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Transcript of NITROBENZENE - who.int .iii CONTENTS ENVIRONMENTAL HEALTH CRITERIA FOR NITROBENZENE PREAMBLE xi...

This report contains the collective views of an international group ofexperts and does not necessarily represent the decisions or the stated policyof the United Nations Environment Programme, the International LabourOrganization or the World Health Organization.

Environmental Health Criteria 230

NITROBENZENE

First draft prepared by L. Davies, Office of Chemical Safety,Therapeutic Goods Administration, Australian Department ofHealth and Ageing, Canberra, Australia

Plese note that the pagination and layout of this webverson are not identical to those of the (to be) printeddocument

Published under the joint sponsorship of the United NationsEnvironment Programme, the International LabourOrganization and the World Health Organization, andproduced within the framework of the Inter-OrganizationProgramme for the Sound Management of Chemicals.

World Health OrganizationGeneva, 2003

The International Programme on Chemical Safety (IPCS), established in 1980,is a joint venture of the United Nations Environment Programme (UNEP), theInternational Labour Organization (ILO) and the World Health Organization (WHO). Theoverall objectives of the IPCS are to establish the scientific basis for assessment of therisk to human health and the environment from exposure to chemicals, throughinternational peer review processes, as a prerequisite for the promotion of chemical safety,and to provide technical assistance in strengthening national capacities for the soundmanagement of chemicals.

The Inter-Organization Programme for the Sound Management of Chemicals(IOMC) was established in 1995 by UNEP, ILO, the Food and Agriculture Organizationof the United Nations, WHO, the United Nations Industrial Development Organization,the United Nations Institute for Training and Research and the Organisation for EconomicCo-operation and Development (Participating Organizations), following recommendationsmade by the 1992 UN Conference on Environment and Development to strengthencooperation and increase coordination in the field of chemical safety. The purpose of theIOMC is to promote coordination of the policies and activities pursued by theParticipating Organizations, jointly or separately, to achieve the sound management ofchemicals in relation to human health and the environment.

WHO Library Cataloguing-in-Publication Data

Nitrobenzene.

(Environmental health criteria ; 230)

1.Nitrobenzenes - toxicity 2.Nitrobenzenes - adverse effects 3.Environmentalexposure 4.Risk assessment I.International Programme for Chemical Safety II.Series

ISBN 92 4 157230 0 (LC/NLM classification: QV 632)ISSN 0250-863X

World Health Organization 2003

All rights reserved. Publications of the World Health Organization can be obtainedfrom Marketing and Dissemination, World Health Organization, 20 Avenue Appia, 1211Geneva 27, Switzerland (tel: +41 22 791 2476; fax: +41 22 791 4857; email:bookorders@who.int). Requests for permission to reproduce or translate WHOpublications whether for sale or for noncommercial distribution should be addressedto Publications, at the above address (fax: +41 22 791 4806; email:permissions@who.int).

The designations employed and the presentation of the material in this publicationdo not imply the expression of any opinion whatsoever on the part of the World HealthOrganization concerning the legal status of any country, territory, city or area or of itsauthorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines onmaps represent approximate border lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers products does notimply that they are endorsed or recommended by the World Health Organization inpreference to others of a similar nature that are not mentioned. Errors and omissionsexcepted, the names of proprietary products are distinguished by initial capital letters.

The World Health Organization does not warrant that the information contained inthis publication is complete and correct and shall not be liable for any damages incurredas a result of its use.

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iii

CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FORNITROBENZENE

PREAMBLE xi

ACRONYMS AND ABBREVIATIONS xx

1. SUMMARY 1

1.1 Identity, physical and chemical properties, andanalytical methods 1

1.2 Sources of human and environmental exposure 11.3 Environmental transport, distribution and

transformation 21.4 Environmental levels and human exposure 41.5 Kinetics and metabolism 51.6 Effects on laboratory mammals and in vitro test

systems 61.7 Effects on humans 81.8 Effects on organisms in the environment 91.9 Hazard and risk evaluation 10

2. IDENTITY, PHYSICAL AND CHEMICALPROPERTIES, AND ANALYTICAL METHODS 12

2.1 Identity 122.2 Physical and chemical properties 122.3 Conversion factors in air 142.4 Analytical methods 14

2.4.1 Sampling and pretreatment 142.4.2 Analysis 15

2.4.2.1 Environmental monitoring 152.4.2.2 Biological monitoring 15

3. SOURCES OF HUMAN AND ENVIRONMENTALEXPOSURE 21

3.1 Natural occurrence 213.2 Anthropogenic sources 21

EHC 230: Nitrobenzene

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3.2.1 Production 213.2.2 Production processes 223.2.3 Production losses to the environment 233.2.4 Non-industrial sources 24

