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

March 2023

Authors:

Australian National University

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, https://youtu.be/35Yh-lArUcM.

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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

Abstract

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: https://www.nasa.gov/jpl/oco2/pia18934.

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

humans)?

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

(1%)

Kidney calcification, decreased bone formation and

increased bone resorption in guinea pigs

6 weeks Schaefer et al., 1979a

10,000 ppm

(1%)

Cognitive impairment, increased diastolic blood

pressure

75 min Tu et al. 2020

8500 ppm Increased lung dead space volume 20 days Rice 2004

7000 ppm

(0.7%)

35% increase in cerebral blood flow (implications for

cognitive effects seen in other studies)

23 days Sliwka et al. 1998

5000-6600

ppm

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

Operational

continuous

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 et.al. 2022

3000 ppm Systemic inflammation and physiological stress in

rodents

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

2000-4000

ppm

Unhealthy blood CO2 levels - 15% above normal

range, sleepiness, headaches, heart rate variations

4 hours Vehviläinen et al. 2016

2000-4000

ppm

Inflammation and vascular damage in mice 2 hours Thom et al.2017

2000-3000

ppm

Restrictive lung behaviour and elevated blood CO2 3 hours Shriram et al. 2019

2000 ppm Kidney effects in animals (likely calcification) -

incomplete study

Chronic

studies

Schaefer 1982

1900 ppm Reduced sleep quality, drowsiness 8 hours Xu et al. 2020

1400-3000

ppm

Significant impairment of cognitive function

including fatigue

2.5 to 8

hours

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

classrooms

Short-term Carreiro-Martins et al. 2014;

Ferreira and Cardoso 2014;

Seppanen et al. 1999

1000 ppm EEG changes in brainwaves associated with mental

impairment

15 min Lee et. al. 2022

950-1400

ppm

Health symptoms (respiratory, skin, eyes, headaches,

cognitive, dizziness, sensory), increase in heart rate

30 min MacNaughton et al. 2016

950-1000

ppm

Moderate impairment of cognitive function 2.5 to 8

hours

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,

6hrs/day

Martrette et al. 2017

420 ppm Current average outdoor air concentration – no clear

effect, possible increase in disease and anxiety

Lifetime NOAA Global Monitoring

Laboratory

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

ppm.

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

future.

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.

11. References

Abolhassani M, Guais A, Chaumet-Riffaud P, Sasco A, Schwartz L. 2009. Carbon dioxide inhalation causes

pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol 296: L657–L665.

Adeva-Andany MM, Carneiro-Freire N, Donapetry-García C, Rañal-Muíño E, and López-Pereiro Y. 2014. The

Importance of the Ionic Product for Water to Understand the Physiology of the Acid-Base Balance in

Humans. BioMed Research International 2014: Article ID 695281, 16 p. https://doi.org/10.1155/2014/695281.

Adeva-Andany MM, Fernandez-Fernandez C, Sanchez-Bello R, Donapetry-García C, Martínez-Rodríguez J. 2015.

The role of carbonic anhydrase in the pathogenesis of vascular

calcification in humans. Atherosclerosis 241: 183-191.

Ainslie PN, Duffin J. 2009. Integration of cerebrovascular CO2 reactivity and chemoreflex control of breathing:

mechanisms of regulation, measurement, and interpretation. Am J Physiol Regul Integr Comp Physiol 296:

R1473–1495.

Allen JG, MacNaughton P, Satish U, Santanam S, Vallarino J, Spengler JD. 2016. Associations of Cognitive

Function Scores with Carbon Dioxide, Ventilation, and Volatite Organic Compound Exposures in Office Workers:

A Controlled Exposure Study of Green and Conventional Office Environments. Environmental Health

Perspectives 124: 805.

Allen JG, MacNaughton P, Cedeno-Laurent JG, Cao X, Flanigan S, Vallarino J, Rueda F, Donnelly-McLay D,

Spengler JD. 2018. Airplane pilot flight performance on 21 maneuvers in a flight simulator under varying

carbon dioxide concentrations. Journal of Exposure Science and Environmental Epidemiology · August, DOI:

10.1038/s41370-018-0055-8.

