Executive summary

This document presents WHO guidelines for the protection of public health from health risks due to a number of chemicals commonly present in indoor air. The guidelines are based on a comprehensive review and evaluation of the accumulated scientific evidence by a multidisciplinary group of experts studying the toxic properties and health effects of these pollutants.

The substances considered in this review (benzene, carbon monoxide, formaldehyde, naphthalene, nitrogen dioxide, polycyclic aromatic hydrocarbons (especially benzo[a]pyrene), radon, trichloroethylene and tetrachloroethylene) have been added to the guidelines considering information on the existence of indoor sources, on the availability of toxicological and epidemiological data and on exposure levels causing health concerns.

Problems of indoor air quality are recognized as important risk factors for human health in both low- and middle- and high-income countries. Indoor air is also important because people spend a substantial proportion of their time in buildings. In residences, day-care centres, retirement homes and other special environments, indoor air pollution affects population groups that are particularly vulnerable owing to their health status or age.

The primary aim of these guidelines is to provide a uniform basis for the protection of public health from adverse effects of indoor exposure to air pollution, and to eliminate or reduce to a minimum exposure to those pollutants that are known or are likely to be hazardous.

The guidelines are targeted at public health professionals involved in preventing health risks of environmental exposures as well as specialists and authorities involved in the design and use of buildings, indoor materials and products. The guidelines are based on the accumulated scientific knowledge available at the time of their development. They have the character of recommendations. Nevertheless, countries may wish to use the guidelines as a scientific basis for legally enforceable standards.

The evidence review supporting the guidelines for each of the selected pollutants includes an evaluation of indoor sources, current indoor concentrations and their relationship with outdoor levels, as well as a summary of the evidence on the kinetics and metabolism and health effects. Based on the accumulated evidence, the experts formulated health risk evaluations and agreed on the guidelines for each of the pollutants as summarized below.

Benzene

Guidelines on exposure levels for indoor air are needed because indoor air is a significant source of benzene exposure and inhalation is the main pathway of human exposure to benzene. Benzene is present in both outdoor and indoor air. However, indoor concentrations are generally higher than those in outdoor air owing to the infiltration of benzene present in outdoor air and to the existence of many other indoor sources. Typically, indoor concentrations are below the lowest levels showing evidence of adverse health effects. Considering that benzene is present indoors and taking into account personal exposure patterns, which are predominantly indoors, indoor guidelines for exposure are needed.

Benzene is a genotoxic carcinogen in humans and no safe level of exposure can be recommended. The risk of toxicity from inhaled benzene would be the same whether the exposure were indoors or outdoors. Thus there is no reason that the guidelines for indoor air should differ from ambient air guidelines. It is also recommended continuing to use the same unit risk factors. The geometric mean of the range of the estimates of the excess lifetime risk of leukaemia at an air concentration of 1 μg/m3 is 6 × 10−6. The concentrations of airborne benzene associated with an excess lifetime risk of 1/10 000, 1/100 000 and 1/1000 000 are 17, 1.7 and 0.17 μg/m3, respectively.

As noted above, there is no known exposure threshold for the risks of benzene exposure. Therefore, from a practical standpoint, it is expedient to reduce indoor exposure levels to as low as possible. This will require reducing or eliminating human activities that release benzene, such as smoking tobacco, using solvents for hobbies or cleaning, or using building materials that off-gas benzene.

Adequate ventilation methods will depend on the site of the building. In modern buildings located near heavy traffic or other major outdoor sources of benzene, inlets for fresh air should be located at the least polluted side of the building.

Carbon monoxide

Exposure to carbon monoxide reduces maximum exercise ability in healthy young individuals and reduces the time to angina and, in some cases, the time to ST-segment depression in people with cardiovascular disease, albeit at a concentration that is lower than that needed to reduce exercise ability in healthy individuals.

The relationship of carbon monoxide exposure and the carboxyhaemoglobin (COHb) concentration in blood can be modelled using the differential Coburn-Forster-Kane equation, which provides a good approximation to the COHb concentration at a steady level of inhaled, exogenous carbon monoxide. Based on laboratory studies of reduction in exercise capacity in both healthy individuals and volunteers with cardiovascular disease, it was determined that COHb levels should not exceed 2%. The Coburn-Forster-Kane equation is used below to determine the levels of carbon monoxide to which a normal adult under resting conditions for various intervals can be exposed without exceeding a COHb level of 2%.

The previous WHO guidelines were established for 15 minutes to protect against short-term peak exposures that might occur from, for example, an unvented stove; for 1 hour to protect against excess exposure from, for example, faulty appliances; and for 8 hours (which is relevant to occupational exposures and has been used as an averaging time for ambient exposures). We do not recommend changing the existing guidelines.

