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On the reduction of health effects from combined exposure to indoor air pollutants in modern offices

Final Report Summary - OFFICAIR (On the reduction of health effects from combined exposure to indoor air pollutants in modern offices)

Executive Summary:
OFFICAIR is a European collaborative project, which has received funding from the European Union, in the 7th Framework Program, under the Theme: ENV.2010.1.2.2-1. The overall objective of the OFFICAIR project was twofold. Firstly, to establish a framework that will provide new knowledge in terms of databases, monitoring and modelling tools and assessment methods towards an integrated approach in evaluating the health risk from indoor air pollution, focusing on modern office buildings. Secondly, to support current EU policies, such as, the Thematic Strategy on Air Pollution and the European Environment and Health Strategy and Action Plan.
For the first time a complete overview on building characteristics, indoor air concentrations of priority pollutants and ambient thermal conditions was provided regarding modern office buildings. Through a general survey (167 buildings), a detailed study (37 buildings) and an intervention study (9 buildings) conducted in eight European countries, a procedure was developed for evaluating the indoor air quality and the related effects of indoor air pollution on human health and well being of office occupants. New analytical methods were developed, validated and demonstrated in real indoor or in simulated environments (test chambers).
Through targeted in vitro and in vivo laboratory studies new knowledge has been acquired regarding the potential toxicological effects from the exposure to single compounds and mixtures of indoor priority chemical compounds. Human reference values for sensory irritation and airflow limitation were derived for several ozone initiated terpene oxidation products. The oxidative activity of three major ambient air pollutants, PM, NO2 and ozone as single components or in combination using an artificial lung fluid was measured. This is the first study in which the oxidative effects of three major ambient air pollutants are compared in the same experimental system. PM was found to be the primary contributor to the oxidative activity in the air we breathe.
HRA was conducted using as target population a group of office workers focusing on their acute and/or longer-term inhalation exposure to the following selected indoor air pollutants: formaldehyde, acrolein, d-limonene, α-pinene, 3-isopropenyl-6-oxo-heptanal (IPOH), 4-oxopentanal (4-OPA), 4-acetyl-1-methyl-1-cyclohexene (4-AMCH), 6-methyl-5-heptene-2-one (6-MHO), ozone and PM2.5.
In order to link emissions of major primary air pollutants and the formation of secondary pollutants a suite of models was developed and applied for the prediction of air concentrations of species of health concern in modern offices located in different parts of Europe. The models consistently showed relatively small effects of printing, cleaning and personal ventilation.
The OFFICAIR database (hosted at the Joint Research Centre of the European Commission in Ispra) on concentrations of key indoor air pollutants observed in modern office buildings was developed based mainly on relevant data obtained during the OFFICAIR campaigns. The database was further enriched with data selected from an extensive review of existing data from the European Indoor Air Monitoring and Exposure Assessment Project (http://web.jrc.ec.europa.eu/airmex/) with appropriate links to the emissions/sources data stored into the Building Materials emission (BUMA) and to the Building material and Consumer product (BUMAC) databases (developed in the context of BUMA and EPHECT projects respectively). It is accessible at http://web.jrc.ec.europa.eu/airmex/officair-db/ after user registration.
Using new methodological approaches and techniques for a better understanding of factors affecting the indoor environment in modern office buildings the OFFICAIR project is substantially contributing to a healthier life at work for building occupants and helping to steer EU policies towards the better protection of office workers by clarifying the mechanisms surrounding exposure conditions and effects.

Project Context and Objectives:
Modern offices usually have several sorts of electronic equipment and other dominant heat sources indoors. Air conditioning and mechanical ventilation, making them almost unaffected by local climatic conditions, coupled with the often excessive levels of artificial lighting, require high levels of energy. At the European Union (EU) level, the Directive 91/2002, (EPBD) and the recast Directive 2010/31/EU, area major step towards rational energy use. An important issue to consider regards Indoor Air Quality (IAQ). It is anticipated that developments in the field of energy use in offices will lead to its reduction through various strategies, including comfort/health standards and ventilation levels. In such a context and given the technological evolution of the functions and services accomplished in offices, it is time to address the issue of IAQ in offices.
The overall objective of the OFFICAIR project is twofold: i) to establish a framework that will provide new knowledge in terms of databases, modelling tools and assessment methods towards an integrated approach in assessing the health risk from indoor air pollution, focusing on modern office buildings; ii) to support current EU policies, such as, the Thematic Strategy on Air Pollution and the European Environment and Health Strategy and Action Plan.
To achieve the overall objective of OFFICAIR, the following scientific and technical objectives have been devised, each corresponding to a specific, scientific Work Package:
• Develop a European database that includes all relevant information on indoor air pollution and its impact, in terms of concentrations, sources and emissions, exposures and health effects.
In WP2 the OFFICAIR database was developed on indoor/outdoor concentrations of key indoor air pollutants observed in modern offices. The design of the database reflects what was done for the European Indoor Air Monitoring and Exposure Assessment Project (AIRMEX) with the addition of new parameters necessary to better characterize and index the data. From the technical point of view, the usage of such a database simplifies the maintenance of the data and its reusability. The specific objectives of WP2 are the gathering of the existing knowledge on indoor concentrations of key air pollutants and particulate matter in office buildings at European level, the identification of the major indoor sources in modern office buildings (e.g. office equipment) and the cataloging of them according to their presence and significance in modern office buildings.
• Identify new, health relevant, primary and secondary pollutants that originate from indoor sources present in typical modern office environments, using novel detection methods and analytical techniques that go beyond the state-of-the-art.
The main goal of WP3 was to develop and optimize test chamber set-ups, sampling methods and analytical techniques aiming at the identification of new health relevant primary and secondary pollutants originating from indoor sources present in a typical modern office room. Several new analytical methods have been developed/validated and two analytical methods were further improved and implemented in indoor air and chamber emission testing. The generated information complemented the field studies (WP4), the toxicological studies (WP5) and the health evaluation (WP7). All these methods were used in emission experiments to determine the primary emissions of office equipment and in ozonolysis experiments (in test chambers and real-life situations) to identify and quantify secondary reaction products as a result of indoor air chemistry. In addition to the primary emission experiments, the influence of environmental parameters in test chamber experiments e.g. relative humidity, temperature and air change rate on the emissions from office equipment was investigated for the tested office equipment.
• Inventory and identify associations (events and sources) that have been identified as possible sources of IAQ problems in European modern offices, via a field investigation (through questionnaires and IAQ monitoring). This includes, on the building side, the space characterization, the assessment of the physical and chemical parameters and, on the occupants’ side, the exposure and health effects for the time spent indoors, as described in the subsequent objectives.
• Evaluate the health risks of poor indoor air quality under different conditions in modern office buildings in Europe, through the study of the associations between health effects, the perceived IAQ by European office workers and their exposure to selected and prioritised indoor air pollutants.
The WP4 - WP7research strategy consisted of three complementary phases: a “General Survey”, that aimed to describe the characteristics of the building and HVAC system, to identify the main causes and sources of pollution (WP4), and to investigate the association between IAQ and related symptoms and IAQ perception and building characteristics, taking into account the potential role of work-related stress and psychological characteristics (167 buildings); a “Detailed study” of summer and winter measurements for both well-established health relevant indoor pollutants and compounds never investigated previously for their health relevance have been performed (WP4) (37 buildings). Associations between exposure to these indoor air pollutants and health effects (i.e. symptoms, eye surface health, performance) have been investigated, taking into account the potential synergistic role of psychosocial stress; an “Intervention study“ that aimed to investigate the benefits of an intervention on IAQ on symptoms based on biological and physiological parameters (e.g. lung function, lung inflammation, endothelial function, etc.). Monitoring of indoor air pollutants (same as in the “Detailed study” plus innovative IAQ investigations e.g. active sampling and on-line monitoring), and symptoms have been performed before and after an intervention related to IAQ (9 buildings), i.e. change in the cleaning procedures or substitution of the floor cleaning products with one ecological friendly product common to all the buildings (with lower content in terpenes and aldehydes).

• Describe and assess the ozone initiated chemical reactions in office air. A number of hypotheses have been studied, which focus on the potential toxicity of pollutants (VOCs, particles and reactive radicals), acute, as well as, long-term, caused by ozone-initiated chemical reactions occurring in modern offices. These studies intend to address these issues in an integrated manner by a combination of toxicological, in vitro and in vivo studies.
The objective of WP5 was to investigate airway effects resulting from exposure to terpenes and possible synergy of ozone-initiated terpene reaction products (i.e. combined and repeated exposure) in office air and emitted from office equipment. The studies addressed these issues in an integrated manner by biological characterization of in vitro and in vivo inhalation models. A number of hypotheses that are related to repeated or combined exposure experiments of reactive compounds, respirable particles and radicals have been studied, which focus on the potential toxicity (acute as well as long-term) caused by ozone-initiated reactions occurring in modern offices and caused by ambient respirable particles. To meet these objectives the following integration of toxicological studies have been carried out: Toxicity potential of biologically reactive VOCs (e.g. formaldehyde and limonene) and possible amplification when combined with other key pollutants (e.g. printer emission particles, ozone), and low relative humidity. Further, the oxidative characteristics of sampled particles in offices have been assessed, and the impact of ozone and nitrogen dioxide evaluated.

• Set up an integrated modelling system to link emissions of key pollutants (ozone, primary VOCs and particles) and major secondary indoor pollutants, which are known for their adverse health effects, to their concentrations and eventually to the assessment of the exposure of office workers, via a suite of modelling tools.
The main aim of WP6 was to develop an integrated modelling system to predict concentrations of air pollutants of health concern within modern offices and to quantify the exposure of office workers. The modelling tools were applied to meet the following major objectives: (i) to simulate the physical distribution of pollutants and hydrothermal conditions within offices, using Computational Fluid Dynamics modelling; (ii) to predict the chemical formation of secondary compounds, and specifically ozone-initiated terpene reaction products using different chemical schemes; and (iii) to assess the changes in indoor air pollutant concentrations in responses to interventions aimed at reducing office worker exposure (e.g. reductions in emissions from cleaning and from computers/printers and changes in ventilation rates). The findings were then used for health risk assessment in WP7 and policy assessment in WP8.
• Make recommendations for IAQ policies for modern office buildings across Europe, and propose adjustments to the current practices and techniques resulting from the development in equipment and spaces organization of offices. This will include the identification of research gaps related to health and the indoor environment
The main objective of WP8 is to prepare policy-relevant recommendations for policies on IAQ in modern office buildings in Europe. The work has taken into account adjustments to practices and techniques for IAQ resulting from the recent evolution of the equipment and spaces organization of offices. This included research identifying gaps in knowledge related to health and the environment as well as related to health and sustainability issues. To make a holistic and integrative assessment possible, based on the outcome of work package 2 to 7, a framework was developed which focused on exposure conditions (e.g. building characteristics) beyond the single components, to allow identification of multi-exposure effects that may otherwise remain unidentified. The work in this WP is closely dependent on the outputs of WP2, WP3, WP4,WP5, WP6 and WP7.This resulted in recommendations and prioritization of IAQ policies related to office buildings. Furthermore, the WP outcome is particularly relevant to the dissemination and exploitation activities involving relevant stakeholder groups (e.g. city planning, construction, industry, policymakers and end users).

