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Nutmeg

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OK, people eat nutmeg as a spice and it doesn't hurt them, but we are talking about massive/ non-spice consumption. That makes things different. A sip of wine may be good for your cardiovascular system, but a liter of vodka is lethal. Wine contains some methanol, but if you drink purified methanol you go blind. Coco leaf tea lets you breathe thin air, but purified cocaine kills. If I were me, I would take the hepatotoxic warnings about safrole SERIOUSLY.

Hawleys Condensed Chemical Dictionary (1993):

Safrole- Toxic by ingestion, may not be used in food products (FDA), a carcinogen.

Dr. Duke:

Safrole- carcinogenic, hepatocarcinogenic, mutagenic, neurotoxic, etc.

If wishing that things were not toxic made them non-toxic I would wash my hands with carbon tetrachloride, my hair with chloroform, and I would drink acetone to rid my body of excess cholesterol. Unfortunatly it doesn't work that way, SORRY!

Granted it is technically possible that they were wrong about safrole, but is it really worth it to risk your life on that one in a thousand chance. It has been proven over and over that if a non-polar compound as simple as this one destroys rat livers there is AT LEAST a good chance that they will destroy human livers too. Besides, I remember reading that there was proof of human liver damage due to safrole in several people, unfortunatly I cant find it right now, perhaps someone else can refresh my memory as to where these pesky data points went.

[This message has been edited by Auxin (edited 09 May 2002).]

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Originally posted by Auxin:

OK, people eat nutmeg as a spice and it doesn't hurt them, but we are talking about massive/ non-spice consumption.

And there is plenty of traditional use of the oil as a massage oil and as a medicine. And as we are talkign about safrole in particular (rather than nutmeg), you should look at the cultural data of safrol containing plants such as sassafras (root beer).

If I were me, I would take the hepatotoxic warnings about safrole SERIOUSLY.

I could have sworn we were talking about carcinogenicity rather than hepatoxicity wink.gif

Hawleys Condensed Chemical Dictionary (1993):

Safrole- Toxic by ingestion, may not be used in food products (FDA), a carcinogen.

Dr. Duke:

Safrole- carcinogenic,

yes, you can quote refs until you are blue in the face. fact is that they are all based on the same flawed studies.

I can also throw a dozen of reliable references at you that state dill apiol to be carcinogenic, but in fact it is not as was proven in trials that were more appropriate to human modelling.

If wishing that things were not toxic made them non-toxic

we are not. it makes no difference either way. if the data was reliable I would gladly accept it. but I also don't make a habit of believeing bad hype backed by poor science.

Granted it is technically possible that they were wrong about safrole, but is it really worth it to risk your life on that one in a thousand chance.

mayeb they should do some tests on me to see if it did any damage wink.gif

It has been proven over and over that if a non-polar compound as simple as this one destroys rat livers there is AT LEAST a 99% chance that they will destroy human livers too.

this is an arbitrary number you just pulled out of your.... hat. In fact, most such rat studies have not been verified in human or even primate studies.

Besides, I remember reading that there was proof of human liver damage due to safrole in several people, unfortunatly I cant find it right now

I think if this was the case then there would not be such vague information cited about rats and modelling. usually when human trials or objective observations are available, the rats don't matter anymore.

Personally I would also advise caution, but to state that soemthign is toxic with such vague scinetific proof is simply propagating scare tactics that are commonly used against herb use. This is no better than the classic reefermadness.

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Sure, responsable use may pose little danger at all. However, don't you think it is better to err on the side of caution?

You keep saying there is no human data, wrong. There is human data, just not much clinical human data. Prison inmates are the 'test group' for most studies. This page: http://www.inchem.org/documents/pims/plant/pim355.htm

has human data, its long so I'll sum up some main info:

7.2 Toxicity

7.2.1 Human data

7.2.1.2 Children

Death by nutmeg intoxication has been reported by Cushny (Weil, 1964) in an 8-year-old boy after consuming 2 nutmegs.

7.3 Carcinogenicity

Safrole is a known mild hepatocarcinogen. Although safrole itself is not carcinogenic, it is metabolized to form 1'-hydroxysafrole which is carcinogenic. Data are not available on the carcinogenicity of nutmeg itself.

9.2 Chronic poisoning

9.2.1 Ingestion

Chronic poisoning by oral administration has caused temporary (up to six months) psychosis in prison inmates.

9.4.5 Hepatic

Hepatic necrosis in heavy poisoning. Fatty degradation of liver.

You can find more human data, just look around the net.

