Org Prep Daily

January 23, 2007

organic solvents are bad for ya

Filed under: Uncategorized — milkshake @ 3:13 am

sloniky21.jpg

The Coronene blog brought up a familiar subject – the solvent exposure.  I am not a tox expert myself – but I guess that after few years in the lab one can rank the most-commonly used solvents according to the seriousness of their long-term exposure effects. So here it is the list:

_________________________________________________

Almost drinkable: EtOH, i-PrOH, acetone, DMSO, 1,2-propylene glycol

Tolerable: MeOH, EtOAc, butanols, THF, TBME, ether, pentane, heptane, cyclohexane, DMAc, AcOH, NMP, tetramethyl urea, sulfolan

Unhealthy:DCM, toluene, hexane, acetonitrile, ethylene glycol, formamide, DMF, nitromethane, 1,2-dimethoxyethane, trifluoroethanol, benzotrifluoride

Just Bad: Dioxane, benzene, chloroform, 1,2-dichloroethane, pyridine, p-xylene, methoxyethanol, ethoxyethanol, TFA, trichloroethylene, tetrachloroethylene, allyl alcohol, chlorobenzene, biphenyl+diphenyl ether (aka Dowtherm), o-DCB

Gangsta Badass: HMPA, CS2, CCl4, nitrobenzene

__________________________________________________

Chemists in synthetic labs should probably have their liver tests and blood count done once a year, to pick up any problem signs related to the chronic exposure. Women in early stages of pregnancy have to be particularly careful when working with organic solvents. Lots of factors can influence relative rates of oxidative metabolism and harmfulness of many  solvents (like dioxane, benzene, hexane, glycol, chloroform etc) is due to the products of their oxidative activation. Some individuals are bound to be more sensitive. 

On a side note, it is interesting how solvent toxicity is species-dependent: EtOAc, dichloroethane and cyclohexane are much more toxic to insects than to humans.

45 Comments »

  1. i thought methanol was pretty bad for ya?
    suppose this means i have to avoid the early stages of pregnancy, then. good. that was the plan anyway :)

    Comment by Ψ*Ψ — January 23, 2007 @ 3:35 am

  2. MeOH is bad only if you drink it. There is a treshold below which not realy much happens – MeOH is a naturally-occuring metabolite. So one can wash the glassware and clean the bench with MeOH without much grief. Besides, any suspected poisoning with MeOH is a good excuse for ingesting a large quantity of ethanol, as an antidote…

    As far as the pregnancy goes – one should avoid it for the sake of graduating… It is good idea to limit the exposure to all solvents in the first trimester. There was couple of bad cases in Prague in seventies, at two Acad Sci institutes, with chemists having malformed babies. It was most likely related to the exposure to chlorinated solvents and monomers. With commies being in power and all, this scandal was hushed up but the fallout was an unofficial policy in the academic labs there, of re-assigning chemists out of lab for the duration of their pregnancy. It was probably an of over-reaction, but with not-so-good hoods and lots of unhealthy stuff around nobody wanted to take chances and have another tragedy.

    Comment by milkshake — January 23, 2007 @ 3:55 am

  3. CS2 landed me in the ER once. It is a CNS depressant. Very scary stuff.

    HMPA, while terribly toxic, is the worlds greatest aprotic polar solvent.

    Comment by Milo — January 23, 2007 @ 10:08 am

  4. That is an eerie picture!

    Anyway, I don’t doubt your listing in any way, but I wonder if you’d mind divulging your source? Is it wisdom/experience/legend? Sifting through MSDS or other safety information? Or is this all compiled much as presetned in a book or something somewhere?

    (The reason I ask is because I am in the process of setting up a new academic research lab, and I’d like to post notes about conventional lab wisdom in said lab, and this would be a good candidate.)

    Cheers

    Comment by Russ — January 23, 2007 @ 10:34 am

  5. I do not agree with the position of toluene on your list, since I believe it is readily metabolized to benzoic acid.
    Don B.

    Comment by Don Butler — January 23, 2007 @ 10:59 am

  6. I don’t think toluene is that healthy, considering the profound brain damage found in toluene sniffers. Toluene is supposed to be about 10 times less toxic in bone marrow than benzene because of the lower metabolic stability – as you pointed out – but it is not like going one step down from benzene is gonna give you an innocuous solvent that one can drink. Besides, I HATE the smell of toluene, hence it’s unhealthy on my list.

    Comment by milkshake — January 23, 2007 @ 1:33 pm

  7. EtOAc — What’s the toxicity profile on this guy? I thought it was pretty much harmless since it is catabolized to Ethanol and Acetic Acid; although it’s a bit lipophilic. Surprised that DMSO is worse than EtOAc.