Project Results:
1.1. Identification of pollutants and their toxicological effect
1.1.1. Laboratory studies on selected chemical reactions mechanisms relevant for indoor environments (WP3)
Test chamber set ups, together with new sampling and analytical methods were developed aiming at the identification of health relevant primary and secondary pollutants present in office rooms or simulated office environments.
The following key analytical methods have been successfully developed, validated and demonstrated: a) SIFT-MS validation for real time monitoring of emission chamber exhaust air in view of profiling and characterizing product emissions; b) a new technique to characterize SVOC/PM and secondary reaction products (SRP) on PDMS/Tenax sorbents by using low-flow active sampling with personal sampling pumps (noiseless) suitable for indoor air and chamber experiments; c) development and validation of an analytical method with LTP-MS for the identification of in-situ ozonolysis products from terpenoids. In addition two analytical methods were further improved and implemented in indoor air and chamber emission testing: the IPT (in vitro pyrogen) test to determine the inflammatory potential of the indoor air constituents, and an analytical method to determine organic carboxylic acids on secondary organic aerosols.
SIFT-MS showed during detailed validation experiments for eight compounds (6 VOC’s and methylbromide, formaldehyde) measurement uncertainty results between 4 and 28 %. The quantitative results obtained, were comparable to methods based on adsorbents. The new innovative thermal desorption GC MS method for SVOC sampling and analysis including PM/SRP (secondary reaction products) showed to be applicable for a wide set of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), phthalate esters (PEs) and selected SRPs such as e.g. 4-OPA (4-oxopentanal), 6-MHO (6-methyl-5-heptene-2-one), 4-AMCH (4-acetyl-1-methylcyclohexene), 3-IPOH (3-isopropenyl-6-oxo-heptanal). The method is characterised by limits of detection in the range of 0.002-0.2 ng/m3 when sampling up to 480 liter and a repeatability of less than 10 % for all studied compounds.
All new methods and a range of background techniques were applied to obtain experimental new product emission data representative for typical emissions occurring in modern offices. The detailed data are included in the OFFICAIR database. Eight products were selected for evaluation: office desk panel, PC, office chair, all-purpose cleaner, screen cleaner, wall board, printer and projector. For the continuous emitting products, especially the wall board has by far the largest amount of total emissions followed by an office desk panel, PC and chair. Printer and projector have relatively low emissions. The discontinuous emitting products all-purpose cleaner and screen cleaner have the highest emissions, but these are clearly at the moment of their use and therefore dependent on the use scenario (also: sampling is done at peak of emission). Overall they will have a lower impact on the longer term exposure, but are more important for short term exposure. The individual analytes being the most important emitters from this typical office configuration and thus key polluters of office air, are a set of 27 pollutants. Overall there are over 100 compounds emitted. The top 10 pollutants can be calculated, assuming all 8 products are simultaneously present in the test chamber. The top 10 (concentration based) emitted compounds are: 1-methoxy-2-propanol, acetonitrile, glutaraldehyde, acetaldehyde, dihydromyrcenol, hexanal, a-pinene, formaldehyde, eucalyptol, propanal. This observation is from the point of view of product emissions. In case of an evaluation from a health impact point of view, one should consider the whole set of emitted pollutants in view of IAQ limit and guideline values (incl LCI’s).
The effect of temperature (T), air change rate (ACH) and humidity (RH) has been quantified in test chamber experiments for the above mentioned office products. The effect of ACH is substantially larger than the impact of increasing temperature and humidity. The effect of temperature as quantified in the experimental part of this study shows a larger impact on product emissions than currently published. On average, for the total emissions of the products tested: the effect of ACH is 47 % increase per 0.1 h-1 decrease; the effect of temperature is 19 % increase per 1 °C increase. The effect of humidity is an increased emission of hydrophilic compounds and is quantified for one product as 28 % increase of total product emissions when humidity increases with 55 % (e.g. approximately 1 % increase of total emissions per 2 % increase of RH).These conclusions illustrate that real encountered concentrations in offices may exceed substantially the one hypothesized from emission testing at standard conditions.
Highly specialised techniques were, in a dedicated subtask, developed for the further identification of reactive species resulting from secondary reactions of terpene ozone mixtures. Limonene and its ozone-initiated reaction products were investigated in situ by low temperature plasma (LTP) ionization quadrupole time-of-flight (QTOF) mass spectrometry. Helium was used as discharge gas and the protruding plasma generated ~850 ppb ozone in front of the glass tube by reaction with the ambient oxygen. Limonene applied to filter paper was placed in front of the LTP afterglow and the MS inlet. Instantly, a wide range of reaction products appeared, ranging from m/z 139 to ca. 1000 in the positive mode and m/z 115 to ca. 600 in the negative mode. Key monomeric oxidation products including levulinic acid, 4-acetyl-1-methylcyclohexene, limonene oxide, 3-isopropenyl-6-oxo-heptanal and the secondary ozonide of limonene could be identified by collision-induced dissociation. Oligomeric products ranged from the non-oxidized dimer of limonene (C20H30) and up to the hexamer with 10 oxygen atoms (C60H90O10).
In a follow up experiment, a low temperature plasma (LTP) ionization interface between a gas chromatograph (GC) and an atmospheric pressure inlet mass spectrometer, was constructed. This enabled time-of-flight mass spectrometric detection of GC eluting compounds. The performance of the setup was evaluated by injection of mixtures of common indoor volatile organic compounds. Amounts down to ca. 0.5 ng (on column) could be detected for most compounds and with a comparable chromatographic performance of that of GC/EIMS. In the positive mode, LTP ionization resulted in a compound specific formation of molecular ions M+•, protonated molecules [M+H]+, and adduct ions such as [(M+O)+H]+ and [M+NO]+. The ion patterns seemed unique for the each of the analysed compound classes and can thus be useful for identification of functional groups. A total of 20 different compounds within 8 functional groups were analysed.
The formation of secondary reaction products resulting from terpene ozone reactions, was studied in targeted chamber experiments simulating realistic indoor use. The study was focused on the effect of concentration levels, NO2 and light on reaction products. Synthetic mixtures were prepared feeding limonene, pinene and ozone into a test chamber, followed by sampling the source and reaction products. Considering the most important secondary reaction products, the results show that the factors darkness and NO2 cause a decreased concentration for 4-OPA, while formaldehyde and UFP formation was not influenced. Increasing the initial limonene level gives more reaction products, faster reactions and higher final concentration levels (except for 4-OPA). The presence of pinene in the mixture has a negative influence on the final concentration of 4-OPA, other reaction products are unaffected. UFP particle formation is a good indicator for the reactions and can amount under realistic concentration levels up to peak concentrations of 40000 particles/cc.
Dedicated chamber experiments were also carried out to determine the air inflammatory potential. In addition the chamber atmosphere has been chemically characterized in terms of selected terpene -secondary reaction products e.g. 4-OPA, IPOH, 6MHO, 4 AMCH and also including monocarboxylic acids in PM. It has not been possible to establish any correlation between the chemicals present in the atmospheres of the test chambers and the IPT measurements. No significant inflammatory potential of air constituents during the various terpeneozonolysis tests carried out in this study has been observed. However the method has been optimized and can now be applied to indoor environments to gather further information on health-relevance of air constituents such as bioaerosols and can be used in field campaigns.
The applicability in real life office environments of the advanced analytical methods newly developed in this WP was successfully demonstrated in two different settings. The first microenvironment consisted of a walk-in type environmental chamber containing a basic office set up (desk, chair and notebook) and was operated dynamically with controlled environmental conditions (e.g. 23 ˚C, 50% RH and 0.5 ach). The second microenvironment consisted in an office space that is currently unoccupied where environmental conditions are monitored but cannot be controlled. Besides the materials present, pollution was caused by 4 defined scenarios using a professional cleaning product. The following set of health relevant air constituents was measured: pyrogens in air, PM and UFP, free acids in particulate matter, carbonyls, ozone, volatile organic compounds and key terpene-ozonolysis secondary reaction products such as e.g. 4-OPA, IPOH, 4-AMCH. The secondary reaction products were for the first time ever quantified in real office circumstances and amounted up to 2-3 µg/m³.The cleaning activity caused only a minor increase of SRP’s, clearly increased were dihydromyrcenol and selected glycolethers.

1.1.2. Targeted toxicological laboratory studies (WP5)
In vitro and in vivo exposure studies were carried out to study airway effects of ozone-initiated terpene reactions under controlled conditions; the terpene limonene (an abundant indoor air VOC), was used as an example. In vitro studies were carried out by air-liquid-interface exposure of human lung cells, the A549 alveolar cell line and BEAS-2B bronchial cell line, respectively.

In vitro studies
A549 human lung cell line was exposed to controlled atmospheres containing individual compounds of limonene, ozone, formaldehyde and mixtures (limonene/ozone). Cells were exposed for 1 and 2 hours. Various endpoints such as cell viability, membrane damage, inflammation and stress oxidation were selected to assess potential lower airway effects. The toxicological studies were performed after optimization of a well-established airway cell culture system (CULTEX) connected to environmental chambers, where the gas atmospheres were generated and concentration of the compounds therein measured. As part of the exposure measurement technique with CULTEX chambers, control experiment (clean air and incubator) were included. Target limonene concentrations were high and low (2.5 ppm (14 mg/m3), 0.5 ppm and 0.02 ppm), ozone (70 ppb), target formaldehyde levels were 100 µg/m3 (WHO indoor air guideline value) and 10 µg/m3 (a realistic indoor level). A mixture of initial 0.02 ppm limonene and 70 ppb ozone was also generated in an environmental chamber, and initial compounds and reactions products were measured. Before cell exposure, the reaction was allowed to proceed till the levels of key ozone initiated reaction products were stable. Based on the endpoints, the exposure experiments with pure limonene, ozone, or formaldehyde, respectively, or the ozone-initiated limonene reaction mixture did not produce cytotoxic effects, nor did they induce inflammation and oxidative stress of the A549 cells as compared to the control experiments.
BEAS-2B cells cultured at the air-liquid interface were exposed for one hour in a VITROCELL system to ozone and limonene, separately, or as a reaction mixture generated in a climate chamber, and tested with a number of biological assays (cytotoxicity, apoptosis, oxidative stress, and inflammation). The results were compared with positive controls (nitrogen dioxide (11ppm) or lipopolysaccharide 20 µg/ml)), and control air. Exposure of the cells up to 5000µg/m3 (0.9 ppm) limonene did not show signs of cytotoxicity or apoptosis. Similarly for BEAS-2B cells exposed to ozone up to 1000 µg/m3 (0.5 ppm) showed no signs of cytotoxicity or apoptosis. However, 0.025 ppm and 0.5 ppm showed a modest and significant induction of oxidative stress by increase of HO1mRNA expression in comparison with control air exposure. Thus, limonene showed no effect on either bronchial or alveolar epithelial cells at the concentrations tested. Exposures of BEAS-2Bcells to climate chamber generated reaction mixtures of limonene and ozone of about 400µg/m3 and 400 µg/m3 (initial concentrations), respectively, were not significantly cytotoxic; furthermore, no apoptosis, oxidative stress, and inflammatory responses were observed. Finally, it was shown that additional contribution of the exhaust (i.e. particles) from a running inkjet printer combined with the limonene/ozone reaction products did not alter the bioresponses of BEAS-2B cells.

