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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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May 14, 2009

TMS Diazomethane: Update On a Fatality

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Posted by Derek

I've been contacted by several people over the last few weeks about the TMS diazomethane-linked fatality in Nova Scotia (first written about here). Many more details are emerging about the case, chief among them that the fume hoods in the lab were apparently down for maintenance during this time.

Here's a newspaper article that's just appeared. I'm quoted in it as saying that I would have refused to work under such conditions, and I stand by that. But that's not surprising: in every industrial lab I've ever worked in, when the fume hoods go down, people roll their eyes and walk out the door. I most especially cannot recommend working with something like TMS diazomethane in such a situation.

Comments (42) + TrackBacks (0) | Category: Chemical News


COMMENTS

1. CMCguy on May 14, 2009 11:47 AM writes...

This is sad, particularly because it likely could have been avoided by relatively simple measures. As suggested most chemists should leave the lab if hoods stop working, even if not a formal written policy that it is most places. Likewise most fume hoods these days should be alarmed if flow stops are drops below set point, which is mandated by some States/Local authorities.

As a Chemical Hygiene Officer I was tasked with going around if hoods went off and/or alarms continued beyond short time, and frequently had to chase people out who wanted to continue working. Was likewise responsible for notifying/coordinating labs if planned maintenance/construction would effect utilities. At the same time I have had to perform myself or help others reach a controlled hold status when hoods/power lost suddenly to prevent potentially more serious event that might occur if a reaction/reagent left unattended.

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2. Hap on May 14, 2009 12:00 PM writes...

I was under the impression (meaning I don't know exactly why I thought this) that TMSCHN2 wasn't preferred because of lower toxicity but because it's easier to handle (it doesn't go boom if you look at it, use ground glassware, etc.). Is that accurate?

What exactly could you do in a chemistry lab if the hoods go down? The article suggest that there were restrictions on the work to be done, but considering it's an organic chem facility, I don't understand what restrictions would have allowed people to do any lab work (well, consistent with any sort of safety regulations or concern for your employees' health).

Then, of course, there's the comment that he could taste the TMSCHN2 in his mouth as he lay dying. I don't know how he knew that and I'm sure I don't want to find out.

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3. organikchemist on May 14, 2009 12:48 PM writes...

Where I am, every time the hoods go down, people voluntarily leave the lab. Those that don't quickly find out how effective the hoods are at pulling various headache inducing things from air around their bench.

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4. pharma chemist on May 14, 2009 1:52 PM writes...

Hap,

In our labs you can't do anything when the ventialation goes down, or rather you really shouldn't. In my research setting (large pharma) whenever the ventilation goes down you are to suspend all work in hoods - close the sash and snuggle up with some paperwork. But the main enforcement is concern for your own wellbeing, I don't particularly remember heath and safety doing rounds during this time. There are always cavalier chemists - wonder if this situation is something like that.

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5. Petros on May 14, 2009 2:24 PM writes...

Dreadful. I remember the day I was in the middle of adding cyanide to an aryl diazonium salt when the hoods whent down!

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6. Hap on May 14, 2009 3:40 PM writes...

The MSDS for the hexane solution here (PDF) of TMSCHN2 doesn't seem real helpful - there seems to be more note of the hazards of the hexane solvent than anything else, though the MSDS does note the potential lung damage from swallowing or inhalation. Seeing this, I wouldn't be thinking of its hazards in the same way as those of diazomethane or phosgene or dimethyl sulfate, though one probably should.

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7. MikeEast on May 14, 2009 3:50 PM writes...

I remember when there was a black-out in California during my post doc. We insisted that everyone leave the building. Power was out for about a 1/2 day and it took several additional hours for the labs to become comfortably habitable. Made me realize how effective the ventilation system was for removing all lab vapors, not just those in the hood.

People should be *forbidden* from working in a lab that has the ventilation system off.

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8. diazomethanemaker on May 14, 2009 4:25 PM writes...

How much of it were they using!!!! I think there is more to this story than just fume hoods going down, most likely someone who didn't know what they were doing to begin with. There are better ways of doing such transformations on large scale.

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9. milkshake on May 14, 2009 4:36 PM writes...

