Apples, Arsenic, and Risk - Part 4: The TCEQ tells the EPA, Phooey!

Consumer Reports writes:

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.

But it's not that simple as the EPA points out:

The behavior of arsenic in the body is very complex. After absorption, inorganic arsenic can undergo a complicated series of enzymatic and non-enzymatic oxidation, reduction, and conjugation reactions. Although all these reactions may occur throughout the body, the rate at which they occur varies greatly from organ to organ. In addition, there are important differences in arsenic metabolism across animal species, and these variations make it difficult to identify suitable animal models for predicting human metabolic patterns. (1)

So with that in mind, the EPA has moved forward to significantly change the estimated carcinogenic potency of arsenic, which the Texas Commission on Environmental Quality (TCEQ) believes "already has a relatively high SFo." (2)

What's the EPA using to support this change?  The TCEQ points out:

USEPA used lung and bladder mortality data from Morales et al. (2000) for the dose-response assessment for the final draft SFo. 

And that "Morales et al. uses these mortality data to calculate standardized mortality ratios (SMRs) and notes:"

“Although the computed SMRs display a large amount of noise, there appear to be higher SMRs at high exposure levels compared to exposures in the lower range, especially for bladder and lung cancer.”

Wait just a dang minute, TCEQ exclaims:

To say that there is “noise” in the SMRs over the eight exposure categories is an understatement. 

What is the TCEQ basing this on?  Well back to square one, it's all about the dose-response curve and the SFo derived from it.  If we are going to except the 17 fold increase in potency then we must accept the dose response curve used to determine the slope.  The TCEQ notes this, stating:

Dose-response is the cornerstone of toxicology, but the lung and bladder mortality data (SMRs) from Morales et al. (2000) provide a poor basis for dose-response assessment as a dose-response is not apparent and not monotonic.

If you recall, the slope is derived from the line representing the dose and response and is based on the assumption that every dose poses a risk.  It is all predicated on a dose-response where the higher the dose the greater the risk.  With that in place you can get a line and a slope:

That line though, is dependent on a linear progression - higher the dose, higher the risk or occurrence.  But that's not apparent in the Morales et al. data the EPA is using according to the TCEQ:

For bladder cancer, the dose-response data from Morales et al. (2000) and used by USEPA do a poor job of characterizing the shape of the dose-response curve, as can be seen from the figure below (line added for emphasis).

What does the dose-response curve look like for bladder cancer?  Take a gander at this:

Page 13

With that shape seen, the TCEQ informs the EPA:

The ability to fit a line through data points does not necessarily mean that the underlying data adequately define the shape of the dose-response curve, including the critical low dose region. Based on the above considerations, the underlying data modeled by USEPA provide a poor basis for dose-response assessment.

The 17 fold increase is based on the Morales et al. data.  The SFo the EPA proposes is based off of a line that used a dose response curve that looks the one above.  How much confidence in that SFo should we have?

So why does Keeve Nachman, the Johns Hopkins scientist, tell Consumer Reports:

The [EPA] proposal "suggests that arsenic's carcinogenic properties have been underestimated for a long time and that the federal drinking-water standard is underprotective based on current science."

You'll have to ask him that.  I suspect he, like a lot of others, just accepts what others professionals have to say as long as it follows their established way of thinking.  Arsenic is toxic ergo any amount in the water is unhealthy.

But "current science" has not brought forth anything that can support lowering the current 10 ppb in drinking water.  So what's the problem?  Well the damage has already been done.  When Consumer Reports writes:

For known human carcinogens such as inorganic arsenic, the EPA assumes there's actually no "safe" level of exposure, so it normally sets exposure limits that include a margin of safety to ideally allow for only one additional case of cancer in a million people, or at worst, no more than one in 10,000. For water with 10 ppb of arsenic, the excess cancer risk is one in 500.

...it has drawn a line in the sand for the public.  The risk of cancer now becomes one in 500 for water the EPA claims has been telling us is "safe."

But that risk of one in 500 is based on a slope generated from a squiggly line akin to a path from the Family Circus.




That Morales et al. dose-response curve is what helped generate a SFo that is 17 times more potent than what we currently accept.

Next post: Apples, Arsenic, and Risk - Part 5: Calculating one in 500

Apples, Arsenic, and Risk - Part 3: EPA's Black Diamond Cancer Slope

Basically, what we want to know is how much gosh darn arsenic in my drinking water, apple juice, or grape juice is "safe?"  Heck, we know it's in there, in fact with arsenic it's darn near in everything we consume.

For now, the amount of arsenic in our drinking water we consider "safe" is 10 ug/L or 10 ppb (parts per billion).  That daily exposure to the human population (including sensitive subgroups) is likely to be without an appreciable risk of deleterious effects during a lifetime (70 years) of drinking water with 10 ppb arsenic in it.