In vivo studies
A well-established mouse bioassay was used as a model to study upper airway (sensory) irritation, bronchoconstrictive (airway limitation) and alveolar level effects after exposure to ozone-initiated limonene reaction products at controlled conditions. The effects were derived from continuous monitoring of a number of respiratory parameters, e.g. the respiratory frequency. Four scenarios were pursued: repeated exposure; airway responses of five specific and common ozone-initiated terpene reaction products; impact of low relative humidity on sensory irritation and sensitization versus non-sensitization; and, adjuvant effect of ozone-initiated limonene reaction products on a model allergen (ovalbumin).
The effect of repeated exposures to ozone-initiated limonene reaction mixtures over ten days was studied. It was concluded that: i) sensory irritation in the airways is not accumulated upon repeated exposures, ii) no sign of inflammation was observed in the exposed airways by analysis of inflammatory markers from bronchoalveolar lavage, iii) a no-observed-effect-level (NOEL) of ≥ 0.1 ppm ozone at elevated limonene concentrations is proposed by extrapolation of the animal data to human data.
Investigation of acute airway effects of five common ozone-initiated terpene (limonene, linalool, geraniol, dihydromyrcenol) oxidation products showed that derived human reference values for sensory irritation were 1.3 0.16 and 0.3 ppm, respectively, for 4-acetyl-1-methylcyclohexene (4-AMCH), 3-isopropenyl-6-oxo-heptanal (IPOH), and 6-methyl-5-heptene-2-one (6-MHO). Derived human reference values for airway limitation were 0.8 0.2 0.03 and 0.5 ppm, respectively, for dihydrocarvone, 4-AMCH, 4-oxo-pentanal (4-OPA), and 6-MHO. Pulmonary irritation was unobserved as a critical effect. The reference values indicate that the oxidation products would not contribute substantially to sensory irritation in eyes and upper airways in office environments. Both IPOH and 4-OPA may be of concern regarding possible respiratory effects in the case of acute and constant emission sources of terpenes.
It was examined if inhalation of the reaction products of ozone and the terpene, limonene (a common and abundant VOC indoors), as well as low-level ozone and limonene themselves, would induce allergic sensitization (formation of specific IgE) and airway inflammation in a subchronic mouse inhalation model in combination with a model allergen “ovalbumin” (OVA). Mice were exposed five days/week for two weeks and thereafter once weekly for 12 weeks. The exposures were, respectively, low-dose OVA in combination with ozone, limonene or ozone/limonene reaction products. OVA alone or OVA+Al(OH)3 served as control groups. Afterwards, all groups were exposed to a high-dose OVA solution on three consecutive days. Serum and bronchoalveolar lavage fluid were collected 24 hours later. Limonene itself neither promoted OVA-specific IgE nor leukocyte inflammation. Low-level ozone promoted eosinophilic airway inflammation, but not OVA-specific IgE formation. Limonene itself showed anti-inflammatory properties.
Normal mice (saline-sensitized) housed in a dry environment responded more vigorously in the lower airways to formaldehyde concentrations at 1.8 and 7 ppm than ovalbumin (OVA)-sensitized mice. We speculate that increased mucus production in the OVA-sensitized mice (three intraperitoneal injections and two aerosol challenges on two consecutive days just before the exposure) has increased the “scrubber effect” in the nose, consequently protecting the lower airways. At high relative humidity no difference in the lower airways was seen between OVA- or saline-sensitized mice up to 1.8 ppm formaldehyde; however, effects occurred in the OVA-sensitized mice compared to the saline-sensitized control mice at 7 ppm formaldehyde. Sensory irritation of the upper airways was unaffected by sensitization and humidity up to 1.8 ppm formaldehyde.”
Particulate matter (PM) is believed to cause pathophysiological actions in the respiratory system, at least in part, through oxidative stress. The oxidative potential (OP) of particulate matter (PM2.5) samples collected inside modern offices, from seven EU countries was found to vary by building type, season, and location. Specifically, evidence of seasonal, regional and site variation in the OPPM2.5 metrics (OP/µg and OP/m3) was observed, as well as statistical variation in the ratio of Indoor:Outdoor OP found across all countries, all cities, and between sites.
The impact of replacing office cleaning products was assessed in Greece, Hungary, Italy, Portugal, and the Netherlands by analysis of PM2.5 OP collected after the Stage 2 Intervention. Following the intervention differences between the Indoor Control and Indoor Intervention rooms were examined. Statistical differences were demonstrated Post-Intervention between the Control and Intervention rooms for the Netherlands (OPGSH/µg and OPGSH/m3) only. As there were insufficient numbers of samples from most countries only one, Greece, could be statistically analyzed to investigate the impact of Intervention on the Indoor OP: Outdoor OP ratio (I:O) and no significant differences were observed. Overall, these finding indicate that the oxidative potential of particulate matter in and around office buildings has different temporal and spatial patterns and that a better understanding of the reasons for this will help guide mitigation strategies which should improve indoor ambient air quality.
Given that ambient air contains a number of gaseous and particulate based pollutants we directly compared the oxidative potential of nitrogen dioxide (NO2), ozone (O3) and particulate matter (PM) in the same experimental system, i.e. a lung lining fluid model. Synthetic lung lining fluid was exposed to either O3 or NO2 (50,150,400,1000ppb) or PM collected from a background or roadside location in London. The change in ascorbate, urate, and glutathione concentrations was quantified by measuring the concentration of the antioxidants in the lung fluid model every 30 minutes for up to 2 hours. Exposure to either O3or NO2 resulted in concentration and time dependent loss of ascorbate and glutathione from lung fluid. There was a clear hierarchy in the antioxidant depletion with ascorbate being the most reactive antioxidant across all air pollutants. Application of the experimentally derived antioxidant depletion rates to the relevant pollutant daily mean concentrations provided direct comparison of the oxidative contribution of each pollutant to the urban airshed at that location. Of the three pollutants considered PM was found to contribute the greatest oxidative activity while the importance of NO2 exposure at roadside locations was apparent. This has relevance for this project as many offices are found at busy roadside locations.
Next, we determined if either of the oxidant gases NO2 or O3 influenced the oxidative potential of PM. In a second set of experiments PM was pre-exposed to either air, NO2 or O3 prior to its oxidant potential being assessed. The co-location of PM with the gaseous oxidants NO2 or O3 was not found to influence its inherent oxidative potential although it is apparent that each pollutant will contribute to the total oxidant potential of the airshed at any particular time and location. This is the first study in which the oxidative effects of the three major ambient air pollutants are compared in the same experimental system. PM was found to be the primary contributor to the oxidative activity of the air we breathe.

1.2. Indoor air quality assessment and health effects in the office buildings
1.2.1. Indoor air quality assessment (WP4)
In a context where little data exists in Europe on modern office buildings and indoor air quality in these workplaces, OFFICAIR Project provided a first complete overview of buildings characteristics, indoor concentrations of numerous pollutants and ambient thermal conditions.
First, the general survey in 167 buildings over Europe confirmed that most of them (74%) have a mechanical ventilation system. Only 14 and 12% respectively have a hybrid/mixed mode and natural ventilation system (openable windows or stack ventilation). It underlined the importance to dimension and maintain correctly and regularly the mechanical ventilation system to ensure good indoor air quality especially when windows are not openable.
In a second step, the detailed study consisted of 5-day sampling in 4 locations of a limited number of buildings, and one outdoor. The field campaign was carried out at two different seasons, summer (37 buildings) and winter (35). Twenty-two indoor pollutants (7 aldehydes, 12 VOCs, ozone, nitrogen dioxide and PM2.5) were measured, in addition to temperature and relative humidity. The comparison with the results from the AIRMEX project showed that indoor concentrations in modern office buildings were in the same order of magnitude except for terpenes (median concentration of alpha-pinene in winter: 4.3 µg m-3; maximum concentration: 68 µg m-3; median concentration of limonene in winter: 16 µg m-3; maximum concentration: 81 µg m-3). Terpenes are emitted mainly by cleaning products. The outdoor air also appeared to be a major contributor as well, for particles, ozone and NO2 especially, even when buildings are mechanically ventilated. The comparison with the existing IAQ guidelines (e.g. from the World Health Organization) showed that indoor concentrations in some office buildings could exceed the reference values for long-term exposure for benzene (maximum measured weekly concentration: 10 µg m-3) and PM2.5 (max: 17 µg m-3).
These measurements also provided new results in terms of spatial and temporal variabilities of indoor concentrations in offices. It appeared clearly that the indoor concentrations in summer and winter vary significantly for some compounds using the Wilcoxon matched pairs test for binary dependent groups. Significantly higher indoor concentrations were observed in winter for benzene, limonene, α-pinene and nitrogen dioxide. Conversely significantly higher indoor concentrations are observed in summer for formaldehyde and ozone. In high-rise buildings, the concentrations may also vary according to the levels. For 11 compounds, the indoor concentrations were statistically significantly different according to the monitored level (non-parametric Kruskal-Wallis test).
On the basis of the detailed study results showing the influence of cleaning products, the third step was oriented to focus on this specific issue. An intervention study based on the use of an alternative floor cleaning product with low VOC-emissions was carried out in seven countries (8 buildings). In one country (one building), the cleaning procedure was changed. The indoor air measurements were carried out before and after four weeks of intervention procedure, at two locations: the intervention room and the control room. Thirty-five indoor pollutants (10 aldehydes, 20 VOCs, ozone, nitrogen dioxide, fine and ultrafine particles, PM2.5) were measured on short time intervals (2 hours or every minute, except for PM2.5) in addition to temperature and relative humidity. The results showed significant differences (before versus after) in aldehyde concentrations in the intervention room (Wilcoxon matched pairs test for binary dependent groups), but not in the control room. No difference regarding VOC indoor concentrations were observed. Similarly, for particles, ozone, nitrogen dioxide, no influence of the intervention was shown; other determinants of these pollutants are predominant in office buildings. For the first time, the contribution of cleaning product emissions on IAQ in office buildings has been shown.
The intervention study also provided interesting results in terms of temporal variabilities of indoor concentrations. It was shown that for VOCs and aldehydes, in the absence of any specific event, the indoor concentrations did not vary significantly within a day, and from a day to another. This was not the case for ultrafine particles. Thus, for VOCs and aldehydes, whereas the detailed study showed that repeated samplings at two different seasons and at different levels in case of high-rise buildings are requested, it seems that one half-day sampling within a week is enough, provided that no outstanding event takes place during the sampling.
Finally this intervention study made it possible to obtain additional data on IAQ in office buildings. For example, for the first time, indoor concentrations of terpene oxidation products, such as 4-OPA and 6-MHO, were measured in real workspaces (mean indoor concentrations around 3 and 1 µg m-3 respectively). The rich data set offers also many perspectives of future additional analyses.

1.2.2. IAQ and exposure modelling in modern office microenvironments (WP6)

On modeling system
The OFFICAIR integrated modeling platform has been developed to evaluating the health risk of office workers from indoor air pollution. This integrated modelling system links emissions of key pollutants (ozone, primary VOCs and particles) and major secondary indoor pollutants, which are known for their adverse health effects, to their concentrations in modern offices and eventually to the assessment of exposure of office workers. The present chemistry modeling work uses the individual models such as DCM, MIAQ and INDAIR-CHEM in parallel for simulations of chosen office scenarios. The three models were initialised with the same parameter values where applicable. The DCM requires detailed parameterisation of its complex chemical schemes, whereas INDAIR-CHEM with the reduced chemical scheme is driven primarily by air exchange rate and office size parameters. MIAQ includes a lumped chemical scheme but has no provision for modelling particulates. In addition, the INDAIR-CHEM model adopts a probabilistic approach for a complete set of intervention scenarios based on a range of critical parameter values derived using data from the OFFICAIR monitoring campaign and literature searches. The required ventilation modeling input for the above chemical models is provided by multizone airflow and contaminant transport model COMIS which has been part of the OFFICAIR modeling platform.To simulate the thermal comfort conditions and the detailed pollutant concentration distribution the CFD commercial code FLUENT has been utilised.

