Critical Appraisal of the Setting and Implementation of Indoor

338 Pages·2005·2.74 MB·English

Final Report
January, 2005

Critical Appraisal of the Setting and Implementation of Indoor Exposure
Limits in the EU

The INDEX project

Institute for Health and Consumer Protection
Physical and Chemical Exposure Unit
I-21020 Ispra (VA), Italy
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Legal notice

Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use which
might be made of the following information.

Foreword

In the past decades a large number of studies have indicated the presence of many different compounds belonging to a
variety of chemical classes in indoor environments (buildings, homes). The presence of these chemicals in indoor air is
the result of infiltration of polluted outdoor air and of emissions from various indoor sources, including building
materials, activities of the occupants, consumer products, smoking etc.

For many of these chemicals, the risk to human health and comfort is almost totally unknown and difficult to predict
because of lack of toxicological data and information on the dose-response characteristics in humans or animal models.
On the other hand, a full toxicological testing as requested by the “existing chemicals” legislation is difficult to
accomplish for these compounds, because it would involve investigation of acute and subacute toxicity, mutagenicity,
carcinogenicity and reproductive toxicity according to testing protocols that are complex, time-consuming and
expensive. Moreover, the EU policy on limitation of unnecessary animal testing further limits the possibility of
advocating a generalized animal testing of these chemicals.

The result of this situation is that there is an objective difficulty in regulating the presence of these substances in indoor
air principally because of the absence of adequate hazard and risk assessment. There is therefore an urgent need to
develop a strategy for the identification of priorities in testing, assessment and regulation.

In the frame of the INDEX project the existing knowledge worldwide has been assessed on
- type and levels of chemicals in indoor air and
- available toxicological information to allow the assessment of risk to health and comfort.

The collection and evaluation of the aforementioned information within the frame of the INDEX project shall contribute
to develop a strategy for prioritization in assessment and regulation of chemicals in indoor environments.

The Steering Committee
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Organisation responsible of the project: European Commission, Joint Research Centre, Institute for Health and
Consumer Protection, Physical and Chemical Exposure Unit, Ispra, Italy (JRC/IHCP/PCE).

Project leader: Dr. Dimtrios Kotzias, JRC/IHCP/PCE

Sources of funding: DG Consumer Protection (SANCO) and JRC/IHCP/PCE

Sub-contractors: University of Milan, Department of Occupational Health, Unit Ospedale Luigi Sacco, Milan, Italy
National Public Health Institute (KTL), Kuopio, Finland

Preparation of documents: All working drafts and this final report were prepared by the Joint Research Centre
(Institute for Health and Consumer Protection, Physical and Chemical Exposure Unit, JRC), the University of Milan
(Department of Occupational Health, Unit Ospedale Luigi Sacco, UNIMI), the National Public Health Institute
(Department of Environmental Hygiene, Kuopio, Finland, KTL) and with the individual contributions and advice in the
course of the work from members of the Steering Committee.

Final drafting:

Hazard Identification / Exposure Assessment:
Dr. Kimmo Koistinen and Dr. Dimitrios Kotzias (JRC)

Dose/Response Assessment / Risk Characterization:
Christian Schlitt, Dr. Paolo Carrer and Prof. Marco Maroni (UNIMI)

Risk Management:
Prof. Matti J. Jantunen (KTL)

Date of last literature search: September 2004

Steering Committee Members:
Dr. Christian Cochet Centre Scientifique et Technique du Bâtiment, Division Santé–Bâtiment,
Marne la Vallée, France

Prof. Matti J. Jantunen KTL, Department of Environmental Hygiene, Kuopio, Finland

Dr. Stylianos Kephalopoulos European Commission, Joint Research Centre, Institute for Health and
Consumer Protection, Physical and Chemical Exposure Unit, Ispra, Italy

Dr. Séverine Kirchner Centre Scientifique et Technique du Bâtiment, Division Santé–Bâtiment,
Marne la Vallée, France

