NPR does Arsenic, Apples, and Rice

On my way home from Texarkana I heard a short story on NPR regarding the FDA developing a threshold for arsenic in Apple Juice.

Here's some news for parents of the sippy-cup crowd: The Food and Drug Administration has proposed a 10 parts-per-billion threshold for levels of inorganic arsenic in apple juice. This is the same level set by the EPA for arsenic in drinking water. Right now, there is no FDA standard for apple juice.

Not this again, I thought.  I wrote about this...a lot, in a number of posts starting with this one for Apple Juice;  Apples, Arsenic, and Risk - Part 1: One in 500 and this one for rice; Arsenic in Rice: Part 1 - We Meet Again.

I am no fan of Dr. Oz and Consumer Reports for taking on this topic.  The science does not support their conclusion of risk.  All you gotta do is read my 30 or so posts to see that.  Or you can trust me, I write a blog.

My argument as to why it is bad science is based on this concept of toxicology:

If the dose is low enough even a highly toxic substance will cease to cause a harmful effect. The toxic potency of a chemical is thus ultimately defined by the dose (the amount) of the chemical that will produce a specific response in a specific biological system.

That's what they tell us on the Yale web page that defines the term "dose." That's the same thing Dr. Honeycutt with the Texas Commission on Environmental Quality (TCEQ) states:

The phrase, “the dose makes the poison,” is attributed to the ‘father’ of toxicology, Paracelsus (1493-1541). What he described was the dose-response concept and it is one of the fundamental ideas in assessing risk, in that, typically at higher doses the severity of an adverse effect increases.

I describe dose as a threshold and have shown it in my past posts as a line in the sand.

So the FDA is going to make "10 ppb" the new safe threshold.  Yay!!  Now apple juice that is less than that will be "safe."  Glad we got that settled.  So what's my issue?  Well for one thing - for the only thing in my opinion - that 10 ppb a'int based on science!

"We are pleased to see the Food and Drug Administration taking this action," says Urvashi Rangan, director of consumer safety and sustainability at Consumer Reports. "Proposing a 10 ppb guidance for apple juice — the same level set for water — is a reasonable first step in protecting consumers from unnecessary exposure to arsenic."

No, no it is not "reasonable."  Reasonable is based on the science of toxicology and risk. That 10 ppb in water, the MCL, is based on the safe dose of arsenic in drinking water.  That safe dose is derived from looking at the risk of 10 ppb in one liter of water.  It is based on a lifetime consumption of 2 liters of water over a 70 year lifetime.

Lifetime HA is for a 70 kg adult. The daily drinking water consumption for the 10 kg child and 70 kg adult are assumed to be 1 L/day and 2 L/day, respectively. The Lifetime HA for the drinking water contaminant is calculated from its associated Drinking Water Equivalent Level (DWEL), obtained from its RfD, and incorporates a drinking water Relative Source Contribution (RSC) factor of contaminant-specific data or a default of 20% of total exposure from all sources. (EPA)

Setting the dose - or safe threshold - for arsenic in apple juice to 10 ppb means that Consumer Reports thinks it reasonable that 2 liters of apple juice will be consumed for 70 years.  That's what I take issue with.  The safe level is not based on science and Consumer Reports should be basing their being "pleased" on science. Period

So what happened here?  FDA caved in to public pressure.  You can fight for science, but you are going to lose when science based organizations like Consumer Reports are incapable of grasping the concept.

Basically FDA found that almost all Apple Juice contains less than 10 ppb of arsenic anyway, so let's give the baby their bottle and make the safe threshold 10 ppb.  Done!.  But...but...that's not based on science.  Put a cork in it Bowman, this battle is over.  Science lost and the public is made stupider for thinking 10 ppb is "safe," but in the end, everyone wins.  Well, except science...

On the positive side, NPR just moved up a couple of notches in my book.  Well at least Allison Aubry did.

Here is how she summed it all up.

I would say, overall, Audie, for apple juice, I think the message is stand down. I mean, I can tell you as a mom of three children, from teen to toddler, I used to worry about all of these things. But if you look at the science here, if arsenic is limited down to 10 parts per billion, I think that this is something that we can mark off our worry list.

Thank you Allison Aubry...thank you!  That's exactly what I spent tens of thousands of words trying to show.  That sounds so good to hear her say that:

But if you look at the science here, if arsenic is limited down to 10 parts per billion, I think that this is something that we can mark off our worry list.

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RfD and Consensus...Part 1

I recently added a section called "consensus" to the Wikipedia page on "Reference Dose."

Yeah, that's what I do for fun.

I was looking for some supporting information to help me put my AHMP presentation together and came across an EPA memo titled:

WASHINGTON STATE DEPARTMENT OF HEALTH’S EVALUATION OF EPA’S PERCHLORATE DRINKING WATER PRELIMINARY REMEDIATION GOAL (PRG).

Back to the question of "safe" is it?  Here is what the memo says about perchlorates found in the Deep Creek area in the state of Washington:

There are no federal or Washington State drinking water standards for perchlorate. However, EPA uses a 24.5 ug/l perchlorate drinking water equivalent level (DWEL) as a preliminary remediation goal (PRG). 

In looking at how perchlorates enter into the human receptor, EPA has decided that the predominate way would be through drinking Deep Creek water which has perchlorate contamination.

Though there is no MCL - "maximum contaminant level" - for perchlorates, the EPA uses the DWEL - "drinking water equivalent level" to establish a "safe level" of perchlorates in the water that may be consumed.

The DWEL is the basis for establishing the MCL, so this is a reasonable approach   The DWEL is calculated for non-carcinogens and uses the reference dose (RfD).

The DWEL, therefore, is defined by EPA as:

"a drinking water lifetime exposure level, assuming 100% exposure from that medium, at which adverse, noncarcinogenic health effects would not be expected to occur."