On model parameterization and evaluation
Model parameterisation was based as far as possible on data collected in the OFFICAIR project (e.g. office dimensions and numbers of printers/photocopiers from office surveys and emissions from cleaning products from WP2 tests) or from literature reviews conducted in OFFICAIR (e.g. on air exchange rates and on emissions from printers and computers). The data obtained from intensive measurements in four offices (Athens (2), Florence (1) and Porto (1)) have been more suitable to test the models for sensible outputs rather than for strict validation. The results of the ventilation modeling exercise in the four offices using COMIS model have shown 0.1 to 0.4 ACH for natural ventilation and1.3 to 3.8 ACH for mechanical ventilation. The application of the chemical as well as CFD models to the above offices has produced reasonable results.
Model parameterisation was based as far as possible on data collected in the OFFICAIR project (e.g. office dimensions and numbers of printers/photocopiers from WP4 office surveys and emissions from cleaning products from WP2 tests) or from literature reviews conducted in OFFICAIR (e.g. on air exchange rates and on emissions from printers and computers). For the INDAIR-CHEM model, all input parameters were described as probability frequency distributions; for other models the mean value was used.

On model application and exposure assessment
The main Science and Technology results from modeling work arose from the model application phase of the work. In order to assess the chemical exposure of workers in modern offices, the parameterised chemical models were used to predict the mean or 95th percentile pollutant office concentrations. The following chemical species, which had been identified as providing a potential risk to human health, were evaluated: formaldehyde (HCHO), ozone (O3), PM2.5 IPOH, and 4-AMCH. Concentrations of HCHO, IPOH, and 4-AMCH were compared with relevant human reference values (HRVs).Since the initially foreseen four offices do not provide a good representation especially in terms of ambient and geographical conditions, it was decided to apply the models using outdoor concentration data for the ‘heat-wave’ summer of 2003, to provide a ‘worst-case’ situation, and a more average summer (2009). The models were run for four cities, two offices per city providing a gradient across Europe from north to south: Helsinki, Paris, Milan and Athens.The models were applied separately to landscape and cellular offices. The four offices have been only kept for the CFD simulations due to the availability of detailed structural, thermal and ventilation data.
Indoor chemistry models. The suite of chemical models were used to assess the effects of policy interventions to improve air quality within modern office buildings; the models were used to predict the impact of changes in the timing of office cleaning, and the chemical emissions from cleaning products, ventilation rate (in terms of a personal ventilation rate – PVR) and emissions from office equipment. The effect of removal of terpenes from cleaning products, removal of printers and photocopiers from offices, and provision of a minimum personal ventilation rate on the predicted concentrations were tested. The predicted concentrations were compared to appropriate human reference values to inform the health effects evaluation in WP7. Risk assessment for this exercise was confined to office workers and based on an assumed working day of 0900-1700.
All three models agreed, in terms of mean concentrations, that all of the tested policy interventions caused only relatively small changes in the concentrations of the five abovementioned species. The effect of all policy interventions was greater in a landscape office than a cellular office. This is most likely due to differences in surface area/volume ratios and emission rates. Comparison of predictions for the four cities showed lower concentrations of HCHO, O3, IPOH and 4-AMCH in the Helsinki offices than in the other three cities, which can be attributed to the much lower outdoor ozone concentrations in this city. Concentrations were also lower in 2009 than in 2003. The INDAIR-CHEM simulations demonstrated that, for all locations and both years, the 95%ile exposure of HCHO, IPOH, and 4-AMCH was 2-4 times greater than the mean concentration. However, these 95%ile concentrations were still well below any relevant human reference value.
In the case of HCHO, the maximum change in the mean peak 30 min. concentration due to a policy intervention was less than 1ppb, and the maximum 30 min HCHO concentration in any model run was 10.5 ppb, a value that is well below the HRV of 80ppb. For IPOH, the maximum change in the mean peak 1h concentration due to policy intervention was less than 10 ppt, and the maximum 1h concentration in any model run was 1250 ppt, well below the HRV of 160 ppb. For 4-AMCH, the maximum change in the mean peak 1h concentration was less than 20 ppt, and the maximum 1h concentration in any model run was 1186 ppt, well below the HRV of 1300 ppb.
There was a greater effect of cleaning in the afternoon than in the morning, probably due to the higher levels of indoor O3.Removing printers reduced indoor O3 concentrations slightly, as they are an emission source, but the contribution of these emissions was small compared to ingress of outdoor ozone. Imposition of a PVR ≥ 4 l s-1 person-1 slightly increased indoor O3 and PM2.5concentrations (due to increased air exchange with outdoors) but slightly reduced indoor HCHO, IPOH and 4-AMCH concentrations during cleaning, due to increased ventilation to outdoors.
Concerning PM2.5exposure WHO air quality guidelines recommendation is less than 25 µg m-3. The 8h mean values remain well below this value in all the INDAIR-CHEM simulations, with a maximum value of around 15 µg m-3. There were important differences in model predictions of concentrations of PM2.5. Comparison of results from the DCM and INDAIR-CHEM models showed the importance of chemical processing outdoors, resulting in the formation of gas-phase precursors of secondary organic aerosol (SOA) indoors through limonene oxidation, a process which is included in the DCM but not INDAIR-CHEM. In Athens in the heat wave of 2003, this process led to an additional 7 µg m-3 of SOA, suggesting that outdoor ‘priming’ of indoor limonene oxidation chemistry may be a significant process in these areas of Europe. The uncertainties in the PM loss rates in modern office air conditioning systems assumed in the models, in the toxicity of SOA compared to other components of PM, and the differences in predictions between models, make formal comparison with air quality guidelines inappropriate for PM2.5.

CFD model: Due to the nature of the problem, the computational domain was extended in all cases beyond the office area in order to take into account the effect of the external environment. Appropriate heat transfer coefficients were used for the walls, the windows and the doors. Furthermore, the air inlet and outlet from the vents, as well as the losses through the cracks of the windows and doors were simulated by using as boundary conditions (and as point of reference) the ventilation results of the COMIS model. These parameters played an important role in the success of the simulations based on the comparison with the measurements. The pollutant was released inside the offices as a volume source placed on the floor knowing that most of the particles originate from there. These simulations provided the possibility to estimate, for all simulated offices, the highest exposure factors at the mean height of the working environment as well as the locations with the highest exposure at the same level. Furthermore, state-of-the-art thermal comfort indexes were estimated at selected locations inside the offices in order to understand: a) how workers feel at selected locations and b) how homogeneous are these indexes in a working environment.
The computational analysis revealed the heterogeneity of the flow, the hygrothermal and the pollutant fields inside the working offices. A high spatial variation in the Predicted Percentage Dissatisfied (PPD) index, as well as in the pollutant concentration at the mean working height, was observed. The main results can be summarized as follows

• The large offices may experience a significant spatial variability both in terms of thermal comfort and pollutant concentrations emitted from the floor and the floor equipment.
• The CFD methodology seems to be a valuable tool in estimating the above mentioned variability.
• Based on the present results and for more conservative exposure studies, a “hot” exposure concentration factor of 1.6 maybe recommended at this stage for pollutants emitted mainly from the ground. Further experimental and modeling studies are needed for more precise recommendations.
• It would be advisable the performance of the selected ventilation pattern to be checked for high thermal comfort and exposure concentration factors especially in the large offices.
• The present methodology can be used for ventilation pattern optimization in terms of thermal comfort and/or exposure impact in large offices.