MSDS often isn't such useful source of exposure risk info, from the formulaic way its written its sometimes hard to tell apart hazards of pure sand from a chemical warfare agent.

The guy should have known about the risks of volatile hard alkylating agents - and his boss definitely should have known. (Many chemists ended up on intensive care unit, or dead, because of exposure to vapors of dimethyl sulfate, magic methyl, methyl triflate and diazomethane). Doing a scale-up work without a functioning hood is a seriously bad idea even with much less nasty reagents (as the exposure in a big scale work is much harder to avoid). It would be worth examining whether the boss of this victim was pushy and encouraged him to finish his synthesis assignment ASAP, despite of the hood shutdown.

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10. m on May 14, 2009 6:49 PM writes...

I find it as #8 that its not the whole story.
If he did taste it, how did he breathe it.If u add TMSDiazomethane with cooling at any reasonable scale it shd be okk....

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11. Hap on May 14, 2009 7:05 PM writes...

If he was tasting it long afterwards (well, not so long, unfortunately), he had to have gotten a really big dose. Winter in NS can't be warm, so I wouldn't think the lab should have gotten that hot, even without hood ventilation. How'd he get such a big dose - even doing a reaction on large scale, he shouldn't have been exposed to it for long, unless it evaporated from the reaction and hung around the lab.

I can see MS's theory - no one in their right mind or with a choice would run scaleup with toxic volatile reagents with the hood off. I don't know how TMSCHN2 smells (another on the list of things I'd prefer not to find out), so I don't know if there would have been warning of dosage.

What a nightmare.

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12. InfMP on May 14, 2009 8:10 PM writes...

I added a note on the wikipedia page about this when it happened. you would be surprised at how many chemists see these pages before ordering from aldrich. the best i can do.

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13. InfMP on May 14, 2009 8:50 PM writes...

you can taste benzyl bromide in the air when people are using, throwing it in waste outside their hoods etc, even though it very low amounts in the air. Im guessing this is the same thing. by the way, I hate that taste. I had an undergrad throw a few mls down the sink and now i can bearly stand the stuff.

Winter in NS is not warm, but it rarely goes below -10, unlike central canada, where the cold is sometimes -30 or worse until april.

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14. Anonymous BMS Researcher on May 14, 2009 10:07 PM writes...


From time to time a notice will be posted at my site saying the hoods will be down for maintenance at 5PM on some near future date, or that water will be off in a particular part of the building, or whatever, and therefore during the shutdown ALL work that would be hazardous as a result of the shutdown MUST cease during that shutdown.

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15. jGault on May 14, 2009 10:53 PM writes...

I have to agree with some of the other comments listed. I think there is something else going on here. When I worked in a combi lab we did very large scale safety catch linker work with TMSCH2N2 with probably less than adequate engineering controls (I am not proud to say some embarassing admissions here) but I know I got some exposure to this stuff. The LD50 numbers in the MSDS suggest you would need a very healthy dose (if your a rat) to cause serious harm. Although I have no doubt this stuff can do some serious dammage in the right doses, my past experience suggest to me this was not a simple incidental exposure.

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16. Jose on May 15, 2009 12:05 AM writes...

Jgault- Any indication if those MSDS numbers are dermal or inhalation? There might be some insidious pulmonary action here?

Another underlying issue is that ER docs simply have NO idea what to do for serious chemical exposure. They just go by the MSDS (often worse than nothing IMHO) and then hope to contact a clinical toxicologist in time. Some ERs won't even admit you, for fear of "contamination."

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17. vasili on May 15, 2009 3:33 AM writes...

Jose's comment is right. When I was at Uni, a girl got a spill of CH2Cl2 in her eye, went to ER and the first question she had after explaining the incident was : is that a base or an acid?

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18. UK Academic on May 15, 2009 3:59 AM writes...

