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-   -   Safrole is not nearly as dangerous as you would think (http://www.homebrewtalk.com/f95/safrole-not-nearly-dangerous-you-would-think-218174/)

rritterson 01-16-2011 12:22 AM

Safrole is not nearly as dangerous as you would think
 
First, let me state that I believe i am qualified to offer an opinion because I am a practicing biochemist and can more easily find and perhaps understand the data out there. However, I am not an expert on safrole or safrole metabolism, so do not take my word as gospel. I encourage you to look at the data and decide for yourself.

I think the safrole health hazards have been significantly overblown. Take a look at these two sources (one a secondary source, the other primary):

http://potency.berkeley.edu/chempages/SAFROLE.html

http://www.sciencedirect.com/science...5d2fc11#sec2.1

In the first page, the TD_50 dose of safrole, that is, the daily dose of safrole required to induce tumors in half of animals that would be otherwise healthy is 441mg/kg in rats and 51.3mg/kg in mice. The mg/kg unit means mg given to the animal per kg of it's own body weight. (e.g. 1mg/kg means a 1kg rat gets 1mg a day, a 2kg rat gets 2mg, etc) On the second link, liver damage is induced by daily dosing of safrole to rats, but it isn't statistically significant until 1000mg/kg doses are used.

Note that the mice and rat toxicity levels are quite different. Since the studies haven't been done on humans, we can't know exactly what the toxicity levels in us are. I suspect they are somewhere in between, but to be cautious, I will assume things are as toxic in humans as mice.

I am a person of average weight at just under 75kg. That means, to get a dose equal to that of mice I would have to consume 51.3mg * 75 = 3847.5mg a day (3.85g after rounding).

Let's say that I drink 1 of my own rootbeers per day. In order to have a 50% chance of cancer, I'd have to have 3.85g of safrole per root beer. Since my batches are 5 gallons (~50 beers), that would mean I'd have to get 192.5g of safrole out of the sassafras I seep. I start with 16oz (1lb) of sassafras root. Well, 1lb is actually only 453g. 192.5g/453g is 42%.

That means that my sassafras would have to be 42% safrole in order to even possibly extract that much

I can absolutely say that is not the case. Wikipedia, citing the Merck chemical index, says sassafras is 'a few percent steam volatile oil, of which 75% is safrole'. A few percent (3%) * 75% = 2.25%. Let's be generous and assume that safrole is ~4% of the total weight of sassafras. That means that if I drink 1 root beer a day, I'd be 1/10th (4%/42% is ~1/10) of the TD_50 dose! (Alternatively, you could say I'd have to drink 10 root beers a day to get to TD_50). If safrole is as toxic in us as in rats, i'd be at nearly 1/100th the TD_50 dose. Now, granted, TD_50 means 50% chance of cancer. I don't want even a 5% chance of getting cancer. However, the probability of cancer falls quickly once you move away from the TD_50. The data I can find don't even look at the probabllity of lower doses of causing cancer, but if safrole behaves like other cancer causing compounds, 1/10th the TD_50 is likely to only cause cancer in fewer than 1% of us.

And remember, I've already probably over estimated how much safrole is in sassafras and how toxic the safrole is to us. Wikipedia indicates that the cancer-causing byproducts found in mice and rat urine are not found in humans after consumption, raising questions about exactly how toxic it even is to us, if at all.

Let's not go too far and say that safrole doesn't cause cancer. It does at the right dose But I think that dose is waaaay higher than you're likely to get. Pollution in the air, chemicals in your kitchen cleaning products, etc, will probably give you cancer first.

So, I am not at all afraid to use raw sassafras in my root beers, and I don't think you should be either.

What do I think the real reason for why the FDA was so quick to act against Safrole? It's one easy chemical reaction away from MDMA, the banned drug most of us know as ecstasy. By eliminating the food needs for sassafras, the industrial production sources all disappeared, making it very hard for an illegal drug house to get enough sassafras to make MDMA.

I'm interested to hear other opinions out there, and especially interested in reading any other sources people can find.

homebirch 01-16-2011 12:50 AM

very very interesting. i always heard that sassafras could be dangerous to your health, and figured because they were testing on rats, you would have to take in a rather large amount of it for it to cause any real damage. ive never looked into any of this myself. thank you for the info.

daugenet 01-16-2011 01:18 AM

I had been looking for this info before and didnt have much luck. thanks for the info! I am not afraid either but have not had the chance to make a batch yet either. I am on the lookout for a good recipe though :)

EFaden 01-16-2011 01:29 AM

What about in relation to pregnant women? I know there are some other issues associated with its abortifacient and emmenagogue effects. Any thoughts?

rritterson 01-16-2011 01:33 AM

EFaden -- Unfortunately, I know very little about health topics related to pregnancy and female-specific anatomy and physiology, so I am less qualified to offer an opinion. In my own searches, I have not found any data related to the qualities/effects of safrole you mention, mostly because I have not been looking for them.