    Comment by DarkSyde — January 23, 2007 @ 2:47 pm

  8. You know, EtOAc vapors make me cough (they irritate lungs) and I don’t like the smell of the stuff. Also, after killing lots of bugs with a EtOAc jar I cannot put EtOAc into the drinkable category.

    Comment by milkshake — January 23, 2007 @ 3:16 pm

  9. EtOAc is sold (not sure of concentration as it would be pointless to paint my nails in the first place) as acetone-free nailpolish remover. I agree about the smell, though. Toluene isn’t fragrant either. It is also NOT NOT NOT a fun recrystallization solvent.

    Comment by Ψ*Ψ — January 23, 2007 @ 8:03 pm

  10. Our deputy lab manager spent two blissful nights in hospital on an ethanol drip after being showered in methanol… I pretty much loath the smell of THF and avoid using it. What is the main danger of dioxane?

    Comment by propter doc — January 24, 2007 @ 12:45 am

  11. I hate THF smell – it smells to me like horse stables and it always gives me a headache. But THF is supposedly not too bad – except for some microbes (if you have a large THF runoff it can ruin the lives of water-purifying microbes employed in sewage treatment plants)

    Dioxane smells very nice and its a great solvent for Suzuki reaction. I like to use it for freeze-drying also. Unfortunately the metabolites (hydroxylated dioxane – hemiacetal and dehydrogenated dioxane with C=C) are reportedly strong carcinogenes.

    Comment by milkshake — January 24, 2007 @ 1:04 am

  12. Gotta love the “gangsta badass” category. Why didn’t I notice that earlier?

    Comment by Ψ*Ψ — January 24, 2007 @ 11:32 am

  13. I changed the wording… Must be Kyle’s influence

    Comment by milkshake — January 24, 2007 @ 2:06 pm

  14. The picture is amazing! Where did you find it?

    Comment by Albert — January 24, 2007 @ 4:05 pm

  15. Isn’t ethyl acetate a food additive? Is allyl alcohol bad because of the possibility (no, fate) of oxidation to acrolein?

    Comment by TNC — January 24, 2007 @ 9:39 pm

  16. I had a prof in grad school that said if your boss ever tells you to use HMPA, turn around, walk away and never return. “Gangsta badass?” Hell yeah!!!!

    Comment by Chemgeek — January 24, 2007 @ 10:47 pm

  17. I would be suprised if they put EtOAc into food as flavoring – it is not very flavorful or hydrolyticaly stable. Couple of other higher esters get used as cheap fruity flavor (banana, bubble-gum, pineaple, rum, etc) but I have not heard of EtOAc itself.

    Funny thing, benzaldehyde is a food additive but when you buy a bottle of the stuff from Aldrich you see stark warnings “Highly toxic! Target organ – nerves!”

    The picture is apparently something from a Komsomol field trip, from a period before WWII. I got it of the Humor section in okoun.cz

    Comment by milkshake — January 24, 2007 @ 11:28 pm

  18. You czechs sure have some sense of humor. Also, I don’t believe that ethyl ether, AcOH, pentane and hexane are bad for you. I’ve practically bathed in the latter.

    Comment by Ryan K. — January 25, 2007 @ 9:07 am

  19. I am a bit surprised at the inclusion of CS2 & CCl4 in your Gangsta Badass category.
    In industry we are allowed to use these whereas benzene is virtually banned

    Comment by BaggieBoy — January 25, 2007 @ 9:17 am

  20. Benzene is not too horrible – a sort of over-reaction developed because of its previous wide-spread use (it is a great solvent and people thought hydrocarbons were innocuous). Carbon tetrachloride is just as bad as benzene with chronic exposure but is worse on acute poisoning – and CS2 is incomparably more so.

    Hexane is rather unhealthy – it is metabolised slowly to hexane-2.5-dione that is pretty neurotoxic. It was found that hexane is not so safe in chronic exposure when workers in a vegetable oil plant developed problems (they were using hexanes for extractions on masive scale). Pentane and heptane are not harmful so it is most likely related to the 6 carbon chain metabolites. It is definitely not on scale of benzene toxicity – but if I were you I would not wash hands in hexane.

    Comment by milkshake — January 25, 2007 @ 9:42 am

  21. Where do you get off calling biphenyl a solvent? I mean, i’ve seen stranger things but, uh, that one is odd.

    CCl4 can’t possibly be as bad as people say. One of my grad profs talked about using the stuff as household cleaner when he was a kid- you know, back when men were men and mercury was still safe. And as he rightly put it, “Most of us are still alive.” I feel the same way about benzene.