When the EPA establishes the "safe" level of a contaminant in drinking water it bases it on the "lifetime health advisory" derived as follows:

The Lifetime HA for the drinking water contaminant is calculated from its associated Drinking Water Equivalent Level (DWEL), obtained from its RfD, and incorporates a drinking water Relative Source Contribution (RSC) factor of contaminant-specific data or a default of 20% of total exposure from all sources. 

As you can see, the RfD is the foundation upon which all these "safe" levels are derived.

Where we have confusion is when we compare a concentration in one media - such as apple juice - with the regulatory level established for drinking water.  Without an understanding of the RfD for non-carcinogens and risk factors for carcinogens, comparing what is found in the apple juice to what is acceptable in drinking water will make the apple juice appear to be tainted.

Case in point.  From the Dr. Oz Website: 

In 2006, the Environmental Protection Agency (EPA) enacted a stringent health standard with respect to arsenic levels in drinking water, stating concentrations should not exceed 10 parts per billion (ppb). Interestingly, the actual goal for arsenic exposure from drinking water, what is termed the maximum contaminant level goal (MCLG), is zero ppb. That bears repeating – the goal is no arsenic in our drinking water. The 10 ppb level 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.

So if our drinking water is "quite safe" why say this right after?

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?

It is, in my opinion, due to a disconnect in how a "safe" level is derived, a disconnect on how the the RfD is calculated, and a disconnect in how a "goal" and "risk" are different.

Let's look at benzene, for example. 

Source

Now benzene is kind of an odd bird, which makes it a good example on how this works.

Because benzene is considered a human carcinogen, there may be some degree of carcinogenic risk even below the MCL. Based upon EPA calculations, the EHP estimates that drinking water containing 5 ppb benzene would be associated with an increased lifetime risk of cancer in the range of between two and eight in one million (2 to 8 excess cancer cases in 1,000,000 people exposed). This estimate is based on a daily intake of two liters of water per day for 70 years. (1)

For this reason - carcinogenicity - benzene is given an MCLG of "0":

MCLG: Maximum Contaminant Level Goal. A non-enforceable health benchmark goal which is set at a level at which no known or anticipated adverse effect on the health of persons is expected to occur and which allows an adequate margin of safety. (2)

The EPA has also developed a toxicity value (Reference Dose or RfD) for non-cancer effects based on a human study.

A decrease in cells which are vital to immune system function (lymphocytes) was the most sensitive effect of several measured blood parameters. The adult drinking water equivalent level (DWEL) for this RfD is a benzene concentration in water of 140 ppb - 0.14 mg/L - ppm.

The benzene DWEL, which is the "lifetime exposure level assuming 100% exposure from that medium," is 0.1 mg/L.  This is based on the following formula:

Source

Plugging the RfD into the formula, we get:

DWEL (mg/L) = (0.001 x 70) / 2 = 0.14 mg/L = 0.1 mg/L or "ppm"

Because we know that there is a risk of cancer, the MCLG is set at zero.  Because we know that zero is unattainable, and we know that there is also a non-cancer risk, we can set the legally enforceable MCL for benzene at 0.005 mg/L or 5 ppb.

When Dr. Oz posts:

Interestingly, the actual goal for arsenic exposure from drinking water, what is termed the maximum contaminant level goal (MCLG), is zero ppb. That bears repeating – the goal is no arsenic in our drinking water. The 10 ppb level 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.

He is acknowledging that the current standard for arsenic is safe even though the goal is zero.  This is the same with benzene and all the other carcinogens.  We want zero, it is safe at the MCL.  Why is it safe?  Because the MCL and MCLG is set lower than the DWEL:

The MCLG is then derived by considering other known or potential sources of exposure, using the relative source contribution (RSC) factor.

• MCLG (mg/L) = DWEL x RSC

The RSC from drinking water is based on actual exposure data, or, if data are not available, a value of 20% is assumed for effects based on lifetime exposure. This allows 80% of the total exposure to come from sources other than drinking water, such as exposure from food, inhalation, or dermal contact. For the few MCLGs based on adverse effects related to exposure in children, an RSC of 100% was usually applied because the source of exposure for the critical study was drinking water. However, in more recent assessments, even when actual data from other sources are available, EPA uses a maximum RSC value of 80% to allow for potential unidentified sources. (3)

In other words, for a chemical such as benzene, a non-cancer RfD is established that generates a DWEL of 0.14 mg/L.  That DWEL is then multiplied by about 0.8 (80%) to compensate for all the other ways the chemical gets into the receptor.  For benzene, however, the MCLG is set at zero and the MCL - the value set as close to the MCLG as feasible using the best available analytical and treatment technologies and taking cost into consideration - is set at 0.005 mg/L.

• We consider the DWEL safe because it is based on the RfD.
• We consider the RfD acceptable because it is based on "an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime." (3)
• The MCL is less than the DWEL
• The MCLG can be less than the MCL and is set at "zero" for carcinogens.

How low can you go (/queue music)

All the way to zero.

Which brings me back to my original question of the RfD.  If the RfD is the foundation, how confident are we in the number we are using?  As the EPA writes:

A change in the RfD could lead to a change in the MCLG and thus possibly also in the MCL. (3)

A good read on all of this can be found here.

Next post: RfD and Consensus...Part 2


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Reference Dose: The foundation of Risk

I am getting ready to prepare my presentation "Apples, Arsenic, and Risk" for the upcoming 2012 AHMP conference in Alaska September 9 -13 in Anchorage. I wrote a lot on this topic in previous posts and need to pare it down (pun intended).

One of the most difficult parts of preparing a presentation is finding the starting point from which to tell your story. I can't just stand up there and whine about Dr. Oz and Chuck Norris. Nor can I present a bunch of facts and figures to prove my case. Boring. I get one shot at this, and I need to make it work.

So, where to start and what to build is where I am in July. I know the story's end, I know the moral, how do I tell it for Environmental Health Safety Professionals who depend on the very information I am going to present but know little about how it works without being condescending, preachy, or uninteresting.