A real tradegy, as everyone above has said, something that could have been avoided and really should not have happened.
In contrast to the young, inexperienced researcher who had the accident with the BuLi at the end of last year, this accident occured to an experienced researcher, which should be a lesson to us all not to become too complacent in our work.
A number of years ago I witnessed an accident with TMS-diazomethane, which maybe people should take note of. An a-diazoketone was being prepared from the acid chloride with TMS-diazomethane, on a reasonable scale, when the reaction was quenched, there was a strong exotherm, green fumes, reaction mixture spilling from the flask and the lab was evacuated. Fortunately the fumehoods were working and everyone was fine. Now I don't know what the chemistry involved in the tragic accident was but I wouldn't be suprised if it was a reaction which exothermed under the reaction conditions or one where there was a quenching type accident.
TMS-diazomethane may not be explosive but it is jst as dangerous, possibly more as it sits on the shelf looking all innocent. Respect it!

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19. R.B. Woodweird on May 15, 2009 6:31 AM writes...

"When I was at Uni, a girl got a spill of CH2Cl2 in her eye, went to ER and the first question she had after explaining the incident was : is that a base or an acid?"

These are all the premeds who we taught. See, they were only interested in what they needed to know for the next exam.

In grad school, I came into the lab one day to find the jagoff PI distilling something out on the benchtop next to my hood. I asked him what it was. When he said "HMPA", I turned around and went home for the day.

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20. diazomethanemaker on May 15, 2009 8:38 AM writes...

The real danger in a lab is the other idiots you have to work with who just don't care about doing things in a prudent manner. Good think no one else was hurt by this idiot, this isn't a tragic story but one of carelessness. If the person was lacking in experience then it's his bosses fault.

It's the mark of a skilled chemist that he can work with dangerous things SAFELY. I've made grams of diazomethane (not tms), worked with kilo's of cyanide, plenty of phosgene, the list goes on. All of it was done with care and planning. This is my job

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21. molecular architect on May 15, 2009 8:41 AM writes...

Milkshake is right about the uselessness of most MSDSs. These evolved into legal documents meant to cover the ass of the supplier company and your employers rather than authoritative sources of useful and timely information. Hence, the worthless statement "to the best of our knowledge, the chemical, physical and toxicological properties have not been thoroughly investigated." that appears on almost every MSDS.

I stopped taking these seriously when I first saw the one that Aldrich publishes on sand and one for another supplier for hplc grade water.

The moral of the story is: whenever you work with chemicals research the hazards first and never work without proper safety controls.

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22. Chemoptoplex on May 15, 2009 9:24 AM writes...

"Chronic: May cause cancer in humans. Prolonged exposure to respirable crystalline quartz may cause delayed lung
injury/fibrosis (silicosis).
Section 4 - First Aid Measures
Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower
eyelids. If irritation develops, get medical aid.
Skin: Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and
shoes. Get medical aid if irritation develops or persists.
Ingestion: Do not induce vomiting. Get medical aid if irritation or symptoms occur.
Inhalation: Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If
breathing is difficult, give oxygen. Get medical aid if cough or other symptoms appear."

Everyone off the beach!

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23. Jose on May 15, 2009 10:14 AM writes...

The only decent source for real exposure info is the NIOSH Pocketguide, here:

http://www.cdc.gov/niosh/npg/

Bookmarking it isn't a bad idea for all chemists!

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24. milkshake on May 15, 2009 4:50 PM writes...

I just searched the NIOSH pocketguide and found this hilarious gem:

Diazomethane (gas, bp -9F)Yellow gas with a musty odor. Note: Shipped as a liquefied compressed gas. Can cause frostbite on skin.

So much for the decent source of info

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25. Hap on May 15, 2009 6:56 PM writes...

A Google search didn't seem to return anything useful. Gelest's page seems to return even less useful data than the previous PDF (once again, the emphasis is on the hexane solvent toxicity). The NIOSH pocket handbook doesn't list it. The mechanism of its reactions should give one pause (and previous toxic exposures like those in Winstein's lab), but there doesn't seem to be anything obvious to make one strap on the respirator when working with TMSCHN2 (well, before now). There doesn't seem to be any good reason to work with the hood off, but once that relevant safety warning has been discarded (by the chemist or management), there aren't any obvious red flags.

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26. Jose on May 15, 2009 7:12 PM writes...

"Shipped as a liquified compressed gas". OK, so much for accuracy....

However, they do list pulmonary edema, which seems odd and specific enough to pay attention...

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27. Coyote on May 15, 2009 7:47 PM writes...

