.5.3 Chronic effects on livestock ...... 56 5.6 Genotoxicity and carcinogenicity ........ 59 5.6.1 Genetic effects and other related end points in short-term tests ....... 59 5.6.2 Carcinogenicity in experimental animals ................. 60 5.7 Experimental caries .............. 60 5.8 Possible essential functions of fluorides . 60 -5-. Page 6. BENEFICIAL EFFECTS ON HUMAN BEINGS .........62 6.1 Effects of fluoride in drinking-water .....62 6.2 Cariostatic mechanisms .............66 6.3 Fluoride in caries prevention .........66 6.3.1 Fluoridated salt (NaCl) .........67 6.3.2 Fluoridated milk ............67 6.3.3 Fluoride tablets ............68 6.3.4 Topical application of fluorides . 68 6.4 Treatment of osteoporosis ...........69 7. TOXIC EFFECTS ON HUMAN BEINGS ............ 72 7.1 Acute toxic effects of fluoride salts ..... 72 7.2 Caustic effects of fluorine and hydrogen fluoride .................... 74 7.3 Chronic toxicity ................ 75 7.3.1 Occupational skeletal fluorosis ..... 75 7.3.2 Endemic skeletal fluorosis ....... 77 7.3.3 Dental fluorosis ............ 79 7.3.4 Effects on kidneys ........... 83 7.4 Carcinogenicity ................ 85 7.5 Teratogenicity ................. 85 7.6 Effecta on mortality patterns ......... 86 7.7 Allergy, hypersensitivity, and dermatological reactions ................... 87 7.8 Biochemical effects .............. 89 8. EVALUATION OF SIGNIFICANCE OF FLUORIDES IN THE ENVIRONMENT ................... 92 8.1 Relative contribution from air, food, and water to total human intake .......... 92 8.2 Doses necessary for beneficial effects in man 92 8.3 Toxic effects in man in relation to exposure . 93 8.3.1 Dental fluorosis ............ 93 8.3.2 Skeletal fluorosis ........... 93 8.3.3 Other effects .............. 94 8.4 Effects on plants and animals ......... 94 8.4.1 Plants ................. 94 8.4.2 Animals ................. 94 REFERENCES.......................96 -6- 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 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. 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 information may be considered in the event of updating and re-evaluation of the conclusions contained in the criteria documents. -7- IPCS TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR FLUORINE AND FLUORIDES Members Dr F. Berglund, Department of Medical Research, KabiVitrum Pharmaceuticals, Stockholm, Sweden Dr A.W. Davison, Department of Plant Biology, The University, Newcastle-Upon-Tyne, United Kingdom (Rapporteur) Professor C.O. Enwonwu, National Institute for Medical Research, Yaba, Lagos, Nigeria Professor W. Kiinzel, Stomatology Section, Erfurt Academy of Medicine, Democratic Republic of Germany Mr F. Murray, Department of Biological Sciences, University of Newcastle, New South Wales, Australia Professor M.D. Noweir, Occupational Health Department, High Institute of Public Health, Alexandria, Egypt (Chairman) Dr P. Phantunivanit, Faculty of Dentistry, Chulalongkorti University, Bangkok, Thailand Dr R.G. Scharnschula, WHO Collaborative Unit for Caries and Periodontal Disease Research, Institute of Dental Research, Sydney, Australia Professor Dr Ch. Schlatter, Swiss Federal Institute of Technology and University of Zurich, Institute of Toxicology, Schwerzenbach, Switzerland Dr D.R. Taves, Department of Radiation Biology and Biophysics,