Sure they understand risk, and regulatory compliance concentrations, and clean up levels, but do they understand why other than that is what they are told - or - what some formula spits out?  Why do we set the limit at 10µg/L for arsenic in our drinking water, 5 mg/L for the level of arsenic in our waste, 0.018 µg/L for ambient water quality criteria, 0.3 mg/L for arsenic in storm water, and 23 µg/L for arsenic in our fruit juice?

We are dealing with the same chemical, yet depending on where we find it, the values assigning the risk change.  As well it should. It is deemed "safe" if it is below the threshold depending on where we find it and what receptor (animal/plant/human) will be exposed to the arsenic, how much (dose), and length of time exposed (acute/chronic).

We draw a line in the sand and say "safe" or "presents a risk."  That line in the sand is drawn from a formula that looks at the length of time exposed as well as how the chemical will enter into the receptor. Since I am interested in protecting human health, the receptor will be based on that.

That formula - for humans - is based on the concept that there is a daily level at which we do not expect harm to take place over a lifetime.  This is what we call the "reference dose" or "RfD."

RfD: An EPA estimate, with uncertainty or safety factors built in, of the daily lifetime dose of a substance that is unlikely to cause harm in humans.

The foundation for risk for all chemicals that are suspected to cause harm to human health are based on this concept.  You must accept that concept - that there is an amount that we can consume every day for a lifetime - of a risk that is unlikely to cause harm in humans.

I've discussed this concept a number of times in previous posts.  This is how we do it in the United States. We set thresholds based on a formula of what we think might take place using a value that we have determined is a "safe" level if there is uptake into the receptor.

When the FDA says that 23 µg/L for arsenic is the maximum "safe" level in our fruit juice it is basing that level on the amount of juice to be consumed that would be put into the human receptor.  Therefore, if consuming juice - normally - over a lifetime, it would be “unlikely” to cause harm from arsenic.

When folks like Dr. Oz, Consumer Reports, and Chuck Norris compare the amount of arsenic found in apple juice to the amount of arsenic deemed safe for drinking water - the MCL - they are forgetting that the MCL and FDA concentration deemed "safe" are based on the same foundation; the RfD.  What is different in these two values is what is considered to be "normal" uptake. We drink more water than apple juice therefore we can consume more arsenic in the apple juice and remain safe.

Why are the two values different?

Because the RfD states that there is "daily lifetime dose of a substance that is unlikely to cause harm in humans."  Consume less than the RfD and there will "unlikely" be harm.  It is all about the RfD and the dose that delivers that RfD, and the length of time you will be exposed to that dose.

Chemical Exposure is similar to wealth, only the inverse.  If it takes $2.00 to buy a cup of coffee and you have no money or $1.99, you are in the same predicament - you will have no coffee.  Same goes with chemicals.  If the RfD concept is to be our foundation, then we have to move away from "less is better" and move toward a threshold based on uptake into the receptor.  Below that concentration in the matrix we are exposed to, we are fine.

Which brings us to another question.  If the foundation is the RfD, then how confident are we in the RfDs we have established?


Next Post: RfD and Consensus


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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!


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Apples, Arsenic, and Risk - Part 19: Like Dysentery, Only Sweeter

Ubiquitous = Everywhere

Consumer Reports tells us:

Arsenic is a naturally occurring element that can contaminate groundwater used for drinking and irrigation in areas where it’s abundant, such as parts of New England, the Midwest, and the Southwest. (1)

If we water our apple trees with ground water that is naturally contaminated with arsenic, or groundwater that is contaminated with arsenic from past pesticide and industrial use, that arsenic will be sucked up the trees and end up in the apples they produce.

That's one way, the other way has a bit more of the yuck factor involved.

If you look at the NHAMES data Consumer Reports references, and focus on this statement they make in their report, you will maybe understand why it is "ubiquitous."

Because most ingested arsenic is excreted in urine, the best measure of recent exposure is a urine test. (1)

Perhaps I can make my point using a song from the play "The Book Of Mormon."  That song, "Joseph Smith American Moses" has lyrics that discuss the spread of dysentery.  Now if you are familiar with South Park, the guys who wrote this play are the same ones who write that, so if you have sensitive ears or eyes you may not want to go looking for them.

So with apologies to Stone and Parker, here are my lyrics to illustrate the ubiquitousness of Inorganic Arsenic.

Arsenic goes out in the urine

Urine goes down the sewer

The sewer ends up in the river

The river irrigates the apple tree

The apple tree makes the apple juice

The apple juice goes in the cup

The cup goes to the mouth

The mouth goes to the stomach

Arsenic goes out in the urine

So now that I have that little ditty out of the way, let me put it all together using Vinny Gambini: - from "My Cousine Vinny - as a way to further illustrate what may be happening.

I'll set the scene: Vinny is in court cross examining Russell H. Greenfield, MD who made this statement:

"...the US government put a stop to the use of inorganic arsenical pesticides years ago. The same action, however, has not been taken by other countries, such as China, which just so happens to be the major source of apple juice products found in American stores. Chinese farmers, including apple farmers, still may use pesticides containing arsenic." (1)

The courtroom audience is hush, the air thick...

Vinny Gambini: And where does apple juice come from?
Dr. Greenfield:  China
Vinny Gambini:  Good...but more specifically....
Dr. Greenfield:  From the apples that grow on apple treesVinny Gambini: And those trees...do they require anything other than sunlight and soil to grow?
Dr. Greenfield: They need water.
Vinny Gambini: Water, that's right, don't be afraid just shout 'em right out when you know 'em.  And where does that water come from?
Dr. Greenfield: The rain
Vinny Gambini:  Rain...that's right, is that all?
Dr. Greenfield: Groundwater
Vinny Gambini: Ahh...pumped up from below the surface.  Anywhere else?
Dr. Greenfield: Rivers...
Vinny Gambini: Yes, rivers, streams. pounds, lakes...tanks - as you call them in Texas.  You mean surface water?
Dr. Greenfield: Yeah...surface water
Vinny Gambini: And is the water pumped up from the ground always free of arsenic?
Dr. Greenfield: No
Vinny Gambini: And that urinary arsenic we've been talkin' about.  Anyway that can get into the surface water?
Dr. Greenfield: Yeah, if that's where the treated water is discharged.
Vinny Gambini: So, what do you think? Isn't it possible that the arsenic is naturally coming from the soil or is present in the surface or groundwater used to irrigate the apple trees and not just from pesticides?
Dr. Greenfield: I suppose.
Vinny Gambini: I'm finished with this guy. 