Antic NA. 2012. Global warming and increased sleep disordered breathing mortality, rising carbon dioxide

levels are a serial pest. Respirology 17: 885–886.

Arlot-Bonnemains Y, Fouchereau-Peron M, Moukhar MS, Benson AA, Milhaud G. 1985. Calcium-regulating

hormones modulate carbonic anhydrase II in the human erythrocyte. Proc. Nati. Acad. Sci. USA 82: 8832-8834.

Aspatwar A, Peltola J, Parkkila S. 2021. Targeting Carbonic Anhydrase Isozymes in the Treatment of

Neurological Disorders. In: The Carbonic Anhydrases: Current and Emerging Therapeutic Targets, (Chegwidden

WR, Carter ND Ed). Springer.

Azuma K, Kagi N, Yanagi U, Osawa H. 2018. Effects of low-level inhalation exposure to carbon dioxide in indoor

environments: A short review on human health and psychomotor performance. Environment International

121: 51–56.

Bakó-Biró Z, Clements-Croome DJ, Kochhar N, Awbi HB, Williams MJ. 2011. Ventilation rates in schools and

pupils’ performance. Building and Environment 48: 1-9.

Battaglia M. 2017. Sensitivity to carbon dioxide and translational studies of anxiety disorders. Neuroscience

346: 434–436

Beheshti A, Cekanaviciute E, Smith DJ, Costes SV. 2018. Global transcriptomic analysis suggests carbon dioxide

as an environmental stressor in spaceflight: a systems biology GeneLab case study. Scientific Reports 8: 4191.

Bierwirth PN. 2018. Are increasing atmospheric carbon dioxide levels lowering our intelligence? ResearchGate

DOI.

Branco PTBS, Alvim-Ferraz MCM, Martins FG, Sousa SIV. 2015. Children's exposure to indoor air in urban

nurseries-part I: CO2 and comfort assessment. Environmental Research 140: 1–9.

Bright MG, Whittaker JR, Driver ID, Murphy K. 2020. Vascular physiology drives functional brain networks.

NeuroImage 217: 116907

Brillante R, Laks L, Cossa G, Peters M, Liu P. 2012. An overnight increase in CO2 predicts mortality in

sleep disordered breathing. Respirology 17: 933-939.

Bruhwiler PA, Stämpfli R, Huber R, Camenzind M. 2005. CO2 and O2 concentrations in integral motorcycle

helmets. Appl Ergon 36(5): 625-633.

Burton RF. 1978. Intracellular buffering. Respiration Physiology 33: 51-58.

Campbell AJ, Bolton DPG, Williams SM, Taylor BJ. 1996. A potential danger of bedclothes covering the face.

Acta Paediatr 85(3): 281-284.

Cao X, Li P, Zhang J, Pang L. 2022. Effects of carbon dioxide exposure on human cognitive abilities in an

enclosed workplace environment. E3S Web of Conferences 356, 05041

Carreiro-Martins P, Viegas J, Papoila AL, Aelenei D, Caires I, Araújo-Martins J, Gaspar-Marques J, Cano

MM, Mendes AS, Virella D, Rosado-Pinto J, Leiria-Pinto P, Annesi-Maesano I, Neuparth N. 2014. CO(2)

concentration in day care centres is related to wheezing in attending children. Eur J Pediatr 173: 1041-1049.

Celebioglu HU, Erden Y, Hamurcu F, Taslimi P, Şentürk OS, Özmen ÜÖ, Tuzun B, Gulçin I. 2021. Cytotoxic

effects, carbonic anhydrase isoenzymes, α-glycosidase and acetylcholinesterase inhibitory properties, and

molecular docking studies of heteroatom-containing sulfonyl hydrazone derivatives. Journal of Biomolecular

Structure and Dynamics 39:15, 5539-5550.

Chegwidden WR, Carter ND. 2021. The Carbonic Anhydrases: Current and Emerging Therapeutic Targets –

Preface, (Chegwidden WR, Carter ND Ed). Springer Nature, Switzerland.

Chiu CF, Chen MH, Chang FH. 2015. Carbon Dioxide Concentrations and Temperatures within Tour Buses under

Real-Time Traffic Conditions. PLoS One 10(4): e0125117.

