Overexposed: The role of environmental toxicants on your brain
By Carlie Hoffman
It
is often said that we are products of our environment: who we are is
shaped by the things, people, and situations with which we surround
ourselves. However, whatever we may like to think, we are not in
control of every facet of our environment. In fact, we are unknowingly
and involuntarily exposed to dozens of man-made environmental chemicals,
called toxicants,
each day that can negatively alter our bodies and even our very brain
matter. In essence, we are becoming literal products of our environment.
Synthetic
chemicals and toxicants are ubiquitous within our surroundings. While some toxicants come from obvious
sources, like cigarette smoke and car exhaust, other sources of exposure
are more subtle. For instance, electrical equipment (like computers
and cell phones), beauty products (like makeup and shampoo), mattresses,
and furniture all contain flame retardants, chemicals used to reduce flammability [3, 13]. Bisphenol A (BPA) and phthalates,
chemicals used to harden plastics, can also be found in dental
sealants, cigarette filters, soda bottles, and the linings of canned
foods [4, 8, 12]. Additionally, dichlorodiphenyltrichloroethane (DDT),
a pesticide commonly used in the mid-1900s to combat outbreaks of
pests, malaria, and lice, was banned in 1972 in the US and yet is still currently present within both the environment and human tissues [12].
The presence of chemicals within almost every facet of our society means we are
subjected to varying levels of environmental exposure throughout our lives– from the womb to the grave. A growing desire to
characterize the effects of this lifetime of exposure resulted in the
creation of a new concept: the “exposome.”
Defined in 2005 by Dr. Christopher Wild as “every exposure to which an
individual is subjected from conception to death,” this definition was
expanded by Dr. Gary Miller and Dr. Dean Jones
in 2014 to be “the cumulative measure of environmental influences and
associated biological responses throughout the lifespan, including
exposures from the environment, diet, behavior, and endogenous
processes” [9, 14, 15]. Indeed, some say the exposome profile may
tell a narrative about our individual lives with astounding accuracy–
including where we’ve traveled, what we’ve eaten, and trends in our
overall behavior.
As Dr. Wild stated, our environmental exposures, and our lives, begin in the womb. After this point, the developing fetus is subject to many
of the environmental chemicals and toxicants to which the mother is
(knowingly or unknowingly) exposed. A study described by CNN illustrated this point and found that pregnant mothers were exposed to pesticides and air
pollutants while engaging in everyday activities. Some of these chemicals were also able to pass through the umbilical cord and enter into the bloodstream of the fetus, resulting in an average of 232 chemicals being found in the cord blood of 10 babies born over the course of the study. Pregnant mothers were also exposed
to chemicals from unexpected sources, like taking a shower, cleaning the
house, and putting on makeup. Some of these chemicals also made it into the fetus and were found in the fetal cord blood. However, it
is important to note that the mere presence of such chemicals within the
blood is not necessarily harmful to human health. Instead, toxicity is
dependent upon the concentration and duration of exposure a person, or
fetus, is subjected to– meaning the presence of exposure does not always lead to the occurrence of detrimental health effects.
That
being said, certain types of environmental exposure can result in
numerous negative consequences for the brain. For instance, exposure to certain
amounts of air pollutants and pesticides during development has been associated with a
reduction in white matter volume in the brain, slower information
processing speed, behavioral problems, attention deficit/hyperactivity
disorder (ADHD) symptoms, and an alteration in mental and psychomotor
development [7, 10]. One study retrospectively examined a group of
adults in Cape Cod, Massachusetts who experienced prenatal and early
childhood exposure to drinking water contaminated with
tetrachloroethylene, a chemical solvent used in dry cleaning, and found
that early exposure was associated with impaired vision, increased
reports of impulsive behavior, and increased risks of developing bipolar
disorder and post-traumatic stress disorder (PTSD) in adulthood [1, 2,
6]. In addition, excessive prenatal exposure to BPA and phthalates has
been found to alter sexually dimorphic development of the brain and can also lead to alterations in anxiety, hyperactivity, and emotional control [4, 8, 12]. Thus, exposure to environmental chemicals can influence how our brains function, affect our mental health, and alter how we interact with the world around us.