    Comment by excimer — January 26, 2007 @ 11:39 pm

  22. In times when men were men (and students were instructed to use CCl4+dry ice for -20C baths in freshman labs because it was simplier and less messy than making the salt slush) nitrobenzene was used as co-solvent in furniture wax polishes and as a cheap household roach repellent/insecticide.
    Mother of my highschool classmate was working in enthomology lab and they had jars of HMPA around as a safe agent for making their bugs sterile. They were using it on routine basis – before they found out it worked in humans too…

    Biphenyl is pretty obscure – although there is a high-boiling and low-freezing cheap diphenyl ether + biphenyl industrial mix that some folks like to use as a solvent for very-high temperature experiments. I won’t mind diphenyl ether but I would avoid the biphenyl part of the mix.

    Comment by milkshake — January 27, 2007 @ 12:40 am

  23. there is nothing so swell as a good ether buzz at around 3:30 PM

    I find MPBK and isopropyl acetate to be rather pleasant smelling

    Comment by anon — January 29, 2007 @ 1:53 am

  24. Acetonitrile on the unhealthy list?? I am suprised at that.

    Badass gangster class- don’t forget dimethyl sulfate (maybe only marginally classifiable as a solvent, but all the same, spooky).

    Best smell ever- trimethyl orthoformate. Sweet, fruity, ethereal.

    Comment by Jose — January 29, 2007 @ 6:07 pm

  25. don’t forget dimethyl sulfate

    Anyone using dimethylsulfate as their solvent definately has balls. And unless they have clean technique, those balls will get methylated.

    How does Me2SO4 stack up against the organomercury compounds?

    Comment by Chris — January 31, 2007 @ 12:52 am

  26. I think dimethylsulfate is usualy lot quicker than dimethyl mercury – that is, unless you survive it but slowly develop cancer afterward in which case dimethyl mercury would be speedier.

    There was case in Prague in 70s, I think. Dr. Hub – he was making trimethyl thalium from dimethyl mercury as a starting material, had a spill, cleaned it up and died few weeks later. Ugly way to go – blind, mute, in spastic seizures combined with paralysis. There was also a postdoc in Prague who worked in a poorly ventilated lab with dimethyl sulfate at night and they found him choked on the floor in the morning… Make a pick.

    Comment by milkshake — January 31, 2007 @ 1:54 am

  27. Although dimethyl sulfate would be absolutely insane to use as a solvent, when it is used for methylation in a fume hood, via gas-tight syringe out of a sure-seal bottle, wouldn’t the risk be minimal? I know all potent methylating agents are massive inhalation hazards, but, are still commonly used.

    Some people even prep magic methyl. That is ballsy.

    Comment by Tom — January 31, 2007 @ 2:27 am

  28. Yeah, dimethyl sulfate is quite overrated, my ex-boss was scaling-up piroxicam in a pharma plant in Czechoslovakia on Saturday night – and he and his colleague managed to dump 200 liters of dimethyl sulfate on the plant floor. You know, they were filling a reagent addition reservoir that had a small test ventil open… (Their supervisor dropped by on Sunday morning and asked: “Say, what’s that oily stuff on my shoes?”) I think the bad part is that dimethyl sulfate has no smell so by the time one starts coughing it’s usualy late.

    I was doing recently methyl triflate methylation on 100 mmol scale, and sure I doubled my gloves and had a large dish of ammonia evaporating nearby in the hood. By the way, it turns out that one can type a hell lot of faster with six-to-eight fingers on each hand…

    Comment by milkshake — January 31, 2007 @ 2:54 am

  29. One has to remember that it is the dose that makes the toxin. Just look at water… water poisoning while rare, can kill (painfully, I think…)

    You would be very surprised to learn what goes into natural and artificial flavors. That whole industry relies on low dose and high impact chemicals.

    in California, CH3CN is considered a cyanide and needs to be disposed of appropriately. Nevermind the fact that it is hydrolyzed in your belly and the a Me-CN bond is a whole lot different than a K-CN one.

    HMPA is a perfectly safe solvent, if you treat it with respect. In the words of the NRA: “guns don’t kill people, people kill people”… treat the HMPA with respect and you will not develop nose cancer.

    Comment by Milo — January 31, 2007 @ 8:52 pm

  30. I agree ~ the dangers of carbon tet and benzene are well established, but, in all honestly, are those solvents going anywhere? Most likely not. The thought of using dimethyl sulfate over methyl iodide to methylate phenolic oxygens and other hard nucleophiles at was a bit unnerving to me at first. However, i’ve used liters of Me2S04, and am still standing on my own two feet.