Colasanti A, Salamon E, Schruers K, van Diest R, van Duinen M, Griez E, 2008. Carbon Dioxide-Induced Emotion

and Respiratory Symptoms in Healthy Volunteers. Neuropsychopharmacology 33: 3103-3110.

Coley DA, Greeves R, Saxby BK. 2007. The effect of low ventilation rates on the cognitive function of a primary

school class. International Journal of Ventilation 6: 107-112.

Constantin D, Mazilescu C, Nagi M, Draghici A, Mihartescu A. 2016. Perception of Cabin Air Quality among

Drivers and Passengers. Sustainability 8: 852; doi:10.3390.

Cronyn PD, Watkins S, Alexander DJ. 2012. Chronic Exposure to Moderately Elevated CO2 during Long-Duration

Space Flight. NASA Technical Report NASA/TP-2012-217358. Available:

http://ston.jsc.nasa.gov/collections/trs/_techrep/TP-2012-217358.pdf [accessed 23 December 2014].

Cui Y, Schubert BA, Jahren AH. 2020. A 23 m.y. record of low atmospheric CO2. Geology 48: 888–892. Available:

https://doi.org/10.1130/G47681.1

Dijken FV, Bronswijk JV, Sundell J. 2005. Indoor environment in Dutch primary schools and health of the pupils.

Proceedings of Indoor Air, Beijing, Vol 1: 623-627.

Di Fiore A, Supuran CT, Scaloni A, De Simone G. 2020. Human carbonic anhydrases and post-translational

modifications: a hidden world possibly affecting protein properties and functions, Journal of Enzyme Inhibition

and Medicinal Chemistry 35(1): 1450-1461.

Du B, Tandoc MC, Mack ML, Siegel JA. 2020. Indoor CO2 concentrations and cognitive function: A critical

Review. Indoor Air 30:1067–1082.

Duarte CM, Jaremko L, Jaremko M. 2020. Hypothesis: Potentially Systemic Impacts of Elevated CO2 on the

Human Proteome and Health. Frontiers in Public Health 8: Article 543322.

Eckenhoff RG, Longnecker DE. 1995. The therapeutic gases. Effects of carbon dioxide. In: Goodman and

Gilman’s The Pharmacological Basis of Therapeutics, 9th Ed (Hardman JG,ed). McGraw Hill, 355-356.

Eggleton T. 2013. A short introduction to climate change. Cambridge University Press.

Ezraty B, Chabalier M, Ducret A, Maisonneuve E, Dukan S. 2011. CO2 exacerbates oxygen toxicity. EMBO

Reports 12: 321–326.

Ferrari M, Lodola L, Dellavalle C, Rotondo P, Ricciardi L, Menghini A. 2005. Indoor air quality in an Italian

military submarine. G Ital Med Lav Ergon 27(3): 308-311.

Ferreira AM, Cardoso M. 2014. Indoor air quality and health in schools. J Bras Pneumol 40(3): 259-268.

Gaihre S, Semple S, Miller J, Fielding S, Turner S. 2014. Classroom carbon dioxide concentration, school

attendance, and educational attainment. J Sch Health 84(9): 569-574.

Gall ET, Cheung T, Luhung I, Schiavon S, Nazaroff WW.2016. Real-time monitoring of personal exposures to

carbon dioxide. Building and Environment 104: 59-67.

Gładyszewska-Fiedoruk K.2011. Concentrations of carbon dioxide in the cabin of a small passenger car.

Transportation Research Part D 16: 327–331.

Gładyszewska-Fiedoruk K.2012. Indoor air quality in the cabin of an airliner. Journal of Air Transport

Management 20: 28-30.

Glodzik L, Randall C, Rusinek H, de Leon MJ. 2013. Cerebrovascular reactivity to carbon dioxide in Alzheimer’s

disease. A review. J Alzheimers Dis. 35(3):427-440

Goromosov MS. 1968. The Physiological Basis of Health Standards for Dwellings. World Health Organization

Geneva. Available: http://apps.who.int/iris/handle/10665/39749 [accessed 26 August 2014].

Guais A, Brand G, Jacquot L, Karrer M, Dukan S, Grevillot G, Jo Molina T, Bonte J, Regnier M, Schwartz L. 2011

Toxicity of Carbon Dioxide: A Review. Chem Res Toxicol 24 2061-2070.