Given
these documented detrimental health effects, we should seek to avoid
excessive environmental exposures. However, while we can limit our
interaction with known sources of environmental
chemicals, such as by avoiding areas that have recently been sprayed
with pesticides or not living in areas subjected to large amounts of car
exhaust, how do we protect ourselves from environmental toxicants coming from largely unknown and unavoidable sources? And why are chemicals are being added to
commonly-used household items in the first place when such substances
have the potential to negatively alter our brains and neurodevelopment?
The
answer to this latter question can be traced to the years surrounding
the Great Depression and World War II. In this era, the fields of human
industry and farming began to employ synthetic chemicals for numerous
beneficial purposes, like controlling pest populations, reducing
flammability, and acting as additives in paints and wood finishes. These
potential useful applications led to the quick introduction of such
compounds to widespread use without thorough examination of their
possible negative impacts on human health. The reason for rapidly adding
these chemicals was described in the 1930s by the president of
the Halowax Corporation: “The problem so far as the chemical
manufacturer is concerned is a question of timing… should we take a
product of which you have developed, say, 5 or 10g and spend $50,000 on
research to determine whether or not it is toxic, or should you wait
until you have determined whether you have a market for it?...You can
see that would run into box car numbers in the way of dollars and cents
until you ever sold any” [12]. Essentially, adequate chemical testing
was not performed because it was not cost-effective, resulting in the
public remaining largely unaware of the adverse health effects that could arise from excessive exposure to these added chemicals.
Unfortunately, this cost-driven lack of investigation still describes how chemical research is performed today. An article in The New England Journal of Medicine
stated that only 200 of the 80,000 chemicals added to products sold
within the US in 2011 were sufficiently tested for carcinogenicity, not to mention the number of chemicals that were inadequately tested for other, non-cancer-related negative outcomes arising from excessive exposure [5].
This mass-production of chemicals without adequate toxicity testing continues in part because of the vague chemical testing regulations that govern chemical companies in the United States. According to
the Environmental Protection Agency’s (EPA) chemical testing policy,
chemical companies are responsible for determining whether their
substances “may present an unreasonable risk of injury to health or the
environment.” The nebulous wording of this regulation, the lack of a
precise definition of “unreasonable risk,” and the increased cost
associated with increased research has resulted in many chemical
companies simply testing their chemicals for acute toxicity (which
involves giving experimental animals large doses of a chemical and
checking for a decrease in lifespan or the presence of illness), instead
of performing long-term testing (which involves giving experimental
animals small doses of a chemical over a long period of time). Thus,
the effects of gradual exposure, as would be experienced through daily
contact with a chemical over the course of a lifetime, are not examined
and the effects of such gradual exposure are only determined as people
are exposed to these chemicals for many years.
Thankfully,
this problem of non-consensual daily exposure to toxic chemicals is not
one without a solution– though working toward this solution will not be
easy. One of the first steps toward a less-polluted and more hospitable future is to
continue characterizing the human exposome. Several organizations
within the United States and Europe, including the HERCULES
exposome research center at Emory University, operate under this goal.
These organizations seek to develop a better understanding of the role
of the environment on brain disease onset and progression, to discover
chemicals that cause disease, and to remove or diminish exposures to
such chemicals [11]. More stringent regulations on chemical testing and
increased collaboration between chemical companies and neuroscientists
will also move chemical testing in the right direction, helping to
elucidate the long-term effects of environmental chemicals on the brain
and leading to more detailed chemical toxicity characterization.
Unfortunately, increased chemical testing is often viewed as an
unnecessary hindrance and is perceived as being less cost-effective than
rapidly mass-producing a chemical. However, more thorough testing and
increased chemical regulation will result in an improved quality of
life, better brain development, and an increase in human liberties for
individuals throughout our society and the world– and that is priceless.
Works Cited
1.
Aschengrau, A, Weinberg, JM, Janulewicz, PA, Romano, ME, Gallagher, LG,
Winter, MR, Martin, BR, Vieira, VM, Webster, TF, White, RF, &
Ozonoff, DM (2011) Affinity for risky behaviors following prenatal and
early childhood exposure to tetrachloroethylene (PCE)-contaminated
drinking water: a retrospective cohort study. Environ Health 10: 102.
doi: 10.1186/1476-069x-10-102
2. Aschengrau, A,
Weinberg, JM, Janulewicz, PA, Romano, ME, Gallagher, LG, Winter, MR,
Martin, BR, Vieira, VM, Webster, TF, White, RF, & Ozonoff, DM (2012)
Occurrence of mental illness following prenatal and early childhood
exposure to tetrachloroethylene (PCE)-contaminated drinking water: a
retrospective cohort study. Environ Health 11: 2. doi:
10.1186/1476-069x-11-2
3. Ballesteros-Gomez, A, de
Boer, J, & Leonards, PE (2014) A novel brominated triazine-based
flame retardant (TTBP-TAZ) in plastic consumer products and indoor dust.
