Summary
Here, we review the scientific literature and other documents which pertain to the effects of inhalation exposure to carbon dioxide (CO2) upon human health. Recent studies have reported linear physiological changes in circulatory, cardiovascular, and autonomic systems at CO2 exposures ranging between 500 and 5,000 ppm; these effects are very evident. Recent experimental studies suggested that CO2 might affect psychomotor performance including decision making or problem resolution, beginning at 1,000 ppm during short-time exposure, although bioeffluents emitted from humans might also be associated with such effects. Many epidemiological studies have demonstrated a relationship between low-level exposure to CO2 and SBSs, although other mixed hazardous chemicals might also involve such effects. Although such uncertainties exist, maintaining a CO2 concentration below 1,000 ppm in the indoor environment of a building would represent an effective means of preventing effects upon human health and psychomotor performance. Further research on the long-term effects of low-level CO2 exposure upon the autonomic system is now required.
Introduction
Since the 19th Century, the indoor carbon dioxide (CO2) concentration has been used as an indicator of air quality in buildings. Several countries have established indoor air quality guidelines of 1,000 ppm for CO2 in non-industrial buildings. CO2 is naturally present in the atmosphere where the typical outdoor CO2 concentrations are approximately 380 ppm, although outdoor levels in urban areas have been reported to be as high as 500 ppm. However, increasing CO2 concentration has contributed to the greenhouse effect and has accelerated global warming. The main source of CO2 in the non-industrial indoor environment is human metabolism, although an increase in the outdoor CO2 concentration will also contribute to an increase in the indoor concentration of CO2. In addition, the need to reduce energy consumption provides an incentive for low rates of ventilation, leading to higher indoor CO2 concentrations. From these insights, the effects of low-level CO2 exposure upon human health should be re-examined. This presentation reports a review of current literature pertaining to the association of low-level CO2 exposure in non-industrial buildings with human health and related human responses.
MATERIALS and METHODS
‘Carbon dioxide’ was used as a search-term in major databases, including PubMed, Google Scholar, CiNii, and J-Dream III for the period 1950–2016, and combined with two additional search-terms; ‘health effect’ or ‘sick building’. References quoted in the literature and documents obtained from the above searches were then examined.
RESULTS
Traditional knowledge and national indoor air quality guidelines
In 1968, the World Health Organization (WHO) reported two criteria relating to the health effects of CO2 (Goromosov, 1968), which described physiological studies showing that, at concentrations greater than 5,000 ppm, CO2 raises the respiration rate above the level required for gas exchange, imposing an additional load upon the respiratory system. Pettenkofer and Flügge had proposed in 1881 that 700–1,000 ppm should be regarded as the permissible atmospheric concentration of CO2. Although the latter criteria had no physiological basis, it proved of considerable practical value as an indirect index of the contamination of air in buildings. However, in 1964, Eliseeva reported a human experimental study which showed that inhalation of 1,000 ppm CO2 for a short time caused marked changes in respiration, circulation, and cerebral electrical activity. Eliseeva concluded that the indoor concentration of CO2 should not be allowed to exceed 1,000 ppm because the presence of a concentration of 1,000 ppm CO2 in the air has a directly harmful effect (Goromosov, 1968). Subsequently, indoor air quality guidelines of 1,000 ppm for CO2 were established in Japan (large buildings) in 1970, in Canada (office environments) in 1995, in Norway (residential spaces) in 1999, in Singapore (office buildings) in 1999, in China (housing and offices) in 2002, in Korea (large stores and medical facilities) in 2003, in Germany (guidance value to prevent harmful effects) in 2008, and in Taiwan in 2012; these guidelines were based upon specific assessments in each individual country (Azuma, 2016a).
Biological effects of carbon dioxide
CO2 is produced by cellular metabolism, and enters the body during respiration when the atmospheric concentration exceeds the alveolar concentration. In the blood, CO2 is transported in three ways: dissolved in solution; buffered with water as carbonic acid; and bound to proteins, particularly hemoglobin. Lowering the pH results in the release of O2 from oxyhemoglobin. Raising the partial pressure of CO2 (pCO2) also favors the release of O2 from oxyhemoglobin (Arthurs, 2005). An increase of the pCO2 in inhaled air induces an increase of pCO2 in the alveoli air. Because CO2 freely diffuses through the alveolar membrane and into the blood, it results in an increase of CO2 tension in arterial blood (PaCO2). In turn, this increase in PaCO2 results in an acute or chronic respiratory acidosis (lower blood pH), due to a lack of acido-basic balance (Guais, 2011). Acute (or acutely worsening chronic) respiratory acidosis causes headache, confusion, anxiety, drowsiness, and stupor (CO2 narcosis). Slowly developing, stable respiratory acidosis may result in memory loss, sleep disturbances, excessive daytime sleepiness, and personality changes. Appearance of respiratory acidosis can be defined from exposure to a CO2 concentration of 10,000 ppm for at least 30 minutes in a healthy adult with a moderate physical load (DFG, 2012). An increase in the inhaled CO2 concentration, can result in increased respiratory rate and brain blood flow, headache, dizziness, confusion, dyspnea, sweating, dim vision, vomiting, disorientation, hypertension, and loss of consciousness (Rise, 2003).