Halperin WE. 2007. National Emergency and Continuous Exposure Guidance Levels for Selected Submarine

Contaminants. Vol. 1. National Research Council of the National academies. National Academies Press.

Available: http://www.nap.edu [accessed 9 April 2015].

Henderson R. 2006. Carbon dioxide measures up as a real hazard. Occupational Health & Safety 75.7 : 64,68-

69.

Heudorf U, Neitzert V, Spark J. 2009. Particulate matter and carbon dioxide in classrooms – The impact of

cleaning and ventilation. Int. J. Hyg. Environ. Health 212: 45–55.

Heuer RM. Grosell M. 2014. Physiological impacts of elevated carbon dioxide and ocean acidification on fish.

Am. J. Physiol. Regul. Integr. Comp. Physiol. 307: R1061–R1084.

Hughson RL, Yee NJ, Greaves K. 2016. Elevated end-tidal Pco2 during long-duration spaceflight. Aerosp. Med.

Hum. Perform. 87: 894–897.

Hulikova A, Aveyard N, Harris AL, Vaughan-Jones RD, Swietach P. 2014. Intracellular Carbonic Anhydrase

Activity Sensitizes Cancer Cell pH Signaling to Dynamic Changes in CO2 Partial

Pressure. The journal of Biological Chemistry 289 (37): 25418-25430.

IPCC. 2022. Climate Change 2022: Impacts, Adaptation, and Vulnerability. Contribution of Working Group II to

the Sixth Assessment Report of the Intergovernmental Panel on Climate Change [H.-O. Pörtner, D.C. Roberts,

M. Tignor, E.S. Poloczanska, K. Mintenbeck, A. Alegría, M. Craig, S. Langsdorf, S. Löschke, V. Möller, A. Okem, B.

Rama (eds.)]. Cambridge University Press. Cambridge University Press, Cambridge, UK and New York, NY, USA,

3056 pp.

Ishimasu A, Hayashi M, Lee KS, Kikkawa T, Kita J. 2005. Physiological effects on fishes in a high-CO2 world. J.

Geophys. Res. 110: C09S09, doi:10.1029/2004JC002564.

Jacobson TA, Kler JS, Hernke MT, Braun RK, Meyer KC, Funk WE. 2019. Direct human health risks of increased

atmospheric carbon dioxide. Nature Sust. 2: 691-701.

James JT, Macatangay A. 2009. Carbon Dioxide – Our Common “Enemy” . NASA Technical report JSC-CN-

18669. SAMAP Submarine Air Monitoring Air Purification Conference, 19-22 October 2009, San Diego, CA.

Available: http://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/20090029352.pdf [accessed 9 April 2015].

Jurado SR, Bankoff ADP, Sanchez A. 2014. Indoor air quality in Brazilian universities. International journal of

environmental research and public health 11(7): 7081-7093.

Kajtar L, Herczeg, L. 2012. Influence of carbon-dioxide concentration on human well-being and intensity of

mental work. Q. J. Hung. Meteorol. Serv 116: 145–169.

Karnauskas KB, Miller SL, Schapiro AC. 2020. Fossil fuel combustion is driving indoor CO2 toward levels harmful

to human cognition. GeoHealth 4, e2019GH000237. https://doi.org/ 10.1029/2019GH000237.

Kim IG, Jo BH, Kang DG, Kim CS, Choi YS, Cha HJ. 2012. Biomineralization-based conversion of carbon dioxide to

calcium carbonate using recombinant carbonic anhydrase. Chemosphere 87: 1091-1096.

Kiray, M, Sisman AR, Camsari UM, Evren, Day A, Baykara B, Aksu I, Ates M, Uysalet N. 2014. Effects of carbon

dioxide exposure on early brain development in rats. Biotech Histochem. 89: 371-383.

Kittanamongkolchai W, Vaughan LE, Enders FT, Dhondup T, Mehta RA, Krambeck AE, McCollough CH, Vrtiska

TJ, Lieske JC, Rule AR. 2018. The changing incidence and presentation of urinary stones Over 3 Decades. Mayo

Clin Proc. 93: 291-299.