Prof. Thomas Lindvall Karolinska Institute, Institute of Environmental Medicine, Stockholm,
Sweden

Prof. Marco Maroni Università di Milano, Department of Occupational Health, Unit Ospedale
Luigi Sacco, Milan, Italy

Dr. James P. McLaughlin University College Dublin, Department of Physics, Dublin, Ireland

Prof. Lars Mølhave Aarhus Universitet, Institut for Miljø– og Arbejdsmedicin, Århus, Denmark

Prof. Eduardo de Oliveira Fernandes Universidade do Porto, Departamento de Engenharia Mecânica, Faculdade
de Engenharia, Porto, Portugal

Prof. Bernd Seifert Umweltbundesamt, Abteilung Umwelthygiene, Berlin, Germany
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Contents

Foreword...........................................................................................................................................................................................................................2
Contents............................................................................................................................................................................................................................4
Executive Summary...........................................................................................................................................................9
Introduction and objectives..........................................................................................................................................................................................9
Methodology................................................................................................................................................................................................................9
Risk assessment of the selected compounds.............................................................................................................................................................10
Risk management tools..............................................................................................................................................................................................14
Recommendations and management options............................................................................................................................................................14
1. Introduction..................................................................................................................................................................16
2. Objectives ....................................................................................................................................................................17
3. Methodology.................................................................................................................................................................18
3.1 Risk Assessment.......................................................................................................................................................................................................18
3.1.1 Selection of Indoor Air Chemicals for Consideration (Hazard Identification).....................................................................................................18
3.1.2 Exposure Assessment............................................................................................................................................................................................21
3.1.3 Dose/Response Assessment...................................................................................................................................................................................21
3.1.4 Risk Characterization and prioritisation of chemicals..........................................................................................................................................25
3.2 Risk Management.....................................................................................................................................................................................................26
4. Risk Assessment of the selected chemicals................................................................................................................28
Formaldehyde...................................................................................................................................................................29
1. Compound Identification............................................................................................................................................................................................29
2. Physical and Chemical Properties..............................................................................................................................................................................29
3. Indoor Air Exposure Assessment...............................................................................................................................................................................29
Emission sources........................................................................................................................................................................................................29
Indoor air and exposure concentrations.....................................................................................................................................................................30
4. Toxicokinetics.............................................................................................................................................................................................................34
Absorption..................................................................................................................................................................................................................34
Distribution................................................................................................................................................................................................................34
Metabolism and elimination......................................................................................................................................................................................34
5. Health effects..............................................................................................................................................................................................................34
Effects of short-term exposure...................................................................................................................................................................................34
Effects of long-term exposure (noncancer)...............................................................................................................................................................38
Carcinogenic effects..................................................................................................................................................................................................42
Interactions with other chemicals..............................................................................................................................................................................45
Odour perception.......................................................................................................................................................................................................46
Summary of Formaldehyde Dose Response Assessment.........................................................................................................................................47
6. Risk Characterization..................................................................................................................................................................................................49
Health hazard evaluation...........................................................................................................................................................................................49
Percentage of population exposed beyond given threshold levels............................................................................................................................49
Cancer risk evaluation...............................................................................................................................................................................................49
Comments..................................................................................................................................................................................................................49
Result.........................................................................................................................................................................................................................50
Carbon monoxide.............................................................................................................................................................51
1. Compound identification............................................................................................................................................................................................51
2. Physical and Chemical properties...............................................................................................................................................................................52
3. Indoor Air Exposure assessment................................................................................................................................................................................52
Indoor air and exposure concentrations.....................................................................................................................................................................52
Emission sources........................................................................................................................................................................................................54
4. Toxicokinetics.............................................................................................................................................................................................................59
Endogenous sources of carbon monoxide:................................................................................................................................................................59
Absorption..................................................................................................................................................................................................................59
Elimination.................................................................................................................................................................................................................61
5. Health effects..............................................................................................................................................................................................................61
Effects of short-term exposure...................................................................................................................................................................................61
Effects of long-term exposure...................................................................................................................................................................................68
Carcinogenic and genotoxic effects...........................................................................................................................................................................70
Summary of Carbon Monoxide Dose Response Assessment...................................................................................................................................71
6. Risk Characterization..................................................................................................................................................................................................72
Health hazard evaluation...........................................................................................................................................................................................72
Percentage of population exposed beyond given threshold CO levels.....................................................................................................................73
Comments..................................................................................................................................................................................................................73
Result.........................................................................................................................................................................................................................75
Nitrogen dioxide...............................................................................................................................................................76
1. Compound identification............................................................................................................................................................................................76
2. Physical and Chemical properties...............................................................................................................................................................................76
3. Indoor Air Exposure assessment................................................................................................................................................................................76
Emission sources........................................................................................................................................................................................................76
Indoor air and exposure concentrations.....................................................................................................................................................................77
4. Toxicokinetics.............................................................................................................................................................................................................80
Absorption..................................................................................................................................................................................................................80
Distribution................................................................................................................................................................................................................80
