How much of a threat are dioxins?

[chroot]

The web seems to be littered with alarmist dioxin propaganda, most of it simultaneously advocating vegan diets by scare tactics. Here's an example:

http://www.ejnet.org/dioxin/

How big of a threat do dioxins really pose to human health?

- Warren

 

[Moonbear]

http://www.aenews.wsu.edu/Dec98AENews/Dec98AENews.htm

There's also a lot out in the news on dioxins currently because that's what Viktor Yushchenko was poisoned with. As the article above corroborates, the main acute effect of high dose exposure is chloracne (that weird acne-like rash visible all over Yshchenko's face in recent photos).

 

[Bystander]

From Chroot's link: " --- dioxin reaffirmed that there is no known "safe dose" or "threshold" below which dioxin will not cause cancer --- " --- shades of Paracelsus --- why just typing the word "dioxin" is enough to cause cancer. Over the century or so of commercial (commodity scale) chlorinated organic syntheses, the total dioxin "byproduction" amounts to kilograms globally. Stir it into the morning coffee? No. Get hands on enough to stir into morning coffee? No. Poison someone with a "massive" dose? How many years am I supposed to wait for it have a fatal effect? Get my hands on enough to constitute a massive dose? Think I'd rather sell it as a "specialty chemical" --- thousands to tens of thousands dollars per milligram? And, I'm going to waste it trying to whack a politician? And, I'm ill informed enough to think it's toxic?

 

[Phobos]

I'm not a toxicologist, but I have enough familiarity with it to know it's a very complicated subject with lots of uncertainty. My impression is that dioxins are still relatively new in the toxicology/risk assessment arena, but a lot of work has been done. In general, the precautionary limits on dioxins on the environment and the regulated cleanup standards are a lot stricter for dioxins than for most other chemicals that are typically of concern in the environment.

If you want technical info, I'd look at EPA's and ATSDR's websites...
http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=55264
http://www.atsdr.cdc.gov/

There are different types of dioxins and you can expect each type to have somewhat different toxicity. But here's an interesting quote from the ATSDR's website...

In certain animal species, 2,3,7,8-TCDD is especially harmful and can cause death after a single exposure.

Of course, the question is "at what dose?"

 

[DocToxyn]

Well, I am a toxicologist and oddly enough I work with dioxin and related compounds, i.e., PCBs, PAHs, etc. First off Bystander mentioned a possible lucrative venture in selling dioxin, it's not really that expensive at $175 for 1 mg, sorry.
http://www.accustandard.com/SearchResults/?ls=20&CHEMICAL=1&subsubcategory=C31&category=Organic+Standards
In my opinion the risk to a healthy adult male consuming a regular diet (as stated that is the main source of background levels of dioxin) is minimal. There are however specific "sensitive" populations which may incur a greater risk following exposure to dioxin, those being: groups of people who consume large amounts of certain aquatic organisms, especially whales and other large predatory species, and women of childbearing age and their progeny. The most interesting group for me being a developmental toxicologist would be the humans exposed during gestation and lactation. There are a lot of complex dynamic processes going on during development that simply don't tolerate insult from external sources, see examples such as thalidomide or retinoic acid overdose during pregnancy for extreme examples. Dioxin is not going to be so dramatic but it has been implicated by laboratory work and epidemiological studies as a developmental toxicant which may affect brain, endocrine and immune system function to name a few. Direct proof in humans of the effects of TCDD is lacking although there have been human exposures such as the industrial accident in Seveso, Italy and as a result of dioxin contamination of agent orange used in Vietnam. These populations are being studied and the results will hopefully shed more light on the risks associated with dioxin exposure in humans. The other thing to remember is that we are exposed to many different chemicals throughout our lives and it may be the cumulative effects of such exposures that lead to chemical interactions and other long-term processes that could eventually lead to an adverse health effect.
In terms of toxicology, the most toxic of the dioxins, 2,3,7,8-TCDD has a LD50 (concentration that will kill 50% of a group) value of about 2 micrograms/kg in a guinea pig. That pretty good, but in the hamster the LD50 is about 5,000 micrograms/kg. Toxicity is a relative terms and has involves numerous complex factors such as route of exposure, time, concentration, species, genetics, etc. It's really a fascinating subject, but I'm a little biased.

