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 effects of chlorinated dioxins on the endocrine system? (Maybe people should stop using PBDEs, too. Sigh.) But my intuition says that chlorotyrosine is more significant.

Bleach is also used sometimes for disinfecting food in commercial facilities, such as vegetables and raw chicken. Here's a study looking at chlorotyrosine levels from washing vegetables with bleach, which concluded that:

3-chlorotyrosine exposure through the lettuce mix could be potentially a great health concern

alternatives

water treatment:

UV or (UV + H2O2) can be used for water disinfection, but it doesn't maintain disinfection while water is piped from treatment to homes. As I've previously posted, it might be possible to use (UV + H2O2) for initial disinfection then add a small amount of nontoxic cationic surfactant such as choline fatty acid ester to prevent microbe replication. This is slightly more expensive than using chlorine, and companies that sell chlorine would be mad.

surface disinfection:

As I've previously posted, peroxyacids can be used for disinfection, but volatile ones are noxious, so (citric acid + H2O2) is relatively suitable as a chlorine-free disinfectant.

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18 comments, sorted by Click to highlight new comments since: Today at 5:33 PM

Small data point: Tap water in Germany is usually not chlorinated but still drinking water of high quality (often said to be better than potted water). This is achieved by protecting water sources, treatment and monitoring.

Has anyone done a study on whether or not bacteria incorporate chlorotyrosine (or other damaged protens) into their proteins at first pass? This seems very doable.

We now know that oxidized DNA bases can be incorporated into the intestines of mouse DNA.

One issue is that a lot of lab processes can cause a little bit of chlorination. Here is a study looking at insect cuticle of insects raised without deliberate chlorine introduction; it found chlorotyrosine at ~0.02% mass content. Tyrosine is typically ~3.2% of protein residues.

I thought most water was now treated with chloramine and not chlorine? Though checking now all I can find are pages saying these are both common methods and nothing about which is more common.

(I don't know if this is better or worse in your analysis, but you may be analyzing an obsolete treatment.)

Chloramine is used less than chlorine for drinking water disinfection, but is still used a lot these days, maybe for some weird regulatory reasons involving limits on reaction products from chlorine. I didn't write about that mostly because it's bad in more obvious ways (like formation of hydrazine groups), and isn't used where I've lived, and thus it's less interesting to me. But maybe I should've included it in this post?

Thanks! I was probably overgeneralizing from my local treatment plant:

MWRA uses ozone and ultaviolet light (UV) to kill any harmful bacteria at the CWTP in Marlborough. ... To protect the water as it travels through the miles of pipe to get to your house, MWRA uses a mild disinfectant called mono-chloramine

Wait, doesn't stomach acid have chlorine at (checks google) 10^-2 to 10^-1 M, and chlorinated water have it at (checks wolframalpha) 2*10^-5 M? I'm confused - are we accidentally chlorinating things all the time? Or does a significant fraction of chlorination in water actually persist in the stomach as Cl2 rather than dissolving as HCl or even HClO?

Chloride ions are different from elemental chlorine. (Hypochlorite + chloride) is in equilibrium with elemental chlorine in water.

Yeah, but it's in equilibrium in stomach acid too.

Disclaimer: spitballing from someone without particularly relevant knowledge.

Chlorine is an oxidant and the damage pathways suggested by bhauth involve oxidation.

Oxidation is a chemical process where the oxidant "wants electrons" and reacts accordingly. Thus, things like oxygen (missing two electrons in outer shell) and chlorine (missing one electron) are oxidants.

A chloride ion, such as occurs in HCl when the covalent bond dissociates (or e.g. in ordinary table salt) is not missing any electrons and thus is not an oxidant.

The relevant question thus is how much the chlorine is persisting in oxidant form from tap water (when added to the stomach acid) vs. how much it is in oxidant form already in natural stomach acid.

Cl is a pretty strong oxidant, so Cl- with something else + is not that prone to shift to unbonded Cl neutral and the other thing neutral.  So it wouldn't be surprising to me if even a very large amount of HCl in stomach acid has relatively little elemental chlorine in equilibrium, and slow production of extra if some that does form reacts with other stuff in the stomach.

Given that water chlorination on the other hand is specifically intended to kill microbes via oxidation-related processes, it doesn't seem surprising to me that there would be relevant amounts of elemental chlorine available. When it combines with the stomach acid - I dunno what happens, but for elemental chlorine to convert to Cl- means it has to get electrons from somewhere. Which means oxidation of something I would think? 

(A complication is that the HCl is evolved to destroy stuff in the stomach via acidity, and acidity is related to oxidation. But it isn't quite the same and it isn't elemental chlorine as such doing it.)

Just as you say, chlorine dissolved in water likes to be Cl- or ClO- anions.

My suspicion after more thought is that dissolving Cl2 in water produces excess metastable ClO, which breaks down into Cl over a few hours, and that out-of-equilibrium ClO is the antimicrobial and also a reasonable chlorinating agent to be concerned about.

Cl- and ClO- are two different things, the latter is an oxidant while the former is not. It seems odd to me to bundle them together.

I don't know what particular oxidants would cause more or worse biological effects. So, not sure whether it would matter if there's "excess metastable" of one particular oxidant or not. But, "excess metastable ClO" seems an odd thing to expect - it sounds like you're expecting a reaction to go past equilibrium, why?

Cl- and ClO- are two different things, the latter is an oxidant while the former is not. It seems odd to me to bundle them together.

Truly, shame on bhauth three comments above. (sarcasm) I figure we're just mentioning them together because they're what you get when reacting chlorine gas with water.