1.2.3. Health effects evaluation in modern office buildings and health risk assessment (WP7)
The health effects of indoor air pollution under different conditions in modern office buildings in Europe have been evaluated, through the study of the associations between health effects and both the perceived IAQ by European office workers and the exposure to selected and prioritised indoor air pollutants monitored in WP4. The benefits on health of an intervention strategy on IAQ (e.g. ventilation improvement, pollutants filtration/reduction) have been investigated. Moreover, psychosocial stress has been investigated, given the growing concern about its potential synergy with indoor air pollution in causing health effects.
A review of the known/hypothesized health effects of selected and prioritized indoor air pollutants has been performed. This also includes a detailed review of risk factors associated with eye symptom development.
A “General Survey” (8 countries: ES, FI, FR, GR, HU, IT, NL and PT; 167 buildings; 7440 office workers) was performed for first, in order to inventory and identify associations between possible characteristics of European modern offices (building, sources and events) and the health and the comfort of the occupants, by a self-administrated on line questionnaire and a walk-through into the building with compilation of checklists.
The questionnaire mainly investigated the environmental perception and symptoms correlated to IAQ; the results are presented hereby: the most frequently reported complaints about indoor environment were “Air too dry” (16%), “Unsatisfactory noise from inside the building” (43%) and “Air too still” (40%) when considering the whole sample (i.e. workers from all investigated European buildings). Spain, France and Greece were the countries with highest rates of these complaints. The most reported symptoms in the past week (at least 3 days) were dry eyes (16%) and dry skin (15%); the percentages differed among countries, ranging from 8% in Greece to 24% in Spain for “dry eyes” and from 5% in Greece to 28% in Hungary for “dry skin”. Other symptoms related to irritative processes in the airways and allergy, lethargy and headache were reported by more than 5% of investigated workers. Overall, eye related symptoms, general symptoms, dry/irritated throat and chest tightness/breath difficulties were reported to be better when not at work in more than 70% of workers that reported these symptoms.
Associations with environmental perceptions and symptoms were investigated. In particular, poor air quality, noise and lighting perception were correlated with an increase of irritative, respiratory, cardiovascular and flu-like symptoms.
Symptoms were influenced by gender, age, smoke and country. For example, females and former smokers complained more for irritative symptoms, while respiratory and flu-like symptoms were positively and negatively related to age, respectively.
Moreover, associations with buildings characteristics, symptoms and environmental perception were tested. Respiratory, irritative and flu-like symptoms were higher in absence of dusting and polishing time schedules; noise, air quality and uncomfortable temperature perception were higher in buildings not equipped with openable windows, and “air too dry” perception was lower in buildings with balanced system with VAV (Variable Air Volume). Cardiovascular symptoms were not associated with buildings characteristics.
A “Detailed study”(8 countries: ES, FI, FR, GR, HU, IT, NL and PT; 32 buildings, 685 office workers) was then performed consisting of summer and winter measurements(indoor and outdoor) of health relevant indoor pollutants and compounds not investigated in former studies (WP4), and associations between exposure to indoor air pollutants and health effects (WP7).
A questionnaire, modified from the general survey, and tests assessing eye health (SBUT and OSDI), performance and memory were performed.
More than 30% of all workers were dissatisfied with the IAQ in both campaigns. The most frequently reported complaints about indoor air were “Air too still”, Air too dry” and “Air stuffy”. More than 30% of workers also reported “Too much glare”. Even though only buildings from the “General survey” with a lower rate of complaints about noise have been selected, “overall noise”, “noise from inside the building” and “noise from outside the building” were the most reported (more than 50%) complaints in all the countries.
A statistically significant increase of negative environmental perceptions related to “air too still”, “air too dry” was observed in the winter season, probably due to the heating. On the other hand a statistically significant decrease of complaints about “too much glare” was observed in winter, probably due to different natural light conditions. Moreover, complaints about noise significantly decreased in winter season; the reason of these differences will be better investigated in relation with the buildings characteristics from the checklist.
As far as concerning the symptoms, both in summer and winter campaign, on the overall sample, more than 20% of workers reported “Dry eyes”. Other symptoms related to eye health (“Burning and irritated eyes”, “Watering or itchy eyes “) were reported by 15-20% of workers. “Dry skin” was complained by more than 20% of workers in winter campaign. Other symptoms related to irritative processes in the airways and allergy (i.e. “Dry/irritated throat” “Blocked/stuffy nose”, and “Sneezing”), “Headache” and” Lethargy” were reported by more than 10% of investigated workers in both campaign. As reported in General Survey, eye-related and general symptoms (i.e. “dry eyes”, “watering/itchy eyes”, “burning eyes”, “headache” and “lethargy”) were better when not at work in more than 70% of workers in both campaigns.
In all European countries a statistically significant increase in “Dry eyes” “Dry/irritated throat” and “Dry skin”, was observed in winter season, probably due to the effect of heating. Moreover, a statistically significant increase in symptoms related to irritative processes in the airways (“runny nose”, “flu-like symptoms” and “cough”) was observed in winter, probably due to seasonal flu.
Self-reported Break Up Time (SBUT) and Ocular Surface Disease Index© (OSDI index) performed to evaluate the eye health showed no significant differences between seasons. Correlations between perception/reported symptoms and SBUT will be evaluated. Simple reaction time test and Memory test will be analyzed to evaluate a possible correlation between environmental monitoring/building characteristic and performance.
Associations between the results from the questionnaire and environmental monitoring as well as building characteristics were investigated in order to clarify the prevalence of airway irritation reported symptoms (i.e. dry eyes, dry/irritated throat etc.) and increase of negative environmental perceptions related to indoor air (i.e. air too dry, air movement too still).
An “Intervention study“(6 countries: FR, GR, HU, IT, NL and PT; 9 buildings, 230 office workers) was performed which consisted of monitoring indoor air pollutants (same as in the “Detailed study” plus innovative IAQ investigation, WP4) and biological and physiological parameters (WP7), before and after an intervention, i.e. change in cleaning procedures or substitution of floor cleaning product with other products with a low terpene and aldehyde content. Workers didn’t know where the intervention had been performed (the Intervention area), and where not (Sham area).
Two different protocols have been used:
The basic one was performed in I, NL, GR, PT, HU and FR (20-30 workers/building) to study the indoor environmental perception, the indoor air related symptoms and performance, lung function, vascular function, autonomic dysfunction, systemic oxidative stress and psychosocial stress. Each worker filled in an online questionnaire and online tests (see “Detailed study”), and underwent lung function test, response of blood pressure to orthostatic challenge, urine and saliva collection (for urinary 8-isoprostane and salivary cortisol measurement respectively). In Italy 80 workers were studied in two buildings with a plus protocol beside the basic one to investigate local lung inflammation, oxidative stress, micro-vascular function and autonomic dysfunction. Each worker underwent an exhaled breath condensate (EBC) collection for pH, cytokines (IL-8, IL-1beta) and 8-isoprostane measurement; FeNO measurement in exhaled air; peripheral arterial tonometry (PAT) and heart rate variability (HRV).
Both in the Intervention area and Sham area, on the overall sample, more than 30% of workers reported complaints about “Air quality unsatisfactory” in general.“Air too still”, “Air too dry”, “Air too stuffy”, “Air smelly”, and “Air unpleasant odour” were the most frequently reported complaints both in Pre and Post Intervention campaigns in both areas.
In the Post campaign of the Intervention area, on the overall sample, was observed a statistically significant decrease of negative environmental perceptions related to “air too still” and “air too dry”. In the Sham area was observed a statistically significant decrease for “Air smelly”.
More than 20% of all investigated workers in the intervention area, reported the symptoms “Dry eyes” and “Burning eyes” before the intervention, decreasing, although in a not statistically significant way, after the intervention. No significant differences were observed between Pre and Post intervention in the Sham area.
Statistical analysis on physiological and biological parameters from the intervention study shows increased pH-EBC levels after the intervention in the Intervention but not in the Sham area, suggestive of lower lung inflammation.
A detailed Health Risk Assessment (HRA) was performed in relation to selected indoor air pollutants reported in the office environment and associated to potential adverse health effects (irritative, respiratory). HRA was conducted using as target population group the one of office workers and focusing on their acute and/or longer-term inhalation exposure to the following selected indoor air pollutants: formaldehyde, acrolein, d-limonene, α-pinene, 3-isopropenyl-6-oxo-heptanal (IPOH), 4-oxopentanal (4-OPA), 4-acetyl-1-methyl-1-cyclohexene (4-AMCH), 6-methyl-5-heptene-2-one (6-MHO), ozone and PM2.5.
As far as the methodology followed for HRA, the following four steps were performed: hazard identification, dose-response relationship, exposure assessment and risk characterization. For the first two steps of the procedure, toxicological data concerning the effects of short- and longer- term inhalation exposure to the selected pollutants were evaluated in order to identify the critical effect and the corresponding limit of exposure for each pollutant studied. Data were retrieved from scientific literature available in databases, targeted toxicological studies (WP5), toxicological reviews of leading Health Organizations (e.g. WHO), and risk assessment reports of major EU projects (e.g. EPHECT, INDEX). For the third step of the HRA procedure, i.e. exposure assessment, depending on the pollutant under investigation, data resulting from two different activities were considered: firstly, the exposure modelling – performed in the frame of WP6 - and, secondly, the field campaigns study – conducted under WP4. For the final step of the procedure, i.e. risk characterization, for each pollutant, modelled (WP6) and monitored (WP4) indoor air concentrations were compared to the corresponding limit of exposure and the outcome was expressed as percentage (%) of the exposure limit.
Regarding the outcome based on the exposure modelling (WP6), the estimated worst-case indoor air concentrations of the pollutants studied did not exceed the corresponding limits of exposure. The modelled exposure to formaldehyde, IPOH and 4-AMCH was well below the exposure limits for the relative time periods, even assuming afternoon cleaning conditions during a ‘heat-wave’ period. Concerning ozone and PM2.5 however, elevated concentration levels were predicted, probably attributed to outdoor rather than indoor sources.
Regarding the outcome based on the field campaigns (WP4), average and maximum measured concentration levels of formaldehyde, acrolein, d-limonene, α-pinene, 6-MHO, 4-OPA and ozone were always lower than the corresponding limits of exposure when either acute or longer-term exposure was assessed. Elevated maximum concentration levels were reported, however, in the case of longer-term exposure to acrolein (‘Detailed investigation’), but the well-known difficulty to analyse this compound has to be taken into consideration. Concerning PM2.5 average and maximum concentration levels (‘Detailed investigation’ and ‘Intervention study’) exceeded the corresponding longer-term limits of exposure (WHO 2005 Air Quality Guidelines, AQG) in most cases; nevertheless, this comparison in terms of risk characterization has to be evaluated with caution, given the elevated outdoor PM2.5 levels as well as the fact that these AQG are related to ambient air.


1.3. Creation of the database, risk management, policies and dissemination
1.3.1. Database development for key indoor air pollutants in modern office buildings (WP2)
The OFFICAIR database and its web interface were developed and hosted by the JRC in Ispra. It is accessible, via login procedure, at http://web.jrc.ec.europa.eu/airmex/officair-db To achieve this, the following tasks have been carried-out: 1) analysis and design of the database, 2) reserved space on an FTP server hosted at the JRC to be made available to all the partners, 3) the experimental data generated by the project’s partners were uploaded into the database via a restricted access procedure and using standardised templates 4) a semi-automatic algorithm was developed to import the data into the database, 5) a new web-interface was also developed to allow for unique access of all experimental data, 6) appropriate links were enabled to the emissions/sources data stored into the Building Materials emission (BUMA) and to the Building material and Consumer product (BUMAC) databases (developed in the context of BUMA and EPHECT projects respectively), 7) an ad hoc section was created to hold and access the creation of the section OFFICAIR general survey data, 8) accessibility to data generated in the European Indoor Air Monitoring and Exposure Assessment Project (AIRMEX http://web.jrc.ec.europa.eu/airmex/) has been permitted.
The database has been populated with data received from the partners with the usage of standard Excel templates. These files have been uploaded into the space reserved on an FTP server managed by the JRC. Before being imported into the database the Excels templates were manually checked to verify the integrity and partially reshaped in CSV (Comma Separated Values) files.
The OFFICAIR general survey section contains the results of the survey that was conducted in 167 office buildings in eight European countries, namely Finland, France, Greece, Hungary, Italy, Portugal, Spain and the Netherlands.
The experimental data imported into the database are available for users under the database section “OFFICAIR Monitoring Campaigns” and can be browsed by country or by campaign report. In the first case it is enough to click on the desired country on the European map to be redirected to a new page in which all the campaign reports for that country are listed. In case data are browsed directly by campaign report, the full list of reports is available just under the map.
In any case by clicking one of the reports, the dedicated page is opened. In this page, information extracted from the selected campaign report is grouped as follows:
• General information on the report (e.g. title, year, institute)
• Data overview: statistical analysis of the data by chemical (e.g. average, standard deviation)
• Sources(s): indoor and/or outdoor environment
• Chemical(s): list of chemical(s) measured
• Measurement Data Set(s): list of dataset available
• Related files: list of additional files related to the selected Measurement Campaign Report
By clicking on the title of each Measurement Data Set (e.g. Concentration of Aldehydes in building GR03), users are redirected to a new page in which all the experimental data are grouped by chemical. At the bottom of the same page all the related additional files related are listed.
Another way that users have to access the data is the Data Filter functionality. For each stage of the project is available a page in which, via six parameters (i.e. data limits, season, chemical, environment, country and building) and/or their combinations, it is possible to filter and retrieve the desired data and export the final into a CSV file.
The web interface of the database makes available one page for each stage in which is present a statistical analysis of the data stored into the database. Data are divided into Indoor and Outdoor data. For each of these two categories and for each chemical the following values are extracted: minimum, maximum, median, average, standard deviation and number of samples. For values less than the limit of quantification (The total number of samples that are included in the database and correspond to all the stages of measurements are 11164.
Concerning emission data, the already existing BUMAC Database was enriched with emissions of consumer products commonly used in offices. Such products are printers, photocopiers, projectors, computers, cleaning agents. Data were derived from literature, from peer-reviewed articles and reliable reports and involve test chamber experiments. The emission results from the test chamber experiments that were performed in WP3 were included into the database.
1.3.2. Risk management & policies/recommendations (WP8)
In order to make a holistic and integrative assessment possible, based on the outcome of work package 2 to 7, a framework was developed which focused on exposure situations (e.g. building characteristics) beyond the single components, to allow identification of multi-exposure effects that may otherwise remain unidentified. The work in this WP was closely dependent on the outputs of WP2, WP3, WP4, WP5, WP6 and WP7.The OFFICAIR framework:
• Covers the full causal chain, beyond the single component: from sources (e.g. building characteristics) to effects.
• Covers the broader range of indoor environmental characteristics, including — in addition to air quality (IAQ) — noise, thermal conditions and lighting, with a focus on IAQ.
• Allows an integrated approach towards identification of causal factors, taking into account factors that may confound or modify relationships (interactions), including individual characteristics (e.g. demographic, lifestyle) as well as contextual factors (e.g. psychosocial environment), and co-exposure to multiple environmental influences.
• Allows looking at the pathway from biological reactivity to actually emerging health effects.
An example of how the framework elements may be employed in an integrated approach to assess the health risk from indoor air pollution was presented for ‘dry eyes’ that appears to be the most prevalent reported symptom in European modern offices.
In brief, from these explorative analyses, 37 physical building variables were identified as significantly associated with dry eyes. It should be noted that these associations are not necessarily causal relationships, and one can only speculate about underlying causes. However, this result provides first important clues towards which factors seem worth to be further investigated.
Building related factors significantly associated with dry eyes included e.g. factors related to occupancy, building procedures, building materials (e.g. partitions in the office consisting of wood, galvanised steel as duct material of ventilation systems), aspects of lighting (incl. control), aspects of the heating and cooling system, ventilation type, openable windows, humidification, height of ventilation system above ground level, design outdoor flow rate, presence of an underground car park, shortest distance from ventilation intake to busy road, location of printers/copy machines, presence of pets, aspects of cleaning (related to frequency and intensity). Results from the analyses in which the interaction between printers/copy machines and ‘use of chemicals during cleaning services’ was explored, indicated a significant interaction between the two variables. Again, as this is an observational study, no conclusions can be drawn on causality. However, if this association would be explained by a ‘true effect’, this would seem in line with the ‘reactive chemistry hypothesis’, where components from office equipment such as printers, react with emissions from chemical cleaning products, leading to ‘irritants’ in the indoor air, which may cause office work related health (eye) symptoms.
As a next step towards unravelling underlying causes, the data collected during the Detailed Study provide a powerful tool. Just a few — out of many possible examples — research questions that could be addressed for illustration:
• E.g. Distance of the ventilation intake to a major road:
Explorative analyses on the General survey database revealed a significant association between the shortest distance of the system intake to a major road and self-reported dry eyes. From this observational analysis, it is unsure if this relationship is causal. It may be hypothesised that traffic emissions entering the building through the ventilation inlet are a possible cause. Traffic related emissions are well known for their adverse health effects. This raises the following questions which need to be further explored, and for which the databases of the Detailed study would provide a valuable basis:
o Is there an observable difference in concentration(s) of traffic related air pollutants between buildings with “comparatively short” versus “comparatively large” distance of the ventilation inlet to a busy road? The use of filters at the ventilation system air intake inlet should be considered as a modifying factor.
o If so: which components are elevated (e.g. NO2 and/or particulate matter)?
o What is the association between these traffic related components and indicators of dry eyes (self-reported dry eyes, SBUT, ODSI)?
o Is there an indication of a clear exposure-response relationship?