Doc

 

[Bystander]

Well, I am a toxicologist and oddly enough I work with dioxin and related compounds, i.e., PCBs, PAHs, etc. First off Bystander mentioned a possible lucrative venture in selling dioxin, it's not really that expensive at $175 for 1 mg, sorry.
http://www.accustandard.com/SearchResults/?ls=20&CHEMICAL=1&subsubcategory=C31&category=Organic+Standards
(snip)

1,3,6,8 @ $1700 in the link --- preparative chromatography's come a ways. Assays cleaned up any? Used to be 95% --- solvent residues plus close congeners, related compounds, and other trash. Cleaning things to a level suitable for meaningful physical property measurements kicks expenses an order of magnitude, and Lucretia Borgia probably ain't going to spring for that much attention to detail when poisoning friends, relatives, neighbors and the like --- toxicology, though --- you'd really like to distinguish between the activities of major components and the trash that hitchhikes in with them. "Biphenyl" includes biphenyl, napthalene, terphenyls, anthracene, and phenanthrene in measurable quantities. Chlorinate and pyrolize these beasts, and you've got some real nasties to separate and handle --- "the usual suspects" in such mixtures mask quite the population of extremely ugly actors.

 

[Moonbear]

DocToxyn, thanks for the insights. Did I read correctly, or infer too much, that your specialty is reproductive/developmental toxicology? I work in reproductive neuroendocrinology. Maybe we can get a thread together on endocrine disrupters, that is if I haven't misunderstood your specialty.

 

[DocToxyn]

1,3,6,8 @ $1700 in the link --- preparative chromatography's come a ways.

I'm not all that familiar with sythetic chemistry but you're right that certain "unfavored" conformations are going to be more expensive than others, but in terms of reactivity at the ligand/receptor level and subsequent activation of toxic processes, the 2,3,7,8-TCDD congener is the most potent and therefore the "best poison" of the group.

Did I read correctly, or infer too much, that your specialty is reproductive/developmental toxicology?

Pretty good inference. I got my graduate degree in neurotoxicology, specifically looking at PCB/methylmercury effects on neurochemistry. At the time I got interested in PCBs as developmental toxicants but opted not to pursue that due to time constraints. Now I have gone on to look at dioxin effects on development as part of my postdoc. So I have been involved with reproductive/developmental/neuro/immunotoxicology over the years. A string on EDCs could be fun, I just taught a section in our toxicology course on Endocrine Mediated Neurotoxicity. It's a hot topic as you know and could spark some good debate.

 

[Phobos]

Well, I am a toxicologist

Excellent! Welcome to Physics Forums!

In terms of toxicology, the most toxic of the dioxins, 2,3,7,8-TCDD has a LD50 (concentration that will kill 50% of a group) value of about 2 micrograms/kg in a guinea pig. That pretty good, but in the hamster the LD50 is about 5,000 micrograms/kg. Toxicity is a relative terms and has involves numerous complex factors such as route of exposure, time, concentration, species, genetics, etc.

In order to answer Chroot's question, it would be helpful to compare the dioxin LD50 to that of other chemicals in order to get a feel for its relative toxicity. (e.g., perhaps common environmental contaminants like PCBs, PCE, benzene, certain nasty PAHs like benzo(a)pyrene, etc.)

More specifically to the question of human health risk, it would also be good to compare the "cancer slope factor" (which is a component related to dosage used in risk calculations) to other carcinogens like I mentioned above.

I'd have to dig into the literature to find these values though.

 

[DocToxyn]

In order to answer Chroot's question, it would be helpful to compare the dioxin LD50 to that of other chemicals in order to get a feel for its relative toxicity. (e.g., perhaps common environmental contaminants like PCBs, PCE, benzene, certain nasty PAHs like benzo(a)pyrene, etc.)

