Apples, Arsenic, and Risk - Part 20: It is - and always will be - about the dose.

"All substances are poisons; there is none which is not a poison. The right dose differentiates a poison…." Paracelsus (1493-1541).

I hate to keep whipp'n that dead horse, but that's what is missing in these discussions on the arsenic that has been found in apple juice.  Let's look at what Russell H. Greenfield, MD says on the Dr. Oz website regarding arsenic in apple juice:

The 10 ppb level [arsenic MCL for drinking water] is simply as close as we can reasonably get considering our natural exposure to arsenic in the environment and other limitations. At that level, almost all experts agree our drinking water is quite safe.

Shouldn't the same goal or, at the very least, similar science-based exposure guidelines, be in place for the juices we commonly give to our children?

What goal would Dr. Greenfield want to see?  Consumer Reports thinks "the standard should be 3 ppb" and the FDA, on December 15, 2008, issued a memo on research they had done regarding arsenic in the juice:

In conclusion, the chronic consumption of apple juice products containing over 23 µg/L (ppb) inorganic arsenic would represent a potential health risk.

The FDA in 2008 says 23 ug/L is the maximum total arsenic in apple juice that would not pose a potential health risk.  That 23 ug/L is based on the actual dose a child would take in (uptake) based on how much apple juice is normally consumed.  That's the way it is supposed to be done, that's the way the FDA did it in 2008, so why does Consumer Reports, Dr. Oz, Dr. Greenfeild, and good ol' Chuck Norris think the FDA has dropped the ball on this?

Let's look at how the FDA came up with that:

Consumption estimates were based on average consumption over two days for individuals who consumed apple juice (eaters only) and were calculated for two population groups: Males and females (MF) from birth to 2 years of age and MF 2 years of age and older.  

The estimates included foods codes for products that were 100% apple juice, including infant apple juice; juice blends that included apple juice as an ingredient were not included.

Relying on results of the more recent 2003-04 NHANES, consumption of apple juice by MF birth to 2 years was estimated to be 16.7 and 36.2 g/kg body weight/day at the mean and 90th percentile, respectively, compared with previous estimates of consumption for all juices of 19.1 and 43.4 g/kg body weight/day.  

For MF 2+ years, consumption of apple juice was 6.0 and 12.9 g/kg body weight/day at the mean and 90th percentile, respectively, compared with the previous estimates for all juices of 6.0 and 13.0 g/kg body weight/day. 

Since consumption estimates from both surveys are similar, the level of concern (LOC) that was calculated for the previous assessment (23 ug/L, or ppb) can be applied in the case of apple juice. 

The 23 ug/L is for inorganic arsenic and is based on the dose a child would take in drinking apple juice.  The reason that number is higher than the 10 ug/L for arsenic in drinking water is that the dose from drinking water is estimated to be 20 ug at the 10 ug/L MCL.  This is because the MCL is based on drinking 2 liters of water per day.

What that means is this:

A 30 kg child (66 pounds) drinking 36.2 grams of apple juice per kilogram of body weight consumes 1086 grams of apple juice which is 1.1 liter.  That's the amount that will deliver the dose of arsenic.  That quantity of apple juice is the 90th percentile highest amount of apple juice estimated to be consumed.  A child drinking that much apple juice would receive 25.3 ug of total arsenic at a maximum FDA acceptable concentration of 23 ug/L.  The highest anticipated "daily dose" for this 30 kg child is 25.3 total arsenic from drinking apple juice.

For drinking water, that same child would consume 2 liters of water at the MCL of 10ug/L for a total daily dose of 20 ug.  That's what the EPA considers a safe dose.

So normal apple juice consumption will see less than 25.3 which is equivalent to what would be consumed if drinking two liters of water at the MCL for arsenic of 10 ug/L.

Drinking apple juice at a total arsenic concentration of less than 23 ug/L is the same as drinking water at the MCL 10 ug/L for arsenic.  The dose is based on the amount consumed per unit of fluid.  You drink less apple juice per day then water so apple juice can contain more ug/L of arsenic and still be considered safe.