Environ Sci Technol 48: 4468-4474. doi: 10.1021/es4057032
4.
Braun, JM, Kalkbrenner, AE, Calafat, AM, Yolton, K, Ye, X, Dietrich,
KN, & Lanphear, BP (2011) Impact of early-life bisphenol A exposure
on behavior and executive function in children. Pediatrics 128: 873-882.
doi: 10.1542/peds.2011-1335
5. Christiani, DC (2011) Combating environmental causes of cancer. N Engl J Med 364: 791-793. doi: 10.1056/NEJMp1006634
6.
Getz, KD, Janulewicz, PA, Rowe, S, Weinberg, JM, Winter, MR, Martin,
BR, Vieira, VM, White, RF, & Aschengrau, A (2012) Prenatal and early
childhood exposure to tetrachloroethylene and adult vision. Environ
Health Perspect 120: 1327-1332. doi: 10.1289/ehp.1103996
7.
Gonzalez-Alzaga, B, Lacasana, M, Aguilar-Garduno, C,
Rodriguez-Barranco, M, Ballester, F, Rebagliato, M, & Hernandez, AF
(2014) A systematic review of neurodevelopmental effects of prenatal and
postnatal organophosphate pesticide exposure. Toxicol Lett 230:
104-121. doi: 10.1016/j.toxlet.2013.11.019
8. Lin, CY,
Shen, FY, Lian, GW, Chien, KL, Sung, FC, Chen, PC, & Su, TC (2015)
Association between levels of serum bisphenol A, a potentially harmful
chemical in plastic containers, and carotid artery intima-media
thickness in adolescents and young adults. Atherosclerosis 241: 657-663.
doi: 10.1016/j.atherosclerosis.2015.06.038
9. Miller,
GW, & Jones, DP (2014) The nature of nurture: refining the
definition of the exposome. Toxicol Sci 137: 1-2. doi:
10.1093/toxsci/kft251
10. Peterson, BS, Rauh, VA,
Bansal, R, Hao, X, Toth, Z, Nati, G, Walsh, K, Miller, RL, Arias, F,
Semanek, D, & Perera, F (2015) Effects of prenatal exposure to air
pollutants (polycyclic aromatic hydrocarbons) on the development of
brain white matter, cognition, and behavior in later childhood. JAMA
Psychiatry 72: 531-540. doi: 10.1001/jamapsychiatry.2015.57
11.
Rappaport, SM, Barupal, DK, Wishart, D, Vineis, P, & Scalbert, A
(2014) The blood exposome and its role in discovering causes of disease.
Environ Health Perspect 122: 769-774. doi: 10.1289/ehp.1308015
12.
Rosner, D, & Markowitz, G (2013) Persistent pollutants: a brief
history of the discovery of the widespread toxicity of chlorinated
hydrocarbons. Environ Res 120: 126-133. doi:
10.1016/j.envres.2012.08.011
13. Venier, M, Salamova,
A, & Hites, RA (2015) Halogenated Flame Retardants in the Great
Lakes Environment. Acc Chem Res. doi: 10.1021/acs.accounts.5b00180
14.
Wild, CP (2005) Complementing the genome with an "exposome": the
outstanding challenge of environmental exposure measurement in molecular
epidemiology. Cancer Epidemiol Biomarkers Prev 14: 1847-1850. doi:
10.1158/1055-9965.epi-05-0456
15. Wild, CP (2012) The exposome: from concept to utility. Int J Epidemiol 41: 24-32. doi: 10.1093/ije/dyr236
Want to cite this post?