Does anyone know the details of the other death, Jason Siddell? If he dropped a container containing TMS diazomethane on his clothes, it must have been a fairly large amount and absorbed/inhaled right away. I would like to think if that happened to me in lab, I would be quick enough to remove my labcoat and clothes while holding my breathe - but, I guess not? That, I think is pretty scary!

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28. milkshake on May 16, 2009 4:22 AM writes...

often its the cleanup that produces a far worse exposure than the initial spill. See, when you smell the stuff but it does not feel irritating you keep wiping it out - and the cough takes few hours to develop...

Skin absorption does not lead to lung edema - it must have been from inhaled vapors

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29. T on May 16, 2009 10:40 AM writes...

This is really unfortunate. I realize too now the power of fume hoods to protect chemists from chemical exposure.

As an illustration, once upon a time in grad school - I was running a simple hexane:ethyl acetate column in the hood when in the middle of the purification the fume hood was abruptly shut off. I proceeded onward, but, by the end on the column, I was sickened by the constant smell of hexane vapors.

And that was just hexane! I shudder when I think what could happen with more acutely toxic chemicals.....

#19: Distilling HMPA on the benchtop? Yikes. Once, someone told me that if your advisor told you to use large quantities of HMPA, you simply turn around, walk away and never come back. Good times.

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30. Jan Teller Jr. on May 16, 2009 3:16 PM writes...

What a disgrace...my blood boils when I read things like that..

Chemistry deserves a lot of respect...

The very third reaction of my PhD was the TMS-N2 esterification of a carboxylic heterocycle. I wasn´t supervised at that time, as usual, but the reaction went perfect and no issues whatsoever.

I remember checking all the literature I could find plus asking every single postdoc I knew in the School. I lost a day or so before putting my hands on. My PI went mental, as usual, but in such moronic circunstances I am happy and actually very proud of having handle with minor incidents many tricky reactions with nasty reagents.

If somebody at the beginning of their career read this and feels is pushed too much. Please, first think about your health and your labmates safety, then think about how to deal with the learn situation and always listen to the experienced guys in the know, and finally...very finally, think about how happy is going to your PI if the reaction works.

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31. Jan Teller Jr. on May 16, 2009 3:38 PM writes...

HMPA is not too bad. Specially if you dont have to distill it.

My personal nightmares in the lab, always with mentally challenged individuals only worried about getting results ASAP by working as less as possible:

- Alkylating agents and Michael acceptors such as MVK not stored properly and left standing at rt in the middle of the summer.

- The excess of TMS-N2 or an alkyl halide evaporated in a Buchi which is not in the fumehood and not cleaned afterwards.

- Guys leaving in a fumehood full of acid bottles, residual unlabelled aqueous solutions of cyanides, HF, azides, etc. Organometallic and inorganic fellas, are quite prone to do this.

- People messing around with solvents bottles and washing bottles. Specially when you want to distill THF or ether.

- Azides not stored in the freezer.

- Guys dihydroxylating with OsO4 messing about.

- Blue, green and massive spots corresponding to metallic salts all around the balance...

.....

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32. Jan Teller Jr. on May 16, 2009 3:39 PM writes...

HMPA is not too bad. Specially if you dont have to distill it.

My personal nightmares in the lab, always with mentally challenged individuals only worried about getting results ASAP by working as less as possible:

- Alkylating agents and Michael acceptors such as MVK not stored properly and left standing at rt in the middle of the summer.

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33. S Siddell on May 18, 2009 11:53 AM writes...

My name is Stephanie, mom of Jason Siddell. Although Jay's accident occurred in January, 2008, we still do not fully know what transpired that day. We have received the OSHA report, and unfortunately, due to exemptions to the Freedom of Information Act, many details have been withheld from us. The knowledge we have has been provided by the coroner's investigation. Since losing my son, I have done much research and have found amazing inconsistencies where TMS Diazomethane MSDS sheets are concerned. As a layperson who has lost a child (yes, he was 24, but he was still my child), this is unfathomable.

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34. Anonymous on May 18, 2009 6:47 PM writes...

I think part of the problem is that we use dangerous chemicals every day without any problems, because our workplaces and workflows are designed to minimize the dangers (which is good and necessary), so we become lazy. The familiarity makes us lose our respect for what we're working with. And then terrible accidents like these happen.