I (almost) rest my case.

Next (and finally the last) Post: Apples, Arsenic, and Risk - Part 20: It is, and always will be, about the dose.


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Apples, Arsenic, and Risk - Part 16: The Great and Powerful Oz

Dorothy: Oh, apple juice! Oh - look! Oh!

Scarecrow: Come along, Dorothy - you don't want any of that apple juice. Hmm!

Apple Tree: Are you hinting my apple juice aren't what they ought to be?

Scarecrow: Oh, no! It's just that she doesn't like arsenic in her apple juice!

Apple Tree: Oh, you!  Have you been listening to Dr. Oz and Chuck Norris?

Scarecrow: Yeah.  But I also read about it in Consumer Reports...

Apple Tree: Sigh...Them too?  What did they have to say about my apple juice?

Scarecrow: Stuff like "mounting scientific evidence suggests that chronic exposure to arsenic and lead even at levels below water standards can result in serious health problems."

Apple Tree:  Really, and how much arsenic did they find in my apple juice?

Scarecrow: 3 ug/L...4 if you want to high-side it.

Apple Tree:  And Consumer Reports told you that at that level it could result in serious health problems.

Scarecrow:  Yeah.  And Dr. Oz said the same thing on his web site...that "the findings raise significant health concerns for us and for our children, and have generated incredulousness that this could happen in our country."

Dr. Oz: I am the great and powerful Oz!

Apple Tree: Yeah, so I've been told.

Scarecrow: Chuck Norris said "Poisonous apples are definitely not just being offered in fictional Snow White adventures."
 
Apple Tree:  So my apple juice is poisonous?

Dorothy:  Oh my goodness!  And I've been drinking it.  And Toto too!

Scarecrow:  Consumer Reports says that "arsenic has been notoriously used as a poison since ancient times. A fatal poisoning would require a single dose of inorganic arsenic about the weight of a postage stamp."  A postage stamp!  Do you know how small a postage stamp is!?!

Dorothy: Oh my!

Apple Tree: And how much did they find in my apple juice?

Scarecrow: 4 ug/L.

Apple Tree. How much do you weigh scarecrow?

Scarecrow:  About 70 kilograms

Apple Tree:  Do you know how much Arsenic in a liter of water it would take to kill you or Dorothy?

Doroethy: Oh my, leave me out of this...

Apple Tree:  Well I looked up on the Google and found the weight of a postage stamp.  0.0533 grams.  Do you know how much that is in micrograms?

Scarecrow:  Nope (points to head).  Haven't got a brain, remember?

Apple Tree:  Okay, work with me here.  There are 1000 milligrams in a gram and 1000 micrograms in a milligram.

Dorothy:  This is why Barbie hated math too!

Apple Tree:  Yeah, but this is important.  Everyone is sayin' my apple juice aren't what they ought to be because of arsenic.  They are trying to compare what 0.0533 grams of arsenic will do to you with the 4 micrograms found in my juice.  0.0533 grams is 53,300 micrograms.  The amount needed to kill you is 13,325 times higher than what one liter of my apple juice contains.

Dorothy: Lions, and Tigers, and inorganic arsenic, oh my!

Scarecrow:  Well on the Dr. Oz web page, it does have a Clinical Assistant Professor of Medicine, some guy by the name of Russell H. Greenfield, MD, that tells us:

Arsenic is naturally abundant in our environment in such places as rock formations, minerals and soil, and is also a byproduct of human agricultural and industrial pursuits. Keep this in mind, because it’s important to understand we are all exposed to small, background amounts of arsenic on a regular basis from the food we eat, the water we drink, and the air we breathe. Concerns only arise when considering the type of arsenic (organic or inorganic) we are exposed to, and especially the degree of exposure.

Apple Tree:  Precisely!  Now you're catching on.  Look at the NHAMES study Consumer Reports reviewed.  The average total urinary arsenic is about 8 ug/L.  Now some of that is organic and some inorganic, but that fact is, Americans are exposed to arsenic without drinking apple juice.  It's the dose that's important.  My apple juice has about 4 ug/L of arsenic.  A juice box holds about 8 ounces - or about 0.25 Liters...so that's about 1 ug of arsenic consumed.

Scarecrow: So what your really telling us is that if arsenic exposure is so bad, why don’t you see more people sick or dying from it?’

Apple Tree:  No.  What I'm saying is to consider the dose...the amount of arsenic being consumed from my apple juice in comparison to the total.  The reason you don't see more people getting sick or dying is that the dose we take in is small.

Scarecrow:  Yeah, I thought that would be your argument.  So did Consumer Reports.  They say "many diseases likely to be increased by exposure even at relatively low levels are so common already that its effects are overlooked simply because no one has looked carefully for the connection.”

Apple Tree: So if no one has looked for a connection, does that mean a connection is there?

Scarecrow: Yer' givin' me a headache Apple Tree!  Consumer Reports says that when they did look, "the connections they've found underscore the need to protect public health by reducing Americans’ exposure to this potent toxin."

Apple Tree:  Once again with the potent toxin....

Scarecrow:  Well it is...a postage stamp amount can kill you.

Apple Tree:  We're not dealing with anything near that amount in my apple juice.  Why bring up a potential harm that's not present?  Let's stick to the arsenic in my apple juice, not what's found elsewhere.

Scarecrow: Well...still, they found connections....

Apple Tree:  You mean the type 2 diabetes study and the study showing poorer scores in global cognition, processing speed and immediate memory?

Scarecrow:  Yeah...and Sharyn Duffy's hyperkeratosis...