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Elimination.................................................................................................................................................................................................................80
5. Health effects..............................................................................................................................................................................................................80
Effects of short-term exposure...................................................................................................................................................................................80
Effects of long-term exposure...................................................................................................................................................................................85
Carcinogenic and mutagenic effects..........................................................................................................................................................................88
Interaction with other chemicals................................................................................................................................................................................88
Odour perception.......................................................................................................................................................................................................89
Summary of Nitrogen dioxide Dose Response Assessment.....................................................................................................................................90
6. Risk characterization...................................................................................................................................................................................................91
Health hazard evaluation of short- and long-term exposure.....................................................................................................................................91
Exposure data of relevance for the European population.........................................................................................................................................91
Result.........................................................................................................................................................................................................................93
Benzene ....................................................................................................................................................................94
1. Compound identification............................................................................................................................................................................................94
2. Physical and Chemical properties...............................................................................................................................................................................94
3. Indoor Air Exposure assessment................................................................................................................................................................................94
Emission sources........................................................................................................................................................................................................94
Indoor air and exposure concentrations.....................................................................................................................................................................95
4. Toxicokinetics.............................................................................................................................................................................................................98
Absorption..................................................................................................................................................................................................................98
Distribution................................................................................................................................................................................................................98
Metabolism and elimination......................................................................................................................................................................................98
5. Health effects..............................................................................................................................................................................................................99
Effects of short-term exposure...................................................................................................................................................................................99
Effects of long-term exposure (noncancer).............................................................................................................................................................104
Genotoxic effects.....................................................................................................................................................................................................108
Carcinogenic effects................................................................................................................................................................................................109
Susceptible population.............................................................................................................................................................................................113
Interactions with other chemicals............................................................................................................................................................................114
Odour perception.....................................................................................................................................................................................................114
Summary of Benzene Dose Response Assessment.................................................................................................................................................115
6. Risk Characterization................................................................................................................................................................................................117
Cancer risk evaluation.............................................................................................................................................................................................117
Population cancer risk estimates of benzene-induced leukemia.............................................................................................................................117
Health hazard evaluation (noncancer).....................................................................................................................................................................119
Comments................................................................................................................................................................................................................120
Result.......................................................................................................................................................................................................................121
Naphthalene ..................................................................................................................................................................122
1. Compound identification..........................................................................................................................................................................................122
2. Physical and Chemical properties.............................................................................................................................................................................122
3. Indoor Air Exposure assessment..............................................................................................................................................................................122
Indoor air and exposure concentrations...................................................................................................................................................................122
4. Toxicokinetics...........................................................................................................................................................................................................125
Absorption................................................................................................................................................................................................................125
Distribution..............................................................................................................................................................................................................125
Metabolism and elimination....................................................................................................................................................................................125
5. Health effects............................................................................................................................................................................................................126
Effects of short-term exposure.................................................................................................................................................................................126
Effects of long-term exposure (noncancer).............................................................................................................................................................128
Genotoxicity.............................................................................................................................................................................................................134
Carcinogenic potential.............................................................................................................................................................................................135
Interactions with other chemicals............................................................................................................................................................................135
Odour perception.....................................................................................................................................................................................................135
Summary of Naphthalene Dose Response Assessment..........................................................................................................................................137
6. Risk Characterization................................................................................................................................................................................................138
Health hazard evaluation of short-term exposure....................................................................................................................................................138
Health hazard and cancer risk evaluation of long-term exposure...........................................................................................................................138
Result.......................................................................................................................................................................................................................138
Relevance of EU-population exposure to naphthalene...........................................................................................................................................139
Acetaldehyde ..................................................................................................................................................................140
1. Compound identification..........................................................................................................................................................................................140
2. Physical and Chemical properties.............................................................................................................................................................................140
3. Indoor Air Exposure assessment..............................................................................................................................................................................140
Contribution of inhalation exposure to total exposure............................................................................................................................................140
Emission sources......................................................................................................................................................................................................141
Indoor air and exposure concentrations...................................................................................................................................................................141
4. Toxicokinetics...........................................................................................................................................................................................................143
Absorption................................................................................................................................................................................................................143
Distribution..............................................................................................................................................................................................................143
Metabolism and elimination....................................................................................................................................................................................143
5. Health effects............................................................................................................................................................................................................144
Effects of short-term exposure.................................................................................................................................................................................144
Effects of long-term exposure.................................................................................................................................................................................145