• E.g. The interaction between location of printers and use of chemical cleaning agents:
o What is the relationship between placement of printers (in buildings with or without use of chemicals during cleaning) and components known to be primary emissions and/or secondary reaction products from these sources?
o What is the association between concentrations and (indicators of) dry eyes?

Support for potential causal relationships may come from experimental field (interventions) or laboratory (toxicological) studies.
The Framework proved to be a powerful tool to identify possible causes and thereby feed of specific recommendations and prioritization of policies related with IAQ in office buildings.
The results obtained from the Project were also used on a first assessment of the potential benefits of some of the proposed policy interventions. Departing from WP6 and WP7 reported results, a summary of the more important findings were presented, in the perspective of policy recommendations. The integrated exposure model developed in WP6 was used to assess the impacts of different policy interventions on indoor concentrations and population exposures and doses, by simulation of specific scenarios.
The simulated interventions and the major conclusions were:
• Office cleaning - the simulation results showed that cleaning activities should be performed in the morning, beforenormal office hours
• Removal of printers- the simulation results showed tha treduces indoor O3 concentrations while it has a minor impact on other pollutants
• Applying a minimum personal ventilation rate - a better understanding of the contributions of outdoor and indoor sources to the indoor air pollution is still needed. Increasing ventilation not always leads to a decrease (dilution) of the indoor concentrations, depending on the pollutant.
The experimental results obtained in the intervention study (WP7) to evaluate the effects on IAQ and potential benefits on health, were also object of analysis to inspire for some interventions and anticipate the potential benefits that could be expected from those interventions. The intervention exercise was focussed on the test of the effects of cleaning products associated with irritation. The more important findings of the study were:
a. The experimental work confirmed a reduction in the intervention zone of the concentration of some aldehydes such as formaldehyde
b. The experimental work showed that for VOCs and aldehydes, in the absence of any specific event, the indoor concentrations do not vary significantly within a day, and from a day to another, over a given week. These findings are useful to improve sampling strategies in office buildings for VOCs and aldehydes. On the contrary, for particles, high variability during a day and between the days in a week has been emphasized.
c. The study did not show consistent results regarding changes in IAQ related complaints and symptoms, as reported by workers in a questionnaire, following an intervention on air quality. Health symptoms as “dry eye” decreased in the intervention zone, although not reaching the significance, but the differences between areas should analyzed in depth considering also the potential role of microclimatic, climatic and psychosocial stress factors.

The Intervention studies that were performed in the field and those investigated by exposure simulation, raised the following questions:
• The in depth analysis of the Outdoor/Indoor concentration relations of typical outdoor pollutants;
• The importance of the chemical indoor reactions;
• The careful planning of the cleaning activities;
• The importance of choosing low emission cleaning products;
• The variance of ventilation rate during the day, according to the performed activities.

It is highly recommended to further research the complexity of the sources and pollutants with special focus on the cleaning agents, and the potential synergies with microclimatic and psychosocial stress factors.
Finally, OFFICAIR allows, then, to express that the future policies must be focused on the following items:
1) Reduction of the entry of pollutants from outdoors assuring that cities comply with ambient air guidelines established by WHO. Outdoor air keeps being a noticeable pollution source indoors.
2) Reduction of the pollutants emissions from indoor sources, through the establishment of limits of emissions for single pollutants and also imposing limits of others to total emissions to avoid the effects of unexpected pollutants, which may result from chemical reactions leading to new and undesirable pollutants.
3) Use ventilation based on health rationality in order to decrease exposure, taking in account the performed activities, while taking into consideration also outdoor air pollution.
4) Support further research on the relationship between building related physical characteristics and observed health effects to identify potential causes, indoor chemical reactivity, indoor/outdoor interaction, interaction between different sources, toxicology of mixtures, auditing/monitoring methodologies.

1.3.3. Dissemination and exploitation (WP9)
The successful completion of the project should be followed by a careful dissemination of the results, in order to make the projects outcomes available to the wider European community. In WP9, a Dissemination Protocol was set up at the beginning of the project to provide a coherent and efficient exploitation plan for the project results. This Protocol increased the added value of the project and ensured that the various aspects of the outcomes are exploited to their full extent. The Dissemination Protocol was initially set up and completed to identify the ways of its implementation and to formally agree on important issues. The Dissemination Protocol was updated during the progress of the project. Furthermore, a Business and Exploitation plan (D9.5) was developed towards the end of the project, which includes the individual partners’ exploitation plans of the OFFICAIR results and achievements.
As all partners have strong cooperation links, they were committed to exploit their individual contacts and collaborations at local and national scale and disseminate the project outcomes amongst them through different routes.
The key scientific conclusions that provide new insights into processes and mechanisms were and will be disseminated first of all, through the usual dissemination channels, i.e participation in conferences, workshops and seminars and publications in appropriate technical or peer reviewed journals. There was and will continue to be strong encouragement for publication of the results by all partners. Until now, there are 16 publications in peer-reviewed journals and 26 participations in conferences.
A further major goal was to obtain an optimal dissemination and exploitation of the project findings through systematic involvement, communication and meetings with all stakeholders i.e. building industry (e.g. architects, building developers, office managers) health professional and policy makers. This was aided by a mailing list of potential end users that received all the information material. This mailing list has been constituted by the partners at the beginning of the project. Until now around 300 people have joined this mailing list.
To help with OFFICAIR’s dissemination plan, periodic newsletters were produced on a six month basis. These newsletters were used in order to highlight the aims of the project, deliverables produced, milestones reached, recent publications of the results and any relevant news and events. Six newsletters were produced in total. Furthermore, a special leaflet (D9.3) was designed including all the important information about the aim and objectives of the project as well as the projects’ consortium. This leaflet was distributed in all the events that OFFICAIR organized or participated. In the framework of further dissemination to the end-users and the society, two special brochures were designed (D9.4). The one is addressed to the office building occupants on how to deal with IAQ at the office; the other is addressed to the office building owners and managers with ‘’tips’’ to provide a good IAQ for a healthy environment at work. All the OFFICAIR newsletters, the OFFICAIR flyer and the OFFICAIR brochures, can be found at the project website.
During the 6th OFFICAIR PSG/LP meeting that took place in Budapest, at the Eötvös Loránd University (ELTE) on the 23-24 May 2013, ELTE organized a national OFFICAIR workshop on indoor air quality in modern office buildings for disseminating the Project and its results so far. The workshop took place on 24 May 2013 right after the end of the Project meeting. The project coordinator along with the WP leaders and the local partner (ELTE) gave relevant presentations to the Hungarian audience.
Additionally, towards the end of the project (Month 36) the Coordinator with the Partners’ contribution, organized a Special Workshop, the OFFICAIR Final Workshop, where the results from the project so far were presented and extensions of the project outcome were discussed. The OFFICAIR Final Workshop took place on October 22nd 2013 in Brussels with 50 participants from all over Europe. Apart from the coordinator and the WP leaders there were also presentations from invited speakers with expertise on IAQ.
The aim of the Final Workshop was among others, to:
1. Discuss the project achievements;
2. Disseminate the obtained results;
3. Identify the opportunities for exploitation, after the formal completion of the project, by policy makers, health professionals and relevant stakeholders, as well as to receive feedback from them.
Amongst the invited parties were selected members of the targeted end-user groups and participants from the European Commission DGs in order to discuss about the possible use of the project results in future policy making.
The Special Workshop was followed by the final Project Steering Group Meeting that was held in Thessaloniki on the 30th of January 2014. A major concern of this meeting was the: “Identification of Opportunities for exploitation and dissemination after the formal completion of the project”.
During the three years of the Project, the Project coordinator took the opportunity to introduce OFFICAIR to networking events with EC representatives, stakeholders, and policy bodies and related EU-funded Projects. In this respect, OFFICAIR was presented twice in EPH (Environment and Public Health in modern society) seminars, once in an event of the European Commission Executive Agency for Health and Consumers – EAHC and in a Meeting of the Experts Group on Indoor Air Quality (IAQ).
In order to ensure a successful and sustainable exploitation of the OFFICAIR results, the exploitation plan was implemented at two strategic levels, namely the National and International level, with a primary focus on the European level.
The engagement of the stakeholders and user communities is key to the creation of impact, and forms part of the core activities of OFFICAIR. In short, the project partners have used their powerful networks and additional multiplier channels to raise the visibility of OFFICAIR. Considering the ambitious coverage goal of the project, which aims to involve the audience from the broadest geographical provenance, the core communication efforts were put on the OFFICAIR online communication tools.
The dissemination material was mainly produced in English; however in some cases translations in the language of each partner were made. Due to the nature and content of OFFICAIR, no products were produced that could have been promoted to the market or patents, or trademarks, or registered designs. The clear scientific character of OFFICAIR allowed for a new insight in IAQ research and the development of new tools for the evaluation of IAQ health effects, exposure and health risk assessment.

