5 ms·

The story of phthalates really highlights the drinking from the fume hood aspects of our commercial norms. Phthalates are designed to squeeze between hydrophobi

The story of phthalates really highlights the drinking from the fume hood aspects of our commercial norms. Phthalates are designed to squeeze between hydrophobic polymers such that their bulk mechanical properties are changed, while remaining chemically inert and not subject to breakdown. The question of what this would do in the human body, which is full of polymers with very sensitively evolved mechanical properties, was obvious - yet it was not asked in a funded capacity until we had been letting it accumulate in our kids for decades. The position of our institutions on this is a clear case of preferring not to know.

timr 2y ago
You can't just say "squeeze between hydrophobic polymers", as if that's a single thing, and therefore any such "hydrophobic polymer" will be vulnerable to a phthalate. In particular, DNA is not hydrophobic -- it's an extremely polar environment. The known DNA/RNA intercalating chemicals are also very polar (at least, in critical selected locations). For example, Ethidium Bromide: https://en.wikipedia.org/wiki/Ethidium_bromide https://en.wikipedia.org/wiki/Ethidium_bromide Point being: assuming that the paper in the headline is true (which I do not assume, but I digress), your theory of the mechanism is probably wrong, and therefore misleading. Edit: having now looked at the paper, they're discussing one specific chemical (bezyl butyl phthalate) which is actually quite polar. It's also an ester, and trivially broken down by common enzymes into a number of different child compounds, any of which could be individually responsible for the claimed effects. Biochemistry is complex.
- deleted 2y ago
  [deleted]
- whatshisface 2y ago
  It gets into hydrophobic binding sites, and accumulates in lipids. > Aromatic compounds, aliphatic hydrocarbons, and halogens are the hydrophobic parts of ligand PAEs. Hydrophobic contact is caused by the spatial proximity of the non-polar amino acid side chains and the hydrophobic substituents on the ligand PAE molecules. Water molecules are released from the hydrophobic region upon hydrophobic contact, and the unconstrained water molecules released can participate in the energy-favorable hydrogen bonding interactions, which enhance the overall binding affinity of the ligand [37,38,39]. Therefore, the hydrophobic interactions between ligands and receptors affect the ability of PAEs to bind to hormone proteins and influence the ability of PAEs to bind to DNA response elements. https://pmc.ncbi.nlm.nih.gov/articles/PMC10488033/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10488033/
  - timr 2y ago
    The paper is about DNA mutation. DNA is not a hydrophobic binding site. It doesn't interact with hydrophobic binding sites. Moreover, the chemical studied in this particular paper is not particularly hydrophobic. Your theory is wrong, at least in this case. Also, this paper says the opposite of what you think it says: > based on the three-dimensional potential energy surface information, it was discovered that the hydrophobic, steric, and electrostatic fields of PAEs significantly influence their endocrine disruption effects on humans. They're saying that hydrophobic effects matter, but non-hydrophobic effects also matter. So everything matters. FWIW, the paper is not particularly worth citing. Someone made an ML model that said what any competent chemist could tell you by looking at a phthalate.
    - whatshisface 2y ago
      Who said DNA was hydrophobic? I'm sorry, but we're not disagreeing. Phtalates are very lithophilic and that's a major mechanism of their accumulation in the body. If phtalates were highly polar, they wouldn't be soluble in plastic. That means they're going to bind to fat tissue and non-polar receptors. >the chemical studied in this particular paper [...] Also, the paper didn't study "a chemical," it covered about 30.
      - timr 2y ago
        I'm telling you that you're overgeneralizing based on incorrect information. The paper being discussed here directly refutes your hypothesis of action, because it's about a particular chemical that is known to be metabolized, causing downstream effects in an extremely polar molecule (DNA). Generally, "pthalates" are not a thing, but rather a whole bunch of different things (some are hydrophobic, some are not), and many of them are metabolized by the human body, so they don't actually accumulate. You have to be more specific. https://pubmed.ncbi.nlm.nih.gov/17604388/ https://pubmed.ncbi.nlm.nih.gov/17604388/ > If phtalates were highly polar, they wouldn't be soluble in plastic. Setting aside "highly polar", which is not specific, you are wrong. Many/most pthalates are far from what chemists consider "hydrophobic", and are in fact esters, alcolhols and acids. > Also, the paper didn't study "a chemical," it covered about 30. The paper in the OP was about one molecule: BBP.
fuzzfactor 2y ago