Carcinogenic potential.............................................................................................................................................................................................150
Genotoxicity.............................................................................................................................................................................................................150
Interactions with other chemicals............................................................................................................................................................................151
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Odour perception.....................................................................................................................................................................................................152
Summary of Acetaldehyde Dose Response Assessment.........................................................................................................................................153
6. Risk Characterization................................................................................................................................................................................................154
Cancer risk and health hazard evaluation................................................................................................................................................................154
Percentage of population exposed beyond given threshold levels..........................................................................................................................154
Comments................................................................................................................................................................................................................154
Result.......................................................................................................................................................................................................................155
Toluene ..................................................................................................................................................................156
1. Compound identification..........................................................................................................................................................................................156
2. Physical and Chemical properties.............................................................................................................................................................................156
3. Indoor Air Exposure assessment..............................................................................................................................................................................156
Emission sources......................................................................................................................................................................................................156
Indoor air and exposure concentrations...................................................................................................................................................................156
4. Toxicokinetics...........................................................................................................................................................................................................160
Absorption................................................................................................................................................................................................................160
Distribution..............................................................................................................................................................................................................160
Metabolism and elimination....................................................................................................................................................................................161
5. Health effects............................................................................................................................................................................................................162
Effects of short-term exposure.................................................................................................................................................................................162
Effects of long-term exposure.................................................................................................................................................................................164
Carcinogenic potential.............................................................................................................................................................................................170
Genotoxicity.............................................................................................................................................................................................................170
Interactions with other chemicals............................................................................................................................................................................170
Odour perception.....................................................................................................................................................................................................171
Summary of Toluene Dose Response Assessment..................................................................................................................................................172
6. Risk Characterization................................................................................................................................................................................................173
Health hazard evaluation of short- and long-term exposure...................................................................................................................................173
Relevance for the EU-population exposure.............................................................................................................................................................174
Result.......................................................................................................................................................................................................................174
Xylenes (ortho-, meta- and para-).................................................................................................................................175
1. Compound identification..........................................................................................................................................................................................175
2. Physical and Chemical properties.............................................................................................................................................................................175
3. Indoor Air Exposure assessment..............................................................................................................................................................................175
Emission sources......................................................................................................................................................................................................175
Indoor air and exposure concentrations...................................................................................................................................................................176
4. Toxicokinetics...........................................................................................................................................................................................................181
Absorption................................................................................................................................................................................................................181
Distribution..............................................................................................................................................................................................................181
Metabolism and elimination....................................................................................................................................................................................181
5. Health effects............................................................................................................................................................................................................183
Differences among individual xylene isomers........................................................................................................................................................183
Effects of short-term exposure.................................................................................................................................................................................183
Effects of long-term exposure.................................................................................................................................................................................185
Carcinogenic potential and genotoxicity.................................................................................................................................................................190
Interactions with other chemicals............................................................................................................................................................................190
Odour perception.....................................................................................................................................................................................................191
Summary of Xylenes Dose Response Assessment..................................................................................................................................................193
6. Risk Characterization................................................................................................................................................................................................194
Health hazard evaluation of short- and long-term exposure...................................................................................................................................194
Relevance of EU-population exposure to xylenes..................................................................................................................................................194
Result.......................................................................................................................................................................................................................195
7. Aromatic compounds: Comparison of relevant data................................................................................................................................................196
The reciprocal calculation approach for mixtures...................................................................................................................................................196
Styrene ..................................................................................................................................................................198
1. Compound identification..........................................................................................................................................................................................198
2. Physical and Chemical properties.............................................................................................................................................................................198
3. Indoor Air Exposure assessment..............................................................................................................................................................................198
Emission sources......................................................................................................................................................................................................198
Indoor air and exposure concentrations...................................................................................................................................................................199
4. Toxicokinetics...........................................................................................................................................................................................................200
Absorption................................................................................................................................................................................................................200
Distribution..............................................................................................................................................................................................................200
Metabolism and elimination....................................................................................................................................................................................200
5. Health effects............................................................................................................................................................................................................201
Effects of short-term exposure.................................................................................................................................................................................201
Effects of long-term exposure (noncancer).............................................................................................................................................................203
Macromolecular adducts and genetic toxicity.........................................................................................................................................................209
Carcinogenic potential.............................................................................................................................................................................................211
Interactions with other chemicals............................................................................................................................................................................213
Odour perception.....................................................................................................................................................................................................213