1.4 Concluding remarks

Health complaints of office workers in modern offices due to the office environment may have a dramatical impact on their wellbeing and on the work performance. OFFICAIR aims at being an important contributor, helping to steer EU policies towards the better protection of office workers by clarifying the mechanisms surrounding exposure conditions and effects. More specifically:

1. The indoor air quality in modern office buildings in Europe was monitored for the first time in association with the evaluation of the workers’ performance, their perception of comfort, including perception of indoor air quality (IAQ), and their self-reported health effects, including psycho-social and personal aspects;
2. A clearer picture has been generated in terms of building characteristics (equipment, types of HVAC systems, cleaning practices, etc.) in modern offices across Europe;
3. New insight has been given on ozone terpene chemistry in terms of products identification and quantification and potential toxicity;
4. A systematic study for evaluating IAQ health effects and health effect reduction via intervention measures to reduce pollutant emissions under different conditions in modern offices was made;
5. New tools have been developed in assessing exposure and health risk in modern offices and indoor microenvironments in general;
6. The OFFICAIR Project have developed new ground on IAQ research and its priorities to ensure healthy working conditions in modern offices across Europe;
7. The OFFICAIR Project Database further enriched with data will be an important instrument utilized by the stakeholders, such as consumers, policy makers, health professionals and industry people in order to assess emission and exposure;
8. The OFFICAIR Modeling Platform further improved in terms of models and data interaction can be more attractive to researchers and stakeholders in estimating indoor air pollution and exposure in modern office buildings and other indoor microenvironments;
9. The outputs of the OFFICAIR project, in association with other past or on-going European initiatives regarding the building stock and correlated products and practices, are expected to have an important great impact on:
• The assessment of the IAQ actual conditions with a reliable, economically acceptable and meaningful way, in terms of health effects and correlated guarantees;
• The setting of good practices and target indicators for the design, construction, maintenance and management of office buildings, bearing in mind the overall “sustainability” assessment, in other words, the IAQ conditions for comfort and health and the energy use conditions.

Potential Impact:
1.1 Strategic impact
The OFFICAIR Project is addressing the “Thematic Strategies on Air pollution” and the “European Environment and Health Action Plan”.
IAQ in office buildings is an issue of paramount interest, as it deals with workers providing services of the highest relevance for the companies/services. Their productivity is a critical parameter, not only because the man power represents one of the most costly production factors, but also, because there are still many uncertainties on how to deal with the issue in the context of the insurances regarding cases of illness in these environments.
The concern regarding productivity is not only related to the absenteeism associated with the diseases that can be due to the work environment, but it may also result from the less comfortable working conditions according to the WHO health definition, i.e. beyond the simple absence of illness. The fact that tobacco smoke is being the object of drastic measures of banning in public spaces and workplaces has reduced significantly the impact of unhealthy IAQ conditions.
However, new environments have been created in the modern offices, as a result of new urban contexts, new concepts for office buildings, where construction costs play an important role favouring standardization, pre-fabrication, new components and materials, as well as new energy strategies (lightning, heating, cooling and ventilation) and generalised use of new equipments and other consumer products.
Thus,
a) Considering that office buildings are some of the most widespread buildings technologies, following the trend of new types of services and new ways of providing services locally and worldwide;
b) Recognising that there is a growing common patron for office buildings; and
c) Understanding that Europe has a natural vocation to concentrate a large spectrum of offices/services in the context its expansion through the admission of new Member States but also to the scientific, technical and managerial interaction with the Global World,
it is to be expected that the “inputs” of the OFFICAIR project, in association with other European initiatives regarding the building stock and correlated products and practices (EPBD - Directive 2002/91/EC; CPD - Directive 89/106/EEC; GPS - Directive 2001/95/EC), will be of great impact in what regards:
• The assessment of the IAQ actual conditions in reliable and economically acceptable and in meaningful conditions in terms of health effects and correlated guarantees;
• The creation of good practices and target indicators for the design, construction, maintenance and management of office buildings bearing in mind the overall “sustainability” assessment, i.e. the IAQ conditions for comfort and health and the energy use conditions to care about local and global negative impacts namely, the global warming and subsequent climatic changes due to the CO2 equivalent emissions.
On the wake of recent proposals (e.g. EnVIE project) and in tune with several signs from recent EC policies [EPBD [COM(2008)780]] the impact of this project will have to take into account growing restrictions regarding the actual energy needs while, and at the same time, provisions must be taken to face the effects of the global warming/climate change in what concerns the energy needs themselves. It is widely accepted that there are nowadays phenomena, such as, the well known “heat island” effect that will impact negatively in the cooling needs and that is not always taken care in the context of the current legislation/standardization.
1.2. The expected impact in the call
The objectives set out by the OFFICAIR project and its stated impacts, were achieved by an integrated multi-disciplinary approach across several research fields that have taken advantage of the expertise, research findings, top-class facilities of the participating organisations. The integrated assessment and the research provided novel findings that significantly increased our knowledge in this field and achieved new ground breaking understanding of the key issue of indoor air pollution and the associated health effects.
OFFICAIR has been designed to provide a structure which combines three major laboratory and field based studies (WP3, 4, 5) with three integrating assessments (WP6, 7, 8). This structure has been adopted partly to enhance the European approach and impact of the study. The field and laboratory studies have been designed to include a geographical spread characteristic of the different EU climatic zones and realistic conditions. These studies were focused on eight (8) European countries that include Finland, Greece, Italy, Portugal, Netherlands, Hungary, Spain and France. The integrated assessments allowed this data to be evaluated in a full European context. The database created (WP2) provided the basis to place the specific laboratory and field results and a mechanism for the inclusion of the results of previous and ongoing studies, both national and European, into the assessment policy of OFFICAIR. The modelling chain will help predict the impacts of measures to reduce the risks from exposure to health relevant indoor pollutants under different conditions, representative of the full range of MS, taking into account different climatic conditions and socio-economic factors.
The crucial factor to achieve the desired impact (health, comfort and productivity in office in modern offices) was the close co-operation of all relevant stakeholders (e.g. building industry, health professionals, policy makers). The OFFICAIR consortium has targeted these groups aiming at introducing the project’s results and heightening awareness and understanding. This was achieved through the OFFICAIRs’ Dissemination Plan and Business and exploitation plan (WP9). Thus, OFFICAIR will directly contribute to EU policy making activities (such as Thematic Strategy on Air Pollution, 7th Environment Action Programme (EAP) to 2020) by setting coherent and harmonised goals throughout Europe.
The wider societal implications of OFFICAIR are described in detail in the part c) of this report in the form of a questionnaire covering the wider societal implications of the project and in D9.6 (Awareness and Wider Societal Implications). In general, OFFICAIR involved ethical issues as it involved adult healthy volunteers, human biological sample and human data collection. All participants signed an informed consent about their participation in the research campaigns. Where research on animals was necessary, this was conducted in line with the respective ethics and legislation. The project had very limited gender-related activity, there were several women involved in the research, including leaders of three work-packages. In the frame of interdisciplinarity, the following associated disciplines are involved in OFFICAIR according to the Frascati Manual 2002Classification of Scientific Disciplines:
1.1 Mathematics and computer sciences
1.3 Chemical sciences
1.5 Biological sciences
3.1 Basic medicine
3.2 Clinical medicine
3.3 Health sciences

OFFICAIR engaged with government/public bodies or policy makers (including international organisations) in communicating, disseminating and using the results of the project. The projects’ outputs can be used by the policy makers in the fields of energy, enterprise, environment, public health and research and innovation in national and European level.
Some wider implications and impact of the project are reflected with the publications and dissemination activities carried out throughout project lifetime, including in open media towards general public awareness. The project findings were widely disseminated by its consortium through publications in peer-reviewed journals, and presentations in conferences and other relevant events which are described in detail in part b) of this report “Plan for use and dissemination of foreground and in D9.5 (Business and exploitation plan). Until now 16 articles were published in peer-reviewed journals, of which only two were published in open access journals. The main reason for not open access of publication is the high cost. Information of the project was communicated to the general public through press release, media briefing, TV coverage/report, posters, flyers, coverage in national press, project website and beneficiaries’ websites, conferences, meetings and workshops. Information and communication products were produced mainly in English and at the languages of the beneficiaries involved. The OFFICAIR dissemination activities will be continued after the end of the Project with coming scientific publications and participations in conferences and relevant workshops.

1.2.1. Potential impact per Scientific WP
Database development for key indoor air pollutants in modern office buildings (WP2)
The use of harmonized criteria and tools for indoor air monitoring in modern office buildings has enabled the development of the OFFICAIR database containing information on key pollutants, relevant to indoor environments in modern offices of eight European countries. Following a cleaning and validation data procedure a reference database has been established, which will become publicly available short after the end of the project.
The OFFICAIR database system allows for data accessibility, compatibility and comparability. Thanks to its modularity and high degree of customization it can be flexibly used by other projects and/or similar applications. The database may constitute an important instrument for stakeholders, such as consumers, policy makers, health professionals and industry people in order to assess emission and exposure profiles and associated health relevant information concerning key pollutants which can be found in modern office buildings in Europe and indoor microenvironments in general.
The data contained in the OFFICAIR database and the direct links and accessibility established with the BUMA and BUMAC databases represent a clear added value and advantage as they could synergistically be used in the evaluation of the impact of relevant policies and exposure trends of indoor air pollutants in office buildings.
The OFFICAIR database was considered and included among the databases pertaining to module 4 ‘products and indoor air monitoring’ of the DG ENV’s IPCheM (Information Portal on Chemical Monitoring Data) under development by DG JRC. This will guarantee a major visibility and long-term accessibility of the OFFICAIR database in support of the implementation of air quality and consumer products related EU policies.

Laboratory studies on selected chemical reaction mechanisms relevant for indoor environments (WP3)
Health complaints of office workers in modern offices due to the office environment may have a dramatical impact on their wellbeing and on the work performance. To better map and consequently help solving this issue, a number of work items have been taken up in this WP. Most important in this context were: a) the development of new sampling and analytical methods to map the pollution better, b) to list the relation between office pollutants, health effects and the measurement methods and c) to actually demonstrate the new methods and produce new data for previously unknown pollutants.
Through dissemination by publications, five in this WP, it is clear that this new information and know how will help stakeholders substantially to reduce the adverse impact of office environments. Building constructors, architects, designers, employers and employee federations will all benefit. The impact of pollution in indoor environments is reduced through this research and the further uptake/implementation by stakeholders: exact quantification of the impact is not studied. The effect of IAQ should not be underestimated and even a minor improvement has already substantial effects. Previous studies indicate the order of magnitude and impact in view of DALYs and BoD.
The contribution of poor IAQ to the loss of healthy life expectancy, expressed as disability adjusted life years (DALY) was calculated in the EU Envie1 study for 7 diseases: asthma, cardiovascular diseases, COPD, lung cancer, sick building syndrome, respiratory infectious diseases and acute CO intoxication. The DALY’s per year for all diseases involved at the EU level, was overall 2 million DALY’s/year within a population of 480 million. A follow up study (IAIAQ2) confirmed that the European burden of disease caused/mediated by indoor air is 3 % of the total BoD (burden of diseases). The health benefits of IAQ improvements in offices, future actions and as such the economic and societal implications may therefore be substantial.
References
1 ENVIE, 6th FP Co-ordination action on indoor air quality and health effects, 2002-2006 http://indoorairenvie.cstb.fr
2 IAIAQ, Indoor air risks and impacts of alternative policy interventions in the EU countries – the IAIAQ study. Jantunen M et al, Indoor air 2010.