Apple Tree:  Okay, and even if there was a connection, was that connection based on 4 ug/L in one juice box...or even two juice boxes a day?

Scarecrow: Ahhh...well, even without a brain, consuming more arsenic can't be good.  Isn't it additive?

Apple Tree:  Yes it is.  But were talking 1.4 ug/L more arsenic in apple juice drinkers.  Does 1.4 ug/L create any additional risk for these apple juice drinkers?  Not based on any of the studies Consumer Reports or Dr. Oz presented.

Dorothy: But what if I don't want to consume any more arsenic than I have to?  What if I want to limit Toto's exposure just in case?  If it is a carcinogen there is some risk right?

Apple Tree:  Yes.  And it is perfectly fine for you to choose not to drink my apple juice.  There is no such thing as zero risk, so if reducing the amount of arsenic you take in is something you think prudent, then by all means stop drinking my apple juice.

Dorothy:  And you won't be mad at me?  You won't throw apples at me?

Apple Tree:  Nope.  All I ask is that you don't tell folks that my apple juice aren't what they ought to be.

Dr. Oz: I am the great and powerful Oz.  Pay not attention to that apple tree!

Chuck Norris:  He's part of a government cover-up, chop him down and buy local!

Apple Tree:  I am local you ignorant munchkin!

Dorothy: Oh my!

Apple Tree: Un-tether that balloon and get those two fear-mongers out of here.

Dorothy:  Well I better be going, but which way is the correct way forward?

Apple Tree:  Follow the path the data leads you down, not where the hype sends you.

Dorothy:  But it's all so confusing and scary!  How will I know when there really is a connection?

Apple Tree:  Be objective.  And when you read something that says there is a correlation, click your heals three times and repeat:

Correlation does not imply causation...

Correlation does not imply causation...

Correlation does not imply causation...

Next Post: Apples, Arsenic, and Risk - Part 17: Generated Incredulousness


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Apples, Arsenic, and Risk - Part 15: 19% more...67 years...carry the 2...

Consumer Reports states in their January 2012 report on arsenic in apple juice:

The resulting analysis of almost 3,000 study participants found that those reporting apple-juice consumption had on average 19 percent greater levels of total urinary arsenic than those subjects who did not.

If the average total urinary arsenic [NHANES] for 12-18 year old's is 8.55 ug/L, Apple juice drinkers would be - on average - 19% higher than that, or 10.17 ug/L.

The "long-term low-level arsenic exposure" was calculated as follows:

We estimated long-term low-level exposure by multiplying current estimated arsenic levels by the number of years residing in current home.

So an 18 year old would have a long-term low-level arsenic exposure of 18 x 8.55 = 153.9 ug/L-year.

And the 18 year old apple juice drinker would have a long-term low-level arsenic exposure of 18 x 10.17 = 183.1 ug/L-year.

So if the unstandardized regression coefficient - B - results are as reported, these are the scores we would predict between the two groups, average & apple juice drinkers, over an 18 year exposure period.

I ran their data in an Excel spread sheet so I could see what the difference would be between the two scores.  That's found in the last column at the bottom.  Notice how not one of those tests has a decrease or increase in the score over one (1).

The question I have is this: If the linear regression calculates an unstandardized regression coefficient called "B," and that we interpret an unstandardized regression coefficient as follows:

For every metric unit change in the independent variable, the dependent variable changes by X units.

The change in score these researchers report is so small as to be of little value.  Yet what was reported in this paper was used by Consumer Reports to make the claim that low-levels of arsenic below the drinking water MCL of 10 ug/L presents "a chronic problem" "related to poor scores in language, memory, and other brain functions."

Consumer Reports is using the conclusion of this paper to support their claim that:

Mounting scientific evidence suggests that chronic exposure to arsenic and lead even at levels below water standards can result in serious health problems.

Is this the" mounting scientific evidence" they are using to support their claim that low-level exposure is related to poor scores in language, memory, and other brain functions?

Did the researchers from Texas Tech and the University of North Texas find that "long-term low-level exposure to arsenic was significantly associated with poorer scores?"

Yes.  And that's the problem that needs to be addressed.

Numbers mean something.  Those "Bs" reported are valid in supporting their conclusion:

Our findings suggest an association between low-level arsenic exposure and neuropsychological functioning, as originally hypothesized. Of particular interest is the association between long-term low-level arsenic exposure and neuropsychological functioning across a broader range of domains than current exposure. Our findings offer the first direct evidence that low level arsenic exposure, extrapolated from current arsenic levels and self report of duration in residence is associated with poorer neuropsychological functioning among community-dwelling adults and elders in the U.S.

They found an association and the statistics - the p-value - supports it.  But what did they really find?

Or, more importantly, did they see results that would support lowering the level of arsenic deemed safe?  Are their results strong enough to stop us from drinking apple juice?  Should we, on the basses of a -0.001 change in a score require apple juice providers to reduce the concentration of arsenic from and average of 4 ug/L to 3 ug/L?

Why did four researchers produce this paper, and why did it it get published in a peer review journal?  Because there is nothing wrong with it in terms of it meeting the standards for publishing.

It's valid, it's honest, it's conclusion is correct.  Unfortunately it does not support the claim of "mounting scientific evidence suggests that chronic exposure to arsenic and lead even at levels below water standards can result in serious health problems."

It shows something that means nothing.  And that right there leads Consumer Reports, Dr. Oz, and good ol' Chuck Norris down the path of requiring a change where one is not needed.

As our investigation found, when scientists and doctors do look, the connections they’ve found underscore the need to protect public health by reducing Americans’ exposure to this potent toxin.

Why is this a big deal?  Let me quote the Texas Commission on Environmental Quality (TCEQ) once again:

[I]f erring on the side of conservatism significantly overestimates risk or hazard and is not  fully  justified, then harm to public health may result from diverting public, industry, and government attention and resources away from chemicals which may represent more of a public health risk at environmental levels. (TCEQ)

Next Post: Apples, Arsenic, and Risk - Part 16: The Great and Powerful Oz

Apples, Arsenic, and Risk - Part 14: A poorer score of -0.001

Once more....