The answer isn't quite as easy as comparing LD50, I only used those values as a dramatic means to demonstrate species differences, but here are some values. Rodent, oral LD50s for- PCBs(technical mixture): 2-10 g/kg, DDT:100 mg/kg, benzo(a)pyrene: 50 mg/kg, cyanide: 5-8.5 mg/kg , ricin: 3 microgram/kg (iv), 30 mirograms/kg (oral). So you can see that dioxin is pretty toxic compared to other well known "poisons". As far as a comparison with PCBs one typically looks at what are called toxic (or dioxin) equivalency factors (TEFs). These are calculated by setting dioxin as "1" and rating all other related compounds against it. Check http://www.epa.gov/toxteam/pcbid/tefs.htm for a nice chart.

More specifically to the question of human health risk, it would also be good to compare the "cancer slope factor" (which is a component related to dosage used in risk calculations) to other carcinogens like I mentioned above.

I'd have to dig into the literature to find these values though.

I don't carry those numbers around with me either, I'm more on the laboratory side of toxicology than in risk assessment and policy and I don't study cancer, more development/molecular/neurotox stuff, but my suspicion is that dioxin is high on the list. I could find them with some searching, but first I've got bench work to get to.

 

[Moonbear]

Pretty good inference. I got my graduate degree in neurotoxicology, specifically looking at PCB/methylmercury effects on neurochemistry. At the time I got interested in PCBs as developmental toxicants but opted not to pursue that due to time constraints. Now I have gone on to look at dioxin effects on development as part of my postdoc. So I have been involved with reproductive/developmental/neuro/immunotoxicology over the years. A string on EDCs could be fun, I just taught a section in our toxicology course on Endocrine Mediated Neurotoxicity. It's a hot topic as you know and could spark some good debate.

Woo hoo! Welcome to the board! (I think I already welcomed you in another thread, but you may not have seen it). Uh oh, now I'm going to actually have to work to keep my Biology Guru status for next year, no resting on my laurels now.

If you think of a good thread-started on that topic, go for it! I'll try to think of something as well, now that I know someone is here who would appreciate it. I don't know much about the toxicology side of things, but as you point out, it's a HOT topic, so I should delve into it some more.

 

[DocToxyn]

Uh oh, now I'm going to actually have to work to keep my Biology Guru status for next year, no resting on my laurels now.

Hey, I'm not out to knock anyone of their pedestal (unless they deserve it! ), I just want to contribute where I can. I'll try to come up with something about EDCs that others can join in on too.

 

[cronxeh]

So what would be a good toxin neutrolizer against any of those toxins?

 

[tribdog]

avoidance.

 

[cronxeh]

I got to give it to you.. you are funny

 

[DocToxyn]

As funny as avoidance sounds, that's really the best course of action. Many environmental toxicants are associated with aquatic ecosystems and bioaccumulate up the food web. Consumption of food products from contaminated bodies of water sources like the Great Lakes or certain marine species like whale, shark, tuna can result in exposure to a complex mixture of toxicants including the nasties we've discussed earlier- dioxin, PCBs- as well as mercury, lead, pesticides, etc. I would also add that even food you buy in the supermarket, especially those high in fat have contaminants in them, so it's not all from wild caught sources. One's best action, if you want to reduce exposure, is to limit one's intake of such food. It's like that old joke: Patient- "Hey Doctor my arm hurts when I do this". Doctor- "So don't do that."
Having said that, there are specific receptor antagonists that are under investigation for potential use as anti-cancer agents due to the role that the dioxin-receptor (aryl hydrocarbon receptor) is belived to have in some forms of cancer. But to take these as some sort of prophylactic against the effects of environmental toxicants may disrupt the necessary role of this receptor in normal physiologic processes. This realm of science is still full of unknowns which makes it rather popular subject for the current crop of toxicologists and developmental types.