Hoffman, C. (2015). Overexposed: The role of environmental toxicants on your brain. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2015/09/overexposed-role-of-environmental.html
It
is often said that we are products of our environment: who we are is
shaped by the things, people, and situations with which we surround
ourselves. However, whatever we may like to think, we are not in
control of every facet of our environment. In fact, we are unknowingly
and involuntarily exposed to dozens of man-made environmental chemicals,
called toxicants,
each day that can negatively alter our bodies and even our very brain
matter. In essence, we are becoming literal products of our environment.
Synthetic
chemicals and toxicants are ubiquitous within our surroundings. While some toxicants come from obvious
sources, like cigarette smoke and car exhaust, other sources of exposure
are more subtle. For instance, electrical equipment (like computers
and cell phones), beauty products (like makeup and shampoo), mattresses,
and furniture all contain flame retardants, chemicals used to reduce flammability [3, 13]. Bisphenol A (BPA) and phthalates,
chemicals used to harden plastics, can also be found in dental
sealants, cigarette filters, soda bottles, and the linings of canned
foods [4, 8, 12]. Additionally, dichlorodiphenyltrichloroethane (DDT),
a pesticide commonly used in the mid-1900s to combat outbreaks of
pests, malaria, and lice, was banned in 1972 in the US and yet is still currently present within both the environment and human tissues [12].
 |
| Pesticides not only harm insects, but certain doses can also have harmful effects on the human body. |
The presence of chemicals within almost every facet of our society means we are
subjected to varying levels of environmental exposure throughout our lives– from the womb to the grave. A growing desire to
characterize the effects of this lifetime of exposure resulted in the
creation of a new concept: the “exposome.”
Defined in 2005 by Dr. Christopher Wild as “every exposure to which an
individual is subjected from conception to death,” this definition was
expanded by Dr. Gary Miller and Dr. Dean Jones
in 2014 to be “the cumulative measure of environmental influences and
associated biological responses throughout the lifespan, including
exposures from the environment, diet, behavior, and endogenous
processes” [9, 14, 15]. Indeed, some say the exposome profile may
tell a narrative about our individual lives with astounding accuracy–
including where we’ve traveled, what we’ve eaten, and trends in our
overall behavior.
As Dr. Wild stated, our environmental exposures, and our lives, begin in the womb. After this point, the developing fetus is subject to many
of the environmental chemicals and toxicants to which the mother is
(knowingly or unknowingly) exposed. A study described by CNN illustrated this point and found that pregnant mothers were exposed to pesticides and air
pollutants while engaging in everyday activities. Some of these chemicals were also able to pass through the umbilical cord and enter into the bloodstream of the fetus, resulting in an average of 232 chemicals being found in the cord blood of 10 babies born over the course of the study. Pregnant mothers were also exposed
to chemicals from unexpected sources, like taking a shower, cleaning the
house, and putting on makeup. Some of these chemicals also made it into the fetus and were found in the fetal cord blood. However, it
is important to note that the mere presence of such chemicals within the
blood is not necessarily harmful to human health. Instead, toxicity is
dependent upon the concentration and duration of exposure a person, or
fetus, is subjected to– meaning the presence of exposure does not always lead to the occurrence of detrimental health effects.
That
being said, certain types of environmental exposure can result in
numerous negative consequences for the brain. For instance, exposure to certain
amounts of air pollutants and pesticides during development has been associated with a
reduction in white matter volume in the brain, slower information
processing speed, behavioral problems, attention deficit/hyperactivity
disorder (ADHD) symptoms, and an alteration in mental and psychomotor
development [7, 10]. One study retrospectively examined a group of
adults in Cape Cod, Massachusetts who experienced prenatal and early
childhood exposure to drinking water contaminated with
tetrachloroethylene, a chemical solvent used in dry cleaning, and found
that early exposure was associated with impaired vision, increased
reports of impulsive behavior, and increased risks of developing bipolar
disorder and post-traumatic stress disorder (PTSD) in adulthood [1, 2,
6]. In addition, excessive prenatal exposure to BPA and phthalates has
been found to alter sexually dimorphic development of the brain and can also lead to alterations in anxiety, hyperactivity, and emotional control [4, 8, 12]. Thus, exposure to environmental chemicals can influence how our brains function, affect our mental health, and alter how we interact with the world around us.