However, chronic carbon monoxide exposure appears different from acute exposure in several important respects. The latest studies available in 2009, especially those epidemiological studies using very large databases and thus producing extremely high-resolution findings, suggest that the appropriate guideline level for longer-term average concentration of carbon monoxide in order to minimize health effects must be positioned below the 8-hour guideline of 10 mg/m3. Thus, a separate guideline is recommended to address 24-hour exposures.

Therefore, a series of guidelines relevant to typical indoor exposures is recommended as follows: 100 mg/m3 for 15 minutes and 35 mg/m3 for 1 hour (assuming light exercise and that such exposure levels do not occur more often than one per day); 10 mg/m3 for 8 hours (arithmetic mean concentration, light to moderate exercise); and 7 mg/m3 for 24 hours (arithmetic mean concentration, assuming that the exposure occurs when the people are awake and alert but not exercising).

Formaldehyde

An indoor air guideline for formaldehyde is appropriate because indoor exposures are the dominant contributor to personal exposures through inhalation and indoor concentrations may be high enough to cause adverse health effects.

The lowest concentration reported to cause sensory irritation of the eyes in humans is 0.36 mg/m3 for four hours. Increases in eye blink frequency and conjunctival redness appear at 0.6 mg/m3, which is considered equal to the no observed adverse effect level (NOAEL). There is no indication of accumulation of effects over time with prolonged exposure.

The perception of odour may result in some individuals reporting subjective sensory irritation, and individuals may perceive formaldehyde at concentrations below 0.1 mg/m3. However, this is not considered to be an adverse health effect. The NOAEL of 0.6 mg/m3 for the eye blink response is adjusted using an assessment factor of 5 derived from the standard deviation of nasal pungency (sensory irritation) thresholds, leading to a value of 0.12 mg/m3, which has been rounded down to 0.1 mg/m3. Neither increased sensitivity nor sensitization is considered plausible at such indoor concentrations in adults and children. This value is thus considered valid for short-term (30-minute) duration, and this threshold should not be exceeded at any 30-minute interval during a day.

Thus, a short-term (30-minute) guideline of 0.1 mg/m3 is recommended as preventing sensory irritation in the general population.

Evaluations of long-term effects, including cancer, based on a NOAEL and assessment factor approach, as well as estimates from the biologically motivated models, yield similar results, with values of approximately 0.2 mg/m3. These values are above the guideline for short-term effects of 0.1 mg/m3. Thus the use of the short-term (30-minute) guideline of 0.1 mg/m3 will also prevent long-term health effects, including cancer.

The use of low-emitting building materials and products, and preventing exposures to environmental tobacco smoke and other combustion emissions, will minimize exposure-related risk. In addition, ventilation can reduce indoor exposure to formaldehyde.

Naphthalene

The principal health concerns of exposure to naphthalene are respiratory tract lesions, including tumours in the upper respiratory tract demonstrated in animal studies and haemolytic anaemia in humans.

Lesions in the nasal olfactory and, at higher concentrations, also in the respiratory epithelia of rats appear to be the critical non-neoplastic effect. At concentrations about 100-fold higher than the lowest lesion level, severe inflammation and tumours have been reported to occur at these sites.

Increased cell proliferation due to cytotoxicity (cell damage) is considered a key element in the development of airway tumours. The likely involvement of cytotoxic metabolites in the carcinogenic response and the apparent primary non-genotoxicity of naphthalene favour the assumption of the existence of a threshold.

Therefore, the use of a lowest observed adverse effect level (LOAEL)/NOAEL as a threshold, combined with safety factors, is considered to be an appropriate approach for setting indoor air guidelines to minimize the carcinogenic risk to the respiratory tract of naphthalene exposure.

Associated with repeated inhalation exposure of 6 hours per day, 5 days a week for 104 weeks, severe effects in terms of inflammation were observed in almost all rats exposed to the lowest (but still relatively high) naphthalene dose of 53 mg/m3. In the absence of adequately published data in relation to less severe effects, this can be taken as a LOAEL, even though it is related to severe effects.

Taking this LOAEL as a starting point and adjusting for continuous exposure (dividing by a factor of 24/6 and 7/5), a value of about 10 mg/m3 is obtained. Further, incorporating a factor of 10 for using a LOAEL rather than a NOAEL, a factor of 10 for inter-species variation and a factor of 10 for inter-individual variation, a guideline value of 0.01 mg/m3 is established. This guideline value should be applied as an annual average.