Sounds counter intuitive, especially when you are talking about toxicity. We are concerned with the amount of the toxin - dose - received not the amount of the toxin found.  This is why you cannot compare the MCL for drinking water to the concentration of arsenic found in apple juice.  The MCL has been established for a dose based on consuming 2 liters per day.  You therefore need to compare the dose the receptor is anticipated to receive with the maximum dose - mg/kg body weight - established as "safe."

This is how it works.   It is - and always will be - about the dose when describing toxicity.

23 ug/L of total arsenic presents less dose than a drinking water MCL of 10 ug/L and is based on the assumptions of how much of each is consumed.  As long as the daily dose does not exceed 20 ug for a 70 kg person - or - 0.28 ug arsenic/kg body weight - we will not expect to see any short term or long term potential health risks over a 70 year lifetime!

That's why Dr. Greenfield states on the Dr. Oz website:

At that level [10 ug/L], almost all experts agree our drinking water is quite safe.

Even ol' Chuck Norris agrees with that, although I am pretty sure he has no idea that he does:

At the very least, the FDA should not allow more arsenic in apple juice than it allows in Americans' drinking water.

"Not so fast!" Yells our hero Chuck Norris, "tell them about the cover-up!"  No, Chuck, you tell them:

Tragically teetering on a huge U.S. health cover-up, the FDA posted eight "previously undisclosed test results" for apple juice samples from across the country that had arsenic levels that superseded even its own "level of concern" for inorganic arsenic. Two of those eight samples had an arsenic level of 27 ppb. One had a level of 42 ppb, and two others were at 45 ppb.

Tragically teetering?  Oh chuck, you are such the drama queen!  Here is what the FDA discloses in another memo dated November 21, 2011:

In July 2011, we issued an Import Bulletin to significantly increase the number of juice products sampled and analyzed for arsenic under the Toxic Elements program. Importantly, of the 74 samples collected as a result of this import bulletin, all were from China. Of these:

• 1 sample was above 23 ug/L total arsenic
• 1 sample was 10 ug/L total arsenic
• 2 samples were 11 ug/L total arsenic
• The remainder, (almost 95 percent), were below 10 ug/L total arsenic.

 Compare that to the arsenic levels reported by Consumer Reports.  But wait, there is more:

[we] now have a total of 160 apple juice samples collected from 2005 to 2011. These include 70 samples posted by FDA on September 27, 2011 and an additional eight samples that were part of this data set. These eight samples, which had not been previously posted, all have total arsenic levels greater than 23 ppb and were in the process of being further verified.

The data set also includes 82 new samples collected in the latter part of 2011 for which the data have just now become available. Of these 160 apple juice samples:

• Almost 88 percent had fewer than 10 ppb total arsenic
• 95 percent had total arsenic levels below 23 ppb total arsenic.

Okay...anything else from the lyin' stinkin' covern' up FDA?

Similarly, from the Total Diet Study program:

• Nearly 77 percent of the 134 composite apple juice samples tested from 1991 to 2009 (including baby food and general consumption samples) had total arsenic levels below 10 ppb.
• 95 percent had total arsenic levels below 23 ppb.

Cover-up?  C'mon Chuck, this ain't nothin' different than what Consumer Reports found.  How many samples do you need to have analyzed to get you to understand that we're not in any danger.  I mean, really Chuck?

Until then, tides of arsenic will continue to flow from foreign produce fields into American bloodstreams.

Tides of arsenic?  Chuck, Chuck, Chuck...

I have written 20 posts on this topic.  I have tried to show how many of these statements from Consumer Reports, Dr. Oz, and Chuck Norris are not substantiated.

As much as I believe we should consume food that is grown locally and with little to no pesticides, I cannot say that the reason for doing so is because foreign grown apple juice contains more arsenic than American. The Consumer Reports data shows that it does not.

I cannot support lowering the inorganic arsenic level to 3 ug/L.  There is no evidence to support that.  None.  Period.  The FDA's level of concern of 23 ug/L appears to be prudent, justified, and can be supported by the same data used to produce the drinking water MCL for arsenic at 10 ug/L.  And at that level, one more time courtesy of Dr. Greenfield:

"almost all experts agree our drinking water is quite safe."