And OK, that 99% isn't clinical fact so I take it back. Nor is it purely scare tactics that I pulled out of my A... uh HAT. OK numbers may have been presumptuous, but it is an educated guess formed by the observation of a strong general trend built up from my years of reading about chemical toxicity that there is a undeniably frequent correlation between hepatotoxicity of simple non-polar aromatic hydrocarbons in rats vs. humans. And the fact is that we don't have any hepatic miracle drugs that will reverse liver damage (closest thing is the silymarin complex obtained from milk thistle seeds) also the liver transplant list is so long that many, many people die while waiting for transplants, so I do not advise taking the risk. You are, however, your own person so you can do what the f*** ever you want, just tell a family member what you are doing so if you die we will have another data point for people to ignore.

And dont even get me started on root beer, its very dilute, modern stuff uses very little of the historical ingredients, and safrole is not water soluable- so that decreases the content even more (way, way more).

[excuse any bluntness, potential for hepatotoxicity makes me mad. All my best friends are being taken away because they turned out to be poisoning my liver (benzene carbon tet, chloroform, CH2Cl2, all the good stuff) and I cant do my proposed research project on synthetic flavonoid antihepatotoxins/hepatorejuvanatives because they wont let me do animal research and even if they did I dont have the money, and even if I did those chemical supply houses make getting stuff hell, and theres always the homegrown US terrorist, scientist burning, insane tree-hugger scum that would firebomb my house for trying to save their messed up lives... damned ALF sons a' friggin bi.. killing people to save rats, what the hell!?! OK I'll stop now before you rename me chemical shaman 2.]

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I never disputed acute poisoning, which is what you mostly refer to above. I am talking about safrole in massage oils, in rootbeer (the real thing), etc. I am not interested in ingesting it anymore as it is way to dangerous simply from the perspective of its unpredictability. And yes, I always left a write up of my experiment before consumption, so in case things go wrong the idiots at the hospital know at least where to look things up. Actually, in many cases I would even write down the antidotes and method of treatment wink.gif

The whole pint of this discussion was about accasional use of small quantities. Quantities below the acute poisoning level. (after all you can even achieve that with water or salt or......). Nothing of what you say indicates that such quantities pose any danger and to extrapolate from small quantities to excessive quantities is silly. As for your faves, most of them are well documented carcinogens, and most are chlorinated - no argument there. But to draw conclusions from the carcinogenicity of one related compound to another is unscientific - as I demonstrated in my apiol vs dill apiol example.

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"to draw conclusions from the carcinogenicity of one related compound to another is unscientific"- Torsten

To state such a comparison as FACT is unscientific, yes. But to state it as a suggestion of caution or as an initial hypothesis in the absence of any clinical proof is scientific. The point of science is to make an initial hypothesis based on observed relationships, and then to experiment and study it to refine, prove, or disprove that hypothesis.

Carbon tet is known to be carcinogenic, etc. so as a matter of CAUTION if I was working with Fluorotrichloromethane I would assume it's a nasty one too, until such time that I find clinical proof as to it being more or less dangerous than CCl4. If it seems I take caution to extremes it is just cause I work with nasty stuff all the time and sometimes when I ignore caution I have come close to death. One time someone said 'open up the valve on that CO2 tank to see if it is full' I ignored caution and did what they said, I'm lucky it was empty because it turned out to be a carbon monoxide tank with a dirty label!!!

"I always left a write up of my experiment before consumption, so in case things go wrong the idiots at the hospital know at least where to look things up. Actually, in many cases I would even write down the antidotes and method of treatment"- Torsten

You, my friend, are one smart dude. I wish more people used such caution when self experimenting. If you ever move to the US please run for a political office, it would be nice to have a politician with a brain for a change.

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I personaly think rats would be better off consuming a little safrole every now and then (or a pill for that matter) than if they were to eat Mc Anything.

Often people will have no idea what's in the ("MD") pill they munch at a club or rave, and even if they are aware of the actives/ purity, there is still bugger all information about long or short term usage.

Personally I'd much prefer natural 'poisons' like sassafras or nutmeg oil, to one that is purchased for $40 as "like, full on MD, mann".

- my AUD$0.02 worth

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sab 'challenging concensus reality since' 2000!

isnt this basically about hype,hysteria and misinformation especially concerning 'drugs'.

t s t.

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Originally posted by t st tantra:

isnt this basically about hype,hysteria and misinformation especially concerning 'drugs'.

t s t.