Yet Consumer Reports tells its readers that "water with 10 ppb of arsenic, the excess cancer risk is one in 500" and Dr. Nachman with Johns Hopkins claims that the current 10 ppb standard for drinking water is "unprotective." (1)

So, which is it?  Is the new EPA proposal based on mortality data from Morales et al. (2000) for the dose-response assessment for the final draft SFo correct, or are we protected from deleterious effects during a lifetime with the current RfD and 10 ppb for drinking water?

It comes down to how much stock you put in the data used to calculate the numbers used in your model.

In my first post on this topic I showed how the CalEPA determines the concentration of a carcinogen which "pose no significant risk" for cancer under California's Proposition 65 regulation.

That's important to understand here, because if there is "no significant risk" of cancer at a particular concentration of a carcinogen, how can we also state, as Consumer Reports does, that EPA assumes there's actually no "safe" level of exposure?"

This is where it gets complicated, and here is where we lose the public.

Back to the question: How much gosh darn arsenic in my drinking water, apple juice, or grape juice is "safe?"

The reason I spend time researching and writing on this stuff is because we as environmental and public health professionals do a terrible job of quantifying risk so that the average person can answer the most basic of questions: Is this stuff in my food & drink going to harm me?  Is the contamination in, or around me, going to harm me or my kids?  Is it safe?

The amount of arsenic Consumer Reports states that will result in one additional cancer in 500 is 10 ppb, which is the amount or arsenic in drinking water that EPA states will not result in an appreciable risk of deleterious effects during a lifetime.

Neither of these statements can be true at the same time.  And for either one to be true, we must have confidence in the data used to calculate the risk.  Ultimate truth in determining a "safe" level of arsenic will never be known, so the best we can do is look at the concentration of arsenic in the drinking water that our current method of determining risk supports.

Either EPA's proposed slope factor is the way to go, or the current model supporting 10 ppb in drinking water is valid.

Forget "less is better" - that's a given - but it plays no part in accepting one model's conclusion over another.

An excess of one additional cancer in 500, as Consumer Reports informs its readers, results from drinking water with 10 ppb arsenic.  This is based on a simple calculation:

([mg/day] * SFo) / 70 kg = risk (CalEPA)

For calculating how much arsenic in drinking water that "pose no significant risk," the EPA uses the concept of "Unit Risk."

Unit Risk: The upper-bound excess lifetime cancer risk estimated to result from continuous exposure to an agent at a concentration of 1 µg/L in water, or 1 µg/m3 in air. The interpretation of unit risk would be as follows: if unit risk = 2 × 10-6 per µg/L, 2 excess cancer cases (upper bound estimate) are expected to develop per 1,000,000 people if exposed daily for a lifetime to 1 µg of the chemical per liter of drinking water. (2)

A bit of confusion takes place here.  What is a significant risk?  For carcinogens, CalEPA uses a "no significant risk level (NSRL) associated with a lifetime cancer risk of 10-5" - or one additional cancer in 100,000.  EPA, as you can see above, bases cancer risk on one additional cancer in 1,000,000 (10-6).

What's all this mean?  Based on the formula above, the [mg/day] calculated for "no significant risk"will be less for the EPA then for California's Proposition 65.

If less is better, wouldn't we want to go with the EPA's one in a million rather the CalEPA's one in 100,000?  Well of course, you know, less is better, right?

This is where it gets really confusing, not to mention difficult to communicate.  That one additional cancer in 100,000 or 1,000,000 is a probability, which is how we describe risk associated with carcinogens.

For example, the probability of you winning the Texas Lottery is 1 in 25,827,165 (3).  Does this mean you will win at least once if you play 25,827,165 different times?  No.  Same with "getting" cancer from drinking water with 10 ppb arsenic.

There is a difference here, though, with the lottery each play has the potential to win since six numbers will be drawn.  For exposure, the carcinogen may cause damage, or it may not.  Then, if it does cause damage, the body may repair that damage, or it may not.  Consequently, the more exposure the more chance for damage to occur.  This then is followed by repair.  Cancer is the result of damage (causing abnormal and unregulated growth of cells) that is not repaired and is then able to grow and spread (metastasis).

Cancer risk is based on the idea that if we know there is a concentration where we see cancer produced, then some concentration less than that will produce cancer at a diminishing rate.  That's not how carcinogens work in the body, but its the best we have - that's why it's known as a "theoretical potency factor."

The cancer slope factor "SFo" for arsenic that the EPA wants to use is based on the idea that there is a dose-response for carcinogens as there is for non-carcinogens.

In order for the Unit Risk that calculates the excess cancer risk per one microgram (1 ug) of arsenic per liter of drinking water to be valid, the cancer slope factor must be valid, that is, can we accept the potency of arsenic causing cancer based on a theoretical value derived from assuming that there is a dose-response for cancer?