Effects of low-level exposure to CO2 in humans
Building-related symptoms
According to a review by Seppänen et al. (1999), around half of a total of 21 carbon dioxide studies suggested that the risk of sick building syndrome symptoms (SBSs) continued to reduce significantly with decreasing CO2 concentrations below 800 ppm. Apte et al. (2000) observed significant associations between mucous membrane and lower respiratory SBS symptoms with increasing indoor minus average outdoor CO2 (dCO2) and maximum indoor 1-h moving average CO2 minus outdoor CO2 concentrations (dCO2MAX) when workday average CO2 levels were always below 800 ppm. Norbäck et al. (2008) further reported that a 100 ppm increase in indoor CO2 concentration (range, 674–1,450 ppm) was significantly associated with headache. Schoolchildren exposed to indoor CO2 levels greater than 1000 ppm also showed significantly higher risk for dry cough and rhinitis (Simoni et al., 2010). Office workers exposed to indoor CO2 levels greater than 800 ppm also reported a significant increase in eye irritation and upper respiratory symptoms (Tsai et al., 2012). A 200 ppm increase in indoor CO2 concentration (range, 1,000–2,000 ppm) in day care centres was significantly associated with reported wheezing (Carreiro-Martins et al., 2014). In earlier reports, we suggested that non-conformation to a CO2 standard of 1,000 ppm in buildings was significantly associated with SBS symptoms in office workers (Azuma et al., 2014) and that a 100 ppm increase in CO2 was correlated with SBS symptoms (Azuma et al., 2016b).
Effects of autonomic function or psychomotor performance
Historically, CO2 exposures below 5,000 ppm were not anticipated to affect blood CO2 levels, but several recent studies have reported linear increases of pCO2 in the blood as exposure to ambient CO2 was increased from 500 to 4,000 ppm through changes in ventilation rate. These studies also reported other physiological responses, which were consistent with increased sympathetic stimulation, including changes to heart rate variability, elevated blood pressure, and increases to peripheral blood circulation at CO2 exposures in the range of 500 to 5,000 ppm (Kaitar 2012, MacNaughton et al., 2016; Vehviläinen et al., 2016). Autonomic dysfunction has a wide array of health impacts upon cognitive, urinary, sexual, and digestive systems. Activation of the autonomic system through stress reduces strategic ability and working memory (Starcke et al., 2012), which supports finding by recent studies showing a decrease in decision making performance between 550 and 2,500 ppm of CO2.
Twenty-two participants were exposed to CO2 at 600, 1,000, and 2,500 ppm (three 2.5-hr sessions, one day) in an office-like chamber. Statistically significant decrements occurred in psychomotor performance (decision making, problem resolution) starting at 1,000 ppm (Satish et al. 2012). Twenty-four participants spent six full work days during two weeks in an environmentally controlled office space, blinded to different test conditions: concentrations of volatile organic compounds (VOCs), outdoor air ventilation rate, and artificially elevated CO2 concentrations were independent of ventilation. VOCs and CO2 were independently associated with cognitive scores in the groups exposed to CO2 at 945 and 1400 ppm compared with controls (Allen et al, 2016). In addition, the same research group reported additional results from the above experimental study, in which a 1000 ppm increase in CO2 was associated with an increase in heart rate and in the number of symptoms (respiratory, eyes and skin, headache, cognitive, and sensory) per participant per day (MacNaughton et al, 2016).