Knoll AH, Bambach RK, Canfield DE, Grotzinger JP. 1996. Comparative Earth History and Late Permian Mass

Extinction. Science 273: 452-457.

Kryvenko V, Vadász I. 2021. Mechanisms of Hypercapnia-Induced Endoplasmic Reticulum Dysfunction.

Frontiers in Physiology 12.

Kukadia V, Ajiboye P, White M. 2005. Ventilation and indoor air quality in schools, BRE Information paper

IP06/05. Watford: BRE publication.

Law J, Watkins S, Alexander, D. 2010. In-Flight Carbon Dioxide Exposures and Related Symptoms: Associations,

Susceptibility and Operational Implications. NASA Report TP–2010–216126. Available:

http://ston.jsc.nasa.gov/collections/trs/_techrep/TP-2010-216126.pdf [accessed 26 August 2014].

Larcombe AN, Papini MG, Chivers EK, Berry LJ, Lucas RM, Wyrwoll CS. 2021. Mouse Lung Structure and

Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change

Modeling. Environmental Health Perspectives 129(1): https://doi.org/10.1289/EHP7305.

Lee J, Kim TW, Lee C, Koo C. 2022. Integrated Approach to Evaluating the Effect of Indoor CO2 Concentration

on Human Cognitive Performance and Neural Responses in Office Environment. Journal of Management in

Engineering 38(1): 04021085.

Lee SC, Chang M. 2000. Indoor and outdoor air quality investigation at schools in Hong Kong. Chemosphere

41(1-2): 109-113.

Lemon N, Canepa E, Ilies MA, Fossati S. 2021. Carbonic Anhydrases as Potential Targets Against Neurovascular

Unit Dysfunction in Alzheimer’s Disease and Stroke. Frontiers in Aging Neuroscience 16 (13) 772278.

Logozzi M, Capasso C, Di Raimoa R, Del Prete S, Mizzoni D, Falchi M, Supuran CT, Faisa S. 2019. Prostate cancer

cells and exosomes in acidic condition show increased carbonic anhydrase IX expression and activity. Journal of

Enzyme Inhibition and Medicinal Chemistry 34 (1): 272-278.

Lu CY, Lin JM, Chen YY, Chen YC. 2015. Building-related symptoms among office employees associated with

indoor carbon dioxide and total volatile organic compounds. International journal of environmental research

and public health 12(6): 5833-5845.

MacNaughton P, Spengler, Vallarino J, Santanam S, Satish U, Allen J. 2016. Environmental perceptions and

health before and after relocation to a green building. Building and Environment 104: 138-144.

Mardones ML, Thatje S, Fenberg PB, Hauton C. 2022. The short and long-term implications of warming

and increased sea water pCO2 on the physiological response of a temperate neogastropod species. Marine

Biology 169 (1): 3.

Martrette JM, Egloff C, Clément C, Yasukawa K, Thornton SN, Trabalon M. 2017. Effects of prolonged exposure

to CO2 on behaviour, hormone secretion and respiratory muscles in young female rats. Physiology & Behavior

177: 257–262.

McNeil B, Sasse T. 2016. Future ocean hypercapnia driven by anthropogenic amplification of the natural CO2

cycle. Nature 529: 383-386.

Muscatiello N, McCarthy, A, Kielb C, Hsu WH, Hwang SA, Lin S. 2015. Classroom conditions and CO2

concentrations and teacher health symptom reporting in 10 New York State Schools. Indoor Air 25(2): 157-167.

National Institute for Occupational Safety and Health (NIOSH). 1996. Criteria for a Recommended Standard,

Occupational Exposure to Carbon Dioxide. August 1976. In: Documentation for Immediately Dangerous to Life

or Health Concentrations (IDLHs) for carbon dioxide. Available: www.cdc.gov/niosh/docs/1970/76-194.html

[accessed 23 December 2014].

Navarro JM, Andrade-Villagran´ PV, Manríquez PH, Duarte C, Chaparro OR. 2022. Long-term effects of

contrasting pCO2 levels on the scope for growth in the carnivorous gastropod Concholepas concholepas.

Marine Environmental Research 175: 105586.

