Exposure limits for indoor volatile substances concerning the general population: The role of population-based differences in sensory irritation of the eyes and airways for assessment factors.

Assessment factors (AFs) are essential in the derivation of occupational exposure limits (OELs) and indoor air quality guidelines. The factors shall accommodate differences in sensitivity between subgroups, i.e., workers, healthy and sick people, and occupational exposure versus life-long exposure for the general population. Derivation of AFs itself is based on empirical knowledge from human and animal exposure studies with immanent uncertainty in the empirical evidence due to knowledge gaps and experimental reliability. Sensory irritation in the eyes and airways constitute about 30-40% of OELs and is an abundant symptom in non-industrial buildings characterizing the indoor air quality and general health. Intraspecies differences between subgroups of the general population should be quantified for the proposal of more 'empirical' based AFs. In this review, we focus on sensitivity differences in sensory irritation about gender, age, health status, and vulnerability in people, based solely on human exposure studies. Females are more sensitive to sensory irritation than males for few volatile substances. Older people appear less sensitive than younger ones. However, impaired defense mechanisms may increase vulnerability in the long term. Empirical evidence of sensory irritation in children is rare and limited to children down to the age of six years. Studies of the nervous system in children compared to adults suggest a higher sensitivity in children; however, some defense mechanisms are more efficient in children than in adults. Usually, exposure studies are performed with healthy subjects. Exposure studies with sick people are not representative due to the deselection of subjects with moderate or severe eye or airway diseases, which likely underestimates the sensitivity of the group of people with diseases. Psychological characterization like personality factors shows that concentrations of volatile substances far below their sensory irritation thresholds may influence the sensitivity, in part biased by odor perception. Thus, the protection of people with extreme personality traits is not feasible by an AF and other mitigation strategies are required. The available empirical evidence comprising age, lifestyle, and health supports an AF of not greater than up to 2 for sensory irritation. Further, general AFs are discouraged for derivation, rather substance-specific derivation of AFs is recommended based on the risk assessment of empirical data, deposition in the airways depending on the substance's water solubility and compensating for knowledge and experimental gaps. Modeling of sensory irritation would be a better 'empirical' starting point for derivation of AFs for children, older, and sick people, as human exposure studies are not possible (due to ethical reasons) or not generalizable (due to self-selection). Dedicated AFs may be derived for environments where dry air, high room temperature, and visually demanding tasks aggravate the eyes or airways than for places in which the workload is balanced, while indoor playgrounds might need other AFs due to physical workload and affected groups of the general population.

Asthma-inducing potential of 28 substances in spray cleaning products-Assessed by quantitative structure activity relationship (QSAR) testing and literature review.

Exposure to spray cleaning products constitutes a potential risk for asthma induction. We set out to review whether substances in such products are potential inducers of asthma. We identified 101 spray cleaning products for professional use. Twenty-eight of their chemical substances were selected. We based the selection on (a) positive prediction for respiratory sensitisation in humans based on quantitative structure activity relationship (QSAR) in the Danish (Q)SAR Database, (b) positive QSAR prediction for severe skin irritation in rabbits and (c) knowledge on the substances' physico-chemical characteristics and toxicity. Combining the findings in the literature and QSAR predictions, we could group substances into four classes: (1) some indication in humans for asthma induction: chloramine, benzalkonium chloride; (2) some indication in animals for asthma induction: ethylenediaminetetraacetic acid (EDTA), citric acid; (3) equivocal data: hypochlorite; (4) few or lacking data: nitriloacetic acid, monoethanolamine, 2-(2-aminoethoxy)ethanol, 2-diethylaminoethanol, alkyldimethylamin oxide, 1-aminopropan-2-ol, methylisothiazolinone, benzisothiazolinone and chlormethylisothiazolinone; three specific sulphonates and sulfamic acid, salicylic acid and its analogue sodium benzoate, propane-1,2-diol, glycerol, propylidynetrimethanol, lactic acid, disodium malate, morpholine, bronopol and benzyl alcohol. In conclusion, we identified an asthma induction potential for some of the substances. In addition, we identified major knowledge gaps for most substances. Thus, more data are needed to feed into a strategy of safe-by-design, where substances with potential for induction of asthma are avoided in future (spray) cleaning products. Moreover, we suggest that QSAR predictions can serve to prioritise substances that need further testing in various areas of toxicology.