In another study, ten healthy participants were exposed to CO2 at 500 ppm and 5000 ppm (artificially elevated CO2 concentrations) for 2.5-hr in a low-emission stainless-steel climate chamber. End-tidal CO2 (ETCO2) at 5000 ppm was increased in comparison with that at 500 ppm. CO2 concentration at 5000 ppm had no effect upon acute health symptoms (respiratory, eyes and skin, headache, and sensory) and performance in cognitive tests (Zhang et al, 2016). Twenty-five participants were exposed to CO2 at 500, 1000 and 3000 ppm (artificially elevated CO2 concentrations, outdoor air supply rate was high enough to remove bioeffluents) for 255 min in a low-emission stainless-steel climate chamber. In two further conditions, the outdoor air supply rate was reduced to reach CO2 levels at 1000 and 3000 ppm by allowing metabolically generated CO2 (in addition, bioeffluents also increased). Exposures to CO2 at 3000 ppm, including bioeffluents, significantly increased the intensity of reported headache, fatigue, and sleepiness. Cognitive performance was significantly reduced in exposure to CO2 at 1000 ppm including bioeffluents (Zhang et al., 2017a). Exposures to CO2 at 3000 ppm, including bioeffluents, significantly increased diastolic blood pressure and reduced nasal peak flow. Salivary α-amylase activity significantly increased during exposure to CO2 at 1000 ppm including bioeffluents. ETCO2 and heart rate significantly increased during exposure to CO2 under all conditions (Zhang et al., 2017b).
Table 1 Summary of the effects of exposure to CO2 in indoor air and relevent exposure guidelines.
CO2 concentration Physiological effect Psychomotor performance Health symptoms Guideline or standard
- Above 500 ppm pCO2, heart rate, heart rate variability, blood pressure, peripheral blood circulation SBS symptoms above 700 ppm
- Above 1000 ppm Cognitive performance (decision making, problem resolution) Respiratory symptoms in school children Recommended IAQ guideline for residential spaces
- Above 5000 ppm Occupational limit (TWA)
- Above 10000 ppm Respiratory rate, respiratory acidosis, metabolic stress, brain blood flow, minute ventilation
- Above 50000 ppm Dizziness, headache, confusion, dyspnea
- Above 100000 ppm Unbearable dyspnea, followed by vomiting, disorientation, hypertension, and loss of consciousness Occupational limit (STEL)
Abbreviations: SBS, sick building syndrome; IAQ, indoor air quality; TWA, time-weighted average; STEL, short-term exposure limit. Occupational limit: American Conference of Governmental Industrial Hygienists, National Institute for Occupational Safety and Health, Occupational Safety and Health Administration.
DISCUSSION
It has been considered that exposure to CO2 below a concentration of 5000 ppm was not anticipated to affect blood CO2 levels. However, several recent studies have reported linear increases of pCO2 in the blood, elevated blood pressure, increased heart rate, and increased sympathetic stimulation at CO2 exposures in the range of 500 to 5000 ppm. As regards the intrinsic effects of CO2 upon autonomic function, several recent experimental studies on humans suggest that CO2 may affect psychomotor performance (decision making, problem resolution) starting at a concentration of 1000 ppm. Even though these effects are sub-clinical, the reduction of performance related to productivity of labor or learning has a profound effect upon social economy or the community. Although bioeffluents emitted from humans might be associated with these effects during short-tere exposure to CO2 at 1000 ppm, the quantitative and physiological evidence relating to this is not sufficient. Further research on the effects (especially long-term effects upon the autonomic system under increased pCO2) of low-level CO2 exposure is now needed.
The effects of low-level exposure to CO2 upon SBSs may be influenced by other mixed hazardous chemicals. However, many epidemiological studies have demonstrated the relationship between low-level exposure to CO2 and SBSs. In addition, mucosal symptoms have been reported at a CO2 exposure of 1000 ppm during two weeks in an environmentally controlled office space. Maintaining CO2 concentration below 1000 ppm would therefore be effective in reducing the total health risk due to multiple low level indoor pollutants in a building. Adverse effects upon psychomotor performance could also be prevented.
CONCLUSIONS
Recent studies have showed clear linear physiological changes in circulatory, cardiovascular, and autonomic systems, including increased pCO2 in the blood, elevated blood pressure, increased heart rate, and increased sympathetic stimulation at CO2 exposures in the range of 500 to 5,000 ppm. Recent short-term exposure studies have suggested that CO2 might affect psychomotor performance such as decision making or problem resolution beginning at 1000 ppm, and many epidemiological studies have demonstrated a relationship between low-level exposure to CO2 and SBSs. While other substances such as bioeffluents, or mixed hazardous chemicals, might also be associated with such effects, maintaining CO2 concentration below 1,000 ppm would be effective in preventing effects upon human health and psychomotor performance. Further research relating to the long-term effects of low-level CO2 exposure from 500 to 3,000 ppm upon the autonomic system is now needed.
ACKNOWLEDGEMENT
This study was financially supported by a Grant-in-Aid for Health and Labour Sciences Research Grant (H26-health/crisis-007) provided by the Japanese Ministry of Health, Labour and Welfare.