NOAA Global monitoring Laboratory. https://gml.noaa.gov/ccgg/trends/ . Accessed March 2023.

OSHA (Occupational Safety and Health Administration). 2012. Sampling and Analytical Methods: Carbon

Dioxide in Workplace Atmospheres. Available: http://www.osha.gov/dts/sltc/methods/ino

rganic/id172/id172.html [accessed 23 December 2014].

Pang L, Zhang J, Cao X, Wang X, Liang J, Zhang L, Guo L. 2020. The effects of carbon dioxide exposure

concentrations on human vigilance and sentiment in an enclosed workplace environment

Indoor Air 31:467–479.

Patton KT, Thibodeau GA. 2009. Anatomy & Physiology. 7th ed. St Louis. Mosby.

Phelan DE, Mota C, Lai C, Kierans SJ, Cummins EP. 2021. Carbon dioxide-dependent signal transduction in

mammalian systems. Interface Focus 11(2):20200033.

Portner HO, Langenbuch M, Reipschlager A. 2004. Biological Impact of Elevated Ocean CO2 Concentrations:

Lessons from Animal Physiology and Earth History. Journal of Oceanography 60:705-718.

Raven P, Johnson G, Mason K, Losos J, Singer S. 2007. Biology. 8th ed. New York. McGraw-Hill.

Reiff T, Barthel O, Schönenberger S, Mundiyanapurath S. 2020. High-normal PaCO2 values might be

associated with worse outcome in patients with subarachnoid hemorrhage – a retrospective cohort study.

BMC Neurology 20:31. https://doi.org/10.1186/s12883-020-1603-0.

Rice SA. 2004. Human health risk assessment of CO2: Survivors of acute high-level exposure and populations

sensitive to prolonged low-level exposure. Third Annual Conference on Carbon Sequestration. 3-6 May 2004,

Alexandria, Virginia, USA. Available: http://www.netl.doe.gov/publications/proceedings/04/carbon-

seq/169.pdf [accessed 13 April 2015].

Robertson DS. 2006. Health effects of increase in concentration of carbon dioxide in the atmosphere. Current

Science 90:1607-1609.

Rodriguez-Navarro C, Cizer O, Kudłacz K, Ibañez-Velasco A, Ruiz-Agudo C, Elert K, Burgos-Cara A, Ruiz-Agudo E.

2019. CrystEngComm 21, 7407.

Romero V, Akpinar P, Assimos DG. 2010. Kidney Stones: A Global Picture of Prevalence, Incidence, and

Associated Risk Factors. Reviews in Urolology 12: e86–e96.

Ryder V, Scully R, Alexander D, Lam C, Young M, Satish U, Basner M. 2017. Effects of acute exposures to carbon

dioxide upon cognitive functions. In: Proceedings of NASA Human Research Program Investigators’ Workshop.

(23–26 Jan 2017. Galveston, TX). Washington, DC.

Santamouris M, Synnefa A, Asssimakopoulos M, Livada I, Pavlou K, Papaglastra M, Gaitani N, Kolokotsa D,

Assimakopoulos V. 2008. Experimental investigation of the air flow and indoor carbon dioxide concentration in

classrooms with intermittent natural ventilation. Energy and Buildings 40; 1833–1843.

Satish U, Mendell MJ, Shekhar K, Hotchi T, Sullivan D, Streufert S, Fisk WJ. 2012. Is CO2 an Indoor Pollutant?

Direct Effects of Low-to-Moderate CO2 Concentrations on Human Decision-Making Performance.

Environmental Health Perspectives 120:1671-1677.

Schaefer KE, Hastings BJ, Carey CR, Nichols JR. 1963. Respiratory acclimatization to carbon dioxide. Journal of

Applied Physiology 18:1071-1078.

Schaefer KE, Niemoller H, Messier A, Heyder E, Spencer J. 1971. Chronic CO2 Toxicity: Species Difference in

Physiological and Histopathological Effects. Report No 656, pp 1_26, US Navy Dept, Bureau of Medicine and

Surgery, Naval Submarine Medical Center, Submarine Medical Research Laboratory, Groton, CT.

Schaefer KE, Pasquale SM, Messier AA, Niemoeller H. 1979a. CO2-Induced Kidney Calcification. Undersea

Biomed Res. Suppl 6:S143-S153.