Consumer Reports claims in their January 2012 article on arsenic in apple juice:

Mounting scientific evidence suggests that chronic exposure to arsenic...even at levels below water standards can result in serious health problems.

A 2011 study examined the long-term effects of low-level exposure on more than 300 rural Texans whose groundwater was estimated to have arsenic at median levels below the federal drinking-water standard.

It found that exposure was related to poor scores in language, memory, and other brain functions.

What I want you to focus on is "even at levels below water standards" and "exposure was related to poor scores in language, memory, and other brain functions."

In my last post I looked at these two claims by the studies authors:

1. Current estimated groundwater arsenic exposure level was significantly associated with poorer scores in language, visuospatial skills, and executive functioning. 
2. Current arsenic exposure significantly classified cognitive dysfunction. 

In this post I want to look at their conclusion for what the term "long-term low-level arsenic exposure:"

We estimated long-term low-level exposure by multiplying current estimated arsenic levels by the number of years residing in current home.

I'm not going to make an argument as to whether or not that that's a valid methodology.  I don't need to.  The B(SE) they report in Table 3 tell me there is nothing to be concerned about:

Source

Once again, I'm no linear regression expert or statistical astute person.  What I know about something is what I have been taught and what is consistently discussed.  I may be wrong on how to interpret those B(SE) scores, but I don't think I am. (Comments are on - feel free to skool' me)

Here is what the Google says about an "unstandardized regression coefficient" - "B":

To interpret an unstandardized regression coefficient: for every metric unit change in the independent variable, the dependent variable changes by X units. For instance, if income is the dependent variable, and years of education is one of the independent variables, and the unstandardized regression coefficient for education is 3,000, then this would mean that for very additional year of education a respondent has, their income increases by $3,000.00 (controlling for the other independent variables in the equation). (1)

and...

As you may remember, in a linear regression model the estimated raw or unstandardized regression coefficient for a predictor variable (referred to as B) is interpreted as the change in the predicted value of the dependent variable for a one unit increase in the predictor variable. Thus a B coefficient of 1.0 would indicate that for every unit increase in the predictor, the predicted value of the dependent variable also increases by one unit. In the common case where there are two or more correlated predictors in the model, the B coefficient is known as a partial regression coefficient, and it represents the predicted change in the dependent variable when that predictor is increased by one unit while holding all other predictors constant. (2)

Let's take the example in the first blurb.

"if income is the dependent variable" will now become "if RBANS Visuopatial score is the dependent variable."

"years of education is one of the independent variables" will now become "long-term low-level arsenic exposure is one of the independent variables."

"and the unstandardized regression coefficient for education is 3,000" will now become "and the unstandardized regression coefficient for  RBANS Visuopatial  is -0.001"

"then this would mean....."

"that for very additional ug/L-year of arsenic a rural Texan is exposed to, their  RBANS Visuopatial score decreases by 0.001 (controlling for the other independent variables in the equation)

Please tell me I am wrong in how this is to be interpreted.  Please don't tell me that these four researchers from Texas Tech and the University of North Texas reported that:

However, we can assert that those individuals who have resided for long periods of time in regions that have historically low levels of arsenic in groundwater supplies are at increased risk for cognitive dysfunction.

...based on unstandardized regression coefficient - B - results as follows:

• MMSE: −0.003
• CLOX 2: −0.001
• FAS: −0.012
• RBANS Language: −0.005
• TMTA:  0.034
• EXIT: 0.006
• RBANS Immediate Memory: −0.010

How does a change in score of -0.003 for each ug/L-year arsenic exposure constitute an "increased risk for cognitive dysfunction?"

Let me do some math...."long-term low-level arsenic exposure:"

We estimated long-term low-level exposure by multiplying current estimated arsenic levels by the number of years residing in current home.

So the ug/L-year = Estimated Arsenic Level x Number of Years in Home...Looking at Table 2....

Source

So....240.15 / 6.33 = 37 years...nah, that can't be right.  972.83 / 15.26 = 63 years.  I'm not sure how they calculated that number of 240.15.  If the highest range was 972.83 ug/L-years and the highest arsenic range was 15.26 ug/L that would mean 63 years of exposure in the same house.  That's possible, I guess, especially for a rural community.

The unstandardized regression coefficient states the for every metric unit change in the independent variable, the dependent variable changes by X units.  So the "X" units we are talking about is the score.  What I don't know is the unit change we could use to calculate that predicted score.

The long-term arsenic range is 2.87 - 972.83 ug/L-years.  I'll assume that the unit change is one ug/L-year.  This would equate to a difference of 972.83 - 2.87 = 969.96 units of change.

If we take that number - 969.96 and multiply it by the B values reported as "significantly associated with poorer scores" we would expect the following score changes for a person exposed to 15.26 ug/L of arsenic for 67 years:

• MMSE: −0.003 x 969.96 = -2.9
• CLOX 2: −0.001 x 969.96 = -0.96
• FAS: −0.012  x 969.96 = -11.6
• RBANS Language: −0.005  x 969.96 = -4.8
• TMTA:  0.034  x 969.96 = 32.9
• EXIT: 0.006  x 969.96 = 5.8
• RBANS Immediate Memory: −0.010  x 969.96 =  -9.6

I'm not sure that a unit of change is calculated like that, but based on a worst case scenario, and from what the Google tells me about how an "unstandardized regression coefficient" works, that's the changes in scores I would predict for a 67 year long exposure to 15.26 ug/L of arsenic.

What would we predict for a person who consumes apple juice for 67 years?


Next Post: Apples, Arsenic, and Risk - Part 15: 19% more...67 years...carry the 2...


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Apples, Arsenic, and Risk - Part 13: How much is "19 percent higher levels?"