It is - and always will be - about the dose received and not the amount detected.  You cannot compare the ug/L established for water with the ug/L found in apple juice.  This is no different than comparing a one pound ingot of lead with a one pound feather pillow.  They both weigh the same but one of them you would not want dropped on your head.

Let me sum it all up.  Here is how it works, it only works this way.

If little 2 year old Johnny weighs 66 pounds (30 kg) and he drinks the upper most amount of apple juice the FDA research found, 1.1 liters (36.2 g/kg body weight/day), and that apple juice contains the highest amount of total arsenic the FDA says is safe - 23 ug/L - he would consume 25.3 ug of total arsenic each day he drank 1.1 liters of apple juice.

That's a pretty big two year old and that's a lot of apple juice to drink, but that's a potential and I'm trying to force a "worst-case" scenario to illustrate my point.

25.3 ug for a 30 kg child comes out to 0.84 ug arsenic/kg body weight.  0.84 ug is 8.4E-4 mg/kg.

The IRIS reference dose (RfD) for inorganic arsenic is 3.0E-4 mg/kg-day.  Now before you say "whoa! That's more than double" remember this:

In general, the RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.

Little Johnny will not drink more apple juice per body weight when he gets older, in fact, the FDA reports that after two years of age, a child drinks about half of that amount per body weight.  And as their body weight increase towards 70 kg, the dose of arsenic received per body weight gets less and less each day they consume apple juice.  So that at the end of 70 years, the dose of arsenic is around 3.0E-4 mg/kg-day based on a max of 23 ug/L.

Oh, and that worst-case amount of arsenic, 8.4E-4 mg/kg-day, is for total arsenic.  Looking at the Consumer Reports data, inorganic arsenic is about 30% less than that.

Nevertheless you may say, this worst case mega-heavy-baby little Johnny is consuming more than the IRIS RfD of 3.0E-4 mg/kg-day of inorganic arsenic based on these FDA estimates and calculations.

True that, but I have another little bit of information that will let me know everything will come out OK.  Even if little Johnny were to drink 1.1 liters of apple juice with 23 ug arsenic every day and never weigh more than 30 kg, the estimated dose of total arsenic - 8.4 mg/kg-day - is just barely above the NOAEL (No Observable Adverse Effect Level) of 8.0E-4 mg/kg-day listed by IRIS for inorganic arsenic and well below the LOAEL (Lowest Observable Adverse Effect Level) of 1.4E-2!

So is the FDA correct in identifying 23 ug/L arsenic in apple juice as a level of concern?  Yes.

Can the FDA substantiate their claim that:

...the chronic consumption of apple juice products containing over 23 µg/L (ppb) inorganic arsenic would represent a potential health risk.

Yes.

Is Dr. Russell H. Greenfield, MD correct when he says:

It remains very unlikely that you have done any harm to yourself or to your children through the drinking of apple juice. 

Yes.

Can you and your kids drink apple juice despite all of the misinformation and assumptions made by Consumer Reports, Dr. Oz, and Chuck Norris?

Yes.

Everything in moderation.

Now, how do you like them apples!


.

Dogs and Phosphoric Acid...one more time.

In the words of Peter Griffin "You know what really grinds my gears?"  How we describe the hazards of a chemical when it is found to be present in the environment.

All chemicals pose a hazard at a particular dose.  If it is under that dose, then the hazard seen at a higher dose does not apply.

Yes, it is that simple.

In two previous posts I tried to explain this concept using dogs and phosphoric acid found in a can of Coke.  To summarize:

If you are describing a dog that you will come in contact with that looks like this:




Don't make it sound like it looks like this:

Which brings me to the EPA's "Imminent and Substantial Endangerment Order to Protect Drinking Water in Southern Parker County." (1)  In the Order, the EPA states:

The EPA says that contaminants are present in the aquifer.  The term "contaminant" means:

[A]ny physical, chemical, biological, or radiological substance or matter in water. (2)

What the EPA is claiming is that they found "substances" in the water.  That definition does not require that the concentration - dose - be at any particular level, only that "any" amount was found to be present. "Any" means any.