>preferring not to know. I think this does have some ongoing influence on why more detailed analysis of common chemicals is not required. From what I can tell, it looks like phthalates started with excess coal tar which contained tonnes of a solid waxy aromatic hydrocarbon called naphthalene that nobody probably had much of a way to monetize for quite some time. Plenty of money was surely being made in other ways so regardless of the accounting methods, the surplus ends up being a no-cost item. When there are tonnes of an unutilized resource like this the full-scale effort would turn every tonne into something useful, and all it has to do is be the least bit useful and the least bit worth money for it look pretty good on paper. Plus the longer it builds up without having a good way to get rid of it can make a difference. Especially if one of the physical properties of the asset has something to do with combustibility and/or toxicity. This gives extreme financial leverage compared to comparable chemical processes where a major raw material has a nominal cost, or even an attractive cost. Anyway, naphthalene was an early source of cheap phthalic acids & anhydrides. Also some oil fields have enough naphthalene content for it to be accumulated in the bigger refineries along with other waxy hydrocarbons which are processed in abundance. Plus to meet increasing demand phthalic anhydride can also be made from ortho-xylene which many more refineries are commonly processing a stream of. This may not be zero-cost raw material, but it is still a hydrocarbon which is in bulk and easy to add value to if you're going to do something other than burn it for fuel. In the 1980's the phthalate I would see the most of was "di-octyl phthalate", known as DOP. It was mostly di-(2-ethylhexyl) phthalate since the "octanol" that formed the diester was usually 2-ethylhexanol, not much n-octanol involved. The 2-EH itself was some nasty-smelling stuff, one drop on your foot and you would have to leave your shoes outside when you got home. It was a byproduct of butanol & isobutanol manufacture, which themselves are relatively clean solvents. The 2-EH was clarified but it is a low-volatility solvent that doesn't dry up very fast, and stinks so bad it is not an ideal paint ingredient. There was no published laboratory testing procedure but I did do some pioneering chromatography anyway and there was a rich array of minor byproducts which are still most likely not fully identified chemically yet. So 2-EH is another low-cost item but not much higher viscosity than the butanols. Esterifying to combine with the phthalic and you get the compound DOP, the syrupy liquid used as a plasticizer that doesn't dry up much faster than the plastic solids themselves, and imparts the increased flexibility desired by the processor. I wouldn't be surprised if there are some minor impurities in the DOP that trace back to the 2-EH raw material, which could be much more potent endocrine disruptors than the known plasticizer chemical itself. The statistical possibility is based on the number and variety of unidentified minor constituents, the way that very small amounts of hormones have very outsized effects, and the correlations that have been seen which incriminate the plasticizer and seem to show some connection. Plus, after a few short years being a leading analyst of 2-EH and DOP, one day some highly purified 2-EH became available in "research grade", purchased it to serve as reference material, and it turned out to be relatively odor-free ! It was the 2-ethylhexyl aldehyde content that made it smell so bold. So I have known something was up for a very long time but still don't have all the details I would want. Now if there is some minor component other than the known plasticizer bulk chemical itself which is causing disruption, and in-vivo work is being done on the highly purified reference material in order to evaluate the target plasticizer itself in the absence of as many unknowns as possible I'm not so sure the findings would apply as much in the real would as I would like. At the beginning, phthalates were not optimized to serve as plasticizers. They just happened to not fail at the task. Got more popular, and non-surplus alternative sources of raw materials for plasticizing will break ground to meet the demand once the more-attractively-priced "chemical waste" has all been spoken for. Something like a playbook that predates the plastic age.
Nahtnah 2y ago
This whole thread is a great example of an interesting phenomenon... whenever people talk about this people come out of the woodwork to nitpick the details of whoever is criticizing the wonton use of likely poisonous compounds. Theyll argue things like this about the details of the exact likely bioactivity of the compound, or go on about how its impossible to have modern society without poisoning everything in a huge perfect enemy of the good argument. Like, go drink from a cup of pthalates if youre so ok with it being in your brain, balls, ovaries, etc. No ones arguing we need to ban plastics, but maybe coating the world in single use water bottles without considering the effects is suboptimal. Shouldnt the onus be on proving its safe before spreading it everywhere, rather than proving its dangerous? https://ethz.ch/en/news-and-events/eth-news/news/2021/06/worrying-insights-into-plastic.html https://ethz.ch/en/news-and-events/eth-news/news/2021/06/wor... Theyll call me extreme/ignorant/naive, but maybe a society where we have to poison ourselves to sustain "growth" isnt worth sustaining. Not to mention the constant alarm bells about rising GI cancers in younger people. "OH BuT YOU HAVNEnT staTIstiCALLY prOved A cAusAL AssOCiaTION".
- timr 2y ago
  I'm not nitpicking the parent. The parent comment is just wrong, full stop. You should not listen to them. They have an incorrect notion of what a phthalate is (usually a slightly greasy ester or an alcohol), how polar/hydrophopic they are (mixed; generally ampiphilic), and whether or not they tend to bioaccumulate (in general, they do not). Your broader point is well-taken, however, but not in the way you intended: chemistry does not reward a shallow understanding. The details matter a lot.
  - Nahtnah 2y ago
    You're arguing as if you understand all the side effects of the biochemistry on the biology. None of us do. Theyre correct about one thing: its probably not good for you. But sure, you might be more right on the basics of the biochemistry. I guess I'm just frustrated about the state of the world - im not a degrowth person I just want a better balance. There seems to be plenty of evidence for, for example, their role in endocrine disruption.