It's the best toxicologist have to tell us what "safe" is.  So let's assume that the premise of a theoretical potency is correct based on the slope factor derived from a dose-response curve for a particular carcinogen, like arsenic.  How that potency is derived is based on the slope as it relates to dose and response.

What is the "slope"?  Same definition here as it has in math:

The slope of a line is a number that measures its "steepness", usually denoted by the letter m. It is the change in y for a unit change in x along the line. (4)

The steeper the dose-response line, the more potent the carcinogen.  All of this is theoretical, of course, because it assumes you can get a straight line for your dose-response data.  

Source

Cancer does not work that way, so you have to assume a straight line based on extrapolating a straight line from the data points you do have - which is predicated on the idea that there is a dose-response relationship at both the high and low dose.

Source

So the slope you calculate is going to be based on this hypothetical line you derive from the dose and the occurrence of cancer you have seen in your studies.  That line is critical in determining the slope.  That slope represents the potency.  The potency will calculate the Unit Risk.  The Unit Risk will tell us the excess cancer cases (upper bound estimate) that are expected to develop per 1,000,000 people if exposed daily for a lifetime to 1 µg of the chemical per liter of drinking water.

When Consumer Reports tells their readers:

For known human carcinogens such as inorganic arsenic, the EPA assumes there's actually no "safe" level of exposure, so it normally sets exposure limits that include a margin of safety to ideally allow for only one additional case of cancer in a million people, or at worst, no more than one in 10,000. For water with 10 ppb of arsenic, the excess cancer risk is one in 500.

consumer Reports and their researchers are telling us that EPA's cancer potency for arsenic, the theoretical slope factor - SFo - has been derived correctly.

In order for one excess cancer risk in 500 for 10 ppb arsenic in drinking water to be valid, the slope factor must be correctly extrapolated from the dose-response curve for the cancer in question.

Has it?

Next Post: Apples, Arsenic, and Risk - Part 4: The TCEQ tells the EPA, Phooey!


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Apples, Arsenic, and Risk - Part 2: EPA's Proposed Cancer Slope Factor

In the January 2012 Consumer Report's article "Arsenic in your juice," they write:

Debate over that [new arsenic] standard is likely to begin anew. The agency's [EPA] latest draft report, from February 2010, proposes that the number used to calculate the cancer risk posed by ingesting inorganic arsenic be increased 17-fold to reflect arsenic's role in causing bladder and lung cancer.

The proposal "suggests that arsenic's carcinogenic properties have been underestimated for a long time and that the federal drinking-water standard is underprotective based on current science," says Keeve Nachman, the Johns Hopkins scientist.

What the EPA proposes in their final draft is to base the "safe" level of arsenic exposure on is an Oral Cancer Slope Factor (SFo) of 25.7 per mg/kg-day.  25.7 is a 17 fold increase over the SFo currently used by IRIS which is 1.5 per mg/kg-day. (3).  In this draft, EPA is basing their risk on work that theoretically determines a cancer potency 17 times more potent than what has been established and used to determine the MCL for drinking water of 10 ppb.

With this new and increased potency, Johns Hopkins' Dr. Nachman is now emboldened to tell Consumer Reports that the current 10 ppb standard for drinking water is "unprotective."  And, as I quoted in my last post, Consumer Reports is able to make their case for concern by reporting that "For water with 10 ppb of arsenic, the excess cancer risk is one in 500."

The current acceptable limit for arsenic in drinking water is 10 ug/L (10 ppb) based on an "oral reference dose" (RfD) of 0.0003 mg/kg-day which was derived from data showing a "no observable adverse effect level (NOAEL) of 0.0008 mg/kg-day and a "lowest observed adverse effect level" (LOAEL) of 0.0014 mg/kg-day. (1)

Here is what all of that RfD, NOAEL, and LOAEL means:

NOAEL: The highest exposure level at which there are no biologically significant increases in the frequency or severity of adverse effect between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered adverse or precursors of adverse effects. (2)

LOAEL: The lowest exposure level at which there are biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group. (2)

RfD: The reference dose is based on the assumption that thresholds exist for certain toxic effects such as cellular necrosis. It is expressed in units of mg/kg-day. 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. (1)

The "deleterious effects during a lifetime" for arsenic is currently based on this possible health effect above the RfD of 0.0003 mg/kg-day:

Hyperpigmentation, keratosis and possible vascular complications.

The EPA, in 2010, proposes to change this from the amount of arsenic that might cause "hyperpigmentation, keratosis and possible vascular complications" to one that uses a cancer slope factor (SFo) based on:

Lung and bladder mortality data from Morales et al. (2000) for the dose-response assessment for the final draft SFo. (3)

This is where it gets a bit, well, complicated.