Indoor gaseous air pollutants determinants in office buildings-The OFFICAIR project.

The aim of this study was to identify determinants of aldehyde and volatile organic compound (VOC) indoor air concentrations in a sample of more than 140 office rooms, in the framework of the European OFFICAIR research project. A large field campaign was performed, which included (a) the air sampling of aldehydes and VOCs in 37 newly built or recently retrofitted office buildings across 8 European countries in summer and winter and (b) the collection of information on building and offices' characteristics using checklists. Linear mixed models for repeated measurements were applied to identify the main factors affecting the measured concentrations of selected indoor air pollutants (IAPs). Several associations between aldehydes and VOCs concentrations and buildings' structural characteristic or occupants' activity patterns were identified. The aldehyde and VOC determinants in office buildings include building and furnishing materials, indoor climate characteristics (room temperature and relative humidity), the use of consumer products (eg, cleaning and personal care products, office equipment), as well as the presence of outdoor sources in the proximity of the buildings (ie, vehicular traffic). Results also showed that determinants of indoor air concentrations varied considerably among different type of pollutants.

Biocidal spray product exposure: Measured gas, particle, and surface concentrations compared with spray model simulations.

The purpose of the study was to compare measured air and surface concentrations after application of biocidal spray products with concentrations simulated with the ConsExpo Web spray simulation tool. Three different biocidal spray products were applied in a 20 m3 climate test chamber with well-controlled environmental conditions (22 ± 1 °C, 50 ± 2% relative humidity, and air exchange rate of 0.5 h-1). The products included an insect spray in a pressurized spray can, another insect spray product, and a disinfectant, the latter two applied separately with the same pumped spray device. The measurements included released particles, airborne organic compounds in both gas and particle phase, and surface concentrations of organic compounds on the wall and floor in front of the spraying position and on the most remote wall. Spraying time was a few seconds and the air concentrations were measured by sampling on adsorbent tubes at 9-13 times points during 4 hr after spraying. The full chamber experiment was repeated 2-3 times for each product. Due to sedimentation the concentrations of the particles in air decayed faster than explained by the air exchange rate. In spite of that, the non-volatile benzalkonium chlorides in the disinfectant could be measured in the air more than 30 min after spraying. ConsExpo Web simulated concentrations that were about half of the measured concentrations of the active substances when as many as possible of the default simulation parameters were replaced by the experimental values. ConsExpo Web was unable to simulate the observed faster decay of the airborne concentrations of the active substances, which might be due to underestimation of the gravitational particle deposition rates. There was a relatively good agreement between measured surface concentrations on the floor and calculated values based on the dislodgeable amount given in the selected ConsExpo Web scenarios. It is suggested to always supplement simulation tool results with practical measurements when assessing the exposure to a spray product.

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment.

In 2010, the World Health Organization (WHO) established an indoor air quality guideline for short- and long-term exposures to formaldehyde (FA) of 0.1 mg/m3 (0.08 ppm) for all 30-min periods at lifelong exposure. This guideline was supported by studies from 2010 to 2013. Since 2013, new key studies have been published and key cancer cohorts have been updated, which we have evaluated and compared with the WHO guideline. FA is genotoxic, causing DNA adduct formation, and has a clastogenic effect; exposure-response relationships were nonlinear. Relevant genetic polymorphisms were not identified. Normal indoor air FA concentrations do not pass beyond the respiratory epithelium, and therefore FA's direct effects are limited to portal-of-entry effects. However, systemic effects have been observed in rats and mice, which may be due to secondary effects as airway inflammation and (sensory) irritation of eyes and the upper airways, which inter alia decreases respiratory ventilation. Both secondary effects are prevented at the guideline level. Nasopharyngeal cancer and leukaemia were observed inconsistently among studies; new updates of the US National Cancer Institute (NCI) cohort confirmed that the relative risk was not increased with mean FA exposures below 1 ppm and peak exposures below 4 ppm. Hodgkin's lymphoma, not observed in the other studies reviewed and not considered FA dependent, was increased in the NCI cohort at a mean concentration ≥0.6 mg/m3 and at peak exposures ≥2.5 mg/m3; both levels are above the WHO guideline. Overall, the credibility of the WHO guideline has not been challenged by new studies.