Schaefer KE, Douglas WHJ, Messier AA, Shea ML, Gohman PA. 1979b. Effect of Prolonged Exposure to 0.5%

CO2 on Kidney Calcification and Ultrastructure of Lungs. Undersea Biomed Res. Suppl 6:S155-S161.

Schaefer K E. 1982. Effects of increased ambient CO2 levels on human and animal health. Experientia 38:1163-

1168.

Schmidt S. 2020. CO2 is trending: See the latest atmospheric concentrations data on Twitter. CSIROscope 28

February, https://blog.csiro.au/co2-data-twitter/

Scripps Institution of Oceanography. 2020. A daily record of global atmospheric carbon dioxide concentration.

UC San Diego. https://scripps.ucsd.edu/programs/keelingcurve/

Scott JL, Kraemer DG, Keller RJ. 2009. Occupational hazards of carbon dioxide exposure. Journal of Chem

Health and Safety 16:18-22.

Scully RR, Basner M, Nasrini J, Lam C, Hermosillo E, Gur RC, Moore T, Alexander DJ, Satish U, Ryder VE. 2019.

Effects of acute exposures to carbon dioxide on decision making and cognition in astronaut-like subjects. NPJ

Microgravity 5: 17.

Seppänen OA, Fisk WJ, Mendell MJ. 1999. Association of Ventilation Rates and CO2-Concentrations with

Health and other Responses in Commercial and Institutional Buildings. Indoor Air 9: 226-252.

Shriram S, Ramamurthy K, Ramakrishnan S. 2019. Effect of occupant-induced indoor CO2 concentration and

bioeffluents on human physiology using a spirometric test. Building and Environment 149: 58–67.

Sliwka U, Krasney JA, Simon SG, Schmidt P, Noth J. 1998. Effects of sustained low-level elevations of carbon

dioxide on cerebral blood flow and autoregulation of the intracerebral arteries in humans. Aviat Space Environ

Med 69:299-306.

Smith KR, Woodward A. 2014. Chapter 11. Human health: impacts, adaptation, and co-benefits. In: IPCC, 2014:

Climate Change 2014: Impacts, Adaptation, and Vulnerability. Part A: Global and Sectoral Aspects. New York,

709-754. Available: http://ipcc-wg2.gov/AR5/report/full-report/ [accessed 26 August 2014].

Snow S, Boyson A, King M, Malik O, Coutts L, Noakes C, Gough H, Barlow J, Schraefel M. 2018. Using EEG to

characterise drowsiness during short duration exposure to elevated indoor Carbon Dioxide

concentrations https://t.co/HaJ0UZRADx #bioRxiv. doi: https://doi.org/10.1101/483750.

Snow S, Boyson AS, Paas KHW, Gough H, King M, Barlow J, Noakes CJ, Schraefel MC. 2019. Exploring the

physiological, neurophysiological and cognitive performance effects of elevated carbon dioxide concentrations

indoors. Building and Environment 156: 243–252.

Song X, Li P, Li Y, Yan X, Yuan L, Zhao C, An Y, Chang X. 2021. Strong association of glaucoma with

atherosclerosis. Scientific Reports 11: 8792.

Stolp H. 2022. Developing in a polluted atmosphere: A link between long-term exposure to elevated

atmospheric CO2 and hyperactivity. Journal of Physiology 600(6): 1275-1276.

Tan S, Han Y, Yua Y, Chiu C, Chang Y, Ouyang S, Fan K, Lo K, Nga I. 2018. Efficient carbon dioxide sequestration

by using recombinant carbonic anhydrase. Process Biochemistry 73: 38-46.

Thom SR, Bhopale VM, Hu J, Yang M. 2017. Inflammatory responses to acute elevations of carbon dioxide in

mice. J Appl Physiol 123: 297-302.

Tsai DH, Lin JS, Chan CC. 2012. Office workers' sick building syndrome and indoor carbon dioxide

concentrations. J Occup Environ Hyg 9(5): 345-351.

Tu Z, Li Y, Geng S, Zhou K, Wang R, Dong X. 2020. Human responses to high levels of carbon dioxide and air

temperature. Indoor Air 00:1–15.