Summary of Styrene Dose Response Assessment..................................................................................................................................................214
6. Risk Characterization................................................................................................................................................................................................215
Health hazard and cancer risk evaluation of short- and long-term exposure..........................................................................................................215
Relevance of EU-population exposure to styrene...................................................................................................................................................216
Result.......................................................................................................................................................................................................................216
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Ammonia ..................................................................................................................................................................217
1. Compound identification..........................................................................................................................................................................................217
2. Physical and Chemical properties.............................................................................................................................................................................217
3. Indoor Air Exposure assessment..............................................................................................................................................................................217
Indoor air and exposure concentrations...................................................................................................................................................................217
4. Toxicokinetics...........................................................................................................................................................................................................219
Absorption................................................................................................................................................................................................................219
Distribution..............................................................................................................................................................................................................219
Metabolism and elimination....................................................................................................................................................................................219
5. Health effects............................................................................................................................................................................................................220
Effects of short-term exposure.................................................................................................................................................................................220
Effects of long-term exposure.................................................................................................................................................................................223
Reproductive, mutagenic and carcinogenic effects.................................................................................................................................................227
Interactions with other chemicals............................................................................................................................................................................227
Odour perception.....................................................................................................................................................................................................227
Summary of Ammonia Dose Response Assessment...............................................................................................................................................229
6. Risk Characterization................................................................................................................................................................................................230
Health hazard evaluation of short-term exposure....................................................................................................................................................230
Health hazard evaluation of long-term exposure.....................................................................................................................................................230
Relevance of EU-population exposure to Ammonia...............................................................................................................................................230
Result.......................................................................................................................................................................................................................230
Limonene ..................................................................................................................................................................231
1. Compound identification..........................................................................................................................................................................................231
2. Physical and Chemical properties.............................................................................................................................................................................231
3. Indoor Air Exposure assessment..............................................................................................................................................................................231
Contribution of inhalation exposure to total exposure............................................................................................................................................231
Terpene/ozone reaction products.............................................................................................................................................................................232
Indoor air and exposure concentrations...................................................................................................................................................................232
4. Toxicokinetics...........................................................................................................................................................................................................234
Absorption................................................................................................................................................................................................................234
Distribution..............................................................................................................................................................................................................234
Metabolism and elimination....................................................................................................................................................................................234
5. Health effects............................................................................................................................................................................................................235
Effects of short-term exposure.................................................................................................................................................................................235
Effects of long-term exposure.................................................................................................................................................................................236
Carcinogenic and genotoxic effects.........................................................................................................................................................................237
Interactions with other chemicals............................................................................................................................................................................238
Odour perception.....................................................................................................................................................................................................238
Summary of Limonene Dose Response Assessment..............................................................................................................................................239
6. Risk Characterization................................................................................................................................................................................................240
Health hazard evaluation of long-term exposure.....................................................................................................................................................240
Relevance of EU-population exposure to limonene................................................................................................................................................240
Result.......................................................................................................................................................................................................................240
alpha-Pinene ..................................................................................................................................................................241
1. Compound identification..........................................................................................................................................................................................241
2. Physical and Chemical properties.............................................................................................................................................................................241
3. Indoor Air Exposure assessment..............................................................................................................................................................................242
Terpene/ozone reaction products.............................................................................................................................................................................242
Indoor air and exposure concentrations...................................................................................................................................................................242
4. Toxicokinetics...........................................................................................................................................................................................................243
Absorption................................................................................................................................................................................................................243
Distribution..............................................................................................................................................................................................................243
Metabolism and elimination....................................................................................................................................................................................243
5. Health effects............................................................................................................................................................................................................244
Effects of short-term exposure.................................................................................................................................................................................244
Effects of long-term exposure.................................................................................................................................................................................245
Carcinogenic and genotoxic potential.....................................................................................................................................................................245
Interactions with other chemicals............................................................................................................................................................................246
Odour perception.....................................................................................................................................................................................................246
Summary of alpha-Pinene Dose Response Assessment...........................................................................................................................................247
6. Risk Characterization................................................................................................................................................................................................248
Health hazard evaluation of long-term exposure.....................................................................................................................................................248
Relevance of EU-population exposure to α-Pinene................................................................................................................................................248
Result.......................................................................................................................................................................................................................248
5. Risk management tools..............................................................................................................................................249
6. Recommendations and management options.........................................................................................................252
6.1 High priority chemicals..........................................................................................................................................................................................252
6.2 Second priority chemicals.......................................................................................................................................................................................253
6.3 Chemicals requiring further research with regard to human exposue or dose response........................................................................................254