(Note I meant "excess metastable ClO" to be parsed as "an excess of metastable ClO," not as if "excess metastable" was an extra fancy kind of excess - un excès métastable. Although I guess that also kind of works.)

it sounds like you're expecting a reaction to go past equilibrium, why?

I do not. So maybe I should explain the three steps I'm thinking of:

State 1 is water and chlorine gas. This is out of equilibrium - the chlorine will react with the water.

State 2 is water, H3O+, and a somewhat-even mixture of Cl- and ClO- ions (and trace Cl2). This is also out of equilibrium, the ClO- will react with the H3O+. But it's less out of equilibrium than state 1.

State 3 is water, H3O+, Cl-, and trace amounts of ClO- (and even tracer Cl2). This is the putative equilibrium.

I expect treated water to go 1->2->3. Not 1->3->2->3 or any such thing. If it just goes 1->3, never 2 at all, then I'm wrong. Also, it if goes 1->2->3 but 1->2 is slow and 2->3 is fast, then I'm wrong.

According to wikipedia:

When dissolved in water, chlorine converts to an equilibrium mixture of chlorine, hypochlorous acid (HOCl), and hydrochloric acid (HCl):

Cl2 + H2O ⇌ HOCl + HCl

In acidic solution, the major species are Cl2 and HOCl, whereas in alkaline solution, effectively only ClO (hypochlorite ion) is present. Very small concentrations of ClO2, ClO3, ClO4 are also found.[18]

So the putative equilibrium is the above (and also including some H3O+ and ClO and Cl  from dissociation of the stuff on the right) and not this:

State 3 is water, H3O+, Cl-, and trace amounts of ClO- (and even tracer Cl2). This is the putative equilibrium.

Note that the total quantity of Cl2 and HOCl (or in more basic solution ClO ) is conserved in the above reaction. You do not get to a point where both are trace, if that's not what you started with. In natural stomach acid, you would presumably not start with either of them, but in chlorinated tap water you do. 

Regarding the specific intermediate steps in a reaction and how fast they are, perhaps you could post a specific equation for what you think will happen.

FWIW (though I really have no expertise on this) intuitively it wouldn't seem surprising to me if the reaction actually used OH- like this: Cl2 + OH- ⇌ HOCl + Cl- , whereas it's harder for me to visualize how it would work with OCl- as an intermediate (like, why is your intermediate reaction stripping both H's off the O, while your final reaction puts them back on?).

Note that the total quantity of Cl2 and HOCl (or in more basic solution ClO ) is conserved in the above reaction

Ah, nice, that reaction is actually an explanation of why you might get roughly equal amounts at first.

So the putative equilibrium is the above (and also including some H3O+ and ClO and Cl  from dissociation of the stuff on the right) and not this:

So can you tell me what the equilibrium is at pH 7? That wikipedia quote solely mentions environments of unspecified levels of acidity / alkali.

It might be important to note that I'm "cheating," because I know as an empirical fact that ClO- is unstable in water - dilute bleach eventually turns into salt water, while salt water does not turn into dilute bleach.

Note that the total quantity of Cl2 and HOCl (or in more basic solution ClO ) is conserved in the above reaction.

Sure, but it's not the only possible reaction. Consider 2HOCl <-> 2HCl + O2.

So can you tell me what the equilibrium is at pH 7?

I unfortunately don't know the Cl2 equilibrium at neutral pH, (I tried to calculate an overall equilibrium constant at fixed neutral pH from the equilibrium constants for acid and base context on wiki, got inconsistent results from them, and since I actually don't know what I'm doing but am just applying half-remembered stuff from the one chemistry course I ever took at university plus looking things up on the fly, don't understand why). But if you just want to know how much is OCl vs HOCl, here's a link with a graph on page 2 (basically should be the same as what you'd calculate using the acid dissociation constant for hypochlorous acid).

Anyway:

It might be important to note that I'm "cheating," because I know as an empirical fact that ClO- is unstable in water - dilute bleach eventually turns into salt water, while salt water does not turn into dilute bleach.

It makes sense that that could happen:

2 ClO → 2 Cl + O2

So yes, you could have oxygen bubbling out too. I guess in this case we wouldn't be as concerned, as presumably the sort of oxidation reaction done by oxygen itself is expected in an oxygen rich environment such as we live in and wouldn't cause additional harm.

So, I guess that's what you meant by metastable ClO. But it sounds like this reaction is slow if not at high temperature? Also, I wouldn't expect it so much to happen directly with HOCl, rather than ClO , because O is the middle atom in HOCl so it seems to me it would be less likely to get pulled out in one step than if it's one of the edge atoms.

At neutral pH HClO + ClO- can obviously react to form oxygen via peroxyhypochlorous acid. That's not what happens to bleach over time because it's sodium hypochlorite. It either loses Cl2 to air or ClO- disproportionates to chlorate and Cl-.

I'm trying to push frontiers. This stuff is on wikipedia.

I hadn't heard of peroxyhypochlorous acid before, but looking it up (HOOCl) I can imagine it forming by the O's of ClO- and HOCl meeting and kicking out one of the Cl's as Cl-. That being said, given that Cl with O's bonded tends to be more of a thing than oxygen-oxygen bonds (and Cl would be the more positive side (?) of the Cl/O bond having more protons and thus more likely to bond with the O than another O?), wouldn't chlorous acid (HOClO) be more likely to be produced by those things reacting (with either of the Cl's bonding with the O of the other and kicking out the other Cl as Cl-)? Which would then presumably lead to further oxychlorine stuff rather than pure oxygen?