Evaluation of airborne sensory irritants for setting exposure limits or guidelines: A systematic approach.

Sensory irritation of eyes and upper airways is an important endpoint for setting occupational exposure limits (OELs) and indoor air guidelines. Sensory irritants cause a painful burning, stinging and itching sensation. Controlled chamber studies are the "golden standard" for evaluations. Well conducted workplace studies offer another possibility. For generalization, the number of participants and their age, smoking, gender, and prior exposure, experience and mood has to be considered. Exposure assessments have to be reliable and exposure duration sufficiently long to establish time-response relationships. A potential confounding by odour has to be assessed. For workplace exposures, mixed exposure and healthy worker effects have to be evaluated. The "Alarie test" is the only validated animal bioassay for prediction of sensory irritation in humans. The mouse bioassay uses the trigeminal reflex-induced decrease in the respiratory rate. The 50% decrease (RD50) has been correlated with OELs set for sensory irritants; predicted OELs for sensory irritants are 0.03xRD50. Evaluation of the bioassay comprises the number of mice and the strain, the reliability of the exposure concentrations and exposure-response relationships, and the similar mode-of-action in mice and humans. These approaches can be used for quality assurance of reported data to set air quality guidelines.

Generation and Characterization of Indoor Fungal Aerosols for Inhalation Studies.

In the indoor environment, people are exposed to several fungal species. Evident dampness is associated with increased respiratory symptoms. To examine the immune responses associated with fungal exposure, mice are often exposed to a single species grown on an agar medium. The aim of this study was to develop an inhalation exposure system to be able to examine responses in mice exposed to mixed fungal species aerosolized from fungus-infested building materials. Indoor airborne fungi were sampled and cultivated on gypsum boards. Aerosols were characterized and compared with aerosols in homes. Aerosols containing 10(7)CFU of fungi/m(3)air were generated repeatedly from fungus-infested gypsum boards in a mouse exposure chamber. Aerosols contained Aspergillus nidulans,Aspergillus niger, Aspergillus ustus, Aspergillus versicolor,Chaetomium globosum,Cladosporium herbarum,Penicillium brevicompactum,Penicillium camemberti,Penicillium chrysogenum,Penicillium commune,Penicillium glabrum,Penicillium olsonii,Penicillium rugulosum,Stachybotrys chartarum, and Wallemia sebi They were all among the most abundant airborne species identified in 28 homes. Nine species from gypsum boards and 11 species in the homes are associated with water damage. Most fungi were present as single spores, but chains and clusters of different species and fragments were also present. The variation in exposure level during the 60 min of aerosol generation was similar to the variation measured in homes. Through aerosolization of fungi from the indoor environment, cultured on gypsum boards, it was possible to generate realistic aerosols in terms of species composition, concentration, and particle sizes. The inhalation-exposure system can be used to study responses to indoor fungi associated with water damage and the importance of fungal species composition.

Indoor air humidity revisited: Impact on acute symptoms, work productivity, and risk of influenza and COVID-19 infection.

Recent epidemiological and experimental findings reconfirm that low indoor air humidity (dry air) increases the prevalence of acute eye and airway symptoms in offices, result in lower mucociliary clearance in the airways, less efficient immune defense, and deteriorate the work productivity. New epidemiological and experimental research also support that the environmental conditions for the risk of infection of influenza and COVID-19 virus is lowest in the Goldilocks zone of 40-60% relative humidity (RH) by decrease of the airways' susceptibility, which can be elevated by particle exposure. Furthermore, low RH increases the generation of infectious virus laden aerosols exhaled from infected people. In general, elevation of the indoor air humidity from dry air increases the health of the airways concomitantly with lower viability of infectious virus. Thus, the negative effects of ventilation with dry outdoor air (low absolute air humidity) should be assessed according to 1) weakened health and functionality of the airways, 2) increased viability and possible increased transmissibility of infectious virus, and 3) evaporation of virus containing droplets to dry out to droplet nuclei (also possible at high room temperature), which increases their floating time in the indoor air. The removal of acid-containing ambient aerosols from the indoor air by filtration increases pH, viability of infectious viruses, and the risk of infection, which synergistically may further increase by particle exposure. Thus, the dilution of indoor air pollutants and virus aerosols by dry outdoor air ventilation should be assessed and compared with the beneficial health effects by control of the center zone of 40-60% RH, an essential factor for optimal functionality of the airways, and with the additional positive impact on acute symptoms, work productivity, and reduced risk of infection.