Annex 1. Phase 1: Exposure and dose-response data for indoor air pollutants collected in the literature
review......................................................................................................................................................255
Annex 2. Phase 2: The selection of compounds to the further analysis...........................................................264
Annex 3. Phase 3: Compounds selected into the detailed risk assessment......................................................271
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Annex 4. The EXPOLIS study: parameters describing the indoor air concentration distributions
plotted to the graphs of this report......................................................................................................276
Annex 5. The National Survey of air pollutants in English homes: parameters describing the indoor
air concentration distributions plotted to the graphs of this report................................................277
Annex 6. The French National Survey on Indoor Air Quality (preliminary results from the ongoing
project): parameters describing the indoor air concentration distributions plotted to the
graphs of this report (Golliot et al 2003, Kirchner 2004)................................................................278
Annex 7. Relevant National and International Guidelines and Recommendations.......................................279

Bibliographic references...............................................................................................................................................281
References in introductory chapters (chapters 1 to 4)..................................................................................................................................................281
References by compounds (chapter 4)..........................................................................................................................................................................282
Formaldehyde..........................................................................................................................................................................................................282
Carbon monoxide.....................................................................................................................................................................................................288
Nitrogen dioxide......................................................................................................................................................................................................292
Benzene....................................................................................................................................................................................................................297
Naphthalene.............................................................................................................................................................................................................300
Acetaldehyde............................................................................................................................................................................................................304
Toluene.....................................................................................................................................................................................................................309
Xylenes.....................................................................................................................................................................................................................315
Styrene.....................................................................................................................................................................................................................321
Ammonia..................................................................................................................................................................................................................327
Limonene.................................................................................................................................................................................................................331
alpha-Pinene.............................................................................................................................................................................................................334
References in Annex 1, 2 and 3....................................................................................................................................................................................336
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Executive Summary