3.3 Uses 26

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTIONAND TRANSFORMATION 28

4.1 Transport and distribution between media 284.1.1 Air 284.1.2 Water 284.1.3 Soil and sediment 29

4.2 Abiotic degradation 314.2.1 Air 31

4.2.1.1 Direct photolysis 314.2.1.2 Indirect photolysis (photo-oxidation) 32

4.2.2 Water 344.2.2.1 Hydrolysis 344.2.2.2 Direct photolysis 344.2.2.3 Indirect photolysis (photo-oxidation) 34

4.2.3 Soil and sediment 354.3 Bioaccumulation 36

4.3.1 Aquatic species 364.3.2 Terrestrial plants 37

4.4 Biotransformation 384.4.1 Aerobic degradation 38

4.4.1.1 Biodegradation by non-acclimatedmicroorganisms 38

4.4.1.2 Biodegradation by acclimatedmicroorganisms 40

4.4.1.3 Degradation of nitrobenzene in soil 444.4.2 Anaerobic degradation 46

4.5 Ultimate fate following use 47

5. ENVIRONMENTAL LEVELS AND HUMANEXPOSURE 49

5.1 Environmental levels 495.1.1 Air 495.1.2 Water 50

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5.1.2.1 Industrial and waste treatmenteffluents 50

5.1.2.2 Surface water 525.1.2.3 Groundwater 535.1.2.4 Drinking-water 55

5.1.3 Sediments 555.1.4 Soils 555.1.5 Food 565.1.6 Occurrence in biota 56

5.2 General population exposure 565.3 Occupational exposure during manufacture,

formulation or use 57

6. KINETICS AND METABOLISM IN LABORATORYANIMALS AND HUMANS 59

6.1 Absorption 596.1.1 Oral exposure 596.1.2 Dermal exposure 596.1.3 Inhalation exposure 61

6.2 Distribution 616.2.1 Oral exposure 616.2.2 Dermal exposure 626.2.3 Inhalation exposure 62

6.3 Metabolic transformation 626.3.1 In vivo metabolic studies 626.3.2 In vitro and ex vivo metabolic studies 676.3.3 Biochemical and mechanistic considerations 686.3.4 Metabolism in erythrocytes 74

6.4 Elimination and excretion 786.4.1 Oral exposure 786.4.2 Dermal exposure 806.4.3 Inhalation exposure 80

6.5 Retention and turnover 816.5.1 Protein binding in vitro 816.5.2 Body burden and (critical) organ burden 81

6.6 Reaction with body components 816.7 Biomarkers of exposure 83

EHC 230: Nitrobenzene

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7. EFFECTS ON LABORATORY MAMMALS ANDIN VITRO TEST SYSTEMS 85

7.1 Single exposure 857.1.1 Oral 857.1.2 Dermal 867.1.3 Inhalation 877.1.4 Intraperitoneal 88

7.2 Short-term exposure 887.2.1 Oral 887.2.2 Dermal 917.2.3 Inhalation 947.2.4 Subcutaneous 96

7.3 Long-term toxicity and carcinogenicity 967.4 Mutagenicity and related end-points 103

7.4.1 DNA interactions 1037.4.2 Mutation 1047.4.3 Chromosomal effects 1067.4.4 Cell transformation 1067.4.5 Genotoxicity of nitrobenzene metabolites 107

7.5 Reproductive toxicity 1087.5.1 Effects on fertility 108

7.5.1.1 Oral 1087.5.1.2 Dermal 1107.5.1.3 Inhalation 110

7.5.2 Testicular toxicity 1127.5.2.1 In vitro studies 1127.5.2.2 In vivo studies 114

7.5.3 Embryotoxicity and teratogenicity 1167.6 Skin and eye irritation and sensitization 1177.7 Haematological toxicity 118

7.7.1 Oral 1187.7.2 Dermal 1227.7.3 Inhalation 122

7.8 Immunological effects 1237.9 Mechanisms of toxicity 126

7.9.1 Methaemoglobinaemia 1267.9.2 Splenic toxicity 1317.9.3 Renal toxicity 1327.9.4 Neurotoxicity 1337.9.5 Carcinogenicity 134

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7.10 Toxicity of metabolites and interactions 1397.10.1 Nitrophenol 1397.10.2 Aniline 1397.10.3 Interactions with other chemicals 140

8. EFFECTS ON HUMANS 141

8.1 Poisoning incidents 1418.1.1 Oral exposure 1418.1.2 Dermal exposure 1438.1.3 Inhalation exposure 144

8.2 Occupational exposure 1458.3 Haematological effects 1478.4 Hepatic effects 1488.5 Renal effects 1498.6 Neurological effects 1498.7 Other effects 1508.8 Subpopulations at special risk 150

9. EFFECTS ON OTHER ORGANISMS IN THELABORATORY AND FIELD 153

9.1 Microorganisms 1539.1.1 Toxicity to bacteria 1539.1.2 Toxicity to protozoa 1539.1.3 Toxicity to fungi 155

9.2 Aquatic organisms 1559.2.1 Toxicity to algae 1559.2.2 Toxicity to invertebrates 1559.2.3 Toxicity to fish 1599.2.4 Toxicity to amphibians 164

9.3 Terrestrial organisms 1649.3.1 Toxicity to plants 1649.3.2 Toxicity to earthworms 164

10. EVALUATION OF HUMAN HEALTH RISKS ANDEFFECTS ON THE ENVIRONMENT 165

10.1 Evaluation of human health risks 16510.1.1 Human exposure 165

10.1.1.1 General population exposure 165