Given
these documented detrimental health effects, we should seek to avoid
excessive environmental exposures. However, while we can limit our
interaction with known sources of environmental
chemicals, such as by avoiding areas that have recently been sprayed
with pesticides or not living in areas subjected to large amounts of car
exhaust, how do we protect ourselves from environmental toxicants coming from largely unknown and unavoidable sources? And why are chemicals are being added to
commonly-used household items in the first place when such substances
have the potential to negatively alter our brains and neurodevelopment?
The
answer to this latter question can be traced to the years surrounding
the Great Depression and World War II. In this era, the fields of human
industry and farming began to employ synthetic chemicals for numerous
beneficial purposes, like controlling pest populations, reducing
flammability, and acting as additives in paints and wood finishes. These
potential useful applications led to the quick introduction of such
compounds to widespread use without thorough examination of their
possible negative impacts on human health. The reason for rapidly adding
these chemicals was described in the 1930s by the president of
the Halowax Corporation: “The problem so far as the chemical
manufacturer is concerned is a question of timing… should we take a
product of which you have developed, say, 5 or 10g and spend $50,000 on
research to determine whether or not it is toxic, or should you wait
until you have determined whether you have a market for it?...You can
see that would run into box car numbers in the way of dollars and cents
until you ever sold any” [12]. Essentially, adequate chemical testing
was not performed because it was not cost-effective, resulting in the
public remaining largely unaware of the adverse health effects that could arise from excessive exposure to these added chemicals.
Unfortunately, this cost-driven lack of investigation still describes how chemical research is performed today. An article in The New England Journal of Medicine
stated that only 200 of the 80,000 chemicals added to products sold
within the US in 2011 were sufficiently tested for carcinogenicity, not to mention the number of chemicals that were inadequately tested for other, non-cancer-related negative outcomes arising from excessive exposure [5].
 |
| EPA |
This mass-production of chemicals without adequate toxicity testing continues in part because of the vague chemical testing regulations that govern chemical companies in the United States. According to
the Environmental Protection Agency’s (EPA) chemical testing policy,
chemical companies are responsible for determining whether their
substances “may present an unreasonable risk of injury to health or the
environment.” The nebulous wording of this regulation, the lack of a
precise definition of “unreasonable risk,” and the increased cost
associated with increased research has resulted in many chemical
companies simply testing their chemicals for acute toxicity (which
involves giving experimental animals large doses of a chemical and
checking for a decrease in lifespan or the presence of illness), instead
of performing long-term testing (which involves giving experimental
animals small doses of a chemical over a long period of time). Thus,
the effects of gradual exposure, as would be experienced through daily
contact with a chemical over the course of a lifetime, are not examined
and the effects of such gradual exposure are only determined as people
are exposed to these chemicals for many years.
Thankfully,
this problem of non-consensual daily exposure to toxic chemicals is not
one without a solution– though working toward this solution will not be
easy. One of the first steps toward a less-polluted and more hospitable future is to
continue characterizing the human exposome. Several organizations
within the United States and Europe, including the HERCULES
exposome research center at Emory University, operate under this goal.
These organizations seek to develop a better understanding of the role
of the environment on brain disease onset and progression, to discover
chemicals that cause disease, and to remove or diminish exposures to
such chemicals [11]. More stringent regulations on chemical testing and
increased collaboration between chemical companies and neuroscientists
will also move chemical testing in the right direction, helping to
elucidate the long-term effects of environmental chemicals on the brain
and leading to more detailed chemical toxicity characterization.
Unfortunately, increased chemical testing is often viewed as an
unnecessary hindrance and is perceived as being less cost-effective than
rapidly mass-producing a chemical. However, more thorough testing and
increased chemical regulation will result in an improved quality of
life, better brain development, and an increase in human liberties for
individuals throughout our society and the world– and that is priceless.
Works Cited
1.
Aschengrau, A, Weinberg, JM, Janulewicz, PA, Romano, ME, Gallagher, LG,
Winter, MR, Martin, BR, Vieira, VM, Webster, TF, White, RF, &
Ozonoff, DM (2011) Affinity for risky behaviors following prenatal and
early childhood exposure to tetrachloroethylene (PCE)-contaminated
drinking water: a retrospective cohort study. Environ Health 10: 102.
doi: 10.1186/1476-069x-10-102
2. Aschengrau, A,
Weinberg, JM, Janulewicz, PA, Romano, ME, Gallagher, LG, Winter, MR,
Martin, BR, Vieira, VM, Webster, TF, White, RF, & Ozonoff, DM (2012)
Occurrence of mental illness following prenatal and early childhood
exposure to tetrachloroethylene (PCE)-contaminated drinking water: a
retrospective cohort study. Environ Health 11: 2. doi:
10.1186/1476-069x-11-2
3. Ballesteros-Gomez, A, de
Boer, J, & Leonards, PE (2014) A novel brominated triazine-based
flame retardant (TTBP-TAZ) in plastic consumer products and indoor dust.