Introduction and objectives

The INDEX project (Critical Appraisal of the Setting and Implementation of Indoor exposure Limits in the EU) started
in December 2002 and had a duration of two years, until December 2004.The project was financially supported by DG
SANCO and it was coordinated and carried out by the JRC in collaboration with a Steering Committee of leading
European experts in the area of indoor air pollution. Scope of INDEX was to identify priorities and to assess the needs
for a Community strategy and action plan in the area of indoor air pollution by:
- setting up a list of compounds to be regulated in indoor environments with priority on the basis of health
impact criteria
- providing suggestions and recommendations on potential exposure limits for these compounds, and
- providing information on links with existing knowledge, ongoing studies, legislation etc. at world scale.

Methodology

The main steps to be followed in the project as they have been defined by the Steering Committee were:
- literature review (step 1)
- setting up criteria to select compounds (step 2)
- review of exposure and dose/response data (step 3)
- risk characterization of the selected compounds (step 4)
- prioritisation of the selected compounds (step 5) and
- recommendations and risk management options on potential exposure limits (step 6)

In the first step the world literature was reviewed to collect background information on exposure concentrations and
dose/response data of the chemical pollutants that have strong indoor sources. In the second step, the Steering
Committee has defined the criteria for the selection of pollutants for further risk analysis. After careful examination of
exposure and toxicological dose response data (step 3), the Steering Committee ended up to a short list of pollutants that
were selected for the risk characterization (step 4). The compounds that probably cause the highest health risk in
European population according to the risk characterization were prioritized (step 5). Finally, recommendations and risk
management options on European exposure limits should be given for a few selected compounds (step 6).

In order to accomplish with the tasks mentioned above the Steering Committee was divided into two working groups,
one for exposure assessment and one for dose/response assessment.

Exposure to selected indoor air pollutants was estimated by reviewing exposure data collected from scientific literature,
from available databases, and by personal communications. The aim of this work was to summarise prevailing indoor
air and personal exposure concentrations of these compounds in Europe and also worldwide. Results from population-
based studies have been preferred to be able to generalise the results from studied individuals to larger populations,
targeting to assess exposures of all the Europeans. Considering the fact that no new data could be generated in this
project, the steering group defined the following criteria to be able to select the chemical compounds to the risk
analyses:

1. Only single compounds will be considered
2. The compound should have common indoor sources, which dominate the exposures of at least significant fraction
of the population
3. The compound should have known health effects.

It was also decided that compounds, which have been regulated by specific guidelines or regulations would be excluded
from theses analyses. For example, radon and tobacco smoke were excluded from the risk assessment process due to
these criteria.

In preparing the dose-response assessment fact sheets of the selected chemicals, information were retrieved from
scientific literature (mainly by electronic search), comprehending toxicological reviews of leading health organizations,
risk evaluation documents and available databases. In addition, Toxline and Medline were searched for relevant
scientific communications published up to September 2004.

Nearly all key-studies referred to in the present assessment, establishing effect levels for appropriate toxicological
endpoints, are those selected by health organizations for the derivation of health based limits of exposure or among risk
The INDEX project Final report 10
assessment requirements. Although not specifically addressing health hazards and risks associated with indoor air
exposure, i.e. not being designed for the expression of effects at lowermost exposure concentrations, nearly all studies
were aimed at identifying the most sensitive endpoint considered to be of relevance to humans. Where relevant, studies
conducted on susceptible sub-populations (e.g. asthmatics, infants, children, pregnant women etc.) were quoted and
taken into consideration in the risk characterization.