I would be interested in looking at and having a discussion about those data, though, too, if you have any links to sources that have studied it.

Other bits of data I would also like, if anyone can find them:
-anything related to human metabolism of safrole (what the metabolic byproducts are, how long it takes to break down in your system)
-the safrole content of dried sassafras. Sometimes, essential oils break down in the drying process of herbs and other plant products, sometimes they do not. (for example, dried basil loses a lot of flavor, dried rosemary keeps most of it) Since dried sassafras doesn't contain the weight of the water, everything that remains will be a higher percentage of the weight compared to fresh. My estimates above could be far off if all or none of the safrole survives the drying process.

EFaden 01-16-2011 01:36 AM

I'll dig around on PubMed and a few medical databases (I have access to a bunch of stuff at school).

EFaden 01-16-2011 08:48 PM

1 Attachment(s)
Alright. So I did some digging around last night. I found a few papers on cancer effects in high doses in rats. I also found some sketchy papers that weren't from anything I would count as peer reviewed. As far as reliable medical sources I found this on Micromedex

fotia 12-20-2013 03:17 AM

You must calculate the Human Equivalent Dose of the mg/kg of the animal. You cannot take the mg/kg from the animal and convert this to a human dose based on weight alone, there are other factors involved. Please see this list of conversion factors: http://1.bp.blogspot.com/-StlCbJtVo-...Ak_MValues.png

Ittiz 05-29-2014 07:38 PM

I know I'm necroing a thread but I felt like I had something to add here. I'm a molecular biologist and my assessment is the same of OPs. Firstly even if it were as bad for humans as it has been proven to be in rats, it would still be pretty safe. Safer than a lot of things we consume.

Beyond that anyone who thinks rats and mice are good models for oxidatively induced carcinogenicity in humans should read this thesis. It's long and dry, but a good read if you understand the jargon. It basically blows a hole in the idea that rats and mice are a good model for safrole and a couple other closely related compounds also found in food. Basically the enzymes in the livers of rats and mice that turn safrole into a carcinogen don't exist in humans. Also the enzymes that humans do have that can oxidize it, do so at a much lower level and exist in much smaller quantities. It also points to preliminary data that show safrole may actually inhibit these enzymes, leading to some protections against other possible carcinogens.

Again like the OP pointed out about himself, don't take anything I say as endorsed medical advice or any such thing. There are still unknowns, also the study suggested there may be people who have a rare mutation that increases the risk of cancer when consuming safrole and it's sister chemicals. Although keep in mind that almost all spices contain one or more of these chemicals so that would apply for almost all spices not just for spices containing safrole!

Basically I'm not afraid to consume safrole containing foods and drinks. Like the OP pointed out the most probable real reason for the ban is to prevent illicit drug manufacture.

aruzinsky 06-08-2014 05:01 PM

Quote:

Originally Posted by rritterson (Post 2555306)
What do I think the real reason for why the FDA was so quick to act against Safrole? It's one easy chemical reaction away from MDMA, the banned drug most of us know as ecstasy. By eliminating the food needs for sassafras, the industrial production sources all disappeared, making it very hard for an illegal drug house to get enough sassafras to make MDMA.

I'm interested to hear other opinions out there, and especially interested in reading any other sources people can find.

MDMA has nothing to do with the FDA ban on safrole which was instituted in 1960, long before MDMA use became a problem. Sassafras oil was easily available until, maybe, around 1980, but not for food use. I have two ounces of real sassafras oil that I purchased in the 1970s from a retail store in Chicago, Dr. Michael's Herb Store.

You may be interested to know that another MDMA precursor, heliotropin (piperonal), is still allowed in food, but, its use in food manufacturing apparently involves too much government red tape to be profitable. Small amounts of Heliotropin are still available without red tape.

Incidentally, pre-1960 root beer typically contained approximately 25 ppm safrole or about 95 mg./gallon.

I suspect that the FDA was bribed by Cola manufacturers. Or, maybe, the ban was the result of government cronyism.


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