My last post had me looking at a study Consumer Reports states in their January 2012 report on arsenic in apple juice that:

A study published in 2011 in the International Journal of Environmental Research and Public Health examined the long-term effects of low-level exposure on more than 300 rural Texans whose groundwater was estimated to have arsenic at median levels below the federal drinking-water standard. It found that exposure was related to poor scores in language, memory, and other brain functions.

This study used linear regression to:

Examine the potential association between current and long-term arsenic exposure and detailed neuropsychological functioning in a sample of rural-dwelling adults and elders.

What we know so far is this:

• Linear regression models were created using raw neuropsychological test scores as outcome variables and either current or long-term arsenic exposure estimates as predictor variables.
• Linear regression is when you want to predict values of one variable, given values of another variable.

So what we can see from Table 3:

Source

Is that when the current arsenic level increases by one unit, the  "RBANS Language scores" decrease by 0.458 (controlling for the other independent variables in the equation).  That's the prediction of their linear regression model for RBANS Language Scores [−0.458 (p = 0.008)].

For the 13 tests administered, the study found that current GIS-based groundwater arsenic exposure was significantly related to poorer scores for three of the tests:

• RBANS Language scores B(SE) = −0.458 (0.171), p = 0.008
• Visuospatial skills CLOX2, B(SE) = −0.118 (0.060), p = 0.048
• Executive functioning CLOX1 B(SE) = −0.225 (0.080), p = 0.005

So for the sake of argument (and to give me something to write about) let's say that this model is predictive as the authors claim.  How much "poorer" would the scores be for children who drink apple juice?

According to Consumer Reports:

The resulting [NHANES] analysis of almost 3,000 study participants found that those reporting apple-juice consumption had on average 19 percent greater levels of total urinary arsenic than those subjects who did not.

Interesting....remember this table from NHANES:

Source

The mean and (95% CL) for kids 6-11 years old is 7.08 (5.68-8.84).

With that, we can calculate how much "19% more total urinary arsenic" would be for 6-11 year old kids who drink apple juice.

Do some math...carry the 2....7.08 x 1.19 = 8.43 ug/L

So apple juice drinking 6-11 year old kids have 1.35 ug/L more arsenic.  If the linear regression model in this study is correct, we would predict their scores to decrease as follows.  The "B" represents the slope of the regression line--the amount of change in Y due to a change of 1 unit of X:

• RBANS Language scores: -0.618
• Visuospatial skills CLOX2: -0.159
• Executive functioning CLOX1: -0.304

Is that decrease in score a concern?  Look at the standard deviations for the test results in Table 2.  (CLOX means are not listed by the authors, I am assuming their range is similar to the other tests)

Source

For RBANS Language the standard deviation is 5.46 points.  Our little apple juice drinkers would see a decrease in their scores of 0.618.

"But"...you say..."the results might understate the correlation between juice consumption and urinary arsenic levels because NHANES urinary data exclude children younger than 6, who tend to be big juice drinkers."

Let's up the arsenic to that found in males; 9.50 ug/L.  19% more...carry the 2...9.50 x 1.19 = 11.3 ug/L

So...2.25 ug/L more arsenic...or 2.25 units...2.25 x -0.458 = 1.03 points lower for RBANS Language.  That's assuming their model holds true.   Look at the range of results they got; 8 - 42.  Would a decrease of one point indicate a concern?  Is this what Consumer Reports means when they state:

"Mounting scientific evidence suggests that chronic exposure to arsenic...even at levels below water standards can result in serious health problems."

But all that's for the current arsenic level.  Let's look at what they found when they ran the linear regression with long-term arsenic - ug/L-years.


Next Post: Apples, Arsenic, and Risk - Part 14: A poorer score of -0.001

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Apples, Arsenic, and Risk - Part 12: Correlation does not imply causation

In my last post I asked the question:

What about Consumer Reports telling its readers about a 2011study in the International Journal of Environmental Research and Public Health that examined the long-term effects of low-level exposure on more than 300 rural Texans whose groundwater?

Consumer Reports claims in their January 2012 article on arsenic in apple juice that these Texans were estimated to have exposure to arsenic at median levels below the MCL and when tested showed poor scores in language, memory, and other brain functions.

That brings me to asking this question: will "low-levels" of arsenic, as was found in the apple juice samples tested by Consumer Reports lead adversely affect those that consume apple juice?  Here is what they state at the beginning of their report:

Mounting scientific evidence suggests that chronic exposure to arsenic...even at levels below water standards can result in serious health problems.

I've looked at cancer, hyperkeratosis, and type 2 diabetes, that leaves this one last study on chronic exposure to look at.  Will this support their claim that levels below the MCL can result is serious health problems?

Here is what Consumer Reports tells their readers about this 2011 study:

It found that exposure was related to poor scores in language, memory, and other brain functions.

Here is what that paper concludes:

The results of the study showed that GIS-based groundwater arsenic exposure (current and long-term) was significantly related to poorer scores in language, visuospatial skills, and executive functioning. Additionally, long-term low-level exposure to arsenic was significantly correlated to poorer scores in global cognition, processing speed and immediate memory.

"Significantly related" and "significantly correlated."

Two things to keep in mind here:

1. The term "significantly" is in reference to statistics.  That is, it is unlikely to have occurred by chance.  Not significant as in "sufficiently great or important to be worthy of attention."
2. The term "correlated" means a statistical measurement of the relationship between two variables.

So "significantly correlated" means a relationship between two variables that is unlikely to have occurred by chance.

Rule number one about correlations:  They do not imply causation!!!

Source

...and so it goes with low-levels of arsenic in our our apple juice and water.

Let's look at the table of results:

Source

I am by no means a statistician, nor am I really that versed to expertly explain "unstandardized regression coefficient" as it is derived from a "linear regression" model.  For more info on this see 1, 2, 3, or 4.

What I do understand about this table is this:

Linear regression models were created using raw neuropsychological test scores as outcome variables and either current or long-term arsenic exposure estimates as predictor variables.

So....

Simple linear regression is when you want to predict values of one variable, given values of another variable.

The purpose of regression analysis is to come up with an equation of a line that fits through that cluster of points with the minimal amount of deviations from the line. The deviation of the points from the line is called "error."

