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.

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.

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.

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.

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.

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.

Chemicals inhaled from spray cleaning and disinfection products and their respiratory effects. A comprehensive review.

Spray cleaning and disinfection products have been associated with adverse respiratory effects in professional cleaners and among residents doing domestic cleaning. This review combines information about use of spray products from epidemiological and clinical studies, in vivo and in vitro toxicological studies of cleaning chemicals, as well as human and field exposure studies. The most frequent chemicals in spray cleaning and disinfection products were compiled, based on registrations in the Danish Product Registry. The chemicals were divided into acids, bases, disinfectants, fragrances, organic solvents, propellants, and tensides. In addition, an assessment of selected cleaning and disinfectant chemicals in spray products was carried out. Chemicals of concern regarding respiratory effects (e.g. asthma) are corrosive chemicals such as strong acids and bases (including ammonia and hypochlorite) and quaternary ammonium compounds (QACs). However, the evidence for respiratory effects after inhalation of QACs is ambiguous. Common fragrances are generally not considered to be of concern following inhalation. Solvents including glycols and glycol ethers as well as propellants are generally weak airway irritants and not expected to induce sensitization in the airways. Mixing of certain cleaning products can produce corrosive airborne chemicals. We discuss different hypotheses for the mechanisms behind the development of respiratory effects of inhalation of chemicals in cleaning agents. An integrative assessment is needed to understand how these chemicals can cause the various respiratory effects.

Indoor air chemistry: Terpene reaction products and airway effects.

Reactive chemistry is ubiquitous indoors with a wealth of complex oxidation reactions; some of these are initiated by both homogeneous and heterogeneous reaction of ozone with unsaturated organic compounds and subsequent the hydroxyl radical, either in the gas-phase or on reactive surfaces. One major focus has been the reaction of common and abundant terpene-based fragrances in indoor air emitted from many wood-based materials, a variety of consumer products, and citrus fruits and flowers. Inhalation of the terpenes themselves are generally not considered a health concern (both acute and long-term) due to their low indoor air concentrations; however, their gas- and surface reactions with ozone and the hydroxyl radical produce a host of products, both gaseous, i. a. formaldehyde, and ultrafine particles formed by condensation/nucleation processes. These reaction products may be of health concern. Human cell bioassays with key reaction products from ozone-initiated terpene reactions have shown some inflammatory reactions, but results are difficult to interpret for human exposure and risk assessment. Acute effects like sensory irritation in eyes and airways are unlikely or present at very low intensity in real life conditions based on rodent and human exposure studies and known thresholds for sensory irritation in eyes and airways and derived human reference values for airflow limitation and pulmonary irritation. Some fragrances and their ozone-initiated reaction products may possess anti-inflammatory properties. However, long-term effects of the reaction products as ultrafine particles are poorly explored. Material and product surfaces with high ozone deposition velocities may significantly impact the perceived air quality by altered emissions from both homogeneous and heterogeneous surface reactions.

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.

The mystery of dry indoor air - An overview.

"Dry air" is a major and abundant indoor air quality complaint in office-like environments. The causality of perceived "dry air" and associated respiratory effects continues to be debated, despite no clear definition of the complaint, yet, has been provided. The perception of "dry air" is semantically confusing without an associated receptor but mimics a proto-state of sensory irritation like a cooling sensation. "Dry air" may also be confused with another common indoor air quality complaint "stuffy air", which mimics the sense of no fresh air and of nasal congestion. Low indoor air humidity (IAH) was dismissed more than four decades ago as cause of "dry air" complaints, rather indoor pollutants was proposed as possible exacerbating causative agents during the cold season. Many studies, however, have shown adverse effects of low IAH and beneficial effects of elevated IAH. In this literature overview, we try to answer, "What is perceived "dry air" in indoor environments and its associated causalities. Many studies have shown that the perception is caused not only by extended exposure to low IAH, but also simultaneously with and possibly exacerbated by indoor air pollutants that aggravate the protective mucous layer in the airways and the eye tear film. Immanent diseases in the nose and airways in the general population may also contribute to the overall complaint rate and including other risk factors like age of the population, use of medication, and external factors like the local ambient humidity. Low IAH may be the single cause of perceived "dry air" in the elderly population, while certain indoor air pollutants may come into play among susceptible people, in addition to baseline contribution of nasal diseases. Thus, perceived "dry air" intercorrelates with dry eyes and throat, certain indoor air pollutants, ambient humidity, low IAH, and nasal diseases.