Reduction of acute respiratory infections in day-care by non-pharmaceutical interventions: a narrative review.

Objective: Children who start in day-care have 2-4 times as many respiratory infections compared to children who are cared for at home, and day-care staff are among the employees with the highest absenteeism. The extensive new knowledge that has been generated in the COVID-19 era should be used in the prevention measures we prioritize. The purpose of this narrative review is to answer the questions: Which respiratory viruses are the most significant in day-care centers and similar indoor environments? What do we know about the transmission route of these viruses? What evidence is there for the effectiveness of different non-pharmaceutical prevention measures? Design: Literature searches with different terms related to respiratory infections in humans, mitigation strategies, viral transmission mechanisms, and with special focus on day-care, kindergarten or child nurseries, were conducted in PubMed database and Web of Science. Searches with each of the main viruses in combination with transmission, infectivity, and infectious spread were conducted separately supplemented through the references of articles that were retrieved. Results: Five viruses were found to be responsible for ≈95% of respiratory infections: rhinovirus, (RV), influenza virus (IV), respiratory syncytial virus (RSV), coronavirus (CoV), and adenovirus (AdV). Novel research, emerged during the COVID-19 pandemic, suggests that most respiratory viruses are primarily transmitted in an airborne manner carried by aerosols (microdroplets). Conclusion: Since airborne transmission is dominant for the most common respiratory viruses, the most important preventive measures consist of better indoor air quality that reduces viral concentrations and viability by appropriate ventilation strategies. Furthermore, control of the relative humidity and temperature, which ensures optimal respiratory functionality and, together with low resident density (or mask use) and increased time outdoors, can reduce the occurrence of respiratory infections.

Gas chromatography interfaced with atmospheric pressure ionization-quadrupole time-of-flight-mass spectrometry by low-temperature plasma ionization.

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 volatile organic compounds. Amounts down to ca. 0.5 ng (on column) could be detected for most compounds and with a chromatographic performance comparable to 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 each of the analyzed compound classes and can therefore be useful for identification of functional groups. A total of 20 different compounds within 8 functional groups were analyzed.

Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment.

We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85-89%) or low (<10%) relative humidity, respectively for 48h prior to a 60-min exposure to either 0.4, 1.8 or about 5ppm FA. Before, during and after exposure, breathing parameters were monitored. These included the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the "scrubber effect" in the nose, consequently protecting the conducting and lower airways.

Recent trend in risk assessment of formaldehyde exposures from indoor air.

Studies about formaldehyde (FA) published since the guideline of 0.1 mg/m(3) by the World Health Organization (WHO) in 2010 have been evaluated; critical effects were eye and nasal (portal-of-entry) irritation. Also, it was considered to prevent long-term effects, including all types of cancer. The majority of the recent toxicokinetic studies showed no exposure-dependent FA-DNA adducts outside the portal-of-entry area and FA-DNA adducts at distant sites were due to endogenously generated FA. The no-observed-adverse-effect level for sensory irritation was 0.5 ppm and recently reconfirmed in hypo- and hypersensitive individuals. Investigation of the relationship between FA exposure and asthma or other airway effects in children showed no convincing association. In rats, repeated exposures showed no point mutation in the p53 and K-Ras genes at ≤15 ppm neither increased cell proliferation, histopathological changes and changes in gene expression at 0.7 ppm. Repeated controlled exposures (0.5 ppm with peaks at 1 ppm) did not increase micronucleus formation in human buccal cells or nasal tissue (0.7 ppm) or in vivo genotoxicity in peripheral blood lymphocytes (0.7 ppm), but higher occupational exposures were associated with genotoxicity in buccal cells and cultivated peripheral blood lymphocytes. It is still valid that exposures not inducing nasal squamous cell carcinoma in rats will not induce nasopharyngeal cancer or lymphohematopoietic malignancies in humans. Reproductive and developmental toxicity are not considered relevant in the absence of sensory irritation. In conclusion, the WHO guideline has been strengthened.

Adjuvant and inflammatory effects in mice after subchronic inhalation of allergen and ozone-initiated limonene reaction products.