timr 2y ago

You can't just say "squeeze between hydrophobic polymers", as if that's a single thing, and therefore any such "hydrophobic polymer" will be vulnerable to a phthalate. In particular, DNA is not hydrophobic -- it's an extremely polar environment. The known DNA/RNA intercalating chemicals are also very polar (at least, in critical selected locations). For example, Ethidium Bromide: https://en.wikipedia.org/wiki/Ethidium_bromide https://en.wikipedia.org/wiki/Ethidium_bromide Point being: assuming that the paper in the headline is true (which I do not assume, but I digress), your theory of the mechanism is probably wrong, and therefore misleading. Edit: having now looked at the paper, they're discussing one specific chemical (bezyl butyl phthalate) which is actually quite polar. It's also an ester, and trivially broken down by common enzymes into a number of different child compounds, any of which could be individually responsible for the claimed effects. Biochemistry is complex.

deleted 2y ago
[deleted]
whatshisface 2y ago
It gets into hydrophobic binding sites, and accumulates in lipids. > Aromatic compounds, aliphatic hydrocarbons, and halogens are the hydrophobic parts of ligand PAEs. Hydrophobic contact is caused by the spatial proximity of the non-polar amino acid side chains and the hydrophobic substituents on the ligand PAE molecules. Water molecules are released from the hydrophobic region upon hydrophobic contact, and the unconstrained water molecules released can participate in the energy-favorable hydrogen bonding interactions, which enhance the overall binding affinity of the ligand [37,38,39]. Therefore, the hydrophobic interactions between ligands and receptors affect the ability of PAEs to bind to hormone proteins and influence the ability of PAEs to bind to DNA response elements. https://pmc.ncbi.nlm.nih.gov/articles/PMC10488033/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10488033/
- timr 2y ago
  The paper is about DNA mutation. DNA is not a hydrophobic binding site. It doesn't interact with hydrophobic binding sites. Moreover, the chemical studied in this particular paper is not particularly hydrophobic. Your theory is wrong, at least in this case. Also, this paper says the opposite of what you think it says: > based on the three-dimensional potential energy surface information, it was discovered that the hydrophobic, steric, and electrostatic fields of PAEs significantly influence their endocrine disruption effects on humans. They're saying that hydrophobic effects matter, but non-hydrophobic effects also matter. So everything matters. FWIW, the paper is not particularly worth citing. Someone made an ML model that said what any competent chemist could tell you by looking at a phthalate.
  - whatshisface 2y ago
    Who said DNA was hydrophobic? I'm sorry, but we're not disagreeing. Phtalates are very lithophilic and that's a major mechanism of their accumulation in the body. If phtalates were highly polar, they wouldn't be soluble in plastic. That means they're going to bind to fat tissue and non-polar receptors. >the chemical studied in this particular paper [...] Also, the paper didn't study "a chemical," it covered about 30.
    - timr 2y ago
      I'm telling you that you're overgeneralizing based on incorrect information. The paper being discussed here directly refutes your hypothesis of action, because it's about a particular chemical that is known to be metabolized, causing downstream effects in an extremely polar molecule (DNA). Generally, "pthalates" are not a thing, but rather a whole bunch of different things (some are hydrophobic, some are not), and many of them are metabolized by the human body, so they don't actually accumulate. You have to be more specific. https://pubmed.ncbi.nlm.nih.gov/17604388/ https://pubmed.ncbi.nlm.nih.gov/17604388/ > If phtalates were highly polar, they wouldn't be soluble in plastic. Setting aside "highly polar", which is not specific, you are wrong. Many/most pthalates are far from what chemists consider "hydrophobic", and are in fact esters, alcolhols and acids. > Also, the paper didn't study "a chemical," it covered about 30. The paper in the OP was about one molecule: BBP.