Yep, that's what I was trying to get at. Even if we accept that a careful stance is important, then we should nonetheless never assume this stance to be fact, but rather simply caution. One of the problems about cautionary warnings is that they become exaggerated by consecutive quotes. Thus a simple toxicity warning for huge quantities of a substance frequently ends up as a warning for gardeners 'not to touch the plants'. This sort of hype is not helpful.

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Stephen Jay Gould wrote a really good article on exactly this phenomenon ' The Case Of The Creeping Fox Terrier Clone '- the conversion of hearsay to scientific fact via repitition.

It's really common in most fields, science is simply no exception. And it does affect future understandings. I think Catalyst on ABC TV recently had a segment on how this had affected research into equine eyesight.

Always refer to your source document smile.gif

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It is the enzyme for conversion of safrole to 1'-hydroxysafrole that humans lack and rats possess. In the case of safrole the use of the rat in animal models is clearly flawed.

There are clear reasons for assuming that radium cyanide would be dangerous but a little cyanide is a wonderful tonic (ref. Diary of a Drug Fiend - Aleister Crowley, please don´t try this at home folks).

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I am a thousand miles from my card files but the following from PubMed may be relevant:

Toxicology 1977 Feb;7(1):69-83

Absorption, metabolism and excretion of safrole in the rat and man.

Benedetti MS, Malnoe A, Broillet AL.

"The main urinary metabolite in both species was 1,2-dihydroxy-4-allylbenzene which was excreted in a conjugated form. Small amounts of eugenol or its isomer 1-methoxy-2-hydroxy-4-allylbenzene were also detected in rat and man. 1'-Hydroxysafrole, a proximate carcinogen of safrole, and 3'-hydroxyisosafrole were detected as conjugates in the urine of the rat. However, in these investigations we were unable to demonstrate the presence of the latter metabolites in man."

Anticancer Res 2001 Jan-Feb;21(1A):461-9

Micronucleus formation in human lymphocytes and in the metabolically competent human hepatoma cell line Hep-G2: results with 15 naturally occurring substances.

Kevekordes S, Spielberger J, Burghaus CM, Birkenkamp P, Zietz B, Paufler P, Diez M, Bolten C, Dunkelberg H.

"Benzyl acetate, emodine, isatidine dihydrate, reserpine, safrole, sanguinarine chloride and thiourea did not reveal any micronucleus inducing activity in either human lymphocytes or in Hep-G2."

However there is a note of caution in:

Carcinogenesis 1999 Dec;20(12):2331-4

Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history.

Chen CL, Chi CW, Chang KW, Liu TY.

"These results suggest that safrole forms stable safrole-DNA adducts in human oral tissue following BQ chewing, which may contribute to oral carcinogenesis."

And I have finally found a paper saying isolated human livers can 1-hydroxylate, though in very high concentrations of allylbenzene derivatives, greater than 1.5 grammes for a small human of methyleugenol per day for 25 days. The 37-fold variation could explain the negative results I have seen reported elsewhere.

"Administration of high doses of methyleugenol to rats (at least 30 mg/kg bw/day for 25 days) caused dose-dependent auto-induction of 1'-hydroxylation of methyleugenol, mediated by various cytochrome P450 isozymes.The auto-induction was not observed in rats treated at a lower dose (10 mg/kg bw/day for5 days). The same authors showed that the rate of 1'-hydroxylation of methyleugenol in vitro in 13 human liver samples varied markedly (by 37-fold), with the highest activities being similar to that evident in control rat liver microsomes."

Gardner, I., Wakazono H., Bergin P., de Waziers I., Beaune P., Kenna J. G. and Caldwell J. Cytochrome P450 Mediated Bioactivation of Methyleugenol to 1'-Hydroxymethyleugenol in Fischer Rat and Human Liver Microsomes. Carcinogenesis, (1997) 18, 1775-1783

Is myristicine safe? In another study "safrole-DNA adducts, and to a greater extent, myristicine-DNA adducts were identified in livers of mice given cola beverages instead of drinking water" (Randerath, K.P., Putman, K.L. and Randerath, E. Flavor constituents in cola drinks induce hepatic DNA adducts in adult and fetal mice. Biochem. Biophys. Res.Commun., (1993) 192, 61-68

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myristicin in cola???

thanks for a thorough background on this theo.

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Thorough? If only I were near a proper Uni library. The one here doesn´t even have a guide to the local spiders. As one of the local spiders is a Black Widow I would have thought someone would be interested. I am not sure if what I saw was a Black Widow (I didn´t feel like turning it over to check for markings underneath, they are very shy and I didn´t want upset it wink.gif ) but the poisonous giant centipede was unmistakeable.

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