Extensive use or misuse of naphthalene mothballs may lead to haemolytic anaemia. Knowledge of the impact of exposure to naphthalene on the risk of haemolytic anaemia in susceptible individuals (glucose 6-phosphate dehydrogenase deficiency) cannot be used to define a guideline owing to the lack of adequate exposure data.

In the absence of mothballs or other sources such as combustion of biomass, indoor air concentrations of naphthalene are just above the typical limit of detection of about 0.001 mg/m3. Since the concentration of naphthalene in the residential environment increases up to 100-fold when mothballs are used, the most efficient way to prevent high exposures would be to abandon (ban) the use of naphthalene-containing mothballs.

Nitrogen dioxide

A 1-hour indoor nitrogen dioxide guideline of 200 μg/m3, consistent with the existing WHO air quality guideline, is recommended.

At about twice this level, asthmatics exhibit small pulmonary function decrements. Those who are sensitized may have small changes in airway responsiveness to a variety of stimuli already at this level. Studies of the indoor environment provide no evidence for an indoor guideline different to the ambient guideline.

An annual average indoor nitrogen dioxide guideline of 40 μg/m3, consistent with the existing WHO air quality guideline, is recommended.

The ambient annual average guideline of 40 μg/m3 was initially based on a meta-analysis of indoor studies. It was assumed that having a gas stove was equivalent to an increased average indoor level of 28 μg/m3 compared to homes with electric stoves, and the meta-analysis showed that an increase in indoor nitrogen dioxide of 28 μg/m3 was associated with a 20% increased risk of lower respiratory illness in children.

Homes with no indoor sources were estimated to have an average level of 15 μg/m3. Several exhaustive reviews to further develop ambient guidelines have not challenged these findings.

Recent well-conducted epidemiological studies that have used measured indoor nitrogen dioxide levels support the occurrence of respiratory health effects at the level of the guideline.

Polycyclic aromatic hydrocarbons

Some polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens and, in air, are typically attached to particles. The primary exposure to carcinogenic PAHs found in air occurs via inhalation of particles. PAHs occur in indoor air as complex mixtures, the composition of which may vary from site to site. Experimental data on metabolism, gene expression and DNA adducts suggest that interactions between PAHs in mixtures may be complex and highly unpredictable for various PAH compositions (inhibitory, additive, synergistic).

In view of the difficulties in developing guidelines for PAH mixtures, benzo[a] pyrene (B[a]P) was considered to represent the best single indicator compound. Its toxicology is best known, most single PAH concentration data in ambient and indoor air are for B[a] P, and B[a]P has widely been used as an indicator compound for exposure in epidemiological studies.

The health evaluation data suggest that lung cancer is the most serious health risk from exposure to PAHs in indoor air. B[a]P is one of the most potent carcinogens among the known PAHs.

In its evaluation of PAHs as ambient air pollutants in 2000, WHO expressed a unit cancer risk as a function of the concentration of B[a]P taken as a marker of the PAH mixture. Use of the same unit risk factor for indoor air implies that B[a]P represents the same proportion of carcinogenic activity of the PAH mixture as in the occupational exposure used to derive the unit risk. This assumption will not always hold, but the associated uncertainties in risk estimates are unlikely to be large.

Reducing exposure to B[a]P may also decrease the risk of other adverse health effects associated with PAHs.

Based on epidemiological data from studies on coke-oven workers, a unit risk for lung cancer for PAH mixtures is estimated to be 8.7 × 10−5 per ng/m3 of B[a] P. This is the guideline for PAH in indoor air. The corresponding concentrations for lifetime exposure to B[a]P producing excess lifetime cancer risks of 1/10 000, 1/100 000 and 1/1 000 000 are approximately 1.2, 0.12 and 0.012 ng/m3, respectively.

Radon

Radon is classified by the International Agency for Research on Cancer as a human carcinogen (Group I). There is direct evidence from residential epidemiological studies of the lung cancer risk from radon. The exposure–response relationship is best described as being linear, without a threshold. The excess relative risk, based on long-term (30-year) average radon exposure is about 16% per increase of 100 Bq/m3, and on this relative scale does not vary appreciably between current smokers, ex-smokers and lifelong non-smokers. Therefore, as the absolute risk of lung cancer at any given radon concentration is much higher in current smokers than in lifelong non-smokers, the absolute risk of lung cancer due to radon is appreciably higher for current and ex-smokers than for lifelong non-smokers. For ex-smokers, the absolute risks will be between those for lifelong non-smokers and current smokers.