Inhalation of ozone (O3), a highly toxic environmental pollutant, produces airway inflammation and exacerbates asthma. However, in indoor air, O3 reacts with terpenes (cyclic alkenes), leading to formation of airway irritating pollutants. The aim of the study was to examine whether inhalation of the reaction products of O3 and the terpene, limonene, as well as limonene and low-level O3 by themselves, induced allergic sensitization (formation of specific immunoglobulin [Ig] E) and airway inflammation in a subchronic mouse inhalation model in combination with the model allergen ovalbumin (OVA). BALB/cJ mice were exposed exclusively by inhalation for 5 d/wk for 2 wk and thereafter once weekly for 12 wk. Exposures were low-dose OVA in combination with O3, limonene, or limonene/O3 reaction products. OVA alone and OVA + Al(OH)3 served as control groups. Subsequently, all groups were exposed to a high-dose OVA solution on three consecutive days. Serum and bronchoalveolar lavage fluid were collected 24 h later. Limonene by itself did not promote neither OVA-specific IgE nor leukocyte inflammation. Low-level O3 promoted eosinophilic airway inflammation, but not OVA-specific IgE formation. The reaction products of limonene/O3 promoted allergic (OVA-specific IgE) sensitization, but lung inflammation, which is a characteristic of allergic asthma, was not observed. In conclusion, the study does not support an allergic inflammatory effect attributed to O3-initiated limonene reaction products in the indoor environment.

Characterization of the aerosol release from spray cleaning and disinfection products - Spray scenarios in a climate chamber.

Cleaning work using spray products has been associated with adverse respiratory effects but little is known of the exposure concentrations. The purpose of this study was to characterize aerosol generation at spray scenarios in a controlled climate chamber. Spraying on vertically and horizontally oriented surfaces, as well as spraying on a cloth, was investigated. Furthermore, the effect of nozzle geometry was tested. The average mass generation rates of six pressurized spray cans and 13 trigger sprays were about 1.7 g/s and did not differ significantly, but the average values of the individual sprays had large variations (0.5-3.1 g/s). The time required to halve the air concentration of aerosol particles, the half-life time, was determined for all spray products. The average half-life time of the total particle mass concentration (TPMC) of the pressurized spray cans was 0.5 h versus 0.25 h for trigger sprays. Gravimetrically determined airborne fractions of pressurized spray cans tended to be higher than those of trigger sprays. However, airborne fractions based on the measured peak TPMC were up to three orders of magnitude smaller. A comparison of different trigger spray nozzles when spraying the same product showed that the TPMC can be up to 18 times higher for the largest emitting nozzle. The distance of the nozzle to a cloth should be 1 cm to significantly reduce the concentration of the generated aerosols. ConsExpo modeling predicted the measured peak TPMC well but less well the decay.

Influence of temperature on the emission of di-(2-ethylhexyl)phthalate (DEHP) from PVC flooring in the emission cell FLEC.

Emissions of di-(2-ethylhexyl) phthalate (DEHP) from one type of polyvinylchloride (PVC) flooring with approximately 13% (w/w) DEHP as plasticizer were measured in the Field and Laboratory Emission Cell (FLEC). The gas-phase concentrations of DEHP versus time were measured at air flow rate of 450 mL·min(-1) and five different temperatures: 23 °C, 35 °C, 47 °C, 55 °C, and 61 °C. The experiments were terminated two weeks to three months after steady-state was reached and the interior surface of the FLECs was rinsed with methanol to determine the surface concentration of DEHP. The most important findings are (1) DEHP steady-state concentrations increased greatly with increasing temperature (0.9 ± 0.1 µg·m(-3), 10 ± 1 µg·m(-3), 38 ± 1 µg·m(-3), 91 ± 4 µg·m(-3), and 198 ± 5 µg·m(-3), respectively), (2) adsorption to the chamber walls decreased greatly with increasing temperature (measured partition coefficient between FLEC air and interior surface are: 640 ± 146 m, 97 ± 20 m, 21 ± 5 m, 11 ± 2 m, and 2 ± 1 m, respectively), (3) gas-phase DEHP concentration in equilibrium with the vinyl flooring surface is close to the vapor pressure of pure DEHP, and (4) with an increase of temperature in a home from 23 to 35 °C, the amount of DEHP in the gas- and particle-phase combined is predicted to increase almost 10-fold. The amount in the gas-phase increases by a factor of 24 with a corresponding decrease in the amount on the airborne particles.