Turney BW, Reynard JM, Noble JG, Keoghane SR. 2011. Trends in urological stone disease. BJU International

109: 1082-1087.

Vehviläinen T, Lindholm H, Rintamäki H, Pääkkönen R, Hirvonen A, Niemi O, Vinha J. 2016. High indoor CO2

concentrations in an office environment increases the transcutaneous CO2 level and sleepiness during

cognitive work. J. Occupational and Environmental Hygiene 13: 19-29.

Waris G, Ahsan H. 2006 Reactive oxygen species: role in the development of cancer and various chronic

conditions. Journal of Carcinogenesis 5: 14.

Widory D, Javoy M. 2003. The carbon isotope composition of atmospheric CO2 in Paris. Earth and Planetary

Science Letters 215: 289-298.

Wikstrom S, Lundin F, Ley D, Pupp IH, Fellman V, Rosén I, Hellström-Westaset L. 2011. Carbon dioxide and

glucose affect electrocortical background in extremely preterm infants. Pediatrics 127(4): e1028-1034.

Wyrwoll CS, Papini MG, Chivers EK, Yuan J, Pavlos NJ, Lucas RM, Bierwirth PN, Larcombe AN. 2022. Long-term

exposure of mice to 890 ppm atmospheric CO2 alters growth trajectories and elicits hyperactive behaviours in

young adulthood. Journal of Physiology 600(6): 1439-1453.

Xia Y, Shikii S, Shimomura Y. 2020. Determining how different levels of indoor carbon dioxide affect human

monotonous task performance and their effects on human activation states using a lab experiment: a tracking

task. Ergonomics, DOI:10.1080/00140139.2020.1784466 Available:

https://doi.org/10.1080/00140139.2020.1784466

Xu X, Lian Z, Shen J, Cao T, Zhu J, Lin X, Qing K, Zhang W, Zhang T. 2020. Experimental study on sleep quality

affected by carbon dioxide concentration. Indoor Air 31:440–453.

Yang Y, Sun C, Sun M. 1997. The effect of moderately increased CO2 concentration on perception of coherent

motion. Aviat Space Environ Med 68: 187-91.

Zachos J, Pagani M, Sloan S, Thomas E, Billups K. 2001. Trends, rhythms, and aberrations in global climate 65

Ma to present. Science; 292, 5517.

Zappulla D. 2008. Environmental stress, erythrocyte dysfunctions, inflammation, and the metabolic syndrome:

adaptations to CO2 increases? J. Cardiometab. Syndr. 3: 30–34.

Zhang J, Pang L, Cao X, Wanyan X, Wang X, Liang J, Zhang L. 2020. The effects of elevated carbon dioxide

concentration and mental workload on task performance in an enclosed environmental chamber. Building and

Environment 178: 106938.

Zhang X, Wargocki P, Lian Z, Thyregod C. 2017. Effects of exposure to carbon dioxide and bioeffluents on

perceivedair quality, self-assessed acute health symptoms, and cognitive performance. Indoor Air 27: 47-63.

Zheutlin AR, Adar SD, Kyun Park S. 2014. Carbon dioxide emissions and change in prevalence of obesity and

diabetes in the United States: an ecological study. Environment International: 73, 111–116.

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Full-text available

Apr 2021

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.

Carbon dioxide-dependent signal transduction in mammalian systems

Article

Full-text available

Feb 2021
Interface Focus

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.

Integrated Approach to Evaluating the Effect of Indoor CO2 Concentration on Human Cognitive Performance and Neural Responses in Office Environment

Article

Jan 2022

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.

Long‐term exposure of mice to 890 ppm atmospheric CO2 alters growth trajectories and elicits hyperactive behaviours in young adulthood

Article

Nov 2021

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.

The Carbonic Anhydrases: Current and Emerging Therapeutic Targets

Book

Jan 2021
Prog Rech Pharm

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.

Targeting Carbonic Anhydrase Isozymes in the Treatment of Neurological Disorders

Chapter

Oct 2021

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.

Mouse Lung Structure and Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change Modeling

Article

Jan 2021

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. https://doi.org/10.1289/EHP7305.

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

Abstract

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