    I know some people even frown upon Stille couplings, but will that reaction ever get discarded? Not likely.

    Comment by Tom — January 31, 2007 @ 10:51 pm

  31. I find it’s easier in the long run to just plain avoid
    the ‘bad players of process chemistry’
    like Dioxane, HMPA, & TCE (which is just nasty viscous)

    & make it happen in scale-up friendly solvents like Acetone, DMF, NMP, EtOH, IPA &
    to a lesser degree, MeOH & THF.

    TBME makes me sick to my stomach & I won’t use it.

    Comment by Anon — February 6, 2007 @ 4:05 pm

  32. Actually benzotrifluoride is not too bad process solvent, bp=100C and the price is becoming more reasonable. They also make now the 2-methyl-THF which is higher boiling than THF and only partly miscible with water, but it is stil somewhat expensive for process

    Comment by milkshake — February 6, 2007 @ 7:37 pm

  33. I think there is no solvent in organic chemistry lab which is safe for organic chemist.

    Comment by Prakash kotame — March 1, 2007 @ 8:55 am

  34. I feel smell of all aliphatic amines inactivate our (ras)ie. reticular activating system which is present in the brain

    Comment by Prakash kotame — March 1, 2007 @ 8:58 am

  35. I have zero background in chemistry, never even took it in highschool! But what I’m seeing of mother nature is that she has perfectly balanced chemicals in foods and it’s when we remove them and use them in unbalanced, higher concentration (unnatural ways) that she bites us on the arse for that.
    I was shocked to find out apples have carcinogens but obviously they’re balanced in such a way to do more good than harm because they certainly help fight cancer!

    Anyway, my question here is about orange oil (limonene, rather). I like to tinker with herbal stuff (although I consider myself very conservative when trying new things) and I put a few teaspoons of some orange oil, together with vodka and water in a spray bottle and started out after a couple of roaches in the kitchen. After a while, I was coughing, so I thought that this natural chemical might be bad for the lungs.
    I started googling, only to find out it is a solvent that can harm the liver if too much is ingested! Solvents seem to be very bad for the body.
    Also, there have been a high number of Alzheimer’s patients who have worked with solvents over the years and although they can’t prove it’s a major cause of Alzheimer’s, it’s certainly good reason to suspect.
    I just read today that the zest of citrus (limonene, essentially) can stop the growth/reduce tumors!

    So, how much is too much? You don’t want to damage the liver or cause other harm that solvents seem to but you want the benefits. Lemon zest tastes great in lemonade, by the way.

    Also, water is a solvent. Could that be a problem for people like myself who drink about 3/4 of a gallon per day?

    Thanks

    Comment by chemically challenged — April 12, 2007 @ 1:26 pm

  36. I am not a tox expert and your quetions are quite vague so I can’t realy answer them.

    Orange oil is supposed to be pretty safe (and it smells nice) but ingesting it or inhaling it is not a good idea. No permanent harm was done to you. FYI, if you inhale grapefruit juice by accident – as it happened to me once – I assure you will cough your lungs out, too.

    To get rouches out, I would call a professional exterminator because by the time you see few, you have a already nice colony sharing the living space with you, you have a rather big problem and repellent does not help much.

    The “balance” has nothing to do with chemical safety – it is more like an evolutionary adaptation to many things found in the nature. But not all that is natural is safe – there is lots of herbs (and molds, and bugs) that can put you under. Think of all these poor cavemen experimenters who have gotten sick (or dead) while doing the edibility experiments.

    Comment by milkshake — April 13, 2007 @ 6:59 am

  37. Combat gel works the best for roaches, it can be bought at the store. Unfortunately, I have critters and can’t apply this stuff everywhere that I need to (for their safety). The kitchen is clean, there’s nothing for them to eat but I live in an apartment and when someone moves out, their roaches come to visit.

    I hate grapefruit juice, so there’s not too much worry of inhaling that. ;)
    Orange oil works great on cleaning wood cabinets but I think next time I use this stuff, the area needs to be well-ventilated!
    It didn’t give me asthma but it sure did make me cough. I did read somewhere that it can affect the liver….I don’t know if that’s from ingestion or what.
    I do know that there are many recipes that use the zest of citrus fruits but I suppose that the amount of limonene ingested from the recipes is not enough to show any immediate health problems.

    I am interested in the possibility that limonene has an effect on tumors, though! I think that is very important and the research should continue.