Next post:  Apples, Arsenic, and Risk - Part 3: EPA's Black Diamond Cancer Slope


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Apples, Arsenic, and Risk - Part 1: One in 500

In the January 2012 Consumer Report's article "Arsenic in your juice," they write:

Our analysis was led by Richard Stahlhut, M.D., M.P.H., an environmental health researcher at the University of Rochester with expertise in NHANES data, working with Consumer Reports statisticians. Ana Navas-Acien, M.D., Ph.D., a physician—epidemiologist at Johns Hopkins University’s Bloomberg School of Public Health, also provided guidance. She was the lead author of a 2008 study in the Journal of the American Medical Association (PDF) that first linked low-level arsenic exposure with the prevalence of type 2 diabetes in the United States.

So Consumer Reports accepts that there is a "link" between type 2 diabetes and low levels of arsenic...which is most likely one of the contributing factors for support of this statement that is also in their report:

But chronic toxicity can result from long-term exposure to much lower levels in food, and even to water that meets the 10-ppb [EPA] drinking-water limit.

as well as printing this quote...

“I suspect there is an awful lot of chronic, low-level arsenic poisoning going on that’s never properly diagnosed.” - Michael Harbut, M.D.

leading to this...

Consumers Union urges federal officials to set a standard for total arsenic in apple and grape juice. Our research suggests that the standard should be 3 ppb. 

Such standards would better protect children, who are most vulnerable to the effects of arsenic... 

Moreover, the EPA should impose stricter drinking-water standards for arsenic...

Ignoring the desire to have zero arsenic in the food and drink we consume, would lowering the level of arsenic to 3 ppb or less make a difference?  Would lowering the amount of arsenic in drinking water to a level less than 10 ppb (as the EPA is proposing) make a difference in preventing chronic toxicity?

Consumer Reports believes it would:

For known human carcinogens such as inorganic arsenic, the EPA assumes there's actually no "safe" level of exposure, so it normally sets exposure limits that include a margin of safety to ideally allow for only one additional case of cancer in a million people, or at worst, no more than one in 10,000. For water with 10 ppb of arsenic, the excess cancer risk is one in 500.

Public Health, especially those that look at chemical exposure risk, have been pigeon-holed by the "no safe level of exposure" for carcinogens statement.  Why?  because it always leads to the "risk of cancer" discussion of one in a million .

How do you think the general public - including medical professionals - understand the statement:

For water with 10 ppb of arsenic, the excess cancer risk is one in 500.

That statement is only true if you accept EPA's model that generated that risk.  And even if you accept their model, there is this little thing called reality that can nullify it.

But the damage has been done.  Drinking water with 10 ppb will bring about one more cancer for every 500 persons according to the EPA.

No...no it will not.  That's what the model predicts, and because the "people demand a number" we have made the model's output sacrosanct.  However, the prediction of one excess cancer risk in 500 for 10 ppb arsenic is nothing more than an answer spit out of an equation:

Source

That risk level - "R" is what we want to see, one in a million, one in 100,000... and that along with the "Cancer Potency" or "q" for the carcinogen in question will tell us how much of that chemical a 70 kg person can be exposed to over a lifetime (70 years) so that out of 1 million or 100,000, or 500 we should not see more than one additional cancer.

Sounds reasonable, until you look at how simple that formula is. The lifetime cancer risk - R - is whatever number we want to put in there.  Same with body weight.  Those numbers are not going to ever come into dispute.  So the "safe" intake, or in this case, the intake that would reduce your lifetime risk to one out of something, is predicated solely on the "theoretical cancer potency estimate for humans" which is also called the "cancer slope factor."

When the EPA produce data that shows arsenic at 10 ppb resulting in "male bladder cancer model outputs" for a "Lifetime Risk" of 3.20E-03 (3.2 per 1000) it is stating that their model's cancer slope factor (CSF) is accurate.  And to know if it is accurate, we need to compare the projected incidence to the actual incidence of bladder cancer in males.

That's reasonable, isn't it?  Well you would think so, but somehow that little bit of common sense seems to be missing.  You know, if the model predicts x is x what we are seeing.  Instead we have a system that has developed a methodology devoid of conformation.

And to top it off, we have lost sight of just what "for water with 10 ppb of arsenic, the excess cancer risk is one in 500" actually means.  That it is based on a theoretical cancer slope factor for one particular type of cancer.

Next post: Apples, Arsenic, and Risk - Part 2: EPA's Proposed Cancer Slope Factor.


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Poisoned Places: Part 4 - XXX

Pending

Poisoned Places: Part 3 - The whole towns contaminated.

Pending.

Back in the Saddle

Okay, been away from my blog for longer than I wanted.  Workload, out of town, and the holidays made the effort it takes to research and write a bit overwhelming.

I am going to switch gears on the last topic - but I want to come back to it.  So I have two posts with nothing in it just so it flows sequentially.

At this point in time, though, Dr. Oz and his arsenic in the apple juice has made news once again.