The Nonlinear Library LW - How bad is chlorinated water? by bhauth
Dec 14, 2023
05:00
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: How bad is chlorinated water?, published by bhauth on December 14, 2023 on LessWrong.
chlorine disinfection
Today, most water distributed to people for drinking is chlorinated. Bleach is also widely used for disinfection of surfaces.
The exact ways chlorine kills microbes aren't fully understood, but the main reasons are believed to be:
oxidation of thiols of enzymes
ring chlorination of amino acids
direct DNA damage
Obviously, high levels of chlorine are bad for humans. Chlorine gas was used as a chemical weapon in WW1, and drinking bleach can kill people. As for longer exposure to lower levels, studies have found associations between lung damage and use of indoor swimming pools, but the extent to which harmful effects of chlorine have thresholds from saturation of enzymes is still unclear.
Dietary studies are notoriously hard to get good results from, and studying chlorinated water has similar issues. Studies have concluded that, eg, over a few weeks, chlorinated water doesn't affect lipid metabolism. But is that what you'd expect to see? If there were effects, what would they be?
effects of ingested chlorine
Engineers try to minimize levels of some compounds in water that can react with chlorine to produce toxic substances, such as chloramines and chloroform. But...there are organic compounds in the stomach. What about reactions of chlorine after it's consumed?
Stomachs are acidic. That means amines are mostly protonated and unlikely to react, but other chlorination reactions are catalyzed. My understanding is that the main types of chlorine reaction in stomachs are:
oxidation of thiols (this doesn't concern me much)
phenol chlorination (eg 3-chlorotyrosine production)
tryptophan oxidation
double bond oxidation to halohydrins
Chlorotyrosine production happening is intuitive, and it's been validated by some rat studies. But the topic of reactions of chlorine in stomachs hasn't been studied very much in general.
What happens to chlorotyrosine and halohydrins afterwards?
In cells, aliphatic chlorinated compounds tend to have chlorine replaced with a ketone group by enzymes. For example, dichloromethane becomes formyl chloride which decomposes to carbon monoxide and HCl, which are less toxic than products from other chloromethanes, making it the least toxic of them. Obviously it's also possible for halocarbons to react spontaneously with amines before an enzyme gets to them; that's less likely with chlorine than bromine, but any amount is still bad.
As for chlorotyrosine...I'm not sure. Yes, people have examined metabolism of chlorotyrosine, and found eg a significant amount of 4-hydroxyphenylacetic acid, which indicates to me that it might be dechlorinated during decarboxylation of 3-chlorohydroxyphenylpyruvate with some sort of quinone methide intermediate. But that's not really the question, is it? The question is what the effects of chlorotyrosine being present are.
That chlorine atom isn't likely to spontaneously react, but how much chlorotyrosine is incorporated into proteins? How does that incorporation affect protein effects? Does chlorotyrosine have some direct signalling effects? How big are the net impacts? I don't know. At this point, I'm probably in the top 100 worldwide for understanding of molecular toxicology, sad as that is to say, and my knowledge here feels inadequate.
When macrophages "eat" pathogens, they will sometimes generate hypochlorite in the phagosome. A little bit of that hypochlorite leaks, and that leakage is a significant fraction of harm from infection. Chlorotyrosine is associated with damage from immune system hypochlorite generation, but it's not clear to what extent it's causative.
Then, there are all the other phenols that could be chlorinated. Chlorination can cause compounds to mimic hormones - for example, who can forget the ef...
chlorine disinfection
Today, most water distributed to people for drinking is chlorinated. Bleach is also widely used for disinfection of surfaces.
The exact ways chlorine kills microbes aren't fully understood, but the main reasons are believed to be:
oxidation of thiols of enzymes
ring chlorination of amino acids
direct DNA damage
Obviously, high levels of chlorine are bad for humans. Chlorine gas was used as a chemical weapon in WW1, and drinking bleach can kill people. As for longer exposure to lower levels, studies have found associations between lung damage and use of indoor swimming pools, but the extent to which harmful effects of chlorine have thresholds from saturation of enzymes is still unclear.
Dietary studies are notoriously hard to get good results from, and studying chlorinated water has similar issues. Studies have concluded that, eg, over a few weeks, chlorinated water doesn't affect lipid metabolism. But is that what you'd expect to see? If there were effects, what would they be?
effects of ingested chlorine
Engineers try to minimize levels of some compounds in water that can react with chlorine to produce toxic substances, such as chloramines and chloroform. But...there are organic compounds in the stomach. What about reactions of chlorine after it's consumed?
Stomachs are acidic. That means amines are mostly protonated and unlikely to react, but other chlorination reactions are catalyzed. My understanding is that the main types of chlorine reaction in stomachs are:
oxidation of thiols (this doesn't concern me much)
phenol chlorination (eg 3-chlorotyrosine production)
tryptophan oxidation
double bond oxidation to halohydrins
Chlorotyrosine production happening is intuitive, and it's been validated by some rat studies. But the topic of reactions of chlorine in stomachs hasn't been studied very much in general.
What happens to chlorotyrosine and halohydrins afterwards?
In cells, aliphatic chlorinated compounds tend to have chlorine replaced with a ketone group by enzymes. For example, dichloromethane becomes formyl chloride which decomposes to carbon monoxide and HCl, which are less toxic than products from other chloromethanes, making it the least toxic of them. Obviously it's also possible for halocarbons to react spontaneously with amines before an enzyme gets to them; that's less likely with chlorine than bromine, but any amount is still bad.
As for chlorotyrosine...I'm not sure. Yes, people have examined metabolism of chlorotyrosine, and found eg a significant amount of 4-hydroxyphenylacetic acid, which indicates to me that it might be dechlorinated during decarboxylation of 3-chlorohydroxyphenylpyruvate with some sort of quinone methide intermediate. But that's not really the question, is it? The question is what the effects of chlorotyrosine being present are.
That chlorine atom isn't likely to spontaneously react, but how much chlorotyrosine is incorporated into proteins? How does that incorporation affect protein effects? Does chlorotyrosine have some direct signalling effects? How big are the net impacts? I don't know. At this point, I'm probably in the top 100 worldwide for understanding of molecular toxicology, sad as that is to say, and my knowledge here feels inadequate.
When macrophages "eat" pathogens, they will sometimes generate hypochlorite in the phagosome. A little bit of that hypochlorite leaks, and that leakage is a significant fraction of harm from infection. Chlorotyrosine is associated with damage from immune system hypochlorite generation, but it's not clear to what extent it's causative.
Then, there are all the other phenols that could be chlorinated. Chlorination can cause compounds to mimic hormones - for example, who can forget the ef...