Professional cleaning and risk of asthma - a Danish nationwide register-based study.

OBJECTIVE: This study aimed to investigate the risk of asthma among professional cleaners in a nationwide population-based study. METHODS: Professional cleaners, aged 16-50 years, were identified according to the yearly assigned administrative job and industrial codes in a register-based, matched cohort study with other manual workers as references (1995-2016). Asthma was defined from national registers based on hospitalization and medication. Associations between recent and cumulative cleaning years and risk of asthma were estimated using Poisson regression, first in a full cohort and then in an inception cohort, among workers aged 16-20 years at the start of follow-up. RESULTS: The risk of asthma was not increased for recent cleaning compared to references [adjusted incidence rate ratio (IRRadj) 1.02 [95% confidence interval (CI) 0.99-1.04]. Similar results were seen for the inception cohort, where cumulative years of cleaning were associated with increased risk of asthma, more prominent for the group with the maximum of six years of cleaning IRRadj 2.53 (95% CI 1.38-4.64). Cumulative years of cleaning were associated with decreased risk of asthma, more pronounced for the maximum of ten compared to one year of cleaning [IRRadj 0.74 (95% CI 0.63-0.88)]. CONCLUSIONS: Asthma risk was increased in the inception cohort for cumulative years of cleaning but decreased in the full cohort. We could not confirm that recent work within cleaning was associated with increased risk of asthma. This may be due to healthy worker bias. Thus, we cannot rule out that long-term professional cleaning may be associated with increased risk of asthma.

Health, work performance, and risk of infection in office-like environments: The role of indoor temperature, air humidity, and ventilation.

Epidemiological and experimental studies have revealed the effects of the room temperature, indoor air humidity, and ventilation on human health, work and cognitive performance, and risk of infection. In this overview, we integrate the influence of these important microclimatic parameters and assess their influence in offices based on literature searches. The dose-effect curves of the temperature describe a concave shape. Low temperature increases the risk of cardiovascular and respiratory diseases and elevated temperature increases the risk of acute non-specific symptoms, e.g., dry eyes, and respiratory symptoms. Cognitive and work performance is optimal between 22 °C and 24 °C for regions with temperate or cold climate, but both higher and lower temperatures may deteriorate the performances and learning efficiency. Low temperature may favor virus viability, however, depending on the status of the physiological tissue in the airways. Low indoor air humidity causes vulnerable eyes and airways from desiccation and less efficient mucociliary clearance. This causes elevation of the most common mucous membrane-related symptoms, like dry and tired eyes, which deteriorates the work performance. Epidemiological, experimental, and clinical studies support that intervention of dry indoor air conditions by humidification alleviates symptoms of dry eyes and airways, fatigue symptoms, less complaints about perceived dry air, and less compromised work performance. Intervention of dry air conditions by elevation of the indoor air humidity may be a non-pharmaceutical treatment of the risk of infection by reduced viability and transport of influenza virus. Relative humidity between 40 and 60% appears optimal for health, work performance, and lower risk of infection. Ventilation can reduce both acute and chronic health outcomes and improve work performance, because the exposure is reduced by the dilution of the indoor air pollutants (including pathogens, e.g., as virus droplets), and in addition to general emission source control strategies. Personal control of ventilation appears an important factor that influences the satisfaction of the thermal comfort due to its physical and positive psychological impact. However, natural ventilation or mechanical ventilation can become sources of air pollutants, allergens, and pathogens of outdoor or indoor origin and cause an increase in exposure. The "health-based ventilation rate" in a building should meet WHO's air quality guidelines and dilute human bio-effluent emissions to reach an acceptable perceived indoor air quality. Ventilation is a modifying factor that should be integrated with both the indoor air humidity and the room temperature in a strategic joint control to satisfy the perceived indoor air quality, health, working performance, and minimize the risk of infection.

Cancer effects of formaldehyde: a proposal for an indoor air guideline value.

Formaldehyde is a ubiquitous indoor air pollutant that is classified as "Carcinogenic to humans (Group 1)" (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39-325, 2006). For nasal cancer in rats, the exposure-response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative ("worst-case") considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure-response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87-91, 2000), 0.08 ppm (0.1 mg m(-3)) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings.