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Long-term carbon dioxide toxicity and climate change: a major unapprehended risk for human health



As atmospheric levels of carbon dioxide continue to escalate and drive climate change, the safe level for breathing is not clear. The toxicity of CO2 has been defined for short-duration exposures at high concentrations but it is unknown what levels will compromise human health when individuals are perpetually exposed for their lifetime. There is now substantial evidence that permanent exposure, to CO2 levels predicted in the future, will have significant effects on humans. Blood CO2 levels in populations are increasing and unhealthy concentrations have been measured from people in common indoor environments where reduced thinking ability, altered brainwaves and health symptoms have been observed at levels of CO2 above 600 ppm for relatively short-term exposures. Although humans and animals are able to deal with elevated levels of CO2 in the short-term due to compensation mechanisms in the body, the eventual failure of these may have severe consequences in a perpetual environment of elevated CO2. Protein malfunctions in cells due to elevated CO2 and associated low pH has the potential to cause threats to life including cancer, neurological disorders, lung disease, diabetes, etc. In particular excess CO2 causes the overexpression of carbonic anhydrase, the enzyme that catalyzes CO2 in the body, causes calcification in the kidneys, arteries and tissues, along with other diseases and this may be an existential threat. Although there is very low awareness of this risk and its proximity is yet to be adequately defined, it is likely that human physical and mental health will be affected in the near-future with the progressive severity dependant on CO2 emissions. See PowerPoint talk,
Long-term carbon dioxide toxicity and climate change: a major
unapprehended risk for human health.
P.N. Bierwirth, PhD
Emeritus Faculty
Australian National University
First draft - Web Posted 25 February, 2014
Current Version – 20 March, 2023
ResearchGate DOI:10.13140/RG.2.2.16787.48168
As atmospheric levels of carbon dioxide continue to escalate and drive climate change, the safe level
for breathing is not clear. The toxicity of CO2 has been defined for short-duration exposures at high
concentrations but it is unknown what levels will compromise human health when individuals are
perpetually exposed for their lifetime. There is now substantial evidence that permanent exposure,
to CO2 levels predicted in the future, will have significant effects on humans. Blood CO2 levels in
populations are increasing and unhealthy concentrations have been measured from people in
common indoor environments where reduced thinking ability, altered brainwaves and health
symptoms have been observed at levels of CO2 above 600 ppm for relatively short-term exposures.
Although humans and animals are able to deal with elevated levels of CO2 in the short-term due to
compensation mechanisms in the body, the eventual failure of these may have severe consequences
in a perpetual environment of elevated CO2. Protein malfunctions in cells due to elevated CO2 and
associated low pH has the potential to cause threats to life including cancer, neurological disorders,
lung disease, diabetes, etc. In particular excess CO2 causes the overexpression of carbonic
anhydrase, the enzyme that catalyses CO2 in the body, causes calcification in the kidneys, arteries
and tissues, along with other diseases and this may be an existential threat. Although there is very
low awareness of this risk and its proximity is yet to be adequately defined, it is likely that human
physical and mental health will be affected in the near-future with the progressive severity
dependant on CO2 emissions.
1. Introduction
An axiom of modern science, as quoted from TS Huxley, is “do not pretend that conclusions are
certain which are not demonstrated or demonstrable”. Carbon dioxide is one of the most frequently
overlooked of all toxic gases. Even to refer to CO2 as a toxic gas is a surprise to many safety
professionals (Henderson 2006). In indoor environments CO2 concentration is often elevated relative
to ambient outdoor levels due to the fact that the exhaled breath from humans contains high CO2
(about 4%) and ventilation may not be adequate to prevent the resulting increase in CO2. Despite
the possible adverse effects on health where many people occupy buildings or vehicles, there is very
little awareness of this issue in the general community.
The average ambient concentration of CO2 (in fresh air) has been rapidly increasing and is recently
around 410 ppm (Scripps Institution of Oceanography 2020; Schmidt 2020) (Figure 1). This increase
is due to humanity’s activities, largely resulting from the burning of fossil fuels (Eggleton 2013).
Figure 1. The atmospheric carbon dioxide concentrations (in ppm) over the last 2000 years, based on measurements of air
trapped in Antarctic ice, shown in blue-grey diamonds, and the modern Cape Grim, Tasmania direct air measurements,
shown in orange. (From Schmidt 2020).
Very early primate ancestors of humans were evolving around 23 million years ago. Throughout all
of the ensuing period of human evolution levels of CO2 in the ambient atmosphere remained
relatively stable at below or close to 300 parts per million (ppm), this being derived from a
combination of studies of relict features including air trapped in ice cores (Schmidt 2020), the
composition of fossil plankton (Zachos et al. 2001) and Carbon-13 (13C) content in fossil plant
material (Cui et al. 2020). Since about 1820, CO2 levels have increased rapidly and are now above
415 ppm (Figure 1). This is a potentially catastrophic problem for many species of animals, including
humans, for a number of reasons. The most well publicised issue is that of climate change. The
mechanisms and history of global warming associated with CO2 increase are well understood and
the increase in atmospheric energy gradients will produce more extreme temperatures and weather
events. To many people, climate change itself may not appear to be catastrophic – for example it
might be possible to escape the effects of even a 5 degree C increase this century by moving to a
cooler and safer geographic location. However, it is possible that humans have overlooked the more
direct and immediate toxicity aspect of increasing atmospheric CO2. The earth’s atmosphere has
already reached CO2 levels that are outside the range breathed by humans throughout their
evolution and these new levels are relatively evenly distributed around the globe (see Figure 2). As
well, in earlier pre-primate epochs, the effect of elevated atmospheric CO2 causing physiological
stress, has been postulated to be a cause of mass extinction events (Knoll et al. 1996).
Figure 2. Global atmospheric carbon dioxide concentrations from Oct. 1 through Nov. 11, 2014 as recorded by NASA's
Orbiting Carbon Observatory-2. Carbon dioxide concentrations are highest above northern Australia, southern Africa and
eastern Brazil. Analysis of the African data showed that the high levels at the time were largely driven by the burning of
savannas and forests. Elevated and more persistent carbon dioxide levels can also be seen above industrialized Northern
Hemisphere regions in China, Europe and North America. Source:
We know that breathing CO2 is toxic to humans when levels are high with numerous deaths reported
based on occupational exposure (Scott et al. 2009). Although the CO2 exposure limit for an 8-hour
working day has been set at 5,000 ppm (OSHA 2012), this limit was decided in 1946 and based on
relatively short-term observations of fit and healthy submariners (Scott et al, 2009). The safe level
for lifetime exposure may be significantly lower than this and a number of researchers suggest there
could be toxicity effects at CO2 levels predicted in the near future with ongoing anthropogenic
emissions (Portner et al. 2004; Robertson 2006; Ezraty et al. 2011; Antic 2012; McNeil and Sasse
2016; Karnauskas et al. 2020). So the question is: how long will it take, at present and future rates of
increase, to reach levels that will impact on human health (no matter where you live) over a
lifetime? To answer this question, the safe level of CO2, for continuous breathing in humans, needs
to be determined. This paper is an attempt to evaluate available knowledge and to examine the
likely and possible risks (for the near to medium-term future).
2. The role of carbon dioxide in breathing
Breathing is one part of physiological respiration and is required to sustain life (Raven et al.
2007). Aerobic organisms like birds, mammals, and reptiles, require oxygen to release energy by
cellular respiration, through the metabolism of molecules such as glucose. During aerobic
respiration, glucose is broken down by oxygen to release energy, while carbon dioxide and water are
the by-products of the reaction. Breathing delivers oxygen to where it is needed in the body and
removes carbon dioxide thereby exchanging oxygen and carbon dioxide between the body and the
environment. Carbon dioxide (CO2) is mostly a waste product and needs to be removed from our
body. CO2 from respiring tissues enters the blood plasma and diffuses into the red cells, where it is
rapidly hydrated to H+ and bicarbonate (HCO3-) by the enzyme carbonic anhydrase (CA) (Arlot et al.
1985; Adeva-Andany et al. 2014). This enzyme enables the breakdown of CO2 which returns to the
plasma as bicarbonate and is then transported to the lungs (Adeva-Andany et al. 2014). When the
bicarbonate reaches the lungs, CA in the alveoli catalyses the reverse reaction generating water and
carbon dioxide which is exhaled as a gas. CA thus allows a large pool of otherwise slowly reacting
plasma HCO3- to be utilized in CO2 excretion (Arlot et al. 1985).
There is an optimal range for the concentrations of CO2 in the air we breathe. Too little can mean
that breathing is too slow and not enough oxygen is brought into the body (Patton and Thibodeau
2009). Too much can compromise our ability to remove CO2 (from our bodies) as a waste product. So
what are the effects of too much CO2 and what is the level that can cause health problems (in
3. Health effects from short term exposure to high levels of CO2
Breathing too much CO2 results in high levels of CO2 in the blood (hypercapnia) associated with a
decrease in blood pH (increased acidity) resulting in a condition known as acidosis. The decreases in
blood and tissue pH produce effects on the respiratory, cardiovascular, and central nervous systems
(CNS) (Eckenhoff and Longnecker 1995). Changes in pH act directly and indirectly on those systems
producing effects such as tremor, headache, hyperventilation, visual impairment, and CNS
impairment. In terms of worker safety, the US Occupational Safety and Health Administration has set
a permissible exposure limit (PEL) for CO2 of 5,000 parts per million (ppm) (or 0.5 %) over an 8-hour
work day (OSHA 2012). They report that exposure to levels of CO2 above this can cause problems
with concentration, an increased heart rate, breathing issues, headaches and dizziness.
Exposures to 1-5 % CO2 for short-term periods have been documented to produce symptoms on
humans and animals such as dyspnea (shortness of breath), modified breathing, acidosis, tremor,
intercostal pain, headaches, visual impairment, lung damage, increased blood pressure, bone
degradation, reduced fertility, alterations to urine and blood chemistry as well as erratic behaviour
(Halperin 2007; Rice 2004; Guais et al. 2011; Schaefer et al. 1963; Yang et al. 1997). These levels of
CO2 also induce panic attacks, interrupt the processes of metabolic enzymes and disrupt normal cell
division processes (Colasanti et al. 2008; Guais et al. 2011; Abolhassani et al. 2009).
Health risks continue to escalate, with progressively higher CO2 concentrations causing more severe
reactions and faster responses. A value of 40,000 ppm is considered immediately dangerous to life
and health given that a 30-minute exposure to 50,000 ppm produces intoxication, and
concentrations around 70,000 ppm produce unconsciousness (NIOSH 1996). Additionally, acute
toxicity data show the lethal concentration for CO2 is 90,000 ppm (9%) for a 5-minute exposure.
There are indoor situations where exhaled human breath and restricted air flow can produce
extreme and dangerous levels of CO2. For example infant deaths have been associated with levels of
up to 8% (80,000 ppm) CO2 for an infant covered by blankets (Campbell et al. 1996).
4. Physiological compensation for elevated CO2
For understanding the long-term effects of breathing sustained elevated CO2, it is important to
consider compensation mechanisms in the body, that regulate for increased CO2 and acidity in the
blood, and how these change over time with persistent exposure. The lowering of blood pH triggers
various compensatory mechanisms, including pH buffering systems in the blood, increased breathing
to reduce excess CO2 in the bloodstream, increased excretion of acid by the kidneys to restore acid-
base balance, and nervous system stimulation to counteract the direct effects of pH changes on
heart contractility and vasodilation (widening of the blood vessels) (Burton 1978; Eckenhoff and
Longnecker 1995). In respiratory acidosis, for a period the kidneys retain bicarbonate helping to
normalise the pH of the blood as it passes through them. This occurs within 6 to 8 hours of exposure
but achieves full effect only after a few days. With continued high levels of CO2 in the blood,
metabolic acidosis occurs and the kidneys do not respond in producing bicarbonate (Schaefer et al
1979a). After this the body uses the bones to help regulate the acid levels in the blood. Bicarbonate
and a positive ion (Ca2+, K+, Na+) are exchanged for H+. The kidneys are involved in a wider array of
physiological compensation responses to CO2 induced pH imbalance (acidosis). The kidney tubule
recovers filtered bicarbonate or secretes bicarbonate into the urine to help maintain acid-base
balance in the blood and this again involves the CA enzyme (Adeva-Andany 2014).
5. Health effects at common indoor CO2 concentrations
5.1 Classrooms
There is a large volume of recent literature that has documented the occurrence and levels of CO2 in
classrooms across the world including kindergartens, day-care centres, primary schools, high schools
and universities (Bako-Biro et al 2011; Widory and Javoy 2003; Kukadia et al. 2005; Dijken et al.
2005; Branco et al. 2015; Heudorf et al. 2009; Santamouris et al. 2008; Ferreira and Cardoso 2014;
Gaihre et al. 2014; Jurado, et al. 2014; Lee and Chang 2000; Muscatiello et al 2015; Carreiro-Martins
et al. 2014). There is general agreement that the levels of CO2 in 20-50% of classrooms commonly
exceed 1,000 ppm and are often much higher, sometimes reaching levels as high as 6000 ppm for
extended periods. A number of studies have identified CO2 associated symptoms and respiratory
diseases such as sneezing, rales, wheezing, rhinitis, and asthma (Carreiro-Martins et al. 2014;
Ferreira and Cardoso 2014). Other symptoms; i.e. cough, headache, and irritation of mucous
membranes, were also identified (Ferreira and Cardoso 2014). Lack of concentration was associated
with CO2 levels above 1000 ppm. Gaihre et al. (2014) found that CO2 concentrations exceeding 1000
ppm is associated with reduced school attendance. Teachers also report neuro-physiologic
symptoms (i.e., headache, fatigue, difficulty concentrating) at CO2 levels greater than 1000 ppm
(Muscatiello et al. 2015).
5.2 Offices
Offices have levels of CO2 similar to classrooms depending on the number or density of workers and
the types of ventilation systems (Lu et al. 2015; Tsai et al. 2012, Seppanen et al. 1999). These studies
have found strong evidence of the relationship between CO2 levels in offices and Sick Building
Syndrome (SBS) health effects such as headaches, dizziness, fatigue, respiratory tract symptoms, eye
symptoms, nasal and mucous membrane symptoms (Seppanen et al. 1999; Lu et al. 2015; Tsai et al.
2012; Vehviläinen et al. 2016; MacNaughton et al. 2016). Seppanen et al. (1999) conducted a review
of available literature and were careful to eliminate other confounding airborne building
contaminants. The reviewed studies included over 30,000 human subjects, and they concluded that
the risk of SBS symptoms decreased significantly with carbon dioxide concentrations below 800
ppm. Whether CO2 itself is responsible for the health symptoms is still a subject of debate since
historically it has been assumed, despite lack of direct evidence, that other airborne contaminants
are the cause (Zhang et al. 2017).
More recently a number of studies have demonstrated that CO2 has direct impacts on human
physiology at levels commonly found in indoor environments (Azuma et al . 2018). Symptoms such
as fatigue and drowsiness caused directly by CO2 have been demonstrated by the use of
electroencephalogram (EEG) techniques (Snow et al. 2018; Pang et al. 2020). In a study of office
workers, a 20% increase in blood CO2, to significantly above normal levels, was measured along with
sleepiness, headaches, heart rate variation and poor concentration in air that averaged 2,800 ppm
CO2 (Vehviläinen et al. 2016) while lowered heart rate and arousal level (fatigue) is clear at 4000
ppm (Xia et al. 2020). Measurements of end-tidal PCO2 show a significant increase of CO2 in human
blood during tests conducted on astronauts after 4 months continually exposed to about 5,000 ppm
(Hughson et al. 2016). Increases in blood CO2 were associated with restricted lung function at levels
between 2,000 and 3000 ppm CO2 (Shriram et al. 2019). Zheutlin et al. 2014 used statistical data to
determine an increasing trend in the average levels of CO2 in the blood for a national sample of
5,000 people from 1999 to 2012. Heart rate variation at 2700 ppm is confirmed by Snow et al. (2019)
for 10 minute exposure. MacNaughton et al. (2016) found that a 1,000 ppm increase in CO2 from
background levels was associated with a 2.3 bpm increase in heart rate after adjusting for potential
confounders. Another older study (Goromosov 1968) reported harmful physiological effects on
humans at only 1,000 ppm CO2 with changes in respiration, circulation, and cerebral electrical
activity. These physiological effects are being observed at much lower levels of CO2 than previously
anticipated (Azuma et al. 2018).
5.3 Vehicles
Although rarely studied for health effects, vehicles can often contain even higher levels of CO2
particularly where there are multiple passengers for relatively long journey times. CO2 levels can
build up to 5,000 ppm after less than an hour of driving with two people in a car with only internal
air (Gładyszewska-Fiedoruk 2011). With five people in a car with recirculated air levels of CO2 can
exceed 10,000 ppm (1%) after only 28 minutes, this being a level that is known to result in
respiratory acidosis (Constantin et al. 2016). Buses with high numbers of passengers consistently
reach average CO2 concentrations of > 2500 ppm (Chiu et al 2015). Airliners can contain levels of
around 2000 ppm for the duration of the flight (Gładyszewska-Fiedoruk 2012). Measurements on an
Italian submarine showed a steady increase to 5000 ppm CO2 after 2 hours of being submerged
(Ferrari et al. 2005). Extremely high CO2 concentrations (10,000-20,000 ppm) are commonly found
inside motorcycle helmets in both stationary and moving situations (Bruhwiler et al. 2005).
5.4 Cognitive impairment and anxiety in elevated CO2 environments
There is now a significant body of research studies involving the detrimental effect of CO2 on
learning and cognitive abilities in humans at common indoor concentrations (Du et al. 2020; Lee et
al. 2022). Testing of students has found that CO2 can negatively affect attention, memory,
concentration and learning ability impacting on academic performance (Bako-Biro et al. 2011; Coley
et al. 2007). Several recent university studies of cognitive effects of CO2 have been notable in their
strong research design (Satish et al 2012; Allen et al 2016; Allen et al 2018; Scully et al 2019) with the
testing environments injected with pure CO2 meaning that the analysis of CO2 effects was not
confounded by the presence of other substances. These studies showed that low level CO2 (between
950 ppm and 2500 ppm CO2) affected the cognitive abilities of students, information professionals
and pilots in the indoor environment. Satish el al. (2012) tested only variations in CO2 over periods
of 2.5 hours of exposure. For seven of nine scales of decision-making performance (basic activity,
applied activity, task orientation, initiative, information usage, breadth of approach, and basic
strategy), performance was significantly impaired in a dose-response manner with higher CO2 levels.
For example, compared with mean raw scores at 600 ppm CO2, mean raw scores at 1,000 ppm CO2
were 11–23% lower, and at 2,500 ppm CO2 were 44–94% lower. As part of a larger study that
included volatile organic compounds (VOCs), Allen et al. (2016) found that, after CO2 was
independently modified (from a baseline of 480-600 ppm) for individual 8-hour exposures, cognitive
function scores were 15% lower at 950 ppm and 50% lower at 1400 ppm. This study used similar
methodology to score cognitive function and the results largely repeated the findings of the earlier
work (Satish et al 2012). However, one difference was that, at 1500 ppm CO2, even focussed activity
was found to have declined (Allen et al 2016). In a study of pilots’ performance, Allen et al. (2018)
found that negative impacts on cognitive function were observed between 700 ppm and 1500 ppm
CO2. Another study found similar negative effects on human cognitive abilities, in experiments
involving 140-minute sessions, as well as increased fatigue at levels of 3000 ppm CO2 compared with
600 ppm (Kajtar and Herczeg 2012). This study also measured some physiological parameters with
heart rate analysis suggesting significantly increased mental effort at 3000-4000 ppm.
These studies are further supported by the finding of CO2-induced changes in human brainwaves,
measured by electroencephalography (EEG), that have known associations with mental impairment
(Lee et. al. 2022). EEG combined with cognitive tests provided evidence of brainwave changes in
frontal, parietal and occipital lobes that showed the negative impact of 1000 ppm and 2500 ppm CO2
on working memory, mental workload and visual concentration after only 15 minutes of exposure.
This is physiological evidence for the effect of CO2 on cognitive decline.
Cognitive and neurological effects are also observed in animal studies. Mice exposed from birth to
1,000 ppm CO2 for 38 days had decreased Insulin-like Growth Factor-1 (IGF-1) which resulted in
greater anxiety and reduced cognitive function (Kiray et al.2014). Neurons were reduced in number
and were malformed at this CO2 level for several areas of the brain, with the largest effect for those
areas associated with learning and memory. Mice exposed to only 890 ppm from preconception to 3
months of age showed increased levels of the stress hormone corticosterone in the blood and brain
(Wyrwoll et al. 2022). Along with anxiety, chronic elevation of brain corticoids associates with
cognitive impairment and could harm the developing brain (Stolp 2022).
5.5 Sleep impacts
Sleep quality is reduced at 1900 ppm CO2 when compared to 800 ppm in both subjective indices and
electroencephalogram (EEG) measurements of brain activity (Xu et al. 2020). When CO2 in arterial
blood rises to a certain extent, it will produce carbon dioxide narcosis respiratory inhibition,
weakened respiration, and hypoxia of human cells resulting in poor sleep quality (Xu et al. 2020).
Another example is people affected by sleep disordered breathing (SDB). Brillante et al (2012) found
that the development of nocturnal hypercapnia in normal indoor CO2 air concentration, quantitated
by a large difference in carbon dioxide in the blood between morning and evening, predicted
increased mortality in SDB patients. This is a result of the lack of efficacy of an individual’s
respiratory regulatory system in sleep for maintaining normal blood gas tensions (Brillante et al.
2012). As CO2 levels in the atmosphere increase into the future, the impacts on and number of
affected individuals will logically increase.
6. Health effects from long term exposure to elevated CO2 levels below 1%
Where indoor levels of CO2 are relatively high and affecting health, it is generally possible to obtain
relief by going outdoors. However this may not be the case in a climate change future where
ambient CO2 is persistently high and effects of continuous long-term exposure must be considered.
There have been very few studies related to long-term exposure at lower CO2 levels, elevated above
ambient, perhaps for logistical reasons since it is difficult to arrange an experiment for relevantly
long timeframes. We are looking for information on the effect on humans of CO2 levels at 1,000
ppm or less – noting that this is the level that some feasible models predict could be reached in the
ambient atmosphere in less than 100 years (Smith and Woodward 2014). Given the lack of research
at these CO2 levels, it seems reasonable to examine the research available for medium-term studies
on levels of CO2 less than 10,000 ppm (1%). Table 1 provides a summary of health effects, found in
the published literature and discussed in this paper, resulting from breathing CO2 at levels at or
below 1%.
Table1. Documented health effects from breathing CO2 at concentrations at or below 1%.
CO2 Level Health effect Exposure Source
10,000 ppm
Kidney calcification, decreased bone formation and
increased bone resorption in guinea pigs
6 weeks Schaefer et al., 1979a
10,000 ppm
Cognitive impairment, increased diastolic blood
75 min Tu et al. 2020
8500 ppm Increased lung dead space volume 20 days Rice 2004
7000 ppm
35% increase in cerebral blood flow (implications for
cognitive effects seen in other studies)
23 days Sliwka et al. 1998
Headaches, lethargy, moodiness, mental slowness,
emotional irritation, sleep disruption
Short-term Chronin et al. 2012; Law et
al. 2010
5000 ppm Kidney calcification, bone degradation in guinea pigs 8 weeks Schaefer et al 1979b
5000 ppm Elevated blood CO2 levels in astronauts 4 months Hughson et al. 2016
5000 ppm Current allowable levels for continuous exposure in
submarines and spacecraft
Halperin et al. 2007; Chronin
et al 2012
5000 ppm Permissible exposure limit (PEL) for a work day 8 hours OSHA 2012
5000 ppm Vascular and neurological changes 1.5 minutes Bright et al. 2020
4000 ppm Increase in heart rate, lowered arousal level/
increased fatigue and sleepiness
17 minutes Xia et al. 2020
3500 ppm Cognitive impairment, reduced human vigilance
(increased sleepiness)
4 hours Pang et al. 2020, Zhang et
al. 2020
3000 ppm Cognitive impairment, anxiety, neural damage,
oxidative stress in mice
38 days Kiray et al. 2014
3000 ppm Impaired visual attention, decision making and
executive ability
Short-term Cao 2022
3000 ppm Systemic inflammation and physiological stress in
9-13 days Beheshti et al. 2018
2700 ppm Drowsiness measured by EEG 10 min Snow et al. 2018
2700 ppm Increase in heart rate 10 min Snow et al. 2019
Unhealthy blood CO2 levels - 15% above normal
range, sleepiness, headaches, heart rate variations
4 hours Vehviläinen et al. 2016
Inflammation and vascular damage in mice 2 hours Thom et al.2017
Restrictive lung behaviour and elevated blood CO2 3 hours Shriram et al. 2019
2000 ppm Kidney effects in animals (likely calcification) -
incomplete study
Schaefer 1982
1900 ppm Reduced sleep quality, drowsiness 8 hours Xu et al. 2020
Significant impairment of cognitive function
including fatigue
2.5 to 8
Satish et al 2012; Allen et al
2016; Kajtar & Herczeg 2012
1200 ppm Reduced cognitive function 2.5 hours Scully et al. 2019
1000 ppm Harmful changes in respiration, circulation, and the
cerebral cortex
A short time Goromosov 1968
1000 ppm Oxidative stress and damage to DNA in bacteria
(implications for cancer diseases in humans)
3 hours Ezraty et al. 2011
1000 ppm Cognitive impairment, anxiety, neural damage,
oxidative stress in mice
38 days Kiray et al. 2014
1000 ppm Level associated with respiratory diseases,
headache, fatigue, difficulty concentrating in
Short-term Carreiro-Martins et al. 2014;
Ferreira and Cardoso 2014;
Seppanen et al. 1999
1000 ppm EEG changes in brainwaves associated with mental
15 min Lee et. al. 2022
Health symptoms (respiratory, skin, eyes, headaches,
cognitive, dizziness, sensory), increase in heart rate
30 min MacNaughton et al. 2016
Moderate impairment of cognitive function 2.5 to 8
Satish et al 2012; Allen et al
2016; Allen et al 2018
890 ppm Impaired lung function in new-born female mice,
slightly lower blood pH. Reduced growth,
hyperactivity, increased stress hormone, anxiety
associated with cognitive impairment
3 months Larcombe et al. 2021;
Wyrwoll et al. 2022
800 ppm Level associated with Sick Building Syndrome -
headaches, dizziness, fatigue, respiratory tract, eye,
nasal and mucous membrane symptoms
Short-term Seppanen et al. 1999; Lu et
al. 2015; Tsai et al. 2012
700-900 ppm Gastropods: reduced growth, reduced food
absorption and oxygen uptake, reproductive failure
6-10 months Navarro et al. 2022;
Mardones et al. 2022
700 ppm Modification of behaviour, stress hormone and
respiratory muscle structure in rats
15 days,
Martrette et al. 2017
420 ppm Current average outdoor air concentration – no clear
effect, possible increase in disease and anxiety
Lifetime NOAA Global Monitoring
280-300 ppm Pre-industrial outdoor level from about 1820 to at
least 25 million years ago - no effect
Lifetime Beerling and Royer 2011;
Zachos 2001.
6.1 Spacecraft
A good information source may be the safety guideline documents for activities where humans are
required to remain in enclosed spaces for long periods such as spacecraft and submarines. NASA
sought to determine the safe levels for long-term exposure to CO2, but found little research focused
on levels below 10,000 ppm CO2; as such, there was no definitive study available to guide standards
(Cronyn et al. 2012). They set the maximum allowable CO2 concentration limits, for long term (1,000
day) habitation of submarines and spacecraft, at 5000 ppm (James and Macatangay 2009).
International Space Station (ISS) crew members have repeatedly reported symptoms associated with
acute CO2 exposure at levels of 5,000 to 6,600 ppm CO2 (see Table 1). The most commonly reported
symptom was headache; other symptoms reported included lethargy, mental slowness, emotional
irritation, and sleep disruption (Law et al. 2010). For space flight, Cronyn et al. (2012) identified three
potential areas of operational impact of elevated CO2: renal calculi (kidney calcification) and bone
reabsorption; cerebral blood flow; and mission performance. With no definitive research to provide
insight into these areas, further evaluation was recommended to examine the effects on human
subjects of various low-to-moderate CO2 concentrations (from ambient levels up to 1%).
Consequently, flight rules have been employed to reduce CO2 limits in the ISS to about 3 mm Hg
(4,000 ppm) (Ryder et al. 2017).
6.2 Submarines
Studies of CO2 effects on humans in enclosed submarines have been reviewed by the US government
(Halperin 2007) although most of these studies are for high (> 1%) CO2 levels at relatively short
exposure durations. At these levels (>1%), many of the debilitating and acute symptoms described
above were noted. Current safe levels for continuous exposure in submarines were deemed to be
around 5,000 ppm CO2. This level is set arbitrarily at one-third of the level where there were obvious
signs of health problems (James and Macatangay 2009). It was also noted that if problems are
observed, a submarine can surface so that its occupants can be exposed to the ambient atmosphere.
Halperin (2007) reports that exposures to CO2 levels as low as 7,000 ppm can lower blood pH by up
to 0.05 units and induce renal (kidney) compensation in healthy subjects. This compensation occurs
over a variable period of time, but effects of lowered pH on clinical status or performance have not
been reported either experimentally or operationally. Given that kidney compensation cannot occur
indefinitely, there is some doubt about whether submariners could sustain the “safe” level of 5,000
ppm CO2 if they spent years exposed to it.
7. Protein malfunctions caused by elevated CO2 in the body
Carbon dioxide is a fundamental physiological gas known to profoundly influence the behaviour and
health of millions of species within the plant and animal kingdoms (Phelan et al 2021). It is known
that CO2 plays a major role in sensing and signalling on a cellular level although the physiological
response is complex and not well understood. Research has found that increases in CO2 resulting in
reduced pH alters mitochondrial metabolism reducing oxygen consumption and releasing
intracellular calcium stores (Phelan et al 2021).
The endoplasmic reticulum (ER) is a large dynamic structure within cells that serves many roles
including protein synthesis and calcium storage. Elevated CO2 levels cause protein malfunctions by
altering ER folding machinery. These malfunctions are associated with ER stress triggering
maladaptive responses and effecting a range of diseases e.g., chronic lung disease and reduced
immunity, tissue and organ malfunction (Kryvenko and Vadasz 2021)
7.1 Elevated CO2 causes carbonic anhydrase enzyme disfunction and related diseases
Carbonic anhydrase (CA) enzymes are widely expressed in the nervous system and tissues
throughout the body where they play important physiological roles (Aspatwar et al 2021). The
reaction that CA catalyses, the reversible hydration of CO2 to bicarbonate and a proton, lies at the
heart of a wide range of vital physiological processes (Chegwidden and Carter 2021; Aspatwar et al
2021). Abnormal regulation of carbonic anhydrase-related proteins causes a range of diseases
conditions including cancer, Alzheimer’s, cardiovascular disease, diabetes, glaucoma, epilepsy,
stroke, bipolar disorder etc. The use of CA isozyme inhibitor drugs for treating these diseases is now
a major science (Celebioglu et al 2021; Lemon et al 2021). However, CA inhibitors can cause CO2
retention and result in cellular malfunctions (Phelan et al 2021). The progressive increase in CA
disfunction due to increasing atmospheric CO2 will result in worsening outcomes for the diseases
mentioned above.
7.2 CO2 induced deposits of calcium in the body
Carbonic anhydrase (CA) enzymes participate in metabolic reactions that convert CO2 and result in
the precipitation of calcium carbonate (Adeva-Andany et al. 2015; Kim et al. 2012; Tan et al. 2018).
CA is implicated in calcification of human tissues, including bone and soft-tissue calcification (Adeva-
Andany et al. 2015). The enzyme may be also involved in bile and kidney stone formation and
carcinoma-associated micro-calcifications. The molecular mechanisms regulating the development
of calcification in human tissues and arteries are similar to those that regulate physiological
mineralization in bone tissue, being poorly understood (Adeva-Andany et al. 2015). Carbon dioxide
conversion by the CA enzyme provides bicarbonate and hydrogen ions that fuel the uptake of
ionized calcium which is then deposited in the body tissues as calcium carbonate. With elevated CO2
in cells there is increased release of calcium from the ER (Kryvenko and Vadasz 2021).
Kidney calcification is known to occur with longer term exposure to elevated CO2 levels (Rice 2004;
Schaefer et al., 1979a). A similar causal link between the activity of CA enzyme, which is mainly
responsible for the reversible breakdown of CO2, and calcium deposits has also been established for
arteries (Adeva-Andany et al. 2014). As part of a US Navy experimental program in the 1960’s and
1970’s investigating impacts of long-term CO2 exposure, Schaefer et al (1979b) found that, in a study
of guinea pigs in an enclosed environment breathing 5,000 ppm CO2 for 8 weeks, the kidneys started
to calcify along with bone degradation (see Table 1). Schaefer (1982) also indicated that preliminary
experiments had found kidney calcification effects in animal studies for CO2 concentration as low as
2,000 ppm. Although these studies did not identify a mechanism, they established the casual link
between CO2 and kidney calcification. More recent studies have found that tissue calcification is
promoted where CA is overexpressed due to increased CO2 in the body (Song et al 2021; Phelan et al
2021). Increased CA activity is also linked to cancer where the enzyme helps create a hostile, low pH
environment suitable for cancers to flourish in (Hulikova et al. 2014; Logozzi et al. 2019; Di Fiore et
al. 2020).
8. Other important physiological CO2 effects on health
8.1 Impaired growth and muscle development
Female mice exposed to 890 ppm CO2 for 3 months from pre-pregnancy showed reduced growth
(Wyrwoll et al 2022) and a range of lung and respiratory impairments including lower lung
compliance (Larcombe et al. 2021). Prolonged exposure to CO2 on behaviour, hormone secretion
and respiratory muscles in young female rats exposed at 700 ppm CO2 during 6 hours per day for 15
days (Martrette et al. 2017) (see Table 1). CO2 exposure, though not continuous, produced
significant disturbances in behaviour and was accompanied by increased plasma levels of
corticosterone, suggesting that prolonged exposure to CO2 was stressful producing anxiety.
Increased corticosterone associated with hyperactivity in mice was also found from long-term
exposure to 890 ppm CO2 (Wyrwoll et al 2022).
8.2 Increased cerebral blood flow
Cerebral blood flow (CBF) effects from breathing CO2 are a significant issue for humans. As CO2 in the
blood increases, CBF increases to effectively wash out CO2 from brain tissue and helps regulate
central pH (Ainslie and Duffin, 2009). In a 23-day experiment on humans, Sliwka et al. (1998) found
that cerebral blood flow is increased in the presence of 7,000 ppm (0.7%) CO2 by as much as 35%
(see Table 1) and that CBF remained elevated until the end of the evaluation period, 2 weeks after
the exposure. The impacts of persistent increase in CBF are unclear although there may be a risk of
raised intracranial pressure (ICP) which can compress and damage delicate brain tissue. There is also
evidence that the CBF response to increased CO2 is impaired in Alzheimer’s patients and that this is
linked to the decline in cognitive abilities (Glodzik et al 2013) which will worsen as CO2 in the
atmosphere increases.
8.3 Oxidative Stress
In humans, carbon dioxide is also known to play a role in oxidative stress caused by reactive oxygen
species (ROS) (Ezraty et al. 2011; Kiray et al. 2014). ROS are produced by aerobic metabolism of
molecular oxygen and play a major role in various clinical conditions including malignant diseases,
diabetes, atherosclerosis, chronic inflammation and neurological disorders such as Parkinson’s and
Alzheimer’s diseases (Waris and Ahsan 2006). In particular, oxidative damage to cellular DNA can
lead to mutations resulting in the initiation and progression of cancer. Ezraty et al (2011)
demonstrated that current atmospheric CO2 levels play a role in oxidative stress and that increasing
CO2 levels between 400 and 1,000 ppm exacerbated oxidative stress and damage to DNA in bacteria.
Kiray et al. (2014) concluded that oxidative stress and oxidative damage to brain tissue in mice is
associated with low Insulin-like Growth Factor 1 (IGF-1) levels in mice impacting the growth of bones
and tissues. Increased CO2 promotes the production of ROS leading to greater incidence of cancers
and other diseases including the promotion of virus activity (Waris and Ahsan 2006). Ezraty et et al
(2011) concluded that with higher atmospheric CO2 concentrations, this exacerbation might be of
great ecological concern with important implications for life on Earth.
8.4 Inflammation
Inflammation is a serious illness that is known to be caused by elevated CO2 exposure in humans and
animals (Thom et al. 2018; Beheshti et al. 2018; Zappulla 2008; Jacobson et al. 2019). CO2 increases
result in higher levels of Interleukin, a protein involved in regulating immune responses, which
causes inflammation and vascular damage in mice (Thom et al. 2017). Rodents exposed to 3,000
ppm CO2 in spacecraft experiments for 9-13 days showed evidence of inflammation and
physiological stress (Beheshti et al. 2018).
8.5 Stroke
Another study has shown that increased CO2 in the blood of patients can increase the severity of
Subarachnoid haemorrhage; a life-threatening form of stroke, due to the dilatation of arterial
cerebral vessels (Reiff et al 2020).
9. Discussion
Evidence reviewed in this paper suggests that there is a direct risk to the human species posed by
the breathing of ambient atmospheric CO2 concentrations that are rapidly increasing. The level of
ambient atmospheric CO2 that provides unacceptable risk and the exact effect on physiology are not
clearly determined. If this level is reached in the near future, the global human society should be
concerned. Some climate models suggest that atmospheric CO2 levels could be as high as 1,000 ppm
in this century. This is completely unknown for the whole primate evolutionary lineage which has
only experienced levels well below and recently up to the current level of around 410 ppm.
Given the seriousness of the risks identified in this paper an important question has to be: why has
there been no societal discussion of this issue uniquely or in relation to climate change? With the
startling rapid rise of CO2; the permanent changing of our breathable air composition, one would
surely expect the question of whether we can physiologically deal with future projected levels of
CO2, to at least be examined. However, it appears that the issue is not even thought of. There is an
assumption even among scientists that if this was a real issue it would have already been
researched, i.e., we would know about it, though this perception is not scientific and precludes novel
investigation. It appears that the issue of long-term CO2 elevated toxicity has never been significantly
investigated since we have never been in this situation before. Our body’s CO2 compensation
system, as discussed earlier, has been perfectly adequate to deal with a stable level of atmospheric
CO2. It is also possible that climate change has become the main focus of rising CO2 levels and there
is a lack of vested interest amongst climate scientists about the potential dangers of long-term
exposure to elevated CO2. The most recent IPCC report on the health impacts of climate change
didn’t discuss the issue at all (IPCC 2022). This is surprising since the previous IPCC report (Smith and
Woodward 2014) described the findings of Satich et al. (2012) as a reported “reduction in mental
performance at 1,000 ppm CO2 and above, within the range that all of humanity would experience in
some extreme climate scenarios by 2100”. Since the earlier report there have been many more
studies of cognitive decline (Du et al. 2020) and the damaging effects of elevated CO2 on physiology
(this paper). It is therefore disturbing and shocking that the latest IPCC report failed to recognise this
serious and fundamental aspect of climate change. CO2 toxicity at elevated levels is a discipline of
environmental medicine which has not focussed on the potential problem because chronic impacts
of increasing environmental CO2 have not yet been recognised. This may also help to explain why
there are very few researchers involved at this stage and public awareness is close to non-existent.
There are few long-term physiological studies of human exposure to 1,000 -2,000 ppm CO2
or less.
However, there are short-term exposure studies describing disease symptoms and physiological
effects as well as reduced cognitive ability in humans at levels around 800 - 950 ppm CO2; these are
CO2 levels that are typically present in offices, classrooms and apartments (Gall et al. 2016). It
appears that many of the physiological effects of CO2 are due to the stimulation of the autonomic
nervous system resulting in elevated blood pressure, respiration, and heart rate (MacNaughton et al.
2016) and this is also associated with a decline in cognitive ability due to increased Cerebral Blood
Flow (CBF) with resulting effects on central nervous system and brain cortical function (Satish et al
2012; Glodzik et al 2013; Bright et al. 2020). The effect on cortical function is supported by a study of
infants that showed an inverse relationship between blood CO2 and electrocortical activity (Wikstrom
et al. 2011). Long-term exposure to environmentally relevant levels of CO2 leads to increases in the
levels of CO2 in human blood (Zheutlin et al. 2014; Hughson et al. 2016; Vehviläinen et al. 2016). This
is retention of CO2 in the human body at greater than normal levels and disturbingly the levels of
CO2 in our blood will continue to increase as atmospheric levels rise.
Increased CO2 in the blood also affects protein behaviour causing inflammation (Thom et al. 2018),
calcification (Schaefer 1982) of body tissue and a range of demonstrated pH-related protein
malfunctions (Duarte et al. 2020), both with potentially serious outcomes. Reduced pH due to CO2
has been found to alter mitochondrial metabolism affecting oxygen consumption (Phelan et al.
2021). Elevated CO2 causing protein malfunctions can trigger diseases including cancer, neurological
disorders, lung disease, reduced immunity and organ failure (Duarte et al 2020; Kryvenko and
Vadász 2021). Perhaps the most significant protein malfunction is the overexpression of the CA
enzyme due to increased CO2 in the body. This widely distributed enzyme plays a vital role allowing
for respiration and the processing of CO2 in all animals and plants. New research is showing that CA
malfunction due to elevated CO2 causes a range of health problems including cancer and diabetes
(Aspatwar et al 2021). Perhaps the most serious of these is tissue calcification which can result in
kidney and cardiovascular failure. Furthermore, the incidence and prevalence of human kidney
calcification (i.e. stones) is increasing globally (Romero et al. 2010; Turney et al. 2011;
Kittanamongkolchai et al. 2018) and it is possible that rising indoor CO2 levels (boosted by increasing
ambient CO2) is the contributing cause.
Perhaps the most informative study about CA behaviour is that of Rodriguez-Navarro et al. (2019).
CA catalyses the formation of the reactive precursors (i.e., HCO3 and CO32− ions) required for
mineralization and accelerates the precipitation of metastable amorphous calcium carbonates. Ca+
and CO32 ions promote the partial unfolding and oligomerization of CA, resulting in fibril- and sheet-
like supramolecular assemblies that template nanostructured calcium carbonate crystallization. The
enzyme then loses its CO2 hydration catalytic activity and elicits a mechanism for arresting calcium
carbonate mineralization. Such a negative feedback mechanism would first help jump-start CaCO3
mineralization and subsequently contribute to the arrest of this process, offering a simple
mechanism for organisms to control CaCO3 biomineralization. Otherwise, if CA endlessly remained
catalytically active once secreted, it would be difficult for an organism to stop the biomineralization
process (Rodriguez-Navarro et al 2019). Despite the significant reduction observed, some enzyme
activity remains even after precipitation of calcite. In a future where increasing atmospheric CO2 will
potentially result in excess CO2 in the body, the resulting excess CA will be converted into calcium
carbonate factories creating an ongoing calcification problem.
What level of permanent CO2 will cause significant calcification and other protein malfunction
effects? It has been suggested that blood pH would be reduced to dangerous levels, if there were no
physiological compensation, at CO2 levels as low as about 430 ppm (Robertson 2006) implying that
ongoing compensation would occur at this level. Ambient conditions may already be dangerously
close to CO2 levels that cause human tissue calcification, particularly when considering the additive
effect of increased ambient levels on indoor CO2 concentrations. In the final paper of the US Navy
CO2 research program in the 1960’s and 1970’s, Schaefer (1982) indicated that this issue had
“become the concern of the Department of Energy and other US government agencies” although it
appears to have been largely forgotten since. If allowed to persist, problems such as kidney and
artery calcification could lead to cardiovascular failure. In the extreme case, lifespans could become
shorter than the time required to reach reproductive age. Calcification of kidneys and arteries can be
fatal through renal and cardiovascular failure. This could threaten the viability of human and animal
species without interventions such as the creation of artificial living environments.
Cognitive decline due to CO2, evidenced by definitive studies (Satish et al 2012; Allen et al 2016;
Allen et al 2018) of indoor environments, would logically produce lower intelligence in humans
which is now being measured around the world (Bratsberg and Rogeberg 2018). It is feasible that
rising outdoor CO2 levels are the cause of the measured decline in human intelligence (Bierwirth
2018). It is possible that such effects occur without recognition in daily life (Satish et al. 2012). The
modest reductions in multiple aspects of decision making, seen as low as 950 ppm (Allen et al. 2016),
may not be critical to individuals, but at a societal level or for employers an exposure that reduces
performance even slightly could be economically significant. The observation of brainwave changes
at elevated levels of CO2 (around 1000 ppm and greater) (Lee et. al. 2022) is significant being
physiological evidence of cognitive impairment. This is concerning since it suggests our brains may
be increasingly affected by rising environmental CO2 levels.
The impacts on students including sickness, reduced attendance and reduced learning abilities
should also be a concern for society. Moreover, the relatively high levels of CO2 in vehicles
associated with declining concentration and fatigue has serious implications for the safety of drivers
and their passengers. This is an issue that does not appear to have been raised in research on driver
fatigue illustrating the general lack of awareness about CO2 effects.
Carbon dioxide is known to cause anxiety and panic attacks in humans (Battaglia 2017). CO2
sensitivity is one of the most basic and general alarm/avoidance systems within the realm of biology.
Once it permeates the blood–brain barrier, CO2 causes temporary acidification of extracellular brain
fluids resulting in enhanced arousal, and subsequent anxiety (Battaglia 2017). While panic and
anxiety attacks generally occur at high levels of CO2, the distribution of liability to CO2 sensitivity is
continuous and normally distributed in humans and animals. This means that there are potentially
small anxiety effects even at the current and near-future elevated levels of atmospheric CO2. To this
effect, increased hormones associated with anxiety have been observed in mammals at levels of CO2
in the range 700 -1000 ppm (Martrette et al. 2017; Wyrwoll et al. 2022; Kiray et al. 2014). Even a small
permanent increase in global human anxiety could have a serious impact on societies – fear, mental
disturbance, conflicts, etc.
The human species is already impaired in indoor environments and this is likely to get worse as rising
outdoor levels of CO2 contribute to increased indoor concentrations (Azuma et al. 2018). It is not
only humans that are at risk. It has been demonstrated that animals have varying degrees of
susceptibility to carbon dioxide (Schaefer et al. 1971). The impacts of elevated CO2 are even greater
for water breathing animals than air breathing animals. In general, land animals have much higher
blood CO2 than aquatic animals and can compensate for hypercapnia by increasing ventilation. In
aquatic animals, compensation by increased ventilation is rare and a small increase in ambient CO2
causes hypercapnic acidosis (Portner et al. 2004; Knoll et al. 1996; McNeil and Sasse 2016). Studies
have shown that hypercapnia in fish produces substantial neurological, behavioural and
physiological effects (Ishimatsu et al. 2005; Heuer and Grosell 2014) for even short-term exposures
at a CO2 concentration predicted to be persistent in the ocean before the year 2100; this level
corresponding with an atmospheric concentration of 650 ppm CO2 (McNeil and Sasse 2016).
Most of the problems associated with elevated indoor CO2 levels greater than about 800 ppm, can
be alleviated by spending time in fresh air. The indoor environments can be restored to acceptable
CO2 levels with effective ventilation although this is often not being achieved. The available resource
of fresh air may be the underlying misguided reason why there is a lack of concern for pollution and
its effects. Significantly this resource may not be available in the future as rising atmospheric CO2
associated with climate change could exceed the 800 ppm level in the current century (Smith and
Woodward, 2014). At that stage, there would be no outdoor escape from the described symptoms.
Under such a condition of permanent exposure, there could be health impacts at levels less than 800
10. Conclusions
There is now a significant body of research work that demonstrate (1) current health impacts of
rising CO2 levels and (2) more serious CO2 health impacts for humans at some time in the near
Current impacts of elevated and increasing ambient CO2 in indoor environments include
inflammation, respiratory diseases, headaches, fatigue, increased heart rate, increased blood
pressure, and other symptoms at levels above about 800 ppm. This finding together with the
impairment of cognitive abilities at CO2 levels just above ambient (between 600 and 950 ppm), along
with observed associated brainwave patterns, is significant in that it has implications at a societal
level for human function particularly for jobs with critical responsibility (e.g., surgery, air-traffic
controllers, drivers etc.) together with the impact on learning, human development and economies.
It also appears likely that there will be growing global levels of human anxiety from breathing higher
levels of CO2. Physiological CO2 effects will be increased and more permanent in a future with
elevated outdoor ambient CO2 concentrations. Ongoing impacts may include the exacerbation by
CO2 of cellular oxidative stress and protein malfunctions resulting in an increase in cancers,
neurological diseases, viruses and many other conditions. Studies of health effects at higher levels of
CO2 at around 2,000-5,000 ppm demonstrate the impact of the inability of the body to fully
compensate for increased CO2 and acidity in the blood. These effects include human tissue
calcification and bone degradation; the former, associated with the overexpression of the enzyme
carbonic anhydrase that is responsible for processing CO2, might represent the greatest existential
threat for many animals. Given there is a lack of studies in humans at lower but elevated CO2 levels,
demonstrated effects in animals and symptoms experienced by humans indicate that longer-term
mechanisms compensating for increased blood CO2 are active when breathing at around 800-1000
ppm CO2. Long-term exposure to these and potentially lower levels would likely cause severe illness.
These levels are predicted for the ambient atmosphere by the end of the century in a “business as
usual” world. At some stage in the near future humans could be experiencing persistent
physiological effects resulting in serious health problems.
The risk from rising CO2 levels for human and animal population health in the near-future is
extremely high with the health or survival of species under threat. Communication and global
awareness of this issue alongside climate change would further strengthen the need to drastically
reduce CO2 emissions. New research on the health effects of long-term exposure to realistic future
atmospheric CO2 levels is urgently needed to quantify this risk.
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Supplementary resource (1)

... It is infinite clean energy, in addition to being free of cost. Also, it does not need a transmission network from the site of generation to the site of consumption [1][2][3]. Solar energy represents the most important source of renewable energy, as solar energy is easily converted into direct current electricity through the photovoltaic (PV) panels. A PV panel contains a number of solar cells, which convert the energy of the incident light on their surface into proportional electricity. ...
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There are many remote buildings that cannot be supplied by alternating electricity of the utility grid. Due to this, this study proposes adopting Direct Current (DC) appliances for a stand-alone remote building. Direct Current can be supplied from a suitable photovoltaic array which can harvest renewable solar energy. This proposal guarantees an efficient power system by removing the necessity of including an inverter, power filter, insulation transformer, and a complicated controller, which are usually needed for producing Alternating Current (AC) power to feed AC loads using a PV system. When the proposal is applied, the PV system will be more efficient, simple, affordable, and more compact. A detailed power requirement calculation for a typical house uses DC appliances, generalized steps to design a suitable PV array, and an Artificial Neural Network (ANN) algorithm for guaranteeing Maximum Power Point Tracking (MPPT); all of which are introduced for remote buildings. The main contribution of this paper is proposing an integrated design of a DC unit of 11 kW·h PV system for stand-alone buildings that eliminates three stages that improves the system performance compared to AC unit. The introduced study includes PV array calculation based on PV module of 220 W with an intelligent algorithm of four layers. The Mean Squared Error (MSE) of the proposed ANN equals 2.7107 × 10−5 to guarantee a fast and accurate MPP tracking for continuously harvesting maximum power from the incident sunlight. An energy storage unit of 12 batteries 12 V/150 Ah of matrix dimensions 3 × 4 is designed in the DC unit for energy saving to feed the DC appliances during night hours. MATLAB/Simulink Version R2015b is used to simulate the introduced DC power unit and collect the testing records for analyzing the unit performance.
... At the same time, it may cause a rapid respiratory rate, irregular heart rate, drowsiness, dizziness, and impaired consciousness as the concentration of carbon dioxides increases. In severe cases, exposure to an extremely high concentration of carbon dioxide may lead to convulsions, coma, permanent brain and organ damage, and even death (Langford 2005, Bierwirth 2017). Maintaining a low and minimum amount of indoor air in the hospital is crucial for the psychomotor performance of staff, especially nurses and doctors in critical areas such as CCU, ICU, and operating theatre. ...
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Indoor Air Quality (IAQ) is the air quality within and around buildings and structures, particularly regarding building occupants’ health and comfort. IAQ assessments were performed using an objective measurement of molecular gaseous pollutants to determine the IAQ profile in the hospital’s critical areas. It also analyses the effects on patients in different environments and the sources that result in deviations from approved criteria. This comparative study is aimed to investigate the concentration of different compounds in different critical departments in the hospital and propose solutions to the related problem as an improvement in indoor air quality. The data was compared with the standards and regulations. It was found that the TVOC level in the CCU department, specifically in the fluoroscopy room, has exceeded the allowable limit. A few suggestions have been raised to lower the exceeded value. The risks and symptoms held by the occupants in the hospital buildings if they face poor indoor air quality were discussed. Further study can be conducted to relate the short and long-term health issues among medical staff to poor indoor air quality.
... As shown in the work of Tsai et al. (2012) and Bierwirth (2018), CO2 levels above 800 ppm may cause increasing Sick Building Syndrome (SBS) symptoms, such as headaches, dizziness, fatigue, respiratory tract, dizziness and nausea. Furthermore, exposure to high CO2 levels could impair occupants' cognitive performance (Lee et al., 2021;Allen et al., 2018). ...
The use of natural ventilation strategies such as wind towers is encouraged by many governmental/non-governmental organisations to enhance indoor air quality (IAQ) and reduce energy consumption in buildings. However, their usage is restricted during unfavourable weather conditions such as in cold/mild-cold periods because it could lead to high ventilation heat loss and thermal discomfort. A potential solution is to incorporate passive solid tube heat recovery (THR) into the wind tower system to recover the exhaust thermal energy. The aero-thermal performance of such a system has been widely studied, but the evaluation of its impact on the indoor CO2 concentration and spatial distribution has been limited. In this work, a validated computational fluid dynamics (CFD) model of a room with a wind tower system with passive THR was employed to investigate the effects of the occupant-influenced and external environment-influenced variables on the indoor CO2 level. The results highlighted that occupant activity levels greatly affected CO2 levels in the ventilated space, with an increase of 44% from sedentary to medium working observed at the breathing heights based on the set conditions. For an occupancy density of 1.7–2.6 m2/p in the classroom model, the indoor above outdoor CO2 levels were within 550 ppm at outdoor wind speeds above 3 m/s. The effect of heating/non-heating seasons on the indoor CO2 levels may be negligible for locations with high wind speeds all year round. Based on the UK's year-round mean climate conditions, the CO2 level in the space ventilated by the wind tower with THR was expected to reach Category I or II, according to EN 16798-1 (2019).
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Pure air is a mixture of several gasses with nitrogen constituting the highest proportion followed by oxygen, argon, carbon dioxide, etc.. During the lockdown phase of COVID-19, the air quality has been found to be much better than non-COVID periods. Due to complete closures of the industries, transport sectors, recreational units, offices, and business houses, the carbon dioxide level of the megacity of Kolkata (India) showed a significant dip, which has been explained in this chapter in details. Even in the mangrove-dominated Indian Sundarbans in the lower Gangetic delta region, the same trend is observed when the air quality data of pre-COVID and COVID lockdown phases were compared.KeywordsAir qualityCOVID-19 lockdownKolkataAtmospheric CO2Indian Sundarbans
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The Neurovascular Unit (NVU) is an important multicellular structure of the central nervous system (CNS), which participates in the regulation of cerebral blood flow (CBF), delivery of oxygen and nutrients, immunological surveillance, clearance, barrier functions, and CNS homeostasis. Stroke and Alzheimer Disease (AD) are two pathologies with extensive NVU dysfunction. The cell types of the NVU change in both structure and function following an ischemic insult and during the development of AD pathology. Stroke and AD share common risk factors such as cardiovascular disease, and also share similarities at a molecular level. In both diseases, disruption of metabolic support, mitochondrial dysfunction, increase in oxidative stress, release of inflammatory signaling molecules, and blood brain barrier disruption result in NVU dysfunction, leading to cell death and neurodegeneration. Improved therapeutic strategies for both AD and stroke are needed. Carbonic anhydrases (CAs) are well-known targets for other diseases and are being recently investigated for their function in the development of cerebrovascular pathology. CAs catalyze the hydration of CO2 to produce bicarbonate and a proton. This reaction is important for pH homeostasis, overturn of cerebrospinal fluid, regulation of CBF, and other physiological functions. Humans express 15 CA isoforms with different distribution patterns. Recent studies provide evidence that CA inhibition is protective to NVU cells in vitro and in vivo, in models of stroke and AD pathology. CA inhibitors are FDA-approved for treatment of glaucoma, high-altitude sickness, and other indications. Most FDA-approved CA inhibitors are pan-CA inhibitors; however, specific CA isoforms are likely to modulate the NVU function. This review will summarize the literature regarding the use of pan-CA and specific CA inhibitors along with genetic manipulation of specific CA isoforms in stroke and AD models, to bring light into the functions of CAs in the NVU. Although pan-CA inhibitors are protective and safe, we hypothesize that targeting specific CA isoforms will increase the efficacy of CA inhibition and reduce side effects. More studies to further determine specific CA isoforms functions and changes in disease states are essential to the development of novel therapies for cerebrovascular pathology, occurring in both stroke and AD.
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Carbonic anhydrases (CAs) catalyze the synthesis of HCO3⁻ from H2O and CO2. The dysfunction of CAs leads to aqueous humor secretion and high intraocular pressure to cause glaucoma pathogenesis. Methazolamide (MTZ), a CA inhibitor, can effectively treat glaucoma by reducing aqueous humor secretion. We previously reported that carbonic anhydrase I (CA1), a CA family member, was highly expressed in atherosclerotic tissues of the aorta and stimulated atherosclerosis (AS) by promoting calcification. MTZ showed therapeutic and preventive effects on AS in a mouse model. The above findings suggest a relationship between AS and glaucoma. This study explored the possible association between AS prevalence and glaucoma prevalence and the therapeutic effect of MTZ on AS by analyzing medical records. Among 10,751 patients with a primary diagnosis of glaucoma, 699 (6.5%) were also diagnosed with AS. However, the incidences of AS in patients with keratitis and scleritis, which are also ophthalmic diseases, were 2.5% (206/8383 patients) and 3.5% (46/1308 patients), respectively. In the population without ophthalmic records, the AS prevalence was only 1.9% (99,416/5,168,481 patients) (all p values between each group were below 0.001). Among 152,425 patients with a primary diagnosis of AS, 1245 (0.82%) were also diagnosed with glaucoma. Among 199,782 patients with a primary diagnosis of hypertension (excluding AS), 1149 (0.57%) were diagnosed with glaucoma, and among 5,313,433 patients without AS or hypertension, 9513 (0.18%) were diagnosed with glaucoma (all p values between each group were below 0.001). Additionally, among 14 patients who suffered from both AS and glaucoma and were treated with MTZ to cure their glaucoma, 9 of them showed reduced low-density lipoprotein (LDL) levels, the main index of AS, within 3 months after medication use (2.81 ± 0.61 mmol/L vs. 2.38 ± 0.58 mmol/L, p = 0.039). The above findings demonstrated a strong relation between AS and glaucoma and suggested that AS patients with glaucoma were more likely to suffer from angle-closure glaucoma.
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Carbon dioxide (CO 2 ) is a fundamental physiological gas known to profoundly influence the behaviour and health of millions of species within the plant and animal kingdoms in particular. A recent Royal Society meeting on the topic of ‘Carbon dioxide detection in biological systems' was extremely revealing in terms of the multitude of roles that different levels of CO 2 play in influencing plants and animals alike. While outstanding research has been performed by leading researchers in the area of plant biology, neuronal sensing, cell signalling, gas transport, inflammation, lung function and clinical medicine, there is still much to be learned about CO 2 -dependent sensing and signalling. Notably, while several key signal transduction pathways and nodes of activity have been identified in plants and animals respectively, the precise wiring and sensitivity of these pathways to CO 2 remains to be fully elucidated. In this article, we will give an overview of the literature relating to CO 2 -dependent signal transduction in mammalian systems. We will highlight the main signal transduction hubs through which CO 2 -dependent signalling is elicited with a view to better understanding the complex physiological response to CO 2 in mammalian systems. The main topics of discussion in this article relate to how changes in CO 2 influence cellular function through modulation of signal transduction networks influenced by pH, mitochondrial function, adenylate cyclase, calcium, transcriptional regulators, the adenosine monophosphate-activated protein kinase pathway and direct CO 2 -dependent protein modifications. While each of these topics will be discussed independently, there is evidence of significant cross-talk between these signal transduction pathways as they respond to changes in CO 2 . In considering these core hubs of CO 2 -dependent signal transduction, we hope to delineate common elements and identify areas in which future research could be best directed.
According to a guideline published by the American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE), people spend 80%-90% of their lives indoors; therefore, managing indoor environmental quality is becoming increasingly significant. In particular, a very high level of indoor CO2 concentration can seriously impair people's comfort, health, and productivity. The ASHRAE recommends maintaining indoor CO2 concentration below 1,000 ppm. This study proposes a novel integrated approach to evaluating the effect of indoor CO2 concentration on human cognitive performance and neural responses in office environments from multiple perspectives. An integrated performance score (IPS) w developed to investigate objectively and comprehensively how indoor CO2 concentration affects the level of cognitive performance compared with the neural responses of the subjects, in which the brain regions were considered along with the brain-wave frequency bands. Thirty participants were asked to engage in nine (three×three) experiments, i.e., three cognitive tasks (i.e., working memory, mental workload, and visual concentration) under three CO2 concentration levels (i.e., a low CO2 level of 500 ppm; a moderate CO2 level of 1,000 ppm; and a high CO2 level of 2,500 ppm). During the experiments, electroencephalography (EEG) signals were recorded. Compared with the individual approach, the integrated approach can explain more clearly that an increase in indoor CO2 concentration had a detrimental effect upon working memory, mental workload, and visual concentration. The study breaks new ground in applying a biometric research strategy in the domain of management in engineering, using EEG-based integrated performance assessment. This study can contribute to properly designing the space size and the number of occupants during space programming. In addition, it can be used for optimally designing and operating ventilation systems at proper size and with proper strategy. Consequently, it is expected that the negative effect of indoor CO2 concentration on occupants can be minimized.
Key points: Long-term exposure to elevated levels of atmospheric CO2 is an uncontrolled experiment already underway. This is the first known study to assess non-respiratory physiological impacts of long-term (conception to young adulthood) exposure of mice to CO2 at levels that may arise in the atmosphere due to global emissions. Exposure to elevated CO2 , in comparison to control mice, altered growth patterns in early life and resulted in hyperactive behaviours in young adulthood. Renal and bone parameters, which are important to balance acid-base levels to compensate for increased CO2 exposure, remained relatively unaffected. This work adds to the body of evidence regarding the effects of carbon emissions on mammalian health and highlights a potential future burden of disease. Abstract: Atmospheric carbon dioxide (CO2 ) levels are currently at 418 parts per million (ppm), and by 2100 may exceed 900 ppm. The biological effects of lifetime exposure to CO2 at these levels is unknown. Previously we have shown that mouse lung function is altered by long-term exposure to 890 ppm CO2 . Here, we assess the broader systemic physiological responses to this exposure. Mice were exposed to either 460 ppm or 890 ppm from preconception to 3 months of age, and assessed for effects on developmental, renal, and osteological parameters. Locomotor, memory, learning, and anxiety-like behaviours of the mice were also assessed. Exposure to 890 ppm CO2 increased birthweight, decreased female body weight after weaning, and, as young adults, resulted in reduced engagement in memory/learning tasks, and hyperactivity in both sexes in comparison to controls. There were no clear anxiety, learning, or memory changes. Renal and osteological parameters were minimally affected. Overall, this study shows that exposure of mice to 890 ppm CO2 from preconception to young adulthood alters growth and some behaviours, with limited evidence of compensatory changes in acid-base balance. These findings highlight the potential for a direct effect of increased atmospheric CO2 on mammalian health outcomes. Abstract figure. The aim of this study is to investigate how rising atmospheric carbon dioxide (CO2 ) levels affect mouse physiology. To achieve this, mice were exposed to either 460 ppm (standard housing conditions) or 890 ppm (may eventuate by 2100) from preconception to 3 months of age. Mice were assessed for effects on developmental, renal, osteological, and behavioural parameters. Exposure to 890 ppm CO2 increased birthweight, decreased female body weight after weaning, and, as young adults, resulted in reduced engagement in memory/learning tasks, and hyperactivity in both sexes in comparison to controls. There were no clear anxiety, learning, or memory changes. Renal and osteological parameters were minimally affected. Overall, this study shows that exposure of mice to 890 ppm CO2 from preconception to young adulthood alters growth and some behaviours, with limited evidence of compensatory changes in acid-base balance. While more work needs to be done, these findings highlight the potential for a direct effect of increased atmospheric CO2 on mammalian health outcomes. This article is protected by copyright. All rights reserved.
This volume assembles and integrates the wealth of diverse information that is now accumulating in this burgeoning field. The existing and potential therapeutic applications of targeting CA cover a remarkably wide-range of diseases and disorders and have generated increasing and extensive interest in recent years. Its inter-disciplinary approach embraces both the most up-to-date therapeutic application of CA-targeting and the latest research data that will provide a platform for the development of novel applications. The interested audience comprises scientists and clinicians from many relevant disciplines within science and medicine.
Carbonic anhydrases (CAs) are widely expressed in the nervous system where they play important physiological roles. In the brain and other parts of the system, different isozymes show unique distribution patterns, some of them being present in neurons (CA II, V, VII, XIV), capillary endothelium (CA IV), microglia (CA III), choroid plexus (CA II, III, XII, XIV), astrocytes (CA II and V), oligodendrocytes (CA II and XIII), and myelin sheath (CA II). Nervous tissues also express three carbonic anhydrase-related proteins (CARP VIII, X, XI), which may be involved in the brain development processes. Future research is needed to define the exact roles of these highly conserved CA isoforms and to design novel treatment strategies for the diseases caused by defects or abnormal regulation of CARPs. Enzymatically active CA isozymes are known drug targets to treat various neurological disorders including epilepsy, acute mountain sickness, pseudotumor cerebri, and brain edema. In this review article, we describe how the clinically approved CA inhibitors are used for the treatment of these diseases.
Background: Climate change models predict that atmospheric carbon dioxide [CO2] levels will be between 700 and 900 ppm within the next 80 y. Despite this, the direct physiological effects of exposure to slightly elevated atmospheric CO2 (as compared with ∼410 ppm experienced today), especially when exposures extend from preconception to adulthood, have not been thoroughly studied. Objectives: In this study we aimed to assess the respiratory structure and function effects of long-term exposure to 890 ppm CO2 from preconception to adulthood using a mouse model. Methods: We exposed mice to CO2 (∼890 ppm) from prepregnancy, through the in utero and early life periods, until 3 months of age, at which point we assessed respiratory function using the forced oscillation technique, and lung structure. Results: CO2 exposure resulted in a range of respiratory impairments, particularly in female mice, including higher tissue elastance, longer chord length, and lower lung compliance. Importantly, we also assessed the lung function of the dams that gave birth to our experimental subjects. Even though these mice had been exposed to the same level of increased CO2 for a similar amount of time (∼8wk), we measured no impairments in lung function. This suggests that the early life period, when lungs are undergoing rapid growth and development, is particularly sensitive to CO2. Discussion: To the best of our knowledge, this study, for the first time, shows that long-term exposure to environmentally relevant levels of CO2 can impact respiratory function in the mouse.