fuzzfactor 2y ago

>preferring not to know. I think this does have some ongoing influence on why more detailed analysis of common chemicals is not required. From what I can tell, it looks like phthalates started with excess coal tar which contained tonnes of a solid waxy aromatic hydrocarbon called naphthalene that nobody probably had much of a way to monetize for quite some time. Plenty of money was surely being made in other ways so regardless of the accounting methods, the surplus ends up being a no-cost item. When there are tonnes of an unutilized resource like this the full-scale effort would turn every tonne into something useful, and all it has to do is be the least bit useful and the least bit worth money for it look pretty good on paper. Plus the longer it builds up without having a good way to get rid of it can make a difference. Especially if one of the physical properties of the asset has something to do with combustibility and/or toxicity. This gives extreme financial leverage compared to comparable chemical processes where a major raw material has a nominal cost, or even an attractive cost. Anyway, naphthalene was an early source of cheap phthalic acids & anhydrides. Also some oil fields have enough naphthalene content for it to be accumulated in the bigger refineries along with other waxy hydrocarbons which are processed in abundance. Plus to meet increasing demand phthalic anhydride can also be made from ortho-xylene which many more refineries are commonly processing a stream of. This may not be zero-cost raw material, but it is still a hydrocarbon which is in bulk and easy to add value to if you're going to do something other than burn it for fuel. In the 1980's the phthalate I would see the most of was "di-octyl phthalate", known as DOP. It was mostly di-(2-ethylhexyl) phthalate since the "octanol" that formed the diester was usually 2-ethylhexanol, not much n-octanol involved. The 2-EH itself was some nasty-smelling stuff, one drop on your foot and you would have to leave your shoes outside when you got home. It was a byproduct of butanol & isobutanol manufacture, which themselves are relatively clean solvents. The 2-EH was clarified but it is a low-volatility solvent that doesn't dry up very fast, and stinks so bad it is not an ideal paint ingredient. There was no published laboratory testing procedure but I did do some pioneering chromatography anyway and there was a rich array of minor byproducts which are still most likely not fully identified chemically yet. So 2-EH is another low-cost item but not much higher viscosity than the butanols. Esterifying to combine with the phthalic and you get the compound DOP, the syrupy liquid used as a plasticizer that doesn't dry up much faster than the plastic solids themselves, and imparts the increased flexibility desired by the processor. I wouldn't be surprised if there are some minor impurities in the DOP that trace back to the 2-EH raw material, which could be much more potent endocrine disruptors than the known plasticizer chemical itself. The statistical possibility is based on the number and variety of unidentified minor constituents, the way that very small amounts of hormones have very outsized effects, and the correlations that have been seen which incriminate the plasticizer and seem to show some connection. Plus, after a few short years being a leading analyst of 2-EH and DOP, one day some highly purified 2-EH became available in "research grade", purchased it to serve as reference material, and it turned out to be relatively odor-free ! It was the 2-ethylhexyl aldehyde content that made it smell so bold. So I have known something was up for a very long time but still don't have all the details I would want. Now if there is some minor component other than the known plasticizer bulk chemical itself which is causing disruption, and in-vivo work is being done on the highly purified reference material in order to evaluate the target plasticizer itself in the absence of as many unknowns as possible I'm not so sure the findings would apply as much in the real would as I would like. At the beginning, phthalates were not optimized to serve as plasticizers. They just happened to not fail at the task. Got more popular, and non-surplus alternative sources of raw materials for plasticizing will break ground to meet the demand once the more-attractively-priced "chemical waste" has all been spoken for. Something like a playbook that predates the plastic age.

Nahtnah 2y ago

This whole thread is a great example of an interesting phenomenon... whenever people talk about this people come out of the woodwork to nitpick the details of whoever is criticizing the wonton use of likely poisonous compounds. Theyll argue things like this about the details of the exact likely bioactivity of the compound, or go on about how its impossible to have modern society without poisoning everything in a huge perfect enemy of the good argument. Like, go drink from a cup of pthalates if youre so ok with it being in your brain, balls, ovaries, etc. No ones arguing we need to ban plastics, but maybe coating the world in single use water bottles without considering the effects is suboptimal. Shouldnt the onus be on proving its safe before spreading it everywhere, rather than proving its dangerous? https://ethz.ch/en/news-and-events/eth-news/news/2021/06/worrying-insights-into-plastic.html https://ethz.ch/en/news-and-events/eth-news/news/2021/06/wor... Theyll call me extreme/ignorant/naive, but maybe a society where we have to poison ourselves to sustain "growth" isnt worth sustaining. Not to mention the constant alarm bells about rising GI cancers in younger people. "OH BuT YOU HAVNEnT staTIstiCALLY prOved A cAusAL AssOCiaTION".

timr 2y ago
I'm not nitpicking the parent. The parent comment is just wrong, full stop. You should not listen to them. They have an incorrect notion of what a phthalate is (usually a slightly greasy ester or an alcohol), how polar/hydrophopic they are (mixed; generally ampiphilic), and whether or not they tend to bioaccumulate (in general, they do not). Your broader point is well-taken, however, but not in the way you intended: chemistry does not reward a shallow understanding. The details matter a lot.
- Nahtnah 2y ago
  You're arguing as if you understand all the side effects of the biochemistry on the biology. None of us do. Theyre correct about one thing: its probably not good for you. But sure, you might be more right on the basics of the biochemistry. I guess I'm just frustrated about the state of the world - im not a degrowth person I just want a better balance. There seems to be plenty of evidence for, for example, their role in endocrine disruption.