Most of us have a mental list of the "really dangerous" chemicals, and take extra caution when using them, but, because these mental lists are influenced by our experiences, and because, for a lot of chemicals, the risks just aren't fully known, these mental lists are incomplete. MSDS's don't really help because they over-emphasize the dangers of everything and seem to be written more to satisfy lawyers than chemists. I have seen lists of chemicals and classes of chemicals that are considered particularly dangerous, and those are helpful, but I don't know if they are helpful enough. This could be a good topic for a wiki, or something like that, for chemists to contribute the chemicals that they feel require special precaution or procedures. A sort of clearinghouse of actual practical advice. I wonder if there is anything like that out there?

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35. Michael Tutton on May 18, 2009 8:09 PM writes...

I have just read the comments that my article generated. I would like chemists and other commentators to know that I would welcome comments to my personal email at michael.tutton@thecanadianpress.com regarding their experiences with TMS diazomethane. It may assist me in covering this story in the weeks and months to come, and it may be valuable to have expert commentators who are willing to be on the record. I would also like to thank Derek Lowe for his interview. In this string of comments I particularly noted the comment of "UK Academic" and would appreciate hearing details of what occurred in that incident.

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36. Carole on May 19, 2009 11:45 AM writes...

This is Roland Daigle's sister, Carole Wheatley. I too have been doing much research to learn how to prevent this from re-occuring to anyone. It's like trying to organize a bowl of spaghetti. Thank you all for your comments though. They are very helpful. But, to the one who calls my brother an "idiot"..... There's no need.

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37. Jose on May 19, 2009 12:20 PM writes...

Mrs Siddell- thank you for posting. The problems you are having with MSDS sheets are well known in the industry- they are simply a joke, and everyone knows it. The American Chemical Council (NOT to be confused with the Am Chem Society), only agreed to adopt the MSDS system if they had limited liability. They are not written to actually inform or educate workers, but simply to keep lawyers at bay. "See! We told you! It could possibly hurt you in any one of the following 65 ways..."

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38. Barry Wheatley on May 19, 2009 9:10 PM writes...

I appreciate most of the professional comments made here. The fact of the matter is even the family does not know exactly what sort of testing was being done or what other chemicals were being used at the time. So, it is pure speculation at this point to try and figure out why this happened.

To the "diazomethanemaker", I have never read such insensitive garbage in my entire life! Perhaps one day you will understand first hand what it feels like to lose someone as brilliant and close to you as I can assure you this person was. I pray that you never do but I can assure you, you will think twice before passing judgement on circumstances which you know absolutely nothing about.

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39. Jan Teller Jr on May 21, 2009 3:35 PM writes...

Mrs Sidell and Mr Wheatley,

I wish I could say something really useful to help. Just to let you know that if there is any technical issue you need to know, I will be very happy to answer them. I would put my actual e-mail here but I think the author wouldnt approve that for obvious reasons.

Best wishes

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40. Lynda MacDonald on May 21, 2009 11:48 PM writes...

Dear Jan Teller Jr.

My name is Lynda MacDonald. I am the sister of Roland Daigle. I am very interested in any information or assistance you might be able to provide. I would very much like to speak with you or exchange emails correspondence with you. I am not sure of the protocol for contacts between interested parties on this site, but at the risk of violating those protocols, you can reach me at: bradmac.@hfx.eastlink.ca . I really hope to hear from you. Thank you for your interest .

Permalink to Comment

41. Lynda MacDonald on May 22, 2009 11:46 AM writes...

Dear Jan Teller Jr.
Further to my earlier posting in # 40, I noticed a misprint in my email address, so here it is again: bradmac@hfx.eastlink.ca

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42. Stevo on June 18, 2009 10:55 AM writes...

We just received a mail forwarded to the whole company about these deaths.

As a matter of interest I always research reagents and quiz coworkers before using reagents for the first time.

My own feeling is that MSDS gives no indications as to how dangerous something is, sugar and salt for instance has the usual crap with discard clothes etc.

Ethanol is listed also as being dangerous and a CMR compound......

We need something a better than MSDSs which just "covers ass".

Nearly everyone in chemistry has some interesting stories to tell, thankfully we are here to tell the tales!

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