    Herbs can indeed be dangerous! My parents used to give me primatene (ephedra er, pseudo-ephedra) as a kid for asthma attacks. Just because they don’t give you a heart attack on the spot doesn’t mean they are not still doing damage!
    When I got older, I got smart and broke them up into quarters and eighths and took only what I absolutely needed, I knew the crap COULDNT be good for the body!
    After the reports came out on ephedra, I got smarter and began using benadryl and strong cocoa for asthma attacks (though I rarely get them anymore).

    I agree that some things are bad even in their natural state, in small quantities but we heap a lot of burden on ourselves by extracting, mining and condensing stuff that wasn’t meant to be. I know that cavemen probably suffered a lot when they started extracting metals.
    I wonder why it took so many centuries for everyone to realize that lead is deadly! They’re finally starting to realize that aluminum and probably many other metals can be bad also.

    Comment by chemically challenged — April 13, 2007 @ 10:26 am

  38. FYI–The best solution I’ve ever found for bugs of any sort is 100% natural. Get several cats. You may never see a living insect in your apartment again. :)

    Comment by Ψ*Ψ — April 22, 2007 @ 10:53 pm

  39. Hi,
    I work with methanol and acetonitrile in analytical lab. I supposed to work under the hood but over the past two years, sometimes I carelessly worked outside the hood with these two solvent, usually around 500 mL to 1 liter amount. Should I be worried? I would like to know how toxic of these two solvents? And how much ppm will go into the air under 500ml – 1 liter outside the hood? Thanks a lot.

    Comment by Kiet — August 15, 2007 @ 2:38 am

  40. Methanol toxicity is overrated – people have been drinking bad moonshine too much. Unless you are ingesting gram quantities of methanol, you are not in danger. But I wouldn’t wash my hands or bench with methanol, just to be sure.

    I believe acetonitrile is worse and getting exposed to lots of acetonitrile repeatedly can affect your health over time. The first thing probably would be tiredness, elevated liver enzymes and changes in kidney function. So try not to pour it over yourself, or huff it needlessly (acetonitrile has a very faint odor and some people cannot smell it at all) and if you get it on your hands you should wash it away promptly. But the risk is not comparable with the really nasty solvents like CS2 or nitrobenzene or CCl4 – those can actually make you pretty sick quickly.

    If you are pregnant or nursing, you should be extremely cautious with any solvents.

    Ananlytical HPLC in the lab should be fine, people mostly have the instrument with bottles on top sitting on the bench, not in the hood. I think more problem have people who do preparative HPLC and deal with gallon quantities of acetonitrile on daily basis.

    Comment by milkshake — August 15, 2007 @ 6:28 am

  41. I have used a lot of solvents, including the nasty ones. The one I hate the most is pyridine. It really makes me sick to the stomach. I get nervous handling pyridine, while I can deal with HMPA, etc. The one thing that has been ingrained into me is: “treat all chemicals the respect they deserve and you are safe”.

    Comment by Vinod Jairaj — February 6, 2009 @ 12:59 am

  42. Since my sister is a working chemist, I wonder what could be the possible diseases she could possibly get with these harmful solvents? but yeah, good thing she is having her liver checked and also taking some supplements L-glutathione in her case to prevent liver problems.

    Comment by Table Saw — February 17, 2012 @ 5:28 am

    • Well she can have a child with a birth defect. There was a problem of this sort in Prague in 70s, with lab technicians giving birth to higher number of children with congenital problems, and the outcome of this affair (swept under the rug) was an unofficial rule that the female co-workers as soon as it became known they got pregnant were assigned away from the synthetic lab duties for the duration, just to be on the safe side.

      Comment by milkshake — February 17, 2012 @ 10:24 am

      • Hi,
        I’m 3 months pregnant and still working in the lab, but just doing the safe things. But my colleague is using DMSO for all her experiments (dissolving products etc.), and she’s is not using the hood at all, but just on her table next to me. I’m so scared right now… should I?

        Comment by Maya — July 23, 2012 @ 4:58 pm

        • DMSO is probably one of the least toxic solvents but it would serve you well to transfer yourself away from the lab for the duration of your pregnancy. One thing to consider is that DMSO absorbs well through the skin and makes skin perfectly permeable, so whatever is dissolved in DMSO it takes right through the skin on your fingers. Also fetus is most sensitive to genotoxic insult during the first trimester… Maybe, if your do research work in a biology lab it is not as dangerous but you would have to be careful to stay away from volatile organics, acrylamide monomer for making gels, ethidium and other stains and so on. I think it is not really worth the risk. Also, there is a few% chance of having a child born with a birth defect from natural causes, and it is hard to determine in retrospect what exactly caused it – then you would be blaming yourself forever that perhaps you somehow caused your child being born with a defect, by working in the lab during the pregancy

          Comment by milkshake — July 23, 2012 @ 8:09 pm


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