In the final step of the general risk assessment process, the incidence of health hazards and risks in the European
population, associated with indoor exposure to individual chemicals, was estimated. Limits of exposure (ELs, following
short- and long-term exposure) were derived for each chemical after selection of a critical study describing the
appropriate toxicological endpoint and by applying the “no-observed-adverse-effect level (NOAEL) / assessment factor
(AS)” approach. Where no NOAEL observation was documented, a lowest-observed-adverse-effect level (LOAEL) was
taken and an additional assessment factor of 10 used for EL derivation. Only for one compound (benzene) the
characterization was based on population cancer risk estimation. Where supported by scientific evidence, susceptible
subpopulations were accounted for, in particular: asthmatic individuals, infants, children, individuals with heart
diseases, pregnant women, individuals with enzyme deficiencies.

On the basis of the available information and after careful examination of the existing data, the steering committee
finally decided to include into a detailed assessment 14 out of initial 41 candidate compounds (phase 4) i.e.:
acetaldehyde, alpha-pinene, benzene, carbon monoxide, d-limonene, formaldehyde, meta-and para xylene, ortho-
xylene, naphthalene, ammonia, nitrogen dioxide, styrene and toluene.

Risk assessment of the selected compounds

Information from the exposure assessment (Chapters 1-3) and toxicity assessment (Chapters 4-5) were integrated and a
risk characterization (Chapter 6) performed on each chemical. Based on the conclusions of the assessments and on the
completeness of individual databases, a priority ranking was arranged with the 14 chemicals assigned to three groups as
given hereafter.

Group 1: High priority chemicals

Formaldehyde : Because of its high chemical reactivity, formaldehyde is the most important sensory irritant
among the chemicals assessed in the present report. Due to being ubiquitous pollutant in
indoor environments and to the increasing evidence indicating that children may be more
sensitive to formaldehyde respiratory toxicity than adults it is considered a chemical of
concern at levels exceeding 1 µg/m3, a concentration more or less corresponding with the
background level in rural areas. Results from available exposure data, although limited,
confirm that almost the entire population is exposed indoors at levels (Median level±sd: 26±6
µg/m3; 90th±sd: 59±7 µg/m3; N = 6) higher than this background level, here established as
the limit of exposure, with at least 20% of the European population exposed at levels
exceeding the no-observed-effect-level (NOAEL: 30 µg/m3). Within the concentration range
measured, mild irritation of the eyes could be experienced by the general population as well
as the odour perceived above 30 µg/m3.
Reported formaldehyde concentrations were lower (99th < 150 µg/m3) than a presumed
threshold for cytotoxic damage to the nasal mucosa (about 1 mg/m3) and hence
considered low enough to avoid any significant risk of upper respiratory tract cancer in
humans. The last statement could be subjected to changes due to the current IARC
revision of the carcinogenicity of formaldehyde.

Carbon monoxide : Available exposure data confirm that Carbon Monoxide (CO) sources in EU-residences are
contributing to short-term rather than to long-term exposures. Personal exposure outcomes
averaged over 1-hour were considered of moderate concern even for the most susceptible
subpopulations. Nevertheless, uncertainties resulting from the predictive capabilities of the
CFK-model* in individuals exposed at low CO concentrations and its applicability to
sensitive subpopulations, suggest that about 10% of the general non-smoking population
experience CO levels which could be hazardous for individuals with heart diseases. Increased
exposures could be expected for residences in the vicinity of busy city streets.
In addition, there is no evidence that long-term CO exposures in EU residences contribute to
carboxyhaemoglobin levels in blood higher than the baseline levels resulting from
endogenous production in normal, non-smoking individuals.