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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: Twitter: Dereklowe

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September 11, 2005

Remind Me Not to Do This Again

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Posted by Derek

As I sit here typing this evening, my right arm is giving me fits. About a week ago, I had the misfortune, while retrieving a mis-thrown frisbee in the back yard with my two children, of reaching into an area with some poison ivy growing in it. And I've been paying for it ever since.

My immune system has been set off by contact with an alkylated catechol called urushiol (lot of information here.) The stuff penetrates the skin quite well, damn it all. It's simultaneously greasy (with a fifteen-carbon tail on it) and has a polar head group (the catechol), so it just wanders in there will all the other lipid molecules and does its thing. Its thing is to get oxidized to an ortho-quinone, which is probably what does the damage.

Quinones are reactive beasts, which is why we don't put catechol groups (or similar precursors) on drug structures if there's any possible way around it. Some years ago, Merck made a big splash in Science and other venues with a small molecule that affected the signaling of the insulin receptor. That was quite a feat, and worthy of the attention - but the molecule itself, derived from a natural product, was a quinone. I rolled my eyes when I first saw it, as did almost everyone else in the industry, and we were correct - Merck was never able to develop the stuff into a real drug.

A notorious exception to this rule is acetominophen, known also by its brand-name form of Tylenol, which gets metabolized to a reactive quinone-like compound. (There's no way that the compound would be seriously developed today, but that almost certainly goes for aspirin, too, and there you have one reason that it's so hard to run a drug company these days.) The acetominophen metabolite is cleared handily by one of the body's standard systems (glutathione conjugation), but if you take enough of the stuff to deplete your reserves you're in for some serious liver damage.

So, this quinone has soaked right into me and reacted with some of my cell-surface proteins, prompting my immune system to mount a big inflammatory attack. This response isn't just available in your back yard, though: it's a little-known occupational hazard in research labs. There are many classes of reactive compounds that can penetrate the skin enough to cause trouble. If a particular person's immune system finds fault with the result, they end up with dermatitis that's indistinguishable from vigorous, prolonged poison ivy contact.

A friend of mine went through this in graduate school. He had an enone derivative that he'd made before without incident, but one batch caused his forearms to redden and swell briefly. He didn't make the connection, but the next time he came through that part of the synthesis he really got the business. Realizing what was happening, he ended up passing on that step of his synthesis to someone else in the lab. His immune system had become sensitized, and it was impossible to say how bad further exposures could be.

Comments (9) + TrackBacks (0) | Category: Toxicology


1. Fred on September 12, 2005 4:28 AM writes...

Thirty five years ago I worked for a small machine shop. We hired a guy with a grand and colorful tattoo on his forearm. After a brief time in our shop, every bit of green in his tattoo erupted. Something in our shop chemistry of cutting oils, coolants, etc. triggered a reaction that caused his body to try to throw off that green dye even if it meant throwing off his skin, too.

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2. tim mayer on September 12, 2005 8:52 AM writes...

I've seen the same thing working with some urethane systems over the years. Getting sensative to a particular isocyanate group is a real problem in polymer labs. Once you break out in a rash it's likely to come back.

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3. Derek Lowe on September 12, 2005 9:04 AM writes...

You know, for the past week I've been working with a particular aryl isocyanate. It's enough to make me wonder if that's not adding to the problem. I would have expected trouble on both hands and forearms in that case, though, since I'm pretty ambidextrous in the lab.

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4. Don Butler on September 12, 2005 10:11 AM writes...


i was a laboratory chemist for 45+ years & have seen many examples in others! The only one that sensitized me was a propargyl alcohol (inadvertent skin contact). I have also had a serious reaction to "iohexanol" a dye injected (IV) to help visualize kidney stones. My only suggestion to chemists is to use gloves & fume hoods.
For poison ivy, there is probably a good herbicide that will kill it in your yard, but getting rid of the dead vine will be a challenge. DON"T try to burn it!

Don Butler

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5. The Novice Chemist on September 12, 2005 11:15 AM writes...

I've heard about DCC as a sensitizer as well. What's the minimum level required to get a reaction from the skin, etc. Is it mass exposure or something a lot less?

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6. Derek Lowe on September 12, 2005 11:37 AM writes...

Novice, that seems to vary widely between individuals. Some people get a strong reaction from small amounts of things like DCC, while other people can spill it over their hands. (This isn't recommended!) And in keeping with the immune component, the sensitivity can change over time, getting much worse or (perversely) disappearing entirely.

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7. SRC on September 12, 2005 2:41 PM writes...

One of my grad students became so sensitized to benzyl bromide that if she even walked into the lab - this after the rest of us spent two days scrubbing it from ceiling to floor, and the BzBr was long gone - her face would puff up until her eyes swelled shut literally before our eyes.

Eventually I had to find her a lab at the other end of the building to solve this problem.

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8. Shannon on September 12, 2005 3:15 PM writes...

Finally, an explanation for that nasty rash I got after mixing up catechol substrate solution for that dorky mashed potato enzyme lab! Btw Fred, some of the newly inked slowly develop allergic reactions to certain colors (e.g. green), so it might not have been the shop chemistry. Fortunately, basic black is always fashionable.

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9. steve on September 12, 2005 7:39 PM writes...

My sympathy to Derek; I once had severe poison ivy on my hands (giant weeping bubble blisters, etc.) for a week and I don't care to repeat it. Come to think of it, a tiny cortisone pill cleared it up in a day or two--pharmaceuticals to the rescue!

By the way, isn't there anybody in the pharma business who thinks that aspirin's inability to penetrate today's regulatory system tells us that the system is broken?

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