IAQ Assessment (WP4)
The WP4 provided interesting outputs in terms of IAQ sampling strategy in office buildings, which will be useful for the establishment of harmonized protocols taking into account the concentration spatial and temporal variabilities. For example, if a worker chronic exposure needs to be assessed, minimum two periods with some contrasted meteorological conditions must be considered. Similarly, if IAQ in a building with more than two levels must be evaluated, a minimum of two sampling points at distant levels is recommended. Finally, for VOCs and aldehydes, one half-day sampling within a week would be enough (provided that no outstanding event takes place during the sampling).Such outputs are fundamental to set relevant sampling strategies, for example, in the context of checking the compliance with guideline values or for IAQ monitoring within the frame of a building audit or “Environment & Health” certification. More basically, the IAQ data set produced by the project can now be considered as a reference on indoor concentrations in recently built or recently refurbished office buildings in Europe. Considering the increasing willingness of people to better know their exposure to indoor air pollution, the OFFICAIR data can be used in the future, in addition to WHO or INDEX IAQ guidelines, to interpret the measured results.

Targeted toxicological laboratory studies (WP5)
Neither single, nor repeated exposure of ozone-initiated limonene reaction products indicated adverse airway effects other than sensory irritation in the upper airways. However, two ozone-initiated reaction products do raise concern about possible airway effects that may occur in the case of acute and longer-term emission sources of terpenes. There is no indication that ozone-initiated generation of aerosols (ultrafines) cause adverse airway effects. This conclusion is exclusive for the ozone/limonene system and cannot be extended to other ozone-initiated terpene system generated gaseous reaction products and aerosols. Cardiovascular effects have also not been investigated in this project. Since consumer products in general contain fragrances which represent a large variety of terpenoids in various amounts, a systematic investigation into ozone-initiated fragrance chemistry and its health effects is warranted, in particular, cleaning and consumer products under both acute and constant emission patterns at realistic ozone levels. Furthermore, a field monitoring campaign of newly identified reactions products (not previously measured) of concern regarding airway effects is warranted to be carried out on a European scale.
Sensory irritation in the upper airways by formaldehyde was unaffected by exposure to either low relative humidity or high relative humidity. However, this conclusion cannot be extended to the eyes. Exposure to low relative humidity appears to affect normal animals more than sensitized animals to sensory irritation by formaldehyde. This indicates a strong need for a more integrated understanding of the multiple effects of relative or absolute humidity in indoor air on respiratory health and comfort. Since eye symptoms show a high prevalence in the office environment, the economic aspects may be substantial about tuning in the optimal conditions of humidity.
The ozone-initiated limonene system may promote allergic (ovalbumin) sensitization, but lung inflammation has not been observed. Thus, an allergic inflammatory effect is not supported. Further studies are necessary to generalize these findings.
Air-liquid-interface in vitro exposure of human lung cells to ozone-initiated reaction products of limonene, either or not in combination with printer emission, did not indicate acute adverse health responses. Further studies are warranted for the improvement of validity and further assessment of associations with in vivo and human exposure studies.
Formaldehyde is a strong sensory irritant in the upper airways and the eyes. Although humidity does not appear to influence the upper airways regarding sensory irritation, our understanding of its impact on eye symptomatology is limited, in particular, at conditions of work- or disease-related destabilization of the eye tear film. Thus, it is recommended to develop a model that integrates all risk factors (environmental, occupational, and personal) with adverse alterations of the eye tear film and associated with eye symptomatology.
When the oxidative potential of NO2, O3 and PM were all examined in the same experimental system, a lung lining fluid model, PM was found to be the primary contributor to the oxidative activity of the air we breathe. Given that PM is believed to cause pathophysiological actions in the respiratory system, at least in part, through oxidative stress these finding emphasize the importance of minimizing the concentrations of PM in the air we breathe. It was also found that oxidative potential of ambient PM could not be changed by the presence of gaseous oxidant pollutants such as NO2 and O3 but rather any impact of these would result from their additive oxidative activities.
Given the importance of minimizing exposure to PM the oxidative potential of PM2.5 samples collected inside modern offices, from seven EU countries was found to vary by building type, season, and location. Specifically, evidence of seasonal, regional and site variation in the OPPM2.5 metrics (OP/µg and OP/m3) was observed, as well as statistical variation in the ratio of Indoor:Outdoor OP found across all countries, all cities, and between sites. When an intervention study was undertaken in which office cleaning products were replaced, differences were demonstrated Post-Intervention between the Control and Intervention rooms in the Netherlands. These findings indicate that the oxidative potential of PM in and around office buildings has different temporal and spatial patterns and that a better understanding of the reasons for this will help guide mitigation strategies which should improve indoor ambient air quality.

IAQ and exposure modelling in modern office microenvironments (WP6)
WP6 has successfully developed a new suite of models to provide an integrated assessment of indoor air pollution concentrations, office worker exposure, and possible health risks in response to different policy interventions, at different locations across Europe. A user-friendly interface has been built on the OFFICAIR website to allow further use of this integrated modelling system in a range of future scientific and policy applications, hence ensuring a long-term legacy of the work.
The results of the chemical models suggested that the background concentrations of HCHO, IPOH and 4-AMCH were low and that any additional formation from cleaning and printing emissions was small, even when the 95%ile concentrations in the worst case summer of 2003 were considered. Therefore the health risk to office workers in modern European offices from these compounds is low, and policy interventions will have limited benefits for any symptoms linked to these compounds. However, in interpreting this key finding, it is important to note that:
- The models could not be fully validated with measurement data and hence some uncertainty exists over the validity of model predictions
- Other groups of workers, and in particular office cleaning staff, may have a greater exposure to these and other compounds of health concern
- Simulations were based on the cleaning products tested in the OFFICAIR programme; other products with greater limonene emissions may be in use in some offices in Europe today
- CFD results showed large spatial variation in worker exposure to primary particles; hence assessments based on the assumption of homogeneous pollutant concentrations within an office, such as the chemical models used in WP6, may underestimate health risks for individual workers
In the case of PM2.5 and ozone, the policy interventions tested also had little effect on office worker exposure, although the background concentrations, without any emissions within offices, especially in 2003 in southern Europe, were close to current air quality guidelines. It is possible that the secondary particles formed within offices have greater toxicity than the ambient particulate on which current guidelines are based, and this needs further evaluation.

Health effects evaluation in modern office buildings and health risk assessment (WP7)
In conclusion, indoor air pollution may cause or aggravate symptoms (eye symptoms) and have an impact on health (inflammatory and oxidative stress; cardiovascular function) and productivity. High terpenes and aldehydes cleaning products could contribute to lowering IAQ perception and to increasing lung inflammation.
A more clear picture has been generated in terms of air quality, air quality perception and comfort in modern offices across Europe: the preliminary results from the three stages of the study performed in WP7 show that the most frequently reported complaints about IAQ are “Air Too still”, Air too dry” and “Air stuffy”; “dry eyes” and “dry skin” are the most reported symptoms. The correlation between complaints and symptoms known to be related to IAQ and the role of noise and IAQ particulate matter on cardiovascular symptoms needs to be further evaluated.
Data from the intervention study will provide evidences on the benefit on health and IAQ of intervention strategies related to IAQ and deeply investigate the sensory irritation, the inflammatory and oxidative effects, both local, i.e. in the airways, and systemic, and the endothelial and autonomic dysfunction due to exposure to targeted indoor air pollutants identified in WP2, WP3 and WP6 (including reaction products), taking into account the potential role of psychosocial stress.
Results from the study confirm the need of deeply studying the complexity of sources of pollutants and the heterogeneity of indoor air pollutants, with a special focus on cleaning agents when studying IA-related health effects. Moreover, synergies with microclimatic and psychosocial stress factors should be considered.
The questionnaire survey on health effects, the detailed investigations on health effects and the intervention study contribute to the improvement of knowledge on IA-related health effects in office buildings. The health risk assessment contributes to improve risk assessment data for the creation of good practices and target indicators for design, construction, maintenance and management of modern office buildings and to suggest the best recommendations and prioritization of IAQ policies related to office buildings.

Risk management & policies/recommendations (WP8)
The outputs of the OFFICAIR project, in association with other European initiatives regarding the building stock and correlated products and practices is expected to have an important great impact on:
• The assessment of the IAQ actual conditions with a reliable, economically acceptable and meaningful way, in terms of health effects and correlated guarantees;
• The setting of good practices and target indicators for the design, construction, maintenance and management of office buildings, bearing in mind the overall “sustainability” assessment, in other words, the IAQ conditions for comfort and health and the energy use conditions.
A set of specific recommendations in order to improve the indoor air quality inside office buildings was presented:
1) Limit entrance of pollutants from outdoor - The OFFICAIR results from modelling as well from the field campaigns demonstrated that better understanding of the contributions of outdoor and indoor sources to the indoor air pollution is still needed. In the case of pre-construction and building design phase, the building location should be a parameter to be assessed as a first component of the source control strategy.
2) Limit pollutants from indoor sources - The OFFICAIR results from the field studies, and in particular the intervention study, highlighted also a very important issue, the reactivity of indoor chemistry, which is not covered by the individual evaluation used presently. So it is recommendable to limit the emissions to minimum values and, in consequence, to opt by low emission cleaning products and by low emission constructions materials.
3) Limit exposure, using ventilation with rationality - OFFICAIR results may lead to exploit the following possibilities:
• The relations of outdoor/indoor concentrations of pollutants typical from outdoor should be analyzed in depth
• The ventilation rate can be variable along the occupational period, according to the scheduled activities
4) Support further research - The OFFICAIR results opened up new windows leading to explore aspects such as:
• The interaction outdoor/indoor air and its potential for assuring the needed ventilation indoors with ambient air
• The indoor chemical reactions, in particular the interaction between building sources, for example between printers/copy machines and ‘use of chemicals during cleaning services
• The study of toxicology of ozone-initiated reaction mixtures. Exposure of new critical respiratory pollutants from ozone terpene chemistry. Multiple sources and field campaign
• The role of noise and IAQ particulate matter on cardiovascular symptoms needs to be further evaluated.
• In vitro and in vivo exposure studies of key oxidation products, in particular, 4-OPA warranting further investigation.

1.3. Societal impact
A significant percentage of the EU MS population is employed as an office workforce. This percentage is expected to rise in the future. Economic activity in the most populous EU states (e.g. Germany, UK, France, Italy) is increasingly relying on services, while arguably, all EU states are heading towards the same direction. Thus, EU countries are increasingly moving away from industry and agriculture, and rely on services for their economic development (based in people working indoors).
Concerns over the effects of GHG on the planet’s climate, coupled with fears over security of energy supply and EU over reliance on oil and gas production, have led to the development of guidelines towards energy conservation, energy efficiency and lower resources consumption in buildings. Without doubting the necessity of such policies/guidelines, a negative side effect has been lower ventilation rates, which led to a deterioration of IAQ, especially in modern offices where ventilation is usually controlled. OFFICAIR aims at being an important contributor, helping to steer EU policies towards the better protection of office workers by clarifying the mechanisms surrounding exposure conditions and effects.
1.4. Economic impact
The main symptoms of a SBS (airway irritation, allergies, respiratory problems) affect the health, comfort and thus productivity and efficiency of the office workers. Arguably, costs for medical care and work lost, burden substantially insurance companies, governments and the society at large. Although OFFICAIR does not claim to have an immediate positive economic impact on the EU or the participating countries, by achieving its stated aims and objectives will, in the long term, contribute towards the improvement of the well being and comfort in office environments.

List of Websites:
http://www.officair-project.eu/

Contact details:
OFFICAIR Coordinator: Prof. John Bartzis

University of Western Macedonia,
Department of Mechanical Engineering,
Environmental Technology Laboratory,
Sialvera and Bacola Str., 50100, Kozani, Greece
e-mail: bartzis@uowm.gr
Tel. +30 24610 56624
Fax.+30 24610 21730