The EPA goes on to say in the order:

These substances, according to the EPA, are in an "any" amount that may present an "imminent and substantial endangerment to the health of persons."

Notice what it says about the ingestion of benzene - one of the contaminants found:

[B]enzene if ingested or inhaled could cause cancer, anemia, neurological impairment and other adverse health impacts."

In other words, the EPA is telling us is that if you walk into this kennel (drink water from this aquifer) you will run into this dog:

What type of dog did the EPA actually find:

And:

Benzene - a "contaminant" - was found to be present in the water at the following concentrations:

3.1 ppb or 0.0031 ppm
6.12 ppb or 0.00612 ppm
4.55 ppb or 0.00455 ppm

The average benzene concentration is:

4.59 ppb or 0.00459 ppm

I wonder if the EPA has anything to say about how much of a "contaminant" can be found in drinking water before it is considered unsafe?  You know, like is there a maximum amount of certain chemicals that determine if the water is safe to drink?  Like maybe something called a "maximum contaminant level" or "MCL?"

Well by golly, there is!  Here is what the EPA has established under the SDWA:

Maximum Contaminant Level (MCL) - The highest level of a contaminant that is allowed in drinking water. MCLs are set as close to MCLGs as feasible using the best available treatment technology and taking cost into consideration. MCLs are enforceable standards.

Maximum Contaminant Level Goal (MCLG) - The level of a contaminant in drinking water below which there is no known or expected risk to health. MCLGs allow for a margin of safety and are non-enforceable public health goals. (3)

So an MCL is the "highest level" of a contaminant allowed in drinking water below which "there is no known or expected risk to health."

In other words, if the concentration of the contaminant found in the drinking water is below the MCL or MCLG, there would be "no known or expected risk to health" according to the EPA.

I wonder if the EPA has established an MCL for benzene?  By golly, they have!

http://water.epa.gov/drink/contaminants/index.cfm

The MCL for benzene is 0.005 ppm.  What was the benzene concentration in the three samples:

3.1 ppb or 0.0031 ppm
6.12 ppb or 0.00612 ppm
4.55 ppb or 0.00455 ppm

The average benzene concentration is:

4.59 ppb or 0.00459 ppm

Only one of the three samples had a concentration above the MCL of 0.005 ppm with the average benzene concentration below it.  Based on this, the EPA should have said that there is no known or expected risk to health associated with the benzene.  Instead the EPA states:

There is no MCL for hexane, propane, or ethane.  The MCL for toluene is 1 ppm.  All three samples were well below this.

This is the same thing as telling a Coke drinker about the phosphoric acid in their drink:

Phosphoric acid is corrosive.  Ingestion may produce burns to the lips, oral cavity, upper airway, esophagus and  possibly the digestive tract. Circulatory collapse. Unconsciousness, possibly death. (post)

Did the water pose an "Imminent and Substantial Endangerment" to public health?  Possibly.  Maybe because of the flammability of the methane, propane, and ethane found.  Flammability - based on flash point, flammable range, or percent LEL - was not determined by the EPA.

Is it possible that enough gas could form in the well?  I'm not sure about that.  The flammable range of methane is 5-15% in the air. (3).  Sampling of the air for LEL within the well would be required to make a flammability determination at the concentrations found.  The fact that the pumps locked up and effervescence was noticed makes further review necessary.

Flammability is the only potential "Imminent and Substantial Endangerment" situation that may be present.  The presence of "any" contaminants found fall below EPA's MCLs and should not have been mentioned as their level in the water presents "no known or expected risk to health."

Rule number 1:  If the contaminants fall below the MCL do not identify them as a possible health concern, or as a health concern greater than what the dose would manifest. (Dogs)

Rule number 2: Do not describe health hazards associated with a chemical at a dose that is higher than what is actually found. (phosphoric acid)


Now, where was I?  Oh yeah, the Seven Deadly Sins...

Next Post: Seven Deadly Sins: I'm not seeing it.


..