Assessment of Indoor Air Quality Problems in Office-Like Environments: Role of Occupational Health Services.

There is an increasing concern about indoor air quality (IAQ) and its impact on health, comfort, and work-performance in office-like environments and their workers, which account for most of the labor force. The Scientific Committee on Indoor Air Quality and Health of the ICOH (Int. Comm. Occup. Health) has discussed the assessment and management of IAQ problems and proposed a stepwise approach to be conducted by a multidisciplinary team. It is recommended to integrate the building assessment, inspection by walk-through of the office workplace, questionnaire survey, and environmental measurements, in that order. The survey should cover perceived IAQ, symptoms, and psychosocial working aspects. The outcome can be used for mapping the IAQ and to prioritize the order in which problems should be dealt with. Individual health surveillance in relation to IAQ is proposed only when periodical health surveillance is already performed for other risks (e.g., video display units) or when specific clinical examination of workers is required due to the occurrence of diseases that may be linked to IAQ (e.g., Legionnaire's disease), recurrent inflammation, infections of eyes, respiratory airway effects, and sensorial disturbances. Environmental and personal risk factors should also be compiled and assessed. Workplace health promotion should include programs for smoking cessation and stress and IAQ management.

Indoor air humidity, air quality, and health - An overview.

There is a long-standing dispute about indoor air humidity and perceived indoor air quality (IAQ) and associated health effects. Complaints about sensory irritation in eyes and upper airways are generally among top-two symptoms together with the perception "dry air" in office environments. This calls for an integrated analysis of indoor air humidity and eye and airway health effects. This overview has reviewed the literature about the effects of extended exposure to low humidity on perceived IAQ, sensory irritation symptoms in eyes and airways, work performance, sleep quality, virus survival, and voice disruption. Elevation of the indoor air humidity may positively impact perceived IAQ, eye symptomatology, and possibly work performance in the office environment; however, mice inhalation studies do not show exacerbation of sensory irritation in the airways by low humidity. Elevated humidified indoor air appears to reduce nasal symptoms in patients suffering from obstructive apnea syndrome, while no clear improvement on voice production has been identified, except for those with vocal fatigue. Both low and high RH, and perhaps even better absolute humidity (water vapor), favors transmission and survival of influenza virus in many studies, but the relationship between temperature, humidity, and the virus and aerosol dynamics is complex, which in the end depends on the individual virus type and its physical/chemical properties. Dry and humid air perception continues to be reported in offices and in residential areas, despite the IAQ parameter "dry air" (or "wet/humid air") is semantically misleading, because a sensory organ for humidity is non-existing in humans. This IAQ parameter appears to reflect different perceptions among other odor, dustiness, and possibly exacerbated by desiccation effect of low air humidity. It is salient to distinguish between indoor air humidity (relative or absolute) near the breathing and ocular zone and phenomena caused by moisture-damage of the building construction and emissions therefrom. Further, residential versus public environments should be considered as separate entities with different characteristics and demands of humidity. Research is needed about particle, bacteria and virus dynamics indoors for improvement of quality of life and with more focus on the impact of absolute humidity. "Dry (or wet) air" should be redefined to become a meaningful IAQ descriptor.

Pulmonary injury associated with spray of a water-based nano-sized waterproofing product: a case study.