Once you have this regression equation, if you knew a person's Long-term or current arsenic level of exposure, you could then predict their score on one of the  neuropsychological tests administered.

The data in Table 3 is reported for:

B = unstandardized regression coefficient.

So...

B coefficients are interpreted as the amount of change in the dependent variable (Y) that is associated with a change in one unit of the independent variable (X).

All B coefficients are unstandardized, which means that the magnitude of their values is relative to the means and standard deviations of the independent and dependent variables in the equation.

It represents the slope of the regression line--the amount of change in Y due to a change of 1 unit of X.

The unstandardized coefficients are used for actually making a prediction, using the independent variables as they were measured.  For example, if a variable is in dollars, the unstandardized coefficient is in dollars, if a variable is in inches, it is in inches.

What Table 3 tells us is this:

If "RBANS Language scores" is the dependent variable, and "current arsenic level" is one of the independent variables, and the unstandardized regression coefficient (B) for  "RBANS Language scores"  is −0.458 (p = 0.008), then this would mean that for every additional ug/L of arsenic exposed to, there would be a decrease of 0.458 in the RBANS Language scores  (controlling for the other independent variables in the equation).

Remember, correlation does not imply causation.  In other words, it may not be the arsenic that drops the score but something else going on.  For example, there was an increase in polio cases correlated to the amount of ice cream sold.  Ice cream was not the cause of polio, polio cases increased in the summer as did sales of ice cream.

But let's say that this model is predictive, as the authors claim:

Groundwater arsenic exposure (current and long-term) was significantly related to poorer scores in language, visuospatial skills, and executive functioning.

What "serious health problems" - or in this case - how much "poorer" would the scores be for children who drink apple juice?

Next post: Apples, Arsenic, and Risk - Part 13: How much is "19 percent higher levels?"


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Apples, Arsenic, and Risk - Part 9: Type 2 diabetes - A very weak link

Ana Navas-Acien, M.D., Ph.D., a physician & epidemiologist at Johns Hopkins University’s Bloomberg School of Public Health, was used by Consumer Reports in their January 2012 article called "Arsenic in your Juice".  According to Consumer Reports:

[Dr. Ana Navas-Acien] was the lead author of a 2008 study in the Journal of the American Medical Association that first linked low-level arsenic exposure with the prevalence of type 2 diabetes in the United States.

If you can remember the "ground rules" I discussed in my last post, we can look at her paper, her data, and her conclusion to see if there is, indeed, a "link" between low-level arsenic exposure and type 2 diabetes.

Let's first look at the paper's claim:

The positive association between total urine arsenic and diabetes after adjustment for markers of seafood intake was consistent for most subgroups examined, with somewhat greater associations in participants who were younger, overweight, and never smokers (FIGURE 2).

Source

We are all taught in our EPI classes, at least I was at Texas A&M's School of Rural Public Health, that if the range of your odds ratio (OR) includes the number one - "1" - there is no statistically significant association.  Period.

Now there is nothing wrong with Dr. Ana Navas-Acien including all her data in her report.  I would have left all the non-associations out, but that's just me.  What's troubling with her work is the graphic she includes in Figure 2.

Source

What can one reasonably conclude from looking at that graphic?  Look how all those black boxes fall on the "favors association" side of the graph.  What is Dr. Ana Navas-Acien trying to convey to her audience?

This is where the "whole truth" comes in.  Her graph makes it look like there is an association between total urine arsenic and diabetes every where she looked.  That's not true.  Look at the ranges.  All but four of them include the number "1."  Look at the P-values reported, all of them are above 0.05 for the interaction.

Remember, we want to reject the null hypothesis that there is ‘no effect of the intervention’ or ‘no differences in the effect of intervention between studies’ (no heterogeneity).  We can only reject the null if the P-Value is less than 0.05 (95%).  The null says there is no association, to reject that notion we need a P-value that is less than 0.05.

Now look at the four Adjusted Ratios in Table 2 that do not include the number "1" in their range:

• 1.71
• 1.35
• 1.55
• 1.54

How large of a difference is that?  They are all less than 2 to 1, so you can't say the association is twice as high.  But there's another factor to consider when looking at those four values.  How many participants - "n" - were in the populations compared?  I'll address that in an upcoming post, because its important.  But let's forget about those four for now and look at the overall "Adjusted Ratio" she reports:

1.26 (1.02-1.56)

How confident should we be in that number?  The range does not include a "1", so we can truthfully state that we see an association here:

After adjustment for biomarkers of seafood intake, total urine arsenic was associated with increased prevalence of type 2 diabetes.

The number spat out, "1.26," does not include the number "1" in its range therefore there is a positive association even though the lower range is only 2/100 higher than "1".

And the whole truth?  Here is what she should have concluded:

Our research shows a weak association between urinary arsenic that has been adjusted for biomarkers of seafood intake and the prevalence of type 2 diabetes.

We have two things working against us here when we calculate ORs and P-values.

1. Statistics looks at the data point as absolute
2. Sample and analytical data points are not absolute numbers - they are a statistical range that we report as a single number.

How much confidence should we have in this Odd Ratio: 1.26 (1.02-1.56)?

Consumer Reports believes there is enough confidence in that number to make the claim that Dr. Ana Navas-Acien "first linked low-level arsenic exposure with the prevalence of type 2 diabetes in the United States."  

That claim was backed up by this journal paper, and in that paper the OR of 1.26 (1.02-1.56) is reported and the conclusion that "This finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water, a widespread exposure worldwide, may play a role in diabetes prevalence." is made.

It all rests on this one bit of data: 1.26 (1.02-1.56).

How much confidence should we have in this Odd Ratio: 1.26 (1.02-1.56)?  It is that number and it's range that allows her to report that:

This finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water, a widespread exposure worldwide, may play a role in diabetes prevalence.

Next Post: Apples, Arsenic, and Risk - Part 10: Type 2 diabetes - 1.26 based on what?

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