Air Quality in the Barnett Shale - Part 9: Dose and Dogs

So now back to TCEQ and their statement:

“In response to these concerns, the TCEQ has committed a tremendous amount of time and resources to the issue of Barnett Shale air quality, and we will continue to do so.  After several months of operation, state-of-the-art, 24-hour air monitors in the Barnett Shale area are showing no levels of concern for any chemicals. This reinforces our conclusion that there are no immediate health concerns from air quality in the area, and that when they are properly managed and maintained, oil and gas operations do not cause harmful excess air emissions.”

How can this statement be made when contradictory statements from Wolf Eagle Environmental and Wilma Subra contend:

• Laboratory results confirmed the presence of multiple Recognized and Suspected Human Carcinogens in fugitive air emissions present on several locations tested in the Town of DISH. (1)
• Xylenes (m & p), a neorotoxin, was present in the highest concentration of all stations sampled and exceeded the Long-term ESL by 2 times. (2)
• Benzene, a know human cancer causing agent, was present in the highest concentration of all stations sampled. (2)

It all comes back to the dose.

Lets say that you wanted to know the possible health effects of human contact with different types of mammals.  The first thing you would do is group them.

1. Cats
2. Dogs
3. Hamsters
4. Pigs
5. Goats

Then you would look at each one to see what health effects occur.  For the sake of simpleness, lets pretend the only health hazards we are concerned with are bites, bone breaks, rabies, and death.

Now through research - some good and some poor - we find that not all bites are the same, so we break them down into small bites, medium bites, and large bites.

So our concern with human exposure to mammals has to do with the following health effects:

1. Small bites
2. Medium bites
3. Large bites
4. Bone breaks
5. Rabies
6. Death

The next thing one would do is look to see what type of exposure to one of the five mammal groups causes any of these health effects.  Through research we find that these health effects are dependent on the size of mammal (dose) and the amount of time in contact with the mammal (duration).

As a rule, we find that the bigger the mammal the larger the bite; the more time spent with the mammal the higher the chance of rabies; and in cases where a large number of mammals is encountered at one time, death may occur.

We also find that in most cases nothing happens.  Also, some large mammals can just nip and some small mammals can bite, although the size of the mammal does impact the size of the bite.  Additionally, any one single contact may have the ability to transmit rabies.

So looking at dogs, for example:

Now we need to determine what a safe level of dog exposure is.  For other than rabies, we look to see if there is a non-linear dose-response relationship, which means it has an effects threshold - an amount of dog for which human exposure is not expected to result in any adverse health effects.

We also find that within a human population, some people are much more prone to have negative health effects when exposed to dogs.  So when determining this safe level, it will need to be based on the most sensitive population (children, elderly) and adjusted for uncertainty and variability.

In toxicological assessments, this safe value is usually based on a determination of no-observed-adverse-effect-level - or - NOAEL.  The NOAEL is than divided by an uncertainty factor.  

For example, benzene - which is not a dog but a chemical - has a BMDL (which is similar in scope to the NOAEL) of 1.2 mg/kg/day is divided by an uncertainty factor of 300 for a reference dose (RfD) of 0.004 mg/kg/day.  The reference dose is the safe level one can be exposed to without any adverse health effects.

This uncertainty makes the safe level of benzene 300 times lower than the amount determined to be at the no-observed-adverse-effect-level (NOAEL).  In other words, at 1.2 mg/kg/day we don't expect anything, so at 0.004 mg/kg/day we are pretty dang sure nothing will happen.  Aint science fun!

It is because of this uncertainty that TCEQ can say:

"If predicted airborne levels of a constituent do not exceed the screening level, adverse health or welfare effects are not expected.  If predicted ambient levels of constituents in air exceed the screening levels, it does not necessarily indicate a problem but rather triggers a review in more depth."

So what would be the safe level of dog?  One that would show consistently a no-observed-adverse-effect-level.   That would probably be a puppy.

And because of uncertainty, not just any puppy, but a really young puppy:

So that's basically how dose and this "safe level" of ESL, RfD, and AMCV works.  Exposure to any of the dogs pictured - as well as encountering a pack of dogs - does not necessarily mean you will get bit or harmed.  And the chance of rabies?  Slim.  Yet these health effects - including rabies - are possible any time you are exposed to a dog.

Next post: Air Quality in the Barnett Shale - Part 10:  How not to describe Toluene

.