BACKGROUND: In most reported cases of lung trauma with water proofing products, volatile organic compounds (VOC) have a prominent role. Here we report on a case involving ten workers exposed to a sprayed product containing nanoparticles in a water solution with only a few percent VOC. CASE PRESENTATION: Ten workers suffered from respiratory symptoms following spray impregnation of hardwood furniture using a waterproofing product that contained positively charged fluorinated acrylate copolymer solid cores with a median diameter of 70 nm (1.3 w%) in aqueous suspension with 3.3 w% VOC and 0.3 w% quaternary ammonium. The worker who applied one liter of the product in a wood workshop, using an air mix spray gun, did not report any health complaints. Another worker, who entered the workshop 3 h later and had rolled and smoked two cigarettes, was hospitalized with severe chemical pneumonitis. A chest X-ray (CXR) showed bilateral infiltrative impairment in the lower lobe regions. On the next day a second CXR showed increased patchiness marking in all fields. A high-resolution Computer Tomography (CT)-scan demonstrated extensive bilateral areas of ground-glass opacities predominantly in the lower regions of the upper lobes, the right middle lobe and the apical regions of the lower lobes, compatible with severe chemical pneumonitis. On the following morning, nine workers in an adjacent workplace in the same building, experienced dry cough, chest tightness and substernal pain upon physical exercise. Reconstruction of the spray application in a climate chamber confirmed trimethyl silanol, glycol ethers and fluoroalkenes in the gas phase. Immediately after the spray application, aerosols were observed at a maximum concentration of 6.3 × 104 cm-3. Mass concentrations were 0.095 and 10 mg/m3 in the size ranges 5.6-560 nm and 0.22-30 µm, respectively, decreasing to less than 10 µg/m3 in both size ranges after 15 h. CONCLUSION: The hospitalized worker had smoked cigarettes contaminated with fluoropolymers which is a plausible explanation for the lung trauma. Respiratory symptoms in the nine workers may be caused by inhalation of particles that became airborne by resuspension from surfaces when workers entered the adjacent workplace the next day. A contribution from VOC appears less likely because measurements and modelling showed that concentrations in the mg/m3 range could have occurred only if the building was assumed to be completely airtight.

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.

Effects by inhalation of abundant fragrances in indoor air - An overview.

Odorous compounds (odors) like fragrances may cause adverse health effects. To assess their importance by inhalation, we have reviewed how the four major abundant and common airborne fragrances (α-pinene (APN), limonene (LIM), linalool (LIL), and eugenol (EUG)) impact the perceived indoor air quality as odor annoyance, sensory irritation and sensitization in the airways. Breathing and cardiovascular effects, and work performance, and the impact in the airways of ozone-initiated gas- and particle phase reactions products have also been assessed. Measured maximum indoor concentrations for APN, LIM and LIL are close to or above their odor thresholds, but far below their thresholds for sensory irritation in the eyes and upper airways; no information could be traced for EUG. Likewise, reported risk values for long-term effects are far above reported indoor concentrations. Human exposure studies with mixtures of APN and LIM and supported by animal inhalation models do not support sensitization of the airways at indoor levels by inhalation that include other selected fragrances. Human exposure studies, in general, indicate that reported lung function effects are likely due to the perception rather than toxic effects of the fragrances. In general, effects on the breathing rate and mood by exposure to the fragrances are inconclusive. The fragrances may increase the high-frequency heart rate variability, but aerosol exposure during cleaning activities may result in a reduction. Distractive effects influencing the work performance by fragrance/odor exposure are consistently reported, but their persistence over time is unknown. Mice inhalation studies indicate that LIM or its reaction mixture may possess anti-inflammatory properties. There is insufficient information that ozone-initiated reactions with APN or LIM at typical indoor levels cause airway effects in humans. Limited experimental information is available on long-term effects of ozone-initiated reaction products of APN and LIM at typical indoor levels.

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.