Environ Sci Technol 48: 4468-4474. doi: 10.1021/es4057032
4.
Braun, JM, Kalkbrenner, AE, Calafat, AM, Yolton, K, Ye, X, Dietrich,
KN, & Lanphear, BP (2011) Impact of early-life bisphenol A exposure
on behavior and executive function in children. Pediatrics 128: 873-882.
doi: 10.1542/peds.2011-1335
5. Christiani, DC (2011) Combating environmental causes of cancer. N Engl J Med 364: 791-793. doi: 10.1056/NEJMp1006634
6.
Getz, KD, Janulewicz, PA, Rowe, S, Weinberg, JM, Winter, MR, Martin,
BR, Vieira, VM, White, RF, & Aschengrau, A (2012) Prenatal and early
childhood exposure to tetrachloroethylene and adult vision. Environ
Health Perspect 120: 1327-1332. doi: 10.1289/ehp.1103996
7.
Gonzalez-Alzaga, B, Lacasana, M, Aguilar-Garduno, C,
Rodriguez-Barranco, M, Ballester, F, Rebagliato, M, & Hernandez, AF
(2014) A systematic review of neurodevelopmental effects of prenatal and
postnatal organophosphate pesticide exposure. Toxicol Lett 230:
104-121. doi: 10.1016/j.toxlet.2013.11.019
8. Lin, CY,
Shen, FY, Lian, GW, Chien, KL, Sung, FC, Chen, PC, & Su, TC (2015)
Association between levels of serum bisphenol A, a potentially harmful
chemical in plastic containers, and carotid artery intima-media
thickness in adolescents and young adults. Atherosclerosis 241: 657-663.
doi: 10.1016/j.atherosclerosis.2015.06.038
9. Miller,
GW, & Jones, DP (2014) The nature of nurture: refining the
definition of the exposome. Toxicol Sci 137: 1-2. doi:
10.1093/toxsci/kft251
10. Peterson, BS, Rauh, VA,
Bansal, R, Hao, X, Toth, Z, Nati, G, Walsh, K, Miller, RL, Arias, F,
Semanek, D, & Perera, F (2015) Effects of prenatal exposure to air
pollutants (polycyclic aromatic hydrocarbons) on the development of
brain white matter, cognition, and behavior in later childhood. JAMA
Psychiatry 72: 531-540. doi: 10.1001/jamapsychiatry.2015.57
11.
Rappaport, SM, Barupal, DK, Wishart, D, Vineis, P, & Scalbert, A
(2014) The blood exposome and its role in discovering causes of disease.
Environ Health Perspect 122: 769-774. doi: 10.1289/ehp.1308015
12.
Rosner, D, & Markowitz, G (2013) Persistent pollutants: a brief
history of the discovery of the widespread toxicity of chlorinated
hydrocarbons. Environ Res 120: 126-133. doi:
10.1016/j.envres.2012.08.011
13. Venier, M, Salamova,
A, & Hites, RA (2015) Halogenated Flame Retardants in the Great
Lakes Environment. Acc Chem Res. doi: 10.1021/acs.accounts.5b00180
14.
Wild, CP (2005) Complementing the genome with an "exposome": the
outstanding challenge of environmental exposure measurement in molecular
epidemiology. Cancer Epidemiol Biomarkers Prev 14: 1847-1850. doi:
10.1158/1055-9965.epi-05-0456
15. Wild, CP (2012) The exposome: from concept to utility. Int J Epidemiol 41: 24-32. doi: 10.1093/ije/dyr236
Want to cite this post?
Hoffman, C. (2015). Overexposed: The role of environmental toxicants on your brain. The Neuroethics Blog. Retrieved on , from http://www.theneuroethicsblog.com/2015/09/overexposed-role-of-environmental.html
Comments
Post a Comment