The cumulative risk of death from radon-induced lung cancer was calculated for lifelong non-smokers and for current smokers (15–24 cigarettes per day). The derived excess lifetime risks (by the age of 75 years) are 0.6 × 10−5 per Bq/m3 and 15 × 10−5 per Bq/m3, respectively. Among ex-smokers, the risk is intermediate, depending on the time since smoking cessation. The radon concentration associated with an excess lifetime risk of 1 per 100 and 1 per 1000 are 67 Bq/m3 and 6.7 Bq/m3 for current smokers and 1670 Bq/m3 and 167 Bq/m3 for lifelong non-smokers, respectively.

As part of the management of the radon problem, the WHO International Radon Project has recommended that there should be a reference level as an essential tool in this process.1

A national Reference Level does not specify a rigid boundary between safety and danger, but defines a level of risk from indoor radon that a country considers to be too high if it continues unchecked into the future. However, protective measures may also be appropriate below this level to ensure radon concentrations in homes are well below that level. In view of the latest scientific data, WHO proposes a Reference Level of 100 Bq/m3 to minimize health hazards due to indoor radon exposure. However, if this level cannot be reached under the prevailing country-specific conditions, the chosen Reference Level should not exceed 300 Bq/m3 which represents approximately 10 mSv per year according to recent calculations by the International Commission on Radiation Protection.

A guide for radon management should include, in addition to the setting of a reference level, building codes, measurement protocols and other relevant components of a national radon programme.

Trichloroethylene

The existence of both positive and negative results has in the past led risk assessors to different interpretations of trichloroethylene (TCE) toxicity and to divergent estimates of human cancer risk. For a health risk evaluation, bearing in mind recent data on a mechanism of action that is not species-specific, the evidence for weak genotoxicity, and the consistency between certain cancers observed in animals and in humans (in particular liver cancer), it is prudent to consider that the carcinogenicity in animals, the positive epidemiological studies and the plausibility of a human cancer risk leads to the recommendation of a non-threshold approach with a risk estimate rather than a safe level.

Therefore, carcinogenicity (with the assumption of genotoxicity) is selected as the end-point for setting the guideline value. The unit risk estimate of 4.3 × 10−7 (μg/m3) −1, derived on the basis of increased Leydig cell tumours (testicular tumours) in rats, is proposed as the indoor air quality guideline. This was also the conclusion of WHO in 2000, the European Union in 2004 and the French Agency for Environmental and Occupational Health in 2009.

The concentrations of airborne TCE associated with an excess lifetime cancer risk of 1/10 000, 1/100 000 and 1/1 000 000 are respectively 230, 23 and 2.3 μg/m3.

Tetrachloroethylene

Carcinogenicity is not selected as the end-point for setting the guideline value for tetrachloroethylene, for three reasons: the epidemiological evidence is equivocal, the animal tumours detected are not considered relevant to humans, and there are no indications that tetrachloroethylene is genotoxic. The derivation of a guideline value is at present based on two non-neoplastic effects as the critical end-point: impaired neurobehavioural performance and early renal changes.

On the basis of a long-term LOAEL for kidney effects of 102 mg/m3 in dry cleaning workers, a guideline value of 0.25 mg/m3 has been calculated. In deriving this guideline value, the LOAEL is converted to continuous exposure (dividing by a factor of 4.2 (168/40)) and divided by an uncertainty factor of 100 (10 for use of an LOAEL and 10 for intra-species variation). Recognizing that some uncertainty in the LOAEL exists because the effects observed at this level are not clear-cut and because of fluctuations in exposure levels, an alternative calculation was made based on the LOAEL in mice of 680 mg/m3 and using an appropriate uncertainty factor of 1000. This calculation yields a guideline value of 0.68 mg/m3.

A chronic inhalation minimal risk level (MRL) of 0.28 mg/m3 (0.04 ppm) has been derived by the Agency for Toxic Substances and Disease Registry based on the LOAEL of 15 ppm. The MRL was calculated from this concentration by expanding to continuous exposure (8/24 hours, 5/7 days) and dividing by an uncertainty factor of 100 (10 for use of a LOAEL and 10 for human variability). This reference found significantly prolonged reaction times in workers occupationally exposed to an average of 15 ppm for about 10 years.

The value and appropriateness of establishing a short-term guideline value is questionable because acute effects occur only at very high concentrations of 50 ppm (340 mg/m3) and higher, compared to generally observed levels in close proximity to dry cleaning facilities. Establishing a long-term value is more protective of human health.

On the basis of the overall health risk evaluation, the recommended guideline for year-long exposure is 0.25 mg/m3. This is the same as the previous WHO guideline.

Summary table

A synthesis of the guidelines for all pollutants considered in this volume is presented in overleaf.

Table A

Summary of indoor air quality guidelines for selected pollutants.

1

WHO handbook on indoor radon: a public health perspective. Geneva, World Health Organization, 2009.